FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Coelho, PG Freire, JN Granato, R Marin, C Bonfante, EA Gil, JN Chuang, SK Suzuki, M AF Coelho, Paulo G. Freire, Jose N. Granato, Rodrigo Marin, Charles Bonfante, Estevam A. Gil, Jose N. Chuang, Sung-Kiang Suzuki, Marcelo TI Bone Mineral Apposition Rates at Early Implantation Times Around Differently Prepared Titanium Surfaces: A Study in Beagle Dogs SO INTERNATIONAL JOURNAL OF ORAL & MAXILLOFACIAL IMPLANTS LA English DT Article DE endosseous implant; in vivo; mineral apposition rate; surface properties ID PLASMA-SPRAYED HYDROXYAPATITE; CALCIUM-PHOSPHATE COATINGS; IN-VIVO; HISTOMORPHOMETRIC EVALUATION; BIOCERAMIC DEPOSITION; ENDOSSEOUS IMPLANTS AB Purpose: This study evaluated the bone mineral apposition rate (MAR) at the bone-implant interface region of alumina-blasted/acid-etched (AB/AE), plasma-sprayed hydroxyapatite (PSHA), and nanometric-scale bioceramic-coated surfaces at early implantation times in a dog tibia model. Materials and Methods: Implants (n = 12 per group) with three different surfaces AB/AE, PSHA, and a bioceramic coating in the 300- to 500-nm thickness range were placed bilaterally along the proximal tibiae of six male beagles. Implants remained for 3 and 5 weeks in vivo. Ten and 2 days prior to euthanization, calcein green and oxytetracycline were administered for bone labeling. Following euthanization, the limbs were retrieved by sharp dissection and the implants and bone were processed nondecalcified into similar to 30-mu m-thick sections along the implant long axis. MAR was measured by the distance between bone labels over time at the interface region (to 0.5 mm from the implant surface) and at regions > 3 mm from the implant surface (remote site). A generalized linear mixed-effects analysis of variance model was conducted with significance levels set at .05. Results: Irrespective of implant surface, the MAR at the interface region was significantly higher than the MAR at the remote site. Significant MAR differences in the interface region were observed between the different surfaces (PSHA > AB/AE > nano). Conclusions: Bone kinetics during early healing stages were influenced by implant surface modifications. INT J ORAL MAXILLOFAC IMPLANTS 2011;26:63-69 C1 [Coelho, Paulo G.; Bonfante, Estevam A.] NYU, Dept Biomat & Biomimetics, New York, NY 10010 USA. [Granato, Rodrigo; Gil, Jose N.] Univ Fed Santa Catarina, Dept Dent, Florianopolis, SC, Brazil. [Marin, Charles] Pontificia Univ Catolica Rio Grande do Sul, Sch Dent, Dept Oral & Maxillofacial Surg, Porto Alegre, RS, Brazil. [Chuang, Sung-Kiang] Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. [Chuang, Sung-Kiang] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Suzuki, Marcelo] Tufts Univ, Sch Dent Med, Dept Prosthodont, Boston, MA 02111 USA. RP Coelho, PG (reprint author), NYU, Dept Biomat & Biomimetics, 345 24th St,Room 806, New York, NY 10010 USA. EM pgcoelho@nyu.edu RI Bonfante, Estevam/F-7238-2012; Marin, Charles/I-1821-2012; Granato, Rodrigo/A-5372-2013 OI Bonfante, Estevam/0000-0001-6867-8350; FU Experimental Research Laboratory and Department of Oral and Maxillofacial Surgery at Universidade Federal de Santa Catarina, Florianopolis, Brazil FX This study was partially supported by the Experimental Research Laboratory and Department of Oral and Maxillofacial Surgery at Universidade Federal de Santa Catarina, Florianopolis, Brazil. NR 34 TC 10 Z9 14 U1 0 U2 3 PU QUINTESSENCE PUBLISHING CO INC PI HANOVER PARK PA 4350 CHANDLER DRIVE, HANOVER PARK, IL 60133 USA SN 0882-2786 J9 INT J ORAL MAX IMPL JI Int. J. Oral Maxillofac. Implants PD JAN-FEB PY 2011 VL 26 IS 1 BP 63 EP 69 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 724HA UT WOS:000287565500005 PM 21365039 ER PT J AU Mulert, C Kirsch, V Pascual-Marqui, R McCarley, RW Spencer, KM AF Mulert, C. Kirsch, V. Pascual-Marqui, Roberto McCarley, Robert W. Spencer, Kevin M. TI Long-range synchrony of gamma oscillations and auditory hallucination symptoms in schizophrenia SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Article DE EEG; ASSR; Gamma-band; 40 Hz; Schizophrenia; Auditory stimulation; LORETA ID WHITE-MATTER ABNORMALITIES; CORPUS-CALLOSUM; ELECTROMAGNETIC TOMOGRAPHY; 1ST-EPISODE SCHIZOPHRENIA; FUNCTIONAL CONNECTIVITY; ONSET SCHIZOPHRENIA; BAND RESPONSE; BRAIN; EEG; CORTEX AB Phase locking in the gamma-band range has been shown to be diminished in patients with schizophrenia. Moreover, there have been reports of positive correlations between phase locking in the gamma-band range and positive symptoms, especially hallucinations. The aim of the present study was to use a new methodological approach in order to investigate gamma-band phase synchronization between the left and right auditory cortex in patients with schizophrenia and its relationship to auditory hallucinations. Subjects were 18 patients with chronic schizophrenia (SZ) and 16 healthy control (HC) subjects. Auditory hallucination symptom scores were obtained using the Scale for the Assessment of Positive Symptoms. Stimuli were 40-Hz binaural click trains. The generators of the 40 Hz-ASSR were localized using eLORETA and based on the computed intracranial signals lagged interhemispheric phase locking between primary and secondary auditory cortices was analyzed. Current source density of the 40 ASSR response was significantly diminished in SZ in comparison to HC in the right superior and middle temporal gyrus (p < 0.05). Interhemispheric phase locking was reduced in SZ in comparison to HC for the primary auditory cortices (p < 0.05) but not in the secondary auditory cortices. A significant positive correlation was found between auditory hallucination symptom scores and phase synchronization between the primary auditory cortices (p < 0.05, corrected for multiple testing) but not for the secondary auditory cortices. These results suggest that long-range synchrony of gamma oscillations is disturbed in schizophrenia and that this deficit is related to clinical symptoms such as auditory hallucinations. (C) 2010 Elsevier B.V. All rights reserved. C1 [Mulert, C.; Kirsch, V.; McCarley, Robert W.; Spencer, Kevin M.] VA Boston Healthcare Syst, Dept Psychiat, Boston, MA 02132 USA. [Mulert, C.; Kirsch, V.; McCarley, Robert W.; Spencer, Kevin M.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Mulert, C.] Univ Med Ctr Hamburg Eppendorf, Dept Psychiat & Psychotherapy, Psychiat Neuroimaging Branch, Hamburg, Germany. [Kirsch, V.] Univ Munich, Dept Psychiat & Psychotherapy, Munich, Germany. [Pascual-Marqui, Roberto] Univ Hosp Psychiat, KEY Inst Brain Mind Res, Zurich, Switzerland. RP Mulert, C (reprint author), Martinistr 52, D-20246 Hamburg, Germany. EM c.mulert@uke.de RI Mulert, Christoph/F-2576-2012; Pascual-Marqui, Roberto/A-2012-2008; McCarley, Robert/N-5562-2014; OI Pascual-Marqui, Roberto/0000-0002-5029-4065; McCarley, Robert/0000-0001-5705-7495; Spencer, Kevin/0000-0002-5500-7627 FU US Department of Veterans Affairs Research Enhancement Award Program and Schizophrenia Center; US National Institute of Mental Health [R01 40799, R03 076760, R01 MH080187]; NARSAD; German Society for Psychiatry, Psychotherapy and Neurology (DGPPN) FX This work was supported by a US Department of Veterans Affairs Research Enhancement Award Program and Schizophrenia Center (RWM); US National Institute of Mental Health Grants R01 40799 (RWM), R03 076760 (KMS), and R01 MH080187 (KMS); and a NARSAD Young Investigator Award (KMS). CM was supported by a grant of the German Society for Psychiatry, Psychotherapy and Neurology (DGPPN). NR 69 TC 56 Z9 57 U1 4 U2 16 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD JAN PY 2011 VL 79 IS 1 SI SI BP 55 EP 63 DI 10.1016/j.ijpsycho.2010.08.004 PG 9 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 728TD UT WOS:000287896500009 PM 20713096 ER PT J AU Flanagan, J Winters, L Habin, K Cashavelly, B AF Flanagan, Jane Winters, Loren Habin, Karleen Cashavelly, Barbara TI The lived experience of women on long-term endocrine based oral treatment for breast cancer SO INTERNATIONAL JOURNAL OF QUALITATIVE METHODS LA English DT Meeting Abstract C1 [Flanagan, Jane] Boston Coll, Chestnut Hill, MA 02167 USA. [Winters, Loren; Habin, Karleen; Cashavelly, Barbara] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV ALBERTA, INT INST QUALITATIVE METHODOLOGY PI EDMONTON PA 5-217, EDMONTON CLINIC HEALTH ACAD, 11405 87 AVENUE, EDMONTON, AB T6G 1C9, CANADA SN 1609-4069 J9 INT J QUAL METH JI Int. J. Qual. Meth. PY 2011 VL 10 IS 4 BP 512 EP 513 PG 2 WC Social Sciences, Interdisciplinary SC Social Sciences - Other Topics GA 059ZL UT WOS:000312744200115 ER PT J AU Korideck, H Ngwa, W Makrigiorgos, M Barbeco, RI AF Korideck, H. Ngwa, W. Makrigiorgos, M. Barbeco, R. I. TI The Quantification Of Gold Nanoparticles As Contrast Agents For Small Animal Volumetric Studies SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract C1 [Korideck, H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Korideck, H.; Ngwa, W.; Makrigiorgos, M.; Barbeco, R. I.] Harvard Univ, Sch Med, Boston, MA USA. [Ngwa, W.; Makrigiorgos, M.; Barbeco, R. I.] Brigham & Women Hosp, Boston, MA USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2011 VL 81 IS 2 SU S BP S887 EP S888 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 840AX UT WOS:000296411701915 ER PT J AU MacDonald, SM Trofimov, A Safai, S Adams, J Fullerton, B Ebb, D Tarbell, NJ Yock, TI AF MacDonald, Shannon M. Trofimov, Alexei Safai, Sairos Adams, Judith Fullerton, Barbara Ebb, David Tarbell, Nancy J. Yock, Torunn I. TI PROTON RADIOTHERAPY FOR PEDIATRIC CENTRAL NERVOUS SYSTEM GERM CELL TUMORS: EARLY CLINICAL OUTCOMES SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 51st Annual Meeting of the American-Society-for-Therapeutic-Radiology-and Oncology CY OCT 31-NOV 05, 2009 CL Chicago, IL SP Amer Soc Therapeut Radiol & Oncol DE Protons; Germ cell tumor; Pediatric brain tumors ID INTENSITY-MODULATED RADIOTHERAPY; MODELING RADIATION-DOSIMETRY; PREDICT COGNITIVE OUTCOMES; CNS EMBRYONAL TUMORS; BRAIN-TUMORS; INTRACRANIAL GERMINOMAS; NEUROPSYCHOLOGICAL STATUS; POSTERIOR-FOSSA; THERAPY; TERM AB Purpose: To report early clinical outcomes for children with central nervous system (CNS) germ cell tumors treated with protons; to compare dose distributions for intensity-modulated photon radiotherapy (IMRT), three-dimensional conformal proton radiation (3D-CPT), and intensity-modulated proton therapy with pencil beam scanning (IMPT) for whole-ventricular irradiation with and without an involved-field boost. Methods and Materials: All children with CNS germinoma or nongerminomatous germ cell tumor who received treatment at the Massachusetts General Hospital between 1998 and 2007 were included in this study. The IMRT, 3D-CPT, and IMPT plans were generated and compared for a representative case. Results: Twenty-two patients were treated with 3D-CPT. At a median follow-up of 28 months, there were no CNS recurrences; 1 patient had a recurrence outside the CNS. Local control, progression-free survival, and overall survival rates were 100%, 95%, and 100%, respectively. Comparable tumor volume coverage was achieved with IMRT, 3D-CPT, and IMPT. Substantial normal tissue sparing was seen with any form of proton therapy as compared with IMRT. The use of IMPT may yield additional sparing of the brain and temporal lobes. Conclusions: Preliminary disease control with proton therapy compares favorably to the literature. Dosimetric comparisons demonstrate the advantage of proton radiation over IMRT for whole-ventricle radiation. Superior dose distributions were accomplished with fewer beam angles utilizing 3D-CPT and scanned protons. Intensity-modulated proton therapy with pencil beam scanning may improve dose distribution as compared with 3D-CPT for this treatment. (C) 2011 Elsevier Inc. C1 [MacDonald, Shannon M.; Trofimov, Alexei; Safai, Sairos; Adams, Judith; Fullerton, Barbara; Ebb, David; Tarbell, Nancy J.; Yock, Torunn I.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP MacDonald, SM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Cox 340,100 Blossom St, Boston, MA 02114 USA. EM smacdonald@partners.org NR 49 TC 38 Z9 39 U1 0 U2 3 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 JAN 1 PY 2011 VL 79 IS 1 BP 121 EP 129 DI 10.1016/j.ijrobp.2009.10.069 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 699IH UT WOS:000285656600018 PM 20452141 ER PT J AU Hong, TS Ryan, DP Blaszkowsky, LS Mamon, HJ Kwak, EL Mino-Kenudson, M Adams, J Yeap, B Winrich, B DeLaney, TF Fernandez-Del Castillo, C AF Hong, Theodore S. Ryan, David P. Blaszkowsky, Lawrence S. Mamon, Harvey J. Kwak, Eunice L. Mino-Kenudson, Mari Adams, Judith Yeap, Beow Winrich, Barbara DeLaney, Thomas F. Fernandez-Del Castillo, Carlos TI PHASE I STUDY OF PREOPERATIVE SHORT-COURSE CHEMORADIATION WITH PROTON BEAM THERAPY AND CAPECITABINE FOR RESECTABLE PANCREATIC DUCTAL ADENOCARCINOMA OF THE HEAD SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Pancreatic cancer; Chemoradiation; Pancreaticoduodenectomy; Short-course radiotherapy; Proton beam ID RANDOMIZED CONTROLLED-TRIAL; RECTAL-CANCER; RADIATION-THERAPY; PERIAMPULLARY CARCINOMA; ADJUVANT CHEMOTHERAPY; RADIOTHERAPY; FAILURE; RESECTION; PATTERNS; SURVIVAL AB Purpose: To evaluate the safety of 1 week of chemoradiation with proton beam therapy and capecitabine followed by early surgery. Methods and Materials: Fifteen patients with localized resectable, pancreatic adenocarcinoma of the head were enrolled from May 2006 to September 2008. Patients received radiation with proton beam. In dose level I, patients received 3 GyE x 10 (Week 1, Monday-Friday; Week 2, Monday-Friday). Patients in Dose Levels 2 to 4 received 5 GyE x Sin progressively shortened schedules: level 2 (Week 1, Monday, Wednesday, and Friday; Week 2, Tuesday and Thursday), Level 3 (Week I, Monday, Tuesday, Thursday, and Friday; Week 2, Monday), Level 4 (Week 1, Monday through Friday). Capecitabine was given as 825 mg/m(2) b.i.d. Weeks 1 and 2 Monday through Friday for a total of 10 days in all dose levels. Surgery was performed 4 to 6 weeks after completion of chemotherapy for Dose Levels 1 to 3 and then after 1 to 3 weeks for Dose Level 4. Results: Three patients were treated at Dose Levels 1 to 3 and 6 patients at Dose Level 4, which was selected as the MTD. No dose limiting toxicities were observed. Grade 3 toxicity was noted in 4 patients (pain in 1; stent obstruction or infection in 3). Eleven patients underwent resection. Reasons for no resection were metastatic disease (3 patients) and unresectable tumor (1 patient). Mean postsurgical length of stay was 6 days (range, 5-10 days). No unexpected 30-day postoperative complications, including leak or obstruction, were found. Conclusions: Preoperative chemoradiation with 1 week of proton beam therapy and capecitabine followed by early surgery is feasible. A Phase II study is underway. (C) 2011 Elsevier Inc. C1 [Hong, Theodore S.; Adams, Judith; Winrich, Barbara; DeLaney, Thomas F.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Ryan, David P.; Blaszkowsky, Lawrence S.; Kwak, Eunice L.; Yeap, Beow] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA. [Mino-Kenudson, Mari] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Fernandez-Del Castillo, Carlos] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Mamon, Harvey J.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiat Oncol,Dana Farber Canc Inst, Boston, MA 02114 USA. RP Hong, TS (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM tshong1@partners.org FU Massachusetts General Hospital, Proton Therapy Research and Treatment Center [C06 CA059267] FX This project was supported by the Federal Share of program income earned by Massachusetts General Hospital on C06 CA059267, Proton Therapy Research and Treatment Center. NR 27 TC 28 Z9 28 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JAN 1 PY 2011 VL 79 IS 1 BP 151 EP 157 DI 10.1016/j.ijrobp.2009.10.061 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 699IH UT WOS:000285656600022 PM 20421151 ER PT J AU Knopf, AC Parodi, K Paganetti, H Bortfeld, T Daartz, J Engelsman, M Liebsch, N Shih, H AF Knopf, Antje-Christin Parodi, Katia Paganetti, Harald Bortfeld, Thomas Daartz, Juliane Engelsman, Martijn Liebsch, Norbert Shih, Helen TI ACCURACY OF PROTON BEAM RANGE VERIFICATION USING POST-TREATMENT POSITRON EMISSION TOMOGRAPHY/COMPUTED TOMOGRAPHY AS FUNCTION OF TREATMENT SITE SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Protons; range verification; positron emission tomography; computed tomography; PET/CT ID THERAPY; DISTRIBUTIONS; PET/CT AB Purpose: For 23 patients, an off-line positron emission tomography scan and a computed tomography scan after proton radiotherapy was performed at the Massachusetts General Hospital to assess in vivo treatment verification. A well-balanced population of patients was investigated to assess the effect of the tumor location on the accuracy of the technique. Methods and Materials: Range verification was achieved by comparing the measured positron emission tomography activity distributions with the corresponding Monte Carlo-simulated distributions. Observed differences in the distal end of the activity distributions were analyzed as potential indicators for the range differences between the actual delivered and planned dose. Results: The average spatial agreement between the measured and simulated activity distribution was within +/- 3 mm, and the corresponding average absolute agreement was within +/- 45% (derived from gamma index analysis). The mean absolute range deviation at 93 randomly chosen positions in 17 treatment fields delivered to 11 patients was 3.6 mm. Characteristic differences in the agreement of the measured and simulated activity distribution for the different tumor/target sites were found. This resulted from the different effect of factors such as biologic washout effects, motion, or limitations in the Monte Carlo-simulated activity patterns. Conclusion: We found that intracranial and cervical spine patients can greatly benefit from off-line positron emission tomography and computed tomography range verification. However, for the successful application of the method to patients with abdominopelvic tumors, major technological and methodologic improvements are needed. Among the intracranial and cervical spine target sites, patients with arteriovenous malformations or metal implants represent groups that could especially benefit from the approach. (C) 2011 Elsevier Inc. C1 [Knopf, Antje-Christin; Paganetti, Harald; Bortfeld, Thomas; Daartz, Juliane; Engelsman, Martijn; Liebsch, Norbert; Shih, Helen] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Knopf, Antje-Christin; Paganetti, Harald; Bortfeld, Thomas; Daartz, Juliane; Engelsman, Martijn; Liebsch, Norbert; Shih, Helen] Harvard Univ, Sch Med, Boston, MA USA. [Knopf, Antje-Christin; Daartz, Juliane] German Canc Res Ctr DKFZ Heidelberg, Dept Med Phys, Heidelberg, Germany. [Parodi, Katia] Heidelberg Ion Beam Therapy Ctr, Heidelberg, Germany. RP Knopf, AC (reprint author), Paul Scherrer Inst, CH-5232 Villigen, Switzerland. EM antje-christin.knopf@psi.ch NR 11 TC 38 Z9 38 U1 0 U2 8 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 JAN 1 PY 2011 VL 79 IS 1 BP 297 EP 304 DI 10.1016/j.ijrobp.2010.02.017 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 699IH UT WOS:000285656600042 PM 20646839 ER PT J AU Alam, HB AF Alam, Hasan B. TI Advances in resuscitation strategies SO INTERNATIONAL JOURNAL OF SURGERY LA English DT Review DE Hemorrhage; Resuscitation; Shock; Sepsis; Bleeding; Blood; Fluids ID HYPERTONIC SALINE RESUSCITATION; I TRAUMA CENTER; HYPOTHERMIC CARDIOPULMONARY BYPASS; AGGRESSIVE FLUID RESUSCITATION; UNCONTROLLED HEMORRHAGIC-SHOCK; MASSIVE TRANSFUSION PROTOCOL; SWINE MODEL; PROFOUND HYPOTHERMIA; SEPTIC SHOCK; LETHAL HEMORRHAGE AB Shock, regardless of etiology is characterized by decreased delivery of oxygen and nutrients to the tissues and our interventions are directed towards reversing the cellular ischemia and preventing its consequences. The treatment strategies that are most effective in achieving this goal obviously depend upon the different types of shock (hemorrhagic, septic, neurogenic and cardiogenic). This brief review focuses on the two leading etiologies of shock in the surgical patients: bleeding and sepsis, and addresses a number of new developments that have profoundly altered the treatment paradigms. The emphasis here is on new research that has dramatically altered our treatment strategies rather than the basic pathophysiology of shock. (C) 2010 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved. C1 [Alam, Hasan B.] Massachusetts Gen Hosp, Div Trauma Emergency Med & Surg Crit Care, Boston, MA 02114 USA. [Alam, Hasan B.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Alam, HB (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Med & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM hbalam@partners.org FU National Institutes of Health; US Department of Defense; Office of Naval Research, US Army Medical Research and Materiel Command, Defense Advanced Research Projects Agency FX National Institutes of Health and US Department of Defense.; The author would like to acknowledge research support provided by numerous grants by the Office of Naval Research, US Army Medical Research and Materiel Command, Defense Advanced Research Projects Agency, and National Institutes of Health. NR 136 TC 4 Z9 9 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1743-9191 J9 INT J SURG JI Int. J. Surg. PY 2011 VL 9 IS 1 BP 5 EP 12 DI 10.1016/j.ijsu.2010.09.001 PG 8 WC Surgery SC Surgery GA 832BI UT WOS:000295775000003 PM 20833279 ER PT S AU Kushniruk, AW Santos, SL Pourakis, G Nebeker, JR Boockvar, KS AF Kushniruk, Andre W. Santos, Susan L. Pourakis, George Nebeker, Jonathan R. Boockvar, Kenneth S. BE Borycki, EM BartleClar, JA Househ, MS Kuziemsky, CE Schraa, EG TI Cognitive Analysis of a Medication Reconciliation Tool: Applying Laboratory and Naturalistic Approaches to System Evaluation SO INTERNATIONAL PERSPECTIVES IN HEALTH INFORMATICS SE Studies in Health Technology and Informatics LA English DT Proceedings Paper CT Information Technology and Communications in Health (ITCH) Conference CY FEB, 2011 CL Univ Victoria, Sch Hlth Informat Sci, Victoria, CANADA HO Univ Victoria, Sch Hlth Informat Sci DE medication reconciliation; patient safety; cognitive analysis AB Adverse drug events can occur as a result of handoffs in patient care. To reduce the possibility of this occurring, the process of medication reconciliation (whereby the patient's medication history is compared to current and previous medications to ensure accuracy) is becoming recognized as becoming increasingly important. To address this, computerized medication reconciliation tools have been developed. This paper describes a combined approach to evaluating the impact of such a tool. The approach has included both an artificial laboratory-based evaluation component (involving observing subjects interacting with standardized patient cases), as well as a naturalistic condition (involving real patient cases). The results indicate that there are differences in the way that subjects interact with the medication reconciliation tool, with significant differences identified in the amount of time spent and accuracy of medication documentation between physician and pharmacist users. C1 [Kushniruk, Andre W.] Univ Victoria, Sch Hlth Informat Sci, Victoria, BC, Canada. [Santos, Susan L.] VA New Jersey Hlth Care Syst, E Orange, NJ USA. [Santos, Susan L.] Univ Med & Dent New Jersey, Dept Hlth Educ & Behav Sci, New Brunswick, NJ USA. [Pourakis, George] Ctr Dis Control & Prevent, Atlanta, GA USA. [Nebeker, Jonathan R.] VA Geriatr Res Educ & Clin Ctr, Salt Lake City, UT USA. [Boockvar, Kenneth S.] James J Peters Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. [Boockvar, Kenneth S.] Mt Sinai Sch Med, Dept Geriatr & Palliat Med, New York, NY USA. [Boockvar, Kenneth S.] Jewish Home Lifecare, New York, NY USA. RP Kushniruk, AW (reprint author), Univ Victoria, Sch Hlth Informat Sci, Victoria, BC, Canada. EM andrek@uvic.ca OI Boockvar, Kenneth/0000-0003-1165-5558 NR 3 TC 7 Z9 7 U1 0 U2 1 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 978-1-60750-709-3 J9 STUD HEALTH TECHNOL PY 2011 VL 164 BP 203 EP 207 DI 10.3233/978-1-60750-709-3-203 PG 5 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA BG8DA UT WOS:000392222000033 PM 21335711 ER PT S AU Lok, J Leung, W Murphy, S Butler, W Noviski, N Lo, EH AF Lok, Josephine Leung, Wendy Murphy, Sarah Butler, William Noviski, Natan Lo, Eng H. BE Zhang, JH Colohan, A TI Intracranial Hemorrhage: Mechanisms of Secondary Brain Injury SO INTRACEREBRAL HEMORRHAGE RESEARCH: FROM BENCH TO BEDSIDE SE Acta Neurochirurgica Supplementum LA English DT Article; Book Chapter DE Intracranial hemorrhage; Heme toxicity; Iron toxicity; Coagulation; Inflammation; Vascular response ID TRAUMATIC INTRACEREBRAL HEMORRHAGE; CEREBRAL-ARTERY OCCLUSION; SUBARACHNOID HEMORRHAGE; CEREBROSPINAL-FLUID; OXIDATIVE STRESS; RAT MODEL; INFLAMMATION; HEME; HAPTOGLOBIN; HEMOGLOBIN AB ICH is a disease with high rates of mortality and morbidity, with a substantial public health impact. Spontaneous ICH (sICH) has been extensively studied, and a large body of data has been accumulated on its pathophysiology. However, the literature on traumatic ICH (tICH) is limited, and further investigations of this important topic are needed. This review will highlight some of the cellular pathways in ICH with an emphasis on the mechanisms of secondary injury due to heme toxicity and to events in the coagulation process that are common to both sICH and tICH. C1 [Lok, Josephine; Leung, Wendy; Lo, Eng H.] Massachusetts Gen Hosp, Neuroprotect Res Lab, Boston, MA 02114 USA. [Lok, Josephine; Leung, Wendy; Murphy, Sarah; Noviski, Natan] Massachusetts Gen Hosp, Dept Pediat Pediat Crit Care Med, Boston, MA 02114 USA. [Butler, William] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Lo, Eng H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Lo, Eng H.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Lok, J (reprint author), Massachusetts Gen Hosp, Neuroprotect Res Lab, Boston, MA 02114 USA. EM jlok1@partners.org FU NINDS NIH HHS [K08 NS057339, K08 NS057339-02, K08NS057339, P01 NS055104, P01 NS055104-04, R01 NS053560, R01 NS053560-05, R01 NS076694, R37 NS037074] NR 69 TC 24 Z9 26 U1 0 U2 3 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, A-1201 VIENNA, AUSTRIA SN 0065-1419 BN 978-3-7091-0692-1 J9 ACTA NEUROCHIR SUPPL JI Acta Neurochir. Suppl. PY 2011 VL 111 BP 63 EP 69 DI 10.1007/978-3-7091-0693-8_11 D2 10.1007/978-3-7091-0693-8 PG 7 WC Medicine, Research & Experimental; Clinical Neurology SC Research & Experimental Medicine; Neurosciences & Neurology GA BGT35 UT WOS:000324076300011 PM 21725733 ER PT J AU Zhang, Y Peng, Q Kiel, JW Rosende, CA Duong, TQ AF Zhang, Yi Peng, Qi Kiel, Jeffrey W. Rosende, Carlos A. Duong, Timothy Q. TI Magnetic Resonance Imaging of Vascular Oxygenation Changes during Hyperoxia and Carbogen Challenges in the Human Retina SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID LASER-DOPPLER FLOWMETRY; CHOROIDAL BLOOD-FLOW; FUNCTIONAL MRI; OPTIC-NERVE; LAMINAR SPECIFICITY; IN-VIVO; 7 TESLA; RESOLUTION; BRAIN; CATS AB PURPOSE. To demonstrate blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) of vascular oxygenation changes in normal, unanesthetized human retinas associated with oxygen and carbogen challenge. METHODS. MRI was performed with a 3-T human scanner and a custom-made surface-coil detector on normal volunteers. BOLD MRI with inversion recovery was used to suppress the vitreous signal. During MRI measurements, volunteers underwent three episodes of air and 100% oxygen or carbogen (5% CO2 and 95% O-2) breathing. Eye movement was effectively managed with eye fixation, synchronized blinks, and postprocessing image coregistration. BOLD time-series images were analyzed using the cross-correlation method. Percent changes due to oxygen or carbogen inhalation versus air were tabulated for whole-retina and different regions of the retina. RESULTS. Robust BOLD responses were detected. BOLD MRI percent change from a large region of interest at the posterior pole of the retina was 5.2 +/- 1.5% (N = 9 trials from five subjects) for oxygen inhalation and 5.2 +/- 1.3% (N = 11 trials from five subjects) for carbogen inhalation. Group-averaged BOLD percent changes were not significantly different between oxygen and carbogen challenges (P > 0.05). The foveal region had greater BOLD response compared with the optic nerve head region for both challenges. CONCLUSIONS. BOLD retinal responses to oxygen and carbogen breathing in unanesthetized humans can be reliably imaged at high spatiotemporal resolution. BOLD MRI has the potential to provide a valuable tool to study retinal physiology and pathophysiology, such as how vascular oxygenation at the tissue level is regulated in the normal retina, and how retinal diseases may affect oxygen response. (Invest Ophthalmol Vis Sci. 2011; 52: 286-291) DOI: 10.1167/iovs.10-6108 C1 [Zhang, Yi; Peng, Qi; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Zhang, Yi; Peng, Qi; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA. [Kiel, Jeffrey W.; Rosende, Carlos A.; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Ophthalmol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Duong, TQ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. EM duongt@uthscsa.edu RI Duong, Timothy/B-8525-2008 FU Pilot grant; Translational Technology Resource [UL1RR025767]; NIH/NEI [R01 EY014211, EY018855]; Department of Veterans Affairs FX Supported by a Pilot grant (TQD); a Translational Technology Resource grant (QP) via the Clinical Translational Science Award (CTSA, parent Grant UL1RR025767); the NIH/NEI (R01 EY014211 and EY018855 to TQD); and the VISN7 Career Development Award and MERIT from the Department of Veterans Affairs (TQD). NR 53 TC 18 Z9 18 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JAN PY 2011 VL 52 IS 1 BP 286 EP 291 DI 10.1167/iovs.10-6108 PG 6 WC Ophthalmology SC Ophthalmology GA 702VW UT WOS:000285925000036 PM 20847121 ER PT J AU Norose, K Kikumura, A Luster, AD Hunter, CA Harris, TH AF Norose, Kazumi Kikumura, Akitoshi Luster, Andrew D. Hunter, Christopher A. Harris, Tajie H. TI CXCL10 Is Required to Maintain T-Cell Populations and to Control Parasite Replication during Chronic Ocular Toxoplasmosis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; BLOOD-RETINA BARRIER; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CHEMOKINE RECEPTOR CXCR3; IFN-GAMMA; IN-VIVO; GONDII INFECTION; LEUKOCYTE TRAFFICKING; UNITED-STATES; MIGRATION AB PURPOSE. Toxoplasma gondii is a major cause of ocular disease, which can lead to permanent vision loss in humans. T cells are critically involved in parasite control, but little is known about the molecules that promote T-cell trafficking and migration in the retina. Thus, the aim of this study was to image and dissect the T-cell response during chronic toxoplasmic retinochoroiditis. METHODS. C57BL/6 mice were infected with the Me49 strain of T. gondii, and T cells that infiltrated the eye were analyzed by flow cytometry and imaged using multiphoton microscopy. IFN-gamma, CXCL9, CXCL10, and CXCR3 mRNA levels were measured by real-time PCR. To investigate the role of CXCL10, mice were treated with anti-CXCL10 antibodies, and histopathology and immunohistochemistry were performed to monitor changes in pathology, cellular infiltration, and parasite burden in the eye. RESULTS. Infection with T. gondii leads to the infiltration of highly activated motile T cells into the eye. These cells express CXCR3 and are capable of producing IFN-gamma and TNF-alpha, and CD8(+) T cells express granzyme B. The expression of CXCL9 and CXCL10 in the retina was significantly upregulated during chronic infection. Treatment of chronically infected mice with anti-CXCL10 antibodies led to decreases in the numbers of CD3(+), CD4(+), and CD8(+) T cells and the amount of IFN-gamma mRNA expression in the retina and an increase in replicating parasites and ocular pathology. CONCLUSIONS. The maintenance of the T-cell response and the control of T. gondii in the eye during chronic infection is dependent on CXCL10. (Invest Ophthalmol Vis Sci. 2011; 52: 389-398) DOI:10.1167/iovs.10-5819 C1 [Hunter, Christopher A.; Harris, Tajie H.] Univ Penn, Sch Vet Med, Dept Pathobiol, Philadelphia, PA 19104 USA. [Norose, Kazumi; Kikumura, Akitoshi] Chiba Univ, Grad Sch Med, Dept Infect & Host Def, Chiba, Japan. [Luster, Andrew D.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Ctr Immunol & Inflammatory Dis, Charlestown, MA USA. RP Harris, TH (reprint author), Univ Penn, Sch Vet Med, Dept Pathobiol, 380 S Univ Ave, Philadelphia, PA 19104 USA. EM tajieh@vet.upenn.edu RI Hunter, Christopher/H-1970-2011; OI Harris, Tajie/0000-0002-1355-2109 FU National Institutes of Health [AI-41158, AI-42334, T32-AI-055400, AI-081478, R01CA069212]; State of Pennsylvania; Japan Society for the Promotion of Science [20592071]; Ministry of Education, Culture, Sports, Science and Technology of Japan FX Supported by National Institutes of Health Grants AI-41158 (CAH), AI-42334 (CAH), T32-AI-055400 (THH), AI-081478 (THH), R01CA069212 (ADL); the State of Pennsylvania; Japan Society for the Promotion of Science Grant-in-Aid for Scientific Research Grant 20592071 (KN); and the Ministry of Education, Culture, Sports, Science and Technology of Japan (KN). NR 53 TC 21 Z9 22 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JAN PY 2011 VL 52 IS 1 BP 389 EP 398 DI 10.1167/iovs.10-5819 PG 10 WC Ophthalmology SC Ophthalmology GA 718CL UT WOS:000287097400008 PM 20811054 ER PT J AU Burjonroppa, SC Varosy, PD Rao, SV Ou, FS Roe, M Peterson, E Singh, M Shunk, KA AF Burjonroppa, Sukesh C. Varosy, Paul D. Rao, Sunil V. Ou, Fang-Shu Roe, Matthew Peterson, Eric Singh, Mandeep Shunk, Kendrick A. TI Survival of Patients Undergoing Rescue Percutaneous Coronary Intervention Development and Validation of a Predictive Tool SO JACC-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE acute myocardial infarction; predictive tool; rescue percutaneous coronary intervention ID ACUTE MYOCARDIAL-INFARCTION; CARDIOVASCULAR DATA REGISTRY; MIDDLESBROUGH EARLY REVASCULARIZATION; IN-HOSPITAL MORTALITY; THROMBOLYTIC THERAPY; FAILED THROMBOLYSIS; NATIONAL REGISTRY; PRIMARY ANGIOPLASTY; RANDOMIZED-TRIALS; CARDIOGENIC-SHOCK AB Objectives This study sought to develop a tool for predicting an individual's risk of mortality following rescue percutaneous coronary intervention (PCI). Background Although fibrinolytic therapy is appropriate and improves survival for certain ST-segment elevation myocardial infarction patients, a substantial proportion suffer ongoing myocardial ischemia, a class I indication for emergent percutaneous coronary intervention (rescue PCI). Methods Using the National Cardiovascular Data Registry (NCDR), rescue PCI was defined as non-elective PCI following failed fibrinolysis in patients with continuing or recurrent myocardial ischemia. Multivariable logistic regression was used to determine mortality predictors and the C-statistic for model discrimination. The NCDR-RESCUE (Real-World Estimator of Survival in Catheterized STEMI Patients Following Unsuccessful Earlier Fibrinolysis) score was developed using a shortened list of 6 pre-angiographic variables and 70% of the cohort; performance was subsequently validated against the remaining 30%. Results Among 166,516 PCI procedures on patients with an admission diagnosis of ST-segment elevation myocardial infarction, 8,007 (4.8%) represented rescue PCI. In-hospital mortality occurred in 464 (5.8%). Factors in the final model were age, glomerular filtration rate, history of congestive heart failure, insulin-treated diabetes, cardiogenic shock, and salvage status. The NCDR-RESCUE score effectively segregated individuals into 6 clinically meaningful risk categories, with 0.4% (0.0% to 1.3%), 1.6% (0.9% to 2.4%), 7.6% (5.3% to 10.4%), 27.5% (20.7% to 35.1%), 64.2% (49.8% to 76.9%), or 100% (59.0% to 100.0%) risk, respectively, of in-hospital mortality (mean +/- 95% confidence interval, C-index = 0.88, Hosmer-Lemeshow p = 0.898). Conclusions In-hospital mortality risk among individuals undergoing rescue PCI varies from minimal to extreme and can be easily calculated using the NCDR-RESCUE score. This information can be of value in counseling patients, families, and referring caregivers. (J Am Coll Cardiol Intv 2011;4: 42-50) (C) 2011 by the American College of Cardiology Foundation C1 [Burjonroppa, Sukesh C.] Ft Worth Heart PA, Ft Worth, TX 76104 USA. [Varosy, Paul D.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Varosy, Paul D.] Univ Colorado, Denver Sch Med, Denver, CO 80202 USA. [Rao, Sunil V.; Peterson, Eric] Duke Univ, Med Ctr, Durham, NC USA. [Ou, Fang-Shu; Roe, Matthew; Peterson, Eric] Duke Clin Res Inst, Durham, NC USA. [Singh, Mandeep] Mayo Clin, Rochester, MN USA. [Shunk, Kendrick A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Shunk, Kendrick A.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Burjonroppa, SC (reprint author), Ft Worth Heart PA, 1300 W Rosedale, Ft Worth, TX 76104 USA. EM sukeshbc@yahoo.com FU Portola; Cordis Corp.; Novartis; Ikaria; Abbott Vascular, and Siemens Medical Systems FX From the *Fort Worth Heart PA, Fort Worth, Texas; dagger Denver Veterans Affairs Medical Center, and University of Colorado, Denver School of Medicine, Denver, Colorado; double dagger Duke University Medical Center, Durham, North Carolina; Duke Clinical Research Institute, Durham, North Carolina; parallel to Mayo Clinic, Rochester, Minnesota; and the University of California-San Francisco and the San Francisco Veterans Affairs Medical Center, San Francisco, California. Dr. Rao is a consultant for sanofi-aventis, Bristol-Myers Squibb, AstraZeneca, Daiichi Sankyo-Lilly, The Medicines Company, and Terumo USA; and has received research funding from Portola, Cordis Corp., Novartis, and Ikaria. Dr. Shunk received research support from Abbott Vascular, and Siemens Medical Systems; he is on the Advisory Board for GE Healthcare; and he has intellectual property rights from SurgiVision Options (modest) and Revascular Therapeutics. All other authors have reported that they have no relationships to disclose. NR 42 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 1936-8798 J9 JACC-CARDIOVASC INTE JI JACC-Cardiovasc. Interv. PD JAN PY 2011 VL 4 IS 1 BP 42 EP 50 DI 10.1016/j.jcin.2010.09.020 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 719EA UT WOS:000287181500006 PM 21251628 ER PT J AU Walensky, RP Wood, R Fofana, MO Martinson, NA Losina, E April, MD Bassett, IV Morris, BL Freedberg, KA Paltiel, AD AF Walensky, Rochelle P. Wood, Robin Fofana, Mariam O. Martinson, Neil A. Losina, Elena April, Michael D. Bassett, Ingrid V. Morris, Bethany L. Freedberg, Kenneth A. Paltiel, A. David CA Cost-Effectiveness Preventing AIDS TI The Clinical Impact and Cost-Effectiveness of Routine, Voluntary HIV Screening in South Africa SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; cost-effectiveness; screening; South Africa ID RESOURCE-LIMITED SETTINGS; ISPOR TASK-FORCE; ANTIRETROVIRAL THERAPY; COTE-DIVOIRE; HIV-1-INFECTED ADULTS; RANDOMIZED-TRIAL; UNITED-STATES; PROPHYLAXIS; INFECTION; OUTCOMES AB Background: Although 900,000 HIV-infected South Africans receive antiretroviral therapy, the majority of South Africans with HIV remain undiagnosed. Methods: We use a published simulation model of HIV case detection and treatment to examine 3 HIV screening scenarios, in addition to current practice as follows: (1) one-time; (2) every 5 years; and (3) annually. South African model input data include the following: 16.9% HIV prevalence, 1.3% annual incidence, 49% test acceptance rate, HIV testing costs of $6.49/patient, and a 47% linkage-to-care rate (including 2 sequential antiretroviral therapy regimens) for identified cases. Outcomes include life expectancy, direct medical costs, and incremental cost-effectiveness. Results: HIV screening one-time, every 5 years, and annually increase HIV-infected quality-adjusted life expectancy (mean age 33 years) from 180.6 months (current practice) to 184.9, 187.6, and 197.2 months. The incremental cost-effectiveness of one-time screening is dominated by screening every 5 years. Screening every 5 years and annually each have incremental cost-effectiveness ratios of $1570/quality-adjusted life year and $1720/quality-adjusted life year. Screening annually is very cost-effective even in settings with the lowest incidence/prevalence, with test acceptance and linkage rates both as low as 20%, or when accounting for a stigma impact at least four-fold that of the base case. Conclusions: In South Africa, annual voluntary HIV screening offers substantial clinical benefit and is very cost-effective, even with highly constrained access to care and treatment. C1 [Walensky, Rochelle P.; Fofana, Mariam O.; Bassett, Ingrid V.; Morris, Bethany L.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Gen Med, Dept Med, Boston, MA 02114 USA. [Walensky, Rochelle P.; Bassett, Ingrid V.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Infect Dis, Dept Med, Boston, MA 02114 USA. [Losina, Elena] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Losina, Elena] Harvard Univ, Ctr AIDS Res, Cambridge, MA 02138 USA. [Walensky, Rochelle P.; Losina, Elena; April, Michael D.; Bassett, Ingrid V.; Freedberg, Kenneth A.] Harvard Univ, Sch Med, Boston, MA USA. [Wood, Robin] Univ Cape Town, Desmond Tutu HIV Ctr, Inst Infect Dis & Mol Med, ZA-7925 Cape Town, South Africa. [Martinson, Neil A.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Martinson, Neil A.] Perinatal HIV Res Unit, Johannesburg, South Africa. [Freedberg, Kenneth A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Paltiel, A. David] Yale Univ, Sch Med, New Haven, CT USA. [Freedberg, Kenneth A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Losina, Elena] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. RP Walensky, RP (reprint author), Massachusetts Gen Hosp, Div Gen Med, Dept Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM rwalensky@partners.org RI Wood, Robin/G-8509-2011; Anglaret, Xavier/F-7333-2013; OI Fofana, Mariam/0000-0002-2874-471X; Walensky, Rochelle P./0000-0002-8795-379X FU NIAID NIH HHS [K23 AI068458, K23 AI068458-05, K24 AI062476, K24 AI062476-05, P30 AI060354, P30 AI060354-02, R01 AI058736, R01 AI058736-08]; NIMH NIH HHS [R01 MH065869, R01 MH065869-05, R01 MH090326] NR 58 TC 27 Z9 28 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JAN 1 PY 2011 VL 56 IS 1 BP 26 EP 35 DI 10.1097/QAI.0b013e3181fb8f24 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 692XC UT WOS:000285188200011 PM 21068674 ER PT J AU Guadalupe, M Pollock, BH Westbrook, S Redding, S Bullock, D Anstead, G Agan, BK Marconi, VC Barbieri, S Sankar, V Rebeles, J Flahive, Y Schoolfield, J Wang, LD Lei, XF Dow, D Yeh, CK Dang, H Infante, AJ Gao, SJ AF Guadalupe, Moraima Pollock, Brad H. Westbrook, Steven Redding, Spencer Bullock, Delia Anstead, Gregory Agan, Brian K. Marconi, Vincent C. Barbieri, Sharon Sankar, Vidya Rebeles, Jennifer Flahive, Yvette Schoolfield, John Wang, Linding Lei, Xiufen Dow, Dorothy Yeh, Chih-Ko Dang, Howard Infante, Anthony J. Gao, Shou-Jiang TI Risk Factors Influencing Antibody Responses to Kaposi's Sarcoma-Associated Herpesvirus Latent and Lytic Antigens in Patients Under Antiretroviral Therapy SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE KSHV; Kaposi's sarcoma; latent and lytic antibodies; risk factors; HIV/AIDS ID HUMAN-IMMUNODEFICIENCY-VIRUS; PROTEASE INHIBITORS; SEROLOGIC ASSAYS; HIV-1 INFECTION; HOMOSEXUAL-MEN; CD4 COUNT; AIDS; HUMAN-HERPESVIRUS-8; TRENDS; SEROPREVALENCE AB Background: Kaposi's sarcoma-associated herpesvirus (KSHV) seropositivity and lytic antibody titer are predictors for Kaposi's sarcoma. Methods: We examined demographic, viral, and immunologic factors that influence KSHV latent and lytic antibodies in HIV-infected patients. Results: Detection rate of KSHV latent but not lytic antibodies was lower in patients with CD4 cells/mm(3) less than 200 than greater than 200 (odds ratio [OR], 0.26; 95% confidence interval [CI], 0.11-0.61) and CD8 cells/mm(3) less than 400 than greater than 400 (OR, 0.26; 95% CI, 0.07-0.67). Overall seropositivity rate was higher in patients with CD4 cells/mm(3) less than 200 than greater than 200 (OR, 2.34; 95% CI, 1.37-4.02) and HIV copies/mL greater than 400 than less than 400 (OR, 1.70; 95% CI, 1.09-2.65). Lytic antibody level was inversely correlated with CD4 count (P < 0.001). Lytic seropositivity (OR, 2.47; 95% CI, 1.35-4.50) and antibody level (adjusted difference mean optical density, 0.324; 95% CI, 0.16-0.46) were higher in patients with HIV infection greater than 15 than less than 15 years. Hispanics had higher lytic seropositivity rate (OR, 1.71; 95% CI, 1.07-2.73) and antibody level (adjusted difference mean optical density, 0.111; 95% CI, 0.03-0.18) than non-Hispanics. Conclusions: Lower CD4 and CD8 counts impair antibody response to KSHV latent antigens. Immune deterioration, long-term HIV infection, and Hispanic status are risk factors for Kaposi's sarcoma predictors. C1 [Guadalupe, Moraima; Rebeles, Jennifer; Flahive, Yvette; Wang, Linding; Lei, Xiufen; Gao, Shou-Jiang] Univ Texas Hlth Sci Ctr San Antonio, Greehey Childrens Canc Res Inst, San Antonio, TX 78229 USA. [Guadalupe, Moraima; Wang, Linding; Lei, Xiufen; Dow, Dorothy; Infante, Anthony J.; Gao, Shou-Jiang] Univ Texas Hlth Sci Ctr San Antonio, Dept Pediat, San Antonio, TX 78229 USA. [Pollock, Brad H.] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. [Westbrook, Steven; Redding, Spencer; Sankar, Vidya; Yeh, Chih-Ko] Univ Texas Hlth Sci Ctr San Antonio, Dept Dent Diagnost Sci, San Antonio, TX 78229 USA. [Bullock, Delia; Anstead, Gregory; Gao, Shou-Jiang] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Dang, Howard] Univ Texas Hlth Sci Ctr San Antonio, Dept Community Dent, San Antonio, TX 78229 USA. [Barbieri, Sharon] Univ Texas Hlth Sci Ctr San Antonio, Dept Dent Hyg, San Antonio, TX 78229 USA. [Schoolfield, John] Univ Texas Hlth Sci Ctr San Antonio, Dept Acad Technol Serv, San Antonio, TX 78229 USA. [Agan, Brian K.; Marconi, Vincent C.] Univ Hlth Sci, Infect Dis Clin Res Program Uniformed Serv, Bethesda, MD USA. [Agan, Brian K.; Marconi, Vincent C.] San Antonio Mil Med Ctr, San Antonio, TX USA. [Westbrook, Steven; Redding, Spencer; Anstead, Gregory; Yeh, Chih-Ko] S Texas Vet Healthcare Syst, San Antonio, TX USA. RP Gao, SJ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Greehey Childrens Canc Res Inst, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. EM gaos@uthscsa.edu RI Gao, Shou-Jiang/B-8641-2012; Marconi, Vincent/N-3210-2014; OI Marconi, Vincent/0000-0001-8409-4689; Agan, Brian/0000-0002-5114-1669 FU National Institute of Health (NIH) [CA119889, CA096512, CA124332, DE017333, RR001346, DE14138]; National Institute of Allergy and Infectious Diseases, NIH [Y1-AI-5072]; Uniformed Services University of the Health Sciences FX This work is in part supported by the National Institute of Health (NIH, grants CA119889, CA096512, CA124332, DE017333, RR001346, and DE14138) and the National Institute of Allergy and Infectious Diseases, NIH, under Interagency Agreement Y1-AI-5072. Support for this work (IDCRP-014) was also provided by the Infectious Disease Clinical Research Program (IDCRP), a Department of Defense (DoD) program executed through the Uniformed Services University of the Health Sciences. NR 41 TC 6 Z9 6 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JAN 1 PY 2011 VL 56 IS 1 BP 83 EP 90 DI 10.1097/QAI.0b013e3181fdc928 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 692XC UT WOS:000285188200019 PM 21084997 ER PT J AU Alsanafi, S Werth, VP AF Alsanafi, Shamael Werth, Victoria P. TI Squamous Cell Carcinomas Arising in Discoid Lupus Erythematosus Scars Unusual Occurrence in an African-American and in a Sun-Protected Area SO JCR-JOURNAL OF CLINICAL RHEUMATOLOGY LA English DT Article DE squamous cell carcinoma; discoid lupus erythematosus; scar; HPV infection; verrucous keratosis AB Squamous cell carcinoma is a known and rare complication of long-standing discoid lupus erythematosus. Most cases have been reported in sun-exposed skin of whites. We report 2 unusual cases of squamous cell carcinoma arising in discoid lupus erythematosus scars: one in a sun-protected area of a white patient and a second in an African-American patient. C1 [Alsanafi, Shamael; Werth, Victoria P.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Alsanafi, Shamael; Werth, Victoria P.] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. RP Alsanafi, S (reprint author), Hosp Univ Penn, Dept Dermatol, PCAM Suite 1-330S,3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM dr_shamael@yahoo.com FU National Institutes of Health (NIH) [NIH K24-AR 02207]; Kuwaiti Government FX This study was supported in part by the National Institutes of Health (NIH K24-AR 02207) to VPW. It was also supported by a grant from the Kuwaiti Government (SA). NR 10 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-1608 J9 JCR-J CLIN RHEUMATOL JI JCR-J. Clin. Rheumatol. PD JAN PY 2011 VL 17 IS 1 BP 35 EP 36 DI 10.1097/RHU.0b013e3182051928 PG 2 WC Rheumatology SC Rheumatology GA 710SV UT WOS:000286537400008 PM 21169850 ER PT J AU Trevino, KM Maciejewski, PK Fasciano, K Prigerson, HG AF Trevino, Kelly M. Maciejewski, Paul K. Fasciano, Karen Prigerson, Holly G. TI Grief and Life Disruption in Young Adults with Advanced Cancer SO JOURNAL OF ADOLESCENT AND YOUNG ADULT ONCOLOGY LA English DT Article DE grief; disability; life disruption AB Purpose: Psychological and physical suffering is inherent in the experience of grief in patients with advanced cancer. Grief due to cancer-related losses has not been examined in young adults with cancer. The purpose of this study is to examine the relationship between grief due to cancer-related losses and life disruption due to cancer symptoms in young adults with advanced cancer. Patients and Methods: Fifty-three young adults (20-40 years old) with advanced cancer completed structured clinical interviews that included measures of grief due to cancer-related losses and life disruption due to cancer symptoms. Regression analyses examined the relationship between grief and life disruption. Results: Higher levels of grief were associated with greater life disruption after controlling for an interviewer rating of physical performance status. Conclusions: These results suggest that grief may constitute a unique burden in the cancer experience for young adults with advanced disease, over and above physical performance status. Longitudinal designs with larger data sets are needed to confirm this finding. Nevertheless, this study suggests that grief is problematic for young adults with advanced cancer. Young adults may benefit from clinical assessment of and interventions for grief. C1 [Trevino, Kelly M.; Maciejewski, Paul K.; Fasciano, Karen; Prigerson, Holly G.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Trevino, Kelly M.; Maciejewski, Paul K.; Fasciano, Karen; Prigerson, Holly G.] Harvard Univ, Sch Med, Boston, MA USA. [Trevino, Kelly M.; Maciejewski, Paul K.; Fasciano, Karen; Prigerson, Holly G.