FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Bent, S Kane, C Shinohara, K Neuhaus, J Hudes, ES Goldberg, H Avins, AL AF Bent, S Kane, C Shinohara, K Neuhaus, J Hudes, ES Goldberg, H Avins, AL TI Saw palmetto for benign prostatic hyperplasia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID DOUBLE-BLIND; CONTROLLED-TRIAL; SERENOA-REPENS; FINASTERIDE; EFFICACY; MEN; DOXAZOSIN; EXTRACT; INDEX AB BACKGROUND: Saw palmetto is used by over 2 million men in the United States for the treatment of benign prostatic hyperplasia and is commonly recommended as an alternative to drugs approved by the Food and Drug Administration. METHODS: In this double-blind trial, we randomly assigned 225 men over the age of 49 years who had moderate-to-severe symptoms of benign prostatic hyperplasia to one year of treatment with saw palmetto extract (160 mg twice a day) or placebo. The primary outcome measures were changes in the scores on the American Urological Association Symptom Index (AUASI) and the maximal urinary flow rate. Secondary outcome measures included changes in prostate size, residual urinary volume after voiding, quality of life, laboratory values, and the rate of reported adverse effects. RESULTS: There was no significant difference between the saw palmetto and placebo groups in the change in AUASI scores (mean difference, 0.04 point; 95 percent confidence interval, -0.93 to 1.01), maximal urinary flow rate (mean difference, 0.43 ml per minute; 95 percent confidence interval, -0.52 to 1.38), prostate size, residual volume after voiding, quality of life, or serum prostate-specific antigen levels during the one-year study. The incidence of side effects was similar in the two groups. CONCLUSIONS: In this study, saw palmetto did not improve symptoms or objective measures of benign prostatic hyperplasia. C1 San Francisco VAMC, Dept Med, Gen Internal Med Sect, San Francisco, CA 94121 USA. San Francisco VAMC, Urol Sect, San Francisco, CA 94121 USA. Univ Calif San Francisco, Osher Ctr Integrat Med, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, Div Gen Internal Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Family Practice, San Francisco, CA 94143 USA. Kaiser Permanente No Calif, Oakland, CA USA. RP Bent, S (reprint author), San Francisco VAMC, Dept Med, Gen Internal Med Sect, 111-A1,4150 Clement St, San Francisco, CA 94121 USA. EM bent@itsa.ucsf.edu FU NCCIH NIH HHS [1 K08 ATO1338-01]; NIDDK NIH HHS [1 R01 DK56199-01] NR 39 TC 183 Z9 191 U1 0 U2 5 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 9 PY 2006 VL 354 IS 6 BP 557 EP 566 DI 10.1056/NEJMoa053085 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 010HF UT WOS:000235177500005 PM 16467543 ER PT J AU Gounder, CR Harris, NL Finn, DS Kay, J Stone, JR AF Gounder, CR Harris, NL Finn, DS Kay, J Stone, JR TI Case 4-2006: A 79-year-old woman with myalgias, fatigue, and shortness of breath - Active giant-cell (temporal) arteritis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID STATIN-ASSOCIATED MYOPATHY; PLACEBO-CONTROLLED TRIAL; POLYMYALGIA-RHEUMATICA; CORTICOSTEROID TREATMENT; FIBROMYALGIA SYNDROME; VESSEL VASCULITIS; DOUBLE-BLIND; ARTHRITIS; DISEASE; METHOTREXATE C1 Massachusetts Gen Hosp, Dept Rheumatol Allergy & Immunol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Gounder, CR (reprint author), Massachusetts Gen Hosp, Dept Rheumatol Allergy & Immunol, Boston, MA 02114 USA. NR 30 TC 5 Z9 5 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 9 PY 2006 VL 354 IS 6 BP 623 EP 630 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 010HF UT WOS:000235177500013 ER PT J AU Posner, MR Wirth, LJ AF Posner, MR Wirth, LJ TI Cetuximab and radiotherapy for head and neck cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID SQUAMOUS-CELL CARCINOMAS; PHASE-II TRIAL; RADIATION-THERAPY; INDUCTION CHEMOTHERAPY; ONCOLOGY; CHEMORADIOTHERAPY; FLUOROURACIL; PACLITAXEL; CISPLATIN C1 Dana Farber Canc Inst, Div Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Posner, MR (reprint author), Dana Farber Canc Inst, Div Adult Oncol, Boston, MA 02115 USA. NR 13 TC 29 Z9 32 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 9 PY 2006 VL 354 IS 6 BP 634 EP 636 DI 10.1056/NEJMe058306 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 010HF UT WOS:000235177500015 PM 16467552 ER PT J AU Cui, R Takahashi, K Takahashi, F Tanabe, KK Fukuchi, Y AF Cui, R Takahashi, K Takahashi, F Tanabe, KK Fukuchi, Y TI Endostatin gene transfer in murine lung carcinoma cells induces vascular endothelial growth factor secretion resulting in up-regulation of in vivo tumorigenecity SO CANCER LETTERS LA English DT Article DE endostatin (ED); vascular endothelial growth factor (VEGF); lung cancer; mouse; tumorigenecity ID TUMOR-GROWTH; MICROVESSEL DENSITY; ANGIOGENIC FACTORS; BREAST-CANCER; EXPRESSION; METASTASES; ANGIOSTATIN; INHIBITION; GENERATION; INDUCTION AB Endostatin (ED) is a carboxyl-terminal fragment of type XVIII collagen with a strong anti-angiogenic activity. The purpose of this study is to determine the effect of ED gene transfer into lung cancer cells on in vivo tumor growth in a murine model. The murine lung cancer cell line, Lewis Lung Carcinoma (LLC), was transfected with ED gene to express and secrete ED. After clones were selected to secrete ED, several stable transfectants with ED gene (LLC/ED) and control transfectants (LLC/Mock) were established. In vitro proliferation of these transfectants demonstrated similar growth speed. In contrast to previous reports, in vivo subcutaneous tumorignecity of LCC/ED transfectants was significantly greater than that of LLC/Mock transfectants. Immunohistochemical staining analysis demonstrated that ED gene transfer induced angiogenesis, suggesting coinduction of another gene implicated for neovascularization. As expected, LLC/ED transfectants secreted not only ED but also vascular endothelial growth factor (VEGF) to a much greater degree than LLC/mock transfectants. Interestingly, culture supernatants of LLC/ED cells enhanced in vitro proliferation of human umbilical vein endothelial cells (HUVEC) to a much greater degree than those of LLC/Mock cells. These results indicate that ED gene transfer in murine lung carcinoma cells induces VEGF secretion, resulting in enhancement of in vivo tumorigenecity in the murine model. More attention should be paid for ED gene therapy into lung cancer cells since it may influence other proteins secretion, which upregulates angiogenesis. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Juntendo Univ, Sch Med, Dept Resp Med, Bunkyo Ku, Tokyo 1138421, Japan. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Surg Oncol, Boston, MA 02114 USA. RP Takahashi, K (reprint author), Juntendo Univ, Sch Med, Dept Resp Med, Bunkyo Ku, 2-1-1 Hongo, Tokyo 1138421, Japan. EM kztakaha@med.juntendo.ac.jp RI cui, ri/P-8507-2014 OI cui, ri/0000-0001-6202-8779 NR 29 TC 11 Z9 18 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD FEB 8 PY 2006 VL 232 IS 2 BP 262 EP 271 DI 10.1016/j.canlet.2005.02.045 PG 10 WC Oncology SC Oncology GA 016AI UT WOS:000235592500015 PM 15876483 ER PT J AU Solt, K Johansson, JS Raines, DE AF Solt, K Johansson, JS Raines, DE TI Kinetics of anesthetic-induced conformational transitions in a four-alpha-helix bundle protein SO BIOCHEMISTRY LA English DT Article ID GATED ION CHANNELS; NICOTINIC ACETYLCHOLINE-RECEPTORS; NONHALOGENATED ALKANE ANESTHETICS; VOLATILE GENERAL-ANESTHETICS; HYDROPHOBIC CORE; SERUM-ALBUMIN; GLYCINE RECEPTORS; ELECTROSTATIC INTERACTIONS; TEMPERATURE-DEPENDENCE; INHALED ANESTHETICS AB Inhaled anesthetics are thought to alter the conformational states of Cys-loop ligand-gated ion channels (LGICs) by binding within discrete cavities that are lined by portions of four a-helical transmembrane domains. Because Cys-loop LGICs are complex molecules that are notoriously difficult to express and purify, scaled-down models have been used to better understand the basic molecular mechanisms of anesthetic action. In this study, stopped-flow fluorescence spectroscopy was used to define the kinetics with which inhaled anesthetics interact with (A alpha(2)-L1M/L38M)(2), a four-alpha-helix bundle protein that was designed to model anesthetic binding sites on Cys-loop LGICs. Stopped-flow fluorescence traces obtained upon mixing (Aa2-LIM/L38M)(2) with halothane revealed immediate, fast, and slow components of quenching. The immediate component, which occurred within the mixing time of the spectrofluorimeter, was attributed to direct quenching of tryptophan fluorescence upon halothane binding to (A alpha(2)-L1M/ L38M)(2). This was followed by a biexponential fluorescence decay containing fast and slow components, reflecting anesthetic-induced conformational transitions. Fluorescence traces obtained in studies using sevoflurane, isoflurane, and desflurane, which poorly quench tryptophan fluorescence, did not contain the immediate component. However, these anesthetics did produce the fast and slow components, indicating that they also alter the conformation of (A alpha(2)-L1M/L38M)(2). Cyclopropane, an anesthetic that acts with unusually low potency on Cys-loop LGICs, acted with low apparent potency on (A alpha(2)-L1M/L38M)(2). These results suggest that four-alpha-helix bundle proteins may be useful models of in vivo sites of action that allow the use of a wide range of techniques to better understand how anesthetic binding leads to changes in protein structure and function. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Univ Penn, Dept Anesthesiol & Crit Care, Philadelphia, PA 19104 USA. RP Raines, DE (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St,Clin Bldg 3, Boston, MA 02114 USA. EM draines@partners.org OI Solt, Ken/0000-0001-5328-2062 FU NIGMS NIH HHS [GM58448, P01 GM058448-10, P01 GM058448, R01 GM061927, P01 GM055876, GM65218, GM61927, GM55876, R01 GM065218] NR 44 TC 7 Z9 7 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD FEB 7 PY 2006 VL 45 IS 5 BP 1435 EP 1441 DI 10.1021/bi052206o PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 011CF UT WOS:000235244500009 PM 16445285 ER PT J AU Neicu, T Berbeco, R Wolfgang, J Jiang, SB AF Neicu, T Berbeco, R Wolfgang, J Jiang, SB TI Synchronized moving aperture radiation therapy (SMART): improvement of breathing pattern reproducibility using respiratory coaching SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID GATED RADIOTHERAPY; TUMOR-TRACKING; SYSTEM; MOTION AB Recently, at Massachusetts General Hospital (NIGH) we proposed a new treatment technique called synchronized moving aperture radiation therapy (SMART) to account for tumour motion during radiotherapy. The basic idea of SMART is to synchronize the moving radiation beam aperture formed by a dynamic multileaf collimator with the tumour motion induced by respiration. The two key requirements for being able to successfully use SMART in clinical practice are the precise and fast detection of tumour position during the simulation/treatment and the good reproducibility of the tumour motion pattern. To fulfil the first requirement, an integrated radiotherapy imaging system is currently being developed at MGH. The results of a previous Study show that breath coaching techniques are required to make SMART an efficient technique in general. In this study, we investigate Volunteer and patient respiratory coaching using a commercial respiratory gating system as a respiration coaching tool. Five healthy volunteers, observed during six sessions, and 33 lung cancer patients, observed during one session when undergoing 4D CT scans, were investigated with audio and visual promptings, with free breathing as a control. For all five volunteers, breath coaching was well tolerated and the intra- and inter-session reproducibility of the breathing pattern was greatly improved. Out of 33 patients, six exhibited it regular breathing pattern and needed no coaching, four could not be coached at all due to the patient's medical condition or had difficulty following the instructions, 13 could only be coached with audio instructions and 10 Could follow the instructions of and benefit from audio-video coaching. We found that, for all volunteers and for those patients who could be properly coached, breath coaching improves the duty cycle of SMART treatment. However, about half of the patients Could not follow both audio and video instructions simultaneously, Suggesting that the current coaching technique requires improvements. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Jiang, SB (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM jiang.steve@mgh.harvard.edu NR 15 TC 102 Z9 102 U1 3 U2 12 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD FEB 7 PY 2006 VL 51 IS 3 BP 617 EP 636 DI 10.1088/0031-9155/51/3/010 PG 20 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 014PQ UT WOS:000235492600010 PM 16424585 ER PT J AU Zhao, YL Wang, YC Wang, ZM Liu, H Shen, YZ Li, W Heller, S Li, HW AF Zhao, YL Wang, YC Wang, ZM Liu, H Shen, YZ Li, W Heller, S Li, HW TI Sonic hedgehog promotes mouse inner ear progenitor cell proliferation and hair cell generation in vitro SO NEUROREPORT LA English DT Article DE mammal; mitosis; morphogen; morphogenesis; otocyst; Shh ID MAMMALIAN COCHLEA; SPECIFICATION; DIFFERENTIATION; CYCLOPAMINE; MECHANISMS; ROLES AB Sonic hedgehog (Shh) signaling is essential for auditory cell fate determination and inner ear dorsal/ventral patterning during development. Here, we show that Shh accelerates inner ear progenitor cell proliferation, and the inhibitor of Shin signaling cycloparnine reduces mitotic growth of otocyst cells in vitro. The number of hair cells in cultures of inner ear progenitor cells that were treated with Shh was significantly higher than that in control cultures. When Shh signaling was blocked with cycloparnine, hair cell generation was largely inhibited. Our results suggest that Shh may be a regulator of inner ear progenitor cell growth and hair cell generation. C1 Fudan Univ, Eye & ENT Hosp, Shanghai Med Sch, Cent Lab, Shanghai 200031, Peoples R China. Fudan Univ, Eye & ENT Hosp, Shanghai Med Sch, Otol Skull Base Surg Dept,Hearing Res Inst, Shanghai 200031, Peoples R China. Fudan Univ, Childrens Hosp, Shanghai 200031, Peoples R China. Affiliated Capital Med Sci Univ, Beijing Tongren Hosp, Dept Otolaryngol Head & Neck Surg, Beijing, Peoples R China. Harvard Univ, Sch Med, Dept Otolaryngol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Li, HW (reprint author), Fudan Univ, Eye & ENT Hosp, Shanghai Med Sch, Cent Lab, 83 Fenyang Rd, Shanghai 200031, Peoples R China. EM hwli@hmu.edu.cn NR 18 TC 10 Z9 11 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD FEB 6 PY 2006 VL 17 IS 2 BP 121 EP 124 DI 10.1097/01.wnr.0000198439.44636.49 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 012OZ UT WOS:000235349800003 PM 16407756 ER PT J AU Hajjar, RJ Leopold, JA AF Hajjar, RJ Leopold, JA TI Xanthine oxidase inhibition and heart failure - Novel therapeutic strategy for ventricular dysfunction? SO CIRCULATION RESEARCH LA English DT Editorial Material DE xanthine oxidase; reactive oxygen species; heart failure; contractility ID OXIDATIVE STRESS; DILATED CARDIOMYOPATHY; FAILING MYOCARDIUM; CARDIAC MYOCYTES; ALLOPURINOL; OXYGEN; PATHWAYS; DOGS; SUPEROXIDE; MECHANISMS C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Div Cardiol, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Cardiol Div, Boston, MA 02115 USA. RP Hajjar, RJ (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Div Cardiol, 149 13th St,Room 4215, Cambridge, MA 02139 USA. EM rhajjar@partners.org FU NHLBI NIH HHS [HL071763, HL078691, HL057623, HL081110] NR 30 TC 13 Z9 13 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD FEB 3 PY 2006 VL 98 IS 2 BP 169 EP 171 DI 10.1161/01.RES.0000204557.09610.01 PG 3 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 008TZ UT WOS:000235064900005 PM 16456108 ER PT J AU Howlett, NG Scuric, Z D'Andrea, AD Schiestl, RH AF Howlett, NG Scuric, Z D'Andrea, AD Schiestl, RH TI Impaired DNA double strand break repair in cells from Nijmegen breakage syndrome patients SO DNA REPAIR LA English DT Article DE non-homolopus end-joining; homologous recombination; NBS; microhomology; double strand break repair; single strand annealing ID HOMOLOGOUS RECOMBINATION; SACCHAROMYCES-CEREVISIAE; V(D)J RECOMBINATION; MAMMALIAN-CELLS; ILLEGITIMATE RECOMBINATION; VERTEBRATE CELLS; WERNER-SYNDROME; PROTEIN; PATHWAYS; DEFECT AB Nijmegen breakage syndrome, caused by mutations in the NBS1 gene, is an autosomal recessive chromosomal instability disorder characterized by cancer predisposition. Cells isolated from Nijmegen breakage syndrome patients display increased levels of spontaneous chromosome aberrations and sensitivity to ionizing radiation. Here, we have investigated DNA double strand break repair pathways of homologous recombination, including single strand annealing, and non-homologous end-joining in Nijmegen breakage syndrome patient cells. We used recently developed GFP-YFP-based plasmid substrates to measure the efficiency of DNA double strand break repair. Both single strand annealing and non-homologous end-joining processes were markedly impaired in NBS1-deficient cells, and repair proficiency was restored upon re-introduction of full length NBS1 cDNA. Despite the observed defects in the repair efficiency, no apparent differences in homologous recombination or non-homologous end-joining effector proteins RAD51, KU70, KU86, or DNA-PKCS were observed. Furthermore, comparative analysis of junction sequences of plasmids recovered from NBS1-deficient and NBS1-complemented cells revealed increased dependence on microhomology-mediated end-joining DNA repair process in NBS1-complemented cells. (c) 2005 Elsevier B.V. All rights reserved. C1 Univ Calif Los Angeles, David Geffen Sch Med & Publ Hlth, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med & Publ Hlth, Dept Environm Hlth & Radiat Oncol, Los Angeles, CA 90095 USA. Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Schiestl, RH (reprint author), Univ Calif Los Angeles, David Geffen Sch Med & Publ Hlth, Dept Pathol & Lab Med, 650 Charles E Young Dr S, Los Angeles, CA 90095 USA. EM rschiestl@mednet.ucla.edu FU NHLBI NIH HHS [P01HL54785, R01HL52725]; NIDDK NIH HHS [R01DK43889]; NIEHS NIH HHS [R01ES09519] NR 33 TC 26 Z9 27 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD FEB 3 PY 2006 VL 5 IS 2 BP 251 EP 257 DI 10.1016/j.dnarep.2005.10.004 PG 7 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 009CX UT WOS:000235089900012 PM 16309973 ER PT J AU Caunt, CJ Finch, AR Sedgley, KR Oakley, L Luttrell, LM McArdle, CA AF Caunt, CJ Finch, AR Sedgley, KR Oakley, L Luttrell, LM McArdle, CA TI Arrestin-mediated ERK activation by gonadotropin-releasing hormone receptors - Receptor-specific activation mechanisms and compartmentalization SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; MAP KINASE KINASE; DYNAMIN-DEPENDENT INTERNALIZATION; SIGNAL-REGULATED KINASE; GROWTH-FACTOR RECEPTOR; BETA-ARRESTIN; NUCLEAR TRANSLOCATION; RAPID DESENSITIZATION; C-SRC; CELLS AB Activation of seven-transmembrane region receptors typically causes their phosphorylation with consequent arrestin binding and desensitization. Arrestins also act as scaffolds, mediating signaling to Raf and ERK and, for some receptors, inhibiting nuclear translocation of ERK. GnRH receptors (GnRHRs) act via G(q/11) to stimulate the phospholipase C/Ca2+/protein kinase C (PKC) cascade and the Raf/MEK/ERK cassette. Uniquely, type I mammalian GnRHRs lack the C-tails that are found in other seven-\transmembrane region receptors ( including nonmammalian GnRHRs) and are implicated in arrestin binding. Here we have compared ERK signaling by human GnRHRs (hGnRHRs) and Xenopus GnRHRs (XGnRHRs). In HeLa cells, XGnRHRs underwent rapid and arrestin-dependent internalization and caused arrestin/green fluorescent protein (GFP) translocation to the membrane and endosomes, whereas hGnRHRs did not. Internalized XGnRHRs were co-localized with arrestin-GFP, whereas hGnRHRs were not. Both receptors mediated transient ERK phosphorylation and nuclear translocation (revealed by immunohistochemistry or by imaging of co-transfected ERK2-GFP), and for both, ERK phosphorylation was reduced by PKC inhibition but not by inhibiting epidermal growth factor receptor autophosphorylation. In the presence of PKC inhibitor, Delta arrestin-(319 - 418) blocked XGnRHR-mediated, but not hGnRHR- mediated, ERK phosphorylation. When receptor number was varied, hGnRHRs activated phospholipase C and ERK more efficiently than XGnRHRs but were less efficient at causing ERK2-GFP translocation. At high receptor number, XGnRHRs and hGnRHRs both caused ERK2-GFP translocation to the nucleus, but at low receptor number, XGnRHRs caused ERK2-GFP translocation, whereas hGnRHRs did not. Thus, experiments with XGnRHRs have revealed the first direct evidence of arrestin-mediated (probably G protein-independent) GnRHR signaling, whereas those with hGnRHRs imply that scaffolds other than arrestins can determine GnRHR effects on ERK compartmentalization. C1 Univ Bristol, Henry Wellcome Labs Integrat Neurosci & Endocrino, Bristol BS1 3NY, Avon, England. Med Univ S Carolina, Dept Med Biochem & Mol Biol, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. RP McArdle, CA (reprint author), Univ Bristol, Henry Wellcome Labs Integrat Neurosci & Endocrino, Whitson St, Bristol BS1 3NY, Avon, England. EM craig.mcardle@bris.ac.uk OI McArdle, Craig/0000-0003-4836-5351 FU Medical Research Council [G9721484]; Wellcome Trust NR 47 TC 43 Z9 45 U1 1 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 FEB 3 PY 2006 VL 281 IS 5 BP 2701 EP 2710 DI 10.1074/jbc.M507242200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 006XT UT WOS:000234931800036 PM 16314413 ER PT J AU Tsao, DY Freiwald, WA Tootell, RBH Livingstone, MS AF Tsao, DY Freiwald, WA Tootell, RBH Livingstone, MS TI A cortical region consisting entirely of face-selective cells SO SCIENCE LA English DT Article ID TEMPORAL CORTEX; INFEROTEMPORAL CORTEX; NEURONS; MONKEY; PERCEPTION; MACAQUE; ORGANIZATION; OBJECTS; AREAS; REPRESENTATIONS AB Face perception is a skill crucial to primates. In both humans and macaque monkeys, functional magnetic resonance imaging (fMRI) reveals a system of cortical regions that show increased blood flow when the subject views images of faces, compared with images of objects. However, the stimulus selectivity of single neurons within these fMRI-identified regions has not been studied. We used fMRI to identify and target the largest face-selective region in two macaques for single-unit recording. Almost all (97%) of the visually responsive neurons in this region were strongly face selective, indicating that a dedicated cortical area exists to support face processing in the macaque. C1 Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Univ Bremen, Ctr Adv Imaging, Brain Res Inst, D-28334 Bremen, Germany. Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Tsao, DY (reprint author), Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. EM doris@nmr.mgh.harvard.edu FU NCRR NIH HHS [P41:RR14075]; NEI NIH HHS [EY13025, EY13135, R01 EY016187, R01 EY016187-01A2] NR 28 TC 488 Z9 498 U1 9 U2 49 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD FEB 3 PY 2006 VL 311 IS 5761 BP 670 EP 674 DI 10.1126/science.1119983 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 011GY UT WOS:000235257400051 PM 16456083 ER PT J AU Adams, GB Chabner, KT Alley, IR Olson, DP Szczepiorkowski, ZM Poznansky, MC Kos, CH Pollak, MR Brown, EM Scadden, DT AF Adams, GB Chabner, KT Alley, IR Olson, DP Szczepiorkowski, ZM Poznansky, MC Kos, CH Pollak, MR Brown, EM Scadden, DT TI Stem cell engraftment at the endosteal niche is specified by the calcium-sensing receptor SO NATURE LA English DT Article ID BONE-MARROW; IN-VIVO; HEMATOPOIETIC MICROENVIRONMENT; MOUSE; MICE; EXPRESSION AB During mammalian ontogeny, haematopoietic stem cells (HSCs) translocate from the fetal liver to the bone marrow, where haematopoiesis occurs throughout adulthood(1). Unique features of bone that contribute to a microenvironmental niche for stem cells might include the known high concentration of calcium ions at the HSC-enriched endosteal surface. Cells respond to extracellular ionic calcium concentrations through the seven-transmembrane-spanning calcium-sensing receptor (CaR), which we identified as being expressed on HSCs. Here we show that, through the CaR, the simple ionic mineral content of the niche may dictate the preferential localization of adult mammalian haematopoiesis in bone. Antenatal mice deficient in CaR had primitive haematopoietic cells in the circulation and spleen, whereas few were found in bone marrow. CaR-/- HSCs from fetal liver were normal in number, in proliferative and differentiative function, and in migration and homing to the bone marrow. Yet they were highly defective in localizing anatomically to the endosteal niche, behaviour that correlated with defective adhesion to the extracellular matrix protein, collagen I. CaR has a function in retaining HSCs in close physical proximity to the endosteal surface and the regulatory niche components associated with it. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Blood Transfus Serv, Boston, MA 02114 USA. Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Membrane Biol Program,Endocrine Hypertens Div, Boston, MA 02115 USA. RP Scadden, DT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med, Boston, MA 02114 USA. EM scadden.david@mgh.harvard.edu RI Szczepiorkowski, Zbigniew/A-1359-2007 OI Szczepiorkowski, Zbigniew/0000-0003-2357-9564 NR 25 TC 395 Z9 420 U1 2 U2 29 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD FEB 2 PY 2006 VL 439 IS 7076 BP 599 EP 603 DI 10.1038/nature04247 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 008IO UT WOS:000235033900043 PM 16382241 ER PT J AU Chen, CL Broom, DC Liu, Y de Nooij, JC Li, Z Cen, CA Samad, OA Jessell, TM Woolf, CJ Ma, QF AF Chen, CL Broom, DC Liu, Y de Nooij, JC Li, Z Cen, CA Samad, OA Jessell, TM Woolf, CJ Ma, QF TI Runx1 determines nociceptive sensory neuron phenotype and is required for thermal and neuropathic pain SO NEURON LA English DT Article ID DORSAL-ROOT GANGLIA; PRIMARY AFFERENT NEURONS; RECEPTOR GENE CHOICE; MOLECULAR-MECHANISMS; CAPSAICIN RECEPTOR; MOTOR-NEURONS; MICE LACKING; EXPRESSION; CHANNEL; FAMILY AB In mammals, the perception of pain is initiated by the transduction of noxious stimuli through specialized ion channels and receptors expressed by nociceptive sensory neurons. The molecular mechanisms responsible for the specification of distinct sensory modality are, however, largely unknown. We show here that Runx1, a Runt domain transcription factor, is expressed in most nociceptors; during embryonic development but in adult mice, becomes restricted to nociceptors marked by expression of the neurotrophin receptor Ret. In these neurons, Runx1 regulates the expression of many ion channels and receptors, including TRP class thermal receptors, Na+-gated, ATP-gated, and H+-gated channels, the opioid receptor MOR, and Mrgpr class G protein coupled receptors. Runx1 also controls the lamina-specific innervation pattern of nociceptive afferents in the spinal cord. Moreover, mice lacking Runx1 exhibit specific defects in thermal and neuropathic pain. Thus, Runx1 coordinates the phenotype of a large cohort of nociceptors, a finding with implications for pain therapy. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Anaesthesia & Crit Care, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Columbia Univ, Howard Hughes Med Inst, Dept Biochem & Mol Biophys, Ctr Neurobiol & Behav, New York, NY 10032 USA. Dartmouth Coll Sch Med, Dept Biochem, Hanover, NH 03755 USA. RP Ma, QF (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 1 Jimmy Fund Way, Boston, MA 02115 USA. EM qiufu_ma@dfci.harvard.edu RI samad, omar/K-1921-2012 NR 68 TC 179 Z9 180 U1 0 U2 12 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD FEB 2 PY 2006 VL 49 IS 3 BP 365 EP 377 DI 10.1016/j.neuron.2005.10.036 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 011IF UT WOS:000235260900009 PM 16446141 ER PT J AU Vanselow, NA Daugherty, R Dilworth-Anderson, P Emmons, K Emory, EK Goldman, DP Grady-Weliky, TA Inui, TS Irby, DM Novack, DH Schneiderman, N Stein, HF AF Vanselow, NA Daugherty, R Dilworth-Anderson, P Emmons, K Emory, EK Goldman, DP Grady-Weliky, TA Inui, TS Irby, DM Novack, DH Schneiderman, N Stein, HF CA Inst Med TI IOM report: Improving medical education - Enhancing the behavioral and social science content of medical school curricula SO ACADEMIC EMERGENCY MEDICINE LA English DT Article C1 Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70118 USA. Univ S Florida, Coll Med, Tampa, FL 33620 USA. Univ N Carolina, Sch Publ Hlth Hlth Policy & Adm, Chapel Hill, NC 27515 USA. Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Cambridge, MA 02138 USA. Emory Univ, Dept Psychol Psychiat & Behav Sci, Atlanta, GA 30322 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. RAND Corp, Santa Monica, CA 90406 USA. Univ Rochester, Sch Med & Dent, Rochester, NY 14627 USA. Indiana Univ, Sch Med, Regenstrief Inst Hlth Care, Bloomington, IN 47405 USA. Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA. Drexel Univ, Coll Med, Philadelphia, PA USA. Univ Miami, Behav Med Res Ctr, Coral Gables, FL 33124 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Family & Prevent Med, Norman, OK 73019 USA. RP Vanselow, NA (reprint author), Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70118 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 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 FEB PY 2006 VL 13 IS 2 BP 230 EP 231 AR PII 1069-6563583 DI 10.1197/j.aem.2005.07.009 PG 2 WC Emergency Medicine SC Emergency Medicine GA 010HW UT WOS:000235179500017 ER PT J AU Vogeli, C Yucel, R Bendavid, E Jones, LM Anderson, MS Louis, KS Campbell, EG AF Vogeli, C Yucel, R Bendavid, E Jones, LM Anderson, MS Louis, KS Campbell, EG TI Data withholding and the next generation of scientists: Results of a national survey SO ACADEMIC MEDICINE LA English DT Article ID SCIENCE AB Purpose To provide the first national data on the nature, extent, and consequences of withholding among life science trainees. Method In 2003, the authors surveyed 1,077 second-year doctoral students and postdoctoral fellows in life sciences at 50 U.S. universities, with a comparison group of trainees in computer science and chemical engineering. The study variables examined trainees' exposure to and the consequences of data withholding. Results Two hundred forty-six trainees (23.0%) reported that they had asked for and been denied access to information, data, materials, or programming associated with published research and 221 (20.6%) to unpublished research. Eighty-five trainees (7.9%) reported that they had denied another academic scientist's request(s) related to their own published research. Five hundred thirty-three trainees (50.8%) reported that withholding had had a negative effect on the progress of their research, 508 (48.5%) on the rate of discovery in their lab/research group, 472 (45.0%) on the quality of their relationships with academic scientists, 346 (33.0%) on the quality of their education, and 299 (28.5%) on the level of communication in their lab/research group. Traineesdenied access to research were significantly more likely to report that data withholding had had a negative effect on several aspects of the educational experience. Conclusions Data withholding had demonstrated negative effects on trainees. The life sciences, more so than chemical engineering or computer science, will have to address this issue among its trainees. Failure to do so could result in delayed research, inefficient training, and a culture of withholding among future life scientists. C1 Massachusetts Gen Hosp, Dept Med, Inst Hlth Policy, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Amherst, MA 01003 USA. St Paul Publ Sch, Ctr Acad Excellence, St Paul, MN USA. Univ Minnesota, Minneapolis, MN USA. RP Campbell, EG (reprint author), Massachusetts Gen Hosp, Dept Med, Inst Hlth Policy, 50 Staniford St 9th Floor, Boston, MA 02114 USA. NR 15 TC 44 Z9 44 U1 3 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD FEB PY 2006 VL 81 IS 2 BP 128 EP 136 DI 10.1097/00001888-200602000-00007 PG 9 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 008EN UT WOS:000235023100005 PM 16436573 ER PT J AU Blumenthal, D Campbell, EG Gokhale, M Yucel, R Clarridge, B Hilgartner, S Holtzman, NA AF Blumenthal, D Campbell, EG Gokhale, M Yucel, R Clarridge, B Hilgartner, S Holtzman, NA TI Data withholding in genetics and the other life sciences: Prevalences and predictors SO ACADEMIC MEDICINE LA English DT Article ID NATIONAL SURVEY; FACULTY; INDUSTRY AB Purpose To better understand the variety and prevalence of data withholding in genetics and the other life sciences and to explore factors associated with these behaviors. withholding. The independent variables related to the personal characteristics, research characteristics of faculty, and previous experience with data withholding. data sharing, and negative past experience with sharing were significantly associated with either verbal or publishing withholding among either geneticists or OLS. Method In 2000, a sample of 2,893 geneticists and other life scientists (OLS) at the 100 most research-intensive universities in the United States were surveyed concerning data withholding and sharing. The instrument was developed and pretested in 1999. The two primary outcome measures were withholding in verbal exchanges with colleagues about unpublished research (verbal withholding) and withholding as part of the publishing process (publishing withholding). The independent variables related to the personal characteristics, research characteristics of faculty, and previous experience with data withholding. Results A total of 1,849 faculty responded (64%): 1,240 geneticists and 600 OLS. Forty-four percent of geneticists and 32% of OLS reported participating in any one of 13 forms of data withholding in the three previous years. Publishing withholding (geneticists 35%, OLS 25%) was more frequent than verbal withholding (geneticists 23%, OLS 12%). In multivariate analyses, male gender, participation in relationships with industry, mentors' discouraging data sharing, receipt of formal instruction in data sharing, and negative past experience with sharing were significantly associated with either verbal or publishing withholding among either geneticists or OLS. Conclusions Data withholding is common in biomedical science, takes multiple forms, is influenced by a variety of characteristics of investigators and their training, and varies by field of science. Encouraging openness during the formative experiences of young investigators may be critical to increased data sharing, but the effects of formal training do not appear straightforward. C1 Massachusetts Gen Hosp, Inst Hlth Policy, Partners HelathCare Syst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Inst Hlth Policy, Dept Med, Boston, MA 02114 USA. Policy Anal Inc, Boston, MA USA. Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Amherst, MA 01003 USA. Cornell Univ, Dept Sci & Technol Studies, Ithaca, NY USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Bloomberg Sch Publ Hlth, Baltimore, MD USA. RP Blumenthal, D (reprint author), Massachusetts Gen Hosp, Inst Hlth Policy, Partners HelathCare Syst, 50 Staniford St, Boston, MA 02114 USA. EM dblumenthal@partners.org FU NHGRI NIH HHS [1R01 HG 601789] NR 21 TC 67 Z9 67 U1 6 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD FEB PY 2006 VL 81 IS 2 BP 137 EP 145 DI 10.1097/00001888-200602000-00008 PG 9 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 008EN UT WOS:000235023100006 PM 16436574 ER PT J AU Klucken, J Ingelsson, M Shin, Y Irizarry, MC Hedley-Whyte, ET Frosch, M Growdon, J McLean, P Hyman, BT AF Klucken, J Ingelsson, M Shin, Y Irizarry, MC Hedley-Whyte, ET Frosch, M Growdon, J McLean, P Hyman, BT TI Clinical and biochemical correlates of insoluble alpha-synuclein in dementia with Lewy bodies SO ACTA NEUROPATHOLOGICA LA English DT Article DE alpha-synuclein; Lewy body dementia; heat shock proteins ID PARKINSONS-DISEASE; BODY DISEASE; ALZHEIMER-DISEASE; CORTEX; ACCUMULATION; SUPPRESSION; MUTATION; BRAIN; NEUROPATHOLOGY; AGGREGATION AB alpha-Synuclein is a major constituent of Lewy bodies, the fibrillar aggregates that form within neurons in Parkinson's disease and dementia with Lewy bodies (DLB). Recent biochemical data show that alpha-synuclein accumulates in Parkinson's disease in a detergent insoluble form. We now examine the relationship between detergent insoluble alpha-synuclein and the presence of Lewy bodies, clinical measures of dementia and biochemical parameters in a series of individuals with DLB. We found that Triton X-100 insoluble alpha-synuclein enriched nearly twofold in the temporal cortex of patients with DLB compared to age-matched controls. By contrast the total amount of alpha-synuclein protein was unchanged. Surprisingly, the degree of Triton X-100 insoluble alpha-synuclein did not correlate with either the duration of illness or the number of Lewy bodies counted using stereological methods from an adjacent block of tissue. However, the Triton X-100 soluble fraction of alpha-synuclein did correlate strongly with the expression of several heat shock proteins (HSPs) in DLB but not control cases, suggesting a coordinated HSP response in DLB neocortex. C1 Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Dept Neurol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Dept Neuropathol, Charlestown, MA 02129 USA. Univ Regensburg, Clin & Policlin Neurol, D-93042 Regensburg, Germany. RP McLean, P (reprint author), Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Dept Neurol, 114 16th St, Charlestown, MA 02129 USA. EM pmclean@partners.org FU NIA NIH HHS [AG05134, P50 AG05134]; NINDS NIH HHS [P50-NS38372] NR 36 TC 28 Z9 31 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD FEB PY 2006 VL 111 IS 2 BP 101 EP 108 DI 10.1007/s00401-005-0027-7 PG 8 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 024RO UT WOS:000236214000002 PM 16482476 ER PT J AU Henderson, DC Copeland, PM Nguyen, DD Borba, CP Cather, C Evins, AE Freudenreich, O Baer, L Goff, DC AF Henderson, DC Copeland, PM Nguyen, DD Borba, CP Cather, C Evins, AE Freudenreich, O Baer, L Goff, DC TI Homocysteine levels and glucose metabolism in non-obese, non-diabetic chronic schizophrenia SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Article DE schizophrenia; homocysteine; cardiovascular risks; glucose metabolism; impaired fasting glucose ID DEPENDENT DIABETES-MELLITUS; TOTAL PLASMA HOMOCYSTEINE; DIETARY-FOLATE; HORDALAND HOMOCYSTEINE; CARDIOVASCULAR-DISEASE; INSULIN SENSITIVITY; VASCULAR-DISEASE; RISK FACTOR; HYPERHOMOCYSTEINEMIA; ASSOCIATION AB Objective: We studied a sample of schizophrenia out-patients to test the hypotheses that serum homocysteine concentrations would correlate positively with measures of glucose metabolism. Method: Subjects underwent a nutritional assessment and fasting plasma, serum insulin and homocysteine tests. Results: Males had a significantly higher homocysteine levels than females (7.69 +/- 1.42 mu m vs. 6.63 +/- 1.40 mu m; P = 0.02). Comparing subjects with normal fasting glucose (NFG) (glucose < 100 mg/dl) and impaired fasting glucose (IFG) (>= 100 mg/dl) subjects with IFG (mean 8.2 +/- 1.5 mu m) had significantly higher homocysteine levels than those with NFG (mean 7.2 +/- 1.4 mu m, P = 0.03). IFG was also associated with greater mean values for a Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) (P = 0.002) and diastolic blood pressure (P = 0.045). Conclusion: The group with IFG had higher fasting serum homocysteine concentrations than those with NFG which supports a connection to an important cardiovascular risk factor. C1 Massachusetts Gen Hosp, Schizophrenia Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, MGH Weight Ctr, Boston, MA 02114 USA. RP Henderson, DC (reprint author), Freedom Trail Clin, 25 Staniford St, Boston, MA 02114 USA. EM dchenderson@partners.org FU NCRR NIH HHS [5M01RR01066-24] NR 29 TC 15 Z9 15 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD FEB PY 2006 VL 113 IS 2 BP 121 EP 125 DI 10.1111/j.1600-0447.2005.00621.x PG 5 WC Psychiatry SC Psychiatry GA 003DX UT WOS:000234662900007 PM 16423163 ER PT J AU Henderson, DC Kunkel, L Nguyen, DD Borba, CP Daley, TB Louie, PM Freudenreich, O Cather, C Evins, AE Goff, DC AF Henderson, DC Kunkel, L Nguyen, DD Borba, CP Daley, TB Louie, PM Freudenreich, O Cather, C Evins, AE Goff, DC TI An exploratory open-label trial of aripiprazole as an adjuvant to clozapine therapy in chronic schizophrenia SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Article DE clozapine; aripiprazole; weight; lipids; schizophrenia ID INDUCED WEIGHT-GAIN; ATYPICAL ANTIPSYCHOTIC AGENTS; DIABETES-MELLITUS; SCHIZOAFFECTIVE DISORDER; RECEPTOR; PHARMACOLOGY; AMISULPRIDE; COMBINATION; RISPERIDONE; MECHANISMS AB Objective: We conducted this 6-week open-label trial to examine the effects of adjunctive aripiprazole in clozapine-treated subjects on weight, lipid and glucose metabolism, as well as positive and negative symptoms of schizophrenia. Method: Ten clozapine-treated subjects received aripiprazole augmentation; eight completed the 6-week trial and two ended at week 4. Eighty percent were male, the mean age was 38.7 +/- 8.9 years and the mean clozapine dose was 455 +/- 83 mg daily. Results: There was a significant decrease in weight (P = 0.003), body mass index (P = 0.004), fasting total serum cholesterol (P = 0.002) and total triglycerides (P = 0.04) comparing baseline to study endpoint. There was no significant change in total Positive and Negative Syndrome Scale scores. Conclusion: This combination may be useful for clozapine-associated medical morbidity and must be studied in placebo-controlled double-blind randomized trials to determine efficacy and safety. C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Schizophrenia Program, Boston, MA 02114 USA. RP Henderson, DC (reprint author), Freedom Trail Clin, 25 Staniford St, Boston, MA 02114 USA. EM dchenderson@partners.org NR 34 TC 72 Z9 74 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD FEB PY 2006 VL 113 IS 2 BP 142 EP 147 DI 10.1111/j.1600-0447.2005.00612.x PG 6 WC Psychiatry SC Psychiatry GA 003DX UT WOS:000234662900010 PM 16423166 ER PT J AU Gordon, JA Shaffer, DW Raemer, DB Pawlowski, J Hurford, WE Cooper, JB AF Gordon, JA Shaffer, DW Raemer, DB Pawlowski, J Hurford, WE Cooper, JB TI A randomized controlled trial of simulation-based teaching versus traditional instruction in medicine: A pilot study among clinical medical students SO ADVANCES IN HEALTH SCIENCES EDUCATION LA English DT Article ID TECHNOLOGY AB Objective: To compare simulator-based teaching with traditional instruction among clinical medical students. Methods: Randomized controlled trial with written pre-post testing. Third-year medical students (n = 38) received either a myocardial infarction (MI) simulation followed by a reactive airways disease (RAD) lecture, or a RAD simulation followed by an MI lecture. Results: Mean pre-post test score improvement was seen across teaching modalities (overall change score [simulation] = 8.8 [95% CI = 2.3-15.3], pretest [62.7]; change score [lecture] = 11.3 [95% CI = 5.7-16.9], pretest [59.7]). However, no significant differences were observed between simulator-based teaching and lecture, in either subject domain. Conclusions: After a single instructional session for clinical medical students, differences between simulator-based teaching and lecture could not be established by the written test protocols used in this pilot. Future studies should consider the effects of iterative exposure assessed by clinical performance measures across multiple centers. C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, GS Beckwith Gilbert & Katharine S Gilbert Med Edu, Cambridge, MA 02138 USA. Ctr Med Simulat, Boston, MA USA. Univ Wisconsin, Dept Educ Psychol, Madison, WI USA. Massachusetts Gen Hosp, Dept Anaesthesia & Crit Care, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Dept Anesthesia & Crit Care, Boston, MA USA. Univ Cincinnati, Dept Anesthesia, Cincinnati, OH 45221 USA. RP Gordon, JA (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 55 Fruit St,Clin 115, Boston, MA 02114 USA. EM jgordon3@partners.org RI Hurford, William/G-6386-2013 OI Hurford, William/0000-0003-1201-0313 NR 14 TC 29 Z9 31 U1 0 U2 7 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1382-4996 J9 ADV HEALTH SCI EDUC JI Adv. Health Sci. Educ. PD FEB PY 2006 VL 11 IS 1 BP 33 EP 39 DI 10.1007/s10459-004-7346-7 PG 7 WC Education & Educational Research; Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 028TD UT WOS:000236510800004 PM 16583282 ER PT J AU Opazo, C Luza, S Villemagne, VL Volitakis, I Rowe, C Barnham, KJ Strozyk, D Masters, CL Cherny, RA Bush, AI AF Opazo, C Luza, S Villemagne, VL Volitakis, I Rowe, C Barnham, KJ Strozyk, D Masters, CL Cherny, RA Bush, AI TI Radioiodinated clioquinol as a biomarker for beta-amyloid: Zn2+ complexes in Alzheimer's disease SO AGING CELL LA English DT Article DE Alzheimer's disease; beta-amyloid; clioquinol; imaging; zinc ID A-BETA; TRANSGENIC MICE; IN-VIVO; PLAQUE-FORMATION; ZINC; BRAIN; COPPER; BINDING; PROTEIN; AGGREGATION AB Neocortical beta-amyloid (A beta) aggregates in Alzheimer's disease (AD) are enriched in transition metals that mediate assembly. Clioquinol (CQ) targets metal interaction with A beta and inhibits amyloid pathology in transgenic mice. Here, we investigated the binding properties of radioiodinated CQ ([I-125]CQ) to different in vitro and in vivo Alzheimer models. We observed saturable binding of [I-125]CQ to synthetic A beta precipitated by Zn2+ (K-d = 0.45 and 1.40 nm for A beta(1-42) and A beta(1-40), respectively), which was fully displaced by free Zn2+, Cu2+, the chelator DTPA (diethylene triamine pentaacetic acid) and partially by Congo red. Sucrose density gradient of post-mortem AD brain indicated that [I-125]CQ concentrated in a fraction enriched for both A beta and Zn, which was modulated by exogenous addition of Zn2+ or DTPA. APP transgenic (Tg2576) mice injected with [I-125]CQ exhibited higher brain retention of tracer compared to non-Tg mice. Autoradiography of brain sections of these animals confirmed selective [I-125]CQ enrichment in the neocortex. Histologically, both thioflavine-S (ThS)-positive and negative structures were labeled by [I-125]CQ. A pilot SPECT study of [I-123]CQ showed limited uptake of the tracer into the brain, which did however, appear to be more rapid in AD patients compared to age-matched controls. These data support metallated A beta species as the neuropharmacological target of CQ and indicate that this drug class may have potential as in vivo imaging agents for Alzheimer neuropathology. C1 Univ Melbourne, Oxidat Disorders Lab, Mental Hlth Res Inst Victoria, Parkville, Vic 3052, Australia. Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia. Austin Hosp, Ctr PET, Dept Nucl Med, Heidelberg, Vic 3084, Australia. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lab Oxidat Biol,Genet & Aging Res Unit, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. Yeshiva Univ Albert Einstein Coll Med, Dept Neurol, Kennedy Ctr, Bronx, NY 10461 USA. RP Bush, AI (reprint author), Univ Melbourne, Oxidat Disorders Lab, Mental Hlth Res Inst Victoria, Parkville, Vic 3052, Australia. EM rcherny@mhri.edu.au; abush@mhri.edu.au RI Bush, Ashley/A-1186-2007 OI Bush, Ashley/0000-0001-8259-9069 NR 44 TC 48 Z9 50 U1 2 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1474-9718 J9 AGING CELL JI Aging Cell PD FEB PY 2006 VL 5 IS 1 BP 69 EP 79 DI 10.1111/j.1474-9726.2005.00196.x PG 11 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 005VW UT WOS:000234853700010 PM 16441845 ER PT J AU Liddicoat, RV Losina, E Kang, M Freedberg, KA Walensky, RP AF Liddicoat, RV Losina, E Kang, M Freedberg, KA Walensky, RP TI Refusing HIV testing in an urgent care setting: Results from the "think HIV" program SO AIDS PATIENT CARE AND STDS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; UNITED-STATES; MISSED OPPORTUNITIES; ROUTINE; POPULATION; ACCEPTANCE; INFECTION; CLIENTS; CLINICS; RISK AB Efforts to increase HIV case identification through routine, voluntary HIV testing are hindered by high refusal rates. Our objective was to identify patients most likely to refuse routine HIV testing. We developed a new HIV testing program at four Massachusetts urgent care centers. Patients were asked if they were interested in routine HIV testing. We performed analyses to assess differences in characteristics between those who refused testing and those who accepted it. Data were available for 9129/10,354 (88%) patients offered routine HIV testing from January to December 2002. Of these 9129 patients, 67% refused testing. In the crude analysis, HIV test refusal was associated with female gender, white race, older age, and higher educational level. In multivariate analysis, non-English-speaking patients who were Hispanic, Haitian, and other race were more likely to refuse testing than their English-speaking counterparts. Among all patients, "not at risk" and "already tested" were the most common reasons for test refusal. Two thirds of patients refused routine HIV testing when it was offered in a statewide urgent care-based program. If routine HIV testing programs are to be successful, strategies must be developed to increase HIV test acceptance among patients most likely to refrain from testing. C1 Greater Los Angeles Vet Affairs, Dept Med, Los Angeles, CA 90073 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Med Genet, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Liddicoat, RV (reprint author), Greater Los Angeles Vet Affairs, Dept Med, Mail 111G,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM rebecca.liddicoat@med.va.gov FU NIAID NIH HHS [P30 AI42851, K23 AI001794, R01 AI42006, K23 AI01794, P30 AI042851, R01 AI042006, K24 AI062476, K25 AI050436, K25 AI50436]; PHS HHS [T32 HP11001] NR 39 TC 47 Z9 47 U1 2 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD FEB PY 2006 VL 20 IS 2 BP 84 EP 92 DI 10.1089/apc.2006.20.84 PG 9 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 019XJ UT WOS:000235871200003 PM 16475889 ER PT J AU Miller, PM Spies, C Neumann, T Javors, MA Hoyumpa, AM Roache, J Webb, A Kashi, M Sharkey, FE Anton, RF Egan, BM Basile, J Nguyen, S Fleming, MF Dillie, KS AF Miller, PM Spies, C Neumann, T Javors, MA Hoyumpa, AM Roache, J Webb, A Kashi, M Sharkey, FE Anton, RF Egan, BM Basile, J Nguyen, S Fleming, MF Dillie, KS TI Alcohol biomarker screening in medical and surgical settings SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE alcohol biomarkers; %CDT; GGT ID CARBOHYDRATE-DEFICIENT TRANSFERRIN; STAGE LIVER-DISEASE; DISORDERS IDENTIFICATION TEST; UPPER DIGESTIVE-TRACT; PRIMARY-HEALTH-CARE; LABORATORY MARKERS; UNIT STAY; CONSUMPTION; SERUM; ABUSE AB This article highlights the proceedings of a symposium presented at the 28th Annual Meeting or the Research Society oil Alcoholism in Santa Barbara, CA, Oil June 28 2005, organized and chaired by Peter Miller. The presentations included (1) Screening for Alcohol Use Disorders in Surgical and Trauma Patients, presented by Claudia Spies; (2) Are Serum Levels or %CDT and GGT Related to Severity of Liver Biopsy Inflammation, Fibrosis, and Steatohepatitis in Patients with Hepatitis C? by Martin Javors; (3) Biochemical Alcohol Screening in the Treatment of Hypertension, presented by Peter Miller; and (4) The Cost-Effectiveness of a New Biomarker, CDT, in a Primary Care Sample, by Michael Fleming. Presentations were discussed by Raymond Anton. C1 Med Univ S Carolina, Ctr Drug & Alcohol Studies, Charleston, SC 29425 USA. Med Univ S Carolina, Div Gen Internal Med, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Radiol, Charleston, SC 29425 USA. Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. Univ Med, Charite Hosp, Dept Anesthesiol & Intens Care Med, Berlin, Germany. Univ Texas, Hlth Sci Ctr, Dept Psychiat, Houston, TX USA. Univ Texas, Hlth Sci Ctr, Dept Pharmacol, Houston, TX USA. Univ Texas, Hlth Sci Ctr, Dept Med, Houston, TX USA. Univ Wisconsin, Dept Family Med, Madison, WI USA. RP Miller, PM (reprint author), Med Univ S Carolina, Ctr Drug & Alcohol Studies, 67 President St,POB 250861, Charleston, SC 29425 USA. EM millerpm@musc.edu NR 55 TC 14 Z9 15 U1 3 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD FEB PY 2006 VL 30 IS 2 BP 185 EP 193 DI 10.1111/j.1530-0277.2006.00029.x PG 9 WC Substance Abuse SC Substance Abuse GA 009RX UT WOS:000235131200004 PM 16441267 ER PT J AU Kranzler, HR Koob, G Gastfriend, DR Swift, RM Willenbring, ML AF Kranzler, HR Koob, G Gastfriend, DR Swift, RM Willenbring, ML TI Advances in the pharmacotherapy of alcoholism: Challenging misconceptions SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE alcohol dependence; pharmacotherapy; alcoholism treatment; medications; development ID CORTICOTROPIN-RELEASING FACTOR; RANDOMIZED CONTROLLED-TRIAL; UNITED-STATES; TREAT ALCOHOLISM; ETHANOL-SEEKING; DRUG-ABUSE; DEPENDENCE; NALTREXONE; ACAMPROSATE; MEDICATIONS AB This article highlights the proceedings of a symposium presented at the 28th Annual Scientific Meeting of the Research Society on Alcoholism in Santa Barbara, CA, June 27. 2005. The organizer and chair was Henry R. Kranzler. The presentations included: (1) Introduction, by Henry R. Kranzler; (2) Neurobiology of Alcohol Dependence: Implications for Medical Treatment, by George Koob; (3) Advances in Alcoholism Pharmacotherapy, by Henry R. Kranzler; (4) Patient Acceptance of Alcoholism Pharmacotherapy, by David R. Gastfriend; (5) System Challenges in the Adoption of Pharmacotherapy, by Robert M. Swift; and (6) Pharmacotherapy for Alcohol Dependence: Strengths, Challenges. and Future Directions, by Mark L. Willenbring. C1 Univ Connecticut, Ctr Hlth, Dept Psychiat, Farmington, CT 06032 USA. Scripps Res Inst, Mol & Integrat Neurosci Dept, La Jolla, CA USA. Massachusetts Gen Hosp, Dept Psychiat, Addict Res Program, Cambridge, MA USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Akermes Inc, Cambridge, MA USA. Brown Univ, Providence VA Med Ctr, Dept Psychiat, Providence, RI 02912 USA. NIAAA, NIH, Bethesda, MD USA. RP Kranzler, HR (reprint author), 263 Farmington Ave, Farmington, CT 06030 USA. EM kranzler@psychiatry.uchc.edu RI koob, george/P-8791-2016 FU NIAAA NIH HHS [K24 AA13736, R01 AA10945] NR 46 TC 7 Z9 7 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD FEB PY 2006 VL 30 IS 2 BP 272 EP 281 DI 10.1111/j.1530-0277.2006.00022.x PG 10 WC Substance Abuse SC Substance Abuse GA 009RX UT WOS:000235131200013 PM 16441276 ER PT J AU Metz, DC Comer, GM Soffer, E Forsmark, CE Cryer, B Chey, W Pisegna, JR AF Metz, DC Comer, GM Soffer, E Forsmark, CE Cryer, B Chey, W Pisegna, JR TI Three-year oral pantoprazole administration is effective for patients with Zollinger-Ellison syndrome and other hypersecretory conditions SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID MANAGEMENT; OMEPRAZOLE; LANSOPRAZOLE; DEFINITION; GASTRINOMA; RESECTION; EFFICACY; THERAPY; SAFETY; TUMORS AB Background Zollinger-Ellison syndrome and idiopathic hypersecretion are gastrointestinal hypersecretory conditions requiring long-term maintenance. Aims The safety and efficacy data for short-term (6-month) treatment of Zollinger-Ellison syndrome and idiopathic hypersecretion with oral pantoprazole were previously published. This study extends the initial observations to 3 years. Methods The primary efficacy end point for this report was the control of gastric acid secretion in the last hour before the next dose of oral pantoprazole (acid output of < 10 mmol/h; < 5 mmol/h in subjects with prior acid-reducing surgery). Dose titration was permitted to a maximum of 240 mg per 24 h. Results Twenty-four subjects completed the study. The acid output of 28 of 34 subjects was controlled at initial enrolment. The mean acid output rates were < 10 mmol/h throughout the 36 months of treatment for 90-100% of the patients. The majority of the patients were controlled with b.d. doses of 40 or 80 mg pantoprazole at 36 months (acid output was controlled in 24 of 24 subjects). Pantoprazole was generally well tolerated with minimal adverse events reported. Conclusion Maintenance oral pantoprazole therapy up to 3 years at dosages of 40-120 mg b.d. was effective and well tolerated in patients with Zollinger-Ellison syndrome and other hypersecretory conditions. C1 Univ Calif Los Angeles, Dept Med, David Geffen Sch Med, Los Angeles, CA 90073 USA. Univ Penn, Med Ctr, Dept Med, Div Gastroenterol, Philadelphia, PA 19104 USA. Wyeth Res, Collegeville, PA USA. Univ Florida, Div Gastroenterol, Gainesville, FL USA. Dallas Vet Affairs Med Ctr, Div Gastroenterol, Dallas, TX USA. Rochester Inst Digest Dis & Sci, Rochester, NY USA. Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA. RP Pisegna, JR (reprint author), Univ Calif Los Angeles, Dept Med, David Geffen Sch Med, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jpisegna@ucla.edu NR 24 TC 14 Z9 15 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD FEB 1 PY 2006 VL 23 IS 3 BP 437 EP 444 DI 10.1111/j.1365-2036.2006.02762.x PG 8 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 003EH UT WOS:000234663900011 PM 16423003 ER PT J AU Smith, EE Cannon, CP Murphy, S Feske, SK Schwamm, LH AF Smith, EE Cannon, CP Murphy, S Feske, SK Schwamm, LH TI Risk factors for stroke after acute coronary syndromes in the Orbofiban in Patients with Unstable Coronary Syndromes-Thrombolysis In Myocardial Infarction (OPUS-TIMI) 16 study SO AMERICAN HEART JOURNAL LA English DT Article ID PLATELET GLYCOPROTEIN IIB/IIIA; INTRACEREBRAL HEMORRHAGE; CEREBROVASCULAR-DISEASE; RANDOMIZED TRIALS; ANGINA; ASPIRIN; HEPARIN; EVENTS; CHOLESTEROL; SIBRAFIBAN AB Background Previous reports have associated acute coronary syndromes (ACSs) with cerebrovascular disease but in general have not included long-term patient follow-up or have not analyzed ischemic and hemorrhagic cerebrovascular events separately. Methods We analyzed stroke outcomes from the OPUS-TIMI 16 study, a multicenter, randomized, placebo-controlled trial. Patients were randomized to aspirin plus either orbofiban or placebo and followed for up to 1 year. Cerebrovascular events were prospectively identified and classified by a committee of cardiologists and neurologists blinded to treatment assignment. Results During 10 months of follow-up, there were 150 (1.5%) patients with cerebrovascular events. Risk factors for ischemic stroke (n = 67) and transient ischemic attack (TIA) (n = 44) were age, prior ischemic stroke, history of hypertension, and increased heart rate. Prior ischemic stroke and history of hypertension were not risk factors for 30-day ischemic stroke or TIA. Risk factors for intracranial hemorrhage (ICH) (n = 14) were age, history of hypertension, history of TIA, and coronary angiography with evidence of coronary artery disease. Compared with placebo, treatment with orbofiban was associated with a nonsignificant increased risk of ischemic stroke or TIA (HR 1.15, 95% CI 0.76-1.74, P = .51) and ICH (HR 1.25, 95% CI 0.39-4.00, P = .70). Conclusions The overall incidence of cerebrovascular events after ACS was highest in the first 30 days then declined; risk factors for cerebrovascular events may be different in the different periods. Orbofiban, despite no significant excess risk of ICH, was not effective in preventing ischemic stroke or TIA. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Cardiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. RP Smith, EE (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. EM eesmith@partners.org RI Smith, Eric/C-5443-2012; OI Smith, Eric/0000-0003-3956-1668; Schwamm, Lee/0000-0003-0592-9145 NR 26 TC 6 Z9 7 U1 0 U2 1 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 FEB PY 2006 VL 151 IS 2 BP 338 EP 344 DI 10.1016/j.ahj.2005.03.031 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 014ZG UT WOS:000235521100011 PM 16442896 ER PT J AU Januzzi, JL Newby, LK Murphy, SA Pieper, K Antman, EM Morrow, DA Sabatine, MS Ohman, EM Cannon, CP Braunwald, E AF Januzzi, JL Newby, LK Murphy, SA Pieper, K Antman, EM Morrow, DA Sabatine, MS Ohman, EM Cannon, CP Braunwald, E TI Predicting a late positive serum troponin in initially troponin-negative patients with non-ST-elevation acute coronary syndrome: Clinical predictors and validated risk score results from the TIMI IIIB and GUSTO IIA studies SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE CHEST-PAIN; UNSTABLE ANGINA; MYOCARDIAL-INFARCTION; SEGMENT ELEVATION; T LEVELS; I LEVELS; STRATIFICATION; BENEFIT; TIROFIBAN; STRATEGIES AB Background Troponin testing is useful for evaluating patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS); however, a significant percentage of patients are troponin negative at presentation and develop late rise of the marker. Methods Patients in the TIMI IIIB study were assessed with respect to their troponin I (TnI) status at presentation and 12 hours. Multivariable analysis identified independent clinical factors associated with TnI rise at 12 hours among subjects initially TnI negative. A score predicting late TnI rise in TIMI IIIB was developed using these factors and validated among patients in the GUSTO IIA study. Results Of 1342 subjects in TIMI IIIB, 200 (14.9%) were negative at baseline, but developed an elevated TnI (>= 0.4 ng/mL) at 12 hours. Six independent predictors of late TnI rise were identified: ST-segment deviation (odds ratio [OR] 3.52, 95% CI 2.38-5.23, P < .001), presentation < 8 hours from symptom onset (OR 2.91, 95% CI 1.92-4.40, P < .001), no prior percutaneous coronary intervention (OR 2.88, 95% CI 1.54-5.39, P = .001), no prior p-blocker use (OR 1.74, 95% CI 1.15-2.63, P = .008), unheralded angina (OR 1.65, 95% CI 1.12-2.42, P = .01), and a history of myocardial infarction (OR 1.59, 95% CI 1.06-2.37, P = .02). ST deviation, presentation < 8 hours from symptoms, and no prior percutaneous coronary intervention were given a score of 2 points, whereas a score of 1 point was assigned to the other factors. Among baseline TnI-negative patients, a rising score was paralleled by an increasing prevalence of late TnI rise from 0% (with a score of 0) to 69% (with a score of 9) (P < .001). In confirmation, the score was able to similarly predict late troponin T rise among 855 patients in the GUSTO IIA study (P < .0001). Conclusion Development of late troponin rise is common in non-ST-segment elevation acute coronary syndromes. Six easily ascertained variables may be used to identify those at higher risk for late rise in troponin levels after an initially negative presentation. C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Duke Clin Res Inst, Durham, NC USA. Univ N Carolina, Sch Med, Chapel Hill, NC USA. Brigham & Womens Hosp, TIMI Grp, Boston, MA 02115 USA. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Div Cardiol, Yawkey 5800,55 Fruit St, Boston, MA 02114 USA. EM jjanuzzi@partners.org NR 25 TC 11 Z9 11 U1 0 U2 1 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 FEB PY 2006 VL 151 IS 2 BP 360 EP 366 DI 10.1016/j.ahj.2005.04.021 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 014ZG UT WOS:000235521100014 PM 16442899 ER PT J AU Magnani, JW Danik, HJS Dec, GW DiSalvo, TG AF Magnani, JW Danik, HJS Dec, GW DiSalvo, TG TI Survival in biopsy-proven myocarditis: A long-term retrospective analysis of the histopathologic, clinical, and hemodynamic predictors SO AMERICAN HEART JOURNAL LA English DT Article ID GIANT-CELL MYOCARDITIS; INTRAVENOUS IMMUNE GLOBULIN; CONGESTIVE-HEART-FAILURE; DILATED CARDIOMYOPATHY; ENDOMYOCARDIAL BIOPSY; LYMPHOCYTIC MYOCARDITIS; CLINICOPATHOLOGICAL DESCRIPTION; IMMUNOSUPPRESSIVE THERAPY; BORDERLINE MYOCARDITIS; PREVALENCE AB Objective We hypothesized that histopathology predicts survival without cardiac transplantation in patients with biopsy-proven myocarditis. Background The role of endomyocardial biopsy in diagnosing myocarditis remains controversial. Histopathology has been integrated with clinical and hemodynamic features to predict prognosis. However, the influence of histopathology on survival > 5 years has not been explored. Methods We retrospectively identified 112 consecutive patients with histopathologic confirmation of myocarditis. We examined these patients' clinical presentation, hemodynamic assessment, hospital course, and treatment. We selected 14 variables that might influence survival without cardiac transplantation. Results A total of 62 (55%) of 112 patients had lymphocytic myocarditis; 88 (79%) and 63 (56%) were alive without cardiac transplantation at 1 and 5 years, respectively. Median follow-up was a mean 95.5 months and median 74.5 months. Among the 55 with complete data of the 14 candidate predictor variables, age, sex, and clinical presentation with congestive heart failure and ventricular (ventricular tachycardia or fibrillation) or atrial arrhythmias (atrial fibrillation or flutter) did not predict the study end point of death or need for transplantation. In univariate analysis, pulmonary capillary wedge pressure >= 15 mm Hg significantly predicted the study end point. In multivariate analysis, pulmonary capillary wedge pressure >= 15 mm Hg and histopathol'ogy of lymphocytic, granulomatous, or giant cell myocarditis each significantly predicted mortality or transplant (P =.047, P =.013, and P =.054, respectively) on cumulative survival without cardiac transplantation. Conclusions Histopathology predicts long-term survival in patients with myocarditis. Clinical presentation, including presentation with congestive heart failure, ventricular tachycardia/ventricular fibrillation, or atrial fibrillation/atrial flutter, does not predict survival without transplantation. Endomyocardial biopsy can play a role in predicting transplant-free survival in patients with myocarditis. C1 Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. Brigham & Womens Hosp, Ctr Cardiovasc Dis Prevent & Cardiovasc Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Vanderbilt Univ Sch Med, Vanderbilt Page Campbell Heart Inst, Div Cardiol, Nashville, TN USA. RP Magnani, JW (reprint author), 11 Hagen Rd, Newton, MA 02459 USA. EM jmagnani@partners.org NR 44 TC 49 Z9 50 U1 0 U2 1 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 FEB PY 2006 VL 151 IS 2 BP 463 EP 470 DI 10.1016/j.ahj.2005.03.037 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 014ZG UT WOS:000235521100030 PM 16442915 ER PT J AU Einhorn, LH Brames, MJ Heinrich, MC Corless, CL Madani, A AF Einhorn, LH Brames, MJ Heinrich, MC Corless, CL Madani, A TI Phase II study of imatinib mesylate in chemotherapy refractory germ cell tumors expressing KIT SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article DE KIT; germ cell tumor; imatinib ID TESTICULAR CANCER; C-KIT; EFFICACY; IFOSFAMIDE; PACLITAXEL; CISPLATIN; THERAPY; SAFETY; KINASE; TRIAL AB Objective: This phase II study was conducted to determine the activity of imatinib (gleevec) in heavily pretreated patients with KIT-positive metastatic germ cell tumor. Materials and Methods: From June 2002 through April 2005, 18 patients with refractory germ cell tumors were tested for KIT expression by immunohistochemistry. All patients screened were deemed to be incurable with further standard chemotherapy or surgery. Six patients were eligible and treated with imatinib 600 mg/d orally. Results: There were no complete or partial remissions. Five of 6 patients had progressive disease and 1 patient had stable disease with a > 50% decline in serum alpha-fetoprotein for 3 months before developing further progression. Conclusion: In this small sample size, there was no evidence of significant antitumor activity of imatinib in patients with KIT-positive refractory germ cell tumors. C1 Indiana Univ, Dept Med, Div Hematol Oncol, Indianapolis, IN USA. Walther Canc Inst, Indianapolis, IN USA. Oregon Hlth & Sci Univ, Inst Canc, Dept Med, Div Hematol Oncol, Portland, OR USA. Portland VA Med Ctr, Portland, OR USA. Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR USA. Hematol & Oncol Assoc So Michigan, Jackson, MI USA. RP Einhorn, LH (reprint author), 535 Barnhill Dr Room 473, Indianapolis, IN 46202 USA. EM leinhorn@iupui.edu NR 15 TC 45 Z9 46 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0277-3732 J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD FEB PY 2006 VL 29 IS 1 BP 12 EP 13 DI 10.1097/01.coc.0000195086.47548.ef PG 2 WC Oncology SC Oncology GA 012GI UT WOS:000235325900004 PM 16462496 ER PT J AU McCollum, AD Wu, BY Clark, JW Kulke, MH Enzinger, PC Ryan, DP Earle, CC Michelini, A Fuchs, CS AF McCollum, AD Wu, BY Clark, JW Kulke, MH Enzinger, PC Ryan, DP Earle, CC Michelini, A Fuchs, CS TI The combination of capecitabine and thalidomide in previously treated, refractory metastatic colorectal cancer SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article DE colorectal cancer; chemotherapy; capecitabine; thalidomide ID FLUOROURACIL PLUS LEUCOVORIN; PHASE-III; ORAL CAPECITABINE; RANDOMIZED-TRIAL; IRINOTECAN; OXALIPLATIN; ANGIOGENESIS; CETUXIMAB; THERAPY; FAILURE AB Background: With the increasing survival of patients with metastatic colorectal cancer (CRC) there is a growing need for effective second- and third-line agents. We conducted a multicenter, phase II study to examine the combination of capecitabine and thalidomide (Cape/Thal) in patients with refractory metastatic CRC. Methods: Patients with previously treated stage IV CRC were eligible. Treatment consisted of capecitabine at 1,000 mg/m(2) po BID for 14 days every 3 weeks and thalidomide, starting at 200 mg po QD continuously. Thalidomide was escalated individually to 600 mg po QD as tolerated. We analyzed overall survival (OS), progression-free survival, response, and toxicity rates. Results: Thirty-four eligible patients were enrolled. The median age was 57 years, and most patients had a normal performance status (65%). All patients had received prior chemotherapy and 19 (56%) had received 2 or 3 prior regimens. The median number of Cape/ Thal cycles administered was 3 (range, 1-15). Grade 3/4 toxicities included fatigue (15%), venous thromboembolic events (12%), somnolence (12%), and constipation (9%). Grade 2 hand-foot syndrome occurred in 5 (15%) patients. There were no radiographic responses; 13 patients (38%) achieved stable disease. The median PFS was 2.6 months (95% confidence interval [CI] = 2.2-3.9) and the median OS was 7.1 month (95% CI = 5.2-12.0). Conclusions: Though well-tolerated, the combination of capecitabine and thalidomide was not associated with objective tumor responses in a population of patients with previously treated metastatic CRC. C1 Baylor Sammons Canc Ctr, Dallas, TX 75246 USA. Texas Oncol PA, Dallas, TX USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Biostat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. RP McCollum, AD (reprint author), Baylor Sammons Canc Ctr, 3535 Worth St,Suite 240, Dallas, TX 75246 USA. EM david.mccollum@usoncology.com NR 26 TC 6 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0277-3732 J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD FEB PY 2006 VL 29 IS 1 BP 40 EP 44 DI 10.1097/01.coc.0000190456.83788.51 PG 5 WC Oncology SC Oncology GA 012GI UT WOS:000235325900009 PM 16462501 ER PT J AU Kratz, A Wood, MJ Siegel, AJ Hiers, JR Van Cott, EM AF Kratz, A Wood, MJ Siegel, AJ Hiers, JR Van Cott, EM TI Effects of marathon running on platelet activation markers - Direct evidence for in vivo platelet activation SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE platelets; sports medicine; coagulation; cell counters; ADVIA 2120 ID HEMATOLOGY SYSTEM; EXERCISE; RUNNERS; RUN; COAGULATION; FIBRINOLYSIS; AGGREGATION; SENSITIVITY; EXERTION; THROMBIN AB We used the ADVIA 2120 Hematology System (Bayer HealthCare, Diagnostics Division, Tarrytown, NY) to study the effects of vigorous exercise on CBC count, WBC differential, RBC fragmentation, and platelet activation parameters in 32 healthy participants in a 26.2-mile (42.2-km) marathon. The runners demonstrated increases in hematocrit and platelet count consistent with dehydration and leukocytosis indicative of demargination of neutrophils or inflammation secondary to tissue destruction (eg, rhabdomyolysis). The number of RBC fragments was increased after the race (P =.008), consistent with exercise-induced hemolysis. The mean platelet component, a measure of platelet granularity, was decreased (P <.0001), and the number of platelet clumps was increased (P =.0026), providing evidence for in vivo platelet activation during the marathon. By using direct measurement of platelet granularity, our study confirms the in vivo activation of platelets by vigorous exercise and establishes the usefulness of automated cell counters for the assessment of platelet activation and of RBC fragmentation in this setting. C1 Massachusetts Gen Hosp, Clin Hematol Lab, Div Lab Med, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. McLean Hosp, Dept Med, Belmont, MA 02178 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Kratz, A (reprint author), Massachusetts Gen Hosp, Clin Hematol Lab, Div Lab Med, Dept Pathol, 55 Fruit St,GRJ 235, Boston, MA 02114 USA. NR 33 TC 28 Z9 29 U1 0 U2 4 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD FEB PY 2006 VL 125 IS 2 BP 296 EP 300 DI 10.1309/PRF5N7P2XM6E243H PG 5 WC Pathology SC Pathology GA 004AU UT WOS:000234725200018 PM 16393676 ER PT J AU Kurth, T Walker, AM Glynn, RJ Chan, KA Gaziano, JM Berger, K Robins, JM AF Kurth, T Walker, AM Glynn, RJ Chan, KA Gaziano, JM Berger, K Robins, JM TI Results of multivariable logistic regression, propensity matching, propensity adjustment, and propensity-based weighting under conditions of nonuniform effect SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE causality; cerebrovascular accident; confounding factors (epidemiology); data interpretation, statistical; logistic models; models, statistical; observational study ID ACUTE ISCHEMIC-STROKE; TISSUE-PLASMINOGEN ACTIVATOR; MARGINAL STRUCTURAL MODELS; IN-HOSPITAL MORTALITY; REGISTERS-STUDY-GROUP; THROMBOLYTIC THERAPY; CAUSAL INFERENCE; CONTROLLED-TRIAL; SCORE METHODS; PREDICTORS AB Observational studies often provide the only available information about treatment effects. Control of confounding, however, remains challenging. The authors compared five methods for evaluating the effect of tissue plasminogen activator on death among 6,269 ischemic stroke patients registered in a German stroke registry: multivariable logistic regression, propensity score-matched analysis, regression adjustment with the propensity score, and two propensity score-based weighted methods-one estimating the treatment effect in the entire study population (inverse-probability-of-treatment weights), another in the treated population (standardized-mortality-ratio weights). Between 2000 and 2001, 212 patients received tissue plasminogen activator. The crude odds ratio between tissue plasminogen activator and death was 3.35 (95% confidence interval: 2.28, 4.91). The adjusted odds ratio depended strongly on the adjustment method, ranging from 1.11 (95% confidence interval: 0.67, 1.84) for the standardized-mortality-ratio weighted to 10.77 (95% confidence interval: 2.47, 47.04) for the inverse-probability-of-treatment-weighted analysis. For treated patients with a low propensity score, risks of dying were high. Exclusion of patients with a propensity score of <5% yielded comparable odds ratios of approximately 1 for all methods. High levels of nonuniform treatment effect render summary estimates very sensitive to the weighting system explicit or implicit in an adjustment technique. Researchers need to be clear about the population for which an overall treatment estimate is most suitable. C1 Harvard Univ, Brigham & Womens Hosp, Div Aging, Sch Med,Dept Med, Boston, MA 02120 USA. Harvard Univ, Brigham & Womens Hosp, Div Prevent Med, Sch Med,Dept Med, Boston, MA 02120 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. i3 Drug Safety, Auburndale, MA USA. Harvard Univ, Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Sch Med,Dept Med, Boston, MA 02120 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Boston VA Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. Univ Munster, Inst Epidemiol & Social Med, D-4400 Munster, Germany. RP Kurth, T (reprint author), Harvard Univ, Brigham & Womens Hosp, Div Aging, Sch Med,Dept Med, 1620 Tremont St, Boston, MA 02120 USA. EM tkurth@rics.bwh.harvard.edu RI Kurth, Tobias/A-9243-2012; OI Kurth, Tobias/0000-0001-7169-2620; Chan, Kinwei/0000-0001-8161-1986 FU NCI NIH HHS [R01 CA097193] NR 37 TC 299 Z9 300 U1 1 U2 28 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD FEB 1 PY 2006 VL 163 IS 3 BP 262 EP 270 DI 10.1093/aje/kwj047 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 004UH UT WOS:000234777300010 PM 16371515 ER PT J AU Weintraub, D Cary, MS Stern, MB Taraborelli, D Katz, IR AF Weintraub, D Cary, MS Stern, MB Taraborelli, D Katz, IR TI Daily affect in Parkinson disease is responsive to life events and motor symptoms SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE Parkinson disease; positive affect; negative affect ID DEPRESSION; METHYLPHENIDATE; POPULATION AB The aims of this study were to examine the daily affective experiences of patients with Parkinson disease (PD) and to determine their association with daily events and motor symptoms. Specifically, it was intended to test the hypothesis that PD, even in the absence of depression, is associated with anhedonia. Method: Nondepressed male subjects with PD (N=24) and a comparison group of healthy elderly males (N=23) completed daily affect rating scales and, for the patients with PD, a supplemental self-assessment questionnaire of PD-related symptoms for 4 consecutive weeks. The effect of daily events and PD- related symptoms on daily affect was examined using linear and logistic mixed regression models. Results: Overall, patients with PD reported significantly less positive and more negative affect than healthy peers over time. There were similar, and expected, associations between negative events and affect in both groups. Although patients with PD reported far fewer positive events than control subjects, they reported as great an improvement in affect in response to them. Regarding self-reported PD-related symptoms, only increasing severity of core motor symptoms was independently associated with worse affect. Conclusions: Although the conclusions of this study are tempered by a comparison group that is not optimal, our results suggest that patients with PD do not demonstrate anhedonia in response to positive life events. The gross intergroup difference in daily events suggests the potential value of interventions that emphasize daily engagement in positive experiences to improve positive affective tone. C1 Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA USA. RP Weintraub, D (reprint author), 3535 Market St,Rm 3003, Philadelphia, PA 19104 USA. EM weintrau@mail.med.upenn.edu FU NIMH NIH HHS [K23MH067894] NR 20 TC 10 Z9 10 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD FEB PY 2006 VL 14 IS 2 BP 161 EP 168 DI 10.1097/01.JGP.0000192494.96543.f4 PG 8 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 011HT UT WOS:000235259600010 PM 16473981 ER PT J AU Weintraub, D Oehlberg, KA Katz, IR Stern, MB AF Weintraub, D Oehlberg, KA Katz, IR Stern, MB TI Test characteristics of the 15-item geriatric depression scale and Hamilton Depression Rating Scale in Parkinson disease SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE Parkinson disease; depression; Geriatric Depression Scale ID NONMOTOR SYMPTOMS; SHORT VERSIONS; PERFORMANCE; PREVALENCE; INSTRUMENT; COMMUNITY; INVENTORY; VALIDITY; GDS-15 AB Objective: The objective of this study was to compare the sensitivity, specificity, and diagnostic accuracy of the 15-item Geriatric Depression Scale (GDS-15) and the Hamilton Depression Rating Scale (HDRS) in patients with Parkinson disease (PD). Method: A convenience sample of 148 outpatients with idiopathic PD receiving specialty care completed the GDS-15 and were administered the HDRS and Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (SCID) depression module by a research psychiatrist or trained research assistant. Receiver-operating characteristic (ROC) curves were plotted for the GDS-15 and HDRS scores with a SCID diagnosis of a depressive disorder as the state variable. Results: Thirty-two subjects (22%) were diagnosed with a depressive disorder. The discriminant validity of the GDS-15 and HDRS were both high (ROC area under the curve: 0.92 and 0.91, respectively), with greatest dichotomization for the GDS-15 at a cutoff of 4/5 (87% accuracy, 88% sensitivity, 85% specificity) and the HDRS at a cutoff of 9/10 (83% accuracy, 88% sensitivity, 78% specificity). Conclusions: The GDS-15 performs well as a screening instrument and in distinguishing depressed from nondepressed patients in PD. Its test characteristics are comparable to the HDRS. Because it is a brief instrument and can be self-administered, it is an excellent depression screening tool in this population. C1 Univ Penn, 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 USA. Philadelphia Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA USA. RP Weintraub, D (reprint author), 3535 Market St,Rm 3003, Philadelphia, PA 19104 USA. EM weintrau@mail.med.upenn.edu FU NIMH NIH HHS [K23 MH067894, K23MH067894] NR 35 TC 97 Z9 97 U1 3 U2 7 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD FEB PY 2006 VL 14 IS 2 BP 169 EP 175 DI 10.1097/01.JGP.0000192488.66049.4b PG 7 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 011HT UT WOS:000235259600011 PM 16473982 ER PT J AU Bergwitz, C Roslin, NM Tieder, M Loredo-Osti, JC Bastepe, M Abu-Zahra, H Frappier, D Burkett, K Carpenter, O Anderson, D Garabedian, M Sermet, I Fujiwara, TM Morgan, K Tenenhouse, HS Juppner, H AF Bergwitz, C Roslin, NM Tieder, M Loredo-Osti, JC Bastepe, M Abu-Zahra, H Frappier, D Burkett, K Carpenter, O Anderson, D Garabedian, M Sermet, I Fujiwara, TM Morgan, K Tenenhouse, HS Juppner, H TI SLC34A3 mutations in patients with hereditary hypophosphatemic rickets with hypercalciuria predict a key role for the sodium-phosphate cotransporter NaPi-IIc in maintaining phosphate homeostasis SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID VITAMIN-D METABOLISM; NA/PI COTRANSPORTER; PARATHYROID-HORMONE; I-COTRANSPORTER; LOD-SCORE; GENE; MICE; EXPRESSION; ABLATION; NPT2 AB Hereditary hypophosphatemic rickets with hypercalciuria ( HHRH) is a rare disorder of autosomal recessive inheritance that was first described in a large consanguineous Bedouin kindred. HHRH is characterized by the presence of hypophosphatemia secondary to renal phosphate wasting, radiographic and/or histological evidence of rickets, limb deformities, muscle weakness, and bone pain. HHRH is distinct from other forms of hypophosphatemic rickets in that affected individuals present with hypercalciuria due to increased serum 1,25-dihydroxyvitamin D levels and increased intestinal calcium absorption. We performed a genomewide linkage scan combined with homozygosity mapping, using genomic DNA from a large consanguineous Bedouin kindred that included 10 patients who received the diagnosis of HHRH. The disease mapped to a 1.6-Mbp region on chromosome 9q34, which contains SLC34A3, the gene encoding the renal sodium-phosphate cotransporter NaPi-IIc. Nucleotide sequence analysis revealed a homozygous single-nucleotide deletion ( c. 228delC) in this candidate gene in all individuals affected by HHRH. This mutation is predicted to truncate the NaPi-IIc protein in the first membrane-spanning domain and thus likely results in a complete loss of function of this protein in individuals homozygous for c. 228delC. In addition, compound heterozygous missense and deletion mutations were found in three additional unrelated HHRH kindreds, which supports the conclusion that this disease is caused by SLC34A3 mutations affecting both alleles. Individuals of the investigated kindreds who were heterozygous for a SLC34A3 mutation frequently showed hypercalciuria, often in association with mild hypophosphatemia and/or elevations in 1,25-dihydroxyvitamin D levels. We conclude that NaPi-IIc has a key role in the regulation of phosphate homeostasis. C1 Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. McGill Univ, Ctr Hlth, Res Inst, Montreal, PQ, Canada. McGill Univ, Dept Human Genet, Montreal, PQ, Canada. McGill Univ, Dept Med, Montreal, PQ, Canada. Tel Aviv Univ, Sackler Sch Med, Assaf Harofeh Med Ctr, Dept Pediat Nephrol, IL-69978 Tel Aviv, Israel. Yale Univ, Sch Med, Dept Pediat Endocrinol, New Haven, CT USA. John Hunter Childrens Hosp, Dept Endocrinol, Newcastle, NSW, Australia. Hop Necker Enfants Malad, Dept Pediat, Paris, France. Simon Fraser Univ, Dept Stat & Actuarial Sci, Burnaby, BC V5A 1S6, Canada. RP Bergwitz, C (reprint author), Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. EM cbergwitz@partners.org FU NICHD NIH HHS [K24 HD001288, K24-HD-01288]; NIDDK NIH HHS [K08 DK078361, R01 DK 46718, R01 DK046718, R03 DK089127] NR 54 TC 183 Z9 191 U1 0 U2 2 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 FEB PY 2006 VL 78 IS 2 BP 179 EP 192 DI 10.1086/499409 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 031ZY UT WOS:000236744900001 PM 16358214 ER PT J AU Poznik, GD Adamska, K Xu, X Krolewski, AS Rogus, JJ AF Poznik, GD Adamska, K Xu, X Krolewski, AS Rogus, JJ TI A novel framework for sib pair linkage analysis SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID GENETICALLY COMPLEX TRAITS; AFFECTED RELATIVE PAIRS; DISEASE SUSCEPTIBILITY; POWERFUL TEST; LOCI; STRATEGIES; MODELS; GENES; TESTS; CONSTRAINTS AB Sib pair linkage analysis of a dichotomous trait is a popular method for narrowing the search for genes that influence complex diseases. Although the pedigree structures are uncomplicated and the underlying genetic principles straightforward, a surprising degree of complexity is involved in implementing a sib pair study and interpreting the results. Ascertainment may be based on affected, discordant, or unaffected sib pairs, as well as on pairs defined by threshold values for quantitative traits, such as extreme discordant sib pairs. To optimize power, various domain restrictions and null hypotheses have been proposed for each of these designs, yielding a wide array of choices for the analyst. To begin, we systematically classify the major sources of discretion in sib pair linkage analysis. Then, we extend the work of Kruglyak and Lander ( 1995), to bring the various forms into a unified framework and to facilitate a more general approach to the analysis. Finally, we describe a new, freely available computer program, SPLAT ( Sib Pair Linkage Analysis Testing), that can perform any sib pair statistical test currently in use, as well as any user-defined test yet to be proposed. SPLAT uses the expectation maximization algorithm to calculate maximum-likelihood estimates of sharing ( subject to user-specified conditions) and then plots LOD scores versus chromosomal position. It includes a novel grid-scanning capability that enables simultaneous visualization of multiple test statistics. This can lead to further insight into the genetic basis of the disease process under consideration. In addition, phenotype definitions can be modified without the recalculation of inheritance vectors, thereby providing considerable flexibility for exploratory analysis. The application of SPLAT will be illustrated with data from studies on the genetics of diabetic nephropathy. C1 Harvard Univ, Sch Publ Hlth, Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Jagiellonian Univ, Inst Informat, Krakow, Poland. RP Rogus, JJ (reprint author), Harvard Univ, Sch Publ Hlth, Joslin Diabet Ctr, Sect Genet & Epidemiol, 665 Huntington Ave, Boston, MA 02115 USA. EM John.Rogus@joslin.harvard.edu FU NIDDK NIH HHS [DK53534, R01 DK058549, DK58549] NR 31 TC 5 Z9 5 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 FEB PY 2006 VL 78 IS 2 BP 222 EP 230 DI 10.1086/499827 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 031ZY UT WOS:000236744900004 PM 16358216 ER PT J AU Lev, MH Vedolin, L AF Lev, MH Vedolin, L TI Premeability versus cerebral blood volume measurement in brain tumor evaluation: Comparative clinical value and advice to authors SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Editorial Material ID PERMEABILITY; MR C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Mae De Deus Hosp, Porto Alegre, RS, Brazil. RP Lev, MH (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 5 TC 5 Z9 5 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 FEB PY 2006 VL 27 IS 2 BP 418 EP 419 PG 2 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 014GJ UT WOS:000235467100048 PM 16484421 ER PT J AU Kwon, JW Jeoung, JW Kim, TI Lee, JH Wee, WR AF Kwon, JW Jeoung, JW Kim, TI Lee, JH Wee, WR TI Argon laser photoablation of conjunctival pigmented nevus SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article AB PURPOSE: To evaluate the efficacy of an argon laser in the ablation of benign conjunctival pigmented nevi. DESIGN: Interventional case series. METHODS: We conducted argon laser ablations for cone junctival pigmented nevus in 30 eyes of 28 patients. Laser ablation was applied directly to the conjunctival pigmented nevus in all patients. All patients were followed up over a period of 12 months. RESULTS: In all patients, the conjunctival lesions to which the argon laser was applied disappeared almost completely within two days after treatment. No recurrence of lesions was detected in any patient during the follow,up period, nor were any conjunctival scars or conjunctival injections. CONCLUSIONS: The argon-laser ablation of conjunctival pigmented nevi uniformly resulted in excellent clinical outcomes. Therefore, this study concludes that argon laser ablation is a safe and effective modality for the treatment of benign conjunctival nevi, and this method could replace the classical surgical procedure. C1 Seoul Natl Univ, Coll Med, Dept Ophthalmol, Seoul 110744, South Korea. Seoul Natl Univ Hosp, Seoul Artificial Eye Ctr, Clin Res Inst, Seoul 110744, South Korea. Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02115 USA. RP Wee, WR (reprint author), Seoul Natl Univ, Coll Med, Dept Ophthalmol, 28 Yongon Dong, Seoul 110744, South Korea. EM wrwee@snu.ac.kr RI Wee, Won Ryang/J-2769-2012 NR 1 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD FEB PY 2006 VL 141 IS 2 BP 383 EP 386 DI 10.1016/j.ajo.2005.08.030 PG 4 WC Ophthalmology SC Ophthalmology GA 013LF UT WOS:000235410100028 PM 16458702 ER PT J AU Al-Aswad, LA Netland, PA Bellows, AR Ajdelsztajn, T Wadhwani, RA Ataher, G Hill, RA AF Al-Aswad, LA Netland, PA Bellows, AR Ajdelsztajn, T Wadhwani, RA Ataher, G Hill, RA TI Clinical experience with the double-plate Ahmed glaucoma valve SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID DRAINAGE IMPLANT; TRIAL AB PURPOSE: To evaluate the clinical efficacy and safety of the double-plate Ahmed Glaucoma Valve. DESIGN: Multicenter, retrospective observational case series. METHODS: We reviewed 50 eyes in 50 patients treated with the double,plate Ahmed Glaucoma Valve with mean follow,up of 11.7 +/- 7.9 months. RESULTS: Average intraocular pressure was reduced from 36.0 +/- 12.4 mm Hg before surgery to 15.8 +/- 7.7 mm Hg at the most recent follow,up after surgery (P < .001). The number of glaucoma medications was decreased from 3.3 +/- 0.8 before surgery to 1.4 +/- 1.4 after surgery (P < .001). The percent of success was 76% of eyes at the latest follow,up. Choroidal effusion occurred in four eyes (8%) and did not require surgical treatment in any eye. CONCLUSIONS: Despite a poor prognosis group of patients in this study, the double-plate Ahmed Glaucoma Valve was effective in lowering intraocular pressure with a low incidence of complications associated with hypotony. C1 Univ Tennessee, Ctr Hlth Sci, Hamilton Eye Inst, Memphis, TN 38163 USA. Ophthalm Consultants Boston, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. Tufts Univ, New England Eye Ctr, Boston, MA 02111 USA. Univ Calif Irvine, Irvine, CA USA. RP Al-Aswad, LA (reprint author), Univ Tennessee, Ctr Hlth Sci, Hamilton Eye Inst, 930 Madison Ave, Memphis, TN 38163 USA. EM mesmith@utmem.edu NR 7 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD FEB PY 2006 VL 141 IS 2 BP 390 EP 391 DI 10.1016/j.ajo.2005.08.036 PG 2 WC Ophthalmology SC Ophthalmology GA 013LF UT WOS:000235410100031 PM 16458705 ER PT J AU Liu, XQ Zhao, Y Pawlyk, B Damaser, M Li, TS AF Liu, XQ Zhao, Y Pawlyk, B Damaser, M Li, TS TI Failure of elastic fiber homeostasis leads to pelvic floor disorders SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID STRESS URINARY-INCONTINENCE; SIMULATED BIRTH TRAUMA; EHLERS-DANLOS-SYNDROME; ORGAN PROLAPSE; CONTINENCE MECHANISM; CONNECTIVE-TISSUE; FEMALE RAT; IN-VIVO; EPIDEMIOLOGY; WOMEN AB Pelvic floor disorders, a group of conditions affecting adult women, include pelvic organ prolapse and urinary incontinence. Vaginal childbirth and aging are risk factors, and weakening of the pelvic support structures is a major aspect of the pathology. However, the underlying molecular mechanism remains unknown. Female reproductive organs are rich in elastic fibers that turn over slowly in most adult tissues but undergo massive remodeling in the reproductive organs through pregnancy and birth. Here we show that a failure to maintain elastic fiber homeostasis in mice causes pelvic floor disorders. Lysyl oxidase-like-1 (LOXL1), a protein essential for the postnatal deposition of elastic fibers, was highly expressed and regulated in the reproductive tract of the mouse, and its expression was diminished during aging. LOXL1 deficiency caused an inability of reproductive tissues to replenish elastic fibers after parturition, leading to pelvic organ prolapse, weakening of the vaginal wall, paraurethral pathology, and lower urinary tract dysfunction. These data demonstrate the importance of elastic fibers for maintaining structural and functional integrity of the female pelvic floor. Our findings raise the possibility that a failure of elastic fiber homeostasis, either due to genetic predisposition or advancing age, could underlie the etiology of pelvic floor dysfunction in women. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. Cleveland Clin Fdn, Dept Biomed Engn, Lerner Res Inst, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Glickman Urol Inst, Cleveland, OH 44195 USA. Louis Stokes Cleveland Vet Adm Med Ctr, Res Serv, Cleveland, OH USA. RP Li, TS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, 243 Charles St, Boston, MA 02114 USA. EM tli@meei.harvard.edu NR 54 TC 82 Z9 96 U1 1 U2 9 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 FEB PY 2006 VL 168 IS 2 BP 519 EP 528 DI 10.2353/ajpath.2006.050399 PG 10 WC Pathology SC Pathology GA 009OV UT WOS:000235122600016 PM 16436666 ER PT J AU Natasha, T Kuhn, M Kelly, O Rittling, SR AF Natasha, T Kuhn, M Kelly, O Rittling, SR TI Override of the osteoclast defect in osteopontin-deficient mice by metastatic tumor growth in the bone SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID HORMONE-RELATED PROTEIN; BREAST-CANCER; IN-VITRO; INTRACELLULAR OSTEOPONTIN; OSTEOPROTEGERIN-LIGAND; CELL-MIGRATION; RESORPTION; EXPRESSION; DIFFERENTIATION; SIALOPROTEIN AB Osteopontin (OPN) is a major noncollagenous protein of bone that is frequently up-regulated in tumors, where it enhances tumor growth. OPN-deficient mice are resistant to stimulated bone resorption, including that occurring after ovariectomy. Using a new syngeneic model of bone metastasis (r3T), we examined whether OPN-deficient mice are similarly resistant to bone loss resulting from osteolytic tumor growth. Transformed mammary epithelial cells, r3T, which express parathyroid hormone-related protein but not receptor activator of nuclear factor-KB ligand, were injected via the intracardiac route into both wild-type and OPN-/- mice. We measured tumor burden in the bone by quantitative polymerase chain reaction assay and evaluated bone loss by X-ray and microCT. Unexpectedly, bone loss was similar in OPN-/- and wildtype mice bearing similar-sized tumors. Osteoclast number was comparable in both genotypes, and the expression of bone sialoprotein was similar in tumorbearing bones of both genotypes, excluding two potential mechanisms of overriding the defect. Taken together, these results indicate that in the absence of OPN, the bone loss associated with tumor growth at the bone site proceeds rapidly despite the osteoclast defects documented in OPN-/- mice, suggesting that the mechanism of bone loss due to tumor growth differs from that occurring hi other pathologies. C1 Rutgers State Univ, Dept Genet, Piscataway, NJ 08855 USA. RP Rittling, SR (reprint author), Forsyth Inst, 140 Fenway, Boston, MA 02115 USA. EM srittling@forsyth.org FU PHS HHS [R01 67685] NR 45 TC 13 Z9 14 U1 0 U2 0 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 FEB PY 2006 VL 168 IS 2 BP 551 EP 561 DI 10.2353/ajpath.2006.050480 PG 11 WC Pathology SC Pathology GA 009OV UT WOS:000235122600019 PM 16436669 ER PT J AU Nakamura, E Abreu-e-Lima, P Awakura, Y Inoue, T Kamoto, T Ogawo, O Kotani, H Manabe, T Zhang, GJ Kondo, K Nose, V Kaelin, WG AF Nakamura, E Abreu-e-Lima, P Awakura, Y Inoue, T Kamoto, T Ogawo, O Kotani, H Manabe, T Zhang, GJ Kondo, K Nose, V Kaelin, WG TI Clusterin is a secreted marker for a hypoxia-inducible factor- independent function of the von Hippel-Lindau tumor suppressor protein SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID RENAL-CELL CARCINOMA; ENDOTHELIAL GROWTH-FACTOR; PROSTATE EPITHELIAL-CELLS; RNA-POLYMERASE-II; GENE-PRODUCT; CHUVASH POLYCYTHEMIA; BETA-DOMAIN; VHL; EXPRESSION; CANCER AB Germline mutations in the von Hippel-Lindau (VHL) tumor suppressor gene predispose people to renal cancer, hemangioblastomas, and pheochromocytomas in an allele-specific manner. The best documented function of the VHL gene product (pVHL) relates to its ability to polyubiquitinate, and hence target for destruction, the a subunits of the heterodimeric transcription factor hypoxia-inducible factor (HIF). pVHL mutants linked to familial pheochromocyctoma (type 2C VHL disease), in contrast to classical VHL disease, appear to be normal with respect to HIF regulation. Using a simple method for identifying proteins that are differentially secreted by isogenic cell line pairs, we confirmed that the HIF targets IGBP3 and PAI-1 are overproduced by pVHL-defective renal carcinoma cells. in addition, cells lacking wild-type pVHL, including cells producing type 2C pVHL mutants, were defective with respect to expression and secretion of clusterin, which does not behave like a HIF target. Decreased clusterin secretion by pVHL-defective tumors was confirmed in vivo by immunohistochemistry. Therefore, clusterin is a secreted marker for a HIF-independent pVHL function that might be especially important in pheochromocytoma development. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Kyoto Univ, Grad Sch Med, Dept Urol, Kyoto, Japan. Kyoto Univ Hosp, Anat Pathol Lab, Kyoto 606, Japan. RP Kaelin, WG (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM William_kaelin@dfci.harvard.edu RI Zhang, Guo-Jun/H-3890-2015 OI Zhang, Guo-Jun/0000-0001-5182-5887 NR 63 TC 46 Z9 47 U1 0 U2 1 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 FEB PY 2006 VL 168 IS 2 BP 574 EP 584 DI 10.2353/ajpath.2006.050867 PG 11 WC Pathology SC Pathology GA 009OV UT WOS:000235122600021 PM 16436671 ER PT J AU Xiao, YF Ma, L Wang, SY Josephson, ME Wang, GK Morgan, JP Leaf, A AF Xiao, YF Ma, L Wang, SY Josephson, ME Wang, GK Morgan, JP Leaf, A TI Potent block of inactivation-deficient Na+ channels by n-3 polyunsaturated fatty acids SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE human cardiac sodium channel ID RAT VENTRICULAR MYOCYTES; GATED SODIUM-CHANNELS; WILD-TYPE; CONTRACTION; FLECAINIDE; MUTATIONS; STATES; DEATH; CELLS AB A voltage-gated, small, persistent Na+ current (I-Na) has been shown in mammalian cardiomyocytes. Hypoxia potentiates the persistent I-Na that may cause arrhythmias. In the present study, we investigated the effects of n-3 polyunsaturated fatty acids (PUFAs) on I-Na in HEK-293t cells transfected with an inactivation-deficient mutant (L409C/A410W) of the alpha-subunit (hH1(alpha)) of human cardiac Na+ channels (hNav1.5) plus beta(1)-subunits. Extracellular application of 5 mu M eicosapentaenoic acid (EPA; C20:5n-3) significantly inhibited I-Na. The late portion of I-Na (I-Na (late), measured near the end of each pulse) was almost completely suppressed. I-Na returned to the pretreated level after washout of EPA. The inhibitory effect of EPA on I-Na was concentration dependent, with IC50 values of 4.0 +/- 0.4 mu M for I-Na peak (I-Na (peak)) and 0.9 +/- 0.1 mu M for I-Na late. EPA shifted the steady-state inactivation of I-Na (peak) by -19 mV in the hyperpolarizing direction. EPA accelerated the process of resting inactivation of the mutant channel and delayed the recovery of the mutated Na+ channel from resting inactivation. Other polyunsaturated fatty acids, docosahexaenoic acid, linolenic acid, arachidonic acid, and linoleic acid, all at 5 mu M concentration, also significantly inhibited I-Na. In contrast, the monounsaturated fatty acid oleic acid or the saturated fatty acids stearic acid and palmitic acid at 5 mu M concentration had no effect on I-Na. Our data demonstrate that the double mutations at the 409 and 410 sites in the D1-S6 region of hH1(alpha) induce inactivation-deficient I-Na and that n-3 PUFAs inhibit mutant I-Na. C1 Beth Israel Deaconess Med Ctr, Charles A Dana Res Inst, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Harvard Thorndike Lab, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Med, Div Cardiovasc, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Anesthesia, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. SUNY Albany, Dept Biol, Albany, NY 12222 USA. RP Massachusetts Gen Hosp E, Dept Med, 149 13th St, Charlestown, MA 02129 USA. EM aleaf@partners.org FU NHLBI NIH HHS [HL-62284]; NIDA NIH HHS [DA-11762]; NIGMS NIH HHS [GM-48090] NR 21 TC 30 Z9 33 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 EI 1522-1563 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD FEB PY 2006 VL 290 IS 2 BP C362 EP C370 DI 10.1152/ajpcell.00296.2005 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 001KH UT WOS:000234531500006 PM 16207794 ER PT J AU Hadigan, C Kamin, D Liebau, J Mazza, S Barrow, S Torriani, M Rubin, R Weise, S Fischman, A Grinspoon, S AF Hadigan, C Kamin, D Liebau, J Mazza, S Barrow, S Torriani, M Rubin, R Weise, S Fischman, A Grinspoon, S TI Depot-specific regulation of glucose uptake and insulin sensitivity in HIV-lipodystrophy SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE positron emission tomography; adipose tissue; insulin resistance; human immunodeficiency virus-lipodystrophy ID ACTIVE ANTIRETROVIRAL THERAPY; SUBCUTANEOUS ADIPOSE-TISSUE; INHIBITOR-ASSOCIATED LIPODYSTROPHY; VIRUS-INFECTED PATIENTS; SKELETAL-MUSCLE; COMPUTED-TOMOGRAPHY; FAT REDISTRIBUTION; DIABETES-MELLITUS; ABDOMINAL FAT; ADIPOCYTE DIFFERENTIATION AB Altered fat distribution is associated with insulin resistance in HIV, but little is known about regional glucose metabolism in fat and muscle depots in this patient population. The aim of the present study was to quantify regional fat, muscle, and whole body glucose disposal in HIV-infected men with lipoatrophy. Whole body glucose disposal was determined by hyperinsulinemic clamp technique ( 80 mU (.) m(-2) (.) min(-1)) in 6 HIV-infected men and 5 age/weight-matched healthy volunteers. Regional glucose uptake in muscle and subcutaneous ( SAT) and visceral adipose tissue ( VAT) was quantified in fasting and insulin-stimulated states using 2-deoxy-[F-18] fluoro-D-glucose positron emission tomography. HIV-infected subjects with lipoatrophy had significantly increased glucose uptake into SAT ( 3.8 +/- 0.4 vs. 2.3 +/- 0.5 mu mol (.) kg tissue(-1) (.) min(-1), P < 0.05) in the fasted state. Glucose uptake into VAT did not differ between groups. VAT area was inversely related with whole body glucose disposal, insulin sensitivity, and muscle glucose uptake during insulin stimulation. VAT area was highly predictive of whole body glucose disposal ( r(2) = 0.94, P < 0.0001). This may be mediated by adiponectin, which was significantly associated with VAT area ( r = - 0.75, P = 0.008), and whole body glucose disposal ( r = 0.80, P = 0.003). This is the first study to directly demonstrate increased glucose uptake in subcutaneous fat of lipoatrophic patients, which may partially compensate for loss of SAT. Furthermore, we demonstrate a clear relationship between VAT and glucose metabolism in multiple fat and muscle depots, suggesting the critical importance of this depot in the regulation of glucose and highlighting the significant potential role of adiponectin in this process. C1 Massachusetts Gen Hosp, Program Nutr Metabol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Nucl Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Musculoskeletal Radiol, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Hadigan, C (reprint author), Massachusetts Gen Hosp, Program Nutr Metabol, 55 Fruit St,LON 207, Boston, MA 02114 USA. EM chadigan@partners.org FU NCRR NIH HHS [K23 RR-018715, M01 RR-300088, K23 RR018715]; NIDDK NIH HHS [T32 DK007477, R01 DK-59535, K23 DK-02844, P30 DK040561-10, P30 DK040561, T32 DK-07477, K23 DK002844, R01 DK059535] NR 54 TC 15 Z9 16 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD FEB PY 2006 VL 290 IS 2 BP E289 EP E298 DI 10.1152/ajpendo.00273.2005 PG 10 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 001JV UT WOS:000234530300012 PM 16131513 ER PT J AU Nierenberg, AA Ostacher, MJ Calabrese, JR Ketter, TA Marangell, LB Miklowitz, DJ Miyahara, S Bauer, MS Thase, ME Wisniewski, SR Sachs, GS AF Nierenberg, AA Ostacher, MJ Calabrese, JR Ketter, TA Marangell, LB Miklowitz, DJ Miyahara, S Bauer, MS Thase, ME Wisniewski, SR Sachs, GS CA STEP-BD Investigators TI Treatment-resistant bipolar depression: A STEP-BD equipoise randomized effectiveness trial of antidepressant augmentation with lamotrigine, inositol, or risperidone SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID PLACEBO-CONTROLLED TRIAL; WEEKLY SYMPTOMATIC STATUS; DOUBLE-BLIND; I-DISORDER; NATURAL-HISTORY; IMIPRAMINE; LITHIUM; TRANYLCYPROMINE; COMBINATION; MONOTHERAPY AB Objective: Clinicians have few evidence-based options for the management of treatment-resistant bipolar depression. This study represents the first randomized trial of competing options for treatment-resistant bipolar depression and assesses the effectiveness and safety of antidepressant augmentation with lamotrigine, inositol, and risperidone. Method: Participants (N=66) were patients with bipolar I or bipolar II disorder enrolled in the NIMH Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). All patients were in a current major depressive episode that was nonresponsive to a combination of adequate doses of established mood stabilizers plus at least one antidepressant. Patients were randomly assigned to open-label adjunctive treatment with lamotrigine, inositol, or risperidone for up to 16 weeks. The primary outcome measure was the rate of recovery, defined as no more than two symptoms meeting DSM-IV threshold criteria for a mood episode and no significant symptoms present for 8 weeks. Results: No significant between-group differences were seen when any pair of treatments were compared on the primary outcome measure. However, the recovery rate with lamotrigine was 23.8%, whereas the recovery rates with inositol and risperidone were 17.4% and 4.6%, respectively. Patients receiving lamotrigine had lower depression ratings and Clinical Global Impression severity scores as well as greater Global Assessment of Functioning scores compared with those receiving inositol and risperidone. Conclusions: No differences were found in primary pairwise comparison analyses of open-label augmentation with lamotrigine, inositol, or risperidone. Post hoc secondary analyses suggest that lamotrigine may be superior to inositol and risperidone in improving treatment-resistant bipolar depression. C1 Massachusetts Gen Hosp, Bipolar Clin & Res Program, Boston, MA 02114 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Baylor Coll Med, Dept Psychiat, Houston, TX 77030 USA. Univ Colorado, Dept Psychol, Boulder, CO 80309 USA. Univ Colorado, Dept Psychiat, Boulder, CO 80309 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA 15260 USA. Brown Med Sch, Providence, RI USA. Western Psychiat Inst & Clin, Pittsburgh, PA USA. RP Nierenberg, AA (reprint author), Massachusetts Gen Hosp, Bipolar Clin & Res Program, Suite 580,50 Staniford St, Boston, MA 02114 USA. EM anierenberg@partners.org OI Wisniewski, Stephen/0000-0002-3877-9860; Ostacher, Michael/0000-0003-0353-7535 FU NIMH NIH HHS [N01 MH 80001] NR 38 TC 148 Z9 152 U1 4 U2 8 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD FEB PY 2006 VL 163 IS 2 BP 210 EP 216 DI 10.1176/appi.ajp.163.2.210 PG 7 WC Psychiatry SC Psychiatry GA 008HO UT WOS:000235031000010 PM 16449473 ER PT J AU Perlis, RH Ostacher, MJ Patel, JK Marangell, LB Zhang, HW Wisniewski, SR Ketter, TA Miklowitz, DJ Otto, MW Gyulai, L Reilly-Harrington, NA Nierenberg, AA Sachs, GS Thase, ME AF Perlis, RH Ostacher, MJ Patel, JK Marangell, LB Zhang, HW Wisniewski, SR Ketter, TA Miklowitz, DJ Otto, MW Gyulai, L Reilly-Harrington, NA Nierenberg, AA Sachs, GS Thase, ME TI Predictors of recurrence in bipolar disorder: Primary outcomes from the systematic treatment enhancement program for bipolar disorder (STEP-BD) SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID WEEKLY SYMPTOMATIC STATUS; PROSPECTIVE FOLLOW-UP; I-DISORDER; RANDOMIZED-TRIAL; NATURAL-HISTORY; MANIA; MAINTENANCE; LITHIUM; PSYCHOEDUCATION; MANAGEMENT AB Objective: Little is known about clinical features associated with the risk of recurrence in patients with bipolar disorder receiving treatment according to contemporary practice guidelines. The authors looked for the features associated with risk of recurrence. Method: The authors examined prospective data from a cohort of patients with bipolar disorder participating in the multicenter Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study for up to 24 months. For those who were symptomatic at study entry but subsequently achieved recovery, time to recurrence of mania, hypomania, mixed state, or a depressive episode was examined with Cox regression. Results: Of 1,469 participants symptomatic at study entry, 858 (58.4%) subsequently achieved recovery. During up to 2 years of follow-up, 416 (48.5%) of these individuals experienced recurrences, with more than twice as many developing depressive episodes (298, 34.7%) as those who developed manic, hypomanic, or mixed episodes (118, 13.8%). The time until 25% of the individuals experienced a depressive episode was 21.4 weeks and until 25% experienced a manic/hypomanic/mixed episode was 85.0 weeks. Residual depressive or manic symptoms at recovery and proportion of days depressed or anxious in the preceding year were significantly associated with shorter time to depressive recurrence. Residual manic symptoms at recovery and proportion of days of elevated mood in the preceding year were significantly associated with shorter time to manic, hypomanic, or mixed episode recurrence. Conclusions: Recurrence was frequent and associated with the presence of residual mood symptoms at initial recovery. Targeting residual symptoms in maintenance treatment may represent an opportunity to reduce risk of recurrence. C1 Harvard Univ, Massachusetts Gen Hosp, Bipolar Clin & Res Program, Sch Med, Boston, MA 02114 USA. Univ Massachusetts, Med Ctr, Worcester, MA 01605 USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Western Psychiat Inst & Clin, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA 15260 USA. Stanford Univ, Sch Med, San Francisco, CA USA. Boston Univ, Boston, MA 02215 USA. Univ Colorado, Boulder, CO 80309 USA. Univ Penn, Philadelphia, PA 19104 USA. RP Perlis, RH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Bipolar Clin & Res Program, Sch Med, ACC 812,15 Parkman St, Boston, MA 02114 USA. EM rperlis@partners.org OI Wisniewski, Stephen/0000-0002-3877-9860; Ostacher, Michael/0000-0003-0353-7535 FU NIMH NIH HHS [K23 MH 067060, N01 MH 80001] NR 37 TC 304 Z9 313 U1 7 U2 22 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD FEB PY 2006 VL 163 IS 2 BP 217 EP 224 DI 10.1176/appi.ajp.163.2.217 PG 8 WC Psychiatry SC Psychiatry GA 008HO UT WOS:000235031000011 PM 16449474 ER PT J AU Perlis, RH Brown, E Baker, RW Nierenberg, AA AF Perlis, RH Brown, E Baker, RW Nierenberg, AA TI Clinical features of bipolar depression versus major depressive disorder in large multicenter trials SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID TREATMENT ENHANCEMENT PROGRAM; ATYPICAL DEPRESSION; II DISORDER; UNIPOLAR DEPRESSION; MOOD STABILIZERS; HIGH PREVALENCE; ANGER ATTACKS; STEP-BD; ILLNESS; ANTIDEPRESSANTS AB Objective: Failure to recognize bipolar disorder in patients who experience a major depressive episode may lead to inappropriate treatment and poorer outcomes. Clinical features that could distinguish bipolar from unipolar depression would facilitate more appropriate treatment selection. Method: The authors used data from nonpsychotic outpatients participating in three large multicenter clinical trials conducted in the United States for the treatment of major depressive episodes to compare 477 subjects with a diagnosis of bipolar disorder and 1,074 with major depressive disorder. Results: Bipolar depression was associated with family history of bipolar disorder, an earlier age at onset, a greater previous number of depressive episodes, and eight individual symptom items on the Montgomery-Asberg Depression Rating Scale and the Hamilton Anxiety Rating Scale. Fears were more common in patients with bipolar disorder, whereas sadness; insomnia; intellectual (cognitive), somatic (muscular), respiratory, genitourinary complaints; and depressed behavior were more common in patients with unipolar depression. A logistic regression model correctly classified 86.9% of the subjects. Conclusions: Bipolar depression and major depressive disorder exhibit subtle differences in presentation, which may help guide the initial diagnosis. C1 Massachusetts Gen Hosp, Bipolar Clin & Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. RP Perlis, RH (reprint author), Massachusetts Gen Hosp, Bipolar Clin & Res Program, ACC 812,15 Parkman St, Boston, MA 02114 USA. EM rperlis@partners.org FU NIMH NIH HHS [K23 MH 067060] NR 42 TC 106 Z9 116 U1 2 U2 9 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD FEB PY 2006 VL 163 IS 2 BP 225 EP 231 DI 10.1176/appi.ajp.163.2.225 PG 7 WC Psychiatry SC Psychiatry GA 008HO UT WOS:000235031000012 PM 16449475 ER PT J AU Leverich, GS Altshuler, LL Frye, MA Suppes, T McElroy, SL Keck, PE Kupka, RW Denicoff, KD Nolen, WA Grunze, H Martinez, MI Post, RM AF Leverich, GS Altshuler, LL Frye, MA Suppes, T McElroy, SL Keck, PE Kupka, RW Denicoff, KD Nolen, WA Grunze, H Martinez, MI Post, RM TI Risk of switch in mood polarity to hypomania or mania in patients with bipolar depression during acute and continuation trials of venlafaxine, sertraline, and Bupropion as adjuncts to mood stabilizers SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID DOUBLE-BLIND; I DEPRESSION; ANTIDEPRESSANT DISCONTINUATION; NETWORK I; DISORDER; 1-YEAR; OUTPATIENTS; LAMOTRIGINE; METHODOLOGY; QUETIAPINE AB Objective: The authors examined the comparative risks of switches in mood polarity into hypomania or mania during acute and continuation trials of adjunctive antidepressant treatment of bipolar depression. Method: One hundred fifty-nine patients with bipolar I disorder or bipolar II disorder participated in a total of 228 acute (10-week) randomized trials of bupropion, sertraline, or venlafaxine as an adjunct to a mood stabilizer. Patients in 87 of these trials entered continuation treatment for up to 1 year. Antidepressant response and the occurrence of subthreshold brief hypomania (emergence of brief hypomania [at least 1 but < 7 days] or recurrent brief hypomania) and threshold switches (emergence of full-duration hypomania [>= 7 days] or mania) were blindly assessed by using clinician-rated daily reports of mood-associated dysfunction on the National Institute of Mental Health Life Chart Method. Results: Threshold switches into full-duration hypomania and mania occurred in 11.4% and 7.9%, respectively, of the acute treatment trials and in 21.8% and 14.9%, respectively, of the continuation trials. The rate of threshold switches was higher in the 169 trials in patients with bipolar I disorder (30.8%) than the 59 trials in patients with bipolar II disorder (18.6%). The ratio of threshold switches to subthreshold brief hypomanias was higher in both the acute (ratio=3.60) and continuation trials (ratio=3.75) of venlafaxine than in the acute and continuation trials of bupropion (ratios=0.85 and 1.17, respectively) and sertraline (ratios=1.67 and 1.66, respectively). In only 37 (16.2%) of the original 228 acute antidepressant trials, or in only 23.3% of the patients, was there a sustained antidepressant response in the continuation phase in the absence of a threshold switch. Conclusions: Adjunctive treatment with antidepressants in bipolar depression was associated with substantial risks of threshold switches to full-duration hypomania or mania in both acute and long-term continuation treatment. Of the three antidepressants included in the study, venlafaxine was associated with the highest relative risk of such switching and bupropion with the lowest risk. C1 NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA USA. Univ Texas, SW Med Ctr, Dallas, TX 75230 USA. Univ Cincinnati, Coll Med, Psychopharmacol Res Program, Dept Psychiat, Cincinnati, OH 45221 USA. Cincinnati VA Med Ctr, Mental Hlth Care Line & Gen Clin Res Ctr, Cincinnati, OH USA. Altrecht Inst Mental Hlth Care, Utrecht, Netherlands. Univ Groningen Hosp, Dept Psychiat, NL-9700 RB Groningen, Netherlands. Univ Munich, Psychiat Clin, Munich, Germany. RP NIMH, Biol Psychiat Branch, Bldg 10,Room 3S239,10 Ctr Dr,MSC-1272, Bethesda, MD 20892 USA. EM levericg@mail.nih.gov RI Nolen, Willem/E-9006-2014 FU NIMH NIH HHS [R01 MH079261] NR 40 TC 245 Z9 249 U1 1 U2 14 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X EI 1535-7228 J9 AM J PSYCHIAT JI Am. J. Psychiat. PD FEB PY 2006 VL 163 IS 2 BP 232 EP 239 DI 10.1176/appi.ajp.163.2.232 PG 8 WC Psychiatry SC Psychiatry GA 008HO UT WOS:000235031000013 PM 16449476 ER PT J AU Tohen, M Calabrese, JR Sachs, GS Banov, MD Detke, HC Risser, R Baker, RW Chou, JCY Bowden, CL AF Tohen, M Calabrese, JR Sachs, GS Banov, MD Detke, HC Risser, R Baker, RW Chou, JCY Bowden, CL TI Randomized, placebo-controlled trial of olanzapine as maintenance therapy in patients with bipolar I disorder responding to acute treatment with olanzapine SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 4th European-Stanley-Foundation Conference on Bipolar Disorder CY SEP 23-24, 2004 CL Aarhus, DENMARK SP European Stanley Fdn ID CONTROLLED 18-MONTH TRIAL; DOUBLE-BLIND; FOLLOW-UP; MANIA; LITHIUM; LAMOTRIGINE; DIVALPROEX; 3-WEEK AB Objective: In a placebo-controlled, double-blind study, the authors investigated the efficacy and safety of olanzapine as monotherapy in relapse prevention in bipolar I disorder. Method: Patients achieving symptomatic remission from a manic or mixed episode of bipolar I disorder (Young Mania Rating Scale [YMRS] total score <= 12 and 21-item Hamilton Depression Rating Scale [HAM-D] score <= 8) at two consecutive weekly visits following 6-12 weeks of open-label acute treatment with 5-20 mg/day of olanzapine were randomly assigned to double-blind maintenance treatment with olanzapine (N=225) or placebo (N=136) for up to 48 weeks. The primary measure of efficacy was time to symptomatic relapse into any mood episode (YMRS score >= 15, HAM-D score >= 15, or hospitalization). Results: Time to symptomatic relapse into any mood episode was significantly longer among patients receiving olanzapine (a median of 174 days, compared with a median of 22 days in patients receiving placebo). Times to symptomatic relapse into manic, depressive, and mixed episodes were all significantly longer among patients receiving olanzapine than among patients receiving placebo. The relapse rate was significantly lower in the olanzapine group (46.7%) than in the placebo group (80.1%). During olanzapine treatment, the most common emergent event was weight gain; during the open-label phase, patients who received olanzapine gained a mean of 3.1 kg (SD=3.4). In double-blind treatment, placebo patients lost a mean of 2.0 kg (SD=4.4) and patients who continued to take olanzapine gained an additional 1.0 kg (SD=5.2). Conclusions: Compared to placebo, olanzapine delays relapse into subsequent mood episodes in bipolar I disorder patients who responded to open-label acute treatment with olanzapine for a manic or mixed episode. C1 Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. Harvard Univ, Sch Med, Dept Psychiat, McLean Hosp, Belmont, MA 02178 USA. Case Western Reserve Univ, Dept Psychiat, Sch Med, Univ Hosp Cleveland, Cleveland, OH 44106 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA. NW Behav Med & NW Behav Res Ctr, Marietta, GA USA. Bellevue Hosp Ctr, Dept Psychiat, New York, NY USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78229 USA. RP Tohen, M (reprint author), Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. EM m.tohen@lilly.com NR 16 TC 188 Z9 193 U1 0 U2 6 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD FEB PY 2006 VL 163 IS 2 BP 247 EP 256 DI 10.1176/appi.ajp.163.2.247 PG 10 WC Psychiatry SC Psychiatry GA 008HO UT WOS:000235031000015 PM 16449478 ER PT J AU Hirshfeld-Becker, DR Biederman, J Henin, A Faraone, SV Cayton, GA Rosenbaum, JF AF Hirshfeld-Becker, DR Biederman, J Henin, A Faraone, SV Cayton, GA Rosenbaum, JF TI Laboratory-observed behavioral disinhibition in the young offspring of parents with bipolar disorder: A high-risk pilot study SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID AGE 3 YEARS; CONDUCT DISORDER; PANIC DISORDER; CHILDREN; INHIBITION; CHILDHOOD; TEMPERAMENT; PERSONALITY; SYMPTOMS; PSYCHOPATHOLOGY AB Objective: This study tested whether behavioral disinhibition is more prevalent among offspring of parents with bipolar disorder than among offspring of parents without bipolar disorder. Method: The authors conducted a secondary analysis of data from a preexisting high-risk study of offspring at risk for panic disorder and depression (N=278) that had included some children with parents who had bipolar disorder (N=34). Children (ages 2-6) had been classified as behaviorally inhibited, disinhibited, or neither in laboratory assessments. Results: Offspring of bipolar parents had significantly higher rates of behavioral disinhibition than offspring of parents without bipolar disorder. Behavioral inhibition did not differ between groups. Differences were not accounted for by parental panic disorder or major depression or by parental history of attention deficit hyperactivity disorder, conduct disorder, antisocial personality, or substance use disorders. Conclusions: Results suggest a familial link between bipolar disorder in parents and behavioral disinhibition in their offspring. Behavioral disinhibition may be a familially transmitted predisposing factor for dysregulatory distress later in life. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Program, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Psychiat, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA. RP Hirshfeld-Becker, DR (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Program, 185 Alewife Brook Pkwy,Suite 2100, Cambridge, MA 02138 USA. EM dhirshfeld@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01 MH 47077-10] NR 43 TC 24 Z9 24 U1 1 U2 2 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD FEB PY 2006 VL 163 IS 2 BP 265 EP 271 DI 10.1176/appi.ajp.163.2.265 PG 7 WC Psychiatry SC Psychiatry GA 008HO UT WOS:000235031000017 PM 16449480 ER PT J AU Altshuler, LL Suppes, T Black, DO Nolen, WA Leverich, G Keck, PE Frye, MA Kupka, R McElroy, SL Grunze, H Kitchen, CMR Post, R AF Altshuler, LL Suppes, T Black, DO Nolen, WA Leverich, G Keck, PE Frye, MA Kupka, R McElroy, SL Grunze, H Kitchen, CMR Post, R TI Lower switch rate in depressed patients with bipolar II than bipolar I disorder treated adjunctively with second-generation antidepressants SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID MANIA; INDUCTION; SCALE AB Objectives: The authors compared the switch rate into hypomania/mania in depressed patients treated with second-generation antidepressants who had either bipolar I or bipolar II disorder. Method: In a 10-week trial, 184 outpatients with bipolar depression (134 with bipolar I disorder, 48 with bipolar II disorder, two with bipolar disorder not otherwise specified) were treated with one of three antidepressants as an adjunct to mood stabilizers. The patients' switch rates were assessed. Switch was defined as a Young Mania Rating Scale (YMRS) score > 13 or a Clinical Global Impression (CGI) mania score >= 3 (mildly ill). Results: Depressed subjects with bipolar II disorder had a significantly lower acute switch rate into hypomania/mania when either YMRS or CGI criteria were used to define switch. Conclusions: These data suggest that depressed patients with bipolar II disorder are less vulnerable than those with bipolar I disorder to switch into hypomania/mania when treated with an antidepressant adjunctive to a mood stabilizer. C1 Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90024 USA. Univ Texas, SW Med Ctr, Dept Psychiat, VA Greater Los Angeles Healthcare Syst,W Los Ange, Dallas, TX 75230 USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75230 USA. Univ Groningen, Med Ctr, Dept Psychiat, Groningen, Netherlands. NIMH, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA. Univ Cincinnati, Coll Med, Dept Psychiat, Psychopharmacol Res Program,Mental Hlth Care Line, Cincinnati, OH USA. Cincinnati VA Med Ctr, Cincinnati, OH USA. Altrech Inst Mental Hlth Care, Utrecht, Netherlands. Univ Munich, Dept Psychiat, D-8000 Munich, Germany. Univ Calif Los Angeles, Sch Publ Hlth, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. RP 300 UCLA Med Plaza,Suite 1544,Box 957057, Los Angeles, CA 90095 USA. EM laltshuler@mednet.ucla.edu RI Nolen, Willem/E-9006-2014 FU NIMH NIH HHS [R01 MH079261] NR 17 TC 104 Z9 108 U1 1 U2 2 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X EI 1535-7228 J9 AM J PSYCHIAT JI Am. J. Psychiat. PD FEB PY 2006 VL 163 IS 2 BP 313 EP 315 DI 10.1176/appi.ajp.163.2.313 PG 3 WC Psychiatry SC Psychiatry GA 008HO UT WOS:000235031000024 PM 16449487 ER PT J AU Moore, CM Biederman, J Wozniak, J Mick, E Aleardi, M Wardrop, M Dougherty, M Harpold, T Hammerness, P Randall, E Renshaw, PF AF Moore, CM Biederman, J Wozniak, J Mick, E Aleardi, M Wardrop, M Dougherty, M Harpold, T Hammerness, P Randall, E Renshaw, PF TI Differences in brain chemistry in children and adolescents with attention deficit hyperactivity disorder with and without comorbid bipolar disorder: A proton magnetic resonance spectroscopy study SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID DEFICIT/HYPERACTIVITY DISORDER; MOOD STABILIZERS; LITHIUM; MANIA; METHYLPHENIDATE; DOPAMINE; ADHD AB Objective: The authors' goal was to investigate phosphatidylinositol and glutamatergic metabolism in the anterior cingulate cortex of children and adolescents with attention deficit hyperactivity disorder (ADHD) alone, children with ADHD plus bipolar disorder, and children with no axis I diagnosis. Method: Proton spectra were acquired from a 4.8-ml voxel placed in the anterior cingulate cortex of 30 subjects who were 6 to 13 years old. Fifteen subjects had ADHD and no comorbid disorder, eight had ADHD plus bipolar disorder, and seven were healthy comparison subjects. Results: Children with ADHD had a significantly higher ratio of glutamate plus glutamine to myo-inositol-containing compounds than children with ADHD plus bipolar disorder and healthy children. Conclusions: myo-Inositol-containing compounds may provide information on the action of antimanic treatments such as lithium, valproate, and carbamazepine. Glutamate and glutamine are measures of glutamatergic neurotransmission and thus may also reflect changes in serotonin and dopamine pathways. C1 McLean Hosp, Brain Imaging Ctr, Boston, MA 02478 USA. Massachusetts Gen Hosp, Pediat Psychopharmacol Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Consolidated Dept Psychiat, Boston, MA 02115 USA. RP Moore, CM (reprint author), McLean Hosp, Brain Imaging Ctr, Boston, MA 02478 USA. EM const@mclean.harvard.edu OI Mick, Eric/0000-0001-8505-8145 FU NIMH NIH HHS [K01 MH001798, MH-01978, K01 MH001978] NR 21 TC 50 Z9 52 U1 1 U2 7 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD FEB PY 2006 VL 163 IS 2 BP 316 EP 318 DI 10.1176/appi.ajp.163.2.316 PG 3 WC Psychiatry SC Psychiatry GA 008HO UT WOS:000235031000025 PM 16449488 ER PT J AU Burman, W Benator, D Vernon, A Khan, A Jones, B Silva, C Lahart, C Weis, S King, B Mangura, B Weiner, M El-Sadr, W AF Burman, W Benator, D Vernon, A Khan, A Jones, B Silva, C Lahart, C Weis, S King, B Mangura, B Weiner, M El-Sadr, W CA Tuberculosis Trials Consortium TI Acquired rifamycin resistance with twice-weekly treatment of HIV-related tuberculosis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE antiretroviral therapy; HIV; rifabutin; rifamycin resistance; tuberculosis ID HUMAN-IMMUNODEFICIENCY-VIRUS; DIAGNOSED PULMONARY TUBERCULOSIS; MYCOBACTERIUM-TUBERCULOSIS; INFECTED PATIENTS; ANTIRETROVIRAL THERAPY; RIFABUTIN; RELAPSE; RIFAMPICIN; MORTALITY; MORBIDITY AB Rationale. Rifabutin was recommended in place of rifampin during treatment of HIV-related tuberculosis (TB) to facilitate concomitant potent antiretroviral therapy, but this approach has not been evaluated in a prospective study. Objective: To evaluate the activity of intermittent rifabutin-based therapy. Methods: Patients with culture-confirmed TB were treated under direct supervision with 2 mo of rifabutin, isoniazid, pyrazinamide, and ethambutol (given daily, thrice-weekly, or twice-weekly per the local tuberculosis control program), followed by 4 mo of twice-weekly rifabutin plus isoniazid. Measurements: Culture-positive treatment failure or relapse. Main Results: A total of 169 eligible patients were enrolled. Most had advanced HIV disease; the median CD4 cell count and HIV-RNA level were 90 cells/mm(3) (interquartile range, 35-175) and 5.3 log(10) copies/ml (interquartile range, 4.8-5.7), respectively. Nine (5.3%) patients had culture-positive treatment failure (n = 3) or relapse (n = 6). Eight of these nine (89%) cases had isolates with acquired rifamycin resistance. Treatment failure or relapse was associated with baseline CD4 lymphocyte count, being 12.3% (9/73; 95% confidence interval, 6.5-22.0%) among patients with CD4 < 100 cells/mm(3) versus 0% (0/65; 95% confidence interval, 0.0-4.5%) among those with higher CD4 lymphocyte counts (p < 0.01). One hundred thirty-seven (81%) patients received antiretroviral therapy during TB treatment. Adverse events were common, but only two patients (1%) permanently discontinued study drugs. Conclusions: Intermittent rifabutin-based therapy for HIV-related TB; was well tolerated, but there was a high risk of treatment failure or relapse with acquired rifamycin resistance among patients with low CD4 lymphocyte counts. C1 Denver Publ Hlth, Denver, CO 80204 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80202 USA. Vet Affairs Med Ctr, Washington, DC 20422 USA. George Washington Univ, Med Ctr, Washington, DC 20037 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Univ So Calif, Med Ctr, Los Angeles, CA USA. Baylor Coll Med, Houston, TX 77030 USA. Univ N Texas, Hlth Sci Ctr, Ft Worth, TX USA. Tarrant Cty Publ Hlth Dept, Ft Worth, TX USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Natl TB Ctr, Newark, NJ 07103 USA. Harlem Hosp Med Ctr, New York, NY USA. Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. RP Burman, W (reprint author), Denver Publ Hlth, 605 Bannock St, Denver, CO 80204 USA. EM bburman@dhha.org NR 35 TC 96 Z9 101 U1 0 U2 3 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 FEB 1 PY 2006 VL 173 IS 3 BP 350 EP 356 DI 10.1164/rccm.200503-417OC PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 007IJ UT WOS:000234962000016 PM 16109981 ER PT J AU Tan, RJ Lee, JS Manni, ML Fattman, CL Tobolewski, JM Zheng, MQ Kolls, JK Martin, TR Oury, TD AF Tan, RJ Lee, JS Manni, ML Fattman, CL Tobolewski, JM Zheng, MQ Kolls, JK Martin, TR Oury, TD TI Inflammatory cells as a source of airspace extracellular superoxide dismutase after pulmonary injury SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE inflammation; neutrophils; pneumonia; proteolysis; superoxide dismutase ID LUNG INJURY; EC-SOD; MOUSE LUNG; HYPEROXIA; EXPOSURE; LOCALIZATION; PURIFICATION; NEUTROPHILS; FIBROSIS; ASBESTOS AB Extracellular superoxide dismutase (EC-SOD) is an antioxidant abundant in the lung. Previous studies demonstrated depletion of lung parenchymal EC-SOD in mouse models of interstitial lung disease coinciding with an accumulation of EC-SOD in airspaces. EC-SOD sticks to the matrix by a proteolytically sensitive heparin-binding domain; therefore, we hypothesized that interstitial inflammation and matrix remodeling contribute to proteolytic redistribution of EC-SOD from lung parenchyma into the airspaces. To determine if inflammation limited to airspaces leads to EC-SOD redistribution, we examined a bacterial pneumonia model. This model led to increases in airspace polymorphonuclear leukocytes staining strongly for EC-SOD. EC-SOD accumulated in airspaces at 24 h without depletion of EC-SOD from lung parenchyma. This led us to hypothesize that airspace EC-SOD was released from inflammatory cells and was not a redistribution of matrix EC-SOD. To test this hypothesis, transgenic mice with lung-specific expression of human EC-SOD were treated with asbestos or bleomycin to initiate an interstitial lung injury. in these studies, EC-SOD accumulating in airspaces was entirely the mouse isoform, demonstrating an extrapulmonary source (inflammatory cells) for this EC-SOD. We also demonstrate that EC-SOD knockout mice possess greater lung inflammation in response to bleomycin and bacteria when compared with wild types. We conclude that the source of accumulating EC-SOD in airspaces in interstitial lung disease is inflammatory cells and not the lung and that interstitial processes such as those found in pulmonary fibrosis are required to remove EC-SOD from lung matrix. C1 Univ Pittsburgh, Med Ctr, Dept Pathol, Dept Med,Div Pulm Allergy & Crit Care Med, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Med Ctr, Dept Pediat, Pittsburgh, PA 15261 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. RP Oury, TD (reprint author), Univ Pittsburgh, Med Ctr, Dept Pathol, Dept Med,Div Pulm Allergy & Crit Care Med, 7th Floor,Scaife Hall,3550 Terrace St, Pittsburgh, PA 15261 USA. EM tdoury@pitt.edu FU NHLBI NIH HHS [HL65892, HL70178, HL073996, HL73996, R01 HL063700, R01HL063700-05, R01HL079142]; NIEHS NIH HHS [5F30ES013621-02]; NIGMS NIH HHS [GM37696] NR 31 TC 23 Z9 23 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD FEB PY 2006 VL 34 IS 2 BP 226 EP 232 DI 10.1165/rcmb.2005-0212OC PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 009MI UT WOS:000235115700013 PM 16224105 ER PT J AU Grant, EG El-Saden, SM Madrazo, BL Baker, JD Kliewer, MA AF Grant, EG El-Saden, SM Madrazo, BL Baker, JD Kliewer, MA TI Innominate artery occlusive disease: Sonographic findings SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE angiography; cardiovascular disease; Doppler sonography; innominate artery; subclavian steal syndrome ID SUBCLAVIAN STEAL; RENAL-ARTERY; STENOSIS; DIAGNOSIS AB OBJECTIVE. The objective of this study was to report the sonographic abnormalities in a group of patients with angiographically proven innominate artery stenosis and occlusion. MATERIALS AND METHODS. A review of all cerebrovascular sonograms at our institutions was undertaken to identify patients with complete or partial flow reversal in the right vertebral artery and reversal or midsystolic deceleration of flow in any one of the three major segments of the right carotid system (common, internal, or external carotid artery). The distribution and appearance of these abnormalities was evaluated, and the presence or absence of tardus-parvus waveforms was noted in any segment of the right carotid artery. Additionally, a left to right common carotid peak systolic velocity ratio (LCCA/RCCA) was calculated and compared to published normal values. All patients had correlative contrast or MR angiography. Correlation was made between the severity of stenosis as determined by angiographic images and waveform aberrations as well as the more objective LCCA/RCCA ratios. RESULTS. Twelve patients were identified as having the abnormalities described above in the right vertebral and carotid arteries. Doppler waveforms from the tight vertebral artery revealed that eight of the 12 patients had complete reversal of flow at rest. Bidirectional flow was found in the remaining four as manifested by the presence of marked midsystolic deceleration. In the carotid arteries, one patient had complete reversal of flow in all segments of the right carotid system. Waveforms with midsystolic deceleration were identified in at least one of the carotid arteries of the remaining I I patients: common carotid artery (8/11 = 73%), internal carotid artery (10/11 = 91%), external carotid artery (3/11 = 27%). The average LCCA/RCCA was 3.1 with a range of 1.7 to 5.7 (normal = 0.7-1.3). All patients had severe innominate artery disease (from 70% to occlusion) by contrast angiography or MR angiography. There was no correlation between the angiographically determined degree of stenosis and the Doppler findings. CONCLUSION. A distinctive pattern of hemodynamic alterations occurs in the right vertebral and carotid arteries of patients with severe innominate artery disease. Findings include reversed or bidirectional flow in the fight vertebral artery, the presence of midsystolic deceleration in any of the branches of the right carotid system, and elevated LCCA/RCCA ratio. C1 W Los Angeles VA Med Ctr, Dept Radiol, Los Angeles, CA USA. Miami Univ, Sch Med, Miami, FL USA. W Los Angeles VA Med Ctr, Dept Vasc Surg, Los Angeles, CA USA. Univ Wisconsin, Sch Med, Madison, WI USA. RP Grant, EG (reprint author), Univ So Calif, Dept Radiol, Keck Sch Med, 1500 San Pablo St, Los Angeles, CA 90033 USA. NR 19 TC 11 Z9 12 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD FEB PY 2006 VL 186 IS 2 BP 394 EP 400 DI 10.2214/AJR.04.1000 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 005ME UT WOS:000234825900017 PM 16423944 ER PT J AU Dalchow, CV Weber, AL Yanagihara, N Bien, S Werner, JA AF Dalchow, CV Weber, AL Yanagihara, N Bien, S Werner, JA TI Digital volume tomography: Radiologic examinations of the temporal bone SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE cochlear implant; CT; digital volume tomography; middle ear; middle-ear implant; stapesplasty; temporal bone ID COCHLEAR IMPLANTATION; CT; SURGERY AB OBJECTIVE. We evaluated the clinical applicability and the value of digital volume tomography for visualization of the lateral skull base using temporal bone specimens. MATERIALS AND METHODS. Twelve temporal bone specimens were used to evaluate digital volume tomography on the lateral skull base. Aside from the initial examination of the temporal bones, radiologic control examinations were performed after insertion of titanium, gold, and platinum middle-ear implants and a cochlear implant. RESULTS. With high-resolution and almost artifact-free visualization of alloplastic middle-ear implants of titanium, gold, or platinum, it was possible to define the smallest bone structures or position of the prosthesis with high precision. Furthermore, the examination proved that digital Volume tomography is useful in assessing the normal position of a cochlear implant. CONCLUSION. Digital volume tomography expands the application of diagnostic possibilities in the lateral skull base. Therefore, we believe improved preoperative diagnosis can be achieved along with more accurate planning of the surgical procedure. Digital volume tomography delivers a small radiation dose and a high resolution coupled with a low purchase price for the equipment. C1 Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA USA. Takanoko Hosp, Dept Otolaryngol, Matsuyama, Ehime, Japan. Univ Marburg, Dept Neuroradiol, Marburg, Germany. RP Dalchow, CV (reprint author), Univ Marburg, Dept Otolaryngol Head & Neck Surg, Deutschhausstr 2, D-35037 Marburg, Germany. EM dalchow@med.uni-marburg.de NR 20 TC 28 Z9 28 U1 0 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD FEB PY 2006 VL 186 IS 2 BP 416 EP 423 DI 10.2214/AJR.04.1353 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 005ME UT WOS:000234825900020 PM 16423947 ER PT J AU Warner, JJP Gill, TJ O'Hollerhan, JD Pathare, N Millett, PJ AF Warner, JJP Gill, TJ O'Hollerhan, JD Pathare, N Millett, PJ TI Anatomical glenoid reconstruction for recurrent anterior glenohumeral instability with glenoid deficiency using an autogenous tricortical iliac crest bone graft SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article; Proceedings Paper CT Interim Meeting of the American-Orthopaedic-Society-for-Sports-Medicine (AOSSM) CY MAR, 2004 CL San Francisco, CA SP Amer Orthopaed Soc Sports Med DE shoulder instability; bone graft; glenoid deficiency; glenoid reconstruction ID MODIFIED BRISTOW PROCEDURE; SHOULDER INSTABILITY; FOLLOW-UP; MULTIDIRECTIONAL INSTABILITY; LATARJET PROCEDURE; BANKART PROCEDURE; END-RESULT; DISLOCATION; LIGAMENT; REPAIRS AB Background: Anterior shoulder instability associated with severe glenoid bone loss is rare, and little has been reported on this problem. Recent biomechanical and anatomical studies have suggested guidelines for bony reconstruction of the glenoid. Hypothesis: Anatomical glenoid reconstruction will restore stability in shoulders with recurrent anterior instability owing to glenoid bone loss. Study Design: Case series; Level of evidence, 4. Methods: Eleven cases of traumatic recurrent anterior instability that required bony reconstruction for severe anterior glenoid bone loss were reviewed. In all cases, the length of the anterior glenoid defect exceeded the maximum anteroposterior radius of the glenoid based on preoperative assessment by 3-dimensional CT scan, Surgical reconstruction was performed using an intra-articular tricortical iliac crest bone graft contoured to reestablish the concavity and width of the glenoid. The graft was fixed with cannulated screws in combination with an anterior-inferior capsular repair. Results: At mean follow-up of 33 months, the mean American Shoulder and Elbow Surgeons score was 94, compared with a preoperative score of 65. The University of California, Los Angeles score improved to 33 from 18. The Rowe score improved to 94 from a preoperative score of 28. The mean motion loss compared with the contralateral, normal shoulder was 7 degrees of flexion, 14 degrees of external rotation in abduction, and one spinous process level for internal rotation. All patients returned to preinjury levels of sport, and only 2 complained of mild pain with overhead sports activities. No patients reported any recurrent instability (dislocation or subluxation). The CT scans with 3-dimensional reconstructions obtained 4 to 6 months postoperatively demonstrated union of the bone graft with incorporation along the anterior glenoid rim and preservation of joint space. Conclusion: Anatomical reconstruction of the glenoid with autogenous iliac crest bone graft for recurrent glenohumeral instability in the setting of bone deficiency is an effective form of treatment for this problem. C1 Steadman Hawkins Clin, Vail, CO 81657 USA. Massachusetts Gen Hosp, Harvard Shoulder Serv, Boston, MA 02114 USA. Brigham & Womens Hosp, Harvard Shoulder Serv, Boston, MA 02115 USA. RP Millett, PJ (reprint author), Steadman Hawkins Clin, 181 W Meadow Dr, Vail, CO 81657 USA. EM drmillett@steadman-hawkins.com NR 51 TC 123 Z9 127 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0363-5465 J9 AM J SPORT MED JI Am. J. Sports Med. PD FEB PY 2006 VL 34 IS 2 BP 205 EP 212 DI 10.1177/0363546505281798 PG 8 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 007XY UT WOS:000235006000005 PM 16303879 ER PT J AU Medeiros, F Muto, MG Lee, Y Elvin, JA Callahan, MJ Feltmate, C Garber, JE Cramer, DW Crum, CP AF Medeiros, F Muto, MG Lee, Y Elvin, JA Callahan, MJ Feltmate, C Garber, JE Cramer, DW Crum, CP TI The tubal fimbria is a preferred site for early adenocarcinoma in women with familial ovarian cancer syndrome SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE BRCA; ovarian neoplasms; fallopian tube neoplasms; familial ovarian cancer; serous carcinoma ID PROPHYLACTIC OOPHORECTOMY SPECIMENS; FALLOPIAN-TUBE; MUTATION CARRIERS; CARCINOMA; TUMORIGENESIS; PREVALENCE; TUMORS AB A proportion of adenocarcinomas in prophylactic adnexectomies (bilateral salpingo-oophorectomies [BSOs]) from women with BRCA mutations (BRCA positive) occur in the fallopian tube. We analyzed a consecutive series of BSOs from BRCA-positive women following an index case of fimbrial serous carcinoma. To determine if the fimbria is a preferred site of origin, we followed a protocol for Sectioning and Extensively Examining the FIMbria (SEE-FIM). Immunostaining for p53 and Ki-67 was also performed. Thirteen BRCA-positive women (cases) and 13 women undergoing BSOs for other disorders (controls) were studied. Tubal carcinoma was detected in 4 cases at the initial histologic evaluation and in no controls. A fifth carcinoma was discovered following further sectioning of the fimbriae. Three were BRCA2 positive and two BRCA1 positive. Three were in the fimbria, one in both the fimbria and proximal tube, and one involved the ampulla. Four were serous carcinomas, four were confined to the tube, and three were noninvasive (intraepithelial). No ovarian carcinomas were identified. All tumors were Ki-67 positive (> 75% of cell nuclei), and excluding one endometrioid carcinoma, p53 positive (> 75% cell nuclei); p53 positivity in the absence of elevated Ki-67 did not correlate with morphologic neoplasia. The fimbria was the most common location for early serous carcinoma in this series of BRCA-positive women. Protocols that extensively examine the fimbria (SEE-FIM) will maximize the detection of early tubal epithelial carcinoma in patients at risk for ovarian cancer. Investigative strategies targeting the fimbriated end of the fallopian tube should further define its role in the pathogenesis of familial and sporadic ovarian serous carcinomas. C1 Brigham & Womens Hosp, Dept Pathol, Div Womens & Perinatal Patol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Gynecol Oncol, Dept Obstet & Gynecol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Crum, CP (reprint author), Brigham & Womens Hosp, Dept Pathol, Div Womens & Perinatal Patol, 75 Francis St, Boston, MA 02115 USA. EM ccrum@partners.org FU NCI NIH HHS [P50 CA10500] NR 16 TC 359 Z9 376 U1 2 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD FEB PY 2006 VL 30 IS 2 BP 230 EP 236 DI 10.1097/01.pas.0000180854.28831.77 PG 7 WC Pathology; Surgery SC Pathology; Surgery GA 007JK UT WOS:000234964800012 PM 16434898 ER PT J AU Bernat, JL D'Alessandro, AM Port, FK Bleck, TP Heard, SO Medina, J Rosenbaum, SH DeVita, MA Gaston, RS Merion, RM Barr, ML Marks, WH Nathan, H O'Connor, K Rudow, DL Leichtman, AB Schwab, P Ascher, NL Metzger, RA Mc Bride, V Graham, W Wagner, D Warren, J Delmonico, FL AF Bernat, JL D'Alessandro, AM Port, FK Bleck, TP Heard, SO Medina, J Rosenbaum, SH DeVita, MA Gaston, RS Merion, RM Barr, ML Marks, WH Nathan, H O'Connor, K Rudow, DL Leichtman, AB Schwab, P Ascher, NL Metzger, RA Mc Bride, V Graham, W Wagner, D Warren, J Delmonico, FL TI Report of a national conference on donation after cardiac death SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Editorial Material DE deceased organ donation ID TRANSPLANTATION AB A national conference on organ donation after cardiac death (DCD) was convened to expand the practice of DCD in the continuum of quality end-of-life care. This national conference affirmed the ethical propriety of DCD as not violating the dead donor rule. Further, by new developments not previously reported, the conference resolved controversy regarding the period of circulatory cessation that determines death and allows administration of pre-recovery pharmacologic agents, it established conditions of DCD eligibility, it presented current data regarding the successful transplantation of organs from DCD, it proposed a new framework of data reporting regarding ischemic events, it made specific recommendations to agencies and organizations to remove barriers to DCD, it brought guidance regarding organ allocation and the process of informed consent and it set an action plan to address media issues. When a consensual decision is made to withdraw life support by the attending physician and patient or by the attending physician and a family member or surrogate (particularly in an intensive care unit), a routine opportunity for DCD should be available to honor the deceased donor's wishes in every donor service area (DSA) of the United States. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Dartmouth Hitchcock Med Ctr, Hanover, NH 03756 USA. Univ Wisconsin Hosp, Madison, WI 53792 USA. Univ Virginia, Charlottesville, VA 22903 USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15260 USA. Univ Massachusetts, Med Ctr, Amherst, MA 01003 USA. Yale Univ, Sch Med, New Haven, CT 06520 USA. Univ Alabama, Birmingham, AL USA. Univ Michigan, Med Ctr, Ann Arbor, MI 48109 USA. Univ So Calif, Los Angeles, CA USA. Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. Swedish Med Ctr, Englewood, CO 80110 USA. Florida Hosp Med Ctr, Orlando, FL 32803 USA. RP Delmonico, FL (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM francis_delmonico@neob.org OI Bleck, Thomas/0000-0002-8267-9787 NR 10 TC 316 Z9 334 U1 0 U2 10 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD FEB PY 2006 VL 6 IS 2 BP 281 EP 291 DI 10.1111/j.1600-6143.2005.01194.x PG 11 WC Surgery; Transplantation SC Surgery; Transplantation GA 004EQ UT WOS:000234735200006 PM 16426312 ER PT J AU Camargo, CA AF Camargo, CA TI Prevention of emergency department visits for acute asthma SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Editorial Material ID MODEL C1 Massachusetts Gen Hosp, EMNet Coordinating Ctr, Boston, MA 02114 USA. RP Camargo, CA (reprint author), Massachusetts Gen Hosp, EMNet Coordinating Ctr, Boston, MA 02114 USA. NR 11 TC 1 Z9 1 U1 0 U2 0 PU AMER COLL ALLERGY ASTHMA IMMUNOLOGY PI ARLINGTON HTS PA 85 WEST ALGONQUIN RD SUITE 550, ARLINGTON HTS, IL 60005 USA SN 1081-1206 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD FEB PY 2006 VL 96 IS 2 BP 258 EP 259 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA 015ON UT WOS:000235560800004 PM 16498845 ER PT J AU Hendee, WR Gazelle, GS AF Hendee, WR Gazelle, GS TI Biomedical Imaging Research Opportunities Workshop III: A white paper SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Article; Proceedings Paper CT 3rd Annual Biomedical Imaging Research Opportunities Workshop CY MAR 11-12, 2005 CL Bethesda, MD SP Acad Radiol Res, Amer Assoc Physicists Med, Amer Inst Med & Biol Engn, Biomed Engn Soc, Radiol Soc N Amer DE image-guided therapy; biomedical informatics; cell trafficking; imaging technology; imaging research opportunities ID CELL THERAPY; STEM; INFORMATICS; TECHNOLOGY; NAVIGATION; RADIOLOGY; GUIDANCE AB The third Biomedical Imaging Research Opportunities Workshop (BIROW III) was held on March 11-12, 2005, in Bethesda, MD. The workshop addressed four areas of imaging that present opportunities for research and development: Multimodality Image-Guided Therapy, Imaging Informatics, Imaging Cell Trafficking, and Technology Improvement and Commercialization. The first three areas were individually addressed in their own plenary sessions, followed by audience discussions that explored research opportunities and challenges. This paper synthesizes these discussions into a strategy for future research directions in biomedical imaging. C1 Med Coll Wisconsin, Milwaukee, WI 53226 USA. Massachusetts Gen Hosp, Data Grp, Inst Technol Assessment, Boston, MA 02114 USA. RP Hendee, WR (reprint author), Med Coll Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. EM whendee@mcw.edu NR 42 TC 13 Z9 13 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0090-6964 J9 ANN BIOMED ENG JI Ann. Biomed. Eng. PD FEB PY 2006 VL 34 IS 2 BP 188 EP 198 DI 10.1007/s10439-005-9040-1 PG 11 WC Engineering, Biomedical SC Engineering GA 028QG UT WOS:000236502300002 PM 16482416 ER PT J AU Simon, JA Lin, F Vittinghoff, E Bittner, V AF Simon, JA Lin, F Vittinghoff, E Bittner, V CA HERS Res Grp TI The relation of postmenopausal hormone therapy to serum uric acid and the risk of coronary heart disease events: The Heart and Estrogen-Progestin Replacement Study (HERS) SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE cardiovascular risk factors; estrogens; hormones; uric acid ID ANTURANE REINFARCTION TRIAL; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; FOLLOW-UP; ESSENTIAL-HYPERTENSION; ATHEROSCLEROSIS RISK; DIABETES-MELLITUS; HONOLULU HEART; WOMEN; MEN AB PURPOSE: To determine whether baseline serum uric acid (UA) levels and estrogen-progestin (E + P)associated change in serum UA in postmenopausal women with coronary disease are associated with recurrent coronary heart disease (CHD) events. METHODS: 2763 postmenopausal women enrolled in the Heart and Estrogen-Progestin Replacement Study (HERS) were randomly assigned to take conjugated E + P or placebo in a secondary CHD prevention study. The primary outcome for these analyses was nonfatal myocardial infarction or CHD death during a mean follow up of 4.1 years. RESULTS: The baseline serum UA for the cohort was 5.4 mg/dl and, compared with placebo, E + P on average lowered serum UA levels slightly (0.2 mg/dl) at one year of follow up (p < 0.0001). Baseline serum UA levels were associated in simple proportional hazards models with CHD events; each standard deviation increase (1.3 mg/dl) was associated with a 22% increased risk of primary CHD events (p =.0001). This association, however, was no longer statistically significant after multivariable adjustment (p = 0.36). There was no association between on-study change in serum UA level and any CHD outcome. CONCLUSION: Treatment with E + P lowered serum UA levels slightly, but neither baseline UA nor charge in UA affected CHD risk. C1 San Francisco VA Med Ctr, Gen Internal Med Sect, Med Serv, San Francisco, CA 94121 USA. Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, Div Clin Res, San Francisco, CA 94143 USA. Univ Alabama, Div Cardiovasc Dis, Birmingham, AL 35294 USA. RP Simon, JA (reprint author), San Francisco VA Med Ctr, Gen Internal Med Sect, Med Serv, 4150 Clement St, San Francisco, CA 94121 USA. EM jasimon@itsa.ucsf.edu OI Bittner, Vera/0000-0001-9456-850X NR 58 TC 22 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 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD FEB PY 2006 VL 16 IS 2 BP 138 EP 145 DI 10.1016/j.annepidem.2005.04.003 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 015LR UT WOS:000235553400010 PM 16039873 ER PT J AU Stone, RM AF Stone, R. M. TI FLT3 inhibitors SO ANNALS OF HEMATOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 29 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0939-5555 J9 ANN HEMATOL JI Ann. Hematol. PD FEB PY 2006 VL 85 SU 1 BP 108 EP 110 PG 3 WC Hematology SC Hematology GA V43YG UT WOS:000202969800098 ER PT J AU Gizatullina, ZZ Lindenberg, KS Harjes, P Chen, Y Kosinski, CM Landwehrmeyer, BG Ludolph, AC Striggow, F Zierz, S Gellerich, FN AF Gizatullina, ZZ Lindenberg, KS Harjes, P Chen, Y Kosinski, CM Landwehrmeyer, BG Ludolph, AC Striggow, F Zierz, S Gellerich, FN TI Low stability of Huntington muscle mitochondria against Ca2+ in R6/2 mice SO ANNALS OF NEUROLOGY LA English DT Article ID PERMEABILITY TRANSITION PORE; SKELETAL-MUSCLE; TRANSGENIC MICE; CAG REPEAT; DISEASE; GENE; DYSFUNCTION; DAMAGE; MOUSE; LIVER AB Objective: The aim of the present work was the detection of Mitochondrial dysfunction of Huntington's disease (HD). Methods: We investigated muscle and muscle mitochondria of 14- to 16-week-old R6/2 mice in comparison with wild-type mice. Results: Atrophic fibers, increased fuchsinophilic aggregates, and reduced cytochrome c oxidase (15%) were found in HD muscle. With swelling measurements and Ca2+ accumulation experiments, a decreased stability of HD mitochondria against Ca2+-induced permeability transition was detected. Complex I-dependent respiration of HD mitochondria was more sensitive to inhibition by adding 10 mu m Ca2+ than wildtype mitochondria. Interpretation: Data suggest that the decreased stability of HD mitochondria against Ca2+ contributes to energetic depression and cell atrophy. C1 KeyNeurorek AG, D-39120 Magdeburg, Germany. Univ Halle Wittenberg, Muskellabor Neurol Klin, D-4010 Halle, Germany. Univ Ulm, Neurol Klin, Ulm, Germany. Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA USA. Max Delbruck Zentrum Mol Med, Berlin, Germany. Univ Aachen, Neurol Klin, D-5100 Aachen, Germany. RP Gellerich, FN (reprint author), KeyNeurorek AG, ZENIT Technol Pk,Leipziger Str 44, D-39120 Magdeburg, Germany. EM frank.gellerich@keyneurotek.de OI Landwehrmeyer, Georg Bernhard/0000-0003-3375-790X NR 20 TC 46 Z9 46 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD FEB PY 2006 VL 59 IS 2 BP 407 EP 411 DI 10.1002/ana.20754 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 010UW UT WOS:000235224400027 PM 16437579 ER PT J AU Partridge, AH AF Partridge, AH TI Non-adherence to endocrine therapy for breast cancer SO ANNALS OF ONCOLOGY LA English DT Editorial Material DE acute myelogenous leukemia; conservative treatment; elderly patients; quality of life ID ADJUVANT TAMOXIFEN; CHEMOTHERAPY; ADHERENCE; TRIALS C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Partridge, AH (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. EM ahpartridge@partners.org NR 16 TC 25 Z9 25 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD FEB PY 2006 VL 17 IS 2 BP 183 EP 184 DI 10.1093/annonc/mdj141 PG 2 WC Oncology SC Oncology GA 007JN UT WOS:000234965100001 PM 16428243 ER PT J AU Hahn, MS Kobler, JB Starcher, BC Zeitels, SM Langer, R AF Hahn, MS Kobler, JB Starcher, BC Zeitels, SM Langer, R TI Quantitative and comparative studies of the vocal fold extracellular matrix - I: Elastic fibers and hyaluronic acid SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE animal model; elastin; hyaluronic acid; lamina propria; quantitative histology; tropoelastin ID LAMINA PROPRIA; LAYER; SKIN AB Objectives: This study examines the elastic fiber and hyaluronic acid (HA) content of the midmembranous vocal fold laminae propriae (LPs) of humans, dogs, pigs, and ferrets. Methods: Lamina propria elastin was quantified by measuring the amino acid desmosine, and HA was measured by an enzyme-linked immunosorbent assay-based technique. Quantitative histology was used to evaluate elastin and HA levels in specific LP regions. The distributions of fibrillin-1, a primary microfibrillar component of elastic fibers, and of tropoelastin, an indicator of elastin synthesis, were immunohistochemically analyzed. Results: Elastin and HA constituted 8.5% 2.1% and 0.82% 0.11% of human LP, respectively, relative to tissue total protein. Although the mean LP desmosine levels were similar across species, the mean HA levels in canine (p < 3.1 x 10(-5)), porcine (p < 1.5 x 10(-5)), and ferret (p < 6.6 x 10(-4)) LPs were 3 to 4 times higher than that in humans. Marked interspecies differences in elastin, fibrillin-1, tropoelastin, and HA distributions were observed histologically. Conclusions: The elastin content of the human LP is roughly twice that of the dermis, whereas the HA content of the human LP is similar to that of the dermis. Although all species had similar levels of desmosine, histologic evaluation indicates that the porcine elastin distribution is most similar to that of the human LP. Fibrillin-1 staining suggests that stress in the human LP may be particularly high in the superior superficial layer, and tropoelastin staining indicates that the rate of LP elastin turnover may vary spatially. C1 Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Dept Surg, Boston, MA 02114 USA. MIT, Dept Elect Engn & Comp Sci, Boston, MA USA. MIT, Dept Chem Engn, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Texas, Hlth Sci Ctr Tyler, Dept Biomed Res, Tyler, TX 75710 USA. RP Zeitels, SM (reprint author), Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Dept Surg, 1 Bowdoin Sq,11th Floor, Boston, MA 02114 USA. RI Hahn, Mariah/G-3998-2014 OI Hahn, Mariah/0000-0001-8794-129X NR 26 TC 64 Z9 65 U1 0 U2 6 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD FEB PY 2006 VL 115 IS 2 BP 156 EP 164 PG 9 WC Otorhinolaryngology SC Otorhinolaryngology GA 012GY UT WOS:000235327500013 PM 16514800 ER PT J AU Yee, AJ Kuter, DJ AF Yee, AJ Kuter, DJ TI Successful recovery after an overdose of argatroban SO ANNALS OF PHARMACOTHERAPY LA English DT Article DE argatroban; fresh frozen plasma; overdose ID HEPARIN-INDUCED THROMBOCYTOPENIA; PROTHROMBIN-COMPLEX CONCENTRATE; RECOMBINANT FACTOR VIIA; CRITICALLY-ILL; ANTICOAGULATION; PHARMACOKINETICS; HEMODIALYSIS AB OBJECTIVE: To report the case of a critically ill man with heparin-induced thrombocytopenia (HIT) who received a 125 mg overdose of the direct thrombin inhibitor argatroban. CASE SUMMARY: A 74-year-old man with a history of Crohn's disease underwent takedown of an ileorectal fistula. He developed HIT postoperatively and was treated with argatroban. He became critically ill and was transferred to the intensive care unit. On postoperative day 24, he accidentally received argatroban 125 mg over 1 hour (26 mu g/kg/min). Treatment with fresh frozen plasma (FFP) was effective, and there were no significant complications. The partial thromboplastin time, however, continued to be prolonged 48 hours after the overdose. DISCUSSION: Medication errors with direct thrombin inhibitors are common. However, there is no known reversal agent for this class of anticoagulants. This patient was treated with FFP and did well, with no bleeding complications. However, the clearance of argatroban was prolonged. CONCLUSIONS: This case illustrates that supratherapeutic doses of argatroban can be managed with FFP and tolerated without significant complications. C1 Massachusetts Gen Hosp, Ctr Hematol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Kuter, DJ (reprint author), Massachusetts Gen Hosp, Ctr Hematol, 55 Fruit St, Boston, MA 02114 USA. EM dkuter@partners.org NR 20 TC 14 Z9 14 U1 0 U2 0 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 USA SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD FEB PY 2006 VL 40 IS 2 BP 336 EP 339 DI 10.1345/aph.1G494 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 015QA UT WOS:000235564700029 PM 16449547 ER PT J AU Netscher, DT Richards, WT AF Netscher, DT Richards, WT TI Rational treatment for multiple digit congenital absence - Case report of nonvasculorized toe phalangeal transfers and distraction lengthening for symbrachydactyly SO ANNALS OF PLASTIC SURGERY LA English DT Article DE symbrachydactyly; toe phalangeal transfer; digital lengthening ID HAND; RECONSTRUCTION; DEFORMITIES; TRANSPLANTATION; OSTEOGENESIS; ANOMALIES; THUMB AB A case is discussed in which a young male was born with symbrachydactyly of multiple digits in whom nonvascularized proximal toe phalanges were transferred to the aphalangic digits when lie was an infant. This initial surgical procedure was later followed by webspace deepening and Ultimately by distraction lengthening of the digits. At 8 years of age, lie has a very functional hand with mobile metacarpophalangeal joints in all reconstructed fingers. In fact, lie uses this reconstructed right hand as his dominant extremity. The case is discussed in context of phalangeal growth potential, specific indications for this type of reconstruction, and final long-term outcome. This case also helps to recommend rational treatment protocols for similar congenital hand anomalies. C1 Baylor Coll Med, Plast Surg Serv, Dept Vet Affairs Med Ctr, Div Plast Surg, Houston, TX 77030 USA. RP Netscher, DT (reprint author), 6624 Fannin,Suite 2730, Houston, TX 77030 USA. EM Netscher@bcm.tmc.edu NR 31 TC 4 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0148-7043 J9 ANN PLAS SURG JI Ann. Plast. Surg. PD FEB PY 2006 VL 56 IS 2 BP 211 EP 215 DI 10.1097/01.sap.0000194244.25602.c5 PG 5 WC Surgery SC Surgery GA 009HU UT WOS:000235103300023 PM 16432336 ER PT J AU Christian, CK Niland, J Edge, SB Ottesen, RA Hughes, ME Theriault, R Wilson, J Hergrueter, CA Weeks, JC AF Christian, CK Niland, J Edge, SB Ottesen, RA Hughes, ME Theriault, R Wilson, J Hergrueter, CA Weeks, JC TI A multi-institutional analysis of the socioeconomic determinants of breast reconstruction - A study of the National Comprehensive Cancer Network SO ANNALS OF SURGERY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; SOCIODEMOGRAPHIC FACTORS; MEDICARE BENEFICIARIES; HEALTH-INSURANCE; OUTCOMES; SURGERY; RACE; WOMEN; MASTECTOMY; SURVIVAL AB Objective: To determine the rate of postmastectomy reconstruction and investigate the impact of socioeconomic status on the receipt of reconstruction. Summary Background Data: The National Comprehensive Cancer Network (NCCN) Outcomes Project is a prospective, multi-institutional database that contains data on all newly diagnosed breast cancer patients treated at one of the participating comprehensive cancer centers. Methods: The study cohort consisted of 2174 patients with DCIS and stage I, II, and III invasive breast cancer who underwent mastectomy at one of 8 NCCN centers. Rates of reconstruction were determined. Logistic regression analyses were used to evaluate whether socioeconomic characteristics are associated with breast reconstruction. Results: Overall, 42% of patients had breast reconstruction following mastectomy. Patients with Medicaid and Medicare were less likely to undergo reconstruction than those with managed care insurance; however, there was no difference for indemnity versus managed care insurance. Homemakers and retired patients had fewer reconstructions than those employed outside the home. Patients with a high school education or less were less likely to have reconstruction than those with more education. Race and ethnicity were not significant predictors of reconstruction. Conclusions: The reconstruction rate in this study (42%) is markedly higher than those previously reported. The type of insurance, education level, and employment status of a patient, but not her race or ethnicity, appear to influence the use of breast reconstruction. Because all patients were treated at an NCCN institution, these socioeconomic differences cannot be explained by access to care. C1 Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. City Hope Natl Med Ctr, Dept Biostat, Duarte, CA 91010 USA. Roswell Pk Canc Ctr, Dept Breast & Soft Tissue Surg, Buffalo, NY USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Univ Texas, MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA. Ohio State Univ, Dept Surg, Arthur G James Canc Hosp, Columbus, OH 43210 USA. Ohio State Univ, Dept Surg, Richard Solove Res Inst, Columbus, OH 43210 USA. Brigham & Womens Hosp, Div Plast Surg, Boston, MA 02115 USA. RP Weeks, JC (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, 44 Binney St,454BRK S21-25, Boston, MA 02115 USA. EM Jane_Weeks@dfci.harvard.edu FU NCI NIH HHS [P50 CA089393, P50CA89393] NR 42 TC 112 Z9 113 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD FEB PY 2006 VL 243 IS 2 BP 241 EP 249 DI 10.1097/01.sla.0000197738.63512.23 PG 9 WC Surgery SC Surgery GA 006QT UT WOS:000234912700014 PM 16432358 ER PT J AU Ferrone, CR Thayer, SP Finkelstein, DM Muzikansky, A Warshaw, AL AF Ferrone, CR Thayer, SP Finkelstein, DM Muzikansky, A Warshaw, AL TI Peri operative CA19-9 levels can predict stage and survival in patients resected for pancreatic adenocarcinoma SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 59th Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 23-26, 2006 CL San Diego, CA SP Soc Surg Oncol C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2006 VL 13 IS 2 SU S BP 38 EP 39 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA 009BG UT WOS:000235085500116 ER PT J AU Dominguez, E Golshan, M Black, DM Hughes, KS Gadd, MA Christian, R Lesnikoski, BA Specht, M Michaelson, J Smith, BL AF Dominguez, E Golshan, M Black, DM Hughes, KS Gadd, MA Christian, R Lesnikoski, BA Specht, M Michaelson, J Smith, BL TI Sentinel node biopsy is important in mastectomy for ductal carcinoma in situ SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 59th Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 23-26, 2006 CL San Diego, CA SP Soc Surg Oncol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2006 VL 13 IS 2 SU S BP 77 EP 77 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 009BG UT WOS:000235085500249 ER PT J AU Taylor, SL Fremont, A Jain, AK McLaughlin, R Peterson, E Ferguson, TB Lurie, N AF Taylor, SL Fremont, A Jain, AK McLaughlin, R Peterson, E Ferguson, TB Lurie, N TI Racial and ethnic disparities in care: The perspectives of cardiovascular surgeons SO ANNALS OF THORACIC SURGERY LA English DT Article ID PHYSICIANS; IMPACT; RACE AB Background. Although racial/ethnic disparities in care are well documented, particularly for cardiac care, we know little about what cardiac surgeons think about them. For educational efforts to be effective in helping physicians address disparities, they must consider providers' knowledge and beliefs about the underlying causes of the disparities. Methods. We conducted a survey in 2004 to assess cardiologists' and cardiac surgeons' knowledge of racial/ethnic disparities in cardiovascular care and their perceptions about the underlying causes. Respondents were recruited from the membership of four cardiovascular professional associations. This paper focuses on cardiovascular surgeons' responses (n = 208). Results. Forty-four percent of cardiovascular surgeons thought that, among patients with cardiac risk factors, black patients were not as likely as white patients to receive cardiac diagnostic tests and procedures. Additionally, 30% thought that black patients were not as likely as white patients to receive therapeutic tests and procedures. However, only 13% agreed that cardiac care disparities occur "often" or "somewhat often" based on patients' race/ethnicity, independent of their insurance and education. Only 3% thought disparities were likely to occur in their clinical setting. Respondents appeared more likely to endorse patient factors (eg, health behaviors or treatment adherence) than system or provider (eg, miscommunication or continuity of care) factors as reasons for disparities. Conclusions. Although some surgeons acknowledge that racial/ethnic disparities in cardiac care occur, very few agree that they occur often, independent of patients' characteristics. Educational efforts tailored to local care settings, such as reviewing quality of care data on patients of different races/ethnicities within a clinic/hospital, may effectively inform all physicians of these disparities. C1 RAND Corp, Santa Monica, CA 90407 USA. RAND Corp, Washington, DC USA. Univ Calif Los Angeles, W Los Angeles VAMC, Div Med, Los Angeles, CA USA. Duke Univ, Durham, NC USA. Amer Coll Cardiol, Bethesda, MD USA. Louisiana State Univ, New Orleans, LA USA. Soc Thorac Surg, Chicago, IL USA. RP Taylor, SL (reprint author), RAND Corp, 1776 Main St,M5S,POB 2138, Santa Monica, CA 90407 USA. EM staylor@rand.org RI Fremont, Allen/A-7752-2009 NR 14 TC 21 Z9 21 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD FEB PY 2006 VL 81 IS 2 BP 531 EP 536 DI 10.1016/j.athoracsur.2005.08.004 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 009VV UT WOS:000235142400020 PM 16427845 ER PT J AU Strahilevitz, J Robicsek, A Hooper, DC AF Strahilevitz, J Robicsek, A Hooper, DC TI Role of the extended alpha 4 domain of Staphylococcus aureus gyrase A protein in determining low sensitivity to quinolones SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID DNA TERNARY COMPLEXES; TOPOISOMERASE-IV; ESCHERICHIA-COLI; STREPTOCOCCUS-PNEUMONIAE; NALIDIXIC-ACID; PRIMARY TARGET; RESISTANCE; FLUOROQUINOLONES; MUTATIONS; MECHANISM AB Fluoroquinolones target two bacterial type II topoisomerases, DNA gyrase and topoisomerase IV. Acquired resistance to quinollones occurs stepwise, with the first mutation occurring in the more sensitive target enzyme. To limit the emergence of resistance, quinolones should ideally possess dual activities against the two enzymes. For reasons that are as yet unclear, Staphylococcus aureus gyrase is less sensitive to quinolones than topoisomerase IV, counter to its greater sensitivity in Escherichia coli, thereby limiting the use of quinolones for the treatment of staphyllococcal infections. Mutations in the alpha A-helix domain of the GyrA subunit of gyrase are important in determining quinolone resistance. We replaced an extended region encompassing the alpha 4 domain in the E. coli GyrA protein with its homolog in S. aureus and tested for its ability to complement a thermo-sensitive gyrase and its catalytic and noncatalytic properties. Purified gyrase reconstituted with chimeric GyrA was more resistant to ciprofloxacin than wild-type gyrase at both inhibition of catalytic activity and stimulation of cleavage complexes, and this difference was more apparent in the presence of K+-glutamate. The chimeric GyrA subunit was able to complement thermosensitive gyrase, similar to wild-type GyrA. Without supplemental K+-glutamate the MICs of ciprofloxacin for thermosensitive E. coli complemented with chimeric DNA gyrase were equal to those for E. coli complemented with wild-type gyrase but were twofold higher in the presence of K+-glutamate. Our findings suggest that the extended alpha 4 domain of S. aureus GyrA is responsible, at least in part, for the increased resistance of S. aureus gyrase to quinolones and that this effect is modulated by K+-glutamate. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Hooper, DC (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. EM dhooper@partners.org FU NIAID NIH HHS [R37 AI023988, AI 23988, R01 AI023988] NR 38 TC 11 Z9 11 U1 1 U2 3 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 FEB PY 2006 VL 50 IS 2 BP 600 EP 606 DI 10.1128/AAC.50.2.600-606.2006 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 011UO UT WOS:000235294200027 PM 16436716 ER PT J AU Dede, G Caplan, D AF Dede, G Caplan, D TI Factor analysis of aphasic syntactic comprehension disorders SO APHASIOLOGY LA English DT Article; Proceedings Paper CT 35th Annual Clinical Aphasiology Conference CY MAY 31-JUN 04, 2005 CL Sanibel Isl, FL ID SENTENCE COMPREHENSION; DETERMINANTS; DEFICITS; TIME; AGE AB Background: Many people with aphasia have impaired sentence comprehension. Previous studies using factor analysis have suggested that a single factor accounts for performance on measures of sentence comprehension (e.g., Caplan, Baker, & Dehaut, 1985). However, this work has been limited to measures of accuracy on single sentence comprehension tasks. Aims: The purpose of this study is to further examine the factor structure underlying aphasic sentence comprehension using accuracy, reaction time (RT), and on-line measures using both exploratory and confirmatory factor analyses. Methods & Procedures: A total of 42 people with aphasia and 40 non-brain-damaged controls were tested on 11 sentence types and five tasks. Accuracy and RT data are reported for the whole sentence presentation version of sentence-picture matching, and accuracy data are reported for object manipulation. Confirmatory factor analyses examining measurement invariance across groups and tasks are presented. Exploratory factor analyses of on-line syntactic processing are also presented. Outcomes & Results: Results indicated that one-factor models best account for accuracy and RT data. Measurement of factors was partially invariant across groups and tasks. Factor structures suggestive of syntactic processes emerged in the analyses of on-line measures. Conclusions: This study suggests that syntactic processes may load on separate factors during on-line parsing and that syntactic processes do not dissociate when the parser's Output is used in the service of a task at the end of the sentence. C1 Boston Univ, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Caplan, D (reprint author), Neuropsychol Lab, 175 Cambridge St,Suite 340,Fruit St, Boston, MA 02114 USA. EM dcaplan@partners.org NR 20 TC 4 Z9 4 U1 2 U2 2 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0268-7038 J9 APHASIOLOGY JI Aphasiology PD FEB-APR PY 2006 VL 20 IS 2-4 BP 123 EP 135 DI 10.1080/02687030500472413 PG 13 WC Clinical Neurology SC Neurosciences & Neurology GA 047PA UT WOS:000237890000004 ER PT J AU McNeil, MR Matthews, CT Hula, WD Doyle, PJ Fossett, TRD AF McNeil, MR Matthews, CT Hula, WD Doyle, PJ Fossett, TRD TI Effects of visual-manual tracking under dual-task conditions on auditory language comprehension and story retelling in persons with aphasia SO APHASIOLOGY LA English DT Article; Proceedings Paper CT 35th Annual Clinical Aphasiology Conference CY MAY 31-JUN 04, 2005 CL Sanibel Isl, FL ID RESOURCE-ALLOCATION; DIVIDED ATTENTION; PERFORMANCE; INDIVIDUALS; FMRI AB Background: Two recent studies (McNeil et al., 2004, 2005) evaluated non-brain-injured (N-BI) elderly persons' dual-task performance oil a story retell procedure (SRP) and a visual-manual line-tracking task. Results of both studies demonstrated a unidirectional cost whereby the difficulty of the language task had an effect on tracking performance; however, the difficulty of the tracking task had no effect on language comprehension as indexed by story retelling. Aims: The specific aim of this investigation was to assess the effects of performing a concurrent visual-manual tracking task on the comprehension of stories in persons with aphasia (PWA). Methods & Procedures: The current study evaluated the performance trading in these tasks in PWA using similar dual-task procedures as those employed ill the McNeil et al (2004 2005) studies. Specifically, two tracking difficulty levels were used to assess concurrent costs under a single difficulty level of the SRP. Outcomes & Results: The results of this study replicate, in PWA, the null effect of tracking, difficulty on story retell performance that was found in the two earlier studies in N-BI elderly persons. Contrary to predictions, there was no significant effect of tracking difficulty on story retell performance. There was also no significant difference between story comprehension or visual manual-tracking tasks performed alone or in the competing conditions. Conclusions: The results of this study do not support the hypothesis that a deficit in allocating processing resources in PWA would result in a concurrent cost of tracking difficulty on story comprehension. The results are discussed relative to the limitations of the story retell procedure for indexing potential dual-task effects and relative to the possible structure of the shared cognitive architecture used in these specific dual-tasks. C1 Univ Pittsburgh, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. RP McNeil, MR (reprint author), Univ Pittsburgh, Dept Commun Sci & Disorders, 4033 Forbes Tower, Pittsburgh, PA 15260 USA. EM mcneil@pitt.edu NR 26 TC 4 Z9 4 U1 0 U2 1 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0268-7038 J9 APHASIOLOGY JI Aphasiology PD FEB-APR PY 2006 VL 20 IS 2-4 BP 167 EP 174 DI 10.1080/02687030500472660 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 047PA UT WOS:000237890000007 ER PT J AU Doyle, PJ Matthews, C Mikolic, JM Hula, W McNeil, MR AF Doyle, PJ Matthews, C Mikolic, JM Hula, W McNeil, MR TI Do measures of language impairment predict patient-reported communication difficulty and distress as measured by the Burden of Stroke Scale (BOSS)? SO APHASIOLOGY LA English DT Article; Proceedings Paper CT 35th Annual Clinical Aphasiology Conference CY MAY 31-JUN 04, 2005 CL Sanibel Isl, FL ID SOCIAL SUPPORT; PSYCHOLOGICAL DISTRESS; FUNCTIONAL STATUS; MENTAL-HEALTH; LIFE; OUTCOMES; SURVIVORS; THERAPY; IMPACT; CANCER AB Background: Patient-reported measures of Communication difficulty and communication-related distress may be used to obtain efficient and valid indices of the functional consequences of aphasia and its treatment on the daily lives of many community-dwelling stroke survivors. However, they have not been employed to evaluate treatment outcomes or to examine hypotheses specifying their relationship to commonly employed measures of speech and language impairment in persons with aphasia. Aims: This study examined whether the Shortened Porch Index of Communicative Abilities. (SPICA) (Disimoni, Keith, & Darley, 1980), 55-item Revised Token Test (55-item RTT) (Arvedson, McNeil, & West, 1986), and BDAE Severity Rating Scale (Good-lass, Kaplan, & Barressi, 2001) scores obtained at 3 months post-onset (MPO) predicted patient-reported communication difficulty and distress as measured by the Burden of Stroke Scale (BOSS) (Doyle et al., 2004) at 12 MPO. Methods & Procedures: A sample of 37 adults with mild to moderate aphasia (M SPICA %ile = 70.4) were identified from a larger sample (n = 178) of community-dwelling stroke survivors who participated in a longitudinal investigation designed to examine the psychometric properties of the BOSS. Speech and language data obtained from the sub-sample of participants with aphasia were retrospectively examined in two sequential regression models in which the 3-MPO test scores served as the predictor variables of interest, and 12-MPO BOSS Communication Difficulty and Communication Distress Scores served as dependent variables. Results: Among the speech and language measures examined, only 3-month BDAE Severity Ratings contributed significantly to the prediction of 12-month patient-reported communication difficulty and distress as measured by the BOSS. Conclusions: The findings suggest that performance-based measures of speech and language impairment such as the SPICA and 55-item RTT may not accurately predict the day-to-day communication difficulty and distress experienced by community-dwelling stroke survivors with mild to moderate aphasia. Replication of these findings in a prospectively designed study employing a larger more representative sample, and more comprehensive assessment instruments is needed to substantiate the relationship between performance-based measures of language impairment and patient-reported communication difficulty and distress in adults with aphasia. C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15260 USA. RP Doyle, PJ (reprint author), VA Pittsburgh Healthcare Syst, 7180 Highland Dr,132A-H, Pittsburgh, PA 15206 USA. EM patrick.doyle@med.va.gov NR 52 TC 4 Z9 4 U1 0 U2 0 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0268-7038 J9 APHASIOLOGY JI Aphasiology PD FEB-APR PY 2006 VL 20 IS 2-4 BP 349 EP 361 DI 10.1080/02687030500475135 PG 13 WC Clinical Neurology SC Neurosciences & Neurology GA 047PA UT WOS:000237890000021 ER PT J AU Stanczak, L Waters, G Caplan, D AF Stanczak, L Waters, G Caplan, D TI Typicality-based learning and generalisation in aphasia: Two case studies of anomia treatment SO APHASIOLOGY LA English DT Article; Proceedings Paper CT 35th Annual Clinical Aphasiology Conference CY MAY 31-JUN 04, 2005 CL Sanibel Isl, FL ID AGRAMMATIC APHASIA; PREFRONTAL CORTEX; LEXICAL DECISION; FRONTAL LESIONS; REHABILITATION; GENERATION; COMPLEXITY; MODELS AB Background: Simulation models (Plant, 1996) and anomia treatment (Kiran & Thompson, 2003b) have found that training with atypical items resulted in greater generalisation than training with typical items. The Complexity Account of Treatment Efficacy (CATE) predicts that therapy will produce greater generalisation when more complex items are trained (Thompson, Shapiro, Kiran, & Sobeck, 2003). Furthermore, learning and generalisation may be maximised when semantic training is directed towards semantic deficits (Plant, 1996). Aims: The clinical application of Plant's model and the CATE was investigated in typicality-based learning and generalisation, following anomia treatment in one participant with mainly phonological deficits and one participant with both phonological and semantic deficits. Methods & Procedures: Participants were trained with a semantic treatment to name typical items in one semantic category and atypical items of a different semantic category. Typicality-based learning and generalisation were compared. Outcomes & Results: The participant with primarily phonological deficits learned typical items faster than atypical items, and showed no generalisation to untrained items. The participant with phonological and semantic deficits learned both typical and atypical items, and showed significant generalisation to untrained typical items and marginally significant generalisation to untrained atypical items. Conclusions: Our results suggest that typical items may be easier to learn than atypical items when the semantic system is intact; however, typical items may be more difficult to learn with impairments in semantic knowledge and/or semantic selection, as these items have highly similar semantic features. Additionally, correspondence between the deficit and treatment may enhance learning and generalisation, as semantic treatment resulted in greater learning and generalisation for the participant with semantic deficits. Finally, family resemblance within semantic categories may produce generalisation to typical or atypical category members, but training with atypical members may produce more global changes within the semantic network, leading to greater generalisation. C1 Boston Univ, Dept Speech Language & Hearing Sci, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Stanczak, L (reprint author), Boston Univ, Dept Speech Language & Hearing Sci, 635 Commonwealth Ave, Boston, MA 02215 USA. EM louises@bu.edu NR 28 TC 10 Z9 10 U1 1 U2 3 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0268-7038 J9 APHASIOLOGY JI Aphasiology PD FEB-APR PY 2006 VL 20 IS 2-4 BP 374 EP 383 DI 10.1080/02687030600587631 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 047PA UT WOS:000237890000023 ER PT J AU Firoz, BF Lee, SJ Nghiem, P Qureshi, AA AF Firoz, BF Lee, SJ Nghiem, P Qureshi, AA TI Role of skin biopsy to confirm suspected acute graft-vs-host disease - Results of decision analysis SO ARCHIVES OF DERMATOLOGY LA English DT Article ID DRUG AB Objective: To estimate the value of skin biopsy in the evaluation of suspected acute cutaneous graft-vs-host disease (GVHD) after allogeneic stem cell transplantation. Design: Decision analysis using parameters specified by expert opinion for skin biopsy characteristics, prevalence of acute GVHD, and value of potential outcomes. One-, 2-, and 3-way sensitivity analyses were performed. Setting: Major stem cell transplantation centers in the United States. Patients: Hypothetical cohort of patients with suspected acute cutaneous GVHD after stem cell transplantation. Interventions: The following 3 interventions were compared: treat immediately for GVHD without performing a skin biopsy, perform a skin biopsy and treat immediately but stop treatment if skin biopsy specimen findings are inconsistent with GVHD, and perform a skin biopsy and await results of the skin biopsy specimen before treating. Main Outcome Measures: Number of patients appropriately and inappropriately treated with each intervention, consistency of physician-reported behavior, individualized decision analyses, and preferred intervention based on the aggregate estimates of respondents. Results: The decision to treat immediately for GVHD without performing a skin biopsy yielded the best clinical outcome for the specified clinical setting and under the parameters specified by expert opinion. One-way sensitivity analyses showed that these conclusions are robust if the prevalence of acute cutaneous GVHD in stem cell recipients with rash is greater than 50%, if the sensitivity of skin biopsy specimen is less than 0.8, and the specificity of skin biopsy specimen is less than 0.9. Only 25% of physicians interviewed chose an intervention consistent with their estimates of prevalence, test characteristics, and outcome evaluations, indicating an opportunity to improve management of this important clinical condition. Conclusions: This decision analysis modeling technique predicts that in patient populations in which the prevalence of GVHD is 30% or greater ( typical for allogeneic stem cell transplantation), the best outcomes were obtained with treatment for GVHD and no skin biopsy. In populations with prevalence of GVHD of 30% or less, obtaining a skin biopsy specimen to guide treatment was predicted to provide the best patient outcomes. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02114 USA. NYU, Dept Dermatol, New York, NY 10016 USA. Dana Farber Canc Inst, Dept Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Qureshi, AA (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Dermatol, 45 Francis St,221, Boston, MA 02114 USA. EM aqureshi@partners.org RI Nghiem, Paul/A-9210-2011 OI Nghiem, Paul/0000-0003-2784-963X NR 15 TC 20 Z9 21 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD FEB PY 2006 VL 142 IS 2 BP 175 EP 182 DI 10.1001/archderm.142.2.175 PG 8 WC Dermatology SC Dermatology GA 014LH UT WOS:000235481200006 PM 16490845 ER PT J AU Pitman, RK AF Pitman, RK TI Combat effects on mental health - The more things change, the more they remain the same SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; VIETNAM VETERANS C1 Massachusetts Gen Hosp, Psychiat Neurosci Program, Dept Psychiat, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Pitman, RK (reprint author), Massachusetts Gen Hosp, Psychiat Neurosci Program, Dept Psychiat, Room 2616,Bldg 149,13th St, Charlestown, MA 02129 USA. EM roger_pitman@hms.harvard.edu NR 12 TC 5 Z9 5 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD FEB PY 2006 VL 63 IS 2 BP 127 EP 128 DI 10.1001/archpsyc.63.2.127 PG 2 WC Psychiatry SC Psychiatry GA 009YZ UT WOS:000235150900002 PM 16461853 ER PT J AU Comer, SD Sullivan, MA Yu, E Rothenberg, JL Kleber, HD Kampman, K Dackis, C O'Brien, CP AF Comer, SD Sullivan, MA Yu, E Rothenberg, JL Kleber, HD Kampman, K Dackis, C O'Brien, CP TI Injectable, sustained-release naltrexone for the treatment of opioid dependence - A randomized, placebo-controlled trial SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 66th Annual Meeting of the College-on-Problems-of-Drug-Dependence CY JUN 14, 2004 CL San Juan, PR SP Coll Problems Drug Dependence ID NARCOTIC-ANTAGONISTS; ALCOHOL DEPENDENCE; METHADONE PATIENTS; HEROIN; BUPRENORPHINE; OVERDOSE; MORPHINE; HUMANS; DEPOT; HEPATOTOXICITY AB Context: Oral naltrexone can completely antagonize the effects produced by opioid agonists. However, poor compliance with naltrexone has been a major obstacle to the effective treatment of opioid dependence. Objective: To evaluate the safety and efficacy of a sustained release depot formulation of naltrexone in treating opioid dependence. Design and Setting: Randomized, double-blind, placebo-controlled, 8-week trial conducted at 2 medical centers. Participants: Sixty heroin-dependent adults. Interventions: Participants were stratified by sex and years of heroin use (>= 5 vs < 5) and then were randomized to receive placebo or 192 or 384 mg of depot naltrexone. Doses were administered at the beginning of weeks 1 and 5. All participants received twice-weekly relapse prevention therapy, provided observed urine samples, and completed other assessments at each visit. Main Outcome Measures: Retention in treatment and percentage of opioid-negative urine samples. Results: Retention in treatment was dose related, with 39%, 60%, and 68% of patients in the placebo, 192 mg of naltrexone, and 384 mg of naltrexone groups, respectively, remaining in treatment at the end of 2 months. Time to dropout had a significant main effect of dose, with mean time to dropout of 27, 36, and 48 days for the placebo, 192 mg of naltrexone, and 384 mg of naltrexone groups, respectively. The percentage of urine samples negative for opioids, methadone, cocaine, benzodiazepines, and amphetamine varied significantly as a function of dose. When the data were recalculated without the assumption that missing urine samples were positive, a main effect of group was not found for any drugs tested except cocaine, where the percentage of cocaine-negative urine samples was lower in the placebo group. Adverse events were minimal and generally mild. This formulation of naltrexone was well tolerated and produced a robust, dose-related increase in treatment retention. Conclusion: These data provide new evidence of the feasibility, efficacy, and tolerability of long-lasting antagonist treatments for opioid dependence. C1 Columbia Univ, New York State Psychiat Inst, Div Subst Abuse, New York, NY 10032 USA. Columbia Univ, Dept Psychiat, Coll Phys & Surg, New York, NY 10032 USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Dept Behav Hlth, Philadelphia, PA USA. RP Comer, SD (reprint author), Columbia Univ, New York State Psychiat Inst, Div Subst Abuse, 1051 Riverside Dr,Unit 120, New York, NY 10032 USA. EM sdc10@columbia.edu FU NCI NIH HHS [P60 CA05186]; NIDA NIH HHS [P60 DA005186, N01DA-1-8817, N01DA-3-8829, P50 DA009236, P50 DA09236] NR 48 TC 166 Z9 175 U1 1 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD FEB PY 2006 VL 63 IS 2 BP 210 EP 218 DI 10.1001/archpsyc.63.2.210 PG 9 WC Psychiatry SC Psychiatry GA 009YZ UT WOS:000235150900012 PM 16461865 ER PT J AU Blindauer, K Shoulson, I Oakes, D Kieburtz, K Schwid, S Fahn, S Stern, M Goetz, C Nutt, J Plumb, S Shinaman, A Truong, D Pahwa, R Factor, S Evans, S Wojcieszek, J Belden, J Adler, C Lind, M Panisset, M Hall, J Suchowersky, O Derwent, L Di Rocco, A Boyar, K Ondo, W Hunter, C Colcher, A Aminoff, M Dowling, G Outlaw, H Dalvi, A Sahay, A Schwieterman, D Elmer, L Weiner, W Cines, M Dignon, C Frucht, S Benabou, R Rajput, A Ewanishin, M Jennings, D Stavris, K Martin, W McInnes, G King, P Feigin, A Shannon, B Gordon, MF Atchison, P Mendis, T Mendis, N Reich, S Dunlop, B Petzinger, G Armstrong, C Welsh, M Pfeiffer, R Pfeiffer, B Tuite, P Calabrese, V Roberge, P Jog, M Horn, C Blackstone, C Growdon, J Tennis, M Hauser, R Gauger, L Stacy, M Williamson, K O'Brien, C Seeberger, L Judd, D Demarcaida, A Belber, S Perlmutter, J McGee-Minnich, L Ramos, CS Berrios, L Bertoni, J Peterson, C Marshall, F Deeley, C Verhagen, L Jaglin, J Koller, W Lyons, K Singer, C Blenke, A Mark, M Caputo, D Tarsy, D Scollins, L Thomas, CA Rivest, J Soucy, D Bausch, J Brocht, A Daigneault, S Eberly, S Irvine, C Lindsay, P Weaver, C Tariot, P Cox, C Leventhal, C Goren, S Sayag, N Scolnik, M Levy, R Eyal, E Salzman, P Pagano, M AF Blindauer, K Shoulson, I Oakes, D Kieburtz, K Schwid, S Fahn, S Stern, M Goetz, C Nutt, J Plumb, S Shinaman, A Truong, D Pahwa, R Factor, S Evans, S Wojcieszek, J Belden, J Adler, C Lind, M Panisset, M Hall, J Suchowersky, O Derwent, L Di Rocco, A Boyar, K Ondo, W Hunter, C Colcher, A Aminoff, M Dowling, G Outlaw, H Dalvi, A Sahay, A Schwieterman, D Elmer, L Weiner, W Cines, M Dignon, C Frucht, S Benabou, R Rajput, A Ewanishin, M Jennings, D Stavris, K Martin, W McInnes, G King, P Feigin, A Shannon, B Gordon, MF Atchison, P Mendis, T Mendis, N Reich, S Dunlop, B Petzinger, G Armstrong, C Welsh, M Pfeiffer, R Pfeiffer, B Tuite, P Calabrese, V Roberge, P Jog, M Horn, C Blackstone, C Growdon, J Tennis, M Hauser, R Gauger, L Stacy, M Williamson, K O'Brien, C Seeberger, L Judd, D Demarcaida, A Belber, S Perlmutter, J McGee-Minnich, L Ramos, CS Berrios, L Bertoni, J Peterson, C Marshall, F Deeley, C Verhagen, L Jaglin, J Koller, W Lyons, K Singer, C Blenke, A Mark, M Caputo, D Tarsy, D Scollins, L Thomas, CA Rivest, J Soucy, D Bausch, J Brocht, A Daigneault, S Eberly, S Irvine, C Lindsay, P Weaver, C Tariot, P Cox, C Leventhal, C Goren, S Sayag, N Scolnik, M Levy, R Eyal, E Salzman, P Pagano, M CA Parkinson Study Grp TI A randomized controlled trial of etilevodopa in patients with Parkinson disease who have motor fluctuations SO ARCHIVES OF NEUROLOGY LA English DT Article ID RESPONSE FLUCTUATIONS; LEVODOPA ETHYLESTER; DUODENAL INFUSION; PHARMACOKINETICS; DYSKINESIA; CROSSOVER AB Background: Motor fluctuations are a common complication in patients with Parkinson disease (PD) receiving long-term levodopa therapy. Slowed gastric emptying and poor solubility of levodopa in the gastrointestinal tract may delay the onset of drug benefit after dosing. Etilevodopa is an ethyl-ester prodrug of levodopa that has greater gastric solubility, passes quickly into the small intestine, is rapidly hydrolyzed to levodopa, and has a shortened time to maximum levodopa concentration. Objective: To determine the efficacy, safety, and tolerability of etilevodopa in patients with PD who have motor fluctuations. Design: A double-blind, randomized, comparative clinical trial. Setting: Forty-four sites in the United States and Canada. Patients: Three hundred twenty-seven patients with PD who had a latency of at least 90 minutes total daily time to "on" (TTON) after levodopa dosing. Intervention: Treatment with either etilevodopa-carbidopa or levodopa-carbidopa for 18 weeks. Main Outcome Measure: Change from baseline in total daily TTON as measured using home diaries. Results: The reduction in mean total daily TTON from baseline to treatment was 0.58 hour in the etilevodopa-carbidopa group and 0.79 hour in the levodopa-carbidopa group (P = .24). There was no significant difference between the etilevodopa-carbidopa and levodopa-carbidopa groups in the reduction of response failures (-6.82% vs -4.69%; P = .20). Total daily "off" time improved in the etilevodopa-carbidopa (-0.85 hour) and levodopa-carbidopa (-0.87 hour) groups without an increase in on time with troublesome dyskinesias. Conclusion: Despite the theoretical pharmacokinetic advantage of etilevodopa, there was no improvement in TTON, response failures, or off time compared with levodopa. C1 Med Coll Wisconsin, Dept Neurol, Milwaukee, WI 53226 USA. Univ Rochester, Rochester, NY USA. Columbia Presbyterian Med Ctr, New York, NY 10032 USA. Univ Penn, Philadelphia, PA 19104 USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Parkinsons & Movement Disorder Inst, Fountain Valley, CA USA. Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. Albany Med Coll, Albany, NY 12208 USA. Indiana Univ, Sch Med, Indianapolis, IN USA. Mayo Clin, Scottsdale, AZ USA. McGill Ctr Studies Aging, Verdun, PQ, Canada. Univ Calgary, Calgary, AB, Canada. Beth Israel Med Ctr, New York, NY 10003 USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Cincinnati, Cincinnati Childrens Hosp, Cincinnati, OH USA. Med Coll Ohio, Toledo, OH 43699 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Columbia Presbyterian Med Ctr, New York, NY 10032 USA. Royal Univ Hosp, Saskatoon Dist Hlth Board, Saskatoon, SK S7N 0W8, Canada. Inst Neurodegenerat Disorders, New Haven, CT USA. Univ Alberta, Edmonton, AB, Canada. N Shore Univ Hosp, Manhasset, NY USA. Long Isl Jewish Med Ctr, New Hyde Pk, NY 11042 USA. Univ Alabama, Birmingham, AL USA. Johns Hopkins Univ, Baltimore, MD USA. Univ So Calif, Los Angeles, CA USA. Univ Tennessee, Memphis, TN USA. Univ Minnesota, Minnesota VA Med Ctr, Minneapolis, MN USA. Hunter Homes McGuire Vet Med Ctr, Richmond, VA USA. London Hlth Sci Ctr, London, ON, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. NIH, Natl Ctr Res Resources, Bethesda, MD 20892 USA. Univ S Florida, Tampa, FL USA. Barrow Neurol Inst, Phoenix, AZ 85013 USA. Colorado Neurol Inst, Englewood, CO USA. Univ Connecticut, Farmington, CT USA. Washington Univ, St Louis, MO USA. Univ Puerto Rico, San Juan, PR 00936 USA. Creighton Univ, Omaha, NE 68178 USA. Univ Rochester, New York, NY USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Univ Miami, Miami, FL 33152 USA. Univ Med & Dent New Jersey, New Brunswick, NJ USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Boston Univ, Boston, MA 02215 USA. Univ Sherbrooke, Sherbrooke, PQ, Canada. Teva Neurosci Inc, N Wales, PA USA. RP Blindauer, K (reprint author), Med Coll Wisconsin, Dept Neurol, 9200 W Wisconsin Ave, Milwaukee, WI 53226 USA. EM kblindau@mcw.edu RI Pfeiffer, Ruth /F-4748-2011 NR 23 TC 18 Z9 18 U1 1 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD FEB PY 2006 VL 63 IS 2 BP 210 EP 216 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 010LH UT WOS:000235195700006 PM 16476809 ER PT J AU Holtzer, R Irizarry, MC Sanders, J Hyman, BT Wegesin, DJ Riba, A Brandt, J Albert, M Stern, Y AF Holtzer, R Irizarry, MC Sanders, J Hyman, BT Wegesin, DJ Riba, A Brandt, J Albert, M Stern, Y TI Relation of quantitative indexes of concurrent alpha-synuclein abnormalities to clinical outcome in autopsy-proven Alzheimer disease SO ARCHIVES OF NEUROLOGY LA English DT Article ID LEWY-BODY VARIANT; ANTI-UBIQUITIN IMMUNOCYTOCHEMISTRY; PARKINSONS-DISEASE; DEMENTIA; BODIES; IMMUNOREACTIVITY; NEUROPATHOLOGY; PREDICTORS; CONSORTIUM; DIAGNOSIS AB Background: Lewy bodies (LBs) and Lewy neurites are frequent concomitant neuropathologic observations in clinical and neuropathologically defined Alzheimer disease (AD), but their relation to clinical features in AD is uncertain. Most studies used semiquantitative measures to determine the presence or absence of LB abnormalities. Objective: To determine the clinical consequences of LB abnormalities in the setting of AD. Design: Prospective study. Setting: Three outpatient research and treatment centers. Participants: Fourteen autopsy cases with a pathologic diagnosis of AD abnormalities and concomitant LBs followed semiannually for up to 8 years (mean age at intake, 72 years; mean age at death, 77 years; mean education, 15 years; 12 women). Main Outcome Measures: The modified Mini-Mental State Examination was used to assess cognitive function. The Unified Parkinson Disease Rating Scale was used to rate extrapyramidal motor signs. Hallucinations were evaluated using the Columbia University Scale for Psychopathology in Alzheimer's Disease. Time from the first evaluation in which diagnostic criteria for probable AD were met to death was used to determine illness duration. Quantitative measures of LB abnormalities were obtained for the frontal cortex, entorhinal cortex, substantia nigra, and hippocampus. Results: Independent-samples t tests were used to assess whether the degree of LB abnormality varied as a function of the presence or absence of hallucinations and extrapyramidal signs. Pearson r correlations were run to examine whether there was a relation among LB abnormalities, cognitive function, and illness duration. There was no relation between quantitative neuropathologic indexes of LB abnormalities and clinical outcome. Conclusion: The variability of clinical features in AD was not related to the presence or degree of LB abnormalities. C1 Columbia Univ Coll Phys & Surg, Gertrude H Sergievsky Ctr, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Neurol, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. Yeshiva Univ, Albert Einstein Coll Med, Ferkauf Grad Sch Psychol, New York, NY 10033 USA. Yeshiva Univ, Albert Einstein Coll Med, Dept Neurol, New York, NY 10033 USA. Harvard Univ, Massachusetts Gen Hosp, Med Ctr, Dept Psychiat, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Med Ctr, Dept Neurol, Boston, MA USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. RP Stern, Y (reprint author), Columbia Univ Coll Phys & Surg, Gertrude H Sergievsky Ctr, 630 W 168th St,P&S Box 16, New York, NY 10032 USA. EM ys11@columbia.edu NR 41 TC 9 Z9 9 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD FEB PY 2006 VL 63 IS 2 BP 226 EP 230 DI 10.1001/archneur.63.2.226 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 010LH UT WOS:000235195700008 PM 16476811 ER PT J AU Kim, IK Dryja, TP Lessell, S Gragoudas, ES AF Kim, IK Dryja, TP Lessell, S Gragoudas, ES TI Melanocytoma of the optic nerve associated with sound-induced phosphenes SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID DISK C1 Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. RP Kim, IK (reprint author), Massachusetts Eye & Ear Infirm, Retina Serv, 243 Charles St, Boston, MA 02114 USA. EM ivana_kim@meei.harvard.edu NR 10 TC 4 Z9 4 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD FEB PY 2006 VL 124 IS 2 BP 273 EP 277 DI 10.1001/archopht.124.2.273 PG 6 WC Ophthalmology SC Ophthalmology GA 012HY UT WOS:000235330400018 PM 16476900 ER PT J AU Yin, A Margolis, HC Yao, Y Grogan, J Oppenheim, FG AF Yin, A Margolis, HC Yao, Y Grogan, J Oppenheim, FG TI Multi-component adsorption model for pellicle formation: The influence of salivary proteins and non-salivary phospho proteins on the binding of histatin 5 onto hydroxyapatite SO ARCHIVES OF ORAL BIOLOGY LA English DT Article DE phosvitin; statherin; histatins; adsorption; enamel pellicle; hydroxyapatite ID ACQUIRED ENAMEL PELLICLE; CALCIUM-PHOSPHATE; WHOLE SALIVA; EGG-YOLK; IN-VIVO; SURFACES; HYDROXYLAPATITE; PRECIPITATION; SECRETIONS; COMPONENTS AB The acquired enamel pellicle formed by selective adsorption of proteins in whole saliva is a protective integument on the tooth surface. The purpose of the present study was to investigate the formation of human acquired enamel pellicle using an in vitro hydroxyapatite (HA) model and H-3-histatin 5 to allow accurate measurement of histatin 5 binding in a multi-component experimental system. A binary system was employed by mixing H-3-histatin 5 with one unlabeled protein prior to incubation with HA or by first incubating H-3-histatin 5 with the HA which had been pre-coated with one of a panel of unlabeled proteins (human albumin, salivary amytase, lysozyme, acidic PIFs, statherin, the N-terminal fragment of statherin, and egg yolk phosvitin). A ternary system was employed by mixing H-3-histatin 5 with HA sequentially pre-coated with two different unlabeled proteins, including recombinant histatin 1. The results showed that only salivary statherin and egg yolk phosvitin promote histatin 5 adsorption significantly. The amount of histatin 5 adsorbed was also found to increase as a function of the amount of phosvitin and statherin used to pre-coat HA up to a maximum level that was two- to four-fotd greater than that observed on untreated HA. These data suggest that specific protein-protein interactions may play important roles in pellicle formation in vivo. (c) 2005 Elsevier Ltd. All rights reserved. C1 Boston Univ, Med Ctr, Dept Periodontol & Oral Biol, Boston, MA 02118 USA. Boston Univ, Med Ctr, Dept Biochem, Boston, MA 02118 USA. Forsyth Inst, Dept Biomineralizat, Boston, MA 02115 USA. RP Oppenheim, FG (reprint author), Boston Univ, Med Ctr, Dept Periodontol & Oral Biol, 700 Albany St,Suite W201, Boston, MA 02118 USA. EM fropp@bu.edu FU NIDCR NIH HHS [DE 15163, DE 07652, DE 14950, DE 05672] NR 35 TC 17 Z9 17 U1 1 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0003-9969 J9 ARCH ORAL BIOL JI Arch. Oral Biol. PD FEB PY 2006 VL 51 IS 2 BP 102 EP 110 DI 10.1016/j.archoralbio.2005.06.003 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 016YJ UT WOS:000235660200004 PM 16055080 ER PT J AU Emerick, KS Cunningham, MJ AF Emerick, KS Cunningham, MJ TI Tubal tonsil hypertrophy - A cause of recurrent symptoms after adenoidectomy SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article; Proceedings Paper CT 20th Annual Meeting of the American-Society-of-Pediatric-Otolaryngology CY MAY 27-30, 2005 CL Las Vegas, NV SP Amer Soc Pediat Otolaryngol ID OTITIS-MEDIA; TYMPANOSTOMY TUBES; CHILDREN; EFFICACY; TRIALS AB Objectives: To assess the incidence of symptomatic tubal tonsil hypertrophy (TTH) after adenoidectomy and to attempt to differentiate the clinicoradiographic presentation of TTH from that of recurrent or residual adenoid. Design: Retrospective case series review Setting: Pediatric otolaryngology practice in a tertiary care hospital. Patients: The charts of all patients scheduled to undergo revision adenoidectomy or nasopharyngeal examination under anesthesia over a 5-year period in 1 pediatric otolaryngologist's practice were reviewed. Main Outcome Measure: Presence of TTH in patients with recurrent symptoms after previous adenoidectomy. Results: Forty-two patients were identified, 24 of whom satisfied the established criteria of recurrent symptoms after previous adenoidectomy. Ten (42%) of these patients were identified as having TTH. The average age at presentation was 7 years 2 months, at an average time interval of 4 years 2 months after adenoidectomy. The comparative incidence of recurrent or residual adenoid was 54%. The symptomatic manifestations of TTH included nasal obstruction, obstructive sleep disorder, rhinosinusitis, recurrent otitis media, and otitis media with effusion. Preoperative radiographic evaluation was not useful in distinguishing TTH from recurrent or residual adenoid; nasopharyngoscopy appears to have better diagnostic potential. Thermal ablation with suction cautery was therapeutically effective. Conclusions: Tubal tonsil hypertrophy is a significant clinical entity as a cause of recurrent symptoms after adenoidectomy. The study patients demonstrated the entire spectrum of signs and symptoms seen in patients with adenoid hypertrophy. Operative nasopharyngeal examination is required to definitively distinguish TTH from recurrent or residual adenoid. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Cunningham, MJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM Michael_Cunningham@meei.harvard.edu NR 10 TC 9 Z9 11 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD FEB PY 2006 VL 132 IS 2 BP 153 EP 156 DI 10.1001/archotol.132.2.153 PG 4 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 011SN UT WOS:000235288500005 PM 16490872 ER PT J AU Renshaw, AA Wang, E Wilbur, D Hughes, JH Haja, J Henry, MR AF Renshaw, AA Wang, E Wilbur, D Hughes, JH Haja, J Henry, MR CA Cytopathology Comm TI Interobserver agreement on microfollicles in thyroid fine-needle aspirates SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID PAPILLARY CARCINOMA; BIOPSY DIAGNOSIS; FOLLOW-UP; CYTOLOGY; MANAGEMENT; CRITERIA; NODULES; NEOPLASM; DILEMMA; DISEASE AB Context-Although microfollicles are a well-known feature of follicular neoplasms in fine-needle aspirates of the thyroid, the level of agreement about classifying groups as microfollicles is not known. Objective.-To determine what features are present in groups that are consistently classified as microfollicles. Design.-We showed 43 small groups of follicular cells each composed of fewer than 50 cells from fine-needle aspirates of the thyroid to 12 members of the College of American Pathologists Cytopathology Committee, who then classified the groups into microfollicles, macrofollicles, and indeterminate groups. Results.-Twenty groups were consistently classified as microfollicles, 7 groups as macrofollicles, and 18 groups as indeterminate. Cases that were consistently classified as microfollicles were composed of fewer than 15 cells (19/20 cases), were arranged in a circle with a lumen (13/20 cases) that was at least two-thirds complete (112/20 cases), and were flat (18/20 cases). Cases that were classified as macrofollicular had between 8 and 35 cells, were arranged in sheets composed of at least 15 cells (5/7 cases) or rows of 8 cells (2/7 cases), and were flat (7/7 cases). In contrast, cases that were indeterminate were composed of either 3-dimensional groups (5/18 cases), flat groups of fewer than 10 cells (11/18 cases), or single cells (1/18 cases). Conclusion.-Not all small groups of follicular cells are consistently classified as microfollicles, and some are more often classified as macrofollicles. The criteria described here for reproducible microfollicles (< 15 cells, arranged in a circle that is at least two-thirds complete, and flat) may help improve the agreement in classification of microfollicles and lead to more consistent classification of thyroid fine-needle aspirates. C1 Baptist Hosp Miami, Dept Pathol, Miami, FL 33176 USA. Coll Amer Pathologists, Norhtfield, IL USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Lab Med Consultants Ltd, Las Vegas, NV USA. Cleveland Clin, Dept Pathol & Lab Med, Naples, FL USA. RP Renshaw, AA (reprint author), Baptist Hosp Miami, Dept Pathol, 8900 N Kendall Dr, Miami, FL 33176 USA. NR 27 TC 18 Z9 19 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD FEB PY 2006 VL 130 IS 2 BP 148 EP 152 PG 5 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 012GG UT WOS:000235325700007 PM 16454552 ER PT J AU Evans, CT LaVela, SL Smith, B Miskevics, S Weaver, FM Goldstein, B AF Evans, CT LaVela, SL Smith, B Miskevics, S Weaver, FM Goldstein, B TI Influenza diagnosis and treatment in veterans with spinal cord injury SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE antiviral agents; influenza; rehabilitation; spinal cord injuries AB Objective: To assess influenza diagnosis and treatment behaviors and prescribing practices for antiviral medications among spinal cord injury (SCI) practitioners. Design: Anonymous cross-sectional survey of practitioners and retrospective review of administrative diagnostic and prescription databases. Setting: Department of Veterans Affairs health care facilities. Participants: One hundred practitioners participated (response rate, 65%). Interventions: Not applicable. Main Outcome Measures: Strategies for diagnosing and treating influenza and type of antivirals prescribed. Results: Ninety-seven percent of practitioners reported using clinical symptoms to diagnose a patient with influenza. The most common treatments included symptom relievers (94%), followed by antivirals (21%). Antivirals reportedly used included amantadine (64%), rimantadine (36%), oseltamivir (32%), and zanamivir (11%). Twenty-one prescriptions for antivirals were identified during the influenza season and all were for amantadine. Conclusions: Despite recommendations by the U.S. Centers for Disease Control and Prevention and high risks of respiratory complications after SCI, antiviral medications and diagnostic tests for influenza are seldom used in the treatment of influenza in this population. Research is needed to identify barriers to diagnosing and administering antivirals in people with SCI. C1 Vet Affairs Edward Hines Jr Hosp, Dept Vet Affairs, Midwest Ctr Hlth Serv & Policy Res, Hines, IL 60141 USA. Northwestern Univ, Dept Neurol, Chicago, IL 60611 USA. Northwestern Univ, Inst Hlth Serv & Policy Res, Chicago, IL 60611 USA. VA Puget Sound Healthcare Syst, Spinal Cord Injury & Disorders Strateg Healthcare, Seattle, WA USA. Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. RP Evans, CT (reprint author), Vet Affairs Edward Hines Jr Hosp, Dept Vet Affairs, Midwest Ctr Hlth Serv & Policy Res, 151H,5th & Roosevelt Rd,POB 5000,Rm D302, Hines, IL 60141 USA. EM Charlesnika.Evans@va.gov NR 9 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD FEB PY 2006 VL 87 IS 2 BP 291 EP 293 DI 10.1016/j.apmr.2005.10.008 PG 3 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 013CJ UT WOS:000235386900023 PM 16442987 ER PT J AU Pollack, MH Simon, NM Zalta, AK Worthington, JJ Hoge, EA Mick, E Kinrys, G Oppenheimer, J AF Pollack, MH Simon, NM Zalta, AK Worthington, JJ Hoge, EA Mick, E Kinrys, G Oppenheimer, J TI Olanzapine augmentation of fluoxetine for refractory generalized anxiety disorder: A placebo controlled study SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 42nd Annual Meeting of the New-Clinical-Drug-Evaluation-Unit CY JUN 10-13, 2002 CL BOCA RATON, FL SP NIMH DE generalized anxiety disorder; olanzapine; treatment refractory ID OBSESSIVE-COMPULSIVE DISORDER; RISPERIDONE AUGMENTATION; DOUBLE-BLIND; CONTROLLED-TRIAL; RATING-SCALE; OPEN-LABEL; DEPRESSION; PAROXETINE; EFFICACY; OCD AB Background: There has been little systematic study of "next-step" interventions for patients with generalized anxiety disorder (GAD) who remain symptomatic despite initial pharmacotherapy. We present one of the first randomized controlled trials for refractory GAD, comprising double blind augmentation with olanzapine or placebo for patients remaining symptomatic on fluoxetine. Methods: Patients remaining symptomatic after 6 weeks of fluoxetine (20 mg/day) were randomized to 6 weeks of olanzapine (mean dose 8.7 +/- 7.1 mg/day) or placebo augmentation. Results: Twenty-four of 46 fluoxetine-treated patients were randomized. Olanzapine resulted in a greater proportion of treatment responders based on a Clinical Global Impression-Severity Scale (CGI-S) end point score of 1 or 2 (Fisher's exact test [FET] p < .05) or a 50% reduction in Hamilton Anxiety Scale (HAMA-A) score (FET p < .05). There were no other statistically significant differences for olanzapine compared with placebo augmentation in outcome measures, though rates of remission (HAM-A <= 7) on olanzapine were higher at the level of a trend (FET, p = 1). Average weight gain for completers was greater with olanzapine than placebo augmentation (11.0 +/- 5.1 vs. -0.7 +/- 2.4 pounds: t = 6.32, p < .001). Conclusions: Olanzapine may have a salutary effect on anxiety for some GAD patients remaining symptomatic despite initial serotonin selective reuptake inhibitor (SSRI) therapy, but the emergence of significant weight gain represents an important clinical consideration. C1 Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Related Disorders, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Cambridge Hlth Alliance, Cambridge, MA USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Pollack, MH (reprint author), Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Related Disorders, WAC-812,15 Parkman St, Boston, MA 02114 USA. EM mpollack@partners.org RI Hoge, Elizabeth/H-5879-2012; OI Hoge, Elizabeth/0000-0002-5513-2292; Zalta, Alyson/0000-0002-5159-8431; Mick, Eric/0000-0001-8505-8145 NR 40 TC 93 Z9 95 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD FEB 1 PY 2006 VL 59 IS 3 BP 211 EP 215 DI 10.1016/j.biopsych.2005.07.005 PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 022IJ UT WOS:000236048600002 PM 16139813 ER PT J AU Biederman, J Monuteaux, MC Mick, E Wilens, TE Fontanella, JA Poetzl, KM Kirk, T Masse, J Faraone, SV AF Biederman, J Monuteaux, MC Mick, E Wilens, TE Fontanella, JA Poetzl, KM Kirk, T Masse, J Faraone, SV TI Is cigarette smoking a gateway to alcohol and illicit drug use disorders? A study of youths with and without attention deficit hyperactivity disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Gateway; smoking; ADHD; substance use; adolescents; substance use disorder ID SUBSTANCE USE DISORDERS; DEFICIT/HYPERACTIVITY DISORDER; CHILDREN; ADHD; ASSOCIATION; ADOLESCENTS; INFORMANTS; BEHAVIORS; DIAGNOSIS; MARIJUANA AB Background: The goal of this study was to assess whether cigarette smoking is a gateway drug for subsequent alcohol and illicit drug abuse and dependence in,youth with Attention Deficit Hyperactivity Disorder (ADHD), and to test if this association is stronger in ADHD youth relative to controls. Methods: We used data from a case-control family study of female youth with and without ADHD. Me studied 97 ADHD and 203 control youth of both sexes, aged at least 12 years. We assessed ADHD, smoking, and substance use status using structured diagnostic interviews. We tested the association between cigarette smoking and subsequent substance use outcomes using Cox proportional hazard regression models. Results: ADHD youth who smoked cigarettes (n = 15), were significantly more likely to subsequently use alcohol and illicit drugs as well as to develop abuse and dependence compared to ADHD youth who did not smoke (n = 76; p < .05). Conclusions: These result extend the gateway hypothesis to an ADHD sample and provide evidence that this effect may be particularly robust in ADHD youth. If replicated in larger, community-based samples, these findings have important public health consequences, and underscore the already pressing need to prevent smoking in ADHD children. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Program, Dept Psychiat, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Program, Dept Psychiat, Pediat Psychopharmacol Unit, Warren 705,55 Fruit St, Boston, MA 02114 USA. EM jbiederman@partners.org OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 FU NIDA NIH HHS [R01 DA14419]; NIMH NIH HHS [R01 MH-41314-01A2] NR 39 TC 66 Z9 66 U1 3 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 FEB 1 PY 2006 VL 59 IS 3 BP 258 EP 264 DI 10.1016/j.biopsych.2005.07.009 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 022IJ UT WOS:000236048600009 PM 16154546 ER PT J AU Cutler, C Li, S Kim, HT Macdonell, R Ho, V Alyea, V Lee, SJ Soiffer, R Antin, JH AF Cutler, C Li, S Kim, HT Macdonell, R Ho, V Alyea, V Lee, SJ Soiffer, R Antin, JH TI Sirolimus and tacrolimus without methotrexate as graft-vs.-host disease prophylaxis after matched, unrelated peripheral blood stem cell transplantation (PBSCT): Excellent GVHD control with low transplant-related morbidity and mortality SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 32nd Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation CY FEB 16-20, 2006 CL Honolulu, HI SP Amer Soc Blood & Marrow Transplantat C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2006 VL 12 IS 2 SU 1 MA 8 BP 5 EP 5 DI 10.1016/j.bbmt.2005.11.022 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 012MU UT WOS:000235344100009 ER PT J AU Saito, AM Cutler, C Zahrieh, D Soiffer, RJ Ho, VT Alyea, EP Antin, JH Lee, SJ AF Saito, AM Cutler, C Zahrieh, D Soiffer, RJ Ho, VT Alyea, EP Antin, JH Lee, SJ TI Comparison of methotrexate- versus sirolimus-containing graft-versus-host disease prophylaxis regimens after myeloablative stem cell transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 32nd Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation CY FEB 16-20, 2006 CL Honolulu, HI SP Amer Soc Blood & Marrow Transplantat C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2006 VL 12 IS 2 SU 1 MA 15 BP 8 EP 8 DI 10.1016/j.bbmt.2005.11.030 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 012MU UT WOS:000235344100017 ER PT J AU Colvin, GA Chung, S Ballen, KK Dey, BR Winer, E Quescenberry, PJ AF Colvin, GA Chung, S Ballen, KK Dey, BR Winer, E Quescenberry, PJ TI The haploimmunostorm syndrome: A distinct clinical entity seen in HLA-haploidentical cellular immunotherapy SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 32nd Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation CY FEB 16-20, 2006 CL Honolulu, HI SP Amer Soc Blood & Marrow Transplantat C1 Adel Decof Canc Ctr, Dept Res, Roger Williams Med Ctr, Providence, RI USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2006 VL 12 IS 2 SU 1 MA 24 BP 11 EP 11 DI 10.1016/j.bbmt.2005.11.038 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 012MU UT WOS:000235344100025 ER PT J AU Kernan, NA Carter, SL Wagner, JE Baxter-Lowe, L Wall, D Kapoor, N Guinan, E Wagner, E Geller, N Kurtzberg, J AF Kernan, NA Carter, SL Wagner, JE Baxter-Lowe, L Wall, D Kapoor, N Guinan, E Wagner, E Geller, N Kurtzberg, J TI Umbilical cord blood transplantation in pediatric patients: Results of the prospective, multi-institutional cord blood transplantation study (COBLT) SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 32nd Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation CY FEB 16-20, 2006 CL Honolulu, HI SP Amer Soc Blood & Marrow Transplantat C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. EMMES Corp, Rockville, MD USA. Univ Minnesota, Minneapolis, MN 55455 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Texas Transplant Inst, San Antonio, TX USA. Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NHLBI, Bethesda, MD 20892 USA. Duke Univ, Ctr Med, Durham, NC USA. NR 0 TC 9 Z9 10 U1 0 U2 1 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2006 VL 12 IS 2 SU 1 MA 33 BP 14 EP 15 DI 10.1016/j.bbmt.2005.11.048 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 012MU UT WOS:000235344100034 ER PT J AU Ho, VT Dranoff, G Pasek, M MacDonell, R Cutler, C Lee, SJ Alyea, EP Antin, JH Soiffer, RJ AF Ho, VT Dranoff, G Pasek, M MacDonell, R Cutler, C Lee, SJ Alyea, EP Antin, JH Soiffer, RJ TI GM-CSF secreting leukemia cell vaccinations after allogeneic non-myeloablative peripheral blood stem cell transplantation in patients with advanced myelodysplastic syndrome or refractory acute myeloid leukemia SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 32nd Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation CY FEB 16-20, 2006 CL Honolulu, HI SP Amer Soc Blood & Marrow Transplantat C1 RJ Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2006 VL 12 IS 2 SU 1 MA 42 BP 17 EP 18 DI 10.1016/j.bbmt.2005.11.057 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 012MU UT WOS:000235344100043 ER PT J AU Georges, GE Maris, MB Maloney, DG Sandmaier, BM Sorror, ML Shizura, JA Niederwieser, DW Agura, ED Bruno, B McSweeney, PA Pulsipher, MA Chauncey, TR Storer, BE Storb, RF AF Georges, GE Maris, MB Maloney, DG Sandmaier, BM Sorror, ML Shizura, JA Niederwieser, DW Agura, ED Bruno, B McSweeney, PA Pulsipher, MA Chauncey, TR Storer, BE Storb, RF TI Nonmyeloablative unrelated donor (URD) hematopoietic cell transplantation (HCT) for the treatment of patients (PTS) with poor-risk, relapsed or refractory multiple myeloma SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 32nd Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation CY FEB 16-20, 2006 CL Honolulu, HI SP Amer Soc Blood & Marrow Transplantat C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Washington, Seattle, WA 98195 USA. Rocky Mt Canc Ctr, Denver, CO USA. Stanford Univ, Palo Alto, CA 94304 USA. Univ Leipzig, D-7010 Leipzig, Germany. Baylor Univ, Med Ctr, Dallas, TX USA. Univ Turin, I-10124 Turin, Italy. Univ Utah, Salt Lake City, UT USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2006 VL 12 IS 2 SU 1 MA 46 BP 19 EP 19 DI 10.1016/j.bbmt.2005.11.061 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 012MU UT WOS:000235344100047 ER PT J AU Armistead, P Mohseni, M Gerwin, R Iravani, M Ghavamzadeh, A Ritz, J Wu, CJ AF Armistead, P Mohseni, M Gerwin, R Iravani, M Ghavamzadeh, A Ritz, J Wu, CJ TI Post-transplant monitoring of erythroid lineage specific chimerism SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 32nd Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation CY FEB 16-20, 2006 CL Honolulu, HI SP Amer Soc Blood & Marrow Transplantat C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Tehran Med Sci, Hematol Oncol & Bone Marrow Transplant Res Ctr, Tehran, Iran. 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 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2006 VL 12 IS 2 SU 1 MA 98 BP 37 EP 37 DI 10.1016/j.bbmt.2005.11.115 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 012MU UT WOS:000235344100099 ER PT J AU Krishnamurti, L Wu, CJ Baker, S Wagner, J AF Krishnamurti, L Wu, CJ Baker, S Wagner, J TI Stable donor engraftment following reduced intensity hematopoietic cell transplantation for sickle cell disease SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 32nd Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation CY FEB 16-20, 2006 CL Honolulu, HI SP Amer Soc Blood & Marrow Transplantat C1 Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Minnesota, Minneapolis, MN USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2006 VL 12 IS 2 SU 1 MA 105 BP 39 EP 39 DI 10.1016/j.bbmt.2005.11.122 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 012MU UT WOS:000235344100106 ER PT J AU Saito, TI Sykes, M AF Saito, TI Sykes, M TI Long-lasting anti-tumor immunity induced by the rejection of donor hematopoietic cells in mixed bone marrow chimeras SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 32nd Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation CY FEB 16-20, 2006 CL Honolulu, HI SP Amer Soc Blood & Marrow Transplantat C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2006 VL 12 IS 2 SU 1 MA 135 BP 49 EP 49 DI 10.1016/j.bbmt.2005.11.153 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 012MU UT WOS:000235344100136 ER PT J AU Sarantopoulos, S Zorn, E Bhuiya, E Kim, HT Soiffer, RJ Cutler, CS Levin, J Antin, JH Ritz, J AF Sarantopoulos, S Zorn, E Bhuiya, E Kim, HT Soiffer, RJ Cutler, CS Levin, J Antin, JH Ritz, J TI Elevated B cell activating factor (BAFF) in patient plasma after allogeneic stem cell transplantation is a potential biomarker for chronic graft versus host disease SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 32nd Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation CY FEB 16-20, 2006 CL Honolulu, HI SP Amer Soc Blood & Marrow Transplantat C1 Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2006 VL 12 IS 2 SU 1 MA 158 BP 56 EP 57 DI 10.1016/j.bbmt.2005.11.177 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 012MU UT WOS:000235344100159 ER PT J AU Duncan, CN Buonanno, MR Callaway, GD Lehmann, LE AF Duncan, CN Buonanno, MR Callaway, GD Lehmann, LE TI Bronchiolitis obliterans and bronchiolitis obliterans organizing pneumonia in pediatric allogeneic stem cell transplant: An institutional experience SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 32nd Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation CY FEB 16-20, 2006 CL Honolulu, HI SP Amer Soc Blood & Marrow Transplantat C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2006 VL 12 IS 2 SU 1 MA 191 BP 67 EP 67 DI 10.1016/j.bbmt.2005.11.211 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 012MU UT WOS:000235344100192 ER PT J AU Haining, WN Ebert, B Subramanian, A Golub, T Kaech, S Wherry, EJ Nadler, LM AF Haining, WN Ebert, B Subramanian, A Golub, T Kaech, S Wherry, EJ Nadler, LM TI Transcriptional mapping of the anti-viral T cell response shows that impaired memory differentiation causes T cell dysfunction SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 32nd Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation CY FEB 16-20, 2006 CL Honolulu, HI SP Amer Soc Blood & Marrow Transplantat C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. MIT, Cambridge, MA 02138 USA. Yale Univ, New Haven, CT USA. Wistar Inst Anat & Biol, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2006 VL 12 IS 2 SU 1 MA 218 BP 76 EP 76 DI 10.1016/j.bbmt.2005.11.239 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 012MU UT WOS:000235344100219 ER PT J AU Buzney, C Lee, J Sackstein, R AF Buzney, C Lee, J Sackstein, R TI Effects of thymoglobulin on lymphocyte L-selectin-mediated adhesive interactions SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 32nd Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation CY FEB 16-20, 2006 CL Honolulu, HI SP Amer Soc Blood & Marrow Transplantat C1 Harvard Univ, Brigham & Womens Hosp, Med Sch, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2006 VL 12 IS 2 SU 1 MA 228 BP 79 EP 80 DI 10.1016/j.bbmt.2005.11.249 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 012MU UT WOS:000235344100229 ER PT J AU McKibbin, T Burzynski, JA Twombly, RG Ochoa, JL Tsai, TW Callander, NS Freytes, CO AF McKibbin, T Burzynski, JA Twombly, RG Ochoa, JL Tsai, TW Callander, NS Freytes, CO TI Paclitaxel followed by filgrastim for peripheral blood stem cell (PBSC) mobilization in patients with hematologic malignancies who experienced prior mobilization failures SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 32nd Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation CY FEB 16-20, 2006 CL Honolulu, HI SP Amer Soc Blood & Marrow Transplantat 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 CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2006 VL 12 IS 2 SU 1 MA 270 BP 96 EP 96 DI 10.1016/j.bbmt.2005.11.293 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 012MU UT WOS:000235344100271 ER PT J AU Schultz, KR Miklos, DB Fowler, D Cooke, K Shizuru, J Zorn, E Holler, E Ferrara, Y Shulman, H Lee, SY Martin, P Filipovich, AH Flowers, MED Weisdorf, D Couriel, D Lachenbruch, PA Mittleman, B Vogelsang, GB Pavletic, SZ AF Schultz, KR Miklos, DB Fowler, D Cooke, K Shizuru, J Zorn, E Holler, E Ferrara, Y Shulman, H Lee, SY Martin, P Filipovich, AH Flowers, MED Weisdorf, D Couriel, D Lachenbruch, PA Mittleman, B Vogelsang, GB Pavletic, SZ TI Toward biomarkers for chronic graft-versus-host disease: National Institutes of Health Consensus Development Project on criteria for clinical trials in chronic graft-versus-host disease: III. Biomarker working group report SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Review DE graft-versus-host disease; biomarkers ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; MINOR HISTOCOMPATIBILITY ANTIGEN; CYTOTOXIC T-LYMPHOCYTES; DENDRITIC CELLS; MONOCLONAL-ANTIBODY; GENE POLYMORPHISMS; FEMALE DONORS; LABIAL SALIVA; BLOOD AB Biology-based markers that can be used to confirm the diagnosis of chronic graft-versus-host disease (GVHD) or monitor progression of the disease could help in the evaluation of new therapies. Biomarkers have been defined as any characteristic that is objectively measured and evaluated as an indicator of a normal biologic or pathogenic process, a pharmacologic response to a therapeutic intervention, or a surrogate end point intended to substitute for a clinical end point. The following applications of biomarkers could be useful in chronic GVHD clinical trials or management: (1) predicting response to therapy; (2) measuring disease activity and distinguishing irreversible damage from continued disease activity; (3) predicting the risk of developing chronic GVHD; (4) diagnosing chronic GVHD: (5) predicting the prognosis of chronic GVHD; (6) evaluating the balance between GVHD and graft-versus-leukemia effects (graft-versus-leukemia or GVT); and (7) serving as a surrogate end point for therapeutic response. Such biomarkers can be identified by either hypothesis-driven testing or by high-throughput discovery-based methods. To date, no validated biomarkers have been established for chronic GVHD, although several candidate biomarkers have been identified from limited hypothesis-driven studies. Both approaches have merit and should be pursued. The consistent treatment and standardized documentation needed to support biomarker studies are most likely to be satisfied in prospective clinical trials. (C) 2006 American Society for Blood and Marrow Transplantation. C1 Univ British Columbia, British Columbia Childrens Hosp, Vancouver, BC V6H 3V4, Canada. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Univ Michigan, Med Ctr, Ann Arbor, MI USA. Harvard Univ, Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Regensburg, D-8400 Regensburg, Germany. Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. Univ Minnesota, Minneapolis, MN USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. US FDA, Rockville, MD 20857 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Schultz, KR (reprint author), Univ British Columbia, British Columbia Childrens Hosp, 4480 Oak St,Room A119, Vancouver, BC V6H 3V4, Canada. EM kschultz@interchange.ubc.ca NR 66 TC 103 Z9 108 U1 0 U2 2 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2006 VL 12 IS 2 BP 126 EP 137 DI 10.1016/j.bbmt.2005.11.010 PG 12 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 011RD UT WOS:000235284900002 PM 16443511 ER PT J AU Rizzo, JD Wingard, YR Tichelli, A Lee, SJ Van Lint, MT Burns, LJ Davies, SM Ferrara, JLM Socie, G AF Rizzo, JD Wingard, YR Tichelli, A Lee, SJ Van Lint, MT Burns, LJ Davies, SM Ferrara, JLM Socie, G TI Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation: Joint recommendations of the European Group for Blood and Marrow Transplantation, the Center for International Blood and Marrow Transplant Research, and the American Society of Blood and Marrow Transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE late effects; HCT (hematopoietic cell transplantation); screening; prevention AB More than 40 000 hematopoietic cell transplants (HCTs) are performed worldwide each year. With improvements in transplant technology, larger numbers of transplant recipients survive free of the disease for which they were transplanted. However, there are late complications that can cause substantial morbidity. Many survivors are no longer under the care of transplant centers, and many community health care providers may be unfamiliar with health matters relevant to HCT. The Center for International Blood and Marrow Transplant Research (CIBMTR), European Group for Blood and Marrow Transplantation (EBMT), and American Society for Bone Marrow Transplantation (ASBMT) have developed these recommendations to offer care providers suggested screening and prevention practices for autologous and allogeneic HCT survivors. (C) 2006 European Group for Blood and Marrow Transplantation, Center fir International Blood and Marrow Transplant Research, and the American Society for Blood and Marrow Transplantation. C1 Hop St Louis, Dept Hematol, F-75475 Paris 10, France. Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. Univ Florida, Coll Med, Gainesville, FL USA. Kantonsspital, CH-4031 Basel, Switzerland. Dana Farber Canc Inst, Boston, MA 02115 USA. San Martino Hosp, Genoa, Italy. Univ Minnesota, Minneapolis, MN USA. Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. Univ Michigan, Ann Arbor, MI 48109 USA. RP Socie, G (reprint author), Hop St Louis, Dept Hematol, 1 Ave Claude Vellefaux, F-75475 Paris 10, France. EM gerard.socie@paris7.jussieu.fr FU NCI NIH HHS [K23-CA82350, U24-CA76518] NR 9 TC 127 Z9 132 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2006 VL 12 IS 2 BP 138 EP 151 DI 10.1016/j.bbmt.2005.09.012 PG 14 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 011RD UT WOS:000235284900003 PM 16443512 ER PT J AU Costello, CA Braddock, D AF Costello, CA Braddock, D TI Care of the immunodeficient patient during hematopoietic stem cell transplant: The Omenn's syndrome patient SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 32nd Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation CY FEB 16-20, 2006 CL Honolulu, HI SP Amer Soc Blood & Marrow Transplantat C1 Childrens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2006 VL 12 IS 2 SU 1 MA 427 BP 148 EP 148 DI 10.1016/j.bbmt.2005.11.456 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 012MU UT WOS:000235344100428 ER PT J AU Schulte, KA Hubner, M Binari, E Gaumer, C AF Schulte, KA Hubner, M Binari, E Gaumer, C TI The complex care challenge of transplant patients and families: How to effectively promote care across the continuum through role development in the program SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 32nd Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation CY FEB 16-20, 2006 CL Honolulu, HI SP Amer Soc Blood & Marrow Transplantat C1 Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2006 VL 12 IS 2 SU 1 MA 456 BP 157 EP 157 DI 10.1016/j.bbmt.2005.11.485 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 012MU UT WOS:000235344100457 ER PT J AU Da Silva, N Silberstein, C Beaulieu, V Pietrement, C Van Hoek, AN Brown, D Breton, S AF Da Silva, N Silberstein, C Beaulieu, V Pietrement, C Van Hoek, AN Brown, D Breton, S TI Postnatal expression of aquaporins in epithelial cells of the rat epididymis SO BIOLOGY OF REPRODUCTION LA English DT Article DE epididymis; male reproductive tract ID MALE REPRODUCTIVE-TRACT; NEPHROGENIC DIABETES-INSIPIDUS; NEUTRAL SOLUTE CHANNEL; CHIP28 WATER CHANNEL; MOLECULAR CHARACTERIZATION; EFFERENT DUCTS; FUNCTIONAL EXPRESSION; PLASMA-MEMBRANE; VAS-DEFERENS; ADULT RATS AB The mammalian aquaporins (AQPs) are a family of 13 transmembrane channel proteins that are involved in the transport of water in numerous organs. In the male excurrent duct, the movement of fluid and solutes across the epithelium is essential for establishing the proper luminal environment in which sperm mature and are stored. AQP9 is abundantly expressed in the efferent ducts, the epididymis, and the vas deferens, where it could represent an important apical pathway for transmembrane water and solute movement. However, other organs in which water transport is critical, including the kidney, the lung, or the eye, express several different AQPs with a cell-specific pattern. To undertake a systematic analysis of the expression of known AQPs in the postnatal and adult rat epididymis, we examined the expression of their respective mRNAs in epithelial cells isolated by laser capture microdissection (LCM), and we determined their corresponding protein expression pattern by immunofluorescence and Western blotting. Our data show that, whereas AQP9 is the main AQP of the epididymis, the mRNA specific for Aqp2, 5, 7, and 11 are also expressed in epididymal epithelial cells. AQP5 protein colocalizes with AQP9 in the apical membrane of a subpopulation of principal cells in the corpus and cauda regions. Aqp2 mRNA was detected in epithelia[ cells after the second postnatal week and the amount significantly increased up to adulthood. However, AQP2 protein was detected only in the distal cauda of young rats (between the second and fourth postnatal week). No AQP2 protein was detected in the adult epididymis, indicating that posttranscriptional mechanisms are involved in the regulation of AQP2 expression. In addition, epididymal epithelial cells express significant amounts of the mRNAs coding for AQP7 and 11. No mRNA or protein for AQPs 0, 4, 6, and 8 were detectable in epithelial cells, and Aqp1 was detected in whole epididymal samples, but not in epithelial cells. Thanks to the recent development of microdissection technologies, our observations suggest that epididymal epithelial cells express several members of the AQP family with a region-specific pattern. AQPs may be involved not only in the transepithelial transport of water in the epididymis but also in the postnatal development of this organ, as suggested by the differential expression of AQP2. C1 Massachusetts Gen Hosp, Div Nephrol, Program Membrane Biol, Boston, MA 02114 USA. RP Da Silva, N (reprint author), Massachusetts Gen Hosp, Div Nephrol, Program Membrane Biol, Boston, MA 02114 USA. EM ndasilva@partners.org FU NIDDK NIH HHS [DK43351, DK57521, DK38452] NR 64 TC 47 Z9 48 U1 0 U2 2 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD FEB PY 2006 VL 74 IS 2 BP 427 EP 438 DI 10.1095/biolreprod.105.044735 PG 12 WC Reproductive Biology SC Reproductive Biology GA 005IU UT WOS:000234816600025 PM 16221990 ER PT J AU Oral, E Malhi, AS Muratoglu, OK AF Oral, E Malhi, AS Muratoglu, OK TI Mechanisms of decrease in fatigue crack propagation resistance in irradiated and melted UHMWPE SO BIOMATERIALS LA English DT Article DE polyethylene; arthroplasty; plasticity; electron beam; fatigue; cross-linking ID MOLECULAR-WEIGHT POLYETHYLENE; CROSS-LINKING; FREE-RADICALS; WEAR; RADIATION; HIP; BEHAVIOR; ALLOARTHROPLASTY; OSTEOLYSIS; DAMAGE AB Adhesive/abrasive wear in ultra-high molecular weight polyethylene (UHMWPE) has been minimized by radiation cross-linking. Irradiation is typically followed by melting to eliminate residual free radicals that cause oxidative embrittlement. Irradiation and subsequent melting reduce the strength and fatigue resistance of the polymer. We determined the radiation dose dependence and decoupled the effects of post-irradiation melting on the crystallinity, mechanical properties and fatigue crack propagation resistance of room temperature irradiated UHMWPE from those of irradiation alone. Stiffness and yield strength, were largely not affected by increasing radiation dose but were affected by changes in crystallinity, whereas plastic properties, ultimate tensile strength and elongation at break, were dominated at different radiation dose ranges by changes in radiation dose or crystallinity. Fatigue crack propagation resistance was shown to decrease with increase in radiation dose and with decrease in crystalline content. Morphology of fracture surfaces revealed loss of ductility with increase in radiation dose and more detrimental effects on ductility at lower radiation doses after post-irradiation melting. (c) 2005 Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Dept Orthopaed Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Muratoglu, OK (reprint author), Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Dept Orthopaed Surg, 55 Fruit St,GRJ 1206, Boston, MA 02114 USA. EM omuratoglu@partners.org FU NIAMS NIH HHS [R01 AR051142, R01 AR051142-01] NR 24 TC 126 Z9 131 U1 4 U2 17 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD FEB PY 2006 VL 27 IS 6 BP 917 EP 925 DI 10.1016/j.bomaterials.2005.06.025 PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 995JE UT WOS:000234095800012 PM 16105682 ER PT J AU Meng, XD Smith, RM Giesecke, AV Joung, JK Wolfe, SA AF Meng, XD Smith, RM Giesecke, AV Joung, JK Wolfe, SA TI Counter-selectable marker for bacterial-based interaction trap systems SO BIOTECHNIQUES LA English DT Article ID PROTEIN-PROTEIN INTERACTIONS; ZINC-FINGER PROTEINS; ONE-HYBRID SYSTEM; ESCHERICHIA-COLI; OROTIDINE-5'-PHOSPHATE DECARBOXYLASE; 3-HYBRID SYSTEM; 2-HYBRID SYSTEM; YEAST; DNA; SELECTION AB Counter-selectable markers can be used in two-hybrid systems to search libraries for a protein or compound that interferes with a macromoleculor interaction or to identify macromolecules from a population that cannot mediate a particular interaction. In this report, we describe the adaptation of the yeast URA3/5-FOA counter-selection system for use in bacterial interaction trap experiments. Two different URA3 reporter systems were developed that allow robust counter-selection: (i) a single copy F' episome reporter and (ii) a co-cistronic HIS3-URA3 reporter vector The HIS3-URA3 reporter can be used for either positive or negative selections in appropriate bacterial strains. These reagents extend the utility of the bacterial two-hybrid system as an alternative to its yeast-based counterpart. C1 Univ Massachusetts, Sch Med, Dept Biochem & Mol Pharmacol, Program Gene Funct & Express, Worcester, MA 01605 USA. Massachusetts Gen Hosp, Charlestown, MA USA. RP Wolfe, SA (reprint author), Univ Massachusetts, Sch Med, Dept Biochem & Mol Pharmacol, Program Gene Funct & Express, 364 Plantat St, Worcester, MA 01605 USA. EM scot.wolfe@umassmed.edu FU NIGMS NIH HHS [R01GM068110, R01GM072621]; NIH HHS [DP1 OD006862]; PHS HHS [R01GN969906] NR 26 TC 10 Z9 11 U1 0 U2 5 PU EATON PUBLISHING CO PI WESTBOROUGH PA ONE RESEARCH DRIVE, SUITE 400A, PO BOX 1070, WESTBOROUGH, MA 01581-6070 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD FEB PY 2006 VL 40 IS 2 BP 179 EP 184 DI 10.2144/000112049 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 012QX UT WOS:000235355300009 PM 16526407 ER PT J AU Evins, AE Demopulos, C Nierenberg, A Culhane, MA Eisner, L Sachs, G AF Evins, AE Demopulos, C Nierenberg, A Culhane, MA Eisner, L Sachs, G TI A double-blind, placebo-controlled trial of adjunctive donepezil in treatment-resistant mania SO BIPOLAR DISORDERS LA English DT Article DE acetylcholine; acetylcholinesterase inhibitor; bipolar affective disorder; donepezil; lithium; mania; valproate ID CYCLING BIPOLAR DISORDER; RATING-SCALE; LITHIUM; PHYSOSTIGMINE; VALPROATE; EFFICACY; DEPRESSION; DIVALPROEX; SYMPTOMS AB Introduction: Because there is a high rate of partial response to standard thymoleptic medication, novel augmentation strategies for treatment-resistant bipolar disorder are needed. In an open trial, donepezil augmentation was associated with improvement in manic symptoms in 9 of 11 subjects. Method: We conducted a 6-week, double-blind, placebo-controlled trial of donepezil for treatment-resistant bipolar mania. Eligible subjects had a Young Mania Rating Scale (YMRS) score of at least 15 despite two or more weeks of proven therapeutic levels of lithium or valproate. Subjects who completed the trial were eligible for an 8-week open trial of donepezil. Subjects were started on donepezil 5 mg/day and were eligible for dose increase to 10 mg/day after 4 weeks. Results: Twelve subjects were enrolled. Eleven subjects received at least 1 week of study medication and were included in the analysis. No subjects in the donepezil group (0/6) and 60% (3/5) in the placebo group met response criteria of > 30% reduction in YMRS score (Fisher's Exact p = 0.061). YMRS scores were higher at trial endpoint in the donepezil group 20.17 (3.66) compared with the placebo group [11.20 (4.60), Z = -2.476, p = 0.01]. There were no differences at trial endpoint in Hamilton Rating Scale for Depression (HAM-D) or Brief Psychiatric Rating Scale (BPRS) scores in either the intent-to-treat or the completer analyses. Conclusions: Donepezil does not appear to be an effective adjunctive treatment for refractory manic symptoms. The strength of the conclusion of this trial is limited by the possibility of a false-negative result due to the small sample. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Harvard Bipolar Res Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA. RP Evins, AE (reprint author), Erich Lindemann Mental Hlth Ctr, Freedom Trail Clin, Schizophrenia Res Program, 25 Staniford St, Boston, MA 02114 USA. EM a_eden_evins@hms.harvard.edu NR 26 TC 22 Z9 23 U1 2 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD FEB PY 2006 VL 8 IS 1 BP 75 EP 80 PG 6 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 001XC UT WOS:000234575000008 ER PT J AU Gilbert, GE AF Gilbert, GE TI Portable tissue factor to the rescue SO BLOOD LA English DT Editorial Material ID BINDING; MOUSE C1 VA Boston Healthcare Syst, Boston, MA USA. RP Gilbert, GE (reprint author), VA Boston Healthcare Syst, Boston, MA USA. NR 5 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 FEB 1 PY 2006 VL 107 IS 3 BP 856 EP 857 PG 2 WC Hematology SC Hematology GA 007TC UT WOS:000234991600011 ER PT J AU Mitsiades, CS Mitsiades, NS McMullan, CJ Poulaki, V Kung, AL Davies, FE Morgan, G Akiyama, M Shringarpure, R Munshi, NC Richardson, PG Hideshima, T Chauhan, D Gu, XS Bailey, C Joseph, M Libermann, TA Rosen, NS Anderson, KC AF Mitsiades, CS Mitsiades, NS McMullan, CJ Poulaki, V Kung, AL Davies, FE Morgan, G Akiyama, M Shringarpure, R Munshi, NC Richardson, PG Hideshima, T Chauhan, D Gu, XS Bailey, C Joseph, M Libermann, TA Rosen, NS Anderson, KC TI Antimyeloma activity of heat shock protein-90 inhibition SO BLOOD LA English DT Article ID MULTIPLE-MYELOMA CELLS; NF-KAPPA-B; PHASE-I; THERAPEUTIC APPLICATIONS; CLINICAL-IMPLICATIONS; ANDROGEN RECEPTOR; BIOLOGIC SEQUELAE; SOLID TUMORS; PROTEASOME; CANCER AB We show that multiple myeloma (MM), the second most commonly diagnosed hematologic malignancy, is responsive to hsp90 inhibitors in vitro and in a clinically relevant orthotopic in vivo model, even though this disease does not depend on HER2/neu, bcr/abl, androgen or estrogen receptors, or other hsp90 chaperoning clients which are hallmarks of tumor types traditionally viewed as attractive clinical settings for use of hsp90 inhibitors, such as the geldanamycin analog 17-AAG. This class of agents simultaneously suppresses in MM cells the expression and/or function of multiple levels of insulin-like growth factor receptor (IGF-1R) and interleukin-6 receptor (IL-6R) signaling (eg, IKK/NF-kappa B, PI-3K/Akt, and Raf/MAPK) and downstream effectors (eg, proteasome, telomerase, and HIF-1 alpha activities). These pleiotropic proapoptotic effects allow hsp90 inhibitors to abrogate bone marrow stromal cell-derived protection on MM tumor cells, and sensitize them to other anticancer agents, including cytotoxic chemotherapy and the proteasome inhibitor bortezomib. These results indicate that hsp90 can be targeted therapeutically in neoplasias that may not express or depend on molecules previously considered to be the main hsp90 client proteins. This suggests a more general role for hsp90 in chaperoning tumor- or tissue-type-specific constellations of client proteins with critical involvement in proliferative and antiapoptotic cellular responses, and paves the way for more extensive future therapeutic applications of hsp90 inhibition in diverse neoplasias, including MM. C1 Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Dept Cell Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Royal Marsden Hosp, Sutton, Surrey, England. Inst Canc Res, Sutton, Surrey, England. Harvard Univ, Beth Israel Deaconess Med Ctr, Inst Med, Genom Ctr, Boston, MA 02215 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Mitsiades, CS (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, 44 Binney St, Boston, MA 02115 USA. EM constantine_mitsiades@dfci.harvard.edu; kenneth_anderson@dfci.harvard.edu RI Libermann, Towia/F-9866-2010; OI Libermann, Towia/0000-0002-4006-8179; Kung, Andrew/0000-0002-9091-488X FU PHS HHS [P0-1 78378, R0-1 50947] NR 46 TC 231 Z9 234 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 1 PY 2006 VL 107 IS 3 BP 1092 EP 1100 DI 10.1182/blood-2005-03-1158 PG 9 WC Hematology SC Hematology GA 007TC UT WOS:000234991600045 PM 16234364 ER PT J AU Liersch, R Nay, F Lu, LG Detmar, M AF Liersch, R Nay, F Lu, LG Detmar, M TI Induction of lymphatic endothelial cell differentiation in embryoid bodies SO BLOOD LA English DT Article ID STEM-CELLS; VESSEL DEVELOPMENT; SYSTEM; ANGIOGENESIS; EXPRESSION; RECEPTOR-3; PROX1; VEINS; MICE; PIG AB The molecular mechanisms that regulate the formation of the lymphatic vascular system remain poorly characterized. Whereas studies in embryonic stem (ES) cells have provided major new insights into the mechanisms of blood vessel formation, the development of lymphatic endothelium has not been previously observed. We established embryoid bodies (EBs) from murine ES cells in the presence or absence of lymphangiogenic growth factors. We found that lymphatic endothelial cells develop at day 18 after EB formation. These cells express CD31 and the lymphatic lineage markers Prox-1 and Lyve-1, but not the vascular marker MECA-32, and they frequently sprout from preexisting blood vessels. Lymphatic vessel formation was potently promoted by VEGF-A and VEGF-C but not by bFGF. Our results reveal, for the first time, that ES cells can differentiate into lymphatic endothelial cells, and they identify the EB assay as a powerful new tool to dissect the molecular mechanisms that control lymphatic vessel formation. C1 ETH, Inst Pharmaceut Sci, CH-8093 Zurich, Switzerland. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Detmar, M (reprint author), ETH, Inst Pharmaceut Sci, Wolfgang Pauli Str 10,HCI H303, CH-8093 Zurich, Switzerland. EM michael.detmar@pharma.ethz.ch FU NCI NIH HHS [CA92644, CA86410, CA69184] NR 25 TC 36 Z9 43 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 1 PY 2006 VL 107 IS 3 BP 1214 EP 1216 DI 10.1182/blood-2005-08-3400 PG 3 WC Hematology SC Hematology GA 007TC UT WOS:000234991600061 PM 16195336 ER PT J AU Rizzo, JD Wingard, JR Tichelli, A Lee, SJ Van Lint, MT Burns, LJ Davies, SM Ferrara, JLM Socie, G AF Rizzo, JD Wingard, JR Tichelli, A Lee, SJ Van Lint, MT Burns, LJ Davies, SM Ferrara, JLM Socie, G TI Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation: Joint recommendations of the European Group for Blood and Marrow Transplantation, Center for International Blood and Marrow Transplant Research, and the American Society for Blood and Marrow Transplantation (EBMT/CIBMTR/ASBMT) SO BONE MARROW TRANSPLANTATION LA English DT Article DE late effects; HCT (hematopoietic cell transplantation); screening; prevention ID DEPRESSION SCALE; HOSPITAL ANXIETY; CANCER AB More than 40 000 hematopoietic cell transplants (HCTs) are performed worldwide each year. With improvements in transplant technology, larger numbers of transplant recipients survive free of the disease for which they were transplanted. However, there are late complications that can cause substantial morbidity. Many survivors are no longer under the care of transplant centers and many community health-care providers may be unfamiliar with health matters relevant to HCT. The Center for International Blood and Marrow Transplant Research (CIBMTR), European Group for Blood and Marrow Transplantation (EBMT), and American Society for Blood and Marrow Transplantation (ASBMT) have developed these recommendations to offer care providers suggested screening and prevention practices for autologous and allogeneic HCT survivors. C1 Hop St Louis, Dept Hematol, F-75475 Paris 10, France. Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. Univ Florida, Coll Med, Gainesville, FL USA. Kantonsspital, CH-4031 Basel, Switzerland. Dana Farber Canc Inst, Boston, MA 02115 USA. San Martino Hosp, Genoa, Italy. Univ Minnesota, Minneapolis, MN USA. Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. Univ Michigan, Ann Arbor, MI 48109 USA. RP Socie, G (reprint author), Hop St Louis, Dept Hematol, 1 Ave Claude Vellefaux, F-75475 Paris 10, France. EM gerard.socie@paris7.jussieu.fr FU NCI NIH HHS [U24-CA76518, K23-CA-82350] NR 17 TC 49 Z9 52 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD FEB PY 2006 VL 37 IS 3 BP 249 EP 261 DI 10.1038/sj.bmt.1705243 PG 13 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 005SN UT WOS:000234844200002 PM 16435004 ER PT J AU Schmahmann, JD Caplan, D AF Schmahmann, JD Caplan, D TI Cognition, emotion and the cerebellum SO BRAIN LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Neurol, Ataxia Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Cognit Behav Neurol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Schmahmann, JD (reprint author), Massachusetts Gen Hosp, Dept Neurol, Ataxia Unit, Boston, MA 02114 USA. NR 5 TC 200 Z9 211 U1 2 U2 17 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD FEB PY 2006 VL 129 BP 290 EP 292 DI 10.1093/brain/awh729 PN 2 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 007JR UT WOS:000234965500003 PM 16434422 ER PT J AU Caplan, D DeDe, G Brownell, H AF Caplan, D DeDe, G Brownell, H TI Effects of syntactic features on sentence-picture matching in Broca's aphasics: A reply to Drai and Grodzinksy (2005) SO BRAIN AND LANGUAGE LA English DT Editorial Material DE Broca's aphasia; sentence comprehension ID COMPREHENSION PERFORMANCE; SINGLE PATTERN; AGRAMMATISM; ISSUES AB We reanalyzed the data in Drai and Grodzinksy (2005), considering individual patients' responses to different sentence types to be non-independent events. The analyses revealed effects of two of the three factors identified by Drai and Grodzinsky-constituent movement and passive mood. The result is inconsistent with the trace deletion hypothesis; we conclude that features of syntactic structure other than constituent movement are relevant to understanding performance variation in patients with Broca's aphasia. (c) 2005 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Neuropsychol Lab, Boston, MA 02114 USA. Boston Univ, Dept Hlth Sci, Sargent Coll Allied Hlth Profess, Boston, MA 02215 USA. Boston Coll, Dept Psychol, Boston, MA USA. Boston Univ, Sch Med, Goodglass Aphasia Res Ctr, Boston, MA 02118 USA. Brandeis Univ, Volen Natl Ctr Complex Syst, Waltham, MA 02254 USA. RP Caplan, D (reprint author), Massachusetts Gen Hosp, Neuropsychol Lab, Boston, MA 02114 USA. EM dcaplan@partners.org FU NIDCD NIH HHS [P30DC0520702, DC05432, DC04608] NR 21 TC 0 Z9 1 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 FEB PY 2006 VL 96 IS 2 BP 129 EP 134 DI 10.1016/j.bandl.2005.06.003 PG 6 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 017MO UT WOS:000235697900002 PM 16054680 ER PT J AU Pritchard, KI Goss, PE Shepherd, L AF Pritchard, K. I. Goss, P. E. Shepherd, L. TI The extended adjuvant NCIC CTG MA.17 trials: Initial and rerandomization studies SO BREAST LA English DT Article DE adjuvant therapy; breast cancer; letrozole; postmenopausal; tamoxifen ID ADVANCED BREAST-CANCER; POSTMENOPAUSAL WOMEN; RANDOMIZED-TRIAL; AROMATASE INHIBITORS; UPDATED FINDINGS; PHASE-III; TAMOXIFEN; THERAPY; LETROZOLE; RECURRENCE AB Based upon the results of the NCIC CTG MA.17 trial, letrozole has become the only approved aromatase inhibitor (AI) in the extended adjuvant treatment setting following 5 years of tamoxifen therapy. In this trial, the Al letrozole decreased the overall risk of breast cancer recurrence by 42% compared with placebo in postmenopausal women completing 5 years of tamoxifen. The benefit of letrozole exceeded the expected difference after median follow-up of more than 2 years and led to the unblinding of the trial. The 30-month updated analyses found a 4.8%, 4-year disease-free survival improvement overall, an improvement in distant disease-free recurrence in both node-negative and node-positive patients, and a survival benefit for node-positive patients. Generally well tolerated, letrozole caused some adverse events including arthralgias and osteoporosis. However, results from the Zometa-Femara adjuvant synergy trial (Z-FAST) suggest that zoledronic acid, when used concomitantly with letrozole, is able to manage bone toss in postmenopausal women with early breast cancer. (c) 2006 Elsevier Ltd. All rights reserved. C1 Toronto Sunnybrook Reg Canc Ctr, Div Clin Trials & Epidemiol, Toronto, ON M4N 3M5, Canada. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Queens Univ, Canc Res Inst, Kingston, ON K7L 3N6, Canada. RP Pritchard, KI (reprint author), Toronto Sunnybrook Reg Canc Ctr, Div Clin Trials & Epidemiol, 2075 Bayview Ave,N York, Toronto, ON M4N 3M5, Canada. EM kathy.pritchard@sw.ca NR 27 TC 6 Z9 6 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 0960-9776 J9 BREAST JI Breast PD FEB PY 2006 VL 15 SU 1 BP S14 EP S20 DI 10.1016/j.breast.2006.01.002 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 058HU UT WOS:000238656900003 PM 16500236 ER PT J AU Sampogna, F Chren, MM Melchi, CF Pasquini, P Tabolli, S Abeni, D AF Sampogna, F Chren, MM Melchi, CF Pasquini, P Tabolli, S Abeni, D CA Improve Study Grp TI Age, gender, quality of life and psychological distress in patients hospitalized with psoriasis SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article DE age; gender; psoriasis; psychological distress; quality of life ID SELF-ADMINISTERED PSORIASIS; PSYCHIATRIC MORBIDITY; SKIN DISEASES; DERMATOLOGICAL OUTPATIENTS; ATOPIC-DERMATITIS; STRESS INVENTORY; SEVERITY INDEX; BODY-IMAGE; IMPACT; VALIDITY AB Background Psoriasis has a great impact on the quality of life of patients, and the ageing population is an important public health issue. Objectives To investigate whether older patients with psoriasis have a different impairment in quality of life compared with younger patients, considering level of severity, duration of disease, gender and psychological distress. Methods The study was performed between February 2000 and February 2002 at the inpatient wards of the Dermatological Institute IDI-IRCCS, Rome, Italy, in the framework of a large project on clinical, epidemiological, emotional and quality of life aspects of psoriasis (IMPROVE study). This is a hospital-based cross-sectional study, with measures of quality of life (Skindex-29, Dermatology Life Quality Index and Psoriasis Disability Index) and of psychological distress, generic (12-item General Health Questionnaire) and psoriasis-related (Psoriasis Life Stress Inventory), all self-assessed by patients. We compared the mean scores of each quality of life instrument in patients aged < 65 years and >= 65 years, in subsets of patients based on clinical and sociodemographic characteristics. Results We analysed 936 patients hospitalized at IDI-IRCCS with a diagnosis of psoriasis. Quality of life was significantly more impaired in the older group for all the Skindex-29 scales, and psychological distress was higher in older patients. In particular, older women suffering from anxiety or depression had the greatest impairment in quality of life. The results were somewhat different using the other quality of life instruments. Conclusions These results should alert dermatologists that similar levels of clinical severity in psoriasis may be associated with different levels of quality of life and psychological distress of patients. Particular attention should be devoted to older patients, and especially to older women. C1 IRCCS, IDI, Hlth Serv Res Unit, I-00167 Rome, Italy. IRCCS, IDI, Dermatol Unit VIII, I-00167 Rome, Italy. IRCCS, IDI, Epidemiol Unit, I-00167 Rome, Italy. San Francisco Vet Affairs Med Ctr, HSR&D Res Enhancement Award Program, San Francisco, CA USA. Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. RP Sampogna, F (reprint author), IRCCS, IDI, Hlth Serv Res Unit, Via Monti Creta 104, I-00167 Rome, Italy. EM f.sampogna@idi.it OI Abeni, Damiano/0000-0002-0167-7617 NR 44 TC 76 Z9 82 U1 2 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-0963 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD FEB PY 2006 VL 154 IS 2 BP 325 EP 331 DI 10.1111/j.1365-2133.2005.06909.x PG 7 WC Dermatology SC Dermatology GA 003RN UT WOS:000234699400019 PM 16433804 ER PT J AU Yasui, H Hideshima, T Richardson, PG Anderson, KC AF Yasui, H Hideshima, T Richardson, PG Anderson, KC TI Novel therapeutic strategies targeting growth factor signalling cascades in multiple myeloma SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Review DE multiple myeloma; growth factor; bone marrow microenvironment; signalling cascade ID NF-KAPPA-B; IN-VIVO MODEL; BONE-MARROW MICROENVIRONMENT; OVERCOMES DRUG-RESISTANCE; TRANSFERASE INHIBITOR R115777; INFLAMMATORY PROTEIN 1-ALPHA; MALIGNANT PLASMA-CELLS; ANTITUMOR-ACTIVITY; HEMATOLOGIC MALIGNANCIES; INTERLEUKIN-6 RECEPTOR AB Multiple myeloma (MM) remains largely incurable despite conventional and high-dose therapies, and novel biologically based treatment approaches are urgently required. Recent studies demonstrate that various growth factors including interleukin (IL)-6, insulin-like growth factor (IGF)-1, vascular endothelial growth factor (VEGF), the tumour necrosis factor (TNF) family proteins, Wnt, and Notch family members play an important role in MM pathogenesis, and mediate tumour cell proliferation, drug resistance and migration in the bone marrow (BM) milieu. Targeting growth factors, therefore, represents a promising therapeutic strategy in MM. Novel agents inhibiting growth factor signalling cascades can target ligands, receptors, and/or downstream signalling cascade proteins in MM cells and the BM microenvironment. Combinations of these novel agents with conventional therapies may not only enhance cytotoxicity, but also avoid drug resistance and thereby improve patient outcome in MM. C1 Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeoloma Ctr, Boston, MA 02115 USA. Sapporo Med Univ, Dept Internal Med, Sapporo, Hokkaido, Japan. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeoloma Ctr, Mayer 557, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu FU NCI NIH HHS [IP50 CA10070-01, P01 CA78378, R0-1 CA50947] NR 107 TC 68 Z9 71 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD FEB PY 2006 VL 132 IS 4 BP 385 EP 397 DI 10.1111/j.1365-2141.2005.05860.x PG 13 WC Hematology SC Hematology GA 001NP UT WOS:000234543900001 PM 16412014 ER PT J AU Iosifescu, DV Renshaw, PF Lyoo, IK Lee, HK Perlis, RH Papakostas, GI Nierenberg, AA Fava, M AF Iosifescu, DV Renshaw, PF Lyoo, IK Lee, HK Perlis, RH Papakostas, GI Nierenberg, AA Fava, M TI Brain white-matter hyperintensities and treatment outcome in major depressive disorder SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID LATE-LIFE DEPRESSION; RISK-FACTORS; SIGNAL HYPERINTENSITIES; FOLLOW-UP; LESIONS; DISEASE; LOCALIZATION; SYMPTOMS; ADULTS; AGE AB Background An increased incidence of brain white-matter hyperintensities has been described in major depressive disorder, but the impact of such hyperintensities on treatment outcome is still controversial. Aims To investigate the relationship of brain white-matter hyperintensities with cardiovascular risk factors and with treatment outcome in younger people with major depressive disorder. Method We assessed brain white-matter hyperintensities and cardiovascular risk factors in 84 people with major depressive disorder prior to initiating antidepressant treatment. We also assessed hyperintensities in 35 matched controls. Results We found no significant difference in the prevalence of white-matter hyperintensities between the depression and the control groups. Left hemisphere subcortical hyperintensities correlated with lower rates of treatment response. We found no correlation between global hyperintensity measures and clinical outcome. Brain white-matter hyperintensities correlated with hypertension and age and with total cardiovascular risk score. Conclusions Subcortical white-matter hyperintensities in the left hemisphere (but not in other brain areas) may be associated with poor response to antidepressant treatment in major depression. C1 Harvard Univ, Massachusetts Gen Hosp, Depress Clin & Res Program, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, McLean Hosp, Brain Imaging Ctr, Boston, MA USA. Sungkyunkwan Univ, Dept Radiol, Seoul, South Korea. RP Iosifescu, DV (reprint author), Harvard Univ, Massachusetts Gen Hosp, Depress Clin & Res Program, Sch Med, 50 Staniford St,Suite 401, Boston, MA 02114 USA. EM diosifescu@partners.org RI Papakostas, George/I-6905-2013 OI Papakostas, George/0000-0002-2465-5103 FU NIMH NIH HHS [MH58681, R01-MH48483] NR 29 TC 34 Z9 34 U1 2 U2 4 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON SW1X 8PG, ENGLAND SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD FEB PY 2006 VL 188 BP 180 EP 185 DI 10.1192/bjp.188.2.180 PG 6 WC Psychiatry SC Psychiatry GA 010PM UT WOS:000235206600014 PM 16449707 ER PT J AU Potter, MJ Szabo, SM Sarraf, D Michels, R Schmidt-Erfurth, U AF Potter, MJ Szabo, SM Sarraf, D Michels, R Schmidt-Erfurth, U TI Photodynamic therapy for subretinal neovascularization in type 2A idiopathic juxtafoveolar telangiectasis SO CANADIAN JOURNAL OF OPHTHALMOLOGY-JOURNAL CANADIEN D OPHTALMOLOGIE LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol DE idiopathic juxtafoveolar retinal telangiectasis; subretinal neovascularization; photodynamic therapy; verteporfin ID RETINAL TELANGIECTASIS; MEMBRANE; VERTEPORFIN AB Background: Photodynamic therapy (PDT) with verteporfin is now the standard of care worldwide for the treatment of choroidal neovascularization, but has been used only rarely in those with subretinal neovascular membranes (SRNVM) due to type 2A idiopathic juxtafoveolar retinal telangiectasis (IJT). We performed a retrospective study to examine the outcome of patients treated with PDT for SRNVM secondary to IJT. Methods: Retrospective interventional case series of 7 eyes of 6 IJT patients with SRNVMs treated with PDT Ophthalmic examination and fluorescein angiography were performed before treatment, with retreatment every 3 months as needed. The main outcome was the proportion of patients avoiding vision loss (change of +/- 4 letters, or better). Results: Baseline Snellen acuity ranged from 20/40 to 20/400 (median 20/80). Mean follow-up was 21 months. Patients received 2.4 treatments on average. Five of 7 patients avoided vision loss; acuity improved in 3 eyes (a I line improvement), stayed the same in 2 eyes ( 4 letters) and decreased in 2 eyes ( >= I line decrease) over time. Median final acuity was 20/80. Five of 7 eyes had final acuities of >= 20/200. No leakage was observed in any eyes following cessation of treatment. Interpretation: Previously reported outcomes for SRNVM in type 2A IJT, in both natural history and after laser or surgical treatment, have been uniformly poor. PDT may be considered for these patients due to its excellent safety profile and clinically favorable outcomes in this study. C1 Univ British Columbia, Dept Ophthalmol, Vancouver, BC V5Z 1M9, Canada. Univ Calif Los Angeles, Jules Stein Eye Inst, Kaiser Permanente, King Drew Med Ctr, Los Angeles, CA 90024 USA. Greater Los Angles VA Healthcare Ctr, Los Angeles, CA USA. Univ Vienna, Dept Ophthalmol, Vienna, Austria. Univ Eye Hosp, Lubeck, Germany. RP Potter, MJ (reprint author), Sect B-2550 Willow St, Vancouver, BC V5Z 3N9, Canada. EM mpotter@interchange.ubc.ca NR 10 TC 18 Z9 19 U1 0 U2 0 PU CANADIAN OPHTHAL SOC PI OTTAWA PA 1525 CARLING AVE SUITE 610, OTTAWA, ONTARIO K1Z 8R9, CANADA SN 0008-4182 J9 CAN J OPHTHALMOL JI Can. J. Opthalmol.-J. Can. Opthalmol. PD FEB PY 2006 VL 41 IS 1 BP 34 EP 37 PG 4 WC Ophthalmology SC Ophthalmology GA 021FK UT WOS:000235968900004 PM 16462869 ER PT J AU Thakker, MM Ray, S AF Thakker, MM Ray, S TI Vision-limiting complications in open-globe injuries SO CANADIAN JOURNAL OF OPHTHALMOLOGY-JOURNAL CANADIEN D OPHTALMOLOGIE LA English DT Article DE open globe; ocular trauma; vision; complication; ruptured globe ID PERFORATING EYE INJURIES; PENETRATING OCULAR INJURIES; RISK-FACTORS; TRAUMA; SYSTEM; SURVIVAL AB Background: To correlate vision-limiting complications of open-globe trauma with anatomical zone and mechanism of injury. Methods: Retrospective review of 235 patients with open-globe injuries at the Massachusetts Eye and Ear Infirmary. Vision-limiting complications were assessed at 2 to 3 months after the injury. Results: Traumatic cataracts and corneal scarring were the most prevalent vision-limiting complications in patients with zone I (cornea-only) lacerations. The most common vision-limiting factors in eyes with zones 11 and III lacerations (involving sclera) were cataracts and retinal detachments. In patients with penetrating injuries, predominant vision-limiting findings were traumatic cataracts and corneal scarring. In patients with blunt-force ruptures, leading causes were traumatic cataracts and retinal detachments. There were increased rates of phthisis and enucleation surgery in patients with ruptures and zones 11 and III injuries. In cases of penetrating and zone I injuries, significantly more patients achieved visual acuities better than 20/50 when compared with eyes that had ruptures or zones 11 and III injuries. Interpretation: Traumatic cataracts were the most common vision-limiting factor in all subcategories of open-globe injuries. Injuries in zones 1111 and III and blunt-force ruptures were associated with increased rates of retinal detachments, phthisis, and enucleation, contributing to the poorer visual prognosis in these patients. C1 Univ Washington, Dept Ophthalmol, Seattle, WA 98195 USA. Harvard Univ, Sch Med, Retina Serv, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. RP Thakker, MM (reprint author), Univ Washington, Dept Ophthalmol, Box 356485, Seattle, WA 98195 USA. EM mthakker@u.washington.edu NR 23 TC 22 Z9 23 U1 0 U2 0 PU CANADIAN OPHTHAL SOC PI OTTAWA PA 1525 CARLING AVE SUITE 610, OTTAWA, ONTARIO K1Z 8R9, CANADA SN 0008-4182 J9 CAN J OPHTHALMOL JI Can. J. Opthalmol.-J. Can. Opthalmol. PD FEB PY 2006 VL 41 IS 1 BP 86 EP 92 PG 7 WC Ophthalmology SC Ophthalmology GA 021FK UT WOS:000235968900015 PM 16462880 ER PT J AU Gianni, L Panzini, I Li, SG Gelber, RD Collins, J Holmberg, SB Crivellari, D Castiglione-Gertsch, M Goldhirsch, A Coates, AS Ravaioli, A AF Gianni, L Panzini, I Li, SG Gelber, RD Collins, J Holmberg, SB Crivellari, D Castiglione-Gertsch, M Goldhirsch, A Coates, AS Ravaioli, A CA IBCSG TI Ocular toxicity during adjuvant chemoendocrine therapy for early breast cancer - Results from International Breast Cancer Study Group Trials SO CANCER LA English DT Article DE ocular; ocular toxicity; breast cancer; chemoendocrine therapy; International Breast Cancer Study Group (IBCSG); tamoxifen; toremifene; endocrine therapy ID LOW-DOSE TAMOXIFEN; CHLORIDE CHANNELS; RANDOMIZED-TRIALS; DRUG-THERAPY; LOW DOSAGE; LONG-TERM; RETINOPATHY; TOREMIFENE; CATARACT; WOMEN AB BACKGROUND. Others have reported ocular toxicity after adjuvant chemoendocrine therapy, but this study looked at ocular toxicity in similarly treated patients from large randomized clinical trials. METHODS. Information was retrieved on incidence and timing of ocular toxicity from the International Breast Cancer Study Group (IBCSG) database of 4948 eligible patients randomized to receive tamoxifen or toremifene alone or in combination with chemotherapy (either concurrently or sequentially). Case reports of patients with ocular toxicity were evaluated to determine whether ocular toxicity occurred during chemotherapy and/or hormonal therapy. Additional information was obtained from participating institutions for patients in whom ocular toxicity occurred after chemotherapy but during administration of tamoxifen or toremifene. RESULTS. Ocular toxicity was reported in 538 of 4948 (10.9%) patients during adjuvant treatment, mainly during chemotherapy. Forty-five of 4948 (0.9%) patients had Ocular toxicity during hormone therapy alone, but only 30 (0.6%) patients had Ocular toxicity reported either without receiving any chemotherapy or beyond 3 months after completing chemotherapy and, thus, possibly related to tamoxifen or toremifene. In 3 cases, retinal alterations, without typical aspects of tamoxifen toxicity, were reported; 4 patients had cataract (2 bilateral), 12 impaired visual acuity, 10 ocular irritation, 1 optical neuritis, and the rest had other symptoms. CONCLUSION. Ocular toxicity during adjuvant therapy is a common side effect mainly represented by irritative symptoms due to chemotherapy. By contrast, ocular toxicity during hormonal therapy is rare and does not appear to justify a regular program of ocular examination. However, patients should be informed of this rare side effect so that they may seek prompt ophthalmic evaluation for ocular complaints. C1 Azienda USL Rimini, Div Oncol & Ematol, Osped Infermi, I-47037 Rimini, Italy. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Int Breast Canc Study Grp, Ctr Stat, Boston, MA 02115 USA. Harvard Univ, Dept Biostat, Sch Publ Hlth, Boston, MA 02115 USA. Frontier Sci & Technol Res Fdn Inc, Boston, MA USA. Royal Melbourne Hosp, Dept Surg, Melbourne, Vic, Australia. SU Moelndals Hosp, Dept Surg, Molndal, Sweden. Ctr Riferimento Oncol, I-33081 Aviano, Italy. Coordinating Ctr, Int Breast Canc Study Grp, Bern, Switzerland. European Inst Oncol, Milan, Italy. Oncol Inst So Switzerland, Lugano, Switzerland. Canc Council Australia, Sydney, NSW, Australia. Univ Sydney, Sydney, NSW 2006, Australia. RP Gianni, L (reprint author), Azienda USL Rimini, Div Oncol & Ematol, Osped Infermi, Via Settembrini 2, I-47037 Rimini, Italy. EM lgianni@auslrn.net FU NCI NIH HHS [CA-75362] NR 61 TC 28 Z9 28 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD FEB 1 PY 2006 VL 106 IS 3 BP 505 EP 513 DI 10.1002/cncr.21651 PG 9 WC Oncology SC Oncology GA 005LC UT WOS:000234822700003 PM 16369994 ER PT J AU Tefferi, A Lasho, TL Schwager, SM Strand, JS Elliott, M Mesa, R Li, CY Wadleigh, M Lee, SJ Gilliland, DG AF Tefferi, A Lasho, TL Schwager, SM Strand, JS Elliott, M Mesa, R Li, CY Wadleigh, M Lee, SJ Gilliland, DG TI The clinical phenotype of wild-type, heterozygous, and homozygous JAK2(V617F) in polycythemia vera SO CANCER LA English DT Article DE polycythemia vera; JAK2(V617F); mutant allele; myeloid cells; heterozygotes; homozygotes ID CHRONIC MYELOPROLIFERATIVE DISORDERS; TYROSINE KINASE JAK2; MYELOID METAPLASIA; MUTATION; MYELOFIBROSIS AB BACKGROUND. Several studies have recently reported on the occurrence of a JAK2(V617F) mutation in myeloid cells from the majority of patients with polycythemia vera (PV). The clinical relevance of this novel observation currently is under study. METHODS. in a single institutional study, mutation screening for JAK(V617F) was performed in DNA derived from archived blood granulocytes from 63 consecutive patients with PV in whom current diagnostic criteria were strictly applied and the diagnosis confirmed by bone marrow histology. RESULTS. The JAK2(V617F) mutant allele was detected in 58 of the 63 patients (92%) with 21% homozygosity. The clinical phenotype of the five patients with the wild-type allele was otherwise typical for the disease. A statistical comparison between JAK2(V617F) heterozygotes (n = 45 patients) and homozygotes (n = 13 patients) did not reveal any significant associations with regard to age, gender, leukocyte or platelet count at the time of diagnosis, duration of disease, or the incidences of thrombosis or bleeding. However, compared with their heterozygote counterparts, JAK2(V617F) homozygote patients displayed a significantly higher hemoglobin level at the time of diagnosis (P = 0.001), an increased incidence of pruritus (69% vs. 38%; P = 0.04), a higher rate of fibrotic transformation (23% vs. 2%; P = 0.009), and higher PRV-1 transcript levels in their blood granulocytes (P = 0.07). CONCLUSIONS. The results of the current clinical study support previous laboratory observations that link JAK2(V617F) with the PV phenotype by demonstrating a mutant allele dose effect on erythrocytosis and clinical and laboratory features characteristic of PV. C1 Mayo Clin, Div Hematol & Lab Med, Rochester, MN 55905 USA. Harvard Univ, Sch Med, Dept Oncol, Dana Farber Canc Inst, Boston, MA USA. RP Tefferi, A (reprint author), Mayo Clin, Div Hematol & Lab Med, 200 1st St SW, Rochester, MN 55905 USA. EM tefferi.ayalew@mayo.edu NR 14 TC 127 Z9 142 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 FEB 1 PY 2006 VL 106 IS 3 BP 631 EP 635 DI 10.1002/cncr.21645 PG 5 WC Oncology SC Oncology GA 005LC UT WOS:000234822700018 PM 16369984 ER PT J AU Barbeau, EM Li, Y Calderon, P Hartman, C Quinn, M Markkanen, P Roelofs, C Frazier, L Levenstein, C AF Barbeau, EM Li, Y Calderon, P Hartman, C Quinn, M Markkanen, P Roelofs, C Frazier, L Levenstein, C TI Results of a union-based smoking cessation intervention for apprentice iron workers (United States) SO CANCER CAUSES & CONTROL LA English DT Article DE smoking cessation; social inequalities; worksite health promotion; labor unions ID BLUE-COLLAR WORKERS; CONSTRUCTION-INDUSTRY; CIGARETTE-SMOKING; HEALTH PROMOTION; OCCUPATION; WORKPLACE; PROGRAMS; CANCER; TRIAL; PREVALENCE AB Objective Blue-collar workers are more likely to smoke, smoke more heavily, and have less success in quitting compared to white-collar workers, and this occupational gap is growing over time. Effective smoking cessation interventions among blue-collar workers are needed to address growing class-based disparities. Methods We used a pre-post study design to test feasibility and effect size of a smoking cessation trial in a union apprenticeship training program for iron workers (n=337). The 4-month intervention drew upon a health promotion-health protection model for smoking cessation among blue-collar workers. We conducted pairwise analyses to assess pre-post intervention differences in 7-day point prevalence smoking abstinence measured 1 month after intervention was completed. Additional secondary outcomes, including smoking frequency, intensity, intention and self-efficacy to quit, were also assessed. Results Baseline smoking prevalence was 41%. We observed a 19.4% post-intervention quit rate among baseline smokers. There were statistically significant positive changes pre- and post-intervention in intention to quit smoking, self-efficacy to quit, and a reduction in the number of days smoked. Participation in pro-active intervention components was associated with a three-fold (OR = 3.0, 1.15, 7.83) increase in the likelihood of quitting. Overall, participation in intervention components was low. Conclusions Labor union apprenticeship programs represent a promising venue for smoking cessation interventions, particularly those that draw upon a health promotion-health protection model. C1 Dana Farber Canc Inst, Ctr Community Based, Boston, MA 02115 USA. RP Barbeau, EM (reprint author), Dana Farber Canc Inst, Ctr Community Based, 44 Binney St, Boston, MA 02115 USA. EM elizabeth_barbeau@dfci.harvard.edu NR 43 TC 20 Z9 20 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD FEB PY 2006 VL 17 IS 1 BP 53 EP 61 DI 10.1007/s10552-005-0271-0 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 005MB UT WOS:000234825600008 PM 16411053 ER PT J AU Bennett, GG Wolin, KY Goodman, M Samplin-Salgado, M Carter, P Dutton, S Hill, R Emmons, K AF Bennett, GG Wolin, KY Goodman, M Samplin-Salgado, M Carter, P Dutton, S Hill, R Emmons, K TI Attitudes regarding overweight, exercise, and health among Blacks (United States) SO CANCER CAUSES & CONTROL LA English DT Article DE Blacks/African Americans; body weight; physical activity; risk reduction behavior ID AFRICAN-AMERICAN WOMEN; WEIGHT-RELATED ATTITUDES; SELF-REPORTED WEIGHT; PHYSICAL-ACTIVITY; US ADULTS; SOCIOECONOMIC-STATUS; LOSS PROGRAM; WHITE WOMEN; LOSE WEIGHT; BODY-IMAGE AB Objective To investigate Blacks' views regarding the connections among overweight, exercise, and health. Methods A national randomized telephone survey of 986 US Blacks, conducted between 6 July 2004 and 15 July 2004. Results The majority (65%) of respondents reported their weight as average or underweight. Most participants also reported being regularly physically active in the last month (84.5%). The majority of participants reported believing that it is possible to be overweight and healthy. Most acknowledged the connection between exercise and health, and just over half of respondents identified the association between overweight and cancer risk. There was little sociodemographic variation in responses, although findings differed by self-reported overweight and physical activity. Conclusions Some Blacks may underestimate the extent of their overweight, perhaps resulting from the high prevalence of the condition in the population. Gaps exist in Blacks' recognition of the connection between weight and health, although the importance of exercise for health promotion was widely acknowledged. These data may highlight an important target for intervention attention. C1 Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. Ctr Community Based Res, Dana Farber Canc Inst, Boston, MA USA. Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Ctr Canc Prevent, Boston, MA 02115 USA. Harvard Univ, Ctr Soc & Hlth, Boston, MA 02115 USA. CBS News Poll, New York, NY USA. Black Entertainment Televis, Washington, DC USA. RP Bennett, GG (reprint author), Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, 44 Binney St, Boston, MA 02115 USA. EM gbennett@hsph.harvard.edu RI Goodman, Melody/F-6768-2011; Wolin, Kathleen/I-2154-2014 OI Goodman, Melody/0000-0001-8932-624X; Wolin, Kathleen/0000-0001-7950-9042 FU NCI NIH HHS [5 P01 CA75308, 5 T32 CA09001-28] NR 46 TC 17 Z9 17 U1 2 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD FEB PY 2006 VL 17 IS 1 BP 95 EP 101 DI 10.1007/s10552-005-0412-5 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 005MB UT WOS:000234825600013 PM 16411058 ER PT J AU Ryu, CJ Chang, S Protopopov, A Luch, A Kang, YH Draganov, DD Fragoso, MF Pai, SG Hong, HJ DePinho, RA Chen, JZ AF Ryu, CJ Chang, S Protopopov, A Luch, A Kang, YH Draganov, DD Fragoso, MF Pai, SG Hong, HJ DePinho, RA Chen, JZ TI Block of T cell development in P53-deficient mice accelerates development of lymphomas with characteristic RAG-dependent cytogenetic alterations SO CANCER CELL LA English DT Article ID DOUBLE-STRAND BREAKS; TUMOR-SUPPRESSOR GENE; TCR-BETA LOCUS; V(D)J RECOMBINATION; GENOMIC INSTABILITY; HEMATOLOGICAL MALIGNANCIES; THYMIC SELECTION; REPAIR; TRANSLOCATIONS; ENHANCER AB Mice deficient in the DNA damage sensor P53 display normal T cell development but eventually succumb to thymic lymphomas. Here, we show that inactivation of the TCR beta gene enhancer (E beta) results in a block of T cell development at stages where recombination-activating genes (RAG) are expressed. Introduction of the E beta mutation into p53(-/-) mice dramatically accelerates the onset of lethal thymic lymphomas that harbor RAG-dependent aberrant rearrangements, chromosome 14 and 12 translocations, and amplification of the chromosomal region 9A1-A5.3. Phenotypic and genetic analyses suggest that lymphomas emerge through a normal thymocyte development pathway. These findings provide genetic evidence that block of lymphocyte development at stages with RAG endonuclease activity can provoke lymphomagenesis on a background with deficient DNA damage responses. C1 MIT, Ctr Canc Res, Cambridge, MA 02139 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. Korea Res Inst Biosci & Biotechnol, Lab Antibody Engn, Taejon 305600, South Korea. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Chungnam Natl Univ, Dept Biol, Taejon 305600, South Korea. MD Anderson Canc Ctr, Dept Mol Genet, Houston, TX 77030 USA. RP Chen, JZ (reprint author), MIT, Ctr Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM jchen@mit.edu NR 51 TC 0 Z9 0 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD FEB PY 2006 VL 9 IS 2 BP 109 EP 120 DI 10.1016/j.ccr.2006.01.004 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 013VJ UT WOS:000235437800006 ER PT J AU Richardson, AL Wang, ZGC De Nicolo, A Lu, X Brown, M Miron, A Liao, XD Iglehart, JD Livingston, DM Ganesan, S AF Richardson, AL Wang, ZGC De Nicolo, A Lu, X Brown, M Miron, A Liao, XD Iglehart, JD Livingston, DM Ganesan, S TI X chromosomal abnormalities in basal-like human breast cancer SO CANCER CELL LA English DT Article ID GENE-EXPRESSION; INACTIVE-X; ACTIVE-X; IMMUNOHISTOCHEMICAL MARKERS; KLINEFELTER-SYNDROME; DOSAGE COMPENSATION; ESTROGEN-RECEPTOR; MAMMARY-CARCINOMA; XIST EXPRESSION; Y-CHROMOSOMES AB Sporadic basal-like cancers (BLC) are a distinct class of human breast cancers that are phenotypically similar to BRCA1-associated cancers. Like BRCA1-deficient tumors, most BLC lack markers of a normal inactive X chromosome (Xi). Duplication of the active X chromosome and loss of Xi characterized almost half of BLC cases tested. Others contained biparental but nonheterochromatinized X chromosomes or gains of X chromosomal DNA. These abnormalities did not lead to a global increase in X chromosome transcription but were associated with overexpression of a small subset of X chromosomal genes. Other, equally aneuploid, but non-BLC rarely displayed these X chromosome abnormalities. These results suggest that X chromosome abnormalities contribute to the pathogenesis of BLC, both inherited and sporadic. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Univ Padua, Dept Oncol & Surg Sci, Sect Oncol, I-35122 Padua, Italy. UMDNJ, Robert Wood Johnson Med Sch, Dept Med, Canc Inst New Jersey, New Brunswick, NJ 08093 USA. RP Livingston, DM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM david_livingston@dfci.harvard.edu; ganesash@umdni.edu RI Myles, Brown/B-6906-2008; OI Brown, Myles/0000-0002-8213-1658 NR 54 TC 461 Z9 472 U1 5 U2 19 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD FEB PY 2006 VL 9 IS 2 BP 121 EP 132 DI 10.1016/j.ccr.2006.01.013 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 013VJ UT WOS:000235437800007 PM 16473279 ER PT J AU Lee, JS John, EM McGuire, V Felberg, A Ostrow, KL DiCioccio, RA Li, FP Miron, A West, DW Whittemore, AS AF Lee, JS John, EM McGuire, V Felberg, A Ostrow, KL DiCioccio, RA Li, FP Miron, A West, DW Whittemore, AS TI Breast and ovarian cancer in relatives of cancer patients, with and without BRCA mutations SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID FAMILY-HISTORY; GENETIC EPIDEMIOLOGY; RISK; DNA; ASSOCIATION; DISEASE; MODELS; TP53 AB Background: First-degree relatives of patients with breast or ovarian cancer have increased risks for these cancers. Little is known about how their risks vary with the patient's cancer site, carrier status for predisposing genetic mutations, or age at cancer diagnosis. Methods: We evaluated breast and ovarian cancer incidence in 2,935 female first-degree relatives of non-Hispanic White female patients with incident invasive cancers of the breast (n = 669) or ovary (n = 339) who were recruited from a population-based cancer registry in northern California. Breast cancer patients were tested for BRCA1 and BRCA2 mutations. Ovarian cancer patients were tested for BRCA1 mutations. We estimated standardized incidence ratios (SIR) and 95% confidence intervals (95% Cl) for breast and ovarian cancer among the relatives according to the patient's mutation status, cancer site, and age at cancer diagnosis. Results: In families of patients who were negative or untested for BRCA1 or BRCA2 mutations, risks were elevated only for the patient's cancer site. The breast cancer SIR was 1.5 (95% Cl, 1.2-1.8) for relatives of breast cancer patients, compared with 1.1 (95% Cl, 0.8-1.6) for relatives of ovarian cancer patients (P = 0.12 for difference by patient's cancer site). The ovarian cancer SIR was 0.9 (95% Cl, 0.5-1.4) for relatives of breast cancer patients, compared with 1.9 (95% Cl, 1.0-4.0) for relatives of ovarian cancer patients (P = 0.04 for difference by site). In families of BRCA1-positive patients, relatives' risks also correlated with the patient's cancer site. The breast cancer SIR was 10.6 (95% Cl, 5.2-21.6) for relatives of breast cancer patients, compared with 3.3 (95% Cl, 1.4-7.3) for relatives of ovarian cancer patients (two-sided P = 0.02 for difference by site). The ovarian cancer SIR was 7.9 (95% Cl, 1.2-53.0) for relatives of breast cancer patients, compared with 11.3 (3.6-35.9) for relatives of ovarian cancer patients (two-sided P = 0.37 for difference by site). Relatives' risks were independent of patients' ages at diagnosis, with one exception: In families ascertained through a breast cancer patient without BRCA mutations, breast cancer risks were higher if the patient had been diagnosed before age 40 years. Conclusion: In families of patients with and without BRCA1 mutations, breast and ovarian cancer risks correlate with the patient's cancer site. Moreover, in families of breast cancer patients without BRCA mutations, breast cancer risk depends on the patient's age at diagnosis. These patterns support the presence of genes that modify risk specific to cancer site, in both carriers and noncarriers of BRCA1 and BRCA2 mutations. C1 Stanford Univ, Sch Med, Dept Hlth Res & Policy, Div Epidemiol, Stanford, CA 94305 USA. Univ Calif San Francisco, Div Endocrinol & Metab, San Francisco, CA 94143 USA. No Calif Canc Ctr, Fremont, CA USA. Roswell Pk Canc Inst, Dept Canc Genet, Buffalo, NY 14263 USA. Dana Farber Canc Inst, Dept Epidemiol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Lee, JS (reprint author), Stanford Univ, Sch Med, Dept Hlth Res & Policy, Div Epidemiol, HRP Redwood Bldg, Stanford, CA 94305 USA. EM catechols@gmail.com FU NCI NIH HHS [CA 69417, CA 94069, CA16056, CA71966, U01 CA069417, U01 CA069417-10] NR 26 TC 21 Z9 24 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD FEB PY 2006 VL 15 IS 2 BP 359 EP 363 DI 10.1158/1055-9965.EPI-05-0687 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 015YJ UT WOS:000235587200026 PM 16492929 ER PT J AU Kazhdan, I Long, L Montellano, R Cavazos, DA Marciniak, RA AF Kazhdan, I Long, L Montellano, R Cavazos, DA Marciniak, RA TI Targeted gene therapy for breast cancer with truncated Bid SO CANCER GENE THERAPY LA English DT Article DE breast cancer; tumor targeting; tBid ID REVERSE-TRANSCRIPTASE PROMOTER; ANTI-APOPTOSIS GENE; SURVIVIN MESSENGER-RNA; TELOMERASE ACTIVITY; BAX GENE; IN-VIVO; EXPRESSION; CELLS; HTERT; ACTIVATION AB We studied the efficiency of the proapoptotic factor tBid, targeted to tumor cells using the promoters of the hTERT, Survivin and Muc1 genes, in killing breast cancer cells. tBid is the active fragment of the proapoptotic protein Bid and is generated in response to death receptor activation. When placed under control of a strong CMV promoter, tBid was highly efficient in killing breast cancer cells. When expression of tBid was driven by tumor-specific promoters, the magnitude of killing was significant in cell lines with high levels of promoter activity. For successful gene therapy with targeted tBid, it is therefore crucial to be able to predict promoter activity prior to selection of the therapeutic construct. To test whether gene expression could serve as a predictor, we correlated expression of Survivin, hTERT and Muc1 genes with the activity of the corresponding promoters in a panel of breast cancer cell lines. Expression of the Muc1 gene correlated well with the activity of its promoter and the resultant tumor cell killing. For the hTERT and Survivin promoters, however, promoter activity did not correlate well with the expression of the corresponding genes. The implications and possible mechanism of these discrepancies are discussed. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Med Oncol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Kazhdan, I (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Med Oncol, 7703 Floyd Curl Dr,MC7884, San Antonio, TX 78229 USA. EM kazhdan@uthscsa.edu FU NCI NIH HHS [5 K12 CA01723-10] NR 52 TC 13 Z9 14 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD FEB PY 2006 VL 13 IS 2 BP 141 EP 149 DI 10.1038/sj.cgt.7700867 PG 9 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 003JS UT WOS:000234678600004 PM 16110313 ER PT J AU Zhuang, J Zhang, JR Willers, H Wang, H Chung, JH van Gent, DC Hallahan, DE Powell, SN Xia, F AF Zhuang, J Zhang, JR Willers, H Wang, H Chung, JH van Gent, DC Hallahan, DE Powell, SN Xia, F TI Checkpoint kinase 2-mediated phosphorylation of BRCA1 regulates the fidelity of nonhomologous end-joining SO CANCER RESEARCH LA English DT Article ID STRAND BREAK REPAIR; DNA-DAMAGE RESPONSE; HOMOLOGOUS RECOMBINATION; MAMMALIAN-CELLS; CANCER SUSCEPTIBILITY; ASSOCIATION; CONNECTION; DEFICIENT; MECHANISM; PROTEIN AB The tumor suppressor gene BRCA1 maintains genomic integrity by protecting cells from the deleterious effects of DNA double-strand breaks (DSBs). Through its interactions with the checkpoint kinase 2 (Chk2) kinase and Rad51, BRCA1 promotes homologous recombination, which is typically an error-free repair process. In addition, accumulating evidence implicates BRCA1 in the regulation of nonhomologous end-joining (NHEJ), which may involve precise religation of the DSB ends if they are compatible (i.e., error-free repair) or sequence alteration upon rejoining (i.e., error-prone or mutagenic repair). However, the precise role of BRCA1 in regulating these different subtypes of NHEJ is not clear. We provide here the genetic and biochemical evidence to show that BRCA1 promotes error-free rejoining of DSBs in human breast carcinoma cells while suppressing microhomology-mediated error-prone end-joining and restricting sequence deletion at the break junction during repair. The repair spectrum in BRCA1-deficient cells was characterized by an increase in the formation of > 2 kb deletions and in the usage of long microhomologies distal to the break site, compared with wild-type (WT) cells. This error-prone repair phenotype could also be revealed by disruption of the Chk2 phosphorylation site of BRCA1, or by expression of a dominant-negative kinase-dead Chk2 mutant in cells with WT BRCA1. We suggest that the differential control of NHEJ subprocesses by BRCA1, in concert with Chk2, reduces the mutagenic potential of NHEJ, thereby contributing to the prevention of familial breast cancers. C1 Vanderbilt Univ, Ctr Med, Dept Radiat Oncol, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Nashville, TN 37212 USA. Washington Univ, Sch Med, St Louis, MO USA. Massachusetts Gen Hosp, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. NHLBI, Bethesda, MD 20892 USA. Erasmus Med Ctr, Dept Cell Biol & Genet, Rotterdam, Netherlands. RP Xia, F (reprint author), Vanderbilt Univ, Ctr Med, Dept Radiat Oncol, 1301 22nd Ave S, Nashville, TN 37232 USA. EM fen_xia@vanderbilt.edu RI Xia, Fen/G-3708-2013 FU NCI NIH HHS [R01 CA 58985] NR 45 TC 76 Z9 80 U1 0 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 2006 VL 66 IS 3 BP 1401 EP 1408 DI 10.1158/0008-5472.CAN-05-3278 PG 8 WC Oncology SC Oncology GA 009FD UT WOS:000235095900022 PM 16452195 ER PT J AU Panka, DJ Wang, W Atkins, MB Mier, JW AF Panka, DJ Wang, W Atkins, MB Mier, JW TI The Raf inhibitor BAY 43-9006 (Sorafenib) induces caspase-independent apoptosis in melanoma cells SO CANCER RESEARCH LA English DT Article ID PROTEIN-KINASE PATHWAY; BRAF MUTATIONS; FACTOR AIF; DEATH; ACTIVATION; SIGNAL; ERK; MITOCHONDRIA; SURVIVAL; BINDING AB Mitogen-activated protein kinase (MAPK) is activated in the majority of melanomas, and its activity is essential for cell survival. In this report, we examined the effects of a novel raf inhibitor BAY 43-9006 on melanoma cell viability and intracellular signaling and found that it induces apoptosis through a caspase-independent mechanism. At concentrations that suppress extracellular signal-regulated kinase (ERK) phosphorylation, BAY 43-9006 dephosphorylates Bad on Ser(75) and Ser(99), activates Bak and Bax, and reduces the mitochondrial transmembrane potential. BAY 43-9006 (sor-afenib) down-modulates the levels of Bcl-2 and Bcl-X-L, in a MAPK-independent manner in A2058 and SKMEL5 melanoma cells but not in the more resistant A375 cells. Of the three lines tested, only A375 cells were rescued from BAY 43-9006-induced apoptosis by knocking down Bad. BAY 43-9006 induced poly(ADP-ribose) polymerase cleavage and the mitochondrial release of cytochrome c and SMAC. However, the pan-caspase inhibitor Z-VAD-fmk had only a modest protective effect against the drug, suggesting that BAY 439006-induced apoptosis is largely caspase independent. BAY 43-9006 but not the MAP/ERK kinase inhibitors PD98059 or U0126 induced the nuclear translocation of apoptosis-inducing factor (AIF) in A2058 and SKMEL5 cells, and the introduction of a small interfering RNA (siRNA) for AIF partially protected these cells from BAY 43-9006-induced apoptosis. The AIF siRNA had little effect in A375 cells, in which drug-induced AIF release was negligible. These data indicate that in sensitive cell lines, BAY 43-9006-induced apoptosis is independent of Bad dephosphorylation and caspase activation and largely mediated through the nuclear translocation of AIF. C1 Beth Israel Deaconess Med Ctr, Div Oncol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Mier, JW (reprint author), Beth Israel Deaconess Med Ctr, Div Oncol, 330 Brookline Ave, Boston, MA 02215 USA. EM jmier@bidmc.harvard.edu FU NCI NIH HHS [P50 CA 93683] NR 42 TC 120 Z9 129 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 2006 VL 66 IS 3 BP 1611 EP 1619 DI 10.1158/0008-5472.CAN-05-0808 PG 9 WC Oncology SC Oncology GA 009FD UT WOS:000235095900047 PM 16452220 ER PT J AU Ansel, GM Silver, MJ Botti, CF Rocha-Singh, K Bates, MC Rosenfield, K Schainfeld, RM Laster, SB Zander, C AF Ansel, GM Silver, MJ Botti, CF Rocha-Singh, K Bates, MC Rosenfield, K Schainfeld, RM Laster, SB Zander, C TI Functional and clinical outcomes of nitinol stenting with and without abciximab for complex superficial femoral artery disease: A randomized trial SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE glycoprotein IIb/IIIa; superficial femoral artery; balloon angioplasty; stent; nitinol; randomized; duplex scan; treadmill ID PERCUTANEOUS CORONARY INTERVENTION; GLYCOPROTEIN IIB/IIIA RECEPTOR; FEMOROPOPLITEAL ARTERY; BALLOON ANGIOPLASTY; SAPHENOUS-VEIN; POLYTETRAFLUOROETHYLENE; REVASCULARIZATION; OCCLUSIONS; EXPERIENCE; CLAUDICATION AB Objective: To evaluate the effect of glycoprotein IIb/IIIa inhibition during nitinol stenting, of superficial femoral occlusive disease. Background: Stent implantation in the superficial femoral artery has been associated with suboptimal results while Glycoprotein IIb/IIIa inhibitors have shown improved procedural results during coronary intervention. We evaluated abciximab infusion during (Smart Stent (R)) implantation in superficial femoral obstructions. Methods: We conducted a randomized placebo controlled trial. The two primary end points include: (1) 9-month restenosis defined as a decrease in ankle brachial index and in-stent duplex ultrasound restenosis: (2) adverse events defined as death (30 days) or repeat revascularization within 9 months. Results: Twenty-seven patients were randomized to abciximab and 24 patients to control (placebo). The primary end point of cumulative restenosis occurred in 15.4% of patients administered abciximab and in 12% administered placebo (P = 0.873). The primary restenosis endpoint in diabetics and total occlusions were similar at 14.3% and 15.4% respectively. The composite end point of 30-day mortality and 9-month revascularization occurred in 5.8% abciximab and 0% (P = 0.274) placebo with no 30-day deaths. Graded treadmill time and Rutherford class were all significantly improved in both groups, but the abciximab group did not appear to demonstrate any identifiable effect. Conclusion: (Smart Stent) nitinol stenting of the superficial femoral artery was associated with favorable functional outcomes at 9 months. Adjunctive abciximab did not appear to demonstrate any identifiable effect. (c) 2006 Wiley-Liss, Inc. C1 MidW Cardiol Res Fdn, Columbus, OH 43214 USA. Riverside Methodist Hosp, Cardiol Sect, Columbus, OH USA. St Johns Hosp, Springfield, IL USA. Charleston Area Med Ctr, Vasc Ctr Excellence, Charleston, WV USA. Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. St Elizabeth Hosp, Dept Vasc Med, Boston, MA USA. St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA. RP Ansel, GM (reprint author), MidW Cardiol Res Fdn, 3745 Olentangy River Rd, Columbus, OH 43214 USA. EM gansel@mocvc.com NR 36 TC 16 Z9 17 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD FEB PY 2006 VL 67 IS 2 BP 288 EP 297 DI 10.1002/ccd.20593 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 009WV UT WOS:000235145100021 PM 16408299 ER PT J AU Goldman, CK Morshedi-Meibodi, A White, CJ Jaff, MR AF Goldman, CK Morshedi-Meibodi, A White, CJ Jaff, MR TI Surveillance imaging for carotid in-stent restenosis SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE computerized tomographic angiography; carotid; stent; restenosis; duplex ID CODED DUPLEX SONOGRAPHY; COMPUTED-TOMOGRAPHY; ARTERY STENOSIS; FOLLOW-UP; CT; ANGIOGRAPHY; PLACEMENT; CRITERIA AB Carotid artery stent placement is the procedure of choice in suitable candidates who require carotid revascularization and are at increased risk for surgical therapy. To ensure late patency of the stent, continued surveillance is required. We present three cases to illustrate the strengths and weaknesses of noninvasive imaging techniques for surveillance of carotid stents, ultimately validated with invasive contrast angiography. (c) 2006 Wiley-Liss, Inc. C1 Ochsner Clin Fdn, Div Vasc Med, Dept Cardiol, New Orleans, LA 70121 USA. Massachusetts Gen Hosp, Sect Vasc Med, Dept Cardiovasc Med, Boston, MA 02114 USA. RP Goldman, CK (reprint author), Ochsner Clin Fdn, Div Vasc Med, Dept Cardiol, 1514 Jefferson Highway, New Orleans, LA 70121 USA. EM cgoldman@ochsner.org RI White, Christopher/J-6686-2012 OI White, Christopher/0000-0001-8618-7539 NR 17 TC 9 Z9 9 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD FEB PY 2006 VL 67 IS 2 BP 302 EP 308 DI 10.1002/ccd.20515 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 009WV UT WOS:000235145100023 PM 16400679 ER PT J AU Cho, GS Szostak, JW AF Cho, GS Szostak, JW TI Directed evolution of ATP binding proteins from a zinc finger domain by using mRNA display SO CHEMISTRY & BIOLOGY LA English DT Article ID IN-VITRO SELECTION; RETINOID-X-RECEPTOR; MOLECULAR RECOGNITION; FUNCTIONAL PROTEINS; RIBOSOME DISPLAY; STRUCTURAL BASIS; LIBRARIES; SPECIFICITY; ANTIBODIES; SCAFFOLDS AB Antibodies have traditionally been used for isolating affinity reagents to new molecular targets, but alternative protein scaffolds are increasingly being used for the directed evolution of proteins with novel molecular recognition properties. We have designed a combinatorial library based on the DNA binding domain of the human retinoid-X-receptor (hRXR alpha). We chose this domain because of its small size, stable fold, and two closely juxtaposed recognition loops. We replaced the two loops with segments of random amino acids, and used mRNA display to isolate variants that specifically recognize adenosine triphosphate (ATP), demonstrating a significant alteration of the function of this protein domain from DNA binding to ATP recognition. Many novel independent sequences were recovered with moderate affinity and high specificity for ATP validating this scaffold for the generation of functional molecules. C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Dept Mol Biol, Boston, MA 02114 USA. EM szostak@frodo.mgh.harvard.edu NR 44 TC 21 Z9 21 U1 4 U2 8 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-5521 J9 CHEM BIOL JI Chem. Biol. PD FEB PY 2006 VL 13 IS 2 BP 139 EP 147 DI 10.1016/j.chembiol.2005.10.015 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 020RQ UT WOS:000235928400007 PM 16492562 ER PT J AU Baren, JM Boudreaux, ED Brenner, BE Cydulka, RK Rowe, BH Clark, S Camargo, CA AF Baren, JM Boudreaux, ED Brenner, BE Cydulka, RK Rowe, BH Clark, S Camargo, CA TI Randomized controlled trial of emergency department interventions to improve primary care follow-up for patients with acute asthma SO CHEST LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Academic-Emergency-Medicine (SAEM) CY MAY 19-23, 2002 CL ST LOUIS, MO SP Soc Acad Emergency Med DE asthma; emergency department; follow-up; primary care ID CHILDREN; QUALITY; VISIT; HOSPITALIZATION; MANAGEMENT; OUTCOMES; RELAPSE; RISK; ROOM AB Objective: Emergency department (ED) visits for asthma are frequent and may indicate increased morbidity and poor primary care access. Our objective was to compare the effect of two interventions on. primary care follow-up after ED treatment for asthma exacerbations. Methods: We performed a randomized controlled trial of patients 2 to 54 years old who were judged safe for discharge receiving prednisone, and who were available for contact at 2 days and 30 days. Patients were excluded if they were previously enrolled or did not speak English. Patients received usual discharge care (group A); free prednisone, vouchers for transport to and from a primary care visit, and either a telephone reminder to schedule a visit (group B); or a prior scheduled appointment (group C). Follow-up with a primary care provider for asthma within 30 days was the main outcome. Secondary outcomes were recurrent ED visits, subsequent hospitalizations, quality of life, and use of inhaled corticosteroids 1 year later. Results: Three hundred eighty-four patients were enrolled. Baseline demographics, chronic asthma severity, and access to care were similar across groups. Primary care follow-up was higher in group C (65%) vs group A (42%) or group B (48%) [p = 0.002]. Group C intervention remained significant (odds ratio, 2.8; 95% confidence interval, 1.5 to 5.1) when adjusted for other factors influencing follow-up (prior primary care relationship, insurance status). There were no differences in ED, hospitalizations, quality of life, or inhaled corticosteroid use at 1 year after the index ED visit. Conclusion: An intervention including free medication, transportation vouchers, and appointment assistance significantly increased the likelihood that discharged asthma patients obtained primary care follow-up but did not impact long-term outcomes. C1 Hosp Univ Penn, Dept Emergency Med, Philadelphia, PA 19104 USA. Cooper Hosp Univ Med Ctr, Camden, NJ 08103 USA. Univ Arkansas, Little Rock, AR 72204 USA. Metrohlth Med Ctr, Cleveland, OH 44109 USA. Univ Alberta, Edmonton, AB T6G 2M7, Canada. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab,Dept Med, Boston, MA 02115 USA. RP Baren, JM (reprint author), Hosp Univ Penn, Dept Emergency Med, 3400 Spruce St,Ground Floor Silverstein Bldg, Philadelphia, PA 19104 USA. EM barenj@uphs.upenn.edu RI Webster, Susan/C-7360-2015; OI Webster, Susan/0000-0002-0684-4226; Boudreaux, Edwin/0000-0002-3223-6371 FU NHLBI NIH HHS [R01 HL63841]; NIEHS NIH HHS [T32 ES07069] NR 33 TC 73 Z9 73 U1 1 U2 5 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD FEB PY 2006 VL 129 IS 2 BP 257 EP 265 DI 10.1378/chest.129.2.257 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 016UM UT WOS:000235646100010 PM 16478839 ER PT J AU Januzzi, JL AF Januzzi, JL TI Natriuretic peptide testing: A window into the diagnosis and prognosis of heart failure SO CLEVELAND CLINIC JOURNAL OF MEDICINE LA English DT Article ID EMERGENCY-DEPARTMENT PRIDE; CORONARY-ARTERY-DISEASE; EJECTION FRACTION; ACUTE DYSPNEA; NT-PROBNP; BNP; MANAGEMENT; MORTALITY; RISK; CARE AB B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) levels can indicate a variety of heart problems, as well as general critical illness. BNP and NT-proBNP assays are useful for evaluating patients with acute dyspnea, as a low level of natriuretic peptide can help rule out congestive heart failure (CHF) and reduce reliance on echocardiography. Conversely, these assays can be particularly useful in recognizing CHF in a patient with acute dyspnea and a history of chronic obstructive pulmonary disease. However, clinical judgment must always be part of the evaluation of BNP or NT-proBNP assay results. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Unit Associates, Boston, MA 02114 USA. RP Januzzi, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Unit Associates, 55 fruit St,YAN 5, Boston, MA 02114 USA. NR 29 TC 16 Z9 24 U1 0 U2 1 PU CLEVELAND CLINIC PI CLEVELAND PA 9500 EUCLID AVE, CLEVELAND, OH 44106 USA SN 0891-1150 J9 CLEV CLIN J MED JI Clevel. Clin. J. Med. PD FEB PY 2006 VL 73 IS 2 BP 149 EP + PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 010HE UT WOS:000235177400006 PM 16478039 ER PT J AU Sun, AY Wei, HM Sun, R Xiao, WH Yang, YG Tian, ZG AF Sun, AY Wei, HM Sun, R Xiao, WH Yang, YG Tian, ZG TI Human interleukin-15 improves engraftment of human T cells in NOD-SCID mice SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID HUMAN PERIPHERAL-BLOOD; NATURAL-KILLER-CELLS; SEVERE COMBINED IMMUNODEFICIENCY; ADOPTIVE CELLULAR IMMUNOTHERAPY; HUMAN LYMPHOCYTE ENGRAFTMENT; VERSUS-HOST-DISEASE; HEMATOPOIETIC PROGENITORS; ANTIBODY-PRODUCTION; ANTITUMOR IMMUNITY; GROWTH-FACTOR AB Human nonobese diabetic-severe combined immune deficiency (NOD-SCID) mouse chimeras have been widely used as an in vivo model to assess human immune function. However, only a small fraction of transferred human T lymphocytes can be detected in human peripheral blood lymphocyte (huPBL)-NOD-SCID chimeras. To improve the reconstitution of human T lymphocytes in NOD-SCID mice, the use of recombinant human interleukin-15 (rhIL-15) as a stimulator of human lymphocytes was explored. Administration of rhIL-15 after transplantation of huPBLs into NOD-SCID mice increased reconstitution of human T lymphocytes in a dose-dependent manner, with an optimal dosage of 1 mu g/mouse. The number of human T lymphocytes (HLA-ABC(+) CD3(+)) in the lymphoid organs or tissue of rhIL-15-treated huPBL-NOD-SCID mice increased 11- to 80-fold, and phytohemagglutinin-induced T-lymphocyte proliferation and cytokine production were significantly enhanced. Additionally, although mature human cells have not been thought to enter the murine thymus, human T lymphocytes were detected in the huPBL-NOD-SCID thymus after rhIL-15 treatment. Thus, rhIL-15 can be used to optimize long-term peripheral T-cell engraftment in these human-mouse chimeras and may also be useful in clinical treatment of T-cell deficiencies. C1 Univ Sci & Technol China, Sch Life Sci, Hefei 230027, Anhui, Peoples R China. Shandong Univ, Sch Pharmaceut Sci, Jinan 250021, Peoples R China. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. RP Tian, ZG (reprint author), Univ Sci & Technol China, Sch Life Sci, 443 Huangshan Rd, Hefei 230027, Anhui, Peoples R China. EM tzg@ustc.edu.cn RI Xiao, Weihua/N-2775-2013; Tian, Zhigang/J-3512-2013 OI Xiao, Weihua/0000-0001-9102-6326; NR 54 TC 10 Z9 11 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD FEB PY 2006 VL 13 IS 2 BP 227 EP 234 DI 10.1128/CVI.13.2.227-234.2006 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 015GG UT WOS:000235539300010 PM 16467330 ER PT J AU Zucker, S Wang, ML Sparano, JA Gradishar, WJ Ingle, JN Davidson, NE AF Zucker, Stanley Wang, Molin Sparano, Joseph A. Gradishar, William J. Ingle, James N. Davidson, Nancy E. TI Plasma matrix metalloproteinases 7 and 9 in patients with metastatic breast cancer treated with marimastat or placebo: Eastern cooperative oncology group trial E2196 SO CLINICAL BREAST CANCER LA English DT Article DE matrix metalloproteinase inhibitors; phase III trials; survival ID MATRIX-METALLOPROTEINASE INHIBITOR; IV COLLAGENASE; LUNG-CANCER; PHASE-I; MATRILYSIN; CARCINOMA; FRACTION; BLOOD AB Background: The purpose of this study was to evaluate the prognostic and predictive utility of measuring plasma levels of matrix metalloproteinase (MMP)-7 and MMP-9 in patients with metastatic breast cancer (MBC) treated with the oral MMP inhibitor (MMPI) marimastat or a placebo. Patients and Methods: We measured plasma levels of MMP-7 and MMP-9 using an enzyme-linked immunoassay method in 140 evaluable patients with MBC enrolled on a multicenter clinical trial that compared the MMPI marimastat with placebo. Specimens were collected after completion of first-line chemotherapy in patients who had responding or stable disease and 3, 6, and 12 months after initiation of marimastat (10 mg orally twice daily) or placebo. Results: Baseline plasma MMP-7 and MMP-9 levels did not correlate with each other or with progression-free or overall survival. In addition, serial evaluation of plasma MMP-7 and MMP-9 levels revealed no significant changes over time in the marimastat or placebo groups or any correlation with trough plasma marimastat level. Conclusion: We conclude that measurement of plasma MMP-7 or MMP-9 levels, as performed in our trial, was not a useful prognostic or predictive factor in patients with MBC or in patients treated with an MMPI. C1 Montefiore Med Ctr, Albert Einstein Canc Ctr, Weiler Div, Bronx, NY 10461 USA. Vet Affairs Med Ctr, Northport, NY USA. SUNY Stony Brook, Stony Brook, NY 11794 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Northwestern Univ, Chicago, IL 60611 USA. Mayo Clin, Rochester, MN USA. Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. RP Sparano, JA (reprint author), Montefiore Med Ctr, Albert Einstein Canc Ctr, Weiler Div, 1825 Eastchester Rd,2 South,Room 47, Bronx, NY 10461 USA. EM sparano@jimmy.harvard.edu FU NCI NIH HHS [CA66636, CA13650, CA14958, CA23318, CA17145, CA21115, CA16116] NR 15 TC 3 Z9 5 U1 0 U2 2 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1526-8209 J9 CLIN BREAST CANCER JI Clin. Breast Cancer PD FEB PY 2006 VL 6 IS 6 BP 525 EP 529 DI 10.3816/CBC.2006.n.006 PG 5 WC Oncology SC Oncology GA 112MJ UT WOS:000242529800006 PM 16595036 ER PT J AU Hodi, FS AF Hodi, FS TI Well-defined melanoma antigens as progression markers for melanoma: Insights into differential expression and host response based on stage SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID CYTOLYTIC T-LYMPHOCYTES; TUMOR-INFILTRATING LYMPHOCYTES; MALIGNANT-MELANOMA; CUTANEOUS MELANOMA; HLA-A2 MELANOMAS; CANCER/TESTIS ANTIGENS; PROGNOSTIC INDICATOR; METASTATIC MELANOMA; MONOCLONAL-ANTIBODY; IMMUNE-RESPONSE C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Hodi, FS (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM stephen-hodi@dfci.harvard.edu NR 69 TC 18 Z9 18 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD FEB 1 PY 2006 VL 12 IS 3 BP 673 EP 678 DI 10.1158/1078-0432.CCR-05-2616 PN 1 PG 6 WC Oncology SC Oncology GA 010NR UT WOS:000235201900001 PM 16467076 ER PT J AU Janne, PA Borras, AM Kuang, YN Rogers, AM Joshi, VA Liyanage, H Lindeman, N Lee, JC Halmos, B Maher, EA Distel, RJ Meyerson, M Johnson, BE AF Janne, PA Borras, AM Kuang, YN Rogers, AM Joshi, VA Liyanage, H Lindeman, N Lee, JC Halmos, B Maher, EA Distel, RJ Meyerson, M Johnson, BE TI A rapid and sensitive enzymatic method for epidermal growth factor receptor mutation screening SO CLINICAL CANCER RESEARCH LA English DT Article ID CELL LUNG-CANCER; PARAFFIN-EMBEDDED TISSUE; TYROSINE KINASE DOMAIN; GENE-MUTATIONS; ACTIVATING MUTATIONS; GEFITINIB TREATMENT; SOMATIC MUTATIONS; EGFR MUTATIONS; RESPONSIVENESS; AMPLIFICATION AB Purpose: Mutations in the epidermal growth factor receptor (EGFR) are associated with clinical and radiographic responses to EGFR tyrosine kinase inhibitors gefitinib and erlotinib. Currently available methods of EGFR mutation detection rely on direct DNA sequencing, which requires isolation of DNA from a relatively pure population of tumor cells, cannot be done on small diagnostic specimens, and lack sensitivity. Here we describe the use of a sensitive screening method that overcomes many of these limitations. Experimental Design: We screened 178 non-small cell lung cancer specimens for mutations in exons 18 to 21 of EGFR using a DNA endonuclease, SURVEYOR, which cleaves mismatched heteroduplexed DNA. Samples were analyzed by high-performance liquid chromatography on the Transgenomic WAVE HS system. Selected specimens that produced digestion products using SURVEYOR were subsequently reanalyzed by size separation or under partially denaturing conditions, followed by fractionation and sequencing. The specimens included DNA isolated from frozen tumor specimens, dissected formalin-fixed, paraffin-embedded tumor specimens undergoing clinical sequencing, and undissected formalin-fixed, paraffin-embedded specimens. One hundred sixty specimens were independently analyzed using direct DNA sequencing in a blinded fashion. Results: EGFR mutations were detected in 16 of 61 fresh frozen tumor specimens, 24 of 91 dissected formalin-fixed, paraffin-embedded tumor specimens, and 11 of 26 undissected formalin-fixed, paraffin-embedded tumor specimens. Compared with sequencing, the sensitivity and specificity of the present method were 100% and 87%. The positive and negative predictive values were 74% and 100%, respectively. SURVEYOR analysis detected 7 (4%) mutations that were not previously detected by direct sequencing. Conclusions: SURVEYOR analysis provides a rapid method for EGFR mutation screening with 100% sensitivity and negative predictive value. This unbiased scanning technique is superior to direct sequencing when used with undissected formalin-fixed, paraffin-embedded specimens. C1 Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Translat Res Lab, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol & Canc Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Biol Chem, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Mol Pharmacol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Partners Ctr Genet & Genom, Mol Med Lab, Cambridge, MA USA. Transgenom Inc, Cambridge, MA USA. Univ Hosp Cleveland, Ireland Canc Ctr, Case Sch Med, Cleveland, OH 44106 USA. RP Janne, PA (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, D1234,44 Binney St, Boston, MA 02115 USA. EM pjanne@partners.org RI Meyerson, Matthew/E-7123-2012; Mendez, Pedro /J-8955-2016 OI Mendez, Pedro /0000-0001-6713-7907 FU NCI NIH HHS [1K 12CA87723-01, 1R01CA114465-01] NR 34 TC 164 Z9 173 U1 0 U2 5 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 FEB 1 PY 2006 VL 12 IS 3 BP 751 EP 758 DI 10.1158/1078-0432.CCR-05-2047 PN 1 PG 8 WC Oncology SC Oncology GA 010NR UT WOS:000235201900010 PM 16467085 ER PT J AU Chute, JP Taylor, E Williams, J Kaye, F Venzon, D Johnson, BE AF Chute, JP Taylor, E Williams, J Kaye, F Venzon, D Johnson, BE TI A metabolic study of patients with lung cancer and hyponatremia of malignancy SO CLINICAL CANCER RESEARCH LA English DT Article ID ATRIAL-NATRIURETIC-FACTOR; ANTIDIURETIC-HORMONE SECRETION; PLASMA ARGININE VASOPRESSIN; TUMOR-CELL LINES; INAPPROPRIATE SECRETION; BRONCHOGENIC CARCINOMA; BLOOD-PRESSURE; PEPTIDE; SODIUM; ANTAGONIST AB Purpose: One-third of patients with lung cancer and hyponatremia have no evidence of ectopic arginine vasopressin (AVP) production and the cause of their hyponatremia is not conclusively established. We sought to distinguish patients with hyponatremia caused by elevated AVP versus those with ectopic atrial natriuretic peptide (ANP) via this detailed metabolic study. Experimental Design: We enrolled 24 patients recently diagnosed with lung cancer in a metabolic study in which patients were placed on sodium and fluid restriction for 4 days. Serum electrolytes, osmolality, urine electrolytes and osmolality, plasma AVP, ANP, aldosterone, urinary cyclic AMP and cyclic guanosine 3',5'-monophosphate were measured daily and tumor tissue was obtained to measure ectopic hormone production. We attempted to characterize the pathophysiology of hyponatremia caused by ectopic ANP production in patients with small cell lung cancer (SCLC) and to determine its effect on the aldosterone axis. Results: Seven of the nine patients with SCLC presented with hyponatremia and three had elevated ANP levels at presentation without elevation of AVR All three patients who presented with hyponatremia and elevated ANP showed a decline in serum sodium following fluid restriction, whereas two patients with SCLC and elevated AVP had normalized serum sodium levels. The combination of hyponatremia and elevated ANP was associated with a persistent natriuresis and inappropriately low aldosterone levels despite sodium restriction, suggesting ANP suppression of the aldosterone axis. Conclusions: Management of patients with hyponatremia and SCLC should be guided by the knowledge that some patients with SCLC have ectopic production of ANP as the cause of their hyponatremia. C1 Duke Univ, Dept Med, Durham, NC 27710 USA. Natl Naval Med Res Inst, Dept Nutr, Bethesda, MD USA. Natl Naval Med Res Inst, Dept Pathol, Bethesda, MD USA. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Chute, JP (reprint author), Duke Univ, Dept Med, 2400 Pratt St,Suite 1100, Durham, NC 27710 USA. EM john.chute@duke.edu RI Venzon, David/B-3078-2008; kaye, frederic/E-2437-2011 NR 48 TC 16 Z9 19 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD FEB 1 PY 2006 VL 12 IS 3 BP 888 EP 896 DI 10.1158/1078-0432.CCR-05-1536 PN 1 PG 9 WC Oncology SC Oncology GA 010NR UT WOS:000235201900028 PM 16467103 ER PT J AU Chen, B Pogue, BW Luna, JM Hardman, RL Hoopes, PJ Hasan, T AF Chen, B Pogue, BW Luna, JM Hardman, RL Hoopes, PJ Hasan, T TI Tumor vascular permeabilization by vascular-targeting photosensitization: Effects, mechanism, and therapeutic implications SO CLINICAL CANCER RESEARCH LA English DT Article ID HUMAN ENDOTHELIAL-CELLS; PHOTODYNAMIC THERAPY; LEUKOCYTE ADHESION; BARRIER FUNCTION; PROSTATE-CANCER; VESSELS; MICROTUBULES; VERTEPORFIN; THROMBIN; MELANOMA AB Purpose: Loss of vascular barrier function has been observed shortly following vascular-targeting photodynamic therapy. However, the mechanism involved in this event is still not clear, and the therapeutic implications associated with this pathophysiologic change have not been fully explored. Experimental Design: The effect of vascular-targeting photodynamic therapy on vascular barrier function was examined in both s.c. and orthotopic MatLyLu rat prostate tumor models and endothelial cells in vitro, using photosensitizer verteporfin. Vascular permeability to macromolecules (Evans blue-albumin and high molecular weight dextran) was assessed with dye extraction (ex vivo) and intravital microscopy (in vivo) methods. Intravital microscopy was also used to monitor tumor vascular functional changes after vascular-targeting photodynamic therapy. The effects of photosensitization on monolayer endothelial cell morphology and cytoskeleton structures were studied with immunofluorescence staining. Results: Vascular-targeting photodynamic therapy induced vascular barrier dysfunction in the MatLyLu tumors. Thus, tumor uptake of macromolecules was significantly increased following photodynamic therapy treatments. In addition to vascular permeability increase, blood cell adherence to vessel wall was observed shortly after treatment, further suggesting the loss of endothelial integrity. Blood cell adhesion led to the formation of thrombi that can occlude blood vessels, causing vascular shutdown. However, viable tumor cells were often detected at tumor periphery after vascular-targeting photodynamic therapy. Endothelial cell barrier dysfunction following photodynamic therapy treatment was also observed in vitro by culturing monolayer endothelial cells on Transwell inserts. Immunofluorescence study revealed microtubule depolymerization shortly after photosensitization treatment and stress actin fiber formation thereafter. Consequently, endothelial cells were found to retract, and this endothelial morphologic change led to the formation of intercellular gaps. Conclusions: Vascular-targeting photodynamic therapy permeabilizes blood vessels through the formation of endothelial intercellular gaps, which are likely induced via endothelial cell microtubule depolymerization following vascular photosensitization. Loss of endothelial barrier function can ultimately lead to tumor vascular shutdown and has significant implications in drug transport and tumor cell metastasis. C1 Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. Dartmouth Coll Sch Med, Dept Surg, Lebanon, NH USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed,Dept Dermatol, Boston, MA USA. RP Pogue, BW (reprint author), Dartmouth Coll, Thayer Sch Engn, 8000 Cummings Hall, Hanover, NH 03755 USA. EM pogue@dartmouth.edu FU NCI NIH HHS [P01CA84203] NR 37 TC 85 Z9 88 U1 2 U2 22 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 FEB 1 PY 2006 VL 12 IS 3 BP 917 EP 923 DI 10.1158/1078-0432.CCR-05-1673 PN 1 PG 7 WC Oncology SC Oncology GA 010NR UT WOS:000235201900031 PM 16467106 ER PT J AU Kim, IA Shin, JH Kim, IH Kim, JH Kim, JS Wu, HG Chie, EK Ha, SW Park, CI Kao, GD AF Kim, IA Shin, JH Kim, IH Kim, JH Kim, JS Wu, HG Chie, EK Ha, SW Park, CI Kao, GD TI Histone deacetylase inhibitor-mediated radiosensitization of human cancer cells: Class differences and the potential influence of p53 SO CLINICAL CANCER RESEARCH LA English DT Article ID CARCINOMA-CELLS; REPAIR ACTIVITY; DNA-REPAIR; CLASS-I; APOPTOSIS; EXPRESSION; ENHANCEMENT; PROLIFERATION; EPIGENETICS; ACTIVATION AB Histone deacetylase inhibitors (HDI) are emerging as potentially useful components of the anticancer armamentarium and as useful tools to dissect mechanistic pathways. HDIs that globally inhibit histone deacetylases (HDAC) have radiosensitizing effects, but the relative contribution of specific HDAC classes remains unclear. Newly characterized HDIs are now available that preferentially inhibit specific HDAC classes, including SK7041 (inhibits class I HDACs) and splitomicin (inhibits class III HDACs). We investigated in human cancer cells the relative radiosensitizations that result from blocking specific HDAC classes. We found that trichostatin A (TSA; inhibitor of both class I and II HDACs) was the most effective radiosensitizer, followed by the class I inhibitor SK7041, whereas splitomicin (inhibitor of class III) had least effect. Interestingly, radiosensitization by TSA in cell lines expressing p53 was more pronounced than in isogenic lines lacking p53. Radiosensitization of cells expressing p53 by TSA was reduced by pifithrin-alpha, a small-molecule inhibitor of p53. In contrast, the radiosensitization by TSA of cells expressing low levels of p53 was enhanced by transfection of wild-type p53- expressing vector or pretreatment with leptomycin B, an inhibitor of nuclear export that increased intracellular levels of p53. These effects on radiosensitization were respectively muted or not seen in cells treated with SK7041 or splitomicin. To our knowledge, this may be among the first systematic investigations of the comparative anticancer effects of inhibiting specific classes of HDACs, with results suggesting differences in the degrees of radiosensitization, which in some cell lines may be influenced by p53 expression. C1 Seoul Natl Univ, Coll Med, Dept Radiat Oncol, Seoul 110744, South Korea. Seoul Natl Univ, Coll Med, Canc Res Inst, Seoul 110744, South Korea. Univ Penn, Sch Med, Philadelphia Vet Affairs Med Ctr, Dept Radiat Oncol, Philadelphia, PA 19104 USA. RP Kim, IH (reprint author), Seoul Natl Univ, Coll Med, Dept Radiat Oncol, 28 Yongon Dong, Seoul 110744, South Korea. EM ihkim@snu.ac.kr RI Chie, Eui Kyu/J-5677-2012; Kim, In Ah/J-5426-2012; Kim, Jae Sung/J-5429-2012; Ha, Sung Whan/J-5699-2012; Wu, Hong Gyun/J-5547-2012; OI Kim, Jin Ho/0000-0002-7918-1072 NR 52 TC 59 Z9 60 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 FEB 1 PY 2006 VL 12 IS 3 BP 940 EP 949 DI 10.1158/1078-0432.CCR-05-1230 PN 1 PG 10 WC Oncology SC Oncology GA 010NR UT WOS:000235201900034 PM 16467109 ER PT J AU Korzenik, JR Podolsky, DK AF Korzenik, JR Podolsky, DK TI Selective use of selective nonsteroidal anti-inflammatory drugs in inflammatory bowel disease SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Editorial Material ID OPEN-LABEL TRIAL; CYCLOOXYGENASE-2 INHIBITORS; GASTROINTESTINAL TOXICITY; ROFECOXIB; COLITIS; RELAPSE C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Dept Med, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Korzenik, JR (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Dept Med, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. NR 18 TC 11 Z9 11 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD FEB PY 2006 VL 4 IS 2 BP 157 EP 159 DI 10.1053/S1542-3565(05)01095-5 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 014SQ UT WOS:000235500700008 PM 16469674 ER PT J AU Bennish, ML Khan, WA Begum, M Bridges, EA Ahmed, S Saha, D Salam, MA Acheson, D Ryan, ET AF Bennish, ML Khan, WA Begum, M Bridges, EA Ahmed, S Saha, D Salam, MA Acheson, D Ryan, ET TI Low risk of hemolytic uremic syndrome after early effective antimicrobial therapy for Shigella dysenteriae type 1 infection in Bangladesh SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID DOUBLE-BLIND; SHIGA TOXIN; CHILDHOOD SHIGELLOSIS; ANTIBIOTIC-TREATMENT; CIPROFLOXACIN; TRIAL; AMPICILLIN; SEROTYPE-1; OUTBREAK; DIARRHEA AB Background. Hemolytic uremic syndrome (HUS) may complicate up to 15% of cases of Shiga toxin (Stx) expressing enterohemorrhagic Escherichia coli (STEC) O157: H7 infections in children. Administration of antimicrobials has been reported to increase the risk of STEC-associated HUS by > 10-fold, presumably by increasing the expression and release of Stx by dying STEC bacteria. Shigella dysenteriae type 1 also expresses Stx. However, the effect of antimicrobial therapy on Stx release and the risk of HUS in humans is unknown. Methods. We measured serial stool Stx concentrations before and after administration of antimicrobials in 20 children infected with S. dysenteriae type 1 who had frank dysentery of < 72 h duration. We also reviewed the results of 7 shigellosis drug trials performed in Bangladesh during 1988-2000 to estimate the risk of HUS. In these studies, antimicrobials were administered within 96 h after the onset of dysentery. Results. Stx levels decreased in stool samples obtained from 17 of 20 children after administration of antimicrobial agents; none of the 20 children developed HUS. Of 378 individuals infected with S. dysenteriae type 1 who were enrolled in drug trials (128 adult men [age, 18-60 years] and 250 children [age, 6 months to 15 years]), 351 (93%) received an antimicrobial agent to which the S. dysenteriae organism was susceptible <= 96 h after the onset of symptoms; HUS developed in 1 child. The risk of developing HUS was 0.0026 for all participants (95% confidence interval, < 0.001 to 0.015) and was 0.004 for children (95% confidence interval, 0.001-0.022). Conclusion. In persons infected with S. dysenteriae type 1, early administration of effective antibiotics is associated with decreased Stx concentrations in stool and a low risk of developing HUS. C1 Massachusetts Gen Hosp, Div Infect Dis, Trop & Geog Med Ctr, Boston, MA 02114 USA. Africa Ctr Hlth & Populat Studies, Mtubatuba, South Africa. Univ Oxford, Nuffield Dept Clin Med, Oxford OX1 2JD, England. Int Ctr Diarrhoeal Dis Res, Int Ctr Hlth & Populat Res, Dhaka 1000, Bangladesh. Tufts New England Med Ctr, Div Geog Med & Infect Dis, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Ryan, ET (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Trop & Geog Med Ctr, Jackson 504,55 Fruit St, Boston, MA 02114 USA. EM etryan@partners.org FU NIAID NIH HHS [R01 AI40725, U01 AI45508-01, U01 AI58935, K24 AI/HDO01671, U01 AI058935]; Wellcome Trust NR 22 TC 26 Z9 28 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 FEB 1 PY 2006 VL 42 IS 3 BP 356 EP 362 DI 10.1086/499236 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 999QD UT WOS:000234404100008 PM 16392080 ER PT J AU Vucic, S Cairns, KD Black, KR Chong, PST Cros, D AF Vucic, S Cairns, KD Black, KR Chong, PST Cros, D TI Cervical nerve root stimulation. Part I: Technical aspects and normal data SO CLINICAL NEUROPHYSIOLOGY LA English DT Article; Proceedings Paper CT 10th Clinical Neurophysiology Workshop of the Australian-Association-of-Neurologists CY APR 19-23, 2005 CL Southport, AUSTRALIA SP Australian Assoc Neurologists DE cervical nerve root stimulation; normal data ID MAGNETIC STIMULATION; BLOCK AB Objective: Cervical nerve root stimulation (CRS) is a technique of assessing the proximal segments of motor axons destined to upper extremity muscles. Few studies report normal values. The objective was to determine CMAP onset-latencies and CMAP amplitude, area, and duration changes in healthy controls for the abductor pollicis brevis (APB), abductor digiti minimi (ADM), biceps, and riceps muscles. In addition, to determine the tolerability of CRS, as measured by the visual analog scale (VAS). Methods: We studied 21 healthy volunteers prospectively with CRS using four target muscles (APB, ADM, biceps, and triceps) bilaterally. Collision studies were used in all APB recordings. VAS was obtained in all subjects. Results: Mean CMAP onset-latencies were: APB 14 +/- 1.5 ms; ADM 14.2 +/- 1.5 ms; biceps 5.4 +/- 0.6 ms; triceps 5.4 +/- 1.0 ms. Onset-latency significantly correlated with height for all nerves. The mean change in CMAP amplitude and area (%) between most distal stimulation and CRS was: APB reduction of 15.1 +/- 11.6 and 4.9 +/- 3.6%; ADM reduction of 21.1 +/- 10.7 and 17.2 +/- 8.8; biceps reduction of 10 +/- 11.5 and reduction of 8.7 +/- 6.8; triceps increase of 3.3 +/- 5.2 and 11.0 +/- 9.9% respectively. Mean CMAP duration change between most distal stimulation and CRS was: APB, increase of 20.4 +/- 7.4%; ADM, increase of 14.4 +/- 8.5%; biceps, increase of 13.9 +/- 10.8%; triceps, increase of 7.7 +/- 6.7%. The mean VAS score was 3.8 +/- 1.2, and all subjects completed the study. Conclusions: The present study establishes normative data and indicates that CRS is a well-tolerated technique. Significance: The normal values may be used as reference data for the needle CRS technique in the assessment of proximal conduction abnormalities. (c) 2005 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Cros, D (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St,GRB 1256, Boston, MA 02114 USA. EM dcros@partners.org NR 12 TC 16 Z9 16 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD FEB PY 2006 VL 117 IS 2 BP 392 EP 397 DI 10.1016/j.clinph.2005.10.011 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 021XM UT WOS:000236019200016 PM 16403485 ER PT J AU Vucic, S Black, K Chong, PST Cros, D AF Vucic, S Black, K Chong, PST Cros, D TI Cervical nerve root stimulation. Part II: Findings in primary demyelinating neuropathies and motor neuron disease SO CLINICAL NEUROPHYSIOLOGY LA English DT Article; Proceedings Paper CT 10th Clinical Neurophysiology Workshop of the Australian-Association-of-Neurologists CY APR 19-23, 2005 CL Southport, AUSTRALIA SP Australian Assoc Neurologists DE cervical nerve root stimulation; demyelinating neuropathy ID DIAGNOSIS; CRITERIA; POLYRADICULONEUROPATHY; POLYNEUROPATHIES; CONDUCTION AB Objective: Cervical nerve root stimulation (CRS) allows the assessment of conduction in the proximal segments of motor fibers destined to the upper extremities, which are not evaluated by, routine nerve conduction studies (NCS). Since many primary demyelinating polyneuropathies (PDP) are multifocal lesions may be confined to the proximal nerve segments. CRS may therefore increase the yield of neurophysiologic studies in diagnosing PDP. Methods: We reviewed clinical and neurophysiologic data from 38 PDP patients and compared them to 35 patients with motor neuron disease (MND), and 21 healthy controls (HC). Results: Mean onset-latency was significantly prolonged in PDP patients. The optimal onset-latency cutoff necessary to distinguish PDP from MND and controls was 17.5 ms for the abductor pollicis brevis (APB) and abductor digiti minimi (ADM), and 7 ms for Biceps and Triceps. Mean reduction in proximal to distal CMAP amplitude to APB and ADM was significantly greater in PDP patients, with an optimal cutoff in proximal to distal CMAP amplitude reduction necessary to distinguish PDP from MND and HC being 45%. Conclusions: CRS is effective in distinguishing PDP from MND and HC based on prolonged onset latency and conduction block criteria. Significance: CRS may increase the diagnostic yield in cases where demyelinating lesions are confined to the proximal peripheral neuraxis. (c) 2005 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Cros, D (reprint author), Massachusetts Gen Hosp, Dept Neurol, Bigelow 1256,55 Fruit St, Boston, MA 02114 USA. EM deros@partners.org NR 22 TC 16 Z9 17 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD FEB PY 2006 VL 117 IS 2 BP 398 EP 404 DI 10.1016/j.clinph.2005.10.012 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 021XM UT WOS:000236019200017 PM 16403674 ER PT J AU Kudolo, GB Wang, W Elrod, R Barrientos, J Haase, A Blodgett, J AF Kudolo, GB Wang, W Elrod, R Barrientos, J Haase, A Blodgett, J TI Short-term ingestion of Ginkgo biloba extract does not alter whole body insulin sensitivity in non-diabetic, pre-diabetic or type 2 diabetic subjects - A randomized double-blind placebo-controlled crossover study SO CLINICAL NUTRITION LA English DT Article DE Ginkgo biloba; insulin resistance; Type 2 diabetes ID PLATELET-ACTIVATING-FACTOR; BETA-CELL FUNCTION; RESISTANCE SYNDROME; GLUCOSE-TOLERANCE; MELLITUS; HYPERTENSION; DISEASE; EGB-761; METAANALYSIS; INDIVIDUALS AB Background Et Aims: Ingestion of Ginkgo biloba Extract (EGb 761) may increase pancreatic beta-cell function in both healthy subjects with normal glucose tolerance (NGT) as well as patients with Type 2 Diabetes mellitus (T2DM). Since hyperinsulinemia is a hallmark of T2DM, it is important to verify that increased insulin production is not due to increased insulin resistance. Method: NGT subjects (n = 10; age, 44.2 +/- 13.9 years old), impaired glucose tolerance (IGT) (n = 8; age 51.3 +/- 6.6 years old) and T2DM subjects (n = 8, 51.6 +/- 15.2 years old) completed a randomized, double-blind, placebo-controlled crossover study. After ingesting either EGb 761 (120mg/day as a single dose) or placebo during each 3-month arm, a 2-step euglycemic insulin clamp was performed. Results: At the low insulin infusion rate (10mU/m(2)/min) the glucose metabolic rates (M values) were 3.5 +/- 1.5 vs. 3.0 +/- 0.5mg/kg (P=0.16), 3.0 +/- 0.4 vs. 2.8 +/- 0.8mg/kg (P=0.19) and 2.6 +/- 0.7 vs. 2.4 +/- 0.5mg/kg (P=0.09) for the placebo and EGb 761 cycles, in the NGT, IGT and T2DM subjects, respectively. At the high insulin infusion rate (40 mU/m(2)/min) the M values were 7.3 +/- 2.3 vs. 8.1 +/- 2.5mg/kg (P=0.07), 6.2 +/- 1.6vs. 6.5 +/- 2.1 mg/kg (P=0.32) and 3.6 +/- 1.6vs. 3.5 +/- 1.0 mg/kg (P=0.34) for placebo vs. EGb 761 cycles, in the NGT, IGT and T2DM subjects, respectively. Conclusion: The ingestion of 120mg of EGb 761 as a single for 3 months did not produce insulin resistance in the non-diabetic or pre-diabetic subjects or exacerbate the disease in the T2DM subjects. (c) 2005 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Dept Clin Lab Sci, San Antonio, TX 78229 USA. Audie L Murphy Vet Affairs Hosp, San Antonio, TX 78284 USA. RP Kudolo, GB (reprint author), Univ Texas, Hlth Sci Ctr, Dept Clin Lab Sci, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM Kudolo@uthscsa.edu FU NCCIH NIH HHS [R01-AT-00832]; NCRR NIH HHS [M01-RR-01346] NR 43 TC 10 Z9 13 U1 1 U2 3 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0261-5614 J9 CLIN NUTR JI Clin. Nutr. PD FEB PY 2006 VL 25 IS 1 BP 123 EP 134 DI 10.1016/j.clnu.2005.10.001 PG 12 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 027SN UT WOS:000236436000014 PM 16293352 ER PT J AU Quirynen, M Vogels, R Peeters, W Steenberghe, D Naert, I Haffajee, A AF Quirynen, M Vogels, R Peeters, W Steenberghe, D Naert, I Haffajee, A TI Dynamics of initial subgingival colonization of 'pristine' peri-implant pockets SO CLINICAL ORAL IMPLANTS RESEARCH LA English DT Article DE colonization; cross-contamination; dental plaque; implants; peri-implantitis; periodontitis; plaque growth; translocation ID PARTIALLY EDENTULOUS PATIENTS; DNA-DNA HYBRIDIZATION; OSSEOINTEGRATED TITANIUM IMPLANTS; ORAL MUCOUS-MEMBRANES; MARGINAL TISSUE-REACTIONS; REAL-TIME PCR; DENTAL IMPLANTS; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; PERIODONTAL PATHOGENS; PLAQUE SAMPLES AB Background: Periodontitis and peri-implantitis are linked to the presence of several key pathogens. The treatment of these infectious processes therefore involves the reduction/eradication of bacteria associated with periodontitis. Methods: This prospective, split-mouth, single-blind study followed the colonization of 'pristine' sulci created in 42 partially edentulous patients during implant surgery (e.g. abutment connection). The hypothesis was that the composition of the maturing subgingival plaque in these 'fresh' peri-implant pockets would soon (within 2 weeks) be comparable to the subgingival microbiota of teeth with similar clinical parameters (reference sites), including the presence of bacteria associated with periodontitis. Per patient, four subgingival plaque samples were taken from shallow and medium pockets around implants (test sites), and teeth within the same quadrant (undisturbed microbiota as control sites), 1, 2, 4, 13, 26 and 78 weeks after abutment connection, respectively. The samples were analysed by either checkerboard DNA-DNA hybridization, or cultural techniques, or real-time polymerase chain reaction (PCR) for intra-subject comparisons (teeth vs. implant, for comparable probing depths). Results: Checkerboard DNA-DNA hybridization and real-time PCR revealed a complex microbiota (including several pathogenic species) in the peri-implant pockets within 2 weeks after abutment connection. After 7 days, the detection frequency for most species (including the bacteria associated with periodontitis) was already nearly identical in samples from the fresh peri-implant pockets (5% and 20% of the microbiota belonging to red and orange complex, respectively) when compared with samples from the reference teeth. Afterwards (e.g. between weeks 2 and 13), the number of bacteria in peri-implant pockets only slightly increased (+/- 0.1 log value), with minor changes in the relative proportions of bacteria associated with periodontitis (8% and 33% of the microbiota belonging to red and orange complex, respectively). Although small differences were seen between teeth and implants at week 2 with cultural techniques, a striking similarity in subgingival microbiota was found with this technique from month 3 on, with nearly identical detection frequencies for bacteria associated with periodontitis for both abutment types. Conclusions: This study indicates that the initial colonization of peri-implant pockets with bacteria associated with periodontitis occurs within 2 weeks. C1 Katholieke Univ Leuven, Dept Periodontol, Fac Med, Sch Dent Oral Pathol & Maxillofacial Surg, B-3000 Leuven, Belgium. Katholieke Univ Leuven, Res Grp Microbial Adhes, Fac Med, Sch Dent Oral Pathol & Maxillofacial Surg, B-3000 Leuven, Belgium. Katholieke Univ Leuven, Dept Prosthet Dent, Fac Med, Sch Dent Oral Pathol & Maxillofacial Surg, B-3000 Leuven, Belgium. Forsyth Inst, Dept Periodontol, Boston, MA USA. RP Quirynen, M (reprint author), Katholieke Univ Leuven, Dept Periodontol, Fac Med, Sch Dent Oral Pathol & Maxillofacial Surg, Kapucijnenvoer 33, B-3000 Leuven, Belgium. EM Marc.Quirynen@med.kuleuven.ac.be NR 68 TC 144 Z9 152 U1 1 U2 8 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0905-7161 J9 CLIN ORAL IMPLAN RES JI Clin. Oral Implant. Res. PD FEB PY 2006 VL 17 IS 1 BP 25 EP 37 DI 10.1111/j.1600-0501.2005.01194.x PG 13 WC Dentistry, Oral Surgery & Medicine; Engineering, Biomedical SC Dentistry, Oral Surgery & Medicine; Engineering GA 005WA UT WOS:000234854400004 PM 16441782 ER PT J AU Atlas, SJ Delitto, A AF Atlas, Steven J. Delitto, Anthony TI Spinal stenosis - Surgical versus nonsurgical treatment SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID LOW-BACK-PAIN; UNITED-STATES TRENDS; MAINE LUMBAR SPINE; LONG-TERM; NEUROGENIC CLAUDICATION; COCHRANE COLLABORATION; REGIONAL-VARIATIONS; DOUBLE-BLIND; FOLLOW-UP; DECOMPRESSIVE LAMINECTOMY AB Lumbar spinal stenosis is being diagnosed increasingly in older people as advanced imaging studies become more widely available and clinicians become more familiar with the presentation of this common condition. For symptomatic patients, the goal of treatment is pain relief and improved function, but there is little empiric evidence to support many of the common interventions used. The relative risks and benefits of various surgical and nonsurgical treatments are poorly understood, and the result has been wide variations in the evaluation and treatment of spinal stenosis across geographic regions. Current practice recommendations are based on expert opinion that incorporates available evidence into existing clinical and biologic paradigms. For most individuals, initial treatment should focus on patient education, medications to control pain, and exercise and physical treatments to regain or maintain activities of daily living. Surgical treatment most commonly is considered in patients not improving with nonsurgical care. Decompressive laminectomy is the standard surgical procedure for patients with spinal stenosis. The addition of fusion with or without instrumentation is considered when spinal stenosis is accompanied by degenerative spondylolisthesis or related to concerns about instability. We review the available evidence for nonsurgical and surgical interventions, and highlight comparative results wherever applicable. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Med Serv,Gen Med Div, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Med Serv,Clin Epidemiol Unit, Boston, MA 02114 USA. Univ Pittsburgh, Sch Hlth & Rehabil Sci, Dept Phys Therapy, Pittsburgh, PA USA. RP Atlas, SJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Med Serv,Gen Med Div, 50 Staniford St, Boston, MA 02114 USA. EM satlas@partners.org FU NIAMS NIH HHS [P60 AR048094, R01-AR/NS45622] NR 93 TC 30 Z9 32 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD FEB PY 2006 IS 443 BP 198 EP 207 DI 10.1097/01.blo.0000198722.70138.96 PG 10 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 119NV UT WOS:000243019900031 PM 16462443 ER PT J AU Zhu, Y Statkevich, P Curtis, D Sugrue, M Kieran, M AF Zhu, Y Statkevich, P Curtis, D Sugrue, M Kieran, M TI Pharmacokinetics of lonafarnib, a farnesyl protein transferase inhibitor, in pediatric patients with brain tumors. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 107th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 08-11, 2006 CL Baltimore, MD SP Amer Soc Clin Pharmacol & Therapeut C1 Schering Plough Corp, Kenilworth, NJ 07033 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2006 VL 79 IS 2 SU S BP P10 EP P10 DI 10.1016/j.clpt.2005.12.036 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 012EA UT WOS:000235319800036 ER PT J AU Spencer, TJ Wilens, TE Biederman, J Weisler, RH Read, SC Pratt, R AF Spencer, TJ Wilens, TE Biederman, J Weisler, RH Read, SC Pratt, R TI Efficacy and safety of mixed amphetamine salts extended release (Adderall XR) in the management of attention-deficit/hyperactivity disorder in adolescent patients: A 4-week, randomized, double-blind, placebo-controlled, parallel-group study SO CLINICAL THERAPEUTICS LA English DT Article DE attention-deficit/hyperactivity disorder; ADHD; stimulant; amphetamine; mixed amphetamine salts extended release; Adderall XR; adolescents ID DEFICIT HYPERACTIVITY DISORDER; ANALOG CLASSROOM ASSESSMENT; 4-YEAR FOLLOW-UP; QUALITY-OF-LIFE; PSYCHIATRIC STATUS; SUBSTANCE USE; CHILDREN; ADHD; CHILDHOOD; CYCLE AB Background: The ability to recognize and diagnose attention-deficit/hyperactivity disorder (ADHD) has increased in recent years. The persistence of ADHD symptoms puts adolescents with ADHD at risk for long-term adverse psychosocial outcomes. Objective: The primary goal of this study was to assess the efficacy and safety of mixed amphetamine salts extended release (MAS XR) in the management of adolescents with ADHD. Methods: This was a 4-week, randomized, multicenter, double-blind, placebo-controlled, parallel-group, forced-dose-titration study. Adolescents aged 13 to 17 years with ADHD were randomized to 1 of 4 active treatments (MAS XR 10, 20, 30, or 40 mg/d) or to placebo. All doses were given in the morning. This study used a forced-dose-titration design in which patients randomized to the 10-mg/d group received 1 dose of 10 mg/d for 4 weeks. Patients randomized to the 20-mg/d group received 1 dose of 10 mg/d for the first week and 1 dose of 20 mg/d for the remaining weeks; patients randomized to the 30-mg/d group received 1 dose of 10 mg/d for the first week, 1 dose of 20 mg/d for the second week, and 1 dose of 30 mg/d for the remaining 2 weeks; and patients randomized to the 40-mg/d group received 1 dose of 10 mg/d for the first week, 1 dose of 20 mg/d for the second week, 1 dose of 30 mg/d for the third week, and 1 dose of 40 mg/d for the fourth week. The primary efficacy measure was change from baseline to end point in the ADHD Rating Scale-IV (ADHD-RS-IV) score. The secondary efficacy measure was the score on the Clinical Global Impressions-Improvement (CGI-I) scale for ADHD. ADHD-RS-IV total scores were analyzed post hoc in patients with low baseline ADHD-RS-IV severity (le, patients with baseline ADHD-RS-IV total scores less than the median) and high baseline ADHD-RS-W severity (le, patients with baseline ADHD-RS-IV total scores greater than the median). Safety was assessed by recording adverse events, vital signs, and body weight at all study visits and 30 days after drug discontinuation. Results: Of the 287 randomized adolescents, 258 completed the study. The intent-to-treat (ITT) population included 278 patients. The majority of patients were male (65.5%) and white (73.7%). The mean weight (57.8 kg [127.1 lb]) at baseline and the mean height (163.8 cm [64.5 in]) at screening were comparable across all MAS XR treatment groups. Patients in the placebo group had a mean weight of 59.8 kg (131.6 lb) and a mean height of 166.1 cm (65.4 in). Most (56.5%) of the patients had ADHD combined inattentive/hyperactive-impulsive subtype. Two hundred nineteen (78.8%) patients were treatment naive, and 59 (21.2%) had received treatment for ADHD within 30 days before screening. ITT analysis of the ADHD-RS-IV revealed statistically significant (P < 0.001) improvement in mean ADHD-RS-IV total scores in all 4 MAS XR treatment groups, compared with placebo, at all weeks throughout the 4-week study; the mean change from baseline to end point was -17.8 in the MAS XR 10- to 40-mg/d groups and -9.4 in the placebo group. Significant treatment effects were observed in both the ADHD-RS-IV inattentive (P < 0.001) and hyperactive-impulsive (P < 0.001) subscales from baseline. In patients with low baseline ADHD-RS-IV severity, statistically significantly (P <=. 0.01) greater improvements were observed in the MAS XR 20-, 30-, and 40-mg/d groups than in the placebo group; in patients with high baseline ADHD-RS-IV severity, statistically significantly (P <= 0.02) greater improvements were observed in all active treatment groups compared with placebo. On the CGI-I scale at end point, a higher percentage of adolescents in all MAS XR treatment groups were considered improved (MAS XR 10 mg/d, 51.9% [P < 0.01]; 20 mg/d, 66.0% [P < 0.001]; 30 mg/d, 70.7% [P < 0.001]; 40 mg/d, 63.9% [P < 0.001]) compared with adolescents receiving placebo (26.9%). The most common adverse events in patients receiving MAS XR versus placebo were anorexia/ decreased appetite (35.6% vs 1.9%), headache (16.3% vs 22.2%), insomnia (12.0% vs 3.7%), abdominal pain (10.7% vs 1.9%), and weight loss (9.4% vs 0%). Most adverse events were mild or moderate in intensity (97.5%); no serious adverse events were reported. Conclusions: The adolescents with ADHD treated with 10- to 40-mg/d MAS XR up to 4 weeks had significant improvements in ADHD symptoms compared with those who received placebo. Results of this study suggest that once-daily dosing with MAS XR up to 40 mg was effective and well tolerated for the management of ADHD in these adolescents. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Yawkey Ctr Outpatient Care,Clin & Res Program Ped, Boston, MA 02114 USA. Univ N Carolina, Chapel Hill, NC USA. Duke Univ, Med Ctr, Durham, NC USA. Shire Pharmaceut Inc, Wayne, PA USA. RP Spencer, TJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Yawkey Ctr Outpatient Care,Clin & Res Program Ped, YAW-4-4A,32 Fruit St, Boston, MA 02114 USA. EM tspencer@partners.org NR 41 TC 55 Z9 55 U1 7 U2 34 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PD FEB PY 2006 VL 28 IS 2 BP 266 EP 279 DI 10.1016/j.clinthera.2006.02.011 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 019QJ UT WOS:000235851500010 PM 16678648 ER PT J AU Biederman, J Wigal, SB Spencer, TJ McGough, JJ Mays, DA AF Biederman, J Wigal, SB Spencer, TJ McGough, JJ Mays, DA TI A post hoc subgroup analysis of an 18-day randomized controlled trial comparing the tolerability and efficacy of mixed amphetamine salts extended release and atomoxetine in school-age girls with attention-deficit/hyperactivity disorder SO CLINICAL THERAPEUTICS LA English DT Article; Proceedings Paper CT 158th Annual Meeting of the American-Psychiatric-Association CY MAY 21-26, 2005 CL Atlanta, GA SP Amer Psychiat Assoc DE girls; attention-deficit/hyperactivity disorder; ADHD; Adderall XR; amphetamine; stimulant; laboratory school study; atomoxetine; Strattera; nonstimulant ID DEFICIT HYPERACTIVITY DISORDER; GENDER-DIFFERENCES; DOUBLE-BLIND; CHILDREN; ADHD; METHYLPHENIDATE; PLACEBO; ADOLESCENTS; ADDERALL; BEHAVIOR AB Background: Because the scientific literature on the pharmacotherapy of attention-deficit/hyperactivity disorder (ADHD) is almost entirely based on the results of studies in samples consisting primarily of boys, much is unknown about the treatment response in girls. Objective: This post hoc analysis compared the efficacy, tolerability, and time course of the effect of mixed amphetamine salts extended release (MAS XR) and atomoxetine in school-age girls with ADHD. Methods: This was an intent-to-treat subanalysis of the data from girls enrolled in a multicenter, 18-day, randomized, double-blind, parallel-group, forced dose-titration, laboratory school study enrolling boys and girls aged 6 to 12 years with ADHD. The study compared the efficacy, tolerability, and time course of the effect of increasing doses of MAS XR (10, 20, and 30 mg/d) and atomoxetine (0.5 and 1.2 mg/kg per day). The laboratory school sessions were organized in cycles to include 12 hours of observation. Efficacy measures included the SKAMP (Swanson, Kotkin, Agler, M-Flynn, and Pelham) deportment rating subscale, the SKAMP attention rating subscale, and academic testing (number of math problems attempted and answered correctly). Adverse events were assessed throughout the study period. Tolerability and efficacy measures were assessed during laboratory school visits on days 7, 14, and 21. Results: This subanalysis included 57 girls (median age, 9 years; 49.1% white, 22.8% black, 17.5% Hispanic) with a diagnosis of ADHD, combined sub-type. Twenty-six girls were randomized to receive MAS XR and 31 were randomized to receive atomoxetine. Mean SKAMP deportment and attention subscale scores in the 2 groups were similar at baseline. Mean changes from baseline were significantly greater for MAS XR compared with atomoxetine on the SKAMP deportment score (-0.48 vs -0.04, respectively; P < 0.001) and SKAMP attention score (-0.45 vs -0.05; P < 0.001). The time course of medication effect, based on change from baseline in SKAMP deportment scores, indicated 12-hour efficacy for MAS XR at hours 2, 4.5, 7, 9.5, and 12 (all time points, P < 0.01 vs baseline) but not for atomoxetine. At the end of the study, both treatment groups had a significant increase from baseline in the mean number of math problems attempted and answered correctly (P < 0.001). Girls who received MAS XR attempted significantly greater numbers of problems compared with those who received atomoxetine (P = 0.04). Both MAS XR and atomoxetine were well tolerated. The most frequently occurring treatment-related adverse events in girls receiving MAS XR were decreased appetite (40.7%), upper abdominal pain (29.6%), insomnia (25.9%), and headache (14.8%). The most frequently occurring treatment-related adverse events in girls receiving atomoxetine were somnolence (28.1%), upper abdominal pain (15.6%), vomiting (15.6%), nausea (12.5%), and decreased appetite (12.5%). Conclusion: This post hoc analysis in a subpopulation of girls with ADHD, combined subtype, found that 18-day treatment with MAS XR was significantly more effective than atomoxetine in terms of ratings of classroom behavior, attention, and academic productivity. C1 Massachusetts Gen Hosp, Yawkey Ctr Outpatient Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Calif Irvine, Child Dev Ctr, Irvine, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. Shire Pharmaceut Inc, Wayne, PA USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Yawkey Ctr Outpatient Care, 55 Fruit St,Suite 6A, Boston, MA 02114 USA. EM jbiederman@partners.org NR 33 TC 19 Z9 21 U1 6 U2 13 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PD FEB PY 2006 VL 28 IS 2 BP 280 EP 293 DI 10.1016/j.clinthera.2006.02.008 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 019QJ UT WOS:000235851500011 PM 16678649 ER PT J AU Milligan, TA Bromfield, EB AF Milligan, TA Bromfield, EB TI A case of "Migralepsy" SO CNS SPECTRUMS LA English DT Article; Proceedings Paper CT 58th Annual Meeting of the American-Epilepsy-Society CY DEC 03-07, 2004 CL New Orleans, LA SP Amer Epilepsy Soc ID MIGRAINE; EPILEPSY; COMORBIDITY AB Migraine and epilepsy are common neurological conditions that may share a pathophysiologic and genetic basis. The following case is presented to illustrate key aspects of their relationship. C1 Brigham & Womens Hosp, Dept Neurol, Div EEG Epilepsy & Sleep Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Bromfield, EB (reprint author), Brigham & Womens Hosp, Dept Neurol, Div EEG Epilepsy & Sleep Neurol, 75 Francis St, Boston, MA 02115 USA. EM ebromfield@partners.org NR 10 TC 3 Z9 4 U1 0 U2 0 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD FEB PY 2006 VL 11 IS 2 SU 2 BP 6 EP 8 PG 3 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 020KH UT WOS:000235907300002 ER PT J AU Thase, ME Fava, M DeBattista, C Arora, S Hughes, RJ AF Thase, ME Fava, M DeBattista, C Arora, S Hughes, RJ TI Modafinil augmentation of SSRI therapy in patients with major depressive disorder and excessive sleepiness and fatigue: A 12-week, open-label, extension study SO CNS SPECTRUMS LA English DT Article ID SEROTONIN REUPTAKE INHIBITORS; ANTIDEPRESSANT THERAPY; BUSPIRONE AUGMENTATION; REFRACTORY DEPRESSION; RESIDUAL SYMPTOMS; TERM TREATMENT; SCALE; AMPHETAMINE; FLUOXETINE; SEVERITY AB Introduction: Many patients with major depressive disorder (MDD) treated with selective serotonin reuptake inhibitors have residual symptoms (eg, persistent fatigue, excessive sleepiness) despite an overall antidepressant response. Placebo-controlled studies indicate that modafinil, a wake-promoting agent, may relieve residual symptoms. Methods: This 12-week, open-label, dose titration, extension study followed an 8-week placebo-controlled study of modafinil augmentation in patients with MDD. The dose was 100-400 mg/ day. The median stable dose was 300 mg/day. Assessments were the Epworth Sleepiness Scale, Brief Fatigue Inventory, Clinical Global Impression of Improvement scale, 17-item Hamilton Rating Scale for Depression, and Montgomery-Asberg Depression Rating Scale. Results: Of the 245 patients treated, 194 completed the study; 70% reported Clinical Global Impression of Improvement scale responses of "much improved" or "very much improved" between open-label baseline and final visit (previous randomized modafinil group: 74%; placebo group: 66%). When data were analyzed for four subsets of patients (former modafinil responders, placebo responders, modafinil nonresponders, and placebo nonresponders), improvements in scores on all outcome measures were at least twice as great among former modafinil and placebo nonresponders compared with responders. Most common adverse events were headache (18%), nausea (9%), and dizziness (7%); all were generally mild to moderate in severity. Conclusion: Twelve weeks of modafinil augmentation relieved excessive sleepiness, reduced fatigue, and improved patients' overall clinical condition, including mood. C1 Univ Pittsburgh, Med Ctr, Sch Med, Div Adult Acad Psychiat, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Mood Disorders Treatment & Res Program, Pittsburgh, PA 15260 USA. Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. Stanford Univ, Depress Res Clin, Stanford, CA 94305 USA. Cephalon Inc, Dept Biostat, Frazer, PA USA. Cephalon Inc, Dept Commun Sci, Frazer, PA USA. RP Thase, ME (reprint author), Univ Pittsburgh, Med Ctr, Sch Med, Div Adult Acad Psychiat, 3811 OHara St, Pittsburgh, PA 15260 USA. EM thaseme@upmc.edu NR 37 TC 44 Z9 44 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 FEB PY 2006 VL 11 IS 2 BP 93 EP 102 PG 10 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 018UB UT WOS:000235789200009 PM 16520686 ER PT J AU Shipherd, JC AF Shipherd, Jillian C. TI Treatment of a case example with PTSD and chronic pain SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; RANDOMIZED CONTROLLED-TRIAL; COGNITIVE-BEHAVIOR THERAPY; CHRONIC-FATIGUE-SYNDROME; MOTOR-VEHICLE ACCIDENT; ANXIETY SENSITIVITY; IMMPACT RECOMMENDATIONS; RECURRING HEADACHES; PROCESSING THERAPY; MUTUAL MAINTENANCE AB This commentary reviews the case of GH, a survivor of a road traffic collision, who has chronic pain and posttraumatic stress disorder (PTSD). The case formulation, assessment strategy, and treatment plan are informed by the relevant experimental literature and empirically supported treatments using a cognitive behavioral perspective. Given this framework, the commentary includes a focus on the treatment of PTSD with an eye toward generalizing the therapeutic strategies to chronic pain problems. Psychoeducation, imaginal exposure to the traumatic event, in vivo exposure to avoided activities, and cognitive interventions including coping self-statements, correction of logical errors, decatastrophizing and developing alternative explanations are all included in the recommendations as Part Of a standard cognitive behavioral treatment for PTSD. Added to this standard PTSD protocol is the suggested use of interoceptive exposure to address GH's feared bodily sensations. In the assessment domain, standard measures for pain and PTSD assessment are suggested along with tracking of depression and anxiety sensitivity. Some recognition of more recent approaches to cognitive behavioral therapy (e.g., Acceptance and Commitment Therapy) is given in considering potential obstacles to treatment. C1 VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA 02130 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. RP Shipherd, JC (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, 116B-3,150 S Huntington Ave, Boston, MA 02130 USA. EM Jillian.Shipherd@med.va.gov NR 79 TC 1 Z9 1 U1 2 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1077-7229 J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD FEB PY 2006 VL 13 IS 1 BP 24 EP 32 DI 10.1016/j.cbpra.2005.03.003 PG 9 WC Psychology, Clinical SC Psychology GA 174HQ UT WOS:000246933300004 ER PT J AU Glynn, SM AF Glynn, Shirley M. TI Kingdon and Turkington's cognitive therapy of schizophrenia SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Book Review ID BEHAVIORAL THERAPY C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. RP Glynn, SM (reprint author), VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 12 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 1077-7229 J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD FEB PY 2006 VL 13 IS 1 BP 105 EP 106 DI 10.1016/j.cbpra.2006.01.003 PG 2 WC Psychology, Clinical SC Psychology GA 174HQ UT WOS:000246933300015 ER PT J AU Mian, SI Gupta, A Pineda, R AF Mian, SI Gupta, A Pineda, R TI Corneal ulceration and perforation with ketorolac tromethamine (Acular (R)) use after PRK SO CORNEA LA English DT Article DE corneal perforation; NSAID; ketorolac tromethamine; Acular (R); PRK ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; LASER PHOTOREFRACTIVE KERATECTOMY; TOPICAL DICLOFENAC; SENSITIVITY; EXPRESSION; SENSATION; KERATITIS; EFFICACY; SURGERY; PAIN AB Purpose: To report a case of corneal ulceration and perforation after PRK connected with high doses of ketorolac tromethamine (Acular (R)). Methods: A 31-year-old man presented 5 days after PRK in the left eye with corneal ulceration and perforation requiring penetrating keratoplasty. The patient admitted to using Acular (R) every hour, ciprofloxocin every hour, and prednisolone acetate 1% QID postoperatively. Results: Laboratory tests, including corneal cultures, were normal A diagnosis of corneal ulceration secondary to incorrect use of high dose ketorolac tromethamine was made. Conclusion: Judicious patient counseling is recommended when using topical NSAIDs in the setting of PRK. C1 Univ Michigan, WK Kellogg Eye Ctr, Cornea & External DisCataract & Refract Surg Serv, Ann Arbor, MI 48105 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Mian, SI (reprint author), Univ Michigan, WK Kellogg Eye Ctr, Cornea & External DisCataract & Refract Surg Serv, 1000 Wall St, Ann Arbor, MI 48105 USA. EM smian@med.umich.edu NR 26 TC 24 Z9 25 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0277-3740 J9 CORNEA JI Cornea PD FEB PY 2006 VL 25 IS 2 BP 232 EP 234 DI 10.1097/01.ico.0000179931.05275.dd PG 3 WC Ophthalmology SC Ophthalmology GA 007TP UT WOS:000234993100023 PM 16371790 ER PT J AU Minneci, PC Deans, KJ Cui, XZ Banks, SM Natanson, C Eichacker, PQ AF Minneci, PC Deans, KJ Cui, XZ Banks, SM Natanson, C Eichacker, PQ TI Antithrombotic therapies for sepsis: A need for more studies SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE antithrombin III; sepsis; septic shock ID ACTIVATED PROTEIN-C; RANDOMIZED CONTROLLED-TRIAL; FACTOR PATHWAY INHIBITOR; DOUBLE-BLIND; SAFETY; MULTICENTER; METAANALYSIS; EFFICACY C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NIH, Dept Crit Care Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Minneci, PC (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 19 TC 14 Z9 17 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD FEB PY 2006 VL 34 IS 2 BP 538 EP 541 DI 10.1097/01.CCM.0000199035.29165.A7 PG 4 WC Critical Care Medicine SC General & Internal Medicine GA 008UF UT WOS:000235065500035 PM 16424739 ER PT J AU Walz, C Sattler, M AF Walz, C Sattler, M TI Novel targeted therapies to overcome imatinib mesylate resistance in chronic myeloid leukemia (CML) SO CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY LA English DT Review DE tyrosine kinase inhibitor; resistance; imatinib mesylate; BCR-ABL; chronic myeloid leukemia ID CHRONIC MYELOGENOUS LEUKEMIA; TYROSINE KINASE INHIBITOR; FARNESYL TRANSFERASE INHIBITOR; CELL MYELOPROLIFERATIVE DISORDER; CHRONIC MYELOMONOCYTIC LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; FACTOR RECEPTOR-BETA; ABL GENE-EXPRESSION; BCR-ABL; IN-VITRO AB Imatinib mesylate (Gleevec) was developed as the first molecularly targeted therapy that specifically inhibits the BCR-ABL tyrosine kinase activity in patients with Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML). Due to its excellent hematologic and cytogenetic responses, particularly in patients with chronic phase CML, imatinib has moved towards first-line treatment for newly diagnosed CML. Nevertheless, resistance to the drug has been frequently reported and is attributed to the fact that transformation of hematopoietic stem cells by BCR-ABL is associated with genomic instability. Point mutations within the ABL tyrosine kinase of the BCR-ABL oncoprotein are the major cause of resistance, though overexpression of the BCR-ABL protein and novel acquired cytogenetic aberrations have also been reported. A variety of strategies derived from structural studies of the ABL-imatinib complex have been developed, resulting in the design of novel ABL inhibitors, including AMN107, BMS-354825, ON012380 and others. The major goal of these efforts is to create new drugs that are more potent than imatinib and/or more effective against imatinib-resistant BCR-ABL clones. Some of these drugs have already been successfully tested in preclinical studies where they show promising results. Additional approaches are geared towards targeting the expression or stability of the BCR-ABL kinase itself or targeting signaling pathways that are chronically activated and required for transformation. In this review, we will discuss the underlying mechanisms of resistance to imatinib and novel targeted approaches to overcome imatinib resistance in CML. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Sattler, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM martin_sattler@dfci.harvard.edu NR 200 TC 72 Z9 78 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1040-8428 J9 CRIT REV ONCOL HEMAT JI Crit. Rev. Oncol./Hematol. PD FEB PY 2006 VL 57 IS 2 BP 145 EP 164 DI 10.1016/j.critrevonc.2005.06.007 PG 20 WC Oncology; Hematology SC Oncology; Hematology GA 013JH UT WOS:000235405100004 PM 16213151 ER PT J AU Stacy, R Eroglu, A Fowler, A Biggers, J Toner, M AF Stacy, R Eroglu, A Fowler, A Biggers, J Toner, M TI Thermal characterization of Nakagata's mouse sperm freezing protocol SO CRYOBIOLOGY LA English DT Article DE murine spermatozoa; cryopreservation; warming rates; cooling rates ID IN-VITRO FERTILIZATION; OSMOTIC TOLERANCE; SPERMATOZOA; CRYOPRESERVATION; MICE; GLYCEROL; FROZEN; TEMPERATURE; RAFFINOSE; SURVIVAL AB This paper reports the results of an experimental study of the warming and cooling rates achieved using the popular Nakagata Protocol for murine sperm cryopreservation. Problems with the storage and maintenance of the huge number of genetically engineered mouse strains have led to an increased need for murine sperm preservation. Recent studies have begun to focus on optimizing the cryopreservation of murine sperm by carefully studying the effects of cooling and warming rates on sperm survival. In current practice, however, the Nakagata protocol is widely used. The actual cooling and warming rates achieved using the Nakagata protocol have not previously been determined; and the Nakagata protocol has a number of unspecified parameters which we have found can significantly affect cooling rates, warming rates and sperm survival. A detailed study of the thermal response of samples frozen and thawed using the Nakagata protocol reveals that the cooling rates range from 30 to almost 300 degrees C per minute depending on the exact manner in which the Nakagata protocol is implemented. Warming rates range from 160 degrees C/min to about 1000 degrees C/min. Sperm survival depended significantly on the particular cooling rate achieved, and less strongly on the warming rates. Overall, it was found that the particular manner in which the Nakagata protocol was implemented could strongly affect cooling rates and sperm survival; and, consistent with the findings of Mazur and Koshimoto, an optimal cooling rate appears to exist in the range of cooling rates that can be achieved using the Nakagata protocol. (C) 2005 Elsevier Inc. All rights reserved. C1 Univ Massachusetts Dartmouth, Dept Mech Engn, N Dartmouth, MA 02748 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. Shriners Burn Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Med Coll Georgia, Inst Mol Med & Genet, Augusta, GA 30912 USA. RP Fowler, A (reprint author), Univ Massachusetts Dartmouth, Dept Mech Engn, N Dartmouth, MA 02748 USA. EM afowler@umassd.edu NR 30 TC 20 Z9 22 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0011-2240 J9 CRYOBIOLOGY JI Cryobiology PD FEB PY 2006 VL 52 IS 1 BP 99 EP 107 DI 10.1016/j.cryobiol.2005.10.006 PG 9 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA 017KO UT WOS:000235692700010 PM 16332363 ER PT J AU Elliott, GD Liu, XH Cusick, JL Menze, M Vincent, J Witt, T Hand, S Toner, M AF Elliott, GD Liu, XH Cusick, JL Menze, M Vincent, J Witt, T Hand, S Toner, M TI Trehalose uptake through P2X(7) purinergic channels provides dehydration protection SO CRYOBIOLOGY LA English DT Article DE P2X(7) receptor channel; J774 macrophages; ATP; trehalose; dehydration; desiccation ID MAMMALIAN-CELLS; DESICCATION TOLERANCE; INTRACELLULAR TREHALOSE; MOUSE MACROPHAGES; EXTRACELLULAR ATP; SWITCHABLE PORE; RECEPTOR; STABILIZATION; APOPTOSIS; MEMBRANES AB The tetra-anionic form of ATP (ATP(4-)) is known to induce monovalent and divalent ion fluxes in cells that express purinergic P2X(7) receptors and with sustained application of ATP it has been shown that dyes as large as 831 Da can permeate the cell membrane. The current study explores the kinetics of loading alpha,alpha-trehalose (342 Da) into ATP stimulated J774.A1 cells, which are known to express the purinergic P2X7 receptor. Cells that were incubated at 37 degrees C in a 50 mM phosphate buffer (pH 7.0) containing 225 mM trehalose and 5 tnM ATP, were shown to load trehalose linearly over time. Concentrations of similar to 50 mM were reached within 90 min of incubation. Cells incubated in the same solution at 4 degrees C loaded minimally, consistent with the inactivity of the receptor at low temperatures. However, extended incubation at 37 degrees C (>60 min) resulted in zero next-day survival, with adverse effects appearing even with incubation periods as short as 30 min. By using a two-step protocol with a short time period at 37 degrees C to allow pore formation, followed by an extended loading period on ice, cells could be loaded with up to 50 mM trehalose while maintaining good next day recovery (49 +/- 12% by Trypan blue exclusion, 56 +/- 20% by alamarBlue assay). Cells porated by this method and allowed an overnight recovery period exhibited improved dehydration tolerance suggesting a role for ATP poration in the anhydrous preservation of cells. (C) 2005 Elsevier Inc. All rights reserved. C1 Univ N Carolina, Dept Mech Engn & Engn Sci, Charlotte, NC 28223 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Louisiana State Univ, Dept Sci Biol, Baton Rouge, LA 70803 USA. RP Elliott, GD (reprint author), Univ N Carolina, Dept Mech Engn & Engn Sci, 9201 Univ City Bldg, Charlotte, NC 28223 USA. EM gdelliot@uncc.edu OI Menze, Michael/0000-0003-1072-5462 FU NIGMS NIH HHS [GM071345-01] NR 46 TC 39 Z9 40 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 0011-2240 J9 CRYOBIOLOGY JI Cryobiology PD FEB PY 2006 VL 52 IS 1 BP 114 EP 127 DI 10.1016/j.cryobiol.2005.10.009 PG 14 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA 017KO UT WOS:000235692700012 PM 16338230 ER PT J AU Oakes, SA Lin, SS Bassik, MC AF Oakes, SA Lin, SS Bassik, MC TI The control of endoplasmic reticulum-initiated apoptosis by the BCL-2 family of proteins SO CURRENT MOLECULAR MEDICINE LA English DT Review ID STRESS-INDUCED APOPTOSIS; INDUCED CELL-DEATH; MITOCHONDRIAL-MEMBRANE PERMEABILIZATION; CYTOCHROME-C RELEASE; PROAPOPTOTIC BAX; INOSITOL 1,4,5-TRISPHOSPHATE; CA2+ CONCENTRATION; BH3-ONLY PROTEINS; CALCIUM SIGNALS; REGULATES BAX AB Irreversible perturbations in the homeostasis of the endoplasmic reticulum (ER) are thought to lead to apoptosis and cell loss in a number of important human diseases, including Alzheimer disease, Parkinson disease, and type 2 diabetes. However, the exact mechanisms that lead from ER stress to cell death remain incompletely understood. Recent work has shown that the BCL-2 family of proteins plays a central role in regulating this form of cell death, both locally at the ER and from a distance at the mitochondrial membrane. C1 Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA. Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Calif San Francisco, Dept Mol & Cellular Pharmacol, San Francisco, CA 94143 USA. RP Oakes, SA (reprint author), Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA. EM scott.oakes@ucsf.edu FU NIAID NIH HHS [K08 AI054650] NR 115 TC 76 Z9 77 U1 0 U2 5 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1566-5240 J9 CURR MOL MED JI Curr. Mol. Med. PD FEB PY 2006 VL 6 IS 1 BP 99 EP 109 DI 10.2174/156652406775574587 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 023QD UT WOS:000236140400009 PM 16472117 ER PT J AU Takahashi, K Ip, WKE Michelow, IC Ezekowitz, RAB AF Takahashi, K Ip, WKE Michelow, IC Ezekowitz, RAB TI The mannose-binding lectin: a prototypic pattern recognition molecule SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID SYNDROME CORONAVIRUS INFECTION; ISCHEMIA-REPERFUSION INJURY; COMPLEMENT ACTIVATION; INNATE IMMUNITY; OXIDATIVE STRESS; INFLUENZA-VIRUS; EARLY-CHILDHOOD; DEFICIENT MICE; PROTEIN; PATHWAY AB The innate immune system is comprised of a sophisticated network of recognition and effector molecules that act together to protect the host in the first minutes or hours of exposure to an infectious challenge. The mannose-binding lectin (MBL) is an evolutionary conserved circulating host defense protein that acts as a broad-spectrum recognition molecule against a wide variety of infectious agents. Target binding triggers the MBL pathway of complement activation. MBL can be considered conceptually as an 'ante-antibody' because it has a role in mammals during the lag period that is required to develop an antibody response against infectious agents. Additionally, there are MBL-like homologues in animals that lack adaptive immunity that activate a primitive complement system, and under these circumstances these MBL-like molecules play an analogous role to antibodies in higher animals. These molecules might be considered to be functional antecedents of antibodies. Recent work also indicates that MBL recognizes altered self-antigens, and as such MBL has a role that extends beyond a traditional role in first line host defense as it appears to play a role as a modulator of inflammation. C1 Harvard Univ, Massachusetts Gen Hosp, Dept Pediat, Lab Dev Immunol, Boston, MA 02114 USA. RP Ezekowitz, RAB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Pediat, Lab Dev Immunol, 55 Fruit St, Boston, MA 02114 USA. EM ezekowitz.alan@mgh.harvard.edu RI Ip, Eddie/C-3042-2012 FU NIAID NIH HHS [U01 AI070330] NR 68 TC 116 Z9 130 U1 2 U2 18 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD FEB PY 2006 VL 18 IS 1 BP 16 EP 23 DI 10.1016/j.coi.2005.11.014 PG 8 WC Immunology SC Immunology GA 007YM UT WOS:000235007400004 PM 16368230 ER PT J AU Sesso, HD AF Sesso, Howard D. TI Carotenoids and cardiovascular disease: what research gaps remain? SO CURRENT OPINION IN LIPIDOLOGY LA English DT Review DE blood; carotenoids; cardiovascular disease; clinical trials; diet; epidemiology AB Purpose of review Dietary and blood carotenoids, including alpha-carotene, beta-carotene, lycopene, lutein/zeaxanthin, and beta-cryptoxanthin, have been examined in a number of epidemiological studies in recent years for the risk of cardiovascular disease. This review assimilated the existing and recent literature on carotenoids and cardiovascular disease and considered what research gaps may remain. Recent findings Numerous large cohort studies have been published in largely American men and women that have examined dietary intake or blood levels of total or individual carotenoids with the risk of various cardiovascular endpoints. Overall, early, promising results have grown increasingly inconsistent over time. More recently, studies examining lycopene and lutein/zeaxanthin have offered more promising data on a possible, but not yet established; inverse association with the risk of cardiovascular disease. Recent epidemiological data on beta-cryptoxanthin and cardiovascular disease are lacking. Primary and secondary prevention trials have extensively examined,B-carotene, but not other carotenoids, for the risk of cardiovascular disease as either the primary or secondary endpoint with largely null results. More recent studies have focused on individual carotenoids in relation to cardiovascular disease and require a more careful evaluation of potential mechanisms of effect. Summary The promise of early epidemiological studies on carotenoids and cardiovascular disease paved the way to largely disappointing results from several large prevention trials of beta-carotene. Emerging recent evidence of potential cardioprotective effects for lycopene and other carotenoids besides beta-carotene in the diet and blood suggest that there is more to be learned in the story of carotenoids and both atherosclerotic progression and clinically manifested cardiovascular disease. C1 [Sesso, Howard D.] Brigham & Womens Hosp, Div Prevent Med & Aging, Dept Med, Boston, MA 02215 USA. [Sesso, Howard D.] Harvard Univ, Sch Med, Boston, MA USA. [Sesso, Howard D.] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. RP Sesso, HD (reprint author), Brigham & Womens Hosp, Div Prevent Med & Aging, Dept Med, 900 Commonwealth Ave E, Boston, MA 02215 USA. EM hsesso@hsph.harvard.edu NR 58 TC 19 Z9 21 U1 3 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0957-9672 J9 CURR OPIN LIPIDOL JI Curr. Opin. Lipidology PD FEB PY 2006 VL 17 IS 1 BP 11 EP 16 DI 10.1097/01.mol.0000203888.42514.27 PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Peripheral Vascular Disease SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Cardiovascular System & Cardiology GA V63FJ UT WOS:000204272700002 PM 16407710 ER PT J AU Mack, JW Wolfe, J AF Mack, JW Wolfe, J TI Early integration of pediatric palliative care: for some children, palliative care starts at diagnosis SO CURRENT OPINION IN PEDIATRICS LA English DT Review DE communication; end-of-life; palliative; pediatric ID OF-LIFE; CANCER; QUALITY; PARENTS; DEATH; THERAPY; SERVICE; TRIALS; IMPACT AB Purpose of review Pediatric palliative care, with its emphasis on symptom management and quality of life, is an important aspect of care of children with life-threatening illnesses. We review recent publications with implications for care of these children. Recent findings Invasive and life-sustaining measures continue to be part of care for many children with life-threatening illnesses, even at the end of life. While these measures may seem reasonable when recovery is possible, they may not fit with a family's preferences for end-of-life care. One possible cause of the prevalence of invasive measures in children at the end of life is that complex illness trajectories in children make it difficult to predict the timing of death. Inadequate communication by clinicians can also lead to poor preparation for the end-of-life period. Early integration of palliative care allows for improved symptom management, parental adjustment, and preparation for the end-of-life care period. Families who have the opportunity to prepare for the end-of-life period, including learning what to expect, are more likely to feel that their care has been of high quality. Bereaved parents also recognize the value of talking about death with their children. Summary Early integration of palliative care can allow children and families to make decisions about care that fit with their values, and should become a standard of care for all children with life-threatening illnesses. C1 Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Boston, MA 02115 USA. RP Wolfe, J (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, 44 Binney St 454, Boston, MA 02115 USA. EM joanne-wolfe@dfci.harvard.edu NR 20 TC 74 Z9 75 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8703 J9 CURR OPIN PEDIATR JI CURR. OPIN. PEDIATR. PD FEB PY 2006 VL 18 IS 1 BP 10 EP 14 DI 10.1097/01.mop.0000193266.86129.47 PG 5 WC Pediatrics SC Pediatrics GA 016TL UT WOS:000235643200002 PM 16470155 ER PT J AU Provot, S Kempf, H Murtaugh, LC Chung, UI Kim, DW Chyung, J Kronenberg, HM Lassar, AB AF Provot, S Kempf, H Murtaugh, LC Chung, UI Kim, DW Chyung, J Kronenberg, HM Lassar, AB TI Nkx3.2/Bapx1 acts as a negative regulator of chondrocyte maturation SO DEVELOPMENT LA English DT Article DE chondrogenesis; Runx2; Nkx3.2; Bapx1; PTHrP ID HORMONE-RELATED PEPTIDE; ENDOCHONDRAL BONE-DEVELOPMENT; DEPENDENT KINASE INHIBITOR; LETHAL SKELETAL DYSPLASIA; PARATHYROID-HORMONE; INDIAN-HEDGEHOG; SOMITIC CHONDROGENESIS; CBFA1-DEFICIENT MICE; TARGETED DISRUPTION; PTH/PTHRP RECEPTOR AB Parathyroid hormone-related protein (PTHrP) is essential to maintain a pool of dividing, immature chondrocytes in the growth plate of long bones. In chick and mouse, expression of Nkx3.2/Bapx1 in the growth plate is restricted to the proliferative zone and is downregulated as chondrocyte maturation begins. Nkx3.2/Bapx1 expression is lost in the growth plates of mice engineered to lack PTHrP signaling and, conversely, is maintained by ectopic expression of PTHrP in developing bones. Artificially preventing Nkx3.2/Bapx1 downregulation, by forced expression of either retroviral-encoded PTHrP or Nkx3.2 inhibits chondrocyte maturation. Although wild-type Nkx3.2 blocks chondrocyte maturation by acting as a transcriptional repressor, a 'reverse function' mutant of Nkx3.2 that has been converted into a transcriptional activator conversely accelerates chondrocyte maturation. Nkx3.2 represses expression of the chondrocyte maturation factor Runx2, and Runx2 misexpression can rescue the Nkx3.2-induced blockade of chondrocyte maturation. Taken together, these results suggest that PTHrP signals block chondrocyte hypertrophy by, in part, maintaining the expression of Nkx3.2/Bapx1, which in turn represses the expression of genes required for chondrocyte maturation. C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA. RP Lassar, AB (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM andrew_lassar@hms.harvard.edu RI Kempf, Herve/F-1171-2011 OI Kempf, Herve/0000-0003-1818-2327 FU NIAMS NIH HHS [AR048524]; NIDDK NIH HHS [DK56246]; NIGMS NIH HHS [GM054879] NR 40 TC 58 Z9 63 U1 0 U2 4 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD FEB PY 2006 VL 133 IS 4 BP 651 EP 662 DI 10.1242/dev.02258 PG 12 WC Developmental Biology SC Developmental Biology GA 021CT UT WOS:000235961500010 PM 16421188 ER PT J AU Eggenschwiler, JT Bulgakov, OV Qin, J Li, TS Anderson, KV AF Eggenschwiler, JT Bulgakov, OV Qin, J Li, TS Anderson, KV TI Mouse Rab23 regulates Hedgehog signaling from Smoothened to Gli proteins SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Sonic Hedgehog; Rab23; Smoothened; Gli2; Gli3; neural tube; patterning ID INTRAFLAGELLAR TRANSPORT PROTEINS; DROSOPHILA CUBITUS INTERRUPTUS; DEVELOPING SPINAL-CORD; NEURAL-TUBE DEFECTS; ZINC-FINGER PROTEIN; NEGATIVE REGULATOR; SUBCELLULAR-LOCALIZATION; ENDOCYTIC PATHWAY; BINDING-SITE; FLOOR PLATE AB Sonic hedgehog (Shh) signaling is required for the growth and patterning of many tissues in vertebrate embryos, but important aspects of the Shh signal transduction pathway are poorly understood. For example, the vesicle transport protein Rab23 is a cell autonomous negative regulator of Shh signaling, but the process affected by Rab23 has not been defined. Here, we demonstrate that Rab23 acts upstream of Gli transcription factors in patterning neural cell types in the spinal cord. Double mutant analysis indicates that the primary target of Rab23 is the Gli2 activator and that Rab23 and Gli3 repressor have additive effects on patterning. Analysis of Gli3 protein suggests that Rab23 also has a role in promoting the production of GO repressor. Although the membrane proteins Patched and Smoothened change subcellular localization in response to Shh, double mutant analysis demonstrates that Rab23 does not work through either Patched or Smoothened. Instead, Rab23 appears to regulate subcellular localization of essential components of the Hedgehog pathway that act downstream of Smoothened and upstream of Gli proteins. (c) 2005 Elsevier Inc. All rights reserved. C1 Sloan Kettering Inst, Dev Biol Program, New York, NY 10021 USA. Princeton Univ, Dept Biol Mol, Princeton, NJ 08544 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. RP Anderson, KV (reprint author), Sloan Kettering Inst, Dev Biol Program, New York, NY 10021 USA. EM k-anderson@ski.mskcc.org OI Anderson, Kathryn/0000-0003-1657-2161 FU NINDS NIH HHS [NS44385] NR 63 TC 84 Z9 90 U1 1 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD FEB 1 PY 2006 VL 290 IS 1 BP 1 EP 12 DI 10.1016/j.ydbio.2005.09.022 PG 12 WC Developmental Biology SC Developmental Biology GA 008KR UT WOS:000235040100001 PM 16364285 ER PT J AU Musen, G Lyoo, IK Sparks, CR Weinger, K Hwang, J Ryan, CM Jimerson, DC Hennen, J Renshaw, PF Jacobson, AM AF Musen, G Lyoo, IK Sparks, CR Weinger, K Hwang, J Ryan, CM Jimerson, DC Hennen, J Renshaw, PF Jacobson, AM TI Effects of type 1 diabetes on gray matter density as measured by voxel-based morphometry SO DIABETES LA English DT Article ID RECURRENT SEVERE HYPOGLYCEMIA; BRAIN METABOLIC ALTERATIONS; IDDM PATIENTS; BLOOD-FLOW; INSULIN; COMPLICATIONS; HYPERGLYCEMIA; MELLITUS; ABNORMALITIES; DYSFUNCTION AB The effects of type I diabetes and key metabolic variables on brain structure are not well understood. Sensitive methods of assessing brain structure, such as voxel-based morphometry (VBM), have not previously been used to investigate central nervous system changes in a diabetic population. Using VBM, we compared type I diabetic patients aged 25-40 years with disease duration of 15-25 years and minimal diabetes complications with an age-matched, nondiabetic control group. We investigated whether lower than expected gray matter densities were present, and if so, whether they were associated with glycemic control and history of severe hypoglycemic events. In comparison with control subjects, diabetic patients showed lower density of gray matter in several brain regions. Moreover, in the patient group, higher HbA(1c) levels and severe hypoglycemic events were associated with lower density of gray matter in brain regions responsible for language processing and memory. Our study represents the first comprehensive study of gray matter density changes in type 1 diabetes and suggests that persistent hyperglycemia and acute severe hypoglycemia have an impact on brain structure. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. McLean Hosp, Brain Imaging Ctr, Belmont, MA 02178 USA. Seoul Natl Univ, Coll Med, Seoul, South Korea. Seoul Natl Univ Hosp, Seoul 110744, South Korea. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA. McLean Hosp, Biostat Lab, Belmont, MA 02178 USA. RP Musen, G (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl,Room 350, Boston, MA 02215 USA. EM gail.musen@joslin.harvard.edu RI Hwang, Jaeuk/F-3481-2010 FU NIDDK NIH HHS [DK-060754] NR 49 TC 148 Z9 155 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 FEB PY 2006 VL 55 IS 2 BP 326 EP 333 DI 10.2337/diabetes.55.02.06.db05-0520 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 010HN UT WOS:000235178400009 PM 16443764 ER PT J AU Jeon, JY Bradley, RL Kokkotou, EG Marino, FE Wang, XM Pissios, P Maratos-Flier, E AF Jeon, JY Bradley, RL Kokkotou, EG Marino, FE Wang, XM Pissios, P Maratos-Flier, E TI MCH-/- mice are resistant to aging-associated increases in body weight and insulin resistance SO DIABETES LA English DT Article ID MELANIN-CONCENTRATING HORMONE; DIET-INDUCED OBESITY; CALORIE RESTRICTION; LIFE-SPAN; VISCERAL FAT; RATS; SIR2; AGE; LONGEVITY; MUCOSA AB Ablation of the hypothalamic peptide, melanin-concentrating hormone (MCH), leads to a lean phenotype and resistance to diet-induced obesity. Observation of MCH-/- mice at older ages suggested that these effects persist in mice >1 year old. Leanness secondary to caloric restriction is known to be associated with improved glucose tolerance as well as an overall increase in life span. Because the MCH-/- model represents leanness secondary to increased energy expenditure rather than caloric restriction, we were interested in determining whether this model of leanness would be associated with beneficial metabolic effects at older ages. To assess the effects of MCH ablation over a more prolonged period, we monitored male and female MCH-/- mice up to 19 months. The lean phenotype of MCH-/- mice persisted over the duration of the study. At 19 months, MCH-/- male and female mice weighed 23.4 and 30.8% less than their wild-type counterparts, a result of reduced fat mass in MCH-/- mice. Aged MCH-/- mice exhibited better glucose tolerance and were more insulin sensitive compared with wild-type controls. Aging-associated decreases in locomotor activity were also attenuated in MCH-/- mice. We also evaluated two molecules implicated in the pathophysiology of aging, p53 and silent inflammatory regulator 2 (Sir2). We found that expression of the tumor suppressor protein p53 was higher in MCH-/- mice at 9 and 19 months of age. In contrast, expression of Sir2 was unchanged. In aggregate, these findings suggest that MCH ablation improves the long-term outcome for several indicators of the aging process. C1 Beth Israel Med Ctr, Dept Med, Div Endocrinol, Boston, MA USA. Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Yonsei Univ, Dept Sport & Leisure Studies, Seoul 120749, South Korea. Beth Israel Med Ctr, Dept Med, Div Gastroenterol, Boston, MA USA. RP Maratos-Flier, E (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol, 330 Brookline Ave, Boston, MA 02215 USA. EM emaratos@bidmc.harvard.edu FU NIDDK NIH HHS [R01-DK-56113, DK-56116, K01-DK-063080] NR 46 TC 29 Z9 31 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD FEB PY 2006 VL 55 IS 2 BP 428 EP 434 DI 10.2337/diabetes.55.02.06.db05-0203 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 010HN UT WOS:000235178400022 PM 16443777 ER PT J AU Meigs, JB O'Donnell, CJ Tofler, GH Benjamin, EJ Fox, CS Lipinska, I Nathan, DM Sullivan, LM D'Agostino, RB Wilson, PWF AF Meigs, JB O'Donnell, CJ Tofler, GH Benjamin, EJ Fox, CS Lipinska, I Nathan, DM Sullivan, LM D'Agostino, RB Wilson, PWF TI Hemostatic markers of endothelial dysfunction and risk of incident type 2 diabetes - The Framingham Offspring study SO DIABETES LA English DT Article ID NITRIC-OXIDE SYNTHASE; C-REACTIVE PROTEIN; PLASMINOGEN-ACTIVATOR INHIBITOR-1; INSULIN-RESISTANCE; CARDIOVASCULAR-DISEASE; DEPENDENT VASODILATION; IN-VIVO; INFLAMMATORY MARKERS; METABOLIC SYNDROME; ADIPOSE-TISSUE AB Endothelial dysfunction may precede development of type 2 diabetes. We tested the hypothesis that elevated levels of hemostatic markers of endothelial dysfunction, plasminogen activator inhibitor-1 (PAI-1) antigen, and von Willebrand factor (vWF) antigen predicted incident diabetes independent of other diabetes risk factors. We followed 2,924 Framingham Offspring subjects (54% women, mean age 54 years) without diabetes at baseline (defined by treatment, fasting plasma glucose >= 7 or 2-h postchallenge glucose >= 11.1 mmol/l) over 7 years for new cases of diabetes (treatment or fasting plasma glucose >= 7.0 mmol/ 1). We used a series of regression models to estimate relative risks for diabetes per interquartile range (IQR) increase in PAI-1 (IQR 16.8 ng/ml) and vWF (IQR 66.8% of control) conditioned on baseline characteristics. Over follow-up, there were 153 new cases of diabetes. Age- and sex-adjusted relative risks of diabetes were 1.55 per IQR for PAI-1 (95% CI 1.41-1.70) and 1.49 for vWF (1.21-1.85). These effects remained after further adjustment for diabetes risk factors (including physical activity; HDL cholesterol, triglyceride, and blood pressure levels; smoking; parental history of diabetes; use of alcohol, nonsteroidal anti-inflammatory drugs, exogenous estrogen, or hypertension therapy; and impaired glucose tolerance), waist circumference, homeostasis model assessment of insulin resistance, and inflammation (assessed by levels of C-reactive protein): the adjusted relative risks were 1.18 per IQR for PAI-1 (1.01-1.37) and 1.39 for vWF (1.09-1.77). We conclude that in this community-based sample, plasma markers of endothelial dysfunction increased risk of incident diabetes independent of other diabetes risk factors including obesity, insulin resistance, and inflammation. C1 Massachusetts Gen Hosp, Div Gen Med, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. Royal N Shore Hosp, Dept Cardiol, Sydney, NSW, Australia. Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Evans Dept Med,Prevent Med Sect, Boston, MA 02118 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Diabet Unit, Boston, MA 02114 USA. Boston Univ, Dept Math, Stat & Consulting Unit, Boston, MA 02215 USA. Med Univ S Carolina, Dept Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA. RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Div Gen Med, Dept Med, 50 Stanford St,9th Floor, Boston, MA 02114 USA. EM jmeigs@partners.org OI Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [N01-HC-25195, R01 HL48157, R01 HL76784] NR 58 TC 102 Z9 111 U1 0 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 FEB PY 2006 VL 55 IS 2 BP 530 EP 537 DI 10.2337/diabetes.55.02.06.db05-1041 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 010HN UT WOS:000235178400036 PM 16443791 ER PT J AU Hsu, WC Cheung, S Ong, E Wong, K Lin, S Leon, K Weinger, K King, GL AF Hsu, WC Cheung, S Ong, E Wong, K Lin, S Leon, K Weinger, K King, GL TI Identification of linguistic barriers to diabetes knowledge and glycemic control in Chinese Americans with diabetes SO DIABETES CARE LA English DT Article ID PRIMARY-CARE PERFORMANCE; MINORITIES; MELLITUS; RATINGS C1 Joslin Diabet Ctr, Asian Amer Diabet Initiat, Boston, MA 02215 USA. Joslin Diabet Ctr, Ctr Innovat Diabet Educ, Boston, MA 02215 USA. RP Hsu, WC (reprint author), Ctr Diabet, 1 Joslin Pl, Boston, MA 02215 USA. EM william.hsu@joslin.harvard.edu NR 17 TC 25 Z9 25 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD FEB PY 2006 VL 29 IS 2 BP 415 EP 416 DI 10.2337/diacare.29.02.06.dc05-1915 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 011KJ UT WOS:000235266700040 PM 16443897 ER PT J AU Wanic, K Malecki, MT Wolkow, PP Klupa, T Skupien, J Bobrel, J Kozek, E Krolewski, AS Sieradzki, J AF Wanic, K Malecki, MT Wolkow, PP Klupa, T Skupien, J Bobrel, J Kozek, E Krolewski, AS Sieradzki, J TI Polymorphisms in the gene encoding hepatocyte nuclear factor-4 alpha and susceptibility to type 2 diabetes in a Polish population SO DIABETES & METABOLISM LA English DT Article DE diabetes; gene; polymorphism; HNF-4 alpha ID NUCLEAR FACTOR-4-ALPHA GENE; CHROMOSOME 20Q; FLUORESCENCE POLARIZATION; UPSTREAM PROMOTER; ASSOCIATION; VARIANTS; MELLITUS; LINKAGE; LOCUS; NIDDM AB Recently, several association studies of type 2 diabetes mellitus (T2DM) and the hepatocyte nuclear factor (HNF)-4 alpha gene were reported with conflicting results. Our aim was to search for association between two polymorphisms of HNF-4 alpha, and T2DM in Polish Caucasians. The study groups comprised of 461 T2DM cases and 366 controls. Genotype-quantitative trait analyses were based on the oral glucose tolerance test (OGTT), glucose and insulin results, and comprised 310 glucose-tolerant subjects. All individuals were geno-typed for two HNF-4 alpha polymorphisms. The frequencies of the minor alleles were as follows: 19.2% in T2DM vs. 17.6% in controls for rs2144908; and 20.6% vs. 20.1% for rs4810424, respectively. The distributions of alleles, genotypes, and haplotypes of the HNF-4 alpha polymorphisms did not differ between the study groups (lowest P = 0.41). None of the examined SNPs showed an association in control subjects with quantitative traits of fasting plasma glucose, fasting insulin, as well as plasma glucose and insulin 2 hours after glucose load in OGTT. We conclude that both examined polymorphisms in HNF-4 alpha are not associated with T2DM and prediabetic phenotypes in Polish Caucasian study groups of this size. C1 Jagiellonian Univ, Coll Med, Dept Metab Dis, PL-31501 Krakow, Poland. Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02115 USA. RP Malecki, MT (reprint author), Jagiellonian Univ, Coll Med, Dept Metab Dis, 15,Kopernika St, PL-31501 Krakow, Poland. EM malecki_malecki@yahoo.com FU FIC NIH HHS [1 R03 TW01351-01]; NIDDK NIH HHS [DK47475] NR 14 TC 9 Z9 9 U1 0 U2 1 PU MASSON EDITEUR PI MOULINEAUX CEDEX 9 PA 21 STREET CAMILLE DESMOULINS, ISSY, 92789 MOULINEAUX CEDEX 9, FRANCE SN 1262-3636 J9 DIABETES METAB JI Diabetes Metab. PD FEB PY 2006 VL 32 IS 1 BP 86 EP 88 DI 10.1016/S1262-3636(07)70252-5 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 018PF UT WOS:000235776600012 PM 16523192 ER PT J AU Heinzerling, KG Kral, AH Flynn, NM Anderson, RL Scott, A Gilbert, ML Asch, SM Bluthenthal, RN AF Heinzerling, KG Kral, AH Flynn, NM Anderson, RL Scott, A Gilbert, ML Asch, SM Bluthenthal, RN TI Unmet need for recommended preventive health services among clients of California syringe exchange programs: Implications for quality improvement SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE preventive services; quality of care; syringe exchange programs; injection drug use; HIV; hepatitis C ID INJECTION-DRUG-USERS; HEPATITIS-C VIRUS; SUBSTANCE-ABUSE TREATMENT; NEW-YORK-CITY; METHADONE-MAINTENANCE TREATMENT; RANDOMIZED CONTROLLED-TRIAL; PRIMARY MEDICAL-CARE; HIV RISK BEHAVIOR; SAN-FRANCISCO; B-VIRUS AB Background: Comprehensive preventive services are recommended for injection drug users (IDU), including screening tests, vaccinations, risk reduction counseling, and sterile syringes. Syringe exchange programs (SEP) may facilitate receipt of preventive services by IDUs, but whether SEP clients receive recommended preventive care is not known. We explained use of recommended preventive services by clients of 23 SEPs throughout California. Methods: Five hundred and sixty SEP clients were recruited from 23 SEPs throughout California between March and September 2003. Receipt of 10 recommended preventive Services and Source of care (SEP versus non-SEP providers) was ascertained from client interviews. Results: Oil average, SEP clients received only 13 % of recommended preventive services and 49% of clients received none of the recommended services. 017 services that were received, 76% were received from SEPs. In multivariate analysis, use of drug treatment and more frequent SEP visits were associated with receipt of recommended preventive services by clients. Conclusions: SEPs are often the only source of preventive care for their IDU clients. Still, SEP clients fail to receive most recommended preventive services. Interventions to increase use of preventive services and improve the quality of preventive care received by IDUs, Such as increased access to drug treatment and SEPs, are needed. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Univ Calif Los Angeles, Robert Wood Johnson Clin Scholars Program, Los Angeles, CA 90024 USA. VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. Univ Calif San Francisco, Dept Family & Community Med, San Francisco, CA 94143 USA. Univ Calif Davis, Dept Internal Med, Div Infect Dis, Sacramento, CA 95817 USA. RAND, Hlth Program, Santa Monica, CA USA. RAND, Drug Policy Res Ctr, Santa Monica, CA USA. Charles R Drew Univ Med & Sci, Drew Ctr AIDS Res Educ & Serv, Dept Psychiat, Los Angeles, CA 90059 USA. RP Heinzerling, KG (reprint author), Univ Calif Los Angeles, Robert Wood Johnson Clin Scholars Program, 911 Broxton Ave,3rd Floor, Los Angeles, CA 90024 USA. EM heinzk@ucla.edu OI Bluthenthal, Ricky/0000-0003-3491-1702 FU NIDA NIH HHS [R01DA14210] NR 94 TC 24 Z9 24 U1 5 U2 7 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD FEB 1 PY 2006 VL 81 IS 2 BP 167 EP 178 DI 10.1016/j.drugalcdep.2005.06.008 PG 12 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 004WJ UT WOS:000234783000008 PM 16043308 ER PT J AU Porter, D Yao, J Polyak, K AF Porter, D Yao, J Polyak, K TI SAGE and related approaches for cancer target identification SO DRUG DISCOVERY TODAY LA English DT Review ID COMPARATIVE GENOMIC HYBRIDIZATION; GENE-EXPRESSION SIGNATURE; BREAST-CANCER; SERIAL ANALYSIS; TRANSCRIPTOME CHARACTERIZATION; MOLECULAR CLASSIFICATION; DESMOPLASTIC RESPONSE; PRIMARY INVASION; WIDE ANALYSIS; SOLID TUMORS AB Comprehensive genetic, epigenetic and transcriptional analyses of normal and cancerous tissues and cells have yielded many candidate diagnostic, predictive, and prognostic markers and therapeutic targets in human cancer. This article provides a brief overview of SAGE and SAGE-like techniques, highlighting their utility and advantages relative to other genomic technologies for the discovery of drug targets. We also summarize the results of recent comprehensive profiling studies that utilize these methods to provide insights into mechanisms of tumor initiation and progression, to improve our molecular understanding of the tumor microenvironment and to reveal new targets and avenues for therapeutic interventions. C1 Novartis Inst Biomed Res, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Polyak, K (reprint author), Novartis Inst Biomed Res, Cambridge, MA 02139 USA. EM Kornelia_Polyak@dfci.harvard.edu NR 62 TC 13 Z9 14 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1359-6446 J9 DRUG DISCOV TODAY JI Drug Discov. Today PD FEB PY 2006 VL 11 IS 3-4 BP 110 EP 118 AR PII S1359-6446(05)03694-9 DI 10.1016/S1359-6446(05)03694-9 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 014QR UT WOS:000235495400004 PM 16533708 ER PT J AU Britton, JC Taylor, SF Berridge, KC Mikels, JA Liberzon, I AF Britton, Jennifer C. Taylor, Stephan F. Berridge, Kent C. Mikels, Joseph A. Liberzon, I. TI Differential subjective and psychophysiological responses to socially and nonsocially generated emotional stimuli SO EMOTION LA English DT Article DE emotion; behavioral; film; skin conductance; heart rate ID NERVOUS-SYSTEM ACTIVITY; VOLUNTARY FACIAL ACTION; FILM STIMULI; INTENSITY; PATTERNS; CONTEXT AB Sociality may determine the subjective experience and physiological response to emotional stimuli. Film segments induced socially and nonsocially generated emotions. Comedy (social positive), bereavement (social negative), pizza scenes (nonsocial positive), and wounded bodies (nonsocial negative) elicited four distinct emotional patterns. Per subjective report, joy, sadness, appetite. and disgust were elicited by the targeted stimulus condition. The social/nonsocial dimension influenced which emotional valence(s) elicited a skin conductance response, a finding that could not be explained by differences in subjective arousal. Heart rate deceleration was more responsive to nonsocially generated emotions. Taken together, these findings suggest that sociality affects the physiological profile of responses to emotional valence. C1 Univ Michigan, Neurosci Program, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Psychol, Ann Arbor, MI 48109 USA. Stanford Univ, Dept Psychol, Stanford, CA 94305 USA. RP Britton, JC (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Bldg 149,13th St, Charlestown, MA 02129 USA. EM jbritton@nmr.mgh.harvard.edu RI Berridge, Kent/C-1525-2009; Taylor, Stephan/A-1211-2007; Britton, Jennifer/J-4501-2013 OI Berridge, Kent/0000-0002-6031-2626; NR 29 TC 16 Z9 17 U1 1 U2 6 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1528-3542 J9 EMOTION JI Emotion PD FEB PY 2006 VL 6 IS 1 BP 150 EP 155 DI 10.1037/1528-3542.6.1.150 PG 6 WC Psychology, Experimental SC Psychology GA 042SM UT WOS:000237549800014 PM 16637758 ER PT J AU Musi, N Goodyear, LJ AF Musi, N Goodyear, LJ TI Insulin resistance and improvements in signal transduction SO ENDOCRINE LA English DT Review DE exercise; glucose transport; type 2 diabetes mellitus; obesity; JNK; PTP1B; AMPK ID ACTIVATED PROTEIN-KINASE; HUMAN SKELETAL-MUSCLE; TYROSINE-PHOSPHATASE 1B; DEPENDENT DIABETES-MELLITUS; IMPAIRED GLUCOSE-TOLERANCE; PHOSPHATIDYLINOSITOL 3-KINASE ACTIVITY; RECEPTOR SUBSTRATE-1 PHOSPHORYLATION; GLYCOGEN-SYNTHASE ACTIVITY; FATTY-ACID OXIDATION; WEIGHT-LOSS AB Type 2 diabetes and obesity are common metabolic disorders characterized by resistance to the actions of insulin to stimulate skeletal muscle glucose disposal. insulin-resistant muscle has defects at several steps of the insulin-signaling pathway, including decreases in insulin-stimulated insulin receptor and insulin receptor substrate-1 tyrosine phosphorylation, and phosphatidylinositol 3-kinase (PI 3-kinase) activation. One approach to increase muscle glucose disposal is to reverse/improve these insulin-signaling defects. Weight loss and thiazolidinediones (TZDs) improve glucose disposal, in part, by increasing insulin-stimulated insulin receptor and IRS-1 tyrosine phosphorylation and Pl 3-kinase activity. in contrast, physical training and metformin improve whole-body glucose disposal but have minimal effects on proximal insulin-signaling steps. A novel approach to reverse insulin resistance involves inhibition of the stress-activated protein kinase Jun N-terminal kinase (JNK) and the protein tyrosine phosphatases (PTPs). A different strategy to increase muscle glucose disposal is by stimulating insulin-independent glucose transport. AMP-activated protein kinase (AMPK) is an enzyme that works as a fuel gauge and becomes activated in situations of energy consumption, such as muscle contraction. Several studies have shown that pharmacologic activation of AMPK increases glucose transport in muscle, independent of the actions of insulin. AMPK activation is also involved in the mechanism of action of metformin and adiponectin. Moreover, in the hypothalamus, AMPK regulates appetite and body weight. The effect of AMPK to stimulate muscle glucose disposal and to control appetite makes it an important pharmacologic target for the treatment of type 2 diabetes and obesity. C1 Texas Diabet Inst, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Harvard Univ, Joslin Diabet Ctr, Div Res, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Goodyear, LJ (reprint author), 1 Joslin Pl, Boston, MA 02215 USA. EM Laurie.Goodyear@joslin.harvard.edu FU NIAMS NIH HHS [AR45670, AR42238] NR 117 TC 57 Z9 62 U1 0 U2 6 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0969-711X J9 ENDOCRINE JI Endocrine PD FEB PY 2006 VL 29 IS 1 BP 73 EP 80 DI 10.1385/ENDO:29:1:73 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 032JZ UT WOS:000236772000009 PM 16622294 ER PT J AU Wang, HJ Lee, SS Dell'Agnello, C Tchipashvili, V D'Avilla, J Czismadia, E Chin, BY Bach, FH AF Wang, HJ Lee, SS Dell'Agnello, C Tchipashvili, V D'Avilla, J Czismadia, E Chin, BY Bach, FH TI Bilirubin can induce tolerance to islet allografts SO ENDOCRINOLOGY LA English DT Article ID PANCREATIC BETA-CELLS; SYNTHASE-DEFICIENT MICE; CORONARY-ARTERY-DISEASE; HEME OXYGENASE-1; CARBON-MONOXIDE; PROTECTS; SURVIVAL; DAMAGE; APOPTOSIS; DANGER AB Induction of heme oxygenase-1 (HO-1) expression in recipients of allogeneic islets can lead to long-term survival (>100 d) of those islets. We tested whether administration of bilirubin would substitute for the beneficial effects of HO-1 expression in islet transplantation. Administering bilirubin to the recipient (B6AF1) or incubating islets in a bilirubin-containing solution ex vivo led to long-term survival of allogeneic islets in a significant percentage of cases. In addition, administering bilirubin to only the donor frequently led to long-term survival of DBA/2 islets in B6AF1 recipients and significantly prolonged graft survival of BALB/c islets in C57BL/6 recipients. Donor treatment with bilirubin up-regulated mRNA expression of protective genes such as HO-1 and bcl-2 and suppressed proinflammatory and proapoptotic genes including monocyte chemoattractant protein-1 and caspase-3 and -8 in the islet grafts before transplantation. Furthermore, treatment of only the donor suppressed the expression of proinflammatory cytokines including TNF-alpha, inducible nitric oxide synthase, monocyte chemoattractant protein-1, and other proapoptotic and proinflammatory genes normally seen in the islets after transplantation. Donor treatment also reduced the number of macrophages that infiltrated the islet grafts in the recipients. Preincubation of beta TC3 cells with bilirubin also protected the cells from lipid peroxidation. Our data suggests that the potent antioxidant and antiinflammatory actions of bilirubin may contribute to islet survival. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. Univ Milano Bicocca, Dept Expt Med & Biotechnol, I-20052 Monza, Italy. RP Wang, HJ (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Surg, 99 Brookline Ave, Boston, MA 02215 USA. EM hwang3@bidmc.harvard.edu NR 38 TC 48 Z9 56 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD FEB PY 2006 VL 147 IS 2 BP 762 EP 768 DI 10.1210/en.2005-0632 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 005NN UT WOS:000234831200016 PM 16254033 ER PT J AU Dalchow, CV Weber, AL Bien, S Yanagihara, N Werner, JA AF Dalchow, CV Weber, AL Bien, S Yanagihara, N Werner, JA TI Value of digital volume tomography in patients with conductive hearing loss SO EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY LA English DT Article DE digital volume tomography; radiology; middle ear; temporal bone; middle-ear implant; ossicular chain; conductive hearing loss ID HIGH-RESOLUTION CT; TEMPORAL BONE; OSSICULAR CHAIN; MIDDLE-EAR; SPIRAL CT; DIAGNOSIS; SURGERY AB Digital volume tomography (DVT) is an extension of panoramic tomography. With this diagnostic technique, characterized by high resolution, a narrow section width (0.125 mm) and three-dimensional display, small pathological processes can be well visualized. Twenty-five patients with the history of a progressive hearing loss were examined with DVT (Accu-I-tomo, Morita, Japan). The results were compared with pre- and intraoperative findings to evaluate the diagnostic value of DVT in cases of erosion of the ossicular chain. With high resolution and artifact-free demonstration of the middle ear and the ossicular chain, it was possible to define its continuity preoperatively by DVT in all 25 cases. An intact ossicular chain was found by DVT in 13 cases and was later confirmed by surgery. The predicted erosion of the ossicles was verified in 12 patients, and a tympanoplasty type III was performed. Digital volume tomography is an excellent technique to examine the middle ear cleft and inner ear, and expands the application of diagnostic possibilities in the lateral skull base. Therefore, improvement in preoperative diagnosis is achieved along with more accurate planning of the surgical procedure. Digital volume tomography delivers a small radiation dose with a high resolution and a low purchase price for the equipment. C1 Univ Marburg, Dept Otorhinolaryngol Head & Neck Surg, D-35037 Marburg, Germany. Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02114 USA. Univ Marburg, Dept Neuroradiol, D-35037 Marburg, Germany. Takanoko Hosp, Dept Otolaryngol Head & Neck Surg, Takanoko, Japan. RP Dalchow, CV (reprint author), Univ Marburg, Dept Otorhinolaryngol Head & Neck Surg, Deutschhausstr 3, D-35037 Marburg, Germany. EM dalchow@med.uni.marburg.de NR 31 TC 28 Z9 30 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0937-4477 J9 EUR ARCH OTO-RHINO-L JI Eur. Arch. Oto-Rhino-Laryn. PD FEB PY 2006 VL 263 IS 2 BP 92 EP 99 DI 10.1007/s00405-005-0995-1 PG 8 WC Otorhinolaryngology SC Otorhinolaryngology GA 006YS UT WOS:000234934500002 PM 16163510 ER PT J AU Januzzi, JL van Kimmenade, R Lainchbury, J Bayes-Genis, A Ordonez-Llanos, J Santalo-Bel, M Pinto, YM Richards, M AF Januzzi, JL van Kimmenade, R Lainchbury, J Bayes-Genis, A Ordonez-Llanos, J Santalo-Bel, M Pinto, YM Richards, M TI NT-proBNP testing for diagnosis and short-term prognosis in acute destabilized heart failure: an international pooled analysis of 1256 patients SO EUROPEAN HEART JOURNAL LA English DT Article DE natriuretic peptides; diagnosis; prognosis ID BRAIN NATRIURETIC PEPTIDE; EMERGENCY-DEPARTMENT PRIDE; PREDICTING MORTALITY; GENERAL-POPULATION; LARGE-SAMPLE; DYSPNEA; BNP; DYSFUNCTION; GENDER; IMPACT AB Aims Experience with amino-terminal pro-brain natriuretic peptide (NT-proBNP) testing for evaluation of dyspnoeic patients with suspected acute heart failure (HF) is limited to single-centre studies. We wished to establish broader standards for NT-proBNP testing in a study involving four sites in three continents. Methods and results Differences in NT-proBNP levels among 1256 patients with and without acute HF and the relationship between NT-proBNP levels and HF symptoms were examined. Optimal cut-points for diagnosis and prognosis were identified and verified using bootstrapping and multi-variable logistic regression techniques. Seven hundred and twenty subjects (57.3%) had acute HF, whose median NT-proBNP was considerably higher than those without (4639 vs. 108 pg/mL, P < 0.001), and levels of NT-proBNP correlated with HF symptom severity (P=0.008). An optimal strategy to identify acute HF was to use age-related cut-points of 450, 900, and 1800 pg/mL for ages < 50, 50-75, and > 75, which yielded 90% sensitivity and 84% specificity for acute HF. An age-independent cut-point of 300 pg/mL had 98% negative predictive value to exclude acute HF. Among those with acute HF, a presenting NT-proBNP concentration > 5180 pg/mL was strongly predictive of death by 76 days [odds ratio=5.2, 95% confidence interval (CI)=2.2-8.1, P < 0.001]. Conclusion In this multi-centre, international study, NT-proBNP testing was valuable for diagnostic evaluation and short-term prognosis estimation in dyspnoeic subjects with suspected or confirmed acute HF and should establish broader standards for use of the NT-proBNP in dyspnoeic patients. C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Univ Hosp, Dept Cardiol, Maastricht, Netherlands. Christchurch Sch Med & Hlth Sci, Dept Med, Christchurch Cardioendocrine Res Grp, Christchurch, New Zealand. Hosp Santa Cruz & San Pablo, Dept Cardiol, E-08025 Barcelona, Spain. Hosp Santa Cruz & San Pablo, Serv Biochem, E-08025 Barcelona, Spain. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Div Cardiol, Yawkey 5984,55 Fruit St, Boston, MA 02114 USA. EM jjanuzzi@partners.org RI Ordonez-Llanos, Jorge/A-9335-2010; Ordonez-Llanos, Jordi/B-4961-2011; Bayes-Genis, Antoni/C-4002-2015; Kimmenade, R.R.J./L-4432-2015 OI Ordonez-Llanos, Jordi/0000-0003-4896-5832; Bayes-Genis, Antoni/0000-0002-3044-197X; NR 28 TC 412 Z9 457 U1 1 U2 17 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD FEB PY 2006 VL 27 IS 3 BP 330 EP 337 DI 10.1093/eurheartj/ehi631 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 002RN UT WOS:000234629200018 PM 16293638 ER PT J AU Aujesky, D Roy, PM Le Manach, CP Verschuren, F Meyer, G Obrosky, DS Stone, RA Cornuz, J Fine, MJ AF Aujesky, D Roy, PM Le Manach, CP Verschuren, F Meyer, G Obrosky, DS Stone, RA Cornuz, J Fine, MJ TI Validation of a model to predict adverse outcomes in patients with pulmonary embolism SO EUROPEAN HEART JOURNAL LA English DT Article DE pulmonary embolism; prognosis; mortality ID MOLECULAR-WEIGHT HEPARIN; DEEP-VEIN THROMBOSIS; OUTPATIENT TREATMENT; UNFRACTIONATED HEPARIN AB Aims To validate a model for quantifying the prognosis of patients with pulmonary embolism (PE). The model was previously derived from 10 534 US patients. Methods and results We validated the model in 367 patients prospectively diagnosed with PE at 117 European emergency departments. We used baseline data for the model's 11 prognostic variables to stratify patients into five risk classes (I-V). We compared 90-day mortality within each risk class and the area under the receiver operating characteristic curve between the validation and the original derivation samples. We also assessed the rate of recurrent venous thrombo-embolism and major bleeding within each risk class. Mortality was 0% in Risk Class I, 1.0% in Class II, 3.1% in Class III, 10.4% in Class IV, and 24.4% in Class V and did not differ between the validation and the original derivation samples. The area under the curve was larger in the validation sample (0.87 vs. 0.78, P=0.01). No patients in Classes I and II developed recurrent thrombo-embolism or major bleeding. Conclusion The model accurately stratifies patients with PE into categories of increasing risk of mortality and other relevant complications. Patients in Risk Classes I and II are at low risk of adverse outcomes and are potential candidates for outpatient treatment. C1 Univ Lausanne, Div Gen Internal Med, Univ Outpatient Clin, Lausanne, Switzerland. Univ Lausanne, Clin Epidemiol Ctr, Lausanne, Switzerland. Univ Angers, Dept Emergency Med, Angers, France. Univ Catholique Louvain, Clin Univ St Luc, Dept Emergency Med, B-1200 Brussels, Belgium. Univ Paris 05, Hop Europeen Georges Pompidou, Dept Resp Care, Paris, France. Univ Pittsburgh, Dept Med, Div Gen Internal Med, Pittsburgh, PA USA. VA Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. RP Aujesky, D (reprint author), CHU Vaudois, Serv Med Interne, BH10-622, CH-1011 Lausanne, Switzerland. EM drahomir.aujesky@chuv.ch FU NHLBI NIH HHS [1 R21 HL075521-01A1] NR 23 TC 143 Z9 149 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD FEB PY 2006 VL 27 IS 4 BP 476 EP 481 DI 10.1093/eurheartj/ehi588 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 011OO UT WOS:000235278100020 PM 16207738 ER PT J AU Hideshima, T Richardson, PG Anderson, KC AF Hideshima, T Richardson, PG Anderson, KC TI Current therapeutic uses of lenalidomide in multiple myeloma SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Article DE clinical trial; immunomodulatory drug; lenalidomide; multiple myeloma; thalidomide ID NF-KAPPA-B; STEM-CELL TRANSPLANTATION; ENDOTHELIAL GROWTH-FACTOR; MEDIATED DRUG-RESISTANCE; ALLOGENEIC BONE-MARROW; HIGH-DOSE THERAPY; PROTEIN-KINASE CASCADE; IN-VITRO; MOLECULAR-MECHANISMS; THALIDOMIDE ANALOGS AB Thalidomide has demonstrated a broad spectrum of pharmacological and immunological effects, with potential therapeutic applications that span a wide spectrum of diseases: cancer and related conditions; infectious diseases; autoimmune diseases; dermatological diseases; and other disorders such as sarcoidosis, macular degeneration and diabetic retinopathy. Immunomodulatory derivative lenalidomide has more potent antitumour and anti-inflammatory effects. The molecular mechanisms of antitumour activity of lenalidomide have been extensively studied in multiple myeloma (MM). it directly induces growth arrest and/or apoptosis of even drug-resistant MM cells; inhibits binding of MM cells to bone marrow extracellular matrix proteins and stromal cells; modulates cytokine secretion and inhibits angiogenesis in the bone marrow milieu; and augments host antitumour immunity. Importantly, lenalidomide induces significant clinical responses even in patients with relapsed/refractory MM. Therefore, lenalidomide represents a new class of antitumour agents that is useful in the treatment of MM. Lenalidomide has received fast track designation from the FDA for the treatment of MM and myelodysplastic syndromes. C1 Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Hideshima, T (reprint author), Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Mayer 549,44 Binney St, Boston, MA 02115 USA. EM teru_hideshima@dfci.harvard.edu NR 81 TC 23 Z9 24 U1 0 U2 0 PU ASHLEY PUBLICATIONS LTD PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1354-3784 J9 EXPERT OPIN INV DRUG JI Expert Opin. Investig. Drugs PD FEB PY 2006 VL 15 IS 2 BP 171 EP 179 DI 10.1517/13543784.15.2.171 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 013SQ UT WOS:000235430100009 PM 16433596 ER PT J AU Haddad, R Allen, A Wirth, L Tishler, R Posner, M AF Haddad, Robert Allen, Aaron Wirth, Lori Tishler, Roy Posner, Marshall TI Integrating novel agents into the curative treatment of head and neck cancer SO EXPERT REVIEW OF ANTICANCER THERAPY LA English DT Editorial Material ID SQUAMOUS-CELL CARCINOMA; INDUCTION CHEMOTHERAPY; IONIZING-RADIATION; PHASE-III; RADIOTHERAPY; ANGIOGENESIS; CISPLATIN; GROWTH C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Head & Neck Oncol Program, Boston, MA 02115 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. RP Haddad, R (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Head & Neck Oncol Program, 44 Binney St, Boston, MA 02115 USA. EM robert_haddad@dfci.harvard.edu NR 15 TC 4 Z9 4 U1 0 U2 0 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7140 J9 EXPERT REV ANTICANC JI Expert Rev. Anticancer Ther PD FEB PY 2006 VL 6 IS 2 BP 157 EP 159 DI 10.1586/14737140.6.2.157 PG 3 WC Oncology SC Oncology GA 090AH UT WOS:000240922500001 PM 16445367 ER PT J AU Freeman, MW AF Freeman, Mason W. TI Statins, cholesterol, and the prevention of coronary heart disease SO FASEB JOURNAL LA English DT Article ID PLACEBO-CONTROLLED TRIAL; SIMVASTATIN; PRAVASTATIN; PROTECTION; EVENTS; MEN C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. RP Freeman, MW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, 55 Fruit St, Boston, MA 02114 USA. EM freeman@frodo.mgh.haarvard.edu NR 13 TC 5 Z9 6 U1 0 U2 1 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 FEB PY 2006 VL 20 IS 2 BP 200 EP 201 DI 10.1096/fj.06-0202ufm PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 044US UT WOS:000237698700003 PM 16449790 ER PT J AU Rivera-Milla, E Oidtmann, B Panagiotidis, CH Baier, M Sklaviadis, T Hoffmann, R Zhou, Y Solis, GP Stuermer, CAO Malaga-Trillo, E AF Rivera-Milla, Eric Oidtmann, Birgit Panagiotidis, Cynthia H. Baier, Michael Sklaviadis, Theodoros Hoffmann, Rudolf Zhou, Yi Solis, Gonzalo P. Stuermer, Claudia A. O. Malaga-Trillo, Edward TI Disparate evolution of prion protein domains and the distinct origin of Doppel- and prion-related loci revealed by fish-to-mammal comparisons SO FASEB JOURNAL LA English DT Article C1 [Rivera-Milla, Eric; Solis, Gonzalo P.; Stuermer, Claudia A. O.; Malaga-Trillo, Edward] Univ Konstanz, Dept Biol, D-78457 Constance, Germany. [Oidtmann, Birgit; Hoffmann, Rudolf] Univ Munich, Inst Zool Fish Biol & Fish Dis, Munich, Germany. [Panagiotidis, Cynthia H.; Sklaviadis, Theodoros] Aristotle Univ Thessaloniki, Sch Pharmaceut Sci, GR-54006 Thessaloniki, Greece. [Panagiotidis, Cynthia H.; Sklaviadis, Theodoros] INA CERTH, Thessaloniki, Greece. [Baier, Michael] Robert Koch Inst, Project Neurodegenerat Dis, D-1000 Berlin, Germany. [Zhou, Yi] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Zhou, Yi] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Malaga-Trillo, E (reprint author), Univ Konstanz, Dept Biol, D-78457 Constance, Germany. EM edward.malaga@uni-konstanz.de NR 0 TC 52 Z9 56 U1 0 U2 3 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 FEB PY 2006 VL 20 IS 2 BP 317 EP 319 DI 10.1096/fj.05-4279fje PG 3 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V17CJ UT WOS:000207915000006 PM 16352647 ER PT J AU Hanley, WD Napier, SL Burdick, MM Schnaar, RL Sackstein, R Konstantopoulos, K AF Hanley, William D. Napier, Susan L. Burdick, Monica M. Schnaar, Ronald L. Sackstein, Robert Konstantopoulos, Konstantinos TI Variant isoforms of CD44 are P- and L-selectin ligands on colon carcinoma cells SO FASEB JOURNAL LA English DT Article C1 [Hanley, William D.; Napier, Susan L.; Konstantopoulos, Konstantinos] Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD 21205 USA. [Konstantopoulos, Konstantinos] Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD USA. [Schnaar, Ronald L.] Johns Hopkins Univ, Sch Med, Dept Pharmacol, Baltimore, MD 21205 USA. [Burdick, Monica M.; Sackstein, Robert] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. [Sackstein, Robert] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Burdick, Monica M.; Sackstein, Robert] Harvard Univ, Sch Med, Harvard Skin Dis Res Ctr, Boston, MA USA. [Sackstein, Robert] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Konstantopoulos, K (reprint author), Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD 21205 USA. EM rsackstein@rics.bwh.harvard.edu; kkonsta1@jhu.edu RI Thomas, Susan/A-9947-2009; Konstantopoulos, Konstantinos/A-7045-2011; Thomas, Susan/B-4592-2016; Schnaar, Ronald/S-8967-2016 OI Thomas, Susan/0000-0003-4651-232X; Schnaar, Ronald/0000-0002-7701-5484 FU NCI NIH HHS [R01 CA 101135]; NHLBI NIH HHS [R01 HL073714, R01 HL60528] NR 0 TC 62 Z9 69 U1 0 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 FEB PY 2006 VL 20 IS 2 BP 337 EP 339 DI 10.1096/fj.05-4574fje PG 3 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V17CJ UT WOS:000207915000013 PM 16352650 ER PT J AU Yamashita, K Ollinger, R McDaid, J Sakahama, H Wang, HJ Tyagi, S Csizmadia, E Smith, NR Soares, MP Bach, FH AF Yamashita, Kenichiro Oellinger, Robert McDaid, James Sakahama, Hideyasu Wang, Hongjun Tyagi, Shivraj Csizmadia, Eva Smith, Neal R. Soares, Miguel P. Bach, Fritz H. TI Heme oxygenase-1 is essential for and promotes tolerance to transplanted organs SO FASEB JOURNAL LA English DT Article DE T regulatory cells (Tregs); co-stimulation ID REGULATORY T-CELLS; CARBON-MONOXIDE; GENE-TRANSFER; CARDIAC ALLOGRAFTS; GRAFT-REJECTION; PROTECTIVE GENE; APOPTOSIS; SUPPRESSES; OVEREXPRESSION; PREVENTS AB This investigation focused on obtaining a further understanding of the role of heme oxygenase-1 (HO-1) in tolerance induction. Hearts from C57BL/6 (H-2(b)) mice survived long-term when transplanted into BALB/c (H-2(d)) recipients treated with the tolerance-inducing regimen of anti-CD40L antibody (MR-1) plus donor-specific transfusion (DST). Grafts did not, however, survive long-term in (HO-1(-/-)) recipients given the same treatment. Similarly, long-term survival induced by DST was ablated when HO-1 activity was blocked by zinc protoporphyrin IX (ZnPPIX). We further asked whether modulation of HO-1 expression/activity could be used to promote the induction of graft tolerance. DST alone (day 0) failed to promote any prolongation of survival of DBA/2 (H-2(d)) hearts transplanted into B6AF1 (H-2(b,k/d)) recipients. However, long-term survival and (dominant peripheral) tolerance were readily induced when DST was combined with induction of HO-1 expression by cobalt protoporphyrin IX (CoPPIX). HO-1 induction plus DST led to a significant up-regulation of Foxp3, TGF-beta, IL-10, and CTLA4, which suggests a prominent role for CD4+CD25+ regulatory T cells (Tregs). In fact, the tolerogenic effect of HO-1 plus DST was dependent on CD4+CD25+ Tregs as suggested by adoptively transferring these cells into irradiated recipients under various regimens. Taken together, these findings show that expression of HO-1 in a graft recipient can be essential for long-term graft survival and for induction of tolerance and that modulation of HO-1 expression/activity can be used therapeutically to synergize in the generation of graft tolerance. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Immunobiol Res Ctr,Dept Surg, Boston, MA 02215 USA. Univ Innsbruck, Dept Surg, Innsbruck, Austria. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. Inst Culbenkian Ciencia, P-2781901 Oeiras, Portugal. RP Bach, FH (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Immunobiol Res Ctr,Dept Surg, 99 Brookline Ave, Boston, MA 02215 USA. EM fritz_bach@hms.harvard.edu RI Ollinger, Robert/D-1538-2009; OI Soares, Miguel/0000-0002-9314-4833 FU NHLBI NIH HHS [HL58688, HL67040] NR 43 TC 76 Z9 85 U1 0 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB PY 2006 VL 20 IS 2 BP 776 EP + DI 10.1096/fj.05-4791fje PG 20 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 044US UT WOS:000237698700023 PM 16473885 ER PT J AU Reue, K Donkor, J AF Reue, Karen Donkor, Jimmy TI Lipin: a determinant of adiposity, insulin sensitivity and energy balance SO FUTURE LIPIDOLOGY LA English DT Review DE adipocyte differentiation; alternative mRNA splicing; animal model; energy expenditure; insulin sensitivity; lipodystrophy; obesity ID QUANTITATIVE TRAIT LOCUS; DYSTROPHY FLD MUTATION; SERUM LEPTIN LEVELS; GENE-EXPRESSION; MAMMALIAN TARGET; RAPAMYCIN; PROTEIN; MOUSE; DIFFERENTIATION; SUSCEPTIBILITY AB Lipodystrophy and obesity represent extreme ends of the adiposity spectrum, and both are associated with conditions such as insulin resistance, diabetes and atherosclerosis. This points to a key role for adipose tissue in metabolic homeostasis and has spurred efforts to identify genes involved in adipose tissue development and function. Lipin is one such gene. Variations in lipin expression levels in mouse models produce wide variations in adiposity ranging from lipodystrophy in lipin-deficient mice, to obesity in mice with enhanced lipin expression in either adipose tissue or muscle. These effects reflect important roles for lipin in key metabolic processes including cell differentiation and lipid storage in adipose tissue, and energy utilization in muscle. This review summarizes the work to date on lipin, focusing on its effects on adipose tissue mass and energy balance, insulin sensitivity and cellular function. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90024 USA. Vet Adm Greater Los Angeles Health Syst, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Med Sci Training Program, Los Angeles, CA 90024 USA. RP Reue, K (reprint author), Univ Calif Los Angeles, Dept Human Genet, 695 Charles E Young Dr S Gonda, Los Angeles, CA 90095 USA. EM reuek@ucla.edu NR 32 TC 5 Z9 5 U1 0 U2 1 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1746-0875 J9 FUTURE LIPIDOL JI Future Lipidol. PD FEB PY 2006 VL 1 IS 1 BP 91 EP 101 DI 10.2217/17460875.1.1.91 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 208YB UT WOS:000249354000017 ER PT J AU Mizoguchi, E AF Mizoguchi, E TI Chitinase 3-like-1 exacerbates intestinal inflammation by enhancing bacterial adhesion and invasion in colonic epithelial cells SO GASTROENTEROLOGY LA English DT Article ID ARTICULAR CHONDROCYTES; CROHNS-DISEASE; BOWEL-DISEASE; ILEAL MUCOSA; PROTEIN; MICE; ANTIBIOTICS; ACTIVATION; COLITIS; ABILITY AB Background &Aims: Dysregulated host/microbial interactions appear to play a central role in the development of inflammatory bowel disease (IBD). However, molecular events leading to the clysregulation have not yet been defined fully. Studies were designed to characterize a key molecule that is involved in the dysregulation. Methods: Colonic mucosal RNA from C57BL/6 mice on days 4 and 8 with administration of 4% dextran sulfate sodium for 5 days were subjected to DNA microarray analysis. Chitinase 3-like-1 (CHi3L1) messenger RNA and protein expressions were examined by reverse-transcription polymerase chain reaction and immunohistochemistry. A gentamicin protection assay of Salmonella typhimurium was performed using epithelial cell lines that are engineered genetically to overexpress or lack mouse CHI3L1. To examine the functional role of CHI3L1 in vivo, anti-CHI31-1 antibody was administered into the dextran sulfate sodium colitis model. Results: Microarray analysis identified that CHI3L1 is up-regulated specifically in inflamed mucosa. The expression of CHI3L1 protein clearly was detectable in lamina propria and colonic epithelial cells (CECs) in several murine colitis models and ulcerative colitis and Crohn's disease patients but absent in normal controls. The gentamicin protection assays using intracellular bacteria showed that CHI3L1 is required for the enhancement of adhesion and internalization of these bacteria in CEC. In vivo neutralization experiments showed that CHI3L1 contributes to the facilitation of bacterial invasion into the intestinal mucosa and the development of acute colitis. Conclusions: CHI3L1 plays a pathogenic role in colitis, presumably by enhancing the adhesion and invasion of bacteria on/into CEC. Inhibition of CHI3L1 activity would be a novel therapeutic approach for IBD. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Ctr Study Inflammatory Bowek Dis,Gastro, Boston, MA 02114 USA. RP Mizoguchi, E (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Ctr Study Inflammatory Bowek Dis,Gastro, GRJ-716,55 Fruit St, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK43351, K08 DK64289] NR 39 TC 96 Z9 101 U1 0 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD FEB PY 2006 VL 130 IS 2 BP 398 EP 411 DI 10.1053/j.gastro.2005.12.007 PG 14 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 015BA UT WOS:000235525700016 PM 16472595 ER PT J AU Abadia-Molina, AC Ji, HB Faubion, WA Julien, A Latchman, Y Yagita, H Sharpe, A Bhan, AK Terhorst, C AF Abadia-Molina, AC Ji, HB Faubion, WA Julien, A Latchman, Y Yagita, H Sharpe, A Bhan, AK Terhorst, C TI CD48 controls T-cell and antigen-presenting cell functions in experimental colitis SO GASTROENTEROLOGY LA English DT Article ID MURINE COLITIS; CUTTING EDGE; SCID MICE; RECEPTOR; ACTIVATION; DISEASE; FAMILY; SUPPRESSION; ENGAGEMENT; EXPRESSION AB Background & Aims: The cell-surface receptor CD48 is a lipid-anchored protein expressed on all antigen-presenting cells and T cells. CD2 and 2134 are known ligands for CD48, which themselves are expressed on the surface of hematopoietic cells. Here we examine the effect of CD48 in the development of chronic experimental colitis and how CD48 affects adaptive and innate immune functions. Methods: The role of CD48 in experimental colitis was first assessed by transferring CD4(+)CD45RB(hi) cells isolated from either wild-type or CD48-/- mice into either Rag-2-/- or CD48-/- X Rag-2-/- mice. Development of chronic colitis in these adoptively transferred mice was assessed by disease activity index, histology, and production of interferon-gamma in mesenteric lymph nodes. Relevant functions of CD48-/-CD4+ T cells and CD48-/- macrophages were examined using in vitro assays. In a second set of experiments, the efficacy of anti-CD48 in prevention or treatment of chronic colitis was determined. Results: CD48-/-CD4+ cells induced colitis when transferred into Rag-2-/- mice, but not when introduced into CD48-/- x Rag-2-/- recipients. However, both recipient mouse strains developed colitis upon adoptive transfer of wild-type CD4(+) cells. Consistent with a CD4+ T-cell defect was the observation that in vitro proliferation of CD48-/-CD4+ T cells was impaired upon stimulation with CD48-/- macrophages. In vitro evidence for a modest macrophage functional defect was apparent because CD48-/- macrophages produced less tumor necrosis factor alpha and interleukin 12 than wild-type cells upon stimulation with lipopolysaccharicle. Peritoneal macrophages also showed a defect in clearance of gram-negative bacteria in vitro. Treatment of the CD4(+)CD45RB(hi) -> Rag-2(-/-) mice or the wildtype BM -> tg epsilon 26 mice with anti-CD48 (HM48-1) ameliorated development of colitis, even after its induction. Conclusions: Both CD48-dependent activation of macrophages and CD48-controlled activation of T cells contribute to maintaining the inflammatory response. Consequently, T cell-induced experimental colitis is ameliorated only when CD48 is absent from both T cells and antigen-presenting cells. Because anti-CD48 interferes with these processes, anti-human CD48 antibody treatment may represent a novel therapy for inflammatory bowel disease patients. C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Inst Med, Div Immunol, Boston, MA 02215 USA. Harvard Univ, Dept Pathol, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. Juntendo Univ, Sch Med, Dept Immunol, Tokyo 113, Japan. Puget Sound Blood Ctr, Div Res, Seattle, WA 98104 USA. RP Abadia-Molina, AC (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Inst Med, Div Immunol, HIM816,77 Ave Louis Pasteur, Boston, MA 02215 USA. EM acbadia@ugr.es FU NIDDK NIH HHS [DK52510, DK47677, DK43351] NR 31 TC 14 Z9 14 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD FEB PY 2006 VL 130 IS 2 BP 424 EP 434 DI 10.1053/j.gastro.2005.12.009 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 015BA UT WOS:000235525700018 PM 16472597 ER PT J AU Auslander, JN Lieberman, DA Sonnenberg, A AF Auslander, JN Lieberman, DA Sonnenberg, A TI Endoscopic procedures and diagnoses are not influenced by seasonal variations SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID PEPTIC-ULCER; COLORECTAL-CANCER; UNITED-STATES; HOSPITAL ADMISSIONS; DUODENAL-ULCER; DISEASE; COLONOSCOPY; MORTALITY; SCOTLAND AB Background: The occurrences of various GI diseases are thought to be influenced by seasonal variations. The present study was clone to test the hypothesis that seasonal variations in endoscopic diagnoses reflect underly ing patterns in the performance of endoscopic procedures. Methods: The Clinical Outcomes Research Initiative (CORI) uses a Computerized endoscopic report generator to collect endoscopic data from 73 diverse practice sites throughout the United States. We used the CORI database to analyze the date-specific occurrence of EGD and colonoscopy, as well as the endoscopic diagnoses of gastric ulcer, duodenal ulcer, and colorectal cancer. Time trends are analyzed by autocorrelation and by linear and nonlinear regression. Results: Between January 2000 and December 2003, the number of EGDs and colonoscopies increased 2.5- and 4.1-fold, respectively. The rate of duodenal ulcer fell from 21.2 (15.6-27.5) to 19.0 (15.8-22.8) per 1000 EGDS. The rate of gastric ulcer fell from 42.6 (33.3-50.1) to 33.4 (29.5-38.7) per 1000 EGDs. The rate of colorectal cancer fell from 109.9 (98.3-122.8) to 72.2 (67.4-77.2) per 1000 colonoscopies. The time trends of neither endoscopic procedures nor endoscopic diagnoses revealed any seasonal variation or other cyclic pattern. Conclusions: The performance of endoscopic procedures is unaffected by any seasonal variation. C1 Portland VA Med Ctr, Gastroenterol Sect, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Div Gastroenterol, Portland, OR USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr, Gastroenterol Sect, P3-GI,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. FU NIDDK NIH HHS [5-R33-DK061778-03, 2-U01-DK057132-06A1] NR 26 TC 4 Z9 4 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 FEB PY 2006 VL 63 IS 2 BP 267 EP 272 DI 10.1016/j.gie.2005.08.052 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 010KT UT WOS:000235194300014 PM 16427933 ER PT J AU Jiang, HY Harrington, D Raby, BA Bertram, L Blacker, D Weiss, ST Lange, C AF Jiang, HY Harrington, D Raby, BA Bertram, L Blacker, D Weiss, ST Lange, C TI Family-based association test for time-to-onset data with time-dependent differences between the hazard functions SO GENETIC EPIDEMIOLOGY LA English DT Article DE weighted family-based association test; logrank test; censoring; quantitative trait ID SURVIVAL; POWERFUL; GENETICS; SAMPLES; TRAITS AB In genetic association studies, the differences between the hazard functions for the individual genotypes are often time-dependent. We address the non-proportional hazards data by using the weighted logrank approach by Fleming and Harrington [1981]:Commun Stat-Theor M 10:763-794. We introduce a weighted FBAT-Logrank whose weights are based on a non-parametric estimator for the genetic marker distribution function under the alternative hypothesis. We show that the computation of the marker distribution under the alternative does not bias the significance level of any subsequently computed FBAT-statistic. Hence, we use the estimated marker distribution to select the Fleming-Harrington weights so that the power of the weighted FBAT-Logrank test is maximized. In simulation studies and applications to an asthma study, we illustrate the practical relevance of the new methodology. In addition to power increases of 100% over the original FBAT-Logrank test, we also gain insight into the age at which a genotype exerts the greatest influence on disease risk. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Channing Lab, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Genet & Aging Res Unit, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Jiang, HY (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 665 Huntington Ave, Boston, MA 02115 USA. EM hjiang@hsph.harvard.edu RI Bertram, Lars/K-3889-2015 OI Bertram, Lars/0000-0002-0108-124X FU NHLBI NIH HHS [HL 66383, HL 66795, P01 HL 67664, R01 HL 66386, T32 HL 67427]; NIAID NIH HHS [R01 AI 24643]; NINR NIH HHS [N01 NR 16044, N01 NR 16045, N01 NR 16046, N01 NR 16047, N01 NR 16048, N01 NR 16049, N01 NR 16050, N01 NR 16051, N01 NR 16052]; PHS HHS [MA 59532] NR 20 TC 16 Z9 16 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD FEB PY 2006 VL 30 IS 2 BP 124 EP 132 DI 10.1002/gepi.20132 PG 9 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 009PP UT WOS:000235124800003 PM 16374805 ER PT J AU Gum, AM Arean, PA Hunkeler, E Tang, LQ Katon, W Hitchcock, P Steffens, DC Dickens, J Unutzer, J AF Gum, AM Arean, PA Hunkeler, E Tang, LQ Katon, W Hitchcock, P Steffens, DC Dickens, J Unutzer, J CA IMPACT Investigators TI Depression treatment preferences in older primary care patients SO GERONTOLOGIST LA English DT Article DE treatment preferences; depression; primary core; collaborative care; counseling ID QUALITY IMPROVEMENT PROGRAMS; RANDOMIZED CONTROLLED TRIAL; LATE-LIFE; MAJOR DEPRESSION; CONSENSUS STATEMENT; AFRICAN-AMERICAN; HEALTH-CARE; MANAGEMENT; OUTCOMES; UPDATE AB Purpose: For depressed older primary care patients, this study aimed to examine (a) characteristics associated with depression treatment preferences; (b) predictors of receiving preferred treatment; and (c) whether receiving preferred treatment predicted satisfaction and depression outcomes. Design and Methods: Data are from 1,602 depressed older primary care patients who participated in a multisite, randomized clinical trial comparing usual care to collaborative care, which offered medication and counseling for up to 12 months. Baseline assessment included demographics, depression, health information, prior depression treatment, potential barriers, and treatment preferences (medication, counseling). At 12 months, services received, satisfaction, and depression outcomes were assessed. Results: More patients preferred counseling (57%) than medication (43%). Previous experience with a treatment type was the strongest predictor of preference. In addition, medication preference was predicted by male gender and diagnosis of major depression (vs dysthymia). The collaborative care model greatly improved access to preferred treatment, especially for counseling (74% vs 33% in usual care). Receipt of preferred treatment did not predict satisfaction or depression outcomes; these outcomes were most strongly impacted by treatment condition. Implications: Many depressed older primary care patients desire counseling, which is infrequently available in usual primary care. Discussion of treatment preferences should include an assessment of prior treatment experiences. A collaborative care model that increases collaboration between primary care and mental health professionals can increase access to preferred treatment. If preferred treatment is not available, collaborative care still results in good satisfaction and depression outcomes. C1 Univ S Florida, Dept Aging & Mental Hlth, Tampa, FL 33612 USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. Kaiser Permanente No Calif, Div Res, Oakland, CA USA. Univ Calif Los Angeles, Ctr Hlth Serv Res, Inst Neuropsychiat, Los Angeles, CA 90024 USA. Univ Washington, Dept Psychiat, Seattle, WA 98195 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Indiana Univ, Dept Psychiat, Indianapolis, IN 46204 USA. RP Gum, AM (reprint author), Univ S Florida, Dept Aging & Mental Hlth, 13301 Bruce B Downs Blvd,MHC 1400, Tampa, FL 33612 USA. EM agum@fmhi.usf.edu NR 43 TC 126 Z9 128 U1 5 U2 13 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 FEB PY 2006 VL 46 IS 1 BP 14 EP 22 PG 9 WC Gerontology SC Geriatrics & Gerontology GA 012BH UT WOS:000235312700002 PM 16452280 ER PT J AU Fisher, SE Burgio, LD Thorn, BE Hardin, JM AF Fisher, SE Burgio, LD Thorn, BE Hardin, JM TI Obtaining self-report data from cognitively impaired elders: Methodological issues and clinical implications for nursing home pain assessment SO GERONTOLOGIST LA English DT Article; Proceedings Paper CT 55th Annual Meeting of the Gerontological-Society-of-America CY NOV 22-26, 2002 CL BOSTON, MA SP Gerontol Soc Amer DE clinical assessment; dementia; pain; self report methodology; nursing home; geriatric pain measure ID MINI-MENTAL-STATE; QUALITY-OF-LIFE; ANALGESIC MEDICATION; NORMATIVE DATA; DATA SET; RESIDENTS; 3MS; MANAGEMENT; DEMENTIA; PRESCRIPTION AB Purpose: We developed and evaluated an explicit procedure for obtaining self-report pain data from nursing home residents across a broad range of cognitive status, and we evaluated the consistency, stability, and concurrent validity of resident responses. Design and Methods: Using a modification of the Geriatric Pain Measure (GPM-M2), we interviewed 61 residents from two nursing homes (Mini-Mental State Examination score, M = 15 +/- 7) once a week for A consecutive weeks. We collected additional data by means of chart review, cognitive status assessments, and surveys of certified nursing assistants. We used descriptive and correlational analyses to address our primary aims. Results: Eighty-nine percent of residents completed all four scheduled interviews. Cognitive status was not significantly correlated with number of nonresponses and prompts for yes-no questions, but it was significantly correlated with nonresponses and prompts for Likert-scole questions (r = -.48, p <.001 and r = -.59, p <.001, respectively). Completion time for the 17-item pain measure (M = 13 min) was not predicted by cognitive status. Residents' scores on the GPM-M2 were significantly correlated with number of chronic pain-associated diagnoses, r = .37, p <.01, and internal consistency was excellent, alpha = 0.87 - 0.91. Residents' GPM-M2 scores were stable over time, r = .74-.80, p <.0001, for all comparisons. Implications: Using explicit protocols and reporting procedural data allows researchers and clinicians to better understand and apply results of self-report studies with cognitively impaired elders. Results suggest that many nursing home residents can provide consistent and reliable self-report pain data, given appropriate time and assistance. C1 Univ Alabama, Dept Psychol, Tuscaloosa, AL 35487 USA. Univ Alabama, Ctr Mental Hlth & Aging, Tuscaloosa, AL 35487 USA. Univ Alabama, Dept Informat Syst Stat & Management Sci, Tuscaloosa, AL 35487 USA. RP Fisher, SE (reprint author), VA Pittsburgh Healthcare Syst, Behav Hlth Serv Line 116A-H,7180 Highland Dr, Pittsburgh, PA 15206 USA. EM sfisher@bama.ua.edu FU CMHS SAMHSA HHS [H79 SM 54569-01]; NINR NIH HHS [R03 NR008517] NR 41 TC 18 Z9 18 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 FEB PY 2006 VL 46 IS 1 BP 81 EP 88 PG 8 WC Gerontology SC Geriatrics & Gerontology GA 012BH UT WOS:000235312700009 PM 16452287 ER PT J AU Virard, I Coquillat, D Bancila, M Kaing, S Durbec, P AF Virard, I Coquillat, D Bancila, M Kaing, S Durbec, P TI Oligodendrocyte precursor cells generate pituicytes in vivo during neurohyophysis development SO GLIA LA English DT Article DE oligodendrocyte precursor cell; pituicyte; neurohypophysis; cell lineage; cell differentiation ID CENTRAL-NERVOUS-SYSTEM; RAT OPTIC-NERVE; FIBRILLARY ACIDIC PROTEIN; GLIAL PROGENITOR-CELL; CNS STEM-CELLS; SPINAL-CORD; ASTROCYTE DIFFERENTIATION; TRANSCRIPTION FACTORS; PITUITARY-GLAND; ADULT-RAT AB In the vertebrate brain, much remains to be understood concerning the origin of glial cell diversity and the potential lineage relationships between the various types of glia. Besides astrocytes and myelin-forming oligodendrocytes, other macroglial cell populations are found in discrete areas of the central nervous system (CNS). They share functional features with astrocytes and oligodendrocytes but also display specific characteristics. Such specialized cells, called pituicytes, are located in the neurohypophysis (NH). Our work focuses on the lineage of the pituicytes during rodent development. First, we show that cells identified with a combination of oligodendrocyte precursor cell (OPC) markers are present in the developing rat NH. in culture, neonatal NH progenitors also share major functional characteristics with OPCs, being both migratory and bipotential, i.e. able to give rise to type 2 astrocytes and oligodendrocytes. We then observe that, either in vitro or after transplantation into myelin-deficient Shiverer brain, pieces of NH generate myelinating oligodendrocytes, confirming the oligodendrogenic potentiality of NH cells. However, no mature oligodendrocyte can be found in the NH. This led us to hypothesize that the OPCs present in the developing NH might be generating other glial cells, especially the pituicytes. Consistent with this hypothesis, the OPCs appear during NH development before pituicytes differentiate. Finally, we establish a lineage relationship between olig1(+) cells, most likely OPCs, and the pituicytes by fate-mapping experiments using genetically engineered mice. This constitutes the first demonstration that OPCs generate glial cells other than oligodendrocytes in vivo. (C) 2005 Wiley-Liss, Inc. C1 Univ Mediterranee, IBDM, Lab Neurogenesis & Morphogenese Dev & Chez Adulte, CNRS,UMR 6156, F-13288 Marseille 9, France. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Durbec, P (reprint author), Univ Mediterranee, IBDM, Lab Neurogenesis & Morphogenese Dev & Chez Adulte, CNRS,UMR 6156, Parc Sci Luminy, F-13288 Marseille 9, France. EM durbec@ibdm.univ-mrs.fr NR 57 TC 7 Z9 7 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-1491 J9 GLIA JI Glia PD FEB PY 2006 VL 53 IS 3 BP 294 EP 303 DI 10.1002/glia.20282 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 014PM UT WOS:000235492200007 PM 16265670 ER PT J AU Million, M Wang, L Wang, Y Adelson, DW Yuan, PQ Maillot, C Coutinho, SV Mcroberts, JA Bayati, A Mattsson, H Wu, V Wei, JY Rivier, J Vale, W Mayer, EA Tache, Y AF Million, M Wang, L Wang, Y Adelson, DW Yuan, PQ Maillot, C Coutinho, SV Mcroberts, JA Bayati, A Mattsson, H Wu, V Wei, JY Rivier, J Vale, W Mayer, EA Tache, Y TI CRF2 receptor activation prevents colorectal distension induced visceral pain and spinal ERK1/2 phosphorylation in rats SO GUT LA English DT Article ID CORTICOTROPIN-RELEASING-FACTOR; IRRITABLE-BOWEL-SYNDROME; STRESS-RELATED ALTERATIONS; GENE-RELATED PEPTIDE; RECTAL DISTENSION; MOTOR FUNCTION; COMPETITIVE ANTAGONISTS; AFFERENT-FIBERS; DORSAL-HORN; MAP KINASE AB Background and aims: Activation of corticotropin releasing factor 1 ( CRF1) receptors is involved in stress related responses and visceral pain, while activation of CRF2 receptors dampens the endocrine and some behavioural stress responses. We hypothesised that CRF2 receptor activation may influence visceral pain induced by colorectal distension ( CRD) in conscious rats, and assessed the possible sites and mechanisms of action. Methods: Male Sprague-Dawley rats were exposed to CRDs ( 60 mm Hg, 10 minutes twice, with a 10 minute rest interval). Visceromotor responses ( VMR) were measured by electromyography or visual observation. Spinal ( L6-S1) extracellular signal regulated kinase 1/2 ( ERK 1/2) activation following in vivo CRD and CRF2 receptor gene expression in the T13-S1 dorsal root ganglia ( DRG) and spinal cord were determined. Inferior splanchnic afferent ( ISA) activity to CRD ( 0.4 ml, 20 seconds) was assessed by electrophysiological recording in an in vitro ISA nerve-inferior mesenteric artery ( intra-arterial)-colorectal preparation. Results: In controls, VMR to the second CRD was mean 31 ( SEM 4)% higher than that of the first ( p < 0.05). The selective CRF2 agonist, human urocortin 2 ( hUcn 2, at 10 and 20 mu g/kg), injected intravenous after the first distension, prevented sensitisation and reduced the second response by 8 ( 1)% and 30 ( 5)% ( p, 0.05) compared with the first response, respectively. RT-PCR detected CRF2 receptor gene expression in the DRG and spinal cord. CRD ( 60 mm Hg for 10 minutes) induced phosphorylation of ERK 1/2 in neurones of lumbosacral laminae I and IIo and the response was dampened by intravenous hUcn 2. CRD, in vitro, induced robust ISA spike activity that was dose dependently blunted by hUcn 2 ( 1-3 mu g, intra-arterially). The CRF2 receptor antagonist, astressin(2)-B ( 200 mu g/kg subcutaneously or 20 mg intra-arterially) blocked the hUcn 2 inhibitory effects in vivo and in vitro. Conclusions: Peripheral injection of hUcn 2 blunts CRD induced visceral pain, colonic afferent, and spinal L6-S1 ERK 1/2 activity through CRF2 receptor activation in rats. C1 Univ Calif Los Angeles, CURE, Digest Dis Res Ctr,Div Digest Dis, VA Greater Los Angeles Healthcare Syst,Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, Ctr Neurovisceral Sci & Womens Hlth, Div Digest Dis, VA Greater Los Angeles Healthcare Syst,Dept Med, Los Angeles, CA USA. Salk Inst Biol Studies, Clayton Fdn Labs Peptide Biol, La Jolla, CA 92037 USA. AstraZeneca R&D, Molndal, Sweden. RP Million, M (reprint author), CURE Bldg 115,Rm 203,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM mmuluget@ucla.edu OI Adelson, David/0000-0002-4623-6030 FU NIDDK NIH HHS [P50 DK064539, P30 DK041301, R01 DK-57238, R01 DK-33061, P01 DK026741, P-50 DK64539, DK41301, DK-57238-01A1S1, DK26741] NR 52 TC 78 Z9 80 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 FEB PY 2006 VL 55 IS 2 BP 172 EP 181 DI 10.1136/gut.2005.051391 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 001RH UT WOS:000234553500010 PM 15985561 ER PT J AU Graham, DY AF Graham, DY TI Helicobacter 2006: A note from the editor SO HELICOBACTER LA English DT Editorial Material ID PYLORI INFECTION; INFLAMMATION C1 Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Houston, TX USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. RP Graham, DY (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Houston, TX USA. NR 8 TC 6 Z9 7 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1083-4389 J9 HELICOBACTER JI Helicobacter PD FEB PY 2006 VL 11 IS 1 BP 1 EP 1 DI 10.1111/j.0083-8703.2006.00378.x PG 1 WC Gastroenterology & Hepatology; Microbiology SC Gastroenterology & Hepatology; Microbiology GA 003QW UT WOS:000234697700001 ER PT J AU Willers, H Held, KD AF Willers, H Held, KD TI Introduction to clinical radiation biology SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID SQUAMOUS-CELL CARCINOMA; FRACTIONATED-IRRADIATION; IONIZING-RADIATION; TREATMENT TIME; LOCAL-CONTROL; NUDE-MICE; CLONOGEN REPOPULATION; RANDOMIZED TRIAL; DOSE-ESCALATION; TUMOR RESPONSE AB Radiation biology is the discipline of radiation oncology that studies the effects of radiation on cells, tissues, and organisms. Over the past decades, insights into radiobiologic mechanisms have provided rational bases for the use of increased radiation doses and fractionated treatment regimens to maximize the effect on cancers while limiting radiation injury to the surrounding normal tissues. In this article, the authors discuss the terminology of radiosensitivity and some of the factors that determine the radiation response of malignant tumors and normal tissues. Although the field of radiation biology is rapidly evolving, a thorough understanding of the established factors that determine radiation responses will remain an important prerequisite for the successful application of multimodality cancer therapies and molecularly targeted approaches. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Willers, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Cox 3,55 Fruit St, Boston, MA 02114 USA. EM hwillers@partners.org FU NCI NIH HHS [P01 CA095227] NR 59 TC 36 Z9 36 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD FEB PY 2006 VL 20 IS 1 BP 1 EP + DI 10.1016/j.hoc.2006.01.007 PG 25 WC Oncology; Hematology SC Oncology; Hematology GA 028IT UT WOS:000236481300002 PM 16580554 ER PT J AU Nahmias, Y Casali, M Barbe, L Berthiaume, F Yarmush, ML AF Nahmias, Y Casali, M Barbe, L Berthiaume, F Yarmush, ML TI Liver endothelial cells promote LDL-R expression and the uptake of HCV-like particles in primary rat and human hepatocytes SO HEPATOLOGY LA English DT Article ID HEPATITIS-C VIRUS; DENSITY-LIPOPROTEIN RECEPTOR; SANDWICH CONFIGURATION; COLLAGEN SANDWICH; GROWTH-FACTOR; HEPG2 CELLS; CULTURE; MAINTENANCE; REPLICATION; SPHEROIDS AB Low-density lipoprotein (LDL) is an important carrier of plasma cholesterol and triglycerides whose concentration is regulated by the liver parenchymal cells. Abnormal LDL regulation is thought to cause atherosclerosis, while viral binding to LDL has been suggested to facilitate hepatitis C infection. Primary hepatocytes quickly lose the ability to clear LDL during in vitro culture. Here we show that the coculture of hepatocytes with liver sinusoidal endothelial cells (LSEC) significantly increases the ability of hepatocytes to uptake LDL in vitro. LDL uptake does not increase when hepatocytes are cocultured with other cell types such as fibroblasts or umbilical vein endothelial cells. We find that LSECs induce the hepatic expression of the LDL receptor and the epidermal growth factor receptor. In addition, while hepatocytes in single culture did not take up hepatitis C virus (HCV)-like particles, the hepatocytes cocultured with LSECs showed a high level of HCV-like particle uptake. We suggest that coculture with LSECs induces the emergence of a sinusoidal surface in primary hepatocytes conducive to the uptake of HCV-Iike particles. In conclusion, our findings describe a novel model of polarized hepatocytes in vitro that can be used for the study of LDL metabolism and hepatitis C infection. C1 Harvard Univ, Sch Med,Dept Surg, Massachusetts Gen Hosp, Shriners Burns Hosp,Ctr Engn Med, Boston, MA 02114 USA. RP Yarmush, ML (reprint author), Harvard Univ, Sch Med,Dept Surg, Massachusetts Gen Hosp, Shriners Burns Hosp,Ctr Engn Med, 51 Blossom St, Boston, MA 02114 USA. EM ireis@sbi.org RI Nahmias, Yaakov/H-4725-2013; Yu, weiting/I-7417-2013; OI Nahmias, Yaakov/0000-0002-6051-616X; Barbe, Laurent/0000-0003-4475-6478 FU NIBIB NIH HHS [P41 EB002503]; NIDDK NIH HHS [R01 DK043371] NR 48 TC 47 Z9 52 U1 1 U2 8 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD FEB PY 2006 VL 43 IS 2 BP 257 EP 265 DI 10.1002/hep.21016 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 009LH UT WOS:000235112900007 PM 16440337 ER PT J AU Yates, J Keeble, W Pals, G Ameziane, N van Spaendonk, R Olson, S Akkari, Y Pasquini, R Bagby, G AF Yates, Jane Keeble, Winifred Pals, Gerard Ameziane, Najim van Spaendonk, Rosalina Olson, Susan Akkari, Yassmine Pasquini, Ricardo Bagby, Grover TI Novel Inactivating Mutations of FANCC in Brazilian Patients with Fanconi Anemia SO HUMAN MUTATION LA English DT Article DE Fanconi; Fanconi anemia; FANCC; splice site mutation; mitomycin C; chromosome instability AB We have identified three novel FANCC mutations, a truncating single base insertion in exon 4 (c.455_456dupA), a point mutation in exon 13 (c.1390C>T), and a splice site mutation leading to deletion of exon 9, in two Brazilian FA-C patients, each a compound heterozygote. Using complementation analyses, we confirmed that two of these mutations inactivate the function of the FANCC protein. Published 2006 Wiley-Liss, Inc. C1 [Yates, Jane; Keeble, Winifred; Bagby, Grover] OHSU Canc Inst, Portland, OR 97239 USA. [Olson, Susan; Akkari, Yassmine; Bagby, Grover] OHSU Canc Inst, Dept Mol & Med Genet, Sch Med, Portland, OR 97239 USA. [Bagby, Grover] Oregon Hlth & Sci Univ, Dept Med, Sch Med, Portland, OR 97201 USA. [Yates, Jane; Keeble, Winifred; Bagby, Grover] Portland VA Med Ctr, Portland, OR USA. [Pals, Gerard; Ameziane, Najim; van Spaendonk, Rosalina] Vrije Univ Amsterdam Med Ctr, Dept Genet, Amsterdam, Netherlands. [Pasquini, Ricardo] Hosp Clin Fed Univ Parana, Curitiba, Parana, Brazil. RP Bagby, G (reprint author), OHSU Canc Inst, CR145,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM grover@ohsu.edu OI Bagby, Grover/0000-0001-6830-2046 FU NIH [P01 HL148546, R01 HL72321-01]; Fanconi Anemia Research Fund; Department of Veterans Affairs FX This study was supported in part by grants from NIH (P01 HL148546, R01 HL72321-01), the Fanconi Anemia Research Fund, and the Department of Veterans Affairs. NR 19 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1059-7794 EI 1098-1004 J9 HUM MUTAT JI Hum. Mutat. PD FEB PY 2006 VL 27 IS 2 DI 10.1002/humu.9402 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA V39QS UT WOS:000209426100008 PM 16429406 ER PT J AU Calpe, S Erdos, E Liao, GX Wang, NH Rietdijk, S Simarro, M Scholtz, B Mooney, J Lee, CH Shin, MS Rajnavolgyi, E Schatzle, J Morse, HC Terhorst, C Lanyi, A AF Calpe, S Erdos, E Liao, GX Wang, NH Rietdijk, S Simarro, M Scholtz, B Mooney, J Lee, CH Shin, MS Rajnavolgyi, E Schatzle, J Morse, HC Terhorst, C Lanyi, A TI Identification and characterization of two related murine genes, Eat2a and Eat2b, encoding single SH2-domain adapters SO IMMUNOGENETICS LA English DT Article DE adapter proteins; EAT-2; SLAM; Src kinases ID LINKED LYMPHOPROLIFERATIVE-DISEASE; SH2 DOMAIN; TYROSINE KINASE; T-CELL; B-CELL; NEGATIVE REGULATION; IMMUNE REGULATION; LEUKEMIA VIRUSES; PRODUCT SAP; C-SRC AB Human EAT-2 (SH2D1B) and SLAM-associated protein (SAP) (SH2D1A) are single SH2-domain adapters, which bind to specific tyrosine residues in the cytoplasmic tail of six signaling lymphocytic activation molecule (SLAM) (SLAMF1)-related receptors. Here we report that, unlike in humans, the mouse and rat Eat2 genes are duplicated with an identical genomic organization. The coding regions of the mouse Eat2a and Eat2b genes share 91% identity at the nucleotide level and 84% at the protein level; similarly, segments of introns are highly conserved. Whereas expression of mouse Eat2a mRNA was detected in multiple tissues, Eat2b was only detectable in mouse natural killer cells, CD8(+) stop T cells, and ovaries, suggesting a very restricted tissue expression of the latter. Both the EAT-2A and EAT-2B coimmunoprecipitated with mouse SLAM in transfected cells and augmented tyrosine phosphorylation of the cytoplasmic tail of SLAM. Both EAT-2A and EAT-2B bind to the Src-like kinases Fyn, Hck, Lyn, Lck, and Fgr, as determined by a yeast two-hybrid assay. However, unlike SAP, the EAT-2 proteins bind to their kinase domains and not to the SH3 domain of these kinases. Taken together, the data suggest that both EAT-2A and EAT-2B are adapters that recruit Src kinases to SLAM family receptors using a mechanism that is distinct from that of SAP. C1 Harvard Univ, Sch Med, Div Immunol, BIDMC, Boston, MA 02115 USA. Univ Debrecen, Med & Hlth Sci Ctr, Inst Immunol, H-4012 Debrecen, Hungary. Univ Debrecen, Med & Hlth Sci Ctr, Dept Biochem & Mol Biol, H-4012 Debrecen, Hungary. NIAID, Immunopathol Lab, Rockville, MD 20852 USA. Univ Texas, SW Med Ctr, Dept Pathol, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Ctr Immunol, Dallas, TX 75390 USA. RP Calpe, S (reprint author), Harvard Univ, Sch Med, Div Immunol, BIDMC, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM scalpe_f@bidmc.harvard.edu; alanyi@dote.hu RI Rajnavolgyi, Eva/D-4384-2013; Simarro, Maria/M-3947-2015; OI Simarro, Maria/0000-0001-8917-7328; Morse, Herbert/0000-0002-9331-3705 FU FIC NIH HHS [R03TW 006472-03]; NIAID NIH HHS [AI 15066] NR 39 TC 22 Z9 25 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0093-7711 EI 1432-1211 J9 IMMUNOGENETICS JI Immunogenetics PD FEB PY 2006 VL 58 IS 1 BP 15 EP 25 DI 10.1007/s00251-005-0056-3 PG 11 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 020SF UT WOS:000235929900003 PM 16425036 ER PT J AU von Boehmer, H Kisielow, P AF von Boehmer, H Kisielow, P TI Negative selection of the T-cell repertoire: where and when does it occur? SO IMMUNOLOGICAL REVIEWS LA English DT Review ID RECEPTOR TRANSGENIC MICE; CD4+8+ THYMOCYTES; BETA-CHAIN; TOLERANCE; TCR; EXPRESSION; ANTIGEN; LINEAGE; THYMUS; DELETION AB Because of the use of somewhat artificial models for the elucidation of negative selection [superantigen, T-cell receptor (TCR) transgenic mice], there is still considerable uncertainty at what stages of T-cell development negative selection can occur and whether it becomes manifest as developmental arrest, lineage diversion, or induction of apoptotic cell death. Here, experimental evidence is reviewed that excludes developmental arrest and lineage diversion as the sole mechanisms of negative selection. The data emphasize that both CD4(+)CD8(+) double-positive cortical as well as semi-mature, single-positive, medullary thymocytes are targets of deletion in experimental models employing superantigen and TCR transgenic mice with premature as well as 'timely' onset of TCR expression. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Polish Acad Sci, Dept Tumor Immunol, Inst Immunol & Expt Therapy, Wroclaw, Poland. RP von Boehmer, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM harald_von_boehmer@dfci.harvard.edu NR 38 TC 34 Z9 36 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD FEB PY 2006 VL 209 BP 284 EP 289 DI 10.1111/j.0105-2896.2006.00346.x PG 6 WC Immunology SC Immunology GA 008LT UT WOS:000235042900020 PM 16448549 ER PT J AU Sifri, CD Baresch-Bernal, A Calderwood, SB von Eiff, C AF Sifri, CD Baresch-Bernal, A Calderwood, SB von Eiff, C TI Virulence of Staphylococcus aureus small colony variants in the Caenorhabditis elegans infection model SO INFECTION AND IMMUNITY LA English DT Article ID HEMB MUTANTS; CYSTIC-FIBROSIS; MURINE MODEL; STRAINS; GROWTH; MUTAGENESIS; PERSISTENT; PHENOTYPE; RESISTANT; SURVIVAL AB Small colony variants (SCVs) of Staphylococcus aureus are slow-growing morphological variants that have been implicated in persistent, relapsing, and antibiotic-resistant infections. The altered phenotype of SCVs in most strains has been attributed to defects in electron transport due to mutations in hemin or menadione biosynthesis. The pathogenic capacity of SCVs compared to phenotypically normal strains is variable depending on the attribute examined, with some studies showing reduced virulence of SCVs and others demonstrating normal or heightened virulence. Recently, the nematode Caenorhabditis elegans has been successfully employed as an alternative host to investigate virulence mechanisms of a variety of bacterial pathogens, including S. aureus. In this study, we show that clinical SCVs as well as hemB- and menD-deficient mutants of S. aureus are greatly reduced in virulence in the C. elegans infection model. C1 Univ Virginia Hlth Syst, Div Infect Dis & Int Hlth, Charlottesville, VA 22908 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA USA. Univ Munster, Inst Med Microbiol, Munster, Germany. RP Sifri, CD (reprint author), Univ Virginia Hlth Syst, Div Infect Dis & Int Hlth, POB 801361, Charlottesville, VA 22908 USA. EM csifri@virginia.org FU NIAID NIH HHS [K08 AI053677] NR 34 TC 35 Z9 41 U1 0 U2 7 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 FEB PY 2006 VL 74 IS 2 BP 1091 EP 1096 DI 10.1128/IAI.74.2.1091-1096.2006 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 009EC UT WOS:000235093100035 PM 16428756 ER PT J AU Gallego, MD de la Fuente, MA Anton, IM Snapper, S Fuhlbrigge, R Geha, RS AF Gallego, MD de la Fuente, MA Anton, IM Snapper, S Fuhlbrigge, R Geha, RS TI WIP and WASP play complementary roles in T cell homing and chemotaxis to SDF-1 alpha SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE WASP; WIP; chemotaxis; SDF-1 alpha ID WISKOTT-ALDRICH-SYNDROME; HEMATOPOIETIC PROGENITOR CELLS; PHYSIOLOGICAL FLOW CONDITIONS; SYNDROME PROTEIN; ENDOTHELIAL-CELLS; ACTIN POLYMERIZATION; CHEMOKINE SDF-1; L-SELECTIN; TRANSENDOTHELIAL MIGRATION; LYMPHOCYTE-ACTIVATION AB Homing of lymphocytes to tissues is a biologically important multistep process that involves selectin-dependent rolling, integrin-dependent adhesion and chemokine-directed chemotaxis. The actin cytoskeleton plays a central role in lymphocyte adhesion and motility. Wiskott-Aldrich syndrome protein (WASP), the product of the gene mutated in Wiskott-Aldrich syndrome, and its partner, the Wiskott-Aldrich syndrome protein-interacting protein (WIP), play important roles in actin re-organization in T lymphocytes. We used mice with disruption of the WASP and WIP genes to examine the role of WASP and WIP in T cell homing. T cell homing to spleen and lymph nodes in vivo was deficient in WASP(-/-) and WIP-/- mice and severely impaired in WASP(-/-)WIP(-/-) double knockout (DKO) mice. Deficiency of WASP, WIP or both did not interfere with selectin-dependent rolling or integrin-dependent adhesion of T cells in vitro. Chemotaxis to stromal cell-derived factor-1 alpha (SDF-1 alpha) in vitro was mildly reduced in T cells from WASP(-/-) mice. In contrast, it was significantly impaired in T cells from WIP-/- mice and severely reduced in T cells from DKO mice. Cellular F-actin increase following SDF-1 alpha stimulation was normal in WASP(-/-) and WIP-/- T cells, but severely reduced in T cells from DKO mice. Actin re-organization and polarization in response to SDF-1 alpha was abnormal in T cells from all knockout mice. Early biochemical events following SDF-1 alpha stimulation that are important for chemotaxis and that included phosphorylation of Lck, cofilin, PAK1 and extracellular regulated kinase (Erk) and GTP loading of Rac-1 were examined in T cells from DKO mice and found to be normal. These results suggest that WASP and WIP are not essential for T lymphocyte rolling and adhesion, but play important and partially redundant roles in T cell chemotaxis in vitro and homing in vivo and function downstream of small GTPases. C1 Childrens Hosp, Div Immunol, Boston, MA 02115 USA. Univ Autonoma Madrid, Ctr Biol Mol Severo Ochoa, E-28049 Madrid, Spain. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Harvard Skin Dis Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. RP Gallego, MD (reprint author), Childrens Hosp, Div Immunol, 300 Longwood Ave, Boston, MA 02115 USA. EM raif.geha@childrens.harvard.edu RI de la Fuente, Miiguel /C-7478-2013; Anton, Ines/G-6090-2015 OI de la Fuente, Miiguel /0000-0003-4619-8756; FU NHLBI NIH HHS [HL59561]; NIAID NIH HHS [AI35714]; NIAMS NIH HHS [P30 AR42689] NR 62 TC 61 Z9 66 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD FEB PY 2006 VL 18 IS 2 BP 221 EP 232 DI 10.1093/intimm/dxh310 PG 12 WC Immunology SC Immunology GA 007KF UT WOS:000234967000001 PM 16141245 ER PT J AU Fadel, SA Cowell, LG Cao, S Ozaki, DA Kepler, TB Steeber, DA Sarzotti, M AF Fadel, SA Cowell, LG Cao, S Ozaki, DA Kepler, TB Steeber, DA Sarzotti, M TI Neonate-primed CD8(+) memory cells rival adult-primed memory cells in antigen-driven expansion and anti-viral protection SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE cytokines; memory; rodent; T lymphocytes; viral ID T-CELLS; NEWBORN MICE; GUERIN VACCINATION; DENDRITIC CELLS; CTL RESPONSES; IN-VIVO; VIRUS; IMMUNITY; INDUCTION; TOLERANCE AB Immunizations early in life, when the host is most susceptible to infection, allow protective immunological memory to develop. Decreasing the dose of Cas-Br-E murine leukemia virus when priming neonatal mice results in adult-like, Type 1 protective responses, but the resulting memory cell populations are smaller than after adult priming. After secondary challenge, virus-specific CD8(+) memory cell populations expand twice as much in neonate-primed mice as in adult-primed mice. We found that when equivalent numbers of virus-specific cells were transferred into virus-susceptible mice, protection from disease was similar whether donor, immune mice were primed as neonates or adults, and IL-4 did not alter in vivo virus-specific CD8(+) memory cell effector function. Hence, neonate-primed CD8(+) cells develop into memory cells that rival adult-primed cells in proliferation and effector function. C1 Duke Univ, Med Ctr, Ctr Bioinformat & Computat Biol, Dept Biostat & Bioinformat, Durham, NC 27708 USA. Tianjin Med Univ, Tianjin Canc Hosp & Inst, Dept Immunol, Tianjin 300060, Peoples R China. Univ Wisconsin, Dept Biol Sci, Milwaukee, WI 53211 USA. Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27710 USA. RP Sarzotti, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis, 149 E 13th St, Charlestown, MA 02129 USA. EM msarzott@duke.edu OI Kepler, Thomas/0000-0002-1383-6865 FU NCI NIH HHS [CA65388] NR 40 TC 13 Z9 13 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 FEB PY 2006 VL 18 IS 2 BP 249 EP 257 DI 10.1093/intimm/dxh360 PG 9 WC Immunology SC Immunology GA 007KF UT WOS:000234967000004 PM 16418189 ER PT J AU Rosol, M Sachdev, K Enzweiler, CN Kwait, DC Millea, R Titus, J Handwerker, J Wicky, S Achenbach, S Brady, TJ Hoffmann, U AF Rosol, M Sachdev, K Enzweiler, CN Kwait, DC Millea, R Titus, J Handwerker, J Wicky, S Achenbach, S Brady, TJ Hoffmann, U TI A novel model to test accuracy and reproducibility of MDCT scan protocols for coronary calcium in vivo SO INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING LA English DT Article DE artery imaging; calcium scoring; coronary artery imaging; MDCT ID ELECTRON-BEAM TOMOGRAPHY; MULTISLICE SPIRAL CT; MULTIDETECTOR ROW CT; ARTERY CALCIUM; COMPUTED-TOMOGRAPHY; HELICAL CT; HEART-RATE; DISEASE; QUANTIFICATION; CALCIFICATION AB Objectives: We compared the accuracy and reliability of prospectively triggered, retrospectively ECG gated, and non-gated CT image reconstruction for measurements of coronary artery calcification (CAC) in vivo using a novel animal model. Materials and Methods: In six Yorkshire farm pigs, prefabricated chains of cortical bone fragments were sutured over the epicardial bed of the major coronary arteries. Using a 4-slice MDCT scanner, each animal was imaged with two different protocols: sequential acquisition with prospective ECG triggering, and spiral acquisition with retrospectively ECG gated image reconstruction- non-gated reconstructions were also generated from these latter scans. Two independent observers measured the 'Agatston score' (AS), the calcified volume (CV), and mineral mass (MM). To calculate accuracy of MM measurements the ash weight of the burned bone fragments was compared to MDCT derived MM. Results: Six pigs successfully underwent surgery and CT imaging (mean heart rate: 86 +/- 12 bpm). MM measurements from prospectively ECG triggered CT sequential scans were more accurate (p < 0.02) and reproducible (p=0.05) than sequential CT scans without ECG triggering or spiral acquisition using retrospective ECG gating. Conclusions: At high heart rates prospective ECG triggered image reconstruction is more accurate and reproducible for CAC scoring than retrospective ECG gated reconstruction and non-gated reconstruction. C1 Childrens Hosp Los Angeles, Dept Radiol, Los Angeles, CA 90027 USA. Univ So Calif, Keck Sch Med, Los Angeles, CA 90027 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Cardiac Surg, Boston, MA 02114 USA. Univ Erlangen Nurnberg, Dept Internal Med 2, D-8520 Erlangen, Germany. RP Rosol, M (reprint author), Childrens Hosp Los Angeles, Dept Radiol, 4650 W Sunset Blvd,M-S 81, Los Angeles, CA 90027 USA. EM mrosol@chla.usc.edu NR 29 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1569-5794 J9 INT J CARDIOVAS IMAG JI Int. J. Cardiovasc. Imaging PD FEB PY 2006 VL 22 IS 1 BP 111 EP 118 DI 10.1007/s10554-005-6535-7 PG 8 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 020MX UT WOS:000235914700019 PM 16374527 ER PT J AU Bueter, M Gasser, M Schramm, N Lebedeva, T Tocco, G Gerstlauer, C Grimm, M Nichiporuk, E Thalheimer, A Thiede, A Meyer, D Benichou, G Waaga-Gasser, AM AF Bueter, M Gasser, M Schramm, N Lebedeva, T Tocco, G Gerstlauer, C Grimm, M Nichiporuk, E Thalheimer, A Thiede, A Meyer, D Benichou, G Waaga-Gasser, AM TI T-cell response to p53 tumor-associated antigen in patients with colorectal carcinoma SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE p53; immune response; T cells; cancer; tumor antigens ID CLASS-I PHENOTYPES; WILD-TYPE; DENDRITIC CELLS; LUNG-CANCER; IMMUNOTHERAPY; EXPRESSION; ANTIBODIES; VIVO; INTERLEUKIN-10; PROTEIN AB Despite the radical surgical resection performed in patients with colorectal carcinoma, there is a high rate of tumor recurrence. Over an observation period of 3 years, 18% of the patients in our collective suffered a tumor relapse with local or distinct metastases after initial R0-resection. Some evidence suggests that this may be due to suppression of antitumor responses, a phenomenon that might be attributed to regulatory T cells. The aim of our study was to investigate the tumor-specific immune response depending on the UICC stage of patients with colorectal cancer. The cellular immune responses against defined antigens that are overexpressed in most of the patients with colorectal cancer were characterized. For this purpose, the tumor suppressor gene, p53, was chosen as the tumor-associated antigen that exhibits mutations and overexpression in up to 60% of colorectal carcinoma. We observed that p53 induced both IFN-gamma and IL-10 secretion. The predominance of IL-10 production indicated that regulatory T cells directly participate in modulating the anti-tumor immune response. IL-10 levels in the blood as well as the expression of regulatory T-cell specific genes at the tumor site correlate with the UICC stage of the disease. These results may provide an explanation for the poor prognosis and increased recurrence rate in patients with advanced carcinoma. C1 Univ Wurzburg, Dept Surg 1, Zentrum Operat Med, D-97080 Wurzburg, Germany. Univ Wurzburg, Dept Mol Oncol & Immunol, D-97080 Wurzburg, Germany. Amer Red Cross, Dedham, MA 02026 USA. Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp,CMI Lab,Transplantat Unit, Boston, MA 02114 USA. RP Waaga-Gasser, AM (reprint author), Univ Wurzburg, Dept Surg 1, Zentrum Operat Med, Oberduerrbacher Str 6, D-97080 Wurzburg, Germany. EM waaga-gasser@chirurgie.uni-wuerzburg.de NR 41 TC 7 Z9 7 U1 0 U2 0 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD FEB PY 2006 VL 28 IS 2 BP 431 EP 438 PG 8 WC Oncology SC Oncology GA 004NF UT WOS:000234758800018 PM 16391798 ER PT J AU Bueter, M Gasser, M Lebedeva, T Benichou, G Waaga-Gasser, AM AF Bueter, M Gasser, M Lebedeva, T Benichou, G Waaga-Gasser, AM TI Influence of p53 on anti-tumor immunity (Review) SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE p53; target immunotherapy; type 1 and 2 T cell responses; cryptic self-determinants ID MAJOR HISTOCOMPATIBILITY COMPLEX; CD4(+) T-CELLS; MULTIPLE-SCLEROSIS; CLONAL DELETION; SELF-TOLERANCE; TUMOR-ANTIGEN; CANCER; IMMUNOTHERAPY; REPERTOIRE; IMMUNOLOGY AB Self-tolerance and tumor-induced peripheral tolerance may be responsible for the limitations of the immune system in controlling tumor growth in cancer patients. It is known, that self-proteins are continuously processed and presented by antigen presenting cells. During development, auto-reactive T cells encountering self peptide/self-MHC complexes are being eliminated in the thymus. This process called 'negative selection' results in the removal of nascent auto-reactive T cells thus preventing an autoimmune attack of our own tissues. Many self-peptides (e.g. parts of p53), despite their high affinity for self-MHC, remain cryptic in the thymus and do not mediate cell deletion. Under conditions that favor up-regulation of cryptic self-determinants, one or more of these subsets of the `protected' T cell repertoires, can be stimulated by these self-determinants, leading to induction of autoreactivity. The latter could eventually result in autoimmunity under permissive conditions governed by MHC and non-MHC genes. Thus, considering tumor tissue a 'modified self-tissue', this process that may have evolved to prevent excessive purge of the T cell repertoire, providing the potential for the development of autoimmune responses and therefore for anti-cancer therapy in adults. C1 Univ Wurzburg, Dept Surg 1, Zentrum Operat Med, D-97080 Wurzburg, Germany. Amer Red Cross, New England Reg, Dedham, MA 02026 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Transplantat Unit, Boston, MA 02114 USA. RP Waaga-Gasser, AM (reprint author), Univ Wurzburg, Dept Surg 1, Zentrum Operat Med, Oberduerrbacher Str 6, D-97080 Wurzburg, Germany. EM waaga-gasser@chirurgie.uni-wuerzburg.de NR 55 TC 9 Z9 11 U1 0 U2 1 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD FEB PY 2006 VL 28 IS 2 BP 519 EP 525 PG 7 WC Oncology SC Oncology GA 004NF UT WOS:000234758800028 PM 16391808 ER PT J AU Boseley, ME Ashland, J Hartnick, CJ AF Boseley, ME Ashland, J Hartnick, CJ TI The utility of the fiberoptic endoscopic evaluation of swallowing (FEES) in diagnosing and treating children with Type I laryngeal clefts SO INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY LA English DT Article DE laryngeal cleft; aspiration; fiberoptic endoscopic evaluation of swallowing (FEES) ID LARYNGOTRACHEOESOPHAGEAL CLEFT; MANAGEMENT; REPAIR AB This case series of three young children with type I laryngeal clefts is presented to demonstrate the utility of fiberoptic endoscopic evaluation of swallowing (FEES) in managing these patients. FEES revealed laryngeal penetration in a posterior to anterior direction in two patients and penetration from lateral to medial, in the third patient. The type of laryngeal penetration helped in making the diagnosis of a type I cleft in two children and helped establish a safe feeding regiment in the third child. Patients with type I laryngeal clefts are often misdiagnosed, most Likely resulting from the complex presentation of signs/symptoms and the difficulty of detecting small clefts with currently available tests. The pattern of laryngeal aspiration seen with FEES can help in diagnosis and management in this patient population. Published by Elsevier Ireland Ltd. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Massachusetts Gen Hosp Children, Dept Speech Language Pathol, Boston, MA USA. RP Boseley, ME (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM M.Boseley@att.net; Christopher_hartnick@meei.harvard.edu NR 19 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-5876 J9 INT J PEDIATR OTORHI JI Int. J. Pediatr. Otorhinolaryngol. PD FEB PY 2006 VL 70 IS 2 BP 339 EP 343 DI 10.1016/j.ijporl.2005.06.026 PG 5 WC Otorhinolaryngology; Pediatrics SC Otorhinolaryngology; Pediatrics GA 009DN UT WOS:000235091600023 PM 16125795 ER PT J AU Boseley, ME Bloch, I Hartnick, CJ AF Boseley, ME Bloch, I Hartnick, CJ TI Charcot-Marie-Tooth Disease type 1 and pediatric true vocal fold paralysis SO INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY LA English DT Article DE Charcot-Marie-Tooth (CMT); bilateral vocal fold paralysis; fiberoptic evaluation of swallowing (FEES) ID FIBEROPTIC ENDOSCOPIC EVALUATION; DYSPHAGIA AB A case study of a child with Charcot-Marie-Tooth type I (CMT1) that presented with bilateral vocal fold paralysis. This is the first case of bilateral vocal fold paralysis in a child with CMT1 and it is the first case to be managed endoscopically. The surgical decision making process is discussed, and in particular the rote of fiberoptic endoscopic evaluation of swallowing (FEES) in determining what surgical options should be entertained. In children with bilateral vocal fold paralysis who also have other neurologic abnormalities, the clinician should consider the possibility of CMT as the cause. Published by Elsevier Ireland Ltd. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Boseley, ME (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM m.boseley@att.net; christopher_hartnick@meei.harvard.edu NR 9 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-5876 J9 INT J PEDIATR OTORHI JI Int. J. Pediatr. Otorhinolaryngol. PD FEB PY 2006 VL 70 IS 2 BP 345 EP 347 DI 10.1016/j.ijporl.2005.06.017 PG 3 WC Otorhinolaryngology; Pediatrics SC Otorhinolaryngology; Pediatrics GA 009DN UT WOS:000235091600024 PM 16084600 ER PT J AU Burstein, HJ Bellon, JR Galper, S Lu, HM Kuter, I Taghian, AG Wong, J Gelman, R Bunnell, CA Parker, LM Garber, JE Winer, EP Harris, JR Powell, SN AF Burstein, HJ Bellon, JR Galper, S Lu, HM Kuter, I Taghian, AG Wong, J Gelman, R Bunnell, CA Parker, LM Garber, JE Winer, EP Harris, JR Powell, SN TI Prospective evaluation of concurrent paclitaxel and radiation therapy after adjuvant doxorubicin and cyclophosphamide chemotherapy for Stage II or III breast cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE breast cancer; radiotherapy; concurrent; paclitaxel; taxane ID CONSERVATIVE SURGERY; COMBINATION CHEMOTHERAPY; SEQUENTIAL PACLITAXEL; RANDOMIZED-TRIAL; PNEUMONITIS; RADIOTHERAPY; ORGANIZATION; OUTCOMES; TAXANES; TUMORS AB Purpose: To evaluate the safety and feasibility of concurrent radiation therapy and paclitaxel-based adjuvant chemotherapy, given either weekly or every 3 weeks, after adjuvant doxorubicin and cyclophosphamide (AC). Methods and Materials: After definitive breast surgery and AC chemotherapy, 40 patients with operable Stage II or III breast cancer received protocol-based treatment with concurrent paclitaxel and radiation therapy. Paclitaxel was evaluated on 2 schedules, with treatment given either weekly X 12 weeks (60 mg/m(2)), or every 3 weeks X 4 cycles (135-175 mg/m(2)). Radiation fields and schedules were determined by the patient's surgery and pathology. The tolerability of concurrent therapy was evaluated in cohorts of 8 patients as a phase I study. Results: Weekly paclitaxel treatment at 60 mg/m(2) per week with concurrent radiation led to dose-limiting toxicity in 4 of 16 patients (25%), including 3 who developed pneumonitis (either Grade 2 [1 patient] or Grade 3 [2 patients]) requiring steroids. Efforts to eliminate this toxicity in combination with weekly paclitaxel through treatment scheduling and CT-based radiotherapy simulation were not successful. By contrast, dose-limiting toxicity was not encountered among patients receiving concurrent radiation with paclitaxel given every 3 weeks at 135-175 mg/m(2). However, Grade 2 radiation pneumonitis not requiring steroid therapy was seen in 2 of 24 patients (8%) treated in such a fashion. Excessive radiation dermatitis was not observed with either paclitaxel schedule. Conclusions: Concurrent treatment with weekly paclitaxel and radiation therapy is not feasible after adjuvant AC chemotherapy for early-stage breast cancer. Concurrent treatment using a less frequent paclitaxel dosing schedule may be possible, but caution is warranted in light of the apparent possibility of pulmonary injury. (C) 2006 Elsevier Inc. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Hematol Oncol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. RP Burstein, HJ (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM hburstein@partners.org NR 29 TC 25 Z9 26 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD FEB 1 PY 2006 VL 64 IS 2 BP 496 EP 504 DI 10.1016/j.ijrobp.2005.07.975 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 006GA UT WOS:000234883300022 PM 16243442 ER PT J AU Lyden, PD Krieger, D Yenari, M Dietrich, WD AF Lyden, Patrick D. Krieger, Derk Yenari, Miclori Dietrich, W. Dalton TI Therapeutic hypothermia for acute stroke SO INTERNATIONAL JOURNAL OF STROKE LA English DT Review ID CEREBRAL-ARTERY OCCLUSION; TRANSIENT GLOBAL-ISCHEMIA; DELAYED POSTISCHEMIC HYPOTHERMIA; MILD RESUSCITATIVE HYPOTHERMIA; TISSUE-PLASMINOGEN ACTIVATOR; PERMANENT FOCAL ISCHEMIA; DAMAGE COOL AID; MODERATE HYPOTHERMIA; SHIVERING THRESHOLD; FOREBRAIN ISCHEMIA AB Hypothermia is the most potent neuroprotective therapy available. Clinical use of hypothermia is limited by technology and homeostatic mechanisms that maintain core body temperature. Recent advances in intravascular cooling catheters and successful trials of hypothermia for cardiac arrest revivified interest in hypothermia for stroke, resulting in Phase 1 clinical trials and plans for further development. Given the recent spate of neuroprotective therapy failures, we sought to clarify whether clinical trials of therapeutic hypothermia should be mounted in stroke patients. We reviewed the preclinical and early clinical trials of hypothermia for a variety of indications, the putative mechanisms for neuroprotection with hypothermia, and offer several hypotheses that remain to be tested in clinical trials. Therapeutic hypothermia is promising, but further Phase 1 and Phase 2 development efforts are needed to ensure that cooling of stroke patients is safe, before definitive efficacy trials. C1 Univ Calif San Diego, Stroke Ctr, San Diego, CA 92103 USA. Univ Calif San Diego, Neurol & Res Serv, San Diego Vet Adm Med Ctr, San Diego, CA 92103 USA. Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. Cleveland Clin Fdn, Sect Stroke & Neurol Crit Care, Cleveland, OH 44195 USA. Univ Calif San Francisco, Sch Med, Dept Neurol, San Francisco, CA 94143 USA. San Francisco Vet Adm Med Ctr, Dept Neurol, San Francisco, CA USA. Univ Miami, Sch Med, Dept Neurol Surg, Miami, FL 33136 USA. RP Lyden, PD (reprint author), Univ Calif San Diego, Stroke Ctr, OPC 3rd Floor,Suite 3,200 W Arbor Dr, San Diego, CA 92103 USA. EM plyden@ucsd.edu NR 119 TC 56 Z9 60 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1747-4930 J9 INT J STROKE JI Int. J. Stroke PD FEB PY 2006 VL 1 IS 1 BP 9 EP 19 DI 10.1111/j.1747-4949.2005.00011.x PG 11 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 178DK UT WOS:000247201200004 PM 18706063 ER PT J AU Cury, RC Houser, SL Furie, KL Stone, JR Ogilvy, CS Sherwood, JB Muller, JE Brady, TJ Hinton, DP AF Cury, RC Houser, SL Furie, KL Stone, JR Ogilvy, CS Sherwood, JB Muller, JE Brady, TJ Hinton, DP TI Vulnerable plaque detection by 3.0 tesla magnetic resonance imaging SO INVESTIGATIVE RADIOLOGY LA English DT Article DE 3.0 tesla MRI; vulnerable plaque; carotid artery; vessel wall imaging ID IN-VIVO; ATHEROSCLEROTIC LESIONS; MOUSE; MICE; MRI AB Rationale and Objectives: A clinical case report is presented on a 76-year-old man who volunteered for a 3.0 T magnetic resonance (MR) carotid protocol. The subject was referred for carotid endarterectomy and histology was performed on the ex vivo specimen an compared with the in vivo images. Methods: The 3.0 and 1.5 T (obtained for comparison) MR protocol consisted of 2-dimensional (2D) and 3-dimensional (3D) multicontrast bright and black blood imaging for detecting the lumen an vessel wall. Results: The combination of multicontrast black blood transverse images and the 3D time of flight transverse images provided visualization of a narrowed internal carotid artery lumen 4 mm above of the bifurcation and the presence of a complex atherosclerotic plaque containing a large lipid pool, calcification, and intact fibrous cap. Quantitative comparisons including vessel lumen and plaque area, signal-to-noise (SNR) and contrast-to-noise (CNR) ratios were obtained for 1.5 and 3.0 T image data. Plaque composition was verified with histology. Macrophages were also detected in the shoulders of the plaque as demonstrated by CD68 staining and corresponded with a small hyperintense area in the T2W images at 3.0 T, but not observed in comparable 1.5 T images. Conclusions: High field 3.0 T multicontrast MRI of atherosclerotic plaque has been validated with histology comparison and provides improved detection of complex atherosclerotic plaque with increased SNR and CNR compared with 1.5 T. Further studies validating contrast mechanisms of plaque at 3.0 T are required, but atherosclerotic plaque imaging has clear benefit from application at the higher magnetic field strength. C1 Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Pathol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Div Neurol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Div Neurosurg, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Div Cardiol, Charlestown, MA 02129 USA. RP Hinton, DP (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St,Room 2301, Charlestown, MA 02129 USA. EM denise@nmr.mgh.harvard.edu NR 10 TC 27 Z9 28 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD FEB PY 2006 VL 41 IS 2 BP 112 EP 115 DI 10.1097/01.rli.0000186419.55504.30 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 011IX UT WOS:000235262900008 PM 16428981 ER PT J AU Cohen, LS Altshuler, LL Harlow, BL Nonacs, R Newport, DJ Viguera, AC Suri, R Burt, VK Hendrick, V Reminick, AM Loughead, A Vitonis, AF Stowe, ZN AF Cohen, LS Altshuler, LL Harlow, BL Nonacs, R Newport, DJ Viguera, AC Suri, R Burt, VK Hendrick, V Reminick, AM Loughead, A Vitonis, AF Stowe, ZN TI Relapse of major depression during pregnancy in women who maintain or discontinue antidepressant treatment SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID SEROTONIN REUPTAKE INHIBITORS; FOLLOW-UP; RECURRENCE; FLUOXETINE; SYMPTOMS; EXPOSURE; PREDICTORS; GUIDELINES; DISORDER; OUTCOMES AB Context Pregnancy has historically been described as a time of emotional well-being, providing "protection" against psychiatric disorder. However, systematic delineation of risk of relapse in women who maintain or discontinue pharmacological treatment during pregnancy is necessary. Objective To describe risk of relapse in pregnant women who discontinued antidepressant medication proximate to conception compared with those who maintained treatment with these medications. Design, Setting, and Patients A prospective naturalistic investigation using longitudinal psychiatric assessments on a monthly basis across pregnancy; a survival analysis was conducted to determine time to relapse of depression during pregnancy. A total of 201 pregnant women were enrolled between March 1999 and April 2003 from 3 centers with specific expertise in the treatment of psychiatric illness during pregnancy. The cohort of women was recruited from (1) within the hospital clinics, (2) self-referral via advertisements and community outreach detailing the study, and (3) direct referrals from the community. Participants were considered eligible if they (1) had a history of major depression prior to pregnancy, (2) were less than 16 weeks' gestation, (3) were euthymic for at least 3 months prior to their last menstrual period, and (4) were currently or recently (<12 weeks prior to last menstrual period) receiving antidepressant treatment. Of the 201 participants, 13 miscarried, 5 electively terminated their pregnancy, 12 were lost to follow-up prior to completion of pregnancy, and 8 chose to discontinue participation in the study. Main Outcome Measure Relapse of major depression defined as fulfilling Structured Clinical Interview for DSM-IV [Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition] Diagnosis (SCID) criteria. Results Among the 201 women in the sample, 86 (43%) experienced a relapse of major depression during pregnancy. Among the 82 women who maintained their medication throughout their pregnancy, 21 (26%) relapsed compared with 44 (68%) of the 65 women who discontinued medication. Women who discontinued medication relapsed significantly more frequently over the course of their pregnancy compared with women who maintained their medication (hazard ratio, 5.0; 95% confidence interval, 2.8-9.1; P<.001). Conclusions Pregnancy is not "protective" with respect to risk of relapse of major depression. Women with histories of depression who are euthymic in the context of ongoing antidepressant therapy should be aware of the association of depressive relapse during pregnancy with antidepressant discontinuation. C1 Harvard Univ, Massachusetts Gen Hosp, Perinatal & Reprod Psychiat Clin Res Program, Sch Med,Dept Psychiat, Boston, MA 02114 USA. Univ Calif Los Angeles, Sch Med, Womens Mood Disorders Res Program, Los Angeles, CA 90024 USA. Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, Boston, MA 02115 USA. Emory Univ, Sch Med, Womens Mental Hlth Program, Atlanta, GA USA. RP Cohen, LS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Perinatal & Reprod Psychiat Clin Res Program, Sch Med,Dept Psychiat, WACC 812,15 Parkman St, Boston, MA 02114 USA. EM lcohen2@partners.org RI Newport, Donald/H-9846-2013; OI Newport, D. Jeffrey/0000-0003-1695-9710 FU NIMH NIH HHS [MH 56492-04, MH 56420-05, MH 56555-01A2] NR 37 TC 414 Z9 425 U1 2 U2 28 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD FEB 1 PY 2006 VL 295 IS 5 BP 499 EP 507 DI 10.1001/jama.295.5.499 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 007SP UT WOS:000234990300017 PM 16449615 ER PT J AU Zalta, AK Keel, PK AF Zalta, AK Keel, PK TI Peer influence on bulimic symptoms in college students SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article DE bulimia; peers; socialization; personality; longitudinal studies ID EATING ATTITUDES; NERVOSA; ADOLESCENCE; VALIDATION; INVENTORY; SCALE AB This longitudinal study examined the influence of peer selection and socialization on bulimic symptoms in college students. Ninety-eight participants completed measures of bulimic symptoms, self-esteem.. perfectionism, and impulsivity in the spring and fall of 2003. Peer influence was assessed by examining similarity among selected peers, unselected peers, and nonpeers over time. Among selected peers, bulimic symptoms demonstrated patterns of socialization. self-esteem and perfectionism demonstrated patterns of selection, and these personality traits longitudinally predicted changes in bulimic symptoms. Unselected peers demonstrated no similarity for bulimia, self-esteem, or perfectionism, but they did evidence socialization for impulsivity. The findings support an etiological model that integrates social and individual risk factors in creating environments that influence disordered eating among college students. C1 Univ Iowa, Dept Psychol, Iowa City, IA 52242 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Keel, PK (reprint author), Univ Iowa, Dept Psychol, E11 Seashore Hall, Iowa City, IA 52242 USA. EM pamela-keel@uiowa.edu OI Zalta, Alyson/0000-0002-5159-8431 FU PHS HHS [R01-63758] NR 20 TC 30 Z9 30 U1 0 U2 7 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD FEB PY 2006 VL 115 IS 1 BP 185 EP 189 DI 10.1037/0021-843X.115.1.185 PG 5 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA 022KV UT WOS:000236055600021 PM 16492110 ER PT J AU Miller, E Silverman, J Raj, A AF Miller, E Silverman, J Raj, A TI Intimate partner violence and pregnancy: Narratives of pregnant and parenting teens SO JOURNAL OF ADOLESCENT HEALTH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD FEB PY 2006 VL 38 IS 2 MA 22 BP 123 EP 124 DI 10.1016/j.jadohealth.2005.11.098 PG 2 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA 007IZ UT WOS:000234963600054 ER PT J AU Gupta, RS Carrion-Carire, V Weiss, KB AF Gupta, RS Carrion-Carire, V Weiss, KB TI The widening black/white gap in asthma hospitalizations and mortality SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE asthma; disparities; hospitalizations; mortality ID HEALTH-INSURANCE PROGRAM; CHILDHOOD ASTHMA; EMERGENCY-DEPARTMENT; ETHNIC DISPARITIES; URBAN CHILDREN; UNITED-STATES; PRIMARY-CARE; GUIDELINES; REDUCTION; MEDICAID AB Background: Large racial differences in asthma morbidity and mortality have prompted research on new interventions, public awareness, and health policy efforts in the past decade. Objective: We sought to characterize recent trends in US asthma hospitalization and mortality for black and white children and adults during the period from 1980 through 2002. Methods: We conducted a successive representative national cohort study of US residents ages 5 to 34 years using data from the National Hospital Discharge Survey and the US vital statistics system. Outcome measures included black/white (B/W) asthma hospitalization and mortality rates, rate ratios, and rate differences. Results: For asthma hospitalizations from 1980 through 2002, children ages 5 to 18 years had a 50% increase in the B/W rate ratio, and the rate difference increased from 22.8 to 28.3 hospitalizations per 10,000 population. For young adults ages 19 to 34 years, the B/W rate ratio increased from 2.3 to 2.8, and the rate difference decreased front 9.6 to 7.9 hospitalizations per 10,000 population. For asthma mortality front 1980 through 2001, children ages 5 to 19 years had a large increase in the B/W rate ratio from 4.5 to 5.6 and in the rate difference from 5.6 to 8.1 deaths per 1,000,000 population. There did not appear to be a significant change in the B/W differences for adults ages 20 to 34 years. Conclusions: For children, there have been notable increases in asthma B/W differences in hospitalizations and mortality since 1980, whereas for adults the increase has been smaller. National efforts to improve asthma care over the past decade do not appear to have reduced this B/W gap. When treating children with asthma, it is important to consider the racial-ethnic factors that might lead to avoidable hospitalizations and premature mortality. C1 Inst Healthcare Studies, Chicago, IL 60611 USA. Northwestern Univ, Feinberg Sch Med, Div Gen Internal Med, Chicago, IL USA. Childrens Mem Hosp, Smith Child Hlth Res Program, Chicago, IL USA. Vet Affairs Edward Hines Jr Hosp, US Dept Vet Affairs, Midwest Ctr Hlth Serv & Policy Res, Hines, IL USA. RP Gupta, RS (reprint author), Inst Healthcare Studies, 339 E Chicago Ave,Room 712, Chicago, IL 60611 USA. EM r-gupta@northwestern.edu RI Dalla Zuanna, Teresa/G-3133-2015 FU AHRQ HHS [T32HS00078-07] NR 41 TC 86 Z9 87 U1 0 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2006 VL 117 IS 2 BP 351 EP 358 DI 10.1016/j.jaci.2005.11.047 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 017IM UT WOS:000235687300018 PM 16461136 ER PT J AU Bermant, C Pratt, A Opsahl, M Sanchez, H Bush, RK AF Bermant, C Pratt, A Opsahl, M Sanchez, H Bush, RK TI Production of a cDNA library to Harmonia axyridis multicolor lady beetle SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 03-07, 2006 CL Miami Beach, FL SP Amer Acad Allergy, Asthma & Immunol C1 William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2006 VL 117 IS 2 SU S MA 1195 BP S310 EP S310 DI 10.1016/j.jaci.2005.12.1222 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 019VR UT WOS:000235865302273 ER PT J AU Camargo, CA Clark, S Kaplan, MS Lieberman, P Wood, RA AF Camargo, CA Clark, S Kaplan, MS Lieberman, P Wood, RA TI Regional differences in EpiPen prescriptions in the United States SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 03-07, 2006 CL Miami Beach, FL SP Amer Acad Allergy, Asthma & Immunol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Kaiser Permanente, Los Angeles, CA USA. Allergy & Asthma Care, Cordova, TN USA. Johns Hopkins Med Ctr, Baltimore, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2006 VL 117 IS 2 SU S MA 541 BP S139 EP S139 DI 10.1016/j.jaci.2005.12.554 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 019VR UT WOS:000235865301038 ER PT J AU Clark, S Pelletier, AJ Gaeta, TJ Camargo, CA AF Clark, S Pelletier, AJ Gaeta, TJ Camargo, CA TI Management of acute allergic reactions and anaphylaxis in the emergency department between 1993-2003 SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 03-07, 2006 CL Miami Beach, FL SP Amer Acad Allergy, Asthma & Immunol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. New York Methodist Hosp, Brooklyn, NY USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2006 VL 117 IS 2 SU S MA 1185 BP S307 EP S307 DI 10.1016/j.jaci.2005.12.1212 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 019VR UT WOS:000235865302263 ER PT J AU Esch, RF Bush, RK Peden, D Lockey, RF AF Esch, RF Bush, RK Peden, D Lockey, RF TI Sublingual-oral administration of standardized allergenic extracts/vaccines: Safety and dosing studies SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 03-07, 2006 CL Miami Beach, FL SP Amer Acad Allergy, Asthma & Immunol C1 Greer Labs, Lenoir, NC USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. Univ N Carolina, Chapel Hill, NC USA. Univ S Florida, Tampa, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2006 VL 117 IS 2 SU S MA 348 BP S89 EP S89 DI 10.1016/j.jaci.2005.12.357 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 019VR UT WOS:000235865300348 ER PT J AU Hesterberg, PE Banerji, A Oren, E Penson, RT Seiden, MV Krasner, CN Wong, JT AF Hesterberg, PE Banerji, A Oren, E Penson, RT Seiden, MV Krasner, CN Wong, JT TI Clinical presentation, evaluation, and management of patients with carboplatin hypersensitivity SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 03-07, 2006 CL Miami Beach, FL SP Amer Acad Allergy, Asthma & Immunol C1 Massachusetts Gen Hosp, Gillette Ctr Womens Canc, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2006 VL 117 IS 2 SU S MA 860 BP S223 EP S223 DI 10.1016/j.jaci.2005.12.880 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 019VR UT WOS:000235865301357 ER PT J AU Hsu, RT Crawford, WW Klaustermeyer, WB AF Hsu, RT Crawford, WW Klaustermeyer, WB TI Patients with intermittent asthma account for a substantial portion of asthma-related hospital emergency department visits SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 03-07, 2006 CL Miami Beach, FL SP Amer Acad Allergy, Asthma & Immunol C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Kaiser Permanente, Harbor City, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2006 VL 117 IS 2 SU S MA 1067 BP S276 EP S276 DI 10.1016/j.jaci.2005.12.1144 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 019VR UT WOS:000235865302145 ER PT J AU Keller, M Spanou, Z Schaerli, P Britschgi, M Yawalkar, N Seitz, M Villiger, PM Pichler, WJ AF Keller, M Spanou, Z Schaerli, P Britschgi, M Yawalkar, N Seitz, M Villiger, PM Pichler, WJ TI T-cell regulated neutrophilic inflammation in auto-inflammatory diseases SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 03-07, 2006 CL Miami Beach, FL SP Amer Acad Allergy, Asthma & Immunol C1 Univ Hosp, Clin Rheumatol, Bern, Switzerland. Univ Hosp, Clin Immunol Allergol, Bern, Switzerland. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Univ Hosp, Dept Dermatol, Bern, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2006 VL 117 IS 2 SU S MA 83 BP S21 EP S21 DI 10.1016/j.jaci.2005.12.087 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 019VR UT WOS:000235865300083 ER PT J AU Knuffman, JE Sanchez, H Opsahl, MA Sorkness, RL Bush, RK AF Knuffman, JE Sanchez, H Opsahl, MA Sorkness, RL Bush, RK TI Effects of allergen challenge on a chronic animal model of Alternaria sensitivity SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 03-07, 2006 CL Miami Beach, FL SP Amer Acad Allergy, Asthma & Immunol C1 Univ Wisconsin, Madison, WI USA. Univ Wisconsin Hosp & Clin, William S Middleton Mem Vet Adm Hosp, Madison, WI 53792 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2006 VL 117 IS 2 SU S MA 443 BP S113 EP S113 DI 10.1016/j.jaci.2005.12.454 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 019VR UT WOS:000235865300443 ER PT J AU Miyahara, N Taube, C Ott, V Swanson, B Takeda, K Miyahara, S Matsubara, S Koya, T Loader, J Shultz, LD Tager, AM Luster, AD Dakhama, A Gelfand, EW AF Miyahara, N Taube, C Ott, V Swanson, B Takeda, K Miyahara, S Matsubara, S Koya, T Loader, J Shultz, LD Tager, AM Luster, AD Dakhama, A Gelfand, EW TI The leukotriene B4 receptor (BLT1) is required for effector CD8+ T-cell-mediated, mast cell-dependent airway hyperresponsiveness SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 03-07, 2006 CL Miami Beach, FL SP Amer Acad Allergy, Asthma & Immunol C1 Natl Jewish Med & Res Ctr, Denver, CO USA. Jackson Lab, Bar Harbor, ME 04609 USA. Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Ctr Immunol & Inflammatory Dis, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2006 VL 117 IS 2 SU S MA 943 BP S244 EP S244 DI 10.1016/j.jaci.2005.12.965 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 019VR UT WOS:000235865302021 ER PT J AU Murali, MR AF Murali, MR TI The implications of hypersensitivity pneumonitis (HP) precipitin assays in the diagnosis of immune lung diseases SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 03-07, 2006 CL Miami Beach, FL SP Amer Acad Allergy, Asthma & Immunol C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Rheumatol Allergy & Clin Immunol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2006 VL 117 IS 2 SU S MA 88 BP S22 EP S22 DI 10.1016/j.jaci.2005.12.092 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 019VR UT WOS:000235865300088 ER PT J AU O'Connor, R Tashkin, D Peters, S Long, A Bleecker, E Parasuraman, B Boggs, R AF O'Connor, R Tashkin, D Peters, S Long, A Bleecker, E Parasuraman, B Boggs, R TI Assessment of asthma exacerbations in a real-world setting over 4 years SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 03-07, 2006 CL Miami Beach, FL SP Amer Acad Allergy, Asthma & Immunol C1 Sharp Rees Stealy Med Grp, San Diego, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. Wake Forest Univ, Winston Salem, NC 27109 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. AstraZeneca, Wilmington, DE USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2006 VL 117 IS 2 SU S MA 1061 BP S275 EP S275 DI 10.1016/j.jaci.2005.12.1138 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 019VR UT WOS:000235865302139 ER PT J AU Randhawa, IS Yanni, G AF Randhawa, IS Yanni, G TI Cartilage-Hair Hypoplasia syndrome: A pediatric case report of nonalcoholic steatohepatitis and liver failure SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 03-07, 2006 CL Miami Beach, FL SP Amer Acad Allergy, Asthma & Immunol C1 Univ Calif Los Angeles, W Los Angeles VA, Los Angeles, CA USA. Loma Linda Univ, Med Ctr, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2006 VL 117 IS 2 SU S MA 1127 BP S292 EP S292 DI 10.1016/j.jaci.2005.12.1101 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 019VR UT WOS:000235865302205 ER PT J AU Shelburne, SA Montes, M Hamill, RJ AF Shelburne, SA Montes, M Hamill, RJ TI Immune reconstitution inflammatory syndrome: more answers, more questions SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article DE HIV; HAART; paradoxical reaction; restoration ID ACTIVE ANTIRETROVIRAL THERAPY; HIV-INFECTED PATIENTS; RESTORATION DISEASE; COMBINATION THERAPY; PROTEASE-INHIBITOR; RISK-FACTORS; INITIATION; TUBERCULOSIS; AIDS; TYPE-1 AB The institution of highly active antiretroviral therapy (HAART) in HIV-infected patients restores protective immune responses against a wide variety of pathogens and dramatically decreases mortality. In a subset of patients receiving HAART, immune reconstitution is associated with a pathological inflammatory response leading to substantial short-term morbidity and even mortality. The past several years have seen marked advances in our clinical understanding of the immune reconstitution inflammatory syndrome (IRIS), but many questions remain. This article summarizes recent data on clinical risk factors for the development of IRIS. A consistent finding from multiple groups is that IRIS develops in a substantial percentage of HIV-infected patients who have an underlying opportunistic infection and receive HAART. As the use of HAART stands to markedly increase over the next several years, optimal care of patients receiving HAART will need to incorporate monitoring for and treating complications of IRIS. C1 Baylor Coll Med, Dept Med, Infect Dis Sect, Houston, TX 77030 USA. Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Sect Infect Dis 111G, Houston, TX 77030 USA. RP Hamill, RJ (reprint author), Baylor Coll Med, Dept Med, Infect Dis Sect, 1 Baylor Plaza, Houston, TX 77030 USA. EM richard.hamill@med.va.gov FU NCRR NIH HHS [K12 RR17665] NR 33 TC 146 Z9 156 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD FEB PY 2006 VL 57 IS 2 BP 167 EP 170 DI 10.1093/jac/dki444 PG 4 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 007KJ UT WOS:000234967400002 PM 16354748 ER PT J AU Aljuri, N Venegas, JG Freitag, L AF Aljuri, N Venegas, JG Freitag, L TI Viscoelasticity of the trachea and its effects on flow limitation SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE static tube law; dynamic tube law; maximal expiratory flow; forced expiration; supramaximal flow ID EXPIRATORY FLOW; WAVE-SPEED AB To test the hypothesis that peak expiratory flow is determined by the wave-speed-limiting mechanism, we studied the time dependency of the trachea and its effects on flow limitation. For this purpose, we assessed the relationship between transmural pressure and cross-sectional area [the tube law (TL)] of six excised human tracheae under controlled conditions of static ( no flow) and forced expiratory flow. We found that TLs of isolated human tracheae followed quite well the mathematical representation proposed by Shapiro (Shapiro AH. J Biomech Eng 99: 126 - 147, 1977) for elastic tubes. Furthermore, we found that the TL measured at the onset of forced expiratory flow was significantly stiffer than the static TL. As a result, the stiffer TL measured at the onset of forced expiratory flow predicted theoretical maximal expiratory flows far greater than those predicted by the more compliant static TL, which in all cases studied failed to explain peak expiratory flows measured at the onset of forced expiration. We conclude that the observed viscoelasticity of the tracheal walls can account for the measured differences between maximal and "supramaximal" expiratory flows seen at the onset of forced expiration. C1 Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02142 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anaesthesia, Boston, MA USA. RP Aljuri, N (reprint author), Harvard Univ, MIT, Div Hlth Sci & Technol, 45 Carleton St,E25-335, Cambridge, MA 02142 USA. EM nikko@mit.edu FU NHLBI NIH HHS [HL-38267] NR 13 TC 2 Z9 2 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD FEB PY 2006 VL 100 IS 2 BP 384 EP 389 DI 10.1152/japplphysiol.00689.2005 PG 6 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 008RV UT WOS:000235059300003 PM 16239614 ER PT J AU Torriani, M Thomas, BJ Barlow, RB Librizzi, J Dolan, S Grinspoon, S AF Torriani, M Thomas, BJ Barlow, RB Librizzi, J Dolan, S Grinspoon, S TI Increased intramyocellular lipid accumulation in HIV-infected women with fat redistribution SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE magnetic resonance spectroscopy; insulin resistance; protease inhibitor; acquired immunodeficiency syndrome ID INSULIN-RESISTANCE; IN-VIVO; LIPODYSTROPHY SYNDROME; BODY-COMPOSITION; MUSCLE; SPECTROSCOPY; MEN; ADIPOSITY; INDEXES; GLUCOSE AB The human immunodeficiency virus (HIV)-lipodystrophy syndrome is associated with fat redistribution and metabolic abnormalities, including insulin resistance. Increased intramyocellular lipid (IMCL) concentrations are thought to contribute to insulin resistance, being linked to metabolic and body composition variables. We examined 46 women: HIV infected with fat redistribution (n = 25), and age- and body mass index-matched HIV-negative controls ( n = 21). IMCL was measured by H-1-magnetic resonance spectroscopy, and body composition was assessed with computed tomography, dual-energy X-ray absorptiometry ( DEXA), and magnetic resonance imaging. Plasma lipid profile and markers of glucose homeostasis were obtained. IMCL was significantly increased in tibialis anterior [135.0 +/- 11.5 vs. 85.1 +/- 13.2 institutional units (IU); P = 0.007] and soleus [643.7 +/- 61.0 vs. 443.6 +/- 47.2 IU, P = 0.017] of HIV-infected subjects compared with controls. Among HIV-infected subjects, calf subcutaneous fat area (17.8 +/- 2.3 vs. 35.0 +/- 2.5 cm(2), P < 0.0001) and extremity fat by DEXA (11.8 +/- 1.1 vs. 15.6 +/- 1.2 kg, P = 0.024) were reduced, whereas visceral abdominal fat (125.2 +/- 11.3 vs. 74.4 +/- 12.3 cm2, P = 0.004), triglycerides (131.1 +/- 11.0 vs. 66.3 +/- 12.3 mg/dl, P = 0.0003), and fasting insulin (10.8 +/- 0.9 vs. 7.0 +/- 0.9 mu IU/ml, P = 0.004) were increased compared with control subjects. Triglycerides (r = 0.39, P = 0.05) and extremity fat as percentage of whole body fat by DEXA (r = -0.51, P = 0.01) correlated significantly with IMCL in the HIV but not the control group. Extremity fat ( beta = -633.53, P = 0.03) remained significantly associated with IMCL among HIV-infected patients, controlling for visceral abdominal fat, abdominal subcutaneous fat, and antiretroviral medications in a regression model. These data demonstrate increased IMCL in HIV-infected women with a mixed lipodystrophy pattern, being most significantly associated with reduced extremity fat. Further studies are necessary to determine the relationship between extremity fat loss and increased IMCL in HIV-infected women. C1 Massachusetts Gen Hosp, Div Musculoskeletal Radiol, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Torriani, M (reprint author), Massachusetts Gen Hosp, Div Musculoskeletal Radiol, Dept Radiol, 55 Fruit St,YAW 6048, Boston, MA 02114 USA. EM mtorriani@partners.org FU NCRR NIH HHS [M01 RR-01066, K23 RR018715, M01 RR001066, K23 RR-018715-02]; NIDDK NIH HHS [P30 DK040561-10, P30 DK040561, R01 DK-49302, R01 DK049302] NR 22 TC 27 Z9 29 U1 0 U2 0 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 FEB PY 2006 VL 100 IS 2 BP 609 EP 614 DI 10.1152/japplphysiol.00797.2005 PG 6 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 008RV UT WOS:000235059300033 PM 16223978 ER PT J AU Bengs, BC Scott, RD AF Bengs, BC Scott, RD TI The effect of distal femoral resection on passive knee extension in posterior cruciate ligament-retaining total knee arthroplasty SO JOURNAL OF ARTHROPLASTY LA English DT Article DE distal femoral resection; passive knee extension; posterior cruciate ligament-preserving total knee arthroplasty; joint line; extension gap ID JOINT LINE-POSITION; FLEXION CONTRACTURE; GONIOMETRIC MEASUREMENTS; NATURAL-HISTORY; RANGE; MOTION; REPLACEMENT; RELIABILITY; OSTEOARTHRITIS; RESTORATION AB Full passive extension in total knee arthroplasty is predicated on creating a large enough extension gap to accommodate any given combined thickness of femoral and tibial components. Additional distal femoral resection can achieve more passive knee extension. The predictable effect of further distal femoral resection has never been studied. We designed a simple institutional review board-approved, intraoperative study to quantify this effect. Routine posterior cruciate ligament-preserving total knee arthroplasty was performed with measured femoral and tibial resections, yielding full passive extension with trial components. Distal femoral augments were then sequentially applied to the back of the femoral trial component, and passive knee extension was measured. The data show that an average value of 9 degrees of femoral contracture is corrected for every 2 mm of distal femoral resection. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, New England Baptist Hosp, Boston, MA USA. RP Bengs, BC (reprint author), Massachusetts Gen Hosp, GRB 6, Boston, MA 02114 USA. NR 58 TC 7 Z9 7 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 EI 1532-8406 J9 J ARTHROPLASTY JI J. Arthroplast. PD FEB PY 2006 VL 21 IS 2 BP 161 EP 166 DI 10.1016/j.arth.2005.06.008 PG 6 WC Orthopedics SC Orthopedics GA 028IJ UT WOS:000236480100003 PM 16520201 ER PT J AU Lavoie, HB Marsh, EE Hall, JE AF Lavoie, HB Marsh, EE Hall, JE TI Absence of apparent circadian rhythms of gonadotropins and free alpha-subunit in postmenopausal women: Evidence for distinct regulation relative to other hormonal rhythms SO JOURNAL OF BIOLOGICAL RHYTHMS LA English DT Article DE aging; thyrotropin; cortisol; neuroendocrine; suprachiasmatic nucleus ID FOLLICLE-STIMULATING-HORMONE; PULSATILE LUTEINIZING-HORMONE; SUPRACHIASMATIC NUCLEUS; PULSE FREQUENCY; MENSTRUAL-CYCLE; NORMAL MEN; IMMUNOFLUOROMETRIC ASSAY; LIGHT EXPOSURE; HEALTHY-YOUNG; BRIGHT LIGHT AB Aging is associated with a decrease in gonadotropin levels in postmenopausal women (PMW) and is also associated with alterations in a number of circadian rhythms. The goals of this study were to determine the presence of circadian rhythms of gonadotropins and glycoprotein free a-subunit (FAS) in young and old PMW. Healthy, euthyroid PMW ages 45 to 55 years (n = 11) and 70 to 80 years (n = 11), were admitted in the morning to start a 24-h constant routine of light, temperature, position, and activity. Subjects remained awake and semirecumbent for the duration of the study and were fed hourly snacks, and activity was monitored continuously. Blood was sampled every 5 min for two 8-h periods corresponding to the estimated acrophase and nadir of the temperature rhythm. Luteinizing hormone (LH) and FAS were measured in all samples and follicle-stimulating hormone (FSH), thyroid-stimulating hormone (TSH), and cortisol in 20-min serum pools. Mean LH (p < 0.001), FSH (p < 0.002), and FAS (p < 0.002) were lower in older compared with younger PMW. Day/night differences in cortisol and TSH (p < 0.001) were present in all subjects. However, there were no day/night differences in LH in younger or older PMW or in FSH in younger or older PMW. There were no day/night differences in mean FAS in younger or older PMW or in FAS pulse frequency or amplitude. Thus, in controlled studies in which differences in cortisol and TSH were demonstrated, there were no day/night differences in LH, FSH, or FAS in PMW. These studies suggest that despite evidence of intact circadian rhythms of cortisol and TSH, gonadotropin secretion does not appear to follow a circadian pattern in PMW. Thus, the age-related decline in gonadotropin secretion in PMW is not associated with a dampening of circadian rhythmicity, The absence of day/night differences in FAS suggests that GnRH plays a more prominent role in FAS regulation than does thyrotropin-releasing hormone in PMW. C1 Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. RP Hall, JE (reprint author), Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, BHX-5,55 Fruit St, Boston, MA 02114 USA. EM jehall@partners.org RI Jelinek, Milan/C-8515-2011 FU NCRR NIH HHS [M01 RR 01066]; NIA NIH HHS [R01 AG013241, R01-AG-13241] NR 70 TC 5 Z9 5 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0748-7304 J9 J BIOL RHYTHM JI J. Biol. Rhythms PD FEB PY 2006 VL 21 IS 1 BP 58 EP 67 DI 10.1177/0748730405283244 PG 10 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA 005DU UT WOS:000234803600006 PM 16461985 ER PT J AU Li, GA Suggs, J Hanson, G Durbhakula, S Johnson, T Freiberg, A AF Li, GA Suggs, J Hanson, G Durbhakula, S Johnson, T Freiberg, A TI Three-dimensional tibiofemoral articular contact kinematics of a cruciate-retaining total knee arthroplasty SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID IN-VIVO KINEMATICS; FLUOROSCOPIC ANALYSIS; FEMORAL ROLLBACK; MOTION; MODELS AB Background: Accurate knowledge of the location of tibiofemoral articular contact following total knee arthroplasty is important in order to understand polyethylene wear and the mechanisms of component failure. The present study was performed to determine the three-dimensional tibiofemoral articular contact patterns of a posterior cruciate ligament-retaining total knee replacement during in vivo weight-bearing flexion. Methods: Nine osteoarthritic patients who were managed with a single design of a posterior cruciate ligament-retaining total knee implant were investigated with the use of an innovative dual orthogonal fluoroscopic imaging system. The position of the components during in vivo weight-bearing flexion was measured from full extension to maximum flexion in 15 degrees intervals. Tibiofemoral articular contact was determined by the overlap of the tibiofemoral articular surfaces. The centroid of the surface intersection was used to report the point of contact location. The average tibiofemoral contact points on both the medial and lateral tibial component surfaces were reported as a function of flexion. Results: The average maximum weight-bearing flexion angle was 113.3 degrees +/- 13.1 degrees (range, 96 degrees to 138 degrees). In the anteroposterior direction, the contact location was relatively constant in the medial compartment and moved posteriorly by 5.6 mm in the lateral compartment as the knee flexed from full extension to 900 of flexion. The range of the contact location in the mediolateral direction was 3.7 mm in the medial compartment and 4.8 mm in the lateral compartment. For both compartments, posterior translation of the contact point was significant from 90 degrees to maximum flexion, but the contact point at maximum flexion was not observed to reach the posterior edge of the polyethylene tibial insert articular surface. Conclusions: While the minimum anteroposterior translation of the contact point on the medial side might be interpreted as a medial pivot rotation during knee flexion, the contact point did move in the mediolateral direction with flexion. Beyond 90 degrees, both medial and lateral contact points were shown to move posteriorly but stopped before reaching the posterior edge of the polyethylene tibial insert articular surface. It seemed that the current component design did not allow the femoral condyle to roll off the polyethylene edge at high degrees of flexion because of the geometry at the posterior lip. Clinical Relevance: These three-dimensional tibiofemoral contact data may provide new insight for determining polyethylene tibial insert wear patterns in vivo and for designing the articulating surfaces by accounting for contact location in both the anteroposterior and mediolateral directions. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg,Bioengn Lab, Boston, MA 02114 USA. RP Li, GA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg,Bioengn Lab, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@partners.org NR 21 TC 38 Z9 44 U1 0 U2 3 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD FEB PY 2006 VL 88A IS 2 BP 395 EP 402 DI 10.2106/JBJS.D.03028 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 009ZP UT WOS:000235152700020 PM 16452753 ER PT J AU Morgan, AL Masoudi, FA Havranek, EP Jones, PG Peterson, PN Krumholz, HM Spertus, JA Rumsfeld, JS AF Morgan, AL Masoudi, FA Havranek, EP Jones, PG Peterson, PN Krumholz, HM Spertus, JA Rumsfeld, JS CA CORC TI Difficulty taking medications, depression, and health status in heart failure patients SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE heart failure; quality of life; depression ID CASE-FINDING INSTRUMENTS; QUALITY-OF-LIFE; MYOCARDIAL-INFARCTION; TREATMENT ADHERENCE; ELDERLY PATIENTS; RISK; DISEASE; SYMPTOMS; MORTALITY; DEATH AB Background: Little is known about medication nonadherence in heart failure populations. We evaluated the association between I aspect of medication nonadherence, patient-reported difficulty taking medications as directed, and health status among heart failure outpatients, and then examined whether this association was explained by depression. Methods and Results: A total of 522 outpatients with left ventricular ejection fraction < 0.40 completed clinical evaluation, Kansas City Cardiomyopathy Questionnaire (KCCQ), Medical Outcomes Study-Depression questionnaire, and categorized their difficulty taking medications (5-level Likert-scale question). Multivariable regression was used to evaluate the cross-sectional association between difficulty taking medications and health status, with incremental adjustment for medical history and depressive symptoms. Patients with difficulty taking medications (n = 64; 12.2%) had worse health status (8.2 +/- 2.7 point lower mean KCCQ summary scores; P =.008) and more depressive symptoms (43.8% versus 27.1%; P =.006). Adjusting for demographic and clinical factors had little effect on the association between difficulty taking medications and health status (8.0 +/- 3.2 point lower KCCQ scores; P=.01); however, the relationship was attenuated with adjustment for depressive symptoms (4.7 +/- 2.9 point lower KCCQ scores; P = 11). Conclusions: Among heart failure outpatients, difficulty taking medications is associated with worse health status. This association appears to be explained, in part, by coexistent depression. Future studies should evaluate interventions such as depression treatment to improve medication adherence and health status. C1 Denver VA Med Ctr, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Denver Hlth Med Ctr, Denver, CO USA. UMKC, Mid Amer Heart Inst, Kansas City, MO USA. Yale Univ, Med Ctr, New Haven, CT USA. RP Rumsfeld, JS (reprint author), Denver VA Med Ctr, 1055 Clermont St, Denver, CO 80220 USA. FU NIA NIH HHS [K08-AG01011] NR 34 TC 56 Z9 56 U1 3 U2 4 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD FEB PY 2006 VL 12 IS 1 BP 54 EP 60 DI 10.1016/j.cardfail.2005.08.004 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 021VH UT WOS:000236013500005 PM 16500581 ER PT J AU Diaconescu, D Eyvazzadeh, JA Alston, TA AF Diaconescu, D Eyvazzadeh, JA Alston, TA TI A couple of long intervals in Intraoperative cardiac pacing SO JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA LA English DT Article DE atrioventricular block; R-on-T phenomenon; temporary cardiac pacing ID ATRIOVENTRICULAR DELAY; BYPASS C1 Harvard Univ, Massachusetts Gen Hosp, Cardiac Anesthesia Grp, Dept Anesthesia & Crit Care,Sch Med, Boston, MA 02114 USA. RP Alston, TA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Cardiac Anesthesia Grp, Dept Anesthesia & Crit Care,Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM talston@partners.org NR 8 TC 0 Z9 0 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1053-0770 J9 J CARDIOTHOR VASC AN JI J. Cardiothorac. Vasc. Anesth. PD FEB PY 2006 VL 20 IS 1 BP 117 EP 118 DI 10.1053/j.jvca.2005.07.022 PG 2 WC Anesthesiology; Cardiac & Cardiovascular Systems; Respiratory System; Peripheral Vascular Disease SC Anesthesiology; Cardiovascular System & Cardiology; Respiratory System GA 014OU UT WOS:000235490300028 PM 16458231 ER PT J AU Gao, XJ Chen, TS Xing, D Wang, F Pei, YH Wei, XB AF Gao, XJ Chen, TS Xing, D Wang, F Pei, YH Wei, XB TI Single cell analysis of PKC activation during proliferation and apoptosis induced by laser irradiation SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID PROTEIN-KINASE-C; RESONANCE ENERGY-TRANSFER; ENDOTHELIAL GROWTH-FACTOR; IN-VITRO; FLUORESCENT PROTEIN; PLASMA-MEMBRANE; LIVING CELLS; OXYGEN; MUSCLE; PHOSPHORYLATION AB Laser irradiation has been shown to trigger cellular proliferation and apoptosis in various cell types. Studying the signaling pathways involved in the laser irradiation is important for understanding these processes. In present study, to monitor the protein kinase Cs (PKCs) activity in living cells in real time, we transfected and screened human lung adenocarcinoma cells (ASTC-a-1) stably expressing C kinase activity reporter (CKAR) constructed based on fluorescence resonance energy transfer (FRET) technique. The CKAR is a specific, reversible reporter of phosphorylation by PKCs and it can monitor the ongoing balance between PKCs and phosphatases. The increasing dynamics of PKCs activity is monitored during cell proliferation induced by low-power laser irradiation (LPLI) (0.8J/cm(2)) in serum-starved ASTC-a-1 cells stably expressing CKAR reporter using FRET imaging on laser scanning confocal microscope and using spectrofluorometric analysis on a luminescence spectrometer, respectively. However, the decreasing dynamics of PKCs activity has been monitored in real time using FRET imaging for the cells treated with high fluence LPLI (60J/cm(2)), which was previously found to induce cell apoptosis. Taken together, LPLI induces the ASTC-a-1 cell proliferation by specifically activating PKCs. However, PKCs activity decreases during cell apoptosis induced by high fluence LPLI Our results indicate that PKCs play an important role in the laser irradiation-induced biological effects. C1 S China Normal Univ, Inst Laser Life Sci, Guangzhou 510631, Peoples R China. Harvard Univ, Sch Med, Wellman Labs Photomed, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Xing, D (reprint author), S China Normal Univ, Inst Laser Life Sci, Guangzhou 510631, Peoples R China. EM xingda@scnu.edu.cn NR 55 TC 69 Z9 84 U1 0 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD FEB PY 2006 VL 206 IS 2 BP 441 EP 448 DI 10.1002/jcp.20484 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 000JR UT WOS:000234458300020 PM 16155941 ER PT J AU Li, WJ Luo, YM Zhang, F Signore, AP Gobbel, GT Simon, RP Chen, J AF Li, WJ Luo, YM Zhang, F Signore, AP Gobbel, GT Simon, RP Chen, J TI Ischemic preconditioning in the rat brain enhances the repair of endogenous oxidative DNA damage by activating the base-excision repair pathway SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE DNA damage and repair; neuroprotection; neuronal survival; oxidative stress; tolerance to ischemia ID FOCAL CEREBRAL-ISCHEMIA; CYCLIN-DEPENDENT KINASES; APOPTOSIS-INDUCING FACTOR; ELEMENT-BINDING PROTEIN; NEURONAL CELL-DEATH; POLYMERASE-BETA; ALKYLATING AGENT; MAMMALIAN-CELLS; STRAND BREAKS; POLY(ADP-RIBOSE) POLYMERASE AB The development of ischemic tolerance in the brain, whereby a brief period of sublethal 'preconditioning' ischemia attenuates injury from subsequent severe ischemia, may involve the activation of multiple intracellular signaling events that promote neuronal survival. In this study, the potential role of inducible DNA base-excision repair (BER), an endogenous adaptive response that prevents the detrimental effect of oxidative DNA damage, has been studied in the rat model of ischemic tolerance produced by three episodes of ischemic preconditioning (IP). This paradigm of IP, when applied 2 and 5 days before 2-h middle cerebral artery occlusion (MCAO), significantly decreased infarct volume in the frontal-parietal cortex 72 h later. Correlated with this protective effect, IP markedly attenuated the nuclear accumulations of several oxidative DNA lesions, including 8-oxodG, AP sites, and DNA strand breaks, after 2-h MCAO. Consequently, harmful DNA damage-responsive events, including NAD depletion and p53 activation, were reduced during postischemic reperfusion in preconditioned brains. The mechanism underlying the decreased DNA damage in preconditioned brain was then investigated by measuring BER activities in nuclear extracts. Beta-polymerase-mediated BER activity was markedly increased after IP, and this activation occurred before ( 24 h) and during the course of ischemic tolerance ( 48 to 72 h). In similar patterns, the activities for AP site and 8-oxodG incisions were also upregulated after IP. The upregulation of BER activities after IP was likely because of increased expression of repair enzymes beta-polymerase, AP endonuclease, and OGG1. These results suggest that the activation of the BER pathway may contribute to IP-induced neuroprotection by enhancing the repair of endogenous oxidative DNA damage after ischemic injury. C1 Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Neurosurg, Pittsburgh, PA 15213 USA. Oregon Hlth Sci Univ, Dept Neurol Physiol & Pharmacol, Portland, OR 97201 USA. RS Dow Neurobiol Labs, Legacy Res, Portland, OR USA. Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA 15261 USA. Vet Affairs Pittsburgh Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. RP Chen, J (reprint author), Univ Pittsburgh, Sch Med, Dept Neurol, S-507,Biomed Sci Tower, Pittsburgh, PA 15213 USA. EM chenj2@upmc.edu FU NINDS NIH HHS [NS35965, NS36736, NS38560, NS45048] NR 77 TC 50 Z9 54 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD FEB PY 2006 VL 26 IS 2 BP 181 EP 198 DI 10.1038/sj.jcbfm.9600180 PG 18 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 021HZ UT WOS:000235975600004 PM 16001017 ER PT J AU Henry, CA Steingard, R Venter, J Guptill, J Halpern, EF Bauman, M AF Henry, CA Steingard, R Venter, J Guptill, J Halpern, EF Bauman, M TI Treatment outcome and outcome associations in children with pervasive developmental disorders treated with selective serotonin reuptake inhibitors: A chart review SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Review ID AUTISTIC SPECTRUM DISORDERS; YOUNG-CHILDREN; DOUBLE-BLIND; FLUOXETINE; TRIAL; SERTRALINE; FAMILIES; ADULTS; CHILDHOOD; BEHAVIORS AB Purpose: The aim of this study was to determine the outcome and predictors of outcome with selective serotonin reuptake inhibitors (SSRIs) in outpatient children and adolescents with pervasive developmental disorders (PDDs). Method: Clinic charts were reviewed for 89 outpatient youths with a Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) diagnosis of a PDD who were treated with SSRIs. Response was determined using the Clinical Global Impressions (CGI) scale. Side-effect and demographic data, including family history, were recorded. Results: Forty-four point nine percent (44.9%) were determined to be much improved and considered responders. Fifty-four percent (54%) of the subjects demonstrated activation side effects. In 35.4% of these subjects, the activation side effects led to drug discontinuation. Pearson chi-squared and regression analysis demonstrated an association between SSRI response and a family history of PDD. There were no significant associations between clinical variables and activation side effects. Conclusions: SSRI treatment led to modest response rate in this group of youths with PDDs. Activation side effects were frequent, often leading to treatment dropouts. Potential outcome associations include a family history of PDDs. C1 Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Univ Massachusetts, Dept Psychiat, Worcester, MA 01605 USA. Duke Univ, Div Neurol, Durham, NC 27706 USA. Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. RP Henry, CA (reprint author), 1 Brookline Pl,Suite 426, Brookline, MA 02445 USA. EM charles_henry@hms.harvard.edu NR 39 TC 13 Z9 14 U1 5 U2 8 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD FEB-APR PY 2006 VL 16 IS 1-2 BP 187 EP 195 DI 10.1089/cap.2006.16.187 PG 9 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 030HJ UT WOS:000236624900018 PM 16553539 ER PT J AU Seidman, LJ Buka, SL Goldstein, JM Tsuang, MT AF Seidman, LJ Buka, SL Goldstein, JM Tsuang, MT TI Intellectual decline in schizophrenia: Evidence from a prospective birth cohort 28 year follow-up study SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article ID 4-SUBTEST SHORT FORMS; HIGH-RISK; WAIS-R; NEUROPSYCHOLOGICAL IMPAIRMENT; NEURODEVELOPMENTAL DISORDER; GENETIC VULNERABILITY; PSYCHIATRIC SAMPLE; COGNITIVE DECLINE; AGE 7; DEFICITS AB It is well established that IQ is lower among persons with schizophrenia than in the general population. However, it remains unclear if there is deterioration beyond a premorbid deficit. In order to assess the question of IQ deterioration, we assessed persons pre- and-post psychosis, comparing those who developed schizophrenia with those who did not. Twenty six patients with schizophrenia and 59 normal controls, evaluated at age 7 in the prospective, longitudinal, National Collaborative Perinatal Project (NCPP), were re-tested approximately 28 years later. We assessed change in an estimate of IQ based on the Vocabulary and Block Design tests from the Wechsler intelligence scales. Persons who later developed schizophrenia were significantly impaired on IQ compared to controls at age 7, especially on measures of attention. At age 35, persons with schizophrenia demonstrated significant impairment and deterioration. C1 Harvard Univ, Dept Psychiat, Sch Med, Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Brockton W Roxbury Vet Affairs Med Ctr, Brockton, MA 02401 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Dept Med, Div Womens Hlth, Connors Ctr Womens Hlth & Gender Biol, Boston, MA 02115 USA. Harvard Univ, Dept Psychiat, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Univ Calif San Diego, Dept Psychiat, Inst Behav Genom, La Jolla, CA 92093 USA. RP Seidman, LJ (reprint author), Harvard Univ, Dept Psychiat, Sch Med, Beth Israel Deaconess Med Ctr, 401 Pk Dr, Boston, MA 02115 USA. EM lseidman@bidmc.harvard.edu RI Buka, Stephen/H-7335-2014 OI Buka, Stephen/0000-0002-8578-9308 FU NIMH NIH HHS [MH-56956, MH-50647, MH-63951] NR 75 TC 64 Z9 65 U1 2 U2 6 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1380-3395 J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PD FEB PY 2006 VL 28 IS 2 BP 225 EP 242 DI 10.1080/13803390500360471 PG 18 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 015EF UT WOS:000235534000005 PM 16484095 ER PT J AU Griffen, SC Oostema, K Stanhope, KL Graham, J Styne, DM Glaser, N Cummings, DE Connors, MH Havel, PJ AF Griffen, SC Oostema, K Stanhope, KL Graham, J Styne, DM Glaser, N Cummings, DE Connors, MH Havel, PJ TI Administration of lispro insulin with meals improves glycemic control, increases circulating leptin, and suppresses ghrelin, compared with regular/NPH insulin in female patients with type 1 diabetes SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BODY-WEIGHT REGULATION; GLUCOSE-METABOLISM; ENERGY HOMEOSTASIS; ADIPOCYTE HORMONES; ADOLESCENT GIRLS; ACYLATED PEPTIDE; PLASMA LEPTIN; ACTIVE FORM; FOOD-INTAKE; SHORT-TERM AB Context: Overweight and obesity are overrepresented in adolescents with type 1 diabetes mellitus (T1DM). Exogenous insulin administration often poorly reproduces normal insulin patterns and may less effectively regulate leptin and ghrelin, two hormones involved in the control of appetite and adiposity. Objective: The objective of the study was to determine whether insulin regimens that better replicate normal insulin patterns and augment postprandial nutrient disposal may help normalize leptin and ghrelin and improve body weight regulation. Design, Setting, and Participants: Ten young women with T1DM were studied in this 2-wk prospective, balanced crossover-design study at the University of California, Davis. Intervention: Participants received either a single injection of regular + NPH insulin (R + N) or two mealtime injections of Lispro insulin in randomized order on 2 separate days. Meal composition and total insulin administered were the same on both treatment days. Main Outcome Measures: Plasma glucose, insulin, leptin, and ghrelin concentrations were monitored over the 10-h study period. Results: Lispro produced two distinct mealtime peaks of insulin, compared with one prolonged rise with R + N. Lispro reduced postprandial hyperglycemia and total glucose area under the curve. Leptin increased more on the Lispro (2.7 +/- 0.7 vs. 0.7 +/- 0.5 ng/ml, P = 0.02). Ghrelin was more suppressed after lunch with Lispro ( P = 0.004). Conclusions: Injection of Lispro insulin with meals produces more physiological insulin patterns, better glucose control, and improved leptin and ghrelin regulation than R + N. More closely mimicking normal insulin, leptin, and ghrelin responses to meals with fast-acting insulin may have implications for body weight regulation in T1DM. C1 Univ Calif Davis, Dept Endocrinol, Davis, CA 95616 USA. Univ Calif Davis, Dept Pediat, Davis, CA 95616 USA. Univ Calif Davis, Sch Med, Davis, CA 95616 USA. Univ Calif Davis, Dept Nutr, Davis, CA 95616 USA. Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Div Endocrinol, Seattle, WA 98108 USA. RP Griffen, SC (reprint author), Univ Calif Davis, Med Ctr, Patient Support & Serv Bldg,Suite G-400,4150 V St, Sacramento, CA 95817 USA. EM scgriffen@ucdavis.edu FU NCRR NIH HHS [RR 019975]; NHLBI NIH HHS [HL 075675]; NIDDK NIH HHS [DK 50129, DK 002619, DK 35747, DK 58108] NR 40 TC 21 Z9 23 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 FEB PY 2006 VL 91 IS 2 BP 485 EP 491 DI 10.1210/jc.2005-1338 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 010CC UT WOS:000235161200021 PM 16317063 ER PT J AU Mukai, Y Rikitake, Y Shiojima, L Wolfrum, S Satoh, M Takeshita, K Hiroi, Y Salomone, S Kim, HH Benjamin, LE Walsh, K Liao, JK AF Mukai, Y Rikitake, Y Shiojima, L Wolfrum, S Satoh, M Takeshita, K Hiroi, Y Salomone, S Kim, HH Benjamin, LE Walsh, K Liao, JK TI Decreased vascular lesion formation in mice with inducible endothelial-specific expression of protein kinase Akt SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID PORCINE CORONARY-ARTERIES; NITRIC-OXIDE SYNTHASE; MOUSE CAROTID-ARTERY; NEOINTIMA FORMATION; PROGENITOR CELLS; ACCELERATES REENDOTHELIALIZATION; REGENERATED ENDOTHELIUM; BLOOD-FLOW; IN-VIVO; ATHEROSCLEROSIS AB To determine whether endothelial Akt could affect vascular lesion formation, mutant mice with a constitutively active Akt transgene, which could be inducibly targeted to the vascular endothelium using the tet-off system (EC-Akt Tg mice), were generated. After withdrawal of doxycycline, EC-Akt Tg mice demonstrated increased endothelial-specific Akt activity and NO production. After blood flow cessation caused by carotid artery ligation, neointimal formation was attenuated in induced EC-Akt Tg mice compared with noninduced EC-Akt Tg mice and control littermates. To determine the role of eNOS in mediating these effects, mice were treated with N-omega-nitro-L-arginine methyl ester (L-NAME). Neointimal formation was attenuated to a lesser extent in induced EC-Akt Tg mice treated with L-NAME, suggesting that some of the vascular protective effects were NO independent. Indeed, endothelial activation of Akt resulted in less EC apoptosis in ligated arteries. Immunostaining demonstrated decreased inflammatory and proliferative changes in induced EC-Akt Tg mice after vascular injury. These findings indicate that endothelial activation of Akt suppresses lesion formation via increased NO production, preservation of functional endothelial layer, and suppression of inflammatory and proliferative changes in the vascular wall. These results suggest that enhancing endothelial Akt activity alone could have therapeutic benefits after vascular injury. C1 Harvard Univ, Brigham & Womens Hosp, Vasc Med Res Unit, Sch Med, Cambridge, MA 02139 USA. Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Mol Cardiol Unit, Boston, MA 02118 USA. Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Boston, MA 02114 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Pathol, Boston, MA 02215 USA. RP Liao, JK (reprint author), Harvard Univ, Brigham & Womens Hosp, Vasc Med Res Unit, Sch Med, 65 Landsdowne St,Room 275, Cambridge, MA 02139 USA. EM jliao@rics.bwh.harvard.edu RI Takeshita, Kyosuke/B-7008-2012; OI Takeshita, Kyosuke/0000-0002-8283-3799; Salomone, Salvatore/0000-0001-5307-6103 FU NHLBI NIH HHS [HL71049, HL52233, HL70274, R01 HL052233, R01 HL052233-06, R01 HL052233-07, R01 HL052233-08, R01 HL070274, R01 HL070274-01, R01 HL070274-02, R01 HL070274-03, R01 HL071049, R01 HL071049-02, R01 HL080187, R01 HL080187-01A1, R01 HL080187-02]; NIDDK NIH HHS [DK62729, R01 DK062729, R01 DK062729-01A1, R01 DK062729-02, R01 DK062729-03]; NINDS NIH HHS [P01 NS010828, P01 NS010828-330036, P50 NS010828, P50 NS010828-290036, P50 NS010828-300036] NR 61 TC 44 Z9 46 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD FEB PY 2006 VL 116 IS 2 BP 334 EP 343 DI 10.1172/JCI26223 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 008MA UT WOS:000235043600009 PM 16453020 ER PT J AU Wang, JS Fathman, JW Lugo-Villarino, G Scimone, L von Andrian, U Dorfman, DM Glimcher, LH AF Wang, JS Fathman, JW Lugo-Villarino, G Scimone, L von Andrian, U Dorfman, DM Glimcher, LH TI Transcription factor T-bet regulates inflammatory arthritis through its function in dendritic cells SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ANTAGONIST-DEFICIENT MICE; IFN-GAMMA PRODUCTION; RHEUMATOID-ARTHRITIS; LINEAGE COMMITMENT; TNF-ALPHA; ACTIVATION; INDUCTION; COLLAGEN; DISEASE; ENCEPHALOMYELITIS AB The transcription factor T-bet (Thx21) plays a major role in adaptive immunity and is required for optimal IFN-gamma production by DCs. Here we demonstrate an essential function for T-bet in DCs in controlling inflammatory arthritis. We show that collagen antibody-induced arthritis (CAIA), a model of human RA, is a bipartite disease characterized by an early innate immune system component intact in RAG2(-/-) mice and a later adaptive immune system phase. Mice lacking T-bet had markedly reduced joint inflammation at both early and late time points and RAG2(-/-)T-bet(-/-) double-deficient mice were essentially resistant to disease. Remarkably, adoptive transfer of T-bet-expressing DCs reconstituted inflammation in a T-bet deficient and T-bet/RAG2-deficient milieu. T-bet regulates the production of proinflammatory cytokine IL-1 alpha and chemokines macrophage inflammatory protein-1 alpha (MIP-1 alpha) and thymus- and activation-related chemokine (TARC) by DCs. Further, T-bet expression in DCs is required for T helper cell activation. We conclude that T-bet plays a vital function in DCs that links innate and adaptive immunity to regulate inflammatory responses. T-bet provides an attractive new target for the development of novel therapeutics for inflammatory arthritis. C1 Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Glimcher, LH (reprint author), Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, 651 Huntington Ave,FXB 205, Boston, MA 02115 USA. EM lglimche@hsph.harvard.edu RI von Andrian, Ulrich/A-5775-2008; OI Lugo, Geanncarlo/0000-0003-4620-8491 FU NIAID NIH HHS [AI56296, K08 AI057434, K08 AI57434, P01 AI056296]; NIAMS NIH HHS [AR46983, R01 AR046983] NR 45 TC 77 Z9 82 U1 0 U2 0 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 FEB PY 2006 VL 116 IS 2 BP 414 EP 421 DI 10.1172/JCI26631 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 008MA UT WOS:000235043600017 PM 16410834 ER PT J AU Liao, JC Mastali, M Gau, V Suchard, MA Moller, AK Bruckner, DA Babbitt, JT Li, Y Gornbein, J Landaw, EM McCabe, ERB Churchill, BM Haake, DA AF Liao, JC Mastali, M Gau, V Suchard, MA Moller, AK Bruckner, DA Babbitt, JT Li, Y Gornbein, J Landaw, EM McCabe, ERB Churchill, BM Haake, DA TI Use of electrochemical DNA biosensors for rapid molecular identification of uropathogens in clinical urine specimens SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID NUCLEIC-ACID AMPLIFICATION; 16S RIBOSOMAL-RNA; ESCHERICHIA-COLI; TRACT-INFECTIONS; UROLOGIC DISEASES; AMERICA PROJECT; AMPEROMETRIC DETECTION; RESOURCE USE; PCR; BACTERIA AB We describe the first species-specific detection of bacterial pathogens in human clinical fluid samples using a microfabricated electrochemical sensor array. Each of the 16 sensors in the array consisted of three single-layer gold electrodes-working, reference, and auxiliary. Each of the working electrodes contained one representative from a library of capture probes, each specific for a clinically relevant bacterial urinary pathogen. The library included probes for Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa, Entero-cococcits spp., and the Klebsiella-Enterobacter group. A bacterial 16S rRNA target derived from single-step bacterial lysis was hybridized both to the biotin-modified capture probe on the sensor surface and to a second, fluorescein-modified detector probe. Detection of the target-probe hybrids was achieved through binding of a horseradish peroxidase (HRP)-conjugated anti-fluorescein antibody to the detector probe. Amperometric measurement of the catalyzed HRP reaction was obtained at a fixed potential of -200 mV between the working and reference electrodes. Species-specific detection of as few as 2,600 uropathogenic bacteria in culture, inoculated urine, and clinical urine samples was achieved within 45 ruin from the beginning of sample processing. In a feasibility study of this amperometric detection system using blinded clinical urine specimens, the sensor array had 100% sensitivity for direct detection of gram-negative bacteria without nucleic acid purification or amplification. Identification was demonstrated for 98% of gram-negative bacteria for which species-specific probes were available. When combined with a microfluidics-based sample preparation module, the integrated system could serve as a point-of-care device for rapid diagnosis of urinary tract infections. C1 VA Greater LA Healthcare, Div Infect Dis, Los Angeles, CA 90073 USA. GenFluides Inc, Montery Pk, CA 91754 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Biomath, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Los Angeles, CA 90095 USA. RP Haake, DA (reprint author), VA Greater LA Healthcare, Div Infect Dis, 111F, Los Angeles, CA 90073 USA. EM dhaake@ucla.edu RI Liao, Joseph/J-5874-2015 FU NIBIB NIH HHS [EB00127, R01 EB000127] NR 52 TC 133 Z9 134 U1 5 U2 37 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 FEB PY 2006 VL 44 IS 2 BP 561 EP 570 DI 10.1128/JCM.44.2.561-570.2006 PG 10 WC Microbiology SC Microbiology GA 012MV UT WOS:000235344200042 PM 16455913 ER PT J AU Marty, FM Yeh, WW Wennersten, CB Venkataraman, L Albano, E Alyea, EP Gold, HS Baden, LR Pillai, SK AF Marty, FM Yeh, WW Wennersten, CB Venkataraman, L Albano, E Alyea, EP Gold, HS Baden, LR Pillai, SK TI Emergence of a clinical daptomycin-resistant Staphylococcus aureus isolate during treatment of methicillin-resistant Staphylococcus aureus bacteremia and osteomyelitis SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID VANCOMYCIN; INFECTIONS; IMPACT AB The emergence of a clinically daptomycin-resistant Staphylococcus aureus isolate occurred during treatment of methicillin-resistant S. aureus bacteremia and probable vertebral osteomyelitis. The breakthrough isolate was indistinguishable from pretreatment daptomycin-susceptible isolates by pulsed-field gel electrophoresis. Daptomycin nonsusceptibility was confirmed by MIC and time-kill curve analyses. C1 Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Med Oncol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Marty, FM (reprint author), Brigham & Womens Hosp, Div Infect Dis, 75 Francis St,PBB-A4, Boston, MA 02115 USA. EM fmarty@partners.org NR 17 TC 112 Z9 118 U1 1 U2 4 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 FEB PY 2006 VL 44 IS 2 BP 595 EP 597 DI 10.1128/JCM.44.2.595-597.2006 PG 3 WC Microbiology SC Microbiology GA 012MV UT WOS:000235344200049 PM 16455920 ER PT J AU Matten, EC Grecu, L AF Matten, EC Grecu, L TI Unilateral empyema as a complication of infectious mononucleosis: a pathogenic variant of Lemierre's syndrome SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article AB We present a case of a healthy 19-year-old female who developed infectious mononucleosis complicated by unilateral empyema. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Grecu, L (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. EM lgrecu@partners.org NR 7 TC 8 Z9 8 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 FEB PY 2006 VL 44 IS 2 BP 659 EP 661 DI 10.1128/JCM.44.2.659-661.2006 PG 3 WC Microbiology SC Microbiology GA 012MV UT WOS:000235344200070 PM 16455941 ER PT J AU Verheijen, RH Massuger, LF Benigno, BB Epenetos, AA Lopes, A Soper, JT Markowska, J Vyzula, R Jobling, T Stamp, G Spiegel, G Thurston, D Falke, T Lambert, J Seiden, MV AF Verheijen, RH Massuger, LF Benigno, BB Epenetos, AA Lopes, A Soper, JT Markowska, J Vyzula, R Jobling, T Stamp, G Spiegel, G Thurston, D Falke, T Lambert, J Seiden, MV TI Phase III trial of intraperitoneal therapy with yttrium-90-labeled HMFG1 murine monoclonal antibody in patients with epithelial ovarian cancer after a surgically defined complete remission SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 10th Meeting of the International-Society-of-Gynecologic-Oncology CY OCT 03-07, 2004 CL Edinburgh, SCOTLAND SP Int Soc Gynecol Oncol ID SOUTHWEST-ONCOLOGY-GROUP; BREAST-CANCER; CONSOLIDATION THERAPY; RADIOIMMUNOTHERAPY; TOXICITY; EFFICACY; PHARMACOKINETICS; CHEMOTHERAPY; LAPAROSCOPY; LAPAROTOMY AB Purpose This was a multinational, open-label, randomized phase III trial comparing yttrium-90-labeled murine HMFG1 (Y-90-muHMFG1) plus standard treatment versus standard treatment alone in patients with epithelial ovarian cancer (EOC) who had attained a complete clinical remission after cytoreductive surgery and platinum-based chemotherapy. Patients and Methods In total, 844 International Federation of Gynecology and Obstetrics stage Ic to IV patients were initially screened, of whom 447 patients with a negative second-look laparoscopy (SILL) were randomly assigned to receive either a single dose of Y-90-muHMFG1 plus standard treatment (224 patients) or standard treatment alone (223 patients). Patients in the active treatment arm received a single intraperitoneal dose of 25 mg of Y-90-muHMFG1 (target dose 666 MBq/m(2)). The primary end point was length of survival; secondary end points included time to relapse and safety. The study had an 80% power to detect a 15% change in survival. Results After a median follow-up of 3.5 years (range, 1 to 6 years), 70 patients had died in the active treatment arm compared with 61 patients in the control arm. Cox proportional hazards analysis of survival demonstrated no difference between treatment arms. In the study drug arm, 104 patients experienced relapse compared with 98 patients in the standard treatment arm. No difference in time to relapse was observed between the two study arms. Active therapy was associated with occasional grade 3 or 4 thrombocytopenia and neutropenia and grade 1 or 2 GI symptoms, abdominal discomfort, arthralgia, and myalgia. Conclusion A single IP administration of Y-90-muHMFG1 to patients with EOC who had a negative SLL after primary therapy did not extend survival or time to relapse. C1 VU Univ, Med Ctr, Div Gynecol Oncol, Dept Obstet & Gynecol, NL-1007 MB Amsterdam, Netherlands. Radboud Univ, Med Ctr, Nijmegen, Netherlands. Groene Hart Ziekenhuis, Gouda, Netherlands. SE Gynecol Oncol, Atlanta, GA USA. Duke Univ, Ctr Med, Durham, NC USA. Scripps Clin, La Jolla, CA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ London Imperial Coll Sci & Technol, Bartholomews Hosp, London, England. Hammersmith Hosp, London, England. Guys & St Thomas Natl Hlth Serv, Fdn Trust, London, England. Poznan Tech Univ, Sch Med Sci, Poznan, Poland. Mararyk Mem Canc Inst, Brno, Czech Republic. Monash Med Ctr, E Bentleigh, Australia. RP Verheijen, RH (reprint author), VU Univ, Med Ctr, Div Gynecol Oncol, Dept Obstet & Gynecol, POB 7057, NL-1007 MB Amsterdam, Netherlands. EM r.verheijen@vumc.nl RI Massuger, Leon/H-8072-2014; OI de Barros Lopes, Alberto/0000-0002-8796-3891 NR 25 TC 102 Z9 105 U1 0 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 1 PY 2006 VL 24 IS 4 BP 571 EP 578 DI 10.1200/JCO.2005.02.5973 PG 8 WC Oncology SC Oncology GA 014QT UT WOS:000235495700008 PM 16446329 ER PT J AU Kraybill, WG Harris, J Spiro, IJ Ettinger, DS DeLaney, TF Blum, RH Lucas, DR Harmon, DC Letson, GD Eiaberg, B AF Kraybill, WG Harris, J Spiro, IJ Ettinger, DS DeLaney, TF Blum, RH Lucas, DR Harmon, DC Letson, GD Eiaberg, B TI Phase II study of neoadjuvant chemotherapy and radiation therapy in the management of high-risk, high-grade, soft tissue sarcomas of the extremities and body wall: Radiation therapy oncology group trial 9514 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ADJUVANT CHEMOTHERAPY; SPARING SURGERY; RADIOTHERAPY; IFOSFAMIDE; OUTCOMES; CANCER; CARE AB Purpose On the basis of a positive reported single-institution pilot study, the Radiation Therapy Oncology Group initiated phase II trial 9514 to evaluate its necradjuvant regimen in a multi-institutional Intergroup setting. Patients and Methods Eligibility included a high-grade soft tissue sarcoma >= 8 cm in diameter of the extremities and body wall. Patients received three cycles of neoadjuvant chemotherapy (CT; modified mesna, doxorubicin, ifosfamide, and dacarbazine [MAID]), intercligitated preoperative radiation therapy (RT; 44 Gy administered in split courses), and three cycles of postoperative CT (modified MAID). Results Sixty-six patients were enrolled, of whom 64 were analyzed. Seventy-nine percent of patients completed their preoperative CT and 59% completed all planned CT. Three patients (5%) experienced fatal grade 5 toxicities (myelodysplasias, two patients;, infection, one patient). Another 53 patients (83%) experienced grade 4 toxicities; 78% experienced grade 4 hematologic toxicity and 19% experienced grade 4 nonhematologic toxicity. Sixty-one patients underwent surgery. Fifty-eight of these were R0 resections, of which five were amputations. There were three R1 resections. The estimated 3-year rate for local-regional failure is 17.6% if amputation is considered a failure and 10.1% if not. Estimated 3-year rates for disease-free, distant-disease-free, and overall survival are 56.6%, 64.5%, and 75.1%, respectively. Conclusion This combined-modality treatment can be delivered successfully in a multi-institutional setting. Efficacy results are consistent with previous single-institution results. C1 New York State Dept Hlth, Roswell Pk Canc Inst, Dept Surg Oncol, Buffalo, NY 14263 USA. Roswell Pk Canc Inst, Buffalo, NY USA. Beth Israel Canc Ctr, New York, NY USA. Radiat Therapy Oncol Grp, Philadelphia, PA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Francis H Burr Proton Therapy Ctr, Boston, MA USA. John Hopkins Med Ctr, Baltimore, MD USA. Univ Michigan, Ctr Med, Ann Arbor, MI USA. H Lee Moffitt Canc Ctr, Tampa, FL USA. Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. RP Kraybill, WG (reprint author), New York State Dept Hlth, Roswell Pk Canc Inst, Dept Surg Oncol, Buffalo, NY 14263 USA. EM william.kraybill@roswellpark.org FU NCI NIH HHS [U10 CA21661, U10 CA32115, U10 CA37422] NR 29 TC 107 Z9 114 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 FEB 1 PY 2006 VL 24 IS 4 BP 619 EP 625 DI 10.1200/JCO.2005.02.5577 PG 7 WC Oncology SC Oncology GA 014QT UT WOS:000235495700015 PM 16446334 ER PT J AU Patenaude, AF Dorval, M DiGianni, LS Schneider, KA Chittenden, A Garber, JE AF Patenaude, AF Dorval, M DiGianni, LS Schneider, KA Chittenden, A Garber, JE TI Sharing BRCA1/2 test results with first-degree relatives: Factors predicting who women tell SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol ID BREAST-OVARIAN CANCER; BREAST/OVARIAN CANCER; HEREDITARY BREAST; COMMUNICATION; RISK; DISCLOSURE; FAMILIES; SUSCEPTIBILITY; EXPERIENCE; KNOWLEDGE AB Purpose Patient communication with relatives about cancer genetic test results is the primary means for alerting those who may benefit from identification of hereditary risk. This study identifies factors predicting patterns of disclosure of BRCA1/2 test results to first-degree relatives (FDRs) among women tested in a clinical protocol. Patients and Methods A total of 273 women completed a family communication measure 4 months after BRCA1/2 result disclosure. chi(2) analyses and logistic regression models identified factors predicting sharing of the test result. Results Most FDRs were informed of the participant's test result by 4 months; female relatives were more likely to be informed than males. Tested women conveyed inconclusive results (variant or negative without known familial mutation) less frequently to their sisters than conclusive (positive/true negative) results (P = .03). Twenty-three percent of participants did not inform their father. Informing brothers was more likely when BRCA1/2 was inherited through paternal lineage (P = .04), but 29% of brothers were not informed. Women older than age 40 were less likely to share their result with their parents (P = .03) than were women <= 40. Children's ages influenced communication to offspring; most children were told. Conclusion Demographic, health-, and test-related factors predicted genetic test result communication to FDRs. Additional research investigating the full spectrum of discussion within families and motives for incomplete sharing of genetic test results with relatives may suggest strategies for providers and targeted educational interventions for patients to enhance family communication. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Univ Laval, Fac Pharm, Laval, PQ, Canada. RP Patenaude, AF (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM andrea_patenaude@dfci.harvard.edu FU NHGRI NIH HHS [5R01HG01244] NR 26 TC 92 Z9 92 U1 1 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 1 PY 2006 VL 24 IS 4 BP 700 EP 706 DI 10.1200/JCO.2005.01.7541 PG 7 WC Oncology SC Oncology GA 014QT UT WOS:000235495700027 PM 16446344 ER PT J AU Trivedi, MH Rush, AJ Wisniewski, SR Warden, D McKinney, W Downing, M Berman, SR Farabaugh, A Luther, JF Nierenberg, AA Callan, JA Sackeim, HA AF Trivedi, MH Rush, AJ Wisniewski, SR Warden, D McKinney, W Downing, M Berman, SR Farabaugh, A Luther, JF Nierenberg, AA Callan, JA Sackeim, HA TI Factors associated with health-related quality of life among outpatients with major depressive disorder: A STAR*D report. SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID SEQUENCED TREATMENT ALTERNATIVES; AFRICAN-AMERICAN WOMEN; ILLNESS RATING-SCALE; REPORT QIDS-SR; PRIMARY-CARE; WHITEHALL-II; PSYCHOSOCIAL DISABILITY; PSYCHOMETRIC EVALUATION; SOCIOECONOMIC-STATUS; DEMOGRAPHIC-FACTORS AB Objective: Major depressive disorder (MDD) is often chronic and is often associated with significant morbidity and mortality. The importance of assessing disability and health-related quality of life (HRQOL) in patients with MDD has only recently been recognized. The aim of this study was to examine sociodemographic and clinical correlates of HRQOL in a large cohort of outpatients with MDD. Method: Baseline assessments were completed for 1500 consecutive patients enrolled in the Sequenced Treatment Alternatives to Relieve Depression trial, including sociodemographic characteristics and measures of depressive symptom severity, clinical features, and HRQOL. Multiple domains of HRQOL were assessed with the 12-item Short Form Health Survey, the Work and Social Adjustment Scale, and the Quality of Life Enjoyment and Satisfaction Questionnaire. The current analyses were conducted on HRQOL data available for 1397 of the 1500 subjects. Results: Greater symptom severity was associated with reduced HRQOL by all measures. Even after age and symptom severity were controlled for, a number of clinical features and sociodemographic characteristics were independently associated with HRQOL in multiple domains, including age at onset of MDD, ethnicity, marital status. employment status, education level, insurance status, and monthly household income. Conclusion: Results strongly suggest the need to assess HRQOL in addition to symptoms in order to gauge the true severity of MDD. This study also highlights the necessity of measuring HRQOL in multiple domains. These results have implications for the assessment of remission and functional recovery in the treatment of MDD. C1 Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75230 USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. Northwestern Univ, Sch Med, Dept Psychiat, Chicago, IL 60611 USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Boston, MA 02114 USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. RP Trivedi, MH (reprint author), Univ Texas, SW Med Ctr, Dept Psychiat, 5323 Harry Hines Blvd, Dallas, TX 75230 USA. EM madhukar.trivedi@utsouthwestern.edu OI Wisniewski, Stephen/0000-0002-3877-9860; Rush, Augustus/0000-0003-2004-2382 FU NIMH NIH HHS [5R01MH064062-2, 5R01MH067692-2, N01MH90003] NR 62 TC 79 Z9 80 U1 3 U2 11 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD FEB PY 2006 VL 67 IS 2 BP 185 EP 195 PG 11 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 020SP UT WOS:000235931000003 PM 16566612 ER PT J AU Fava, M Nurnberg, HG Seidman, SN Holloway, W Nicholas, S Tseng, LJ Stecher, VJ AF Fava, M Nurnberg, HG Seidman, SN Holloway, W Nicholas, S Tseng, LJ Stecher, VJ TI Efficacy and safety of sildenafil in men with serotonergic anti-depressant-associated erectile dysfunction: Results from a randomized, double-blind, placebo-controlled trial. SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 156th Annual Meeting of the American-Psychiatric-Association CY MAY 17-22, 2003 CL SAN FRANCISCO, CA SP Amer Psychiat Assoc ID INDUCED SEXUAL DYSFUNCTION; FLEXIBLE-DOSE-ESCALATION; ORAL SILDENAFIL; RADICAL PROSTATECTOMY; INTERNATIONAL INDEX; CITRATE VIAGRA((R)); MULTICENTER; NONCOMPLIANCE; PREVALENCE; SYMPTOMS AB Objective: To evaluate the efficacy of short-term treatment with sildenafil citrate in men with serotonin reuptake inhibitor (SRI)-associated erectile dysfunction (ED). Method: Men (aged 18 years) with major depressive disorder (MDD; DSM-IV criteria) in remission and taking SRIs who experienced SRI-associated ED were enrolled in this multicenter, 6-week, randomized, flexille-dose, double, blind, placebo-controlled trial. The primary study measures were questions 3 (Q3: frequency of penetration) and 4 (Q4: frequency of maintained erections after penetration) of the International Index of Erectile Function (IIEF) questionnaire. Secondary study measures were all other questions and domains of the IIEF, the Erectile Dysfunction Index of Treatment Satisfaction (EDITS), a global A efficacy questionnaire (GEQ), and a patient maintained event log of sexual activity. Results: Patients receiving sildenafil (N = 71) versus placebo (N = 71) reported significantly higher mean SE scores on Q3 (3.9 +/- 0.2 vs. 3.1 +/- 0.2, p = .003) and Q4 (3.7 +/- 0.2 vs. 2.8 +/- 0.2, p < .001) of the IIEF and significantly higher scores on all domains of the HER Patients receiving sildenafil also reported significantly improved scores on all questions of the EDITS questionnaire (p < .02) and the GEQ (p < .0001) and an increased number of successful sexual intercourse attempts per week (p < .0001) compared with patients receiving placebo. All patients remained in MDD remission (score ! 10 on the Hamilton Rating Scale for Depression). Adverse events in patients taking sildenafil (vs. placebo) were headache (9% vs. 9%), dyspepsia (9% vs. 1%), anxiety (6% vs. 4%), and abnormal vision (3% vs. 0%). Conclusions: Short-term (6-week) administration of sildenafil was well tolerated and significantly improved erectile function and overall sexual satisfaction in men with ED associated with SRI therapy for MDD. Sildenafil may be successfully used to treat SRI-associated ED without interruption of antidepressant therapy. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Dept Psychiat, Boston, MA 02114 USA. Univ New Mexico, Dept Psychiat, Albuquerque, NM 87131 USA. Columbia Presbyterian Med Ctr, Dept Psychiat, New York, NY 10032 USA. Cutting Edge Res, Oklahoma City, OK USA. Pfizer Inc, New York, NY USA. RP Fava, M (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, Dept Psychiat, 15 Parkman St,ACC 812, Boston, MA 02114 USA. EM mfava@partners.org NR 39 TC 45 Z9 46 U1 3 U2 3 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD FEB PY 2006 VL 67 IS 2 BP 240 EP 246 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 020SP UT WOS:000235931000010 PM 16566619 ER PT J AU Joffe, H Kim, DR Foris, JM Baldassano, CF Gyulai, L Hwang, CH McLaughlin, WL Sachs, GS Thase, ME Harlow, BL Cohen, LS AF Joffe, H Kim, DR Foris, JM Baldassano, CF Gyulai, L Hwang, CH McLaughlin, WL Sachs, GS Thase, ME Harlow, BL Cohen, LS TI Menstrual dysfunction prior to onset of psychiatric illness is reported more commonly by women with bipolar disorder than by women with unipolar depression and healthy controls SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID REPRODUCTIVE ENDOCRINE DISORDERS; POLYCYSTIC-OVARY-SYNDROME; TEMPORAL-LOBE ORIGIN; PREMENOPAUSAL WOMEN; PARTIAL SEIZURES; PROLACTIN LEVELS; STEP-BD; MOOD; VALPROATE; EPILEPSY AB Background: Preliminary reports suggest that menstrual cycle irregularities occur more commonly in women with bipolar disorder and unipolar depression than in the general population. However, it is not always clear whether such abnormalities, reflecting disruption of the hypothalamic-pituitary-gonadal (HPG) axis. are caused by psychotropic treatments or associated with the disorder per se. Method: The prevalence of early-onset (within the first 5 postmenarchal years) menstrual cycle dysfunction (menstrual cycle length unpredictable within 10 days or menstrual cycle length < 25 days or > 35 days) occurring before onset of psychiatric illness was compared between subjects with DSM-IV bipolar disorder participating in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) and subjects with DSM-IV unipolar depression or no psychiatric illness participating in the Harvard Stud), of Moods and Cycles. Data from the Harvard Study of Moods and Cycles were gathered from September 1995 to September 1997, and data from STEP-BD were gathered from November 1999 to May 2001. Results: Early-onset menstrual cycle dysfunction was reported to have occurred in 101/295 women with bipolar disorder (34.2%), 60/245 women with depression (24.5%). and 134/619 healthy controls (21.7%). Women with bipolar disorder were more likely to have early-onset menstrual cycle dysfunction than health), controls (chi(2) = 16.58 p < .0001) and depressed women (chi(2) = 6.08 p = .01), while depressed women were not more likely to have early-onset menstrual cycle dysfunction than healthy controls (chi(2) = 0.81, p = .37). Conclusions: Compared with healthy controls and women with Unipolar depression, women with bipolar disorder retrospectively report early-onset menstrual dysfunction more commonly prior to onset of bipolar disorder. Future studies should evaluate potential abnormalities in the hypothalamic-pituitary-gonadal axis that are associated with bipolar disorder. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Perinatal & Reprod Psychiat Clin Res Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Bipolar Clin & Res Program, Boston, MA 02115 USA. Hosp Univ Penn, Mood & Anxiety Disorders Program, Philadelphia, PA 19104 USA. Univ Pittsburgh, Med Ctr, Epidemiol Data Ctr, Pittsburgh, PA USA. Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, Boston, MA 02115 USA. RP Joffe, H (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 185 Cambridge St,2nd Floor, Boston, MA 02114 USA. EM hjoffe@partners.org FU NIMH NIH HHS [MH80001, R01-MH50013] NR 40 TC 21 Z9 21 U1 1 U2 3 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD FEB PY 2006 VL 67 IS 2 BP 297 EP 304 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 020SP UT WOS:000235931000018 PM 16566627 ER PT J AU Papakostas, GI Perlis, RH Scalia, MJ Petersen, TJ Fava, M AF Papakostas, GI Perlis, RH Scalia, MJ Petersen, TJ Fava, M TI A meta-analysis of early sustained response rates between antidepressants and placebo for the treatment of major depressive disorder SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID IMPRESSIONS RATING-SCALE; TRUE DRUG RESPONSE; PATTERN-ANALYSIS; CLINICAL-TRIALS; RELATIVE SENSITIVITY; EARLY IMPROVEMENT; DOUBLE-BLIND; FLUOXETINE; ONSET; RELAPSE AB Context: Pattern analysis suggests that "true" drug response is characterized by clinical improvement that is not subsequently followed by a worsening of symptoms (sustained clinical response). To date, several reports demonstrate that early response rates are equivalent between antidepressant-treated and placebo-treated groups of patients with major depressive disorder, suggesting that patients who demonstrate significant and sustained symptom improvement during the first 2 weeks of treatment are not responding to the antidepressant itself, but to nonspecific, placebo-like factors. Objective: To compare early sustained response rates between antidepressant- and placebo-treated adults with major depressive disorder. Data Sources: Medline/Pubmed were searched. No year of publication limits were used. Study Selection: Randomized, double-blind, placebo-controlled antidepressant trials or pooled reports/meta-analyses of such trials reporting early sustained response rates for major depressive disorder. The decision to include studies in the meta-analysis was performed by 2 reviewers. Data Extraction: Data were extracted with the use of a precoded form. Data Synthesis: Analyses were performed on the proportion of patients who achieved a sustained response the first 2 weeks of treatment, as well as the first week of treatment. A random-effects model with fixed drug effects was used to combine the studies and make comparisons of sustained early response rates between antidepressant- and placebo-treated groups. Data from 8 reports involving a total of 7121 major depressive disorder patients (4076 randomized to treatment with an antidepressant and 3045 randomized to placebo) were analyzed. Antidepressant-treated patients were more likely to demonstrate sustained clinical response by 2 weeks (odds ratio 2.06, 95% CI: 1.52-2.8) or 1 week of treatment (odds ratio 1.50, 95% CI: 1.08-2.08) than placebo-treated patients. Conclusions: The results of the present analysis suggest that "true" drug response can occur the first 2 week as well as the first week of treatment of major depressive disorder with conventional antidepressants. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program,Dept Psychiat, Boston, MA 02114 USA. RP Papakostas, GI (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program,Dept Psychiat, 15 Parkman St,WAC 812, Boston, MA 02114 USA. EM gpapakostas@partners.org RI Papakostas, George/I-6905-2013 OI Papakostas, George/0000-0002-2465-5103 FU NIMH NIH HHS [K23 MH069629] NR 42 TC 73 Z9 73 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD FEB PY 2006 VL 26 IS 1 BP 56 EP 60 DI 10.1097/01.jcp.0000195042.62724.76 PG 5 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 004SY UT WOS:000234773700012 PM 16415707 ER PT J AU Jellinek, M AF Jellinek, M TI Suicidal ideation in prepubertal children: What does it mean? What to do? SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Editorial Material DE suicidal ideation; prepubertal children C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jellinek, M (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 5 TC 1 Z9 1 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-206X J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD FEB PY 2006 VL 27 IS 1 BP 40 EP 41 DI 10.1097/00004703-200602000-00006 PG 2 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA 016MH UT WOS:000235623800006 PM 16511367 ER PT J AU Biese, KJ Brown, DFM Nadel, ES AF Biese, KJ Brown, DFM Nadel, ES TI Heart block and rash SO JOURNAL OF EMERGENCY MEDICINE LA English DT Editorial Material ID LYME-DISEASE; CARDIAC MANIFESTATIONS; BORRELIA-BURGDORFERI C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Emergency Med, Boston, MA USA. Harvard Univ, Sch Med, Div Emergency Med, Harvard Affiliated Emergency Med Residency, Boston, MA USA. RP Brown, DFM (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Bulfinch 105,Fruit St, Boston, MA 02114 USA. NR 14 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD FEB PY 2006 VL 30 IS 2 BP 215 EP 218 DI 10.1016/j.jemermed.2005.12.010 PG 4 WC Emergency Medicine SC Emergency Medicine GA 028GQ UT WOS:000236475500017 PM 16567261 ER PT J AU Hendriks, JM Zindler, JD van der Lugt, A Pattynarna, PMT van Sambeek, MRHM Bosch, JL van Dijk, LC AF Hendriks, JM Zindler, JD van der Lugt, A Pattynarna, PMT van Sambeek, MRHM Bosch, JL van Dijk, LC TI Ernbolic protection filters for carotid stenting: Differences in flow obstruction depending on filter construction SO JOURNAL OF ENDOVASCULAR THERAPY LA English DT Article DE carotid artery; stent; embolus protection devices; hemodynamics; pressure gradient ID CEREBRAL PROTECTION; ANGIOPLASTY; FREQUENCY; DEVICES AB Purpose: To investigate the pressure gradient and degree of flow reduction associated with embolus protection filters for carotid stenting in an in vitro experiment. Methods: Three filter devices with a perforated membrane design and one wire mesh type filter were tested. At a pressure of 70 mmHg, the flow reduction and pressure gradient were measured in a 5-mm tube using blood-mimicking fluid. Results: The pressure gradient in the wire mesh filter was 1.65 +/- 0.49 mmHg (95% Cl 1.32 to 1.86). The mean pressure gradient in the perforated membrane filters was 6.88 +/- 2.62 mmHg (95% CI 6.22 to 7.55, p < 0.0001). There was also a significant correlation between pressure gradient and flow reduction (r=-0.77, p < 0.01). Conclusion: Embolic protection filters cause a pressure gradient and obstruct blood flow. This effect is marked in perforated membrane filters and almost absent in the wire mesh filter. C1 Erasmus Univ, Dept Vasc Surg, Med Ctr, NL-3015 GD Rotterdam, Netherlands. Erasmus Univ, Dept Radiol, Med Ctr, NL-3015 GD Rotterdam, Netherlands. Erasmus Univ, Dept Biostat & Epidemiol, Med Ctr, NL-3015 GD Rotterdam, Netherlands. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Inst Technol Assessment, Cambridge, MA 02138 USA. RP Hendriks, JM (reprint author), Erasmus Univ, Dept Surg, Med Ctr, Dr Molewaterplein 40, NL-3015 GD Rotterdam, Netherlands. EM j.m.hendriks@erasmusmc.nl NR 11 TC 18 Z9 20 U1 1 U2 1 PU ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 1526-6028 J9 J ENDOVASC THER JI J. Endovascular Ther. PD FEB PY 2006 VL 13 IS 1 BP 47 EP 50 DI 10.1583/04-1325.1 PG 4 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 014DP UT WOS:000235459300006 PM 16445323 ER PT J AU Allen, NL Leeth, RR Finan, KR Tishler, DS Vickers, SM Wilcox, CM Hawn, MT AF Allen, NL Leeth, RR Finan, KR Tishler, DS Vickers, SM Wilcox, CM Hawn, MT TI Outcomes of cholecystectomy after endoscopic sphincterotomy for choledocholithiasis SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-of-American-Gastrointestinal-Endoscopic-Surgeons (SAGES) CY MAR 31-APR 03, 2004 CL Denver, CO SP Soc Amer Gastrointestinal Endoscop Surg DE cholecystectomy; choledocholithiasis; endoscopic; sphincterotomy; outcomes ID BILE-DUCT STONES; GALLBLADDER IN-SITU; TERM-FOLLOW-UP; LAPAROSCOPIC CHOLECYSTECTOMY; ACUTE CHOLECYSTITIS; 10-YEAR EXPERIENCE; PROSPECTIVE TRIAL; RANDOMIZED TRIAL; MANAGEMENT; RISK AB Laparoscopic cholecystectomy (LC) for treatment of symptomatic common bile duct stones (CBDS) after endoscopic sphincterotomy (ES) is associated with increased conversion and complications compared with other indications. We examined factors associated with conversion and complications of LC after ES. A retrospective study of 32 patients undergoing ES for CBDS followed by cholecystectomy was undertaken. Surgical outcomes for this group were compared with a control population of 499 LCs for all other indications. Factors associated with open cholecystectomy and complications in the ES group were analyzed. Patients undergoing LC preceded by ES had a significantly higher complication (odds ratio [OR] 7.97; 95% CI, 2.84-22.5) and conversion rate (OR = 3.45; 95% CI, 1.56-7.66) compared with LC for all other indications. Pre-ES serum bilirubin greater than 5 mg/dL was predictive of conversion (positive predictive value = 63 %, P < 0.005). Patients with symptomatic CBDS that undergo LC after ES have higher complication and conversion rates than patients undergoing LC without ES. Pre-ES serum bilirubin is useful in identifying patients who may not have a successful laparoscopic approach at cholecystectomy. C1 Univ Alabama, Dept Surg, Birmingham, AL 35294 USA. Univ Alabama, Dept Gastroenterol, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Deep S Ctr Effectiveness, Birmingham, AL USA. RP Hawn, MT (reprint author), Univ Alabama, Dept Surg, KB 417,1530 3rd Ave S, Birmingham, AL 35294 USA. EM mhawn@uab.edu NR 17 TC 17 Z9 18 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD FEB PY 2006 VL 10 IS 2 BP 292 EP 296 DI 10.1016/j.gassur.2005.05.013 PG 5 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 013DB UT WOS:000235388700025 PM 16455464 ER PT J AU Givens, JL Datto, CJ Ruckdeschel, K Knott, K Zubritsky, C Oslin, DW Nyshadham, S Vanguri, P Barg, FK AF Givens, JL Datto, CJ Ruckdeschel, K Knott, K Zubritsky, C Oslin, DW Nyshadham, S Vanguri, P Barg, FK TI Older patients' aversion to antidepressants - A qualitative study SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc Gen Internal Med DE antidepressants; patient preferences; qualitative research; geriatrics ID PRIMARY-CARE PATIENTS; RANDOMIZED CONTROLLED-TRIAL; GERIATRIC DEPRESSION; GENERAL-PRACTICE; MENTAL-ILLNESS; HEALTH-CARE; LATE-LIFE; DISORDERS; MEDICINES; ADHERENCE AB BACKGROUND: Depression is common among older patients yet is often inadequately treated. Patient beliefs about antidepressants are known to affect treatment initiation and adherence, but are often not expressed in clinical settings. OBJECTIVE: To explore attitudes toward antidepressants in a sample of depressed, community-dwelling elders who were offered treatment. DESIGN: Cross-sectional, qualitative study utilizing semi-structured interviews. PARTICIPANTS: Primary care patients age 60 years and over with depression, from academic and community primary care practices of the University of Pennsylvania Health System and the Philadelphia Department of Veterans Affairs. Patients participated in either the Prevention of Suicide in Primary Care Elderly: Collaborative Trial or the Primary Care Research in Substance Abuse and Mental Health for the Elderly Trial. Sixty-eight patients were interviewed and responses from 42 participants with negative attitudes toward medication for depression were analyzed. MEASUREMENTS: Interviews were audiotaped, transcribed, and entered into a qualitative software program for coding and analysis. A multidisciplinary team of investigators coded the transcripts and identified key features of narratives expressing aversion to antidepressants. RESULTS: Four themes characterized resistance to antidepressants: (1) fear of dependence; (2) resistance to viewing depressive symptoms as a medical illness; (3) concern that antidepressants will prevent natural sadness; (4) prior negative experiences with medications for depression. CONCLUSIONS: Many elders resisted the use of antidepressants. Patients expressed concerns that seem to reflect their concept of depression as well as their specific concerns regarding antidepressants. These findings may enhance patient-provider communication about depression treatment in elders. C1 Univ Penn, Div Gen Internal Med, Philadelphia, PA 19104 USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA USA. Univ Penn, Sch Arts & Sci, Philadelphia, PA 19104 USA. Univ Penn, Dept Family Practice & Community Med, Philadelphia, PA 19104 USA. Univ Penn, Dept Anthropol, Philadelphia, PA 19104 USA. RP Givens, JL (reprint author), 1226 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM jagivens@mail.med.upenn.edu FU CMHS SAMHSA HHS [1UD1SM53033]; NIMH NIH HHS [P30-MH066270, 5P30MH52129, P30 MH066270] NR 40 TC 60 Z9 63 U1 2 U2 12 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD FEB PY 2006 VL 21 IS 2 BP 146 EP 151 DI 10.1111/j.1525-1497.2005.00296.x PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 019WK UT WOS:000235867800011 PM 16336620 ER PT J AU Saha, S AF Saha, S TI The relevance of cultural distance between patients and physicians to racial disparities in health care SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material ID OF-VETERANS-AFFAIRS; PERCEPTIONS; PERFORMANCE; QUALITY; RATINGS; STYLE; RACE C1 Oregon Hlth Sci Univ, Portland VA Med Ctr, Dept Med, Gen Internal Med Sect, Portland, OR USA. RP Saha, S (reprint author), Portland VAMC P3MED, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sahas@ohsu.edu NR 23 TC 5 Z9 5 U1 1 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD FEB PY 2006 VL 21 IS 2 BP 203 EP 205 DI 10.1007/s11606-006-0262-1 PG 3 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 019WK UT WOS:000235867800023 PM 16606385 ER PT J AU Fihn, SD AF Fihn, SD TI Moving implementation science forward SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material C1 VA Puget Sound Hlth Care Syst, HSR&D 152, Seattle, WA 98108 USA. RP Fihn, SD (reprint author), VA Puget Sound Hlth Care Syst, HSR&D 152, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 4 TC 5 Z9 5 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD FEB PY 2006 VL 21 SU 2 BP S65 EP S66 DI 10.1111/j.1525-1497.2006.00365.x PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 024QH UT WOS:000236210600011 PM 16637963 ER PT J AU Hagedorn, H Hogan, M Smith, JL Bowman, C Curran, GM Espadas, D Kimmel, B Kochevar, L Legro, MW Sales, AE AF Hagedorn, H Hogan, M Smith, JL Bowman, C Curran, GM Espadas, D Kimmel, B Kochevar, L Legro, MW Sales, AE TI Lessons learned about implementing research evidence into clinical practice - Experiences from VA QUERI SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT State of the Art of Implementation Conference CY AUG 30-SEP 01, 2004 CL Washington, DC SP Dept Vet Affairs, Off Res & Dev, Hlth Serv Res & Dev Serv DE implementation research; quality improvement; evidence-based medicine; guidelines ID QUALITY IMPROVEMENT; MEDICAL-RECORD; VETERANS AB The mission of the Veterans Health Administration's [VHA) quality enhancement research initiative (QUERI) is to enhance the quality of VHA health care by implementing clinical research findings into routine care. This paper presents lessons that QUERI investigators have learned through their initial attempts to pursue the QUERI mission. The lessons in this paper represent those that were common across multiple QUERI projects and were mutually agreed on as having substantial impact on the success of implementation. While the lessons are consistent with commonly recognized ingredients of successful implementation efforts, the examples highlight the fact that, even with a thorough knowledge of the literature and thoughtful planning, unexpected circumstances arise during implementation efforts that require flexibility and adaptability. The findings stress the importance of utilizing formative evaluation techniques to identify barriers to successful implementation and strategies to address these barriers. C1 VA Med Ctr, Subst Use Disorders QUERI, Minneapolis, MN 55417 USA. VA Ann Arbor Healthcare Syst, Diabet Mellitus QUERI, Ann Arbor, MI USA. Cent Arkansas Vet Healthcare Syst, Mental Hlth QUERI, Little Rock, AR USA. VA San Diego Healthcare Syst, HIV QUERI, San Diego, CA USA. Houston VA Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. Minneapolis VA Med Ctr, Colerectal Canc QUERI, Minneapolis, MN USA. VA Puget Sound Healthcare Syst, Spinal Cord Injury QUERI, Seattle, WA USA. VA Puget Sound Healthcare Syst, Ischem Heart Dis QUERI, Seattle, WA USA. RP Hagedorn, H (reprint author), VA Med Ctr, Subst Use Disorders QUERI, 1 Vet Dr 116A9, Minneapolis, MN 55417 USA. EM Hildi.Hagedorn@va.gov RI Sales, Anne/D-9678-2012; OI Sales, Anne/0000-0001-9360-3334 NR 17 TC 38 Z9 39 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD FEB PY 2006 VL 21 SU 2 BP S21 EP S24 DI 10.1111/j.1525-1497.2006.00358.x PG 4 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 024QH UT WOS:000236210600004 PM 16637956 ER PT J AU Kiefe, CI Sales, A AF Kiefe, CI Sales, A TI A state-of-the-art conference on implementing evidence in health care - Reasons and recommendations SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material ID CONCEPTUAL-FRAMEWORK; QUALITY; VETERANS; DISSEMINATION; SYSTEM C1 Univ Alabama, Birmingham VA Med Ctr, Birmingham, AL 35294 USA. Univ Alabama, Dept Med, Div Prevent Med, Birmingham, AL 35294 USA. Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. RP Kiefe, CI (reprint author), Univ Alabama, Birmingham VA Med Ctr, Birmingham, AL 35294 USA. EM ckiefe@mail.dopm.uab.edu RI Sales, Anne/D-9678-2012 NR 29 TC 9 Z9 9 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD FEB PY 2006 VL 21 SU 2 BP S67 EP S70 DI 10.1007/s11606-006-0278-6 PG 4 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 024QH UT WOS:000236210600012 PM 16637964 ER PT J AU Kochevar, LK Yano, EM AF Kochevar, LK Yano, EM TI Understanding health care organization needs and context - Beyond performance gaps SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT State of the Art of Implementation Conference CY AUG 30-SEP 01, 2004 CL Washington, DC SP Dept Vet Affairs, Off Res & Dev, Hlth Serv Res & Dev Serv DE needs assessment; quality improvement; methods; systems analysis ID FAULT-DIAGNOSIS; DYNAMIC-SYSTEMS; INTERVENTIONS; METHODOLOGY; QUALITY; DESIGN AB Significant efforts have been invested in improving our understanding of how to accelerate and magnity the impact of research on clinical practice. While approaches to fostering translation of research into practice are numerous, none appears to be superior and the evidence for their effectiveriess is mixed. Lessons learned from formative evaluation have given us a greater-appreciation of the contribution of context to successful implementation of quality improvement interventions. While formative evaluation is a powerful tool for addressing context effects during implementation, lessons learned from the social sciences (including management and operations research, sociology, and public health) show us that there are also powerful preimple-mentation. tools available to us. This paper discusses how we might integrate these tools into implementation research. We provide a theoretical framework for our need to understand organizational contexts and how organizational characteristics can alert us to situations where preimplementation tools will prove most valuable. C1 Minneapolis VA Med Ctr, Ctr Chron Dis Outcomes Res, Minneapolis, MN 55417 USA. Minneapolis VA Med Ctr, VA Colerectal Canc QUERI, Minneapolis, MN 55417 USA. VA Greater Los Angeles HSR&D Ctr Excellence, Sepulveda, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. RP Kochevar, LK (reprint author), Minneapolis VA Med Ctr, Ctr Chron Dis Outcomes Res, 2E-152,1 Vet Dr, Minneapolis, MN 55417 USA. EM laura.kochevar@med.va.gov NR 44 TC 36 Z9 38 U1 2 U2 7 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD FEB PY 2006 VL 21 SU 2 BP S25 EP S29 DI 10.1111/j.1525-1497.2006.00359.x PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 024QH UT WOS:000236210600005 PM 16637957 ER PT J AU Rubenstein, LV Pugh, J AF Rubenstein, LV Pugh, J TI Strategies for promoting organizational and practice change by advancing implementation research SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT State of the Art of Implementation Conference CY AUG 30-SEP 01, 2004 CL Washington, DC SP Dept Vet Affairs, Off Res & Dev, Hlth Serv Res & Dev Serv DE health services research; quality of care; implementation; organizational change; clinical practice ID QUALITY IMPROVEMENT PROGRAM; HEALTH-CARE-SYSTEM; PATIENT OUTCOMES; MANAGED CARE; OF-CARE; INTERVENTIONS; DIFFUSION; FRAMEWORK; SERVICES; LESSONS AB BACKGROUND: The persistence of a large quality gap between what we know about how to produce high quality clinical care and what the public receives has prompted interest in developing more effective methods to get evidence into practice. Implementation research aims to supply such methods. PURPOSE: This article proposes a set of recommendations aimed at establishing a common understanding of what implementation research is, and how to foster its development. METHODS: We developed the recommendations in the context of a translation research conference hosted by the VA for VA and non-VA health services researchers. IMPACTS: Healthcare organizations, journals, researchers and academic institutions can use these recommendations to advance the field of implementation science and thus increase the impact of clinical and health services research on the health and health care of the public. C1 Vet Adm Greater Los Angeles, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. RAND Corp, Santa Monica, CA USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Med, Div Gen Med, San Antonio, TX 78285 USA. RP Rubenstein, LV (reprint author), VA Med Ctr 152, 16111 Plummer St, Sepulveda, CA 91343 USA. EM lisar@rand.org OI Pugh, Jacqueline/0000-0003-4933-141X NR 42 TC 91 Z9 92 U1 1 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD FEB PY 2006 VL 21 SU 2 BP S58 EP S64 DI 10.1111/j.1525-1497.2006.00364.x PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 024QH UT WOS:000236210600010 PM 16637962 ER PT J AU Sales, A Smith, J Curran, G Kochevar, L AF Sales, A Smith, J Curran, G Kochevar, L TI Models, strategies, and tools - Theory in implementing evidence-based findings into health care practice SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT State of the Art of Implementation Conference CY AUG 30-SEP 01, 2004 CL Washington, DC SP Dept Vet Affairs, Off Res & Dev, Hlth Serv Res & Dev Serv DE evidence-based medicine; organizational change; professional practice; behavior ID SOCIAL COGNITIVE THEORY; NO MAGIC BULLETS; QUALITY IMPROVEMENT; CONCEPTUAL-FRAMEWORK; GENERAL-PRACTICE; REASONED ACTION; DISSONANCE; INTERVENTIONS; BEHAVIOR; PROGRAM AB This paper presents a case for careful consideration of theory in planning to implement evidence-based practices into clinical care. As described, theory should be tightly linked to strategic planning through careful choice or creation of an implementation framework. Strategies should be linked to specific interventions and/or intervention components to be implemented, and the choice of tools should match the interventions and overall strategy, linking back to the original theory and framework. The thesis advanced is that in most studies where there is an attempt to implement planned change in clinical processes, theory is used loosely. An example of linking theory to intervention design is presented from a Mental Health Quality Enhancement Research Initiative effort to increase appropriate use of antipsychotic medication among patients with schizophrenia in the Veterans Health Administration. C1 VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence 152, Seattle, WA 98108 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Little Rock VA Med Ctr, Little Rock, AR USA. Univ Arkansas, Dept Psychiat, Little Rock, AR 72204 USA. Minneapolis VA Med Ctr, Minneapolis, MN USA. RP Sales, A (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence 152, 1660 S Columbian Way, Seattle, WA 98108 USA. EM ann.sales@med.va.gov RI Sales, Anne/D-9678-2012; OI Sales, Anne/0000-0001-9360-3334 NR 70 TC 55 Z9 55 U1 2 U2 15 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD FEB PY 2006 VL 21 SU 2 BP S43 EP S49 DI 10.1111/j.1525-1497.2006.00362.x PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 024QH UT WOS:000236210600008 PM 16637960 ER PT J AU Stetler, CB Legro, MW Wallace, CM Bowman, C Guihan, M Hagedorn, H Kimmel, B Sharp, ND Smith, JL AF Stetler, CB Legro, MW Wallace, CM Bowman, C Guihan, M Hagedorn, H Kimmel, B Sharp, ND Smith, JL TI The role of formative evaluation in implementation research and the QUERI experience SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT State of the Art of Implementation Conference CY AUG 30-SEP 01, 2004 CL Washington, DC SP Dept Vet Affairs, Off Res & Dev, Hlth Serv Res & Dev Serv DE process assessment (health care); evaluation methodology; evaluation studies ID DISEASE PREVENTION PROGRAMS; QUALITY IMPROVEMENT; HEALTH-PROMOTION; COMPLEX INTERVENTIONS; FRAMEWORK; SCIENCE AB This article describes the importance and role of 4 stages of formative evaluation in our growing understanding of how to implement research findings into practice in order to improve the quality of clinical care. It reviews limitations of traditional approaches to implementation research and presents a rationale for new thinking and use of new methods. Developmental, implementation-focused, progress-focused, and interpretive evaluations are then defined and illustrated with examples from Veterans Health Administration Quality Enhancement Research Initiative projects. This article also provides methodologic details and highlights challenges encountered in actualizing formative evaluation within implementation research. C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. VA San Diego Healthcare Syst, San Diego, CA USA. Edward Hines Jr VA Healthcare Syst, Hines, IL USA. Minneapolis VA Med Ctr, Minneapolis, MN USA. Baylor Coll Med, Houston, TX 77030 USA. Vet Affairs Med Ctr, Houston, TX 77030 USA. Cent Arkansas Vet Healthcare Syst, Little Rock, AR USA. RP Stetler, CB (reprint author), 321 Middle St, Amherst, MA 01002 USA. EM cheryl.stetler@the-spa.com NR 61 TC 127 Z9 127 U1 3 U2 17 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD FEB PY 2006 VL 21 SU 2 BP S1 EP S8 DI 10.1111/j.1525-1497.2006.00355.x PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 024QH UT WOS:000236210600001 PM 16637954 ER PT J AU Soong, M Jupiter, J Rosenthal, D AF Soong, M Jupiter, J Rosenthal, D TI Radiofrequency ablation of osteoid osteoma in the upper extremity SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE ablation; osteoid; osteoma; radiofrequency ID OPERATIVE TREATMENT; LOCALIZATION; COAGULATION; BONE AB Purpose: To examine the results of radiofrequency ablation (RFA) of osteoid osteoma in the upper extremity. Methods: Twenty-nine patients with a clinical and radiographic diagnosis of an upper-extremity osteoid osteoma were referred for treatment between 1990 and 2003. All had computed tomography-guided percutaneous RFA performed by the senior investigator. Records were reviewed for patient age and gender, lesion size and location, prior treatment, and pathology results. Outcomes were determined by questionnaire via mail or telephone. Complete success was defined as complete resolution of pain without further treatment. Partial Success was defined as occasional pain with activities that did not require another procedure. Failure was defined as recurrence, no change in symptoms, and/or the need for another procedure. Results: Follow-up data were available for 25 patients at a minimum of I year. Lesion locations included 17 humerus, 5 scapula, 2 radius, I ulna. Results for 19 patients were rated completely Successful, 4 were rated partially successful, and 2 were rated failures. Two patients whose results were not completely successful received decreased RFA temperature or duration because of the proximity of a neurovascular bundle. There were no complications. Outcomes did not correlate with any patient or tumor characteristics. Conclusions: Radiofrequency ablation is a safe and effective treatment for most osteoid osteomas in the shoulder, arm, and forearm. Lesions that do not allow a safe distance between the electrode and a major neurovascular structure may require surgical excision. This may be of particular importance in lesions of the hand and carpus. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Musculoskeletal Radiol, Boston, MA 02114 USA. RP Soong, M (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, 55 Fruit St,VBK-210, Boston, MA 02114 USA. EM msoong@partners.org OI Soong, Maximillian/0000-0003-0333-8181 NR 16 TC 29 Z9 29 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD FEB PY 2006 VL 31A IS 2 BP 279 EP 283 DI 10.1016/j.jhsa.2005.10.012 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 015NU UT WOS:000235558900017 PM 16473691 ER PT J AU Mudgal, CS AF Mudgal, CS TI Management of tophaceous gout of the distal interphalangeal joint SO JOURNAL OF HAND SURGERY-BRITISH AND EUROPEAN VOLUME LA English DT Article DE gout; tophus; finger; interphalangeal joint AB Surgical management of acute tophaceous gout of the distal interphalangeal joint is often associated with delayed wound healing. Aspiration through neighbouring uninvolved skin is a safe method of treating these tophi. For persistently symptomatic, unstable DIP joints, arthrodesis should be considered. C1 Massachusetts Gen Hosp, Orthopaed hand Serv, Yawkey Ctr, Boston, MA 02114 USA. RP Mudgal, CS (reprint author), Massachusetts Gen Hosp, Orthopaed hand Serv, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM cmudgal@partners.org NR 6 TC 7 Z9 8 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 0266-7681 J9 J HAND SURG-BRIT EUR JI J. Hand Surg.-Br. Eur. Vol. PD FEB PY 2006 VL 31B IS 1 BP 101 EP 103 DI 10.1016/j.jhsb.2005.09.003 PG 3 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 011GO UT WOS:000235256400016 PM 16243417 ER PT J AU Ferencik, M Gregory, SA Achenbach, S Yeh, RW Hoffmann, U Inglessis, I Cury, RC Nieman, K Raffel, OC McNulty, IA Brady, TJ Semigran, MJ Jang, IK AF Ferencik, M. Gregory, S. A. Achenbach, S. Yeh, R. W. Hoffmann, U. Inglessis, I. Cury, R. C. Nieman, K. Raffel, O. C. McNulty, I. A. Brady, T. J. Semigran, M. J. Jang, I. K. TI Image quality of 64-slice multi-detector computed tomography coronary angiograpry in heart transplant recipients SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract C1 [Ferencik, M.; Gregory, S. A.; Yeh, R. W.; Hoffmann, U.; Inglessis, I.; Cury, R. C.; Nieman, K.; Raffel, O. C.; McNulty, I. A.; Brady, T. J.; Semigran, M. J.; Jang, I. K.] Harvard Univ, Sch Med, Boston, MA USA. [Ferencik, M.; Hoffmann, U.; Cury, R. C.; Nieman, K.; Brady, T. J.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Gregory, S. A.; Yeh, R. W.; Inglessis, I.; Raffel, O. C.; McNulty, I. A.; Semigran, M. J.; Jang, I. K.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA USA. [Achenbach, S.] Univ Erlangen Nurnberg, Dept Med 2, Erlangen, Germany. 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 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2006 VL 25 IS 2 SU S MA 277 BP S140 EP S140 DI 10.1016/j.healun.2005.11.288 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA V50KO UT WOS:000203407400277 ER PT J AU Kitchens, WH Chase, CM Uebara, S Colvin, RB Russell, PS Madsen, JC AF Kitchens, W. H. Chase, C. M. Uebara, S. Colvin, R. B. Russell, P. S. Madsen, J. C. TI Macrophage depletion suppresses cardiac allograft vasculopathy in mice SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract C1 [Kitchens, W. H.; Chase, C. M.; Uebara, S.; Russell, P. S.] Massachusetts Gen Hosp, Dept Transplantat Surg, Boston, MA 02114 USA. [Colvin, R. B.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Madsen, J. C.] Massachusetts Gen Hosp, Dept Cardiac Surg, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2006 VL 25 IS 2 SU S MA 328 BP S157 EP S157 DI 10.1016/j.healun.2005.11.340 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA V50KO UT WOS:000203407400327 ER PT J AU Shoji, T Sahara, H Muniappan, A Guenther, DA Wain, JC Houser, SL Bravard, MA Pujara, AC Sachs, DH Madsen, JC Allan, JS AF Shoji, T. Sahara, H. Muniappan, A. Guenther, D. A. Wain, J. C. Houser, S. L. Bravard, M. A. Pujara, A. C. Sachs, D. H. Madsen, J. C. Allan, J. S. TI Pulmonary allograft tolerance can be incuced across a class I MHC barrier in swine sensitized to MHC class I allopepitdes prior to transplantation SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract C1 [Shoji, T.; Sahara, H.; Muniappan, A.; Guenther, D. A.; Wain, J. C.; Houser, S. L.; Bravard, M. A.; Pujara, A. C.; Sachs, D. H.; Madsen, J. C.; Allan, J. S.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. [Shoji, T.; Sahara, H.; Muniappan, A.; Guenther, D. A.; Wain, J. C.; Houser, S. L.; Bravard, M. A.; Pujara, A. C.; Sachs, D. H.; Madsen, J. C.; Allan, J. S.] Harvard Univ, Sch Med, Boston, MA USA. [Wain, J. C.; Allan, J. S.] Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. [Madsen, J. C.] Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2006 VL 25 IS 2 SU S MA 248 BP S130 EP S130 DI 10.1016/j.healun.2005.11.258 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA V50KO UT WOS:000203407400248 ER PT J AU Williams, JS Williams, GH Raji, A Jeunemaitre, X Brown, NJ Hopkins, PN Conlin, PR AF Williams, JS Williams, GH Raji, A Jeunemaitre, X Brown, NJ Hopkins, PN Conlin, PR TI Prevalence of primary hyperaldosteronism in mild to moderate hypertension without hypokalaemia SO JOURNAL OF HUMAN HYPERTENSION LA English DT Article DE hyperaldosteronism; dietary sodium; essential hypertension ID HUMAN PERIPHERAL PLASMA; PRIMARY ALDOSTERONISM; RENIN-ACTIVITY; ANGIOTENSIN-II; SCREENING-TEST; IDIOPATHIC ALDOSTERONISM; ADRENAL RESPONSIVENESS; SODIUM-INTAKE; DIAGNOSIS; RATIO AB Screening for primary hyperaldosteronism (PHA) is often indicated in individuals with resistant hypertension or hypokalaemia. However, in the far larger subset of the hypertensive population who do not fit into these criteria, the evidence for screening is conflicting and dependent on the disease prevalence. The purpose of this study was to examine the prevalence of PHA in a large population with mild to moderate hypertension and without hypokalaemia using a carefully controlled study protocol including a normotensive control population. Hypertensive subjects underwent medication washout and both hypertensive and normotensive subjects placed on a high-sodium diet prior to biochemical and haemodynamic testing. Study specific cutoff values were based on results from the normotensive population studied under identical conditions. A screening test (serum aldosterone/PRA ratio [ARR] >25 with a serum aldosterone level >8 ng/dl) was followed by a confirmatory test (urine aldosterone excretion rate [AER] >17 mu g/24 h) to demonstrate evidence of PHA. An elevated ARR with a concomitant elevated serum aldosterone was present in 26 (7.5%) individuals. Of these, 11 (3.2%) had an elevated AER, consistent with evidence of PHA. Individuals with PHA had higher blood pressure and lower serum potassium levels while on a high-sodium diet. Sodium restriction neutralized these differences between PHA and essential hypertensives. The prevalence of PHA in this mild to moderate hypertensive population without hypokalaemia is at most 3.2%, a rate that might lead to excessive false positives with random screening in comparable populations. Hyperaldosteronism, when present, is responsive to sodium restriction. C1 Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Hop European Georges Pompidou, Dept Genet, INSERM, AP,Ctr Invest Clin 92401, Paris, France. Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA. Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA. Univ Utah, Sch Med, Dept Med, Salt Lake City, UT USA. VA Boston Healthcare Syst, Med Serv, Boston, MA USA. RP Williams, JS (reprint author), Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Dept Med, 221 Longwood Ave, Boston, MA 02115 USA. EM Jwilliams5@partners.org OI Williams, Jonathan/0000-0001-7152-765X FU NCRR NIH HHS [M01 RR 00064, M01 RR 02635]; NHLBI NIH HHS [HL55000, HL47651, HL59424, HL77234]; NIDDK NIH HHS [DK63214] NR 43 TC 54 Z9 57 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9240 J9 J HUM HYPERTENS JI J. Hum. Hypertens. PD FEB PY 2006 VL 20 IS 2 BP 129 EP 136 DI 10.1038/sj.jhh.1001948 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 005CY UT WOS:000234801400006 PM 16292348 ER PT J AU Moller-Kristensen, M Ip, WKE Shi, L Gowda, LD Hamblin, MR Thiel, S Jensenius, JC Ezekowitz, RAB Takahashi, K AF Moller-Kristensen, M Ip, WKE Shi, L Gowda, LD Hamblin, MR Thiel, S Jensenius, JC Ezekowitz, RAB Takahashi, K TI Deficiency of mannose-binding lectin greatly increases susceptibility to postburn infection with Pseudomonas aeruginosa SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; THERMAL-INJURY; SERINE-PROTEASE; INNATE IMMUNITY; HOST-DEFENSE; STAPHYLOCOCCUS-AUREUS; COMPLEMENT ACTIVATION; WOUND INFECTIONS; MICE; BURN AB Burn injury disrupts the mechanical and biological barrier that the skin presents against infection by symbionts like the Pseudomonas aeruginosa, a Gram-negative bacteria. A combination of local factors, antimicrobial peptides, and resident effector cells form the initial response to mechanical injury of the skin. This activity is followed by an inflammatory response that includes influx of phagocytes and serum factors, such as complement and mannose-binding lectin (MBL), which is a broad-spectrum pattern recognition molecule that plays a key role in innate immunity. A growing consensus from studies in humans and mice suggests that lack of MBL together with other comorbid factors predisposes the host to infection. In this study we examined whether MBL deficiency increases the risk of P. aeruginosa infection in a burned host. We found that both wild-type and MBL null mice were resistant to a 5% total body surface area burn alone or s.c. infection with P. aeruginosa alone. However, when mice were burned then inoculated s.c. with P. aeruginosa at the burn site, all MBL null mice died by 42 h from septicemia, whereas only one-third of wild-type mice succumbed (p = 0.0005). This result indicates that MBL plays a key role in containing and preventing a systemic spread of P. aeruginosa infection following burn injury and suggests that MBL deficiency in humans maybe a premorbid variable in the predisposition to infection in burn victims. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat,Lab Dev Immunol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Lab Photomed,Dept Dermatol, Boston, MA 02114 USA. Univ Aarhus, Dept Med Microbiol & Immunol, Aarhus, Denmark. RP Takahashi, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat,Lab Dev Immunol, GRJ 1402,55 Fruit St, Boston, MA 02114 USA. EM ktakahashi1@partners.org RI Ip, Eddie/C-3042-2012; OI Hamblin, Michael/0000-0001-6431-4605 FU NIAID NIH HHS [R01 AI042788, R01 AI050875, R01 AI050875-04, R01AI42788] NR 66 TC 62 Z9 62 U1 1 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 2006 VL 176 IS 3 BP 1769 EP 1775 PG 7 WC Immunology SC Immunology GA 004QF UT WOS:000234766600056 PM 16424207 ER PT J AU Stratigos, AJ Yang, G Dimisianos, R Nicolaou, V Stefanaki, I Katsambas, AD Tsao, H AF Stratigos, Alexander J. Yang, Guang Dimisianos, Remos Nicolaou, Vasiliki Stefanaki, Irene Katsambas, Andreas D. Tsao, Hensin TI Germline CDKN2A mutations among Greek patients with early-onset and multiple primary cutaneous melanoma SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID INDIVIDUALS AB The genetic basis of melanoma susceptibility among Greek patients is uncharacterized. From 107 consecutive cutaneous melanoma patients, we analyzed the CDKN2A and CDK4 loci among 18 early-onset (<= 40 years) and two multiplex melanoma cases. Overall, we found three CDKN2A mutations (3/20; 15%), including one novel nonsense mutation (Trp110Stop) and two Arg24Pro missense alterations. There were no mutations in ARF or CDK4. CDKN2A mutations are not uncommon among Greek melanoma patients considering that none of the mutation carriers reported a family history of melanoma. C1 Massachusetts Gen Hosp, Dept Dermatol, Wellman Ctr Photomed, Boston, MA 02114 USA. Univ Athens, Sch Med, Dept Dermatol, Andreas Sygros Hosp, GR-11527 Athens, Greece. Univ Athens, Sch Med, Dept Med Genet, Agia Sophia Childrens Hosp, GR-11527 Athens, Greece. RP Tsao, H (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Wellman Ctr Photomed, 622 Bartlett Hall,48 Blossom St, Boston, MA 02114 USA. EM tsao.hensin@mgh.harvard.edu NR 9 TC 7 Z9 7 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD FEB PY 2006 VL 126 IS 2 BP 399 EP 401 DI 10.1038/sj.jid.5700078 PG 3 WC Dermatology SC Dermatology GA 062TV UT WOS:000238968400023 PM 16374456 ER PT J AU Middelkamp-Hup, MA Park, HY Lee, J Gilchrest, BA Gonzalez, S AF Middelkamp-Hup, Maritza A. Park, H. -Y. Lee, Jin Gilchrest, Barbara A. Gonzalez, Salvador TI Detection of UV-induced pigmentary and epidermal changes over time using in vivo reflectance confocal microscopy SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID GUINEA-PIG SKIN; SCANNING LASER MICROSCOPY; MELANOCYTES; MODEL; INCREASE; MELANIN AB In vivo reflectance confocal microscopy (RCM) provides high-resolution optical sections of the skin in its native state, without needing to fix or section the tissue. Melanin provides an excellent contrast for RCM, giving a bright signal in the confocal images. The pigmented guinea-pig is a common animal model to study human pigment induction and modulation, as its tanning response is comparable to human tanning after exposure to ultraviolet radiation (UVR). We investigated the applicability of RCM to detecting UVR-induced pigmentary changes in this model. Animals were exposed to solar simulator radiation for 7 days. RCM was performed during the irradiation and follow-up period. Compared to non-irradiated skin, an increase in melanocyte size, dendricity, and number, as well as increased pigment in keratinocytes, was seen in the irradiated epidermis. Interestingly, these changes could be detected even before a tanning response was clinically visible. UVR-induced epidermal hyperplasia could also be detected and quantified. In conclusion, in vivo RCM is a sensitive non-invasive imaging technique that can repeatedly measure epidermal pigmentation and thickness, as demonstrated in the guinea-pig model. This technique should greatly enhance our appreciation of dynamic pigmentary changes in human or animal skin over time and in response to specific stimuli. C1 Mem Sloan Kettering Canc Ctr, Dermatol Serv, New York, NY 10022 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed,Dept Dermatol, Boston, MA USA. Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02118 USA. RP Gonzalez, S (reprint author), Mem Sloan Kettering Canc Ctr, Dermatol Serv, Rockefeller Pavil,160 E 53rd St,2nd Floor, New York, NY 10022 USA. EM gonzals6@mskcc.org NR 20 TC 21 Z9 22 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD FEB PY 2006 VL 126 IS 2 BP 402 EP 407 DI 10.1038/sj.jid.5700055 PG 6 WC Dermatology SC Dermatology GA 062TV UT WOS:000238968400024 PM 16374468 ER PT J AU Young, HS Summers, AM Read, IR Fairhurst, DA Plant, DJ Campalani, E Smith, CH Barker, JNWN Detmar, MJ Brenchley, PEC Griffiths, CEM AF Young, Helen S. Summers, Angela M. Read, Ian R. Fairhurst, David A. Plant, Darren J. Campalani, Emanuela Smith, Catherine H. Barker, Jonathan N. W. N. Detmar, Michael J. Brenchley, Paul E. C. Griffiths, Christopher E. M. TI Interaction between genetic control of vascular endothelial growth factor production and retinoid responsiveness in psoriasis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID HUMAN KERATINOCYTES; FACTOR VEGF; ANGIOGENESIS; POLYMORPHISMS; SKIN; PROLIFERATION; ASSIGNMENT; REGIONS; POTENT; CELLS AB Vascular endothelial growth factor (VEGF) promotes angiogenesis, and elevated levels are found in plaques of psoriasis. Two VEGF polymorphisms, + 405 and - 460, are associated with early-onset psoriasis and are close to the functional activator protein-1 site (+ 419) through which retinoids, an established systemic therapy for psoriasis, can block production of VEGF. We report that peripheral blood mononuclear cells (PBMCs) and epidermal keratinocytes (KC) from patients with psoriasis demonstrate differential, genotype-dependent, regulation of VEGF. For PBMCs, VEGF genotype distinguishes two groups of patients with psoriasis - "high and low VEGF producers'' (P < 0.001). In contrast, KC production of VEGF is not genotype dependent. However, the effects of all-trans retinoic acid (RA) on cellular expression of VEGF are determined by both cell type and genotype. RA inhibits KC production of VEGF in a genotype-dependent manner (P < 0.005) whereas RA stimulates PBMCs production irrespective of VEGF genotype (P < 0.001). We also report that the -460 VEGF polymorphism appears to have a clinical pharmacogenetic role in predicting response or non-response of psoriasis to acitretin (P = 0.01). In future, determination of VEGF gene polymorphisms and thus individual patient VEGF "signatures'' may be used as a prognostic factor for psoriasis susceptibility/severity and as a means for optimizing treatment response. C1 Univ Manchester, Hope Hosp, Dermatol Ctr, Sch Med, Salford M6 8HD, Lancs, England. Manchester Royal Infirm, Inst Nephrol & Transplantat, Manchester M13 9WL, Lancs, England. St Thomas Hosp, St Johns Inst Dermatol, London, England. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cutaneous Biol Res Ctr, Boston, MA USA. RP Young, HS (reprint author), Univ Manchester, Hope Hosp, Dermatol Ctr, Sch Med, Stott Lane, Salford M6 8HD, Lancs, England. EM helen_s_young@hotmail.com RI Smith, Catherine/G-5268-2012; Griffiths, Christopher/P-5448-2014; Young, Helen/H-5247-2015; OI Smith, Catherine/0000-0001-9918-1144; Griffiths, Christopher/0000-0001-5371-4427; Young, Helen/0000-0003-1538-445X; Brenchley, Paul/0000-0003-1290-9919 FU Wellcome Trust NR 36 TC 63 Z9 67 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD FEB PY 2006 VL 126 IS 2 BP 453 EP 459 DI 10.1038/sj.jid.5700096 PG 7 WC Dermatology SC Dermatology GA 062TV UT WOS:000238968400030 PM 16385345 ER PT J AU Purnell, JQ Bland, LB Garzotto, M Lemmon, D Wersinger, EM Ryan, CW Brunzell, JD Beer, TM AF Purnell, JQ Bland, LB Garzotto, M Lemmon, D Wersinger, EM Ryan, CW Brunzell, JD Beer, TM TI Effects of transdermal estrogen on levels of lipids, lipase activity, and inflammatory markers in men with prostate cancer SO JOURNAL OF LIPID RESEARCH LA English DT Article DE estradiol; apolipoprotein; inflammation; androgen deprivation therapy ID ANDROGEN DEPRIVATION THERAPY; HORMONE REPLACEMENT THERAPY; RANDOMIZED CONTROLLED-TRIAL; CORONARY-HEART-DISEASE; POSTMENOPAUSAL WOMEN; PLASMA-LIPOPROTEINS; ESTRAMUSTINE PHOSPHATE; PARENTERAL ESTROGEN; SERUM-CHOLESTEROL; BODY-COMPOSITION AB Androgen deprivation therapy (ADT) for prostate cancer is now used in earlier disease stages and as adjuvant treatment. Recognizing and reducing the toxicity of this therapy, including worsened lipid levels and cardiovascular disease (CVD) risks, has become an important clinical concern. Oral estrogen therapy induces hypogonadism and mitigates many side effects of ADT, but has a high thrombosis risk. Transdermal estrogen therapy (TDE) has a lower thrombosis risk than oral estrogen and may improve CVD risk compared with ADT. This prospective pilot study of 18 men with androgen-independent prostate cancer receiving ADT measured effects of TDE on lipid and inflammatory CVD risk factors before and after 8 weeks of TDE ( estradiol 0.6 mg/day). During treatment, estradiol levels rose 17-fold; total cholesterol, LDL cholesterol, and apolipoprotein B levels decreased. HDL2 cholesterol increased, with no changes in triglyceride or VLDL cholesterol levels. Dense LDL cholesterol decreased and LDL buoyancy increased in association with a decrease in HL activity. Highly sensitive C-reactive protein levels and other inflammatory markers did not worsen. Compared with ADT, short-term TDE therapy of prostate cancer improves lipid levels without deterioration of CVD-associated inflammatory markers and may, on longer-term follow-up, improve CVD and mortality rates.-Purnell, J. Q., L. B. Bland, M. Garzotto, D. Lemmon, E. M. Wersinger, C. W. Ryan, J. D. Brunzell, and T. M. Beer. Effects of transdermal estrogen on levels of lipids, lipase activity, and inflammatory markers in men with prostate cancer. C1 Oregon Hlth Sci Univ, Dept Med, Div Endocrinol Diabet & Clin Nutr, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Ctr Study Weight Regulat, Portland, OR 97239 USA. Portland VA Med Ctr, Div Urol, Portland, OR 97239 USA. Portland VA Med Ctr, Div Hematol & Med Oncol, Portland, OR 97239 USA. Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. RP Purnell, JQ (reprint author), Oregon Hlth Sci Univ, Dept Med, Div Endocrinol Diabet & Clin Nutr, Portland, OR 97239 USA. EM purnellj@ohsu.edu FU NCRR NIH HHS [M01 RR00334]; NHLBI NIH HHS [R01 HL-64322]; NIDDK NIH HHS [R03-DK-61996, K23-DK-02689]; PHS HHS [03-3839-504384] NR 55 TC 15 Z9 17 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD FEB PY 2006 VL 47 IS 2 BP 349 EP 355 DI 10.1194/jlr.M500276-JLR200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 005SS UT WOS:000234844700011 PM 16299398 ER PT J AU Schneider, PL Bramstedt, KA AF Schneider, PL Bramstedt, KA TI When psychiatry and bioethics disagree about patient decision making capacity (DMC) SO JOURNAL OF MEDICAL ETHICS LA English DT Article ID CONSULTATION-LIAISON PSYCHIATRY; CLINICAL ETHICS AB The terms "competency'' and "decision making capacity'' (DMC) are often used interchangeably in the medical setting. Although competency is a legal determination made by judges, "competency'' assessments are frequently requested of psychiatrists who are called to consult on hospitalised patients who refuse medical treatment. In these situations, the bioethicist is called to consult frequently as well, sometimes as a second opinion or "tie breaker''. The psychiatric determination of competence, while a clinical phenomenon, is based primarily in legalism and can be quite different from the bioethics approach. This discrepancy highlights the difficulties that arise when a patient is found to be "competent'' by psychiatry but lacking in DMC by bioethics. Using a case, this dilemma is explored and guidance for reconciling the opinions of two distinct clinical specialties is offered. C1 Univ Calif Los Angeles, Sch Med, Bioeth Comm, Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Cleveland Clin Fdn, Dept Bioeth, Cleveland, OH 44195 USA. RP Schneider, PL (reprint author), Univ Calif Los Angeles, Sch Med, Bioeth Comm, Vet Adm Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM Paul.Schneider@med.va.gov NR 7 TC 15 Z9 16 U1 0 U2 5 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0306-6800 J9 J MED ETHICS JI J. Med. Ethics PD FEB 1 PY 2006 VL 32 IS 2 BP 90 EP 93 DI 10.1136/jme.2005.013136 PG 4 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 007XF UT WOS:000235004000007 PM 16446413 ER PT J AU Blackard, JT Komurian-Pradel, F Perret, M Sodoyer, M Smeaton, L St Clair, JB Chapman, S Taylor, LE Paranhos-Baccala, G Chung, RT AF Blackard, JT Komurian-Pradel, F Perret, M Sodoyer, M Smeaton, L St Clair, JB Chapman, S Taylor, LE Paranhos-Baccala, G Chung, RT TI Intrahepatic cytokine expression is downregulated during HCV/HIV co-infection SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE hepatitis C virus; human immunodeficiency virus; co-infection; liver; antiretroviral therapy ID HEPATITIS-C VIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; MESSENGER-RNA EXPRESSION; ALPHA-2A PLUS RIBAVIRIN; NECROSIS-FACTOR-ALPHA; REAL-TIME PCR; ANTIRETROVIRAL THERAPY; LIVER-DISEASE; INTERFERON THERAPY; INFECTED PATIENTS AB HIV co-infection is associated with reduced HCV treatment response rates and accelerated HCV-related liver disease. Cytokines play an important role in regulating hepatic inflammation and fibrogenesis during chronic HCV infection, yet the roles of HIV and/or its therapies on cytokine expression are unknown. Total RNA was extracted from liver biopsies of 12 HCV monoinfected and 14 HCV/HIV co-infected persons. We used real-time PCR to quantify cytokines that contribute to innate and adaptive immune responses, including IFN alpha., IFN gamma, TNF alpha, TGF beta(1), IL-2, IL-4, IL-8, IL-10, and IL-12p40. Positive- and negative-strand HCV RNA levels were quantified using a molecular beacon approach. Detection of positive-strand HCV RNA was 100% in both groups; negative-strand HCV RNA was detected in four (33%) HCV mono-infected persons and in nine (64%) HCV/HIV co-infected persons. Median strand-specific HCV RNA levels were not significantly different between the two groups. Detection rates of cytokine mRNAs were lower for the HCV/HIV co-infected group compared to the HCV mono-infected group; the detection rates for TNF alpha, IL-8, and IL-10 were statistically significant. Overall, cytokine mRNA quantities were lower for HCV/HIV co-infected compared to HCV monoinfected persons, with the exception of TGF beta(1). These data suggest that a defect in cytokine activation may occur in HCV/HIV co-infected persons that limits efficient clearance of HCV from the liver. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. CNRS BioMetrieux, UMR2714, IFR 128 BioSci Lyon Gerland, Lyon, France. Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. Miriam Hosp, Providence, RI 02906 USA. Brown Univ, Sch Med, Dept Med, Providence, RI 02912 USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, GRJ 825, Boston, MA 02114 USA. EM rtchung@partners.org FU NIAID NIH HHS [P30-AI42851] NR 36 TC 24 Z9 25 U1 2 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD FEB PY 2006 VL 78 IS 2 BP 202 EP 207 DI 10.1002/jmv.20528 PG 6 WC Virology SC Virology GA 001LA UT WOS:000234533400009 PM 16372286 ER PT J AU Li, J Harris, L Mamon, H Kulke, MH Zhu, WH Zhu, P Makrigiorgos, GM AF Li, J Harris, L Mamon, H Kulke, MH Zhu, WH Zhu, P Makrigiorgos, GM TI Whole genome amplification of plasma-circulating DNA enables expanded screening for allelic imbalance in plasma SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Article ID BREAST-CANCER PATIENTS; LIQUID-CHROMATOGRAPHY DHPLC; SQUAMOUS-CELL CARCINOMA; P53 MUTATION ANALYSIS; TUMOR DNA; MICROSATELLITE ALTERATIONS; DISPLACEMENT AMPLIFICATION; GENETIC ALTERATIONS; COLORECTAL-CANCER; SERUM DNA AB Apoptotic and necrotic tumor cells release DNA into plasma, providing an accessible tumor biomarker. Tumor-released plasma-circulating DNA can be screened for tumor specific genetic changes, including mutation, methylation, or allelic imbalance. However, technical problems relating to the quantity and quality of DNA collected from plasma hinder downstream genetic screening and reduce biomarker detection sensitivity. Here, we present a new methodology, blunt-end ligation-mediated whole genome amplification (BL-WGA), that efficiently amplifies small apoptotic fragments (< 200 bp) as well as intermediate and large necrotic fragments (> 5 kb) and enables reliable high-throughput analysis of plasma-circulating DNA. In a single-tube reaction, purified double-stranded DNA was blunted with T4 DNA polymerase, self-ligated or cross-ligated with T4 DNA ligase and amplified via random primer initiated multiple displacement amplification. Using plasma DNA from breast cancer patients and normal controls, we demonstrate that BL-WGA amplified the plasma-circulating genome by similar to 1000-fold Of 25 informative polymorphic sites screened via polymerase chain reaction-denaturating high-performance liquid chromatography, 24 (95%) were correctly determined by BL-WGA to be allelic retention or imbalance compared to 44% by multiple displacement amplification. By enabling target magnification and application of high-throughput genome analysis, BL-WGA improves sensitivity for detection of circulating tumor-specific biomarkers from bodily fluids or for recovery of nucleic acids from suboptimally stored specimens. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Makrigiorgos, GM (reprint author), Brigham & Womens Hosp, Dana Farber Brigham & Womens Canc Ctr, 75 Francis St,Level L2, Boston, MA 02115 USA. EM mmakrigiorgos@partners.org FU NCI NIH HHS [R21 CA115439, CA111994-01A1, R21 CA111994] NR 49 TC 18 Z9 20 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD FEB PY 2006 VL 8 IS 1 BP 22 EP 30 DI 10.2353/jmoldx.2006.050074 PG 9 WC Pathology SC Pathology GA 011CK UT WOS:000235245100004 PM 16436631 ER PT J AU Belofsky, G Carreno, R Lewis, K Ball, A Casadei, G Tegos, GP AF Belofsky, G Carreno, R Lewis, K Ball, A Casadei, G Tegos, GP TI Metabolites of the "Smoke tree", Dalea spinosa, potentiate antibiotic activity against multidrug-resistant Staphylococcus aureus SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID FLUOROQUINOLONE RESISTANCE; MELILOTUS-ALBA; CONSTITUENTS; PTEROCARPAN; ISOFLAVONES; BACTERIA; EFFLUX; ROOTS AB Two new 2-arylbenzofuran aldehydes (1 and 2) and three known phenolic compounds (3-5) were isolated from organic extracts of Dalea spinosa. These compounds were evaluated for their intrinsic antimicrobial activity and. their ability to perform as multidrug-resistance inhibitors by potentiating the activity of known antimicrobials against a variety of pathogenic microorganisms. Compound 1 and its acetate derivative 6 exhibited no direct antimicrobial activity but enhanced the effect of the weak plant antimicrobial berberine when tested against Staphylococcus aureus. Additional potentiation assays with S. aureus overexpression and knockout isogenic efflux mutants for the NorA pump were done in order to assess whether the potentiating effects were associated with inhibition of this known pump mechanism. C1 Univ Tulsa, Dept Chem & Biochem, Tulsa, OK 74101 USA. Northeastern Univ, Dept Biol, Boston, MA 02115 USA. Univ Teramo, Dept Food Sci, Sch Vet Med, I-64100 Teramo, Italy. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, Boston, MA 02114 USA. RP Belofsky, G (reprint author), Univ Tulsa, Dept Chem & Biochem, Tulsa, OK 74101 USA. EM gbelofskv@efficas.com RI Tegos, George/C-8830-2011 FU NIAID NIH HHS [R21AI059483] NR 24 TC 34 Z9 37 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD FEB PY 2006 VL 69 IS 2 BP 261 EP 264 DI 10.1021/np050857s PG 4 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 020WH UT WOS:000235943400016 PM 16499327 ER PT J AU Vanderwerker, LC Jacobs, SC Parkes, CM Prigerson, HG AF Vanderwerker, LC Jacobs, SC Parkes, CM Prigerson, HG TI An exploration of associations between separation anxiety in childhood and complicated grief in later life SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE grief; bereavement; separation anxiety; attachment ID PANIC-AGORAPHOBIC SPECTRUM; TRAUMATIC GRIEF; BEREAVEMENT; ATTACHMENT; SYMPTOMS; RISK AB Recent studies have suggested that the vulnerability to complicated grief (CG) may be rooted in insecure attachment styles developed in childhood. The aim of this study was to examine the etiologic relevance of childhood separation anxiety (CSA) to the onset of CG relative to major depressive disorder, posttraumatic stress disorder, and generalized anxiety disorder in bereaved individuals. The Structured Clinical Interview for the DSM-IV, Inventory of Complicated Grief-Revised, and CSA items from the Panic Agoraphobic Spectrum Questionnaire were administered to 283 recently bereaved community-dwelling residents at an average of 10.6 months postloss. CSA was significantly associated with CG (OR = 3.2; 95% CI, 1.2-8.9), adjusting for sex, level of education, kinship relationship to the deceased, prior history of psychiatric disorder, and history of childhood abuse. CSA was not significantly associated with major depressive disorder, posttraumatic stress disorder, or generalized anxiety disorder. C1 Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Psychiat, Brigham & Womens Hosp, Boston, MA 02115 USA. Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. St Christophers Hospice, Sydenham, England. St Josephs Hosp, Hackney, England. RP Prigerson, HG (reprint author), Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, 44 Binney St,SW G440A, Boston, MA 02215 USA. FU NCI NIH HHS [R01 CA106370, CA106370]; NIMH NIH HHS [MH56529, MH63892] NR 17 TC 40 Z9 42 U1 3 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD FEB PY 2006 VL 194 IS 2 BP 121 EP 123 DI 10.1097/01.nmd.0000198146.28182.d5 PG 3 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 014OE UT WOS:000235488700008 PM 16477190 ER PT J AU Bambauer, KZ Prigerson, HG AF Bambauer, KZ Prigerson, HG TI The stigma receptivity scale and its association with mental health service use among bereaved older adults SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE stigma; mental health; bereavement; widowhood; health services utilization ID CARE AB The purpose of this article was to determine whether the Stigma Receptivity Scale (SRS) predicts use of mental health services among community-dwelling bereaved older adults. We analyzed interviews of 135 people in Connecticut to evaluate whether three subscales and 12 SRS items were associated with access to any mental health service in the past 60 days using logistic regression analysis. Two SRS items predicted recent use of mental health services among bereaved individuals with and without complicated grief. receptivity to a bereavement support group (adjusted OR = 5.14; 95% CI, 1.11, 23.85) and individuals who were not concerned about meeting criteria for a mental illness (adjusted OR = 0.07; 95% CI, 0.01, 0.58). The SRS significantly predicted recent access to mental health treatment among bereaved elderly people. This type of measure could be used to determine those most likely in need of education and support to increase their likelihood of accessing mental health services. C1 Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02115 USA. Harvard Pilgrim Hlth Care, Boston, MA USA. RP Prigerson, HG (reprint author), Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, 44 Binney St,SW G440A, Boston, MA 02115 USA. FU NCI NIH HHS [R01 CA106370-02, R01 CA106370, R01 CA106370-01, R01 CA106370-03, R01 CA106370-04]; NIMH NIH HHS [R01 MH056529, R01 MH056529-01A2, R01 MH056529-02, R01 MH056529-03, R01 MH063892, R01 MH063892-01A1, R01 MH063892-02] NR 10 TC 18 Z9 18 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD FEB PY 2006 VL 194 IS 2 BP 139 EP 141 DI 10.1097/01.nmd.0000198200.20936.03 PG 3 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 014OE UT WOS:000235488700013 PM 16477195 ER PT J AU Zhai, GG Malhotra, R Delaney, M Latham, D Nestler, U Zhang, M Mukherjee, N Song, QH Robe, P Chakravarti, A AF Zhai, GG Malhotra, R Delaney, M Latham, D Nestler, U Zhang, M Mukherjee, N Song, QH Robe, P Chakravarti, A TI Radiation enhances the invasive potential of primary glioblastoma cells via activation of the rho signaling pathway SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE glioblastoma; invasion; motility; radiation; Rho ID PANCREATIC-CANCER CELLS; PLASMINOGEN-ACTIVATOR; PHOSPHATIDYLINOSITOL 3-KINASE; MATRIX METALLOPROTEINASES; MEDIATES RESISTANCE; MALIGNANT GLIOMAS; GTPASES; UROKINASE; MOTILITY; CDC42 AB Glioblastoma multiforme (GBM) is among the most treatment-refractory of all human tumors. Radiation is effective at prolonging survival of GBM patients; however, the vast majority of GBM patients demonstrate progression at or near the site of original treatment. We have identified primary GBM cell lines that demonstrate increased invasive potential upon radiation exposure. As this represents a novel mechanism by which radiation-treated GBMs can fail therapy, we further investigated the identity of downstream signaling molecules that enhance the invasive phenotype of irradiated GBMs. Matrigel matrices were used to compare the extent of invasion of irradiated vs. non-irradiated GBM cell lines UN3 and GM2. The in vitro invasive potential of these irradiated cells were characterized in the presence of both pharmacologic and dominant negative inhibitors of extracellular matrix and cell signaling molecules including MMP, uPA, IGFR, EGFR, PI-3K, AKT, and Rho kinase. The effect of radiation on the expression of these signaling molecules was determined with Western blot assays. Ultimately, the in vitro tumor invasion results were confirmed using an in vivo 9L GBM model in rats. Using the primary GBM cell lines UN3 and GM2, we found that radiation enhances the invasive potential of these cells via activation of EGFR and IGFR1. Our findings suggest that activation of Rho signaling via PI-3K is required for radiation-induced invasion, although not required for invasion under physiologic conditions. This report clearly demonstrates that radiation-mediated invasion is fundamentally distinct from invasion under normal cellular physiology and identifies potential therapeutic targets to overcome this phenomenon. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Chakravarti, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Founders House,Room 536, Boston, MA 02114 USA. EM achakravarti@partner.org RI Nestler, Ulf/D-6503-2014; OI Nestler, Ulf/0000-0002-2963-4344; Mukherjee, Neelanjan/0000-0003-0017-1400; Malhotra, Rajeev/0000-0003-0120-4630 FU NCI NIH HHS [KO882163CA] NR 42 TC 70 Z9 72 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD FEB PY 2006 VL 76 IS 3 BP 227 EP 237 DI 10.1007/s11060-005-6499-4 PG 11 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 026ZI UT WOS:000236381800002 PM 16200346 ER PT J AU Ryu, H Smith, K Camelo, SI Carreras, I Lee, J Iglesias, AH Dangond, F Cormier, KA Cudkowicz, ME Brown, RH Ferrante, RJ AF Ryu, H Smith, K Camelo, SI Carreras, I Lee, J Iglesias, AH Dangond, F Cormier, KA Cudkowicz, ME Brown, RH Ferrante, RJ TI Sodium phenylbutyrate prolongs survival and regulates expression of anti-apoptotic genes in transgenic amyotrophic lateral sclerosis mice (vol 93, pg 1087, 2005) SO JOURNAL OF NEUROCHEMISTRY LA English DT Correction C1 Bedford VA Med Ctr, Ctr Geriatr Res Educ & Clin, Bedford, MA 01730 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol,Lab Transcript & Immune Regulat, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Days Neuromuscular Labs, Charlestown, MA USA. RP Ryu, H (reprint author), Bedford VA Med Ctr, Ctr Geriatr Res Educ & Clin, Bedford, MA 01730 USA. NR 1 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD FEB PY 2006 VL 96 IS 3 BP 908 EP 908 DI 10.1111/j.1471-4159.2005.03447.x PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 003GV UT WOS:000234670700027 ER PT J AU Oshima, M Maruta, T Ohtani, M Deitiker, PR Mosier, DR Atassi, MZ AF Oshima, M Maruta, T Ohtani, M Deitiker, PR Mosier, DR Atassi, MZ TI Vaccination with a MHC class II peptide in Alum and inactive pertussis strongly ameliorates clinical MG in C57BL/6 mice SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE antigen presentation; autoimmunity; MHC; immunotherapy; EAMG ID AUTOIMMUNE MYASTHENIA-GRAVIS; RECEPTOR-ALPHA-SUBUNIT; CALIFORNICA ACETYLCHOLINE-RECEPTOR; T-CELL RECOGNITION; IN-VITRO; SYNTHETIC PEPTIDES; EPITOPE; CHAIN; SUPPRESSION; LYMPHOCYTES AB We have investigated the efficacy of immunization against peptides from predisposing MHC class II molecules in human-compatible adjuvants for ameliorating experimental autoimmune myasthenia gravis (EAMG). C57BL/6 mice were immunized three times with the peptide I-A beta(b)62-76 in Alum + killed pertussis organisms (PT) prior to two injections with tAChR. The treatment greatly reduced the occurrence and severity of clinical MG relative to controls that received saline/Alum + PT or none. It also reduced antibody and T-cell responses against tAChR. The results have important implications for the possible immunotherapy of MG by targeting disease-associated MHC. (c) 2005 Elsevier B.V. All rights reserved. C1 Baylor Coll Med, Dept Biochem & Mol Biol, Houston, TX 77030 USA. Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. Baylor Coll Med, Dept Immunol, Houston, TX 77030 USA. ME DeBakey VA Med Ctr, Neurol & Med Res Serv, Houston, TX 77030 USA. RP Oshima, M (reprint author), Baylor Coll Med, Dept Biochem & Mol Biol, 1 Baylor Plaza, Houston, TX 77030 USA. EM moshima@bcm.tmc.edu NR 46 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD FEB PY 2006 VL 171 IS 1-2 BP 8 EP 16 DI 10.1016/j.jneuroim.2005.09.015 PG 9 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 009LW UT WOS:000235114500002 PM 16271400 ER PT J AU Bohnen, NI Kaufer, DI Hendrickson, R Ivanco, LS Lopresti, BJ Constantine, GM Mathis, CA Davis, JG Moore, RY DeKosky, ST AF Bohnen, NI Kaufer, DI Hendrickson, R Ivanco, LS Lopresti, BJ Constantine, GM Mathis, CA Davis, JG Moore, RY DeKosky, ST TI Cognitive correlates of cortical cholinergic denervation in Parkinson's disease and parkinsonian dementia SO JOURNAL OF NEUROLOGY LA English DT Article DE acetylcholinesterase; cognitive; dementia; Parkinson's disease; positron emission tomography ID CEREBRAL ACETYLCHOLINESTERASE ACTIVITY; POSITRON-EMISSION-TOMOGRAPHY; ALZHEIMERS-DISEASE; IN-VIVO; NUCLEUS BASALIS; MEYNERT; BRAIN; DYSFUNCTION; PROPIONATE; DEFICITS AB We recently reported findings that loss of cortical acetylcholinesterase (AChE) activity is greater in parkinsonian dementia than in Alzheimer's disease (AD). In this study we determined cognitive correlates of in vivo cortical AChE activity in patients with parkinsonian dementia (PDem, n = 11), Parkinson's disease without dementia (PD, n = 13), and in normal controls (NC, n = 14) using N-C-11]methyl-piperidin-4-yl propionate ([C-11]PMP) AChE positron emission tomography (PET). Cortical AChE activity was significantly reduced in the PDem (-20.9%) and PD (-12.7 %) subjects (P < 0.001) when compared with the control subjects. Analysis of the cognitive data within the patient groups demonstrated that scores on the WAIS-III Digit Span, a test of working memory and attention, had most robust correlation with cortical AChE activity (R = 0.61, p < 0.005). There were also significant correlations between cortical AChE activity and other tests of attentional and executive functions, such as the Trail Making and Stroop Color Word tests. There was no significant correlation between cortical AChE activity and duration of motor disease (R = -0.01, ns) or severity of parkinsonian motor symptoms (R = 0.14, ns). We conclude that cortical cholinergic denervation in PD and parkinsonian dementia is associated with decreased performance on tests of attentional and executive functioning. C1 Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Radiol, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Univ Pittsburgh, Dept Math & Stat, Pittsburgh, PA 15213 USA. RP Bohnen, NI (reprint author), Univ Pittsburgh, Dept Neurol, Liliane S Kaufmann Bldg,Suite 811,3471 5th Ave, Pittsburgh, PA 15213 USA. EM nbohnen@pitt.edu RI Bohnen, Nicolaas/A-1312-2007; Mathis, Chester/A-8607-2009 FU NIA NIH HHS [AG05133] NR 43 TC 140 Z9 146 U1 3 U2 15 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY SN 0340-5354 J9 J NEUROL JI J. Neurol. PD FEB PY 2006 VL 253 IS 2 BP 242 EP 247 DI 10.1007/s00415-005-0971-0 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 013ZP UT WOS:000235448800016 PM 16133720 ER PT J AU Lopez, OL Becker, JT Jagust, WJ Fitzpatrick, A Carlson, MC DeKosky, ST Breitner, J Lyketsos, CG Jones, B Kawas, C Kuller, LH AF Lopez, OL Becker, JT Jagust, WJ Fitzpatrick, A Carlson, MC DeKosky, ST Breitner, J Lyketsos, CG Jones, B Kawas, C Kuller, LH TI Neuropsychological characteristics of mild cognitive impairment subgroups SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article ID CARDIOVASCULAR HEALTH; MEMORY IMPAIRMENT; ALZHEIMERS-DISEASE; DEMENTIA; PREVALENCE; POPULATION; CLASSIFICATION; QUESTIONNAIRE; PERFORMANCE; DECLINE AB Objective: To describe the neuropsychological characteristics of mild cognitive impairment (MCI) subgroups identified in the Cardiovascular Health Study (CHS) cognition study. Methods: MCI was classified as MCI-amnestic type (MCI-AT): patients with documented memory deficits but otherwise normal cognitive function; and MCI-multiple cognitive deficits type (MCI-MCDT): impairment of at least one cognitive domain (not including memory), or one abnormal test in at least two other domains, but who had not crossed the dementia threshold. The MCI subjects did not have systemic, neurological, or psychiatric disorders likely to affect cognition. Results: MCI-AT (n = 10) had worse verbal and non-verbal memory performance than MCI-MCDT (n = 28) or normal controls (n = 374). By contrast, MCI-MCDT had worse language, psychomotor speed, fine motor control, and visuoconstructional function than MCI-AT or normal controls. MCI-MCDT subjects had memory deficits, though they were less pronounced than in MCI-AT. Of the MCI-MCDT cases, 22 (78.5%) had memory deficits, and 6 (21.5%) did not. MCI-MCDT with memory disorders had more language deficits than MCI-MCDT without memory disorders. By contrast, MCI-MCDT without memory deficits had more fine motor control deficits than MCI-MCDT with memory deficits. Conclusions: The most frequent form of MCI was the MCI-MCDT with memory deficits. However, the identification of memory impaired MCI groups did not reflect the true prevalence of MCI in a population, as 16% of all MCI cases and 21.5% of the MCI-MCDT cases did not have memory impairment. Study of idiopathic amnestic and non-amnestic forms of MCI is essential for an understanding of the aetiology of MCI. C1 Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. Univ Calif Berkeley, Dept Neurol, Berkeley, CA 94720 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Mental Hyg, Baltimore, MD USA. Johns Hopkins Univ, Dept Psychiat, Baltimore, MD USA. Wake Forest Univ, Dept Psychiat, Winston Salem, NC 27109 USA. Univ Calif Irvine, Dept Neurol, Irvine, CA 92717 USA. RP Lopez, OL (reprint author), 3501 Forbes Ave,Suite 830,Oxford Bldg, Pittsburgh, PA 15213 USA. EM lopezol@upmc.edu FU NHLBI NIH HHS [N01-HC-15103, N01-HC-35129, N01-HC-85079, N01-HC-85086]; NIA NIH HHS [R56 AG020098, AG15928, AG20098, R01 AG015928, R01 AG020098]; NIMH NIH HHS [MH07033] NR 51 TC 88 Z9 91 U1 2 U2 6 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD FEB PY 2006 VL 77 IS 2 BP 159 EP 165 DI 10.1136/jnnp.2004.045567 PG 7 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 011QY UT WOS:000235284400008 PM 16103044 ER PT J AU Santos, TM Han, S Bowser, M Sazani, K Beauchamp, RL Murthy, V Bhide, PG Ramesh, V AF Santos, TM Han, S Bowser, M Sazani, K Beauchamp, RL Murthy, V Bhide, PG Ramesh, V TI Alternative splicing in protein associated with Myc (Pam) influences its binding to c-Myc SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE tuberous sclerosis complex; tuberin; axons; HIW ID DEVELOPMENTAL EXPRESSION; HAMARTIN; RPM-1; INHIBITION; ORTHOLOG; ELEGANS; TUBERIN; GENE AB We recently identified Pam (for protein associated with c-Myc), as a binding partner for the tuberous sclerosis complex (TSC) protein tuberin in brain. The highly conserved Pam homologs in Drosophila and C. elegans are neuron-specific proteins that regulate synaptic growth. The Pam gene contains 83 exons and encodes a 4,641-amino-acid polypeptide with a predicted molecular weight of similar to 510 kDa. In a previous study, we demonstrated that Pam is expressed as two forms, similar to 450 kDa in rat embryonic and a similar to 350 kDa in rat adult brain. Here we have extended that work to show the similar to 450 kDa form is expressed in rat embryonic kidney, heart, and lung and in rat cell lines, and the similar to 350 kDa form is expressed in adult rat tissues as well as in human and mouse brain and human and mouse cell lines. To understand the size difference, we investigated alternative splicing of Pam in brain and detected six isoforms in the Myc-binding region resulting from splicing of exon 53, and three new exons, 52A, 56, and 56A. We also demonstrate that the presence of exon 52A in Pam significantly enhances binding to Myc, suggesting functional importance of this alternative splicing. The presence of Pam in many cellular compartments, its spliced variants, as well as its multiple binding partners, including tuberin, make it a complex, yet intriguing protein in the nervous system. (C) 2005 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Ctr Human Genet Res, Mol Neurogenet Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Charlestown, MA USA. RP Ramesh, V (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Mol Neurogenet Unit, 185 Cambridge St,Room 5232, Boston, MA 02114 USA. EM ramesh@helix.mgh.harvard.edu OI Bhide, Pradeep/0000-0003-4236-9415 FU NINDS NIH HHS [NS24279, NS41917] NR 20 TC 10 Z9 10 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD FEB 1 PY 2006 VL 83 IS 2 BP 222 EP 232 DI 10.1002/jnr.20723 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 013UC UT WOS:000235434300006 PM 16342205 ER PT J AU Rattan, R Giri, S Singh, AK Singh, I AF Rattan, R Giri, S Singh, AK Singh, I TI Rho/ROCK pathway as a target of tumor therapy SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE statin; Rho GTPases; tumor; apoptosis; ROCK ID LOVASTATIN-INDUCED APOPTOSIS; 3-HYDROXY-3-METHYLGLUTARYL-COENZYME-A REDUCTASE INHIBITORS; SMOOTH-MUSCLE-CELLS; PROTEIN-KINASE; GLIOMA-CELLS; RHO-GTPASES; HEPATOCELLULAR-CARCINOMA; ACTIN CYTOSKELETON; GROWTH-INHIBITION; INDUCE APOPTOSIS AB This study emphasizes the importance of Rho/ROCK pathway in lovastatin-induced apoptosis as replenishment with exogenous isoprenoid, geranylgeranylpyrophosphate (GGPP), resulted in inhibition of apoptosis in cultured tumor cells. Treatment of C6 glioma cells with Toxin B and exoenzyme C3 resulted in cell death suggesting the role of geranylgeranylated protein(s) in the survival of glioma cells. Relative apoptotic death observed in cells transfected with dominant negative constructs of RhoA, Rac, and cdc42 imply Rho A as playing the major role in cell survival. Furthermore, the inhibition of Rho A kinase (ROCK), a direct downstream effector of Rho A, by Y-27632 or dominant negative of ROCK, induced apoptosis in glioma cells. These findings indicate that RhoA/ROCK pathway is involved negatively in the regulation of glioma cell death pathway. Moreover, in vivo studies of lovastatin treatment in animals implanted with C6 glioma cell tumors also resulted in smaller tumor size and induced apoptosis in the tumor tissue. The implantation of stably transfected C6 glioma cells with expression vector of C3 exoenzyme, dominant negative of RhoA and ROCK, resulted in significant smaller tumor mass, further establishing the importance of geranylgeranylated proteins, specifically RhoA and its downstream effecter ROCK, in cell survival and tumor genesis (C) 2005 Wiley-Liss, Inc. C1 Med Univ S Carolina, Childrens Res Inst, Dept Pediat, Charleston, SC 29425 USA. Ralph Johnson Vet Affairs Med Ctr, Dept Pathol & Lab Med, Charleston, SC USA. RP Singh, I (reprint author), Med Univ S Carolina, Childrens Res Inst, Dept Pediat, 173 Ashley Ave,509, Charleston, SC 29425 USA. EM singhi@musc.edu FU NCRR NIH HHS [C06 RR018823]; NINDS NIH HHS [NS 37766, NS-22576, NS-34741, NS-40144, NS-40810] NR 68 TC 50 Z9 58 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD FEB 1 PY 2006 VL 83 IS 2 BP 243 EP 255 DI 10.1002/jnr.20707 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 013UC UT WOS:000235434300008 PM 16385577 ER PT J AU Aghi, M Kluwe, L Webster, MT Jacoby, LB Barker, FG Ojemann, RG Mautner, VF MacCollin, M AF Aghi, M Kluwe, L Webster, MT Jacoby, LB Barker, FG Ojemann, RG Mautner, VF MacCollin, M TI Unilateral vestibular schwannoma with other neurofibromatosis Type 2-related tumors: clinical and molecular study of a unique phenotype SO JOURNAL OF NEUROSURGERY LA English DT Article DE vestibular schwannoma; neurofibromatosis Type 2; tumor suppressor gene; mosaicism; molecular genetics ID GENE; NF2; FREQUENCY; MOSAICISM AB Object. Although the manifestations of neurofibromatosis Type 2 (NF2) vary, the hallmark is bilateral vestibular schwannomas (VSs). The authors studied the clinical course and genetic basis of unilateral VSs associated with other NF2-related tumors. Methods. Forty-four adults presenting with unilateral VSs and other NF2-related tumors were identified. A comprehensive review of patient records and cranial imaging was conducted. Molecular analysis of the NF2 locus was performed in available tumors and paired blood specimens. Patient age at symptomatic onset ranged from 11 to 63 years (mean 32 years). Twenty-two patients (50%) presented with eighth cranial nerve dysfunction. Twenty-six presented with multiple lesions. Thirty-eight harbored other intracranial tumors and 27 had spinal tumors, with most lesions situated ipsilateral to the VS. No patient had a relative with NF2, although two of 63 offspring had isolated NF2-related findings. A contralateral VS developed in four patients 3 to 46 years after the symptomatic onset of a unilateral VS, and two of these patients experienced rapid progression to total deafness. Results of a Kaplan-Meier analysis identified actuarial chances of developing contralateral VS: 2.9% (3-17 years after the VS symptomatic onset of unilateral VS), 11% (18-24 years), and 28.8% (25-40 years). Mosaicism for the NF2 gene mutation was proven in eight patients. Conclusions. The authors describe the clinical features of this unique phenotype-unilateral VS with other NF2-related tumors. Persons with this phenotype should undergo evaluation and monitoring similar to that conducted in patients with NF2, and the possibility of aggressive contralateral VS fort-nation should be considered in their treatment. Molecular genetic analysis is best performed using resected tumor specimens and will enable future studies to determine the genetic risks of individuals with mosaicism. C1 Massachusetts Gen Hosp, Serv Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Univ Hamburg, Hosp Eppendorf, Dept Maxillofacial Surg, D-20246 Hamburg, Germany. RP MacCollin, M (reprint author), Ctr Neurosci, MGH E,Bldg 149,13th St, Charlestown, MA 02129 USA. EM maccollin@helix.mgh.harvard.edu FU NINDS NIH HHS [NS40527-01] NR 15 TC 16 Z9 17 U1 0 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD FEB PY 2006 VL 104 IS 2 BP 201 EP 207 DI 10.3171/jns.2006.104.2.201 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 009CY UT WOS:000235090000007 PM 16509493 ER PT J AU Higami, Y Barger, JL Page, GP Allison, DB Smith, SR Prolla, TA Weindruch, R AF Higami, Y Barger, JL Page, GP Allison, DB Smith, SR Prolla, TA Weindruch, R TI Energy restriction lowers the expression of genes linked to inflammation, the cytoskeleton, the extracellular matrix, and angiogenesis in mouse adipose tissue SO JOURNAL OF NUTRITION LA English DT Article DE microarray; energy restriction; dietary restriction; aging ID HEPATIC INSULIN-RESISTANCE; CALORIC RESTRICTION; VISCERAL FAT; ADIPSIN EXPRESSION; ADIPOCYTE DIFFERENTIATION; LEPTIN RESISTANCE; DEFICIENT MICE; CATHEPSIN-S; OBESITY; PROTEIN AB Using high-density oligonucleotide microarrays, we examined the actions of energy restriction (ER) on the expression of > 11,000 genes in epididymal white adipose tissue (WAT) of 10- to 11-mo-old male C57B16 mice. Four groups were studied: controls not subjected to food restriction (CO), food-restricted 18 h before being killed (FR), short-term ER for 23 d (SER), and long-term ER for 9 mo (LER). As we reported previously, compared with CO mice, FR and SER minimally influenced the gene expression profiles; however, 345 transcripts of 6266 genes determined to be expressed in WAT were significantly altered by LER. We focus here on the 109 (31%) of these genes that were involved in either inflammation (56 genes), cytoskeleton (16 genes), extracellular matrix (23 genes), or angiogenesis (14 genes). Among these 109 genes, 104 transcripts (95%) were downregulated by LER. Western blotting for heat shook protein 47 and osteonectin, and immunohistochemical staining for hypoxia inducible factor (HIF-1 alpha), supportec the microarray data that LER downregulated the expressions of these genes. Additionally, a 75% reduction in adipocyte size with LER reflected the change in the expression of genes involved in cell morphology. Our findings provide evidence that LER suppresses the expression of genes encoding inflammatory molecules in WAT while promoting structural remodeling of the cytoskeleton, extracellular matrix, and vasculature. These alterations may play an important role in the protection against WAT-derived inflammation and in lifespan extension by LER. C1 Univ Wisconsin, Dept Med, Madison, WI 53705 USA. Wisconsin Natl Primate Res Ctr, Madison, WI 53715 USA. Nagasaki Univ, Dept Pathol & Gerontol, Sch Biomed Sci, Nagasaki 8528523, Japan. Univ Alabama, Sect Stat Genet, Dept Biostat, Birmingham, AL 35249 USA. Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. Univ Wisconsin, Dept Genet, Madison, WI 53706 USA. Univ Wisconsin, Dept Med Genet, Madison, WI 53706 USA. William S Middleton Mem Vet Adm Med Ctr, Educ & Clin Ctr, Madison, WI 53705 USA. RP Weindruch, R (reprint author), Univ Wisconsin, Dept Med, Madison, WI 53705 USA. EM rhweindr@wisc.edu OI Allison, David/0000-0003-3566-9399 FU NIA NIH HHS [R01 AG18922, T32AG00213] NR 67 TC 72 Z9 76 U1 1 U2 8 PU AMER SOCIETY NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD FEB PY 2006 VL 136 IS 2 BP 343 EP 352 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 006JU UT WOS:000234894600002 PM 16424110 ER PT J AU Thurmuller, P Troulis, MJ Rosenberg, A Chuang, SK Kaban, LB AF Thurmuller, P Troulis, MJ Rosenberg, A Chuang, SK Kaban, LB TI Microscopic changes in the condyle and disc in response to distraction osteogenesis of the minipig mandible SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID HUMAN TEMPOROMANDIBULAR-JOINT; INTERNAL DERANGEMENT; EXPERIMENTAL-MODEL; CARTILAGE; OSTEOARTHROSIS; THICKNESS; DISPLACEMENT; AUTOPSY; MONKEYS; DISEASE AB Purpose: Unilateral mandibular distraction osteogenesis (DO) has been shown to cause gross changes in the mandibular condyle and articular disc. The purpose of this study was to correlate histologic findings with these gross changes in a minipig distraction model. Materials and Methods: Semiburied distractors were placed via submandibular incisions in 15 minipigs. Two unoperated animals served as controls. The protocol consisted of 0-day latency and rates of 1, 2, or 4 mm/day for a 12-mm gap. After the minipigs were killed (at 0, 24, or 90 days), ipsilateral and contralateral condyles and discs were harvested, decalcified, prepared for standard paraffin embedding, and evaluated to determine changes in 1) morphology and thickness of the articular cartilage and subchondral bone and 2) morphology of the disc. Results: In control animals, there were no degenerative changes in the articular cartilage and underlying condylar bone; there were no significant differences in the mean articular cartilage thickness. The temporomandibular joint discs were normal. In experimental animals, distracted condyles showed increasing degenerative changes and mean articular cartilage thickness as the DO rate increased. The discs were thinner. These changes were present, but to a lesser degree, in the contralateral condyles. After 90 days, degenerative changes in the condyles and discs were reduced, after remodeling, except in the 4 mm/day DO group. Conclusions: Histologic changes in the condyles and temporomandibular joint discs in response to mandibular DO correlated with previously reported gross changes. These changes were greater at higher distraction rates and remodeling back to normal occurred in mandibular condyles distracted at I mm/day. (c) 2006 American Association of Oral and Maxillofacial Surgeons. C1 Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Oral & Maxillofacial Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Kaban, LB (reprint author), Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Oral & Maxillofacial Surg Serv, Fruit St,Warren Bldg 1201, Boston, MA 02114 USA. EM LKaban@partners.org NR 36 TC 15 Z9 16 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD FEB PY 2006 VL 64 IS 2 BP 249 EP 258 DI 10.1016/j.joms.2005.10.010 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 005PV UT WOS:000234837200015 PM 16413897 ER PT J AU Ritter, L Yeshwant, K Seldin, EB Kaban, LB Gateno, JI Keeve, E Kikinis, R Troulis, MJ AF Ritter, L Yeshwant, K Seldin, EB Kaban, LB Gateno, JI Keeve, E Kikinis, R Troulis, MJ TI Range of curvilinear distraction devices required for treatment of mandibular deformities SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article; Proceedings Paper CT 85th Annual Meeting of the American-Association-of-Oral-and-Maxillofacial-Surgeons CY SEP 10-14, 2003 CL Orlando, FL SP Amer Assoc Oral & Maxillofacial Surg ID OSTEOGENESIS AB Purpose: The purpose of this study was to determine the range of fixed trajectory curvilinear distraction devices required to correct a variety of severe mandibular deformities. Materials and Methods: Preoperative computed tomography (CT) scans from 18 patients with mandibular deformities were imported into a CT-based software program (Osteoplan). Three-dimensional virtual models of the individual skulls were made with landmarks to track movements. An ideal treatment Plan was created for each patient. Upper and lower boundaries for the dimensions of curvilinear distractors were established based on manufacturing and geometric constraints. Then, anatomically acceptable distractor attachment points were identified on the models using proximal and distal grids. Treatment plans were simulated for a series of distractors with varying radii of curvature, elongations (arc-length of device), and placements along the grids. The outcomes using these distractors,were compared with the ideal treatment plans. Discrepancies were quantified in millimeters by comparing landmarks in the Simulated versus ideal movements. Results: Approximately 400,000 simulated 3-dimensional movements, based on the distractor parameters and variations in placement were computationally evaluated for the 18 cases. It was determined that. by varying distractor placement, a family of 5 distractors, with 3, 5, 7, and 10 cm radii of curvature and a straight-line device, could be used to treat all 18 cases to within 1.8 mm of error. Conclusions: The results of this study indicate that a family of 5 curvilinear distractors may suffice to treat a broad range of mandibular deformities. (c) 2006 American Association of Oral and Maxillofacial Surgeons. C1 Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Univ Texas, Dent Branch, Dept Oral & Maxillofacial Surg, Houston, TX USA. CAESAR, Surg Syst Lab, Bonn, Germany. Brigham & Womens Hosp, Harvard Surg Planning Lab, Boston, MA 02115 USA. RP Troulis, MJ (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 55 Fruit St,Warren Bldg 1201, Boston, MA 02114 USA. EM mtroulis@partners.org RI Keeve, Erwin/D-6228-2014 OI Keeve, Erwin/0000-0001-8466-520X FU NIDCR NIH HHS [K23-DE14080-02] NR 12 TC 24 Z9 24 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD FEB PY 2006 VL 64 IS 2 BP 259 EP 264 DI 10.1016/j.joms.2005.10.015 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 005PV UT WOS:000234837200016 PM 16413898 ER PT J AU Bhattacharyya, T Crichlow, R Gobezie, R Kim, E Vrahas, MS AF Bhattacharyya, T Crichlow, R Gobezie, R Kim, E Vrahas, MS TI Complications associated with the posterolateral approach for pilon fractures SO JOURNAL OF ORTHOPAEDIC TRAUMA LA English DT Article ID TIBIAL PLAFOND; PROTOCOL AB Objective: To review the complication rates of open reduction and internal fixation (ORIF) of tibial pilon fractures using the posterolateral approach. Design: Retrospective review. Setting: Two level 1 trauma centers. Patients: Nineteen consecutive pilon fractures at an average of 13 (range, 13-45) months follow-up. Average age 46 (range, 21-72) years. Four of 19 were open fractures. Intervention: Because of the high incidence of wound complications associated with the anterior approach for pilon fractures, patients were treated with initial temporary external fixation followed by delayed ORIF through the posterolateral approach to the distal tibia. The hypothesis was that the abundant soft-tissue coverage of the posterior distal tibia would decrease the rate of wound complications. Main Outcome Measurements: The incidence of wound complications, nonunion, and early posttraumatic arthritis. This was a chart and radiograph retrospective review. Results: The mean time to definitive treatment was 13 (range 2-30) days. Nine of 19 patients (47%) developed complications. There were 6 patients with wound problems, 2 patients with aseptic nonunions, 2 patients with infected nonunions, 3 tibiotalar fusions, and 1 patient with a 3-mm step off. In total, there were 14 major complications in 9 patients. Ten of 19 patients did not have any complication. Conclusions: The posterolateral approach does not eliminate the complications common to other approaches, but does offer a potential alternative when soft tissue concerns prevent other approaches. We do not recommend the posterolateral approach for the routine treatment of tibial pilon fractures. C1 Massachusetts Gen Hosp, Partners Orthopaed Trauma Serv, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Bhattacharyya, T (reprint author), Massachusetts Gen Hosp, Partners Orthopaed Trauma Serv, 15 Parkman St,WAC 525, Boston, MA 02114 USA. EM tbhattacharyya@partners.org NR 13 TC 35 Z9 47 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-5339 J9 J ORTHOP TRAUMA JI J. Orthop. Trauma PD FEB PY 2006 VL 20 IS 2 BP 104 EP 107 DI 10.1097/01.bot.0000201084.48037.5d PG 4 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 014YI UT WOS:000235516500004 PM 16462562 ER PT J AU Nishimori, M Kulich, RJ Carwood, CM Okoye, V Kalso, E Ballantyne, JC AF Nishimori, M Kulich, RJ Carwood, CM Okoye, V Kalso, E Ballantyne, JC TI Successful and unsuccessful outcomes with long-term opioid therapy: A survey of physicians' opinions SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID CHRONIC PAIN AB Background: The attitudes, beliefs, and experience of physicians will influence how they view the use of opioids for chronic nonterminal pain. Objective: To survey pain specialists and primary care providers (PCPs) to obtain their opinion and attitude on aberrant drug-taking behaviors. Design: We surveyed three physician groups, mailing 250 surveys followed by two follow-ups. The survey consisted of (1) questions about beliefs in the effectiveness of long-term opioid therapy and successful and unsuccessful outcomes and (2) a ratings section for possible indicators of unsuccessful long-term opioid treatment. Results: In total 147 questionnaires (82 PCPs, 65 pain specialists) were returned. Pain specialists reported a greater number of patients undergoing long-term opioid therapy compared to nonpain specialists. Opinion regarding the effectiveness of long-term opioid therapy among all physicians was mixed but there was no significant difference between pain specialists and PCPs. There was agreement among physicians with regard to highly aberrant behaviors being indicators of failed long-term opioid therapy. The ratings of the following indicators showed differences between each group: no improvement in pain control, not being able to return to work, and a deterioration in relationships with others. Physicians reported increases or decreases in function to be the most important successful or unsuccessful outcome, respectively. Conclusions: This preliminary survey showed consensus among physicians that highly aberrant behaviors indicate a failure of chronic opioid therapy. However, when considering less egregious behaviors, it would appear a physician's experience and the number of patients they had taking opioids influenced their opinion. C1 Massachusetts Gen Hosp, Pain Ctr, Dept Anesthesia, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Helsinki, Cent Hosp, Pain Clin, Dept Anaesthesia & Intens Care Med, Helsinki, Finland. RP Nishimori, M (reprint author), Massachusetts Gen Hosp, Pain Ctr, Dept Anesthesia, 101 Merrimac St,Suite 610, Boston, MA 02114 USA. EM nmishimori@partners.org NR 9 TC 10 Z9 10 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD FEB PY 2006 VL 9 IS 1 BP 50 EP 56 DI 10.1089/jpm.2006.9.50 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 044LQ UT WOS:000237674300016 PM 16430344 ER PT J AU Minzenberg, MJ Fisher-Irving, M Poole, JH Vinogradov, S AF Minzenberg, MJ Fisher-Irving, M Poole, JH Vinogradov, S TI Reduced self-referential source memory performance is associated with interpersonal dysfunction in borderline personality disorder SO JOURNAL OF PERSONALITY DISORDERS LA English DT Article ID AUDITORY HALLUCINATIONS; SCHIZOPHRENIA; SYMPTOMATOLOGY; DEPRESSION; INVENTORY; HOSTILITY; SCALES; ITEM AB Source memory is impaired in schizophrenia, and this deficit is related to symptoms of interpersonal antagonism such as suspiciousness and hostility. The present study evaluated source memory in borderline personality disorder (BPD) and its relation to interpersonal antagonism. Forty-one noninpatient adults with BPD according to the DSM-IV and 26 healthy control subjects performed a verbal source memory test requiring completion of sentences with and without emotional content ("Hot" vs. "Cold" sentences). Subjects also completed self-report measures of suspiciousness and interpersonal antagonism (Buss-Durkec Hostility Inventory) and depression (Beck Depression Inventory). The BPD group showed no significant difference from the control group in self-referential source memory, recognition memory, response bias, and performance enhancement for items with emotion content. However, in the BPD group, poorer self-referential source memory was significantly related to Hostility measures including suspiciousness, but not with Depression scores. In contrast, generic item recognition memory was unrelated to Hostility. Heterogeneity in source memory function may be specifically related to some of the hallmark interpersonal disturbances of BPD, independent of the effects of general negative affect or general memory impairment. C1 Univ Calif Davis, Med Ctr, Davis, CA 95616 USA. Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. RP Minzenberg, MJ (reprint author), Univ Calif Davis Hlth Syst, Imaging Res Ctr, 4701 X St, Sacramento, CA 95817 USA. EM michael.minzenberg@ucdmc.ucdavis.edu NR 39 TC 5 Z9 6 U1 3 U2 7 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0885-579X J9 J PERS DISORD JI J. Pers. Disord. PD FEB PY 2006 VL 20 IS 1 BP 42 EP 54 DI 10.1521/pedi.2006.20.1.42 PG 13 WC Psychiatry SC Psychiatry GA 020PL UT WOS:000235921900005 PM 16563078 ER PT J AU Bearden, CE Glahn, DC Monkul, ES Barrett, J Najt, P Kaur, S Sanches, M Villarreal, V Bowden, C Soares, JC AF Bearden, CE Glahn, DC Monkul, ES Barrett, J Najt, P Kaur, S Sanches, M Villarreal, V Bowden, C Soares, JC TI Sources of declarative memory impairment in bipolar disorder: Mnemonic processes and clinical features SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE bipolar disorder; clinical state; declarative memory; cognition; gender ID PREFRONTAL CORTEX; MOOD DISORDERS; NEUROPSYCHOLOGICAL FUNCTION; NEUROCOGNITIVE FUNCTION; COGNITIVE IMPAIRMENT; EUTHYMIC PATIENTS; VERBAL MEMORY; HIPPOCAMPAL FUNCTION; GENDER-DIFFERENCES; ATTENTION-DEFICIT AB Background: There is mounting evidence that declarative memory processes are impaired in patients with bipolar disorder. However, predictors of the observed impairment are not well understood. This study seeks to: (i) better characterize the nature of declarative memory impairment in bipolar disorder, and (ii) determine the relationship between clinical variables and memory function in bipolar disorder. Methods: 49 adult patients with bipolar disorder in varying mood states and 38 demographically matched healthy participants completed a comprehensive neurocognitive battery assessing general cognitive functioning, processing speed, and declarative memory. The California verbal learning test was used to characterize learning and memory functions. Results: Although patients with bipolar disorder utilized a similar semantic clustering strategy to healthy controls, they recalled and recognized significantly fewer words than controls, suggesting impaired encoding of verbal information. In contrast, lack of rapid forgetting suggests relative absence of a storage deficit in bipolar patients. While severity of mood symptomatology and illness duration were not associated with task performance, gender and family history significantly affected memory function. Conclusions: Results suggest that declarative memory impairments in bipolar patients: (1) are consistent with deficits in learning, but do not appear to be related to different organizational strategies during learning, and (2) do not appear to be secondary to clinical state, but rather may be associated with the underlying pathophysiology of the illness. (c) 2005 Elsevier Ltd. All rights reserved. C1 Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, Div Schizophrenia & Related Disorders, San Antonio, TX 78284 USA. Dokuz Eylul Univ, Sch Med, Dept Psychiat, Izmir, Turkey. Univ Texas, Hlth Sci Ctr, Dept Psychiat, Div Mood & Anxiety Disorders, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RP Bearden, CE (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, 300 Bldg Med Plaza,Suite 2265, Los Angeles, CA 90095 USA. EM cbearden@mednet.ucla.edu FU NCRR NIH HHS [M01-RR-01346]; NIMH NIH HHS [MH01736] NR 72 TC 47 Z9 49 U1 0 U2 4 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 FEB PY 2006 VL 40 IS 1 BP 47 EP 58 DI 10.1016/j.jpsychires.2005.08.006 PG 12 WC Psychiatry SC Psychiatry GA 014GA UT WOS:000235466200005 PM 16199055 ER PT J AU Hollon, SD Shelton, RC Wisniewski, S Warden, D Biggs, MM Friedman, ES Husain, M Kupfer, DJ Nierenberg, AA Petersen, TJ Shores-Wilson, K Rush, AJ AF Hollon, SD Shelton, RC Wisniewski, S Warden, D Biggs, MM Friedman, ES Husain, M Kupfer, DJ Nierenberg, AA Petersen, TJ Shores-Wilson, K Rush, AJ TI Presenting characteristics of depressed outpatients as a function of recurrence: Preliminary findings from the STAR*D clinical trial SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE depression; recurrent; chronic; risk ID PLACEBO-CONTROLLED TRIAL; LONG-TERM TREATMENT; MILD DEPRESSION; RATING SCALE AB Objectives: Recurrent depression predicts risk for subsequent episodes, but it is unclear how it relates to demographic features, course of illness, and clinical presentation. Methods: We report on the baseline data for the first 1500 patients enrolled in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study (www.star-d.org). Patients were required to have a DSM-IV diagnosis of nonpsychotic major depression and to score >= 14 on the 17-item Hamilton rating scale for depression. Status with respect to recurrent depression and other aspects of illness course and demographic features were ascertained at intake, along with measures of depression and concurrent general medical illness. Results: Patients with recurrent depression were older, had an earlier age of onset, and were more likely to have a positive family history of depression than first episode patients. However, recurrent patients were less likely to be chronic and reported shorter current episodes than first episode patients, something that was largely confined to females. Recurrent patients were more likely than first episode patients to report non-essential aspects of mood, cognition, and somatic symptoms, although largely as a consequence of greater overall depressive symptom severity. Conclusions: As compared to single episode depressions, recurrent depression was associated with greater symptom severity and illness characteristics suggestive of greater underlying risk, but not other demographic characteristics than age. Risk for recurrence appeared to be distinct from chronic depression. A subset of chronic first episode patients may lack the capacity to remit and may therefore be distinct from those with recurrent episodes. (c) 2005 Elsevier Ltd. All rights reserved. C1 Vanderbilt Univ, Dept Psychol, Nashville, TN 37203 USA. Vanderbilt Univ, Med Ctr, Dept Psychiat, Nashville, TN USA. Univ Pittsburgh, Epidemiol Data Coordinating Ctr, Pittsburgh, PA 15260 USA. Univ Texas, SW Med Ctr, Dept Psychiat, Natl Coordinating Ctr, Dallas, TX USA. Univ Pittsburgh, Med Ctr, Dept Psychiat, Pittsburgh, PA 15260 USA. Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hollon, SD (reprint author), Vanderbilt Univ, Dept Psychol, 306 Wilson Hall, Nashville, TN 37203 USA. EM steven.d.hollon@vanderbilt.edu RI Biggs, Dr. Melanie/C-1468-2010; OI Wisniewski, Stephen/0000-0002-3877-9860; Rush, Augustus/0000-0003-2004-2382 FU NIMH NIH HHS [K24 MH17401, N01MH90003, K02 MH01697] NR 18 TC 53 Z9 56 U1 0 U2 1 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 FEB PY 2006 VL 40 IS 1 BP 59 EP 69 DI 10.1016/j.jpsychires.2005.07.008 PG 11 WC Psychiatry SC Psychiatry GA 014GA UT WOS:000235466200006 PM 16243357 ER PT J AU Hula, W Doyl, PJ McNeil, MR Mikolic, JM AF Hula, W Doyl, PJ McNeil, MR Mikolic, JM TI Rasch modeling of revised token test performance: Validity and sensitivity to change SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH LA English DT Article; Proceedings Paper CT 34th Annual Clinical Aphasiology Conference CY 2004 CL Park City, UT DE assessment; aphasia; auditory comprehension; spoken language comprehension assessment; standardized assessment ID SENTENCE COMPREHENSION; SCALE; APHASIA; IMPACT; SCIENCE AB The purpose of this research was to examine the validity of the 55-item Revised Token Test (RTT) and to compare traditional and Rasch-based scores in their ability to detect group differences and change over time. The 55-item RTT was administered to 108 left- and right-hemisphere stroke survivors, and the data were submitted to Rasch analysis. Traditional and Rasch-based scores for a subsample of 60 stroke survivors were submitted to analyses of variance with group (left hemisphere with aphasia vs. right hemisphere) and time post onset (3 vs. 6 months post onset) as factors. The 2 scoring methods were compared using an index of relative precision. Forty-eight items demonstrated acceptable model fit. Misfitting items came primarily from Subtest IX. The Rasch model accounted for 71% of the variance in the responses to the remaining items. Intersubtest patterns of item difficulty were well predicted by item content, but unexpected within-subtest differences were found. Both traditional and Rasch person scores demonstrated significant group differences, but only the latter demonstrated statistically significant change over time. Analysis of relative precision, however, failed to confirm a significant difference between the 2 methods. The findings generally support the RTT's validity, but a minority of items appears to respond to a different construct. Also, within-subtest differences in item difficulty suggest the need for further examination of variability in impaired language performance. Finally, the results suggest an equivocal advantage for Rasch scores in detecting change over time. C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. RP Hula, W (reprint author), VA Pittsburgh Healthcare Syst, 7180 Highland Dr,132A-H, Pittsburgh, PA 15206 USA. EM william.hula@med.va.gov NR 85 TC 13 Z9 13 U1 1 U2 4 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 FEB PY 2006 VL 49 IS 1 BP 27 EP 46 DI 10.1044/1092-4388(2006/003) PG 20 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 030JZ UT WOS:000236632000003 PM 16533071 ER PT J AU Henry, JA Schechter, MA Zaugg, TL Griest, S Jastreboff, PJ Vernon, JA Kaelin, C Meikle, MB Lyons, KS Stewart, BJ AF Henry, James A. Schechter, Martin A. Zaugg, Tara L. Griest, Susan Jastreboff, Pawel J. Vernon, Jack A. Kaelin, Christine Meikle, Mary B. Lyons, Karen S. Stewart, Barbara J. TI Outcomes of clinical trial: Tinnitus masking versus tinnitus retraining therapy SO JOURNAL OF THE AMERICAN ACADEMY OF AUDIOLOGY LA English DT Article DE clinical trial; hearing disorders; military veterans; rehabilitation; tinnitus ID HANDICAP QUESTIONNAIRE; MANAGEMENT AB A controlled clinical study was conducted to evaluate prospectively the clinical efficacy of tinnitus masking (TM) and tinnitus retraining therapy (TRT) in military veterans having clinically significant tinnitus. Qualifying patients were placed into the two groups in an alternating manner (to avoid selection bias), and treatment was administered at 0, 3, 6, 12, and 18 months. Outcomes of treatment were evaluated using three self-administered tinnitus questionnaires (Tinnitus Handicap Inventory, Tinnitus Handicap Questionnaire, Tinnitus Severity Index) and the verbally administered TRT interview forms. Findings are presented from the three written questionnaires, and from two of the interview questions (percentage time aware of, and annoyed by, tinnitus). Outcomes were analyzed on an intent-to-treat basis, using a multilevel modeling approach. Of the 123 patients enrolled, 118 were included in the analysis. Both groups showed significant declines (improvements) on these measures, with the TRT decline being significantly greater than for TM. The greater declines in TRT compared to TM occurred most strongly in patients who began treatment with a "very big" tinnitus problem. When patients began treatment with a,"moderate" tinnitus problem, the benefits of TRT compared to TM were more modest. C1 [Henry, James A.; Schechter, Martin A.; Zaugg, Tara L.; Griest, Susan; Jastreboff, Pawel J.; Kaelin, Christine] Portland VA Med Ctr, VA RR&D Natl Ctr Rehabilitat Auditory Res, Portland, OR USA. [Griest, Susan; Vernon, Jack A.; Meikle, Mary B.] Oregon Hlth & Sci Univ, Dept Otolaryngol, Portland, OR 97201 USA. [Schechter, Martin A.] Portland VA Med Ctr, VA Audiol Clin, Portland, OR USA. [Jastreboff, Pawel J.] Emory Univ, Tinnitus & Hyperacusis Ctr, Dept Otolaryngol, Atlanta, GA 30322 USA. [Lyons, Karen S.; Stewart, Barbara J.] Oregon Hlth & Sci Univ, Sch Nursing, Portland, OR 97201 USA. RP Henry, JA (reprint author), VA Med Ctr NCRAR, PO Box 1034, Portland, OR 97207 USA. EM james.henry@med.va.gov NR 48 TC 61 Z9 64 U1 1 U2 16 PU AMER ACAD AUDIOLOGY PI RESTON PA 11730 PLAZA DR, STE 300, RESTON, VA 20190 USA SN 1050-0545 EI 2157-3107 J9 J AM ACAD AUDIOL JI J. Am. Acad. Audiol. PD FEB PY 2006 VL 17 IS 2 BP 104 EP 132 DI 10.3766/jaaa.17.2.4 PG 29 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA 241UE UT WOS:000251680500004 PM 16640064 ER PT J AU Wilens, TE Kratochvil, C Newcorn, JH Gao, HT AF Wilens, TE Kratochvil, C Newcorn, JH Gao, HT TI Do children and adolescents with ADHD respond differently to atomoxetine? SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE age; atomoxetine; adolescents; attention-deficit/hyperactivity disorder; children ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; ONCE-DAILY ATOMOXETINE; DOUBLE-BLIND; CONTROLLED TRIAL; RESIDUAL TYPE; PLACEBO; METHYLPHENIDATE; DESIPRAMINE; SYMPTOMS AB Objective: Controversy exists over changes in tolerability and response to medications across the life span. Here the authors report data contrasting the efficacy and tolerability of atomoxetine between children and adolescents with attention-deficit/hyperactivity disorder (ADHD). Method: Data were analyzed for children ages 6-11 (510 atomoxetine, 341 placebo) and adolescents ages 12-17 (107 atomoxetine, 69 placebo) with DSM-IV-defined ADHD enrolled in similarly designed, double-blind, placebo-controlled trials. Efficacy measures included response rates, times to response, and mean changes from baseline to endpoint in the ADHD Rating Scale, Conners' Parent Rating Scale, and Clinical Global Impressions. Results: Adolescents had lower baseline ADHD scores compared with children. There were no statistically significant differences in the overall effects on ADHD symptoms, response rates, or time to response between age groups. Children, but not adolescents, had higher rates of somnolence and headache relative to placebo. No other clinically meaningful treatment differences were seen in adverse event rates, vital signs, weight, height, laboratory values, or ECG between children and adolescents. Conclusions: Acute atomoxetine treatment appears to be equally effective and tolerated in children and adolescents. These findings suggest that pharmacological differences in tolerability or ADHD symptom response are negligible between children and adolescents. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Yawkey Ctr Outpatient Care, Boston, MA 02114 USA. Univ Nebraska Med Ctr, Omaha, NE 68198 USA. Mt Sinai Med Ctr, New York, NY 10029 USA. Lilly Res Labs, Indianapolis, IN USA. RP Wilens, TE (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Yawkey Ctr Outpatient Care, YAW 6-6A,32 Fruit St, Boston, MA 02114 USA. EM twilens@partners.org OI Newcorn, Jeffrey /0000-0001-8993-9337 NR 47 TC 27 Z9 27 U1 3 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD FEB PY 2006 VL 45 IS 2 BP 149 EP 157 DI 10.1097/01.chi.0000190352.90946.0b PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 005FM UT WOS:000234808000004 PM 16429085 ER PT J AU Salter, SA Kimball, AB AF Salter, SA Kimball, AB TI Rising educational debt levels in recent dermatology trainees and effects on career choices SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article; Proceedings Paper CT Meeting of the Society-for-Investigative-Dermatology CY MAY, 2005 CL St Louis, MO SP Soc Investigative Dermatol AB Background: Educational debt levels are outpacing inflation. Objective: To determine whether debt levels influence career choices of graduating dermatology residents. Methods: Anonymous surveys of graduating dermatology residents. Results: The presence of debt was associated negatively with pursuing fellowship training in 1999 and 2004 (P < .05) but did not affect choices about entering solo practice or job dissatisfaction levels. Limitations: This study relies on self-reported data, and some surveys were incomplete. Conclusion: Debt levels do not appear to significantly influence the career choices of dermatology residents. C1 Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kimball, AB (reprint author), Brigham & Womens Hosp, Dept Dermatol, 221 Longwood Ave, Boston, MA 02115 USA. EM harvardskinstudies@partners.org NR 9 TC 8 Z9 8 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD FEB PY 2006 VL 54 IS 2 BP 329 EP 331 DI 10.1016/j.jaad.2005.10.047 PG 3 WC Dermatology SC Dermatology GA 008VL UT WOS:000235068700021 PM 16443068 ER PT J AU Hutt, E Pepper, GA Vojir, C Fink, R Jones, KR AF Hutt, E Pepper, GA Vojir, C Fink, R Jones, KR TI Assessing the appropriateness of pain medication prescribing practices in nursing homes SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE pain management; nursing home; dementia; quality of care ID NONMALIGNANT PAIN; OLDER-ADULTS; MANAGEMENT; CANCER; RESIDENTS; INTERVENTION; PREVALENCE; CARE; OSTEOARTHRITIS; OUTPATIENTS AB OBJECTIVES: To test a tool for screening the quality of nursing home (NH) pain medication prescribing. DESIGN: Validity and reliability of measurement tool developed for a pre/postintervention with untreated comparison group. SETTING: Six treatment NHs and six comparison NHs in rural and urban Colorado. PARTICIPANTS: NH staff, physicians, and repeated 20% random sample of each home's residents (N=2,031). INTERVENTION: Nurse and physician education; NH internal pain team to champion better pain management using a pain vital sign, consultations, and rounds. MEASUREMENTS: An expert panel reviewed the Pain Medication Appropriateness Scale (PMAS) for content validity. Research assistants interviewed NH residents, assessed them for pain using standardized instruments, and reviewed their medical records for prescriptions and use of pain and adjuvant medication. Construct validity was assessed by comparing the PMAS of residents in pain with the PMAS of those not in pain and comparing scores in homes in which the intervention was more effective with those in which it was less effective, using the Fisher exact and Student t tests. Interrater and test-retest reliability were measured. RESULTS: The mean total PMAS was 64% of optimal. Fewer than half of residents with predictably recurrent pain were prescribed scheduled pain medication; 23% received at least one high-risk medication. PMAS scores were better for residents not in pain (68% vs 60%, P=.004) and in homes where nurses' knowledge of pain assessment and management improved or stayed the same during the intervention (69% vs 61%, P=.03). CONCLUSION: The PMAS is useful for assessing pain medication prescribing in NHs and elucidates why so many residents have poorly controlled pain. C1 Univ Colorado, Denver VA Med Ctr 151, Denver, CO 80220 USA. Univ Colorado, Dept Med, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Sch Nursing, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80262 USA. Univ Utah, Coll Nursing, Salt Lake City, UT 84112 USA. Yale Univ, Sch Nursing, New Haven, CT 06536 USA. RP Hutt, E (reprint author), Univ Colorado, Denver VA Med Ctr 151, 1055 Clermont St, Denver, CO 80220 USA. EM Evelyn.Hutt@uchsc.edu FU AHRQ HHS [U18-HS11093] NR 46 TC 32 Z9 32 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD FEB PY 2006 VL 54 IS 2 BP 231 EP 239 DI 10.1111/j.1532-5415.2005.00582.x PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 009FZ UT WOS:000235098300005 PM 16460373 ER PT J AU Barton, C Miller, B Yaffe, K AF Barton, Cynthia Miller, Bruce Yaffe, Kristine TI Improved evaluation and management of cognitive impairment: Results of a comprehensive intervention in long.-term care SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Article DE cognitive impairment; dementia; long-term care ID NURSING-HOME PLACEMENT; QUALITY STANDARDS SUBCOMMITTEE; ACADEMY-OF-NEUROLOGY; MINIMUM DATA SET; ALZHEIMERS-DISEASE; DOUBLE-BLIND; PRACTICE PARAMETER; CONTROLLED-TRIAL; DEMENTIA; DONEPEZIL AB Objectives: Although as many as 50% of patients in long-term care have dementia, it is often not diagnosed and therefore, undertreated. We determined whether an intervention could improve the diagnosis and management of patients with cognitive impairment (CI) in long-term care. Design, Setting, and Participants: The assessment phase consisted of a record review of 60 consecutively admitted patients to the San Francisco VA Nursing Home Care Unit (NHCU). Cognitive impairment was determined by admission MMSE <= 24, indication of cognitive problem on MDS, or chart diagnosis of dementia. The evaluation consisted of a repeat chart review of 60 additional consecutively admitted patients. Intervention: The intervention consisted of low-cost and easy-to-implement educational activities (training, focus groups), strategies to document cognitive status, and consultation with dementia experts. Measurements/results: The 2 cohorts of 60 patients did not differ on demographics or on other characteristics (P >.25 for all). Prior to the intervention, of the 23 patients with Cl, 52% had an identified etiology, 35% had a physician management plan, and 22% had a multidisciplinary care plan. Postintervention, of the 22 patients with Cl, 91% had an identified etiology (P =.007), 86% had a physician plan (P =.001), and 59% had a multidisciplinary plan (P =.016). Conclusions: Initial results confirmed the underdiagnosis and undertreatment of Cl in our long-term care facility. Our intervention with educational programs, increased documentation of cognitive status, and consultation resulted in increased identification of etiology and improved plans for management of patients with Cl. C1 Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94121 USA. San Francisco VA Med Ctr, San Francisco, CA USA. RP Barton, C (reprint author), Univ Calif San Francisco, Dept Neurol, Box 116A,4150 Clement St, San Francisco, CA 94121 USA. EM cfb756@itsa.ucsf.edu FU NIA NIH HHS [R01 AG 021918-02] NR 34 TC 15 Z9 15 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-8610 J9 J AM MED DIR ASSOC JI J. Am. Med. Dir. Assoc. PD FEB PY 2006 VL 7 IS 2 BP 84 EP 89 DI 10.1016/j.jamda.2005.06.008 PG 6 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 081JU UT WOS:000240314700004 PM 16461249 ER PT J AU Woods, TD Patel, A AF Woods, TD Patel, A TI A critical review of patent foramen ovale detection using saline contrast echocardiography: When bubbles lie SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Review ID ATRIAL SEPTAL ANEURYSM; TO-LEFT SHUNT; RECURRENT CEREBROVASCULAR EVENTS; CRYPTOGENIC STROKE; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; PARADOXICAL EMBOLISM; TRANSTHORACIC ECHOCARDIOGRAPHY; PLATYPNEA-ORTHODEOXIA; MEDICAL-TREATMENT; HEART-DISEASE AB Saline and indocyanine green dye were the first agents noted to produce a contrast effect when injected peripherally during M-mode echocardiographic imaging, although it was subsequently found that almost any type of injected solution would have this effect. These first-generation contrast agents were limited to opacification of right heart structures, and they prompted subsequent development of agents that traverse pulmonary circulation. Although opacification limited to right heart structures is considered a limitation of these first-generation agents, this is an advantage when attempting to identify the presence of right-to-left shunt. First-generation air contrast is considered the gold standard for identification of patent foramen ovale (PFO). However, PFO investigators have used varying criteria to define abnormal contrast studies. There are also multiple mechanisms by which saline contrast studies may produce both false-positive and false-negative results for presence of PFO. There is mounting experimental evidence that PFO is associated with cerebral ischemia and migraine headache, with a resulting evolution of devices for percutaneous closure of these shunts. Echocardiographic physicians must be aware of potential pitfalls of the air contrast technique to avoid exposing patients to unnecessary risk of closure devices, and missing the potential benefit of shunt closure in appropriately selected patients. C1 Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA. William S Middleton Mem Vet Adm Med Ctr, Serv Cardiol, Madison, WI 53705 USA. RP Woods, TD (reprint author), Med Coll Wisconsin, Dept Med, 9200 W Wisconsin Ave, Milwaukee, WI 53226 USA. EM twoods@mcw.edu NR 52 TC 72 Z9 73 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD FEB PY 2006 VL 19 IS 2 BP 215 EP 222 DI 10.1016/j.echo.2005.09.023 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 012DV UT WOS:000235319300016 PM 16455428 ER PT J AU Panzer, U Steinmetz, OM Reinking, RR Meyer, TN Fehr, S Schneider, A Zahner, G Wolf, G Helmchen, U Schaerli, P Stahl, RAK Thaiss, F AF Panzer, Ulf Steinmetz, Oliver M. Reinking, Ruediger R. Meyer, Tobias N. Fehr, Susanne Schneider, Andre Zahner, Gunther Wolf, Gunter Helmchen, Udo Schaerli, Patrick Stahl, Rolf A. K. Thaiss, Friedrich TI Compartment-specific expression and function of the chemokine IP-10/CXCL10 in a model of renal endothelial microvascular injury SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; T-CELL RECRUITMENT; EXPERIMENTAL GLOMERULONEPHRITIS; THERAPEUTIC TARGETS; MRL-FAS(LPR) MICE; DISEASE; RECEPTORS; PROGRESSION; CXCR3; GLOMERULOSCLEROSIS AB The recruitment of inflammatory cells into renal tissue, mainly T cells and monocytes, is a typical feature of various renal diseases such as glomerulonephritis, thrombotic angiopathies, allograft rejection, and vasculitis. T cells predominantly infiltrate the tubulointerstitium, whereas monocytes are present in the tubulointerstitial and glomerular compartment. Because chemokines play a pivotal role in leukocyte trafficking under inflammatory conditions, this study investigated whether a differential expression of chemokines contributes to the precise coordination of leukocyte subtype trafficking in a rat model of renal microvascular endothelial injury. Renal microvascular endothelial injury was induced in rats by selective renal artery perfusion with an anti-endothelial antibody. Induction of the disease led to severe glomerular and tubulointerstitial endothelial injury with subsequent upregulation of chemokines followed by inflammatory cell recruitment. Among the analyzed chemokine mRNA, IP-10/CXCL10 (119-fold), acting via CXCR3 on activated T cells, and MCP-1/CCL2 (65-fold), acting via CCR2 on monocytes, were by far the most strongly upregulated chemokines. In situ hybridization revealed that IP-10/CXCL10 mRNA was selectively expressed by endothelial cells in the tubulointerstitial area, co-localizing with infiltrating T cells. Despite extensive damage of glomerular vasculature, no IP-10/CXCL10 expression by glomerular endothelial cells was detected. MCP-1/CCL2 mRNA in contrast was detectable in the glomerulus and the tubulointerstitium. Treatment with a neutralizing anti-IP-10/CXCL10 antibody significantly reduced the number of infiltrating tubulointerstitial T cells without affecting monocyte migration and led to an improved renal function. Our study demonstrates a role of IP-10/CXCL10 on T cell recruitment in a rat model of renal endothelial microvascular injury. Furthermore, a differential chemokine expression profile by endothelial cells in different renal compartments was found. These findings are consistent with the hypothesis that functional heterogeneity of endothelial cells from different vascular sites exists and provide an insight into the molecular mechanisms that may mediate compartment-specific T cell and monocyte recruitment in inflammatory renal disease. C1 Univ Hamburg, Krankenhaus Eppendorf, Inst Pathol, D-2000 Hamburg, Germany. Univ Hamburg, Krankenhaus Eppendorf, Med Klin 4, D-2000 Hamburg, Germany. Zentrum Mol Neurobiol, Hamburg, Germany. Univ Klin Jena, Innere Med Klin 3, Jena, Germany. Harvard Univ, Sch Med, Dept Pathol, CBR Inst Biomed Res, Boston, MA 02115 USA. RP Panzer, U (reprint author), Univ Hamburg, Zentrum Innere Med, Med Klin 4, Martinistr 52, D-20246 Hamburg, Germany. EM panzer@uke.uni-hamburg.de OI Thaiss, Friedrich/0000-0002-0357-4726 NR 32 TC 57 Z9 61 U1 0 U2 1 PU AMERICAN SOCIETY NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD FEB PY 2006 VL 17 IS 2 BP 454 EP 464 DI 10.1681/ASN.2005040364 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 106SD UT WOS:000242120200020 PM 16382019 ER PT J AU Zheng, GP Wang, YP Xiang, SH Tay, YC Wu, HL Watson, D Coombes, J Rangan, GK Alexander, SI Harris, DCH AF Zheng, Guoping Wang, Yiping Xiang, Shi-Hua Tay, Yuet-Ching Wu, Huiling Watson, Debbie Coombes, Jason Rangan, Gopala K. Alexander, Stephen I. Harris, David C. H. TI DNA vaccination with CCL2 DNA modified by the addition of an adjuvant epitope protects against "nonimmune" toxic renal injury SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the American-Society-of-Nephrology CY OCT 27-NOV 01, 2004 CL St Louis, MO SP Amer Soc Nephrol ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; FACTOR-KAPPA-B; IMMUNE-COMPLEX GLOMERULONEPHRITIS; MURINE ADRIAMYCIN NEPHROPATHY; PROXIMAL TUBULE CELLS; GENE-EXPRESSION; URINARY PROTEIN; SELF PROTEIN; VACCINES; DISEASE AB CC-chemokine-encoding DNA vaccine has been reported to be capable of inducing immunologic memory to corresponding pathogenic self CC-chemokines in animal models of autoimmune disease. This study investigated whether introduction of a foreign T helper epitope into monocyte chemoattractant protein 1 (CCL2) DNA vaccine could boost its immunogenicity by inducing strong neutralizing autoantibody against the pathogenic chemokine CCL2 sufficiently to be protective in a classically nonimmune model of disease, Adriamycin nephropathy (AN). Modification of the CCL2 DNA vaccine by replacing a surface loop region of CCL2 sequence with tetanus toxoid T helper epitope P30 elicited a strong self-specific CCL2 autoantibody as well as an IFN-gamma-producing T cell cellular response. The increased immunogenicity of modified CCL2 DNA vaccination but not unmodified CCL2 DNA vaccination was protective against functional and structural renal injury in rat AN. The protective effect of the modified CCL2 DNA vaccine was associated with blockade of glomerular and interstitial macrophage recruitment by neutralizing autoantibody against CCL2, which plays a critical role in eliciting renal injury in AN. Therefore, modification with a foreign T helper epitope breaks self-tolerance by inducing a cellular and humoral response against self-protein and provides a strategy to increase the potency of DNA vaccination sufficiently to afford protection in toxin-induced chronic renal disease. C1 Univ Sydney, Westmead Millenium Inst, Ctr Transplantat & Renal Res, Sydney, NSW 2145, Australia. Univ Sydney, Alfred Hosp, Dept Renal Med, Sydney, NSW 2145, Australia. Childrens Hosp, Ctr Kidney Res, Westmead, NSW, Australia. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol, Boston, MA USA. RP Zheng, GP (reprint author), Univ Sydney, Westmead Millenium Inst, Ctr Transplantat & Renal Res, Sydney, NSW 2145, Australia. EM guoping_zheng@wmi.usyd.edu.au RI Coombes, Jason/N-2331-2016 NR 42 TC 21 Z9 24 U1 1 U2 2 PU AMERICAN SOCIETY NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD FEB PY 2006 VL 17 IS 2 BP 465 EP 474 DI 10.1681/ASN.2005020164 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 106SD UT WOS:000242120200021 PM 16396966 ER PT J AU Schrag, D Earle, C Xu, F Panageas, KS Yabroff, KR Bristow, RE Trimble, EL Warren, JL AF Schrag, D Earle, C Xu, F Panageas, KS Yabroff, KR Bristow, RE Trimble, EL Warren, JL TI Associations between hospital and surgeon procedure volumes and patient outcomes after ovarian cancer resection SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID OPERATIVE MORTALITY; UNITED-STATES; COLON-CANCER; HIGH-RISK; SURVIVAL; IMPACT; CARE AB Background. Strong associations between provider (i.e., hospital or surgeon) procedure volumes and patient outcomes have been demonstrated for many types of cancer operation. We performed a population-based cohort stud), to examine these associations for ovarian cancer resections. Method: We used the Surveillance, Epidemiology, and End Results (SEER)Medicare linked database to identify 2952 patients aged 65 years or older who had surgery for a primary ovarian cancer diagnosed from 1992 through 1999. Hospital- and surgeon-specific procedure volumes were ascertained based on the number of claims submitted during the 8-year study period. Primary outcome measures were mortality at 60 days and 2 years after surgery, and overall survival. Length of hospital stay was also examined. Patient age at diagnosis, race, marital status, comorbid illness, cancer stage, and median income and population density in the area of residence were used to adjust for differences in case mix. All P values are two-sided. Results: Neither hospital- nor surgeon-specific procedure volume was statistically significantly associated with 60-day mortality following primary ovarian cancer resection. However, differences by hospital volume were seen with 2-year mortality; patients treated at the low-, intermediate-, and high-volume hospitals had 2-year mortality rates of 45.2% (95%, confidence interval [CI] = 42.1% to 48.4%), 41.1% (95% Cl = 38.1% to 44.3%), and 40.4% (95% Cl = 37.4% to 43.4%), respectively. The inverse association between hospital procedure volume and 2-year mortality was statistically significant both before (P=.011) and after (P=.006) case-mix adjustment but not after adjustment for surgeon volume. Two-year mortality for patients treated by low-, intermediate-, and high-volume surgeons was 43.20%(95% CI=40.70% to 45.8%),42.9% (95% CI = 39.5% to 46.4%), and 39.5% (95% CI = 36.0% to 43.2%), respectively,; there was no association between 2-year mortality and surgeon procedure volume, with or without case-mix adjustment. After case-mix adjustment, neither hospital volume (P = .031) nor surgeon volume (P = .062) was strongly associated with overall survival. Conclusion: Hospital- and surgeon-specific procedure volumes are not strong predictors of survival outcomes following surgery for ovarian cancer among women aged 65 years or older. C1 Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. Johns Hopkins Med Inst, Dept Obstet & Gynecol, Baltimore, MD 21205 USA. Natl Canc Inst, Appl Res Program, Bethesda, MD USA. Natl Canc Inst, Canc Therapy & Evaluat Program, Bethesda, MD USA. RP Schrag, D (reprint author), Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, Box 221,1275 York Ave, New York, NY 10021 USA. EM schragd@mskcc.org OI Yabroff, K. Robin/0000-0003-0644-5572 NR 27 TC 99 Z9 99 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD FEB 1 PY 2006 VL 98 IS 3 BP 163 EP 171 DI 10.1093/jnci/djj018 PG 9 WC Oncology SC Oncology GA 010SR UT WOS:000235218700008 PM 16449676 ER PT J AU Earle, CC Schrag, D Neville, BA Yabroff, KR Topor, M Fahey, A Trimble, EL Bodurka, DC Bristow, RE Carney, M Warren, JL AF Earle, CC Schrag, D Neville, BA Yabroff, KR Topor, M Fahey, A Trimble, EL Bodurka, DC Bristow, RE Carney, M Warren, JL TI Effect of surgeon specialty on processes of care and outcomes for ovarian cancer patients SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID COMORBIDITY INDEX; UNITED-STATES; CHEMOTHERAPY; CARCINOMA; SURVIVAL; PATTERNS; IMPACT; WOMEN AB Background. For many diseases, specialized care (i.e., care rendered by a specialist) has been associated with superior-quality care (i.e., better outcomes). We examined associations between physician specialty and outcomes in a population-based cohort of elderly ovarian cancer surgery patients. Methods: We analyzed the Medicare claims, by physician specialty, of all women aged 65 years or older who,underwent surgery for pathologically confirmed invasive epithelial ovarian cancer between January 1, 1992, and December 31, 1999, while living in an area monitored by the Surveillance, Epidemiology, and End Results (SEER) program to assess important care processes (i.e., the appropriate extent of surgery and use of adjuvant chemotherapy) and outcomes (i.e., surgical complications, ostomy rates, and survival). All statistical tests were two-sided. Results: Among 3067 ovarian cancer patients who underwent surgery, 1017 patients (33%) were treated by a gynecologic oncologist, 1377 patients (45%) by a general gynecologist, and 673 patients (22%) by a general surgeon. Among patients with stage I or II disease, those treated by a gynecologic oncologist (60%) were more likely to undergo lymph node dissection than those treated by a general gynecologist (36%) or a general surgeon (16%). Patients with stage III or IV disease were more likely to undergo a debulking procedure if the initial surgery was performed by a gynecologic oncologist (58%) than by a general gynecologist (51 %) or a general surgeon (40%; P <.001) and were more likely to receive postoperative chemotherapy when operated on by a gynecologic oncologist (79%) or a general gynecologist (76%) than by a general surgeon (62%, P <.001). Survival among patients operated on by gynecologic oncologists (hazard ratio [HR] of death from any cause = 0.85, 95% confidence interval [CI] = 0.76 to 0.95) or general gynecologists (HR = 0.86, 95% CI = 0.78 to 0.96) was better than that among patients operated on by general surgeons. Conclusions: Ovarian cancer patients treated by gynecologic oncologists had marginally better outcomes than those treated by general gynecologists and clearly superior outcomes compared with patients treated by general surgeons. C1 Dana Farber Canc Ctr, Dept Med Oncol, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. Natl Canc Inst, Appl Res Program, Bethesda, MD USA. Natl Canc Inst, Canc Therapy Evaluat Program, Bethesda, MD USA. Informat Management Serv Inc, Rockville, MD USA. Univ Texas, MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA. Univ Hawaii, Kapiolani Med Ctr, Dept Obstet Gynecol & Womens Hlth, Honolulu, HI 96822 USA. RP Earle, CC (reprint author), Dana Farber Canc Ctr, Dept Med Oncol, Ctr Outcomes & Policy Res, 44 Binney St, Boston, MA 02115 USA. EM craig_earle@dfci.harvard.edu OI Yabroff, K. Robin/0000-0003-0644-5572 NR 24 TC 208 Z9 210 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD FEB 1 PY 2006 VL 98 IS 3 BP 172 EP 180 DI 10.1093/jnci/djj019 PG 9 WC Oncology SC Oncology GA 010SR UT WOS:000235218700009 PM 16449677 ER PT J AU DiGirolamo, CM Zhang, L Pru, JK AF DiGirolamo, CM Zhang, L Pru, JK TI A sub-fraction of Sca-1-negative uterine stromal cells exhibits stem/progenitor cell qualities. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 53rd Annual Scientific Meeting of the Society-for-Gynecologic-Investigation CY MAR 22-25, 2006 CL Toronto, CANADA SP Soc Gynecolog Investigation C1 Massachusetts Gen Hosp, Harvard Med Sch, Vincent Obstet & Gynecol Serv, Vincent Ctr Reprod Biol, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2006 VL 13 IS 2 SU S MA 48 BP 79A EP 80A PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 017KZ UT WOS:000235693800049 ER PT J AU Skaznik-Wikiel, ME Niikura, Y Johnson, J Tschudy, K Tilly, JL AF Skaznik-Wikiel, ME Niikura, Y Johnson, J Tschudy, K Tilly, JL TI Regulation of mammalian female germ cell dynamics by the senescence-associated gene locus, Ink4a. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 53rd Annual Scientific Meeting of the Society-for-Gynecologic-Investigation CY MAR 22-25, 2006 CL Toronto, CANADA SP Soc Gynecolog Investigation C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Vincent Obstet & Gynecol Serv, Vincent Ctr Reprod Biol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2006 VL 13 IS 2 SU S MA 310 BP 164A EP 165A PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 017KZ UT WOS:000235693800309 ER PT J AU Niikura, Y Skaznik-Wikiel, ME Johnson, J Tilly, JL AF Niikura, Y Skaznik-Wikiel, ME Johnson, J Tilly, JL TI Germline stem cell transplantation does not reverse age-related ovarian failure. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 53rd Annual Scientific Meeting of the Society-for-Gynecologic-Investigation CY MAR 22-25, 2006 CL Toronto, CANADA SP Soc Gynecolog Investigation C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol, Boston, MA USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2006 VL 13 IS 2 SU S MA 372 BP 187A EP 187A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 017KZ UT WOS:000235693800371 ER PT J AU Pejovic, T Liu, HY Cappuccini, F Cain, JM Bagby, GC AF Pejovic, T Liu, HY Cappuccini, F Cain, JM Bagby, GC TI Fanconi pathway dysfunction in ovarian cancer: Tissue specific cytogenetic instability in ovarian epithelial cells in high risk women. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 53rd Annual Scientific Meeting of the Society-for-Gynecologic-Investigation CY MAR 22-25, 2006 CL Toronto, CANADA SP Soc Gynecolog Investigation C1 Oregon Hlth & Sci Univ, Portland, OR USA. Portland VA Med Ctr, NW VA Canc Res Ctr, Portland, OR 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2006 VL 13 IS 2 SU S MA 373 BP 187A EP 187A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 017KZ UT WOS:000235693800372 ER PT J AU Linden, PA Gilbert, RJ Yeap, BY Boyle, K Deykin, A Jaklitsch, MT Sugarbaker, DJ Bueno, R AF Linden, PA Gilbert, RJ Yeap, BY Boyle, K Deykin, A Jaklitsch, MT Sugarbaker, DJ Bueno, R TI Laparoscopic fundoplication in patients with end-stage lung disease awaiting transplantation SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT 85th Annual Meeting of the American-Association-for-Thoracic-Surgery CY APR 10-13, 2005 CL San Francisco, CA SP Amer Assoc Thorac Surg ID GASTROESOPHAGEAL-REFLUX DISEASE; IDIOPATHIC PULMONARY-FIBROSIS; INCREASED PREVALENCE; ASTHMATICS; SYMPTOMS; THERAPY; COPD AB Objective: There is a strong association between reflux and end-stage lung disease, especially idiopathic pulmonary fibrosis. The presence of reflux after lung transplantation might predispose to the development of bronchiolitis obliterans. We evaluated the risk and physiologic effect of laparoscopic fundoplication in patients on the lung transplant waiting list. Methods: One hundred forty-nine patients on the lung transplant waiting list between March 2001 and January 2005 were evaluated. Nineteen were found to have a history of reflux, continued symptoms, and severe reflux by means of pH and manometric studies and underwent laparoscopic fundoplication. The postoperative course of these 19 patients, including lung function, was retrospectively reviewed. Postoperatively, the lung function of the 14 patients with idiopathic pulmonary fibrosis who underwent the laparoscopic Nissen procedure was compared with that of 31 patients with idiopathic pulmonary fibrosis on the transplant waiting list who did not undergo fundoplication. Results: There were no perioperative complications and no decrease in lung function over the 15-month average follow-up. Exercise capacity remained stable, as determined on the basis of 6-minute walk distance. Patients with idiopathic pulmonary fibrosis treated with fundoplication had stable oxygen requirements, whereas control patients with idiopathic pulmonary fibrosis on the waiting list had a statistically significant deterioration in oxygen requirement. Conclusions: Laparoscopic fundoplication can be performed safely in patients with end-stage lung disease awaiting lung transplantation. Overall, these patients maintained stable lung function during the follow-up period. When compared with a control group of patients with idiopathic pulmonary fibrosis not undergoing fundoplication, there was stabilization of oxygen requirement. A larger prospective trial evaluating the effect of laparoscopic fundoplication on underlying lung function in this patient population is warranted. C1 Brigham & Womens Hosp, Div Thorac Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Tufts Univ, St Elizabeths Hosp, Div Gastroenterol, Boston, MA USA. Tufts Med Sch, Boston, MA USA. Massachusetts Gen Hosp, Hematol Oncol Unit, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Pulm Med, Boston, MA 02115 USA. RP Linden, PA (reprint author), Brigham & Womens Hosp, Div Thorac Surg, 75 Francis St, Boston, MA 02115 USA. EM plinden@partners.org NR 16 TC 78 Z9 83 U1 0 U2 0 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 FEB PY 2006 VL 131 IS 2 BP 438 EP 446 DI 10.1016/j.jtcvs.2005.10.014 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 010MK UT WOS:000235198600027 PM 16434276 ER PT J AU Bauer, KA AF Bauer, KA TI New anticoagulants: Anti IIa vs anti Xa - Is one better? SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Article; Proceedings Paper CT 8th National Conference on Anticoagulant Therapy CY MAY 05-07, 2005 CL Orlando, FL DE anticoagulants; venous thromboembolism; thrombin; factor Xa ID RANDOMIZED DOUBLE-BLIND; THROMBIN INHIBITOR XIMELAGATRAN; HIP-REPLACEMENT SURGERY; VENOUS THROMBOEMBOLISM; POSTOPERATIVE FONDAPARINUX; INITIAL TREATMENT; PREVENTION; ENOXAPARIN; TRIAL; WARFARIN AB Traditional anticoagulant drugs, including unfractionated heparin and warfarin, have several limitations. A new strategy for the design of new antithrombotic drugs is based on selective inhibition of a specific coagulation factor. These include direct thrombin inhibitors and factor Xa inhibitors. Two parenteral direct thrombin inhibitors, lepirudin and argatroban, have FDA approval for the management of heparin-induced thrombocytopenia. Ximelagatran, an oral prodrug of the direct thrombin inhibitor melagatran, has shown efficacy in the prevention and treatment of venous thromboembolism as well as stroke prevention in patients with atrial fibrillation. Fondaparinux is a synthetic pentasaccharide, which binds to antithrombin, thereby indirectly selectively inhibiting factor Xa. Fondaparinux has demonstrated its efficacy compared to low-molecular-weight heparin in randomized clinical trials and is FDA approved for the prevention and treatment of venous thromboembolism. A number of oral direct factor Xa inhibitors as well as other oral direct thrombin inhibitors are in clinical development for the prevention and treatment of thrombosis. C1 VA Boston Healthcare Syst, W Roxbury, MA 02132 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. RP Bauer, KA (reprint author), VA Boston Healthcare Syst, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM kbauer@bidmc.harvard.edu NR 16 TC 61 Z9 65 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5305 J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD FEB PY 2006 VL 21 IS 1 BP 67 EP 72 DI 10.1007/s11239-006-5579-4 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 011YC UT WOS:000235304300011 PM 16475045 ER PT J AU Benacerraf, BR Shipp, TD Bromley, B AF Benacerraf, BR Shipp, TD Bromley, B TI Improving the efficiency of Gynecologic Sonography wiffi 3-dimensional volumes - A pilot study SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE efficiency comparison; gynecologic scan; ovaries; 3-climensional sonography; transvaginal sonography ID ULTRASOUND AB Objective. The purpose of this study was to determine whether 3-dimensional (3D) sonography can provide a rapid, efficient, and accurate way to do a transvaginal gynecologic scan compared with traditional 2-dimensional (2D) sonography. Methods. Thirty-five consecutive patients who underwent gynecologic sonography formed the study cohort. After a standard 2D transvaginal scan was done, including measurements of the endometrium and abnormalities, 4 volume acquisitions were obtained, encompassing the uterus (2 volumes) and the ovaries. These volumes were reviewed offline without any patient information. Endometrium and other measurements were performed on the volumes. The 2D and 3D results were compared by paired t tests. Results. The mean time needed for the standard 2D scan was 2.6 minutes compared with 1.07 minutes for the 3D volume acquisitions. The mean time for the reconstruction, measurement, and interpretation of the volumes offline was 1.19 minutes. The mean time for the entire 3D examination (both parts) was 2.26 minutes (P = .047, comparing 2D with total 3D). There was no significant difference between the measurements of the endometrium, fibroids, and ovarian cysts when comparing 2D and reconstructed 3D images. Two-dimensional and 3D sonography differed little in their ability to identify the organs and the abnormalities on the scans. Conclusions. This study shows that a complete transvaginal gynecologic examination can be done in 1.07 minutes of scan time and interpreted offline in an additional 1.19 minutes. The 35 cases were scanned and interpreted with the use of 3D sonography in 79.17 minutes total compared with 91.46 minutes of 2D scan time (P =.047). The accuracy of the scan was similar for both techniques. C1 Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. RP Benacerraf, BR (reprint author), Diagnost Ultrasound Associates PC, 333 Longwood Ave,Suite 400, Boston, MA 02115 USA. NR 10 TC 20 Z9 20 U1 0 U2 0 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD FEB PY 2006 VL 25 IS 2 BP 165 EP 171 PG 7 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 011GJ UT WOS:000235255900004 PM 16439779 ER PT J AU Freedland, SJ Platz, EA Presti, JC Aronson, WJ Amling, CL Kane, CJ Terris, MK AF Freedland, SJ Platz, EA Presti, JC Aronson, WJ Amling, CL Kane, CJ Terris, MK TI Obesity, serum prostate specific antigen and prostate size: Implications for prostate cancer detection SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic neoplasms; prostatectomy; obesity; prostate-specific antigen ID BODY-MASS INDEX; FOLLOW-UP; HYPERPLASIA; BIOPSY; RISK; MEN; ANTHROPOMETRY; POPULATION; PREDICTOR; INSULIN AB Purpose: Obesity has been associated with lower serum testosterone, theoretically resulting in decreased PSA production. Obesity has also been associated with prostatic enlargement, making the detection of existent cancer more difficult. Together these findings would result in an apparent protective effect of obesity on prostate cancer risk due to technical detection issues unrelated to cancer biology. We examined the association between BMI, and PSA and prostate weight in a cohort of men undergoing RP. Materials and Methods: We evaluated the association of BMI with prostate weight and PSA using linear regression, adjusting for patient age at RP, year of RP, race, and pathological stage and grade in 1,414 men treated with RP between 1988 and 2004 at the 5 equal access medical centers that comprise the Shared Equal Access Regional Cancer Hospital Database. Results: On multivariate analysis increasing BMI was associated with increasing prostate weight but only in men younger than 63 years and not in men 63 years or older (p-trend < 0.001 and 0.44, respectively). In men younger than 63 years mean multivariate adjusted prostate weight +/- SE in those with a BMI of less than 25 vs 30 to 34.9 kg/m(2) was 33.8 +/- 1.4 vs 41.4 +/- 1.6 gm. There was no significant association between BMI and preoperative PSA (p-trend = 0.70). Conclusions: In a cohort of men undergoing RP obesity was associated with larger prostate size but only in younger men. There was no association between BMI and PSA. Assuming equal PSA, the degree of prostatic enlargement observed in younger obese men in this study would be expected to result in a modest decrease in the odds of detecting prostate cancer in a contemporary series of PSA screened men due to the decreased sensitivity of cancer detection related to larger prostate size. Obesity may appear protective for prostate cancer in younger men due to technical issues unrelated to cancer biology. C1 Johns Hopkins Univ, Sch Med, Dept Urol, Baltimore, MD USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Johns Hopkins Med Inst, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21205 USA. Stanford Univ, Sch Med, Dept Urol, Palo Alto, CA 94304 USA. Vet Adm Med Ctr, Dept Surg, Palo Alto, CA USA. Univ Calif Los Angeles, Sch Med, Dept Surg, Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Urol, Los Angeles, CA USA. San Diego Naval Hosp, Dept Urol, San Diego, CA USA. Vet Adm Med Ctr, Dept Surg, San Francisco, CA 94121 USA. Univ Calif San Francisco, Sch Med, Dept Urol, San Francisco, CA 94143 USA. Med Coll Georgia, Dept Surg, Vet Adm Med Ctr, Augusta, GA 30912 USA. Med Coll Georgia, Urol Sect, Augusta, GA 30912 USA. RP Freedland, SJ (reprint author), Johns Hopkins Sch Med, Div Urol, Box 3850, Durham, NC 27710 USA. EM steve.freedland@duke.edu OI Terris, Martha/0000-0002-3843-7270 FU NCI NIH HHS [R01CA100938, P50 CA92131-01A1, P50CA58236] NR 21 TC 96 Z9 97 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD FEB PY 2006 VL 175 IS 2 BP 500 EP 504 DI 10.1016/S0022-5347(05)00162-X PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 001XO UT WOS:000234576200022 PM 16406980 ER PT J AU Guzzo, TJ Vira, M Wang, YL Tomaszewski, J D'amico, A Wein, AJ Malkowicz, SB AF Guzzo, TJ Vira, M Wang, YL Tomaszewski, J D'amico, A Wein, AJ Malkowicz, SB TI Preoperative parameters, including percent positive biopsy, in predicting seminal vesicle involvement in patients with prostate cancer SO JOURNAL OF UROLOGY LA English DT Article DE prostatic neoplasms; seminal vesicles; prostatectomy ID SPARING RADICAL PROSTATECTOMY; RETROPUBIC PROSTATECTOMY; INVASION; ADENOCARCINOMA; RESECTION; TRENDS AB Purpose: Complete dissection of the SVs during RP can contribute to increased morbidity including erectile dysfunction and incontinence. Therefore we evaluated the clinical parameters associated with a positive SV finding on final pathology and identified those patients with a minimal risk of SV involvement for potential SV sparing surgery. Materials and Methods: We retrospectively reviewed our RP database from 1991 to 1999 to evaluate the incidence and clinical correlates of SV invasion. Variables studied included preoperative total serum PSA, percent positive biopsy cores, DRE and biopsy Gleason score. Statistical analysis included univariate, multivariate regression analysis and ROC curves. Results: Of our 1,056 patients 79 (7.4%) had SV involvement. Of the 356 patients with less than 17% positive biopsies, only 2 (0.5%) had SV involvement on final pathology. Preoperative PSA, biopsy Gleason score and percent positive biopsies were all highly predictive of SV invasion on multivariate analysis. Percent positive biopsy was found to be the single best predictor of seminal vesicle invasion (p < 0.0001). Conclusions: In our series percent positive biopsy was the single best predictor of SV invasion at the time of RP. An analysis of preoperative parameters including percent positive biopsy, biopsy Gleason score and preoperative PSA may define a subset of patients in which prospective studies could be used to determine the value and safety of SV sparing surgery. C1 Hosp Univ Penn, Dept Urol, Philadelphia, PA 19104 USA. Hosp Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. Hosp Univ Penn, Dept Pathol, Philadelphia, PA 19104 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Malkowicz, SB (reprint author), Hosp Univ Penn, Dept Urol, 3400 Spruce St,9 Penn Tower, Philadelphia, PA 19104 USA. EM bruce.malkowicz@uphs.upenn.edu NR 20 TC 14 Z9 16 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD FEB PY 2006 VL 175 IS 2 BP 518 EP 521 DI 10.1016/S0022-5347(05)00235-1 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 001XO UT WOS:000234576200029 PM 16406985 ER PT J AU Dawson, S AF Dawson, S TI Procedural simulation: A primer SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Editorial Material ID VIRTUAL-REALITY; MEDICAL-EDUCATION; ERRORS; LIFE AB Procedural simulation will be a revolutionary change in how health care providers maintain their proficiency and skill. Visionary leaders are already examining how this educational technique will be integrated into traditional curricula, and interventional specialties will be at the leading edge of this revolution. The role must be defined that simulation will play, new educational models must be developed around it, and studies must be performed that will meet the demands of a skeptical profession. Only then will the first truly revolutionary change in medical learning have been achieved since the advent of animal experimentation nearly 1,000 years ago. C1 Massachusetts Gen Hosp, Dept Radiol, Ctr Integrat Med & Innovat Technol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Dawson, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, Ctr Integrat Med & Innovat Technol, 55 Fruit St, Boston, MA 02114 USA. EM steven@mgh.harvard.edu NR 19 TC 30 Z9 30 U1 4 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD FEB PY 2006 VL 17 IS 2 BP 205 EP 213 DI 10.1097/01.RVI.0000194871.97225.CA PN 1 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 020ZN UT WOS:000235952100001 PM 16517765 ER PT J AU Brown, DB Cardella, JF Sacks, D Goldberg, SN Gervais, DA Rajan, D Vedantham, S Miller, DL Brountzos, EN Grassi, CJ Towbin, RB AF Brown, DB Cardella, JF Sacks, D Goldberg, SN Gervais, DA Rajan, D Vedantham, S Miller, DL Brountzos, EN Grassi, CJ Towbin, RB TI Quality improvement guidelines for transhepatic arterial chemoembolization, embolization, and chemotherapeutic infusion for hepatic malignancy SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID UNRESECTABLE HEPATOCELLULAR-CARCINOMA; TRANSCATHETER OILY CHEMOEMBOLIZATION; RANDOMIZED CONTROLLED TRIAL; RADIOFREQUENCY THERMAL ABLATION; METASTATIC COLORECTAL-CARCINOMA; INFERIOR PHRENIC ARTERY; LIVER-DISEASE MELD; PHASE-II TRIAL; TRANSARTERIAL CHEMOEMBOLIZATION; LIPIODOL CHEMOEMBOLIZATION C1 Washington Univ, Sch Med, Mallinckrodt Inst Radiol, Siteman Canc Ctr, St Louis, MO 63110 USA. Univ Colorado, Hlth Sci Ctr, Dept Radiol, Denver, CO 80262 USA. Reading Hosp Med Ctr, Dept Radiol, W Reading, PA USA. Childrens Hosp Philadelphia, Dept Radiol, Philadelphia, PA 19104 USA. Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Radiol, Gastrointestinal Genitourinary Div, Boston, MA 02114 USA. Lahey Clin Med Ctr, Dept Radiol, Burlington, MA 01803 USA. Univ Toronto, Div Intervent Radiol, Dept Med Imaging, Toronto, ON, Canada. Uniformed Serv Univ Hlth Sci, Dept Radiol & Radiol Sci, F Edward Hebert Sch Med,NCI, Med Oncol Clin Res Unit,Ctr Canc Res, Bethesda, MD 20814 USA. Univ Athens, Dept Radiol, Athens, Greece. RP Brown, DB (reprint author), Washington Univ, Sch Med, Mallinckrodt Inst Radiol, Siteman Canc Ctr, 510 S Kingshighway Blvd,Box 8131, St Louis, MO 63110 USA. EM brownda@mir.wustl.edu NR 71 TC 66 Z9 73 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD FEB PY 2006 VL 17 IS 2 BP 225 EP 232 DI 10.1097/01.RVI.0000195330.47954.48 PN 1 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 020ZN UT WOS:000235952100004 PM 16517768 ER PT J AU Meissner, OA Rieber, J Babaryka, G Oswald, M Reim, S Siebert, U Redel, T Reiser, M Mueller-Lisse, U AF Meissner, OA Rieber, J Babaryka, G Oswald, M Reim, S Siebert, U Redel, T Reiser, M Mueller-Lisse, U TI Intravascular optical coherence tomography: Comparison with histopathology in atherosclerotic peripheral artery specimens SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID HIGH-FREQUENCY ULTRASOUND; CORONARY-ARTERY; PLAQUE MORPHOLOGY; BIOPSY AB PURPOSE: Intravascular optical coherence tomography (OCT) is a new imaging modality that provides microstructural information on atherosclerotic plaques and has an axial resolution of 10-20 mu m. OCT of coronary arteries characterizes different atherosclerotic plaque components by their distinctive signal patterns. Peripheral human arteries were examined ex vivo by means of OCT, and attempts to distinguish among fibrous, lipid-rich, and calcified atherosclerotic plaques were made based on imaging criteria previously established for coronary arteries. MATERIALS AND METHODS: One hundred fifty-one atherosclerotic arterial segments were obtained from 15 below-knee amputations. OCT imaging criteria for different plaque types (fibrous, lipid-rich, calcified) were established in a subset of 30 arterial segments. The remaining 121 OCT images were analyzed by two independent readers. Each segment was divided into four quadrants. Agreement between histopathology and OCT was quantified by the K test of concordance, as were interobserver, intraobserver, and intermethod variability. RESULTS: Four hundred sixty-nine of 484 quadrants (97%) were available for comparison. Sensitivity and specificity for OCT criteria (consensus readers 1. and 2) were 86% and 86% for fibrous plaques, 78% and 93% for lipid-rich plaques, and 84% and 95% for calcified plaques, respectively (overall agreement, 84%). The interobserver and intraobserver reliabilities of OCT assessment were high (kappa values of 0.84 and 0.87, respectively). The intermethod agreement was 0.74 for consensus OCT versus consensus histology. CONCLUSIONS: OCT of peripheral human arteries ex vivo characterized different atherosclerotic plaque types with a high degree of agreement with histopathologic findings. Findings were comparable to those reported for coronary arteries. OCT promises to improve understanding of the progression or regression of peripheral atherosclerosis in vivo. C1 Univ Munich, Inst Clin Radiol, D-80336 Munich, Germany. Univ Munich, Div Cardiol, D-80336 Munich, Germany. Univ Munich, Inst Pathol, D-80336 Munich, Germany. Univ Munich, Inst Med Informat Biostat & Epidemiol, D-80336 Munich, Germany. Siemens AG, Forchheim, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. RP Meissner, OA (reprint author), Univ Munich, Inst Clin Radiol, Ziemssenstr 1, D-80336 Munich, Germany. EM oliver.meissner@med.uni-muenchen.de NR 22 TC 25 Z9 27 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD FEB PY 2006 VL 17 IS 2 BP 343 EP 349 DI 10.1097/01.RVI.0000195324.52104.00 PN 1 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 020ZN UT WOS:000235952100017 PM 16517781 ER PT J AU Black, JH Cambria, RP AF Black, JH Cambria, RP TI Current results of open surgical repair of descending thoracic aortic aneurysms SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID CEREBROSPINAL-FLUID DRAINAGE; SPINAL-CORD PROTECTION; NATURAL-HISTORY; PARAPLEGIA; EXPERIENCE; SURGERY; RISK; OPERATIONS; MORTALITY; TRIAL C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. RP Cambria, RP (reprint author), Massachusetts Gen Hosp, WACC 458,15 Parkman St, Boston, MA 02114 USA. NR 33 TC 13 Z9 13 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD FEB PY 2006 VL 43 SU A BP 6A EP 11A DI 10.1016/j.jvs.2005.10.047 PG 6 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 017JV UT WOS:000235690800003 PM 16473172 ER PT J AU Atkins, MD Black, JH Cambria, RP AF Atkins, MD Black, JH Cambria, RP TI Aortic dissection: Perspectives in the era of stent-graft repair SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID INTRAMURAL HEMATOMA; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; INTERNATIONAL REGISTRY; ENDOVASCULAR TREATMENT; SURGICAL-MANAGEMENT; COMPUTED-TOMOGRAPHY; ANEURYSM REPAIR; THORACIC AORTA; FALSE LUMEN; FOLLOW-UP C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. RP Cambria, RP (reprint author), Massachusetts Gen Hosp, WACC 458,15 Parkman St, Boston, MA 02114 USA. EM rcambria@partners.org NR 52 TC 27 Z9 28 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD FEB PY 2006 VL 43 SU A BP 30A EP 43A DI 10.1016/j.jvs.2005.10.052 PG 14 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 017JV UT WOS:000235690800007 PM 16473168 ER PT J AU Rigberg, DA McGory, ML Zingmond, DS Maggard, MA Agustin, M Lawrence, PF Ko, CY AF Rigberg, DA McGory, ML Zingmond, DS Maggard, MA Agustin, M Lawrence, PF Ko, CY TI Thirty-day mortality statistics underestimate the risk of repair of thoracoabdominal aortic aneurysms: A statewide experience SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 59th Annual Meeting of the Society-for-Vascular-Surgery CY JUN 16-19, 2005 CL Chicago, IL SP Soc Vasc Surg ID UNITED-STATES; IMMEDIATE; ACCURACY; SURGERY AB Objective: The purpose of this study was to determine the 30-day and 365-day mortality for the repair of thoracoabdominal aortic aneurysms (TAA), when stratified by age, in the general population. These data provide clinicians with information more applicable to an individual patient than mortality figures from a single institutional series. Methods. Data were obtained from the California Office of Statewide Health Planning and Development (OSHPD) for the years 1991 to 2002. These data were linked to the state death certificate file, allowing for continued information oil the status of the patients after hospital discharge. All patients undergoing elective and ruptured TAA repair as coded by International Classification of Diseases, 9th Clinical Modification (ICD-9, CM) in California were identified. Patients aged < 50 or > 90 years old were excluded. We determined 30- and 365-day mortality and stratified our findings by decade of patient age (eg, 50 to 59). Demographics of elective and ruptured cases were also compared. Results: We identified 1010 patients (797 elective, 213 ruptured) who underwent TAA repair. Mean patient ages were 70.0 (elective) and 72.1 years (ruptured). Men comprised 62% of elective and 68% of ruptured aneurysm patients, and 80% (elective) and 74% (ruptured) were white. Overall elective patient mortality was 19% at 30 days and 31% at 365 days. There was a steep increase in mortality with increasing age, such that elective 365-day mortality increased from about 18% for patients 50 to 59 years old to 40% for patients 80 to 89 years old. The elective case 31-day to 365-day mortality ranged from 7.8% for the youngest patients to 13.5%. Mortality for ruptured cases was 48.4% at 30 days and 61.5% at 365 days, and these rates also increased with age. Conclusions: Our observed 30-day mortality for TAA repairs is consistent with previous reports; however, mortality at 1 year demonstrates a significant risk beyond the initial perioperative period, and this risk increases with age. These data reflect surgical mortality for TAA repair in the general population and may provide more useful data for surgeons and patients contemplating TAA surgery. C1 Univ Calif Los Angeles, Sch Med, Ctr Surg Outcomes & Qual, W Los Angeles Vet Adm Med Ctr, Los Angeles, CA 90024 USA. RP Rigberg, DA (reprint author), GONDA Goldschmied Vasc Ctr, Div Vasc Surg, 200 UCLA Med Plaza,Suite 510-6, Los Angeles, CA 90095 USA. EM drigberg@mednet.ucla.edu NR 21 TC 176 Z9 180 U1 1 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD FEB PY 2006 VL 43 IS 2 BP 217 EP 222 DI 10.1016/j.jvs.2005.10.070 PG 6 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 014PN UT WOS:000235492300003 PM 16476589 ER PT J AU Rigberg, DA Zingmond, DS McGory, ML Maggard, MA Agustin, M Lawrence, PF Ko, CY AF Rigberg, DA Zingmond, DS McGory, ML Maggard, MA Agustin, M Lawrence, PF Ko, CY TI Age stratified, perioperative, and one-year mortality after abdominal aortic aneurysm repair: A statewide experience SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 33rd Annual Symposium of the Society-for-Clinical-Vascular-Surgery CY MAR 09-13, 2005 CL Coral Gables, FL SP Soc Clin Vasc Surg ID UNITED-STATES; STENT-GRAFT; OPERATIVE MORTALITY; SURGERY; MORBIDITY; INTACT; ENDOGRAFT; VOLUME; TRIAL; RATES AB Objective: The purpose of this study was to determine the in-hospital, 30-day, and 365-day mortality for the open repair of abdominal aortic aneurysms (AAAs), when stratified by age, in the general population. Age stratification could provide clinicians with information more applicable to an individual patient than overall mortality figures. Methods: In a retrospective analysis, data were obtained from the California Office of Statewide Health Planning and Development (OSHPD) for the years 1995 to 1999. Out-of-hospital mortality was determined via linkage to the state death registry. All patients undergoing AAA repair as coded by International Classification of Diseases, 9th Revision (ICD-9) procedure code 38.44 and diagnosis codes 441.4 (intact) and 441.3/441.5 (ruptured) in California were identified. Patients < 50 years of age were excluded. We determined in-hospital, 30-day, and 365-day mortality, and stratified our findings by patient age. Multivariate logistic regression was used to determine predictors of mortality in the intact and ruptured AAA cohorts. Results: We identified 12,406 patients (9,778 intact, 2,628 ruptured). Mean patient age was 72.4 +/- 7.2 years (intact) and 73.9 +/- 8.2 (ruptured). Men comprised 80.9% of patients, and 90.8% of patients were white. Overall, intact AAA patient mortality was 3.8% in-hospital, 4% at 30 days, and 8.5% at 365 days. There was a steep increase in mortality with increasing age, such that 365-day mortality increased from 2.9% for patients 51 to 60 years old to 15% for patients 81 to 90 years old. Mortality from day 31 to 365 was greater than both in-hospital and 30-day mortality for all but the youngest intact AAA patients. Perioperative (in-hospital and 30-day) mortality for ruptured cases was 45%, and mortality at 1 year was 54%. Conclusions. There is continued mortality after the open repair of AAAs during postoperative days 31 to 365 that, for many patients, is greater than the perioperative death rate. This mortality increases dramatically with age for both intact and ruptured AAA repair. C1 Univ Calif Los Angeles, Sch Med, Ctr Surg Outcomes & Qual, W Los Angeles Vet Adm Med Ctr, Los Angeles, CA USA. RP Rigberg, DA (reprint author), GONDA Goldschmied Vasc Ctr, Div Vasc Surg, 200 UCLA Med Plaza,Suite 510-6, Los Angeles, CA 90095 USA. EM drigberg@mednet.ucla.edu NR 32 TC 23 Z9 24 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD FEB PY 2006 VL 43 IS 2 BP 224 EP 229 DI 10.1016/j.jvs.2005.10.071 PG 6 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 014PN UT WOS:000235492300006 PM 16476591 ER PT J AU Henao, EA Hodge, MD Felkai, DD McCollum, CH Noon, GP Lin, PH Lumsden, AB Bush, RL AF Henao, EA Hodge, MD Felkai, DD McCollum, CH Noon, GP Lin, PH Lumsden, AB Bush, RL TI Contrast-enhanced Duplex surveillance after cndovascular abdominal aortic aneurysm repair: Improved efficacy using a continuous infusion technique SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 59th Annual Meeting of the Society-for-Vascular-Surgery CY JUN 16-19, 2005 CL Chicago, IL SP Soc Vasc Surg ID ENDOLUMINAL AAA REPAIR; COMPUTED-TOMOGRAPHY; ULTRASOUND SCAN; BLOOD-FLOW; FOLLOW-UP; ENDOLEAKS; AGENT; EXPOSURE; US AB Introduction: Currently, postoperative endoleak Surveillance after endovascular aortic aneurysm repair (EVAR) is primarily done by computed tomography (CT). The purpose of this study was to determine the efficacy of contrast-enhanced ultrasonography scans to detect endoleaks by using a novel infusion method and compare these findings with those of CT angiography (CTA). Methods: Twenty male patients (mean age, 70.4 years) underwent surveillance utilizing both CTA and contrast-enhanced color Duplex imaging. One 3-mL vial of Optison (Perfluten Protein A microspheres for injection) and 57 mL normal saline, for a total of 60 mL, were administered to each patient as a continuous infusion at 4 mL/min via a peripheral vein. Each Study was optimized with harmonic imaging, and a reduced mechanical index of 0.4 to 0.5, compression of I to 3, and a focal zone below the aorta to minimize microsphere rupture. One minute was allowed from the time of infusion to the appearance of contrast in the endograft. Flow was evaluated within the lumen of the graft and its components, as was the presence or absence of endoleaks. Findings were compared with standard color-flow Duplex imaging and CT utilizing CTA reconstruction protocols. Results: All patients evaluated had modular endografts implanted for elective aneurysm repair. Contrast-enhanced duplex scans identified nine endoleaks: one type I and eight type II. No additional endoleaks were seen on CTA. However, CTA failed to recognize three type II endoleaks seen by contrast-enhanced ultrasound. The continuous infusion method allowed for longer and more detailed imaging. An average of 46.8 mL of the contrast infusion solution was used per patient. Conclusions. Contrast enhanced Duplex ultrasonography accurately demonstrates endoleaks after EVAR and may be considered as a primary surveillance modality. Continuous infusion permits longer imaging time. C1 Baylor Coll Med, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Methodist Hosp, Houston, TX USA. Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. RP Henao, EA (reprint author), Care of Corke J, 1 Baylor Plaza,404D, Houston, TX 77030 USA. EM surgmax@hotmail.com NR 22 TC 50 Z9 52 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD FEB PY 2006 VL 43 IS 2 BP 259 EP 263 DI 10.1016/j.jvs.2005.09.045 PG 5 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 014PN UT WOS:000235492300014 PM 16476596 ER PT J AU Stoner, MC Abbott, WM Wong, DR Hua, HT LaMuraglia, GM Kwolek, CJ Watkins, MT Agnihotri, AK Henderson, WG Khuri, S Cambria, RP AF Stoner, MC Abbott, WM Wong, DR Hua, HT LaMuraglia, GM Kwolek, CJ Watkins, MT Agnihotri, AK Henderson, WG Khuri, S Cambria, RP TI Defining the high-risk patient for carotid endarterectomy: An analysis of the prospective National Surgical Quality Improvement Program database SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 59th Annual Meeting of the Society-for-Vascular-Surgery CY JUN 16-19, 2005 CL Chicago, IL SP Soc Vasc Surg ID ABDOMINAL AORTIC-ANEURYSM; MAJOR VASCULAR-SURGERY; RENAL-INSUFFICIENCY; POSTOPERATIVE COMPLICATIONS; CARDIAC COMPLICATIONS; LOCAL-ANESTHESIA; MORTALITY; OUTCOMES; STROKE; TRIAL AB Background Carotid endarterectomy (CEA) is the gold standard for the treatment of carotid stenosis, but carotid angioplasty and stenting has been advocated in high-risk patients. The definition of such a population has been elusive, particularly because the data are largely retrospective. Our study examined results for CEA in the National Surgical Quality Improvement Program database (both Veterans Affairs and private sector). Methods: National Surgical Quality Improvement Program data were gathered prospectively for ill patients undergoing primary isolated CEA during the interval 2000 to 2003 at 123 Veterans Affairs and 14 private sector academic medical centers. Study end Points included the 30-day occurrence of any stroke, death, or cardiac event. A variety of clinical, demographic, and operative variables were assessed with multivariate models to identify risk factors associated with the composite (stroke, death, or cardiac event) end point. Adjudication of end points was by trained nurse reviewers (previously validated). Results: A total of 13,622 CEAs were performed during the study period; 95% were oil male patients, and 91% of cases were conducted within the Veterans Affairs sector. The average age was 68.6 +/- 0.1 years, and 42.1% of the population had no prior neurologic event. The composite stroke, death, or cardiac event rate was 4.0%; the stroke/death rate was 3.4%. Multivariate correlates of the composite outcome were (odds ratio, P value) as follows: deciles of age (1.13,.018), insulin-requiring diabetes (1.73, <.001), oral agent-controlled diabetes (1.39,.003), decade of pack-years smoking (1.04, >.001), history of transient ischemic attack (1.41, >.001.), history of stroke (1.51, >.001), creatinine > 1.5 mg/dL (1.48, >.001), hypoalbuminemia (1.49, >.001), and fourth quartile of operative time (1.44, >.001). Cardiopulmonary comorbid features did not affect the composite outcome in this model. Regional anesthesia was used in 2437 (18%) cases, with a resultant relative risk reduction for stroke (17%), death (24%), cardiac event (33%), and the composite outcome (31%; odds ratio, 0.69; P =.008). Conclusions. Carotid endarterectomy results across a spectrum of Veterans Affairs and private sector hospitals compare favorably to contemporary studies. These data will assist in selecting patients who are at all increased risk for adverse outcomes. Use of regional anesthetic significantly reduced perioperative complications in a risk-adjusted model, thus suggesting that it is the anesthetic of choice when CEA is performed in high-risk patients. C1 Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Clin Effectiveness Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. Univ Colorado, Hlth Outcomes Program, Aurora, CO USA. Vet Affairs Boston Healthcare Syst, W Roxbury, MA USA. RP Stoner, MC (reprint author), E Carolina Univ, Brody Sch Med, Dept Surg, Div Vasc & Endovasc Surg, Greenville, NC 27834 USA. EM stonerm@ecu.edu NR 62 TC 75 Z9 77 U1 1 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD FEB PY 2006 VL 43 IS 2 BP 285 EP 294 DI 10.1016/j.jvs.2005.10.069 PG 10 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 014PN UT WOS:000235492300022 PM 16476603 ER PT J AU Silberfein, EJ Lin, PH Bush, RL Zhou, W Lumsden, AB AF Silberfein, EJ Lin, PH Bush, RL Zhou, W Lumsden, AB TI Aortic endograft infection due to Pasteurella multocida following a rabbit bite SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID PROSTHETIC JOINT INFECTION; GRAFT INFECTION; VASCULAR GRAFT; ANEURYSM AB Abdominal aortic endograft infection is a serious complication after an endovascular abdominal aortic aneurysm repair. Pasteurella multocida, a gram-negative bacterium, is a commonly found organism in the mouth flora of many house pets. We report a case of an aortic endograft infection caused by P multocida after a rabbit bite. Successful treatment was performed by extra-anatomic revascularization followed by endograft removal. C1 Houston VAMC, Baylor Coll Med, Dept Surg, Houston, TX 77030 USA. Houston VAMC, Baylor Coll Med, Dept Surg, Houston, TX 77030 USA. Houston VAMC, Baylor Coll Med, Div Vasc Surg & Endovasc Therapy, Houston, TX 77030 USA. RP Lin, PH (reprint author), Houston VAMC, Baylor Coll Med, Dept Surg, 2002 Holcomb Blvd, Houston, TX 77030 USA. EM plin@bcm.tmc.edu NR 15 TC 21 Z9 21 U1 0 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD FEB PY 2006 VL 43 IS 2 BP 393 EP 395 DI 10.1016/j.jvs.2005.10.067 PG 3 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 014PN UT WOS:000235492300042 PM 16476621 ER PT J AU Komatsu, H Lauer, G Pybus, OG Ouchi, K Wong, D Ward, S Walker, B Klenerman, P AF Komatsu, H Lauer, G Pybus, OG Ouchi, K Wong, D Ward, S Walker, B Klenerman, P TI Do antiviral CD8+T cells select hepatitis C virus escape mutants? Analysis in diverse epitopes targeted by human intrahepatic CD8+T lymphocytes SO JOURNAL OF VIRAL HEPATITIS LA English DT Article DE CD8+T cell; evolution; HCV; immune escape; liver ID CYTOTOXIC T-LYMPHOCYTES; HUMAN-IMMUNODEFICIENCY-VIRUS; I PEPTIDE TETRAMERS; IMMUNE-RESPONSES; PERIPHERAL-BLOOD; VIRAL ESCAPE; INFECTION; VARIANTS; LIVER; HIV AB Hepatitis C virus (HCV) is a variable RNA virus that can readily establish persistent infection. Cellular immune responses are important in the early control of the virus. Evidence from animal models suggests that mutation in epitopes recognized by CD8+ T lymphocytes may play an important role in the establishment of persistence but in human persistent infection, equivalent evidence is lacking. We investigated this by analysing a unique resource: viruses from a set of chronically HCV-infected individuals in whom the CD8+ T-cell responses in liver had previously been accurately mapped. Virus was sequenced in seven individuals at 10 epitopes restricted by 10 human leucocyte antigen (HLA) molecules. Two main patterns emerged: in the majority of epitopes sequenced, no variation was seen. In three epitopes, mutations were identified which were compatible with immune escape as assessed using phylogenetic and/or functional studies. These data suggest that - even where specific intrahepatic T cells are detectable - many epitopes do not undergo mutation in chronic human infection. On the contrary, virus may escape from intrahepatic CD8+ T-cell responses in a 'patchy' manner in certain specific epitopes. Furthermore, longitudinal studies to identify the differences between 'selecting' and 'nonselecting' intrahepatic CD8+ T-cell responses are needed in HCV infection. C1 Univ Oxford, Nuffield Dept Med, Oxford OX1 3SY, England. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Univ Oxford, Dept Zool, Oxford OX1 3PS, England. Univ Toronto, Toronto Gen Hosp, Toronto, ON M5G 1L7, Canada. RP Klenerman, P (reprint author), Univ Oxford, Nuffield Dept Med, S Parks Rd,Peter Medawar Bldg, Oxford OX1 3SY, England. EM paul.klenerman@medawar.ox.ac.uk RI pybus, oliver/B-2640-2012; OI Pybus, Oliver/0000-0002-8797-2667; Wong, David/0000-0002-3310-3538 FU Wellcome Trust NR 35 TC 15 Z9 16 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1352-0504 J9 J VIRAL HEPATITIS JI J. Viral Hepatitis PD FEB PY 2006 VL 13 IS 2 BP 121 EP 130 DI 10.1111/j.1365-2893.2005.00676.x PG 10 WC Gastroenterology & Hepatology; Infectious Diseases; Virology SC Gastroenterology & Hepatology; Infectious Diseases; Virology GA 005WI UT WOS:000234855300007 PM 16436130 ER PT J AU Brockman, MA Tanzi, GO Walker, BD Allen, TM AF Brockman, MA Tanzi, GO Walker, BD Allen, TM TI Use of a novel GFP reporter cell line to examine replication capacity of CXCR4- and CCR5-tropic HIV-1 by flow cytometry SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE human immunodeficiency virus; fitness; flow cytometry; green fluorescent protein ID HUMAN-IMMUNODEFICIENCY-VIRUS; DRUG SUSCEPTIBILITY; TYPE-1 INFECTION; SUBTYPE-C; IN-VITRO; FITNESS; TROPISM; EVOLUTION; ESCAPE; ENTRY AB The rate of HIV-1 disease progression correlates strongly with plasma viral load and is likely to be influenced by both host and viral determinants. Though interest in the impact of viral replication capacity during HIV-1 infection has been increasing, especially with respect to drug resistance mutations, its influence on disease course remains poorly understood. This is due in part to significant drawbacks in conventional means of measuring HIV-1 growth in vitro (i.e. expense, inconvenience, and experimental variability). A FACS-based method is described here to measure HIV-1 replication sensitively and a modification of this method can be used to determine viral titer accurately. Importantly, the target cells used are permissive to CXCR4- and CCR5-tropic HIV-1 strains. In pilot experiments, the growth kinetics of laboratory-adapted strains NL4-3 and 11113 were examined carefully. Using this method, differences were observed in growth kinetics between three laboratory strains and seven primary isolates, indicating the potential for a broad range of in vitro replication capacities among individual isolates. In conclusion, this FACS-based method provides a sensitive approach to measure the replication capacity of HIV-1 and may prove useful in studies examining the impact of viral fitness on disease progression. (c) 2005 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Div Aids, Boston, MA 02129 USA. Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02129 USA. RP Allen, TM (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA. EM tallen2@partners.org RI Allen, Todd/F-5473-2011; OI Brockman, Mark/0000-0001-6432-1426 FU NIAID NIH HHS [AI054178] NR 34 TC 40 Z9 40 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD FEB PY 2006 VL 131 IS 2 BP 134 EP 142 DI 10.1016/j.jviromet.2005.08.003 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 011JN UT WOS:000235264500004 PM 16182382 ER PT J AU Irimia, D Liu, SY Tharp, WG Samadani, A Toner, M Poznansky, MC AF Irimia, D Liu, SY Tharp, WG Samadani, A Toner, M Poznansky, MC TI Microfluidic system for measuring neutrophil migratory responses to fast switches of chemical gradients SO LAB ON A CHIP LA English DT Article ID HUMAN POLYMORPHONUCLEAR LEUKOCYTES; CHEMOTAXIS; POLARITY; CHEMOATTRACTANT AB Experimental systems that provide temporal and spatial control of chemical gradients are required for probing into the complex mechanisms of eukaryotic cell chemotaxis. However, no current technique can simultaneously generate stable chemical gradients and allow fast gradient changes. We developed a microfluidic system with microstructured membranes for exposing neutrophils to fast and precise changes between stable, linear gradients of the known chemoattractant Interleukin-8 (IL-8). We observed that rapidly lowering the average concentration of IL-8 within a gradient, while preserving the direction of the gradient, resulted in temporary neutrophil depolarization. Fast reversal of the gradient direction while increasing or decreasing the average concentration also resulted in temporary depolarization. Neutrophils adapted and maintained their directional motility, only when the average gradient concentration was increased and the direction of the gradient preserved. Based on these observations we propose a two-component temporal sensing mechanism that uses variations of chemokine concentration averaged over the entire cell surface and localized at the leading edge, respectively, and directs neutrophil responses to changes in their chemical microenvironment. C1 Massachusetts Gen Hosp, BioMEMS Resource Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02129 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. MIT, Dept Phys, Cambridge, MA 02139 USA. RP Massachusetts Gen Hosp, BioMEMS Resource Ctr, Boston, MA 02114 USA. EM dirimia@hms.harvard.edu OI Irimia, Daniel/0000-0001-7347-2082 FU NIAID NIH HHS [AI49757]; NIBIB NIH HHS [P41 EB002503] NR 29 TC 128 Z9 130 U1 1 U2 17 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1473-0197 EI 1473-0189 J9 LAB CHIP JI Lab Chip PD FEB PY 2006 VL 6 IS 2 BP 191 EP 198 DI 10.1039/b511877h PG 8 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA 017HO UT WOS:000235684900010 PM 16450027 ER PT J AU Zehnder, AF Kristiansen, AG Adams, JC Kujawa, SG Merchant, SN McKenna, MJ AF Zehnder, AF Kristiansen, AG Adams, JC Kujawa, SG Merchant, SN McKenna, MJ TI Osteoprotegrin knockout mice demonstrate abnormal remodeling of the otic capsule and progressive hearing loss SO LARYNGOSCOPE LA English DT Article DE bone remodeling; osteoprotegerin (OPG); otic capsule; RANK ligand (RANKL); receptor activator of nuclear factor Kappa B (RANK) ID BONE; OTOSCLEROSIS AB Objectives. The otic capsule, when compared with other bones in the body, is unique in that it undergoes no significant remodeling of bone after development. We previously demonstrated that osteoprotegerin (OPG), which inhibits formation and function of osteoclasts, is produced at high levels in the inner ear of normal mice and secreted into the perilymph from where it diffuses into the surrounding otic capsule bone through a lacunocanalicular system. To test our hypothesis that the high level of OPG may be important in the inhibition of otic capsule remodeling, we studied the light microscopic histology of the otic capsule in OPG knockout mice for evidence of abnormal remodeling of bone. We also tested the hearing in OPG knockout mice to determine whether OPG and its influence on surrounding bone is important for auditory function. Methods: Temporal bone histopathology and pathophysiology were compared in homozygous OPG knockout mice and C57BL/6 (116) mice, the background strain for the knockouts. Auditory function in age-matched animals from each group was evaluated at approximately 4-week intervals from 8 to 21 weeks using frequency-specific auditory brainstem responses (ABR) and distortion product otoacoustic emissions (DPOAE). After each of the last three evaluations, the cochleae from one mouse of each group were harvested, processed, and examined by light microscopy. Results: Osteoprotegerin knockout mice demonstrated abnormal remodeling of bone within the otic capsule with multiple foci showing osteoclastic bone resorption and formation of new bone. Such changes were not seen in the age-matched B6 controls. The active bone remodeling process in the knockout animals showed many similarities to otosclerosis seen in human temporal bones. Over the time period that we monitored, auditory function was significantly and progressively compromised in the knockout animals relative to B6 controls. At the earliest age of test (8 wk), the loss was apparent as a mild, high-frequency reduction in sensitivity by AER. In contrast, DPOAE losses in the knockouts were substantial even at 8 weeks, and by 21 weeks, these losses exceeded our equipment limits. Results of ABR testing showed hearing sensitivity changes in the animals of the background strain were confined largely to the high frequencies, whereas OPG knockouts demonstrated substantial low-frequency shifts in addition to those at high frequencies. Conclusions. The histopathological and pathophysiological findings in OPG knockout mice support the hypothesis that OPG is important in the inhibition of bone remodeling within the otic capsule and the maintenance of normal auditory function. This mouse may provide a valuable animal model of human otosclerosis. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Univ Basel, HNO Klin, CH-4003 Basel, Switzerland. RP McKenna, MJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM michael_mckenna@meei.harvard.edu FU NIDCD NIH HHS [R01 DC003929] NR 14 TC 55 Z9 60 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD FEB PY 2006 VL 116 IS 2 BP 201 EP 206 DI 10.1097/01.mlg.0000191466.09210.9a PG 6 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 015QO UT WOS:000235566100007 PM 16467704 ER PT J AU Merchant, SN Burgess, B O'Malley, J Jones, D Adams, JC AF Merchant, SN Burgess, B O'Malley, J Jones, D Adams, JC TI Polyester wax: A new embedding medium for the histopathologic study of human temporal bones SO LARYNGOSCOPE LA English DT Article ID MITOCHONDRIAL-DNA; AMPLIFICATION; SPECIMENS; HISTOLOGY; SECTIONS AB Background: Celloidin and paraffin are the two common embedding mediums used for histopathologic study of the human temporal bone by light microscopy. Although celloidin embedding permits excellent morphologic assessment, celloidin is difficult to remove, and there are significant restrictions on success with immunostaining. Embedding in paraffin allows immunostaining to be performed, but preservation of cellular detail within the membranous labyrinth is relatively poor. Objectives/Hypothesis. Polyester wax is an embedding medium that has a low melting point (37 degrees C), is soluble in most organic solvents, is water tolerant, and sections easily. We hypothesized that embedding in polyester wax would permit good preservation of the morphology of the membranous labyrinth and, at the same time, allow the study of proteins by immunostaining. Methods: Nine temporal bones from individuals aged 1 to 94 years removed 2 to 31 hours postmortem, from subjects who had no history of otologic disease, were used. The bones were fixed using 10% formalin, decalcified using EDTA, embedded in polyester wax, and serially sectioned at a thickness of 8 to 12 mu m on a rotary microtome. The block and knife were cooled with frozen CO2 (dry ice) held in a funnel above the block. Sections were placed on glass slides coated with a solution of 1% fish gelatin and 1% bovine albumin, followed by staining of selected sections with hematoxylin and eosin (H&E). Immunostaining was also performed on selected sections using antibodies to 200 kD neurofilament and Na-K-ATPase. Results: Polyester wax-embedded sections demonstrated good preservation of cellular detail of the organ of Corti and other structures of the membranous labyrinth, as well as the surrounding otic capsule. The protocol described in this paper was reliable and consistently yielded sections of good quality. Immunostaining was successful with both antibodies. Conclusion. The use of polyester wax as an embedding medium for human temporal bones offers the advantage of good preservation of morphology and ease of immunostaining. We anticipate that in the future, polyester wax embedding will also permit other molecular biologic assays on temporal bone sections such as the retrieval of nucleic acids and the study of proteins using mass spectrometry-based proteomic analysis. C1 Massachusetts Eye & Ear Infirm, Otopathol Lab, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Merchant, SN (reprint author), Massachusetts Eye & Ear Infirm, Otopathol Lab, 243 Charles St, Boston, MA 02114 USA. EM saumil_merchant@meei.harvard.edu FU NIDCD NIH HHS [R01 DC003929] NR 18 TC 11 Z9 11 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD FEB PY 2006 VL 116 IS 2 BP 245 EP 249 DI 10.1097/01.mlg.0000192171.85406.47 PG 5 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 015QO UT WOS:000235566100016 PM 16467713 ER PT J AU Laubach, HJ Tannous, Z Anderson, RR Manstein, D AF Laubach, HJ Tannous, Z Anderson, RR Manstein, D TI Skin responses to fractional photothermolysis SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE ablative resurfacing; confocal microscopy; fractional resurfacing; fractional photothermolysis; histology; human; immunohistochemistry; in vivo; laser; melanin shuttle; microscopic epidermal necrotic debris; MEND; Microthermal zones; MTZ; non-ablative resurfacing; non-ablative remodeling; skin rejuvenation ID PROFILOMETRIC EVALUATION; YAG LASER; MYOFIBROBLASTS; REJUVENATION; MICROSCOPY; HISTOLOGY AB Background and Objective: Fractional photothermolysis (FP) is a new concept using arrays of microscopic thermal damage patterns to stimulate a therapeutic response. We analyzed epidermal and dermal response to FP with the aim of correlating histological and clinical response. Study Design/Materials and Methods: Twelve subjects received a single treatment with a prototype diode laser emitting at a wavelength of 1,500 nm, delivering 5 mJ per microscopic treatment zone (MTZ), and a density of 1,600 MTZS/cm(2) on the forearm. Biopsies were procured over a period of 3 months. The biopsies were analyzed by two blinded dermatopathologists using hematoxylin and eosin (Hematoxylin and Eosin Stain), Elastica von Gieson, nitro-blue-tetrazolium-chloride (NBTC) viability, and immunohistochemistry stains. Furthermore, the treatment sites were evaluated in vivo by confocal microscopy. Results and Discussion: Twenty-four hours after fractional photothermolysis, the continuity of the epidermal basal cell layer is restored. Complete epidermal regeneration is obtained 7 days after the treatment. Microscopic epidermal necrotic debris (MENDs) are seen as early as I day after FP. MENDs contain melanin pigment, and are shed from the epidermis within 7 days. Evidence of increased collagen III production is shown with immunohistochemistry (IHC) staining 7 days after FP. IHC for heat shock protein 70 (HSP 70) shows the expression of HSP I day after FP, and IHC for alpha smooth muscle actin shows the presence of myofibroblasts 7 days after FP. These findings are concordant with the induction of a wound healing response by FP. There is no evidence of residual dermal fibrosis 3 months after treatment. Conclusion: A single treatment with fractional photothermolysis induces a wound healing response in the dermis. A mechanism for the precise removal of epidermal melanin is described, in which MENDs act as a melanin shuttle. C1 Harvard Univ, Wellman Ctr Photomed, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Laubach, HJ (reprint author), Harvard Univ, Wellman Ctr Photomed, Sch Med, Massachusetts Gen Hosp, BAR 305,50 Blossom St, Boston, MA 02114 USA. EM hlaubach@partners.org NR 18 TC 247 Z9 258 U1 0 U2 11 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD FEB PY 2006 VL 38 IS 2 BP 142 EP 149 DI 10.1002/lsm.20254 PG 8 WC Dermatology; Surgery SC Dermatology; Surgery GA 020OR UT WOS:000235919700011 PM 16392146 ER PT J AU Stam, RW den Boer, ML Passier, MMCJ Janka-Schaub, GE Sallan, SE Armstrong, SA Pieters, R AF Stam, RW den Boer, ML Passier, MMCJ Janka-Schaub, GE Sallan, SE Armstrong, SA Pieters, R TI Silencing of the tumor suppressor gene FHIT is highly characteristic for MLL gene rearranged infant acute lymphoblastic leukemia SO LEUKEMIA LA English DT Article DE infant ALL; MLL rearrangements; FHIT; hypermethylation; tumor suppressor gene ID EXPRESSION INDUCES APOPTOSIS; POOR PROGNOSTIC-FACTOR; VITRO DRUG-RESISTANCE; HISTIDINE TRIAD GENE; CANCER CELL-LINES; CLINICAL-SIGNIFICANCE; CIGARETTE-SMOKING; CERVICAL-CANCER; BREAST-CANCER; TUMORIGENICITY AB MLL rearranged acute lymphoblastic leukemia ( MLL) is an aggressive type of acute lymphoblastic leukemia ( ALL), diagnosed predominantly in infants (< 1 years of age). Since current chemotherapy fails in 450% of patients with MLL, new therapeutic strategies are desperately needed. For this, understanding the biological features characterizing MLL is necessary. Analysis of gene expression profiles revealed that the expression of the tumor suppressor gene FHIT is reduced in children with MLL rearranged ALL as compared to ALL patients carrying germ line MLL. This finding was confirmed by quantitative real-time PCR. In 100% of the infant MLL cases tested, methylation of the FHIT 5'CpG region was observed, resulting in strongly reduced mRNA and protein expression. In contrast, FHIT methylation in infant and non-infant ALL patients carrying germ line MLL was found in only similar to 60% (P <= 0.004). FHIT expression was restored upon exposing leukemic cells to the demethylating agent decitabine, which induced apoptosis. Likewise and more specifically, leukemic cell death was induced by transfecting MLL rearranged leukemic cells with expression vectors encoding wild-type FHIT, confirming tumor suppressor activity of this gene. These observations imply that suppression of FHIT may be required for the development of MLL, and provide new insights into leukemogenesis and therapeutic possibilities for MLL. C1 Sophia Childrens Univ Hosp, Dept Pediat Oncol Hematol, Erasmus MC, NL-3000 CB Rotterdam, Netherlands. COALL Study Grp, Hamburg, Germany. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. RP den Boer, ML (reprint author), Sophia Childrens Univ Hosp, Dept Pediat Oncol Hematol, Erasmus MC, Room Sp 2456,Dr Molewaterpl 60,POB 2060, NL-3000 CB Rotterdam, Netherlands. EM m.l.denboer@erasmusmc.nl NR 40 TC 33 Z9 39 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD FEB PY 2006 VL 20 IS 2 BP 264 EP 271 DI 10.1038/sj.leu.2404074 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA 005SQ UT WOS:000234844500014 PM 16357833 ER PT J AU Copeland, LA Zeber, JE Rosenheck, RA Miller, AL AF Copeland, LA Zeber, JE Rosenheck, RA Miller, AL TI Unforeseen inpatient mortality among veterans with schizophrenia SO MEDICAL CARE LA English DT Article DE aging; comorbidity; health services; mortality; schizophrenia; veterans ID SYSTEM SERVICE USE; MENTAL-DISORDERS; MYOCARDIAL-INFARCTION; PSYCHIATRIC-PATIENTS; MEDICAL-SERVICES; CARE; QUALITY; OUTPATIENTS; DISEASE; AFFAIRS AB Background: Patients with schizophrenia have co-occurring medical conditions, like other patients, but may lack the capacity to provide good self-care or to work with their providers to ensure appropriate medical treatment. We hypothesized that death among patients with schizophrenia occurs more frequently after minimal care of comorbid conditions. Methods: All patients who died in veterans affairs (VA) hospitals during FY02 were categorized as to type of death: unforeseen (age < 80 years, 1-2 inpatient days past year), cancer, organ failure (heart, lungs, kidneys), frailty (dementias, hip fractures, dehydration, etc.), or other deaths. Logistic regression explored factors in unforeseen death. Results: During the year, 27,798 patients died in VA facilities; 3% had schizophrenia (n = 943). Roughly two-thirds of all deaths were from cancer or organ failure, 11% frailty, 9% other, and 8% met criteria for unforeseen death. Among patients with schizophrenia however, 20% fell into the unforeseen death category. In an adjusted model, schizophrenia was associated with a 2-fold increased risk of unforeseen death compared with any other category (odds ratio = 2.4, 95% confidence interval 1.6-3.4). Unforeseen death was less likely among patients with substance abuse diagnoses in the year before death and more likely when patients had no outpatient medical care. Conclusions: VA patients with schizophrenia were more likely to die as inpatients with little previous-year care compared with other inpatient decedents without schizophrenia. Outreach efforts may be necessary to engage patients with schizophrenia in treatment of potentially life-threatening conditions. C1 S Texas Vet Hlth Care Syst, VERDICT HSR&D, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. Vet Affairs Connecticut Healthcare Syst, NE Program Evaluat Ctr, West Haven, CT USA. Yale Univ, Sch Med, New Haven, CT USA. RP Copeland, LA (reprint author), S Texas Vet HCS ALMD, VERDICT Ctr, 7400 Merton Minter 11C6, San Antonio, TX 78229 USA. EM copelandl@uthscsa.edu OI Copeland, Laurel/0000-0002-9478-0209 NR 28 TC 22 Z9 22 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0025-7079 J9 MED CARE JI Med. Care PD FEB PY 2006 VL 44 IS 2 BP 110 EP 116 DI 10.1097/01.mlr.0000196973.99080.fb PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 007EE UT WOS:000234950400003 PM 16434909 ER PT J AU MacLean, CH Louie, R Shekelle, PG Roth, CP Saliba, D Higashi, T Adams, J T Chang, J Kamberg, CJ Solomon, DH Young, RT Wenger, NS AF MacLean, CH Louie, R Shekelle, PG Roth, CP Saliba, D Higashi, T Adams, J T Chang, J Kamberg, CJ Solomon, DH Young, RT Wenger, NS TI Comparison of administrative data and medical records to measure the quality of medical care provided to vulnerable older patients SO MEDICAL CARE LA English DT Article DE quality of care; performance; administrative data ID OF-CARE; AMBULATORY CARE; ELDERS; BENEFICIARIES; INFORMATION; IMPROVEMENT; COMMUNITY; ACCURACY; VALIDITY; PROJECT AB Background: Administrative data are used to determine performance for publicly reported in health plan "report cards," accreditation status, and reimbursement. However, it is unclear how performance based on administrative data and medical records compare. Methods: We compared applicability, eligibility, and performance on 182 measures of health care quality using medical records and administrative data during a 13-month period for a random sample of 399 vulnerable older patients enrolled in managed care. Results: Of 182 quality indicators (QIs) spanning 22 conditions, 145 (80%) were applicable only to medical records and 37 (20%) to either medical records or administrative data. Among 48 QIs specific to geriatric conditions, all were applicable to medical records; 2 of these also were applicable to administrative data. Eligibility for the 37 QIs that were applicable to both medical records and administrative data was similar for both data sources (94% agreement, K = 0.74). With the use of medical records, 152 of the 182 the QIs that were applicable to medical records were triggered and yielded an overall performance of 55%. Using administrative data, 30 of the 37 QIs that were applicable to administrative data were triggered and yielded overall performance of 83% (P < 0.05 vs. medical records). Restricting to QIs applicable to both data sources, overall performance was 84% and 83% (P = 0.21) for medical records and administrative data, respectively. Conclusions: The number and spectrum of QIs that can be measured for vulnerable elderly patients is far greater for medical records than for administrative data. Although summary estimates of health care quality derived from administrative data and medical records do not differ when using identical measures, summary scores from these data sources vary substantially when the totality of care that can be measured by each data source is measured. C1 RAND Hlth, Santa Monica, CA 90407 USA. Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. RAND Hlth, Arlington, VA USA. Univ Calif Los Angeles, Div Rheumatol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med, Los Angeles, CA 90024 USA. RP MacLean, CH (reprint author), RAND Hlth, 1776 Main St,M-26, Santa Monica, CA 90407 USA. EM maclean@rand.org FU BHP HRSA HHS [PE-19001] NR 32 TC 28 Z9 28 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0025-7079 J9 MED CARE JI Med. Care PD FEB PY 2006 VL 44 IS 2 BP 141 EP 148 DI 10.1097/01.mlr.0000196960.12860.de PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 007EE UT WOS:000234950400007 PM 16434913 ER PT J AU Rietzel, E Chen, GTY AF Rietzel, E Chen, GTY TI Improving retrospective sorting of 4D computed tomography data SO MEDICAL PHYSICS LA English DT Article DE 4D computed tomography; retrospective sorting ID RESPIRATORY MOTION; MULTISLICE CT; ARTIFACTS AB Respiratory correlated CT is commercially available, and we have implemented its routine clinical use in planning lung tumor patients. Its value is determined by the fidelity of the spatiotemporal data set after processing the acquired reconstructed slices. Retrospective sorting of reconstructed slices is based on respiratory phase. However, the existing commercial software inadequately models respiratory phase for about 30% of the patients, mainly due to irregularities in the respiratory cycle. We have developed software that improves phase determination and consequently leads to an improvement of retrospective data sorting to make 4DCT data acquisition feasible for routine clinical use. Peak inhalation and exhalation respiratory, states are selected manually; intermediate phases are interpolated. Residual motion artifacts in the resulting 4DCT volumes are reduced and allow use of the 4D imaging Studies for treatment planning. (c) 2006 American Association of Physicists in Medicine. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Gesell Schwerionenforsch mbH, D-6100 Darmstadt, Germany. RP Rietzel, E (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. FU PHS HHS [P01-21239] NR 12 TC 57 Z9 61 U1 0 U2 5 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD FEB PY 2006 VL 33 IS 2 BP 377 EP 379 DI 10.1118/1.2150780 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 017GR UT WOS:000235682600015 PM 16532943 ER PT J AU Reiser, I Nishikawa, RM Giger, ML Wu, T Rafferty, EA Moore, R Kopans, DB AF Reiser, I Nishikawa, RM Giger, ML Wu, T Rafferty, EA Moore, R Kopans, DB TI Computerized mass detection for digital breast tomosynthesis directly from the projection images SO MEDICAL PHYSICS LA English DT Article DE breast imaging; tomosynthesis; computer-aided detection; mass detection ID FLAT-PANEL DETECTOR; AIDED DIAGNOSIS; MAMMOGRAPHY; SEGMENTATION; PERFORMANCE; ALGORITHM; PROTOTYPE; LESIONS; SYSTEM AB Digital breast tomosynthesis (DBT) has recently emerged as a new and promising three-dimensional modality in breast imaging. In DBT, the breast volume is reconstructed from 11 projection images, taken at source angles equally spaced over an arc of 50 degrees. Reconstruction algorithms for this modality are not fully optimized yet. Because computerized lesion detection in the reconstructed breast volume will be affected by the reconstruction technique, we are developing a novel mass detection algorithm that operates instead on the set of raw projection images. Mass detection is done in three stages. First, lesion candidates are obtained for each projection image separately, using a mass detection algorithm that was initially developed for screen-film mammography. Second, the locations of a lesion candidate are backprojected into the breast volume. In this feature volume, voxel intensities are a combined measure of detection frequency (e.g., the number of projections in which a given lesion candidate was detected), and a measure of the angular range over which a given lesion was detected. Third, features are extracted after reprojecting the three-dimensional (3-D) locations of lesion candidates into projection images. Features are combined using linear discriminant analysis. The database used to test the algorithm consisted of 21 mass cases (13 malignant, 8 benign) and 15 cases without mass lesions. Based on this database, the algorithm yielded a sensitivity of 90% at 1.5 false positives per breast volume. Algorithm performance is positively biased because this dataset was used for development, training, and testing, and because the number of algorithm parameters was approximately the same as the number of patient cases. Our results indicate that computerized mass detection in the sequence of projection images for DBT may be effective despite the higher noise level in those images. (c) 2006 American Association of Physicists in Medicine. C1 Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. OI Nishikawa, Robert/0000-0001-7720-9951; Giger, Maryellen/0000-0001-5482-9728 FU NCI NIH HHS [CA109963] NR 33 TC 66 Z9 66 U1 0 U2 8 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD FEB PY 2006 VL 33 IS 2 BP 482 EP 491 DI 10.1118/1.2163390 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 017GR UT WOS:000235682600028 PM 16532956 ER PT J AU Seco, J Evans, PM AF Seco, J Evans, PM TI Assessing the effect of electron density in photon dose calculations SO MEDICAL PHYSICS LA English DT Article DE photon dose calculation algorithm; mass-density heterogeneity correction; electron-density heterogeneity correction ID COLLAPSED CONE CONVOLUTION; MONTE-CARLO SIMULATIONS; RADIATION-THERAPY; RADIOTHERAPY; TRANSPORT; NUMBERS; ENERGY; FIELDS; WATER; BEAMS AB Photon dose calculation algorithms (such as the pencil beam and collapsed cone, CC) model the attenuation of a primary photon beam in media other than water, by using pathlength scaling based on the relative mass density of the media to water. In this study, we assess if differences in the electron density between the water and media, with different atomic composition, can influence the accuracy of conventional photon dose calculations algorithms. A comparison is performed between an electron-density scaling method and the standard mass-density scaling method for (i) tissues present in the human body (such as bone, muscle, etc.), and for (ii) water-equivalent plastics, used in radiotherapy dosimetry and quality assurance. We demonstrate that the important material property that should be taken into account by photon dose algorithms is the electron density, and not the mass density. The mass-density scaling method is shown to overestimate, relative to electron-density predictions, the primary photon fluence for tissues in the human body and water-equivalent plastics, where 6%-7% and 10% differences were observed respectively for bone and air. However, in the case of patients, differences are expected to be smaller due to the large complexity of a treatment plan and of the patient anatomy and atomic composition and of the smaller thickness of bone/air that incident photon beams of a treatment plan may have to traverse. Differences have also been observed for conventional dose algorithms, such as CC, where an overestimate of the lung dose occurs, when irradiating lung tumors. The incorrect lung dose can be attributed to the incorrect modeling of the photon beam attenuation through the rib cage (thickness of 2-3 cm in bone upstream of the lung tumor) and through the lung and the oversimplified modeling of electron transport in convolution algorithms. In the present study, the overestimation of the primary photon fluence, using the mass-density scaling method, was shown to be a consequence of the differences in the hydrogen content between the various media studied and water. On the other hand, the electron-density scaling method was shown to predict primary photon fluence in media other than water to within 1%-2% for all the materials studied and for energies up to 5 MeV. For energies above 5 MeV, the accuracy of the electron-density scaling method was shown to depend on the photon energy, where for materials with a high content of calcium (such as bone, cortical bone) or for primary photon energies above 10 MeV, the pair-production process could no longer be neglected. The electron-density scaling method was extended to account for pair-production attenuation of the primary photons. Therefore the scaling of the dose distributions in media other than water became dependent on the photon energy. The extended electron-scaling method was shown to estimate the photon range to within 1% for all materials studied and for energies from 100 keV to 20 MeV, allowing it to be used to scale dose distributions to media other than water and generated by clinical radiotherapy photon beams with accelerator energies from 4 to 20 MV. (c) 2006 American Association of Physicists in Medicine. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Francis H Burr Proton Therapy Ctr, Boston, MA 02114 USA. Inst Canc Res, Joint Dept Phys, Sutton SM2 5PT, Surrey, England. Royal Marsden NHS Fdn Trust, Sutton SM2 5PT, Surrey, England. RP Seco, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Francis H Burr Proton Therapy Ctr, 30 Fruit St, Boston, MA 02114 USA. EM jseco@partners.org RI Evans, Philip/A-6257-2009; Seco, Joao/J-4451-2012 NR 24 TC 52 Z9 53 U1 0 U2 8 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD FEB PY 2006 VL 33 IS 2 BP 540 EP 552 DI 10.1118/1.2161407 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 017GR UT WOS:000235682600033 PM 16532961 ER PT J AU Agredano, YZ Chan, JL Kimball, RC Kimball, AB AF Agredano, YZ Chan, JL Kimball, RC Kimball, AB TI Accessibility to air travel correlates strongly with increasing melanoma incidence SO MELANOMA RESEARCH LA English DT Article; Proceedings Paper CT 65th Annual Meeting of the Society-for-Investigative-Dermatology CY APR 28-MAY 01, 2004 CL Providence, RI SP Soc Investigat Dermatol DE epidemiology; melanoma; travel ID CUTANEOUS MALIGNANT-MELANOMA; SOLAR ULTRAVIOLET-RADIATION; SUN EXPOSURE; SITE DISTRIBUTION; RISING TRENDS; COCKPIT CREW; NEW-ZEALAND; MORTALITY; CANCER; CANADA AB As the cost of air travel has decreased substantially in the USA and Europe over the past few decades, leisure travel to vacation destinations during the winter months has expanded significantly. This trend has probably increased the incidence of significant ultraviolet radiation exposure and sunburn in a broader population who could not previously afford this kind of travel. The purpose of this study was to analyse the correlation between increasing accessibility to air travel and melanoma incidence. This ecological study surveyed air travel patterns and melanoma incidence over the past three decades. Melanoma age-adjusted incidence was obtained from the United States Surveillance, Epidemiology, and End Results 9 Registry Database, 1975-2000, and the Cancer Registry of Norway, 1965-2000. United States mean inflation-adjusted airfare prices for four airports linked to leisure destinations (Miami, Los Angeles, San Diego, Phoenix) were compared with melanoma incidence. Parallel analyses were performed using annual domestic passenger-kilometres and melanoma incidence in Norway. Declining United States leisure-specific airfares corresponded strongly with increasing melanoma incidence (r = 0.96, r(2) = 0.92, P < 0.001). Modelling a 5-year time lag between airfare and melanoma diagnosis strengthened the association (r = 0.98, r(2) = 0.96, P < 0.001). Longer time lags could not be modelled due to data limitations. Data from Norway similarly showed that increasing air passenger mileage corresponded strongly with increasing melanoma incidence. Although correlation does not equate to causality, the very strong relationship between increasing access to air travel and melanoma incidence suggests that changes in recreational patterns may be contributing significantly to the public health problem of melanoma. C1 Massachusetts Gen Hosp, Dermatol Clin Studies Unit, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Stanford Univ, Med Ctr, Dept Dermatol, Stanford, CA 94305 USA. RP Kimball, AB (reprint author), Massachusetts Gen Hosp, Dermatol Clin Studies Unit, 221 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM harvardskinstudies@partners.org NR 48 TC 27 Z9 27 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0960-8931 J9 MELANOMA RES JI Melanoma Res. PD FEB PY 2006 VL 16 IS 1 BP 77 EP 81 DI 10.1097/01.cmr.0000195696.50390.23 PG 5 WC Oncology; Dermatology; Medicine, Research & Experimental SC Oncology; Dermatology; Research & Experimental Medicine GA 017FF UT WOS:000235678800012 PM 16432460 ER PT J AU Crowson, AN Magro, CM Mihm, MC AF Crowson, AN Magro, CM Mihm, MC TI Malignant adnexal neoplasms SO MODERN PATHOLOGY LA English DT Review DE eccrine carcinoma; sebaceous neoplasia ID PAPILLARY ECCRINE ADENOMA; SWEAT-GLAND CARCINOMA; EXTRAMAMMARY PAGETS-DISEASE; MUIR-TORRE-SYNDROME; MUCINOUS ADENOCYSTIC CARCINOMA; BASAL-CELL CARCINOMA; PILAR NEUROCRISTIC HAMARTOMA; OCULAR SEBACEOUS CARCINOMA; OF-THE-LITERATURE; CUTANEOUS MUCOEPIDERMOID CARCINOMA AB Malignant cutaneous adnexal neoplasms are one of the most challenging areas of dermatopathology. Tumors of the pilosebaceous apparatus can occur as single-lineage neoplasms or may manifest as complex proliferations with multilineal differentiation patterns including not only the germinative component of the hair bulb, the inner or outer root sheath epithelium and the sebaceous gland and duct, but also the sweat duct components that relate to the apocrine secretory apparatus which empties into the follicle near the follicular bulge. Eccrine and apocrine neoplasms present a bewildering array of morphologies, which often defy precise classification. The purpose of this review is to discuss in detail the malignant neoplasms of the cutaneous adnexae and their benign and prognostically indeterminate mimics. C1 St Johns Med Ctr, Reg Med Labs, Tulsa, OK 74114 USA. Univ Oklahoma, Dept Dermatol, Tulsa, OK USA. Univ Oklahoma, Dept Pathol, Tulsa, OK USA. Univ Oklahoma, Dept Surg, Tulsa, OK USA. Ohio State Univ, Dept Pathol, Div Dermatopathol, Columbus, OH 43210 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Crowson, AN (reprint author), St Johns Med Ctr, Reg Med Labs, 1923 S Utica St, Tulsa, OK 74114 USA. EM ncrowson@sjmc.org NR 336 TC 18 Z9 18 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2006 VL 19 SU 2 BP S93 EP S126 DI 10.1038/modpathol.3800511 PG 34 WC Pathology SC Pathology GA 006KU UT WOS:000234897200008 PM 16446719 ER PT J AU Crowson, AN Magro, CM Mihm, MC AF Crowson, AN Magro, CM Mihm, MC TI Prognosticators of melanoma, the melanoma report, and the sentinel lymph node SO MODERN PATHOLOGY LA English DT Review DE sentinel lymph node; prognostic microstaging; melanoma ID CUTANEOUS MALIGNANT-MELANOMA; AMERICAN JOINT COMMITTEE; STAGE-I MELANOMA; MIB-1 PROLIFERATIVE ACTIVITY; CELL NUCLEAR ANTIGEN; S-PHASE FRACTION; DESMOPLASTIC MELANOMA; MICROSCOPIC SATELLITES; LENTIGO-MALIGNA; THIN MELANOMAS AB Since the 1960s, the clinical characteristics of melanoma, its histopathology and its biological basis have been the subject of intense study at pigmented lesion clinics in North America, Europe, and Australia. More recently, the immense database of the Melanoma Committee of the American Joint Committee on Cancer (AJCC) has been exploited through complex mathematical models to measure the impact of various histologic features of primary melanomas and of sentinel lymph node deposits and to correlate these parameters with patient survival. The wealth of modern information available to pathologists and clinicians has become of vital interest to the prognostication of the individual patient with melanoma. The purpose of this review is to bring to the attention of anatomic pathologists the essential characteristics of the pathology report for primary cutaneous melanoma in the modern era. C1 St Johns Med Ctr, Reg Med Labs, Tulsa, OK 74104 USA. Univ Oklahoma, Dept Dermatol, Tulsa, OK USA. Univ Oklahoma, Dept Pathol, Tulsa, OK USA. Univ Oklahoma, Dept Surg, Tulsa, OK USA. Ohio State Univ, Dept Pathol, Div Dermatopathol, Columbus, OH 43210 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP Crowson, AN (reprint author), St Johns Med Ctr, Reg Med Labs, 1923 S Utica Ave, Tulsa, OK 74104 USA. EM ncrowson@sjmc.org NR 105 TC 26 Z9 28 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2006 VL 19 SU 2 BP S71 EP S87 DI 10.1038/modpathol.3800517 PG 17 WC Pathology SC Pathology GA 006KU UT WOS:000234897200006 PM 16446717 ER PT J AU Magro, CM Crowson, AN Mihm, MC AF Magro, CM Crowson, AN Mihm, MC TI Unusual variants of malignant melanoma SO MODERN PATHOLOGY LA English DT Review DE melanoma; variants; phenotype; immunohistochemistry; morphology ID CELLULAR BLUE NEVUS; MINIMAL DEVIATION MELANOMA; OF-THE-LITERATURE; EXTRASKELETAL MYXOID CHONDROSARCOMA; DESMOPLASTIC NEUROTROPIC MELANOMA; PILAR NEUROCRISTIC HAMARTOMA; NEEDLE ASPIRATION BIOPSY; NERVE SHEATH TUMORS; GRADE FIBROMYXOID SARCOMA; ANIMAL-TYPE MELANOMA AB A potential diagnostic pitfall in the histologic assessment of melanoma is the inability to recognize unusual melanoma variants. Of these, the more treacherous examples include the desmoplastic melanoma, the nevoid melanoma, the so-called 'minimal-deviation melanoma,' melanoma with prominent pigment synthesis or,animal-type melanoma,' and the malignant blue nevus. Also problematic are the unusual phenotypic profiles seen in vertical growth phase melanomas; these include those tumors whose morphological peculiarities mimic cancers of nonmelanocytic lineage and those melanomas that express aberrant antigenic profiles not commonly associated with a melanocytic histogenesis. Metaplastic change in melanoma, balloon cell melanoma, signet-ring cell melanoma, myxoid melanoma, small cell melanoma and rhabdoid melanoma all have the potential to mimic metastatic and primary neoplasms of different lineage derivations. Abnormal immunohistochemical expression of CID 34, cytokeratins, epithelia[ membrane antigen, and smooth muscle markers as well as the deficient expression of S100 protein and melanocyte lineage-specific markers such as GIR100 protein (ie HMB-45 antibody) and A103 (ie Melan-A) also present confusing diagnostic challenges. In this review, we will discuss in some detail certain of these novel clinicopathologic types of melanoma, as well as the abnormal phenotypic expressions seen in vertical growth phase melanoma. C1 Ohio State Univ, Div Dermatopathol, Dept Pathol, Columbus, OH 43215 USA. Univ Oklahoma, Dept Dermatol, Tulsa, OK USA. Univ Oklahoma, Dept Pathol, Tulsa, OK USA. Univ Oklahoma, Dept Surg, Tulsa, OK USA. St Johns Hosp, Reg Med Labs, Tulsa, OK USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP Magro, CM (reprint author), Ohio State Univ, Div Dermatopathol, Dept Pathol, 410 W 10th Ave,N305 Doan Hall, Columbus, OH 43215 USA. EM magro-1@medctr.osu.edu NR 204 TC 87 Z9 90 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2006 VL 19 SU 2 BP S41 EP S70 DI 10.1038/modpathol.3800516 PG 30 WC Pathology SC Pathology GA 006KU UT WOS:000234897200005 PM 16446716 ER PT J AU Basseres, DS Levantini, E Ji, HB Monti, S Elf, S Dayaram, T Fenyus, M Kocher, O Golub, T Wong, KK Halmos, B Tenen, DG AF Basseres, DS Levantini, E Ji, HB Monti, S Elf, S Dayaram, T Fenyus, M Kocher, O Golub, T Wong, KK Halmos, B Tenen, DG TI Respiratory failure due to differentiation arrest and expansion of alveolar cells following lung-specific loss of the transcription factor C/EBP alpha in mice SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID BINDING-PROTEIN-ALPHA; FETAL-RAT LUNG; HEDGEHOG SIGNALING PATHWAY; KERATINOCYTE GROWTH-FACTOR; ACUTE MYELOID LEUKEMIAS; II CELLS; DISTRESS-SYNDROME; TUMOR-SUPPRESSOR; DOWN-REGULATION; SKIN TUMORS AB The leucine zipper family transcription factor CCAAT enhancer binding protein alpha (C/EBP alpha) inhibits proliferation and promotes differentiation in various cell types. In this study, we show, using a lung-specific conditional mouse model of C/EBP alpha deletion, that loss of C/EBP alpha in the respiratory epithelium leads to respiratory failure at birth due to an arrest in the type II alveolar cell differentiation program. This differentiation arrest results in the lack of type I alveolar cells and differentiated surfactant-secreting type II alveolar cells. In addition to showing a block in type II cell differentiation, the neonatal lungs display increased numbers of proliferating cells and decreased numbers of apoptotic cells, leading to epithelial expansion and loss of airspace. Consistent with the phenotype observed, genes associated with alveolar maturation, survival, and proliferation were differentially expressed. Taken together, these results identify C/EBP alpha as a master regulator of airway epithelial maturation and suggest that the loss of C/EBP alpha could also be an important event in the multistep process of lung tumorigenesis. Furthermore, this study indicates that exploring the C/EBP alpha pathway might have therapeutic benefits for patients with respiratory distress syndromes. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. MIT, Broad Inst, Cambridge, MA 02139 USA. RP Tenen, DG (reprint author), Harvard Univ, Inst Med, Rm 954,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM dtenen@bidmc.harvard.edu RI Basseres, Daniela/C-6623-2013; OI Basseres, Daniela/0000-0001-7745-3567; Monti, Stefano/0000-0002-9376-0660; wong, kwok kin/0000-0001-6323-235X; Tenen, Daniel/0000-0002-6423-3888 FU NCI NIH HHS [CA90578, P20 CA090578, P50 CA090578]; NHLBI NIH HHS [HL56745, R01 HL056745] NR 78 TC 36 Z9 38 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD FEB PY 2006 VL 26 IS 3 BP 1109 EP 1123 DI 10.1128/MCB.26.3.1109-1123.2006 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 006GT UT WOS:000234885300032 PM 16428462 ER PT J AU Shin, JW Min, M Larrieu-Lahargue, F Canron, X Kunstfeld, R Nguyen, L Henderson, JE Bikfalvi, A Detmar, M Hong, YK AF Shin, JW Min, M Larrieu-Lahargue, F Canron, X Kunstfeld, R Nguyen, L Henderson, JE Bikfalvi, A Detmar, M Hong, YK TI Prox1 promotes lineage-specific expression of fibroblast growth factor (FGF) receptor-3 in lymphatic endothelium: A role for FGF signaling in lymphangiogenesis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID VASCULAR DEVELOPMENT; TRANSCRIPTION FACTOR; GENE-EXPRESSION; CELLS; BINDING; PROSPERO; IDENTIFICATION; INDUCTION; PHENOTYPE; AFFINITY AB Fibroblast growth factors play important roles in angiogenesis, but their functions in lymphangiogenesis remain poorly understood. The homeodomain transcription factor Prox1 is essential for development of the lymphatic system by specifying lymphatic endothelial cell (LEC) fate. Here, we identify fibroblast growth factor (FGF) receptor (FGFR)-3 as a novel Prox1 target gene. Ectopic overexpression of Prox1 in blood vascular endothelial cells up-regulates FGFR-3. Prox1 induces the expression of the IIIc isoform, which we also found to be the major isoform of FGFR-3 expressed in LECs. This transcriptional activation is mediated by a direct binding of Prox1 to newly identified Prox1-response elements in the FGFR-3 promoter. Consistently, FGFR-3 is up-regulated in Prox1-positive newly formed lymphatic vessels during embryogenesis and its lymphatic-specific expression is maintained throughout development. We also found that FGF-1 and FGF-2 promote proliferation, migration, and survival of cultured LECs without involvement of vascular endothelial cell growth factor receptor-3. We show that FGF-2 binds to low- and high-affinity receptors on LECs and is efficiently internalized and processed. Moreover, functional inhibition of FGFR-3 using small interfering RNA represses LEC proliferation. Together, these results indicate that FGFR-3 is an initial target of Prox1 during the lymphatic cell fate specification and that FGF signaling may play an important role in lymphatic vessel development. C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Dermatol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. ETH, Inst Pharmaceut Sci, CH-8092 Zurich, Switzerland. Univ Bordeaux 1, Mol Angiogenesis Lab, INSERM, E 0113, F-33405 Talence, France. McGill Univ, Dept Med, Montreal, PQ H3A 1A4, Canada. McGill Univ, Ctr Bone & Periodontal Res, Montreal, PQ H3A 1A4, Canada. Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Dept Surg, Los Angeles, CA 90089 USA. RP Hong, YK (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. EM young.hong@usc.edu FU NCI NIH HHS [CA-86410, CA-69184, CA-92644, P01 CA092644, R01 CA069184, R01 CA086410] NR 46 TC 101 Z9 106 U1 4 U2 7 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD FEB PY 2006 VL 17 IS 2 BP 576 EP 584 DI 10.1091/mbc.E05-04-0368 PG 9 WC Cell Biology SC Cell Biology GA 009MX UT WOS:000235117300003 PM 16291864 ER PT J AU Liu, F Pore, N Kim, M Voong, KR Dowling, M Maity, A Kao, GD AF Liu, F Pore, N Kim, M Voong, KR Dowling, M Maity, A Kao, GD TI Regulation of histone deacetylase 4 expression by the SP family of transcription factors SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; CELL-CYCLE ARREST; END RULE PATHWAY; GENE-EXPRESSION; SKELETAL-MUSCLE; NUCLEAR EXPORT; RECEPTOR GENE; N-COR; DIHYDROFOLATE-REDUCTASE; UBIQUITIN CONJUGATION AB Histone deacetylases mediate critical cellular functions but relatively little is known about mechanisms controlling their expression, including expression of HDAC4, a class II HDAC implicated in the modulation of cellular differentiation and viability. Endogenous HDAC4 mRNA, protein levels and promoter activity were all readily repressed by mithramycin, suggesting regulation by GC-rich DNA sequences. We validated consensus binding sites for Sp1/Sp3 transcription factors in the HDAC4 promoter through truncation studies and targeted mutagenesis. Specific and functional binding by Sp1/Sp3 at these sites was confirmed with chromatin immunoprecipitation (ChIP) and electromobility shift assays (EMSA). Cotransfection of either Sp1 or Sp3 with a reporter driven by the HDAC4 promoter led to high activities in SL2 insect cells (which lack endogenous Sp1/Sp3). In human cells, restored expression of Sp1 and Sp3 up-regulated HDAC4 protein levels, whereas levels were decreased by RNA-interference-mediated knockdown of either protein. Finally, variable levels of Sp1 were in concordance with that of HDAC4 in a number of human tissues and cancer cell lines. These studies together characterize for the first time the activity of the HDAC4 promoter, through which Sp1 and Sp3 modulates expression of HDAC4 and which may contribute to tissue or cell-line-specific expression of HDAC4. C1 Philadelphia Vet Affairs Med Ctr, Dept Radiat Oncol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Kao, GD (reprint author), Philadelphia Vet Affairs Med Ctr, Dept Radiat Oncol, Philadelphia, PA 19104 USA. EM Kao@xrt.upenn.edu FU NCI NIH HHS [CA107956, R01 CA093638, R01 CA107956, CA093638] NR 85 TC 27 Z9 27 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD FEB PY 2006 VL 17 IS 2 BP 585 EP 597 DI 10.1091/mbc.E05-08-0775 PG 13 WC Cell Biology SC Cell Biology GA 009MX UT WOS:000235117300004 PM 16280357 ER PT J AU Yang, J Adamian, M Li, TS AF Yang, J Adamian, M Li, TS TI Rootletin interacts with C-Nap1 and may function as a physical linker between the pair of centrioles/basal bodies in cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID CENTROSOMAL PROTEIN C-NAP1; COILED-COIL PROTEIN; CILIARY ROOTLET; COHESION; KINASE; CANCER; NEK2 AB Rootletin, a major structural component of the ciliary rootlet, is located at the basal bodies and centrosomes in ciliated and nonciliated cells, respectively. Here we investigated its potential role in the linkage of basal bodies/centrioles and the mechanism involved in such linkages. We show that rootletin interacts with C-Nap1, a protein restricted at the ends of centrioles and functioning in centrosome cohesion in interphase cells. Their interaction in vivo is supported by their colocalization at the basal bodies/centrioles and coordinated association with the centrioles during the cell cycle. Ultrastructural examinations demonstrate that rootletin fibers connect the basal bodies in ciliated cells and are present both at the ends of and in between the pair of centrioles in nonciliated cells. The latter finding stands in contrast with C-Nap1, which is present only at the ends of the centrioles. Transient expression of C-Nap1 fragments dissociated rootletin fibers from the centrioles, resulting in centrosome separation in interphase. Overexpression of rootletin in cells caused multinucleation, micronucleation, and irregularity of nuclear shape and size, indicative of defects in chromosome separation. These data suggest that rootletin may function as a physical linker between the pair of basal bodies/centrioles by binding to C-Nap1. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. RP Yang, J (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. EM jun_yang@meei.harvard.edu FU NEI NIH HHS [P30 EY014104, P30 EY14104, EY14426] NR 20 TC 65 Z9 70 U1 1 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD FEB PY 2006 VL 17 IS 2 BP 1033 EP 1040 DI 10.1091/mbc.E05-10-0943 PG 8 WC Cell Biology SC Cell Biology GA 009MX UT WOS:000235117300042 PM 16339073 ER PT J AU Eggert, US Field, CM Mitchison, TJ AF Eggert, US Field, CM Mitchison, TJ TI Small molecules in an RNAi world SO MOLECULAR BIOSYSTEMS LA English DT Editorial Material ID DOUBLE-STRANDED-RNA; CHEMICAL GENETICS; INTERFERENCE; CYTOKINESIS; INHIBITORS; GENOMICS; SCREENS C1 Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Eggert, US (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 01225 USA. EM ulrike_eggert@hms.harvard.edu FU NCI NIH HHS [P01 CA078048]; NIGMS NIH HHS [GM023928-25] NR 15 TC 18 Z9 20 U1 0 U2 1 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1742-206X J9 MOL BIOSYST JI Mol. Biosyst. PD FEB PY 2006 VL 2 IS 2 BP 93 EP 96 DI 10.1039/b515335b PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 011XN UT WOS:000235302200006 PM 16880926 ER PT J AU Nanni, S Priolo, C Grasselli, A D'Eletto, M Merola, R Moretti, F Gallucci, M De Carli, P Sentinelli, S Cianciulli, AM Mottolese, M Carlini, P Arcelli, D Helmer-Citterich, M Gaetano, C Loda, M Pontecorvi, A Bacchetti, S Sacchi, A Farsetti, A AF Nanni, S Priolo, C Grasselli, A D'Eletto, M Merola, R Moretti, F Gallucci, M De Carli, P Sentinelli, S Cianciulli, AM Mottolese, M Carlini, P Arcelli, D Helmer-Citterich, M Gaetano, C Loda, M Pontecorvi, A Bacchetti, S Sacchi, A Farsetti, A TI Epithelial-restricted gene profile of primary cultures from human prostate tumors: A molecular approach to predict clinical behavior of prostate cancer SO MOLECULAR CANCER RESEARCH LA English DT Article ID TELOMERASE ACTIVITY; EXPRESSION PROFILES; GROWTH-FACTOR; IN-VITRO; CELLS; TISSUE; PROGRESSION; LINES; OLD; INSTABILITY AB The histopathologic and molecular heterogeneity of prostate cancer and the limited availability of human tumor tissue make unraveling the mechanisms of prostate carcinogenesis a challenging task. Our goal was to develop an ex vivo model that could be reliably used to define a prognostic signature based on gene expression profiling of cell cultures that maintained the tumor phenotype. To this end, we derived epithelial cultures from tissue explanted from 59 patients undergoing radical prostatectomy or cistoprostatectomy because of prostate benign hyperplasia/prostate cancer or bladder carcinoma. Patient selection criteria were absence of hormonal neoadjuvant treatment before surgery and diagnosis of clinically localized disease. Using this unique experimental material, we analyzed expression of 22,500 transcripts on the Affymetrix Human U133A GeneChip platform (Affymetrix, Inc., High Wycombe, United Kingdom). Cultures from normal/ hyperplastic tissues with a prevalent luminal phenotype and from normal prostate epithelial tissue with basal phenotype (PrEC) served as controls. We have established a large number of prostate primary cultures highly enriched in the secretory phenotype. From them, we derived an epithelial-restricted transcriptional signature that (a) differentiated normal from tumor cells and (b) clearly separated cancer-derived lines into two distinct groups, which correlated with indolent or aggressive clinical behavior of the disease. Our findings provide (a) a method to expand human primary prostate carcinoma cells with a luminal phenotype, (b) a powerful experimental model to study primary prostate cancer biology, and (c) a novel means to characterize these tumors from a molecular genetic standpoint for prognostic and/or predictive purposes. C1 Regina Elena Inst Canc Res, Expt Canc Res Ctr, Mol Oncogenesis Lab, Dept Expt Oncol, I-00158 Rome, Italy. Regina Elena Inst Canc Res, Dept Urol, I-00158 Rome, Italy. Regina Elena Inst Canc Res, Dept Pathol, I-00158 Rome, Italy. Regina Elena Inst Canc Res, Dept Clin Pathol, I-00158 Rome, Italy. Regina Elena Inst Canc Res, Dept Med Oncol, I-00158 Rome, Italy. Regina Elena Inst Canc Res, Rome Oncogenom Ctr, I-00158 Rome, Italy. Catholic Univ Rome, Ist Dermopat Immacolata, Rome, Italy. Catholic Univ Rome, Dept Endocrinol, Rome, Italy. CNR, INeMM, Rome, Italy. Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Farsetti, A (reprint author), Regina Elena Inst Canc Res, Expt Canc Res Ctr, Mol Oncogenesis Lab, Dept Expt Oncol, Via Messi Oro 156, I-00158 Rome, Italy. EM farsetti@ifo.it RI Moretti, Fabiola/I-5647-2013; Gallucci, Michele/K-9600-2016; OI Moretti, Fabiola/0000-0002-2691-1254; Gallucci, Michele/0000-0002-3637-6531; Gaetano, Carlo/0000-0002-5238-1832 NR 52 TC 64 Z9 65 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD FEB PY 2006 VL 4 IS 2 BP 79 EP 92 DI 10.1158/1541-7786.MCR-05-0098 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 021CL UT WOS:000235960400003 PM 16513839 ER PT J AU Lien, YC Lin, SM Nithipongvanitch, R Oberley, TD Noel, T Zhao, Q Daosukho, C St Clair, DK AF Lien, YC Lin, SM Nithipongvanitch, R Oberley, TD Noel, T Zhao, Q Daosukho, C St Clair, DK TI Tumor necrosis factor receptor deficiency exacerbated Adriamycin-induced cardiomyocytes apoptosis: an insight into the Fas connection SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID MANGANESE SUPEROXIDE-DISMUTASE; DOXORUBICIN-INDUCED APOPTOSIS; CYTOCHROME-C RELEASE; INDUCED CARDIOMYOPATHY; MEDIATED APOPTOSIS; CARDIAC MYOCYTES; MITOCHONDRIAL DYSFUNCTION; INDUCED CARDIOTOXICITY; OLIGOMERIZES BAK; TRANSGENIC MICE AB Cardiomyopathy is a major dose-limiting factor for applications of Adriamycin, a potent chemotherapeutic agent. The present study tested the hypothesis that increased tumor necrosis factor (TNF)-alpha signaling via its receptors protects against Adriamycin-induced cardiac injury. We used mice in which both TNF receptor I and II have been selectively inactivated (DKO) with wild-type mice as controls. Morphometric studies of cardiac tissue following Adriamycin treatment revealed greater ultrastructural damage in cardiomyocyte mitochondria from DKO mice. Biochemical studies of cardiac tissues showed cytochrome c release and the increase in proapoptotic protein levels, suggesting that lack of TNF-alpha receptor I and II exacerbates Adriamycin-induced cardiac injury. The protective role of TNF receptor I and II was directly confirmed in isolated primary cardiomyocytes. Interestingly, following Adriamycin treatment, the levels of Fas decreased in the wild-type mice. In contrast, DKO mice had an increase in Fas levels and its downstream target, mitochondrial truncated Bid. These results suggested that TNF-alpha receptors play a critical role in cardioprotection by suppression of the mitochondrial-mediated associated cell death pathway. C1 Univ Kentucky, Grad Ctr Toxicol, Lexington, KY 40536 USA. Univ Wisconsin, William S Middleton Mem Vet Hosp, Dept Pathol & Lab Med Serv, Madison, WI USA. Mahidol Univ, Fac Med Technol, Bangkok, Thailand. RP St Clair, DK (reprint author), Univ Kentucky, Grad Ctr Toxicol, 454 Hlth Sci Res Bldg, Lexington, KY 40536 USA. EM dstcl00@uky.edu FU NCI NIH HHS [CA 80152, CA 94853] NR 43 TC 17 Z9 22 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD FEB PY 2006 VL 5 IS 2 BP 261 EP 269 DI 10.1158/1535-7163.MCT-05-0390 PG 9 WC Oncology SC Oncology GA 017VM UT WOS:000235721400009 PM 16505099 ER PT J AU Qin, W Peng, Y Ksiezak-Reding, H Ho, L Stetka, B Lovati, E Pasinetti, GM AF Qin, W Peng, Y Ksiezak-Reding, H Ho, L Stetka, B Lovati, E Pasinetti, GM TI Inhibition of cyclooxygenase as potential novel therapeutic strategy in N141I presenilin-2 familial Alzheimer's disease SO MOLECULAR PSYCHIATRY LA English DT Article DE COX-2; PS2; apoptosis; GSK-3 beta; b-catenin ID RANDOMIZED CONTROLLED-TRIAL; TRANSGENIC MOUSE MODEL; WNT SIGNALING PATHWAY; CELL-CYCLE ACTIVITY; BETA-CATENIN; EPIDEMIOLOGIC EVIDENCE; EXPRESSION; APOPTOSIS; PLACEBO; PHOSPHORYLATION AB The present study was designed to further explore the potential cause/effect relationship between the expression of both the N141I presenilin (PS) 2 mutant familial Alzheimer's disease (FAD) gene and cyclooxgenase (COX) in respect to the mechanism associated with programmed cell death in Alzheimer's disease (AD). We found that expression of mutant N141I PS2 resulting in apoptotic cell death in H4 neuronal cells coincided with >4-fold induction in the expression of the inducible form of COX-2, but not the constitutive COX-1. Moreover, we found that the expression of the N141I PS2 FAD gene strongly promoted (>2-fold) glycogen synthase kinase (GSK)-3 beta activity coincidental with a reduction in the level of beta-catenin translocated from the cytoplasmic to the nuclear compartment. Most interestingly, we found that inhibition of COX-2-mediated generation of prostaglandin (PG)-E-2 in H4 neuronal cells with the preferential COX-2 inhibitor nimesulide protects against N141I PS2-mediated apoptotic cell death coincidental with an inhibition of GSK-3 beta activity and subsequent normalization of beta-catenin cellular distribution. The clinical relevance of this finding was confirmed by the evidence that COX-2 protein and PG-E-2 concentrations were selectively increased >2-fold in the cerebral cortex of subjects harboring the N141I PS2 FAD mutation relative to wild-type PS2 AD cases. This study demonstrates for the first time that COX-2 may be a downstream effector of mutant N141I PS2-mediated apoptotic cell death and that inhibition of COX-2 may neuroprotect in AD through modulation of a GSK-3 beta-beta-catenin-mediated response. The study provides support for the potential pharmacogenomic identification of N141I PS2 FAD cases that might preferentially benefit from inhibition of COX-2 during the progression of clinical dementia. C1 Mt Sinai Sch Med, Dept Psychiat, Neuroinflammat Res Labs, New York, NY 10029 USA. Mt Sinai Sch Med, Bronx Vet Affairs Med Ctr, GRECC, Bronx, NY USA. RP Pasinetti, GM (reprint author), Mt Sinai Sch Med, Dept Psychiat, Neuroinflammat Res Labs, Box 1230,1 Gustave L Levy Pl, New York, NY 10029 USA. EM giulio.pasinetti@mssm.edu FU NIA NIH HHS [P50 AG05136, AG13799] NR 38 TC 17 Z9 18 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD FEB PY 2006 VL 11 IS 2 BP 172 EP 181 DI 10.1038/sj.mp.4001773 PG 10 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 007FJ UT WOS:000234953700011 PM 16331303 ER PT J AU Friedman, JRL Thiele, EA Wang, D Levine, KB Cloherty, EK Pfeifer, HH De Vivo, DC Carruthers, A Natowicz, MR AF Friedman, JRL Thiele, EA Wang, D Levine, KB Cloherty, EK Pfeifer, HH De Vivo, DC Carruthers, A Natowicz, MR TI Atypical GLUT1 deficiency with prominent movement disorder responsive to ketogenic diet SO MOVEMENT DISORDERS LA English DT Article DE glucose transport protein; glut1; ketogenic diet; hypoglycorrhacia; movement disorder; dystonia; choreoathetosis; ataxia ID BLOOD-BRAIN-BARRIER; GLUCOSE-TRANSPORTER AB Glucose transport protein deficiency due to mutation in the GLUT1 gene is characterized by infantile onset and chronic seizure disorder, microcephaly, global developmental delays, and hypoglycorrhachia. We describe a 10-year-old normocephalic male with prominent ataxia, dystonia, choreoathetosis, and GLUT1 deficiency whose motor abnormalities improved with a ketogenic diet. We illustrate the motor abnormalities, at baseline and after ketogenic diet, that characterize this unusual case. This case broadens the phenotype of GLUT1 deficiency and illustrates the importance of cerebrospinal fluid (CSF) evaluation in detecting potentially treatable conditions in children with undiagnosed movement disorders. (C) 2005 Movement Disorder Society. C1 Massachusetts Gen Hosp, Dept Neurol, Pediat Epilepsy Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Pediat Epilepsy Program, Boston, MA 02114 USA. Columbia Univ, Dept Neurol, Colleen Giblin Labs Pediat Neurol Res, New York, NY USA. Univ Massachusetts, Dept Mol Pharmacol & Biochem, Worcester, MA 01605 USA. Cleveland Clin Fdn, Dept Neurol, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Dept Pathol, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Dept Pediat, Cleveland, OH 44195 USA. RP Friedman, JRL (reprint author), San Diego Childrens Hosp, 8010 Frost St, San Diego, CA 92123 USA. EM jfriedma@helix.mgh.harvard.edu FU NIDDK NIH HHS [DK 44888] NR 14 TC 44 Z9 44 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD FEB PY 2006 VL 21 IS 2 BP 241 EP 245 DI 10.1002/mds.20660 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 016DW UT WOS:000235601900016 PM 16149086 ER PT J AU Krivickas, LS Hochberg, FH Freeman, S AF Krivickas, LS Hochberg, FH Freeman, S TI Chronic inflammatory demyelinating polyradiculoneuropathy with tumefactive central demyelination SO MUSCLE & NERVE LA English DT Article DE central demyelination; chronic inflammatory demyelinating polyradiculoneuropathy; CIDP; mass lesion; multiple sclerosis; polyneuropathy ID NERVOUS-SYSTEM DEMYELINATION; RESEARCH CRITERIA; POLYNEUROPATHY; NEUROPATHY; LESIONS; CIDP; MRI AB A 46-year-old man with a 1-year history of distal paresthesias and mild distal weakness subacutely developed paralysis of the left hand. Electrodiagnostic evaluation revealed a demyelinating peripheral neuropathy that met criteria for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Magnetic resonance imaging of the brain revealed a mass that enhanced with contrast, but revealed focal myelin loss with intense macrophage activity and axonal preservation on biopsy. The mass and hand weakness improved following steroid therapy. The combination of CIDP and central demyelination with mass effect broadens the spectrum of demyelinating disease in association with CIDP. C1 Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA 02114 USA. Spaulding Rehabil Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Krivickas, LS (reprint author), Harvard Univ, Sch Med, Dept Phys Med & Rehabil, 125 Nashua St, Boston, MA 02114 USA. EM lkrivickas@partners.org NR 18 TC 8 Z9 8 U1 0 U2 1 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 FEB PY 2006 VL 33 IS 2 BP 283 EP 288 DI 10.1002/mus.20412 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 008VQ UT WOS:000235069200017 PM 16086427 ER PT J AU Hurtado-Lorenzo, A Skinner, M El Annan, J Futai, M Sun-Wada, GH Bourgoin, S Casanova, J Wildeman, A Bechoua, S Ausiello, DA Brown, D Marshansky, V AF Hurtado-Lorenzo, A Skinner, M El Annan, J Futai, M Sun-Wada, GH Bourgoin, S Casanova, J Wildeman, A Bechoua, S Ausiello, DA Brown, D Marshansky, V TI V-ATPase interacts with ARNO and Arf6 in early endosomes and regulates the protein degradative pathway SO NATURE CELL BIOLOGY LA English DT Article ID ADP-RIBOSYLATION FACTOR; VACUOLAR H+-ATPASE; RECEPTOR-MEDIATED ENDOCYTOSIS; KIDNEY PROXIMAL TUBULES; EXCHANGE FACTOR ARNO; PROTON PUMP ATPASE; NUCLEOTIDE EXCHANGE; PLASMA-MEMBRANE; OSTEOCLAST DIFFERENTIATION; A3 ISOFORM AB The recruitment of the small GTPase Arf6 and ARNO from cytosol to endosomal membranes is driven by V-ATPase-dependent intra-endosomal acidification. The molecular mechanism that mediates this pH-sensitive recruitment and its role are unknown. Here, we demonstrate that Arf6 interacts with the c-subunit, and ARNO with the a2-isoform of V-ATPase. The a2-isoform is targeted to early endosomes, interacts with ARNO in an intra-endosomal acidification-dependent manner, and disruption of this interaction results in reversible inhibition of endocytosis. Inhibition of endosomal acidification abrogates protein trafficking between early and late endosomal compartments. These data demonstrate the crucial role of early endosomal acidification and V-ATPase/ARNO/Arf6 interactions in the regulation of the endocytic degradative pathway. They also indicate that V-ATPase could modulate membrane trafficking by recruiting and interacting with ARNO and Arf6; characteristics that are consistent with the role of V-ATPase as an essential component of the endosomal pH-sensing machinery. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Richard Simches Res Ctr,Program Membrane Biol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Richard Simches Res Ctr,Nephrol Div, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. Univ Guelph, Dept Mol & Cellular Biol, Guelph, ON N1G 2W1, Canada. Microbial Chem Res Ctr, Futai Special Lab, Tokyo 1410021, Japan. Doshisha Womens Coll, Dept Biochem, Kyoto 6100395, Japan. Univ Laval, CHUL, Quebec City, PQ G1V 4G2, Canada. Univ Virginia, Hlth Sci Ctr, Dept Cell Biol, Charlottesville, VA 22908 USA. RP Marshansky, V (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Richard Simches Res Ctr,Program Membrane Biol, Boston, MA 02114 USA. EM Vladimir_Marshansky@hms.harvard.edu RI Hurtado-Lorenzo, Ph.D., Andres/A-8331-2009 FU NIDDK NIH HHS [DK42956, DK38452, DK43341, DK57521] NR 49 TC 270 Z9 274 U1 2 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD FEB PY 2006 VL 8 IS 2 BP 124 EP U8 DI 10.1038/ncb1348 PG 16 WC Cell Biology SC Cell Biology GA 008SA UT WOS:000235059800007 PM 16415858 ER PT J AU Feldman, N Gerson, A Fang, J Li, E Zhang, Y Shinkai, Y Cedar, H Bergman, Y AF Feldman, N Gerson, A Fang, J Li, E Zhang, Y Shinkai, Y Cedar, H Bergman, Y TI G9a-mediated irreversible epigenetic inactivation of Oct-3/4 during early embryogenesis SO NATURE CELL BIOLOGY LA English DT Article ID DE-NOVO METHYLATION; HISTONE METHYLTRANSFERASE; TRANSCRIPTION FACTOR; LYSINE-9 METHYLATION; GENE-EXPRESSION; DNA METHYLATION; STEM-CELLS; GERMLINE; BINDING; NUCLEI AB Oct-3/4 is a POU domain homeobox gene that is expressed during gametogenesis and in early embryonic cells(1,2), where it has been shown to be important for maintaining pluripotency(3). Following implantation, this gene undergoes a novel multi-step programme of inactivation. Transcriptional repression is followed by a pronounced increase in histone H3 methylation on Lys 9 that is mediated by the SET-containing protein, G9a. This step sets the stage for local heterochromatinization via the binding of HP1 and is required for subsequent de novo methylation at the promoter by the enzymes Dnmt3a/3b. Genetic studies show that these epigenetic changes actually have an important role in the inhibition of Oct-3/4 reexpression, thereby preventing reprogramming. C1 Hebrew Univ Jerusalem, Sch Med, Dept Expt Med, IL-91120 Jerusalem, Israel. Hebrew Univ Jerusalem, Sch Med, Dept Cellular Biochem, IL-91120 Jerusalem, Israel. Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Kyoto Univ, Inst Virus Res, Expt Res Ctr Infect Dis, Sakyo Ku, Kyoto 6068507, Japan. RP Bergman, Y (reprint author), Hebrew Univ Jerusalem, Sch Med, Dept Expt Med, IL-91120 Jerusalem, Israel. EM yberg@md.huji.ac.il RI Shinkai, Yoichi/N-3909-2014 OI Shinkai, Yoichi/0000-0002-6051-2484 NR 30 TC 370 Z9 383 U1 3 U2 24 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD FEB PY 2006 VL 8 IS 2 BP 188 EP U55 DI 10.1038/ncb1353 PG 10 WC Cell Biology SC Cell Biology GA 008SA UT WOS:000235059800014 PM 16415856 ER PT J AU Dretler, SP AF Dretler, SP TI Prevention of retrograde stone migration during ureteroscopy SO NATURE CLINICAL PRACTICE UROLOGY LA English DT Editorial Material ID PROXIMAL URETERAL STONES; CONE; LITHOTRIPSY; HOLMIUM; DEVICE; LASER C1 Massachusetts Gen Hosp, Dept Urol, Kidney Stone Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Dretler, SP (reprint author), Massachusetts Gen Hosp, Dept Urol, Kidney Stone Ctr, 15 Parkman St,WAC 486, Boston, MA 02114 USA. EM sdretler@partners.org NR 10 TC 11 Z9 12 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1743-4270 J9 NAT CLIN PRACT UROL JI Nat. Clin. Pract. Urol. PD FEB PY 2006 VL 3 IS 2 BP 60 EP 61 DI 10.1038/ncpuro0376 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 012MF UT WOS:000235342600002 PM 16470185 ER PT J AU Drake, JA Bird, C Nemesh, J Thomas, DJ Newton-Cheh, C Reymond, A Excoffier, L Attar, H Antonarakis, SE Dermitzakis, ET Hirschhorn, JN AF Drake, JA Bird, C Nemesh, J Thomas, DJ Newton-Cheh, C Reymond, A Excoffier, L Attar, H Antonarakis, SE Dermitzakis, ET Hirschhorn, JN TI Conserved noncoding sequences are selectively constrained and not mutation cold spots SO NATURE GENETICS LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISMS; NON-GENIC SEQUENCES; HUMAN GENOME; NONGENIC SEQUENCES; REGIONS; MAMMALS; DISEASE; IDENTIFICATION; POPULATION; DELETIONS AB Noncoding genetic variants are likely to influence human biology and disease, but recognizing functional noncoding variants is difficult. Approximately 3% of noncoding sequence is conserved among distantly related mammals(1-4), suggesting that these evolutionarily conserved noncoding regions (CNCs) are selectively constrained and contain functional variation. However, CNCs could also merely represent regions with lower local mutation rates. Here we address this issue and show that CNCs are selectively constrained in humans by analyzing HapMap genotype data. Specifically, new ( derived) alleles of SNPs within CNCs are rarer than new alleles in nonconserved regions (P = 3 x 10(-18)), indicating that evolutionary pressure has suppressed CNC-derived allele frequencies. Intronic CNCs and CNCs near genes show greater allele frequency shifts, with magnitudes comparable to those for missense variants. Thus, conserved noncoding variants are more likely to be functional. Allele frequency distributions highlight selectively constrained genomic regions that should be intensively surveyed for functionally important variation. C1 Childrens Hosp, Program Genom, Boston, MA 02115 USA. Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. Harvard Univ, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02139 USA. MIT, Cambridge, MA 02139 USA. Wellcome Trust Sanger Inst, Hinxton CB10 1SA, England. Univ Calif Santa Cruz, Dept Biomol Engn, Santa Cruz, CA 95064 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland. Univ Bern, Inst Zool, CH-3012 Bern, Switzerland. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Hirschhorn, JN (reprint author), Childrens Hosp, Program Genom, 300 Longwood Ave, Boston, MA 02115 USA. EM md4@sanger.ac.uk; joelh@broad.mit.edu RI Dermitzakis, Emmanouil/B-7687-2013; Excoffier, Laurent/D-3498-2013; Antonarakis, Stylianos/N-8866-2014 OI Excoffier, Laurent/0000-0002-7507-6494; Antonarakis, Stylianos/0000-0001-8907-5823 FU Wellcome Trust NR 30 TC 150 Z9 155 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD FEB PY 2006 VL 38 IS 2 BP 223 EP 227 DI 10.1038/ng1710 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 007FE UT WOS:000234953200019 PM 16380714 ER PT J AU Frahm, N Kiepiela, P Adams, S Linde, CH Hewitt, HS Sango, K Feeney, ME Addo, MM Lichterfeld, M Lahaie, MP Pae, E Wurcel, AG Roach, T St John, MA Altfeld, M Marincola, FM Moore, C Mallal, S Carrington, M Heckerman, D Allen, TM Mullins, JI Korber, BT Goulder, PJR Walker, BD Brander, C AF Frahm, N Kiepiela, P Adams, S Linde, CH Hewitt, HS Sango, K Feeney, ME Addo, MM Lichterfeld, M Lahaie, MP Pae, E Wurcel, AG Roach, T St John, MA Altfeld, M Marincola, FM Moore, C Mallal, S Carrington, M Heckerman, D Allen, TM Mullins, JI Korber, BT Goulder, PJR Walker, BD Brander, C TI Control of human immunodeficiency virus replication by cytotoxic T lymphocytes targeting subdominant epitopes SO NATURE IMMUNOLOGY LA English DT Article ID HLA-B; IMMUNE ESCAPE; HIV; RESPONSES; AIDS; TRANSMISSION; PROGRESSION; VACCINE; ADAPTATION; MUTATIONS AB Despite limited data supporting the superiority of dominant over subdominant responses, immunodominant epitopes represent the preferred vaccine candidates. To address the function of subdominant responses in human immunodeficiency virus infection, we analyzed cytotoxic T lymphocyte responses restricted by HLA-B*1503, a rare allele in a cohort infected with clade B, although common in one infected with clade C. HLA-B*1503 was associated with reduced viral loads in the clade B cohort but not the clade C cohort, although both shared the immunodominant response. Clade B viral control was associated with responses to several subdominant cytotoxic T lymphocyte epitopes, whereas their clade C variants were less well recognized. These data suggest that subdominant responses can contribute to in vivo viral control and that high HLA allele frequencies may drive the elimination of subdominant yet effective epitopes from circulating viral populations. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div AIDS, Boston, MA 02115 USA. Univ KwaZulu Natal, ZA-4015 Durban, South Africa. Clin Ctr Natl Inst Hlth, Bethesda, MD 20892 USA. Fenway Community Hlth Ctr, Boston, MA 02115 USA. Lemuel Shattuck Hosp, Boston, MA 02115 USA. Queen Elizabeth Hosp, Bridgetown, Barbados. Royal Perth Hosp, Ctr Clin Immunol & Biomed Stat, Murdoch, WA 6000, Australia. Murdoch Univ, Murdoch, WA 6150, Australia. NCI, Frederick Canc Res & Dev Ctr, Lab Genom Divers, Basic Res Program, Frederick, MD 21702 USA. Microsoft Corp, Redmond, WA 98052 USA. Univ Washington, Seattle, WA 98195 USA. Santa Fe Inst, Santa Fe, NM 87501 USA. Los Alamos Natl Lab, Los Alamos, NM 87545 USA. Univ Oxford, Oxford OX1 3SY, England. Howard Hughes Med Inst, Chevy Chase, MD 20185 USA. RP Brander, C (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02115 USA. EM cbrander@partners.org RI Allen, Todd/F-5473-2011; OI Brander, Christian/0000-0002-0548-5778; Korber, Bette/0000-0002-2026-5757 FU NCI NIH HHS [N01-CO-12400]; NIAID NIH HHS [N01-AI-15422, R01-AI-067077] NR 32 TC 163 Z9 168 U1 2 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD FEB PY 2006 VL 7 IS 2 BP 173 EP 178 DI 10.1038/ni1281 PG 6 WC Immunology SC Immunology GA 005DB UT WOS:000234801700018 PM 16369537 ER PT J AU Rabin, O Perez, JM Grimm, J Wojtkiewicz, G Weissleder, R AF Rabin, O Perez, JM Grimm, J Wojtkiewicz, G Weissleder, R TI An X-ray computed tomography imaging agent based on long-circulating bismuth sulphide nanoparticles SO NATURE MATERIALS LA English DT Article ID QUANTUM DOTS; GOLD NANOPARTICLES; CANCER; FLUORESCENT; NANOWIRES; BI2S3; SIZE AB Nanomaterials have become increasingly important in the development of new molecular probes for in vivo imaging(1-8), both experimentally and clinically. Nanoparticulate imaging probes have included semiconductor quantum dots(9-12), magnetic(13) and magnetofluorescent nanoparticles(14,15), gold nanoparticles and nanoshells(16-19), among others. However, the use of nanomaterials for one of the most common imaging techniques, computed tomography (CT), has remained unexplored. Current CT contrast agents are based on small iodinated molecules. They are effective in absorbing X-rays, but non-specific distribution and rapid pharmacokinetics have rather limited their microvascular and targeting performance. Here we propose the use of a polymer-coated Bi2S3 nanoparticle preparation as an injectable CT imaging agent. This preparation demonstrates excellent stability at high concentrations (0.25 M Bi3+), high X-ray absorption (fivefold better than iodine), very long circulation times (> 2 h) in vivo and an efficacy/safety profi comparable to or better than iodinated imaging agents. We show the utility of these polymer-coated Bi2S3 nanoparticles for enhanced in vivo imaging of the vasculature, the liver and lymph nodes in mice. These nanoparticles and their bioconjugates are expected to become an important adjunct to in vivo imaging of molecular targets and pathological conditions. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. EM weissleder@helix.mgh.harvard.edu RI Grimm, Jan/B-1937-2008; Rabin, Oded/E-5791-2011 FU NCI NIH HHS [P50 CA86355, R24 CA92782, U54 CA119349]; NHLBI NIH HHS [UO1 HL080731]; NIBIB NIH HHS [R01-EB004626A01] NR 28 TC 472 Z9 482 U1 35 U2 234 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1476-1122 J9 NAT MATER JI Nat. Mater. PD FEB PY 2006 VL 5 IS 2 BP 118 EP 122 DI 10.1038/nmat1571 PG 5 WC Chemistry, Physical; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Materials Science; Physics GA 008SC UT WOS:000235060000019 PM 16444262 ER PT J AU Flaumenhaft, R Lo, EH AF Flaumenhaft, R Lo, EH TI Different strokes for rodent folks SO NATURE METHODS LA English DT Editorial Material AB Understanding of the sequelae of cerebral microvascular injury has been hampered by a Lack of animal models to enable precise Localization of injury. In this issue, Nishimura et al. describe a stroke model that couples two-photon Laser-scanning mapping of the cerebral cortex with femtosecond laser technology to produce three distinct microvascular injuries characterized by hemorrhage, vessel leakage or vessel occlusion. C1 Harvard Univ, Sch Med, Div Hemostasis & Thrombosis, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Neurol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Radiol, Charlestown, MA 02129 USA. RP Flaumenhaft, R (reprint author), Harvard Univ, Sch Med, Div Hemostasis & Thrombosis, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. EM rflaumen@bidmc.harvard.edu; lo@helix.mgh.harvard.edu NR 9 TC 2 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 J9 NAT METHODS JI Nat. Methods PD FEB PY 2006 VL 3 IS 2 BP 79 EP 80 DI 10.1038/nmeth0206-79 PG 2 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 007HQ UT WOS:000234960000008 PM 16432514 ER PT J AU Zhao, LX Ma, QL Calon, F Harris-White, ME Yang, FS Lim, GP Morihara, T Ubeda, OJ Ambegaokar, S Hansen, JE Weisbart, RH Teter, B Frautschy, SA Cole, GM AF Zhao, LX Ma, QL Calon, F Harris-White, ME Yang, FS Lim, GP Morihara, T Ubeda, OJ Ambegaokar, S Hansen, JE Weisbart, RH Teter, B Frautschy, SA Cole, GM TI Role of p21-activated kinase pathway defects in the cognitive deficits of Alzheimer disease SO NATURE NEUROSCIENCE LA English DT Article ID AMYLOID PRECURSOR PROTEIN; MENTAL-RETARDATION; SYNAPTIC PLASTICITY; MISSENSE MUTATION; DENDRITIC SPINES; ACTIN DYNAMICS; DOWN-SYNDROME; MEMORY LOSS; LIM-KINASE; DREBRIN AB Defects in dendritic spines are common to several forms of cognitive deficits, including mental retardation and Alzheimer disease. Because mutation of p21-activated kinase ( PAK) can lead to mental retardation and because PAK-cofilin signaling is critical in dendritic spine morphogenesis and actin dynamics, we hypothesized that the PAK pathway is involved in synaptic and cognitive deficits in Alzheimer disease. Here, we show that PAK and its activity are markedly reduced in Alzheimer disease and that this is accompanied by reduced and redistributed phosphoPAK, prominent cofilin pathology and downstream loss of the spine actin-regulatory protein drebrin, which cofilin removes from actin. We found that beta-amyloid ( A beta) was directly involved in PAK signaling deficits and drebrin loss in A beta oligomer-treated hippocampal neurons and in the Appswe transgenic mouse model bearing a double mutation leading to higher A beta production. In addition, pharmacological PAK inhibition in adult mice was sufficient to cause similar cofilin pathology, drebrin loss and memory impairment, consistent with a potential causal role of PAK defects in cognitive deficits in Alzheimer disease. C1 Greater Los Angeles Vet Affairs Healthcare Syst, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. Univ Laval, Med Ctr, Mol Endocrinol & Oncol Res Ctr, Quebec City, PQ G1V 4G2, Canada. Univ Laval, Fac Pharm, Ste Foy, PQ G1K 7P4, Canada. Educ & Clin Ctr, Sepulveda, CA 91343 USA. Osaka Univ, Sch Med, Div Psychiat & Behav Proteom, Dept Post Genom & Dis, Suita, Osaka 565, Japan. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. RP Cole, GM (reprint author), Greater Los Angeles Vet Affairs Healthcare Syst, Sepulveda, CA 91343 USA. EM gmcole@ucla.edu FU NIA NIH HHS [AG10685, AG022080, AG10415, AG16793, P01 AG16570, P50 AG 16570, P50 AG016570, P50 AG05142, R01 AG010685, R01 AG013741, R01 AG13741]; NINDS NIH HHS [NS43946] NR 50 TC 180 Z9 187 U1 2 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD FEB PY 2006 VL 9 IS 2 BP 234 EP 242 DI 10.1038/nn1630 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 007SN UT WOS:000234990100019 PM 16415866 ER PT J AU Taniguchi, CM Emanuelli, B Kahn, CR AF Taniguchi, CM Emanuelli, B Kahn, CR TI Critical nodes in signalling pathways: insights into insulin action SO NATURE REVIEWS MOLECULAR CELL BIOLOGY LA English DT Review ID PROTEIN-KINASE-B; STIMULATED GLUCOSE-TRANSPORT; PHOSPHATIDYLINOSITOL 3-KINASE/AKT PATHWAY; TYROSINE PHOSPHORYLATION SITES; RECEPTOR SUBSTRATE PROTEINS; P85 REGULATORY SUBUNIT; SKELETAL-MUSCLE CELLS; PHOSPHOINOSITIDE 3-KINASE; MICE LACKING; 3T3-L1 ADIPOCYTES AB Physiologically important cell-signalling networks are complex, and contain several points of regulation, signal divergence and crosstalk with other signalling cascades. Here, we use the concept of 'critical nodes' to define the important junctions in these pathways and illustrate their unique role using insulin signalling as a model system. C1 Joslin Diabet Ctr, Boston, MA 02215 USA. RP Kahn, CR (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM c.ronald.kahn@joslin.harvard.edu RI Emanuelli, Brice/M-2097-2016; OI Emanuelli, Brice/0000-0001-5795-5666 NR 125 TC 1216 Z9 1285 U1 19 U2 170 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0072 J9 NAT REV MOL CELL BIO JI Nat. Rev. Mol. Cell Biol. PD FEB PY 2006 VL 7 IS 2 BP 85 EP 96 DI 10.1038/nrm1837 PG 12 WC Cell Biology SC Cell Biology GA 015ZL UT WOS:000235590100012 PM 16493415 ER PT J AU Vitiello, MV Moe, KE Merriam, GR Mazzoni, G Buchner, DH Schwartz, RS AF Vitiello, MV Moe, KE Merriam, GR Mazzoni, G Buchner, DH Schwartz, RS TI Growth hormone releasing hormone improves the cognition of healthy older adults SO NEUROBIOLOGY OF AGING LA English DT Article DE aging; elderly; cognition; GHRH; GH; IGF-I; cognitive function ID FACTOR-I; HUMAN-BRAIN; ALZHEIMERS-DISEASE; DEFICIENT ADULTS; AGE; MEN; INSULIN-LIKE-GROWTH-FACTOR-1; DECREASES; RECEPTORS; INCREASES AB Declines in the activity of the somatotrophic axis have been implicated in the age-related changes observed in a number of physiological functions, including cognition. Such a-e-related changes may be arrested or partially reversed by hormonal Supplementation. We examined the effect of 6 months treatment with daily growth hormone releasing hormone (GHRH) or placebo oil the cognition Of a group of 89 healthy older (68.0 +/- 0.7) adults. GHRH resulted in improved performance on WAIS-R performance IQ (p<0.01) WAIS-R Picture arrangement (p<0.01), finding A's (p<0.01), verbal sets (p<0.01) and single-dual task (p<0.04). GHRH-based improvements were independent of gender. estrogen Status or baseline cognitive capacity. These results demonstrate that the age-related decline in the somatotrophic axis may be related to age-related decline in cognition. Further they indicate that supplementation of this neuro-hormonal axis may partially ameliorate such cognitive declines in healthy normal older adults and potentially in individuals with impaired cognitive function (i.e., mild cognitive impairment and Alzheimer's disease). (C) 2005 Elsevier Inc. All rights reserved. C1 Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Seton Hall Univ, Dept Psychol, S Orange, NJ 07079 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. RP Vitiello, MV (reprint author), Univ Washington, Dept Psychiat & Behav Sci, BB-1520D Hlth Sci Bldg,Box 356560,1959 NE Pacific, Seattle, WA 98195 USA. EM vitiello@u.washington.edu OI Vitiello, Michael/0000-0002-9776-0473 FU NCRR NIH HHS [M01-RR-00037]; NIA NIH HHS [AG10943]; NIMH NIH HHS [K02-MH01158, MH53575] NR 28 TC 32 Z9 33 U1 2 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD FEB PY 2006 VL 27 IS 2 BP 318 EP 323 DI 10.1016/j.neurobiolaging.2005.01.010 PG 6 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 004WD UT WOS:000234782400015 PM 16399214 ER PT J AU Wright, CI Wedig, MM Williams, D Rauch, SL Albert, MS AF Wright, CI Wedig, MM Williams, D Rauch, SL Albert, MS TI Novel fearful faces activate the amygdala in healthy young and elderly adults SO NEUROBIOLOGY OF AGING LA English DT Article DE functional magnetic resonance imaging; human; face perception; emotion; neuroimaging; aging ID AGE-RELATED DIFFERENCES; SURFACE-BASED ANALYSIS; FACIAL EXPRESSIONS; ALZHEIMERS-DISEASE; CORTICAL SURFACE; HUMAN BRAIN; SUBSTANTIA INNOMINATA; COORDINATE SYSTEM; NEURAL ACTIVITY; HUMAN NEOCORTEX AB Activation of the amygdala to emotionally valenced stimuli, and particularly to fearful faces, has been widely demonstrated ill healthy Young adults. However, recent Studies assessing amygdala responses to fearful emotional faces in the normal elderly have not shown similar results. The reason for this is uncertain, but it may relate to life-span developmental changes in processing emotional stimuli or structural alterations in the amygdala with aging. In order to examine whether the amygdala Could he activated in the elderly, we developed a paradigm designed to engage the amygdala on several levels. Based on recent imaging work indicating that novelty and stimulus change activates the amygdala, we assessed amygdala responses in Young and elderly adults to novel fearful faces (versus familiar neutral ones). We demonstrate a robust activation in both groups, indicating that the amygdala remains responsive in aging. This activation did not differ between the two groups when we examined regions of interest in the amygdala based oil functional or Structural criteria. However, there were significantly greater activations in the inferior temporal cortex in the young versus elderly subjects. (C) 2005 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Psychiat Neuroimaging Res Program, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gerontol Res Unit, Charlestown, MA 02129 USA. Brigham & Womens Hosp, Dept Neurol, Brigham Behav Neurol Grp, Boston, MA 02115 USA. RP Wright, CI (reprint author), Massachusetts Gen Hosp, Psychiat Neuroimaging Res Program, 13th St,Bldg 149,CNY-2613, Charlestown, MA 02129 USA. EM ciwright@partners.org FU NIMH NIH HHS [MH64806] NR 72 TC 62 Z9 62 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD FEB PY 2006 VL 27 IS 2 BP 361 EP 374 DI 10.1016/j.neurobiolaging.2005.01.014 PG 14 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 004WD UT WOS:000234782400020 PM 16399218 ER PT J AU Yin, W Cao, GD Johnnides, MJ Signore, AP Luo, YM Hickey, RW Chen, J AF Yin, W Cao, GD Johnnides, MJ Signore, AP Luo, YM Hickey, RW Chen, J TI TAT-mediated delivery of Bcl-xL protein is neuroprotective against neonatal hypoxic-ischemic brain injury via inhibition of caspases and AIF SO NEUROBIOLOGY OF DISEASE LA English DT Article DE protein transduction; hypoxia; ischemia; apoptosis; cerebral ID APOPTOSIS-INDUCING FACTOR; CEREBRAL-ARTERY OCCLUSION; NEURONAL CELL-DEATH; RAT-BRAIN; IN-VIVO; INFLAMMATORY MEDIATORS; TRANSDUCTION DOMAIN; DNA FRAGMENTATION; FUSION PROTEIN; CYTOCHROME-C AB Systemic delivery of recombinant Bcl-xL fusion protein containing the TAT protein transduction domain attenuated neonatal brain damage following hypoxic ischemia (H-I). Within 30 min after intraperitoneal injection of TAT-Bcl-xL protein into 7-day-old rats, substantially enhanced levels of Bcl-xL were found in several brain regions. Administration of TAT-Bcl-xL at the conclusion of the H-I insult decreased cerebral tissue loss in a dose-dependent manner measured I and 8 weeks later. Neuroprotection provided by TAT-Bcl-xL was significantly greater than that of the pan-caspase inhibitor BAF, suggesting that protection is only partially attributable to caspase inhibition by TAT-Bcl-xL. TAT-Bcl-xL not only inhibited caspases-3 and -9 activities after H-I but also prevented nuclear translocation of AIF. Taken together, these results substantiate the feasibility of peripheral delivery of an anti-apoptotic factor into the brain of neonatal animals to reduce H-I-induced brain injury. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Med, Pittsburgh Inst Neurodegenerat Dis, Pittsburgh, PA 15261 USA. Childrens Hosp Pittsburgh, Div Pediat Emergency Med, Pittsburgh, PA 15213 USA. Vet Affairs Pittsburgh Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA 15261 USA. RP Univ Pittsburgh, Sch Med, Dept Neurol, S-507,Biomed Sci Tower, Pittsburgh, PA 15213 USA. EM chenj2@upmc.edu FU NINDS NIH HHS [NS45048, NS36736, NS43802] NR 58 TC 64 Z9 69 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 0969-9961 EI 1095-953X J9 NEUROBIOL DIS JI Neurobiol. Dis. PD FEB PY 2006 VL 21 IS 2 BP 358 EP 371 DI 10.1016/j.nbd.2005.07.015 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 008KW UT WOS:000235040600010 PM 16140540 ER PT J AU Pekary, AE Stevens, SA Sattin, A AF Pekary, AE Stevens, SA Sattin, A TI Rapid modulation of TRH and TRH-like peptide levels in rat brain and peripheral tissues by corticosterone SO NEUROCHEMISTRY INTERNATIONAL LA English DT Article DE corticosterone; TRH; limbic system; cortex; pancreas; reproductive system ID THYROTROPIN-RELEASING-HORMONE; ALPHA-AMIDATING MONOOXYGENASE; NECROSIS-FACTOR-ALPHA; GLUCOCORTICOIDS STIMULATE; INTERFERON-GAMMA; GENE-EXPRESSION; CELL APOPTOSIS; ADRENAL-CORTEX; IN-VITRO; KAPPA-B AB Disturbance of glucocorticoid signaling has been implicated in several neuropsychiatric disorders including unipolar and bipolar depression and anxiety induced by maternal deprivation. Antidepressants have been shown to be neuroprotective and able to reverse damage to glia and neurons. Thyrotropin-releasing hormone (TRH) is an endogenous antidepressant that reduces the expression of glycogen synthase kinase-3 beta (GSK-3 beta), an enzyme that hyperphosphorylates tau and is implicated in bipolar depression, diabetes and Alzheimer's disease. In order to understand the potential role of TRH and TRH-like peptides both as mediators of the depressogenic effects of glucocorticoids and as potential therapeutics for neuropsychiatric disease, 300 a male Sprague-Dawley rats were injected i.p. with 4 mg corticosterone/0.5 ml 50% DMSO + 50% ethanol and sacrificed 0, 2, 4 and 8 h later. Levels of TRH and TRH-like peptides were measured in various brain regions involved in mood regulation and pancreas and reproductive tissues that mediate the metabolic and reproductive impairments associated with high glucocorticoid levels. Significant increases, ranging from 2- to 12-fold, in TRH or TRH-like peptide levels were observed in almost all brain regions studied at 4 h after corticosterone injection. In cerebellum, TRH and TRH-like peptides increased 4-14-fold by 8 h. TRH-like peptide levels fell 86-98% at 4 h after treatment in testis. TRH, derived only from Leydig cells, was not affected. TRH and TRH-like peptides increased 2-4-fold at 8 h in pancreas. TRH and TRH-like peptide concentrations in prostate were not affected by corticosterone up to 8 h after injection. The 4 h needed to detect a highly significant change in the TRH and TRH-like peptide levels in brain and peripheral tissues is consistent with the mediation of most corticosterone-effects via alterations in gene transcription. Published by Elsevier Ltd. C1 VA Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA 90073 USA. VA Greater Los Angeles Healthcare Syst, Psychiat Serv, Los Angeles, CA 90073 USA. VA Greater Los Angeles Healthcare Syst, Ctr Ulcer Res & Educ, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Biobehav Sci, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90073 USA. RP Pekary, AE (reprint author), VA Greater Los Angeles Healthcare Syst, Res Serv, Bldg 114,Room 229,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM eugene.pekary@med.va.gov NR 71 TC 18 Z9 18 U1 0 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0197-0186 J9 NEUROCHEM INT JI Neurochem. Int. PD FEB PY 2006 VL 48 IS 3 BP 208 EP 217 DI 10.1016/j.neuint.2005.10.003 PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 016BX UT WOS:000235596700007 PM 16293347 ER PT J AU Leite, FP Mandeville, JB AF Leite, FP Mandeville, JB TI Characterization of event-related designs using BOLD and IRON fMRI SO NEUROIMAGE LA English DT Article ID RAT SOMATOSENSORY CORTEX; RODENT BARREL CORTEX; CEREBRAL-BLOOD-FLOW; FUNCTIONAL MRI; HEMODYNAMIC-RESPONSES; NEURONAL-ACTIVITY; IMPULSE-RESPONSE; NEURAL ACTIVITY; CONTRAST AGENT; STIMULATION AB Despite many desirable characteristics, event-related (ER) stimulus designs for BOLD and IRON suffer from low detection power relative to block designs because the hemodynamic impulse response function (IRF) acts as a low-pass filter on neural activation to attenuate the size of differential responses to alternate stimuli. While the use of exogenous contrast agent (IRON technique) provides an alternative fMRI method in animal models to improve sensitivity and spatial localization, the inherently slower hemodymanuic IRF causes IRON detection efficiency to decrease faster than BOLD efficiency as the interstimulus interval (ISI) is shortened. Using simulations based upon assumptions of stimulus-response linearity and experimental data obtained in awake, non-human primates, this study compared detection efficiencies for fixed, random and semi-random ISI distributions for BOLD and IRON techniques. A larger relative gain in detection efficiency at short ISI was obtained by randomized designs using IRON contrast relative to BOLD contrast due to the slower IRF of the IRON method. To quantify tradeoffs between detection efficiency and the predictability of stimulus presentation, the Shannon entropy was introduced as an objective measure of predictability. Small amounts of entropy can be traded for large gains in efficiency, particularly for the IRON method. (c) 2005 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, MIT, HMS Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02138 USA. RP Leite, FP (reprint author), Massachusetts Gen Hosp, MIT, HMS Athinoula A Martinos Ctr Biomed Imaging, Bldg 149,13th St, Charlestown, MA 02129 USA. EM fpl@mit.edu OI Leite, Francisca/0000-0003-2550-2616 FU NIBIB NIH HHS [R01 EB001782-02] NR 52 TC 7 Z9 8 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PD FEB 1 PY 2006 VL 29 IS 3 BP 901 EP 909 DI 10.1016/j.neuroimage.2005.08.022 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 010WA UT WOS:000235227400022 PM 16213164 ER PT J AU Sagar, P Grant, PE AF Sagar, P Grant, PE TI Diffusion-weighted MR imaging: Pediatric clinical applications SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Article ID ACUTE DISSEMINATED ENCEPHALOMYELITIS; SYRUP-URINE-DISEASE; POSTERIOR REVERSIBLE ENCEPHALOPATHY; MAGNETIC-RESONANCE SPECTROSCOPY; PARTIAL STATUS EPILEPTICUS; ARTERIAL ISCHEMIC-STROKE; TRAUMATIC BRAIN-INJURY; KEARNS-SAYRE-SYNDROME; SICKLE-CELL-DISEASE; CLOSED-HEAD INJURY AB We have summarized the diffusion-weighed imaging (DWI) findings in a number of different cerebral disorders. in many cases, DWI with the accompanying apparent diffusion coefficient (ADC) map provides additional useful information to the standard imaging sequences. Pathophysiologic mechanisms resulting in baseline normal ADC values and changes with disease processes are not well understood; therefore, caution should be used when prognosticating the outcome of regions with abnormal ADCs. DWI should be used as an adjunct to routine imaging and interpreted in the context of the routine imaging findings and clinical scenario. As our understanding of ADC mechanisms increases and we begin to incorporate information about tissue organization from diffusion tensor imaging or diffusion spectrum imaging, the role of these methods in clinical diagnosis should continue to increase. C1 Massachusetts Gen Hosp, Dept Radiol, Div Pediat Radiol, Boston, MA 02114 USA. RP Sagar, P (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Pediat Radiol, 34 Fruit St, Boston, MA 02114 USA. EM psagar@partners.org NR 95 TC 10 Z9 10 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1052-5149 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD FEB PY 2006 VL 16 IS 1 BP 45 EP + DI 10.1016/j.nic.2005.11.003 PG 31 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 029DI UT WOS:000236538200005 PM 16543085 ER PT J AU Amirnovin, R Williams, ZM Cosgrove, GR Eskandar, EN AF Amirnovin, R Williams, ZM Cosgrove, GR Eskandar, EN TI Experience with microelectrode guided subthalamic nucleus deep brain stimulation SO NEUROSURGERY LA English DT Article DE deep brain stimulation; Parkinson; subthalamic nucleus ID ADVANCED PARKINSONS-DISEASE; BILATERAL STIMULATION; TECHNICAL APPROACH; GLOBUS-PALLIDUS; FOLLOW-UP; PALLIDOTOMY; SURGERY; COMPLICATIONS; PLACEMENT; OUTCOMES AB OBJECTIVE: Subthalamic deep brain stimulation (DBS) has rapidly become the standard surgical therapy for medically refractory Parkinson disease. However, in spite of its wide acceptance, there is considerable variability in the technical approach. This study details our technique and experience in performing microelectrode recording (MER) guided subthalamic nucleus (STN) DBS in the treatment of Parkinson disease. METHODS: Forty patients underwent surgery for the implantation of 70 STN DBS electrodes. Stereotactic localization was performed using a combination of magnetic resonance and computed tomographic imaging. We used an array of three microelectrodes, separated by 2 mm, for physiological localization of the STN. The final location was selected based on MER and macrostimulation through the DBS electrode. RESULTS: The trajectory selected for the DBS electrode had an average pass through the STN of 5.6 +/- 0.4 mm on the left and 5.7 +/- 0.4 mm on the right. The predicted location was used in 42% of the cases but was modified by MER in the remaining 58%. Patients were typically discharged on the second postoperative day. Eighty-five percent of patients were sent home, 13% required short-term rehabilitation, and one patient required long-term nursing services. Seven complications occurred over 4 years. Four patients suffered small hemorrhages, one patient experienced a lead migration, one developed an infection of the pulse generator, and one patient suffered from a superficial cranial infection. CONCLUSION: Simultaneous bilateral MER-guided subthalamic DBS is a relatively safe and well-tolerated procedure. MER plays an important role in optimal localization of the DBS electrodes. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA USA. RP Eskandar, EN (reprint author), Massachusetts Gen Hosp 03 331, Wang Ambulatory Care Ctr, 15 Parkman St, Boston, MA 02114 USA. EM eeskandar@partners.org NR 38 TC 16 Z9 17 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD FEB PY 2006 VL 58 IS 2 SU S BP 96 EP 102 DI 10.1227/01.NEU.0000192690.45680.C2 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 013KS UT WOS:000235408800023 ER PT J AU Carter, BS Sheth, S Chang, E Sethl, M Ogilvy, CS AF Carter, BS Sheth, S Chang, E Sethl, M Ogilvy, CS TI Epidemiology of the size distribution of intracranial bifurcation aneurysms: Smaller size of distal aneurysms and increasing size of unruptured aneurysms with age SO NEUROSURGERY LA English DT Article DE aneurysm; distal aneurysms; size; subarachnoid hemorrhage ID ANTERIOR CEREBRAL-ARTERY; SACCULAR ANEURYSMS AB OBJECTIVE: To explore the epidemiology of the size distribution of intracranial bifurcation aneurysms at different locations and to specifically test the hypothesis that distal vessels develop, on average, smaller aneurysms. METHODS: A database detailing all aneurysm cases admitted to Massachusetts General Hospital from 1991 to 2003 was reviewed. Aneurysms were classified by location and size. The distribution of aneurysms by sizes at differing origin sites was then compared. RESULTS: We identified 1673 aneurysms for study; 854 were ruptured and 819 were unruptured; 58 lesions were classified as distal middle cerebral artery and anterior cerebral artery, of which 26 were unruptured and 32 were ruptured. Analysis of the kernel density estimates for the distribution of aneurysm sizes revealed that aneurysms at distal locations and the posterior-inferior cerebellar artery location were smaller than those at other locations in the circle of Willis. The mean size of ruptured distal aneurysms at 5.7 mm (95% confidence interval 4.8-6.5), or ruptured posterior-inferior cerebellar artery aneurysms at 7.1 mm (95% confidence interval 6.3-7.8) was smaller than the average size for basilar, middle cerebral artery, or ICA aneurysms occurring proximally in the Circle of Willis. The decrease in the mean size of the distal lesions is caused by a relative paucity of aneurysms above 10 mm in size. Although ruptured aneurysms showed no change in size with age, unruptured lesions at most intracranial locations increased in size with age. CONCLUSION: The distribution of aneurysm sizes differs according to location in the intracranial vasculature in this single institution series. Smaller aneurysm sizes are observed for "distal" aneurysms than at other locations in the Circle of Willis. We hypothesize that this may be related to Laplace's Law, which states that the "critical" size for aneurysm rupture is related to the parent artery wall thickness. The larger size of unruptured aneurysms in older patients in this study may reflect referral bias or a biological model in which a subset of smaller "unstable" aneurysms are prone to rupture. Because distal aneurysms present at smaller sizes compared with aneurysms originating proximally on the Circle of Willis, prospective studies that focus on the rupture risk of this subset of intracranial aneurysms are appropriate for future investigation. C1 Massachusetts Gen Hosp, Dept Neurosurg, Aneurysm Ctr, Boston, MA 02114 USA. RP Carter, BS (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, Aneurysm Ctr, Yawkey 9026, Boston, MA 02114 USA. EM bcarter@partners.org NR 12 TC 37 Z9 47 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD FEB PY 2006 VL 58 IS 2 BP 217 EP 222 DI 10.1227/01.NEU.0000194639.37803.F8 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 011CT UT WOS:000235246000010 PM 16462474 ER PT J AU Szentirmai, O Baker, CH Lin, N Szucs, S Takahashi, M Kiryu, S Kung, AL Mulligan, RC Carter, BS AF Szentirmai, O Baker, CH Lin, N Szucs, S Takahashi, M Kiryu, S Kung, AL Mulligan, RC Carter, BS TI Noninvasive bioluminescence imaging of luciferase expressing intracranial U87 xenografts: Correlation with magnetic resonance imaging determined tumor volume and longitudinal use in assessing tumor growth and antiangiogenic treatment effect SO NEUROSURGERY LA English DT Article DE bioluminescence; brain tumor; in vivo imaging; magnetic resonance imaging ID REPORTER GENE-EXPRESSION; IN-VIVO; RENILLA LUCIFERASE; CANCER-RESEARCH; BRAIN-TUMORS; LIVING MICE; MOUSE MODEL; FACTOR VEGF; RECEPTORS; GLIOMA AB OBJECTIVE: Outcome studies in rodent tumor models rely on both histological and noninvasive study end points. Intracranial models require special tools to observe tumor growth over time noninvasively, such as magnetic resonance imaging (MRI), computed tomographic scanning, or cranial window techniques. These techniques share disadvantages in terms of cost, technical expertise required, and overall animal throughput for analysis. In this report, we sought to validate the use of the relatively newer technique of bioluminescence imaging (BLI) of intracranial glioblastoma xenograft growth by comparing it with gadolinium-enhanced MRI. METHODS: U87MG glioma cell lines genetically engineered to express the firefly luciferase gene were stereotactically injected into nude mice in the left frontal lobe. Weekly BLI and MRI were performed after the inoculation of tumor cells. For BLI, tumor growth was assessed as the peak BLI after systemic injection of luciferin substrate. MRI-based growth curves were created by three-dimensional volumetric reconstruction of axial gadolinium-enhanced MRI data covering the whole brain. In a separate experiment, mice were treated with adenoviruses encoding antiangiogenic soluble vascular endothelial growth factor receptors, and treatment effect was monitored by BLI. RESULTS: Untreated tumor growth was readily detected and observed over time by serial BLI measurements. Furthermore, tumor-derived light emission was highly correlated with volume of tumor as assessed by MRI. Furthermore, the tested antiangiogenic treatment effect was readily detected using this technique, suggesting the power of the technique for sensitive monitoring of novel therapeutics. CONCLUSION: BLI offers a simple and rapid technique for assessing intracranial glioblastoma growth in rodent models noninvasively, which correlates well with MRI. The speed of the BLI technique can increase experimental throughput, allows for targeted histological analysis in animals showing the greatest treatment effects, and provides new insights into the kinetics of intracranial tumor growth in the setting of different treatments. C1 Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Univ Texas, MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA. Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Carter, BS (reprint author), Massachusetts Gen Hosp, Neurosurg Serv, Yawkey Bldg,Room 9026, Boston, MA 02114 USA. EM bcarter@partners.org OI Kung, Andrew/0000-0002-9091-488X; Kiryu, Shigeru/0000-0003-1440-9483 NR 24 TC 80 Z9 83 U1 0 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD FEB PY 2006 VL 58 IS 2 BP 365 EP 372 DI 10.1227/01.NEU.0000195114.24819.4F PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 011CT UT WOS:000235246000044 PM 16462491 ER PT J AU Zhang, YM Tung, CH He, J Liu, N Yanachkov, I Liu, GZ Rusckowski, M Vanderheyden, JL AF Zhang, YM Tung, CH He, J Liu, N Yanachkov, I Liu, GZ Rusckowski, M Vanderheyden, JL TI Construction of a novel chimera consisting of a chelator-containing Tat peptide conjugated to a morpholino antisense oligomer for technetium-99m labeling and accelerating cellular kinetics SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE Tc-99m labeling; Tat peptide; morpholino; antisense; cell culture ID IN-VIVO; PROTEIN TRANSDUCTION; NUCLEAR-MEDICINE; GENE-EXPRESSION; MESSENGER-RNA; OLIGONUCLEOTIDES; DNA; DELIVERY; BINDING; MOUSE AB The attempt to tat-get the limited copies of messenger RNA (mRNA) in vivo with radiolabeled nucleobase oligomers as antisense probes is challenging. Selecting an antisense molecule With superior properties, enhancing the cellular kinetics, and improving the radiolabeling chemistry would be the reasonable approach to accomplish this goal. The present study reports a method to construct a chimera of phosphorodiamidate morpholino nucleobase oligomer (MORF) covalently conjugated to a peptide containing a cell membrane transduction Tat peptide and an N2S2 chelator for technetium-99m (Tc-99m) radiolabeling (N2S2-Tat-MORF). The radiolabeling properties and cellular kinetics of Tc-99m-N2S2-Tat-MORF were measured. As hypothesized, the preparation of Tc-99m-N2S2-Tat-MORF Could be achieved by an instant one-step method with labeling efficiency greater than 95%, and the Tc-99m-N2S2-Tat-MORF showed distinct properties in cell Culture from those of a control, the same MORF sequence without Tat but with mercaptoacetyltriglycine (MAG(3)) as chelator for Tc-99m (Tc-99m-MAG(3)-MORF). Tc-99m-N2S2-Tat-MORF achieved maximum accumulation of about 35% within 2 11, while Tc-99m-MAG(3)-MORF showed lower and steadily increasing accumulations but of less than 1% in 24 h. These preliminary results demonstrated that the proposed chimera has properties for easy labeling, and Tc-99m-N2S2-Tat-MORF prepared by this method possesses enhanced cellular kinetics and merits further investigation for in vivo mRNA targeting. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Massachusetts, Sch Med, Dept Radiol, Div Nucl Med, Worcester, MA 01655 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. GlSynth, Worcester, MA 01605 USA. RP Zhang, YM (reprint author), Millennium Pharmaceut Inc, Dept Imaging Sci Platform Technol, Cambridge, MA 02139 USA. EM yumin.zhang@mpi.com RI Yanachkov, Ivan/B-7908-2010; OI Tung, Ching-Hsuan/0000-0001-6648-6195 NR 39 TC 11 Z9 11 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD FEB PY 2006 VL 33 IS 2 BP 263 EP 269 DI 10.1016/j.nucmedbio.2005.10.009 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 030EI UT WOS:000236616500014 PM 16546682 ER PT J AU Chan, JL Mun, EC Stoyneva, V Mantzoros, CS Goldfine, AB AF Chan, JL Mun, EC Stoyneva, V Mantzoros, CS Goldfine, AB TI Peptide YY levels are elevated after gastric bypass surgery SO OBESITY LA English DT Article DE peptide YY; ghrelin; fasting; gastric bypass ID PLASMA GHRELIN LEVELS; OBESE SUBJECTS; WEIGHT-LOSS; FOOD-INTAKE; GUT HORMONE; PYY3-36; LEPTIN AB Objective: Mechanisms that promote effective and sustained weight loss in persons who have undergone Roux-en-Y gastric bypass surgery are incompletely understood but may be mediated, in part, by changes in appetite. Peptide YY (PYY) is a gut-derived hormone with anorectic properties. We sought to determine whether gastric bypass surgery alters PYY levels or response to glucose. Research Methods and Procedures: PYY and ghrelin levels after a 75-gram oral glucose tolerance test were measured in 6 morbidly obese patients 1.5 +/- 0.7 (SE) years after gastric bypass compared with 5 lean and 12 obese controls. Results: After substantial body weight loss (36.8 +/- 3.6%) induced by gastric bypass, the PYY response to an oral glucose tolerance test was significantly higher than in controls (p = 0.01). PYY increased similar to 10-fold after a 75-gram glucose load to a peak of 303.0 +/- 37.0 pg/mL at 30 minutes (p = 0.03) and remained significantly higher than fasting levels for all subsequent time-points. In contrast, PYY levels in obese and lean controls increased to a peak of similar to 2-fold, which was only borderline significant. Ghrelin levels decreased in a symmetric but opposite fashion to that of PYY. Discussion: Gastric bypass results in a more robust PYY response to caloric intake, which, in conjunction with decreased ghrelin levels, may contribute to the sustained efficacy of this procedure. The findings provide further evidence for a role of gut-derived hormones in mediating appetite changes after gastric bypass and support further efforts to determine whether PYY3-36 replacement could represent an effective therapy for obesity. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Div Endocrinol Diabet & Metab, Boston, MA USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA USA. RP Goldfine, AB (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02115 USA. EM agoldfine@joslin.harvard.edu FU NCRR NIH HHS [M01-RR01032, K23 RR018860]; NIDDK NIH HHS [K08-DK02604]; PHS HHS [R01-58785] NR 16 TC 63 Z9 66 U1 0 U2 2 PU NORTH AMER ASSOC STUDY OBESITY PI SILVER SPRING PA 8630 FENTON ST, SUITE 918, SILVER SPRING, MD 20910 USA SN 1071-7323 J9 OBESITY JI Obesity PD FEB PY 2006 VL 14 IS 2 BP 194 EP 198 DI 10.1038/oby.2006.25 PG 5 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 055KA UT WOS:000238448000003 PM 16571843 ER PT J AU Nadler, E Eckert, B Neumann, PJ AF Nadler, Eric Eckert, Ben Neumann, Peter J. TI Do oncologists believe new cancer drugs offer good value? SO ONCOLOGIST LA English DT Editorial Material DE health policy; cost-benefit analysis; chemotherapy; healthcare economic ID COLORECTAL-CANCER; CHEMOTHERAPY; ATTITUDES; FUTURE; HEALTH AB Background. Substantial debate centers on the high cost and relative value of new cancer therapies. Oncologists play a pivotal role in treatment decisions, yet it is unclear whether they perceive high-cost new treatments to offer good value or how therapeutic costs factor into their treatment recommendations. Methods. We surveyed 139 academic medical oncologists at two academic hospitals in Boston. We asked respondents to provide estimates for the cost and effectiveness of bevacizumab and whether they believed the treatment offered "good value." We also asked respondents to judge how large a gain in life expectancy would justify a hypothetical cancer drug that costs $70,000 a year. Using this information, we calculated implied cost-effectiveness thresholds. Finally, we explored respondents' views on the role of cost in treatment decisions. Results. Ninety academic oncologists (65%) completed the survey. Seventy-eight percent stated that patients should have access to "effective" care regardless of cost. Implied cost-effectiveness thresholds, derived from the bevacizumab and hypothetical scenarios, averaged roughly $300,000 per quality-adjusted-life-year (QALY). Only 25% of oncologists felt that bevacizumab offered "good value." Conclusions. A majority of academic oncologists stated that cost does not influence their clinical practice, nor should it limit access to "effective" care. Yet respondents did not consider all effective drugs to be of good value. Implied cost-effectiveness thresholds were $300,000/QALY-a value higher than the $50,000 standard often cited. A subset of oncologists were sensitive to cost, believing it should factor into clinical decisions. These findings reflect the ongoing controversies within the medical community as expensive new therapies enter the system. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Tufts Univ, New England Med Ctr, Boston, MA 02111 USA. RP Nadler, E (reprint author), Baylor Univ, Med Ctr, Sammons Ctr, 3535 Worth St, Dallas, TX 75226 USA. EM Enadler2000@mac.com NR 19 TC 104 Z9 104 U1 1 U2 4 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD FEB PY 2006 VL 11 IS 2 BP 90 EP 95 DI 10.1634/theoncologist.11-2-90 PG 6 WC Oncology SC Oncology GA 085TG UT WOS:000240626700001 PM 16476830 ER PT J AU Reardon, DA Wen, PY AF Reardon, David A. Wen, Patrick Y. TI Therapeutic advances in the treatment of glioblastoma: Rationale and potential role of targeted agents SO ONCOLOGIST LA English DT Review DE angiogenesis inhibitors; glioblastoma multiforme; targeted therapy; tyrosine kinase inhibitors ID GROWTH-FACTOR RECEPTOR; PHASE-II TRIAL; RECURRENT MALIGNANT GLIOMA; TYROSINE KINASE INHIBITOR; HIGH-GRADE GLIOMAS; BRAIN-TUMORS; ANTITUMOR-ACTIVITY; RADIATION-THERAPY; CLINICAL-TRIAL; IN-VIVO AB Despite advances in standard therapy, including surgical resection followed by radiation and chemotherapy, the prognosis for patients with glioblastoma multiforme (GBM) remains poor. Unfortunately, most patients die within 2 years of diagnosis of their disease. Molecular abnormalities vary among individual patients and also within each tumor. Indeed, one of the distinguishing features of GBM is its marked genetic heterogeneity. Nonetheless, recent developments in the field of tumor biology have elucidated signaling pathways and genes involved in the development of GBM, and several novel agents that target these signaling pathways are being developed. As new details on the genetic characteristics of this disease become available, innovative treatment regimens, including a variety of traditional treatment modalities such as surgery, radiation, and cytotoxic chemotherapy, will be combined with newer targeted therapies. This review introduces these new targeted therapies in the context of current treatment options for patients with GBM. It is hoped that this combined approach will overcome the current limitations in the treatment of patients with GBM and result in a better prognosis for these patients. C1 Duke Univ, Med Ctr, Preston Robert Tisch Brain Tumor Ctr, Durham, NC 27710 USA. Dana Farber Canc Inst, Brighman & Womens Canc Ctr, Ctr NeuroOncol, Boston, MA 02115 USA. RP Reardon, DA (reprint author), Duke Univ, Med Ctr, Preston Robert Tisch Brain Tumor Ctr, DUMC 3624, Durham, NC 27710 USA. EM reard003@mc.duke.edu; patrick_wen@dfci.harvard.edu NR 103 TC 127 Z9 133 U1 1 U2 3 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD FEB PY 2006 VL 11 IS 2 BP 152 EP 164 DI 10.1634/theoncologist.11-2-152 PG 13 WC Oncology SC Oncology GA 085TG UT WOS:000240626700007 PM 16476836 ER PT J AU Abel, GA Penson, RT Joffe, S Schapira, L Chabner, BA Lynch, TJ AF Abel, Gregory A. Penson, Richard T. Joffe, Steven Schapira, Lidia Chabner, Bruce A. Lynch, Thomas J., Jr. TI Direct-to-consumer advertising in oncology SO ONCOLOGIST LA English DT Article DE cancer; support; psychosocial; personal; communication; connection ID PRESCRIPTION MEDICATIONS; PATIENT-RELATIONSHIP; PROMOTION; ATTITUDES; REQUESTS; BEHAVIOR; DRUGS; CARE AB Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (NIGH), founded The Kenneth B. Schwartz Center at MGH. The Schwartz Center is a nonprofit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to patients and support to caregivers while encouraging the healing process. The center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum in which caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. Increasingly, cancer patients are subjected to advertisements related to oncologic therapies and other cancer-related products in the popular media. Such direct-to-consumer advertising is controversial: while it may inform, educate, and perhaps even empower patients, it also has the ability to misinform patients, and strain their relationships with oncology providers. The U.S. Food and Drug Administration requires that direct-to-consumer advertising provide a balanced presentation of a product's benefits, risks, and side effects, but this can be difficult to achieve. Through a discussion of this topic by an oncology fellow, ethicist, cancer survivor, and senior oncologist, the role of direct-to-consumer advertising and its often subtle effects on clinical practice in oncology are explored. Although sparse, the medical literature on this increasingly prevalent type of medical communication is also reviewed. C1 Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02114 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Penson, RT (reprint author), Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, 55 Fruit St,Yawkey 9066, Boston, MA 02114 USA. EM rpenson@partners.org OI Joffe, Steven/0000-0002-0667-7384 NR 32 TC 9 Z9 9 U1 2 U2 7 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD FEB PY 2006 VL 11 IS 2 BP 217 EP 226 DI 10.1634/theoncologist.11-2-217 PG 10 WC Oncology SC Oncology GA 085TG UT WOS:000240626700013 PM 16476842 ER PT J AU Seddon, JM Sharma, S Adelman, RA AF Seddon, JM Sharma, S Adelman, RA TI Evaluation of the clinical age-related maculopathy staging system SO OPHTHALMOLOGY LA English DT Article ID MACULAR DEGENERATION; PROGRESSION; AGREEMENT; DISEASE; EYE; CLASSIFICATION; INTEROBSERVER; ASSOCIATION; RELIABILITY; SCALES AB Objective: To evaluate a clinical classification system, the Clinical Age-Related Maculopathy Staging (CARMS) system, for age-related maculopathy (ARM) using a simple grading scale designed for clinical practice and clinical research protocols. Participants: Two hundred forty-six male and female participants with various stages of ARM who were enrolled during the first 4 years of a longitudinal study were selected for the evaluation of the CARMS system. Design: Cross-sectional comparison study. Methods: The CARMS system divides patients into 5 mutually exclusive categories based on slit-lamp assessment of drusen, retinal pigment epithelial irregularities, geographic atrophy, retinal pigment epithelial detachment, and choroidal neovascularization. Fundus photographs and clinical data of the subjects were used to evaluate this scale. Clinical grades assigned for 492 eyes of 246 patients with varying stages of ARM were compared with grades obtained from photographs evaluated by a reading center. To compare grades obtained from an inexperienced grader with those of an experienced grader, observations based on photographs from 50 randomly selected patients were reviewed. To quantify intraobserver agreement for photographic grades, observations from one observer were compared with those made at a later date by the same observer. Main Outcome Measures: Reliability and validity of the CARMS system in grading various stages of ARM based on clinical examination and photography. Results: The degree of overall agreement between the clinically assigned grade and photographic assessment for 492 eyes was substantial (exact overall agreement, 75%; unweighted kappa, 0.63; weighted kappa, 0.78). For advanced age-related macular degeneration, the sensitivity was 0.83, and specificity was 0.97. When assessing photographic grades, the degree of agreement between an inexperienced and an experienced grader was very high (unweighted kappa, 0.79; weighted kappa, 0.86), and the degree of intraobserver agreement was excellent (unweighted kappa, 0.92; weighted kappa, 0.97). Conclusions: The CARMS system, a 5-level clinical scale, is a valid and reliable staging system that can be used in both clinical practice and in clinical research protocols involving patients with all stages of ARM. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Epidemiol Unit,Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02114 USA. Queens Univ, Dept Ophthalmol, Kingston, ON K7L 3N6, Canada. Queens Univ, Dept Epidemiol, Kingston, ON K7L 3N6, Canada. Yale Univ, Med Ctr, Dept Ophthalmol & Visual Sci, New Haven, CT 06520 USA. RP Seddon, JM (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Epidemiol Unit,Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 26 TC 131 Z9 139 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD FEB PY 2006 VL 113 IS 2 BP 260 EP 266 DI 10.1016/j.ophtha.2005.11.001 PG 7 WC Ophthalmology SC Ophthalmology GA 011HL UT WOS:000235258800013 PM 16458093 ER PT J AU Thakker, MM Rubin, PAD Chang, E AF Thakker, MM Rubin, PAD Chang, E TI Pre-b-cell acute lymphoblastic leukemia presenting as an orbital mass in an 8-month-old SO OPHTHALMOLOGY LA English DT Article ID INVOLVEMENT AB Purpose: To present the case of an 8-month-old girl with undiagnosed pre-B-cell acute lymphoblastic leukemia (ALL) presenting as an orbital mass. Design: Observational case report and literature review. Methods: Review of clinical history, radiologic findings, histology of cervical lymph node and orbital biopsies, and follow-up. Results: An 8-month-old girl presented with a 2-week history of right-sided tearing, lid swelling, proptosis and rhinorrhea. A computed tomographic scan of the orbits revealed a homogeneous, retrobulbar orbital mass eroding into the ethmoid sinuses and nasal cavity, as well as cervical lymphadenopathy. Biopsy of the lesion and enlarged lymph node disclosed medium-sized, uniform, cytologically atypical lymphocytes in a starry sky pattern. Immunohistochemical analysis showed reactivity to antibodies against CD-10, CD-19, CD-34, and terminal deoxynucleotidyl transferase. Cytogenetic analysis of the tumor also revealed a gene rearrangement on chromosome 11 q23. Based on these findings, the diagnosis of pre-B-cell acute lymphoblastic leukemia was made, and systemic as well as intrathecal chemotherapy was instituted, which resulted in rapid remission of the leukemia. Conclusions: The initial presentation of ALL as an orbital mass is exceedingly rare. To the best of the authors' knowledge, this is the earliest reported case of pre-B-cell ALL presenting as an orbital lesion. C1 Univ Washington, Dept Ophthalmol, Seattle, WA 98195 USA. Massachusetts Eye & Ear Infirm, Dept Eye Plast Orbital & Cosmet Surg, Boston, MA 02114 USA. Doheny Eye Inst, Dept Ophthalm Plast Orbital & Reconstruct Surg, Los Angeles, CA 90033 USA. RP Thakker, MM (reprint author), Univ Washington, Dept Ophthalmol, Box 356485, Seattle, WA 98195 USA. EM mthakker@u.washington.edu NR 11 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD FEB PY 2006 VL 113 IS 2 BP 343 EP 346 DI 10.1016/j.ophtha.2005.10.016 PG 4 WC Ophthalmology SC Ophthalmology GA 011HL UT WOS:000235258800024 PM 16406546 ER PT J AU Vakoc, BJ Yun, SH Tearney, GJ Bouma, BE AF Vakoc, BJ Yun, SH Tearney, GJ Bouma, BE TI Elimination of depth degeneracy in optical frequency-domain imaging through polarization-based optical demodulation SO OPTICS LETTERS LA English DT Article ID COHERENCE TOMOGRAPHY; SWEPT-SOURCE; FIBER; INTERFEROMETRY; SENSITIVITY; COUPLERS; REMOVAL; SPEED AB A novel optical frequency-domain imaging system is demonstrated that employs a passive optical demodulation circuit and a chirped digital acquisition clock derived from a voltage-controlled oscillator. The demodulation circuit allows the separation of signals from positive and negative depths to better than 50 dB, thereby eliminating depth degeneracy and doubling the imaging depth range. Our system design is compatible with dual-balanced and polarization-diverse detection, important techniques in the practical biomedical application of optical frequency-domain imaging. (c) 2006 Optical Society of America. C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Vakoc, BJ (reprint author), Harvard Univ, Sch Med, 55 Fruit St,BAR 703, Boston, MA 02114 USA. EM bvakoc@partners.org FU NCI NIH HHS [R33 CA110130, R01 CA103769-02, R01 CA103769, R33 CA110130-02]; NHLBI NIH HHS [R01 HL070039, R01 HL076398, R01 HL70039, R01 HL076398-02, R01 HL070039-02] NR 11 TC 70 Z9 71 U1 1 U2 6 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD FEB 1 PY 2006 VL 31 IS 3 BP 362 EP 364 DI 10.1364/OL.31.000362 PG 3 WC Optics SC Optics GA 007IB UT WOS:000234961100024 PM 16480209 ER PT J AU Zeitels, SM Burns, JA AF Zeitels, SM Burns, JA TI Laser applications in laryngology: Past, present, and future SO OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID PULSED DYE-LASER; VOCAL FOLD; LARYNGEAL PAPILLOMAS; CLINICAL EXPERIENCE; MANAGEMENT; CO2-LASER; SURGERY; PHONOMICROSURGERY; CARCINOMA; CO2 AB Since their introduction in laryngology over 30 years ago, lasers have facilitated critically important innovations. These advances accommodated well to otolaryngology, which has led in minimally invasive surgical approaches since mirror-guided interventions in the nineteenth century. The lasers discussed in this article will provide new platform technologies that will likely lead to enhanced treatment of a number of benign and malignant laryngeal disorders. There is an expanding group of centers in which fiber-based technologies have already caused many procedures to be performed by means of local anesthesia in the clinic or office, especially for chronic diseases such as papillomatosis and dysplasia. This approach is likely to expand significantly because of the diminished patient morbidity along with socioeconomic pressures of health care delivery. C1 Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. RP Zeitels, SM (reprint author), Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, 1 Bowdoin Sq, Boston, MA 02114 USA. EM zeitels.steven@mgh.harvard.edu NR 46 TC 13 Z9 13 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0030-6665 J9 OTOLARYNG CLIN N AM JI Otolaryngol. Clin. N. Am. PD FEB PY 2006 VL 39 IS 1 BP 159 EP + DI 10.1016/j.otc.2005.10.001 PG 15 WC Otorhinolaryngology SC Otorhinolaryngology GA 018WN UT WOS:000235795600012 PM 16469661 ER PT J AU Busaba, NY Shin, HJ Faquin, WC AF Busaba, NY Shin, HJ Faquin, WC TI Correlation between middle turbinate and ipsilateral ethmoid histopathology in chronic rhinosinusitis SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT 109th Annual Meeting of the American-Academy-of-Otolaryngology-Head-and-Neck-Surgery-Foundation CY SEP 25-28, 2005 CL Los Angeles, CA SP Amer Acad Otol Head & Neck Surg Fdn ID ENDOSCOPIC ENDONASAL SURGERY; RECURRING RHINOSINUSITIS; SINUSITIS; RESECTION AB OBJECTIVE: Study the concept of "rhinosinusitis" in patients with inflammatory paranasal sinus disease (IPSD). STUDY DESIGN AND SETTING: Prospective case control series in a tertiary care facility. Twenty-two consecutive patients with IPSD without polyposis were enrolled. A partial middle turbinectomy and ethmoidectomy were performed and the histopathologic findings of the surgical specimens from the 2 sites was studied. The general degree of inflammation, epithelial thickening, and inflammatory cell count were measured. RESULTS: The degree of middle turbinate inflammation correlated with that of the ipsilateral ethmoid sinus (Spearman's rho coefficient = 0.450; P < 0.05). Epithelial thickness was more prominent in the ethmoid sinus. The total inflammatory cell count was comparable. There was a statistically significant correlation among total inflammatory cell count, plasma cell Count, and eosinophil Count between the 2 sites. CONCLUSION: The ethmoid sinus inflammation in IPSD is accompanied by a commensurate ipsilateral middle turbinate inflammation. SIGNIFICANCE: The data support the use of the term "rhinosinusitis.". C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. VA Boston Healthcare Syst, Div Otolaryngol, Boston, MA USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Busaba, NY (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA. EM nicolas_busaba@meei.harvard.edu NR 14 TC 7 Z9 9 U1 0 U2 0 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 FEB PY 2006 VL 134 IS 2 BP 250 EP 254 DI 10.1016/j.otohns.2005.10.023 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 011UJ UT WOS:000235293600012 PM 16455373 ER PT J AU Mehta, RP Rosowski, JJ Voss, SE O'Neil, E Merchant, SN AF Mehta, RP Rosowski, JJ Voss, SE O'Neil, E Merchant, SN TI Determinants of hearing loss in perforations of the tympanic membrane SO OTOLOGY & NEUROTOLOGY LA English DT Article DE audiometry; conductive hearing loss; perforation; tympanic membrane; tympanometry ID MIDDLE-EAR FUNCTION AB Background: Although tympanic membrane perforations are common, there have been few systematic studies of the structural features determining the magnitude of the resulting conductive hearing loss. Our recent experimental and modeling studies predicted that the conductive hearing loss will increase with increasing perforation size, be independent of perforation location (contrary to popular otologic belief), and increase with decreasing size of the middle-car and mastoid air space (an idea new to otology). Objective: To test our predictions regarding determinants of conductive hearing loss in tympanic membrane perforations against clinical data gathered from patients. Study Design: Prospective clinical study. Setting: Tertiary referral center. Inclusion Criteria: Patients with tympanic membrane perforations without other middle-ear disease. Main Outcome Measures: Size and location of perforation; air-bone gap at 250, 500, 1,000, 2,000, and 4,000 Hz; and tympanometric estimate of volume of the middle-ear air spaces. Results: Isolated tympanic membrane perforations in 62 ears from 56 patients met inclusion criteria. Air-bone gaps were largest at the lower frequencies and decreased as frequency increased. Air-bone gaps increased with perforation size at each frequency. Ears with small middle-ear volumes, <= 4.3 ml (n = 23), had significantly larger air-bone gaps than ears with large middle-ear volumes, > 4.3 ml (n = 39), except at 2,000 Hz. The mean air-bone gaps in ears with small volumes were 10 to 20 dB larger than in ears with large volumes. Perforations in anterior versus posterior quadrants showed no significant differences in air-bone gaps at any frequency, although anterior perforations had, on average, air-bone gaps that were smaller by 1 to 8 dB, at lower frequencies. Conclusion: The conductive hearing loss resulting from a tympanic membrane perforation is frequency-dependent, with the largest losses occurring at the lowest sound frequencies; increases as size of the perforation increases; varies inversely with volume of the middle-ear and mastoid air space (losses are larger in ears with small volumes); and does not vary appreciably with location of the perforation. Effects of location, if any, are small. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Dept Otol & Laryngol, Sch Med, Boston, MA 02114 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02138 USA. Smith Coll, Picker Engn Program, Northampton, MA 01063 USA. RP Merchant, SN (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM saumil_merchant@meei.harvard.edu FU NIDCD NIH HHS [R01 DC004798, R01 DC004798-05, R01DC04798] NR 13 TC 48 Z9 51 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD FEB PY 2006 VL 27 IS 2 BP 136 EP 143 DI 10.1097/01.mao.0000176177.17636.53 PG 8 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 012NR UT WOS:000235346400002 PM 16436981 ER PT J AU Lee, DJ Maseyesva, B Westra, W Long, DL Niparko, JK Califano, J AF Lee, DJ Maseyesva, B Westra, W Long, DL Niparko, JK Califano, J TI Microsatellite analysis of recurrent vestibular schwannoma (acoustic neuroma) following stereotactic radiosurgery SO OTOLOGY & NEUROTOLOGY LA English DT Article DE vestibular schwannoma; stereotactic radiation; microsatellite; loss of heterozygosity ID MOLECULAR-GENETIC ANALYSIS; GAMMA-KNIFE RADIOSURGERY; NEUROFIBROMATOSIS TYPE-2; TUMOR-SUPPRESSOR; CELL CARCINOMA; SHADOW BANDS; BRAIN-TUMOR; NF2 GENE; DNA; CHROMOSOME-22 AB Hypothesis: Genetic and immunohistochemical studies may provide insight into the mechanisms of vestibular schwannoma (VS) recurrence following radiation therapy. Background: Stereotactic radiation therapy is an increasingly common alternative to microsurgical resection for the primary management of sporadic VS. The molecular mechanisms associated with recurrent vestibular schwannoma (VS) following radiation therapy are not known. Methods: Primary or irradiated VS tumors were fresh-frozen at the time of surgical resection and microdissected to undergo DNA extraction. Lymphocytic control DNA was isolated from blood obtained by venipuncture. Paired normal and tumor DNA specimens were analyzed for allelic loss by PCR amplification of polymorphic dinucleotide repeat sequences. Immunohistochemical studies were performed on paraffin-embedded, irradiated surgical specimens. Results: Using 16 polymorphic microsatellite markers, 20 of 26 non-irradiated VS demonstrated loss of heterozygosity (LOH) in at least one locus of chromosome 22q. In contrast, none of the four irradiated recurrent VS demonstrated LOH on chromosome 22q (p = 0.008). No allelic loss was seen in either the primary or irradiated VS utilizing markers mapping to chromosome 10. Deletions on chromosome 10 are seen in both benign and higher-grade meningiomas and intracranial malignancies associated with radiotherapy. Immunohistochemical studies were performed to detect the protein product of the NF2 gene, merlin, in the four irradiated VS. NF2 staining was not observed. Conclusion: This study represents the first microsatellite and immunohistochemical analysis of recurrent VS following radiation therapy. Our preliminary observations suggest an alternative mechanism of NF2 inactivation that may correlate with radioresistance in VS. C1 Univ Massachusetts, Med Ctr, Dept Otolaryngol, Worcester, MA 01655 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Johns Hopkins Sch Med, Dept Otolaryngol Head & Neck Surg, Baltimore, MD USA. Johns Hopkins Sch Med, Dept Neurol Surg, Baltimore, MD USA. RP Lee, DJ (reprint author), Univ Massachusetts, Med Ctr, Dept Otolaryngol, 55 Lake Ave N, Worcester, MA 01655 USA. EM djlee@massmed.org NR 46 TC 6 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD FEB PY 2006 VL 27 IS 2 BP 213 EP 219 DI 10.1097/01.mao.0000199753.44191.73 PG 7 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 012NR UT WOS:000235346400013 PM 16436992 ER PT J AU Oaklander, AL Rissmiller, JG Gelman, LB Zheng, L Chang, YC Gott, R AF Oaklander, AL Rissmiller, JG Gelman, LB Zheng, L Chang, YC Gott, R TI Evidence of focal small-fiber axonal degeneration in complex regional pain syndrome-I (reflex sympathetic dystrophy) SO PAIN LA English DT Article DE CRPS; RSD; complex regional pain syndrome; skin biopsy; PGP9.5; human research ID FACILITATED NEUROGENIC INFLAMMATION; POSTHERPETIC NEURALGIA; CUTANEOUS INNERVATION; SENSORY NEUROPATHY; SYNDROME CRPS; NERVE-FIBERS; SKIN; PATHOLOGY; DENSITY; SIGNS AB CRPS-I consists of post-traumatic limb pain and autonomic abnormalities that continue despite apparent healing of inciting injuries. The cause of symptoms is unknown and objective findings are few, making diagnosis and treatment controversial, and research difficult. We tested the hypotheses that CRPS-I is caused by persistent minimal distal nerve injury (MDNI), specifically distal degeneration of small-diameter axons. These subserve pain and autonomic function. We studied 18 adults with IASP-defined CRPS-I affecting their arms or legs. We studied three sites on subjects' CRPS-affected and matching contralateral limb; the CRPS-affected site, and nearby unaffected ipsilateral and matching contralateral control sites. We performed quantitative mechanical and thermal sensory testing (QST) followed by quantitation of epidermal neurite densities within PGP9.5-immunolabeled skin biopsies. Seven adults with chronic leg pain, edema, disuse, and prior surgeries from trauma or osteoarthritis provided symptom-matched controls. CRPS-I subjects had representative histories and symptoms. Medical procedures were unexpectedly frequently associated with CRPS onset. QST revealed mechanical allodynia (P < 0.03) and heat-pain hyperalgesia (P < 0.04) at the CRPS-affected site. Axonal densities were highly correlated between subjects' ipsilateral and contralateral control sites (r = 0.97) but were diminished at the CRPS-affected sites of 17/18 subjects, on average by 29% (P < 0.001). overall, control subjects had no painful-site neurite reductions (P = 1.00), suggesting that pain, disuse, or prior surgeries alone do not explain CRPS-associated neurite losses. These results support the hypothesis that CRPS-I is specifically associated with post-traumatic focal MDNI affecting nociceptive small-fibers. This type of nerve injury will remain undetected in most clinical settings. (c) 2005 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Nerve Injury Unit, Dept Anesthesiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neuropathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Oaklander, AL (reprint author), Massachusetts Gen Hosp, Nerve Injury Unit, Dept Anesthesiol, Boston, MA 02114 USA. EM aoaklander@partners.org FU NINDS NIH HHS [R01 NS 42866] NR 44 TC 151 Z9 155 U1 2 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD FEB PY 2006 VL 120 IS 3 BP 235 EP 243 DI 10.1016/j.pain.2005.09.036 PG 9 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 016OX UT WOS:000235630700003 PM 16427737 ER PT J AU Kocher, MS Lee, B Dolan, M Weinberg, J Shulman, ST AF Kocher, MS Lee, B Dolan, M Weinberg, J Shulman, ST TI Pediatric orthopedic infections: Early detection and treatment SO PEDIATRIC ANNALS LA English DT Article ID RESISTANT STAPHYLOCOCCUS-AUREUS; ACUTE HEMATOGENOUS OSTEOMYELITIS; ACUTE SEPTIC ARTHRITIS; C-REACTIVE PROTEIN; METHICILLIN-RESISTANT; JOINT INFECTIONS; TRANSIENT SYNOVITIS; B VACCINATION; RISK-FACTORS; CHILDREN C1 Childrens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Orthoped, Boston, MA 02114 USA. Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. Childrens Mem Hosp, Div Infect Dis, Chicago, IL 60614 USA. RP Kocher, MS (reprint author), Childrens Hosp, Dept Orthoped Surg, 300 Longwood Ave, Boston, MA 02115 USA. EM mininder.kocher@childrens.harvard.edu NR 40 TC 10 Z9 13 U1 0 U2 2 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0090-4481 J9 PEDIATR ANN JI Pediatr. Annu. PD FEB PY 2006 VL 35 IS 2 BP 112 EP 122 PG 11 WC Pediatrics SC Pediatrics GA 009VL UT WOS:000235141400008 PM 16493918 ER PT J AU Suchomelova, L Baldwin, RA Kubova, H Thompson, KW Sankar, R Wasterlain, CG AF Suchomelova, L Baldwin, RA Kubova, H Thompson, KW Sankar, R Wasterlain, CG TI Treatment of experimental status epilepticus in immature rats: Dissociation between anticonvulsant and antiepileptogenic effects SO PEDIATRIC RESEARCH LA English DT Article ID HYPOXIA-INDUCED SEIZURES; INDUCED NEURONAL INJURY; PILOCARPINE MODEL; POSTTRAUMATIC SEIZURES; DEVELOPING BRAIN; TOPIRAMATE; EPILEPTOGENESIS; EPILEPSY; EXPRESSION; PREVENTION AB We Studied the effects of treating Status epilepticus (SE) induced by lithium and pilocarpine at postnatal day 15 (P15) or 28 (P28), on the severity of acute SE and of SE-induced epileptogenesis. Rats received topiramate (10 or 50 mg/kg IP) or diazepam C (5 mg/kg, IP) 20, 40 or 70 min after pilocarpine, and three months after SE 24-h video/EEG recordings were obtained for one (P28) Or two weeks (P15) continuously. In P15 rats, topiramate did not modify the course of SE, yet treatment at 20 or 40 min completely prevented the development of spotaneous recurrent seisures (SRS) while later treatment (70 min) was partially effective in reducing the severity and frequency of SRS. Diazepam was effective against acute SE at all time points tested. Early (20 min) but not late treatment with diazepam had the effect of reducing the frequency and severity of SRS. In P28 rats, both drugs reduced the cumulative seizure time. Early treatment (20 min) with either drug reduced the incidence of chronic epilepsy. Late treatment (40/70 min) did not alter the incidence of SRS, but decreased their frequency. This study demonstrates that, in the treatment of SE, anticonvulsant and antiepileptogenic effects call be dissociated in a development-specific manner: topiramate was antiepileplogenic without being in effective anticonvulsant in P15 animals at the doses tested. Diazepam, on the other hand, was a better anticonvulsant than in antiepileptogenic agent in the P15 animals at the dose tested. Such effects were not seen in the older animals. C1 Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Los Angeles, CA 90073 USA. Acad Sci Czech Republ, Inst Physiol, CR-14220 Prague, Czech Republic. RP Suchomelova, L (reprint author), Vet Adm Greater Los Angeles Healthcare Syst, 11 301 Wilshire Blvd,Bldg 114,Rm 139, Los Angeles, CA 90073 USA. EM lsuchomc@ucla.edu RI Kubova, Hana/C-4210-2012 OI Kubova, Hana/0000-0002-2016-7428 FU NINDS NIH HHS [NS045911, NS046516, NS13515] NR 40 TC 51 Z9 51 U1 1 U2 3 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 FEB PY 2006 VL 59 IS 2 BP 237 EP 243 DI 10.1203/01.pdr.0000196333.16608.30 PG 7 WC Pediatrics SC Pediatrics GA 004PG UT WOS:000234764100014 PM 16439585 ER PT J AU Wilkinson, CW AF Wilkinson, CW TI Roles of acetylation and other post-translational modifications in melanocortin function and interactions with endorphins SO PEPTIDES LA English DT Review DE MSH; acetylation; pro-opiomelanocortin; endorphin ID MELANOCYTE-STIMULATING-HORMONE; AGOUTI-RELATED PROTEIN; GAMMA-MSH PEPTIDES; CENTRAL-NERVOUS-SYSTEM; PROOPIOMELANOCORTIN-DERIVED PEPTIDES; ANTERIOR LOBE CORTICOTROPES; INTRACELLULAR FREE CALCIUM; INCREASED SECRETORY DRIVE; BETA-ENDORPHIN; ALPHA-MSH AB Phylogenetic, developmental, anatomic, and stimulus-specific variations in post-translational processing of POMC are well established. For melanocortins, the role of alpha-N-acetylation and the selective activities of alpha, beta, and gamma forms are of special interest. Acetylation may shift the predominant activity of POMC products between endorphinergic and melanocortinergic actions-which are often in opposition. This review addresses: (1) variations in POMC processing; (2) the influence of acetylation on the functional activity of alpha-MSH; (3) state- and stimulus-dependent effects on the proportional distribution of forms of melanocortins and endorphins; (4) divergent effects of alpha-MSH and beta-endorphin administration; (5) potential roles of beta- and gamma-MSH. Published by Elsevier Inc. C1 VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Wilkinson, CW (reprint author), VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, S-182 GRECC,1660 S Columbian Way, Seattle, WA 98108 USA. EM wilkinso@u.washington.edu NR 147 TC 33 Z9 33 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD FEB PY 2006 VL 27 IS 2 BP 453 EP 471 DI 10.1016/j.peptides.2005.05.029 PG 19 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 014NR UT WOS:000235487400024 PM 16280185 ER PT J AU Lee, WCA Huang, H Feng, GP Sanes, JR Brown, EN So, PT Nedivi, E AF Lee, WCA Huang, H Feng, GP Sanes, JR Brown, EN So, PT Nedivi, E TI Dynamic remodeling of dendritic arbors in GABAergic interneurons of adult visual cortex SO PLOS BIOLOGY LA English DT Article ID MASSIVE CORTICAL REORGANIZATION; OCULAR DOMINANCE COLUMNS; CRITICAL-PERIOD; STRIATE CORTEX; SOMATOSENSORY CORTEX; SPINE STABILITY; IN-VIVO; PLASTICITY; NEURONS; RAT AB Despite decades of evidence for functional plasticity in the adult brain, the role of structural plasticity in its manifestation remains unclear. To examine the extent of neuronal remodeling that occurs in the brain on a day-to-day basis, we used a multiphoton-based microscopy system for chronic in vivo imaging and reconstruction of entire neurons in the superficial layers of the rodent cerebral cortex. Here we show the first unambiguous evidence ( to our knowledge) of dendrite growth and remodeling in adult neurons. Over a period of months, neurons could be seen extending and retracting existing branches, and in rare cases adding new branch tips. Neurons exhibiting dynamic arbor rearrangements were GABA-positive non-pyramidal interneurons, while pyramidal cells remained stable. These results are consistent with the idea that dendritic structural remodeling is a substrate for adult plasticity and they suggest that circuit rearrangement in the adult cortex is restricted by cell type-specific rules. C1 MIT, Picower Inst Learning & Memory, Cambridge, MA 02139 USA. MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. MIT, Dept Mech Engn, Cambridge, MA 02139 USA. MIT, Div Biol Funct, Cambridge, MA 02139 USA. Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27710 USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. MIT Harvard Div Hlth Sci & Technol, Cambridge, MA USA. Massachusetts Gen Hosp, Neurosci Stat Res Lab, Dept Anaesthesia & Crit Care, Boston, MA 02114 USA. MIT, Dept Biol, Cambridge, MA USA. RP Nedivi, E (reprint author), MIT, Picower Inst Learning & Memory, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM nedivi@mit.edu FU NEI NIH HHS [R01 EY017656, R01 EY017656-01A2] NR 51 TC 134 Z9 138 U1 1 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1544-9173 J9 PLOS BIOL JI PLoS. Biol. PD FEB PY 2006 VL 4 IS 2 BP 271 EP 280 AR e29 DI 10.1371/journal.pbio.0040029 PG 10 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 012MI UT WOS:000235342900013 PM 16366735 ER PT J AU Korves, CT Goldie, SJ Murray, MB AF Korves, CT Goldie, SJ Murray, MB TI Cost-effectiveness of alternative blood-screening strategies for West Nile virus in the United States SO PLOS MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; NEW-YORK-CITY; ESTIMATED RISK; HEPATITIS-B; INFECTION; TRANSFUSION; TRANSMISSION; ENCEPHALITIS; EPIDEMIC; DONATIONS AB Background West Nile virus (WNV) is endemic in the US, varying seasonally and by geographic region. WNV can be transmitted by blood transfusion, and mandatory screening of blood for WNV was recently introduced throughout the US. Guidelines for selecting cost-effective strategies for screening blood for WNV do not exist. Methods and Findings We conducted a cost-effectiveness analysis for screening blood for WNV using a computer-based mathematical model, and using data from prospective studies, retrospective studies, and published literature. For three geographic areas with varying WNV-transmission intensity and length of transmission season, the model was used to estimate lifetime costs, quality-adjusted life expectancy, and incremental cost-effectiveness ratios associated with alternative screening strategies in a target population of blood-transfusion recipients. We compared the status quo (baseline screening using a donor questionnaire) to several strategies which differed by nucleic acid testing of either pooled or individual samples, universal versus targeted screening of donations designated for immunocompromised patients, and seasonal versus year-long screening. In low-transmission areas with short WNV seasons, screening by questionnaire alone was the most cost-effective strategy. In areas with high levels of WNV transmission, seasonal screening of individual samples and restricting screening to blood donations designated for immunocompromised recipients was the most cost-effective strategy. Seasonal screening of the entire recipient pool added minimal clinical benefit, with incremental cost-effectiveness ratios exceeding US$1.7 million per quality-adjusted life-year gained. Year-round screening offered no additional benefit compared to seasonal screening in any of the transmission settings. Conclusions In areas with high levels of WNV transmission, seasonal screening of individual samples and restricting screening to blood donations designated for immunocompromised recipients is cost saving. In areas with low levels of infection, a status-quo strategy using a standard questionnaire is cost-effective. C1 Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Columbia Univ, Earth Inst, New York, NY 10027 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy, Harvard Ctr Risk Anal, Boston, MA 02115 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. RP Korves, CT (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. EM ck2187@columbia.edu FU NIAID NIH HHS [R01 AI052284, R01 AI052284-02, T32 AI007535] NR 36 TC 22 Z9 22 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD FEB PY 2006 VL 3 IS 2 BP 211 EP 221 AR e21 DI 10.1371/journal.pmed.0030021 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 034OC UT WOS:000236937300014 PM 16381598 ER PT J AU Feldman, L Wang, YX Rhim, JS Bhattacharya, N Loda, M Sytkowski, AJ AF Feldman, L Wang, YX Rhim, JS Bhattacharya, N Loda, M Sytkowski, AJ TI Erythropoietin stimulates growth and STAT5 phosphorylation in human prostate epithelial and prostate cancer cells SO PROSTATE LA English DT Review DE erythropoietin; erythropoietin receptor; prostate cancer; STAT5 ID BCL-X-L; RECOMBINANT-HUMAN-ERYTHROPOIETIN; LOW-BIRTH-WEIGHT; QUALITY-OF-LIFE; IN-VITRO; ENDOTHELIAL-CELLS; ERYTHROID-CELLS; EPOETIN ALPHA; NECROTIZING ENTEROCOLITIS; NEOPLASTIC TRANSFORMATION AB BACKGROUND. Erythropoietin (Epo), the principal regulator of erythroid progenitor survival, growth, and differentiation, initiates its action by binding to its cognate cell surface receptor (EpoR). EpoR have been identified on a variety of non-hematopoietic cells, both normal and malignant, however, little is known about the function of EpoR on malignant cells. METHODS. RT-PCR, Western blotting, and immunohistochemistry were used to demonstrate that prostate cancer cells express EpoR at both the gene and protein level. Cell proliferation assays and STAT5 phosphorylation were used to demonstrate Epo's mitogenic action and intracellular signaling, respectively. RESULTS. We have demonstrated that transformed prostate epithelial and prostate cancer cell lines, as well as primary prostate tissue, express the EpoR. Importantly, the EpoR on prostate cells are functional, as demonstrated by the observation that each of the cell lines exhibited a dose-dependent proliferative response to Epo, and that Epo triggered STAT5b phosphorylation in the cells. CONCLUSION. Human prostatic epithelial cells and prostate cancer cells express functional EpoR, and Epo serves as a growth factor for these cells. These results have implications for our understanding of normal prostatic growth and development and of the pathobiology of human prostate cancer. C1 Beth Israel Deaconess Med Ctr, Lab Cell & Mol Biol, Div Hematol & Oncol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Uniformed Serv Univ Hlth Sci, Ctr Prostate Dis Res, Bethesda, MD USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Feldman, L (reprint author), Beth Israel Deaconess Med Ctr, Lab Cell & Mol Biol, Div Hematol & Oncol, 330 Brookline Ave-W BL 548, Boston, MA 02215 USA. EM lfeldman@bidmc.harvard.edu FU NCI NIH HHS [R01 CA89204, R03 CA96047] NR 103 TC 68 Z9 72 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-4137 J9 PROSTATE JI Prostate PD FEB 1 PY 2006 VL 66 IS 2 BP 135 EP 145 DI 10.1002/pros.20310 PG 11 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 005QG UT WOS:000234838300003 PM 16161153 ER PT J AU Fasciano, K Berman, H DeFrino, B Jameson, R Moore, C Kennedy, V Golant, M Colantuono, J AF Fasciano, K Berman, H DeFrino, B Jameson, R Moore, C Kennedy, V Golant, M Colantuono, J TI When a parent has cancer: A multi-site community-based intervention for school personnel SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Wellness Community Greater Miami, Miami, FL USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Wellness Community Natl, Los Angeles, CA USA. Hurricane Voices, Newton, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD FEB PY 2006 VL 15 IS 1 SU S BP S46 EP S46 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 016XZ UT WOS:000235659000083 ER PT J AU Greer, JA Zhang, BH Vanderwerker, LC Prigerson, HG AF Greer, JA Zhang, BH Vanderwerker, LC Prigerson, HG TI Prevalence and correlates of anxiety in patients with advanced cancer SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Harvard Univ, Ctr Psychooncol & Palliat Care Res, Dana Farber Canc Inst, Sch Med,Brigham & Womens Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD FEB PY 2006 VL 15 IS 1 SU S BP S81 EP S82 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 016XZ UT WOS:000235659000152 ER PT J AU Kornblith, AB Dowell, JM Herndon, JE Rosenberg, S Engelman, B Small, EJ Morrison, VA Atkins, J Muss, H Holland, JC AF Kornblith, AB Dowell, JM Herndon, JE Rosenberg, S Engelman, B Small, EJ Morrison, VA Atkins, J Muss, H Holland, JC TI Telephone monitoring: Early identification of psychological, physical and social distress in older advanced-stage cancer patients SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Duke Univ, Med Ctr, Ctr Stat, Canc & Leukemia Grp B, Durham, NC USA. Amer Coll Surg Oncol Grp, Durham, NC USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Calif San Francisco, San Francisco, CA USA. Minneapolis Vet Adm Med Ctr, Minneapolis, MN USA. SE Canc Control Consortium, Winston Salem, NC USA. Vermont Canc Ctr, Burlington, VT USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD FEB PY 2006 VL 15 IS 1 SU S BP S21 EP S22 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 016XZ UT WOS:000235659000037 ER PT J AU Licht, IB Ford, JS Oeffinger, KC Recklitis, CJ AF Licht, IB Ford, JS Oeffinger, KC Recklitis, CJ TI Screening adult survivors of childhood cancer with the Distress Thermometer: A comparison with the SCL-90-R SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Suffolk Univ, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Texas, SW Med Ctr, Dallas, TX USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD FEB PY 2006 VL 15 IS 1 SU S BP S39 EP S40 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 016XZ UT WOS:000235659000071 ER PT J AU Lucas, MR AF Lucas, MR TI Hyper-vigilance: Inevitable outcome of a cancer diagnosis? SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Stephen E & Catherine Pappas Ctr Neurooncol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD FEB PY 2006 VL 15 IS 1 SU S BP S81 EP S81 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 016XZ UT WOS:000235659000151 ER PT J AU Mertens, AC Schultz, KA Ness, KK Whitton, J Recklitis, C Zebrack, B Zeltzer, L Robison, LL AF Mertens, AC Schultz, KA Ness, KK Whitton, J Recklitis, C Zebrack, B Zeltzer, L Robison, LL TI Social adjustment in survivors of childhood cancer: A report from the Childhood Cancer Survivor Study (CCSS) SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ So Calif, Sch Social Work, Los Angeles, CA 90089 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD FEB PY 2006 VL 15 IS 1 SU S BP S40 EP S41 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 016XZ UT WOS:000235659000073 ER PT J AU Moore, CW Muriel, AC Beiser, ME Pirl, WF Rauch, PK AF Moore, CW Muriel, AC Beiser, ME Pirl, WF Rauch, PK TI Parenting concerns among adult cancer patients: A pilot study SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD FEB PY 2006 VL 15 IS 1 SU S BP S47 EP S48 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 016XZ UT WOS:000235659000086 ER PT J AU Norris, RL Liu, Q Bauer-Wu, S AF Norris, RL Liu, Q Bauer-Wu, S TI Self-care and coping activities of metastatic breast cancer patients: Description and factors associated with use SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Massachusetts, Med Ctr, Worcester, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD FEB PY 2006 VL 15 IS 1 SU S BP S77 EP S77 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 016XZ UT WOS:000235659000144 ER PT J AU Norris, RL Bauer-Wu, S Charboneau, J Gerberick, A Ciovacco, J Kubicek, L Healey, M Kaiser, B AF Norris, RL Bauer-Wu, S Charboneau, J Gerberick, A Ciovacco, J Kubicek, L Healey, M Kaiser, B TI Development and implementation of a Web-based writing intervention for research with young breast cancer patients SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Dana Farber Harvard Canc Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD FEB PY 2006 VL 15 IS 1 SU S BP S57 EP S58 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 016XZ UT WOS:000235659000107 ER PT J AU Pirl, WF Temel, J Cashavelly, B Lynch, TJ AF Pirl, WF Temel, J Cashavelly, B Lynch, TJ TI Coping with illness and depressive symptoms in thoracic oncology patients SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD FEB PY 2006 VL 15 IS 1 SU S BP S78 EP S79 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 016XZ UT WOS:000235659000147 ER PT J AU Tomarken, A Holland, J Schachter, S Vanderwerker, L Zuckerman, E Nelson, C Coups, E Prigerson, H AF Tomarken, A Holland, J Schachter, S Vanderwerker, L Zuckerman, E Nelson, C Coups, E Prigerson, H TI Factors of complicated grief pre-death in caregivers of cancer patients SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Calvary Hosp, New York, NY USA. Dana Farber Canc Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD FEB PY 2006 VL 15 IS 1 SU S BP S17 EP S17 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 016XZ UT WOS:000235659000028 ER PT J AU Faraone, SV Biederman, J Mick, E AF Faraone, SV Biederman, J Mick, E TI The age-dependent decline of attention deficit hyperactivity disorder: a meta-analysis of follow-up studies SO PSYCHOLOGICAL MEDICINE LA English DT Review ID PSYCHIATRIC STATUS; DEFICIT/HYPERACTIVITY DISORDER; BOYS; CHILDREN; ADULTS; PERSISTENCE; CHILDHOOD; ADHD; ADOLESCENCE; DEFINITION AB Background. This study examined the persistence of attention deficit hyperactivity disorder (ADHD) into adulthood. Method. We analyzed data from published follow-up studies of ADHD. To be included in the analysis, these additional studies had to meet the following criteria: the study included a control group and it was clear from the methods if the diagnosis of ADHD included subjects who did not meet full criteria but showed residual and impairing signs of the disorder. We used a meta-analysis regression model to separately assess the syndromatic and symptomatic persistence of ADHD. Results. When we define only those meeting full criteria for ADHD as having 'persistent ADHD', the rate of persistence is low, similar to 15% at age 25 years. But when we include cases consistent with DSM-IV's definition of ADHD in partial remission, the rate of persistence is much higher, similar to 65%. Conclusions. Our results show that estimates of ADHD's persistence rely heavily on how one defines persistence. Yet, regardless of definition, our analyses show that evidence for ADHD lessens with age. More work is needed to determine if this reflects true remission of ADHD symptoms or is due to the developmental insensitivity of diagnostic criteria for the disorder. C1 SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA. SUNY Upstate Med Univ, Med Genet Res Program, Syracuse, NY 13210 USA. Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Child Psychiat Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Faraone, SV (reprint author), SUNY Upstate Med Univ, Dept Psychiat, 750 E Adams St, Syracuse, NY 13210 USA. EM faraones@upstate.edu OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 FU NICHD NIH HHS [R01HD37694]; NIMH NIH HHS [R01MH57934, R13MH59126] NR 36 TC 668 Z9 681 U1 13 U2 83 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD FEB PY 2006 VL 36 IS 2 BP 159 EP 165 DI 10.1017/S003329170500471X PG 7 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 010NG UT WOS:000235200800002 PM 16420712 ER PT J AU Biederman, J Monuteaux, MC Mick, E Spencer, T Wilens, TE Silva, JM Snyder, LE Faraone, SV AF Biederman, J Monuteaux, MC Mick, E Spencer, T Wilens, TE Silva, JM Snyder, LE Faraone, SV TI Young adult outcome of attention deficit hyperactivity disorder: a controlled 10-year follow-up study SO PSYCHOLOGICAL MEDICINE LA English DT Article ID DSM-III-R; BIPOLAR DISORDER; PSYCHIATRIC STATUS; DEFICIT/HYPERACTIVITY DISORDER; CONDUCT DISORDER; MAJOR DEPRESSION; RISK-FACTORS; CHILDREN; COMORBIDITY; BOYS AB Background. Out-objective was to estimate the lifetime prevalence of psychopathology in a sample of youth with and without attention deficit hyperactivity disorder (ADHD) through young adulthood using contemporaneous diagnostic and analytic techniques. Method. We conducted a case-control, 10-year prospective study of ADHD youth. At baseline, we assessed consecutively referred male, Caucasian children with (n = 140) and without (n = 120) DSM-III-R ADHD, aged 6-18 years, ascertained from psychiatric and pediatric sources to allow for generalizability of results. At the 10-year follow-up, 112 (80%) and 105 (88%) of the ADHD and control children, respectively, were reassessed (mean age 22 years). We created the following categories of psychiatric disorders: Major Psychopathology (mood disorders and psychosis), Anxiety Disorders, Antisocial Disorders (conduct, oppositional-defiant, and antisocial personality disorder), Developmental Disorders (elimination, language, and tics disorder), and Substance Dependence Disorders (alcohol, drug, and nicotine dependence), as measured by blinded structured diagnostic interview. Results. The lifetime prevalence for all categories of psychopathology were significantly greater in ADHD young adults compared to controls, with hazard ratios and 95% confidence intervals of 6(.)1 (3(.)5-10(.)7), 2(.)2 (1(.)5-3(.)2), 5(.)9 (3(.)9-8(.)8), 2(.)5 (1(.)7-3(.)6), and 2(.)0 (1(.)3-3(.)0), respectively, for the categories described above. Conclusions. By their young adult years, ADHD Youth were at high risk for a wide range of adverse psychiatric outcomes including markedly elevated rates of antisocial, addictive, mood and anxiety disorders. These prospective findings provide further evidence for the high morbidity associated with ADHD across the life-cycle and stress the importance of early recognition of this disorder for prevention and intervention strategies. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Yawkey Ctr Outpatient Care, Dept Psychiat, Boston, MA 02114 USA. SUNY Upstate Med Univ, Dept Psychiat & Behav Sci, Syracuse, NY USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Yawkey Ctr Outpatient Care, Dept Psychiat, YAW 6A 6900,32 Fruit St, Boston, MA 02114 USA. EM jbiederman@partners.org OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 FU NICHD NIH HHS [5R01 HD-36317-07] NR 58 TC 362 Z9 378 U1 7 U2 43 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD FEB PY 2006 VL 36 IS 2 BP 167 EP 179 DI 10.1017/S0033291705006410 PG 13 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 010NG UT WOS:000235200800003 PM 16420713 ER PT J AU Lyoo, IK Pollack, MH Silveri, MM Ahn, KH Diaz, CI Hwang, J Kim, SJ Yurgelun-Todd, DA Kaufman, MJ Renshaw, PF AF Lyoo, IK Pollack, MH Silveri, MM Ahn, KH Diaz, CI Hwang, J Kim, SJ Yurgelun-Todd, DA Kaufman, MJ Renshaw, PF TI Prefrontal and temporal gray matter density decreases in opiate dependence SO PSYCHOPHARMACOLOGY LA English DT Article DE opiate; brain imaging; abuse; voxel-based morphometry ID VOXEL-BASED MORPHOMETRY; HEROIN ABUSERS; BLOOD-FLOW; WITHDRAWAL; SPECT; ACTIVATION; DISORDER; ADDICTS; COCAINE; USERS AB Rationale: There have been only a few structural brain-imaging studies, with varied findings, of opiate-dependent subjects. Voxel-based morphometry (VBM) is suitable for studying whole brain-wise structural brain changes in opiate-dependent subjects. Objectives: The objective of the current study is to explore gray matter density in opiate-dependent subjects. Methods: Gray matter density in 63 opiate-dependent subjects and 46 age- and sex-matched healthy comparison subjects was compared using VBM. Results: Relative to healthy comparison subjects, opiate-dependent subjects exhibited decreased gray matter density in bilateral prefrontal cortex [Brodmann areas (BA) 8, 9, 10, 11, and 47], bilateral insula (BA 13), bilateral superior temporal cortex (BA 21 and 38), left fusiform cortex (BA 37), and right uncus (BA 28). Conclusions: This study reports that opiate-dependent subjects have gray matter density decreases in prefrontal and temporal cortex, which may be associated with behavioral and neuropsychological dysfunction in opiate-dependent subjects. C1 Harvard Univ, McLean Hosp, Sch Med, Brain Imaging Ctr, Belmont, MA 02178 USA. Harvard Univ, Sch Med, Dept Psychiat, Belmont, MA 02178 USA. Seoul Natl Univ Hosp, Coll Med, Dept Psychiat, Seoul 110744, South Korea. Massachusetts Gen Hosp, Boston, MA 02114 USA. Habit Management Inst Inc, Boston, MA USA. Gil Med Ctr, Gachon Med Sch, Dept Psychiat, Inchon, South Korea. RP Lyoo, IK (reprint author), Harvard Univ, McLean Hosp, Sch Med, Brain Imaging Ctr, Belmont, MA 02178 USA. EM inkylyoo@yahoo.com RI Hwang, Jaeuk/F-3481-2010; Kim, Seog Ju/J-5403-2012 FU NIDA NIH HHS [DA11231, DA09448, DA15116, DA017324] NR 25 TC 68 Z9 73 U1 3 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD FEB PY 2006 VL 184 IS 2 BP 139 EP 144 DI 10.1007/s00213-005-0198-x PG 6 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 002HE UT WOS:000234601300002 PM 16369836 ER PT J AU Alpay, M Koroshetz, WJ AF Alpay, M Koroshetz, WJ TI Quetiapine in the treatment of behavioral disturbances in patients with Huntington's disease SO PSYCHOSOMATICS LA English DT Article AB The effect of quetiapine (an atypical antipsychotic with minimal extrapyramidal side effects) on motor as well as behavioral symptoms was studied in five consecutive patients with Huntington's disease in a long-term facility. Improvement of behavioral symptoms (i.e., psychotic symptoms, agitation, irritability, and insomnia) without worsening of motor functioning were noted. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Alpay, M (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. EM malpay@partners.org NR 10 TC 29 Z9 29 U1 3 U2 3 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD FEB PY 2006 VL 47 IS 1 BP 70 EP 72 DI 10.1176/appi.psy.47.1.70 PG 3 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 997TD UT WOS:000234270000010 PM 16384811 ER PT J AU Sahani, DV Kadavigere, R Blake, M Castillo, CFD Lauwers, GY Hahn, PF AF Sahani, DV Kadavigere, R Blake, M Castillo, CFD Lauwers, GY Hahn, PF TI Intraductal papillary mucinous neoplasm of pancreas: Multi-detector row CT with 20 curved reformations - Correlation with MRCP SO RADIOLOGY LA English DT Article ID HISTOPATHOLOGIC CORRELATION; CYSTIC NEOPLASM; HELICAL CT; TUMORS; CHOLANGIOPANCREATOGRAPHY; DUCT; ADENOCARCINOMA; MALIGNANCY; DIAGNOSIS; RESECTION AB Purpose: To retrospectively compare accuracy of multi-detector row computed tomography (CT), combined with two-dimensional (2D) curved reformations, and that of magnetic resonance (MR) cholangiopancreatography (MRCP) for characterization of intraductal papillary mucinous neoplasm (IPMN) as malignant, with pathologic examination as reference standard. Materials and Institutional review board approval was obtained, in: formed consent was waived, and study was HIPAA compliant. Twenty-five patients (12 women, 13 men; age range, 44-88 years) with pathologically proved IPMN were examined with dual-phase CT with 1.25-mm-thick sections for pancreatic phase; 2D curved reformations along main pancreatic duct (MPD) were generated. T2-weighted MRCP included thick- and thin-slab single-shot fast spin-echo imaging and transverse fast spin-echo imaging. Two radiologists, blinded. to surgical and pathologic findings, evaluated images for lesion location, septa, mural nodules, communication with MPD, extent and diameter of MPD dilatation, calcifications, and vascular encasement. Malignancy was suspected when one of the following was present: MPD diameter larger than 10 mm, mural nodules, vascular encasement, peripancreatic lymphadenopathy, or metastases. Sensitivity and specificity values for prediction of malignancy were calculated for CT and MRCP. Interobserver variability was determined (K analysis). Results: Excellent correlation between modalities was observed. Cyst communication was seen in 20 and 21 of 24 branch pancreatic duct (BPD) IPMNs with CT and MRCP, respectively. Sensitivity, specificity, and accuracy for detection of malignancy were 70%, 87%, and 76% (CT) and 70%, 92%, and 80% (MRCP), respectively. Interobserver agreement was good to perfect for both readers in all comparisons (overall, kappa = 0.70-1.00). Conclusion: CT combined with 2D curved reformation can provide imaging details of IPMN, including communication of BPD IPMN with MPD, that are at-most equivalent to those provided at MRCP. Presence of mural nodules, dilated MPD (> 10-mm diameter), or thick septa at CT or MRCP may be used as independent predictors of malignancy. (c) RSNA, 2006 C1 Massachusetts Gen Hosp, Dept Abdominal Imaging & Intervent, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Sahani, DV (reprint author), Massachusetts Gen Hosp, Dept Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02114 USA. EM dsahani@partners.org NR 31 TC 112 Z9 122 U1 0 U2 5 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 FEB PY 2006 VL 238 IS 2 BP 560 EP 569 DI 10.1148/radiol.2382041463 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 005XG UT WOS:000234859100022 PM 16436817 ER PT J AU Blake, MA Kalra, MK Sweeney, AT Lucey, BC Maher, MM Sahani, DV Halpern, EF Mueller, PR Hahn, PF Boland, GW AF Blake, MA Kalra, MK Sweeney, AT Lucey, BC Maher, MM Sahani, DV Halpern, EF Mueller, PR Hahn, PF Boland, GW TI Distinguishing benign from malignant adrenal masses: Multi-detector row CT protocol with 10-minute delay SO RADIOLOGY LA English DT Article ID CONTRAST-ENHANCED CT; CHEMICAL-SHIFT; HELICAL CT; ADENOMAS; DIFFERENTIATION; NONADENOMAS; PHEOCHROMOCYTOMA; WASHOUT; CURVES; TUMORS AB Purpose: To retrospectively evaluate the accuracy of precontrast attenuation, relative percentage washout (RPW), and absolute percentage washout (APW) in distinguishing benign from malignant adrenal masses at multi- detector row computed tomography (CT). Materials and Methods: This HIPAA-compliant retrospective study had institutional review board approval; the need for informed consent was waived. One hundred twenty-two adrenal masses were evaluated in 99 patients (51 men, 48 women; age range, 37-86 years) who had undergone CT performed according to the study protocol and who either were given a pathologic diagnosis or underwent follow-up imaging. Unenhanced images were obtained before administration of 120 mL of an intravenous contrast agent with a 75-second scan delay. Delayed images were obtained after 10 minutes. RPW and APW were computed. Receiver operating characteristic (ROC) analysis was performed to compare mean attenuation and both RPW and APW. Analysis was first performed with the exclusion of pheochromocytomas, myelolipomas, and cysts. Precontrast attenuation criteria specific for benignity or malignancy were determined, and ROC analysis of results for the entire nonpheochromocytoma group was then performed. Results: By using an RPW of 37.5% and excluding cysts and myelolipomas, all malignant lesions were detected with a sensitivity of 100% (17 of 1.7 lesions) and a specificity of 95% (90 of 95 lesions). Area under the binomial ROC curve (A(z)) values were 0.912, 0.985, and 0.892 for precontrast attenuation, RPW, and APW, respectively. Precontrast attenuation, of less than 0 or more than 43 HU indicated benign and malignant entities, respectively. Incorporation of these criteria into the APW analysis yielded a sensitivity of 100% (17 of 17 lesions) and a specificity of 98% (93 of 95 lesions) for a threshold washout value of 52.0%. This attenuation-corrected APW generated the greatest A. value (ie, 0.988). Combining all the information available from the protocol yielded a sensitivity of 100% (17 of 17 lesions) and a specificity of 98% (98 of 100 lesions) for differentiating benign from malignant masses. Conclusion: Precontrast attenuation of less than 0 HU supercedes the washout profile in the evaluation of an individual adrenal mass. Noncalcified, nonhemorrhagic adrenal lesions with precontrast attenuation of more than 43 HU should be considered suspicious for malignancy. (c) RSNA, 2005 C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. St Elizabeths Med Ctr, Dept Med, Div Endocrinol, Boston, MA USA. RP Blake, MA (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, White 270,55 Fruit St, Boston, MA 02114 USA. EM mblake2@partners.org NR 27 TC 106 Z9 122 U1 0 U2 4 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD FEB PY 2006 VL 238 IS 2 BP 578 EP 585 DI 10.1148/radiol.2382041514 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 005XG UT WOS:000234859100024 PM 16371582 ER PT J AU Turner, AP Kivlahan, DR Rimmele, CT Bombardier, CH AF Turner, AP Kivlahan, DR Rimmele, CT Bombardier, CH TI Does preinjury alcohol use or blood alcohol level influence cognitive functioning after traumatic brain injury? SO REHABILITATION PSYCHOLOGY LA English DT Article DE alcohol; traumatic brain injury; cognition; rehabilitation; BAL ID DISORDERS IDENTIFICATION TEST; SPINAL-CORD-INJURY; SUBSTANCE-ABUSE; NATURAL-HISTORY; SELF-REPORTS; INTOXICATION; DRINKING; VALIDITY; ETHANOL; STATE AB Objective: To examine the relations among preinjury alcohol use patterns and admission blood alcohol level (BAL) and postinjury cognitive functioning among individuals with recent TBI. Design: Cohort survey with chart review and follow-up cognitive assessment. Setting: Acute inpatient rehabilitation program in a Level I trauma center. Participants: 124 consecutive initial admissions meeting inclusion criteria. Measures: Admission BAL, preinjury alcohol consumption, consequences, and symptoms of dependence, as well as initial injury severity and subsequent cognitive functioning. Results: Higher BAL at hospital admission was related to greater initial injury severity (lower Glasgow Coma Scale score). Preinjury alcohol consumption and admission BAL were not consistently related to any postinjury assessment of cognition. Conclusion: Alcohol use at the time of injury may exacerbate the initial severity of TBI. Cognitive functioning soon after injury does not appear to be related to any preinjury drinking behavior. C1 VA Puget Sound Hlth Care Syst, Rehabil Care Serv, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Rehabil Med, Seattle, WA 98195 USA. VA Puget Cound Hlth Care Syst, Seattle, WA USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Rehabil Med, Seattle, WA 98195 USA. RP Turner, AP (reprint author), VA Puget Sound Hlth Care Syst, Rehabil Care Serv, S-117,1660 S Columbian Way, Seattle, WA 98108 USA. EM aaron.turner@med.va.gov OI Turner, Aaron/0000-0001-6897-8003 NR 49 TC 5 Z9 5 U1 3 U2 5 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0090-5550 EI 1939-1544 J9 REHABIL PSYCHOL JI Rehabil. Psychol. PD FEB PY 2006 VL 51 IS 1 BP 78 EP 86 DI 10.1037/0090-5550.51.1.78 PG 9 WC Psychology, Clinical; Rehabilitation SC Psychology; Rehabilitation GA 022FH UT WOS:000236040000011 ER PT J AU Schumacher, HR Chen, LX AF Schumacher, HR Chen, LX TI Newer therapeutic approaches: Gout SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID SERUM URIC-ACID; PURINE SELECTIVE INHIBITOR; MYOCARDIAL-INFARCTION; XANTHINE-OXIDASE; CARDIOVASCULAR-DISEASE; INDUCED HYPERURICEMIA; RENAL-FUNCTION; RISK-FACTOR; URATE; ALLOPURINOL AB Newer approaches to the treatment of gout have included modifications and further attention to aspects of current therapies, and development of interesting new therapies. Colchicine prophylaxis appears to be needed longer than previously recognized after introduction of a urate-lowering agent. Diet has received attention, though most dietary effects are small. New agents under investigation include pegylated formulations of uricase and a new potent xanthine oxidase inhibitor, febuxostat. Some cardiovascular drugs have been shown to be uricosuric. C1 Philadelphia Vet Affairs Med Ctr, Div Rheumatol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Penn Presbyterian Med Ctr, Philadelphia, PA USA. RP Schumacher, HR (reprint author), Philadelphia Vet Affairs Med Ctr, Div Rheumatol, 151K,Univ & Woodlands Ave, Philadelphia, PA 19104 USA. EM schumacr@mail.med.upenn.edu NR 62 TC 11 Z9 15 U1 1 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-857X J9 RHEUM DIS CLIN N AM JI Rheum. Dis. Clin. North Am. PD FEB PY 2006 VL 32 IS 1 BP 235 EP + DI 10.1016/j.rdc.2005.10.003 PG 11 WC Rheumatology SC Rheumatology GA 025ZV UT WOS:000236307400017 PM 16504833 ER PT J AU Meissner, OA Rieber, J Babaryka, G Oswald, M Reim, S Siebert, U Redel, T Eibel, R Mueller-Lisse, U Reiser, M Mueller-Lisse, UG AF Meissner, OA Rieber, J Babaryka, G Oswald, M Reim, S Siebert, U Redel, T Eibel, R Mueller-Lisse, U Reiser, M Mueller-Lisse, UG TI Intravascular optical coherence tomography: Differentiation of atherosclerotic plaques and quantification of vessel dimensions in crural arterial specimens SO ROFO-FORTSCHRITTE AUF DEM GEBIET DER RONTGENSTRAHLEN UND DER BILDGEBENDEN VERFAHREN LA German DT Article DE experimental study; arteries; treatment planning ID IN-VIVO; ULTRASOUND; BIOPSY; VISUALIZATION; ANGIOPLASTY; RESTENOSIS; RUPTURE AB Purpose: Intravascular optical coherence tomography (OCT) is a new technique based on infrared light that visualizes the arteries with a resolution of 10 - 20 mu m. Intravascular ultrasound (IVUS) is the Current in vivo reference standard and provides a resolution of 100 - 150 mu m. This study compared OCT to IVUS and histopathology with respect to the ability to differentiate atherosclerotic plaques and quantify vascular dimensions in peripheral crural arteries ex vivo. Materials and Methods: 50 segments of atherosclerotic arteries derived from five amputated human lower extremities were examined. The different plaque types (fibrous, high-lipid content, calcified) were assigned by two independent examiners, and the sensitivity and specificity of OCT in comparison with histopathology as well as intra- and interobserver consensus were calculated. A comparison of OCT with IVUS addressed the parameters: luminal area (LA), vascular wall area (VA) and plaque area (PA). Results: When comparing OCT and histopathology with respect to the differentiation of various plaque types, sensitivities of 81% and specificities of 89% for fibrous plaques, of 100% and 93% for lipid-rich plaques and of 80% and 89% for calcified plaques were achieved (overall correlation 83%). Intra- and interobserver consensus was very high (kappa=0.86 and kappa=0.89, p < 0.001, respectively). There was also a high correlation between quantitative measurements (Bland-Altman plot [LA]: mean bias, 0.1 mm(2) accuracy +/- 1.8 mm(2), r = 0.95 [p < 0.001] Bland-Altman plot [VA]: mean bias, 0.3 mm(2) accuracy +/- 23 mm(2), r = 0.94 [p < 0.001] Bland-Altman plot [PA]: mean bias, 0.4 mm(2) accuracy 2.3 mm(2), r = 0.80 [p < 0.01]. Conclusion: OCT allows the differentiation of atherosclerotic plaque types in crural arteries with high accuracy compared to histopathology. Quantitative measurements show a high correlation with IVUS, the current reference standard. C1 Univ Munich, Inst Klin Radiol, Munich, Germany. Univ Munich, Abt Kardiol, Med Poliklin, Munich, Germany. Univ Munich, Inst Pathol, D-8000 Munich, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Inst Technol Assessment, Boston, MA 02115 USA. Univ Munich, Inst Med Informat Biometrie & Epidemiol, Munich, Germany. Univ Munich, Urol Klin & Poliklin, Munich, Germany. RP Meissner, OA (reprint author), Pettenkoferstr 38, D-80336 Munich, Germany. EM oliver.meissner@med.uni-muenchen.de NR 25 TC 9 Z9 10 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 1438-9029 J9 ROFO-FORTSCHR RONTG JI Rofo-Fortschr. Gebiet Rontgenstrahlen Bildgeb. Verfahr. PD FEB PY 2006 VL 178 IS 2 BP 214 EP 220 DI 10.1055/s-2005-858922 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 009SQ UT WOS:000235133400009 PM 16435253 ER PT J AU Khanna, D Arnold, EL Pencharz, JN Grossman, JM Traina, SB Lal, A MacLean, CH AF Khanna, D Arnold, EL Pencharz, JN Grossman, JM Traina, SB Lal, A MacLean, CH TI Measuring process of arthritis care: The Arthritis Foundation's Quality Indicator Set for Rheumatoid Arthritis SO SEMINARS IN ARTHRITIS AND RHEUMATISM LA English DT Review DE rheumatoid arthritis; quality of care; quality measures; process of care ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; CORTICOSTEROID-INDUCED OSTEOPOROSIS; GLUCOCORTICOID-INDUCED OSTEOPOROSIS; RANDOMIZED CONTROLLED-TRIAL; LOW-DOSE METHOTREXATE; BONE-MINERAL DENSITY; TOTAL HIP-ARTHROPLASTY; 5-YEAR FOLLOW-UP; FEE-FOR-SERVICE; DOUBLE-BLIND AB OBJECTIVE To describe the scientific evidence that supports each of the explicit process measures in the Arthritis Foundation's Quality Indicator Set for Rheumatoid Arthritis. METHODS For each of the 27 measures in the Arthritis Foundation's Quality Indicator set, a comprehensive literature review was performed for evidence that linked the process of care defined in the indicator with relevant clinical outcomes and to summarize practice guidelines relevant to the indicators. RESULTS Over 7500 titles were identified and reviewed. For each of the indicators the scientific evidence to support or refute the quality indicator was summarized. We found direct evidence that supported a process-outcome link for 15 of the indicators, an indirect link for 7 of the indicators, and no evidence to support or refute a link for 5. The processes of care described in the indicators for which no supporting/refuting data were found have been assumed to be so essential to care that clinical trails assessing their importance have not, and probably never will be, performed. The process of care described in all but 2 of the indicators is recommended in 1 or more practice guidelines. CONCLUSION There are sufficient scientific evidence and expert consensus to support the Arthritis Foundation's Quality Indicator Set for Rheumatoid Arthritis, which defines a minimal standard of care that can be used to assess health care quality for patients with rheumatoid arthritis. C1 RAND, Hlth, Santa Monica, CA 90407 USA. Univ Cincinnati, Div Immunol, Cincinnati, OH 45221 USA. VAMC, Cincinnati, OH USA. Univ Calif Los Angeles, Div Rheumatol, Los Angeles, CA 90024 USA. Toronto Gen Hosp, Toronto Gen Res Inst, Toronto, ON, Canada. Univ Toronto, Fac Med, Inst Med Sci, Toronto, ON, Canada. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Greater Los Angeles Vet Adm Hlth Care Syst, Los Angeles, CA 90024 USA. RP MacLean, CH (reprint author), RAND, Hlth, 1776 Main St, Santa Monica, CA 90407 USA. EM maclean@rand.org NR 194 TC 29 Z9 29 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0049-0172 J9 SEMIN ARTHRITIS RHEU JI Semin. Arthritis Rheum. PD FEB PY 2006 VL 35 IS 4 BP 211 EP 237 DI 10.1016/j.semarthit.2005.08.004 PG 27 WC Rheumatology SC Rheumatology GA 015GV UT WOS:000235540800003 PM 16461068 ER PT J AU Kradin, RL Mark, EI AF Kradin, Richard L. Mark, Eugene J. TI Distinguishing benign mesothelial hyperplasia from neoplasia: a practical approach SO SEMINARS IN DIAGNOSTIC PATHOLOGY LA English DT Article DE mesothelioma; mesothelial hyperplasia; asbestos; immunohistochemistry ID MALIGNANT MESOTHELIOMA; IN-SITU; P53; DIFFERENTIATION; DIAGNOSIS; CELLS AB This paper examines the spectrum of challenges that confront the diagnostic surgical pathologist in distinguishing benign mesothelial hyperplasia from malignant mesothelioma. The current state of the art with respect to the morphological, immunohistological, and molecular features that can assist in the evaluation of benign and malignant pleural disease is examined. Practical guidelines are offered that should reduce the risk of diagnostic error in this problematic area of surgical pathology. (c) 2006 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Kradin, RL (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 253, Boston, MA 02114 USA. EM rkradin@partners.org NR 20 TC 7 Z9 7 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0740-2570 J9 SEMIN DIAGN PATHOL JI Semin. Diagn. Pathol. PD FEB PY 2006 VL 23 IS 1 BP 4 EP 14 DI 10.1053/semdp.2006.06.005 PG 11 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 091WU UT WOS:000241059800002 PM 17044190 ER PT J AU Mark, EJ Kradin, RL AF Mark, Eugene J. Kradin, Richard L. TI Pathological recognition of diffuse malignant mesothelioma of the pleura: The significance of the historical perspective as regards this signal tumor SO SEMINARS IN DIAGNOSTIC PATHOLOGY LA English DT Article DE diffuse malignant mesothelioma; asbestos; history ID ASBESTOS EXPOSURE; GLOBAL BURDEN; MORTALITY; DISEASE AB Diffuse malignant mesothelioma (DMM) is a distinctive tumor which provides an uncommon opportunity to observe the gradual appreciation and increasing incidence of a new disease. DMM is a new disease. One cannot comment intelligently about the pathology of sporadic cases that might have occurred before the beginnings of anatomic pathology, but we do know that there were so few cases before 1930 that the very existence of the disease was not accepted in general before 1930 and not accepted by all pathologists even up until 1960. Because DMM is increasing on a worldwide basis and is making its appearance in the developing world, where it has not previously been diagnosed, appreciation of how the disease came to be noticed sheds light on its causation. As a signal tumor for exposure to asbestos, and knowing that all special exposures contribute to the development of the disease, knowledge of its continuing escalation underscores the importance of recognition of previously unimplicated or occult exposures for reasons of public health in both developed and developing countries. (c) 2006 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Mark, EI (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. EM Mark@helix.mgh.harvard.edu NR 40 TC 5 Z9 5 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0740-2570 J9 SEMIN DIAGN PATHOL JI Semin. Diagn. Pathol. PD FEB PY 2006 VL 23 IS 1 BP 25 EP 34 DI 10.1053/j.semdp.2006.06.004 PG 10 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 091WU UT WOS:000241059800005 PM 17044193 ER PT J AU Furie, KL Kelly, PJ AF Furie, KL Kelly, PJ TI Homocyst(e)ine and stroke SO SEMINARS IN NEUROLOGY LA English DT Review DE homocysteine; folate; vitamins; genetics ID BETA-SYNTHASE GENE; PYRIDOXINE-RESPONSIVE HOMOCYSTINURIA; C-REACTIVE PROTEIN; METHYLENETETRAHYDROFOLATE REDUCTASE GENE; PLASMA HOMOCYSTEINE CONCENTRATIONS; TRANSIENT ISCHEMIC ATTACK; CERVICAL ARTERY DISSECTION; INDEPENDENT RISK FACTOR; CORONARY-HEART-DISEASE; FOLIC-ACID AB Homocyst(e)ine elevation is associated with a two- to threefold fold increased risk of ischemic stroke. Although most commonly associated with large-artery atherosclerosis and venous thrombosis, hyperhomocysteinemia may contribute to stroke by other mechanisms as well. Levels of homocysteine are determined by genetic regulation of the enzymes involved in homocyst(e)ine metabolism and by levels of the vitamin cofactors (folate, B-6, and B-12) associated with those reactions. Emerging evidence suggests that genetic variation within this pathway, such as the methyleneterahydrofolate reductase and cystathionine beta-synthase and nicotinamide N-methyltransferase genes, increases the risk of ischemic stroke. The introduction of grain folate fortification in 1998 has reduced homocyst(e)ine concentrations in the U.S. population. However, it is important to screen for vitamin B-12 deficiency and be cognizant that vitamin B-6 levels may be low in the elderly and in individuals with inflammatory disorders. The Vitamin Intervention in Stroke Prevention study failed to prove that high-dose supplementation with folate, B-6, and B-12 reduced the risk of recurrent stroke or myocardial infarction at 2 years; however, there is an ongoing clinical trial evaluating the potential benefit of vitamin supplementation. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke Serv, Boston, MA 02114 USA. Mater Misericordiae Hosp, Neurovasc Clin Sci Unit, Dublin 7, Ireland. RP Furie, KL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke Serv, VBK 802,55 Fruit St, Boston, MA 02114 USA. FU NINDS NIH HHS [K23 NS42720] NR 101 TC 19 Z9 23 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0271-8235 J9 SEMIN NEUROL JI Semin. Neurol. PD FEB PY 2006 VL 26 IS 1 BP 24 EP 32 DI 10.1055/s-2006-933306 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 042VK UT WOS:000237558500005 PM 16479441 ER PT J AU Kushida, CA Morgenthaler, TI Littner, MR Alessi, CA Bailey, D Coleman, J Friedman, L Hirshkowitz, M Kapen, S Kramer, M Lee-Chiong, T Owens, J Pancer, JP AF Kushida, Clete A. Morgenthaler, Timothy I. Littner, Michael R. Alessi, Cathy A. Bailey, Dennis Coleman, Jack, Jr. Friedman, Leah Hirshkowitz, Max Kapen, Sheldon Kramer, Milton Lee-Chiong, Teofilo Owens, Judith Pancer, Jeffrey P. TI Practice parameters for the treatment of snoring and obstructive sleep apnea with oral appliances: An update for 2005 SO SLEEP LA English DT Article DE practice parameters; practice guidelines; standards of practice; snoring; obstructive sleep apnea syndrome; oral appliances; dental devices ID CARDIOVASCULAR-DISEASE AB These practice parameters are an update of the previously published recommendations regarding use of oral appliances in the treatment of snoring and Obstructive Sleep Apnea (OSA). Oral appliances (OAs) are indicated for use in patients with mild to moderate OSA who prefer them to continuous positive airway pressure (CPAP) therapy, or who do not respond to, are not appropriate candidates for, or who fail treatment attempts with CPAP. Until there is higher quality evidence to suggest efficacy, CPAP is indicated whenever possible for patients with severe OSA before considering OAs. Oral appliances should be fitted by qualified dental personnel who are trained and experienced in the overall care of oral health, the temporomandibular joint, dental occlusion and associated oral structures. Follow-up polysomnography or an attended cardiorespiratory (Type 3) sleep study is needed to verify efficacy, and may be needed when symptoms of OSA worsen or recur. Patients with OSA who are treated with oral appliances should return for follow-up office visits with the dental specialist at regular intervals to monitor patient adherence, evaluate device deterioration or maladjustment, and to evaluate the health of the oral structures and integrity of the occlusion. Regular follow up is also needed to assess the patient for signs and symptoms of worsening OSA. Research to define patient characteristics more clearly for OA acceptance, success, and adherence is needed. C1 Stanford Univ, Ctr Excellence Sleep Disorders, Stanford, CA 94305 USA. Mayo Clin, Mayo Sleep Disorders Ctr, Rochester, MN USA. VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Sepulveda, CA USA. Middle Tennessee ENT, Murfreesboro, TN USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Baylor Coll Med, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. VA Med Ctr, Detroit, MI USA. Wayne State Univ, Detroit, MI USA. Maimonides Hosp, Dept Psychiat, Brooklyn, NY 11219 USA. NYU, Sch Med, New York, NY USA. Natl Jewish Med & Res Ctr, Sleep Clin, Denver, CO USA. Rhode Isl Hosp, Dept Pediat, Providence, RI USA. RP Kushida, CA (reprint author), Stanford Univ, Ctr Excellence Sleep Disorders, Stanford, CA 94305 USA. OI Morgenthaler, Timothy/0000-0002-2614-3793 NR 8 TC 273 Z9 290 U1 2 U2 10 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 FEB 1 PY 2006 VL 29 IS 2 BP 240 EP 243 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 078SK UT WOS:000240123500016 PM 16494092 ER PT J AU Scheer, FAJL Zeitzer, JM Ayas, NT Brown, R Czeisler, CA Shea, SA AF Scheer, FAJL Zeitzer, JM Ayas, NT Brown, R Czeisler, CA Shea, SA TI Reduced sleep efficiency in cervical spinal cord injury; association with abolished night time melatonin secretion SO SPINAL CORD LA English DT Article DE circadian; melatonin; polysomnography; tetraplegia; sleep; spinal cord injuries ID PROPENSITY; HUMANS; EEG AB Study design: Case-controlled preliminary observational study. Objective: Melatonin is usually secreted only at night and may influence sleep. We previously found that complete cervical spinal cord injury (SCI) interrupts the neural pathway required for melatonin secretion. Thus, we investigated whether the absence of night time melatonin in cervical SCI leads to sleep disturbances. Setting: General Clinical Research Center, Brigham & Women's Hospital, Boston, USA. Methods: In an ancillary analysis of data collected in a prior study, we assessed the sleep patterns of three subjects with cervical SCI plus absence of nocturnal melatonin ( SCI levels: C4A, C6A, C6/7A) and two control patients with thoracic SCI plus normal melatonin rhythms ( SCI levels: T4A, T5A). We also compared those results to the sleep patterns of 10 healthy control subjects. Results: The subjects with cervical SCI had significantly lower sleep efficiency ( median 83%) than the control subjects with thoracic SCI (93%). The sleep efficiency of subjects with thoracic SCI was not different from that of healthy control subjects (94%). There was no difference in the proportion of the different sleep stages, although there was a significantly increased REM-onset latency in subjects with cervical SCI ( 220 min) as compared to subjects with thoracic SCI ( 34 min). The diminished sleep in cervical SCI was not associated with sleep apnea or medication use. Conclusion: We found that cervical SCI is associated with decreased sleep quality. A larger study is required to confirm these findings. If confirmed, the absence of night time melatonin in cervical SCI may help explain their sleep disturbances, raising the possibility that melatonin replacement therapy could help normalize sleep in this group. Sponsorship: This work was supported by the NIH (GCRC Grant M01-RR-02635 and Grant HL-64815). Dr Ayas is supported by the BCLA, CIHR, and MSFHR. C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Sleep Med, Boston, MA 02115 USA. Stanford Univ, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA. Vancouver Gen Hosp, Dept Med, Ctr Clin Epidemiol & Evaluat, Vancouver, BC, Canada. Massachusetts Gen Hosp, Pulm & Clin Care Unit, Boston, MA 02114 USA. RP Scheer, FAJL (reprint author), Harvard Univ, Sch Med, 221 Longwood Ave, Boston, MA 02115 USA. RI Scheer, Frank/C-2795-2012; OI Shea, Steven/0000-0003-1949-0954 FU NCRR NIH HHS [M01-RR-02635, M01 RR002635]; NHLBI NIH HHS [K24 HL076446-04, K24 HL076446, R01 HL064815, HL-64815] NR 16 TC 35 Z9 36 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1362-4393 J9 SPINAL CORD JI Spinal Cord PD FEB PY 2006 VL 44 IS 2 BP 78 EP 81 DI 10.1038/sj.sc.3101784 PG 4 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 008VK UT WOS:000235068600002 PM 16130027 ER PT J AU Amarenco, P Moskowitz, MA AF Amarenco, P Moskowitz, MA TI The dynamics of statins - From event prevention to neuroprotection SO STROKE LA English DT Editorial Material DE prevention & control; statins, HMG-CoA ID NITRIC-OXIDE SYNTHASE; RANDOMIZED CONTROLLED-TRIAL; CEREBRAL-BLOOD-FLOW; STROKE PROTECTION; REDUCTASE INHIBITORS; L-ARGININE; CHOLESTEROL; DISEASE; ATHEROSCLEROSIS; ATORVASTATIN C1 Hop Xavier Bichat, Sch Med, Dept Neurol, F-75018 Paris, France. Denis Diderot Univ, Dept Neurol, Paris, France. Denis Diderot Univ, Stroke Ctr, Paris, France. Hop Xavier Bichat, Sch Med, Stroke Ctr, F-75018 Paris, France. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Stroke & Neurovasc Regulat Lab, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Stroke & Neurovasc Regulat Lab, Charlestown, MA USA. RP Amarenco, P (reprint author), Hop Xavier Bichat, Sch Med, Dept Neurol, 46 Rue Henri Huchard, F-75018 Paris, France. EM pierre.amarenco@bch.aphp.fr NR 22 TC 17 Z9 20 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2006 VL 37 IS 2 BP 294 EP 296 DI 10.1161/01.STR.0000201856.90105.ab PG 3 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 005NJ UT WOS:000234829800008 PM 16410465 ER PT J AU Matsumori, Y Northington, FJ Hong, SHM Kayama, T Sheldon, A Vexler, ZS Ferriero, DM Weinstein, PR Liu, JL AF Matsumori, Y Northington, FJ Hong, SHM Kayama, T Sheldon, A Vexler, ZS Ferriero, DM Weinstein, PR Liu, JL TI Reduction of caspase-8 and-9 cleavage is associated with increased c-FLIP and increased binding of Apaf-1 and Hsp70 after neonatal hypoxic/ischemic injury in mice overexpressing Hsp70 SO STROKE LA English DT Article DE apoptosis; mitochondria; stress proteins ID PROGRAMMED CELL-DEATH; CYTOCHROME-C; HYPOXIA-ISCHEMIA; BRAIN-DAMAGE; IN-VIVO; APOPTOSIS; RAT; HEAT-SHOCK-PROTEIN-70; ACTIVATION; PROCASPASE-9 AB Background and Purpose - Caspase-8 and caspase-9 are essential proteases of the extrinsic and intrinsic apoptotic pathways, respectively. We investigated whether neuroprotection associated with overexpression of heat-shock protein 70 (Hsp70), a natural cellular antiapoptotic protein, is mediated by caspase-8 and caspase-9 signaling in the neonatal mouse brain after hypoxia/ ischemia (H/I) injury. Methods - Postnatal day 7 transgenic mice overexpressing rat Hsp70 (Hsp70 Tg) and their wild-type (Wt) littermates underwent unilateral common carotid artery ligation followed by 30 minutes of exposure to 8% O-2. The expression of apoptotic proteins was quantified by Western blot analysis, and the specific interaction between Hsp70 and apoptotic protease activating factor 1 (Apaf-1) was determined by coimmunoprecipitation. Results - Hsp70 overexpression reduced cytosolic translocation of cytochrome c without affecting the levels of Apaf-1 and pro - caspase-9 24 hours after H/I. The expression of these apoptotic proteins in the naive neonatal brains was also not affected by Hsp70 overexpression. Reduced caspase-9 cleavage occurred in Hsp70 Tg mice compared with Wt littermates 24 hours after H/I and correlated with increased binding of Hsp70 and Apaf-1. Increased cellular Fas-associated death domain-like interleukin-1 beta-converting enzyme inhibitory protein (FLIP) expression and decreased caspase-8 cleavage were also observed in Hsp70 Tg compared with Wt mice 24 hours after H/I. Conclusions - Our results suggest that the extrinsic and intrinsic apoptotic pathways mediate the neuroprotective effects of Hsp70 overexpression in neonatal H/I, specifically by upregulating FLIP and sequestering Apaf-1, leading to reduced cleavage of caspase-8 and caspase-9. C1 Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. Yamagata Univ, Sch Med, Dept Neurol Surg, Yamagata 99023, Japan. Johns Hopkins Univ, Sch Med, Dept Pediat, Eudowood Neonatal Pulm Div, Baltimore, MD 21205 USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. RP Liu, JL (reprint author), Univ Calif San Francisco, Dept Neurol Surg 112C, 4150 Clement St, San Francisco, CA 94121 USA. EM miro@itsa.ucsf.edu RI Liu, Jialing/A-8627-2012 OI Liu, Jialing/0000-0003-4420-4382 FU NINDS NIH HHS [NS44025, NS35902, NS45059, P50 NS035902, NS33997, R01 NS040469, R01 NS044025, R01 NS40469, R21 NS051576] NR 26 TC 46 Z9 58 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2006 VL 37 IS 2 BP 507 EP 512 DI 10.1161/01.STR.0000199057.00365.20 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 005NJ UT WOS:000234829800077 PM 16397188 ER PT J AU Viswanathan, A Chabriat, H AF Viswanathan, A Chabriat, H TI Cerebral microhemorrhage SO STROKE LA English DT Article DE CADASIL; cerebral hemorrhage; cerebral amyloid angiopathy; stroke ID SPONTANEOUS INTRACEREBRAL HEMORRHAGE; GRADIENT-ECHO MRI; AMYLOID ANGIOPATHY; CAVERNOUS MALFORMATIONS; NATURAL-HISTORY; T2-ASTERISK-WEIGHTED MRI; STROKE RECURRENCE; LOBAR HEMORRHAGE; ISCHEMIC-STROKE; RISK-FACTORS AB Background and Purpose - With the advent of modern MRI imaging techniques, cerebral microhemorrhages have been increasingly recognized on gradient-echo (GE) or T2*-weighted MRI sequences in different populations. However, in clinical practice, their diagnostic value, associated risk, and prognostic significance are often unclear. This review summarizes the pathophysiology, differential diagnosis, epidemiology, and clinical significance of cerebral microhemorrhages. Summary of Review - Focal areas of signal loss on GE MRI imaging pathologically represent focal hemosiderin deposition associated with previous hemorrhagic events. Cerebral microhemorrhages have been noted in healthy elderly, ischemic cerebrovascular disease, intracerebral hemorrhage (ICH), cerebral amyloid angiopathy (CAA), and in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Microhemorrhages have been associated with older age, hypertension, smoking, white matter disease, lacunar infarcts, previous ischemic stroke, or ICH. In CAA, microhemorrhages predict both the risk of recurrent lobar ICH and future clinical decline. In patients with ischemic cerebrovascular disease, microhemorrhage number and location may be associated with executive dysfunction and may predict the occurrence of ICH and lacunar infarction. Conclusions - When cerebral microhemorrhages are diagnosed on MRI, conclusions regarding their significance and associated risks should be made based on the population examined. Further studies to characterize the associated risks of cerebral microhemorrhages in different stroke populations are needed to use this new imaging marker in therapeutic decisions. C1 CHU Lariboisiere, Assistance Publ Hop Paris, Dept Neurol, Paris, France. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Clin Trials Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Chabriat, H (reprint author), Hop Lariboisiere, Serv Neurol, 2 Rue Ambroise Pare, F-75010 Paris, France. EM hugues.chabriat@lrb.ap-hop-paris.fr RI Chabriat, Hugues/G-5699-2010 OI Chabriat, Hugues/0000-0001-8436-6074 NR 59 TC 137 Z9 160 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2006 VL 37 IS 2 BP 550 EP 555 DI 10.1161/01.STR.0000199847.96188.12 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 005NJ UT WOS:000234829800087 PM 16397165 ER PT J AU Kleindorfer, D Lindsell, C White, G Curtis, T Brass, L Koroshetz, W Broderick, JP AF Kleindorfer, D Lindsell, C White, G Curtis, T Brass, L Koroshetz, W Broderick, JP TI National US estimates of rtPA use: ICD-9 codes substantially underestimate SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 16-18, 2006 CL Kissimmee, FL SP Amer Stroke Assoc C1 Univ Cincinnati, Cincinnati, OH USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Yale Univ, New Haven, CT USA. Johnson & Johnson Inc, New Brunswick, NJ 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 0039-2499 J9 STROKE JI Stroke PD FEB PY 2006 VL 37 IS 2 BP 621 EP 622 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 005NJ UT WOS:000234829800104 ER PT J AU Schwamm, LH LaBresh, KA Pan, WQ Frankel, M AF Schwamm, LH LaBresh, KA Pan, WQ Frankel, M CA GWTG Steering Committee Investigat TI Get With The Guidelines-Stroke produces sustainable improvements in hospital-based acute stroke care SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 16-18, 2006 CL Kissimmee, FL SP Amer Stroke Assoc C1 Dule Clin Res Inst, Durham, NC USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. MassPRO, Waltham, MA USA. Emory Univ, Sch Med, Atlanta, GA USA. RI LaBresh, Kenneth/A-6995-2017 OI LaBresh, Kenneth/0000-0001-9040-1956 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 0039-2499 J9 STROKE JI Stroke PD FEB PY 2006 VL 37 IS 2 BP 624 EP 624 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 005NJ UT WOS:000234829800117 ER PT J AU Kim, HH Zhou, ZP Moskowitz, MA Liao, JK AF Kim, HH Zhou, ZP Moskowitz, MA Liao, JK TI Synergistic effects of statins and dipyridamole on stroke protection: Mechanisms beyond lipid lowering and platelet inhibition SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 16-18, 2006 CL Kissimmee, FL SP Amer Stroke Assoc C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Moskowitz, Michael/D-9916-2011 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 0039-2499 J9 STROKE JI Stroke PD FEB PY 2006 VL 37 IS 2 BP 627 EP 627 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 005NJ UT WOS:000234829800130 ER PT J AU Savitz, SI Degterev, A Yuan, JY Moskowitz, M AF Savitz, SI Degterev, A Yuan, JY Moskowitz, M TI Oxygen-glucose deprivation causes necroptosis in neurons and endothelial cells SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 16-18, 2006 CL Kissimmee, FL SP Amer Stroke Assoc C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2006 VL 37 IS 2 BP 629 EP 629 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 005NJ UT WOS:000234829800138 ER PT J AU Tang, XN Xu, LJ Qiao, YL Giffard, R Yenari, MA AF Tang, XN Xu, LJ Qiao, YL Giffard, R Yenari, MA TI Microglia-derived reactive oxygen species potentiate blood-brain barrier disruption after stroke SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 16-18, 2006 CL Kissimmee, FL SP Amer Stroke Assoc C1 UCSF, San Francisco VAMC, San Francisco, CA USA. Stanford Univ, Stanford, CA 94305 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 0039-2499 J9 STROKE JI Stroke PD FEB PY 2006 VL 37 IS 2 BP 630 EP 630 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 005NJ UT WOS:000234829800143 ER PT J AU Abdullah, AR Smith, EE Biddinger, P Kalenderian, D Schwamm, LH AF Abdullah, AR Smith, EE Biddinger, P Kalenderian, D Schwamm, LH TI Hospital notification by EMS in acute stroke is associated with shorter door-to-CT time and increased likelihood of tPA administration SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 16-18, 2006 CL Kissimmee, FL SP Amer Stroke Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Smith, Eric/C-5443-2012 OI Smith, Eric/0000-0003-3956-1668 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 0039-2499 J9 STROKE JI Stroke PD FEB PY 2006 VL 37 IS 2 BP 635 EP 635 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 005NJ UT WOS:000234829800170 ER PT J AU Ay, H Koroshetz, WJ Lopez, CJ Menezes, NM Zhu, MW Benner, T Melinosky, C Arsava, EM Wu, O Sorensen, AG AF Ay, H Koroshetz, WJ Lopez, CJ Menezes, NM Zhu, MW Benner, T Melinosky, C Arsava, EM Wu, O Sorensen, AG TI A spatial component to the risk of infarction in acute ischemic stroke SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 16-18, 2006 CL Kissimmee, FL SP Amer Stroke Assoc C1 Massachusetts Gen Hosp, Stroke Serv, Ctr Biomed Imaging, Boston, MA 02114 USA. Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2006 VL 37 IS 2 BP 637 EP 637 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 005NJ UT WOS:000234829800176 ER PT J AU Reeves, MJ Moomaw, CJ Miller, R Li, GX Broderick, JP Frankel, M Schwamm, L LaBresh, KA AF Reeves, MJ Moomaw, CJ Miller, R Li, GX Broderick, JP Frankel, M Schwamm, L LaBresh, KA CA Paul Coverdell Prototype Registrie TI Hospital characteristics and the quality of acute stroke care: Findings from the Paul Coverdell National Acute Stroke prototype Registry SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 16-18, 2006 CL Kissimmee, FL SP Amer Stroke Assoc C1 Michigan State Univ, E Lansing, MI 48824 USA. Univ Cincinnati, Cincinnati, OH USA. Emory Univ, Atlanta, GA 30322 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. MassPro, Waltham, MA USA. RI LaBresh, Kenneth/A-6995-2017 OI LaBresh, Kenneth/0000-0001-9040-1956 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 0039-2499 J9 STROKE JI Stroke PD FEB PY 2006 VL 37 IS 2 BP 637 EP 637 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 005NJ UT WOS:000234829800179 ER PT J AU Liu, CH Kim, YR Rosen, BR Liu, PK AF Liu, CH Kim, YR Rosen, BR Liu, PK TI Cerebral ischemia-induced gene expression in the brain of live animals can be imaged using MRI SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 16-18, 2006 CL Kissimmee, FL SP Amer Stroke Assoc C1 Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2006 VL 37 IS 2 BP 645 EP 645 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 005NJ UT WOS:000234829800217 ER PT J AU Tang, XN Blankenberg, F Cheng, DY Yenari, MA AF Tang, XN Blankenberg, F Cheng, DY Yenari, MA TI Imaging apoptosis by Tc-99m-labeled annexin V spect after stroke SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 16-18, 2006 CL Kissimmee, FL SP Amer Stroke Assoc C1 UCSF, San Francisco, CA USA. San Francisco VAMC, San Francisco, CA USA. Stanford Univ, Stanford, CA 94305 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 0039-2499 J9 STROKE JI Stroke PD FEB PY 2006 VL 37 IS 2 BP 645 EP 645 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 005NJ UT WOS:000234829800215 ER PT J AU Chu, BC Ferguson, M Underhill, H Takaya, N Small, R Hatsukami, TS Yuan, C AF Chu, BC Ferguson, M Underhill, H Takaya, N Small, R Hatsukami, TS Yuan, C TI Multicontrast weighted, high-resolution MRI characterization of carotid ulceration/rupture and thrombus: An MRI-histology study SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 16-18, 2006 CL Kissimmee, FL SP Amer Stroke Assoc C1 Univ Washington, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2006 VL 37 IS 2 BP 650 EP 650 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 005NJ UT WOS:000234829800237 ER PT J AU Romero, JM Babiarz, LS Forero, NP Gonzalez, RG Lev, MH AF Romero, JM Babiarz, LS Forero, NP Gonzalez, RG Lev, MH TI Vasa vasorum enhancement on CT angiography of the carotid bifurcation predicts symptomatic plaque SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 16-18, 2006 CL Kissimmee, FL SP Amer Stroke Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2006 VL 37 IS 2 BP 650 EP 650 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 005NJ UT WOS:000234829800235 ER PT J AU Lev, MH Garcia, AM Camargo, EC Cunnane, ME Singhal, AB Harris, GJ Borczuk, P Smith, W Gonzalez, RG Furie, KL Koroshetz, WJ AF Lev, MH Garcia, AM Camargo, EC Cunnane, ME Singhal, AB Harris, GJ Borczuk, P Smith, W Gonzalez, RG Furie, KL Koroshetz, WJ TI Location/size-weighted CTA source-image ASPECT score is a stronger predictor of admission clinical status than conventional ASPECTS in acute stroke patients SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 16-18, 2006 CL Kissimmee, FL SP Amer Stroke Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2006 VL 37 IS 2 BP 652 EP 653 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 005NJ UT WOS:000234829800248 ER PT J AU Osmani, B Camargo, EC Garcia, AM Hamedanchi, R Singhal, AB Harris, GJ Smith, W Gonzalez, RG Furie, KL Koroshetz, WJ Lev, MH AF Osmani, B Camargo, EC Garcia, AM Hamedanchi, R Singhal, AB Harris, GJ Smith, W Gonzalez, RG Furie, KL Koroshetz, WJ Lev, MH TI Ischemic lesion volume mismatch between admission noncontrast CT and CTA source images suggests acute (< 6 hours) stroke onset SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 16-18, 2006 CL Kissimmee, FL SP Amer Stroke Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2006 VL 37 IS 2 BP 652 EP 652 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 005NJ UT WOS:000234829800244 ER PT J AU Zhu, MW Hiroki, M Zy, H Menezes, NM Ning, MM Lopez, CJ Sorensen, G AF Zhu, MW Hiroki, M Zy, H Menezes, NM Ning, MM Lopez, CJ Sorensen, G TI The role of CT angiography in evaluation of collateral circulation in acute ischemic stroke SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 16-18, 2006 CL Kissimmee, FL SP Amer Stroke Assoc C1 Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2006 VL 37 IS 2 BP 652 EP 652 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 005NJ UT WOS:000234829800247 ER PT J AU Hamedanchi, R Camargo, EC Gulick, SM Furie, KL Koroshetz, WJ Lev, MH AF Hamedanchi, R Camargo, EC Gulick, SM Furie, KL Koroshetz, WJ Lev, MH TI Improved signal-to-noise ratio in thick versus thin slice CT perfusion maps SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 16-18, 2006 CL Kissimmee, FL SP Amer Stroke Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2006 VL 37 IS 2 BP 653 EP 653 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 005NJ UT WOS:000234829800251 ER PT J AU Sheikh, S Lev, MH Gonzalez, RG Schaefer, P AF Sheikh, S Lev, MH Gonzalez, RG Schaefer, P TI Detection of intracranial thrombus in acute ischemic stroke by CTA and susceptibility changes on gradient echo echo planar perfusion imaging prior to bolus arrival SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 16-18, 2006 CL Kissimmee, FL SP Amer Stroke Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2006 VL 37 IS 2 BP 654 EP 654 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 005NJ UT WOS:000234829800255 ER PT J AU Schwamm, LH LaBresh, KA Pan, WQ Peterson, E Frankel, M AF Schwamm, LH LaBresh, KA Pan, WQ Peterson, E Frankel, M CA GWTG Steering Comm Investigators TI Get with the guidelines stroke improves the rate of "defect-free" acute stroke care SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 16-18, 2006 CL Kissimmee, FL SP Amer Stroke Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. MassPRO, Waltham, MA USA. Duke Clin Res Inst, Durham, NC USA. Emory Univ, Sch Med, Atlanta, GA USA. RI LaBresh, Kenneth/A-6995-2017 OI LaBresh, Kenneth/0000-0001-9040-1956 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 0039-2499 J9 STROKE JI Stroke PD FEB PY 2006 VL 37 IS 2 BP 659 EP 659 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 005NJ UT WOS:000234829800281 ER PT J AU Schwamm, LH Frankel, M Lantz, L Peterson, E LaBresh, K AF Schwamm, LH Frankel, M Lantz, L Peterson, E LaBresh, K CA GWTG Steering Comm Investigators TI Effect of age in acute stroke care for patients hospitalized with ischemic stroke or TIA in get with the guidelines stroke SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 16-18, 2006 CL Kissimmee, FL SP Amer Stroke Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Emory Univ, Sch Med, Atlanta, GA USA. Duke Clin Res Inst, Durham, NC USA. MassPRO, Waltham, MA USA. RI LaBresh, Kenneth/A-6995-2017 OI LaBresh, Kenneth/0000-0001-9040-1956 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 0039-2499 J9 STROKE JI Stroke PD FEB PY 2006 VL 37 IS 2 BP 660 EP 660 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 005NJ UT WOS:000234829800286 ER PT J AU Schwamm, LH Frankel, M Lantz, L Cairns, CB LaBresh, KA AF Schwamm, LH Frankel, M Lantz, L Cairns, CB LaBresh, KA CA GWTG Steering Comm Investigators TI Effect of gender in acute stroke care for patients hospitalized with ischemic stroke or TIA in get with the guidelines stroke SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 16-18, 2006 CL Kissimmee, FL SP Amer Stroke Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Emory Univ, Sch Med, Atlanta, GA USA. Duke Clin Res Inst, Durham, NC USA. MassPRO, Waltham, MA USA. RI LaBresh, Kenneth/A-6995-2017 OI LaBresh, Kenneth/0000-0001-9040-1956 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 0039-2499 J9 STROKE JI Stroke PD FEB PY 2006 VL 37 IS 2 BP 661 EP 662 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 005NJ UT WOS:000234829800292 ER PT J AU Schwamm, LH LaBresh, KA Chen, A Frankel, M AF Schwamm, LH LaBresh, KA Chen, A Frankel, M CA GWTG Steering Comm Investigators TI Get with the guidelines stroke improves hospital-based acute stroke care and secondary prevention SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 16-18, 2006 CL Kissimmee, FL SP Amer Stroke Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. MassPRO, Waltham, MA USA. Duke Clin Res Inst, Durham, NC USA. Emory Univ, Sch Med, Atlanta, GA USA. RI LaBresh, Kenneth/A-6995-2017 OI LaBresh, Kenneth/0000-0001-9040-1956 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 0039-2499 J9 STROKE JI Stroke PD FEB PY 2006 VL 37 IS 2 BP 664 EP 664 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 005NJ UT WOS:000234829800306 ER PT J AU Levine, JM Finkelstein, D Gurol, ME Chanderraj, R Snider, R Smith, EE Greenberg, SM Rosand, J AF Levine, JM Finkelstein, D Gurol, ME Chanderraj, R Snider, R Smith, EE Greenberg, SM Rosand, J TI Is early edema related to severity of coagulopathy after warfarin-related intracerebral hemorrhage? SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 16-18, 2006 CL Kissimmee, FL SP Amer Stroke Assoc C1 Hosp Univ Penn, Philadelphia, PA 19104 USA. Univ Massachusetts, Med Ctr, Worcester, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Smith, Eric/C-5443-2012 OI Smith, Eric/0000-0003-3956-1668 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 0039-2499 J9 STROKE JI Stroke PD FEB PY 2006 VL 37 IS 2 BP 676 EP 676 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 005NJ UT WOS:000234829800366 ER PT J AU Atochin, DN Wang, A Critchlow, JD Dantas, APV Looft-Wilson, R Murata, T Salomone, S Moskowitz, MA Michel, T Sessa, WC Huang, PL AF Atochin, DN Wang, A Critchlow, JD Dantas, APV Looft-Wilson, R Murata, T Salomone, S Moskowitz, MA Michel, T Sessa, WC Huang, PL TI Phosphorylation of eNOS at serine 1179 modulates vascular reactivity and cerebral ischemia-reperfusion injury in transgenic mice SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 16-18, 2006 CL Kissimmee, FL SP Amer Stroke Assoc C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. Georgetown Univ, Washington, DC USA. Ctr Study Sex Differences Hlth, Washington, DC USA. Coll William & Mary, Williamsburg, VA USA. Yale Univ, Sch Med, Boyer Ctr Mol Med, New Haven, CT USA. Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Charlestown, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. RI Moskowitz, Michael/D-9916-2011; Dantas, Ana Paula/I-4100-2015; Atochin, Dmitriy/Q-3150-2016 OI Dantas, Ana Paula/0000-0001-8514-4094; NR 0 TC 0 Z9 0 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2006 VL 37 IS 2 BP 678 EP 678 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 005NJ UT WOS:000234829800373 ER PT J AU Liu, YT D'Arceuil, H He, J Duggan, M Menezes, N Gonzalez, G Pryor, J de Crespigny, A AF Liu, YT D'Arceuil, H He, J Duggan, M Menezes, N Gonzalez, G Pryor, J de Crespigny, A TI Abnormal spontaneous vasomotor MRI signals in an acute stroke model SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 16-18, 2006 CL Kissimmee, FL SP Amer Stroke Assoc C1 Massachusetts Gen Hosp, Charlestown, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2006 VL 37 IS 2 BP 678 EP 678 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 005NJ UT WOS:000234829800375 ER PT J AU Kim, YR Tejima, E Lo, EH Atochin, D Huang, P Bogdanov, A Rosen, BR AF Kim, YR Tejima, E Lo, EH Atochin, D Huang, P Bogdanov, A Rosen, BR TI Vascular water permeability increases during the hyperacute phase of permanent stroke models: In vivo MRI study SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 16-18, 2006 CL Kissimmee, FL SP Amer Stroke Assoc C1 MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA USA. Massachusetts Gen Hosp, Neuroprotect Res Lab, Charlestown, MA USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. Univ Massachusetts, Sch Med, Worcester, MA USA. RI Atochin, Dmitriy/Q-3150-2016 NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2006 VL 37 IS 2 BP 681 EP 681 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 005NJ UT WOS:000234829800389 ER PT J AU Tsuji, K Tejima, E Lee, SR Guo, SZ Zhao, BQ Zhang, CG Lo, EH Wang, XY AF Tsuji, K Tejima, E Lee, SR Guo, SZ Zhao, BQ Zhang, CG Lo, EH Wang, XY TI Neuroglobin protects against hypoxia/ischemia-induced neuron death by improving mitochondria function and reducing oxidative stress SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 16-18, 2006 CL Kissimmee, FL SP Amer Stroke Assoc C1 Massachusetts Gen Hosp, Charlestown, MA USA. Cheju Natl Univ, Cheju, South Korea. Beijing Inst Radiat Med, Beijing, Peoples R China. NR 0 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2006 VL 37 IS 2 BP 682 EP 682 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 005NJ UT WOS:000234829800396 ER PT J AU Danielyan, K Ganguly, K Atochin, D Fisher, D Zaytsev, S Cines, D Muzykantov, V AF Danielyan, K Ganguly, K Atochin, D Fisher, D Zaytsev, S Cines, D Muzykantov, V TI Prophylactic fibrinolysis of cerebral thrombi by erythrocyte-bound tissue type plasminogen activator protects against ischemic stroke SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 16-18, 2006 CL Kissimmee, FL SP Amer Stroke Assoc C1 Univ Penn, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Charlestown, MA USA. RI Atochin, Dmitriy/Q-3150-2016 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 0039-2499 J9 STROKE JI Stroke PD FEB PY 2006 VL 37 IS 2 BP 683 EP 683 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 005NJ UT WOS:000234829800400 ER PT J AU Gao, BB Clermont, A Rook, S Fonda, SJ Avery, RL Arrigg, PG Bursell, SE Aiello, LP Feener, EP AF Gao, BB Clermont, A Rook, S Fonda, SJ Avery, RL Arrigg, PG Bursell, SE Aiello, LP Feener, EP TI Extracellular carbonic anhydrase I induces retinal and cerebral edema SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 16-18, 2006 CL Kissimmee, FL SP Amer Stroke Assoc C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Santa Barbara Cottage Hosp Eye Ctr, Santa Barbara, 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 0039-2499 J9 STROKE JI Stroke PD FEB PY 2006 VL 37 IS 2 BP 686 EP 686 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 005NJ UT WOS:000234829800413 ER PT J AU Babiarz, LS Brobeck, B Dault, N Gonzalez, RG Schaefer, PW Romero, JM Lev, MH AF Babiarz, LS Brobeck, B Dault, N Gonzalez, RG Schaefer, PW Romero, JM Lev, MH TI Added benefit of enhanced versus unenhanced MR angiography in determining greater than 70% internal carotid artery stenosis? Not! SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 16-18, 2006 CL Kissimmee, FL SP Amer Stroke Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2006 VL 37 IS 2 BP 698 EP 699 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 005NJ UT WOS:000234829800478 ER PT J AU Babiarz, LS Romero, JM Forero, NP Murphy, EK Shaefer, PW Lev, MH AF Babiarz, LS Romero, JM Forero, NP Murphy, EK Shaefer, PW Lev, MH TI Low CT density of carotid bifurcation atheroma correlates with symptomatic plaque in patients with high-grade stenosis SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 16-18, 2006 CL Kissimmee, FL SP Amer Stroke Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2006 VL 37 IS 2 BP 700 EP 700 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 005NJ UT WOS:000234829800486 ER PT J AU Ay, H Koroshetz, WJ Vangel, MG Arsava, EM Zhu, MW Sorensen, AG AF Ay, H Koroshetz, WJ Vangel, MG Arsava, EM Zhu, MW Sorensen, AG TI Variability in the "time is brain" concept SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 16-18, 2006 CL Kissimmee, FL SP Amer Stroke Assoc C1 Massachusetts Gen Hosp, Ctr Biomed Imaging, Stroke Serv, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2006 VL 37 IS 2 BP 702 EP 702 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 005NJ UT WOS:000234829800496 ER PT J AU Wu, ON Roccatagliata, L Zhu, MW Lopez, CJ Schaefer, PW Melinosky, C Buonanno, FS Lo, EH Koroshetz, WJ Sorensen, AG Singhal, AB AF Wu, ON Roccatagliata, L Zhu, MW Lopez, CJ Schaefer, PW Melinosky, C Buonanno, FS Lo, EH Koroshetz, WJ Sorensen, AG Singhal, AB TI Evaluating effects of normobaric oxygen therapy in acute stroke patients using MRI-based multiparametric algorithms SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 16-18, 2006 CL Kissimmee, FL SP Amer Stroke Assoc C1 Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neuroprotect Res Lab, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2006 VL 37 IS 2 BP 704 EP 704 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 005NJ UT WOS:000234829800505 ER PT J AU Schwamm, LH Smith, EE Abdullah, AR Palmeri, G Prvu, J Goyette, L McElligott, C Dreyer, P AF Schwamm, LH Smith, EE Abdullah, AR Palmeri, G Prvu, J Goyette, L McElligott, C Dreyer, P CA Primary Stroke Service Advisory Co TI Hospital characteristics associated with successful state-based licensure for acute stroke services: The Massachusetts experience SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 16-18, 2006 CL Kissimmee, FL SP Amer Stroke Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Dept Publ Hlth, Boston, MA USA. RI Smith, Eric/C-5443-2012 OI Smith, Eric/0000-0003-3956-1668 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 0039-2499 J9 STROKE JI Stroke PD FEB PY 2006 VL 37 IS 2 BP 719 EP 719 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 005NJ UT WOS:000234829800580 ER PT J AU Hiroki, M Singhal, AB Benner, T Ay, H Zhu, MW Wisco, J Pratt, JS Sorensen, GA AF Hiroki, M Singhal, AB Benner, T Ay, H Zhu, MW Wisco, J Pratt, JS Sorensen, GA TI Severe linear hyperintensity objects in the cerebral white matter reflect the cause of hypertensive intracerebral hemorrhage SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 16-18, 2006 CL Kissimmee, FL SP Amer Stroke Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2006 VL 37 IS 2 BP 723 EP 723 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 005NJ UT WOS:000234829800603 ER PT J AU Smith, EE Chen, YW Gurol, ME Viswanathan, A Rakich, SM Groover, TR Rosand, J Greenberg, SM AF Smith, EE Chen, YW Gurol, ME Viswanathan, A Rakich, SM Groover, TR Rosand, J Greenberg, SM TI Progression of white matter lesions and hemorrhages in cerebral amyloid angiopathy SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 16-18, 2006 CL Kissimmee, FL SP Amer Stroke Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Li Shin Hosp, Ping Chen City, Taiwan. Natl Taiwan Univ Hosp, Ping Chen City, Taiwan. Univ Iowa, Iowa City, IA USA. RI Smith, Eric/C-5443-2012 OI Smith, Eric/0000-0003-3956-1668 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 0039-2499 J9 STROKE JI Stroke PD FEB PY 2006 VL 37 IS 2 BP 723 EP 723 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 005NJ UT WOS:000234829800600 ER PT J AU Ay, H Ay, I Arsava, EM Prunier, F Buonanno, FS Sorensen, AG Koroshetz, WJ AF Ay, H Ay, I Arsava, EM Prunier, F Buonanno, FS Sorensen, AG Koroshetz, WJ TI Plasma glycogen phosphorylase-BB levels following cerebral ischemia SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 16-18, 2006 CL Kissimmee, FL SP Amer Stroke Assoc C1 Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Stroke Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiovasc Res Lab, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2006 VL 37 IS 2 BP 728 EP 728 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 005NJ UT WOS:000234829800629 ER PT J AU Zhao, BQ Wang, S Kim, HY Wang, XY Lo, EH AF Zhao, BQ Wang, S Kim, HY Wang, XY Lo, EH TI Role of matrix metalloproteinases in stroke remodeling SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 16-18, 2006 CL Kissimmee, FL SP Amer Stroke Assoc C1 Massachusetts Gen Hosp, Neuroprotect Res Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 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 0039-2499 J9 STROKE JI Stroke PD FEB PY 2006 VL 37 IS 2 BP 730 EP 730 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 005NJ UT WOS:000234829800640 ER PT J AU Khan, M Elango, C Singh, AK Johnson, RH Singh, I AF Khan, M Elango, C Singh, AK Johnson, RH Singh, I TI Ceramide participates in the penumbral damage in a rat model of experimental stroke by a mechanism involving c-Jun N-Terminal kinase and reactive oxygen species SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 16-18, 2006 CL Kissimmee, FL SP Amer Stroke Assoc C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC 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 0039-2499 J9 STROKE JI Stroke PD FEB PY 2006 VL 37 IS 2 BP 731 EP 731 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 005NJ UT WOS:000234829800645 ER PT J AU Kelly, PJ Morrow, JD Koroshetz, WJ Terry, E Lederer, M Barron, M Furie, KL AF Kelly, PJ Morrow, JD Koroshetz, WJ Terry, E Lederer, M Barron, M Furie, KL TI Early elevation in plasma F2-isoprostanes provides evidence of oxidative stress in human acute ischemic stroke SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 16-18, 2006 CL Kissimmee, FL SP Amer Stroke Assoc C1 Mater Univ Hosp, Dublin, Ireland. Vanderbilt Univ, Nashville, TN USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2006 VL 37 IS 2 BP 733 EP 733 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 005NJ UT WOS:000234829800652 ER PT J AU Earnshaw, SR Joshi, AV Wilson, MR Rosand, J AF Earnshaw, SR Joshi, AV Wilson, MR Rosand, J TI Cost-effectiveness of recombinant activated factor VII in the treatment of intracerebral hemorrhage SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 16-18, 2006 CL Kissimmee, FL SP Amer Stroke Assoc C1 RTI Hlth Solut, Res Triangle Pk, NC USA. Novo Nordisk Inc, Princeton, NJ USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2006 VL 37 IS 2 BP 742 EP 742 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 005NJ UT WOS:000234829800700 ER PT J AU Nezami, AG Poy, F Eck, MJ AF Nezami, AG Poy, F Eck, MJ TI Structure of the autoinhibitory switch in formin mDia1 SO STRUCTURE LA English DT Article ID ACTIN CYTOSKELETON; HOMOLOGY-2 DOMAIN; PROTEIN; ACTIVATION; NUCLEATION; PROFILIN; GTPASE; YEAST; PAK1; CRYSTALLOGRAPHY AB Diaphanous-related formins (DRFs) regulate the nucleation and polymerization of unbranched actin filaments. The activity of DRFs is inhibited by an intramolecular interaction between their N-terminal regulatory region and a conserved C-terminal segment termed the Diaphanous autoinhibitory domain (DAD). Binding of GTP bound Rho to the mDia1 N terminus releases this autoinhibitory restraint. Here, we describe the crystal structure of the DAD segment of mDial in complex with the relevant N-terminal fragment, termed the DID domain. The structure reveals that the DAD segment forms an amphipathic helix that binds a conserved, concave surface on the DID domain. Comparison with the structure of the mDial N terminus bound to RhoC suggests that release of the autoinhibitory DAD interaction is accomplished largely by Rho-induced restructuring of the adjacent GTPase binding subdomain (GBD), but also by electrostatic repulsion and a small, direct steric occlusion of the DAD binding cleft by Rho itself. C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Eck, MJ (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, 44 Binney St, Boston, MA 02115 USA. EM eck@red.dfci.harvard.edu FU NIGMS NIH HHS [GM 075698, GM071834] NR 34 TC 62 Z9 65 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0969-2126 J9 STRUCTURE JI Structure PD FEB PY 2006 VL 14 IS 2 BP 257 EP 263 DI 10.1016/j.str.2005.12.003 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 013TF UT WOS:000235431700013 PM 16472745 ER PT J AU Mulley, AG AF Mulley, AG TI Developing skills for evidence-based surgery: Ensuring that patients make informed decisions SO SURGICAL CLINICS OF NORTH AMERICA LA English DT Article ID BENIGN PROSTATIC HYPERPLASIA; BREAST-CANCER; PROGRAM; QUALITY; TRIAL; MASTECTOMY; LUMPECTOMY; SYMPTOMS; RISKS; LIFE AB Ensuring that the surgical decisions made by and with patients are fully informed is a challenge. Doctors and patients must work together, and to be successful they need support in the form of knowledge management and decision aids. This article emphasizes the importance of eliciting and honoring patients' personal valuations of alternative future health states, their attitudes to the specific risks and risk differences that are central to surgical decisions, and their attitudes to time trade-offs. The skills and habits necessary to accomplish this critical objective begin with nothing less than a genuine concern for patients and an ability to relate to the unique meaning that the present illness and its treatment have in their lives. C1 Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Mulley, AG (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50 Staniford St,Suite 900, Boston, MA 02114 USA. EM amulley@partners.org NR 32 TC 7 Z9 7 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0039-6109 J9 SURG CLIN N AM JI Surg. Clin.-North Am. PD FEB PY 2006 VL 86 IS 1 BP 181 EP + DI 10.1016/j.suc.2005.11.001 PG 13 WC Surgery SC Surgery GA 014ZR UT WOS:000235522200014 PM 16442428 ER PT J AU Rattner, D AF Rattner, D TI Introduction to NOTES White Paper SO SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES LA English DT Editorial Material C1 Massachusetts Gen Hosp, Div Gen Surg, Boston, MA 02114 USA. RP Rattner, D (reprint author), Massachusetts Gen Hosp, Div Gen Surg, 55 Fruit St Wang 337, Boston, MA 02114 USA. NR 0 TC 26 Z9 28 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0930-2794 J9 SURG ENDOSC JI Surg. Endosc. PD FEB PY 2006 VL 20 IS 2 BP 185 EP 185 DI 10.1007/sOO464-005-3007-z PG 1 WC Surgery SC Surgery GA 008RZ UT WOS:000235059700001 PM 16402289 ER PT J AU Rattner, D Kalloo, A AF Rattner, D Kalloo, A CA SAGES ASGE Working Grp TI ASGE/SAGES working group on natural orifice translumenal endoscopic surgery - October 2005 SO SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES LA English DT Article C1 Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mayo Clin, Rochester, MN 55905 USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. Case Western Reserve Univ, Sch Med, Cleveland, OH 44106 USA. Vanderbilt Univ, Med Ctr, Nashville, TN 37240 USA. Dartmouth Hitchcock Med Ctr, Hanover, NH 03756 USA. Northwestern Univ, Sch Med, Evanston, IL 60208 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Kalloo, A (reprint author), Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. NR 9 TC 495 Z9 533 U1 1 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0930-2794 J9 SURG ENDOSC JI Surg. Endosc. PD FEB PY 2006 VL 20 IS 2 BP 329 EP 333 DI 10.1007/s00464-005-3006-0 PG 5 WC Surgery SC Surgery GA 008RZ UT WOS:000235059700030 PM 16402290 ER PT J AU Gelfenbeyn, M Goodkin, R Kliot, M AF Gelfenbeyn, M Goodkin, R Kliot, M TI Sterile recurrent spinal epidural abscess in a patient with Crohn's disease: a case report SO SURGICAL NEUROLOGY LA English DT Article DE spinal epidural abscess; Crohn's disease; case report ID EXTRADURAL ABSCESS; BACTERIAL-MENINGITIS; MANAGEMENT; DIAGNOSIS; COMPLICATION; DRAINAGE AB Background: The frequency of SEA is increasing. There are several well-established predisposing factors. Case Description: Our case presents certain unusual features that include an association with CD, persistent sterile cultures, and multiple recurrences of lesions at adjacent levels. Conclusions: A review of the literature showed only 13 case reports of SEA in patients with CD with an additional patient mentioned in one series. Recurrence of SEA at the same location was reported only twice. The diagnostic workup and treatment modalities pertinent to this case are discussed. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Washington, Dept Neurol Surg, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. RP Gelfenbeyn, M (reprint author), Univ Washington, Dept Neurol Surg, Seattle, WA 98195 USA. NR 39 TC 8 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 0090-3019 J9 SURG NEUROL JI Surg. Neurol. PD FEB PY 2006 VL 65 IS 2 BP 178 EP 184 DI 10.1016/j.surneu.2005.05.028 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 012ZQ UT WOS:000235379800015 PM 16427419 ER PT J AU Moran-Gates, T Gan, L Park, YS Zhang, KH Baldessarini, RJ Tarazi, FI AF Moran-Gates, T Gan, L Park, YS Zhang, KH Baldessarini, RJ Tarazi, FI TI Repeated antipsychotic drug exposure in developing rats: Dopamine receptor effects SO SYNAPSE LA English DT Article DE caudate-putamen; childhood-onset schizophrenia; clozapine; fluphenazine; olanzapine; prefrontal cortex ID CHILDHOOD-ONSET SCHIZOPHRENIA; ATYPICAL ANTIPSYCHOTICS; PSYCHOTIC DISORDERS; ADOLESCENTS; CHILDREN; BRAIN; EXPRESSION; D-3; OLANZAPINE; AGENTS AB Antipsychotic drugs are often prescribed to juvenile psychiatric patients, though their cerebral effects during development are incompletely described. Accordingly, we studied the effects of repeated treatment with dissimilar antipsychotic drugs on dopamine (DA) receptors in juvenile vs. adult rats. Tissue levels of DA receptor types (D-1, D-2, D-3, and D-4) in forebrain regions of juvenile rats were quantified after 3 weeks of daily treatment with representative first- (fluphenazine) and second-generation (clozapine and olanzapine) antipsychotics, and compared with similarly treated adult rats examined in previous studies. Fluphenazine, clozapine, and olanzapine all decreased D-1 receptors in dorsolateral frontal and medial prefrontal cortex (MPC) of juvenile, but not adult rats. Conversely, all three test agents increased D-2 labeling in MPC of adult, but not young animals. Fluphenazine and olanzapine, but not clozapine, also increased D-2 receptor levels in hippocampus, and D-4 levels in nucleus accumbens (NAc) and caudate-putamen (CPu) in both juvenile and adult brain. D-3 receptors were not altered by any treatment in any brain region at either age. Only some DA receptor adaptations to antipsychotic treatment are shared by developing and mature animals. Developmental differences in DA receptor responses may account for differences in clinical effects of antipsychotic drugs between young and adult psychiatric patients. C1 Harvard Univ, Sch Med, McLean Hosp, Lab Psychiat Neurosci, Belmont, MA 02478 USA. Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, Belmont, MA USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA USA. Inje Univ, Sch Biotechnol & Biomed Sci, Kimhae 621749, South Korea. RP Tarazi, FI (reprint author), Harvard Univ, Sch Med, McLean Hosp, Lab Psychiat Neurosci, 115 Mill St, Belmont, MA 02478 USA. EM ftarazi@hms.harvard.edu RI Park, Young Shik/E-7317-2017 OI Park, Young Shik/0000-0002-8808-4530 FU NICHD NIH HHS [HD-043649]; NIMH NIH HHS [MH-068359, MH-068507] NR 56 TC 29 Z9 29 U1 2 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD FEB PY 2006 VL 59 IS 2 BP 92 EP 100 DI 10.1002/syn.20220 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 000ON UT WOS:000234471800004 PM 16270300 ER PT J AU Tetzlaff, MT Teh, BS Timme, TL Fujita, T Satoh, T Tabata, KI Mai, WY Vlachaki, MT Amato, RJ Kadmon, D Miles, BJ Ayala, G Wheeler, TM Aguilar-Cordova, E Thompson, TC Butler, EB AF Tetzlaff, MT Teh, BS Timme, TL Fujita, T Satoh, T Tabata, KI Mai, WY Vlachaki, MT Amato, RJ Kadmon, D Miles, BJ Ayala, G Wheeler, TM Aguilar-Cordova, E Thompson, TC Butler, EB TI Expanding the therapeutic index of radiation therapy by combining in situ gene therapy in the treatment of prostate cancer SO TECHNOLOGY IN CANCER RESEARCH & TREATMENT LA English DT Article DE radiation therapy; gene therapy; prostate cancer; therapeutic index ID THYMIDINE KINASE GENE; DOUBLE-SUICIDE GENE; INTENSITY-MODULATED RADIOTHERAPY; TK PLUS GCV; TRANSGENE EXPRESSION SENSITIZES; UNFAVORABLE-PROGNOSIS CARCINOMA; ORTHOTOPIC MOUSE MODEL; TUMOR-SUPPRESSOR GENE; PHASE-III TRIAL; REPLICATION-COMPETENT AB The advances in radiotherapy (3D-CRT, IMRT) have enabled high doses of radiation to be delivered with the least possible associated toxicity. However, the persistence of cancer (local recurrence after radiotherapy) despite these increased doses as well as distant failure suggesting the existence of micro-metastases, especially in the case of higher risk disease, have underscored the need for continued improvement in treatment strategies to manage local and micro-metastatic disease as definitively as possible. This has prompted the idea that an increase in the therapeutic index of radiotherapy might be achieved by combining it with in situ gene therapy. The goal of these combinatorial therapies is to maximize the selective pressure against cancer cell growth while minimizing treatment-associated toxicity. Major efforts utilizing different gene therapy strategies have been employed in conjunction with radiotherapy. We reviewed our and other published clinical trials utilizing this combined radio-genetherapy approach including their associated pre-clinical in vitro and in vivo models. The use of in situ gene therapy as an adjuvant to radiation therapy dramatically reduced cell viability in vitro and tumor growth in vivo. No significant worsening of the toxicities normally observed in single-modality approaches were identified in Phase I/II clinical studies. Enhancement of both local and systemic T-cell activation was noted with this combined approach suggesting anti-tumor immunity. Early clinical outcome including biochemical and biopsy data was very promising. These results demonstrate the increased therapeutic efficacy achieved by combining in situ gene therapy with radiotherapy in the management of local prostate cancer. The combined approach maximizes tumor control, both local-regional and systemic through radio-genetherapy induced cytotoxicity and anti-tumor immunity. C1 Baylor Coll Med, Dept Radiol, Sect Radiat Oncol, Houston, TX 77030 USA. Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA. Michael E DeBakey Dept Vet Affairs Med Ctr, Houston, TX 77030 USA. Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. Methodist Hosp, Dept Radiat Oncol, Houston, TX 77030 USA. Methodist Hosp, GU Oncol Program, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. RP Teh, BS (reprint author), Baylor Coll Med, Dept Radiol, Sect Radiat Oncol, Houston, TX 77030 USA. EM bteh@bcm.tmc.edu FU PHS HHS [P50-58204] NR 95 TC 5 Z9 7 U1 1 U2 1 PU ADENINE PRESS PI SCHENECTADY PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA SN 1533-0346 J9 TECHNOL CANCER RES T JI Technol. Cancer Res. Treat. PD FEB PY 2006 VL 5 IS 1 BP 23 EP 36 PG 14 WC Oncology SC Oncology GA 013MN UT WOS:000235413500004 PM 16417399 ER PT J AU Mann, K Hiemke, C Schmidt, LG Bates, DW AF Mann, K Hiemke, C Schmidt, LG Bates, DW TI Appropriateness of therapeutic drug monitoring for antidepressants in routine psychiatric inpatient care SO THERAPEUTIC DRUG MONITORING LA English DT Article DE therapeutic drug monitoring; antidepressants; quality of care; improvement strategies ID COMPUTER-BASED INTERVENTION; COST-EFFECTIVENESS; CLINICAL-PRACTICE; STRATEGIES; REDUNDANT; PATIENT; TESTS AB Although there is sufficient evidence of the benefits of therapeutic drug monitoring (TDM) for optimizing antidepressant therapy, its current use in routine care is far from optimal. As a prerequisite for developing improvement strategies, the appropriateness of TDM use was investigated in a psychiatric hospital in which TDM4 is applied routinely to a large extent. A retrospective analysis of all patients admitted in 2003 with a Unipolar depressive disorder was performed. Based on detailed chart review, for all TDM tests, the time of blood sample taking in relation to the medication process and the consequences of the TDM results for clinical decision making were analyzed. Altogether, 748 plasma levels were measured for antidepressants. The evaluation identified considerable inappropriate use of TDM. After a preceding change of dose, only the minority of TDM tests was performed within an optimum time interval. Overall, 30% of blood samples were taken too early, before steady state had been reached. The high number of repeat tests without preceding change of drug dose points to potentially redundant use. There also was evidence of underuse of TDM, as in many cases additional plasma level determinations might have been useful to speed up optimal dosing. Frequent discrepancies were found between the laboratory's recommendations and actual clinical decision making. Suggested dose changes were followed in only 30%. The findings clearly indicate the need for measures to improve the implementation of TDM in routine care. Based on the identified pattern of current TDM utilization and experiences from other fields of medicine, a combination of strateaies, including both educational and electronic interventions, may have the greatest potential for improvement. C1 Univ Mainz, Dept Psychiat, D-55101 Mainz, Germany. Brigham & Womens Hosp, Div Gen Med & Primary Care, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. RP Mann, K (reprint author), Univ Mainz, Dept Psychiat, Untere Zahlbacher Str 8, D-55101 Mainz, Germany. EM mann@psychiatrie.klinik.uni-mainz.de NR 28 TC 30 Z9 32 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0163-4356 J9 THER DRUG MONIT JI Ther. Drug Monit. PD FEB PY 2006 VL 28 IS 1 BP 83 EP 88 DI 10.1097/01.ftd.0000189897.16307.65 PG 6 WC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology SC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology GA 009RG UT WOS:000235129400018 PM 16418699 ER PT J AU Xu, JM Hershman, JM AF Xu, JM Hershman, JM TI Histone deacetylase inhibitor depsipeptide represses nicotinamide N-methyltransferase and hepatocyte nuclear factor-1 beta gene expression in human papillary thyroid cancer cells SO THYROID LA English DT Article ID PARKINSONS-DISEASE; GROWTH-INHIBITION; CARCINOMA CELLS; TRANSCRIPTION; FK228; IDENTIFICATION; ACTIVATION; MARKER; P53; HOMEOPROTEIN AB Nicotinamide N-methyltransferase (NNMT) catalyzes N-methylation of nicotinamide and other structural analogues. NNMT gene expression is enhanced in many papillary thyroid cancer cells and activated by hepatocyte nuclear factor (HNF)-1 beta. In this work, we studied the effects of depsipeptide, a histone deacetylase inhibitor, on NNMT gene expression in BHP 18-21 papillary thyroid cancer cells. Depsipeptide reduced NNMT mRNA level in a dose-dependent and time-dependent manner as determined by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR). In contrast, expression of the sodium iodide symporter (NIS), a gene with differentiated function, was enhanced in the treated cells. NNMT protein level determined by Western blot analysis and NNMT catalytic activity was also reduced significantly in the depsipeptide-treated cells. To study the mechanism of NNMT gene repression by depsipeptide, effects of depsipeptide on NNMT promoter activity were determined by luciferase reporter gene assay. NNMT promoter activity was significantly reduced in the HNF-1 beta-positive BHP 18-21 cells but not in the HNF-1 beta-negative BHP 14-9 papillary cancer cells. A mutant reporter construct with mutations in a HNF-1 site in the NNMT basal promoter region did not respond to depsipeptide in both HNF-1 beta-positive and -negative cells. Depsipeptide reduced steady-state HNF-1 beta mRNA level, depleted nuclear HNF-1,6 protein levels, and abolished activity of DNA binding to the HNF-1 site in the NNMT promoter region. Protein synthesis inhibitor cycloheximide and proteasome inhibitor MG-132 enhanced HNF-1 beta stability in the depsipeptide-treated cells. In summary, depsipeptide represses NNMT and HNF-1 beta gene expression in some papillary thyroid cancer cells. The repression of NNMT by depsipeptide is at the transcription level through downregulation of transcription activator HNF-1 beta. C1 Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Endocrinol & Diabet Div, Los Angeles, CA USA. RP Hershman, JM (reprint author), VA Greater Los Angeles Healthcare Syst, Endocrinol Div 111D, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jhershman@ucla.edu NR 49 TC 9 Z9 9 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 J9 THYROID JI Thyroid PD FEB PY 2006 VL 16 IS 2 BP 151 EP 160 DI 10.1089/thy.2006.16.151 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 025HM UT WOS:000236256100005 PM 16676400 ER PT J AU Sabolic, I Herak-Kramberger, CM Antolovic, R Breton, S Brown, D AF Sabolic, I Herak-Kramberger, CM Antolovic, R Breton, S Brown, D TI Loss of basolateral invaginations, in proximal tubules of cadmium-intoxicated rats is independent of microtubules and clathrin SO TOXICOLOGY LA English DT Article DE cell membrane; cytoskeleton; heavy metal nephrotoxicity; kidney; Na/K-ATPase ID BORDER MEMBRANE-VESICLES; CORTICAL BRUSH-BORDER; AMINO-ACID-TRANSPORT; TREATED RATS; IN-VITRO; LIPID-PEROXIDATION; OXIDATIVE STRESS; RENAL TOXICITY; NA+/K+-ATPASE; KIDNEY CORTEX AB Experimental cadmium (Cd) nephrotoxicity after treating rats with CdCl2 (2 mg Cd/kg b.m./day) for 2 weeks (subchronic nephrotoxicity) or with Cd-metallothionein (CdMT, a single dose of 0.4 mg Cd/kg b.m.) for it few hours (acute nephrotoxicity) is characterized by significant damage to cortical proximal tubules (PT) that results in reabsorptive and secretory defects. Most of the damage, studied so far, has been reported at the PT cell apical domain. This includes the loss of apical transporters and brush-border microvilli, and is considered to be the main cause of the kidney malfunction seen in this condition. However, in some studies the loss of basolaterall (BL) invaginations and the activity of Na/K-ATPase in PT cells was also observed, but this "basolateral" aspect of intracellular Cd toxicity has been poorly investigated. In this report we induced subchronic and acute Cd nephrotoxicity in rats, and we studied the expression and intracellular distribution of microtubules and clathtin, and the abundance of Na/K-ATPase associated with BL invaginations in renal cortical tubules. Methods used were immunofluorescence microscopy, transmission and immunogold microscopy and immunoblotting Of tissue homogenates and isolated total cell membranes. In both experimental models, in the cortical FIT we demonstrated: (a) significantly damaged morphology of the cells, (b) fragmentation and depolymerization of microtubules, (c) loss of clathrin in the subapical domain and its relocation into vesicles scattered throughout the cytoplasm and (d) loss of BL invaginations and the associated Na/K-ATPase immunostaining. A similar loss of microtubules and redistribution of clathrin in the cortical PT was observed in rats treated with microtubule depolymerizing agent colchicine, but without any detectable loss of BL invaginations. We conclude that the loss of BL invaginations and the associated Na/K-ATPase in the cortical PT of Cd-intoxicated rats may contribute to the loss of PT function that characterizes Cd nephrotoxicity. This loss is accompanied by, but it is not dependent on perturbation Of microtubule organization and loss of membrane-associated clathrin. (C) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Inst Med Res & Occupat Hlth, Unit Mol Toxicol, HR-10001 Zagreb, Croatia. Pliva Res Inst Ltd, Zagreb 10000, Croatia. Massachusetts Gen Hosp, Renal Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Program Membrane Biol, Charlestown, MA 02129 USA. RP Sabolic, I (reprint author), Inst Med Res & Occupat Hlth, Unit Mol Toxicol, Ksaverska Cesta 2,POB 291, HR-10001 Zagreb, Croatia. EM sabolic@imi.hr NR 49 TC 18 Z9 19 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD FEB 1 PY 2006 VL 218 IS 2-3 BP 149 EP 163 DI 10.1016/j.tox.2005.10.009 PG 15 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 005SR UT WOS:000234844600007 PM 16288946 ER PT J AU Nadler, RB Collins, MM Propert, KJ Mikolajczyk, SD Knauss, JS Landis, JR Fowler, JE Schaeffer, AJ Alexander, RB AF Nadler, RB Collins, MM Propert, KJ Mikolajczyk, SD Knauss, JS Landis, JR Fowler, JE Schaeffer, AJ Alexander, RB CA Chronic Prostatis Collaborative TI Prostate-specific antigen test in diagnostic evaluation of chronic prostatitis/chronic pelvic pain syndrome SO UROLOGY LA English DT Article ID INSTITUTES-OF-HEALTH; CATEGORY-IV PROSTATITIS; SERUM; MEN; CANCER; INFLAMMATION; PERCENTAGE; IMPROVE; COHORT; NG/ML AB Objectives. To determine whether prostate-specific antigen (PSA), the percent free PSA, or free PSA isoforms may be used as diagnostic markers for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS; National Institutes of Health category IIIa and IIIb). Methods. We evaluated 421 patients enrolled in the Chronic Prostatitis Cohort Study and 112 age-matched controls. Subjects were stratified by the number of white blood cells (WBCs) in their expressed prostatic secretions and pain as determined by the National Institutes of Health Chronic Prostatitis Symptom Index. Results. Total PSA, free PSA, and [-2]proPSA ([-2]pPSA) were significantly elevated in those with CP/CPPS compared with controls (mean PSA 1.97 ng/mL versus 1.72 ng/mL, P = 0.03; mean free PSA 0.76 ng/mL versus 0.70 ng/mL, P = 0.01; and [-2]pPSA 2.38 ng/mL versus 1.80 ng/mL, P = 0.04). The percent free PSA was not significantly different between the patients and controls. For those with CP/CPPS, the percent free PSA was significantly lower as the WBC count rose in the expressed prostatic secretions (0 WBCs = 43.29 versus more than 25 WBCs = 26.52; P <.0001). A PSA level of 4.0 ng/mL or greater was found in 10% of patients and 7% of controls (P = 0.03). Conclusions. Men with elevated PSA values and CP/CPPS should be treated as one would any other patient screened for prostate cancer with an elevated PSA level. Although PSA, free PSA, and [-2]pPSA were slightly elevated in men with CP/CPPS, the low sensitivity and specificity do not warrant using them as biomarkers for CP/CPPS. C1 Northwestern Univ, Feinberg Sch Med, Dept Urol, Chicago, IL 60611 USA. Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. Beckman Coulter Inc, San Diego, CA USA. Univ Mississippi, Sch Med, Jackson, MS 39216 USA. US Dept Vet Affairs, Maryland Hlth Care Syst, Urol Sect, Baltimore, MD USA. RP Nadler, RB (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Urol, 303 E Chicago Ave,Tarry Bldg 16-703, Chicago, IL 60611 USA. EM r-nadler@northwestern.edu RI Landis, J. Richard/A-9330-2010; OI Landis, J Richard/0000-0001-8099-0988 FU NIDDK NIH HHS [U01 DK53730, U01 DK53732, U01 DK53734, U01 DK53736, U01 DK53738, U01 DK53746, U01 DK53752] NR 22 TC 31 Z9 34 U1 0 U2 2 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 FEB PY 2006 VL 67 IS 2 BP 337 EP 342 DI 10.1016/j.urology.2005.08.031 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 024EO UT WOS:000236178500022 PM 16442595 ER PT J AU Mourikis, P Hurlbut, GD Artavanis-Tsakonas, S AF Mourikis, P Hurlbut, GD Artavanis-Tsakonas, S TI Enigma, a mitochondrial protein affecting lifespan and oxidative stress response in Drosophila SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE beta-oxidation; longevity; mitochondria ID CAENORHABDITIS-ELEGANS; CALORIC RESTRICTION; INSULIN-RECEPTOR; BETA-OXIDATION; DIETARY RESTRICTION; MELANOGASTER; LONGEVITY; GENE; EXTENSION; SYSTEM AB Deregulation of energy metabolism by external interventions or mutations in metabolic genes can extend lifespan in a wide range of species. We describe mutations in Drosophila melanogaster that confer resistance to oxidative stress and display a longevity phenotype. These phenotypes are associated with molecular lesions in a hitherto uncharacterized gene we named Enigma. We show that Enigma encodes a mitochondrial protein with homology to enzymes of the beta-oxidation of fatty acids and that mutations in this locus affect lipid homeostasis. Our analysis provides further support to the notion that lipid metabolism may play a central role in metazoan lifespan regulation. C1 Harvard Univ, Sch Med, Dept Cell Biol, Massachusetts Gen Hosp,Canc Ctr, Charlestown, MA 02129 USA. Univ Paris 11, Fac Sci Orsay, F-91405 Orsay, France. Coll France, F-75231 Paris, France. RP Artavanis-Tsakonas, S (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Massachusetts Gen Hosp,Canc Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. EM tsakonas@helix.mgh.harvard.edu NR 39 TC 26 Z9 28 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 31 PY 2006 VL 103 IS 5 BP 1307 EP 1312 DI 10.1073/pnas.0510564103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 009EO UT WOS:000235094300029 PM 16434470 ER PT J AU Shapiro, KA Moo, LR Caramazza, A AF Shapiro, KA Moo, LR Caramazza, A TI Cortical signatures of noun and verb production SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE actions; cortex; language; objects ID INFERIOR PREFRONTAL CORTEX; NEURAL BASIS; TEMPORAL DISCRIMINATION; CONCEPTUAL KNOWLEDGE; ANATOMICAL BASIS; RETRIEVAL; OBJECTS; PET; REPRESENTATION; DISTINCTIONS AB Categories like "noun" and "verb" represent the basic units of grammar in all human languages, and the retrieval of categorical information associated with words is an essential step in the production of grammatical speech. Studies of brain-damaged patients suggest that knowledge of nouns and verbs can be spared or impaired selectively; however, the neuroanatomical correlates of this dissociation are not well understood. We used event-related functional MRI to identify cortical regions that were active when English-speaking subjects produced nouns or verbs in the context of short phrases. Two regions, in the left prefrontal cortex and left superior parietal lobule, were selectively activated for verb trials compared with noun trials; one region in the left inferior temporal lobe was more active during noun production than verb production. We propose that these regions are involved in representing core conceptual properties of nouns and verbs. C1 Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Caramazza, A (reprint author), Harvard Univ, Dept Psychol, 33 Kirkand St, Cambridge, MA 02138 USA. EM caram@wjh.harvard.edu FU NIDCD NIH HHS [DC 04542, DC 05068, K23 DC005068, R01 DC004542]; NINDS NIH HHS [F30 NS050906, NS 50906] NR 50 TC 116 Z9 118 U1 2 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 31 PY 2006 VL 103 IS 5 BP 1644 EP 1649 DI 10.1073/pnas.0504142103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 009EO UT WOS:000235094300087 PM 16432232 ER PT J AU Demirci, U Toner, M AF Demirci, U Toner, M TI Direct etch method for microfludic channel and nanoheight post-fabrication by picoliter droplets SO APPLIED PHYSICS LETTERS LA English DT Article ID EJECTOR ARRAYS AB Photolithography is an expensive and significant step in microfabrication. Approaches that could change lithography would create an impact on semiconductor industry and microelectromechanical systems technologies. We demonstrate a direct etching method by ejecting etchant droplets at desired locations by using microdroplet ejector arrays. This method could be used for easy fabrication of poly(dimethylsiloxane) microfluidic channels and nanometer height postlike structures in microfluidic channels. (c) 2006 American Institute of Physics. C1 Harvard Univ, Sch Med, BioMEMS Resource Ctr, Ctr Engn Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Demirci, U (reprint author), Harvard Univ, Sch Med, BioMEMS Resource Ctr, Ctr Engn Med, 114 16th St,Room 1239, Charlestown, MA 02129 USA. EM utkan@stanfordalumni.org; mtoner@hms.harvard.edu NR 14 TC 3 Z9 3 U1 2 U2 5 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0003-6951 J9 APPL PHYS LETT JI Appl. Phys. Lett. PD JAN 30 PY 2006 VL 88 IS 5 AR 053117 DI 10.1063/1.2170143 PG 3 WC Physics, Applied SC Physics GA 009TQ UT WOS:000235136700083 ER PT J AU Broom, WJ Ay, I Pasinelli, P Brown, RH AF Broom, WJ Ay, I Pasinelli, P Brown, RH TI Inhibition of SOD1 expression by mitomycin C is a non-specific consequence of cellular toxicity SO NEUROSCIENCE LETTERS LA English DT Article DE mitomycin C; SOD1; gene expression; ALS ID AMYOTROPHIC-LATERAL-SCLEROSIS; SUPEROXIDE-DISMUTASE; MUTATIONS; MODEL; ALS; COMBINATION; DOXORUBICIN; DRUGS; GENE; MICE AB Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative condition that results in the death of the large motor neurons of the brain and spinal cord. Familial ALS accounts for 10% of all ALS cases. Approximately 25% of these cases are due to mutations in the SOD1 gene. Several lines of evidence argue that mutant SOD 1 causes ALS by a toxic gain of function. We therefore anticipate that measures that reduce the levels of mutant SOD1 expression should be beneficial in mutant SOD1-associated ALS patients. Mitomycin C (MC) is an antitumor antibiotic previously demonstrated to reduce SOD I expression in a reporter gene system. We investigated whether MC reduces endogenous SOD I expression levels both in vitro and in vivo. MC reduced human and rat SOD 1 protein levels in vitro, with a concomitant decrease in actin and increase in p53 protein levels, as detected by Western blotting. However, this decrease in SOD 1 protein levels was paralleled by a similar decrease in cell viability. In contrast, intracerebroventricular administration of MC to rats and mice failed to produce any effect on brain or spinal cord SOD1 protein levels. Our data indicate the apparent inhibition of SOD1 expression by MC is a non-specific consequence of MC-induced cellular toxicity. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Day Neuromuscular Res Lab, Charlestown, MA 02129 USA. RP Broom, WJ (reprint author), Massachusetts Gen Hosp, Day Neuromuscular Res Lab, MGH E,114 16th St,Navy Yard, Charlestown, MA 02129 USA. EM wbroom@partners.org; rhbrown@partners.org NR 16 TC 4 Z9 4 U1 1 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD JAN 30 PY 2006 VL 393 IS 2-3 BP 184 EP 188 DI 10.1016/j.neulet.2005.09.064 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 002AE UT WOS:000234583000022 PM 16242241 ER PT J AU Yasar, AS Monkul, ES Sassi, RB Axelson, D Brambilla, P Nicoletti, MA Hatch, JP Keshavan, M Ryan, N Birmaher, B Soares, JC AF Yasar, AS Monkul, ES Sassi, RB Axelson, D Brambilla, P Nicoletti, MA Hatch, JP Keshavan, M Ryan, N Birmaher, B Soares, JC TI MRI study of corpus callosum in children and adolescents with bipolar disorder SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE mood disorders; neuroimaging; white matter ID UNIPOLAR AB This structural magnetic resonance imaging study examined the length, areas, and circularity of the corpus callosum (CC) in 16 children and adolescents with bipolar disorder and 21 healthy controls. Bipolar disorder patients had lower circularity of the CC splenium compared with healthy controls. No significant differences in CC length or area were observed, suggesting that reported CC abnormalities appear late in the course of bipolar disorder. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, Div Mood & Anxiety Disorders,MOOD CNS Program, San Antonio, TX 78229 USA. Univ Sao Paulo, Sch Med, Inst Psychiat, Dept Psychiat, Sao Paulo, Brazil. Univ Pittsburgh, Ctr Med, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA USA. Univ Verona, Dept Med & Publ Hlth, Sect Psychiat, I-37100 Verona, Italy. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78284 USA. RP Soares, JC (reprint author), Univ Texas, Hlth Sci Ctr, Dept Psychiat, Div Mood & Anxiety Disorders,MOOD CNS Program, 7703 Floyd Curl Dr,MC-7792, San Antonio, TX 78229 USA. EM soares@uthscsa.edu RI brambilla, paolo/B-4184-2010 OI brambilla, paolo/0000-0002-4021-8456 FU NCRR NIH HHS [RR020571]; NIMH NIH HHS [MH 01736, MH 30915, MH 55123, MH 59929] NR 15 TC 30 Z9 30 U1 2 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD JAN 30 PY 2006 VL 146 IS 1 BP 83 EP 85 DI 10.1016/j.pscychresns.2005.09.004 PG 3 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 029EE UT WOS:000236541100010 PM 16337778 ER PT J AU Caetano, SC Hatch, JP Brambilla, P Sassi, RB Nicolletti, M Malinger, AG Frank, E Kupfer, DJ Keshavan, MS Soares, JC AF Caetano, SC Hatch, JP Brambilla, P Sassi, RB Nicolletti, M Malinger, AG Frank, E Kupfer, DJ Keshavan, MS Soares, JC TI Anatomical MRI study of hippocampus and amygdala in patients with current and remitted major depression (vol 132, pg 141, 2004) SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Correction C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, Div Mood & Anxiety Disorders, San Antonio, TX 78229 USA. Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA USA. Univ Sao Paulo, Sch Med, Inst Psychiat, Dept Psychiat, BR-01051 Sao Paulo, Brazil. Univ Udine, Sect Psychiat, Dept Pathol & Expt & Clin Med, I-33100 Udine, Italy. Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78285 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, Div Mood & Anxiety Disorders, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM soares@uthscsa.edu RI brambilla, paolo/B-4184-2010; Caetano, Sheila/H-5010-2012 OI brambilla, paolo/0000-0002-4021-8456; Caetano, Sheila/0000-0001-8403-7078 NR 1 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD JAN 30 PY 2006 VL 146 IS 1 BP 103 EP 103 DI 10.1016/j.pscychresns.2005.10.001 PG 1 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 029EE UT WOS:000236541100013 ER PT J AU Larsson, J Scadden, D AF Larsson, J Scadden, D TI Nervous activity in a stem cell niche SO CELL LA English DT Editorial Material ID HEMATOPOIETIC STEM; BONE-MARROW; MOBILIZATION AB In this issue of Cell, Katayama et al. (2006) report a new regulatory axis for the mobilization of hematopoietic stem cells that links these cells to the nervous system and bone in an unanticipated way. The new findings suggest that the nervous system, which has the inherent ability to integrate information from throughout the organism, may govern the local relationship between stem cells and their niches. C1 Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. Harvard Univ, Stem Cell Inst, Cambridge, MA 02138 USA. RP Scadden, D (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. EM scadden.david@mgh.harvard.edu NR 11 TC 15 Z9 15 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD JAN 27 PY 2006 VL 124 IS 2 BP 253 EP 255 DI 10.1016/j.cell.2006.01.006 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 008VJ UT WOS:000235068500011 PM 16439198 ER PT J AU Duchaine, TF Wohlschlegel, JA Kennedy, S Bei, YX Conte, D Pang, KM Brownell, DR Harding, S Mitani, S Ruvkun, G Yates, JR Mello, CC AF Duchaine, TF Wohlschlegel, JA Kennedy, S Bei, YX Conte, D Pang, KM Brownell, DR Harding, S Mitani, S Ruvkun, G Yates, JR Mello, CC TI Functional proteomics reveals the biochemical niche of C-elegans DCR-1 in multiple small-RNA-mediated pathways SO CELL LA English DT Article ID PROTEIN IDENTIFICATION TECHNOLOGY; DOUBLE-STRANDED-RNA; CAENORHABDITIS-ELEGANS; GENETIC INTERFERENCE; SHOTGUN PROTEOMICS; FISSION YEAST; DICER; PHOSPHATASE; MICRORNAS; COMPLEXES AB In plants, animals, and fungi, members of the Dicer family of RNase III-related enzymes process double-stranded RNA (dsRNA) to initiate small-RNA-mediated gene-silencing mechanisms. To learn how C. elegans Dicer, DCR-1, functions in multiple distinct silencing mechanisms, we used a mass-spectrometry-based proteomics approach to identify DCR-1-interacting proteins. We then generated and characterized deletion alleles for the corresponding genes. The interactors are required for production of three species of small RNA, including (1) small interfering RNAs (siRNAs), derived from exogenous dsRNA triggers (exo-siRNAs); (2) siRNAs derived from endogenous triggers (endo-siRNAs); and (3) developmental regulatory microRNAs (miRNAs). One interactor, the conserved RNA-phosphatase homolog PIR-1, is required for the processing of a putative amplified DCR-1 substrate. Interactors required for endo-siRNA production include ERI-1 and RRF-3, whose loss of function enhances RNAi Our findings provide a first glimpse at the complex biochemical niche of Dicer and suggest that competition exists between DCR-1-mediated small-RNA pathways. C1 Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA. Univ Massachusetts, Sch Med, Howard Hughes Med Inst, Worcester, MA 01605 USA. Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA. Univ Wisconsin, Dept Pharmacol, Madison, WI 53701 USA. Tokyo Womens Med Univ, Sch Med, Dept Physiol, Tokyo 1628666, Japan. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Mello, CC (reprint author), Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA. EM craig.mello@umassmed.edu RI pang, ka ming/H-4082-2011 OI pang, ka ming/0000-0001-7262-3918 FU NIGMS NIH HHS [GM58800] NR 42 TC 234 Z9 262 U1 3 U2 20 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD JAN 27 PY 2006 VL 124 IS 2 BP 343 EP 354 DI 10.1016/j.cell.2005.11.036 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 008VJ UT WOS:000235068500022 PM 16439208 ER PT J AU Kim, RS Ji, HK Wong, WH AF Kim, RS Ji, HK Wong, WH TI An improved distance measure between the expression profiles linking co-expression and co-regulation in mouse SO BMC BIOINFORMATICS LA English DT Article ID REGULATORY ELEMENTS; GENE-EXPRESSION; GENOME-WIDE; IDENTIFICATION; SEQUENCES AB Background: Many statistical algorithms combine microarray expression data and genome sequence data to identify transcription factor binding motifs in the low eukaryotic genomes. Finding cis-regulatory elements in higher eukaryote genomes, however, remains a challenge, as searching in the promoter regions of genes with similar expression patterns often fails. The difficulty is partially attributable to the poor performance of the similarity measures for comparing expression profiles. The widely accepted measures are inadequate for distinguishing genes transcribed from distinct regulatory mechanisms in the complicated genomes of higher eukaryotes. Results: By defining the regulatory similarity between a gene pair as the number of common known transcription factor binding motifs in the promoter regions, we compared the performance of several expression distance measures on seven mouse expression data sets. We propose a new distance measure that accounts for both the linear trends and fold-changes of expression across the samples. Conclusion: The study reveals that the proposed distance measure for comparing expression profiles enables us to identify genes with large number of common regulatory elements because it reflects the inherent regulatory information better than widely accepted distance measures such as the Pearson's correlation or cosine correlation with or without log transformation. C1 Stanford Univ, Dept Stat, Stanford, CA 94305 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Dept Stat, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Wong, WH (reprint author), Stanford Univ, Dept Stat, Stanford, CA 94305 USA. EM ryung_kim@dfci.harvard.edu; jihk@stanford.edu; whwong@stanford.edu FU NCI NIH HHS [P01 CA095616]; NHGRI NIH HHS [R01 HG002341, HG-HG02341] NR 25 TC 17 Z9 18 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD JAN 26 PY 2006 VL 7 AR 44 DI 10.1186/1471-2105-7-44 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 022NJ UT WOS:000236062200001 PM 16438730 ER PT J AU Yuan, HS Luo, J Weissleder, R Cantley, L Josephson, L AF Yuan, HS Luo, J Weissleder, R Cantley, L Josephson, L TI Wortmannin-C20 conjugates generate wortmannin SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID PHOSPHATIDYLINOSITOL 3-KINASE; PHOSPHOINOSITIDE 3-KINASE; IN-VITRO; ANTITUMOR-ACTIVITY; INHIBITION; PATHWAY; CANCER; AGENTS; CELLS; VIVO AB We report on C20-6-(N-methylamino)hexanoic conjugates of wortmannin featuring a tertiary enamine attached to the C20 that inhibit phosphoinositol-3-OH kinase (PI3K) by producing wortmannin (Win) through an intramolecular attack. The generation of Win by these conjugates permits the design of Wm based PI3K inhibitors that need not fit into the ATP pocket of PI3K, including Win conjugates of BSA, IgG, or beads. Win generating WmC20-N(Me)-hexanoate conjugates offer an approach to the design of targeted or slow release forms of Win which may inhibit PI3K in tissues more selectively than the parent Win, a compound which has desirable anti-inflammatory and anti-proliferative activities but which also has a variety of toxic effects. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02129 USA. Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA. RP Josephson, L (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, 149 13th St, Charlestown, MA 02129 USA. EM ljosephson@partners.org RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NCI NIH HHS [CA85240]; NHLBI NIH HHS [HL078641]; NIBIB NIH HHS [EB004626]; NIGMS NIH HHS [R01 GM041890] NR 39 TC 15 Z9 16 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JAN 26 PY 2006 VL 49 IS 2 BP 740 EP 747 DI 10.1021/jm050699p PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 005PL UT WOS:000234836200034 PM 16420059 ER PT J AU Keogh, MC Kim, JA Downey, M Fillingham, J Chowdhury, D Harrison, JC Onishi, M Datta, N Galicia, S Emili, A Lieberman, J Shen, XT Buratowski, S Haber, JE Durocher, D Greenblatt, JF Krogan, NJ AF Keogh, MC Kim, JA Downey, M Fillingham, J Chowdhury, D Harrison, JC Onishi, M Datta, N Galicia, S Emili, A Lieberman, J Shen, XT Buratowski, S Haber, JE Durocher, D Greenblatt, JF Krogan, NJ TI A phosphatase complex that dephosphorylates gamma H2AX regulates DNA damage checkpoint recovery SO NATURE LA English DT Article ID DOUBLE-STRAND BREAK; SACCHAROMYCES-CEREVISIAE; BUDDING YEAST; HISTONE H2AX; G2/M ARREST; CELL-CYCLE; REPAIR; PROTEIN; PHOSPHORYLATION; RECOMBINATION AB One of the earliest marks of a double-strand break (DSB) in eukaryotes is serine phosphorylation of the histone variant H2AX at the carboxy-terminal SQE motif to create gamma H2AX-containing nucleosomes(1). Budding-yeast histone H2A is phosphorylated in a similar manner by the checkpoint kinases Tel1 and Mec1 (ref. 2; orthologous to mammalian ATM and ATR, respectively) over a 50-kilobase region surrounding the DSB3. This modification is important for recruiting numerous DSB-recognition and repair factors to the break site, including DNA damage checkpoint proteins(4,5), chromatin remodellers(6) and cohesins(7,8). Multiple mechanisms for eliminating gamma H2AX as DNA repair completes are possible, including removal by histone exchange followed potentially by degradation, or, alternatively, dephosphorylation. Here we describe a three-protein complex (HTP-C, for histone H2A phosphatase complex) containing the phosphatase Pph3 that regulates the phosphorylation status of gamma H2AX in vivo and efficiently dephosphorylates gamma H2AX in vitro. gamma H2AX is lost from chromatin surrounding a DSB independently of the HTP-C, indicating that the phosphatase targets gamma H2AX after its displacement from DNA. The dephosphorylation of gamma H2AX by the HTP-C is necessary for efficient recovery from the DNA damage checkpoint. C1 Univ Toronto, Dept Med Genet, Toronto, ON M5G 1L6, Canada. Univ Toronto, Dept Microbiol, Toronto, ON M5G 1L6, Canada. Univ Toronto, Banting & Best Dept Med Res, Toronto, ON M5G 1L6, Canada. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Brandeis Univ, Rosenstiel Ctr, Waltham, MA 02454 USA. Brandeis Univ, Dept Biol, Waltham, MA 02454 USA. Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. CBR Inst Biomed Res, Boston, MA 02115 USA. MD Anderson Canc Ctr, Dept Carcinogenesis, Smithville, TX 78957 USA. RP Durocher, D (reprint author), Univ Toronto, Dept Med Genet, Toronto, ON M5G 1L6, Canada. EM durocher@mshri.on.ca; jack.greenblatt@utoronto.ca RI Durocher, Daniel/A-7733-2010; Lieberman, Judy/A-2717-2015 OI Durocher, Daniel/0000-0003-3863-8635; NR 30 TC 273 Z9 289 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JAN 26 PY 2006 VL 439 IS 7075 BP 497 EP 501 DI 10.1038/nature04384 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 005XH UT WOS:000234859200052 PM 16299494 ER PT J AU Schapiro, RH Maher, MM Misdraji, J Bounds, BC Harris, NL Daskalakis, D AF Schapiro, RH Maher, MM Misdraji, J Bounds, BC Harris, NL Daskalakis, D TI A woman with jaundice and a pancreatic mass - Mycobacterium tuberculosis infection of the pancreas and peripancreatic lymph nodes SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID OBSTRUCTIVE-JAUNDICE; RARE CAUSE; IMMUNOCOMPETENT PATIENTS; HODGKINS-DISEASE; DIAGNOSIS; SECONDARY; INVOLVEMENT; EXPERIENCE; MANAGEMENT; CARCINOMA C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Schapiro, RH (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. NR 37 TC 4 Z9 5 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 26 PY 2006 VL 354 IS 4 BP 398 EP 406 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 005VY UT WOS:000234854000013 PM 16436772 ER PT J AU Vlahakes, GJ AF Vlahakes, GJ TI The value of phase 4 clinical testing SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID CARDIOPULMONARY BYPASS; APROTININ C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Vlahakes, GJ (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 5 TC 34 Z9 35 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 26 PY 2006 VL 354 IS 4 BP 413 EP 415 DI 10.1056/NEJMe058272 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 005VY UT WOS:000234854000016 PM 16436775 ER PT J AU MacLean, CH Newberry, SJ Mojica, WA Khanna, P Issa, AM Suttorp, MJ Lim, YW Traina, SB Hilton, L Garland, R Morton, SC AF MacLean, CH Newberry, SJ Mojica, WA Khanna, P Issa, AM Suttorp, MJ Lim, YW Traina, SB Hilton, L Garland, R Morton, SC TI Effects of omega-3 fatty acids on cancer risk - A systematic review SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID DIETARY-FAT INTAKE; BREAST-CANCER; PROSTATE-CANCER; COLON-CANCER; LUNG-CANCER; COLORECTAL-CANCER; ENTERAL IMMUNONUTRITION; METHODOLOGICAL QUALITY; NETHERLANDS-COHORT; PANCREATIC-CANCER AB Context Omega-3 fatty acids are purported to reduce the risk of cancer. Studies have reported mixed results. Objective To synthesize published and unpublished evidence to determine estimates of the effect of omega-3 fatty acids on cancer risk in prospective cohort studies. Data Sources Articles published from 1966 to October 2005 identified through MEDLINE, PREMEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and CAB Health; unpublished literature sought through letters to experts in the neutraceutical industry. Study Selection A total of 38 articles with a description of effects of consumption of omega-3 fatty acids on tumor incidence, prospective cohort study design, human study population; and description of effect of omega-3 among groups with different levels of exposure in the cohort were included. Two reviewers independently reviewed articles using structured abstraction forms; disagreements were resolved by consensus. Data Extraction Two reviewers independently abstracted detailed data about the incidence of cancer, the type of cancer, the number and characteristics of the patients, details on the exposure to omega-3 fatty acids, and the elapsed time between the intervention and outcome measurements. Data about the methodological quality of the study were also abstracted. Data Synthesis Across 20 cohorts from 7 countries for 11 different types of cancer and using up to 6 different ways to categorize omega-3 fatty acid consumption, 65 estimates of the association between omega-3 fatty acid consumption were reported. Among these, only 8 were statistically significant. The high degree of heterogeneity across these studies precluded pooling of data. For breast cancer 1 significant estimate was for increased risk (incidence risk ratio [RR], 1.47; 95% confidence interval [CI], 1.10-1.98) and 3 were for decreased risk (RR, 0.68-0.72); 7 other estimates did not show a significant association. For colorectal cancer, there was 1 estimate of decreased risk (RR, 0.49; 95% Cl, 0.27-0.89) and 17 estimates without association. For lung cancer one of the significant associations was for increased cancer risk (IRR, 3.0; 95% Cl, 1.2-7.3), the other was for decreased risk (RR, 0.32; 95% Cl, 0.13-0.76), and 4 other estimates were not significant. For prostate cancer, there was 1 estimate of decreased risk (RR, 0.43; 95% Cl, 0.22-0.83) and 1 of increased risk (RR, 1.98; 95% Cl, 1.34-2.93) for advanced prostate cancer; 15 other estimates did not show a significant association. The study that assessed skin cancer found an increased risk (RR, 1.13; 95% CI, 1.01-1.27). No significant associations between omega-3 fatty acid consumption and cancer incidence were found for aerodigestive cancer, bladder cancer, lymphoma, ovarian cancer, pancreatic cancer, or stomach cancer. Conclusions A large body of literature spanning numerous cohorts from many countries and with different demographic characteristics does not provide evidence to suggest a significant association between omega-3 fatty acids and cancer incidence. Dietary supplementation with omega-3 fatty acids is unlikely to prevent cancer. C1 So Calif Evidence Based Practice Ctr, Santa Monica, CA USA. Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. Wright State Univ, Sch Med, Dayton, OH USA. RP MacLean, CH (reprint author), RAND Corp, 1776 Main St,M4W, Santa Monica, CA 90407 USA. EM maclean@rand.org FU PHS HHS [290-02-0003] NR 60 TC 279 Z9 289 U1 9 U2 38 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 25 PY 2006 VL 295 IS 4 BP 403 EP 415 DI 10.1001/jama.295.4.403 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 005QJ UT WOS:000234838600021 PM 16434631 ER PT J AU Strissel, KJ Sokolov, M Trieu, LH Arshavsky, VY AF Strissel, KJ Sokolov, M Trieu, LH Arshavsky, VY TI Arrestin translocation is induced at a critical threshold of visual signaling and is superstoichiometric to bleached rhodopsin SO JOURNAL OF NEUROSCIENCE LA English DT Article DE arrestin; photoreceptor; protein translocation; rhodopsin; vision; retina ID LIGHT-DEPENDENT REDISTRIBUTION; ROD PHOTORECEPTOR CELLS; RETINAL RODS; DRIVEN TRANSLOCATION; KNOCKOUT MOUSE; CONE ARRESTIN; RAT RETINA; S-ANTIGEN; TRANSDUCIN; ADAPTATION AB Light induces massive translocation of major signaling proteins between the subcellular compartments of photoreceptors. Among them is visual arrestin responsible for quenching photoactivated rhodopsin, which moves into photoreceptor outer segments during illumination. Here, for the first time, we determined the light dependency of arrestin translocation, which revealed two key features of this phenomenon. First, arrestin translocation is triggered when the light intensity approaches a critical threshold corresponding to the upper limits of the normal range of rod responsiveness. Second, the amount of arrestin entering rod outer segments under these conditions is superstoichiometric to the amount of photoactivated rhodopsin, exceeding it by at least 30-fold. We further showed that it is not the absolute amount of excited rhodopsin but rather the extent of downstream cascade activity that triggers translocation. Finally, we demonstrated that the total amount of arrestin in the rod cell is nearly 10-fold higher than previously thought and therefore sufficient to inactivate the entire pool of rhodopsin at any level of illumination. Thus, arrestin movement to the outer segment leads to an increase in the free arrestin concentration and thereby may serve as a powerful mechanism of light adaptation. C1 Duke Univ, Med Ctr, Dept Ophthalmol, Albert Eye Res Inst 5008, Durham, NC 27710 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. W Virginia Univ, Dept Ophthalmol, Morgantown, WV 26506 USA. W Virginia Univ, Inst Eye, Morgantown, WV 26506 USA. Duke Univ, Dept Neurobiol, Durham, NC 27710 USA. RP Duke Univ, Med Ctr, Dept Ophthalmol, Albert Eye Res Inst 5008, 2351 Erwin Rd, Durham, NC 27710 USA. EM vadim.arshavsky@duke.edu FU NEI NIH HHS [R01 EY10336, EY14104, P30 EY005722, P30 EY005722-21] NR 45 TC 90 Z9 93 U1 0 U2 4 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 JAN 25 PY 2006 VL 26 IS 4 BP 1146 EP 1153 DI 10.1523/JNEUROSCI.4289-05.2006 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 006KK UT WOS:000234896200012 PM 16436601 ER PT J AU Viswanathan, A Rakich, SM Engel, C Snider, R Rosand, J Greenberg, SM Smith, EE AF Viswanathan, A Rakich, SM Engel, C Snider, R Rosand, J Greenberg, SM Smith, EE TI Antiplatelet use after intracerebral hemorrhage SO NEUROLOGY LA English DT Article ID ISCHEMIC STROKE; RISK; METAANALYSIS; RECURRENCE; TRIALS AB Background: Survivors of intracerebral hemorrhage are at risk for recurrent intracerebral hemorrhage and ischemic cardiovascular and cerebrovascular disease. Objective: To determine whether antiplatelet therapy increases the risk of recurrent intracerebral hemorrhage. Methods: The authors reviewed data from consecutive survivors of primary intracerebral hemorrhage enrolled in a single-center prospective cohort study. Survivors were followed by telephone interview; recurrent intracerebral hemorrhage and post-index antiplatelet agent use and duration were recorded. Cox proportional hazards models was used with antiplatelet agent exposure as a time-dependent variable to assess the effect of antiplatelet agent use on recurrent intracerebral hemorrhage, stratified by lobar and deep hemispheric location. Results: Recurrent intracerebral hemorrhage was more common in survivors of lobar hemorrhage compared with survivors of deep hemorrhage (cumulative 2-year rate 22% vs 4%; p = 0.007). Antiplatelet agents were prescribed in 22% of intracerebral hemorrhage survivors (27/127 lobar, 19/80 deep hemispheric), most commonly for prevention of ischemic heart disease. Antiplatelet agent use was not associated with intracerebral hemorrhage recurrence in survivors of either lobar hemorrhage (hazard ratio [HR] 0.8, 95% CI 0.3 to 2.3, p = 0.73) or of deep hemorrhage (HR 1.2, 95% CI 0.1 to 14.3, p = 0.88). Conclusion: Antiplatelet agent use is relatively common following intracerebral hemorrhage but did not appear to be associated with a large increased risk of intracerebral hemorrhage recurrence in this observational study. C1 Massachusetts Gen Hosp, MGH Stroke Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurol Clin Trials Unit, Dept Neurol, Boston, MA 02114 USA. RP Smith, EE (reprint author), Massachusetts Gen Hosp, MGH Stroke Serv, 55 Fruit St,VBK 802, Boston, MA 02114 USA. EM eesmith@partners.org OI Smith, Eric/0000-0003-3956-1668 NR 15 TC 75 Z9 80 U1 0 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JAN 24 PY 2006 VL 66 IS 2 BP 206 EP 209 DI 10.1212/01.wnl.0000194267.09060.77 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 005SA UT WOS:000234842900014 PM 16434655 ER PT J AU Hersch, SM Gevorkian, S Marder, K Moskowitz, C Feigin, A Cox, M Como, P Zimmerman, C Lin, M Zhang, L Ulug, AM Beal, MF Matson, W Bogdanov, M Ebbel, E Zaleta, A Kaneko, Y Jenkins, B Hevelone, N Zhang, H Yu, H Schoenfeld, D Ferrante, R Rosas, HD AF Hersch, SM Gevorkian, S Marder, K Moskowitz, C Feigin, A Cox, M Como, P Zimmerman, C Lin, M Zhang, L Ulug, AM Beal, MF Matson, W Bogdanov, M Ebbel, E Zaleta, A Kaneko, Y Jenkins, B Hevelone, N Zhang, H Yu, H Schoenfeld, D Ferrante, R Rosas, HD TI Creatine in Huntington disease is safe, tolerable, bioavailable in brain and reduces serum 8OH2 ' dG SO NEUROLOGY LA English DT Article ID SUPPLEMENTATION; SYMPTOMS; THERAPY; MODEL AB In a randomized, double-blind, placebo-controlled study in 64 subjects with Huntington disease (HD), 8 g/day of creatine administered for 16 weeks was well tolerated and safe. Serum and brain creatine concentrations increased in the creatine-treated group and returned to baseline after washout. Serum 8-hydroxy-2=-deoxyguanosine (8OH2'dG) levels, an indicator of oxidative injury to DNA, were markedly elevated in HD and reduced by creatine treatment. C1 MassGen Inst Neurogenerat Dis, Dept Neurol, Charlestown, MA 02129 USA. MassGen Inst Neurogenerat Dis, Dept Biostat, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. Columbia Univ, Ctr Parkinsons Dis & Other Movement Disorders, New York, NY 10027 USA. Columbia Univ, Dept Neurol, Sergievsky Ctr, New York, NY 10027 USA. Columbia Univ, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY 10027 USA. N Shore LIJ Hlth Syst, Inst Med Res, Ctr Neurosci, Manhasset, NY USA. Univ Rochester, Dept Neurol, Rochester, NY USA. Cornell Univ, Weill Med Coll, Dept Neurol, New York, NY USA. Cornell Univ, Weill Med Coll, Dept Neurosci, New York, NY USA. Cornell Univ, Weill Med Coll, Dept Radiol, New York, NY USA. Geriatr Res & Educ & Clin Ctr, Bedford, MA USA. Edith Nourse Vet Adm Med Ctr, Bedford, MA USA. Boston Univ, Sch Med, Dept Neurol Pathol, Boston, MA USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA USA. Boston Univ, Sch Med, Dept Biochem, Boston, MA USA. RP Hersch, SM (reprint author), MassGen Inst Neurogenerat Dis, Dept Neurol, MGH E Bldg 114-2001,114 16th St, Charlestown, MA 02129 USA. EM hersch@helix.mgh.harvard.edu RI Ulug, Aziz/F-6592-2011; OI Ulug, Aziz/0000-0002-2315-0322; Hevelone, Nathanael/0000-0003-4740-2085 FU NCCIH NIH HHS [AT00613]; NCRR NIH HHS [M01-RR00645, M01-RR01066]; NINDS NIH HHS [NS35255, NS042861] NR 10 TC 166 Z9 172 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JAN 24 PY 2006 VL 66 IS 2 BP 250 EP 252 DI 10.1212/01.wnl.0000194318.74946.b6 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 005SA UT WOS:000234842900025 PM 16434666 ER PT J AU Kisucka, J Butterfield, CE Duda, DG Eichenberger, SC Saffaripour, S Ware, J Ruggeri, ZM Jain, RK Folkman, J Wagner, DD AF Kisucka, J Butterfield, CE Duda, DG Eichenberger, SC Saffaripour, S Ware, J Ruggeri, ZM Jain, RK Folkman, J Wagner, DD TI Platelets and platelet adhesion support angiogenesis while preventing excessive hemorrhage SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE thrombocytopenic mice; blood vessel; alpha-granule; cornea; collagen receptor ID ENDOTHELIAL GROWTH-FACTOR; GLYCOPROTEIN IB-ALPHA; VON-WILLEBRAND-FACTOR; MICROPARTICLES INDUCE ANGIOGENESIS; SPHINGOSINE 1-PHOSPHATE; THROMBUS FORMATION; IN-VITRO; RELEASE; MICE; HEMOSTASIS AB Platelets contain both pro- and antiangiogenic factors, but their regulatory role in angiogenesis is poorly understood. Although previous studies showed that platelets stimulate angiogenesis in vitro, the role of platelets in angiogenesis in vivo is largely uncharacterized. To address this topic, we used two in vivo approaches, the cornea micropocket assay and the Matrigel model, in four animal models: thrombocytopenic, Lyst(bg) (platelet storage pool deficiency), glycoprotein (GP) Ib alpha/IL4R transgenic (lacking extracellular GPIb alpha, the receptor for von Willebrand factor as well as other adhesive and procoagulant proteins), and Fc gamma R-/- (lacking functional GPVI, the collagen receptor) mice. Adult mice were rendered thrombocytopenic by i.p. administration of an antiplatelet antibody. The number of growing vessels in the thrombocytopenic mice was lower in the cornea assay, and they showed significantly increased appearance of hemorrhage compared with mice treated with control IgG. The thrombocytopenic mice also showed more protein leakage and developed hematomas in the Matrigel model. GPIlb alpha/IL4R transgenic mice presented increased hemorrhage in both assays, but it was less severe than in the platelet-depleted mice. Fc gamma R-/- and LyStbg mice showed no defect in experimental angiogenesis. Intravital microscopy revealed a > 3-fold increase in platelet adhesion to angiogenic vessels of Matrigel compared with mature quiescent skin vessels. Our results suggest that the presence of platelets not only stimulates angiogenic vessel growth but also plays a critical role in preventing hemorrhage from the angiogenic vessels. The adhesion function of platelets, as mediated by GPIba, significantly contributes to the process. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Surg,Vasc Biol Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol,Edwin L Steele Lab, Boston, MA 02115 USA. Scripps Res Inst, La Jolla, CA 92037 USA. Univ Arkansas Med Sci, Dept Physiol & Biophys, Little Rock, AR 72205 USA. RP Wagner, DD (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, 800 Huntington Ave, Boston, MA 02115 USA. EM wagner@cbr.med.harvard.edu FU NCI NIH HHS [P01 CA080124, CA064481, CA80124, R01 CA064481]; NHLBI NIH HHS [HL31950, HL41102, HL42846, HL50545, HL56949, P01 HL031950, P01 HL056949, R01 HL041002, R01 HL042846, R01 HL050545, R01 HL050545-14, R37 HL041002, R37 HL042846] NR 61 TC 154 Z9 163 U1 1 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 JAN 24 PY 2006 VL 103 IS 4 BP 855 EP 860 DI 10.1073/pnas.0510412103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 007AC UT WOS:000234938300006 PM 16418262 ER PT J AU Aujesky, D Obrosky, DS Stone, RA Auble, TE Perrier, A Cornuz, J Roy, PM Fine, MJ AF Aujesky, D Obrosky, DS Stone, RA Auble, TE Perrier, A Cornuz, J Roy, PM Fine, MJ TI A prediction rule to identify low-risk patients with pulmonary embolism SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID DEEP-VEIN THROMBOSIS; MOLECULAR-WEIGHT HEPARIN; RIGHT-VENTRICULAR DYSFUNCTION; OUTPATIENT TREATMENT; UNFRACTIONATED HEPARIN; VENOUS THROMBOEMBOLISM; PROGNOSTIC VALUE; TROPONIN-T; TOTAL HIP; ADMISSION AB Background: A simple prognostic model could help identify patients with pulmonary embolism who are at low risk of death and are candidates for outpatient treatment. Methods: We randomly allocated 15 531 retrospectively identified inpatients who had a discharge diagnosis of pulmonary embolism from 186 Pennsylvania hospitals to derivation (67%) and internal validation (33%) samples. We derived our rule to predict 30-day mortality using classification tree analysis and patient data routinely available at initial examination as potential predictor variables. We used data from a European prospective study to externally validate the rule among 221 inpatients with pulmonary embolism. We determined mortality and nonfatal adverse medical outcomes across derivation and validation samples. Results: Our final model consisted of 10 patient factors (age >= 70 years: history of cancer, heart failure, chronic lung disease, chronic renal disease, and cerebrovascular disease; and clinical variables of pulse rate >= 110 beats/min, systolic blood pressure < 100 mm Hg, altered mental status, and arterial oxygen saturation <90%). Patients with none of these factors were defined as low risk. The 30-day mortality rates for low-risk patients were 0.6%, 1.5%, and 0% in the derivation, internal validation, and external validation samples, respectively. The rates of nonfatal adverse medical outcomes were less than 1% among low-risk patients across all study samples. Conclusions: This simple prediction rule accurately identifies patients with pulmonary embolism who are at low risk of short-term mortality and other adverse medical outcomes. Prospective validation of this rule is important before its implementation as a decision aid for outpatient treatment. C1 Univ Pittsburgh, Dept Med, Div Gen Internal Med, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Emergency Med, Pittsburgh, PA USA. VA Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Univ Lausanne, Univ Outpatient Clin, Dept Internal Med, Lausanne, Switzerland. Univ Lausanne, Clin Epidemiol Ctr, Lausanne, Switzerland. Univ Geneva, Dept Internal Med, Div Gen Internal Med, Geneva, Switzerland. Univ Angers, Dept Emergency Med, Angers, France. RP Aujesky, D (reprint author), CHU Vaudois, Serv Med Interne, BH 10-622, CH-1011 Lausanne, Switzerland. EM aujesky@swissonline.ch RI Perrier, Arnaud/M-2263-2014 FU NHLBI NIH HHS [1 R21 HL075521-01A1] NR 44 TC 101 Z9 106 U1 1 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JAN 23 PY 2006 VL 166 IS 2 BP 169 EP 175 DI 10.1001/archinte.166.2.169 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 004RH UT WOS:000234769400005 PM 16432084 ER PT J AU Zhang, M Alicot, EM Chiu, I Li, JN Verna, N Vorup-Jensen, T Kessler, B Shimaoka, M Chan, R Friend, D Mahmood, U Weissleder, R Moore, FD Carroll, MC AF Zhang, M Alicot, EM Chiu, I Li, JN Verna, N Vorup-Jensen, T Kessler, B Shimaoka, M Chan, R Friend, D Mahmood, U Weissleder, R Moore, FD Carroll, MC TI Identification of the target self-antigens in reperfusion injury SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID ISCHEMIA/REPERFUSION-INDUCED INJURY; INTESTINAL ISCHEMIA-REPERFUSION; COMPLEMENT RECEPTOR TYPE-1; MEMBRANE ATTACK COMPLEX; CELLS IN-VIVO; NATURAL ANTIBODY; SKELETAL-MUSCLE; FUNCTIONAL PROTEOMICS; C6-DEFICIENT RABBITS; MICE AB Reperfusion injury ( RI), a potential life-threatening disorder, represents an acute inflammatory response after periods of ischemia resulting from myocardial infarction, stroke, surgery, or trauma. The recent identification of a monoclonal natural IgM that initiates RI led to the identification of nonmuscle myosin heavy chain type II A and C as the self-targets in two different tissues. These results identify a novel pathway in which the innate response to a highly conserved self-antigen expressed as a result of hypoxic stress results in tissue destruction. C1 CBR Inst Biomed Res Inc, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Declmmune Therapeut, Boston, MA 02115 USA. RP Carroll, MC (reprint author), CBR Inst Biomed Res Inc, Boston, MA 02115 USA. EM carroll@cbr.med.harvard.edu OI Vorup-Jensen, Thomas/0000-0002-4140-6563; Kessler, Benedikt/0000-0002-8160-2446 FU NIAID NIH HHS [R44 AI051045, R43 AI051045]; NIGMS NIH HHS [P50 GM052585, P50 GM52585] NR 58 TC 143 Z9 144 U1 0 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JAN 23 PY 2006 VL 203 IS 1 BP 141 EP 152 DI 10.1084/jem.20050390 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 007XB UT WOS:000235003600017 PM 16390934 ER PT J AU Yu, LQ Schwarzschild, MA Chen, JF AF Yu, LQ Schwarzschild, MA Chen, JF TI Cross-sensitization between caffeine- and L-dopa-induced behaviors in hemiparkinsonian mice SO NEUROSCIENCE LETTERS LA English DT Article DE adenosine A(2A) receptor; caffeine; L-dopa; Parkinson's disease; cross-sensitization ID ADENOSINE A(2A) RECEPTORS; MPTP-TREATED MONKEYS; PARKINSONS-DISEASE; LOCOMOTOR-ACTIVITY; ANTAGONIST; TOLERANCE; WITHDRAWAL; AGONISTS; RATS; D-1 AB Adenosine A(2A) receptor (A(2A)R) antagonists, including the non-specific adenosine antagonist caffeine, have been proposed as a novel, non-dopaminergic treatment strategy for Parkinson's disease (PD). However, the long-term interaction between caffeine and L-dopa treatment in PD models has not been characterized. We examined the interaction between caffeine and L-dopa following a repeated treatment paradigm in hemiparkinsonian mice. In contrast to the progressively sensitized rotational behavior induced by daily L-dopa (2.0 mg/kg) treatment, tolerance for the rotational response to daily caffeine (2.5 or 10 mg/kg) treatment tended to develop over several weeks. However, after a subsequent two-week washout, challenge with same drug demonstrated an extinction of the sensitized L-dopa-induced rotation, but a sensitization of the caffeine-induced rotation. In a cross-challenge paradigm, daily treatment of mice with L-dopa (compared to daily saline) produced a three-fold enhancement in the rotational response to a subsequent re-challenge with caffeine. Similarly, daily treatment of mice with caffeine produced a six-fold enhancement in the rotational response to a subsequent re-challenge with L-dopa. Furthermore, daily co-administration of caffeine plus L-dopa produced enhanced rotational behavior, compared to caffeine or L-dopa alone, indicating an additive or synergistic interaction between caffeine and L-dopa during repeated treatment. Cross-sensitization between caffeine and L-dopa following repeated treatment and their positive interaction during chronic co-adminstration in hemiparkinsonian mice suggest that repeated exposure to caffeine may alter L-dopa responses in PD. (C) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. RP Chen, JF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. EM chenjf@bu.edu FU NIEHS NIH HHS [ES10804]; NINDS NIH HHS [NS37403] NR 34 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD JAN 23 PY 2006 VL 393 IS 1 BP 31 EP 35 DI 10.1016/j.neulet.2005.09.036 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 997XI UT WOS:000234281800007 PM 16236444 ER PT J AU Oh, WY Bouma, BE Iftimia, N Yun, SH Yelin, R Tearney, GJ AF Oh, WY Bouma, BE Iftimia, N Yun, SH Yelin, R Tearney, GJ TI Ultrahigh-resolution full-field optical coherence microscopy using InGaAs camera SO OPTICS EXPRESS LA English DT Article ID THERMAL-LIGHT; SPATIAL-RESOLUTION; TOMOGRAPHY; SCATTERING; NM AB Full-field optical coherence microscopy (FFOCM) is an interferometric technique for obtaining wide-field microscopic images deep within scattering biological samples. FFOCM has primarily been implemented in the 0.8 mu m wavelength range with silicon-based cameras, which may limit penetration when imaging human tissue. In this paper, we demonstrate FFOCM at the wavelength range of 0.9 - 1.4 mu m, where optical penetration into tissue is presumably greater owing to decreased scattering. Our FFOCM system, comprising a broadband spatially incoherent light source, a Linnik interferometer, and an InGaAs area scan camera, provided a detection sensitivity of 86 dB for a 2 sec imaging time and an axial resolution of 1.9 mu m in water. Images of phantoms, tissue samples, and Xenopus Laevis embryos were obtained using InGaAs and silicon camera FFOCM systems, demonstrating enhanced imaging penetration at longer wavelengths. (c) 2006 Optical Society of America. C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Oh, WY (reprint author), Harvard Univ, Sch Med, 50 Blossom St,BAR 704, Boston, MA 02114 USA. EM woh1@partners.org RI Oh, Wang-Yuhl/C-2055-2011 FU NCI NIH HHS [R41 CA132256, R43 CA119501] NR 21 TC 63 Z9 66 U1 0 U2 14 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD JAN 23 PY 2006 VL 14 IS 2 BP 726 EP 735 DI 10.1364/OPEX.14.000726 PG 10 WC Optics SC Optics GA 008AG UT WOS:000235012000032 PM 19503391 ER PT J AU Ho, NH Weissleder, R Tung, CS AF Ho, NH Weissleder, R Tung, CS TI Development of water-soluble far-red fluorogenic dyes for enzyme sensing SO TETRAHEDRON LA English DT Article DE fluorogenic; fluorescent probe; water-soluble; nile blue; protease; leucine aminopeptidase ID AGGREGATION EQUILIBRIA; XANTHENE DYES; SPECTRA; ASSAYS; SALTS AB A series of Nile Blue analogs, 5-amino-9-dialkylamino benzo[a]phenoxazine dyes, 7-9, were prepared by condensation of N-alkyl or N-sulfo-propyl 4-arylazo-substituted 3-hydroxyaniline with 4-arylazo-substituted 1-naphthlamines or 8-amino-2-naphthalene-sulfonic acid in the presence of perchloric acid. These fluorochromes have excitation and emission maxima near 640 and 680 rim, respectively. The fluorescence intensity in aqueous solution increases as additional sulfonate groups are added to the benzo[a]phenoxazine core. Compound 7, which has two sulfonate groups, is ten-times brighter than Nile Blue. Fluorogenic substrates containing this hydrophilic far-red dye were synthesized and applied to detect enzymatic activities of two model proteases, trypsin and leucine aminopeptidase. Given their excellent fluorogenic property, these novel far-red dyes should be useful for enzyme sensing in biological assays. (c) 2005 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Tung, CS (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. EM tung@helix.mgh.harvard.edu OI Tung, Ching-Hsuan/0000-0001-6648-6195 NR 22 TC 47 Z9 47 U1 4 U2 26 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0040-4020 J9 TETRAHEDRON JI Tetrahedron PD JAN 23 PY 2006 VL 62 IS 4 BP 578 EP 585 DI 10.1016/j.tet.2005.10.020 PG 8 WC Chemistry, Organic SC Chemistry GA 004WG UT WOS:000234782700007 ER PT J AU Metlay, JP Fishman, NO Joffe, M Edelstein, PH AF Metlay, JP Fishman, NO Joffe, M Edelstein, PH TI Impact of pediatric vaccination with pneumococcal conjugate vaccine on the risk of bacteremic pneumococcal pneumonia in adults SO VACCINE LA English DT Article; Proceedings Paper CT 4th International Symposium on Pneumococci and Pneumococcal Diseases CY MAY 09-13, 2004 CL Helsinki, FINLAND DE pneumococcal infections; pneumococcal vaccines; bacteremia; herd immunity ID POLYSACCHARIDE VACCINE; DISEASE; CARRIAGE AB Invasive pneumococcal disease in adults may be declining, reflecting a form of herd protection from a new pediatric pneumococcal conjugate vaccine. Our aim was to determine whether vaccination of children protects adults in the same home from bacteremic pneumococcal pneumonia. We conducted a case-control study with 43 participating hospitals across a five-county region in Pennsylvania. Eligible cases were adults with bacteremic pneumococcal pneumonia identified by the microbiology laboratories at participating hospitals. Controls were healthy adults from the region identified through random digit dialing. Cases and controls were interviewed by telephone. We analyzed vaccine protection in those adults who reported living in homes with at least one child <= 6 years of age. From April 2002 through June 2004, there was a significant decline in the proportion of adult pneumococcal bacteremia due to any of the seven serotypes in the conjugate vaccine (p = 0.006). Within this time period, 17% of cases and controls reported living in homes with at least one child <= 6 years of age. In adjusted analysis, vaccination of the youngest child in the home was associated with an 80% reduction in the odds of bacteremic pneumococcal pneumonia among adults with children in the home (OR= 0.2, 95% Cl 0.1-0.8). We conclude that introduction of a pneumococcal conjugate vaccine for children has reduced the population rate of adult pneumococcal bacteremia due to vaccine serotypes and is associated with a reduced risk of bacteremic pneumococcal pneumonia for adults with children in the home. (c) 2005 Elsevier Ltd. All rights reserved. C1 Vet Affairs Med Ctr, Dept Vet Affairs, Philadelphia, PA 19104 USA. Univ Penn, Dept Med, Sch Med, Philadelphia, PA 19104 USA. Univ Penn, Dept Biostat & Epidemiol, Sch Med, Philadelphia, PA 19104 USA. Univ Penn, Ctr Educ & Res Therapeut, Sch Med, Philadelphia, PA 19104 USA. Univ Penn, Dept Pathol & Lab Med, Sch Med, Philadelphia, PA 19104 USA. RP Metlay, JP (reprint author), Vet Affairs Med Ctr, Dept Vet Affairs, 9th Floor, Philadelphia, PA 19104 USA. EM jmetlay@cceb.med.upenn.edu FU NIAID NIH HHS [R01 AI 46645] NR 18 TC 31 Z9 34 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD JAN 23 PY 2006 VL 24 IS 4 BP 468 EP 475 DI 10.1016/j.vaccine.2005.07.095 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 008OZ UT WOS:000235051600010 PM 16125826 ER PT J AU Liu, Y Teeter, MM DuRand, CJ Neve, KA AF Liu, Y Teeter, MM DuRand, CJ Neve, KA TI Identification of a Zn2+-binding site on the dopamine D-2 receptor SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE allosteric modulation; zinc ion-binding site; dopamine D-2 receptor; site-directed mutagenesis ID BINDING-SITE; BETA(2)-ADRENERGIC RECEPTOR; ALLOSTERIC MODULATION; OPIOID RECEPTOR; ZINC; ACTIVATION; MECHANISMS; SODIUM; INHIBITION; PROTEINS AB Zinc (II) modulates the function of many integral membrane proteins. To identify the Zn2+-binding site responsible for allosteric modulation of the D-2 dopamine receptor, we first demonstrated that the binding site is likely located in extracellular loops or in transmembrane regions that are accessible from the extracellular milieu. We mutated every histidine in these regions to alanine; two mutants, H394A and H399A, exhibited a reduced response to Zn2+. Combined mutation of H394 and H399 caused a larger effect of zinc than did either single mutation. Mutation of other potential Zn2+-binding residues predicted to be in proximity to H394 or H399 did not substantially alter the potency of Zn2+. The double mutant H394A/H399A was similar to D-2 in affinity for [H-3]spiperone and ability to inhibit cyclic AMP accumulation. We conclude that binding of Zn2+ to H394 and H399 on the dopamine D, receptor contributes to allosteric regulation of antagonist binding. (c) 2005 Elsevier Inc. All rights reserved. C1 Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. Portland Vet Affairs Med Ctr, Portland, OR 97239 USA. Univ Calif Davis, Dept Psychiat, Davis, CA 95616 USA. Univ Calif Davis, Dept Chem, Davis, CA 95616 USA. Boston Coll, Dept Chem, Chestnut Hill, MA 02467 USA. RP Neve, KA (reprint author), Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. EM nevek@ohsu.edu OI Neve, Kim/0000-0003-0109-7345 NR 38 TC 14 Z9 15 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JAN 20 PY 2006 VL 339 IS 3 BP 873 EP 879 DI 10.1016/j.bbrc.2005.11.110 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 000CT UT WOS:000234439200023 PM 16332354 ER EF