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Prigerson, HG (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM holly_prigerson@dfci.harvard.edu FU National Institute of Mental Health [MH63892]; National Cancer Institute [CA106370, CA156732]; Adolescent and Young Adults with Cancer Closing the Gap Fund; Center for Psycho-Oncology and Palliative Care Research, Dana-Farber Cancer Institute FX This research was supported in part by the following grants to Dr. Prigerson: MH63892 from the National Institute of Mental Health; CA106370 and CA156732 from the National Cancer Institute; the Adolescent and Young Adults with Cancer Closing the Gap Fund; and the Center for Psycho-Oncology and Palliative Care Research, Dana-Farber Cancer Institute. NR 36 TC 3 Z9 3 U1 0 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 2156-5333 EI 2156-535X J9 J ADOLESC YOUNG ADUL JI J. Adolesc. Young Adult Oncol. PY 2011 VL 1 IS 4 BP 168 EP 172 DI 10.1089/jayao.2011.0024 PG 5 WC Oncology SC Oncology GA V39IH UT WOS:000209404200004 ER PT J AU Austin, SB Spadano-Gasbarro, J Greaney, ML Richmond, TK Feldman, HA Osganian, SK Hunt, AT Mezgebu, S Peterson, KE AF Austin, S. Bryn Spadano-Gasbarro, Jennifer Greaney, Mary L. Richmond, Tracy K. Feldman, Henry A. Osganian, Stavroula K. Hunt, Anne T. Mezgebu, Solomon Peterson, Karen E. TI Disordered Weight Control Behaviors in Early Adolescent Boys and Girls of Color: An Under-Recognized Factor in the Epidemic of Childhood Overweight SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article DE Adolescence; Eating disorders; Overweight; Disparities ID PROTECTIVE FACTORS; RISK AB Objectives: Ethnic disparities in childhood overweight are well-documented. In addition, disordered weight control behaviors (DWCB) have been linked to overweight and weight gain in multiple ways, but little is known about DWCB in youth of color, especially boys. We examined the distribution and determinants of ethnic and gender disparities in DWCB in early adolescents. Methods: In fall 2005, 47 Massachusetts middle schools participating in the Healthy Choices overweight prevention study administered a self-report baseline survey assessing student sociodemographics, height, weight, and DWCB (vomiting or use of laxatives or diet pills in the past month to control weight). Data from 16,978 girls and boys were used in multivariate logistic regression models to estimate the odds of DWCB in youth of color compared with their white peers, controlling for individual-and school-level factors. Results: Among white youth, 2.7% of girls and 2.3% of boys reported DWCB. The odds of DWCB were elevated 2-10 times in most ethnic groups relative to whites. Disparities were attenuated but persisted after controlling for multiple individual-and school-level factors. Conclusions: Ethnic disparities in DWCB must be considered in efforts to address the epidemic of childhood overweight. (C) 2011 Society for Adolescent Health and Medicine. All rights reserved. C1 [Austin, S. Bryn; Richmond, Tracy K.] Childrens Hosp, Div Adolescent & Young Adult Med, Boston, MA 02115 USA. [Austin, S. Bryn] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Spadano-Gasbarro, Jennifer; Peterson, Karen E.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Feldman, Henry A.; Osganian, Stavroula K.] Childrens Hosp, Clin Res Program, Boston, MA 02115 USA. [Greaney, Mary L.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Mezgebu, Solomon] Massachusetts Dept Publ Hlth, Boston, MA USA. [Hunt, Anne T.] Hunt Consulting Associates, Lyme, NH USA. [Peterson, Karen E.] Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Human Nutr Program, Ann Arbor, MI 48109 USA. RP Austin, SB (reprint author), Childrens Hosp, Div Adolescent & Young Adult Med, 300 Longwood Ave, Boston, MA 02115 USA. EM bryn.austin@childrens.harvard.edu FU NICHD NIH HHS [K01 HD058042, K01 HD058042-03]; PHS HHS [U58/CCU12282] NR 10 TC 21 Z9 21 U1 2 U2 7 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 JAN PY 2011 VL 48 IS 1 BP 109 EP 112 DI 10.1016/j.jadohealth.2010.05.017 PG 4 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA 698XT UT WOS:000285629200020 PM 21185534 ER PT J AU Radwin, LE Ananian, L Cabral, HJ Keeley, A Currier, PF AF Radwin, Laurel E. Ananian, Lillian Cabral, Howard J. Keeley, Adele Currier, Paul F. TI Effects of a patient/family-centered practice change on the quality and cost of intensive care: research protocol SO JOURNAL OF ADVANCED NURSING LA English DT Article DE critically ill adults; end of life care; medical record data; nursing; patient/family-centered care; protocol; quasi-experimental ID DESIRED HEALTH OUTCOMES; OF-LIFE CARE; FAMILY-MEMBERS; UNIT; END; SATISFACTION; VALIDATION; NEEDS; ICU; INTERVENTION AB Aim. This paper is a description of a protocol for studying the impact of a patient/family-centered, evidence-based practice change on the quality, cost and use of services for critically ill patients at the end of life. Background. International attention currently is focused on the quality and cost/use of intensive care services. Empirical literature and expert opinion suggest that early, enhanced communication among the clinical team and the patient and family results in higher quality and less costly care at the end of life. Design. Our Medical Intensive Care Unit practice change involves three components: teaching sessions for all Registered Nurses and physicians assigned to the unit; patient/family meetings held in 72 hours of the patient's admission to the unit; and formal documentation to support communication among clinicians. Ethical approval was obtained in April 2009. A two-group post-test design is used, with one group comprising patients hospitalized before the practice change and their families, and the second group of patients/families after the practice change. Data comprise medical record information and families' responses to surveys. Final analytic models will result from multivariable regression techniques. Discussion. The study represents translational research in that interventions are brought to the bedside to reach the people for whom the interventions were designed. The practice change is likely to endure after the study because our research team is composed of both clinicians and scientists. Also, direct care clinicians endorse and are responsible for the practice change. C1 [Radwin, Laurel E.] Univ Massachusetts Boston, Chelmsford, MA USA. [Ananian, Lillian; Keeley, Adele] Massachusetts Gen Hosp, Med Intens Care Unit, Boston, MA 02114 USA. [Cabral, Howard J.] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Currier, Paul F.] Massachusetts Gen Hosp, Dept Pulm & Crit Care Med, Boston, MA 02114 USA. [Currier, Paul F.] Harvard Univ, Sch Med, Boston, MA USA. RP Radwin, LE (reprint author), Univ Massachusetts Boston, Chelmsford, MA USA. EM ler627@gmail.com OI Cabral, Howard/0000-0002-1185-8331 FU Massachusetts General Hospital (MGH); Partners HealthCare System High Performance Medicine: Team 5 FX Funding for this study was awarded via peer-review from the Massachusetts General Hospital (MGH) Clinical Innovation Award Program, an initiative of the MGH Quality and Safety Program. Funding was also given from Partners HealthCare System High Performance Medicine: Team 5. NR 33 TC 5 Z9 5 U1 3 U2 10 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0309-2402 J9 J ADV NURS JI J. Adv. Nurs. PD JAN PY 2011 VL 67 IS 1 BP 215 EP 224 DI 10.1111/j.1365-2648.2010.05448.x PG 10 WC Nursing SC Nursing GA 693TO UT WOS:000285248500022 PM 21077929 ER PT J AU Vivrette, RL Rubenstein, LZ Martin, JL Josephson, KR Kramer, BJ AF Vivrette, Rebecca L. Rubenstein, Laurence Z. Martin, Jennifer L. Josephson, Karen R. Kramer, B. Josea TI Development of a Fall-Risk Self-Assessment for Community-Dwelling Seniors SO JOURNAL OF AGING AND PHYSICAL ACTIVITY LA English DT Article DE falls; qualitative research methods; preventive medicine; preventive care; preventive services ID OLDER-ADULTS; PREVENTION; INTERVENTIONS; MODEL AB Objective: To determine seniors' beliefs about falls and design a fall-risk self-assessment and educational materials to promote early identification of evidence-based fall risks and encourage prevention behaviors. Methods: Focus groups with community-dwelling seniors, conducted in two phases to identify perceptions about fall risks and risk reduction and to assess face validity of the fall-risk self-assessment and acceptability of educational materials. Results: Lay perception of fall risks was in general concordance with evidence-based research. Maintaining independence and positive tone were perceived as key motivators for fall prevention. Seniors intended to use information in the educational tool to stimulate discussions about falls with health care providers. Implications: An evidence-based, educational fall-risk self-assessment acceptable to older adults can build on existing lay knowledge about fall risks and perception that falls are a relevant problem and can educate seniors about their specific risks and how to minimize them. C1 [Vivrette, Rebecca L.; Martin, Jennifer L.; Josephson, Karen R.] VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, North Hills, CA USA. [Rubenstein, Laurence Z.] Univ Oklahoma, Coll Med, Donald W Reynolds Dept Geriatr Med, Oklahoma City, OK 73104 USA. [Kramer, B. Josea] Univ Calif Los Angeles, David Geffen Sch Med, Div Geriatr, Los Angeles, CA 90095 USA. RP Vivrette, RL (reprint author), VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, North Hills, CA USA. FU Centers for Disease Control and Prevention [05FED28430]; National Institutes of Health [K23AG028452]; Archstone Foundation [01-01-10]; Archstone Foundation FX This study was funded in part by the Centers for Disease Control and Prevention (05FED28430), National Institutes of Health (K23AG028452), and the Archstone Foundation (01-01-10).; We acknowledge the contributions of the Archstone Foundation funded Fall Prevention Center of Excellence for assistance with graphic materials used in this research project. We also acknowledge Judy Stevens, PhD, and Shane Diekman, PhD, for their contributions to the focus-group discussion guides and to the development of the brochure. NR 24 TC 6 Z9 6 U1 0 U2 3 PU HUMAN KINETICS PUBL INC PI CHAMPAIGN PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA SN 1063-8652 J9 J AGING PHYS ACTIV JI J. Aging Phys. Act. PD JAN PY 2011 VL 19 IS 1 BP 16 EP 29 PG 14 WC Geriatrics & Gerontology; Gerontology; Sport Sciences SC Geriatrics & Gerontology; Sport Sciences GA 705QI UT WOS:000286152600002 PM 21285473 ER PT J AU Shi, M Sui, YT Peskind, ER Li, G Hwang, H Devic, I Ginghina, C Edgar, JS Pan, C Goodlett, DR Furay, AR Gonzalez-Cuyar, LF Zhang, J AF Shi, Min Sui, Yu-Ting Peskind, Elaine R. Li, Ge Hwang, HyeJin Devic, Ivana Ginghina, Carmen Edgar, John Scott Pan, Catherine Goodlett, David R. Furay, Amy R. Gonzalez-Cuyar, Luis F. Zhang, Jing TI Salivary Tau Species are Potential Biomarkers of Alzheimer's Disease SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; amyloid-beta; biomarkers; saliva; tau protein ID MILD COGNITIVE IMPAIRMENT; PERIPHERAL NERVOUS-SYSTEM; CEREBROSPINAL-FLUID; ALPHA-SYNUCLEIN; CSF BIOMARKERS; DIAGNOSIS; HEALTH AB Phosphorylation of tau protein is a critical event in the pathogenesis of Alzheimer's disease (AD). Increased phosphorylated tau and total tau levels, combined with reduced concentrations of amyloid-beta 1-42 (A beta(42)) in cerebrospinal fluid (CSF), but not in plasma or serum, have been generally accepted as sensitive AD diagnostic markers. However, obtaining CSF is a relatively invasive procedure that requires participation of specially trained medical professionals, i.e., CSF is not an ideal sample source for screening or early diagnosis of AD, which is essential to current and future neuroprotective treatments for the disease. Here, we identified tau, but not A beta species, with mass spectrometry in human saliva, a body fluid that is much more accessible compared to CSF or even blood. Quantitative assessment of salivary levels of total tau, phosphorylated tau, and A beta(42) using highly sensitive Luminex assays revealed that, while A beta(42) was not detectable, the phosphorylated tau/tau ratio significantly increased in patients with AD compared to healthy controls. These results suggest that salivary tau species could be ideal biomarkers for AD diagnosis, especially at early stages of the disease or even screening asymptomatic subjects, allowing for a much larger therapeutic window for AD patients. C1 [Shi, Min; Sui, Yu-Ting; Hwang, HyeJin; Devic, Ivana; Ginghina, Carmen; Pan, Catherine; Furay, Amy R.; Gonzalez-Cuyar, Luis F.; Zhang, Jing] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98104 USA. [Peskind, Elaine R.; Li, Ge; Furay, Amy R.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98104 USA. [Peskind, Elaine R.] Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. [Edgar, John Scott; Goodlett, David R.] Univ Washington, Sch Pharm, Dept Med Chem, Seattle, WA 98104 USA. RP Zhang, J (reprint author), Univ Washington, Sch Med, Dept Pathol, HMC Box 359635,325 9th Ave, Seattle, WA 98104 USA. EM zhangj@uw.edu RI Shi, Min/G-6165-2012 OI Shi, Min/0000-0002-6901-2558 FU National Institutes of Health [AG033398, ES004696-5897, ES007033-6364, ES016873, NS057567, NS062684-6221, AG005136]; NINDS Institutional Center [Neuroproteomic P30 (NS055088)]; Cheng-Mei Shaw Endowment; Friends of Alzheimer's Research; Alzheimer's Association of Western and Central Washington; Department of Veterans Affairs FX This work was supported by the National Institutes of Health grants (AG033398, ES004696-5897, ES007033-6364, ES016873, NS057567, NS062684-6221 and AG005136), NINDS Institutional Center Core Grant-Neuroproteomics P30 (NS055088) as well as grants from the Cheng-Mei Shaw Endowment, Friends of Alzheimer's Research, Alzheimer's Association of Western and Central Washington and the Department of Veterans Affairs. We thank Clete Barrick for his assistance in preliminary experiments, and also deeply appreciate those who have donated their saliva for our study. NR 26 TC 24 Z9 25 U1 7 U2 21 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2011 VL 27 IS 2 BP 299 EP 305 DI 10.3233/JAD-2011-110731 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 850RQ UT WOS:000297215900007 PM 21841250 ER PT J AU Kim, WS Hill, AF Fitzgerald, ML Freeman, MW Evin, G Garner, B AF Kim, Woojin S. Hill, Andrew F. Fitzgerald, Michael L. Freeman, Mason W. Evin, Genevieve Garner, Brett TI Wild Type and Tangier Disease ABCA1 Mutants Modulate Cellular Amyloid-beta Production Independent of Cholesterol Efflux Activity SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE ABCA1; A beta PP processing; Alzheimer's disease; lipid transport; membrane biology; Tangier disease ID CASSETTE TRANSPORTER A1; DETERGENT-RESISTANT MEMBRANE; PRECURSOR PROTEIN; ALZHEIMERS-DISEASE; APOLIPOPROTEIN-E; GAMMA-SECRETASE; LIPID MICROENVIRONMENT; HIPPOCAMPAL-NEURONS; BRAIN-CELLS; IN-VITRO AB Cerebral amyloid-beta (A beta) deposition is a critical feature of Alzheimer's disease. A beta is derived from the amyloid-beta protein precursor (A beta PP) via two sequential cleavages that are mediated by beta-secretase and the gamma-secretase complex. Such amyloidogenic A beta PP processing occurs in lipid raft microdomains of cell membranes and it is thought that modulating the distribution of lipids in rafts may regulate A beta PP processing and A beta production. Certain ATP-binding cassette (ABC) transporters regulate lipid transport across cell membranes and, as recent studies reveal, within membrane microdomains. ABCA1 also regulates A beta metabolism in the brain although its direct impact on A beta PP remains an open question. Here we assessed the capacity of three ABCA1 mutants (that do not promote lipid efflux) to modulate A beta PP processing. Unexpectedly, these non-functional mutants also reduced A beta production similar to wild type ABCA1. ABCA1 expression did not alter A beta PP localization in lipid rafts, and co-immunoprecipitation experiments indicated ABCA1 and A beta PP physically interact. These data suggest that ABCA1 may regulate A beta PP processing independent of its impact on membrane lipid homeostasis. C1 [Garner, Brett] Univ Wollongong, Illawarra Hlth & Med Res Inst, Wollongong, NSW 2522, Australia. [Garner, Brett] Univ Wollongong, Sch Biol Sci, Wollongong, NSW 2522, Australia. [Evin, Genevieve] Univ Melbourne, Dept Pathol, Melbourne, Vic 3010, Australia. [Freeman, Mason W.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Fitzgerald, Michael L.; Freeman, Mason W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lipid Metab Unit,Ctr Computat & Integrat Biol, Boston, MA USA. [Hill, Andrew F.] Univ Melbourne, Dept Biochem & Mol Biol, Inst Bio21, Melbourne, Vic 3010, Australia. [Kim, Woojin S.] Univ New S Wales, Sch Med Sci, Sydney, NSW, Australia. [Kim, Woojin S.] Neurosci Res Australia, Sydney, NSW, Australia. RP Garner, B (reprint author), Univ Wollongong, Illawarra Hlth & Med Res Inst, Wollongong, NSW 2522, Australia. EM brettg@uow.edu.au RI Evin, Genevieve/E-5891-2013; Hill, Andrew/B-4527-2009 OI Hill, Andrew/0000-0001-5581-2354 FU National Health and Medical Research Council of Australia (NHMRC) [510148]; Australian Research Council [FT0991986] FX We are grateful to Prof Kerry-Anne Rye for provision of human apoA-I, to Prof Colin Masters and Dr Qiao-Xin Li for providing WO2 antibody, and to Dr Janetta Culvenor for providing 98/1 antibody. This work was supported by the National Health and Medical Research Council of Australia (NHMRC Grant No. 510148). Prof Garner is supported by a Fellowship from the Australian Research Council (FT0991986). NR 62 TC 5 Z9 5 U1 0 U2 3 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2011 VL 27 IS 2 BP 441 EP 452 DI 10.3233/JAD-2011-110521 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 850RQ UT WOS:000297215900019 PM 21860089 ER PT J AU Lebbadi, M Julien, C Phivilay, A Tremblay, C Emond, V Kang, JX Calon, F AF Lebbadi, Meryem Julien, Carl Phivilay, Alix Tremblay, Cyntia Emond, Vincent Kang, Jing X. Calon, Frederic TI Endogenous Conversion of Omega-6 into Omega-3 Fatty Acids Improves Neuropathology in an Animal Model of Alzheimer's Disease SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer disease; docosahexaenoic acids; n-3 fatty acid desaturase; n-3 polyunsaturated fatty acid; transgenic mice ID POLYUNSATURATED FATTY-ACIDS; AMYLOID-BETA-PROTEIN; BRAIN DOCOSAHEXAENOIC ACID; MILD COGNITIVE IMPAIRMENT; TRIPLE-TRANSGENIC MODEL; A-BETA; MOUSE MODEL; IN-VIVO; NEUROFIBRILLARY DEGENERATION; LEARNING-ABILITY AB Dietary supplementation with n-3 polyunsaturated fatty acids (n-3 PUFA) reduces amyloid-beta (A beta) and tau pathology and improves cognitive performance in animal models of Alzheimer's disease (AD). To exclude confounding variables associated with the diet, we crossed 3xTg-AD mice (modeling AD neuropathology) with transgenic Fat-1 mice that express the fat-1 gene encoding a PUFA desaturase, which endogenously produces n-3 PUFA from n-6 PUFA. The expression of fat-1 shifted the n-3:n-6 PUFA ratio upward in the brain (+11%, p < 0.001), including docosahexaenoic acid (DHA; +5%, p < 0.001) in 20 month-old mice. The expression of fat-1 decreased the levels of soluble A beta(42) (-41%, p < 0.01) at 20 months without reducing the level of insoluble forms of A beta(40) and A beta(42) in the brain of 3xTg-AD mice. The 3xTg-AD/Fat-1 mice exhibited lower cortical levels of both soluble (-25%, p < 0.05) and insoluble phosphorylated tau (-55%, p < 0.05) compared to 3xTg-AD mice, but only in 20 month-old animals. Whereas a decrease of calcium/calmodulin-dependent protein kinase II was observed in 3xTg-AD/Fat-1 mice (-39%, p < 0.05), altered tau phosphorylation could not be related to changes in glycogen synthase kinase 3 beta, cyclin-dependent kinase 5, or protein phosphatase type 2A enzymatic activity. In addition, the expression of the fat-1 transgene prevented the increase of glial fibrillary acidic protein (-37%, p < 0.01) observed in 20 month-old 3xTg-AD mice. In conclusion, the expression of fat-1 in 3xTg-AD mice increases brain DHA and induces biomarker changes that are consistent with a beneficial effect against an AD-like neuropathology. C1 [Lebbadi, Meryem; Julien, Carl; Phivilay, Alix; Tremblay, Cyntia; Emond, Vincent; Calon, Frederic] CHUL, Res Ctr, Quebec City, PQ G1V 4G2, Canada. [Lebbadi, Meryem; Julien, Carl; Phivilay, Alix; Tremblay, Cyntia; Emond, Vincent; Calon, Frederic] Univ Laval, Fac Pharm, Quebec City, PQ, Canada. [Kang, Jing X.] Harvard Univ, Sch Med, Boston, MA USA. [Kang, Jing X.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Calon, F (reprint author), CHUL, Res Ctr, Room TR 72,2705 Laurier Blvd, Quebec City, PQ G1V 4G2, Canada. EM frederic.calon@crchul.ulaval.ca FU Canadian Institutes of Health Research (CIHR) [MOP 102532, IAO74443]; Alzheimer Society Canada; Canada Foundation for Innovation [10307]; Fonds de la Recherche en Sante du Quebec (FRSQ); Laval University; Clinical Research Initiative; CIHR Institute of Aging [CAN76833] FX This work was supported by grants from the Canadian Institutes of Health Research (CIHR) (FC - MOP 102532 and IAO74443), the Alzheimer Society Canada (FC), and the Canada Foundation for Innovation (10307). CJ was supported by studentships from the Alzheimer Society Canada, the Fonds de la Recherche en Sante du Quebec (FRSQ) and Laval University "Fonds d'Enseignement et de Recherche". The work of FC was supported by a New Investigator Award from the Clinical Research Initiative and the CIHR Institute of Aging (CAN76833). NR 125 TC 36 Z9 38 U1 3 U2 15 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2011 VL 27 IS 4 BP 853 EP 869 DI 10.3233/JAD-2011-111010 PG 17 WC Neurosciences SC Neurosciences & Neurology GA 866GI UT WOS:000298368100017 PM 21914946 ER PT J AU Fennema-Notestine, C Panizzon, MS Thompson, WR Chen, CH Eyler, LT Fischl, B Franz, CE Grant, MD Jak, AJ Jernigan, TL Lyons, MJ Neale, MC Seidman, LJ Tsuang, MT Xian, H Dale, AM Kremen, WS AF Fennema-Notestine, Christine Panizzon, Matthew S. Thompson, Wesley R. Chen, Chi-Hua Eyler, Lisa T. Fischl, Bruce Franz, Carol E. Grant, Michael D. Jak, Amy J. Jernigan, Terry L. Lyons, Michael J. Neale, Michael C. Seidman, Larry J. Tsuang, Ming T. Xian, Hong Dale, Anders M. Kremen, William S. TI Presence of ApoE epsilon 4 Allele Associated with Thinner Frontal Cortex in Middle Age SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Magnetic resonance imaging; cerebral cortex; brain; frontal lobe; apolipoproteins E; apolipoprotein E2; apolipoprotein E3; apolipoprotein E4; genetic association studies; aging ID APOLIPOPROTEIN-E EPSILON-4; FAMILIAL ALZHEIMER-DISEASE; MILD COGNITIVE IMPAIRMENT; SURFACE-BASED ANALYSIS; HUMAN CEREBRAL-CORTEX; VIETNAM ERA TWIN; HIPPOCAMPAL VOLUME; LONGITUDINAL CHANGES; CORTICAL THICKNESS; NORMAL INDIVIDUALS AB The presence of an ApoE epsilon 4 allele (epsilon 4+) increases the risk of developing Alzheimer's disease (AD). Previous studies support an adverse relationship between epsilon 4+ status and brain structure and function in mild cognitive impairment and AD; in contrast, the presence of an epsilon 2 allele may be protective. Whether these findings reflect disease-related effects or pre-existing endophenotypes, however, remains unclear. The present study examined the influence of ApoE allele status on brain structure solely during middle-age in a large, national sample. Participants were 482 men, ages 51-59, from the Vietnam Era Twin Study of Aging (VETSA). T1-weighted images were used in volumetric segmentation and cortical surface reconstruction methods to measure regional volume and thickness. Primary linear mixed effects models predicted structural measures with ApoE status (epsilon 3/3, epsilon 2/3, epsilon 3/4) and control variables for effects of site, non-independence of twin data, age, and average cranial vault or cortical thickness. Relative to the epsilon 3/3 group, the epsilon 3/4 group demonstrated significantly thinner cortex in superior frontal and left rostral and right caudal midfrontal regions; there were no significant effects of epsilon 4 status on any temporal lobe measures. C1 [Fennema-Notestine, Christine; Panizzon, Matthew S.; Thompson, Wesley R.; Chen, Chi-Hua; Eyler, Lisa T.; Franz, Carol E.; Jak, Amy J.; Jernigan, Terry L.; Tsuang, Ming T.; Kremen, William S.] Univ Calif San Diego, Sch Med, Dept Psychiat, La Jolla, CA 92093 USA. [Fennema-Notestine, Christine; Jernigan, Terry L.; Dale, Anders M.] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA. [Eyler, Lisa T.; Jak, Amy J.; Kremen, William S.] Vet Adm San Diego Healthcare Syst, San Diego, CA USA. [Fischl, Bruce] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Fischl, Bruce] Harvard Univ, Sch Med, Boston, MA USA. [Fischl, Bruce] MIT, Comp Sci & AI Lab, Cambridge, MA 02139 USA. [Grant, Michael D.; Lyons, Michael J.; Seidman, Larry J.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Jernigan, Terry L.] Univ Calif San Diego, Dept Cognit Sci, La Jolla, CA 92093 USA. [Jernigan, Terry L.] Univ Calif San Diego, Ctr Human Dev, La Jolla, CA 92093 USA. [Neale, Michael C.] Virginia Commonwealth Univ, Sch Med, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA. [Tsuang, Ming T.; Kremen, William S.] Univ Calif San Diego, Ctr Behav Genom, La Jolla, CA 92093 USA. [Tsuang, Ming T.] Harvard Univ, Sch Med, Harvard Inst Psychiat Epidemiol & Genet, Boston, MA USA. [Tsuang, Ming T.] Sch Publ Hlth, Boston, MA USA. [Dale, Anders M.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [Xian, Hong] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. RP Fennema-Notestine, C (reprint author), Univ Calif San Diego, Sch Med, Dept Psychiat, 9500 Gilman Dr 0738, La Jolla, CA 92093 USA. EM Fennema@UCSD.edu FU National Institutes of Health (NIH) [R01 AG018386, RO1 AG018384, RO1 AG022381, RO1 AG022982, U24 RR021382, P41 RR14075, R01 EB006758, R01 NS052585-01]; U.S. Department of Veterans Affairs; Ellison Medical Foundation FX The VETSA project is supported by National Institutes of Health (NIH) Grants R01 AG018386, RO1 AG018384, RO1 AG022381, RO1 AG022982, and U24 RR021382. The U.S. Department of Veterans Affairs has provided support for the development and maintenance of the Vietnam Era Twin Registry. Additional support for this research was provided in part by NIH grants P41 RR14075, R01 EB006758, and R01 NS052585-01, and the Autism & Dyslexia Project funded by the Ellison Medical Foundation. Dr. A. M. Dale is a founder and holds equity in CorTechs Labs, and also serves on its Scientific Advisory Board. The terms of this arrangement have been reviewed and approved by the University of California, San Diego, in accordance with its conflict of interest policies. NR 75 TC 33 Z9 33 U1 0 U2 1 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2011 VL 26 SU 3 BP 49 EP 60 DI 10.3233/JAD-2011-0002 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 858ZM UT WOS:000297842800003 PM 21971450 ER PT J AU Canu, E McLaren, DG Fitzgerald, ME Bendlin, BB Zoccatelli, G Alessandrini, F Pizzini, FB Ricciardi, GK Beltramello, A Johnson, SC Frisoni, GB AF Canu, Elisa McLaren, Donald G. Fitzgerald, Michele E. Bendlin, Barbara B. Zoccatelli, Giada Alessandrini, Franco Pizzini, Francesca B. Ricciardi, Giuseppe K. Beltramello, Alberto Johnson, Sterling C. Frisoni, Giovanni B. TI Mapping the Structural Brain Changes in Alzheimer's Disease: The Independent Contribution of Two Imaging Modalities SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Diffusion Tensor Imaging (DTI); Alzheimer's disease (AD); Microstructure; Fractional Anisotropy (FA); Mean Diffusivity (MD) ID MILD COGNITIVE IMPAIRMENT; WHITE-MATTER CHANGES; MOTOR CORTEX INVOLVEMENT; AGE-RELATED-CHANGES; IN-VIVO; CORPUS-CALLOSUM; NEURODEGENERATIVE DISORDERS; AMYLOID DEPOSITS; TRACT INTEGRITY; WATER DIFFUSION AB The macrostructural atrophy of Alzheimer's disease (AD) has been fully described. Current literature reports that also microstructural alterations occur in AD since the early stages. However, whether the microstructural changes offer unique information independent from macrostructural atrophy is unclear. Aim of this study is to define the independent contribution of macrostructural atrophy and microstructural alterations on AD pathology. The study involved 17 moderate to severe AD patients and 13 healthy controls. All participants underwent conventional and non conventional MRI (respectively, T1-weighted and diffusion-weighted MR scanning). We processed the images in order to obtain gray and white matter volumes to assess macrostructural atrophy, and fractional anisotropy and mean diffusivity to assess the microstructural damage. Analyses of covariance between patients and controls were performed to investigate microstructural tissue damage independent of macrostructural tissue loss, and viceversa, voxel by voxel. We observed microstructural differences, independent of macrostructural atrophy, between patients and controls in temporal and retrosplenial regions, as well as in thalamus, corticopontine tracts, striatum and precentral gyrus. Volumetric differences, independent of microstructural alterations, were observed mainly in the entorhinal cortex, posterior cingulum, and splenium. Measures of microstructural damage provide unique information not obtainable with volumetric mapping in regions known to be pivotal in AD as well as in others thought to be spared. This work expands the understanding of the topography of pathological changes in AD that can be captured with imaging techniques. C1 [McLaren, Donald G.; Fitzgerald, Michele E.; Bendlin, Barbara B.; Johnson, Sterling C.] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI USA. [McLaren, Donald G.] Univ Wisconsin, Neurosci Training Program, Madison, WI 53706 USA. [McLaren, Donald G.; Fitzgerald, Michele E.; Bendlin, Barbara B.; Johnson, Sterling C.] Univ Wisconsin, Dept Med, Wisconsin Alzheimers Dis Res Ctr, Madison, WI USA. [Zoccatelli, Giada; Alessandrini, Franco; Pizzini, Francesca B.; Ricciardi, Giuseppe K.; Beltramello, Alberto] Osped Maggiore, Serv Neuroradiol, Verona, Italy. [Canu, Elisa; Frisoni, Giovanni B.] Natl Ctr Res & Care Alzheimers & Mental Dis, IRCCS Ctr San Giovanni di Dio FBF, LENITEM Lab Epidemiol Neuroimaging & Telemed, Brescia, Italy. RP Frisoni, GB (reprint author), IRCCS San Giovanni di Dio FBF, LENITEM Lab Epidemiol Neuroimaging & Telemed, Via Pilastroni 4, I-25125 Brescia, Italy. EM gfrisoni@fatebenefratelli.it RI Frisoni, Giovanni B/K-1360-2016; Pizzini, Francesca Bendetta/O-5291-2016; Canu, Elisa/K-1423-2016; OI Frisoni, Giovanni B/0000-0002-6419-1753; Pizzini, Francesca Bendetta/0000-0002-6285-0989; Ricciardi, Giuseppe Kenneth/0000-0001-8536-5794; Canu, Elisa/0000-0001-5804-3378; Bendlin, Barbara/0000-0002-0580-9875 FU Italian Ministry of Health; Ricerca Finalizzata "Malattie neurodegenerative legate all' invecchiamento: dalla patogenesi alle prospettive terapeutiche per un progetto traslazionale"; Lundbeck Italia SpA; National Institutes of Health [AG021155, AG000213] FX This work has been supported by research grant 125/2004 of the Italian Ministry of Health, Ricerca Finalizzata "Malattie neurodegenerative legate all' invecchiamento: dalla patogenesi alle prospettive terapeutiche per un progetto traslazionale" and by Lundbeck Italia SpA. This study was also supported by National Institutes of Health grants AG021155 and AG000213, and by the facilities and resources at the William S. Middleton Memorial Veterans Hospital. All authors report no conflicts of interest. NR 68 TC 17 Z9 17 U1 0 U2 3 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2011 VL 26 SU 3 BP 263 EP 274 DI 10.3233/JAD-2011-0040 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 858ZM UT WOS:000297842800019 PM 21971466 ER PT J AU Humbert, IA McLaren, DG Malandraki, G Johnson, SC Robbins, J AF Humbert, Ianessa A. McLaren, Donald G. Malandraki, Georgia Johnson, Sterling C. Robbins, JoAnne TI Swallowing Intentional Off-State in Aging and Alzheimer's Disease: Preliminary Study SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; cognitive aging; deglutition; fMRI ID MILD COGNITIVE IMPAIRMENT; CEREBRAL CORTICAL REPRESENTATION; EVENT-RELATED FMRI; RESPONSE-INHIBITION; PREFRONTAL CORTEX; OLDER-ADULTS; NO-GO; BRAIN; ACTIVATIONS; PARIETAL AB Frontal cortical activation is elicited when subjects have been instructed not to initiate a sensorimotor task. The goal of this preliminary fMRI study was to examine BOLD response to a "Do Not Swallow" instruction (an intentional "off-state") in the context of other swallowing tasks in 3 groups of participants (healthy young, healthy old, and early Alzheimer's disease (AD)). Overall, the older group had larger, bilaterally active clusters in the cortex, including the dorsomedial prefrontal cortex during the intentional swallowing off-state; this region is commonly active in response inhibition studies. Disease-related differences were evident where the AD group had significantly greater BOLD response in the insula/operculum than the old. These findings have significant clinical implications for control of swallowing across the age span and in neurodegenerative disease. Greater activation in the insula/operculum for the AD group supports previous studies where this region is associated with initiating swallowing. The AD group may have required more effort to "turn off" swallowing centers to reach the intentional swallowing off-state. C1 [Humbert, Ianessa A.] Johns Hopkins Univ, Dept Phys Med & Rehabil, Baltimore, MD USA. [McLaren, Donald G.] Massachusetts Gen Hosp, Dept Neurol,Harvard Med Sch, Athinoula Martinos Ctr Biomed Imaging, Geriatr Res,Educ & Clin Ctr,ENRM VA Med Ctr, Boston, MA 02114 USA. [Malandraki, Georgia; Johnson, Sterling C.; Robbins, JoAnne] William S Middleton Mem Hosp, Geriatr Res Educ & Clin Ctr, Madison, WI USA. [Malandraki, Georgia; Johnson, Sterling C.; Robbins, JoAnne] Univ Wisconsin, Madison, WI USA. RP Humbert, IA (reprint author), CCC SLP, 98 N Broadway,Suite 403, Baltimore, MD 21231 USA. EM ihumber1@jhmi.edu RI McLaren, Donald/G-9906-2011 FU Wisconsin Comprehensive Memory Program; National Institutes of Health and National Institute on Aging [T32AG000213-18] FX Swallowing Physiology and Neurophysiology in Alzheimer's and Lewy Body Disease. Wisconsin Comprehensive Memory Program (Pilot Funding 2006-2008).; National Institutes of Health and National Institute on Aging grant no. 5 T32AG000213-18 and the William S. Middleton Memorial VA Hospital Geriatric Research Education and Clinical Center (GRECC). NR 33 TC 6 Z9 7 U1 0 U2 4 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2011 VL 26 IS 2 BP 347 EP 354 DI 10.3233/JAD-2011-110380 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 818OR UT WOS:000294763100012 PM 21654061 ER PT J AU Hook, G Hook, V Kindy, M AF Hook, Gregory Hook, Vivian Kindy, Mark TI The Cysteine Protease Inhibitor, E64d, Reduces Brain Amyloid-beta and Improves Memory Deficits in Alzheimer's Disease Animal Models by Inhibiting Cathepsin B, but not BACE1, beta-Secretase Activity SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer disease; amyloid-beta; BACE1; cathepsin B; guinea pig; memory deficits; oral E64d; transgenic mice ID PRECURSOR PROTEIN; TRANSGENIC MICE; IN-VIVO; A-BETA; GUINEA-PIGS; RAT-BRAIN; WILD-TYPE; PEPTIDES; VITRO; OLIGOMERIZATION AB The cysteine protease cathepsin B is a potential drug target for reducing brain amyloid-beta (A beta) and improving memory in Alzheimer's disease (AD), as reduction of cathepsin B in transgenic mice expressing human wild-type amyloid-beta protein precursor (A beta PP) results in significantly decreased brain A beta. Cathepsin B cleaves the wild-type beta-secretase site sequence in A beta PP to produce A beta, and cathepsin B inhibitors administered to animal models expressing A beta PP containing the wild-type beta-secretase site sequence reduce brain A beta in a manner consistent with beta-secretase inhibition. But such inhibitors could act either by direct inhibition of cathepsin B beta-secretase activity or by off-target inhibition of the other beta-secretase, the aspartyl protease BACE1. To evaluate that issue, we orally administered a cysteine protease inhibitor, E64d, to normal guinea pigs or transgenic mice expressing human A beta PP, both of which express the human wild-type beta-secretase site sequence. In guinea pigs, oral E64d administration caused a dose-dependent reduction of up to 92% in brain, CSF, and plasma of A beta(40) and A beta(42), a reduction of up to 50% in the C-terminal beta-secretase fragment (CTF beta), and a 91% reduction in brain cathepsin B activity, but increased brain BACE1 activity by 20%. In transgenic AD mice, oral E64d administration improved memory deficits and reduced brain A beta(40) and A beta(42), amyloid plaque, brain CTF beta, and brain cathepsin B activity, but increased brain BACE1 activity. We conclude that E64d likely reduces brain A beta by inhibiting cathepsin B and not BACE1 beta-secretase activity and that E64d therefore may have potential for treating AD patients. C1 [Hook, Gregory] Amer Life Sci Pharmaceut, San Diego, CA 92109 USA. [Hook, Vivian] Univ Calif San Diego, Dept Neurosci, Dept Med & Pharmacol, Skaggs Sch Pharm & Pharmaceut Sci,Sch Med, La Jolla, CA 92093 USA. [Kindy, Mark] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Kindy, Mark] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [Kindy, Mark] Appl Neurotechnol Inc, Charleston, SC USA. RP Hook, G (reprint author), Amer Life Sci Pharmaceut, 3030 Bunker Hill St,Suite 104, San Diego, CA 92109 USA. EM ghook@alspinc.com FU National Institute on Aging, National Institutes of Health, Bethesda, MD [R21AG0311963, R44AG030865, R44AG032784]; Alzheimer's Drug Discovery Foundation, New York City, NY [20100304] FX We thank Drs. M. D. Pierschbacher and Danny Levin for their review of the manuscript. This work was supported by grant Nos. R21AG0311963, R44AG030865, and R44AG032784 from the National Institute on Aging, National Institutes of Health, Bethesda, MD, and grant No. 20100304 from the Alzheimer's Drug Discovery Foundation, New York City, NY to American Life Science Pharmaceuticals (ALSP). Dr. Gregory Hook is an employee and has equity in ALSP. Professor Vivian Hook is the Chairperson of ALSP's Scientific Advisory Board and holds equity in ALSP and that relationship has been disclosed to the University of California, San Diego, which is managing that relationship. Professor Mark Kindy is affiliated with Applied Neurotechnology, Inc. and holds equity in the company and the relationship has been disclosed to the Medical University of South Carolina, which is managing the relationship. NR 89 TC 34 Z9 36 U1 1 U2 12 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2011 VL 26 IS 2 BP 387 EP 408 DI 10.3233/JAD-2011-110101 PG 22 WC Neurosciences SC Neurosciences & Neurology GA 818OR UT WOS:000294763100016 PM 21613740 ER PT J AU Wharton, W Baker, LD Gleason, CE Dowling, M Barnet, JH Johnson, S Carlsson, C Craft, S Asthana, S AF Wharton, Whitney Baker, Laura D. Gleason, Carey E. Dowling, Maritza Barnet, Jodi H. Johnson, Sterling Carlsson, Cynthia Craft, Suzanne Asthana, Sanjay TI Short-term Hormone Therapy with Transdermal Estradiol Improves Cognition for Postmenopausal Women with Alzheimer's Disease: Results of a Randomized Controlled Trial SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; clinical trial; cognition; estradiol; estrogen; hormone therapy; medroxyprogesterone; memory ID ESTROGEN-REPLACEMENT THERAPY; CONJUGATED EQUINE ESTROGENS; PLACEBO-CONTROLLED TRIAL; NITRIC-OXIDE SYNTHASE; LONG-TERM; DOUBLE-BLIND; OLDER WOMEN; AGED WOMEN; MEMORY; MOOD AB We aimed to conduct a placebo-controlled, double-blind, parallel-group design intervention study to evaluate the therapeutic efficacy of hormone therapy (HT) in postmenopausal women with mild to moderate Alzheimer's disease (AD). The trial was designed to evaluate the dose-dependent effects of transdermal 17-beta estradiol, unopposed and opposed with medroxyprogesterone (MPA, Provera (c)), for 12 months in 43 postmenopausal women with AD. Participants were assessed using cognitive measures at baseline, months 1, 3, 6, and 12 of treatment and eight weeks post treatment (month 15). The dropout rate was 49% across 12 months. As a result of the Women's Health Initiative (WHI) and anticipated increased attrition, the protocol was modified to examine data only at time points where attrition was less than 30%. The results of sensitivity analyses indicated robust and reliable data collected in the first three months of the trial. Data collected in the first three months of the trial for forty-three participants were analyzed. HT had favorable cognitive effects across multiple cognitive domains, including visual memory (p-values < 0.030) and semantic memory (p-values < 0.037) in postmenopausal women with AD. Moreover, treatment-related changes in plasma estradiol were positively correlated with improvements in visual memory. Short-term HT that includes the use of estradiol has favorable effects on cognition in women with AD. C1 [Wharton, Whitney] Univ Wisconsin, Sch Med & Publ Hlth, William S Middleton Mem VA Hosp, Madison, WI 53705 USA. [Wharton, Whitney; Gleason, Carey E.; Dowling, Maritza; Barnet, Jodi H.; Johnson, Sterling; Carlsson, Cynthia; Asthana, Sanjay] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI USA. [Baker, Laura D.; Craft, Suzanne] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Baker, Laura D.; Craft, Suzanne] Univ Washington, Sch Med, Seattle, WA USA. RP Wharton, W (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, William S Middleton Mem VA Hosp, 2500 Overlook Terrace,GRECC 11G, Madison, WI 53705 USA. EM wlwharto@medicine.wisc.edu FU NIH [AG029624, K07AG021582, K23AG024302, K23AG026752, P50AG033514, 1UL1RR025011] FX The study utilized the resources of the School of Medicine and Public Health at the University of Wisconsin, UW Department of Medicine Division of Geriatrics and Gerontology, the Geriatric Research Education and Clinical Center (GRECC) of the William S. Middleton Memorial Veterans Hospital, Madison WI. This research was supported by NIH grants AG029624, K07AG021582, K23AG024302, K23AG026752, P50AG033514 and 1UL1RR025011. NR 74 TC 35 Z9 36 U1 2 U2 15 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2011 VL 26 IS 3 BP 495 EP 505 DI 10.3233/JAD-2011-110341 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 822GU UT WOS:000295032800009 PM 21694454 ER PT J AU Haapasalo, A Kovacs, DM AF Haapasalo, Annakaisa Kovacs, Dora M. TI The Many Substrates of Presenilin/gamma-Secretase SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Review DE Alzheimer's disease; amyloid-beta protein precursor; gamma-secretase; presenilin; regulated intramembrane processing ID AMYLOID-PRECURSOR-PROTEIN; REGULATED INTRAMEMBRANE PROTEOLYSIS; P75 NEUROTROPHIN RECEPTOR; DEPENDENT GAMMA-SECRETASE; FAMILIAL ALZHEIMERS-DISEASE; C-TERMINAL FRAGMENTS; INTRACELLULAR-DOMAIN FRAGMENT; ALPHA-CONVERTING-ENZYME; GATED SODIUM-CHANNELS; TRANS-GOLGI NETWORK AB The Alzheimer's disease (AD)-associated amyloid-beta protein precursor (A beta PP) is cleaved by alpha-, beta-, and presenilin (PS)/gamma-secretases through sequential regulated proteolysis. These proteolytic events control the generation of the pathogenic amyloid-beta (A beta) peptide, which excessively accumulates in the brains of individuals afflicted by AD. A growing number of additional proteins cleaved by PS/gamma-secretase continue to be discovered. Similarly to A beta PP, most of these proteins are type-I transmembrane proteins involved in vital signaling functions regulating cell fate, adhesion, migration, neurite outgrowth, or synaptogenesis. All the identified proteins share common structural features, which are typical for their proteolysis. The consequences of the PS/gamma-secretase-mediated cleavage on the function of many of these proteins are largely unknown. Here, we review the current literature on the proteolytic processing mediated by the versatile PS/gamma-secretase complex. We begin by discussing the steps of A beta PP processing and PS/gamma-secretase complex composition and localization, which give clues to how and where the processing of other PS/gamma-secretase substrates may take place. Then we summarize the typical features of PS/gamma-secretase-mediated protein processing. Finally, we recapitulate the current knowledge on the possible physiological function of PS/gamma-secretase-mediated cleavage of specific substrate proteins. C1 [Haapasalo, Annakaisa] Univ Eastern Finland, Inst Clin Med Neurol, Kuopio 70211, Finland. [Kovacs, Dora M.] Massachusetts Gen Hosp, Neurobiol Dis Lab, Genet & Aging Res Unit, Charlestown, MA USA. [Kovacs, Dora M.] Harvard Univ, Sch Med, Charlestown, MA USA. RP Haapasalo, A (reprint author), Univ Eastern Finland, Inst Clin Med Neurol, Yliopistonranta 1 C, Kuopio 70211, Finland. EM annakaisa.haapasalo@uef.fi FU Health Research Council of the Academy of Finland; NIH/NIA FX This work is supported by the Health Research Council of the Academy of Finland (AH) and two grants from the NIH/NIA (DMK). NR 243 TC 131 Z9 133 U1 0 U2 10 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2011 VL 25 IS 1 BP 3 EP 28 DI 10.3233/JAD-2011-101065 PG 26 WC Neurosciences SC Neurosciences & Neurology GA 800QE UT WOS:000293377700002 PM 21335653 ER PT J AU Fiala, M Mahanian, M Rosenthal, M Mizwicki, MT Tse, E Cho, T Sayre, J Weitzman, R Porter, V AF Fiala, Milan Mahanian, Michelle Rosenthal, Mark Mizwicki, Matthew T. Tse, Eric Cho, Tiffany Sayre, James Weitzman, Rachel Porter, Verna TI MGAT3 mRNA: A Biomarker for Prognosis and Therapy of Alzheimer's Disease by Vitamin D and Curcuminoids SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; amyloid-beta; MGAT3; surgical anesthesia; vitamin D3 ID AMYLOID-BETA; COGNITIVE DECLINE; FOLLOW-UP; PLASMA; RISK; ASSOCIATION; MACROPHAGES; PERSPECTIVE; CLEARANCE; DIAGNOSIS AB Practical biomarkers of Alzheimer's disease (AD) prognosis are lacking. Correspondingly, no drugs are known to decrease disease progression, although vitamin D3 has positive effects on cognition in vivo and 1 alpha, 25-dihydroxyvitamin D3 (1,25 D3) on amyloid-beta 1-42 (A beta) phagocytosis in vitro. We have examined in a pilot study a new biomarker in peripheral blood mononuclear cells, the transcription of mRNA of beta-1,4-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase (MGAT3), the essential gene for A beta phagocytosis. The transcription of MGAT3 stimulated by A beta distinguishes macrophages into Type 0 (very low MGAT3 transcription), Type I (low MGAT3 transcription up regulated by bisdemethoxycurcumin), and Type II (high MGAT3 transcription down regulated by bisdemethoxycurcumin). In this pilot study of 20 AD patients and 20 control subjects, 45% patients, but only 10% control subjects, were Type 0 (p-value = 0.009). Type 0 AD patients had worse 2-year prognosis regarding loss of independence than Type I and Type II patients (p-value = 0.013). Phagocytosis of A beta in Type I and II patients was shown to be dependent on 1,25 D3 using a specific inhibitor of the 1,25 D3-VDR activated nuclear receptor transcription factor. In a Type II patient, recovery from cognitive dysfunction related to surgical anesthesia was preceded by an improvement in phagocytosis of A beta. The results of this pilot study suggest that the MGAT3 Type biomarker may characterize subgroups of AD patients with different disease progression. In vitro results suggest that vitamin D3 supplementation might be beneficial in both Type I and II patients, whereas curcuminoids only in Type I. These results must be investigated in a large prospective study. C1 [Porter, Verna] UCLA Sch Med, Dept Neurol, Los Angeles, CA USA. [Fiala, Milan; Mahanian, Michelle; Rosenthal, Mark; Tse, Eric; Cho, Tiffany; Weitzman, Rachel] Greater Los Angeles VA Med Ctr, Dept Med, Los Angeles, CA USA. [Mizwicki, Matthew T.] Univ Calif Riverside, Dept Biochem, Riverside, CA 92521 USA. [Sayre, James] Univ Calif Sch Publ Hlth, Dept Biostat, Los Angeles, CA USA. RP Fiala, M (reprint author), UCLA CHS 23-338,650 Charles E Young Dr S, Los Angeles, CA 90095 USA. EM fiala@mednet.ucla.edu NR 31 TC 9 Z9 10 U1 1 U2 11 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2011 VL 25 IS 1 BP 135 EP 144 DI 10.3233/JAD-2011-101950 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 800QE UT WOS:000293377700014 PM 21368380 ER PT J AU Trittschuh, EH Crane, PK Larson, EB Cholerton, B McCormick, WC McCurry, SM Bowen, JD Baker, LD Craft, S AF Trittschuh, Emily H. Crane, Paul K. Larson, Eric B. Cholerton, Brenna McCormick, Wayne C. McCurry, Susan M. Bowen, James D. Baker, Laura D. Craft, Suzanne TI Effects of Varying Diagnostic Criteria on Prevalence of Mild Cognitive Impairment in a Community Based Sample SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Age-related memory disorders; aging; Alzheimer's disease; cognition; dementia; diagnosis; epidemiology; individual differences; neuropsychological tests; normative; prevalence ID IQ-ADJUSTED NORMS; ALZHEIMERS-DISEASE; DEMENTIA; OLDER; RISK; AGE; PROGRESSION; POPULATION; SUBTYPES; MCI AB Mild cognitive impairment (MCI) is proposed to be a prodrome to dementia in some older adults. However, the presentation of MCI in the community can differ substantially from clinic-based samples. The aim of the current study is to demonstrate the effects of different operational definitions of MCI on prevalence estimates in community-dwelling older adults. A consecutive series of 200 participants aged 65 and over from the Adult Changes in Thought (ACT) community-based cohort were approached to undergo comprehensive neuropsychological and medical evaluation; 159 were included in the final analyses. Nondemented subjects were categorized using various diagnostic criteria for MCI. In a novel approach, neuropsychological test scores were evaluated using an individualized benchmark as a point of test comparison, as well as traditional methods that entail comparison to age-based normative data. Diagnostic criteria were further subdivided by severity of impairment (1.0 vs. 1.5 standard deviations [sd] below the benchmark) and extent of impairment (based on a single test or an average of tests within a cognitive domain). MCI prevalence rates in the sample were highly dependent on these diagnostic factors, and varied from 11% to 92% of the sample. Older groups tended to show higher prevalence rates, although this was not the case across all diagnostic schemes. The use of an individualized benchmark, less severe impairment cutoff, and impairment on only a single test all produced higher rates of MCI. Longitudinal follow-up will determine whether varying diagnostic criteria improves sensitivity and specificity of the MCI diagnosis as a predictor for dementia. C1 [Trittschuh, Emily H.; Cholerton, Brenna; Baker, Laura D.; Craft, Suzanne] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Trittschuh, Emily H.; Baker, Laura D.; Craft, Suzanne] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Crane, Paul K.; Larson, Eric B.; Cholerton, Brenna] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Bowen, James D.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. [McCurry, Susan M.] Univ Washington, Sch Med, Dept Psychosocial & Community Hlth, Seattle, WA USA. [Larson, Eric B.] Grp Hlth Cooperat Res Inst, Ctr Hlth Studies, Seattle, WA USA. [Bowen, James D.] Swedish Med Ctr, Swedish Neurosci Inst, Seattle, WA USA. RP Cholerton, B (reprint author), VA Puget Sound Hlth Care Syst, GRECC-A-182,9600 Vet Dr SW, Tacoma, WA 98493 USA. EM bchol@u.washington.edu RI Crane, Paul/C-8623-2014; OI Crane, Paul/0000-0003-4278-7465 FU National Institute on Aging [R01AG024180, U01AG006781]; Department of Veterans Affairs; Group Health Research Institute FX This work was supported by National Institute on Aging grants R01AG024180 and U01AG006781, the Department of Veterans Affairs, and the Group Health Research Institute. The funding sources did not provide scientific input for the study. NR 61 TC 9 Z9 9 U1 2 U2 8 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2011 VL 25 IS 1 BP 163 EP 173 DI 10.3233/JAD-2011-101821 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 800QE UT WOS:000293377700017 PM 21368379 ER PT J AU Yu, J Gattoni-Celli, M Zhu, H Bhat, NR Sambamurti, K Gattoni-Celli, S Kindy, MS AF Yu, Jin Gattoni-Celli, Marco Zhu, Hong Bhat, Narayan R. Sambamurti, Kumar Gattoni-Celli, Sebastiano Kindy, Mark S. TI Vitamin D-3-Enriched Diet Correlates with a Decrease of Amyloid Plaques in the Brain of A beta PP Transgenic Mice SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; amyloid-beta; animal models; transgenic mice; vitamin D ID ALZHEIMERS-DISEASE; HYPOVITAMINOSIS-D; RAT; RECEPTOR; 1,25-DIHYDROXYVITAMIN-D3; DEFICIENCY; EXPRESSION; OLIGOMERS; BEHAVIOR; PROTEIN AB In addition to its function in calcium and bone metabolism, vitamin D is neuroprotective and important for mitigating inflammation. Alzheimer's disease (AD) is a progressive neurodegenerative disorder of the central nervous system, characterized by neuronal loss in many areas of the brain, and the formation of senile (neuritic) plaques, which increase in number and size over time. The goal of this project was to investigate whether vitamin D-3 supplementation would affect amyloid plaque formation in amyloid-beta protein precursor (A beta PP) transgenic mice that spontaneously develop amyloid plaques within 3-4 months of birth. A beta PP mice were fed control, vitamin D-3-deficient or vitamin D-3-enriched diets for five months, starting immediately after weaning. At the end of the study, the animals were subjected to behavioral studies, sacrificed, and examined for bone changes and brain amyloid load, amyloid-beta (A beta) peptide levels, inflammatory changes, and nerve growth factor (NGF) content. The results obtained indicate that a vitamin D-3-enriched diet correlates with a decrease in the number of amyloid plaques, a decrease in A beta peptides, a decrease in inflammation, and an increase in NGF in the brains of A beta PP mice. These observations suggest that a vitamin D-3-enriched diet may benefit AD patients. C1 [Yu, Jin; Gattoni-Celli, Marco; Zhu, Hong; Bhat, Narayan R.; Sambamurti, Kumar; Kindy, Mark S.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29403 USA. [Gattoni-Celli, Sebastiano] Med Univ S Carolina, Dept Radiat Oncol, Charleston, SC 29403 USA. [Gattoni-Celli, Sebastiano; Kindy, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Kindy, MS (reprint author), Med Univ S Carolina, Dept Neurosci, Strom Thurmond Biomed Res Bldg,Room 503,114 Dough, Charleston, SC 29403 USA. EM kindyms@musc.edu FU National Institutes of Health [ES 016774, R01 NS051575, AG023055]; Veterans Administration; National Science Foundation EPSCoR [EPS-0132573, EPS-0447660] FX We thank Drs. Srinivasan Shanmugarajan, William L. Ries, and Sakamuri V. Reddy for helping with the bone-related studies; we also thank Dr. Bruce W. Hollis for measuring the serum levels of circulating vitamin D in mice. This project was funded by grants from the National Institutes of Health (MSK, ES 016774; NRB, R01 NS051575; KS, AG023055), Veterans Administration (MSK and SG-C), and the National Science Foundation EPSCoR grants (MSK, EPS-0132573 and EPS-0447660). NR 40 TC 46 Z9 49 U1 1 U2 13 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2011 VL 25 IS 2 BP 295 EP 307 DI 10.3233/JAD-2011-101986 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 800QJ UT WOS:000293378300010 PM 21422528 ER PT J AU Yang, WL Lui, RLM Gao, JH Chan, TF Yau, ST Sperling, RA Huang, XD AF Yang, Wenlu Lui, Ronald L. M. Gao, Jia-Hong Chan, Tony F. Yau, Shing-Tung Sperling, Reisa A. Huang, Xudong TI Independent Component Analysis-Based Classification of Alzheimer's Disease MRI Data SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; independent component analysis; magnetic resonance imaging; mild cognitive impairment; neuroimaging biomarker; support vector machine ID MILD COGNITIVE IMPAIRMENT; SOURCE-BASED MORPHOMETRY; FUNCTIONAL MRI; DIAGNOSIS; NETWORKS; GRAY; ADNI AB There is an unmet medical need to identify neuroimaging biomarkers that allow us to accurately diagnose and monitor Alzheimer's disease (AD) at its very early stages and to assess the response to AD-modifying therapies. To a certain extent, volumetric and functional magnetic resonance imaging (fMRI) studies can detect changes in structure, cerebral blood flow, and blood oxygenation that distinguish AD and mild cognitive impairment (MCI) subjects from healthy control (HC) subjects. However, it has been challenging to use fully automated MRI analytic methods to identify potential AD neuroimaging biomarkers. We have thus proposed a method based on independent component analysis (ICA) for studying potential AD-related MR image features that can be coupled with the use of support vector machine (SVM) for classifying scans into categories of AD, MCI, and HC subjects. The MRI data were selected from the Open Access Series of Imaging Studies (OASIS) and the Alzheimer's Disease Neuroimaging Initiative databases. The experimental results showed that the ICA method coupled with SVM classifier can differentiate AD and MCI patients from HC subjects, although further methodological improvement in the analytic method and inclusion of additional variables may be required for optimal classification. C1 [Yang, Wenlu; Huang, Xudong] Brigham & Womens Hosp, Dept Radiol, Ctr Adv Med Imaging, Boston, MA 02115 USA. [Yang, Wenlu; Huang, Xudong] Brigham & Womens Hosp, Biomed Informat & Cheminformat Grp, Conjugate & Med Chem Lab, Div Nucl Med & Mol Imaging, Boston, MA 02115 USA. [Yang, Wenlu; Sperling, Reisa A.; Huang, Xudong] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Yang, Wenlu] Shanghai Maritime Univ, Informat Engn Coll, Dept Elect Engn, Shanghai, Peoples R China. [Lui, Ronald L. M.; Yau, Shing-Tung] Harvard Univ, Dept Math, Cambridge, MA 02138 USA. [Gao, Jia-Hong] Univ Chicago, Brain Res Imaging Ctr, Chicago, IL 60637 USA. [Chan, Tony F.] Hong Kong Univ Sci & Technol, Hong Kong, Hong Kong, Peoples R China. [Sperling, Reisa A.] Brigham & Womens Hosp, Memory Disorders Unit, Dept Neurol, Boston, MA 02115 USA. [Huang, Xudong] Massachusetts Gen Hosp, Dept Psychiat, Neurochem Lab, Boston, MA 02114 USA. RP Huang, XD (reprint author), Brigham & Womens Hosp, Dept Radiol, Ctr Adv Med Imaging, 75 Francis St, Boston, MA 02115 USA. EM xhuang3@partners.org RI Chan, Tony F/A-4166-2013 OI Chan, Tony F/0000-0001-6196-2068 FU Shanghai Maritime University [20080471, 20090175]; Science and Technology Commission of Shanghai Municipality [09511502502]; Ministry of Transport of the People's Republic of China [2010318810019]; national natural science foundation of China [60905056]; Radiology Department of Brigham and Women's Hospital (BWH); Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]; National Institute on Aging; National Institute of Biomedical Imaging and Bioengineering; NIH [P30 AG010129, K01 AG030514]; Dana Foundation FX The authors would like to express their gratitude for the support from the Shanghai Maritime University (Grant No. 20080471, 20090175), the Science and Technology Commission of Shanghai Municipality (Grant No. 09511502502), the Ministry of Transport of the People's Republic of China (2010318810019), the national natural science foundation of China (Grant No. 60905056), and the research funds from the Radiology Department of Brigham and Women's Hospital (BWH). We are thankful for the manuscript editing by Ms. Kimberly Lawson of the BWH Radiology Department.; ADNI data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott, AstraZeneca AB, Bayer Schering Pharma AG, Bristol-Myers Squibb, Eisai Global Clinical Development, Elan Corporation, Genentech, GE Healthcare, GlaxoSmithKline, Innogenetics, Johnson and Johnson, Eli Lilly and Co., Medpace, Inc., Merck and Co., Inc., Novartis AG, Pfizer Inc., F. Hoffman-La Roche, Schering-Plough, Synarc, Inc., and Wyeth, as well as non-profit partners the Alzheimer's Association and Alzheimer's Drug Discovery Foundation, with participation from the U.S. Food and Drug Administration. Private sector contributions to ADNI are facilitated by the Foundation for the National Institutes of Health (http://www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angeles. This research was also supported by NIH grants P30 AG010129, K01 AG030514, and the Dana Foundation. NR 28 TC 17 Z9 17 U1 2 U2 12 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2011 VL 24 IS 4 BP 775 EP 783 DI 10.3233/JAD-2011-101371 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 788XE UT WOS:000292476900014 PM 21321398 ER PT J AU Lu, PH Thompson, PM Leow, A Lee, GJ Lee, A Yanovsky, I Parikshak, N Khoo, T Wu, S Geschwind, D Bartzokis, G AF Lu, Po H. Thompson, Paul M. Leow, Alex Lee, Grace J. Lee, Agatha Yanovsky, Igor Parikshak, Neelroop Khoo, Theresa Wu, Stephanie Geschwind, Daniel Bartzokis, George TI Apolipoprotein E Genotype is Associated with Temporal and Hippocampal Atrophy Rates in Healthy Elderly Adults: A Tensor-Based Morphometry Study SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Aging; Alzheimer's disease; Apolipoprotein E; asymmetry; healthy elderly; hippocampus; magnetic resonance imaging; tensor-based morphometry; temporal lobe; white matter ID E EPSILON-4 ALLELE; MILD COGNITIVE IMPAIRMENT; WHITE-MATTER INTEGRITY; ALZHEIMERS-DISEASE; BRAIN ATROPHY; APOE GENOTYPE; CHOLESTEROL TRANSPORT; IMAGE REGISTRATION; MYELIN BREAKDOWN; CEREBRAL-CORTEX AB Apolipoprotein E (ApoE) epsilon 4 genotype is a strong risk factor for developing Alzheimer's disease (AD). Conversely, the presence of the epsilon 2 allele has been shown to mitigate cognitive decline. Tensor-based morphometry (TBM), a novel computational approach for visualizing longitudinal progression of brain atrophy, was used to determine whether cognitively intact elderly participants with the epsilon 4 allele demonstrate greater volume reduction than those with the epsilon 2 allele. Healthy "younger elderly" volunteers, aged 55-75, were recruited from the community and hospital staff. They were evaluated with a baseline and follow-up MRI scan (mean scan interval = 4.72 years, s.d. = 0.55) and completed ApoE genotyping. Twenty-seven participants were included in the study of which 16 had the epsilon 4 allele (all heterozygous epsilon 3 epsilon 4 genotype) and 11 had the epsilon 2 epsilon 3 genotype. The two groups did not differ significantly on any demographic characteristics and all subjects were cognitively "normal" at both baseline and follow-up time points. TBM was used to create 3D maps of local brain tissue atrophy rates for individual participants; these spatially detailed 3D maps were compared between the two ApoE groups. Regional analyses were performed and the epsilon 4 group demonstrated significantly greater annual atrophy rates in the temporal lobes (p = 0.048) and hippocampus (p = 0.016); greater volume loss was observed in the right hippocampus than the left. TBM appears to be useful in tracking longitudinal progression of brain atrophy in cognitively asymptomatic adults. Possession of the epsilon 4 allele is associated with greater temporal and hippocampal volume reduction well before the onset of cognitive deficits. C1 [Thompson, Paul M.; Leow, Alex; Lee, Agatha; Parikshak, Neelroop; Bartzokis, George] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Lab Neuroimaging, Los Angeles, CA 90095 USA. [Yanovsky, Igor] Univ Calif Los Angeles, Dept Math, Los Angeles, CA 90095 USA. [Leow, Alex; Bartzokis, George] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Geschwind, Daniel] Univ Calif Los Angeles, David Geffen Sch Med, Neurogenet Program, Los Angeles, CA 90095 USA. [Bartzokis, George] Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. RP Lu, PH (reprint author), Mary S Easton Ctr Alzheimers Dis Res, 10911 Weyburn Ave,Suite 200, Los Angeles, CA 90095 USA. EM plu@mednet.ucla.edu RI Bartzokis, George/K-2409-2013; Leow, Alex/K-3236-2014 OI Leow, Alex/0000-0002-5660-8651 FU National Institute of Aging (NIA) [K23-AG028727]; Alzheimer's Association [NIRG-07-60424]; Alzheimer's Disease Research Center [P50 AG-16570]; Alzheimer's Disease Research Center of California; NIH [MH51928, MH6357-01A1, MH066029-01A2, AG027342-01A2, U54 RR021813]; NIBIB; National Library of Medicine; National Center for Research Resources [AG016570, EB01651, LM05639, RR019771] FX This work was supported by grant K23-AG028727 from the National Institute of Aging (NIA), a grant from the Alzheimer's Association (NIRG-07-60424), the Alzheimer's Disease Research Center grant P50 AG-16570, and Alzheimer's Disease Research Center of California grant. Further support for this study came from NIH grants (MH51928; MH6357-01A1; MH066029-01A2; AG027342-01A2; U54 RR021813 to GB). Algorithm development for this study was also funded by the NIA, NIBIB, the National Library of Medicine, and the National Center for Research Resources (AG016570, EB01651, LM05639, RR019771 to PT). NR 73 TC 36 Z9 37 U1 3 U2 7 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2011 VL 23 IS 3 BP 433 EP 442 DI 10.3233/JAD-2010-101398 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 721KE UT WOS:000287351200006 PM 21098974 ER PT J AU De Taboada, L Yu, J El-Amouri, S Gattoni-Celli, S Richieri, S McCarthy, T Streeter, J Kindy, MS AF De Taboada, Luis Yu, Jin El-Amouri, Salim Gattoni-Celli, Sebastiano Richieri, Steve McCarthy, Thomas Streeter, Jackson Kindy, Mark S. TI Transcranial Laser Therapy Attenuates Amyloid-beta Peptide Neuropathology in Amyloid-beta Protein Precursor Transgenic Mice SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; amyloid; animal models; laser therapy; transgenic mice ID FAMILIAL ALZHEIMERS-DISEASE; TERM NEUROLOGICAL DEFICITS; MYOCARDIAL-INFARCTION; ASPARTIC PROTEASE; SPINAL-CORD; SECRETASE CLEAVAGE; MISSENSE MUTATIONS; APOLIPOPROTEIN-E; ISCHEMIC-STROKE; IRRADIATION AB Transcranial laser therapy (TLT) was tested for efficacy in a mouse model of Alzheimer's disease (AD) using a near-infrared energy laser system. TLT is thought to stimulate ATP production, increase mitochondrial activity, and help maintain neuronal function. Studies were performed to determine the effect of TLT in an amyloid-beta protein precursor (A beta PP) transgenic mouse model. TLT was administered 3 times/week at various doses, starting at 3 months of age, and was compared to a control group (no laser treatment). Treatment was continued for a total of six months. Animals were examined for amyloid load, inflammatory markers, brain amyloid-beta (A beta) levels, plasma A beta levels, cerebrospinal fluid A beta levels, soluble A beta PP (sA beta PP) levels, and behavioral changes. The numbers of A beta plaques were significantly reduced in the brain with administration of TLT in a dose-dependent fashion. Administration of TLT was associated with a dose-dependent reduction in amyloid load. All TLT doses mitigated the behavioral effects seen with advanced amyloid deposition and reduce the expression of inflammatory markers in the A beta PP transgenic mice. All TLT doses produced an increase in sA beta PP alpha and a decrease in CTF beta levels consistent with inhibition of the beta-secretase activity. In addition, TLT showed an increase in ATP levels, mitochondrial function, and c-fos suggesting an overall improvement in neurological function. These studies suggest that TLT is a potential candidate for treatment of AD. C1 [Yu, Jin; El-Amouri, Salim; Kindy, Mark S.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29524 USA. [De Taboada, Luis; Richieri, Steve; McCarthy, Thomas] PhotoThera Inc, Carlsbad, CA USA. [Gattoni-Celli, Sebastiano; Kindy, Mark S.] Med Univ S Carolina, Dept Radiat Oncol, Charleston, SC 29524 USA. [Gattoni-Celli, Sebastiano] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Streeter, Jackson] Banyan Biomarkers Inc, Alachua, FL USA. [Kindy, Mark S.] Neurol Testing Serv Inc, Charleston, SC USA. RP Kindy, MS (reprint author), Med Univ S Carolina, Dept Neurosci, 114 Doughty St,Room 503, Charleston, SC 29524 USA. EM kindyms@musc.edu FU PhotoThera, Inc.; Neurological Testing Service, Inc.; National Institutes of Health [ES 016774-01A1]; Veterans Administration FX This study was supported by funding from PhotoThera, Inc., Neurological Testing Service, Inc. and in part by grants from the National Institutes of Health ES 016774-01A1(M. K.), and the Veterans Administration (M. K.). Mr. De Taboada and Richieri and Drs. Streeter and McCarthy have interest in PhotoThera. Dr. Kindy has an interest in Neurological Testing Service, Inc. NR 53 TC 49 Z9 49 U1 1 U2 9 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2011 VL 23 IS 3 BP 521 EP 535 DI 10.3233/JAD-2010-100894 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 721KE UT WOS:000287351200014 PM 21116053 ER PT J AU Austin, D Hayes, TL Kaye, J Mattek, N Pavel, M AF Austin, Daniel Hayes, Tamara L. Kaye, Jeffrey Mattek, Nora Pavel, Misha TI On the disambiguation of passively measured in-home gait velocities from multi-person smart homes SO JOURNAL OF AMBIENT INTELLIGENCE AND SMART ENVIRONMENTS LA English DT Article DE Gait; passive infrared (PIR) motion detectors; smart homes; unobtrusive monitoring; walking speed ID LOWER-EXTREMITY FUNCTION; SUBSEQUENT DISABILITY; COGNITIVE IMPAIRMENT; EXECUTIVE FUNCTION; OLDER PERSONS; PREDICTOR; PERFORMANCE; DEMENTIA; INCHIANTI; SENSORS AB In-home monitoring of gait velocity with passive PIR sensors in a smart home has been shown to be an effective method of continuously and unobtrusively measuring this important predictor of cognitive function and mobility. However, passive measurements of velocity are nonspecific with regard to who generated each measurement or walking event. As a result, this method is not suitable for multi-person homes without additional information to aid in the disambiguation of gait velocities. In this paper we propose a method based on Gaussian mixture models (GMMs) combined with infrequent clinical assessments of gait velocity to model in-home walking speeds of two or more residents. Modeling the gait parameters directly allows us to avoid the more difficult problem of assigning each measured velocity individually to the correct resident. We show that if the clinically measured gait velocities of residents are separated by at least 15 cm/s a GMM can be accurately fit to the in-home gait velocity data. We demonstrate the accuracy of this method by showing that the correlation between the means of the GMMs and the clinically measured gait velocities is 0.877 (p value < 0.0001) with bootstrapped 95% confidence intervals of (0.79, 0.94) for 54 measurements of 20 subjects living in multi-person homes. Example applications of using this method to track in-home mean velocities over time are also given. C1 [Austin, Daniel; Hayes, Tamara L.; Pavel, Misha] Oregon Hlth & Sci Univ, Dept Biomed Engn, Portland, OR 97201 USA. [Kaye, Jeffrey; Mattek, Nora] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Kaye, Jeffrey; Mattek, Nora] Portland VA Med Ctr, Portland, OR USA. RP Austin, D (reprint author), Oregon Hlth & Sci Univ, Dept Biomed Engn, Portland, OR 97201 USA. EM austidan@bme.ogi.edu OI Austin, Daniel/0000-0002-3248-5503; Kaye, Jeffrey/0000-0002-9971-3478 FU National Institute of Health [P30-AG008017, P30-AG024978, R01-AG024059, K01-AG23014]; Department of Veterans Affairs [P30-AG008017, M01-RR000334]; Intel Corporation FX The authors would like to thank the volunteer subjects who participated in this research and the staff from the Oregon Center for Aging & Technology who assisted in this study. This work was supported in part by the National Institute of Health grants P30-AG008017, P30-AG024978, R01-AG024059, K01-AG23014, the Department of Veterans Affairs grants P30-AG008017 and M01-RR000334, and Intel Corporation. Dr. Hayes has a significant financial interest in Intel Corporation, a company that provided funds to purchase some of the computers used in this study. Intel Corporation may have a commercial interest in the results of this research. This potential conflict has been reviewed and managed by OHSU. NR 35 TC 11 Z9 11 U1 0 U2 5 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1876-1364 J9 J AMB INTEL SMART EN JI J. Ambient Intell. Smart Environ. PY 2011 VL 3 IS 2 BP 165 EP 174 DI 10.3233/AIS-2011-0107 PG 10 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Telecommunications SC Computer Science; Telecommunications GA 778FM UT WOS:000291688100006 PM 21572911 ER PT J AU Cukrowicz, KC Schlegel, EF Smith, PN Jacobs, MP Van Orden, KA Paukert, AL Pettit, JW Joiner, TE AF Cukrowicz, Kelly C. Schlegel, Erin F. Smith, Phillip N. Jacobs, Matthew P. Van Orden, Kimberly A. Paukert, Ambert L. Pettit, Jeremy W. Joiner, Thomas E. TI Suicide Ideation Among College Students Evidencing Subclinical Depression SO JOURNAL OF AMERICAN COLLEGE HEALTH LA English DT Article DE college students; depression; subclinical depression; suicidal ideation ID QUESTIONNAIRE; INVENTORY; HOPELESSNESS; ADOLESCENCE; MODEL AB Identifying elevated suicide ideation in college students is a critical step in preventing suicide attempts and deaths by suicide on college campuses. Although suicide ideation may be most prominent in students with severe depression, this should not suggest that only students with severe depression experience significant risk factors for suicide. Objective: The purpose of these 3 studies was to explore the relation between suicide ideation and severity of depressive symptoms in college students. Participants: In each study a sample of college students were recruited for participation. Methods: Participants completed self-report assessments of depressive symptoms and suicide ideation. Results: The results of these studies suggest that although the greatest elevation in suicide ideation occurs at the highest depressive symptoms, significant suicide ideation is also experienced by college students with mild and moderate depressive symptoms. Conclusions: The implications of these findings for the assessment of suicide ideation are discussed. C1 [Cukrowicz, Kelly C.; Schlegel, Erin F.; Jacobs, Matthew P.] Texas Tech Univ, Dept Psychol, Lubbock, TX 79409 USA. [Smith, Phillip N.] Univ S Alabama, Dept Psychol, Mobile, AL 36688 USA. [Van Orden, Kimberly A.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Paukert, Ambert L.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Pettit, Jeremy W.] Florida Int Univ, Dept Psychol, Miami, FL 33199 USA. [Joiner, Thomas E.] Florida State Univ, Dept Psychol, Tallahassee, FL 32306 USA. RP Cukrowicz, KC (reprint author), Texas Tech Univ, Dept Psychol, Mail Stop 42051, Lubbock, TX 79409 USA. EM kelly.cukrowicz@ttu.edu FU NIMH NIH HHS [T32 MH020061] NR 22 TC 30 Z9 33 U1 0 U2 8 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0744-8481 J9 J AM COLL HEALTH JI J. Am. Coll. Health PY 2011 VL 59 IS 7 BP 575 EP 581 DI 10.1080/07448481.2010.483710 PG 7 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA 881IY UT WOS:000299478100001 PM 21823951 ER PT J AU Spadea, MF Baroni, G Gierga, DP Turcotte, JC Chen, GTY Sharp, GC AF Spadea, Maria Francesca Baroni, Guido Gierga, David P. Turcotte, Julie C. Chen, George T. Y. Sharp, Gregory C. TI Evaluation and commissioning of a surface based system for respiratory sensing in 4D CT SO JOURNAL OF APPLIED CLINICAL MEDICAL PHYSICS LA English DT Article DE 4D CT; respiratory motion; surface imaging; multi sensor analysis ID 4-DIMENSIONAL COMPUTED-TOMOGRAPHY; RADIATION-THERAPY; RADIOTHERAPY AB The purpose of this study is to assess the temporal and reconstruction accuracy of a surface imaging system, the GateCT under ideal conditions, and compare the device with a commonly used respiratory surrogate: the Varian RPM. A clinical CT scanner, run in cine mode, was used with two optical devices, GateCT and RPM, to detect respiratory motion. A radiation detector, GM-10, triggers the X-ray on/off to GateCT system, while the RPM is directly synchronized with the CT scanner through an electronic connection. Two phantoms were imaged: the first phantom translated on a rigid plate along the anterior-posterior (AP) direction, and was used to assess the temporal synchronization of each optical system with the CT scanner. The second phantom, consisting of five spheres translating 3 cm peak-to-peak in the superior-inferior direction, was used to assess the quality of rebinned images created by GateCT and RPM. Calibration assessment showed a nearly perfect synchronization with the scanner for both the RPM and GateCT systems, thus demonstrating the good performance of the radiation detector. Results for the volume rebinning test showed discrepancies in volumes for the 3D reconstruction (compared to ground truth) of up to 36% for GateCT and up to 40% for RPM. No statistical difference was proven between the two systems in volume sorting. Errors are mainly due to phase detection inaccuracies and to the large motion of the phantom. This feasibility study assessed the consistency of two optical systems in synchronizing the respiratory signal with the image acquisition. A new patient protocol based on both RPM and GateCT will be soon started. C1 [Spadea, Maria Francesca] Magna Graecia Univ Catanzaro, Dept Expt & Clin Med, I-88100 Catanzaro, Italy. [Spadea, Maria Francesca; Baroni, Guido] Politecn Milano Univ, Dept Bioengn, Milan, Italy. [Gierga, David P.; Turcotte, Julie C.; Chen, George T. Y.; Sharp, Gregory C.] Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. [Gierga, David P.; Turcotte, Julie C.; Chen, George T. Y.; Sharp, Gregory C.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Spadea, MF (reprint author), Magna Graecia Univ Catanzaro, Dept Expt & Clin Med, Viale Europa, I-88100 Catanzaro, Italy. EM mfspadea@unicz.it RI Baroni, Guido/D-3012-2011; Spadea, Maria Francesca/I-2468-2012 FU MIT; Politecnico di Milano FX This work was supported in part by the "Progetto Rocca" Foundation, a collaboration program between MIT and Politecnico di Milano. NR 10 TC 4 Z9 4 U1 1 U2 2 PU MULTIMED INC PI TORONTO PA 66 MARTIN ST, TORONTO, ON L9T 2R2, CANADA SN 1526-9914 J9 J APPL CLIN MED PHYS JI J. Appl. Clin. Med. Phys PY 2011 VL 12 IS 1 BP 162 EP 169 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 750MO UT WOS:000289551600017 ER PT J AU Goodman, MS Li, Y Tiwari, RC AF Goodman, Melody S. Li, Yi Tiwari, Ram C. TI Detecting multiple change points in piecewise constant hazard functions SO JOURNAL OF APPLIED STATISTICS LA English DT Article DE survival analysis; change points; piecewise constant; hazard function; cancer ID 2-PHASE REGRESSION; RATE MODEL; INFERENCE; LIKELIHOOD; CANCER AB The National Cancer Institute (NCI) suggests a sudden reduction in prostate cancer mortality rates, likely due to highly successful treatments and screening methods for early diagnosis. We are interested in understanding the impact of medical breakthroughs, treatments, or interventions, on the survival experience for a population. For this purpose, estimating the underlying hazard function, with possible time change points, would be of substantial interest, as it will provide a general picture of the survival trend and when this trend is disrupted. Increasing attention has been given to testing the assumption of a constant failure rate against a failure rate that changes at a single point in time. We expand the set of alternatives to allow for the consideration of multiple change-points, and propose a model selection algorithm using sequential testing for the piecewise constant hazard model. These methods are data driven and allow us to estimate not only the number of change points in the hazard function but where those changes occur. Such an analysis allows for better understanding of how changing medical practice affects the survival experience for a patient population. We test for change points in prostate cancer mortality rates using the NCI Surveillance, Epidemiology, and End Results dataset. C1 [Goodman, Melody S.] SUNY Stony Brook, Grad Program Publ Hlth, Dept Prevent Med, Sch Med, Stony Brook, NY 11794 USA. [Li, Yi] Harvard Univ, Dept Biostat, Boston, MA 02115 USA. [Li, Yi] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Tiwari, Ram C.] US FDA, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Goodman, MS (reprint author), Washington Univ, Sch Med, Dept Surg, Div Publ Hlth Sci, St Louis, MO 63110 USA. EM goodmanm@wudosis.wustl.edu RI Goodman, Melody/F-6768-2011 OI Goodman, Melody/0000-0001-8932-624X FU National Institute of Child Health and Human Development [5 F31 HD043695]; National Institute of Health [R01CA95747] FX The research of M. S. G. was supported by National Institute of Child Health and Human Development grant 5 F31 HD043695. The research of Y.L. was supported by National Institute of Health grant R01CA95747. Views expressed by R. C. T. here are his own and do not necessarily represent those of Food and Drug Administration. NR 17 TC 13 Z9 13 U1 2 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0266-4763 J9 J APPL STAT JI J. Appl. Stat. PY 2011 VL 38 IS 11 BP 2523 EP 2532 DI 10.1080/02664763.2011.559209 PG 10 WC Statistics & Probability SC Mathematics GA 873YY UT WOS:000298923300010 PM 22707842 ER PT J AU Yue, B Varadarajan, KM Ai, ST Tang, TT Rubash, HE Li, GA AF Yue, Bing Varadarajan, Kartik M. Ai, Songtao Tang, Tingting Rubash, Harry E. Li, Guoan TI Differences of Knee Anthropometry Between Chinese and White Men and Women SO JOURNAL OF ARTHROPLASTY LA English DT Article DE knee geometry; total knee arthroplasty; Chinese; Caucasian; male; female ID PROXIMAL TIBIA; ARTHROPLASTY; DESIGN; POPULATION; PROSTHESIS; FEMUR; SLOPE AB Whether there are differences in knee anthropometry between Asian and white knees remains unclear. Three-dimensional knee models were constructed using computed tomography or magnetic resonance imaging of healthy Chinese and white subjects. The morphologic measurements of the femur included mediolateral, anteroposterior dimensions, and aspect ratio. The tibial measurements included mediolateral, medial/lateral anteroposterior dimension, aspect ratio, and posterior slope of medial/lateral plateau. The results showed that Chinese knees were generally smaller than white knees. In addition, the femoral aspect ratio of Chinese females was significantly smaller than that of white females (1.24 +/- 0.04 vs 1.28 +/- 0.06). Tibial aspect ratio differences between Chinese and white males (1.82 +/- 0.07 vs 1.75 +/- 0.11), though significant, were likely a reflection of differences in knee size between races. These racial differences should be considered in the design of total knee arthroplasty prosthesis for Asian population. C1 [Li, Guoan] Harvard Univ, Sch Med, Bioengn Lab, Massachusetts Gen Hosp,Dept Orthoped Surg, Boston, MA 02114 USA. [Yue, Bing; Varadarajan, Kartik M.; Rubash, Harry E.; Li, Guoan] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Yue, Bing; Ai, Songtao; Tang, Tingting] Shanghai Jiao Tong Univ, Sch Med, Dept Orthoped Surg, Shanghai Key Lab Orthopaed Implant,Shanghai Ninth, Shanghai 200030, Peoples R China. [Varadarajan, Kartik M.] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. RP Li, GA (reprint author), Harvard Univ, Sch Med, Bioengn Lab, Massachusetts Gen Hosp,Dept Orthoped Surg, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. RI Tang, Tingting/B-1361-2013; OI yan, wei/0000-0001-5575-7017 FU National Institutes of Health [R01-AR052408, R21-AR05107]; Shanghai Science and Technology Development Fund [09dz2200400]; Program for Shanghai Key Laboratory of Orthopedic Implant [08DZ2230330]; National Natural Science Foundation of China [30901517] FX This study was made possible through grants received from the National Institutes of Health (R01-AR052408, R21-AR05107). The authors also gratefully acknowledge the support of the Shanghai Science and Technology Development Fund (09dz2200400), the Program for Shanghai Key Laboratory of Orthopedic Implant (08DZ2230330), and National Natural Science Foundation of China (30901517). NR 29 TC 51 Z9 62 U1 0 U2 7 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD JAN PY 2011 VL 26 IS 1 BP 124 EP 130 DI 10.1016/j.arth.2009.11.020 PG 7 WC Orthopedics SC Orthopedics GA 707KV UT WOS:000286286200021 PM 20149574 ER PT J AU Wen, Y Feng, J Scott, DR Marcus, EA Sachs, G AF Wen, Yi Feng, Jing Scott, David R. Marcus, Elizabeth A. Sachs, George TI A cis-Encoded Antisense Small RNA Regulated by the HP0165-HP0166 Two-Component System Controls Expression of ureB in Helicobacter pylori SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ESCHERICHIA-COLI; ACID RESISTANCE; UREASE EXPRESSION; ALLELIC EXCHANGE; GENE-EXPRESSION; NONCODING RNAS; PH; IDENTIFICATION; BACTERIA; COLONIZATION AB Expression of urease is essential for gastric colonization by Helicobacter pylori. The increased level of urease in gastric acidity is due, in part, to acid activation of the two-component system (TCS) consisting of the membrane sensor HP0165 and its response regulator, HP0166, which regulates transcription of the seven genes of the urease gene cluster. We now find that there are two major ureAB transcripts: a 2.7-kb full-length ureAB transcript and a 1.4-kb truncated transcript lacking 3' ureB. Acidic pH (pH 4.5) results in a significant increase in transcription of ureAB, while neutral pH (pH 7.4) increases the truncated 1.4-kb transcript. Northern blot analysis with sense RNA and strand-specific oligonucleotide probes followed by 5' rapid amplification of cDNA ends detects an antisense small RNA (sRNA) encoded by the 5' ureB noncoding strand consisting of similar to 290 nucleotides (5'ureB-sRNA). Deletion of HP0165 elevates the level of the truncated 1.4-kb transcript along with that of the 5'ureB-sRNA at both pH 7.4 and pH 4.5. Overexpression of 5'ureB-sRNA increases the 1.4-kb transcript, decreases the 2.7-kb transcript, and decreases urease activity. Electrophoretic mobility shift assay shows that unphosphorylated HP0166 binds specifically to the 5'ureB-sRNA promoter. The ability of the HP0165-HP0166 TCS to both increase and decrease ureB expression at low and high pHs, respectively, facilitates gastric habitation and colonization over the wide range of intragastric pHs experienced by the organism. C1 [Wen, Yi] Univ Calif Los Angeles, David Geffen Sch Med, Membrane Biol Lab, Dept Physiol, Los Angeles, CA 90073 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Wen, Y (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Membrane Biol Lab, Dept Physiol, 11301 Wilshire Blvd,Bldg 113,Rm 324, Los Angeles, CA 90073 USA. EM ywen@ucla.edu FU U.S. Department of Veterans Affairs; NIH [DK46917, 53462, 58333] FX This work was supported by U.S. Department of Veterans Affairs and NIH grants DK46917, 53462, and 58333. NR 77 TC 14 Z9 14 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JAN PY 2011 VL 193 IS 1 BP 40 EP 51 DI 10.1128/JB.00800-10 PG 12 WC Microbiology SC Microbiology GA 692GY UT WOS:000285142500003 PM 20971914 ER PT J AU Chew, RB Bryson, CL Au, DH Maciejewski, ML Bradley, KA AF Chew, Ryan B. Bryson, Chris L. Au, David H. Maciejewski, Matthew L. Bradley, Katharine A. TI Are Smoking and Alcohol Misuse Associated with Subsequent Hospitalizations for Ambulatory Care Sensitive Conditions? SO JOURNAL OF BEHAVIORAL HEALTH SERVICES & RESEARCH LA English DT Article ID PREVENTABLE HOSPITALIZATIONS; SOCIOECONOMIC-STATUS; CIGARETTE-SMOKING; SCREENING SCORES; HEALTH-CARE; MEDICARE BENEFICIARIES; COST-EFFECTIVENESS; DRINK ALCOHOL; MANAGED CARE; IMPACT AB Hospitalizations for ambulatory care sensitive conditions (ACSCs) are used to assess quality of care, but studies rarely adjust for health behaviors. This study evaluated whether results of smoking or alcohol screening were associated with hospitalizations for ACSCs. Participants included 33,273 male Veterans Affairs general medicine outpatients who returned mailed surveys. The main outcome was hospitalization with a primary discharge diagnosis for an ACSC in the year following screening. Analyses were adjusted for demographics, comorbidity, and other health behaviors. Current and previous smoking and abstaining from alcohol were associated with significantly increased risk of hospitalization for ACSCs, but alcohol misuse was not. However, severe alcohol misuse was associated with increased risk of hospitalizations with a primary or secondary ACSC discharge diagnosis. When ACSCs are used to evaluate the quality of care, health systems caring for populations with higher rates of smoking or nondrinking could falsely appear to have poorer quality care if alcohol and tobacco use are not considered. C1 [Chew, Ryan B.; Bryson, Chris L.; Au, David H.; Bradley, Katharine A.] VA Puget Sound Hlth Care Syst, VA Hlth Serv Res & Dev, Seattle, WA 98101 USA. [Bryson, Chris L.; Bradley, Katharine A.] VA Puget Sound Hlth Care Syst, Gen Med Serv, Seattle, WA 98101 USA. [Au, David H.; Bradley, Katharine A.] Univ Washington, Dept Med, Seattle, WA USA. [Bradley, Katharine A.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Maciejewski, Matthew L.] Durham VA Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC USA. [Maciejewski, Matthew L.] Duke Univ, Sch Med, Durham, NC USA. [Chew, Ryan B.] Overlake Hosp Med Ctr, Bellevue, WA USA. [Bradley, Katharine A.] VA Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA 98101 USA. RP Bradley, KA (reprint author), VA Puget Sound Hlth Care Syst, VA Hlth Serv Res & Dev, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM rbchew@gmail.com; christopher.bryson@va.gov; david.au@va.gov; matthew.maciejewski@va.gov; katharine.bradley@va.gov NR 55 TC 6 Z9 6 U1 2 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1094-3412 J9 J BEHAV HEALTH SER R JI J. Behav. Health Serv. Res. PD JAN PY 2011 VL 38 IS 1 BP 3 EP 15 DI 10.1007/s11414-010-9215-x PG 13 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 703RQ UT WOS:000285999400002 PM 20464519 ER PT J AU Wenk, JF AF Wenk, Jonathan F. TI Numerical Modeling of Stress in Stenotic Arteries With Microcalcifications: A Parameter Sensitivity Study SO JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME LA English DT Article DE microcalcifications; sensitivity study; plaque; finite elements ID HUMAN ATHEROSCLEROTIC PLAQUES; VULNERABLE PLAQUE; FIBROUS CAP; CELLULAR MICROCALCIFICATIONS; STABILITY; THICKNESS; RUPTURE; ULTRASOUND; PATHOLOGY; IMPACT AB As a follow-up to the work presented in Wenk et al. (2010, "Numerical Modeling of Stress in Stenotic Arteries With Microcalcifications: A Micromechanical Approximation," ASME J. Biomech. Eng., 132, p. 091011), a formal sensitivity study was conducted in which several model parameters were varied. The previous work only simulated a few combinations of the parameters. In the present study, the fibrous cap thickness, longitudinal position of the region of microcalcifications, and volume fraction of microcalcifications were varied over a broader range of values. The goal of the present work is to investigate the effects of localized regions of microcalcifications on the stress field of atherosclerotic plaque caps in a section of carotid artery. More specifically, the variations in the magnitude and location of the maximum circumferential stress were assessed for a range of parameters using a global sensitivity analysis method known as Sobol' indices. The stress was calculated by performing finite element simulations of three-dimensional fluid-structure interaction models, while the sensitivity indices were computed using a Monte Carlo scheme. The results indicate that cap thickness plays a significant role in the variation in the magnitude of the maximum circumferential stress, with the sensitivity to volume fraction increasing when the region of microcalcification is located at the shoulder. However, the volume fraction played a larger role in the variation in the location of the maximum circumferential stress. This matches the finding of the previous study (Wenk et al., 2010, "Numerical Modeling of Stress in Stenotic Arteries With Microcalcifications: A Micromechanical Approximation," ASME J. Biomech. Eng., 132, p. 091011), which indicates that the maximum circumferential stress always shifts to the region of microcalcification. [DOI: 10.1115/1.4003128] C1 [Wenk, Jonathan F.] Univ Calif San Francisco, Dept Bioengn, San Francisco, CA 94121 USA. [Wenk, Jonathan F.] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94121 USA. [Wenk, Jonathan F.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Wenk, JF (reprint author), Univ Calif San Francisco, Dept Bioengn, San Francisco, CA 94121 USA. EM jwenk1@me.berkeley.edu NR 24 TC 10 Z9 10 U1 0 U2 4 PU ASME-AMER SOC MECHANICAL ENG PI NEW YORK PA THREE PARK AVE, NEW YORK, NY 10016-5990 USA SN 0148-0731 J9 J BIOMECH ENG-T ASME JI J. Biomech. Eng.-Trans. ASME PD JAN PY 2011 VL 133 IS 1 AR 014503 DI 10.1115/1.4003128 PG 6 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 700TQ UT WOS:000285767600015 PM 21186905 ER PT J AU Cohen, J Zaleski, KL Nourissat, G Julien, TP Randolph, MA Yaremchuk, MJ AF Cohen, Jonah Zaleski, Katherine L. Nourissat, Geoffroy Julien, Terrill P. Randolph, Mark A. Yaremchuk, Michael J. TI Survival of porcine mesenchymal stem cells over the alginate recovered cellular method SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A LA English DT Article DE mesenchymal stem cells; tissue engineering; scaffold; alginate hydrogel; cartilage ID CHONDROGENIC DIFFERENTIATION; IN-VITRO; CARTILAGE; CULTURE; CHONDROCYTES; MARROW; BONE; PHENOTYPE; MODELS; BEAD AB Although previous studies have established alginate as a three-dimensional scaffold for chondrogenic differentiation of mesenchymal stem cells (MSCs), little is known about the cytotoxic effects of the polymerizing and chelating reagents used in the alginate recovered cellular method. Swine MSCs (sMSC) were suspended in the polymerizing agent, CaCl(2), and viability was assessed using a trypan blue exclusion assay at intervals over 2 h. MSCs were also suspended in two different chelating agents, 55 mM sodium citrate and 50 mM EDTA, and viability was calculated. Finally, sMSCs and human MSCs were encapsulated and cultured in vitro. The sMSC were collected at day 4 and the cells were recovered by chelation. Encapsulated hMSCs were cultured with TGF beta 3 and IGF-1 and assayed by qRT-PCR for collagen types I and II and sox9 with encapsulated human dermal fibroblasts and chondrocytes as controls recovered on days 0, 7, and 14. Only 53% of sMSCs were viable after 10 min in CaCl(2), the standard polymerization period, whereas 94% of encapsulated sMSCs in polymerized alginate were alive at 15 days. After 20 min in chelating agents, sodium citrate and EDTA, only 46% and 17% of the cells, were viable, respectively. The alginate recovered sMSCs yielded 12% survival. Human MSCs unregulated cartilage-specific collagen type II over the 14-day culture. Collagen I remained unchanged in the hMSCs. Alginate is a suitable agent for chondrodifferentiation of MSCs and can be dissolved by chelation, but the agents involved in hydrogel polymerization and cell recovery should be altered to improve MSC survival. (C) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 96A: 93-99, 2011. C1 [Cohen, Jonah; Zaleski, Katherine L.; Nourissat, Geoffroy; Julien, Terrill P.; Randolph, Mark A.; Yaremchuk, Michael J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Plast Surg, Boston, MA 02114 USA. [Cohen, Jonah] Brown Univ, Brown Med Sch, Providence, RI 02912 USA. RP Randolph, MA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Plast Surg, WAC 453,15 Parkman St, Boston, MA 02114 USA. EM randolph.mark@MGH.Harvard.edu OI Cohen, Jonah/0000-0001-9630-0531 FU American Foundation FX Contract grant sponsor: The American Foundation for Surgery of the Hand NR 19 TC 14 Z9 15 U1 1 U2 12 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1549-3296 J9 J BIOMED MATER RES A JI J. Biomed. Mater. Res. Part A PD JAN PY 2011 VL 96A IS 1 BP 93 EP 99 DI 10.1002/jbm.a.32961 PG 7 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 690WX UT WOS:000285041400011 PM 21105156 ER PT J AU Runnels, JM Carlson, AL Pitsillides, C Thompson, B Wu, J Spencer, JA Kohler, JMJ Azab, A Moreau, AS Rodig, SJ Kung, AL Anderson, KC Ghobrial, IM Lin, CP AF Runnels, Judith M. Carlson, Alicia L. Pitsillides, Costas Thompson, Brian Wu, Juwell Spencer, Joel A. Kohler, John M. J. Azab, AbdelKareem Moreau, Anne-Sophie Rodig, Scott J. Kung, Andrew L. Anderson, Kenneth C. Ghobrial, Irene M. Lin, Charles P. TI Optical techniques for tracking multiple myeloma engraftment, growth, and response to therapy SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE In vivo cell tracking; multiple myeloma; intravital imaging; in vivo flow cytometry; confocal microscopy; bioluminescence ID PROTEASOME INHIBITOR PS-341; GREEN FLUORESCENT PROTEIN; IN-VIVO VIDEOMICROSCOPY; HUMAN BONE-MARROW; CANCER METASTASIS; CIRCULATING CELLS; CHEMOKINE SDF-1; GENE-EXPRESSION; NOD/SCID MICE; LIVING MICE AB Multiple myeloma (MM), the second most common hematological malignancy, initiates from a single site and spreads via circulation to multiple sites in the bone marrow (BM). Methods to track MM cells both in the BM and circulation would be useful for developing new therapeutic strategies to target MM cell spread. We describe the use of complementary optical techniques to track human MM cells expressing both bioluminescent and fluorescent reporters in a mouse xenograft model. Long-term tumor growth and response to therapy are monitored using bioluminescence imaging (BLI), while numbers of circulating tumor cells are detected by in-vivo flow cytometry. Intravital microscopy is used to detect early seeding of MM cells to the BM, as well as residual cancer cells that remain in the BM after the bulk of the tumor is eradicated following drug treatment. Thus, intravital microscopy provides a powerful, albeit invasive, means to study cellular processes in vivo at the very early stage of the disease process and at the very late stage of therapeutic intervention when the tumor burden is too small to be detected by other imaging methods. (C) 2011 Society of Photo-Optical Instrumentation Engineers (SPIE). [DOI: 10.1117/1.3520571] C1 [Runnels, Judith M.; Carlson, Alicia L.; Pitsillides, Costas; Thompson, Brian; Wu, Juwell; Spencer, Joel A.; Kohler, John M. J.; Lin, Charles P.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Runnels, Judith M.; Carlson, Alicia L.; Pitsillides, Costas; Thompson, Brian; Wu, Juwell; Spencer, Joel A.; Kohler, John M. J.; Lin, Charles P.] Ctr Syst Biol, Adv Microscopy Program, Boston, MA 02114 USA. [Runnels, Judith M.; Azab, AbdelKareem; Moreau, Anne-Sophie; Anderson, Kenneth C.; Ghobrial, Irene M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Runnels, Judith M.; Carlson, Alicia L.; Azab, AbdelKareem; Moreau, Anne-Sophie; Kung, Andrew L.; Lin, Charles P.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Rodig, Scott J.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Kung, Andrew L.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Kung, Andrew L.] Childrens Hosp, Dept Hematol Oncol, Boston, MA 02115 USA. RP Lin, CP (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM irene_ghobrial@dfci.harvard.edu; lin@helix.mgh.harvard.edu RI Spencer, Joel/A-4590-2013; OI Kung, Andrew/0000-0002-9091-488X FU NIH [R01 CA125690, R01 CA133799, P50 CA086355] FX We wish to thank David Rowe for providing the Col2.3 mice, Christina LoCelso for maintaining the colony of mice, and Daniel Cote for providing the image capture software, iPhoton. This work was supported by NIH R01 CA125690, R01 CA133799, and P50 CA086355. NR 70 TC 16 Z9 16 U1 1 U2 4 PU SPIE-SOC PHOTOPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD JAN PY 2011 VL 16 IS 1 AR 011006 DI 10.1117/1.3520571 PG 13 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 725HW UT WOS:000287636800005 PM 21280893 ER PT J AU Tian, PF Devor, A Sakadzic, S Dale, AM Boas, DA AF Tian, Peifang Devor, Anna Sakadzic, Sava Dale, Anders M. Boas, David A. TI Monte Carlo simulation of the spatial resolution and depth sensitivity of two-dimensional optical imaging of the brain SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE light scattering; Monte Carlo simulation; biological tissues; biomedical optical imaging; light absorption; absorption imaging; fluorescence imaging ID TISSUES; LIGHT; REPRESENTATION; SPECTROSCOPY; ORGANIZATION; TRANSPORT; SIGNAL; MEDIA; MODEL AB Absorption or fluorescence-based two-dimensional (2-D) optical imaging is widely employed in functional brain imaging. The image is a weighted sum of the real signal from the tissue at different depths. This weighting function is defined as "depth sensitivity." Characterizing depth sensitivity and spatial resolution is important to better interpret the functional imaging data. However, due to light scattering and absorption in biological tissues, our knowledge of these is incomplete. We use Monte Carlo simulations to carry out a systematic study of spatial resolution and depth sensitivity for 2-D optical imaging methods with configurations typically encountered in functional brain imaging. We found the following: (i) the spatial resolution is <200 mu m for NA <= 0.2 or focal plane depth <= 300 mu m. (ii) More than 97% of the signal comes from the top 500 mu m of the tissue. (iii) For activated columns with lateral size larger than spatial resolution, changing numerical aperature (NA) and focal plane depth does not affect depth sensitivity. (iv) For either smaller columns or large columns covered by surface vessels, increasing NA and/or focal plane depth may improve depth sensitivity at deeper layers. Our results provide valuable guidance for the optimization of optical imaging systems and data interpretation. (C) 2011 society of Photo-Optical Instrumentation Engineers (SPIE). [DOI: 10.1117/1.3533263] C1 [Tian, Peifang] John Carroll Univ, Dept Phys, University Hts, OH 44118 USA. [Tian, Peifang; Devor, Anna; Dale, Anders M.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [Devor, Anna; Dale, Anders M.] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA. [Devor, Anna; Sakadzic, Sava; Boas, David A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Tian, PF (reprint author), John Carroll Univ, Dept Phys, 20700 N Pk Blvd, University Hts, OH 44118 USA. EM ptian@jcu.edu FU NINDS [NS-051188, NS-057198, NS-057476]; NIBIB [EB-009118]; John Carroll University FX We thank Ivan Teng and Dr. Qianqian Fang for their help on the simulation program. We gratefully acknowledge support from the NINDS (Grant Nos. NS-051188 and NS-057198 to A. D. and Grant No. NS-057476 to D. A. B.) and NIBIB (Grant No. EB-009118 to A. MD.). We also acknowledge the support from John Carroll University through the Summer Research Fellowship to P. T. NR 27 TC 16 Z9 16 U1 0 U2 8 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 EI 1560-2281 J9 J BIOMED OPT JI J. Biomed. Opt. PD JAN PY 2011 VL 16 IS 1 AR 016006 DI 10.1117/1.3533263 PG 13 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 725HW UT WOS:000287636800024 PM 21280912 ER PT J AU Li, YQ Alam, HB AF Li, Yongqing Alam, Hasan B. TI Modulation of Acetylation: Creating a Pro-survival and Anti-Inflammatory Phenotype in Lethal Hemorrhagic and Septic Shock SO JOURNAL OF BIOMEDICINE AND BIOTECHNOLOGY LA English DT Review ID HISTONE DEACETYLASE INHIBITORS; NF-KAPPA-B; SUBEROYLANILIDE HYDROXAMIC ACID; MULTIPLE ORGAN FAILURE; AMYOTROPHIC-LATERAL-SCLEROSIS; SPINAL MUSCULAR-ATROPHY; HEAT-INDUCED APOPTOSIS; GENE-EXPRESSION; TRICHOSTATIN-A; VALPROIC ACID AB Histone deacetylases (HDACs) play a key role in homeostasis of protein acetylation in histone and nonhistone proteins and in regulating fundamental cellular activities. In this paper we review and discuss intriguing recent developments in the use of histone deacetylase inhibitors (HDACIs) to combat some critical conditions in an animal model of hemorrhagic and septic shock. HDACIs have neuroprotective, cardioprotective, renal-protective, and anti-inflammatory properties; survival improvements have been significantly shown in these models. We discuss the targets and mechanisms underlying these effects of HDACIs and comment on the potential new clinical applications for these agents in the future. This paper highlights the emerging roles of HDACIs as acetylation modulators in models of hemorrhagic and septic shock and explains some contradictions encountered in previous studies. C1 [Li, Yongqing; Alam, Hasan B.] Harvard Univ, Sch Med, Div Trauma Emergency Surg & Surg Crit Care, Massachusetts Gen Hosp,Dept Surg, Boston, MA 02114 USA. RP Alam, HB (reprint author), Harvard Univ, Sch Med, Div Trauma Emergency Surg & Surg Crit Care, Massachusetts Gen Hosp,Dept Surg, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM hbalam@partners.org FU National Institutes of Health [RO1 GM084127]; Defense Advanced Research Projects Agency [W911NF-06-1-0220]; Office of Naval Research [N000140910378]; US Army Medical Research Material Command [GRANTT00521959] FX Dr. Alam acknowledges grant support from the National Institutes of Health (RO1 GM084127), Defense Advanced Research Projects Agency (W911NF-06-1-0220), Office of Naval Research (N000140910378), and the US Army Medical Research Material Command (GRANTT00521959). NR 145 TC 25 Z9 26 U1 1 U2 7 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1110-7243 J9 J BIOMED BIOTECHNOL JI J. Biomed. Biotechnol. PY 2011 AR 523481 DI 10.1155/2011/523481 PG 15 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 744LI UT WOS:000289095600001 ER PT J AU Hou, Y Ding, V Li, K Zhou, XH AF Hou, Yan Ding, Victoria Li, Kang Zhou, Xiao-Hua TI Two New Covariate Adjustment Methods for Non-Inferiority Assessment of Binary Clinical Trials Data SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Clinical trials; Covariate adjustment; Effect modification; Mann-Whitney test; Nonparametric ID 5 INTERVAL ESTIMATORS; STATISTICAL TESTS; ROC CURVE; EQUIVALENCE; RATIO; NONINFERIORITY; MORTALITY; DESIGN; MARGIN; RISK AB In clinical trials, examining the adjusted treatment difference has become the preferred way to establish non-inferiority (NI) in cases involving a binary endpoint. However, current methods are inadequate in the area of covariate adjustment. In this paper, we introduce two new methods, nonparametric and parametric, of using the probability and probability (P-P) curve to address the issue of unadjusted categorical covariates in the traditional assessment of NI in clinical trials. We also show that the area under the P-P curve is a valid alternative for assessing NI using the adjusted treatment difference, and we compute this area using Mann-Whitney nonparametric statistics. Our simulation studies demonstrate that our proposed methods can not only control type I error at a predefined significance level but also achieve higher statistical power than those of traditional parametric and nonparametric methods that overlook covariate adjustment, especially when covariates are unbalanced in the two treatment groups. We illustrate the effectiveness of our methodology with data from clinical trials of a therapy for coronary heart disease. C1 [Hou, Yan; Li, Kang] Harbin Med Coll, Dept Biostat, Harbin 150081, Peoples R China. [Zhou, Xiao-Hua] VA Puget Sound Hlth Care Syst, HSR&D Ctr Excellence, Seattle, WA USA. [Ding, Victoria; Zhou, Xiao-Hua] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. RP Li, K (reprint author), Harbin Med Coll, Dept Biostat, Harbin 150081, Peoples R China. EM likang@hrbmu.edu.cn; azhou@u.washington.edu FU National Natural Science Foundation of China [NSFC 30728019] FX The authors thank Harbin's Pharmaceutical Plant No. 2 for providing the data for their study. This research is partially supported by a grant from the National Natural Science Foundation of China (NSFC 30728019). Xiao-Hua Zhou, PhD, is presently a core investigator and Biostatistics Unit Director at the Northwest HSR&D Center of Excellence, Department of Veterans Affairs Medical Center, Seattle, WA. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. NR 27 TC 1 Z9 2 U1 0 U2 6 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2011 VL 21 IS 1 BP 77 EP 93 AR PII 931668703 DI 10.1080/10543406.2010.494267 PG 17 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 700SQ UT WOS:000285765000007 PM 21191856 ER PT J AU Franco, GEL Blank, RD Akhter, MP AF Lopez Franco, Gloria E. Blank, Robert D. Akhter, Mohammed P. TI Intrinsic material properties of cortical bone SO JOURNAL OF BONE AND MINERAL METABOLISM LA English DT Article DE Intrinsic properties; Nano-indentation; Bone; LRP5; Mice ID GENETIC-DETERMINANTS; WNT/BETA-CATENIN; TOBACCO SMOKING; ELASTIC-MODULUS; BETA-CATENIN; INBRED MICE; MASS; INDENTATION; STRENGTH; HARDNESS AB The G171V mutation (high bone mass, HBM) is autosomal dominant and is responsible for high bone mass in humans. Transgenic HBM mice in which the human LRP5 G171V gene is inserted also show a similar phenotype with greater bone mass and biomechanical performance than wild-type mice, as determined by whole bone testing. Whole bone mechanics, however, depend jointly on bone mass, architecture, and intrinsic bone tissue mechanical properties. To determine whether the HBM mutation affects tissue-level biomechanical performance, we performed nano-indentation testing of unembedded cortical bone from HBM mice and their nontransgenic (NTG) littermates. Femora from 17-week-old mice (female, 8 mice/genotype) were subjected to nano-indentation using a Triboscope (Hysitron, Minneapolis, MN, USA). For each femoral specimen, approximately 10 indentations were made on the midshaft anterior surface with a target force of either 3 or 9 mN at a constant loading rate of 400 mN/s. The load-displacement data from each test were used to calculate indentation modulus and hardness for bone tissue. The intrinsic material property that reflected the bone modulus was greater (48%) in the HBM as compared to the NTG mice. Our results of intrinsic properties are consistent with the published structural and material properties of the midshaft femur in HBM and NTG mice. The greater intrinsic modulus in HBM reflects greater bone mineral content as compared to NTG (wild-type, WT) mice. This study suggests that the greater intrinsic property of cortical bone is derived from the greater bone mineral content and BMD, resulting in greater bone strength in HBM as compared to NTG (WT) mice. C1 [Akhter, Mohammed P.] Creighton Univ, ORC, Omaha, NE 68131 USA. [Lopez Franco, Gloria E.; Blank, Robert D.] William S Middleton Mem Vet Adm Med Ctr, GRECC Serv, Madison, WI USA. [Lopez Franco, Gloria E.; Blank, Robert D.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Sect Endocrinol Diabet & Metab, Madison, WI USA. RP Akhter, MP (reprint author), Creighton Univ, ORC, Suite 4820,601 N,30th St, Omaha, NE 68131 USA. EM akhtermp@creighton.edu OI Blank, Robert Daniel/0000-0003-2950-1944 FU Office of Research and Development; Biomedical Laboratory RD Service; Department of Veterans Affairs; Clinical Center at the William S. Middleton Memorial Veterans Hospital FX We appreciate the valuable help of Daniel Wells, John Danforth, and Adam Stibbe. This article is based upon work supported in part by the Office of Research and Development, Biomedical Laboratory R&D Service, Department of Veterans Affairs and performed in the Geriatrics Research, Education, and Clinical Center at the William S. Middleton Memorial Veterans Hospital. This report is Madison GRECC manuscript 2008-12. NR 26 TC 4 Z9 4 U1 1 U2 6 PU SPRINGER TOKYO PI TOKYO PA 1-11-11 KUDAN-KITA, CHIYODA-KU, TOKYO, 102-0073, JAPAN SN 0914-8779 J9 J BONE MINER METAB JI J. Bone Miner. Metab. PD JAN PY 2011 VL 29 IS 1 BP 31 EP 36 DI 10.1007/s00774-010-0194-z PG 6 WC Endocrinology & Metabolism; Medicine, Research & Experimental SC Endocrinology & Metabolism; Research & Experimental Medicine GA 705HH UT WOS:000286119000004 ER PT J AU Ishizuka, H Garcia-Palacios, V Lu, GW Subler, MA Zhang, HJ Boykin, CS Choi, SJ Zhao, LE Patrene, K Galson, DL Blair, HC Hadi, TM Windle, JJ Kurihara, N Roodman, GD AF Ishizuka, Hisako Garcia-Palacios, Veronica Lu, Ganwei Subler, Mark A. Zhang, Heju Boykin, Christina S. Choi, Sun Jin Zhao, Liena Patrene, Kenneth Galson, Deborah L. Blair, Harry C. Hadi, Tamer M. Windle, Jolene J. Kurihara, Noriyoshi Roodman, G. David TI ADAM8 Enhances Osteoclast Precursor Fusion and Osteoclast Formation In Vitro and In Vivo SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE ADAM8; TRANSGENIC/KNOCKOUT MICE; ADHESION MOLECULES; CELL DIFFERENTIATION; OSTEOCLAST ID STIMULATING FACTOR; DC-STAMP; BONE; CELL; MICE; DIFFERENTIATION; ALPHA(9)BETA(1); DISINTEGRIN; ACTIVATION; EXPRESSION AB ADAM8 expression is increased in the interface tissue around a loosened hip prosthesis and in the pannus and synovium of patients with rheumatoid arthritis, but its potential role in these processes is unclear. ADAM8 stimulates osteoclast (OCL) formation, but the effects of overexpression or loss of expression of ADAM8 in vivo and the mechanisms responsible for the effects of ADAM8 on osteoclastogenesis are unknown. Therefore, to determine the effects of modulating ADAM expression, we generated tartrate-resistant acid phosphatase (TRAP)-ADAM8 transgenic mice that overexpress ADAM8 in the OCL lineage and ADAM8 knockout (ADAM8 KO) mice. TRAP-ADAM8 mice developed osteopenia and had increased numbers of OCL precursors that formed hypermultinucleated OCLs with an increased bone-resorbing capacity per OCL. They also had an enhanced differentiation capacity, increased TRAF6 expression, and increased NF-kappa B, Erk, and Akt signaling compared with wild-type (WT) littermates. This increased bone-resorbing capacity per OCL was associated with increased levels of p-Pyk2 and p-Src activation. In contrast, ADAMS KO mice did not display a bone phenotype in vivo, but unlike WT littermates, they did not increase RANKL production, OCL formation, or calvarial fibrosis in response to tumor necrosis factor alpha (TNF-alpha) in vivo. Since loss of ADAM8 does not inhibit basal bone remodeling but only blocks the enhanced OCL formation in response to TNF-TNF-alpha, these results suggest that ADAM8 may be an attractive therapeutic target for preventing bone destruction associated with inflammatory disease. (C) 2011 American Society for Bone and Mineral Research. C1 [Roodman, G. David] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. [Ishizuka, Hisako; Garcia-Palacios, Veronica; Lu, Ganwei; Zhao, Liena; Patrene, Kenneth; Galson, Deborah L.; Kurihara, Noriyoshi; Roodman, G. David] Univ Pittsburgh, Med Ctr, Dept Med Hematol Oncol, Pittsburgh, PA USA. [Ishizuka, Hisako; Garcia-Palacios, Veronica; Lu, Ganwei; Zhao, Liena; Patrene, Kenneth; Galson, Deborah L.; Kurihara, Noriyoshi; Roodman, G. David] Univ Pittsburgh, Med Ctr, Ctr Bone Biol, Pittsburgh, PA USA. [Subler, Mark A.; Boykin, Christina S.; Hadi, Tamer M.; Windle, Jolene J.] Virginia Commonwealth Univ, Dept Human & Mol Genet, Richmond, VA USA. [Zhang, Heju; Windle, Jolene J.] Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA USA. [Choi, Sun Jin] Natl Inst Dent & Craniofacial Res, Bethesda, MD USA. [Blair, Harry C.] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA. RP Roodman, GD (reprint author), VA Pittsburgh Healthcare Syst, R&D 151-U,Univ Dr C, Pittsburgh, PA 15240 USA. EM roodmangd@upmc.edu RI Galson, Deborah/E-9370-2010; OI Galson, Deborah/0000-0002-2045-8807; Windle, Jolene/0000-0001-6690-385X FU Novartis Pharmaceuticals; NIH [RO1AR041336, P30 CA016059, R01 AR057310] FX GDR reports having served as a consultant to Amgen, Celgene, Acceleron, and Millenium and receives grant support from Novartis Pharmaceuticals. All the other authors state that they have no conflicts of interest.; This work was supported by a VA Merit Review Grant and by NIH Grants RO1AR041336 (to GDR), P30 CA016059 (to JJW), and R01 AR057310 (to DLG). The materials are the result of work supported with resources and the use of facilities at the VA Pittsburgh Healthcare System, Research and Development. NR 25 TC 17 Z9 17 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JAN PY 2011 VL 26 IS 1 BP 169 EP 181 DI 10.1002/jbmr.199 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 704FD UT WOS:000286035600019 PM 20683884 ER PT J AU Mosier, MJ Pham, TN Klein, MB Gibran, NS Arnoldo, BD Gamelli, RL Tompkins, RG Herndon, DN AF Mosier, Michael J. Pham, Tam N. Klein, Matthew B. Gibran, Nicole S. Arnoldo, Brett D. Gamelli, Richard L. Tompkins, Ronald G. Herndon, David N. TI Early Enteral Nutrition in Burns: Compliance With Guidelines and Associated Outcomes in a Multicenter Study SO JOURNAL OF BURN CARE & RESEARCH LA English DT Article ID CLINICAL-PRACTICE GUIDELINES; ILL ADULT PATIENTS; PREVENTION; SUPPORT; HYPERMETABOLISM; INJURY; RESUSCITATION; TRANSLOCATION; MANAGEMENT; CATABOLISM AB Early nutritional support is an essential component of burn care to prevent ileus, stress ulceration, and the effects of hypermetabolism. The American Burn Association practice guidelines state that enteral feedings should be initiated as soon as practical. The authors sought to evaluate compliance with early enteral nutrition (EN) guidelines, associated complications, and hospitalization outcomes in a prospective multicenter observational study. They conducted a retrospective review of mechanically ventilated burn patients enrolled in the prospective observational multicenter study "Inflammation and the Host Response to Injury." Timing of initiation of tube feedings was recorded, with early EN defined as being started within 24 hours of admission. Univariate and multivariate analyses were performed to distinguish barriers to initiation of EN and the impact of early feeding on development of multiple organ dysfunction syndrome, infectious complications, days on mechanical ventilation, intensive care unit (ICU) length of stay, and survival. A total of 153 patients met study inclusion criteria. The cohort comprised 73% men, with a mean age of 41 +/- 15 years and a mean %TBSA burn of 46 +/- 18%. One hundred twenty-three patients (80%) began EN in the first 24 hours and 145 (95%) by 48 hours. Age, sex, inhalation injury, and full-thickness burn size were similar between those fed by 24 hours vs after 24 hours, except for higher mean Acute Physiology and Chronic Health Evaluation II scores (26 vs 23, P = .03) and smaller total burn size (44 vs 54% TBSA burn, P = .01) in those fed early. There was no significant difference in rates of hyperglycemia, abdominal compartment syndrome, or gastrointestinal bleeding between groups. Patients fed early had shorter ICU length of stay (adjusted hazard ratio 0.57, P = 0.03, 95% confidence interval 0.35-0.94) and reduced wound infection risk (adjusted odds ratio 0.28, P = 0.01, 95% confidence interval 0.10-0.76). The investigators have found early EN to be safe, with no increase in complications and a lower rate of wound infections and shorter ICU length of stay. Across institutions, there has been high compliance with early EN as part of the standard operating procedure in this prospective multicenter observational trial. The investigators advocate that initiation of EN by 24 hours be used as a formal recommendation in nutrition guidelines for severe burns, and that nutrition guidelines be actively disseminated to individual burn centers to permit a change in practice. (J Burn Care Res 2011;32:104-109) C1 [Mosier, Michael J.] Loyola Univ, Med Ctr, Dept Surg, Maywood, IL 60153 USA. [Pham, Tam N.; Klein, Matthew B.; Gibran, Nicole S.] Univ Washington, Harborview Med Ctr, Burn Ctr, Seattle, WA 98104 USA. [Arnoldo, Brett D.] Univ Texas SW Parkland Mem Hosp, Dallas, TX USA. [Tompkins, Ronald G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Herndon, David N.] Univ Texas Med Branch, Galveston, TX USA. RP Mosier, MJ (reprint author), Loyola Univ, Med Ctr, Dept Surg, EMS Bldg 110,2160 S 1st Ave, Maywood, IL 60153 USA. FU National Institute of General Medical Sciences; National Institute of General Medical Sciences [2-U54-GM062119]; National Center for Research Resources (NCCR) [1KL2RR025015-01]; David and Nancy Auth-Washington Research Foundation Endowment FX Supported by the National Institute of General Medical Sciences.; The investigators acknowledge the contribution of the Inflammation and the Host Response to Injury Large-Scale Collaborative Project Award 2-U54-GM062119 from the National Institute of General Medical Sciences, the National Center for Research Resources (NCCR) Grant 1KL2RR025015-01, and the David and Nancy Auth-Washington Research Foundation Endowment. NR 25 TC 23 Z9 26 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1559-047X J9 J BURN CARE RES JI J. Burn Care Res. PD JAN-FEB PY 2011 VL 32 IS 1 BP 104 EP 109 DI 10.1097/BCR.0b013e318204b3be PG 6 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA 703QR UT WOS:000285996000020 PM 21116188 ER PT J AU Sun, Y Li, YX Wu, HJ Wu, SH Wang, YA Luo, DZ Liao, DJ AF Sun, Yuan Li, Ying-xia Wu, Hai-jun Wu, Si-hung Wang, Y. Alan Luo, Dian-zhong Liao, D. Joshua TI Effects of an Indolocarbazole-Derived CDK4 Inhibitor on Breast Cancer Cells SO JOURNAL OF CANCER LA English DT Article DE NPCD; CDK4 Inhibitor; breast cancer cell lines AB Introduction: Cyclin D1 (D1) binds to cyclin-dependent kinases (CDK) 4 or 6 to form a holoenzyme that phosphorylates the Rb protein to promote cell cycle progression from G1 to S phase. Therefore, targeting CDK4/6 may be a good strategy for chemotherapy of cancer. We performed a proof-of-principle study to determine the effect of Naphtho [2, 1-alpha] pyrrolo [3, 4-c] carbazole-5, 7 (6H, 12H)-dione (NPCD), a novel CDK4 inhibitor, on breast cancer cell lines. Methods: NPCD was synthesized and purified to over 99% purity verified by HPLC. MCF7, MB231, MCF15, T47D and GI101Ap human breast cancer cells were analyzed for the efficacy of NPCD with MTT and clonogenic assays, with FACS and staining for ethidium bromide and acridine orange for cell death and cell cycle profile. Western blot, reverse transcription and PCR were used for studies of gene expression, and co-immunoprecipitation for protein-complex formation. Results: MTT assay showed that NPCD caused growth arrest and apoptosis of MCF7, MDA-MB231, T47D, MCF15 and GI101Ap cells with an IC50 ranging between 3 to 8 mu M given as a single dose. The growth arrest persisted for many days after cessation of the treatment, as shown in a clonogenic assay. NPCD could induce or reduce the D1 and CDK4 protein levels, depending on the cell line, but this effect was not correlated with its efficacy. Phosphorylation of D1 at Thr286 was decreased but it unexpectedly did not correlate with the change in D1 level in the cell lines studied. Phosphorylation of the Rb protein was decreased as expected whereas the p27kip1 protein level was decreased unexpectedly. Protein levels of p21 cip1, CDK2 and cyclin E were also decreased in some, but not all, of the cell lines, whereas the mRNA levels of D1, CDK4, cyclin E, CDK2, p27kip1 and p21cip1 were increased in different cell lines. Conclusions: NPCD can cause long-lasting growth arrest and cell death of breast cancer cell lines at an IC50 of 3-8 mu M. Decreased phosphorylation of Rb by D1-CDK4/6 and decreased p27kip1 protein level may be part of the underlying mechanism. C1 [Sun, Yuan; Wu, Si-hung; Liao, D. Joshua] Univ Minnesota, Hormel Inst, Austin, MN 55912 USA. [Li, Ying-xia; Wu, Hai-jun] Fudan Univ, Sch Pharm, Shanghai 201203, Peoples R China. [Wang, Y. Alan] Harvard Univ, Dana Farber Canc Inst, Discovery Ctr Appl Canc Sci, Boston, MA 02115 USA. [Sun, Yuan; Luo, Dian-zhong] Guanxi Med Univ, Dept Pathol, Nanning 530021, Guangxi, Peoples R China. RP Li, YX (reprint author), Fudan Univ, Sch Pharm, Shanghai 201203, Peoples R China. EM liyx417@hotmail.com; djliao@hi.umn.edu FU Major scientific and technological special project for new drug creation in China [2009ZX09102-014]; National Institute of Health grant [RO1CA100864] FX We thank Dr. Fred Bogott at Austin Medical Center, Austin of Minnesota, USA, for his excellent English editing of this manuscript. This work is supported by a grant of Major scientific and technological special project for new drug creation in China (2009ZX09102-014) to Y-X Li and by a National Institute of Health grant (RO1CA100864) to D.J. Liao. NR 84 TC 11 Z9 11 U1 1 U2 5 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1837-9664 J9 J CANCER JI J. Cancer PY 2011 VL 2 BP 36 EP 51 DI 10.7150/jca.2.36 PG 16 WC Oncology SC Oncology GA V28QM UT WOS:000208695300004 PM 21234300 ER PT J AU Shlipak, MG Lash, JP Yang, W Teal, V Keane, M Cappola, T Keller, C Jamerson, K Kusek, J Delafontaine, P He, JA Miller, ER Schreiber, M Go, AS AF Shlipak, Michael G. Lash, James P. Yang, Wei Teal, Valerie Keane, Martin Cappola, Tom Keller, Chris Jamerson, Kenneth Kusek, John Delafontaine, Patrice He, Jiang Miller, Edgar R., III Schreiber, Martin Go, Alan S. CA CRIC Investigators TI Symptoms Characteristic of Heart Failure Among CKD Patients Without Diagnosed Heart Failure SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE Hemoglobin; glomerular filtration rate ID ACUTE MYOCARDIAL-INFARCTION; RENAL-INSUFFICIENCY; HEALTH-STATUS; CYSTATIN-C; SERUM CREATININE; KIDNEY-FUNCTION; RISK-FACTOR; INDIVIDUALS; DISEASE; PREDICTORS AB Background: Epidemiological studies typically diagnose heart failure (HF) at the time of hospitalization, and have not evaluated the prevalence of HF symptoms in CKD patients without a prior HF diagnosis. Methods and Results: We modified the Kansas City Cardiomyopathy Questionnaire (KCCQ) to detect and quantify symptoms characteristic of HF (dyspnea, edema, and fatigue) among 2883 chronic kidney disease (CKD) patients without diagnosed heart failure in the Chronic Renal Insufficiency Cohort (CRIC). The KCCQ is a 23-item instrument that quantifies the impact of dyspnea, fatigue, and edema on physical, social, and emotional functions (scored 0 to 100). The median KCCQ score was 92, and 25% had KCCQ scores <75. Compared with cystatin C-based estimated glomerular filtration rate >50 mL . min . 1.73m(2) (reference), estimated glomerular filtration rate 40 to 50, 30 to 40, and <30 were independently associated with lower KCCQ scores ( <75); adjusted odds ratios and (95% CI): 1.38 (1.06-1.78), 1.39 (1.09-1.82), and 2.15 (1.54-3.00), respectively. Lower hemoglobin (Hb) levels also had independent associations with KCCQ <75: Hb >14 g/dL (reference), Mb 13 to 14 g/dL (1.03; 0.76-1.40), Hb 12 to 13 g/dL (1.41; 1.04-1.91), Mb 11 to 12 g/dL (1.56; 1.12-2.16); and Hb <1 g/dL (1.65; 1.15-2.37). Conclusion: CKD patients without diagnosed HF have a substantial burden of symptoms characteristic of HF, particularly among those with lower estimated glomerular filtration rate and hemoglobin levels. (J Cardiac Fail 2011;17:17-23) C1 [Shlipak, Michael G.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94109 USA. [Shlipak, Michael G.] San Francisco VA Med Ctr, San Francisco, CA USA. [Lash, James P.] Univ Illinois, Dept Med, Chicago, IL USA. [Yang, Wei; Teal, Valerie] Univ Penn, Dept Biostat & Epidemiol, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Keane, Martin; Cappola, Tom] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Keller, Chris] Boise Kidney & Hypertens Inst, Boise, ID USA. [Jamerson, Kenneth] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Kusek, John] NIDDK, Bethesda, MD USA. [Delafontaine, Patrice; He, Jiang] Tulane Univ, Dept Med, New Orleans, LA 70118 USA. [Miller, Edgar R., III] Johns Hopkins Univ, Sch Publ Hlth, Dept Med, Baltimore, MD USA. [Schreiber, Martin] Cleveland Clin, Dept Hypertens & Nephrol, Stongsville, OH USA. [Go, Alan S.] Kaiser Permanente No Calif, Oakland, CA USA. RP Shlipak, MG (reprint author), Univ Calif San Francisco, Dept Med, 4150 Clement St,111A1, San Francisco, CA 94109 USA. EM michael.shlipak@ucsf.edu RI Yang, Wei/A-9223-2009; OI Yang, Wei/0000-0001-8984-4389; Teal, Valerie/0000-0001-7116-5353; Delafontaine, Patrice/0000-0003-3744-3617 FU University of Pennsylvania [UL1 RR-024134]; Johns Hopkins University [UL1 RR-025005]; University of Maryland [M01 RR-16500]; Case Western Reserve University [UL1 RR-024989]; University of Michigan [M01 RR-000042, UL1 RR-024986]; University of Illinois at Chicago [UL1 RR-029879]; [R01 DK066488] FX Supported by M.S.'s R01 DK066488 award (principal investigator M.S.). In addition, we would like to acknowledge the CRIC GCRC and CTSA awards: University of Pennsylvania (UL1 RR-024134), Johns Hopkins University (UL1 RR-025005), University of Maryland (M01 RR-16500), Case Western Reserve University (UL1 RR-024989), University of Michigan (M01 RR-000042, UL1 RR-024986), and University of Illinois at Chicago (UL1 RR-029879). NR 19 TC 12 Z9 13 U1 0 U2 1 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 JAN PY 2011 VL 17 IS 1 BP 17 EP 23 DI 10.1016/j.cardfail.2010.08.009 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 709AK UT WOS:000286407300004 PM 21187260 ER PT J AU Zhang, MH Na, B Schiller, NB Whooley, MA AF Zhang, Mary H. Na, Beeya Schiller, Nelson B. Whooley, Mary A. TI Association of Resistin With Heart Failure and Mortality in Patients With Stable Coronary Heart Disease: Data From the Heart and Soul Study SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE Adipocytokine; inflammation; adverse cardiovascular events; hospitalization ID INSULIN-RESISTANCE; CARDIOVASCULAR EVENTS; MYOCARDIAL-INFARCTION; HORMONE RESISTIN; ATHEROSCLEROSIS; RISK; ADIPONECTIN; HEALTH; INFLAMMATION; PROGNOSIS AB Background: Resistin is a pro-inflammatory signaling molecule that is thought to contribute to atherosclerosis. We sought to evaluate whether resistin is predictive of worse cardiovascular outcomes among ambulatory patients with stable coronary heart disease (CHD). Methods and Results: We measured baseline serum resistin in 980 participants with documented CHD. After a mean follow-up of 6.1 (range, 0.1 to 9.0) years, 358 (36.5%) were hospitalized for myocardial infarction or heart failure or had died. As compared with participants who had resistin levels in the lowest quartile, those with resistin levels in the highest quartile were at an increased risk of heart failure (hazard ratio [HR], 2.06; 95% confidence interval [CI] 1.26-3.39) and death (HR, 1.56; 95% CI, 1.11-2.18), adjusted for age, sex, and race. Further adjustments for obesity, hypertension, insulin resistance, dyslipidemia, and renal dysfunction eliminated these associations. Resistin levels were not associated with an increased risk of non-fatal myocardial infarction (unadjusted HR, 1.18; 95% CI, 0.68-2.05). Conclusions: Elevated serum resistin is associated with higher rates of mortality and hospitalization for heart failure. However, this appears to be explained by the association of resistin with traditional measures of cardiovascular risk. Thus, serum resistin does not add prognostic information among high-risk persons with established CHD. (J Cardiac Fail 2011;17:24-30) C1 [Schiller, Nelson B.; Whooley, Mary A.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94121 USA. [Zhang, Mary H.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Na, Beeya; Whooley, Mary A.] Vet Affairs Med Ctr, San Francisco, CA 94121 USA. [Whooley, Mary A.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94121 USA. RP Whooley, MA (reprint author), Univ Calif San Francisco, Dept Med, 4150 Clement St 111A1, San Francisco, CA 94121 USA. EM Mary.Whooley@ucsf.edu FU American Federation for Aging Research; American Heart Association; Philanthropic Educational Organization; Department of Veterans Affairs; National Heart, Lung and Blood Institute; Robert Wood Johnson Foundation; Ischemia Research and Education Foundation; Nancy Kirwan Heart Research Fund FX Supported by grants from the American Federation for Aging Research (M.H.Z., M.A.W.), the American Heart Association (M.H.Z.), the Philanthropic Educational Organization Scholars Program (M.H.Z.), the Department of Veterans Affairs, the National Heart, Lung and Blood Institute, the Robert Wood Johnson Foundation, the Ischemia Research and Education Foundation, and the Nancy Kirwan Heart Research Fund. None of these funding sources had any role in design, analysis, or preparation of the manuscript. NR 25 TC 26 Z9 27 U1 1 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 JAN PY 2011 VL 17 IS 1 BP 24 EP 30 DI 10.1016/j.cardfail.2010.08.007 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 709AK UT WOS:000286407300005 PM 21187261 ER PT J AU Dougherty, CM Steele, BG Hunziker, J AF Dougherty, Cynthia M. Steele, Bonnie G. Hunziker, Jim TI Testing an Intervention to Improve Functional Capability in Advanced Cardiopulmonary Illness SO JOURNAL OF CARDIOPULMONARY REHABILITATION AND PREVENTION LA English DT Article DE COPD; exercise; health care costs; heart failure; quality of life ID CHRONIC HEART-FAILURE; RANDOMIZED CONTROLLED-TRIAL; OBSTRUCTIVE PULMONARY-DISEASE; OLDER-ADULTS; CARDIAC REHABILITATION; HOSPITAL UTILIZATION; EXERCISE; COPD; EFFICACY; PROGRAM AB The development of a conceptually driven exercise and self-management intervention for improving functional capability and reducing health care costs using social cognitive theory is described. The intervention has 2 components: a 1-month outpatient exercise intervention followed by a home component, lasting 5 months. The intervention is expected to have significant impact on daily function, quality of life, gait/balance, self-efficacy, and health care utilization in persons with advanced heart failure or chronic obstructive pulmonary disease. We report preliminary results related to process-related variables, including feasibility, safety, and intervention adherence. Intervention outcomes are currently under study and will be reported when available. C1 [Dougherty, Cynthia M.; Steele, Bonnie G.; Hunziker, Jim] VA Puget Sound Healthcare Syst, Seattle Div, Hlth Serv Res & Dev Dept, Seattle, WA 98109 USA. [Dougherty, Cynthia M.; Steele, Bonnie G.] Univ Washington, Sch Nursing, Dept Biobehav Nursing & Hlth Syst, Seattle, WA 98195 USA. RP Dougherty, CM (reprint author), VA Puget Sound Healthcare Syst, Seattle Div, Hlth Serv Res & Dev Dept, 1660 S Columbian Way,S-118, Seattle, WA 98109 USA. EM cynthia.dougherty@va.gov FU VA Health Services Research and Development Service, Nursing Research Initiative [NRI 04-242] FX This study is funded by the VA Health Services Research and Development Service, Nursing Research Initiative (NRI 04-242). NR 31 TC 2 Z9 2 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1932-7501 J9 J CARDIOPULM REHABIL JI J. Cardiopulm. Rehabil. Prev. PD JAN-FEB PY 2011 VL 31 IS 1 BP 35 EP 41 DI 10.1097/HCR.0b013e3181f1fd77 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 704LA UT WOS:000286053300004 PM 20861749 ER PT J AU Beinart, R Heist, EK Newell, JB Holmvang, G Ruskin, JN Mansour, M AF Beinart, Roy Heist, E. Kevin Newell, John B. Holmvang, Godtfred Ruskin, Jeremy N. Mansour, Moussa TI Left Atrial Appendage Dimensions Predict the Risk of Stroke/TIA in Patients With Atrial Fibrillation SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE atrial fibrillation; cerebral vascular accident; transient ischemic event; left atrial appendage; magnetic resonance imaging: catheter ablation ID MITRAL-VALVE DISEASE; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; SYSTEMIC EMBOLISM; CLINICAL RISK; FLOW VELOCITY; PREVENTION; THROMBOEMBOLISM; PREVALENCE; THROMBUS; CONTRAST AB Methods: The study included 144 patients with nonvalvular AF who were not receiving warfarin and who underwent MRI/MRA prior to catheter ablation for AF. LAA volume, LAA depth, short and long axes of LAA neck, and numbers of lobes were measured. Results: Of the 144 patients, 18 had a prior stroke or transient ischemic attack (TIA) (13 and 5, respectively). Compared with patients who had no history of stroke/TIA, these patients were older, had higher prevalence of hypertension and hyperlipidemia and had higher LAA volume (22.9 +/- 9.6 cm3 vs. 14.5 +/- 7.1 cm3, P < 0.001). Their LAA depth (3.76 +/- 0.9 cm vs. 3.21 +/- 0.8 cm, P = 0.006) and the long and short axes of the LAA neck (3.12 +/- 0.7 cm vs. 2.08 +/- 0.7 cm, P < 0.001; 2.06 +/- 0.5 cm vs. 1.37 +/- 0.4 cm, P < 0.001, respectively) were larger. Using stepwise logistic regression model, the only statistically significant multivariable predictors of events were age (OR = 1.21 per year, 95% CI 1.06-1.38, P = 0.004), aspirin use (OR = 0.039, 95% CI 0.005-0.28, P = 0.001), and LAA neck dimensions (short axis x long axis) (OR = 3.59 per cm2, 95% CI 1.93-6.69, P < 0.001). Conclusion: LAA dimensions predict strokes/TIAs in patients with AF. LAA assessment by MRI/MRA can potentially be used as an adjunctive tool for risk stratification for embolic events in AF patients. (J Cardiovasc Electrophysiol, Vol. 22, pp. 10-15, January 2011). C1 [Mansour, Moussa] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Ctr Heart, Boston, MA 02114 USA. RP Mansour, M (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Ctr Heart, Gray 109,55 Fruit St, Boston, MA 02114 USA. EM mmansour@partners.org FU Deane Institute for Integrative Research in Stroke and Atrial Fibrillation at the Massachusetts General Hospital FX The study was supported by a grant from the Deane Institute for Integrative Research in Stroke and Atrial Fibrillation at the Massachusetts General Hospital. NR 34 TC 39 Z9 42 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD JAN PY 2011 VL 22 IS 1 BP 10 EP 15 DI 10.1111/j.1540-8167.2010.01854.x PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 706IQ UT WOS:000286212000003 PM 20662984 ER PT J AU Mannix, RC Zhang, J Park, J Zhang, X Bilal, K Walker, K Tanzi, RE Tesco, G Whalen, MJ AF Mannix, Rebekah C. Zhang, Jimmy Park, Juyeon Zhang, Xuan Bilal, Kiran Walker, Kendall Tanzi, Rudolph E. Tesco, Giuseppina Whalen, Michael J. TI Age-dependent effect of apolipoprotein E4 on functional outcome after controlled cortical impact in mice SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE traumatic brain injury; genetics; developmental biology; Alzheimer's disease ID TRAUMATIC BRAIN-INJURY; CLOSED-HEAD INJURY; AMYLOID PRECURSOR PROTEIN; ALZHEIMERS-DISEASE; TRANSGENIC MICE; A-BETA; APOE GENOTYPE; MOUSE MODEL; PEPTIDE; DEPOSITION AB The apolipoprotein E4 (APOE4) gene leads to increased brain amyloid beta (Ab) and poor outcome in adults with traumatic brain injury (TBI); however, its role in childhood TBI is controversial. We hypothesized that the transgenic expression of human APOE4 worsens the outcome after controlled cortical impact (CCI) in adult but not immature mice. Adult and immature APOE4 mice had worse motor outcome after CCI (P < 0.001 versus wild type (WT)), but the Morris water maze performance was worse only in adult APOE4 mice (P = 0.028 at 2 weeks, P = 0.019 at 6 months versus WT), because immature APOE4 mice had performance similar to WT for up to 1 year after injury. Brain lesion size was similar in adult APOE4 mice but was decreased (P = 0.029 versus WT) in injured immature APOE4 mice. Microgliosis was similar in all groups. Soluble brain A beta(40) was increased at 48 hours after CCI in adult and immature APOE4 mice and in adult WT (P < 0.05), and was dynamically regulated during the chronic period by APOE4 in adults but not immature mice. The data suggest age-dependent effects of APOE4 on cognitive outcome after TBI, and that therapies targeting APOE4 may be more effective in adults versus children with TBI. Journal of Cerebral Blood Flow & Metabolism (2011) 31, 351-361; doi:10.1038/jcbfm.2010.99; published online 30 June 2010 C1 [Mannix, Rebekah C.] Harvard Univ, Dept Med, Childrens Hosp Boston, Sch Med,Div Emergency Med, Boston, MA 02115 USA. [Zhang, Jimmy; Park, Juyeon; Zhang, Xuan; Bilal, Kiran; Whalen, Michael J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Neurosci, Charlestown, MA USA. [Zhang, Jimmy; Park, Juyeon; Zhang, Xuan; Bilal, Kiran; Whalen, Michael J.] Harvard Univ, Dept Pediat, Massachusetts Gen Hosp, Sch Med, Charlestown, MA USA. [Walker, Kendall; Tesco, Giuseppina] Tufts Univ, Dept Neurosci, Boston, MA 02111 USA. [Tanzi, Rudolph E.] Massachusetts Gen Hosp, MIND Inst, Dept Neurol, Charlestown, MA USA. RP Mannix, RC (reprint author), Harvard Univ, Dept Med, Childrens Hosp Boston, Sch Med,Div Emergency Med, 300 Longwood Ave, Boston, MA 02115 USA. EM rebekah.Mannix@childrens.harvard.edu FU NICHD [5K12HD052896]; Cure Alzheimer's Fund; NIA [1RO1AGO33016]; NINDS [5RO1NS047447] FX This work was supported by grants from NICHD 5K12HD052896 (RCM), the Cure Alzheimer's Fund (RET), NIA 1RO1AGO33016 (GT), and NINDS 5RO1NS047447 (MJW). NR 41 TC 19 Z9 19 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JAN PY 2011 VL 31 IS 1 BP 351 EP 361 DI 10.1038/jcbfm.2010.99 PG 11 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 702BX UT WOS:000285870700036 PM 20588316 ER PT J AU Huckans, M Seelye, A Woodhouse, J Parcel, T Mull, L Schwartz, D Mitchell, A Lahna, D Johnson, A Loftis, J Woods, SP Mitchell, SH Hoffman, W AF Huckans, Marilyn Seelye, Adriana Woodhouse, Jonathan Parcel, Tiffany Mull, Lisa Schwartz, Daniel Mitchell, Alex Lahna, David Johnson, Amy Loftis, Jennifer Woods, Steven Paul Mitchell, Suzanne H. Hoffman, William TI Discounting of delayed rewards and executive dysfunction in individuals infected with hepatitis C SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article DE Hepatitis C; Neuropsychology; Impulsive behavior; Substance-related disorders; Delay discounting ID METHAMPHETAMINE-DEPENDENT INDIVIDUALS; VIRUS-INFECTION; DECISION-MAKING; CIGARETTE SMOKERS; MONETARY REWARDS; WORKING-MEMORY; HEROIN-ADDICTS; HIV-INFECTION; RISK-FACTORS; DRUG-USERS AB Objective: Determine whether adults with hepatitis C (HCV), regardless of substance use disorder, are more likely to discount delayed rewards than adults without hepatitis C, and explore the relationship between delay discounting and neuropsychological functioning. Methods: Procedures included clinical interviews, neuropsychological testing, and a delay discounting task. Results: Regardless of substance abuse history, adults with hepatitis C were significantly more likely to choose smaller immediate rewards over larger delayed rewards. Delay discounting correlated with performance on executive functioning tasks. Conclusions: Increased discounting is associated with broad executive dysfunction, suggesting that HCV-associated executive dysfunction may lead to altered decision-making style. C1 [Huckans, Marilyn; Seelye, Adriana; Woodhouse, Jonathan; Parcel, Tiffany; Mull, Lisa; Johnson, Amy; Loftis, Jennifer] Portland VA Med Ctr, NW Hepatitis Resource Ctr C, Portland, OR USA. [Huckans, Marilyn; Seelye, Adriana; Woodhouse, Jonathan; Parcel, Tiffany; Mull, Lisa; Schwartz, Daniel; Mitchell, Alex; Lahna, David; Johnson, Amy; Loftis, Jennifer; Hoffman, William] Portland VA Med Ctr, Div Res, Portland, OR USA. [Huckans, Marilyn; Schwartz, Daniel; Mitchell, Alex; Lahna, David; Loftis, Jennifer; Hoffman, William] Portland VA Med Ctr, Behav Hlth & Clin Neurosci Div, Portland, OR USA. [Huckans, Marilyn; Schwartz, Daniel; Mitchell, Alex; Lahna, David; Loftis, Jennifer; Mitchell, Suzanne H.; Hoffman, William] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Mitchell, Suzanne H.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. [Seelye, Adriana] Washington State Univ, Pullman, WA 99164 USA. [Woodhouse, Jonathan] George Fox Univ, Portland, OR USA. [Parcel, Tiffany; Mull, Lisa] Univ Pacific, Forest Grove, OR USA. [Woods, Steven Paul] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. RP Huckans, M (reprint author), Portland VA Med Ctr P3MHN, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM marilyn.huckans@va.gov OI Mitchell, Suzanne/0000-0002-0225-7200 FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Clinical Sciences Research and Development; Oregon Health and Science University; Northwest Health Foundation; VA FX The first author would like to thank Diane Howieson for her initial input into the analysis plan and conceptualization of this study; Daniel Kriz, Hannah Luber, Renee Anderson, and Michael Kolessar for their many contributions as current research assistants within Marilyn Huckans' research program; Emily Kizer, Danell Bjornson, Laura Parisi, and Samantha Ruimy for administrative and recruitment support over the years; Daniel Storzbach and Arthur Vandenbark for their continued mentorship and consultation; Betsy Zucker, Anna Sasaki, Michael Chang, and the other providers of the Portland VA Medical Center Liver Clinic for their ongoing collaborative support of Marilyn Huckans' research. This material is based upon work in part supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Clinical Sciences Research and Development, as well as by the Oregon Health and Science University. This study was supported in part by a Northwest Health Foundation Grant and a VA Career Development Award to Marilyn Huckans. NR 78 TC 23 Z9 24 U1 4 U2 14 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. PY 2011 VL 33 IS 2 BP 176 EP 186 AR PII 925284232 DI 10.1080/13803395.2010.499355 PG 11 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 715OV UT WOS:000286894700003 PM 20694872 ER PT J AU Thames, AD Kim, MS Becker, BW Foley, JM Hines, LJ Singer, EJ Heaton, RK Castellon, SA Hinkin, CH AF Thames, April D. Kim, Michelle S. Becker, Brian W. Foley, Jessica M. Hines, Lindsay J. Singer, Elyse J. Heaton, Robert K. Castellon, Steven A. Hinkin, Charles H. TI Medication and finance management among HIV-infected adults: The impact of age and cognition SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article DE Neuropsychology; HIV; Aging; Functional abilities; Medication management; Finance management ID HUMAN-IMMUNODEFICIENCY-VIRUS; NEUROPSYCHOLOGICAL IMPAIRMENT; SELF-REPORT; NEUROCOGNITIVE DISORDERS; OLDER-ADULTS; ADHERENCE; INDIVIDUALS; DYSFUNCTION; COMPLAINTS; PERFORMANCE AB This study examined the effects of aging and cognitive impairment on medication and finance management in an HIV sample. We observed main effects of age (older younger) and neuropsychological impairment on functional task performance. Interactions between age and cognition demonstrated that older impaired individuals performed significantly more poorly than all other comparison groups. There were no relationships between laboratory performance and self-reported medication and finance management. The interaction of advancing age and cognitive impairment may confer significant functional limitations for HIV individuals that may be better detected by performance-based measures of functional abilities rather than patient self-report. C1 [Thames, April D.; Hines, Lindsay J.; Singer, Elyse J.; Castellon, Steven A.; Hinkin, Charles H.] UCLA Sch Med, Los Angeles, CA USA. [Kim, Michelle S.; Becker, Brian W.; Castellon, Steven A.; Hinkin, Charles H.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Foley, Jessica M.] Boston VA Healthcare Syst, Boston, MA USA. [Foley, Jessica M.] Harvard Univ, Sch Med, Boston, MA USA. [Heaton, Robert K.] UCSD Sch Med, San Diego, CA USA. RP Thames, AD (reprint author), 760 Westwood Plaza,C8-746, Los Angeles, CA 90024 USA. EM athames@mednet.ucla.edu RI Thames, April/K-1964-2014 OI Thames, April/0000-0001-8414-7189 FU NIMH NIH HHS [U24 MH100929, R25 MH080663, T32 MH019535] NR 48 TC 36 Z9 36 U1 1 U2 4 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. PY 2011 VL 33 IS 2 BP 200 EP 209 AR PII 925281966 DI 10.1080/13803395.2010.499357 PG 10 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 715OV UT WOS:000286894700005 PM 20694873 ER PT J AU Huckans, M Loftis, JM AF Huckans, Marilyn Loftis, Jennifer M. TI Handbook of medical neuropsychology: Applications of cognitive neuroscience, 1st edition SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Book Review ID OF-THE-LITERATURE; ALZHEIMER-DISEASE; REHABILITATION; SIGNATURE; DIAGNOSIS; TRIAL C1 [Huckans, Marilyn] Portland VA Med Ctr, Res & Dev Serv, Mental Hlth & Clin Neurosci Div, Portland, OR USA. Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. RP Huckans, M (reprint author), Portland VA Med Ctr, Res & Dev Serv, Mental Hlth & Clin Neurosci Div, Portland, OR USA. NR 19 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1380-3395 J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PY 2011 VL 33 IS 5 BP 606 EP 608 AR PII 934036278 DI 10.1080/13803395.2011.556460 PG 3 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 773AQ UT WOS:000291279800013 ER PT J AU Foley, J AF Foley, Jessica TI Neuropsychology and cardiovascular disease SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Book Review C1 [Foley, Jessica] Harvard Univ, Sch Med, Dept Psychiat, VA Boston Healthcare Syst, Boston, MA 02115 USA. RP Foley, J (reprint author), Harvard Univ, Sch Med, Dept Psychiat, VA Boston Healthcare Syst, Boston, MA 02115 USA. NR 1 TC 0 Z9 0 U1 1 U2 1 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. PY 2011 VL 33 IS 6 BP 718 EP 720 DI 10.1080/13803395.2011.583541 PG 3 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 882GA UT WOS:000299550100012 ER PT J AU Butler, PM McNamara, P Ghofrani, J Durso, R AF Butler, Paul M. McNamara, Patrick Ghofrani, Jessica Durso, Raymon TI Disease-associated differences in religious cognition in patients with Parkinson's disease SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article DE Semantic memory; Neurodegenerative disorders; Religion; Gain/decay hypothesis; Frontal lobes; Dopamine ID TEMPORAL-LOBE EPILEPSY; ANXIETY STRESS SCALES; SEMANTIC ACTIVATION; INTERICTAL BEHAVIOR; MENTAL-HEALTH; SPIRITUALITY; DEPRESSION; ATTENDANCE; MECHANISMS; ASYMMETRY AB Objective: We sought to establish whether patients with Parkinson's disease (PD) exhibit change in religiosity as a function of disease progression and asymmetry, medication regimens, mood dysfunction, sex, and age. Method: We assessed both controlled (conscious reflection) and automatic (semantic priming) modes of religiosity. In the main study, self-reported religiosity, cognitive, and clinical measures were assessed in 71 patients with midstage PD and 75 age-matched controls with non-neurological chronic health conditions. To understand a potential mechanism associated with change in religiosity in PD patients, we supplemented the findings with pilot investigations. The pilot included 21 PD patients and utilized a different self-report measure than that of the main study and assessed automatic activation of religious concepts both on and off levodopa. Results: The main study results demonstrated that PD patients consistently scored lower in five of six dimensions of religiosity. Multivariate linear regression demonstrated that self-reported religiosity was related to disease stage, asymmetry, and male gender. Results are discussed in the context of other neurologic correlates of religiosity. The pilot study on religious concept activation suggested that the mechanism is organic and hemisphere dependent. On/off drug testing confirmed these findings to be independent of medication effects. Gain/decay semantic modeling suggested that right and left forebrain pathways selectively mediated the time constant of gain and decay, respectively, for religious concepts. Conclusion: PD patients exhibit significant differences in both controlled and automatic access to religious concepts with mid/late-stage, male, left-onset patients most impaired in access to religious cognition. The findings indicate that aspects of religious/spiritual cognition appear related to specific cerebral structures. C1 [Butler, Paul M.; McNamara, Patrick; Durso, Raymon] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Butler, Paul M.; McNamara, Patrick; Durso, Raymon] VA Boston Healthcare Syst, Dept Neurol, Boston, MA USA. [Ghofrani, Jessica] Boston Univ, Dept Neurosci, Coll Arts & Sci, Boston, MA 02118 USA. RP Butler, PM (reprint author), Boston Univ, Sch Med, Dept Neurol, 72 E Concord St,Robinson Bldg,5th Floor,Room 528, Boston, MA 02118 USA. EM pmbutler@bu.edu FU Office of Research Development, Medical Research Service, Department of Veterans Affairs; National Institute of Deafness and other Communication Disorders (NIDCD) [5RO1DC007956-03] FX The authors thank Ariel Brown and Erica Harris for assistance in participant recruiting, testing, and data management. The authors report no conflicts of interest. This is based on work supported by the Office of Research Development, Medical Research Service, Department of Veterans Affairs and the National Institute of Deafness and other Communication Disorders (NIDCD) Grant 5RO1DC007956-03. NR 83 TC 6 Z9 7 U1 3 U2 14 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1380-3395 EI 1744-411X J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PY 2011 VL 33 IS 8 BP 917 EP 928 DI 10.1080/13803395.2011.575768 PG 12 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 882HG UT WOS:000299553800008 PM 21656414 ER PT J AU Lu, PH Lee, GJ Raven, EP Tingus, K Khoo, T Thompson, PM Bartzokis, G AF Lu, Po H. Lee, Grace J. Raven, Erika P. Tingus, Kathleen Khoo, Theresa Thompson, Paul M. Bartzokis, George TI Age-related slowing in cognitive processing speed is associated with myelin integrity in a very healthy elderly sample SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article DE Healthy aging; Cognition; Information processing speed; Myelin; White matter; Magnetic resonance imaging; Alzheimer's disease; Dementia ID INDUCED INTRAMYELINIC EDEMA; WHITE-MATTER INTEGRITY; PRIMARY VISUAL-CORTEX; MAGNETIC-RESONANCE; MULTIPLE-SCLEROSIS; RHESUS-MONKEY; HUMAN BRAIN; CORPUS-CALLOSUM; NERVE-FIBERS; CORTICAL DISCONNECTION AB Performance on measures of cognitive processing speed (CPS) slows with age, but the biological basis associated with this cognitive phenomenon remains incompletely understood. We assessed the hypothesis that the age-related slowing in CPS is associated with myelin breakdown in late-myelinating regions in a very healthy elderly population. An in vivo magnetic resonance imaging (MRI) biomarker of myelin integrity was obtained from the prefrontal lobe white matter and the genu of the corpus callosum for 152 healthy elderly adults. These regions myelinate later in brain development and are more vulnerable to breakdown due to the effects of normal aging. To evaluate regional specificity, we also assessed the splenium of the corpus callosum as a comparison region, which myelinates early in development and primarily contains axons involved in visual processing. The measure of myelin integrity was significantly correlated with CPS in highly vulnerable late-myelinating regions but not in the splenium. These results have implications for the neurobiology of the cognitive changes associated with brain aging. C1 [Raven, Erika P.; Thompson, Paul M.; Bartzokis, George] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Lab Neuro Imaging, Los Angeles, CA 90095 USA. [Raven, Erika P.; Bartzokis, George] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Bartzokis, George] Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. RP Lu, PH (reprint author), Mary S Easton Ctr Alzheimers Dis Res, 10911 Weyburn Ave,Suite 200, Los Angeles, CA USA. EM plu@mednet.ucla.edu RI Bartzokis, George/K-2409-2013 FU National Institute of Aging (NIA) [K23-AG028727]; Alzheimer's Association [NIRG-07-60424]; National Institutes of Health (NIH) [MH 0266029, AG027342]; Alzheimer's Disease Research Center [P50 AG 16570]; California Alzheimer's Disease Centers; Risk Control Strategies Inc. (RCS) Alzheimer's Foundation; Department of Veterans Affairs FX This work was supported by Grant K23-AG028727 from the National Institute of Aging (NIA), a grant from the Alzheimer's Association (NIRG-07-60424), National Institutes of Health (NIH) grants (MH 0266029; AG027342), the Alzheimer's Disease Research Center Grant P50 AG 16570, and the California Alzheimer's Disease Centers. Additional support for the study came from the Risk Control Strategies Inc. (RCS) Alzheimer's Foundation and the Department of Veterans Affairs. NR 102 TC 31 Z9 32 U1 2 U2 8 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. PY 2011 VL 33 IS 10 BP 1059 EP 1068 DI 10.1080/13803395.2011.595397 PG 10 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 882HM UT WOS:000299554400002 PM 22133139 ER PT J AU Marakovitz, SE Wagmiller, RL Mian, ND Briggs-Gowan, MJ Carter, AS AF Marakovitz, Susan E. Wagmiller, Robert L. Mian, Nicholas D. Briggs-Gowan, Margaret J. Carter, Alice S. TI Lost Toy? Monsters Under the Bed? Contributions of Temperament and Family Factors to Early Internalizing Problems in Boys and Girls SO JOURNAL OF CLINICAL CHILD AND ADOLESCENT PSYCHOLOGY LA English DT Article ID GENERALIZED ANXIETY DISORDER; EMOTIONAL ASSESSMENT ITSEA; BEHAVIORAL-INHIBITION; DEPRESSED MOTHERS; EARLY-CHILDHOOD; MATERNAL DEPRESSION; PRESCHOOL-CHILDREN; GENDER-DIFFERENCES; MIDDLE CHILDHOOD; SOCIAL ANXIETY AB This study was designed to examine the contribution of multiple risk factors to early internalizing problems and to investigate whether family and ecological context moderated the association between child temperament and internalizing outcomes. A sample of 1,202 mothers of 2- and 3-year-old children completed a survey of child social-emotional functioning, family environment, and violence exposure. Child temperament, maternal affective symptoms, and family expressiveness were associated with child anxiety and depression problems. Violence exposure was related only to child anxiety. When maternal affective symptoms were elevated, inhibited girls but not boys were rated as more anxious and youngsters with heightened negative emotionality were rated as more depressed. Family expressiveness moderated the association between inhibited temperament and anxiety symptoms. C1 [Marakovitz, Susan E.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. [Briggs-Gowan, Margaret J.] Univ Connecticut, Dept Psychiat, Ctr Hlth, Storrs, CT 06269 USA. [Wagmiller, Robert L.] SUNY Buffalo, Dept Sociol, Buffalo, NY 14260 USA. [Mian, Nicholas D.; Carter, Alice S.] Univ Massachusetts Boston, Dept Psychol, Boston, MA USA. RP Marakovitz, SE (reprint author), Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, 185 Cambridge St, Boston, MA 02114 USA. EM smarakovitz@pngu.mgh.harvard.edu FU NIMH NIH HHS [R01 MH055278] NR 72 TC 9 Z9 10 U1 5 U2 17 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 1537-4416 J9 J CLIN CHILD ADOLESC JI J. Clin. Child Adolesc. Psychol. PY 2011 VL 40 IS 2 BP 233 EP 244 AR PII 934563205 DI 10.1080/15374416.2011.546036 PG 12 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA 733LS UT WOS:000288264800006 PM 21391020 ER PT J AU Hershman, JM Cheng, SY Gianoukakis, AG AF Hershman, Jerome M. Cheng, Sheue-yann Gianoukakis, Andrew G. TI Update in Thyroidology 2010 SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BRAF(V600E) MUTATION ANALYSIS; UNITED-STATES; INCREASING INCIDENCE; HORMONE RECEPTORS; CANCER; NODULES; OPHTHALMOPATHY; HYPOTHYROIDISM; PREVALENCE; SPECIMENS AB This has been an exciting year in thyroid research. In this article, we summarize the new developments in selected areas of thyroid research by reporting on key papers published during the period June 2009 to June 2010. We selected those papers that, in our opinion, have significant clinical or translational impact. Selection criteria were applied for inclusion of papers for the Year in Thyroid lecture at the 92nd Annual Meeting of The Endocrine Society in San Diego, June, 2010. Papers relating to translational and clinical discovery in thyroidology were reviewed. Papers were chosen if they provided new insight into the understanding of thyroid disease and advanced clinical science, or advanced the diagnosis of disease, or proposed new therapy, or provided new data on important clinical questions in thyroidology. Here we review and discuss these papers and show how they provide new insights into clinical thyroidology. (J Clin Endocrinol Metab 96: 9-14, 2011) C1 [Hershman, Jerome M.] W Los Angeles VA Med Ctr, Endocrinol & Diabet Div, Los Angeles, CA 90073 USA. [Cheng, Sheue-yann] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20814 USA. [Gianoukakis, Andrew G.] Harbor Univ Calif Los Angeles UCLA Med Ctr, Los Angeles Biomed Res Inst, Torrance, CA 90502 USA. [Hershman, Jerome M.; Gianoukakis, Andrew G.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. RP Hershman, JM (reprint author), W Los Angeles VA Med Ctr, Endocrinol & Diabet Div, Endocrinolgy 111D, Los Angeles, CA 90073 USA. EM jhershmn@ucla.edu NR 27 TC 0 Z9 0 U1 1 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2011 VL 96 IS 1 BP 9 EP 14 DI 10.1210/jc.2010-2350 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 710HW UT WOS:000286502900002 PM 21209040 ER PT J AU Stanley, TL Chen, CY Branch, KL Makimura, H Grinspoon, SK AF Stanley, Takara L. Chen, Cindy Y. Branch, Karen L. Makimura, Hideo Grinspoon, Steven K. TI Effects of a Growth Hormone-Releasing Hormone Analog on Endogenous GH Pulsatility and Insulin Sensitivity in Healthy Men SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ABDOMINAL FAT ACCUMULATION; RANDOMIZED CONTROLLED-TRIAL; HEPATIC-STEROID METABOLISM; HIV-INFECTED PATIENTS; FACTOR-I LEVELS; OBESE SUBJECTS; (GH)-RELEASING HORMONE; CARDIOVASCULAR RISK; CLAMP TECHNIQUE; GLUCOSE-UPTAKE AB Context and Objective: Strategies to augment pulsatile GH may be beneficial in patients with excess visceral adiposity, in whom GH secretion is reduced. The objective of this study was to determine the effects of a novel GHRH (GHRH(1-44)) analog, tesamorelin, on endogenous GH pulsatility and insulin sensitivity in healthy men. Design, Participants, and Intervention: Thirteen males (mean age 45 +/- 3 yr and body mass index 27.3 +/- 1.2 kg/m(2)) received tesamorelin 2 mg sc once daily for 2 wk, with assessment made at baseline, after 2 wk of treatment, and after 2 wk of withdrawal. Outcome Measures: The primary end point was change in mean overnight GH as determined by overnight frequent sampling. Secondary end points included insulin-stimulated glucose uptake as measured by euglycemic hyperinsulinemic clamp; IGF-I; and GH secretion parameters, including pulse area, pulse frequency, and basal secretion. Results: Tesamorelin treatment increased mean overnight GH (change +0.5 +/- 0.1 mu g/liter, P = 0.004), average log(10) GH peak area (change +0.4 +/- 0.1 log(10) mu g/liter, P = 0.001), and basal GH secretion (change +0.008 +/- 0.003 mu g/liter . min, P = 0.008). IGF-I increased by 181 +/- 22 mu g/liter (P < 0.0001). Neither fasting glucose (P = 0.93) nor insulin-stimulated glucose uptake (P = 0.61) was significantly affected by tesamorelin. Conclusions: Once-daily short-term treatment with a GHRH(1-44) analog, tesamorelin, augments basal and pulsatile GH secretion. Moreover, although tesamorelin significantly increases IGF-I, peripheral insulin-stimulated glucose uptake appears to be preserved. (J Clin Endocrinol Metab 96: 150-158, 2011) C1 [Stanley, Takara L.; Chen, Cindy Y.; Makimura, Hideo; Grinspoon, Steven K.] Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. [Stanley, Takara L.; Chen, Cindy Y.; Makimura, Hideo; Grinspoon, Steven K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Branch, Karen L.] Massachusetts Gen Hosp, Clin Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Grinspoon, SK (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, LON5-207,55 Fruit St, Boston, MA 02114 USA. EM sgrinspoon@partners.org FU National Institutes of Health (NIH) [R01DK063639, M01-RR-01066, 1 UL1 RR025758-01, T32 HD052961-03, F32 DK080642-02, K23 DK089910-01, K24 DK064545-08]; Harvard Clinical and Translational Science Center from the National Center for Research Resources FX This work was supported by National Institutes of Health (NIH) Grant R01DK063639 (to S.G.), and NIH Grants M01-RR-01066 and 1 UL1 RR025758-01, Harvard Clinical and Translational Science Center from the National Center for Research Resources. NIH funding was also provided through Grants T32 HD052961-03, F32 DK080642-02, and K23 DK089910-01 (to T.L.S.) and Grant K24 DK064545-08 (to S.K.G.). The study drug (tesamorelin) was donated by Theratechnologies, Inc. NR 43 TC 24 Z9 24 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 EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2011 VL 96 IS 1 BP 150 EP 158 DI 10.1210/jc.2010-1587 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 710HW UT WOS:000286502900024 PM 20943777 ER PT J AU Stanley, TL Zanni, MV Johnsen, S Rasheed, S Makimura, H Lee, H Khor, VK Ahima, RS Grinspoon, SK AF Stanley, Takara L. Zanni, Markella V. Johnsen, Stine Rasheed, Sarah Makimura, Hideo Lee, Hang Khor, Victor K. Ahima, Rexford S. Grinspoon, Steven K. TI TNF-alpha Antagonism with Etanercept Decreases Glucose and Increases the Proportion of High Molecular Weight Adiponectin in Obese Subjects with Features of the Metabolic Syndrome SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID TUMOR-NECROSIS-FACTOR; RHEUMATOID-ARTHRITIS; INSULIN-RESISTANCE; ADIPOSE-TISSUE; SENSITIVITY; EXPRESSION; ATHEROSCLEROSIS; RECEPTOR AB Context and Objective: Obesity is associated with activation of the TNF-alpha system, increased inflammatory markers, and insulin resistance. Although studies in rodents suggest that attenuation of TNF activity improves glucose homeostasis, the effect of prolonged inhibition of TNF-alpha with etanercept on inflammation and glucose homeostasis in a human model of obesity is not known. Design and Participants: Forty obese subjects with features of metabolic syndrome were randomized to etanercept or placebo, 50 mg twice weekly for 3 months, followed by 50 mg once weekly for 3 months. Outcome Measures: Subjects underwent oral glucose tolerance testing and measurement of serum inflammatory biomarkers and adipokines. Subcutaneous fat biopsy was performed in a subset for measurement of adipokine and TNF-alpha mRNA expression. Results: Visceral adiposity was significantly associated with serum concentrations of TNF receptor 1 (TNFR1), TNFR2, and vascular cell adhesion molecule-1 and adipose tissue expression of TNF-alpha and SOCS-3 (all P < 0.05). Insulin resistance as assessed by homeostasis model assessment was significantly associated with TNFR1, C-reactive protein, IL-6, and soluble intracellular adhesion molecule-1 (sICAM-1) (all P < 0.05). Etanercept significantly improved fasting glucose (treatment effect vs. placebo over 6 months, -10.8 +/- 4.4%, P = 0.02). Etanercept also increased the ratio of high molecular weight adiponectin to total adiponectin (+22.1 +/- 9.2% vs. placebo, P = 0.02), and decreased levels of sICAM-1 (-11 +/- 2% vs. placebo, P < 0.0001). In contrast, body composition, lipids, C-reactive protein, and IL-6 were unchanged after 6 months. Conclusions: Prolonged therapy with etanercept improved fasting glucose, increased the ratio of high molecular weight to total adiponectin, and decreased sICAM-1 in obese subjects with abnormal glucose homeostasis and significant subclinical inflammation. (J Clin Endocrinol Metab 96: E146-E150, 2011) C1 [Stanley, Takara L.; Zanni, Markella V.; Johnsen, Stine; Rasheed, Sarah; Makimura, Hideo; Grinspoon, Steven K.] Harvard Univ, Sch Med, Program Nutr Metab, Boston, MA 02114 USA. [Stanley, Takara L.; Zanni, Markella V.; Johnsen, Stine; Rasheed, Sarah; Makimura, Hideo; Grinspoon, Steven K.] Harvard Univ, Sch Med, Neuroendocrine Unit, Boston, MA 02114 USA. [Lee, Hang] Harvard Univ, Sch Med, Ctr Biostat, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Khor, Victor K.; Ahima, Rexford S.] Univ Penn, Sch Med, Dept Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA. RP Grinspoon, SK (reprint author), MGH Program Nutr Metab, LON5-207,55 Fruit St, Boston, MA 02114 USA. EM sgrinspoon@partners.org FU Amgen; National Institutes of Health (NIH) [M01-RR-01066, 1 UL1 RR025758-01]; Harvard Clinical and Translational Science Center, National Center for Research Resources; NIH [F32 DK080642-02, K23 DK089910-01, K24 DK064545-06, PO1-DK049210, F32 DK085969-01]; Danish Agency for Science, Technology, and Innovation FX S.K.G. received funding from Amgen in the form of an investigator-initiated research grant. Funding was also provided by National Institutes of Health (NIH) M01-RR-01066 and 1 UL1 RR025758-01, Harvard Clinical and Translational Science Center, from the National Center for Research Resources. NIH funding was also provided through F32 DK080642-02 and K23 DK089910-01 to T.L.S., K24 DK064545-06 to S.G., PO1-DK049210 to R.S.A., and F32 DK085969-01 to M.V.Z. Funding to S.J. was provided by The Danish Agency for Science, Technology, and Innovation. NR 19 TC 106 Z9 110 U1 1 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2011 VL 96 IS 1 BP E146 EP E150 DI 10.1210/jc.2010-1170 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 732LB UT WOS:000288185400021 PM 21047923 ER PT J AU Bloch, MJ Basile, JN AF Bloch, Michael J. Basile, Jan N. TI Treating the Black Hypertensive in 2010: Achieve Lower Targets While Awaiting More Definitive Evidence SO JOURNAL OF CLINICAL HYPERTENSION LA English DT Editorial Material ID BLOOD-PRESSURE CONTROL; AMLODIPINE C1 [Bloch, Michael J.] St Marys Reg Med Ctr, Risk Reduct Ctr, Reno, NV 89503 USA. [Bloch, Michael J.] Univ Nevada, Sch Med, Div Gen Internal Med, Div Cardiol, Reno, NV 89557 USA. [Basile, Jan N.] Med Univ S Carolina, Seinsheimer Cardiovasc Hlth Program, Div Gen Internal Med Geriatr, Charleston, SC 29425 USA. [Basile, Jan N.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Bloch, MJ (reprint author), St Marys Reg Med Ctr, Risk Reduct Ctr, 645 N Arlington St,Suite 460, Reno, NV 89503 USA. EM mbloch@aol.com NR 10 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1524-6175 J9 J CLIN HYPERTENS JI J. Clin. Hypertens. PD JAN PY 2011 VL 13 IS 1 BP 1 EP 4 DI 10.1111/j.1751-7176.2010.00411.x PG 4 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 703RY UT WOS:000286000200001 PM 21214713 ER PT J AU Richmond, J Tuzova, M Parks, A Adams, N Martin, E Tawa, M Morrison, L Chaney, K Kupper, TS Curiel-Lewandrowski, C Cruikshank, W AF Richmond, Jillian Tuzova, Marina Parks, Ashley Adams, Natalie Martin, Elizabeth Tawa, Marianne Morrison, Lynne Chaney, Keri Kupper, Thomas S. Curiel-Lewandrowski, Clara Cruikshank, William TI Interleukin-16 as a Marker of Sezary Syndrome Onset and Stage SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE Cutaneous T cell lymphoma; Sezary syndrome; interleukin-16; caspase 3; CD26; malignant T cells ID T-CELL LYMPHOMA; MYCOSIS-FUNGOIDES; PERIPHERAL-BLOOD; CHEMOKINE RECEPTORS; HUMAN LYMPHOKINES; DENDRITIC CELLS; UNITED-STATES; LYMPHOCYTES; ACTIVATION; EXPRESSION AB S,zary syndrome is one of the most common forms of cutaneous T cell lymphoma (CTCL). It is characterized by skin infiltration of malignant T cells. We examined interleukin-16, a potent T cell chemoattractant and cell-cycle regulator, as a prospective marker of disease onset and stage. The correlation of total intracellular interleukin-16 and surface CD26 was studied by flow cytometry. Confocal microscopy was performed to determine localization of interleukin-16 at different stages of the disease. The levels of interleukin-16 in plasma and culture supernatants were examined by enzyme-linked immunoassay. Additionally, lymphocytes from stage IB patients were cultured in the presence of interleukin-16 alone and in combination with interleukin-15, and their ability to survive and proliferate was determined by cell counts and [3H]TdR incorporation. The data indicate that loss of both nuclear and intracellular pro-interleukin-16 highly correspond to disease stage, with a concomitant increase in secreted mature interleukin-16 in both culture supernatants and patients' plasma that peaks at stage IB. Loss of intracellular interleukin-16 strongly corresponded to loss of surface CD26, which has been shown to occur with more advanced stage of CTCL. Nuclear translocation of pro-interleukin-16 was not observed in late stages of S,zary syndrome, indicating this loss is not reversible. We propose that it is feasible to use plasma levels of IL-16 as a potential diagnostic marker of S,zary syndrome and to use loss of intracellular IL-16 as a prognostic indicator of disease severity and stage. C1 [Richmond, Jillian; Tuzova, Marina; Parks, Ashley; Cruikshank, William] Boston Univ, Sch Med, Ctr Pulm, Boston, MA 02118 USA. [Adams, Natalie; Martin, Elizabeth; Tawa, Marianne; Chaney, Keri; Kupper, Thomas S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Morrison, Lynne; Curiel-Lewandrowski, Clara] Arizona State Univ, Arizona Canc Ctr, Tucson, AZ 85719 USA. RP Cruikshank, W (reprint author), Boston Univ, Sch Med, Ctr Pulm, 72 E Concord St, Boston, MA 02118 USA. EM bcruiksh@bu.edu FU NIH [R01CA122737-01A2] FX This work was supported by NIH R01CA122737-01A2. All flow cytometric data were acquired using equipment maintained by the Boston University Medical Campus Core Facilities. NR 49 TC 13 Z9 14 U1 0 U2 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD JAN PY 2011 VL 31 IS 1 BP 39 EP 50 DI 10.1007/s10875-010-9464-8 PG 12 WC Immunology SC Immunology GA 740PS UT WOS:000288807500006 PM 20878214 ER PT J AU Isaacs, SN AF Isaacs, Stuart N. TI A stimulating way to improve T cell responses to poxvirus-vectored vaccines SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID VIRUS; DNA; VACCINATION; EXPRESSION; IMMUNITY; CLONING; SAFETY AB Vaccines remain one of the most cost-effective public health measures Despite ongoing efforts, protective vaccines against cancer and many infectious diseases, including malaria, tuberculosis, and HIV/AIDS, are still not in hand Most investigators believe that to succeed against these difficult targets, vaccines that generate potent T cell responses are needed In this issue of the Salek-Ardakani et al show how the relative virulence of a virus/vaccine vector affects the memory CD8(+) T cells generated and how the response may be enhanced The work has important implications for the development of future vaccines that aim to trigger CD8(+) T cell responses C1 [Isaacs, Stuart N.] Univ Penn, Sch Med, Dept Med, Div Infect Dis, Philadelphia, PA 19104 USA. [Isaacs, Stuart N.] Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Isaacs, SN (reprint author), Univ Penn, Sch Med, Dept Med, Div Infect Dis, 502 Johnson Pavilion, Philadelphia, PA 19104 USA. FU NIAID NIH HHS [U01-AI077913, U01-AI066333, U01 AI066333, U54 AI057168, U01 AI077913, U54-AI057168] NR 16 TC 2 Z9 2 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 JAN PY 2011 VL 121 IS 1 BP 19 EP 21 DI 10.1172/JCI45726 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 702KF UT WOS:000285892300006 PM 21183782 ER PT J AU Seale, P Conroe, HM Estall, J Kajimura, S Frontini, A Ishibashi, J Cohen, P Cinti, S Spiegelman, BM AF Seale, Patrick Conroe, Heather M. Estall, Jennifer Kajimura, Shingo Frontini, Andrea Ishibashi, Jeff Cohen, Paul Cinti, Saverio Spiegelman, Bruce M. TI Prdm16 determines the thermogenic program of subcutaneous white adipose tissue in mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID NERVOUS-SYSTEM ACTIVITY; CORONARY-HEART-DISEASE; BROWN ADIPOCYTES; PPAR-GAMMA; TRANSCRIPTIONAL COMPLEX; UNCOUPLING PROTEIN-1; ABDOMINAL ADIPOSITY; INSULIN SENSITIVITY; COREPRESSOR RIP140; ENERGY-EXPENDITURE AB The white adipose organ is composed of both subcutaneous and several intra-abdominal depots Excess abdominal adiposity is a major risk factor for metabolic disease in rodents and humans, while expansion of subcutaneous fat does not carry the same risks Brown adipose produces heat as a defense against hypothermia and obesity, and the appearance of brown-like adipocytes within white adipose tissue depots is associated with improved metabolic phenotypes Thus, understanding the differences in cell biology and function of these different adipose cell types and depots may be critical to the development of new therapies for metabolic disease Here, we found that Prdm16, a brown adipose determination factor, is selectively expressed in subcutaneous white adipocytes relative to other white fat depots in mice Transgenic expression of Prdm16 in fat tissue robustly induced the development of brown-like adipocytes in subcutaneous, but not epididymal, adipose depots Prdm16 transgenic mice displayed increased energy expenditure, limited weight gain, and improved glucose tolerance in response to a high-fat diet shRNA-mediated depletion of Prdm16 in isolated subcutaneous adipocytes caused a sharp decrease in the expression of thermogenic genes and a reduction in uncoupled cellular respiration Finally, Prdm16 haploinsufficiency reduced the brown fat phenotype in white adipose tissue stimulated by beta-adrenergic agonists These results demonstrate that Prdm16 is a cell-autonomous determinant of a brown fat-like gene program and thermogenesis in subcutaneous adipose tissues C1 [Seale, Patrick; Ishibashi, Jeff] Univ Penn, Sch Med, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA. [Seale, Patrick; Ishibashi, Jeff] Univ Penn, Sch Med, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA. [Conroe, Heather M.; Estall, Jennifer; Kajimura, Shingo; Cohen, Paul; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Conroe, Heather M.; Estall, Jennifer; Kajimura, Shingo; Cohen, Paul; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Frontini, Andrea; Cinti, Saverio] Univ Ancona, Sch Med, Politecn Marche, Dept Mol Pathol & Innovat Therapies, Ancona, Italy. RP Seale, P (reprint author), Univ Penn, Sch Med, Inst Diabet Obes & Metab, Clin Res Bldg 727,415 Curie Blvd, Philadelphia, PA 19104 USA. FU NIH [DK081605, DK31405 24]; Keystone Innovation Starter Kit (KISK); Institute for Diabetes, Obesity, and Metabolism (IDOM) at the University of Pennsylvania School of Medicine FX We are grateful to Bryan Bjork and David R. Beier for Prdm16 deficient mice We thank Mary Selak and Nicolai Dolibai for assistance with oxygen consumption assays and Dina Laznik and Matthew Brown for technical assistance This work was supported by NIH grant DK081605 and a Keystone Innovation Starter Kit (KISK) program grant to P Seale, by NIH grant DK31405 24 to B M Spiegelman, and by the Institute for Diabetes, Obesity, and Metabolism (IDOM) at the University of Pennsylvania School of Medicine NR 73 TC 379 Z9 398 U1 7 U2 56 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 JAN PY 2011 VL 121 IS 1 BP 96 EP 105 DI 10.1172/JCI44271 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 702KF UT WOS:000285892300016 PM 21123942 ER PT J AU Staquicini, FI Ozawa, MG Moya, CA Driessen, WHP Barbu, EM Nishimori, H Soghomonyan, S Flores, LG Liang, XW Paolillo, V Alauddin, MM Basilion, JP Furnari, FB Bogler, O Lang, FF Aldape, KD Fuller, GN Hook, M Gelovani, JG Sidman, RL Cavenee, WK Pasqualini, R Arap, W AF Staquicini, Fernanda I. Ozawa, Michael G. Moya, Catherine A. Driessen, Wouter H. P. Barbu, E. Magda Nishimori, Hiroyuki Soghomonyan, Suren Flores, Leo G., II Liang, Xiaowen Paolillo, Vincenzo Alauddin, Mian M. Basilion, James P. Furnari, Frank B. Bogler, Oliver Lang, Frederick F. Aldape, Kenneth D. Fuller, Gregory N. Hook, Magnus Gelovani, Juri G. Sidman, Richard L. Cavenee, Webster K. Pasqualini, Renata Arap, Wadih TI Systemic combinatorial peptide selection yields a non-canonical iron-mimicry mechanism for targeting tumors in a mouse model of human glioblastoma SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID BLOOD-BRAIN-BARRIER; RECEPTOR MONOCLONAL-ANTIBODY; HUMAN SERUM TRANSFERRIN; GENE-EXPRESSION; ENHANCED PERMEABILITY; CONFORMATIONAL-CHANGE; NERVOUS-SYSTEM; PHAGE DISPLAY; N-LOBE; DELIVERY AB The management of CNS tumors is limited by the blood-brain barrier (BBB), a vascular interface that restricts the passage of most molecules from the blood into the brain Here we show that phage particles targeted with cc rum ligand motifs selected in vivo from a combinatorial peptide library can cross the BBB under normal and pathological conditions Specifically, we demonstrated that phage clones displaying an iron-mimic peptide were able to target a protein complex of transferrin and transferrin receptor (TfR) through a non-canonical allosteric binding mechanism and that this functional protein complex mediated transport of the corresponding viral particles into the normal mouse brain We also showed that, in an orthotopic mouse model of human glioblastoma, a combination of TfR overexpression plus extended vascular permeability and ligand retention resulted m remarkable brain tumor targeting of chimeric adeno-associated virus/phage particles displaying the iron-mimic peptide and carrying a gene of interest As a proof of concept, we delivered the HSV thymidine kinase gene for molecular-genetic imaging and targeted therapy of intracranial xenografted tumors Finally, we established that these experimental findings might be clinically relevant by determining through human tissue microarrays that many primary astrocytic tumors strongly express TfR. Together, our combinatorial selection system and results may provide a translational avenue for the targeted detection and treatment of brain tumors C1 [Staquicini, Fernanda I.; Ozawa, Michael G.; Moya, Catherine A.; Driessen, Wouter H. P.; Barbu, E. Magda; Pasqualini, Renata; Arap, Wadih] Univ Texas MD Anderson Canc Ctr, David H Koch Ctr, Houston, TX 77030 USA. [Nishimori, Hiroyuki; Furnari, Frank B.; Cavenee, Webster K.] Univ Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA. [Soghomonyan, Suren; Flores, Leo G., II; Alauddin, Mian M.; Gelovani, Juri G.; Pasqualini, Renata; Arap, Wadih] Univ Texas MD Anderson Canc Ctr, Dept Expt Diagnost Imaging, Houston, TX 77030 USA. [Liang, Xiaowen; Hook, Magnus] Texas A&M Univ Syst Hlth Sci Ctr, Houston, TX USA. [Basilion, James P.] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. [Basilion, James P.] Massachusetts Gen Hosp, NFCR, Ctr Mol Anal & Imaging, Dept Radiol, Boston, MA 02114 USA. [Bogler, Oliver; Lang, Frederick F.] Univ Texas MD Anderson Canc Ctr, Dept Neurosurg, Houston, TX 77030 USA. [Aldape, Kenneth D.; Fuller, Gregory N.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Sidman, Richard L.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Neurol, Boston, MA 02215 USA. RP Pasqualini, R (reprint author), Univ Texas MD Anderson Canc Ctr, David H Koch Ctr, 1515 Holcombe Blvd, Houston, TX 77030 USA. OI Bogler, Oliver/0000-0002-3700-0480; Fuller, Gregory/0000-0001-9447-2647 FU National Institutes of Health; National Cancer Institute; Department of Defense; Gillson Longenbaugh Foundation; AngelWorks; Marcus Foundation; Center for Targeted Therapy of The University of Texas; National Foundation for Cancer Research; Harry S and Isabel C Cameron Foundation; Schissler Foundation FX We thank E Helene Sage for critical reading of the manuscript, Richard G Brennan, Emmanuel Dias Neto, and Rebecca Richards Kortum for helpful discussions, and David Bier for graphic design This work was supported by grants from the National Institutes of Health (to R Pasqualini and W Arap), National Cancer Institute (to R. Pasqualini, W Arap, and W K Cavenee), and Department of Defense (to R. Pasqualini and W Arap) and by awards from the Gillson Longenbaugh Foundation, AngelWorks, and the Marcus Foundation (to R Pasqualini and W Arap) O Bogler was supported by a grant from the Center for Targeted Therapy of The University of Texas M D Anderson Cancer Center W K Cavenee was supported by a grant from the National Foundation for Cancer Research C A Moya received pre doctoral fellowships from the Harry S and Isabel C Cameron Foundation and the Schissler Foundation NR 53 TC 46 Z9 47 U1 3 U2 24 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 JAN PY 2011 VL 121 IS 1 BP 161 EP 173 DI 10.1172/JCI44798 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 702KF UT WOS:000285892300022 PM 21183793 ER PT J AU Gaglia, JL Guimaraes, AR Harisinghani, M Turvey, SE Jackson, R Benoist, C Mathis, D Weissleder, R AF Gaglia, Jason L. Guimaraes, Alexander R. Harisinghani, Mukesh Turvey, Stuart E. Jackson, Richard Benoist, Christophe Mathis, Diane Weissleder, Ralph TI Noninvasive imaging of pancreatic islet inflammation in type 1A diabetes patients SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID MELLITUS; VOLUME; ONSET; MACROPHAGES; INSULITIS; PART; AGE AB Type 1A diabetes (T1D) is an autoimmune disease characterized by leukocyte infiltration of the pancreatic islets of Langerhans A major impediment to advances in understanding, preventing, and curing T1D has been the inability to "see" the disease inmate, progress, or regress, especially during the occult phase Here, we report the development of a noninvasive method to visualize T1D at the target organ level in patients with active insulitis Specifically, we visualized islet inflammation, manifest by microvascular changes and monocyte/macrophage recruitment and activation, using magnetic resonance imaging of magnetic nanoparticles (MNPs) As a proof of principle for this approach, imaging of infused ferumoxtran-10 nanoparticles permitted effective visualization of the pancreas and distinction of recent-onset diabetes patients from nondiabetic controls The observation that MNPs accumulate in the pancreas of T1D patients opens the door to exploiting this noninvasive imaging method to follow T1D progression and monitoring the ability of immunomodulatory agents to clear insulitis C1 [Gaglia, Jason L.; Benoist, Christophe; Mathis, Diane] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Gaglia, Jason L.; Guimaraes, Alexander R.; Harisinghani, Mukesh; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Gaglia, Jason L.; Turvey, Stuart E.; Jackson, Richard; Benoist, Christophe; Mathis, Diane] Brigham & Womens Hosp, Joslin Diabet Ctr, Boston, MA 02115 USA. [Gaglia, Jason L.; Turvey, Stuart E.; Jackson, Richard; Benoist, Christophe; Mathis, Diane] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Guimaraes, Alexander R.; Harisinghani, Mukesh; Weissleder, Ralph] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Benoist, Christophe; Mathis, Diane; Weissleder, Ralph] MIT & Harvard, Broad Inst, Cambridge, MA USA. [Mathis, Diane; Weissleder, Ralph] Harvard Stem Cell Inst, Cambridge, MA USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Mathis, D (reprint author), Harvard Univ, Sch Med, Dept Pathol, NRB 1052F,77 Ave Louis Pasteur, Boston, MA 02115 USA. OI Gaglia, Jason/0000-0003-2904-312X; Turvey, Stuart/0000-0003-1599-1065 FU US National Institute of Allergy and Infectious Disease [P01 A1 054904]; NIH [UL1 RR025758]; [U01 HL080731]; [P50 CA86355]; [U54 CA119349]; [U24 CA092782] FX This work was supported by US National Institute of Allergy and Infectious Disease grant P01 A1 054904 and in part by U01 HL080731, P50 CA86355, U54 CA119349, and U24 CA092782 for technology development Additional support was provided by Harvard Catalyst Harvard Clinical and Translational Science Center (NIH Award UL1 RR025758 and contributions from Harvard University and affiliated academic health care centers) The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health care centers, the National Center for, Research Resources, or the NIH This study utilized the Joslin Clinical Research Center, which receives financial support from philanthropic donors J L Gaglia acknowledges support from Irvington Institute/Dana Foundation Fellowship of the Cancer Research Institute and Clinical Investigator Training Program Harvard/MIT Health Sciences and Technology Beth Israel Deaconess Medical Center, in collaboration with Pfizer Inc and Merck & Co A R Guimaraes acknowledges support from the RSNA Research and Education Foundation Scholar Award We thank R Phillips for study subject coordination, R Betensky for statistical assistance, and T Orban for measuring autoAbs Ferumoxtran 10 (Combidex) was provided by AMAG Pharmaceuticals Inc NR 21 TC 91 Z9 93 U1 1 U2 9 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JAN PY 2011 VL 121 IS 1 BP 442 EP 445 DI 10.1172/JCI44339 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 702KF UT WOS:000285892300045 PM 21123946 ER PT J AU Cohen, T Wilson, D Wallengren, K Samuel, EY Murray, M AF Cohen, Ted Wilson, Douglas Wallengren, Kristina Samuel, Elizabeth Y. Murray, Megan TI Mixed-Strain Mycobacterium tuberculosis Infections among Patients Dying in a Hospital in KwaZulu-Natal, South Africa SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID MOLECULAR EPIDEMIOLOGY; EXOGENOUS REINFECTION; RECURRENT TUBERCULOSIS; DIVERSITY; DATABASE AB We performed spoligotyping and 24-locus mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) typing on M. tuberculosis culture-positive biopsy specimens collected from adults dying in a hospital in KwaZulu-Natal. Of 56 culture-positive samples genotyped, we detected mixed strains in five (9%) and clonal heterogeneity in an additional four (7%). C1 [Cohen, Ted; Murray, Megan] Brigham & Womens Hosp, Div Global Hlth Equ, Boston, MA 02115 USA. [Cohen, Ted; Wallengren, Kristina; Murray, Megan] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Wilson, Douglas] Univ KwaZulu Natal, Edendale Hosp, Dept Med, Pietermaritzburg, South Africa. [Samuel, Elizabeth Y.] Inkosi Albert Luthuli Cent Hosp, Natl Hlth Lab Serv, Mayville, South Africa. [Murray, Megan] Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. RP Cohen, T (reprint author), Brigham & Womens Hosp, Div Global Hlth Equ, 75 Francis St, Boston, MA 02115 USA. EM tcohen@hsph.harvard.edu RI Cohen, Ted/G-8101-2011 FU KwaZulu-Natal Department of Health; Office of the Director, U.S. National Institutes of Health [DP2OD006663]; Massachusetts General Hospital; BMS Secure the Future; Harvard University CFAR; Ragon Institute; Gary and Lauren Cohen; Mark and Lisa Schwartz Foundation; Witten Family Foundation; Edendale Hospital FX We acknowledge the contributions of Mary-Jane Khumalo, Robin Draper, Keith Rasmussen, Langa Ngubane, Stanley Carries, Maria Kempner, Shaakir Khader, Matanja Coetzee, Molly Franke, Krista Dong, Rocio Hurtado, and Bruce Walker. We acknowledge the support of the KwaZulu-Natal Department of Health.; T.C. received support through Award Number DP2OD006663 from the Office of the Director, U.S. National Institutes of Health. Additional funding was provided by Massachusetts General Hospital, BMS Secure the Future, and Edendale Hospital, Harvard University CFAR, the Ragon Institute, Gary and Lauren Cohen, the Mark and Lisa Schwartz Foundation, and the Witten Family Foundation. NR 33 TC 35 Z9 35 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JAN PY 2011 VL 49 IS 1 BP 385 EP 388 DI 10.1128/JCM.01378-10 PG 4 WC Microbiology SC Microbiology GA 701AQ UT WOS:000285787100053 PM 20980576 ER PT J AU Van Cutsem, E Lambrechts, D Prenen, H Jain, RK Carmeliet, P AF Van Cutsem, Eric Lambrechts, Diether Prenen, Hans Jain, Rakesh K. Carmeliet, Peter TI Lessons From the Adjuvant Bevacizumab Trial on Colon Cancer: What Next? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID METASTATIC COLORECTAL-CANCER; PACLITAXEL PLUS BEVACIZUMAB; GLIOBLASTOMA PATIENTS; BREAST-CANCER; RECTAL-CANCER; TUMOR-GROWTH; POLYMORPHISMS; CHEMOTHERAPY; CEDIRANIB; INHIBITOR C1 [Van Cutsem, Eric; Prenen, Hans] Katholieke Univ Leuven, Univ Hosp Gasthuisberg Leuven, Louvain, Belgium. [Lambrechts, Diether; Carmeliet, Peter] Katholieke Univ Leuven, Vlaams Inst Biotechnol, Vesalius Res Ctr, Louvain, Belgium. [Jain, Rakesh K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jain, Rakesh K.] Harvard Univ, Sch Med, Boston, MA USA. RP Van Cutsem, E (reprint author), Katholieke Univ Leuven, Univ Hosp Gasthuisberg Leuven, Louvain, Belgium. RI leng, xianwei/F-9073-2011; Verdrengh, Evelien/H-4571-2012 NR 24 TC 34 Z9 34 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 1 PY 2011 VL 29 IS 1 BP 1 EP 4 DI 10.1200/JCO.2010.32.2701 PG 4 WC Oncology SC Oncology GA 700DB UT WOS:000285712400011 ER PT J AU Matei, D Sill, MW Lankes, HA DeGeest, K Bristow, RE Mutch, D Yamada, SD Cohn, D Calvert, V Farley, J Petricoin, EF Birrer, MJ AF Matei, Daniela Sill, Michael W. Lankes, Heather A. DeGeest, Koen Bristow, Robert E. Mutch, David Yamada, S. Diane Cohn, David Calvert, Valerie Farley, John Petricoin, Emanuel F. Birrer, Michael J. TI Activity of Sorafenib in Recurrent Ovarian Cancer and Primary Peritoneal Carcinomatosis: A Gynecologic Oncology Group Trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PHASE-II TRIAL; SQUAMOUS-CELL CARCINOMAS; RAF-1 MESSENGER-RNA; K-RAS MUTATIONS; GROWTH-FACTOR; HEPATOCELLULAR-CARCINOMA; EPITHELIAL TUMORS; SEROUS CARCINOMA; CLINICAL-TRIALS; ACTIVATION AB Purpose Sorafenib is a kinase inhibitor targeting Raf and other kinases (ie, vascular endothelial growth factor receptor [VEGFR], platelet-derived growth factor receptor [PDGFR], Flt3, and c-KIT). This study assessed its activity and tolerability in patients with recurrent ovarian cancer (OC) or primary peritoneal carcinomatosis (PPC). Methods This open-label, multi-institutional, phase II study used a two-stage design. Eligible patients had persistent or recurrent OC/PPC after one to two prior cytotoxic regimens, and they experienced progression within 12 months of platinum-based therapy. Treatment consisted of sorafenib 400 mg orally twice per day. Primary end points were progression-free survival (PFS) at 6 months and toxicity by National Cancer Institute criteria. Secondary end points were tumor response and duration of PFS and overall survival. Biomarker analyses included measurement of ERK and b-Raf expression in tumors and phosphorylation of ERK (pERK) in peripheral-blood lymphocytes (PBLs) before and after 1 month of treatment. Results Seventy-three patients were enrolled, of which 71 were eligible. Fifty-nine eligible patients (83%) had measurable disease, and 12 (17%) had detectable disease. Significant grade 3 or 4 toxicities included the following: rash (n = 7), hand-foot syndrome (n = 9), metabolic (n = 10), GI (n = 3), cardiovascular (n = 2), and pulmonary (n = 2). Only patients with measurable disease were used to assess efficacy. Fourteen survived progression free for at least 6 months (24%; 90% CI, 15% to 35%). Two patients had partial responses (3.4%; 90% CI, 1% to 10%); 20 had stable disease; 30 had progressive disease; and seven could not have their tumor assessed. ERK and b-Raf were expressed in all tumors. Exploratory analyses indicated that pERK in post-treatment PBL specimens was associated with PFS. Conclusion Sorafenib has modest antitumor activity in patients with recurrent OC, but the activity was at the expense of substantial toxicity. C1 [Matei, Daniela] Indiana Univ, Sch Med, Div Hematol Oncol, Indianapolis, IN 46202 USA. Simon Canc Ctr, Indianapolis, IN USA. Roswell Pk Canc Inst, Stat & Data Ctr, Gynecol Oncol Grp, Buffalo, NY 14263 USA. SUNY Buffalo, Buffalo, NY 14260 USA. Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA. Johns Hopkins Univ, Sch Med, Johns Hopkins Oncol Ctr, Baltimore, MD 21205 USA. Washington Univ, Sch Med, St Louis, MO USA. Univ Chicago, Chicago, IL 60637 USA. Columbus Canc Council, Columbus, OH USA. George Mason Univ, Ctr Appl Prote & Mol Med, Manassas, VA USA. Univ Hlth Sci, Uniformed Serv, Bethesda, MD USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Matei, D (reprint author), Indiana Univ, Sch Med, Div Hematol Oncol, RT-457,535 Barnhill Dr, Indianapolis, IN 46202 USA. EM dmatei@iupui.edu FU National Cancer Institute [CA 27469, CA 37517]; American Cancer Society [MRSG107613]; Cancer Therapy and Evaluation Program FX Supported by National Cancer Institute grants No. CA 27469 to the Gynecologic Oncology Group Administrative Office and CA 37517 to the Gynecologic Oncology Group Statistical and Data Center and by grant No. MRSG107613 from the American Cancer Society (D.M.), and by the Cancer Therapy and Evaluation Program. NR 53 TC 93 Z9 96 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 1 PY 2011 VL 29 IS 1 BP 69 EP 75 DI 10.1200/JCO.2009.26.7856 PG 7 WC Oncology SC Oncology GA 700DB UT WOS:000285712400022 PM 21098323 ER PT J AU Steensma, DP Sloan, JA Dakhil, SR Dalton, R Kahanic, SP Prager, DJ Stella, PJ Rowland, KM Novotny, PJ Loprinzi, CL AF Steensma, David P. Sloan, Jeff A. Dakhil, Shaker R. Dalton, Robert Kahanic, Stephen P. Prager, Diane J. Stella, Philip J. Rowland, Kendrith M., Jr. Novotny, Paul J. Loprinzi, Charles L. TI Phase III, Randomized Study of the Effects of Parenteral Iron, Oral Iron, or No Iron Supplementation on the Erythropoietic Response to Darbepoetin Alfa for Patients With Chemotherapy-Associated Anemia SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID QUALITY-OF-LIFE; EVERY 3 WEEKS; INTRAVENOUS IRON; CANCER-PATIENTS; STIMULATING AGENTS; CHRONIC DISEASE; MULTICENTER; EPOETIN; TRIAL; ONCOLOGY AB Purpose Functional iron deficiency may impair response to erythropoiesis-stimulating agents (ESAs) in iron-replete patients with chemotherapy-associated anemia (CAA). This study evaluated whether coadministration of parenteral iron improves ESA efficacy in patients with CAA. Patients and Methods This prospective, multicenter, randomized trial enrolled 502 patients with hemoglobin (Hb) less than 11 g/dL who were undergoing chemotherapy for nonmyeloid malignancies. All patients received darbepoetin alfa once every 3 weeks and were randomly assigned to receive either ferric gluconate 187.5 mg intravenously (IV) every 3 weeks, oral daily ferrous sulfate 325 mg, or oral placebo for 16 weeks. Results There was no difference in the erythropoietic response rate (ie, proportion of patients achieving Hb >= 12 g/dL or Hb increase >= 2 g/dL from baseline): 69.5% (95% CI, 61.9% to 76.5%) of IV iron-treated patients achieved an erythropoietic response compared with 66.9% (95% CI, 59.1% to 74.0%) who received oral iron and 65.0% (95% CI, 57.2% to 72.3%) who received oral placebo (P = .75). There were also no differences in the proportion of patients requiring red cell transfusions, changes in quality of life, or the dose of darbepoetin administered. Adverse events (AEs) tended to be more common in the IV iron arm: grade 3 or higher AEs occurred in 54% (95% CI, 46% to 61%) of patients receiving IV iron compared with 44% (95% CI, 36% to 52%) who received oral iron and 46% (95% CI, 38% to 54%) who received oral placebo (P = .16). Conclusion In patients with CAA, addition of IV ferric gluconate to darbepoetin failed to provide additional benefit compared with oral iron or oral placebo. J Clin Oncol 29:97-105. (C) 2010 by American Society of Clinical Oncology C1 Mayo Canc Ctr, Res Consortium, Rochester, MN USA. Mayo Clin Rochester, Rochester, MN USA. Immanuel St Joseph Hosp Mayo Hlth Syst, Mankato, MN USA. Wichita Community Clin Oncol, Wichita, KS USA. Siouxland Hematol Oncol Associates, Sioux City, IA USA. Illinois Oncol Res Assoc, Community Clin Oncol Program, Peoria, IL USA. Carle Canc Ctr, Community Clin Oncol Program, Urbana, IL USA. Michigan Canc Res Consortium, Ann Arbor, MI USA. RP Steensma, DP (reprint author), Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, 44 Binney St,Suite D1B30, Boston, MA 02115 USA. EM david_steensma@dfci.harvard.edu OI Steensma, David/0000-0001-5130-9284 FU Public Health Service [CA-124477]; Amgen (Thousand Oaks, CA); Amgen FX Supported in part by Public Health Service Grant No. CA-124477 and a grant from Amgen (Thousand Oaks, CA) to the Mayo Clinic Cancer Research Consortium.; Charles L. Loprinzi, Amgen NR 24 TC 50 Z9 54 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 1 PY 2011 VL 29 IS 1 BP 97 EP 105 DI 10.1200/JCO.2010.30.3644 PG 9 WC Oncology SC Oncology GA 700DB UT WOS:000285712400026 PM 21098317 ER PT J AU Biederman, J Fried, R Petty, CR Wozniak, J Doyle, AE Henin, A Corkum, L Claudat, K Faraone, SV AF Biederman, Joseph Fried, Ronna Petty, Carter R. Wozniak, Janet Doyle, Alysa E. Henin, Aude Corkum, Lyndsey Claudat, Kim Faraone, Stephen V. TI Cognitive Development in Adults With Attention-Deficit/Hyperactivity Disorder: A Controlled Study in Medication-Naive Adults Across the Adult Life Cycle SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID DEFICIT-HYPERACTIVITY DISORDER; NEUROPSYCHOLOGICAL FUNCTION; SUBTHRESHOLD DIAGNOSES; LATE-ONSET; PERFORMANCE; CHILDREN; ADHD; ADOLESCENTS AB Objective: This study evaluated the association between attention-deficit/hyperactivity disorder (ADHD) and psychometrically defined cognitive variables across the adult life span, using data from a large controlled study of adults with and without ADHD. Method: Comparisons were made between 2 groups of adults: participants with DSM-IV-diagnosed ADHD who had never received pharmacotherapy for their ADHD (n=116) and 146 control participants. Subjects received a battery assessing IQ, neuropsychological measures, and academic testing. We modeled cognitive measures as a function of age and group status using linear regression. The study was conducted at Massachusetts General Hospital, Boston, between 1998 and 2003. Results: ADHD and control subjects maintained similar, statistically significant differences in all psychometrically assessed measures of cognition within each decade that was represented (all P values < .01). Conclusion: The negative impact of ADHD on multiple, nonoverlapping, psychometrically assessed measures of cognition remained constant across the life cycle, suggesting that the association between ADHD and cognition neither improves nor deteriorates across the life cycle. Clin Psychiatry 2011;72(1):11-16 (C) Copyright 2010 Physicians Postgraduate Press, Inc. C1 [Biederman, Joseph] Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Dept Psychiat, Clin Program Pediat Psychiat & Adult ADHD, Boston, MA 02114 USA. [Biederman, Joseph; Fried, Ronna; Petty, Carter R.; Wozniak, Janet; Doyle, Alysa E.; Henin, Aude; Corkum, Lyndsey; Claudat, Kim] Massachusetts Gen Hosp, Res Program Pediat Psychiat & Adult ADHD, Dept Psychiat, Boston, MA 02114 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Dept Psychiat, Clin Program Pediat Psychiat & Adult ADHD, 55 Fruit St,YAW 6A-6900, Boston, MA 02114 USA. EM jbiederman@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU Alza; AstraZeneca; Bristol-Myers Squibb; Eli Lilly; Janssen; McNeil; Merck; Organon; Otsuka; Shire; National Institute of Mental Health (NIMH); National Institute of Child Health and Human Development; Abbott; Celltech; Cephalon; Esai; Forest; GlaxoSmithKline; Gliatech; Janssen, McNeil; NARSAD; National Institute on Drug Abuse; New River; Novartis; Noven; Neurosearch; Pfizer; Pharmacia; The Prechter Foundation; The Stanley Foundation; UCB Pharma; Wyeth; Boehringer-Ingelheim; UCB (Schwarz) Pharma; Sepracor; MGH Academy; American Academy of Child and Adolescent Psychiatry (AACAP); NIMH; Harvard University; Reed Medical Education; AACAP; MGH; Oxford University Press; Sanofi Aventis; NIH [R01MH57934] FX Dr Biederman currently receives research support from Alza, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen, McNeil, Merck, Organon, Otsuka, Shire, the National Institute of Mental Health (NIMH), and the National Institute of Child Health and Human Development; and in previous years, received research support, consultation fees, or speaker's fees for/from Abbott, AstraZeneca, Celltech, Cephalon, Eli Lilly, Esai, Forest, GlaxoSmithKline, Gliatech, Janssen, McNeil, NARSAD, the National Institute on Drug Abuse, New River, Novartis, Noven, Neurosearch, Pfizer, Pharmacia, The Prechter Foundation, Shire, The Stanley Foundation, UCB Pharma, and Wyeth. Dr Fried has received honoraria from Shire. Dr Wozniak authored Is Your Child Bipolar? published May 2008, by Bantam Books. Dr Wozniak's spouse, Dr John Winkelman, is/was on the speakers bureau for Boehringer-Ingelheim, GlaxoSmithKline, Sanofi-Aventis, Sepracor, and Takeda; is/was on advisory boards for Axon, Boehringer-Ingelheim, GlaxoSmithKline, Jazz, Novartis, Neurogen, Pfizer, UCB (Schwarz) Pharma, and Takeda; and receives/d research support from Boehringer-Ingelheim, GlaxoSmithKline, UCB (Schwarz) Pharma, and Sepracor. Dr Doyle has received consulting fees and honoraria from the MGH Academy, the American Academy of Child and Adolescent Psychiatry (AACAP), Pfizer, Eli Lilly, and McNeil; her research is/has been funded by the NIMH and Harvard University. Dr Henin has received honoraria from Shire, Abbott, the MGH Academy, Reed Medical Education, and AACAP; her research is funded by the NIMH, NARSAD, Harvard University, and the MGH; she receives royalties from Oxford University Press. The education programs conducted by the MGH Psychiatry Academy were, in part, supported through Independent Medical Education grants from pharmaceutical companies, including AstraZeneca, Eli Lilly, McNeil, Shire, Forest, Sanofi Aventis, Janssen, Bristol-Myers Squibb, and Pfizer. Dr Faraone has received research support or consulting fees from or has been on advisory boards for Shire, Eli Lilly, Pfizer, McNeil, and the National Institutes of Health (NIH). Mr Petty, Ms Corkum, and Ms Claudat report no competing interests.; This work was supported in part by the Neal-Kimmerly Fund for the Study of Cognition, Boston, Massachusetts, and by grants to Dr Faraone from the NIH (R01MH57934). NR 39 TC 12 Z9 12 U1 0 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 JAN PY 2011 VL 72 IS 1 BP 11 EP 16 DI 10.4088/JCP.09m05420pur PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 719BT UT WOS:000287175100002 PM 21034681 ER PT J AU Nierenberg, AA Leon, AC Price, LH Shelton, RC Trivedi, MH AF Nierenberg, Andrew A. Leon, Andrew C. Price, Lawrence H. Shelton, Richard C. Trivedi, Madhukar H. TI The Current Crisis of Confidence in Antidepressants SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Editorial Material ID MENTAL-DISORDERS; DEPRESSION; PSYCHOTHERAPY; METAANALYSIS; SEVERITY; THERAPY; TRIAL; RECOMMENDATIONS; PUBLICATION; EFFICACY C1 [Nierenberg, Andrew A.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Nierenberg, Andrew A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Leon, Andrew C.] Weill Cornell Med Coll, Dept Psychiat, New York, NY USA. [Leon, Andrew C.] Weill Cornell Med Coll, Dept Publ Hlth, New York, NY USA. [Price, Lawrence H.] Brown Univ, Dept Psychiat & Human Behav, Providence, RI 02912 USA. [Price, Lawrence H.] Butler Hosp, Providence, RI 02906 USA. [Shelton, Richard C.] Vanderbilt Univ, Med Ctr, Dept Psychiat, Nashville, TN USA. [Trivedi, Madhukar H.] Univ Texas SW Med Ctr Dallas, Mood Disorders Res Program, Dallas, TX 75390 USA. [Trivedi, Madhukar H.] Univ Texas SW Med Ctr Dallas, Mood Disorders Res Clin, Dallas, TX 75390 USA. RP Nierenberg, AA (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. NR 20 TC 8 Z9 8 U1 1 U2 5 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JAN PY 2011 VL 72 IS 1 BP 27 EP 33 DI 10.4088/JCP.10035co1c PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 719BT UT WOS:000287175100004 PM 21272514 ER PT J AU Tedeschini, E Fava, M Papakostas, GI AF Tedeschini, Enrico Fava, Maurizio Papakostas, George I. TI Placebo-Controlled, Antidepressant Clinical Trials Cannot Be Shortened to Less Than 4 Weeks' Duration: A Pooled Analysis of Randomized Clinical Trials Employing a Diagnostic Odds Ratio Based Approach SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID MAJOR DEPRESSION; DOUBLE-BLIND; RUN-IN; SCALE; DISORDERS; CRITERIA; DESIGN AB Objective: In double-blind, randomized, placebocontrolled clinical trials for major depressive disorder (MDD), the impact of study duration on outcome has not been adequately studied. Our aim was to examine whether placebo-controlled antidepressant trials in MDD could be shortened to less than 4 weeks. In order to accomplish this, we examined the relationship between a "positive" or "negative" finding early on (weeks 1-4), and outcome at end point. Data Sources: MEDLINE/PubMed publication databases were searched for randomized, double-blind, placebo-controlled trials of antidepressants for adults with MDD published between January 1, 1980, and July 1, 2009 (inclusive). Data Selection: One hundred seventy-five articles were found eligible. We obtained required measures during the required time points for 101 articles (57.7%). Final inclusion of articles was determined by consensus among the authors. Data Synthesis: One hundred eighty-two drug-placebo comparisons from 104 clinical trials were pooled (29,213 patients). The strength of the relationship between early and end point outcome increased progressively. However, only at week 4 did the diagnostic odds ratio (27.44) indicate strong concordance between early and end point outcome. The specificity of early outcome as a predictor of end point outcome did not vary substantially from visit to visit (0.91-0.92), while the sensitivity increased proportionally with each visit (from 0.17 to 0.72). Conclusions: The present analysis suggests that antidepressant clinical trials cannot be shortened to less than 4 weeks' duration, primarily due to the increased risk of erroneously concluding that an effective treatment is ineffective. Four weeks is the minimum adequate length of a trial in order to reliably detect drug versus placebo differences. J Clin Psychiatry 2011;72(1):98-103 (C) Copyright 2010 Physicians Postgraduate Press, Inc. C1 [Tedeschini, Enrico; Fava, Maurizio; Papakostas, George I.] Harvard Univ, Depress Clin & Res Program, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Tedeschini, Enrico] Univ Modena & Reggio Emilia, Dept Psychiat, Modena, Italy. RP Tedeschini, E (reprint author), Harvard Univ, Depress Clin & Res Program, Massachusetts Gen Hosp, Sch Med, 50 Stanford St, Boston, MA 02114 USA. EM etedeschini@partners.org RI Papakostas, George/I-6905-2013 OI Papakostas, George/0000-0002-2465-5103 FU Bristol-Myers Squibb; Forest; National Institute of Mental Health; Abbott; Alkermes; Aspect Medical Systems; AstraZeneca; Bio Research; BrainCells; Cephalon; Clinical Trial Solutions; Eli Lilly; Ganeden; GlaxoSmithKline; Johnson Johnson; Lichtwer; Lorex; NARSAD; National Center for Complementary and Alternative Medicine; National Institute on Drug Abuse; NIMH; Novartis; Organon Inc; Pamlab; Pfizer; Pharmavite; Roche; sanofi-aventis; Shire; Solvay; Synthelabo; Wyeth-Ayerst FX Dr Fava has served as an advisor/consultant for Abbott, Amarin, Aspect Medical Systems, AstraZeneca, Auspex, Bayer, Best Practice Project Management, Biovail, BrainCells, Bristol-Myers Squibb, Cephalon, Clinical Trials Solutions, CNS Response, Compellis, Cypress, Dov, Eli Lilly, EPIX, Fabre-Kramer, Forest, GlaxoSmithKline, Grunenthal, Janssen, Jazz, Johnson & Johnson, Knoll, Labopharm, Lorex, Lundbeck, MedAvante, Merck, Methylation Sciences, Neuronetics, Novartis, Nutrition 21, Organon, Pamlab, Pfizer, PharmaStar, Pharmavite, Precision Human Biolaboratory, Roche, sanofi-aventis, Sepracor, Schering-Plough, Solvay, Somaxon, Somerset, Synthelabo, Takeda, Tetragenex, Transcept, Vanda, and WyethAyerst; has received research support from Abbott, Alkermes, Aspect Medical Systems, AstraZeneca, Bio Research, BrainCells, Bristol-Myers Squibb, Cephalon, Clinical Trial Solutions, Eli Lilly, Forest, Ganeden, GlaxoSmithKline, Johnson & Johnson, Lichtwer, Lorex, NARSAD, the National Center for Complementary and Alternative Medicine, the National Institute on Drug Abuse, the NIMH, Novartis, Organon Inc, Pamlab, Pfizer, Pharmavite, Roche, sanofi-aventis, Shire, Solvay, Synthelabo, and Wyeth-Ayerst; has served as a speaker for Advanced Meeting Partners, American Psychiatric Association, AstraZeneca, Belvoir, Boehringer-Ingelheim, Bristol-Myers Squibb, Cephalon, Eli Lilly, Forest, GlaxoSmithKline, Imedex, Novartis, Organon, Pfizer, PharmaStar, MGH Psychiatry Academy/Primedia, MGH Psychiatry Academy/ Reed-Elsevier, UBC, Wyeth-Ayerst Laboratories; has equity Holdings in Compellis; and has patent applications for SPCD and for a combination of azapirones and bupropion in MDD and copyright royalties for the MGH Cognitive and Physical Functioning Questionnaire, the MGH Sexual Functioning Inventory, the MGH Antidepressant Treatment Response Questionnaire, the Discontinuation-Emergent Signs and Symptoms scale, and SAFER. Dr Papakostas has served as a consultant for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Evotec, Inflabloc, Jazz, Otsuka, Pamlab, Pfizer, Pierre Fabre, Shire, and Wyeth; has received honoraria from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Evotec, GlaxoSmithKline, Inflabloc, Jazz, Lundbeck, Otsuka, Pamlab, Pfizer, Pierre Fabre, Shire, Titan, and Wyeth; has received research support from Bristol-Myers Squibb, Forest, and the National Institute of Mental Health; and has served on the speakers bureaus for Bristol-Myers Squibb and Pfizer. Dr Tedeschini reports no competing interests. NR 24 TC 14 Z9 14 U1 0 U2 2 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JAN PY 2011 VL 72 IS 1 BP 98 EP 103 DI 10.4088/JCP.09m05725blu PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 719BT UT WOS:000287175100013 PM 21208576 ER PT J AU Choi, YW Shepard, JAO Kim, J Jeon, SC Park, CK Heo, JN Paik, DJ AF Choi, Yo Won Shepard, Jo-Anne O. Kim, Jinoo Jeon, Seok Chol Park, Choong Ki Heo, Jeong-Nam Paik, Doo Jin TI Left Costomediastinal Recess of the Pleura, the Potential Pleural Space Anterior to the Heart SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE pleura; anatomy; cross-sectional; pleural diseases; pericardiocentesis ID ECHOCARDIOGRAPHICALLY GUIDED PERICARDIOCENTESIS; INTERCOSTAL APPROACH; PERICARDIAL-EFFUSIONS; DRAINAGE; CT; COMPLICATIONS; EXPERIENCE; LUNG AB Objective: To investigate clinical implications of the left costomediastinal recess of the pleura. Methods: The left anterior pleural anatomy was studied in 12 cadavers. Chest computed tomography (CT) scans of 68 healthy/near-healthy patients were reviewed for the recess. Twenty pleural lesions in the recess were analyzed on CT. Eight cases of left paracardiac pericardiocentesis were analyzed for pleural complications. Results: Two fresh cadavers showed the recess to be wider downward, measuring 75 and 55 mm in width at the sixth intercostal space. None of the 68 healthy/near-healthy CT scans displayed the recess. Twenty recess lesions were connected to similar pleural lesions surrounding the left lung (n = 19) or showed an isolated lesion therein only partly facing the left lung (n = 1). Ipsilateral pleural effusion complicated 3 of 7, successful left paracardiac pericardiocentesis. Conclusion: Regardless of their contiguity with the lung, the differential diagnosis of precordial lesions should include pleural diseases in the recess. Left anterior pericardiocentesis unavoidably violates the intervening recess, sometimes causing pleural effusion. C1 [Choi, Yo Won; Kim, Jinoo; Jeon, Seok Chol; Park, Choong Ki; Heo, Jeong-Nam] Hanyang Univ, Dept Radiol, Coll Med, Seoul 133792, South Korea. [Shepard, Jo-Anne O.] Massachusetts Gen Hosp, Div Thorac Radiol, Boston, MA 02114 USA. [Paik, Doo Jin] Hanyang Univ, Dept Anat & Cell Biol, Coll Med, Seoul 133792, South Korea. RP Choi, YW (reprint author), Hanyang Univ, Seoul Hosp, Dept Radiol, 17 Haengdang Dong, Seoul 133792, South Korea. EM ywchoi@hanyang.ac.kr OI Choi, Yo Won/0000-0003-0508-9430 FU Hanyang University [HY-2006-I] FX This work was supported by the research fund of Hanyang University (HY-2006-I). NR 20 TC 9 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD JAN-FEB PY 2011 VL 35 IS 1 BP 135 EP 140 DI 10.1097/RCT.0b013e3181f59099 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 708QB UT WOS:000286377900025 PM 21160431 ER PT J AU Fohn, L Dias-Santagata, D Su, Z Duke, M Vnencak-Jones, C Sosman, J Iafrate, A Pao, W AF Fohn, L. Dias-Santagata, D. Su, Z. Duke, M. Vnencak-Jones, C. Sosman, J. Iafrate, A. Pao, W. TI A RAPID SENSITIVE TEST FOR DETECTION OF 43 MUTATIONS WITH RELEVANCE TO TARGETED THERAPY IN MELANOMA SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Meeting Abstract C1 [Fohn, L.; Vnencak-Jones, C.; Sosman, J.; Pao, W.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Dias-Santagata, D.; Iafrate, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Su, Z.; Duke, M.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD JAN PY 2011 VL 38 IS 1 BP 86 EP 86 PG 1 WC Dermatology; Pathology SC Dermatology; Pathology GA 682AI UT WOS:000284367300038 ER PT J AU Sepehr, A Chao, E Mihm, M Tsao, H AF Sepehr, A. Chao, E. Mihm, M., Jr. Tsao, H. TI SPITZ-TYPE MELANOCYTIC TUMORS: A CLINICAL OUTCOME ANALYSIS SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Meeting Abstract C1 [Sepehr, A.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Sepehr, A.; Chao, E.] Harvard Univ, Sch Med, Boston, MA USA. [Mihm, M., Jr.; Tsao, H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD JAN PY 2011 VL 38 IS 1 BP 92 EP 92 PG 1 WC Dermatology; Pathology SC Dermatology; Pathology GA 682AI UT WOS:000284367300059 ER PT J AU Kaplan, J Frankenthaler, R Tahan, S Faulkner-Jones, B AF Kaplan, J. Frankenthaler, R. Tahan, S. Faulkner-Jones, B. TI MALIGNANT MELANOMA ARISING IN ASSOCIATION WITH A CELLULAR BLUE NEVUS SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Meeting Abstract C1 [Kaplan, J.; Frankenthaler, R.; Tahan, S.; Faulkner-Jones, B.] Beth Israel Deaconess Med Ctr Boston, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD JAN PY 2011 VL 38 IS 1 BP 114 EP 114 PG 1 WC Dermatology; Pathology SC Dermatology; Pathology GA 682AI UT WOS:000284367300147 ER PT J AU Gimbel, D Sohani, A Prasad, BSV Nazarian, R AF Gimbel, D. Sohani, A. Prasad, B. S. V. Nazarian, R. TI MODEL FOR TELEDERMATOPATHOLOGY IN AFRICA: FROM CONCEPT TO CONSULTATION SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Meeting Abstract C1 [Gimbel, D.; Sohani, A.; Nazarian, R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Prasad, B. S. V.] Aga Khan Hosp, Kisumu, Kenya. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD JAN PY 2011 VL 38 IS 1 BP 135 EP 135 PG 1 WC Dermatology; Pathology SC Dermatology; Pathology GA 682AI UT WOS:000284367300238 ER PT J AU Kaplan, J Cheng, C Piris, A Kroshinsky, D Sepehr, A AF Kaplan, J. Cheng, C. Piris, A. Kroshinsky, D. Sepehr, A. TI EMBRYONAL RHABDOMYOSARCOMA ARISING IN A CONGENITAL MELANOCYTIC NEVUS SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Meeting Abstract C1 [Kaplan, J.; Sepehr, A.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Cheng, C.] Harvard Univ, Sch Med, Boston, MA USA. [Piris, A.; Kroshinsky, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD JAN PY 2011 VL 38 IS 1 BP 135 EP 136 PG 2 WC Dermatology; Pathology SC Dermatology; Pathology GA 682AI UT WOS:000284367300241 ER PT J AU Dekker, JP Gimbel, D Piris, A AF Dekker, J. P. Gimbel, D. Piris, A. TI METASTATIC BASAL CELL CARCINOMA WITH EXTENSIVE PERINEURAL INFILTRATION SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Meeting Abstract C1 [Dekker, J. P.; Gimbel, D.; Piris, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD JAN PY 2011 VL 38 IS 1 BP 147 EP 148 PG 2 WC Dermatology; Pathology SC Dermatology; Pathology GA 682AI UT WOS:000284367300290 ER PT J AU Baker, G Oliva, E Hodin, R Duncan, L Wu, C Wu, R AF Baker, G. Oliva, E. Hodin, R. Duncan, Lyn Wu, C. Wu, R. TI SCAR METASTASIS OF ADRENOCORTICAL CARCINOMA SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Meeting Abstract C1 [Baker, G.; Oliva, E.; Hodin, R.; Duncan, Lyn; Wu, C.; Wu, R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD JAN PY 2011 VL 38 IS 1 BP 166 EP 166 PG 1 WC Dermatology; Pathology SC Dermatology; Pathology GA 682AI UT WOS:000284367300364 ER PT J AU Baran, J Hoang, M AF Baran, J. Hoang, M. TI NEUROTHEKEOMA OF THE PALM: AN UNUSUAL LOCATION SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Meeting Abstract C1 [Baran, J.; Hoang, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD JAN PY 2011 VL 38 IS 1 BP 166 EP 167 PG 2 WC Dermatology; Pathology SC Dermatology; Pathology GA 682AI UT WOS:000284367300367 ER PT J AU Chan, M Chan, M Sepehr, A AF Chan, M. Chan, M. Sepehr, A. TI ATYPICAL MIXED TUMORS OF THE DIGITS: REPORT OF TWO CASES SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Meeting Abstract C1 [Chan, M.; Chan, M.] Beth Israel Deaconess Med Ctr Boston, Boston, MA USA. [Sepehr, A.] Harvard Univ, Sch Med, Boston, MA USA. [Sepehr, A.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD JAN PY 2011 VL 38 IS 1 BP 173 EP 173 PG 1 WC Dermatology; Pathology SC Dermatology; Pathology GA 682AI UT WOS:000284367300392 ER PT J AU Jagdeo, J Kroshinsky, D AF Jagdeo, Jared Kroshinsky, Daniela TI A Case of Post-herpetic Itch Resolved With Gabapentin SO JOURNAL OF DRUGS IN DERMATOLOGY LA English DT Article ID HERPES-ZOSTER; UREMIC PRURITUS; PAIN; INFECTION; HYPNOSIS; PATIENT; SKIN AB Herpes zoster is a skin disease encountered commonly in dermatologic practice While post herpetic neuralgia (PHN) is a familiar side effect of this condition it is not the only neuropathic symptom that can result Post herpetic itch (PHI) is less well known but should be considered when evaluating a patient after an occurrence of zoster Gabapentin has been successfully used to treat cutaneous pain and pruritus in a variety of conditions The authors describe a case of PHI successfully treated with a course of gabapentin and propose that this agent be considered for use in patients who present with PHI C1 [Jagdeo, Jared] Suny Downstate Med Ctr, Dept Dermatol, Brooklyn, NY 11203 USA. [Kroshinsky, Daniela] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA USA. RP Jagdeo, J (reprint author), Suny Downstate Med Ctr, Dept Dermatol, 450 Clarkson Ave, Brooklyn, NY 11203 USA. NR 30 TC 6 Z9 6 U1 0 U2 4 PU JOURNAL OF DRUGS IN DERMATOLOGY PI NEW YORK PA 377 PARK AVE SOUTH, 6TH FLOOR, NEW YORK, NY 10016 USA SN 1545-9616 J9 J DRUGS DERMATOL JI J. Drugs Dermatol. PD JAN PY 2011 VL 10 IS 1 BP 85 EP 88 PG 4 WC Dermatology SC Dermatology GA 703CS UT WOS:000285952300015 PM 21197529 ER PT J AU Bernardy, NC Hamblen, JL Friedman, MJ Kivlahan, DR AF Bernardy, Nancy C. Hamblen, Jessica L. Friedman, Matthew J. Kivlahan, Daniel R. TI Co-occurring Posttraumatic Stress Disorder and Substance Use Disorder: Recommendations for Management and Implementation in the Department of Veterans Affairs SO JOURNAL OF DUAL DIAGNOSIS LA English DT Article DE co-occurring disorders; posttraumatic stress disorder; substance use disorder; implementation ID COCAINE-DEPENDENT INDIVIDUALS; INTEGRATING TOBACCO CESSATION; COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; NATIONAL COMORBIDITY SURVEY; VIETNAM COMBAT VETERANS; MENTAL-HEALTH PROBLEMS; ALCOHOL-USE DISORDERS; PRIMARY-CARE; SEEKING-SAFETY AB The recently revised Department of Veterans Affairs (VA) and Department of Defense Clinical Practice Guideline for the Management of Posttraumatic Stress Disorder (PTSD) offers guidance to treat co-occurring PTSD and substance use disorder. The release of the guideline occurred at a time of cultural shifts in recognizing and managing substance use disorders and when major changes were made in the VA to address co-occurring PTSD and substance use disorders. The release also coincided with an increasing number of veterans returning from the wars in Afghanistan and Iraq who were coming to the VA for PTSD treatment. A key augmentation in mental health staffing has brought many new clinicians to the VA and has made it more feasible to address the two disorders in a coordinated way. In this article the authors describe the recommendations in the revised 2010 PTSD clinical practice guideline to address co-occurring PTSD and substance use disorder, review the supporting research evidence behind the recommendations, and examine methods of new VA programs to address the two disorders. A description of what is working and where obstacles still exist is provided. The new recommendations have moved the field forward by offering clinical guidance to practitioners who are working with patients with the commonly observed co-occurring PTSD and substance use disorder. (Journal of Dual Diagnosis, 7:242-261, 2011) C1 [Bernardy, Nancy C.; Hamblen, Jessica L.; Friedman, Matthew J.] White River Junction VAMC, Natl Ctr PTSD, White River Jct, VT USA. [Bernardy, Nancy C.; Hamblen, Jessica L.; Friedman, Matthew J.] Dartmouth Med Sch, Dept Psychiat, Lebanon, NH USA. [Friedman, Matthew J.] Dartmouth Med Sch, Dept Pharmacol & Toxicol, Lebanon, NH USA. [Kivlahan, Daniel R.] VA Puget Sound Healthcare Syst, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA USA. [Kivlahan, Daniel R.] Univ Washington, Sch Med, Dept Psychiat, Seattle, WA USA. RP Bernardy, NC (reprint author), White River Junction Vet Affairs Med Ctr, Natl Ctr PTSD 116D, 215 N Main, White River Jct, VT 05009 USA. EM nancy.bernardy@va.gov NR 81 TC 4 Z9 4 U1 2 U2 8 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1550-4263 J9 J DUAL DIAGN JI J. Dual Diagn. PY 2011 VL 7 IS 4 SI SI BP 242 EP 261 DI 10.1080/15504263.2011.620446 PG 20 WC Psychology, Clinical; Substance Abuse; Psychiatry SC Psychology; Substance Abuse; Psychiatry GA 888MK UT WOS:000300007600005 ER PT J AU Kaysen, D Atkins, DC Moore, SA Lindgren, KP Dillworth, T Simpson, T AF Kaysen, Debra Atkins, David C. Moore, Sally A. Lindgren, Kristen P. Dillworth, Tiara Simpson, Tracy TI Alcohol Use, Problems, and the Course of Posttraumatic Stress Disorder: A Prospective Study of Female Crime Victims SO JOURNAL OF DUAL DIAGNOSIS LA English DT Article DE posttraumatic stress disorder; alcohol abuse; rape; crime victims; comorbidity ID NATIONAL COMORBIDITY SURVEY; RISK-FACTORS; SUBSTANCE USE; TRAUMA SURVIVORS; MENTAL-HEALTH; PTSD; SYMPTOMS; ASSAULT; WOMEN; DEPENDENCE AB Objective: In this study the authors examine whether alcohol use disorder status and consequences of drinking moderate the course of posttraumatic stress disorder (PTSD) over the first 6 months following trauma exposure in a sample of female victims of interpersonal violence. Methods: Female sexual and physical assault victims (N = 64) were recruited through police, hospital, and victim service agencies. Women completed structured clinical interviews and self-report measures within the first 5 weeks, 3 months, and 6 months post-trauma with 73% retention across all three time points (n = 47). Analyses were conducted using Hierarchical Linear Modeling using alcohol abuse/dependence, peak alcohol use, and consequences during the 30 days prior to assault as moderators of the course of PTSD over time. Results: Women with alcohol use disorder at baseline had lower initial PTSD symptoms but also less symptom recovery over time than women without alcohol use disorder. This pattern of results was also found for those with high negative drinking consequences during the month prior to the assault. Baseline alcohol use was not found to significantly moderate PTSD course over the 6 months. Conclusions: Findings suggest that negative consequences associated with alcohol use may be a risk factor for PTSD. Incorporating assessment of drinking problems for women presenting early post-trauma may be useful for identifying PTSD risk. (Journal of Dual Diagnosis, 7:262-279, 2011) C1 [Kaysen, Debra; Atkins, David C.; Moore, Sally A.; Lindgren, Kristen P.; Dillworth, Tiara; Simpson, Tracy] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Moore, Sally A.; Simpson, Tracy] VA Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr MIRECC, Seattle, WA USA. [Simpson, Tracy] VA Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ CESAT, Seattle, WA USA. RP Kaysen, D (reprint author), Univ Washington, Dept Psychiat & Behav Sci, 1100 NE 45th St,Suite 300,UW Box 354944, Seattle, WA 98195 USA. EM dkaysen@uw.edu OI Lindgren, Kristen/0000-0002-0244-1016; Atkins, David/0000-0002-5781-9880 FU NIAAA NIH HHS [F32 AA014728, F32 AA014728-03] NR 58 TC 11 Z9 11 U1 7 U2 15 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1550-4263 J9 J DUAL DIAGN JI J. Dual Diagn. PY 2011 VL 7 IS 4 SI SI BP 262 EP 279 DI 10.1080/15504263.2011.620449 PG 18 WC Psychology, Clinical; Substance Abuse; Psychiatry SC Psychology; Substance Abuse; Psychiatry GA 888MK UT WOS:000300007600006 PM 23538605 ER PT J AU Sethuraman, KN Duong, D Mehta, S Director, T Crawford, D George, JS Rathlev, NK AF Sethuraman, Kinjal N. Duong, David Mehta, Supriya Director, Tara Crawford, Darcey George, Jill St. Rathlev, Niels K. TI COMPLICATIONS OF TUBE THORACOSTOMY PLACEMENT IN THE EMERGENCY DEPARTMENT SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE thoracostomy; tube; chest trauma; pneumothorax; hemothorax ID TRAUMA AB Background: Emergency medicine residents frequently perform invasive procedures, including tube thoracostomy (TT), that inherently place patients at risk for complications. Objectives: The purpose of the study was to assess the prevalence and types of complications from TT in an academic emergency department (ED). Methods: A combined prospective and retrospective, observational study of all patients who had TT between December 2002 and January 2006 was performed. Exclusion criteria included age < 15 years and tube placement at an outside facility. Complications detected in the ED were defined as immediate, whereas those discovered later were defined as delayed. Complications requiring corrective surgical intervention, administration of blood products, or intravenous antibiotics were defined as major. Bivariate and multivariate analyses were used to identify operator and patient factors associated with complications. Results: TTs were placed in 242 patients, and 90 (37%; 95% confidence interval [CI] 31.1-43.3%) experienced a complication. Major complications included one intercostal artery laceration, one retroperitoneal placement, and empyema in 2 patients. In multivariate analysis, blunt injury excluding motor vehicle accidents (odds ratio [OR] 2.57; 95% CI 1.27-5.21) and spontaneous pneumothorax (OR 3.84; 95% CI 1.80-8.18) were associated with all complications. TT size < 36 French and blunt injury excluding motor vehicle accidents were associated with immediate complications and spontaneous pneumothorax was associated with delayed complications. Conclusions: The vast majority of complications from TT in the ED were minor. The prevalence of complications was consistent with previous reports of TTs placed by non-emergency-medicine-trained physicians outside the ED. The findings can be used to identify avoidable complications and improve residency training. (C) 2011 Elsevier Inc. C1 [Rathlev, Niels K.] Boston Univ, Sch Med, Dept Emergency Med, Med Ctr, Boston, MA 02118 USA. [Sethuraman, Kinjal N.] N Shore Univ Hosp, Med Ctr, Long Isl Jewish Med Ctr, Dept Emergency Med, New Hyde Pk, NY USA. [Mehta, Supriya] Univ Illinois Chicago Sch Publ Hlth, Dept Epidemiol & Biostat, Chicago, IL USA. [Director, Tara] St Vincents Med Ctr, Dept Emergency Med, New York, NY USA. [Crawford, Darcey] Gateway Med Ctr, Dept Emergency Med, Clarksville, TN USA. [George, Jill St.] Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. RP Rathlev, NK (reprint author), Boston Univ, Sch Med, Dept Emergency Med, Med Ctr, Dowling 1 S,1 Boston Med Ctr Pl, Boston, MA 02118 USA. OI Mehta, Supriya/0000-0002-7926-2489 NR 11 TC 15 Z9 17 U1 0 U2 1 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 JAN PY 2011 VL 40 IS 1 BP 14 EP 20 DI 10.1016/j.jemermed.2008.06.033 PG 7 WC Emergency Medicine SC Emergency Medicine GA 712CY UT WOS:000286643500003 PM 19097724 ER PT J AU Thomas, LE Binder, W Brown, DFM Nadel, ES AF Thomas, Lisa E. Binder, William Brown, David F. M. Nadel, Eric S. TI FEVER AND RASH IN A YOUNG MAN SO JOURNAL OF EMERGENCY MEDICINE LA English DT Editorial Material ID PRIMARY HIV-INFECTION; TREAT C1 [Thomas, Lisa E.; Nadel, Eric S.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Thomas, Lisa E.; Binder, William; Brown, David F. M.; Nadel, Eric S.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Nadel, ES (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. NR 14 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 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD JAN PY 2011 VL 40 IS 1 BP 58 EP 61 DI 10.1016/j.jemermed.2010.05.078 PG 4 WC Emergency Medicine SC Emergency Medicine GA 712CY UT WOS:000286643500012 PM 20947280 ER PT J AU Menconi, F Hasham, A Tomer, Y AF Menconi, F. Hasham, A. Tomer, Y. TI Environmental triggers of thyroiditis: Hepatitis C and interferon-alpha SO JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION LA English DT Review DE Autoimmunity; hepatitis C; infection; interferon; thyroiditis ID CHRONIC VIRAL-HEPATITIS; AUTOIMMUNE ENDOCRINE DISEASE; HUMAN THYROCYTE CULTURES; HCV CHRONIC HEPATITIS; IFN-ALPHA; GENETIC SUSCEPTIBILITY; VIRUS-INFECTION; GRAVES-DISEASE; I INTERFERONS; RISK-FACTOR AB Autoimmune thyroid diseases (AITD) are postulated to develop as a result of a complex interplay between several genetic and environmental influences. The pathogenesis of AITD is still not clearly defined. However, among the implicated triggers (e.g. iodine, infections, medications), more recent data confirmed strong associations of AITD with the hepatitis C virus (HCV) infection and interferon-alpha (IFN alpha) therapy. Moreover, it is likely that HCV and IFN act in synergism to trigger AITD in patients. Indeed, approximately 40% of HCV patients develop either clinical or subclinical disease while receiving IFN alpha. Interferon induced thyroiditis (IIT) can manifest as non-autoimmune thyroiditis (presenting as destructive thyroiditis, or non-autoimmune hypothyroidism), or autoimmune thyroiditis [presenting with clinical features of Graves' disease (GD) or Hashimoto's thyroiditis (HT)]. Although not yet clearly understood, it is thought that IFN alpha can induce thyroiditis via both immune stimulatory and direct toxic effects on the thyroid. In view of the high frequency of IIT, routine screening and surveillance of HCV patients receiving IFN alpha is recommended to avoid the complications, such as cardiac arrhythmias, associated with thyrotoxicosis. In summary, IIT is a common clinical problem that can be readily diagnosed with routine thyroid function screening of HCV patients receiving IFN. The treatment of IIT consists of the standard therapy for differing clinical manifestations of IIT such as GD, HT, or destructive thyroiditis. However, anti-thyroid medications are not recommended in this setting since they can potentially be hepatotoxic. (J. Endocrinol. Invest. 34: 78-84, 2011) (C)2011, Editrice Kurtis C1 [Menconi, F.; Hasham, A.] Mt Sinai Med Ctr, Dept Med, Div Endocrinol, New York, NY 10029 USA. [Tomer, Y.] James J Peters VA Med Ctr, New York, NY USA. RP Menconi, F (reprint author), Mt Sinai Med Ctr, Dept Med, Div Endocrinol, Box 1118,1 Gustave L Levy Pl, New York, NY 10029 USA. EM Francesca.Menconi@mssm.edu NR 78 TC 18 Z9 24 U1 0 U2 3 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 0391-4097 J9 J ENDOCRINOL INVEST JI J. Endocrinol. Invest. PD JAN PY 2011 VL 34 IS 1 BP 78 EP 84 DI 10.3275/7499 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 743OZ UT WOS:000289029500014 PM 21297381 ER PT J AU Akiba, Y Kaunitz, JD AF Akiba, Yasutada Kaunitz, Jonathan D. TI Duodenal chemosensing: Master control for epigastric sensation? SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Editorial Material ID FUNCTIONAL DYSPEPSIA; CARBONIC-ANHYDRASES; NONULCER DYSPEPSIA; ACID; SENSITIVITY; GENERATION; SECRETION; STOMACH; MUCOSA C1 Univ Calif Los Angeles, Dept Med, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90024 USA. Brentwood Biomed Res Inst, Los Angeles, CA USA. RP Akiba, Y (reprint author), W Los Angeles VA Med Ctr, Bldg 114,Room 217,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM yakiba@mednet.ucla.edu FU NIDDK NIH HHS [R01 DK54221, R01 DK054221] NR 20 TC 6 Z9 6 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0815-9319 J9 J GASTROEN HEPATOL JI J. Gastroenterol. Hepatol. PD JAN PY 2011 VL 26 IS 1 BP 6 EP 7 DI 10.1111/j.1440-1746.2010.06580.x PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 700SY UT WOS:000285765800004 PM 21073675 ER PT J AU Nadkarni, M Reddy, S Bates, CK Fosburgh, B Babbott, S Holmboe, E AF Nadkarni, Mohan Reddy, Siddharta Bates, Carol K. Fosburgh, Blair Babbott, Stewart Holmboe, Eric TI Ambulatory-Based Education in Internal Medicine: Current Organization and Implications for Transformation. Results of A National Survey of Resident Continuity Clinic Directors SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE clinic; resident education; ACGME; primary care ID PRIMARY-CARE; TASK-FORCE; QUALITY; SATISFACTION; PREPAREDNESS; SETTINGS; REFORM AB BACKGROUND: Many have called for ambulatory training redesign in internal medicine (IM) residencies to increase primary care career outcomes. Many believe dysfunctional, clinic environments are a key barrier to meaningful ambulatory education, but little is actually known about the educational milieu of continuity clinics nationwide. OBJECTIVE: We wished to describe the infrastructure and educational milieu at resident continuity clinics and assess clinic readiness to meet new IM-RRC requirements. DESIGN: National survey of ACGME accredited IM training programs. PARTICIPANTS: Directors of academic and community-based continuity clinics. RESULTS: Two hundred and twenty-one out of 365 (62%) of clinic directors representing 49% of training programs responded. Wide variation amongst continuity clinics in size, structure and educational organization exist. Clinics below the 25th percentile of total clinic sessions would not meet RRC-IM requirements for total number of clinic sessions. Only two thirds of clinics provided a longitudinal mentor. Forty-three percent of directors reported their trainees felt stressed in the clinic environment and 25% of clinic directors felt overwhelmed. LIMITATIONS: The survey used self reported data and was not anonymous. A slight predominance of larger clinics and university based clinics responded. Data may not reflect changes to programs made since 2008. CONCLUSIONS: This national survey demonstrates that the continuity clinic experience varies widely across IM programs, with many sites not yet meeting new ACGME requirements. The combination of disadvantaged and ill patients with inadequately resourced clinics, stressed residents, and clinic directors suggests that many sites need substantial reorganization and institutional commitment. New paradigms, encouraged by ACGME requirement changes such as increased separation of inpatient and outpatient duties are needed to improve the continuity clinic experience. C1 [Nadkarni, Mohan] Univ Virginia Hlth Syst UVAHS, Charlottesville, VA USA. [Reddy, Siddharta; Holmboe, Eric] Amer Board Internal Med, Philadelphia, PA USA. [Bates, Carol K.] Beth Israel Deaconess Med Ctr, Div Gen Internal Med & Primary Care, Boston, MA 02215 USA. [Fosburgh, Blair] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Babbott, Stewart] Univ Kansas, Kansas City, KS USA. RP Nadkarni, M (reprint author), Box 800744, Charlottesville, VA 22908 USA. EM mmn9y@virginia.edu FU American Board of Internal Medicine FX Funding for the survey and analysis provided by the American Board of Internal Medicine. Portions of this data were presented at the annual meeting of the Society of General Internal Medicine April 2008. NR 31 TC 19 Z9 19 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JAN PY 2011 VL 26 IS 1 BP 16 EP 20 DI 10.1007/s11606-010-1437-3 PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 708CJ UT WOS:000286338900011 PM 20628830 ER PT J AU Singh, H Esquivel, A Sittig, DF Murphy, D Kadiyala, H Schiesser, R Espadas, D Petersen, LA AF Singh, Hardeep Esquivel, Adol Sittig, Dean F. Murphy, Daniel Kadiyala, Himabindu Schiesser, Rachel Espadas, Donna Petersen, Laura A. TI Follow-up Actions on Electronic Referral Communication in a Multispecialty Outpatient Setting SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE referrals; primary care; sub-specialty care; electronic health records; patient safety; health information technology; communication; diagnostic errors; patient follow-up ID PRIMARY-CARE; INTERNAL-MEDICINE; CONSULTATIONS; SPECIALISTS; INTERFACE; SYSTEM; IMPACT AB OBJECTIVES: Electronic health records (EHR) enable transmission and tracking of referrals between primary-care practitioners (PCPs) and subspecialists. We used an EHR to examine follow-up actions on electronic referral communication in a large multispecialty VA facility. METHODS: We retrieved outpatient referrals to five subspecialties between October 2006 and December 2007, and queried the EHR to determine their status: completed, discontinued (returned to PCP), or unresolved (no action taken by subspecialist). All unresolved referrals, and random samples of discontinued and completed referrals were reviewed to determine whether subspecialists took follow-up actions (i.e., schedule appointments anytime in the future) within 30 days of referral-receipt. For referrals without timely follow-up, we determined whether inaction was supported by any predetermined justifiable reasons or associated with certain referral characteristics. We also reviewed if PCPs took the required action on returned information. RESULTS: Of 61,931 referrals, 22,535 were discontinued (36.4%), and 474 were unresolved (0.8%). We selected 412 discontinued referrals randomly for review. Of these, 52% lacked follow-up actions within 30 days. Appropriate justifications for inaction were documented in 69.8% (150/215) of those without action and included lack of prerequisite testing by the PCP and subspecialist opinion that no intervention was required despite referral. We estimated that at 30 days, 6.3% of all referrals were associated with an unexplained lack of follow-up actions by subspecialists. Conversely, 7.4% of discontinued referrals returned to PCPs were associated with an unexplained lack of follow-up. CONCLUSIONS: Although the EHR facilitates transmission of valuable information at the PCP-subspecialist interface, unexplained communication breakdowns in the referral process persist in a subset of cases. C1 [Singh, Hardeep; Esquivel, Adol; Murphy, Daniel; Espadas, Donna; Petersen, Laura A.] Michael E DeBakey VA Med Ctr, Houston VA HSR&D Ctr Excellence, Houston, TX USA. [Singh, Hardeep; Esquivel, Adol; Murphy, Daniel; Espadas, Donna; Petersen, Laura A.] Michael E DeBakey VA Med Ctr, Ctr Inquiry Improve Outpatient Safety Effect Elec, Houston, TX USA. [Singh, Hardeep; Esquivel, Adol; Murphy, Daniel; Espadas, Donna; Petersen, Laura A.] Sect Hlth Serv Res, Houston, TX USA. [Singh, Hardeep; Esquivel, Adol; Murphy, Daniel; Kadiyala, Himabindu; Schiesser, Rachel; Espadas, Donna; Petersen, Laura A.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Sittig, Dean F.] Univ Texas Houston, Sch Hlth Informat Sci, Houston, TX USA. [Sittig, Dean F.] UT Mem Hermann Ctr Healthcare Qual & Safety, Houston, TX USA. [Murphy, Daniel] Baylor Coll Med, Dept Family & Community Med, Houston, TX 77030 USA. RP Singh, H (reprint author), VA Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM hardeeps@bcm.tmc.edu RI Murphy, Daniel/G-5017-2013 OI Murphy, Daniel/0000-0002-2329-668X FU NIH [K23CA125585]; VA National Center of Patient Safety; Houston VA HSR&D Center of Excellence [HFP90-020] FX The study was supported by an NIH K23 career development award (K23CA125585) to Dr. Singh, the VA National Center of Patient Safety, and in part by the Houston VA HSR&D Center of Excellence (HFP90-020). NR 26 TC 22 Z9 22 U1 0 U2 6 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 JAN PY 2011 VL 26 IS 1 BP 64 EP 69 DI 10.1007/s11606-010-1501-z PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 708CJ UT WOS:000286338900019 PM 20848235 ER PT J AU Gordon, AJ Kunins, HV Rastegar, DA Tetrault, JM Walley, AY AF Gordon, Adam J. Kunins, Hillary V. Rastegar, Darius A. Tetrault, Jeanette M. Walley, Alexander Y. TI Update in Addiction Medicine for the Generalist SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE review; substance-related disorders; primary health care; primary care; alcoholism and addictive behavior; drug abuse; smoking cessation ID RANDOMIZED CONTROLLED-TRIAL; ALCOHOL-USE DISORDERS; IDENTIFICATION TEST AUDIT; BRIEF PHYSICIAN ADVICE; PRIMARY-CARE; BRIEF INTERVENTION; SCREENING-TEST; BEHAVIORAL-INTERVENTIONS; BUPRENORPHINE TREATMENT; PROBLEM DRINKING C1 [Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15206 USA. [Gordon, Adam J.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Kunins, Hillary V.] Albert Einstein Coll Med, New York, NY USA. [Kunins, Hillary V.] Montefiore Med Ctr, New York, NY USA. [Rastegar, Darius A.] Johns Hopkins Sch Med, Baltimore, MD USA. [Tetrault, Jeanette M.] Yale Univ, Sch Med, New Haven, CT USA. [Walley, Alexander Y.] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Gordon, AJ (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, 7180 Highland Dr 151-C-H, Pittsburgh, PA 15206 USA. EM adam.gordon@va.gov OI Walley, Alexander/0000-0002-8158-4882 NR 56 TC 4 Z9 4 U1 2 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JAN PY 2011 VL 26 IS 1 BP 77 EP 82 DI 10.1007/s11606-010-1461-3 PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 708CJ UT WOS:000286338900021 PM 20697971 ER PT J AU Halvorson, SAC Cedfeldt, AS Hunter, AJ AF Halvorson, Stephanie A. C. Cedfeldt, Andrea S. Hunter, Alan J. TI Fulminant, Non-antibiotic Associated Clostridium difficile Colitis Following Salmonella Gastroenteritis SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE Clostridium difficile; Salmonella; community-acquired infections ID INFECTION; DISEASE; COMMUNITY; DIARRHEA; RISK; VANCOMYCIN; PATTERNS AB In the last decade there has been increasing awareness of the virulence and changing epidemiology of Clostridium difficile (C. difficile). While the vast majority of clinical cases of C. difficile are associated with antimicrobial or nosocomial exposure, this syndrome has been well described in the absence of antibiotic use. We present an unusual case of fatal, non-antibiotic associated C. difficile colitis following Salmonella serotype Saintpaul gastroenteritis in a previously healthy young person. We review the typical risk factors for C. difficile colitis and fulminant disease. We also review the epidemiology of community-acquired C. difficile-associated disease (CA-CDAD) and highlight Salmonella infection as a potential risk factor for development of CA-CDAD. C1 [Halvorson, Stephanie A. C.; Cedfeldt, Andrea S.; Hunter, Alan J.] Oregon Hlth & Sci Univ, Dept Med, Div Hosp Med, Portland, OR 97239 USA. [Cedfeldt, Andrea S.] Portland VA Med Ctr, Sect Hosp & Subspecialty Med, Portland, OR USA. RP Halvorson, SAC (reprint author), Oregon Hlth & Sci Univ, Dept Med, Div Hosp Med, 3181 SW Sam Jackson Pk Rd,BTE 119, Portland, OR 97239 USA. EM halvorss@ohsu.edu NR 20 TC 2 Z9 2 U1 1 U2 1 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 JAN PY 2011 VL 26 IS 1 BP 95 EP 97 DI 10.1007/s11606-010-1466-y PG 3 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 708CJ UT WOS:000286338900025 PM 20697966 ER PT J AU Wakeman, SE AF Wakeman, Sarah E. TI Final Moments SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Charlestown, Charlestown, MA 02129 USA. RP Wakeman, SE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Charlestown, 73 High St, Charlestown, MA 02129 USA. EM swakeman@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JAN PY 2011 VL 26 IS 1 BP 98 EP 98 DI 10.1007/s11606-010-1459-x PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 708CJ UT WOS:000286338900026 PM 20697972 ER PT J AU Soong, M van Leerdam, R Guitton, TG Got, C Katarincic, J Ring, D AF Soong, Maximillian van Leerdam, Roderick Guitton, Thierry G. Got, Christopher Katarincic, Julia Ring, David TI Fracture of the Distal Radius: Risk Factors for Complications After Locked Volar Plate Fixation SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Complications; distal radius fracture; volar plate ID PROSPECTIVE RANDOMIZED-TRIAL; INTERNAL-FIXATION AB Purpose To identify risk factors for complications after volar locking plate fixation of distal radius fractures. Methods We assessed early postoperative complications in 594 patients with fracture of the distal radius repaired with a volar locking plate and a minimum 1-month evaluation in the medical record. Later complications were assessed among 321 patients as a subset of the original cohort with a minimum 6 months' evaluation. We compared patient demographics, fracture characteristics, and aspects of management between patients with and without complications in bivariate analysis. Multivariable logistic regression analysis was applied to identify the factors independently associated with complications. Results A total of 47 complications were documented in the medical record. Early complications occurred in 24 of 594, including 8 intra-articular screws and 7 patients with loss of fixation. Late complications occurred in 23 of 321, including 14 patients diagnosed with tendon irritation (one rupture of the flexor pollicis longus tendon) and 5 patients who had subsequent surgery to address dysfunction of the distal radioulnar joint (malunion, synostosis, and arthrofibrosis). Of the 47 complications, 26 were attributed to the plate, of which 9 were considered major (intra-articular screws and tendon rupture; 1.3% (8 out of 594) and less than 1% (1 out of 321) of the early and late groups, respectively). In the logistic regression models, fall from a height and an ipsilateral elbow injury were positive independent predictors of early complications, whereas high-volume surgeons and plates other than the most commonly used plate were positive independent predictors of later complications. Conclusions Volar locking plate fixation of distal radius fractures was associated with relatively few plate-related complications in our institutions. Factors indicating higher energy or complexity predicted early complications. The most common late complication was tendon irritation, which is less discrete and perhaps variably diagnosed. Further study is warranted regarding plate design and familiarity, which may help reduce complications. (J Hand Surg 2011;36A:3-9. (C) 2011 Published by Elsevier Inc. on behalf of the American Society for Surgery of the Hand.) C1 [Ring, David] Massachusetts Gen Hosp, Dept Orthopaed Surg, Yawkey Ctr, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. Lahey Clin Fdn, Dept Orthopaed Surg, Burlington, MA USA. Rhode Isl Hosp, Dept Orthopaed Surg, Providence, RI USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Yawkey Ctr, Orthopaed Hand & Upper Extrem Serv, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org OI Guitton, Thierry/0000-0002-2599-1985; Soong, Maximillian/0000-0003-0333-8181 NR 10 TC 38 Z9 40 U1 0 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD JAN PY 2011 VL 36A IS 1 BP 3 EP 9 DI 10.1016/j.jhsa.2010.09.033 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 704YH UT WOS:000286091200002 PM 21193123 ER PT J AU Wiggers, JK Ring, D AF Wiggers, Jimme K. Ring, David TI Osteonecrosis After Open Reduction and Internal Fixation of a Bicolumnar Fracture of the Distal Humerus: A Report of Four Cases SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Distal humerus fracture; avascular necrosis; arthrosis ID AVASCULAR NECROSIS; ADULT ELBOW; CAPITELLUM AB Four cases with osteonecrosis of the trochlea after open reduction and internal fixation of a fracture involving both the medial and lateral columns of the distal humerus above the base of the olecranon fossa (a bicolumnar fracture of the distal humerus) are reported to bring attention to this complication. (J Hand Surg 2011;36A:89-93. (C) 2011 Published by Elsevier Inc. on behalf of the American Society for Surgery of the Hand.) C1 [Ring, David] Massachusetts Gen Hosp, Yawkee Ctr, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Yawkee Ctr, Orthopaed Hand & Upper Extrem Serv, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org FU Acumed; Biomet; Tornier; Wright Medical Technology, Incorporated FX D.R. has a financial involvement with Acumed, Biomet, Tornier, and Wright Medical Technology, Incorporated. NR 14 TC 1 Z9 1 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD JAN PY 2011 VL 36A IS 1 BP 89 EP 93 DI 10.1016/j.jhsa.2010.09.001 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 704YH UT WOS:000286091200015 PM 21115299 ER PT J AU Matthews, PB Jhun, CS Yaung, S Azadani, AN Guccione, JM Ge, LA Tseng, EE AF Matthews, Peter B. Jhun, Choon-Sik Yaung, Stephanie Azadani, Ali N. Guccione, Julius M. Ge, Liang Tseng, Elaine E. TI Finite Element Modeling of the Pulmonary Autograft at Systemic Pressure before Remodeling SO JOURNAL OF HEART VALVE DISEASE LA English DT Article ID ROSS PROCEDURE; AORTIC ROOT; PORCINE PULMONARY; VALVE; OPERATION; REPLACEMENT; DILATION; REOPERATIONS; DILATATION; ANEURYSM AB Background and aim of the study: Pulmonary autograft dilatation requiring reoperation is an Achilles' heel of the Ross procedure, as exposure to systemic pressure increases autograft wall stress, which may in turn lead to tissue remodeling and aneurysmal pathology. However, the magnitude of autograft wall stress with the Ross procedure is unknown. The study aim was to develop a realistic finite element (FE) model of the autograft, and to perform simulations at systemic pressure to determine wall stress distribution immediately after the Ross operation. Methods: The porcine pulmonary root geometry was generated from high-resolution microcomputed tomography (microCT) images to create a mesh composed of hexahedral elements. Previously defined constitutive equations were used to describe the regional material properties of the native porcine pulmonary root. The anterior and posterior pulmonary arteries, and each of the pulmonary sinuses, were best described by non-linear, anisotropic Fung strain energy functions, and input individually into the model. Autograft dilatation and wall stress distribution during pulmonary and systemic loading prior to remodeling were determined using explicit FE analysis in LS-DYNA. Results: The autograft was highly compliant in the low-strain region, and the majority of dilation occurred with <30 mmHg of pressurization. During pulmonic loading, a typical inflation/deflation was observed between systole and diastole, but the autograft remained almost completely dilated throughout the cardiac cycle at systemic pressure. Although the systolic blood pressure was 380% greater in the aortic than in the pulmonary position, the peak systolic diameter was increased by only 28%. The maximum principal wall stress increased approximately 10-fold during systole and 25-fold during diastole, and was greater in the sinus than the distal artery for all simulations. Conclusion: Under systemic loading conditions, the pulmonary autograft remained fully dilated and experienced large wall stresses concentrated in the sinus. The future correlation of this model with explanted autografts may lead to an improved understanding of tissue remodeling following the Ross procedure. C1 [Tseng, Elaine E.] UCSF, Med Ctr, Div Cardiothorac Surg, Dept Surg, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA USA. RP Tseng, EE (reprint author), UCSF, Med Ctr, Div Cardiothorac Surg, Dept Surg, 500 Parnassus Ave,Suite W405,Box 0118, San Francisco, CA 94143 USA. EM elaine.tseng@ucsfmedctr.org FU American Heart Association; Northern the California Institute for Research and Education FX These studies were supported by the American Heart Association and Northern the California Institute for Research and Education. The authors have no financial conflicts of interest to disclose. NR 34 TC 5 Z9 5 U1 2 U2 2 PU I C R PUBLISHERS PI NORTHWOOD PA CRISPIN HOUSE, 12/A SOUTH APPROACH, MOOR PARK, NORTHWOOD HA6 2ET, ENGLAND SN 0966-8519 J9 J HEART VALVE DIS JI J. Heart Valve Dis. PD JAN PY 2011 VL 20 IS 1 BP 45 EP 52 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 720GC UT WOS:000287267700008 PM 21404897 ER PT J AU Dalal, AK Poon, EG Karson, AS Gandhi, TK Roy, CL AF Dalal, Anuj K. Poon, Eric G. Karson, Andrew S. Gandhi, Tejal K. Roy, Christopher L. TI Lessons Learned From Implementation of a Computerized Application for Pending Tests at Hospital Discharge SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article DE communication; continuity of care transition and discharge planning; electronic medical record; information technology; patient safety ID RESULTS MANAGEMENT; PATIENT SAFETY; CARE; SYSTEM; COMMUNICATION; PRINCIPLES; IMPACT AB BACKGROUND: Patients are often discharged from the hospital before test results are finalized. Awareness of these results is poor and therefore an important patient safety concern. Few computerized systems have been deployed at care transitions to address this problem. We describe an attempt to implement a computerized application to help inpatient physicians manage these test results. METHODS: We modified an ambulatory electronic medical record (EMR)-based results management application to track pending tests at hospital discharge (Hospitalist Results Manager, HRM). We trained inpatient physicians at 2 academic medical centers to track these tests using this application. We surveyed inpatient physicians regarding usage of and satisfaction with the application, barriers to use, and the characteristics of an ideal system to track pending tests at discharge. RESULTS: Of 29 survey respondents, 14 (48%) reported never using HRM, and 13 (45%) used it 1 to 2 times per week. A total of 23 (79%) reported barriers prohibiting use, including being inundated with clinically "irrelevant" results, not having sufficient time, and a lack of integration of post-discharge test result management into usual workflow. Twenty-one (72%) wanted to receive notification of abnormal and clinician-designated pending test results. Twenty-seven physicians (93%) agreed that an ideally designed computerized application would be valuable for managing pending tests at discharge. CONCLUSIONS: Although inpatient physicians would highly value a computerized application to manage pending tests at discharge, the characteristics of an ideal system are unclear and there are important barriers prohibiting adoption and optimal usage of such systems. We outline suggestions for future electronic systems to manage pending tests at discharge. Journal of Hospital Medicine 2011;6:16-21. (C) 2010 Society of Hospital Medicine. C1 [Dalal, Anuj K.] Brigham & Womens Hosp, BWH Acad Hospitalist Serv, Div Gen Med & Primary Care, Boston, MA 02115 USA. [Karson, Andrew S.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Dalal, AK (reprint author), Brigham & Womens Hosp, BWH Acad Hospitalist Serv, Div Gen Med & Primary Care, 15 Francis St, Boston, MA 02115 USA. EM adalal1@partners.org FU Harvard Risk Management Foundation, Cambridge, MA FX This study was funded by a grant from the Harvard Risk Management Foundation, Cambridge, MA. NR 16 TC 16 Z9 16 U1 1 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1553-5592 J9 J HOSP MED JI J. Hosp. Med. PD JAN PY 2011 VL 6 IS 1 BP 16 EP 21 DI 10.1002/jhm.794 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 710AU UT WOS:000286483800005 PM 21241037 ER PT J AU Dinescu, A Fernandez, H Ross, JS Karani, R AF Dinescu, Anca Fernandez, Helen Ross, Joseph S. Karani, Reena TI Audit and Feedback: An Intervention to Improve Discharge Summary Completion SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article DE continuity of care transition and discharge planning; geriatric patient; practice-based learning and improvement ID PRIMARY-CARE PHYSICIANS; GENERAL-PRACTITIONERS; COMMUNICATION; QUALITY; INFORMATION; CONTINUITY; ATTITUDES; HEALTH; IMPACT AB Discharge summaries (DS) communicate important clinical information from inpatient to outpatient settings. Previous studies noted increased adverse events and rehospitalization due to poor DS quality. We postulated that an audit and feedback intervention of DS completed by geriatric medicine fellows would improve the completeness of their summaries. We conducted a preintervention post intervention study. In phase 1 (AUDIT #1 and FEEDBACK) we scored all DS (n = 89) completed by first year fellows between July 2006 to December 2006 using a 21-item checklist. Individual performance scores were reviewed with each fellow in 30-minute feedback sessions. In phase 2 (AUDIT #2) we scored all DS (n = 79) completed after the first phase between February 2007 to July 2007 using the same checklist. Data were analyzed using generalized estimating equations. Fellows were more likely to complete all required DS data after feedback when compared with prior to feedback (91% vs. 71%, P < 0.001). Feedback was also associated with improved admission (93% vs. 70%, P < 0.001), duration of hospitalization (93% vs 78%, P < 0.001), discharge planning (93% vs. 18%, P < 0.02) and postdischarge care (83% vs. 57%., P < 0.001) section-specific information. In conclusion, audit and feedback sessions were associated with better DS completeness in areas of particular importance to geriatric care. Journal of Hospital Medicine 2011;6:28-32. (C) 2011 Society of Hospital Medicine. C1 [Dinescu, Anca; Fernandez, Helen; Ross, Joseph S.; Karani, Reena] Mt Sinai Sch Med, Brookdale Dept Geriatr & Palliat Med, New York, NY USA. [Ross, Joseph S.] James J Peters VA Med Ctr, Bronx, NY USA. [Dinescu, Anca; Fernandez, Helen; Ross, Joseph S.; Karani, Reena] Mt Sinai Sch Med, Samuel M Bronfman Dept Med, New York, NY USA. RP Dinescu, A (reprint author), 1 Gustave L Levy Pl,Box 1070, New York, NY 10029 USA. EM anca.dinescu@mssm.edu FU NIA NIH HHS [K08 AG032886, K08 AG032886-03] NR 18 TC 10 Z9 10 U1 0 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1553-5592 J9 J HOSP MED JI J. Hosp. Med. PD JAN PY 2011 VL 6 IS 1 BP 28 EP 32 DI 10.1002/jhm.831 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 710AU UT WOS:000286483800007 PM 21241038 ER PT J AU Fiorina, P Jurewicz, M Vergani, A Petrelli, A Carvello, M D'Addio, F Godwin, JG Law, K Wu, EX Tian, Z Thoma, G Kovarik, J La Rosa, S Capella, C Rodig, S Zerwes, HG Sayegh, MH Abdi, R AF Fiorina, Paolo Jurewicz, Mollie Vergani, Andrea Petrelli, Alessandra Carvello, Michele D'Addio, Francesca Godwin, Jonathan G. Law, Kenneth Wu, Erxi Tian, Ze Thoma, Gebhard Kovarik, Jiri La Rosa, Stefano Capella, Carlo Rodig, Scott Zerwes, Hans-Guenter Sayegh, Mohamed H. Abdi, Reza TI Targeting the CXCR4-CXCL12 Axis Mobilizes Autologous Hematopoietic Stem Cells and Prolongs Islet Allograft Survival via Programmed Death Ligand 1 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RESPONSES IN-VIVO; BONE-MARROW; PROGENITOR CELLS; DENDRITIC CELLS; RENAL-TRANSPLANTATION; TOLERANCE INDUCTION; SYSTEMIC-SCLEROSIS; C-KIT; DONOR; GENERATION AB Antagonism of CXCR4 disrupts the interaction between the CXCR4 receptor on hematopoietic stem cells (HSCs) and the CXCL12 expressed by stromal cells in the bone marrow, which subsequently results in the shedding of HSCs to the periphery. Because of their profound immunomodulatory effects, HSCs have emerged as a promising therapeutic strategy for autoimmune disorders. We sought to investigate the immunomodulatory role of mobilized autologous HSCs, via target of the CXCR4-CXL12 axis, to promote engraftment of islet cell transplantation. Islets from BALB/c mice were transplanted beneath the kidney capsule of hyperglycemic C57BL/6 mice, and treatment of recipients with CXCR4 antagonist resulted in mobilization of HSCs and in prolongation of islet graft survival. Addition of rapamycin to anti-CXCR4 therapy further promoted HSC mobilization and islet allograft survival, inducing a robust and transferable host hyporesponsiveness, while administration of an ACK2 (anti-CD117) mAb halted CXCR4 antagonist-mediated HSC release and restored allograft rejection. Mobilized HSCs were shown to express high levels of the negative costimulatory molecule programmed death ligand 1 (PD-L1), and HSCs extracted from wild-type mice, but not from PD-L1 knockout mice, suppressed the in vitro alloimmune response. Moreover, HSC mobilization in PD-L1 knockout mice failed to prolong islet allograft survival. Targeting the CXCR4-CXCL12 axis thus mobilizes autologous HSCs and promotes long-term survival of islet allografts via a PD-L1-mediated mechanism. The Journal of Immunology, 2011, 186: 121-131. C1 [Fiorina, Paolo; Jurewicz, Mollie; Vergani, Andrea; Petrelli, Alessandra; D'Addio, Francesca; Godwin, Jonathan G.; Sayegh, Mohamed H.; Abdi, Reza] Harvard Univ, Sch Med, Transplantat Res Ctr, Childrens Hosp, Boston, MA 02115 USA. [Law, Kenneth; Rodig, Scott] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Hematopathol,Dept Pathol, Boston, MA 02115 USA. [Carvello, Michele] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wu, Erxi; Tian, Ze] MIT, Harvard Mit Div Hlth Sci & Technol, Childrens Hosp, Informat Program, Cambridge, MA 02139 USA. [Fiorina, Paolo; Vergani, Andrea; Petrelli, Alessandra; D'Addio, Francesca] Ist Sci San Raffaele, I-20132 Milan, Italy. [Wu, Erxi; Tian, Ze] N Dakota State Univ, Dept Pharmaceut Sci, Fargo, ND 58102 USA. [Thoma, Gebhard; Kovarik, Jiri; Zerwes, Hans-Guenter] Novartis Inst Biomed Res, Basel, Switzerland. [La Rosa, Stefano; Capella, Carlo] Univ Insubria, Dept Human Morphol, Varese, Italy. RP Fiorina, P (reprint author), Harvard Univ, Sch Med, Transplantat Res Ctr, Childrens Hosp, 221 Longwood Ave, Boston, MA 02115 USA. EM paolo.fiorina@childrens.harvard.edu; rabdi@rics.bwh.harvard.edu RI Petrelli, Alessandra/B-7972-2011; Petrelli, Alessandra/M-7004-2015; D'Addio, Francesca/F-3417-2017 OI Petrelli, Alessandra/0000-0002-5639-9415; D'Addio, Francesca/0000-0002-0345-0694 FU Juvenile Diabetes Research Foundation; American Society of Nephrology; American Society of Transplantation/Juvenile Diabetes Research Foundation; Boston Area Diabetes Endocrinology Research Center [5P30DK57521]; Juvenile Diabetes Research Foundation [4-2007-1065]; National Institutes of Health [P01 AI041521, R01 AI070820, R01 AI051559, P01 AI056299] FX This work was supported by an American Society of Transplantation/Juvenile Diabetes Research Foundation Faculty grant, a Juvenile Diabetes Research Foundation Career Development award, and an American Society of Nephrology Career Development award (all to P. F.). A. V. is the recipient of an American Society of Transplantation/Juvenile Diabetes Research Foundation Fellowship grant. P. F. received support from a pilot and feasibility award from the Boston Area Diabetes Endocrinology Research Center (5P30DK57521). This work also was supported by Juvenile Diabetes Research Foundation Grant 4-2007-1065, a Juvenile Diabetes Research Foundation regular grant (to R. A.) and National Institutes of Health Grants P01 AI041521, R01 AI070820, R01 AI051559, and P01 AI056299 (to M. H. S.). NR 47 TC 35 Z9 38 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN PY 2011 VL 186 IS 1 BP 121 EP 131 DI 10.4049/jimmunol.1000799 PG 11 WC Immunology SC Immunology GA 699UP UT WOS:000285688700019 PM 21131428 ER PT J AU Leu, SW Shi, LY Xu, CQ Zhao, YL Liu, BL Li, YQ Shiedlin, A Xiang, C Shen, HH Quinn, DA Hales, CA Zhao, H AF Leu, Shaw-Wei Shi, Liyun Xu, Changqing Zhao, Yili Liu, Baoling Li, Yongqing Shiedlin, Aviva Xiang, Charlie Shen, Huahao Quinn, Deborah A. Hales, Charles A. Zhao, Hang TI TLR4 through IFN-beta Promotes Low Molecular Mass Hyaluronan-Induced Neutrophil Apoptosis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ACUTE LUNG INJURY; RESPIRATORY-DISTRESS-SYNDROME; NECROSIS-FACTOR-ALPHA; TOLL-LIKE RECEPTORS; SOLUBLE FAS LIGAND; IN-VIVO; INTERFERON-BETA; INFLAMMATION; EXPRESSION; CELLS AB Intratracheal administration of low molecular mass (LMM) hyaluronan (200 kDa) results in greater neutrophil infiltration in the lungs of TLR4(-/-) mice compared with that in wild-type mice. In general, enhanced neutrophil infiltration in tissue is due to cell influx; however, neutrophil apoptosis also plays an important role. We have assessed the effects of TLR4 in the regulation of neutrophil apoptosis in response to administration of LMM hyaluronan. We found that apoptosis of inflammatory neutrophils is impaired in TLR4(-/-) mice, an effect that depends upon the IFN-beta-mediated TRAIL/TRAILR system. IFN-beta levels were decreased in LMM hyaluronan-treated TLR4-deficient neutrophils. The treatment of inflammatory neutrophils with IFN-beta enhanced the levels of TRAIL and TRAILR 2. LMM hyaluronan-induced inflammatory neutrophil apoptosis was substantially prevented by anti-TRAIL neutralizing mAb. We conclude that decreased IFN-beta levels decrease the activity of the TRAIL/TRAILR system in TLR4-deficient neutrophils, leading to impaired apoptosis of neutrophils and resulting in abnormal accumulation of neutrophils in the lungs of LMM hyaluronan-treated mice. Thus, TLR4 plays a novel homeostatic role in noninfectious lung inflammation by accelerating the elimination of inflammatory neutrophils. The Journal of Immunology, 2011, 186: 556-562. C1 [Leu, Shaw-Wei; Shi, Liyun; Quinn, Deborah A.; Hales, Charles A.; Zhao, Hang] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Zhao, Yili; Liu, Baoling; Li, Yongqing] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Dept Surg, Boston, MA 02114 USA. [Leu, Shaw-Wei; Shi, Liyun; Zhao, Yili; Liu, Baoling; Li, Yongqing; Quinn, Deborah A.; Hales, Charles A.; Zhao, Hang] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Leu, Shaw-Wei] Chang Gung Mem Hosp, Div Pulm & Crit Care Med, Chiayi, Taiwan. [Shi, Liyun] Hangzhou Normal Univ, Dept Immunol, Hangzhou, Zhejiang, Peoples R China. [Xu, Changqing; Zhao, Hang] Hangzhou Normal Univ, Dept Resp Med, Affiliated Hosp, Sch Med, Hangzhou, Zhejiang, Peoples R China. [Shiedlin, Aviva] Genzyme Corp, Framingham, MA 01701 USA. [Xiang, Charlie] Zhejiang Univ, Sch Med, Affiliated Hosp 1, State Key Lab Diag & Treatment Infect Dis, Hangzhou 310003, Zhejiang, Peoples R China. [Shen, Huahao] Zhejiang Univ, Sch Med, Hosp 2, Dept Resp Med, Hangzhou 310003, Zhejiang, Peoples R China. [Shen, Huahao] Zhejiang Univ, Inst Resp Dis, Hangzhou 310003, Zhejiang, Peoples R China. RP Zhao, H (reprint author), Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Bulfinch 148,55 Fruit St, Boston, MA 02114 USA. EM hzhao5@partners.org FU Genzyme Corporation [HL007874, HL039150]; Susannah Wood Fund FX This work was supported by Grants HL007874 and HL039150, an unrestricted grant from the Genzyme Corporation, and by the Susannah Wood Fund. NR 39 TC 14 Z9 14 U1 1 U2 8 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN PY 2011 VL 186 IS 1 BP 556 EP 562 DI 10.4049/jimmunol.1001630 PG 7 WC Immunology SC Immunology GA 699UP UT WOS:000285688700063 PM 21098223 ER PT J AU Hirsch, MS AF Hirsch, Martin S. TI A New Publisher for The Journal of Infectious Diseases SO JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material C1 Massachusetts Gen Hosp, Div Infect Dis, Cambridge, MA 02139 USA. RP Hirsch, MS (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 65 Landsdowne St,Rm 419, Cambridge, MA 02139 USA. EM mshirsch@partners.org NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD JAN 1 PY 2011 VL 203 IS 1 BP 1 EP 2 DI 10.1093/infdis/jiq011 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 699QI UT WOS:000285677500001 PM 21148488 ER PT J AU Wang, LJ Trebicka, E Fu, Y Waggoner, L Akira, S Fitzgerald, KA Kagan, JC Cherayil, BJ AF Wang, Lijian Trebicka, Estela Fu, Ying Waggoner, Lisa Akira, Shizuo Fitzgerald, Katherine A. Kagan, Jonathan C. Cherayil, Bobby J. TI Regulation of Lipopolysaccharide-Induced Translation of Tumor Necrosis Factor-Alpha by the Toll-Like Receptor 4 Adaptor Protein TRAM SO JOURNAL OF INNATE IMMUNITY LA English DT Review DE Macrophage; Lipopolysaccharide; Toll-like receptor; Inflammation; Signal transduction ID PATTERN-RECOGNITION RECEPTORS; ENTERICA SEROVAR TYPHIMURIUM; HEREDITARY HEMOCHROMATOSIS; SIGNALING PATHWAY; INTERFERON-BETA; TOLL-LIKE-RECEPTOR-4; BIOSYNTHESIS; MOLECULE; TRIF; INFLAMMATION AB Lipopolysaccharide (LPS)-induced production of tumor necrosis factor (TNF)-alpha requires the recruitment of two pairs of adaptors to the Toll-like receptor 4 cytoplasmic domain. The contribution of one pair - Toll-interleukin-1 receptor domain-containing adaptor inducing interferon-beta (TRIF) and TRIF-related adaptor molecule (TRAM)-to TNF-alpha expression is not well understood. To clarify this issue, we studied TRAM knockout bone marrow-derived macrophages (BMDM). LPS-stimulated TRAM-deficient BMDM had decreased TNF-alpha protein expression even at times when TNF-alpha mRNA levels were normal, suggesting impaired translation. Consistent with this idea, knockdown of TRAM in RAW264.7 macrophages decreased translation of a reporter controlled by the TNF-alpha 3' untranslated region, while transfection of TRAM in HEK293T cells increased translation of this reporter. Also consistent with a role for TRAM in TNF-alpha translation, LPS-induced activation of MK2, a kinase involved in this process, was impaired in TRAM-deficient BMDM. TRIF did not increase translation of the TNF-alpha 3' untranslated region reporter when expressed in HEK293T cells. However, BMDM that lacked functional TRIF produced reduced levels of TNF-alpha protein in response to LPS despite normal amounts of the mRNA. Unlike BMDM, LPS-stimulated TRAM-deficient peritoneal macrophages displayed equivalent reductions in TNF-alpha protein and mRNA. Our results indicate that TRAM- and TRIF-dependent signals have a previously unappreciated, cell type-specific role in regulating TNF-alpha translation. Copyright (C) 2011 S. Karger AG, Basel C1 [Cherayil, Bobby J.] Massachusetts Gen Hosp, Pediat Gastroenterol Unit, Div Pediat Gastroenterol, Mucosal Immunol Lab, Charlestown, MA 02129 USA. [Kagan, Jonathan C.; Cherayil, Bobby J.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Kagan, Jonathan C.] Childrens Hosp, Div Gastroenterol, Boston, MA 02115 USA. [Waggoner, Lisa; Fitzgerald, Katherine A.] Univ Massachusetts, Sch Med, Dept Med, Div Infect Dis & Immunol, Worcester, MA USA. [Akira, Shizuo] Osaka Univ, Host Def Lab, WPI Immunol Frontier Res Ctr, Osaka, Japan. RP Cherayil, BJ (reprint author), Massachusetts Gen Hosp, Pediat Gastroenterol Unit, Div Pediat Gastroenterol, Mucosal Immunol Lab, Bldg 114,16th St, Charlestown, MA 02129 USA. EM cherayil@helix.mgh.harvard.edu RI Fu, Ying/G-2899-2015 FU Broad Medical Research Program [IBD-0253]; National Institute of Allergy and Infectious Diseases [R56AI089700]; Wyeth Nutrition; National Institutes of Health [R01AI067497, 5R00AI072955] FX This work was supported by grants from the Broad Medical Research Program (IBD-0253) and the National Institute of Allergy and Infectious Diseases (R56AI089700) to B.J.C., by an unrestricted educational grant from Wyeth Nutrition to L. Wang, and by National Institutes of Health award number R01AI067497 to K.A.F. and 5R00AI072955 to J.C.K. We are very grateful to Dr. Shobha Vasudevan and Dr. Joan Steitz of Yale University for kindly providing the luciferase reporter constructs used in this study. NR 32 TC 9 Z9 10 U1 1 U2 8 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1662-811X J9 J INNATE IMMUN JI J. Innate Immun. PY 2011 VL 3 IS 5 BP 437 EP 446 DI 10.1159/000324833 PG 10 WC Immunology SC Immunology GA 816BA UT WOS:000294572500002 PM 21494017 ER PT J AU Lajous, M Mozaffarian, D Mozaffarian, R Schrag, D Adami, HO AF Lajous, M. Mozaffarian, D. Mozaffarian, R. Schrag, D. Adami, H. -O. TI Lifestyle prescriptions for cancer survivors and their communities SO JOURNAL OF INTERNAL MEDICINE LA English DT Article ID CORONARY-HEART-DISEASE; CARDIOVASCULAR-DISEASE; PHYSICAL-ACTIVITY; SCIENTIFIC STATEMENT; RISK; PREVENTION; MORTALITY; HEALTH; METAANALYSIS; ASSOCIATION C1 [Lajous, M.; Mozaffarian, D.; Adami, H. -O.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Lajous, M.] Natl Inst Publ Hlth, Ctr Populat Hlth Res, Cuernavaca, Morelos, Mexico. [Mozaffarian, D.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Mozaffarian, D.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Mozaffarian, D.; Schrag, D.] Harvard Univ, Sch Med, Boston, MA USA. [Mozaffarian, D.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Mozaffarian, R.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Schrag, D.] Dana Farber Harvard Canc Ctr, Dept Med Oncol, Boston, MA USA. [Adami, H. -O.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. RP Lajous, M (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA. EM mlajous@hsph.harvard.edu NR 21 TC 8 Z9 8 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0954-6820 J9 J INTERN MED JI J. Intern. Med. PD JAN PY 2011 VL 269 IS 1 BP 88 EP 93 DI 10.1111/j.1365-2796.2010.02273.x PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 695QS UT WOS:000285388300011 PM 21158981 ER PT J AU Mullen, TD Spassieva, S Jenkins, RW Kitatani, K Bielawski, J Hannun, YA Obeid, LM AF Mullen, Thomas D. Spassieva, Stefka Jenkins, Russell W. Kitatani, Kazuyuki Bielawski, Jacek Hannun, Yusuf A. Obeid, Lina M. TI Selective knockdown of ceramide synthases reveals complex interregulation of sphingolipid metabolism SO JOURNAL OF LIPID RESEARCH LA English DT Article DE dihydroceramide; hexosylceramide; sphingomyelin; long-chain sphingolipids; very-long-chain sphingolipids; glucosylceramide synthase; short interfering RNA ID LONGEVITY ASSURANCE GENE-1; SQUAMOUS-CELL CARCINOMAS; (DIHYDRO)CERAMIDE SYNTHASE; SPHINGOSINE 1-PHOSPHATE; SUBSTRATE-SPECIFICITY; MASS-SPECTROMETRY; SALVAGE PATHWAY; FAMILY-MEMBERS; BREAST-CANCER; HUMAN HEAD AB Mammalian ceramide synthases 1 to 6 ( CerS1-6) generate Cer in an acyl-CoA-dependent manner, and expression of individual CerS has been shown to enhance the synthesis of ceramides with particular acyl chain lengths. However, the contribution of each CerS to steady-state levels of specific Cer species has not been evaluated. We investigated the knockdown of individual CerS in the MCF-7 human breast adenocarcinoma cell line by using small-interfering RNA ( siRNA). We found that siRNA-induced down-regulation of each CerS resulted in counter-regulation of nontargeted CerS. Additionally, each CerS knockdown produced unique effects on the levels of multiple sphingolipid species. For example, downregulation of CerS2 decreased very long-chain Cer but increased levels of CerS4, CerS5, and CerS6 expression and upregulated long-chain and medium-long-chain sphingolipids. Conversely, CerS6 knockdown decreased C16:0-Cer but increased CerS5 expression and caused non-C16:0 sphingolipids to be upregulated. Knockdown of individual CerS failed to decrease total sphingolipids or upregulate sphingoid bases. Treatment with siRNAs targeting combined CerS, CerS2, CerS5, and CerS6, did not change overall Cer or sphingomyelin mass but caused upregulation of dihydroceramide and hexosyl-ceramide and promoted endoplasmic reticulum stress. These data suggest that sphingolipid metabolism is robustly regulated by both redundancy in CerS-mediated Cer synthesis and counter-regulation of CerS expression.-Mullen, T. D., S. Spassieva, R. W. Jenkins, K. Kitatani, J. Bielawski, Y. A. Hannun, and L. M. Obeid. Selective knockdown of ceramide synthases reveals complex interregulation of sphingolipid metabolism. J. Lipid Res. 2011. 52:68-77. C1 [Mullen, Thomas D.; Spassieva, Stefka; Obeid, Lina M.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Jenkins, Russell W.; Kitatani, Kazuyuki; Bielawski, Jacek; Hannun, Yusuf A.; Obeid, Lina M.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Obeid, Lina M.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. RP Obeid, LM (reprint author), Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. EM obeidl@musc.edu OI Kitatani, Kazuyuki/0000-0002-8516-6135; obeid, lina/0000-0002-0734-0847 FU Medical University of South Carolina [5T32ES012878]; NIH/NIEHS [F30 ES016975-01]; NIH [R01 AG016583]; National Institutes of Health/National Cancer Institute [P01 CA097132]; American Heart Association [081509E]; National Institutes of Health [GM08716]; National Center for Research Resources (National Institutes of Health) [C06 RR018823]; Office of Research and Development, Department of Veterans Affairs; Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC FX Support for this research was provided by Medical University of South Carolina Department of Pharmaceutical Sciences Training Program in Environmental Stress Signaling (National Institutes of Health/National Institute of Environmental Health Science) Grant 5T32ES012878 and Ruth L. Kirschstein National Research Service Award (NIH/NIEHS) Grant 1 F30 ES016975-01 (T.D.M.); NIH Grant R01 AG016583 (to L.M.O.); National Institutes of Health/National Cancer Institute Grant P01 CA097132 (Y.A.H.); American Heart Association pre-doctoral fellowship Grant 081509E (R.W.J.); and National Institutes of Health Medical Scientist Training Program Grant (GM08716) (R.W.J.). HPLC/MS analysis at the MUSC Lipidomics Core Facility was supported by the Extramural Research Facilities Program of the National Center for Research Resources (National Institutes of Health Grant C06 RR018823). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health or other granting agencies. This work also received supportin part by a Method to Extend Research in Time (MERIT) Award (L.M.O.) from the Office of Research and Development, Department of Veterans Affairs, Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC. NR 43 TC 53 Z9 53 U1 0 U2 4 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 JAN PY 2011 VL 52 IS 1 BP 68 EP 77 DI 10.1194/jlr.M009142 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 692WA UT WOS:000285185400007 PM 20940143 ER PT J AU Schrader, KA Masciari, S Boyd, N Salamanca, C Senz, J Saunders, DN Yorida, E Maines-Bandiera, S Kaurah, P Tung, N Robson, ME Ryan, PD Olopade, OI Domchek, SM Ford, J Isaacs, C Brown, P Balmana, J Razzak, AR Miron, P Coffey, K Terry, MB John, EM Andrulis, IL Knight, JA O'Malley, FP Daly, M Bender, P Moore, R Southey, MC Hopper, JL Garber, JE Huntsman, DG AF Schrader, K. A. Masciari, S. Boyd, N. Salamanca, C. Senz, J. Saunders, D. N. Yorida, E. Maines-Bandiera, S. Kaurah, P. Tung, N. Robson, M. E. Ryan, P. D. Olopade, O. I. Domchek, S. M. Ford, J. Isaacs, C. Brown, P. Balmana, J. Razzak, A. R. Miron, P. Coffey, K. Terry, M. B. John, E. M. Andrulis, I. L. Knight, J. A. O'Malley, F. P. Daly, M. Bender, P. Moore, R. Southey, M. C. Hopper, J. L. Garber, J. E. Huntsman, D. G. CA kConFab TI Germline mutations in CDH1 are infrequent in women with early-onset or familial lobular breast cancers SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID DIFFUSE GASTRIC-CANCER; E-CADHERIN MUTATIONS; RESOURCE; CARRIERS; BRCA1; GENE AB Background Germline mutations in CDH1 are associated with hereditary diffuse gastric cancer; lobular breast cancer also occurs excessively in families with such condition. Method To determine if CDH1 is a susceptibility gene for lobular breast cancer in women without a family history of diffuse gastric cancer, germline DNA was analysed for the presence of CDH1 mutations in 318 women with lobular breast cancer who were diagnosed before the age of 45 years or had a family history of breast cancer and were not known, or known not, to be carriers of germline mutations in BRCA1 or BRCA2. Cases were ascertained through breast cancer registries and high-risk cancer genetic clinics (Breast Cancer Family Registry, the kConFab and a consortium of breast cancer genetics clinics in the United States and Spain). Additionally, Multiplex Ligation-dependent Probe Amplification was performed for 134 cases to detect large deletions. Results No truncating mutations and no large deletions were detected. Six non-synonymous variants were found in seven families. Four (4/318 or 1.3%) are considered to be potentially pathogenic through in vitro and in silico analysis. Conclusion Potentially pathogenic germline CDH1 mutations in women with early-onset or familial lobular breast cancer are at most infrequent. C1 [Kaurah, P.; Huntsman, D. G.] British Columbia Canc Agcy, Hereditary Canc Program, Vancouver, BC V5Z 4E6, Canada. [Schrader, K. A.; Boyd, N.; Salamanca, C.; Senz, J.; Saunders, D. N.; Yorida, E.; Maines-Bandiera, S.; Huntsman, D. G.] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V5Z 1M9, Canada. [Masciari, S.; Razzak, A. R.; Garber, J. E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Tung, N.; Coffey, K.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Robson, M. E.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Ryan, P. D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Olopade, O. I.] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Domchek, S. M.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Ford, J.; John, E. M.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Isaacs, C.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. [Brown, P.] Baylor Coll Med, Breast Ctr, Houston, TX 77030 USA. [Balmana, J.] Hosp Valle De Hebron, Barcelona, Spain. [Miron, P.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Terry, M. B.] Columbia Univ, New York, NY USA. [John, E. M.] Inst Calif, No Calif Canc Ctr Prevent, Fremont, CA USA. [Andrulis, I. L.] Univ Toronto, Mt Sinai Hosp, Samuel Lunenfeld Res Inst,Dept Mol Genet, Fred A Litwin Ctr Canc Genet,Ontario Canc Genet N, Toronto, ON, Canada. [Knight, J. A.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Div Epidemiol & Biostat, Toronto, ON M5G 1X5, Canada. [O'Malley, F. P.] Univ Toronto, Toronto, ON, Canada. [O'Malley, F. P.] St Michaels Hosp, Toronto, ON M5B 1W8, Canada. [Daly, M.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Bender, P.] NIH, Bethesda, MD 20892 USA. [kConFab] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Moore, R.] Genome Sci Ctr, Vancouver, BC, Canada. [Southey, M. C.] Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia. [Hopper, J. L.] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia. RP Huntsman, DG (reprint author), British Columbia Canc Agcy, Hereditary Canc Program, Room 3427,600 W 10th Ave, Vancouver, BC V5Z 4E6, Canada. EM dhuntsma@bccancer.bc.ca RI Saunders, Darren/B-7677-2008; Knight, Julia/A-6843-2012; Andrulis, Irene/E-7267-2013; Tang, Macy/B-9798-2014; OI Robson, Mark/0000-0002-3109-1692; Saunders, Darren/0000-0003-0924-0513 FU NHMRC [145684, 288704, 454508]; National Cancer Institute, National Institutes of Healt [RFA-CA-06-503]; Cancer Care Ontario [U01 CA69467]; Columbia University [U01 CA69398]; Fox Chase Cancer Center [U01 CA69631]; Northern California Cancer Center [U01 CA69417]; University of Melbourne [U01 CA69638]; Research Triangle Institute Informatics Support Center [N02PC45022-46]; National Breast Cancer Foundation; National Health and Medical Research Council; Queensland Cancer Fund; Cancer Councils of New South Wales, Victoria, Tasmania and South Australia; Cancer Foundation of Western Australia; Breast Cancer Research Foundation; Canadian Cancer Society [18381]; Dana Farber/Harvard Cancer Center Breast SPORE (NIH/NCI) [P50-CA89393]; University of British Columbia; Cancer Institute NSW; Charles A. King Trust; Bank of America; Co-Trustee (Boston, MA); Humane Society; Harvard Catalyst; Harvard Clinical and Translational Science Center [UL1 RR 025758]; Harvard University FX Samples from the Fox Chase Cancer Center, Huntsman Cancer Institute and Northern California Cancer Center were processed and distributed by the Coriell Cell Repositories through cooperative agreements. The content of this article does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centres in the Breast CFR, nor does mention of trade names, commercial products or organizations imply endorsement by the US government or the Breast CFR. The authors thank Heather Thorne, Eveline Niedermayr, all the kConFab research nurses and staff, and the heads and staff of the Family Cancer Clinics and the clinical follow-up study (funded by NHMRC grants 145684, 288704 and 454508) for their contributions to this resource and the many families who contribute to kConFab. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic healthcare centres, the National Center for Research Resources or the National Institutes of Health. The authors would like to acknowledge Kenneth Offit and Lisa Balistreri (Memorial Sloan-Kettering Cancer Center), Katherine L. Nathanson (University of Pennsylvania), Nicki Chun, Kerry Kingham and Meredith Mills (Stanford University), Vanessa Sem and Katherine Corso (Dana Farber Cancer Institute), Patel Devanshi (Massachussets General Hospital) and the Niehaus, Southworth, Weissenbach Cancer Research Initiative, the Lymphoma Foundation and the Sabin Family Cancer Research Initiative.; The collection of resources from the Breast CFR was supported by the National Cancer Institute, National Institutes of Health under RFA-CA-06-503 and through cooperative agreements with members of the Breast Cancer Family Registry (CFR) and principal investigators including those from Cancer Care Ontario (U01 CA69467), Columbia University (U01 CA69398), Fox Chase Cancer Center (U01 CA69631), the Northern California Cancer Center (U01 CA69417), the University of Melbourne (U01 CA69638) and Research Triangle Institute Informatics Support Center (RFP No. N02PC45022-46). kConFab is supported by grants from the National Breast Cancer Foundation and the National Health and Medical Research Council and by the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. The Breast Cancer Genetics Consortium was funded by a Breast Cancer Research Foundation grant to JG and the consortium (Dana Farber Cancer Institute, Beth Israel Deaconess Medical Center, Massachusetts General Hospital, Memorial Sloan-Kettering Cancer Center, University of Chicago, University of Pennsylvania, Stanford University, Georgetown University, Baylor College of Medicine and Hospital Vall d'Hebron). DNA and mutation analysis was performed at the Huntsman Laboratory, British Columbia Cancer Agency and the Genome Sciences Centre, and was supported by the Canadian Cancer Society (principal investigator: David Huntsman; grant No. 18381). This research was supported in part by the Dana Farber/Harvard Cancer Center Breast SPORE (grant number: NIH/NCI (P50-CA89393)). KAS is supported by the University of British Columbia's Clinician Investigator Program. DNS is supported by a Cancer Institute NSW fellowship. SM was supported by Charles A. King Trust, Bank of America Fellowship, Co-Trustee (Boston, MA) and The Humane Society of the Commonwealth of Massachusetts Postdoctoral Research Fellowship. This work was conducted with support from the Scholars in Clinical Science Program of Harvard Catalyst, The Harvard Clinical and Translational Science Center (award No. UL1 RR 025758) and with financial contributions from Harvard University and its affiliated academic healthcare centres. NR 16 TC 35 Z9 35 U1 0 U2 3 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD JAN PY 2011 VL 48 IS 1 BP 64 EP 68 DI 10.1136/jmg.2010.079814 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 695PB UT WOS:000285383600009 PM 20921021 ER PT J AU Heilman, JM Kemmann, E Bonert, M Chatterjee, A Ragar, B Beards, GM Iberri, DJ Harvey, M Thomas, B Stomp, W Martone, MF Lodge, DJ Vondracek, A de Wolff, JF Liber, C Grover, SC Vickers, TJ Mesko, B Laurent, MR AF Heilman, James M. Kemmann, Eckhard Bonert, Michael Chatterjee, Anwesh Ragar, Brent Beards, Graham M. Iberri, David J. Harvey, Matthew Thomas, Brendan Stomp, Wouter Martone, Michael F. Lodge, Daniel J. Vondracek, Andrea de Wolff, Jacob F. Liber, Casimir Grover, Samir C. Vickers, Tim J. Mesko, Bertalan Laurent, Michael R. TI Wikipedia: A Key Tool for Global Public Health Promotion SO JOURNAL OF MEDICAL INTERNET RESEARCH LA English DT Article DE Internet; Wikipedia; public health; health information; knowledge dissemination; patient education; medical education ID WORLD-WIDE-WEB; INFORMATION; INTERNET; MEDICINE; QUALITY; CONSUMERS; EDUCATION; DATABASE; SEARCH; IMPACT AB The Internet has become an important health information resource for patients and the general public. Wikipedia, a collaboratively written Web-based encyclopedia, has become the dominant online reference work. It is usually among the top results of search engine queries, including when medical information is sought. Since April 2004, editors have formed a group called WikiProject Medicine to coordinate and discuss the English-language Wikipedia's medical content. This paper, written by members of the WikiProject Medicine, discusses the intricacies, strengths, and weaknesses of Wikipedia as a source of health information and compares it with other medical wikis. Medical professionals, their societies, patient groups, and institutions can help improve Wikipedia's health-related entries. Several examples of partnerships already show that there is enthusiasm to strengthen Wikipedia's biomedical content. Given its unique global reach, we believe its possibilities for use as a tool for worldwide health promotion are underestimated. We invite the medical community to join in editing Wikipedia, with the goal of providing people with free access to reliable, understandable, and up-to-date health information. C1 [Laurent, Michael R.] Univ Hosp Leuven, Dept Internal Med, B-3000 Louvain, Belgium. [Heilman, James M.] Univ Saskatchewan, Coll Med, Saskatoon, SK S7N 0W0, Canada. [Heilman, James M.] Moose Jaw Union Hosp, Dept Emergency Med, Moose Jaw, SK, Canada. [Kemmann, Eckhard] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Obstet Gynecol & Reprod Sci, New Brunswick, NJ USA. [Bonert, Michael] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada. [Chatterjee, Anwesh] Poole Gen Hosp, Dept Resp Med, Poole, Dorset, England. [Ragar, Brent] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Internal Med, Boston, MA USA. [Ragar, Brent] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat, Boston, MA USA. [Beards, Graham M.] Walsall Manor Hosp, Walsall, W Midlands, England. [Iberri, David J.] Univ Vermont, Coll Med, Burlington, VT USA. [Harvey, Matthew] Royal Brisbane & Womens Hosp, Dept Anat Pathol, Brisbane, Qld, Australia. [Harvey, Matthew] Univ Queensland, Sch Med, Div Cellular & Mol Pathol, Brisbane, Qld, Australia. [Thomas, Brendan] Univ Illinois, Dept Dermatol, Chicago, IL USA. [Stomp, Wouter] Leiden Univ, Med Ctr, Dept Radiol, Leiden, Netherlands. [Martone, Michael F.] Rush Univ, Coll Med, Chicago, IL 60612 USA. [Lodge, Daniel J.] Univ Toronto, Dept Cardiac Surg, Toronto, ON, Canada. [Vondracek, Andrea] Univ Colorado, Sch Med, Dept Immunol, Denver, CO USA. [de Wolff, Jacob F.] Univ Coll Hosp, Dept Acute Med, London, England. [Liber, Casimir] Bankstown Hlth Serv, Dept Psychiat, Sydney, NSW, Australia. [Liber, Casimir] Univ New S Wales, Coll Med, Sch Psychiat, Sydney, NSW, Australia. [Grover, Samir C.] Univ Toronto, Div Gastroenterol, Toronto, ON, Canada. [Vickers, Tim J.] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA. [Mesko, Bertalan] Univ Debrecen, Sch Med, Debrecen, Hungary. [Mesko, Bertalan] Univ Debrecen, Hlth Sci Ctr, Debrecen, Hungary. [Vondracek, Andrea] Univ Colorado, Natl Jewish Hlth, Denver, CO 80202 USA. RP Laurent, MR (reprint author), Univ Hosp Leuven, Dept Internal Med, Herestr 49, B-3000 Louvain, Belgium. EM michael.laurent@gmail.com OI Beards, Graham/0000-0002-9928-1302; Laurent, Michael/0000-0001-9681-8330 NR 68 TC 67 Z9 68 U1 2 U2 24 PU JOURNAL MEDICAL INTERNET RESEARCH PI TORONTO PA TORONTO GENERAL HOSPITAL, R FRASER ELLIOTT BLDG, 4TH FL, R 4S435, 190 ELIZABETH ST, TORONTO, ON M5G 2C4, CANADA SN 1438-8871 J9 J MED INTERNET RES JI J. Med. Internet Res. PD JAN-MAR PY 2011 VL 13 IS 1 BP 153 EP 164 AR e14 DI 10.2196/jmir.1589 PG 12 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 722PP UT WOS:000287447100012 PM 21282098 ER PT J AU Adluri, RS Thirunavukkarasu, M Zhan, LJ Akita, Y Samuel, SM Otani, H Ho, YS Maulik, G Maulik, N AF Adluri, Ram Sudheer Thirunavukkarasu, Mahesh Zhan, Lijun Akita, Yuzo Samuel, Samson Mathews Otani, Hajime Ho, Ye-Shih Maulik, Gautam Maulik, Nilanjana TI Thioredoxin 1 enhances neovascularization and reduces ventricular remodeling during chronic myocardial infarction: A study using thioredoxin 1 transgenic mice SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE Apoptosis; Myocardial infarction; Neovascularization; Oxidative stress; Thioredoxin 1; Ventricular remodeling ID ENDOTHELIAL-CELLS; THERAPEUTIC ANGIOGENESIS; DOWN-REGULATION; RAT MYOCARDIUM; GROWTH-FACTOR; NITRIC-OXIDE; SYNTHASE; EXPRESSION; HYPOXIA; BARRIER AB Oxidative stress plays a crucial role in disruption of neovascularization by alterations in thioredoxin 1 (Trx1) expression and its interaction with other proteins after myocardial infarction (MI). We previously showed that Trx1 has angiogenic properties, but the possible therapeutic significance of overexpressing Trx1 in chronic MI has not been elucidated. Therefore, we explored the angiogenic and cardioprotective potential of Trx1 in an in vivo MI model using transgenic mice overexpressing Trx1. Wild-type (W) and Trx1 transgenic (Trx1(Tg/+)) mice were randomized into W sham (WS), Trx1(Tg/+) sham (TS), WMI, and TMI. MI was induced by permanent occlusion of LAD coronary artery. Hearts from mice overexpressing Trx1 exhibited reduced fibrosis and oxidative stress and attenuated cardiomyocyte apoptosis along with increased vessel formation compared to WMI. We found significant inhibition of Trx1 regulating proteins, TXNIP and AKAP 12, and increased p-Akt, p-eNOS, p-GSK-3 beta, HIF-1 alpha, beta-catenin, VEGF, Bcl-2, and survivin expression in TMI compared to WMI. Echocardiography performed 30 days after MI revealed significant improvement in myocardial functions in TMI compared to WMI. Our study identifies a potential role for Trx1 overexpression and its association with its regulatory proteins TXNIP, AKAP12, and subsequent activation of Akt/GSK-3 beta/beta-catenin/ HIF-1 alpha-mediated VEGF and eNOS expression in inducing angiogenesis and reduced ventricular remodeling. Hence, Trx1 and other proteins identified in our study may prove to be potential therapeutic targets in the treatment of ischemic heart disease. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Adluri, Ram Sudheer; Thirunavukkarasu, Mahesh; Zhan, Lijun; Akita, Yuzo; Samuel, Samson Mathews; Maulik, Nilanjana] Univ Connecticut, Sch Med, Dept Surg, Mol Cardiol & Angiogenesis Lab, Farmington, CT 06032 USA. [Otani, Hajime] Kansai Med Univ, Moriguchi, Osaka 570, Japan. [Ho, Ye-Shih] Wayne State Univ, Inst Environm Hlth Sci, Detroit, MI USA. [Maulik, Gautam] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Maulik, N (reprint author), Univ Connecticut, Sch Med, Dept Surg, Mol Cardiol & Angiogenesis Lab, Farmington Ave, Farmington, CT 06032 USA. EM nmaulik@neuron.uchc.edu FU [HL-56803]; [HL-85804] FX This study was supported by the grants HL-56803 and HL-85804 to N.M. NR 36 TC 41 Z9 41 U1 2 U2 13 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD JAN PY 2011 VL 50 IS 1 BP 239 EP 247 DI 10.1016/j.yjmcc.2010.11.002 PG 9 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 710HV UT WOS:000286502800030 PM 21074540 ER PT J AU Su, ZL Dias-Santagata, D Duke, M Hutchinson, K Lin, YL Borger, DR Chung, CH Massion, PP Vnencak-Jones, CL Lafrate, AJ Pao, W AF Su, Zengliu Dias-Santagata, Dora Duke, MarKeesa Hutchinson, Katherine Lin, Ya-Lun Borger, Darrell R. Chung, Christine H. Massion, Pierre P. Vnencak-Jones, Cindy L. Lafrate, A. John Pao, William TI A Platform for Rapid Detection of Multiple Oncogenic Mutations With Relevance to Targeted Therapy in Non-Small-Cell Lung Cancer SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Article ID RECEPTOR GENE-MUTATIONS; INTEGRATED GENOMIC ANALYSIS; SOMATIC MUTATIONS; PIK3CA MUTATIONS; KINASE DOMAIN; NEVER SMOKERS; ADENOCARCINOMA; GEFITINIB; EGFR; TUMORS AB The identification of somatically acquired tumor mutations is increasingly important in the clinical management of cancer because the sensitivity of targeted drugs is related to the genetic makeup of individual tumors. Thus, mutational profiles of tumors can help prioritize anticancer therapy. We report herein the development and validation of two multiplexed assays designed to detect in DNA from FFPE tissue more than 40 recurrent mutations in nine genes relevant to existing and emerging targeted therapies in lung cancer. The platform involves two methods: a screen (SNaPshot) based on multiplex PCR, primer extension, and capillary electrophoresis that was designed to assess for 38 somatic mutations in eight genes (AKT1, BRAF, EGFR, KRAS, MEK1, NRAS, PIK3C4, and PTEN) and a PCR-based sizing assay that assesses for EGFR exon 19 deletions, EGFR exon 20 insertions, and HER2 exon 20 insertions. Both the SNaPshot and sizing assays can be performed rapidly, with minimal amounts of genetic material. Compared with direct sequencing, in which mutant DNA needs to compose 25% or more of the total DNA to easily detect a mutation, the SNaPshot and sizing assays can detect mutations in samples in which mutant DNA composes 1.56% to 12.5% and 1.56% to 6.25% of the total DNA, respectively. These robust, reliable, and relatively inexpensive assays should help accelerate adoption of a genotype-driven approach in the treatment of lung cancer. (J Mol Diagn 2011, 13:74-84; DOI: 10.1016/j.jmoldx.2010.11.010) C1 [Su, Zengliu; Duke, MarKeesa; Hutchinson, Katherine; Lin, Ya-Lun; Chung, Christine H.; Pao, William] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Dept Med,Div Hematol Oncol, Nashville, TN 37232 USA. [Dias-Santagata, Dora; Borger, Darrell R.; Lafrate, A. John] Massachusetts Gen Hosp, Translat Res Lab, Boston, MA 02114 USA. [Massion, Pierre P.] Vanderbilt Univ, Div Allergy Pulm & Crit Care Med, Vanderbilt Ingram Canc Ctr, Sch Med, Nashville, TN 37232 USA. [Vnencak-Jones, Cindy L.] Vanderbilt Univ, Dept Pathol, Med Ctr, Nashville, TN 37232 USA. [Vnencak-Jones, Cindy L.] Vanderbilt Univ, Dept Pediat, Med Ctr, Nashville, TN 37232 USA. RP Pao, W (reprint author), Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Dept Med,Div Hematol Oncol, 2220 Pierce Ave,777 Preston Res Bldg, Nashville, TN 37232 USA. EM william.pao@vanderbilt.edu RI Su, Zengliu /E-3156-2010 FU NIH/National Cancer Institute [R01 CA121210, P01 CA129243, U54 CA143798, CA102353, RC2-CA148394-01]; VICC [CA90949, CA68485]; V Foundation; TJ Martell Foundation; Kleberg Foundation; Vanderbilt DNA sequencing core facility FX Supported by the NIH/National Cancer Institute (grants R01 CA121210, P01 CA129243, U54 CA143798, CA102353, and RC2-CA148394-01), the VICC Specialized Program of Research Excellence in Lung Cancer grant (CA90949), the Vanderbilt-Ingram Cancer Center Core grant (CA68485), the V Foundation, the TJ Martell Foundation, the Kleberg Foundation, and an anonymous donor.; We thank Dr. Jennifer Pietenpol, Dr. David Johnson, Dr. Sam Santoro, Dr. Michael Laposata, Robert Woodhall, Gladys Garrison, Dr. Alfred George, and the Vanderbilt DNA sequencing core facility for support; Ryn Miake-Lye for helpful discussions; and Dr. Margaret Spitz (University of Texas M. D. Anderson Cancer Center, Houston, TX) for sharing DNA samples from tumors collected at her institution on Lung SPORE CA70907. NR 37 TC 114 Z9 114 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-1578 EI 1943-7811 J9 J MOL DIAGN JI J. Mol. Diagn. PD JAN PY 2011 VL 13 IS 1 BP 74 EP 84 DI 10.1016/j.jmoldx.2010.11.010 PG 11 WC Pathology SC Pathology GA 707LE UT WOS:000286287200011 PM 21227397 ER PT J AU Li, M Balamuthusamy, S Khan, AM Maderdrut, JL Simon, EE Batuman, V AF Li, Min Balamuthusamy, Saravanan Khan, Altaf M. Maderdrut, Jerome L. Simon, Eric E. Batuman, Vecihi TI Pituitary Adenylate Cyclase-Activating Polypeptide Prevents Cisplatin-Induced Renal Failure SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE Apoptosis; Cancer chemotherapy; Extracellular matrix; Inflammation; p53; Renoprotection ID VASOACTIVE-INTESTINAL-PEPTIDE; 4 SPLICE VARIANTS; MULTIPLE-MYELOMA; INDUCED NEPHROTOXICITY; PATHOLOGICAL ROLE; OXIDATIVE STRESS; CELL APOPTOSIS; IN-VITRO; KIDNEY; PACAP AB Cisplatin is widely used for cancer chemotherapy, but nephrotoxicity is a major dose-limiting side effect. Our recent studies in vitro have shown that pituitary adenylate cyclase-activating polypeptide (PACAP) ameliorated cisplatin nephrotoxicity and that the renoprotection with PACAP38 was mediated by the PAC(1) receptor and through the p53-dependent and -independent suppression of apoptosis of human renal proximal tubular epithelial cells. In the present studies, PACAP38 prevented the rise in blood urea nitrogen and serum creatinine in mice treated with cisplatin. Cisplatin-exposed mice treated with PACAP38 had relatively well-preserved tubular integrity, even when the treatment started 24 h after cisplatin exposure. PACAP38 also reduced plasma and kidney levels of tumor necrosis factor-alpha and restored collagen IV levels. The damage to mouse kidney tubules caused by cisplatin involved p53 accumulation and was partially reversed by treatment with PACAP38. PACAP38 ameliorates cisplatin-induced acute kidney injury even when treatment started 24 h after the onset of injury and increases tubular regeneration, which further facilitates restoration of kidney function in addition to its anti-apoptotic effects. C1 [Li, Min; Balamuthusamy, Saravanan; Khan, Altaf M.; Simon, Eric E.; Batuman, Vecihi] Tulane Univ, Sch Med, Sect Nephrol & Hypertens, Dept Med, New Orleans, LA 70112 USA. [Maderdrut, Jerome L.] Peptide Res Lab, Dept Med, New Orleans, LA 70112 USA. [Simon, Eric E.; Batuman, Vecihi] US Dept Vet Affairs, SE Louisiana Vet Hlth Care Syst, New Orleans, LA 70112 USA. RP Li, M (reprint author), Tulane Univ, Sch Med, Sect Nephrol & Hypertens, Dept Med, 1430 Tulane Ave,SL 45, New Orleans, LA 70112 USA. EM minlee@tulane.edu OI Batuman, Vecihi/0000-0002-1800-9009 FU Louisiana Board of Regents [013RCEEP-07]; Dialysis Clinic, Inc.; Arimura Foundation FX This work was supported in part by the Research Commercialization and Educational Enhancement Program of the Louisiana Board of Regents (013RCEEP-07 to M. L., J.L.M. and V. B.), the Dialysis Clinic, Inc. (research endowment to V. B.), and the Arimura Foundation (research grant to M. L.). NR 36 TC 11 Z9 11 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD JAN PY 2011 VL 43 IS 1 BP 58 EP 66 DI 10.1007/s12031-010-9394-1 PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 705CJ UT WOS:000286106100010 PM 20514524 ER PT J AU Lu, YX Germano, P Ohning, GV Vu, JP Pisegna, JR AF Lu, Yuxin Germano, Patrizia Ohning, Gordon V. Vu, John P. Pisegna, Joseph R. TI PAC1 Deficiency in a Murine Model Induces Gastric Mucosa Hypertrophy and Higher Basal Gastric Acid Output SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE PACAP; PAC1 deficient; Gastric acid secretion ID CYCLASE-ACTIVATING POLYPEPTIDE; ADENYLATE-CYCLASE; ECL CELLS; TYPE-1 RECEPTOR; SECRETION; MICE; PROLIFERATION; RAT; NEUROPEPTIDE; RELEASE AB Pituitary adenylate cyclase-activating polypeptide (PACAP) has been shown to increase the histamine release from gastric enterochromaffin-like (ECL) cells and promote gastric acid secretion in rats. In contrast, in mice, PACAP has been demonstrated to induce a decrease of gastric acid secretion, an effect presumably due to somatostatin release. To more clearly define the role of PACAP in the regulation of gastric acid output, a knockout mouse model for the PACAP-specific receptor PAC1 was applied in this study. Measurements of the basal and stimulated gastric acid secretion and morphological studies on the gastric mucosa were performed in both wild-type and PAC1-deficient mice. Compared with the wild-type mice, the PAC1-deficient mice showed a nearly threefold higher basal gastric acid output, increased gastric mucosa thickness and glands height, and proportional increases in parietal and total cell counts in the gastric mucosa. The PAC1-deficient mice also showed a trend of increased plasma gastrin levels and gastrin gene expression in the gastric mucosa. This study indicates that the expression of PAC1 is clearly important for maintaining the homeostasis of gastric acid secretion. Loss of PACAP receptor during development may lead to a compensatory mechanism regulating gastric acid secretion. C1 [Lu, Yuxin; Ohning, Gordon V.; Vu, John P.; Pisegna, Joseph R.] Vet Adm Greater Angeles Healthcare Syst, Div Gastroenterol & Hepatol, Los Angeles, CA 90073 USA. [Lu, Yuxin; Germano, Patrizia; Ohning, Gordon V.; Vu, John P.; Pisegna, Joseph R.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. RP Pisegna, JR (reprint author), Vet Adm Greater Angeles Healthcare Syst, Div Gastroenterol & Hepatol, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jpisegna@ucla.edu FU Department of Veterans Affairs; NIH [DK41301] FX This work was supported by the Department of Veterans Affairs Merit Review Grant (JRP). Antibody #S607 raised against somatostatin was provided by the CURE Digestive Diseases Research Center, Antibody/RIA Core, NIH Grant #DK41301. NR 19 TC 6 Z9 6 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD JAN PY 2011 VL 43 IS 1 BP 76 EP 84 DI 10.1007/s12031-010-9440-z PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 705CJ UT WOS:000286106100012 PM 20821075 ER PT J AU Turner, TH Goldstein, J Hamilton, JM Jacobson, M Pirogovsky, E Peavy, G Corey-Bloom, J AF Turner, Travis H. Goldstein, Jody Hamilton, Joanne M. Jacobson, Mark Pirogovsky, Eva Peavy, Guerry Corey-Bloom, Jody TI Behavioral Measures of Saccade Latency and Inhibition in Manifest and Premanifest Huntington's Disease SO JOURNAL OF MOTOR BEHAVIOR LA English DT Article DE behavioral test; eye-tracking; Huntington's disease; oculomotor functioning; predictive testing; presymptomatic; saccade; saccadic eye movements ID MOTOR ABNORMALITIES; PREDICT-HD; RELIABILITY; PROGRESSION AB Initiation and inhibition of saccadic eye movements has been shown to be impaired in patients with Huntington's disease (HD) and premanifest gene carriers (PMGC), and may provide biomarkers useful in tracking phenotypic change. Computerized behavioral tests of prosaccade latency and disinhibition presented to 31 non-gene carriers (NGC), 25 PMGC, and 12 HD patients. These tests provided quantitative performance measures without use of eye-tracking equipment. Significant differences on saccade tests were found, with PMGC intermediate between NGC and HD patients. Saccade latency discriminated PMGC from NGC, whereas saccade disinhibition discriminated PMGC from HD patients. Results suggest utility of behavioral saccade measures as premanifest indicators of phenoconversion in HD. C1 [Turner, Travis H.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Turner, Travis H.] Med Univ S Carolina, Dept Neurosci, Charleston, SC USA. [Goldstein, Jody; Hamilton, Joanne M.; Pirogovsky, Eva; Peavy, Guerry; Corey-Bloom, Jody] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. [Jacobson, Mark] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. RP Turner, TH (reprint author), Charleston Mem Hosp, Movement Disorders Program Neurol, 326 Calhoun St,Suite 308,POB 250108, Charleston, SC 29401 USA. EM turnertr@musc.edu OI Pirogovsky, Eva/0000-0002-2941-9070 FU UCSD Huntington's Disease Society of America (HDSA) Center of Excellence; UCSD Alzheimer's Disease Research Center [NIH P50 AG 005131] FX This work was supported by the UCSD Huntington's Disease Society of America (HDSA) Center of Excellence and the UCSD Alzheimer's Disease Research Center (NIH P50 AG 005131). NR 22 TC 5 Z9 5 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0022-2895 J9 J MOTOR BEHAV JI J. Mot. Behav. PY 2011 VL 43 IS 4 BP 295 EP 302 DI 10.1080/00222895.2011.580390 PG 8 WC Neurosciences; Psychology; Psychology, Experimental; Sport Sciences SC Neurosciences & Neurology; Psychology; Sport Sciences GA 888KT UT WOS:000300003100002 PM 21774606 ER PT J AU Rogers, LR LoRusso, P Nadler, P Malik, G Shields, A Kaelin, W AF Rogers, Lisa R. LoRusso, Patricia Nadler, Paul Malik, Ghaus Shields, Anthony Kaelin, William TI Erlotinib therapy for central nervous system hemangioblastomatosis associated with von Hippel-Lindau disease: a case report SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Erlotinib; Von Hippel-Lindau syndrome; Hemangioblastoma; CNS neoplasm ID GROWTH-FACTOR RECEPTOR; LEPTOMENINGEAL HEMANGIOBLASTOMATOSIS; INHIBITOR SU5416 AB There is a need for effective systemic therapy for central nervous system (CNS) hemangioblastomas (HBs). We report a case of erlotinib therapy for CNS HBs in a patient with von Hippel-Lindau disease, in whom the HBs were associated with diffuse leptomeningeal seeding. We provide the first report of paired serum and cerebrospinal fluid (CSF) levels of erlotinib while on standard dosing. The patient exhibited neurologic and imaging signs of recurrent CNS HBs and progressive leptomeningeal metastasis following surgery, radiation, and stereotactic radiosurgery. The patient was treated with erlotinib 150 mg daily. The patient achieved a minor response to erlotinib therapy, including clinical improvement, reduction in size of two enhancing brain lesions (one of which, however, proved at autopsy to be radiation necrosis) and stabilization of leptomeningeal enhancement. In addition, the CSF white count improved. The duration of response was 9 months. The median plasma and CSF levels of erlotinib while on treatment were 1146.06 and 247.83 ng/ml, respectively (CSF 21.6% of plasma). Erlotinib may have antitumor activity in CNS HBs. C1 [Rogers, Lisa R.] Univ Hosp Case Med Ctr, Neurol Inst, Neurooncol Program, Cleveland, OH 44106 USA. [Rogers, Lisa R.] Henry Ford Hosp, Dept Neurol, Detroit, MI 48202 USA. [Rogers, Lisa R.; Malik, Ghaus] Henry Ford Hosp, Dept Neurosurg, Detroit, MI 48202 USA. [LoRusso, Patricia; Shields, Anthony] Karmanos Canc Inst, Dept Med Oncol, Detroit, MI USA. [Nadler, Paul] OSI Pharmaceut, Melville, NY USA. [Kaelin, William] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Rogers, LR (reprint author), Univ Hosp Case Med Ctr, Neurol Inst, Neurooncol Program, 11100 Euclid Ave,Hanna House Room 506, Cleveland, OH 44106 USA. EM Lisa.Rogers1@UHhospitals.org FU Howard Hughes Medical Institute; NCI NIH HHS [P50 CA101942, R01 CA068490] NR 19 TC 6 Z9 7 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD JAN PY 2011 VL 101 IS 2 BP 307 EP 310 DI 10.1007/s11060-010-0244-3 PG 4 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 689VW UT WOS:000284959600017 PM 20524042 ER PT J AU Kalinchuk, AV McCarley, RW Porkka-Heiskanen, T Basheer, R AF Kalinchuk, Anna V. McCarley, Robert W. Porkka-Heiskanen, Tarja Basheer, Radhika TI The time course of adenosine, nitric oxide (NO) and inducible NO synthase changes in the brain with sleep loss and their role in the non-rapid eye movement sleep homeostatic cascade SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE adenosine; cholinergic basal forebrain; nitric oxide; frontal cortex; inducible nitric oxide synthase; sleep homeostasis ID MODULATE ACETYLCHOLINE-RELEASE; BASAL FOREBRAIN NEURONS; IN-VIVO MICRODIALYSIS; PREFRONTAL CORTEX; CHOLINE-ACETYLTRANSFERASE; BEHAVIORAL STATE; CINGULATE CORTEX; C57BL/6J MOUSE; RECOVERY SLEEP; EEG POWER AB P>Both adenosine and nitric oxide (NO) are known for their role in sleep homeostasis, with the basal forebrain (BF) wakefulness center as an important site of action. Previously, we reported a cascade of homeostatic events, wherein sleep deprivation (SD) induces the production of inducible nitric oxide synthase (iNOS)-dependent NO in BF, leading to enhanced release of extracellular adenosine. In turn, increased BF adenosine leads to enhanced sleep intensity, as measured by increased non-rapid eye movement sleep EEG delta activity. However, the presence and time course of similar events in cortex has not been studied, although a frontal cortical role for the increase in non-rapid eye movement recovery sleep EEG delta power is known. Accordingly, we performed simultaneous hourly microdialysis sample collection from BF and frontal cortex (FC) during 11 h SD. We observed that both areas showed sequential increases in iNOS and NO, followed by increases in adenosine. BF increases began at 1 h SD, whereas FC increases began at 5 h SD. iNOS and Fos-double labeling indicated that iNOS induction occurred in BF and FC wake-active neurons. These data support the role of BF adenosine and NO in sleep homeostasis and indicate the temporal and spatial sequence of sleep homeostatic cascade for NO and adenosine. C1 [Kalinchuk, Anna V.; McCarley, Robert W.; Basheer, Radhika] VA Boston Healthcare Syst, Neurosci Lab, Dept Psychiat, W Roxbury, MA 02132 USA. [Kalinchuk, Anna V.; McCarley, Robert W.; Basheer, Radhika] Harvard Univ, Sch Med, W Roxbury, MA 02132 USA. [Porkka-Heiskanen, Tarja] Univ Helsinki, Inst Biomed, Helsinki, Finland. RP Kalinchuk, AV (reprint author), VA Boston Healthcare Syst, Neurosci Lab, Dept Psychiat, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM anna_kalinchuk@hms.harvard.edu; radhika_basheer@hms.harvard.edu RI Sanguansri, Luz/B-6630-2011; McCarley, Robert/N-5562-2014; OI Sanguansri, Luz/0000-0003-1908-7604; McCarley, Robert/0000-0001-5705-7495; Stenberg, Tarja/0000-0003-1843-7625 FU Department of Veterans Affairs; SRSF; National Institute of Mental Health [NIMH39683]; Academy of Finland FX This work was supported by the Department of Veterans Affairs Medical Research Service Award to RB, SRSF Christian Gillin Research Award to AVK, the National Institute of Mental Health Grant (NIMH39683) to RWM and Academy of Finland. We thank Drs Ritchie E. Brown, James T. McKenna and Robert E. Strecker for stimulating discussions, Farzana Pervin Nipa, Pirjo Saarelainen, Sari Leevo-Siitari and Ernst Mecke for excellent technical assistance, Peter Hirsch, Diane Ghera and Dewayne Williams for providing animal care. NR 78 TC 30 Z9 31 U1 0 U2 5 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JAN PY 2011 VL 116 IS 2 BP 260 EP 272 DI 10.1111/j.1471-4159.2010.07100.x PG 13 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 695TF UT WOS:000285394800010 PM 21062286 ER PT J AU Strozyk, D Mehta, BP Meyers, PM Nogueira, RG AF Strozyk, Dorothea Mehta, Brijesh P. Meyers, Philip M. Nogueira, Raul G. TI Coil Embolization of Intracranial Dissecting Vertebral Artery Aneurysms with Subclavian Steal SO JOURNAL OF NEUROIMAGING LA English DT Article DE Vertebral dissection; subclavian steal; subarachnoid hemorrhage; endovascular AB Subclavian steal phenomenon occurs when cerebral blood flow is diverted to supply the arm. We report 3 patients with asymptomatic subclavian steal phenomenon with retrograde blood flow in the vertebral artery who presented with subarachnoid hemorrhage due to dissecting aneurysms of the involved vertebral artery. The association of subclavian steal phenomenon complicated by subarachnoid hemorrhage due to dissecting vertebral aneurysms has not been previously described. C1 [Strozyk, Dorothea; Meyers, Philip M.] Columbia Univ Coll Phys & Surg, New York Presbyterian Hosp, Dept Radiol, New York, NY 10032 USA. [Strozyk, Dorothea; Meyers, Philip M.] Columbia Univ Coll Phys & Surg, New York Presbyterian Hosp, Dept Neurol Surg, New York, NY 10032 USA. [Mehta, Brijesh P.; Nogueira, Raul G.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Nogueira, Raul G.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp,Endovasc Neurosurg Interve, Boston, MA 02115 USA. RP Strozyk, D (reprint author), Columbia Univ Coll Phys & Surg, New York Presbyterian Hosp, Dept Radiol, Milstein Hosp Bldg,8S Knuckle,177 Ft Washington A, New York, NY 10032 USA. EM ds2775@columbia.edu NR 9 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1051-2284 J9 J NEUROIMAGING JI J. Neuroimaging PD JAN PY 2011 VL 21 IS 1 BP 62 EP 64 DI 10.1111/j.1552-6569.2009.00428.x PG 3 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 700PK UT WOS:000285756200011 PM 19747236 ER PT J AU Dickerson, BC Wolk, DA AF Dickerson, Bradford C. Wolk, David A. CA Alzheimer's Dis Neuroimaging Initi TI Dysexecutive versus amnesic phenotypes of very mild Alzheimer's disease are associated with distinct clinical, genetic and cortical thinning characteristics SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article ID COGNITIVE IMPAIRMENT; MEMORY DEFICIT; AD DEMENTIA; SIGNATURE; CONNECTIVITY; DIAGNOSIS; CORTEX AB Objective To investigate whether some patients with very mild Alzheimer's disease (AD) demonstrate disproportionate executive dysfunction relative to amnesia and how this relates to functional impairment in daily life, future clinical decline, APOE genotype and regional cortical thickness measured from MRI scan data. Methods The Alzheimer's Disease Neuroimaging Initiative dataset was interrogated for a primary sample of patients with very mild AD dementia (n=100) and a secondary confirmatory sample of patients with mild cognitive impairment (n=396). An executive predominant subgroup was defined as having executive performance >= 2 SDs worse than memory performance and a memory predominant subgroup was defined conversely. A priori regions of interest from a previous study of an AD patient sample were used to obtain cortical thickness measures. Results Despite equivalent global measures of impairment (Mini-Mental State Examination, Clinical Dementia Rating (CDR) Sum of Boxes), executive predominant patients (n=88) were more impaired on other executive measures and in the CDR Judgement and Problem Solving box (p<0.005) while memory predominant patients (n=56) were more impaired on other memory measures (p<0.05). The APOE-epsilon 4 allele was much more frequent in the memory predominant subgroup (p<0.0001). Frontoparietal cortical regions were thinner in the executive predominant group than in the memory predominant group (p<0.05). Conclusions A dysexecutive clinical phenotype of very mild AD is not rare and is associated with more problem solving difficulties and possibly more rapid progression compared with patients with a predominant amnesic phenotype. Executive predominant AD may reflect an alternative underlying pathophysiology related to genetic status, reflected in more prominent pathological alterations in frontoparietal regions subserving executive function. These findings, which deserve further investigation, may have implications for diagnosis, prognostication, monitoring and related issues involved in clinical research and care. C1 [Dickerson, Bradford C.] Frontotemporal Dementia Unit, Boston, MA USA. [Dickerson, Bradford C.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Dickerson, Bradford C.] Massachusetts Alzheimers Dis Res Ctr, Boston, MA USA. [Dickerson, Bradford C.] Harvard Univ, Sch Med, Boston, MA USA. [Dickerson, Bradford C.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Wolk, David A.] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Wolk, David A.] Alzheimers Dis Core Ctr, Philadelphia, PA USA. [Wolk, David A.] Univ Penn, Penn Memory Ctr, Philadelphia, PA 19104 USA. RP Dickerson, BC (reprint author), Frontotemporal Dementia Unit, 149 13th St,Suite 2691, Charlestown, MA 02129 USA. EM bradd@nmr.mgh.harvard.edu RI Scharre, Douglas/E-4030-2011 FU Alzheimer's Disease Neuroimaging Initiative (ADNI, NIH) [U01 AG024904]; National Institute of Ageing (NIA) [R01-AG29411, R21-AG29840, P50-AG005134, K23-AG028018, P30AG010124]; National Institute of Biomedical Imaging and Bioengineering (NIBIB); Foundation for the National Institutes of Health; Alzheimer's Association FX This work was primarily funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI, Principal Investigator: Michael Weiner; NIH grant No U01 AG024904). ADNI is funded by the National Institute of Ageing, the National Institute of Biomedical Imaging and Bioengineering (NIBIB) and the Foundation for the National Institutes of Health, through generous contributions from the following companies and organisations: Pfizer Inc, Wyeth Research, Bristol-Myers Squibb, Eli Lilly and Company, GlaxoSmithKline, Merck & Co Inc, AstraZeneca AB, Novartis Pharmaceuticals Corporation, the Alzheimer's Association, Eisai Global Clinical Development, Elan Corporation plc, Forest Laboratories and the Institute for the Study of Ageing (ISOA), with participation from the US Food and Drug Administration. The grantee organisation is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. This analysis was also supported by grants from the NIA R01-AG29411, R21-AG29840, P50-AG005134, K23-AG028018, P30AG010124 and the Alzheimer's Association. NR 28 TC 43 Z9 43 U1 0 U2 7 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 JAN PY 2011 VL 82 IS 1 BP 45 EP 51 DI 10.1136/jnnp.2009.199505 PG 7 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 692VF UT WOS:000285183000013 PM 20562467 ER PT J AU Mercer, AJ Rabl, K Riccardi, GE Brecha, NC Stella, SL Thoreson, WB AF Mercer, A. J. Rabl, K. Riccardi, G. E. Brecha, N. C. Stella, S. L., Jr. Thoreson, W. B. TI Location of Release Sites and Calcium-Activated Chloride Channels Relative to Calcium Channels at the Photoreceptor Ribbon Synapse SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID TIGER SALAMANDER RETINA; CA2+-ACTIVATED CL-CHANNEL; CELL AFFERENT SYNAPSE; TRANSMITTER RELEASE; INTRACELLULAR CALCIUM; ROD PHOTORECEPTORS; CONE PHOTORECEPTORS; CA2+ CHANNELS; PRESYNAPTIC TERMINALS; QUANTITATIVE-ANALYSIS AB Mercer AJ, Rabl K, Riccardi GE, Brecha NC, Stells SL Jr, Thoreson WB. Location of release sites and calcium-activated chloride channels relative to calcium channels at the photoreceptor ribbon synapse. J Neurophysiol 105: 321-335, 2011. First published November 17, 2010; doi:10.1152/jn.00332.2010. Vesicle release from photoreceptor ribbon synapses is regulated by L-type Ca2+ channels, which are in turn regulated by Cl- moving through calcium-activated chloride [Cl(Ca)] channels. We assessed the proximity of Ca2+ channels to release sites and Cl(Ca) channels in synaptic terminals of salamander photoreceptors by comparing fast (BAPTA) and slow (EGTA) intracellular Ca2+ buffers. BAPTA did not fully block synaptic release, indicating some release sites are <100 nm from Ca2+ channels. Comparing Cl(Ca) currents with predicted Ca2+ diffusion profiles suggested that Cl(Ca) and Ca2+ channels average a few hundred nanometers apart, but the inability of BAPTA to block Cl(Ca) currents completely suggested some channels are much closer together. Diffuse immunolabeling of terminals with an antibody to the putative Cl(Ca) channel TMEM16A supports the idea that Cl(Ca) channels are dispersed throughout the presynaptic terminal, in contrast with clustering of Ca2+ channels near ribbons. Cl(Ca) currents evoked by intracellular calcium ion concentration ([Ca2+](i)) elevation through flash photolysis of DM-nitrophen exhibited EC50 values of 556 and 377 nM with Hill slopes of 1.8 and 2.4 in rods and cones, respectively. These relationships were used to estimate average submembrane [Ca2+](i) in photoreceptor terminals. Consistent with control of exocytosis by [Ca2+] nanodomains near Ca2+ channels, average submembrane [Ca2+](i) remained below the vesicle release threshold (similar to 400 nM) over much of the physiological voltage range for cones. Positioning Ca2+ channels near release sites may improve fidelity in converting voltage changes to synaptic release. A diffuse distribution of Cl(Ca) channels may allow Ca2+ influx at one site to influence relatively distant Ca2+ channels. C1 [Mercer, A. J.] Univ Nebraska Med Ctr, Dept Ophthalmol & Visual Sci, Durham Res Ctr 4050, Omaha, NE 68198 USA. [Mercer, A. J.; Thoreson, W. B.] Univ Nebraska Med Ctr, Dept Pharmacol & Expt Neurosci, Omaha, NE 68198 USA. [Rabl, K.] Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA 94143 USA. [Brecha, N. C.] Univ Calif Los Angeles, Dept Med, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Riccardi, G. E.; Brecha, N. C.; Stella, S. L., Jr.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA. [Brecha, N. C.] Univ Calif Los Angeles, Ctr Ulcer Res & Educ, Digest Dis Res Ctr, Los Angeles, CA 90024 USA. [Brecha, N. C.] Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Thoreson, WB (reprint author), Univ Nebraska Med Ctr, Dept Ophthalmol & Visual Sci, Durham Res Ctr 4050, Omaha, NE 68198 USA. EM wbthores@unmc.edu RI Mercer, Aaron/G-4163-2010; riccardi, gabriele/A-9269-2012; OI Mercer, Aaron/0000-0002-9586-6610; Stella Jr., Salvatore/0000-0003-1971-2537; Thoreson, Wallace/0000-0001-7104-042X FU Research to Prevent Blindness, National Eye Institute [EY-10542, EY-15573]; National Institutes of Health; Department of Veterans Affairs; University of Nebraska Medical Center FX This work was supported by Research to Prevent Blindness, National Eye Institute Grants EY-10542 to W. B. Thoreson and EY-15573 to N. C. Brecha, National Institutes of Health American Recovery and Reinvestment Act award to support G. E. Riccardi (to N. C. Brecha), a Senior Career Scientist Award from the Department of Veterans Affairs to N. C. Brecha, Fight for Sight grant to K. Rabl, and a University of Nebraska Medical Center Graduate Student Fellowship to A. Mercer. NR 97 TC 24 Z9 25 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JAN PY 2011 VL 105 IS 1 BP 321 EP 335 DI 10.1152/jn.00332.2010 PG 15 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 705MU UT WOS:000286139900027 PM 21084687 ER PT J AU Ogilvy, CS Yang, XY Jamil, OA Hauck, EF Hopkins, LN Siddiqui, AH Levy, EI AF Ogilvy, Christopher S. Yang, Xinyu Jamil, Osama A. Hauck, Erik F. Hopkins, L. Nelson Siddiqui, Adnan H. Levy, Elad I. TI Neurointerventional procedures for unruptured intracranial aneurysms under procedural sedation and local anesthesia: a large-volume, single-center experience Clinical article SO JOURNAL OF NEUROSURGERY LA English DT Article DE conscious sedation; hospital stay; local anesthesia; morbidity; mortality; neurointerventional procedure; unruptured intracranial aneurysm ID GUGLIELMI DETACHABLE COILS; CEREBRAL-ARTERY ANEURYSMS; TERM-FOLLOW-UP; ENDOVASCULAR TREATMENT; EMBOLIZATION; MORBIDITY; MORTALITY; FEASIBILITY; OCCLUSION; OUTCOMES AB Object. In this paper, the authors' goal was to report the outcome of patients with unruptured intracranial aneurysms undergoing endovascular treatment under conscious sedation (local anesthesia). Methods. Between November 5, 2001, and February 5, 2009, the authors treated 340 patients with 358 unruptured aneurysms by using neurointerventional procedures at Millard Fillmore Gates Hospital (Buffalo, New York). The data were retrospectively reviewed for periprocedural safety and long-term follow-up. Results. A total of 496 procedures were performed under local anesthesia. Of those, 370 procedures (74.6%) were completed successfully. In 82 procedures (16.5%), an associated medical or technical event occurred. Forty-four procedures (8.9%) were aborted. Rates of overall procedure-related morbidity and mortality were 1.2% (6 of 496) and 0.6% (3 of 496), respectively. The average hospital stay was 1.5 +/- 2.5 days. Long-term follow-up was available in 261 (82.1%) of 318 patients whose procedures were performed with local anesthesia. Of those, 246 patients (94.3%) had a good outcome (modified Rankin Scale score <= 2), 6 patients (2.3%) had an unfavorable outcome, not related to the procedure, and 9 patients (3.4%) had a poor outcome (modified Rankin Scale score > 2) as a result of the intervention. Conclusions. Interventional treatment under conscious sedation (local anesthesia) can be effectively performed in most patients with unruptured intracranial aneurysms and is associated with a short hospital stay and low morbidity and mortality. (DOI: 10.3171/2010.3.JNS091384) C1 [Ogilvy, Christopher S.] Massachusetts Gen Hosp, Neurosurg Serv, Wang Ambulatory Care Ctr ACC 745, Boston, MA 02114 USA. [Ogilvy, Christopher S.; Hauck, Erik F.; Hopkins, L. Nelson; Siddiqui, Adnan H.; Levy, Elad I.] SUNY Buffalo, Dept Neurosurg, Buffalo, NY 14260 USA. [Ogilvy, Christopher S.; Hauck, Erik F.; Hopkins, L. Nelson; Siddiqui, Adnan H.; Levy, Elad I.] SUNY Buffalo, Toshiba Stroke Res Ctr, Buffalo, NY 14260 USA. [Hopkins, L. Nelson; Siddiqui, Adnan H.; Levy, Elad I.] SUNY Buffalo, Sch Med & Biomed Sci, Dept Radiol, Buffalo, NY 14260 USA. [Ogilvy, Christopher S.; Hauck, Erik F.; Hopkins, L. Nelson; Siddiqui, Adnan H.; Levy, Elad I.] Kaleida Hlth, Millard Fillmore Gates Hosp, Dept Neurosurg, Buffalo, NY USA. [Yang, Xinyu] Tianjin Med Univ Gen Hosp, Dept Neurosurg, Tianjin, Peoples R China. RP Ogilvy, CS (reprint author), Massachusetts Gen Hosp, Neurosurg Serv, Wang Ambulatory Care Ctr ACC 745, Parkman St, Boston, MA 02114 USA. EM cogilvy@partners.org FU Abbott; Cordis; ev3; Toshiba; AccessClosure; Boston Scientific; Micrus; Stent-Assisted Recanalization in acute Ischemic Stroke, SARIS; University at Buffalo; National Institutes of Health (MINDS) [1R01NS064592-01A1] FX Dr. Hopkins receives research study grants from Abbott (ACT I Choice), Boston Scientific (CABANA), Cordis (SAPPHIRE WW), and ev3 (CREATE) and a research grant from Toshiba (for the Toshiba Stroke Research Center); has an ownership/financial interest in AccessClosure, Boston Scientific, and Micrus; serves on the Abbott Vascular Speakers' Bureau; receives honoraria from Bard, Boston Scientific, Cordis, and from the following for speaking at conferences Complete Conference Management, Cleveland Clinic, and SCAI; serves as a consultant to or on the advisory boards for Abbott, AccessClosure, Bard, Boston Scientific, Cordis, Gore, Lumen Biomedical, Miens, and Toshiba; and serves as the conference director for Nurcon Conferences/Strategic Medical Seminars LLC.; Dr. Levy receives research grant support (principal investigator: Stent-Assisted Recanalization in acute Ischemic Stroke, SARIS; other research support (devices), and honoraria from Boston Scientific and research support from Micrus Endovascular and ev3; has ownership interests in Intratech Medical Ltd. and Mynx/Access Closure; serves as a consultant on the board of Scientific Advisors to Codman Neurovascular/Cordis Corp.; serves as a consultant per project and/or per hour for Micrus Endovascular, ev3, and TheraSyn Sensors, Inc.; and receives fees for carotid stent training from Abbott Vascular and ev3. Dr. Levy receives no consulting salary arrangements. All consulting is per project and/or per hour.; Dr. Siddiqui has received research grants from the University at Buffalo and from the National Institutes of Health (MINDS Grant No. 1R01NS064592-01A1); is a consultant to Codman Neurovascular/Cordis Corp., Concentric Medical, ev3, and Micrus Endovascular; serves on speakers' bureaus for Codman Neurovascular/Cordis Corp. and Genentech; and has received honoraria from Genentech, Neocure Group LLC, an American Association of Neurological Surgeons' course, and an Emergency Medicine Conference and from Codman Neurovascular/Cordis Corporation for training other neurointerventionists. Dr. Siddiqui receives no consulting salary arrangements. All consulting is per project and/or per hour. NR 33 TC 8 Z9 8 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD JAN PY 2011 VL 114 IS 1 BP 120 EP 128 DI 10.3171/2010.3.JNS091384 PG 9 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 699NG UT WOS:000285669500024 PM 20397895 ER PT J AU Mazzuca, M Jambaque, I Hertz-Pannier, L Bouilleret, V Archambaud, F Caviness, V Rodrigo, S Dulac, O Chiron, C AF Mazzuca, Michel Jambaque, Isabelle Hertz-Pannier, Lucie Bouilleret, Viviane Archambaud, Frederique Caviness, Verne Rodrigo, Sebastian Dulac, Olivier Chiron, Catherine TI F-18-FDG PET Reveals Frontotemporal Dysfunction in Children with Fever-Induced Refractory Epileptic Encephalopathy SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE PET; epilepsy; encephalopathy; child; cognitive impairment ID CEREBRAL GLUCOSE-METABOLISM; TEMPORAL-LOBE EPILEPSY; EMISSION-TOMOGRAPHY; MEMORY IMPAIRMENT; INFANTILE SPASMS; EEG-FMRI; ENCEPHALITIS; SURGERY; SLEEP; MRI AB Fever-induced refractory epileptic encephalopathy in school-age children (FIRES) is a recently described epileptic entity whose etiology remains unknown. Brain abnormalities shown by MRI are usually limited to mesial-temporal structures and do not account for the catastrophic neuropsychologic findings. Methods: We conducted FIRES studies in 8 patients, aged 6-13 y, using F-18-FDG PET to disclose eventual neocortical dysfunction. Voxel-based analyses of cerebral glucose metabolism were performed using statistical parametric mapping and an age-matched control group. Results: Group analysis revealed a widespread interictal hypometabolic network including the temporoparietal and orbitofrontal cortices bilaterally. The individual analyses in patients identified hypometabolic areas corresponding to the predominant electroencephalograph foci and neuropsychologic deficits involving language, behavior, and memory. Conclusion: Despite clinical heterogeneity, F-18-FDG PET reveals a common network dysfunction in patients with sequelae due to fever-induced refractory epileptic encephalopathy. C1 [Chiron, Catherine] Hop Necker Enfants Malad, AP HP, Serv Neurol & Metab, Neuropediat Dept,U663, F-75015 Paris, France. [Jambaque, Isabelle; Hertz-Pannier, Lucie; Bouilleret, Viviane; Archambaud, Frederique; Rodrigo, Sebastian; Dulac, Olivier; Chiron, Catherine] Univ Paris 05, INSERM, U663, Paris, France. [Jambaque, Isabelle] Inst Psychol, Boulogne, France. [Hertz-Pannier, Lucie; Bouilleret, Viviane; Archambaud, Frederique; Rodrigo, Sebastian; Chiron, Catherine] Hosp Frederic Joliot, I2BM, CEA, Orsay, France. [Hertz-Pannier, Lucie; Rodrigo, Sebastian; Dulac, Olivier; Chiron, Catherine] IFR 49, F-91191 Gif Sur Yvette, France. [Caviness, Verne] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Chiron, C (reprint author), Hop Necker Enfants Malad, AP HP, Serv Neurol & Metab, Neuropediat Dept,U663, 145 Rue Sevres, F-75015 Paris, France. EM catherine.chiron@nck.aphp.fr RI Chiron, Catherine/E-8506-2016 FU Fondation pour la Recherche sur le Cerveau FX This work was supported by a grant provided by the Fondation pour la Recherche sur le Cerveau. NR 40 TC 16 Z9 19 U1 1 U2 4 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD JAN 1 PY 2011 VL 52 IS 1 BP 40 EP 47 DI 10.2967/jnumed.110.077214 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 699TT UT WOS:000285686400012 PM 21149491 ER PT J AU Catana, C Benner, T van der Kouwe, A Byars, L Hamm, M Chonde, DB Michel, CJ El Fakhri, G Schmand, M Sorensen, G AF Catana, Ciprian Benner, Thomas van der Kouwe, Andre Byars, Larry Hamm, Michael Chonde, Daniel B. Michel, Christian J. El Fakhri, Georges Schmand, Matthias Sorensen, Gregory TI MRI-Assisted PET Motion Correction for Neurologic Studies in an Integrated MR-PET Scanner SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE PET; MRI; multimodality imaging; motion tracking; motion correction ID POSITRON-EMISSION-TOMOGRAPHY; LIST-MODE RECONSTRUCTION; SENSITIVITY IMAGE; BRAIN; IMPLEMENTATION; NORMALIZATION; ALGORITHM; TRACKING; SYSTEM; SCHEME AB Head motion is difficult to avoid in long PET studies, degrading the image quality and offsetting the benefit of using a high-resolution scanner. As a potential solution in an integrated MR-PET scanner, the simultaneously acquired MRI data can be used for motion tracking. In this work, a novel algorithm for data processing and rigid-body motion correction (MC) for the MRI-compatible BrainPET prototype scanner is described, and proof-of-principle phantom and human studies are presented. Methods: To account for motion, the PET prompt and random coincidences and sensitivity data for postnormalization were processed in the line-of-response (LOR) space according to the MRI-derived motion estimates. The processing time on the standard BrainPET workstation is approximately 16 s for each motion estimate. After rebinning in the sinogram space, the motion corrected data were summed, and the PET volume was reconstructed using the attenuation and scatter sinograms in the reference position. The accuracy of the MC algorithm was first tested using a Hoffman phantom. Next, human volunteer studies were performed, and motion estimates were obtained using 2 high-temporal-resolution MRI-based motion-tracking techniques. Results: After accounting for the misalignment between the 2 scanners, perfectly coregistered MRI and PET volumes were reproducibly obtained. The MRI output gates inserted into the PET list-mode allow the temporal correlation of the 2 datasets within 0.2 ms. The Hoffman phantom volume reconstructed by processing the PET data in the LOR space was similar to the one obtained by processing the data using the standard methods and applying the MC in the image space, demonstrating the quantitative accuracy of the procedure. In human volunteer studies, motion estimates were obtained from echo planar imaging and cloverleaf navigator sequences every 3 s and 20 ms, respectively. Motion-deblurred PET images, with excellent delineation of specific brain structures, were obtained using these 2 MRI-based estimates. Conclusion: An MRI-based MC algorithm was implemented for an integrated MR-PET scanner. High-temporal-resolution MRI-derived motion estimates (obtained while simultaneously acquiring anatomic or functional MRI data) can be used for PET MC. An MRI-based MC method has the potential to improve PET image quality, increasing its reliability, reproducibility, and quantitative accuracy, and to benefit many neurologic applications. C1 [Catana, Ciprian; Benner, Thomas; van der Kouwe, Andre; Chonde, Daniel B.; Sorensen, Gregory] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Marinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Catana, Ciprian; Benner, Thomas; van der Kouwe, Andre; Chonde, Daniel B.; Sorensen, Gregory] Harvard Univ, Sch Med, Charlestown, MA USA. [El Fakhri, Georges] Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. [El Fakhri, Georges] Harvard Univ, Sch Med, Boston, MA USA. RP Catana, C (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Marinos Ctr Biomed Imaging, Bldg 149,Rm 2301,13th St, Charlestown, MA 02129 USA. EM ccatana@nmr.mgh.harvard.edu FU NIH [1R01CA137254-01A1] FX This work was partly supported by NIH grant 1R01CA137254-01A1. NR 28 TC 68 Z9 68 U1 0 U2 11 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD JAN 1 PY 2011 VL 52 IS 1 BP 154 EP 161 DI 10.2967/jnumed.110.079343 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 699TT UT WOS:000285686400029 PM 21189415 ER PT J AU Rice, MB Cavallari, J Fang, SN Christiani, D AF Rice, Mary Berlik Cavallari, Jenn Fang, Shona Christiani, David TI Acute Decrease in HDL Cholesterol Associated With Exposure to Welding Fumes SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID PARTICULATE AIR-POLLUTION; OXIDATIVE STRESS; NITROGEN-DIOXIDE; ATHEROSCLEROSIS; WELDERS; DISEASE; MATTER; CIRCULATION; MECHANISMS; POLLUTANTS AB Objective: To investigate acute changes in circulating lipids after exposure to relatively high levels of particulate matter through welding. Methods: Using a repeated measures panel study, lipid levels before and after welding and personal exposures to fine particulate matter (PM(2.5)) were measured in 36 male welders over 63 exposure and/or control days. Results: There was a trend toward decrease in HDL(-2.3mg/dL, P = 0.08) 18 hours after welding. This effect became significant (-2.6 mg/dL, P = 0.05) after adjustment for possible confounders. The effect was strongest (-4.3 mg/dL, P = 0.02) among welders who did not weld the day before the study. There were no significant changes in other lipids associated with welding or PM2.5 exposure. Conclusion: Welding exposure was associated with an acute decrease in circulating HDL, which may relate to the inflammatory and proatherosclerotic effects of fine particle exposure. C1 [Rice, Mary Berlik; Christiani, David] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Dept Med, Boston, MA 02114 USA. [Cavallari, Jenn; Fang, Shona; Christiani, David] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Boston, MA 02115 USA. RP Rice, MB (reprint author), Massachusetts Gen Hosp, Pulm & Crit Care Unit, Dept Med, 55 Fruit St, Boston, MA 02114 USA. EM mrice2@partners.org OI Rice, Mary/0000-0003-2538-391X FU National Institute of Environmental Health Sciences (NIEHS) [ES009860, ES00002, T42 OH008416]; National Institute for Occupational Safety and Health (NIOSH) [T32 ES 07069]; Flight Attendants Medical Research Institute FX The study and staff were funded by the National Institute of Environmental Health Sciences (NIEHS) grants ES009860, ES00002, and T42 OH008416 and National Institute for Occupational Safety and Health (NIOSH) grant T32 ES 07069 and the Flight Attendants Medical Research Institute. NR 32 TC 3 Z9 3 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD JAN PY 2011 VL 53 IS 1 BP 17 EP 21 DI 10.1097/JOM.0b013e3182028d20 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 704KL UT WOS:000286051800004 PM 21187793 ER PT J AU Kim, A Kamyab, K Zhu, JS Volpp, K AF Kim, Annice Kamyab, Kian Zhu, Jingsan Volpp, Kevin TI Why are Financial Incentives not Effective at Influencing Some Smokers to Quit? Results of a Process Evaluation of a Worksite Trial Assessing the Efficacy of Financial Incentives for Smoking Cessation SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; WEIGHT-LOSS; PROGRAM; SUCCESS AB Objective: Process evaluation of a worksite intervention in which employees were offered $750 to complete a cessation program and to quit smoking. Methods: Awareness and attitudes about financial incentives were assessed following a randomized controlled trial of 878 smokers at a US-based company. Results: Cessation program attendance was higher in incentive group versus control (20.2% vs 7.1%, P < 0.01). Most quitters (69.8%) in the incentive group who were already motivated to quit and reported that they would have quit for less money, said incentives were "not at all" or only "somewhat" important. Most nonquitters in the incentive group reported that even $1500 would not have motivated them to quit. Conclusions: Financial incentives are ineffective at motivating some smokers to quit. Internal motivation and readiness to quit need to be sufficiently high for relatively modest incentives to be effective. C1 [Kim, Annice; Kamyab, Kian] RTI Int, Publ Hlth Policy Res Program, Res Triangle Pk, NC 27709 USA. [Zhu, Jingsan; Volpp, Kevin] Univ Penn, Sch Med, Dept Hlth Care Syst, Philadelphia, PA 19104 USA. [Volpp, Kevin] Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. [Volpp, Kevin] Univ Penn, Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. [Zhu, Jingsan; Volpp, Kevin] Univ Penn, Leonard Davis Inst Hlth Econ, Ctr Hlth Incent, Philadelphia, PA 19104 USA. RP Kim, A (reprint author), RTI Int, Publ Hlth Policy Res Program, 3040 E Cornwallis Rd, Res Triangle Pk, NC 27709 USA. EM akim@rti.org NR 22 TC 14 Z9 14 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD JAN PY 2011 VL 53 IS 1 BP 62 EP 67 DI 10.1097/JOM.0b013e31820061d7 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 704KL UT WOS:000286051800011 PM 21187795 ER PT J AU Yue, B Varadarajan, KM Moynihan, AL Liu, F Rubash, HE Li, GA AF Yue, Bing Varadarajan, Kartik M. Moynihan, Angela L. Liu, Fang Rubash, Harry E. Li, Guoan TI Kinematics of Medial Osteoarthritic Knees before and after Posterior Cruciate Ligament Retaining Total Knee Arthroplasty SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE tibiofemoral joint; kinematics; osteoarthritis; total knee arthroplasty; weight-bearing flexion ID IN-VIVO KINEMATICS; WEIGHT-BEARING; FEMORAL ROLLBACK; REPLACEMENT; FLEXION; NAVIGATION; RESECTION; SYSTEM; FORCES; JOINT AB Total knee arthroplasty (TKA) is a widely accepted surgical procedure for the treatment of patients with end-stage osteoarthritis (OA). However, the function of the knee is not always fully recovered after TKA. We used a dual fluoroscopic imaging system to evaluate the in vivo kinematics of the knee with medial compartment OA before and after a posterior cruciate ligament-retaining TKA (PCR-TKA) during weight-bearing knee flexion, and compared the results to those of normal knees. The OA knees displayed similar internal/external tibial rotation to normal knees. However, the OA knees had less overall posterior femoral translation relative to the tibia between 0 and 105 flexion and more varus knee rotation between 0 and 45 flexion, than in the normal knees. Additionally, in the OA knees the femur was located more medially than in the normal knees, particularly between 30 and 60 flexion. After PCR-TKA, the knee kinematics were not restored to normal. The overall internal tibial rotation and posterior femoral translation between 0 and 105 knee flexion were dramatically reduced. Additionally, PCR-TKA introduced an abnormal anterior femoral translation during early knee flexion, and the femur was located lateral to the tibia throughout weight-bearing flexion. The data help understand the biomechanical functions of the knee with medial compartment OA before and after contemporary PCR-TKA. They may also be useful for improvement of future prostheses designs and surgical techniques in treatment of knees with end-stage OA. (C) 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29: 40-46, 2011 C1 [Yue, Bing; Varadarajan, Kartik M.; Moynihan, Angela L.; Liu, Fang; Rubash, Harry E.; Li, Guoan] Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab, Boston, MA 02114 USA. [Yue, Bing; Varadarajan, Kartik M.; Moynihan, Angela L.; Liu, Fang; Rubash, Harry E.; Li, Guoan] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Yue, Bing] Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 9, Dept Orthopaed Surg,Shanghai Key Lab Orthopaed Im, Shanghai, Peoples R China. [Varadarajan, Kartik M.] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. RP Li, GA (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@partners.org FU Department of Orthopaedics, MGH; Program for Shanghai Key Laboratory of Orthopaedic Implant [08DZ2230330]; National Natural Science Foundation of China [30901517] FX This study was supported by an AEF grant of Department of Orthopaedics, MGH. The authors acknowledge support of the Program for Shanghai Key Laboratory of Orthopaedic Implant (08DZ2230330) and the National Natural Science Foundation of China (30901517). NR 41 TC 27 Z9 28 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0736-0266 EI 1554-527X J9 J ORTHOP RES JI J. Orthop. Res. PD JAN PY 2011 VL 29 IS 1 BP 40 EP 46 DI 10.1002/jor.21203 PG 7 WC Orthopedics SC Orthopedics GA 694TM UT WOS:000285321900007 PM 20607694 ER PT J AU Chou, CW Wong, GTC Lim, G Wang, SX Irwin, MG Mao, JR AF Chou, Chiu-Wen Wong, Gordon T. C. Lim, Grewo Wang, Shuxing Irwin, Michael G. Mao, Jianren TI Spatiotemporal Pattern of Concurrent Spinal and Supraspinal NF-kappa B Expression After Peripheral Nerve Injury SO JOURNAL OF PAIN LA English DT Article DE Neuropathic pain; NF-kappa B; affective; somatosensory cortex; thalamus; anterior cingulate cortex; amygdala ID ANTERIOR CINGULATE CORTEX; PRIMARY SOMATOSENSORY CORTEX; NEUROPATHIC PAIN; SCIATIC-NERVE; ESCAPE/AVOIDANCE BEHAVIOR; TRANSCRIPTION FACTOR; INFLAMMATORY PAIN; CORD-INJURY; RAT MODEL; MECHANISMS AB The expression of NF-kappa B in the spinal cord is associated with neuropathic pain. However, little is known about its expression beyond the spinal cord. Here we examined a spatial and temporal pattern of the NF-kappa B expression in both spinal and supraspinal regions. After chronic constriction injury (CCI) of the sciatic nerve, NF-kappa B (p65) expression was significantly increased in the ipsilateral spinal cord. In contrast, the NF-kappa B expression in the contralateral primary somatosensory cortex was decreased with no significant differences seen in the thalamus. In the contralateral anterior cingulate cortex, the NF-kappa B expression was increased significantly on day 14 as compared with the sham group. In the contralateral amygdala, the NF-kappa B expression showed a time-dependent downregulation after CCI, which became significant on day 14. MK-801 reduced nociceptive behaviors and reversed the direction of NF-kappa B expression. These results indicate that the CCI-induced expression of p65 NF-kappa B is both time-dependent and region-specific, in areas that process both sensory-discriminative and motivational-affective dimensions of pain. Perspective: This article presents a spatiotemporal mapping of the NF-kappa B expression in spinal and supraspinal regions after peripheral nerve injury. These findings point to an involvement of NF-kappa B beyond the spinal cord in both the sensory discriminative and emotional affective aspects of neuropathic pain processing. (C) 2011 by the American Pain Society C1 [Chou, Chiu-Wen; Lim, Grewo; Wang, Shuxing; Mao, Jianren] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Anesthesia & Crit Care, MGH Ctr Translat Pain Res, Boston, MA 02114 USA. [Chou, Chiu-Wen; Wong, Gordon T. C.; Irwin, Michael G.] Univ Hong Kong, Dept Anaesthesiol, Li Ka Shing Fac Med, Hong Kong, Hong Kong, Peoples R China. RP Mao, JR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Anesthesia & Crit Care, MGH Ctr Translat Pain Res, WACC 324, Boston, MA 02114 USA. EM jmao@partners.org FU NIH [DE18214, DE18538, NS45681] FX Supported by NIH RO1 grants DE18214, DE18538, and NS45681. NR 53 TC 4 Z9 7 U1 1 U2 4 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD JAN PY 2011 VL 12 IS 1 BP 13 EP 21 DI 10.1016/j.jpain.2010.03.018 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 710XG UT WOS:000286549700003 PM 20537956 ER PT J AU Jackson, V Arnold, RM AF Jackson, Vicki Arnold, Robert M. TI Using Small Groups To Promote Self-Awareness Introduction SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Editorial Material C1 [Jackson, Vicki] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jackson, V (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM VJackson@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD JAN PY 2011 VL 14 IS 1 BP 89 EP 89 DI 10.1089/jpm.2010.9744 PG 1 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 708SI UT WOS:000286384200019 PM 21244258 ER PT J AU Macauley, R Billings, JA AF Macauley, Robert Billings, J. Andrew TI Teaching Small Groups in Palliative Care SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID PERCEPTIONS; TUTORS AB Small group learning (i.e., tutorial, seminar, or small problem-solving class) is uniquely suited to transformative change as the ultimate goal of education, and especially appropriate for use in teaching about palliative care. The small group can be a fertile environment for both individual and communal development on both personal and professional levels by recognizing the unique needs of small group facilitation, and developing necessary faculty skills, and by modeling thoughtful preparation, reflective execution, and perceptive feedback. The small group learning approach focuses on learning facilitation and enhancing students' communications skills, which are vital to providing effective, patient-centered palliative care. C1 [Macauley, Robert] Fletcher Allen Hlth Care, Dept Clin Eth, Burlington, VT 05401 USA. [Macauley, Robert] Fletcher Allen Hlth Care, Dept Pediat, Burlington, VT 05401 USA. [Macauley, Robert] Univ Vermont, Coll Med, Burlington, VT USA. [Billings, J. Andrew] Massachusetts Gen Hosp, Palliat Care Serv, Boston, MA 02114 USA. [Billings, J. Andrew] Harvard Univ, Sch Med, Ctr Palliat Care, Boston, MA USA. RP Macauley, R (reprint author), Fletcher Allen Hlth Care, Dept Clin Eth, 111 Colchester Ave,Smith 266, Burlington, VT 05401 USA. EM Robert.Macauley@vtmednet.org NR 21 TC 3 Z9 3 U1 0 U2 3 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 JAN PY 2011 VL 14 IS 1 BP 91 EP 95 DI 10.1089/jpm.2010.0215 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 708SI UT WOS:000286384200020 PM 21244259 ER PT J AU Castilla, MA Moreno-Bueno, G Romero-Perez, L Van De Vijver, K Biscuola, M Lopez-Garcia, MA Prat, J Matias-Guiu, X Cano, A Oliva, E Palacios, J AF Angeles Castilla, Maria Moreno-Bueno, Gema Romero-Perez, Laura Van De Vijver, Koen Biscuola, Michele Angeles Lopez-Garcia, Maria Prat, Jaime Matias-Guiu, Xavier Cano, Amparo Oliva, Esther Palacios, Jose TI Micro-RNA signature of the epithelial-mesenchymal transition in endometrial carcinosarcoma SO JOURNAL OF PATHOLOGY LA English DT Article DE miRNA; epithelial-mesenchymal transition; endometrial carcinosarcoma; differentiation; E-cadherin ID MIR-200 FAMILY; CANCER-CELLS; REPRESSORS ZEB1; BHLH FACTORS; STEM-CELLS; EMT; EXPRESSION; PHENOTYPE; DISEASE; PROGRESSION AB Endometrial carcinosarcomas (ECSs) undergo a true epithelial-mesenchymal transition (EMT). The molecular determinants of the EMT in vivo are unclear, although a role for some miRNAs, mainly involving the miR-200 family, was recently suggested from in vitro cellular models. We analysed the microRNA (miRNA) signatures associated to EMT in human carcinosarcomas, and determined their relationships with EMT markers and repressors of E-cadherin transcription. The expression of E-, P- and N-cadherin, cadherin-11, p120, vimentin, SPARC, fascin and caveolin-1 was studied in a group of 76 ECS by immunohistochemistry. In addition, real-time PCR was used to measure the differences in the expression of 384 miRNAs, E-cadherin, cadherin-11, SPARC, SNAIL, ZEB1, ZEB2, TWIST-1, TCF4, TGF beta 1 and TGF beta 2 between the epithelial and mesenchymal components of 23 ECSs. A loss of epithelial characteristics, including cadherin switching and the acquisition of a mesenchymal phenotype, was accompanied by changes in the profile of miRNA expression and the up-regulation of all the E-cadherin repressors analysed. A greater than five-fold difference in the expression of 14 miRNAs between both neoplastic components was seen. Members of the miR-200 family were down-regulated in the mesenchymal part of the ECS. In addition, miR-23b and miR-29c, which are involved in the inhibition of mesenchymal markers, and miR-203, which is involved in the inhibition of cell stemness, were also down-regulated. Up-regulated miRNAs included miR-155, miR-369-5p, miR-370, miR-450a and miR-542-5p. These data suggest that in human ECS, the interplay between transcriptional repressors of E-cadherin and miRNAs provides a link between EMT-activation and the maintenance of stemness. Copyright (C) 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. C1 [Angeles Castilla, Maria; Romero-Perez, Laura; Biscuola, Michele; Angeles Lopez-Garcia, Maria; Palacios, Jose] Hosp Univ Virgen del Rocio IBIS, Inst Biomed Sevilla, Dept Pathol, Seville, Spain. [Moreno-Bueno, Gema; Cano, Amparo] Inst Invest La Paz IdiPAZ, Dept Biochem UAM, Inst Invest Biomed Alberto Sols CSIC UAM, Madrid, Spain. [Van De Vijver, Koen; Oliva, Esther] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Prat, Jaime] Hosp Santa Creu & Sant Pau, Dept Pathol, Barcelona, Spain. [Matias-Guiu, Xavier] Univ Lleida, Dept Pathol & Mol Genet, Hosp Univ Arnau de Vilanova, IRBLLEIDA, Lleida, Spain. RP Palacios, J (reprint author), Hosp Univ Virgen del Rocio IBIS, Inst Biomed Sevilla, Dept Pathol, Seville, Spain. EM jose.palacios.sspa@juntadeandalucia.es RI Prat, Jaime/G-4679-2011; matias-guiu, xavier/C-3039-2009; Romero-Perez, Laura/C-8314-2015; Castilla, M Angeles/C-9454-2015; Moreno-Bueno, Gema/K-9354-2016 OI matias-guiu, xavier/0000-0002-7201-6605; Romero-Perez, Laura/0000-0003-3196-4382; Moreno-Bueno, Gema/0000-0002-5030-6687 FU Instituto de Salud Carlos III (ISCIII) [PI07/90324, PI 080971, RD06/0020/0013]; Ministerio de Ciencia e Innovacion (ISCIII); European Development Regional Fund, ERDF [RD06/0020/0013]; Junta de Andalucia (Consejeria de Salud) [PI-0384/2007]; Consejeria de Innovacion (Proyecto de Excelencia) [P07-CVI-03100]; MICINN [SAF2007-63051, CDS2007-00017, SAF2007-63065]; Fundacion Mutua Madrilena; PFIS [F109/00193]; Asociacion de padres de ninos oncologicos; Fondo de Investigaciones Sanitarias [CM06/00163]; Breast Cancer Research Centre (UK); Red Tematica de Investigacion Cooperativa en Cancer (RTICC); Fondo Europeo de Desarrollo Regional (FEDER) FX This study was supported by grants from the Instituto de Salud Carlos III (ISCIII; Grant Nos PI07/90324 and PI 080971) and the Ministerio de Ciencia e Innovacion (ISCIII), co-financed by the European Development Regional Fund, 'A way to achieve Europe' ERDF (Grant No. RD06/0020/0013), the Junta de Andalucia (Consejeria de Salud; Grant No. PI-0384/2007) and the Consejeria de Innovacion (Proyecto de Excelencia, Grant No. P07-CVI-03100) to JP. Partial support from the MICINN (SAF2007-63051; Consolider Grant No. CDS2007-00017 to AC; Grant No. SAF2007-63065 to GM-B), by grants from the Fundacion Mutua Madrilena to GMB (2007) and AC (2009) is also acknowledged. We are grateful to Ana Santos, Concepcion Morillo and Maria Jose Hernandez for excellent technical assistance. MAC is a postdoctoral researcher funded by the ISCIII (Grant No. RD06/0020/0013); LR-P is a graduate student (PFIS; Grant No. F109/00193); MB is a researcher funded by the Asociacion de padres de ninos oncologicos (Andex); MAL-G is the recipient of a research grant from the Fondo de Investigaciones Sanitarias (Grant No. CM06/00163) and is partially funded by the Breakthrough Breast Cancer Research Centre (UK) and the Red Tematica de Investigacion Cooperativa en Cancer (RTICC), Fondo Europeo de Desarrollo Regional (FEDER). NR 40 TC 111 Z9 122 U1 2 U2 32 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0022-3417 J9 J PATHOL JI J. Pathol. PD JAN PY 2011 VL 223 IS 1 BP 72 EP 80 DI 10.1002/path.2802 PG 9 WC Oncology; Pathology SC Oncology; Pathology GA 696FH UT WOS:000285426800009 PM 21125666 ER PT J AU Pao, W Iafrate, AJ Su, ZL AF Pao, William Iafrate, A. John Su, Zengliu TI Genetically informed lung cancer medicine SO JOURNAL OF PATHOLOGY LA English DT Review DE lung cancer; signal transduction pathway; gene mutation; protein kinase; targeted therapy; genetic analysis; sequencing; gene fusion; gene rearrangement ID SMALL-CELL LUNG; RECEPTOR TYROSINE KINASE; HEPATOCYTE GROWTH-FACTOR; EML4-ALK FUSION GENE; PHASE-II; C-MET; ACQUIRED-RESISTANCE; MUTATIONAL ANALYSIS; SOMATIC MUTATIONS; SIGNALING PATHWAY AB Knowledge of tumour mutation status has become increasingly important for the prioritization of targeted therapies for cancer. We review here the major known 'driver' mutations with therapeutic relevance in non-small cell lung cancer. We also discuss a variety of methods now being employed in molecular diagnostic laboratories to detect genetic alterations in lung tumours. A genetically-informed approach to lung cancer medicine is rapidly becoming the standard of care worldwide and should lead to improved outcomes for patients. Copyright (C) 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. C1 [Pao, William; Su, Zengliu] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Dept Med,Div Hematol Oncol, Nashville, TN 37232 USA. [Iafrate, A. John] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Pao, W (reprint author), Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Dept Med,Div Hematol Oncol, 2220 Pierce Ave,777 Preston Res Bldg, Nashville, TN 37232 USA. EM william.pao@vanderbilt.edu RI Su, Zengliu /E-3156-2010 FU Xcovery FX We report the following potential conflicts of interest: (a) AJI submitted a patent application for the SNaPshot genotyping methods described herein, which is the subject of licensing discussions; (b) WP has been a consultant for MolecularMD and rights to EGFR T790M testing were licensed on behalf of WP and others by MSKCC to MolecularMD. WP has received research funding from Xcovery and has been a consultant for AstraZeneca, Bristol-Myers Squibb and Symphony Evolution. NR 107 TC 41 Z9 43 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3417 J9 J PATHOL JI J. Pathol. PD JAN PY 2011 VL 223 IS 2 SI SI BP 230 EP 240 DI 10.1002/path.2788 PG 11 WC Oncology; Pathology SC Oncology; Pathology GA 697YB UT WOS:000285554600012 PM 21125677 ER PT J AU Ko, JM Fisher, DE AF Ko, Justin M. Fisher, David E. TI A new era: melanoma genetics and therapeutics SO JOURNAL OF PATHOLOGY LA English DT Review DE melanoma; pathogenesis; oncogenes; targeted therapy ID RECOMBINANT INTERLEUKIN-2 THERAPY; INHIBITOR AZD6244 ARRY-142886; PRIMARY CUTANEOUS MELANOMA; ENDOTHELIAL GROWTH-FACTOR; STAGE IV MELANOMA; MALIGNANT-MELANOMA; METASTATIC MELANOMA; BRAF MUTATIONS; TUMOR PROGRESSION; PHASE-II AB We have recently witnessed an explosion in our understanding of melanoma. Knowledge of the molecular basis of melanoma and the successes of targeted therapies have pushed melanoma care to the precipice of a new era. Identification of significant pathways and oncogenes has translated to the development of targeted therapies, some of which have produced major clinical responses. In this review, we provide an overview of selected key pathways and melanoma oncogenes as well as the targeted agents and therapeutic approaches whose successes suggest the promise of a new era in melanoma and cancer therapy. Despite these advances, the conversion of transient remissions to stable cures remains a vital challenge. Continued progress towards a better understanding about the complexity and redundancy responsible for melanoma progression may provide direction for anti-cancer drug development. Copyright (C) 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. C1 [Ko, Justin M.; Fisher, David E.] Harvard Univ, Dept Dermatol, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Fisher, DE (reprint author), Harvard Univ, Dept Dermatol, Sch Med, Massachusetts Gen Hosp, 55 Fruit St,Their 204, Boston, MA 02114 USA. EM dfisher3@partners.org FU NIAMS NIH HHS [R01 AR043369] NR 120 TC 60 Z9 61 U1 1 U2 17 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0022-3417 J9 J PATHOL JI J. Pathol. PD JAN PY 2011 VL 223 IS 2 SI SI BP 241 EP 250 DI 10.1002/path.2804 PG 10 WC Oncology; Pathology SC Oncology; Pathology GA 697YB UT WOS:000285554600013 PM 21125678 ER PT J AU Aster, JC Blacklow, SC Pear, WS AF Aster, Jon C. Blacklow, Stephen C. Pear, Warren S. TI Notch signalling in T-cell lymphoblastic leukaemia/lymphoma and other haematological malignancies SO JOURNAL OF PATHOLOGY LA English DT Review DE Notch signalling; oncogene; T-cell lymphoblastic leukaemia/lymphoma; chromosomal rearrangements; targeted therapy ID GAMMA-SECRETASE INHIBITORS; NF-KAPPA-B; CHRONIC LYMPHOCYTIC-LEUKEMIA; MOUSE THYMIC LYMPHOMAS; C-MYC; ALAGILLE-SYNDROME; TRANSGENIC MICE; GENE-EXPRESSION; TRANSCRIPTIONAL ACTIVATION; PROGNOSTIC-SIGNIFICANCE AB Notch receptors participate in a highly conserved signalling pathway that regulates normal development and tissue homeostasis in a context-and dose-dependent manner. Deregulated Notch signalling has been implicated in many diseases, but the clearest example of a pathogenic role is found in T-cell lymphoblastic leukaemia/lymphoma (T-LL), in which the majority of human and murine tumours have acquired mutations that lead to aberrant increases in Notch1 signalling. Remarkably, it appears that the selective pressure for Notch mutations is virtually unique among cancers to T-LL, presumably reflecting a special context-dependent role for Notch in normal T-cell progenitors. Nevertheless, there are some recent reports suggesting that Notch signalling has subtle, yet important roles in other forms of haematological malignancy as well. Here, we review the role of Notch signalling in various blood cancers, focusing on T-LL with an eye towards targeted therapeutics. Copyright (C) 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. C1 [Aster, Jon C.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Blacklow, Stephen C.] Harvard Univ, Dept Pathol, Sch Med, Boston, MA 02115 USA. [Blacklow, Stephen C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Pear, Warren S.] Univ Penn, Dept Pathol, Philadelphia, PA 19104 USA. RP Aster, JC (reprint author), Brigham & Womens Hosp, Dept Pathol, Room 652G,New Res Bldg,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM jaster@rics.bwh.harvard.edu FU National Institute of Health [P01CA119070, R01CA092433, R01AI047833, P01CA 119070]; Leukemia and Lymphoma Society FX This work was supported by grants from the National Institute of Health to JCA (P01CA119070), SCB (P01CA119070 and R01CA092433), and WSP (R01AI047833, P01CA 119070), and a Leukemia and Lymphoma Society SCOR Award to JCA, SCB, and WSP. NR 130 TC 86 Z9 94 U1 1 U2 13 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0022-3417 J9 J PATHOL JI J. Pathol. PD JAN PY 2011 VL 223 IS 2 SI SI BP 262 EP 273 DI 10.1002/path.2789 PG 12 WC Oncology; Pathology SC Oncology; Pathology GA 697YB UT WOS:000285554600015 PM 20967796 ER PT J AU Flavin, R Zadra, G Loda, M AF Flavin, Richard Zadra, Giorgia Loda, Massimo TI Metabolic alterations and targeted therapies in prostate cancer SO JOURNAL OF PATHOLOGY LA English DT Review DE prostate cancer; lipogenesis; fatty acid synthase; AMPK; inhibitors ID FATTY-ACID SYNTHASE; ACTIVATED PROTEIN-KINASE; PEUTZ-JEGHERS-SYNDROME; ATP CITRATE LYASE; BREAST-CANCER; CELL-GROWTH; LUNG-CANCER; JAPANESE POPULATION; LKB1-AMPK PATHWAY; DIABETIC-PATIENTS AB Cancer cells synthesize de novo large amounts of fatty acids and cholesterol, irrespective of the circulating lipid levels and benefit from this increased lipid synthesis in terms of growth advantage, self-survival and drug resistance. Key lipogenic alterations that commonly occur in prostate cancer include over-expression of the enzyme fatty acid synthase (FASN) and deregulation of the 5-AMP-activated protein kinase (AMPK). FASN is a key metabolic enzyme that catalyses the synthesis of palmitate from the condensation of malonyl-CoA and acetyl-CoA de novo and plays a central role in energy homeostasis, by converting excess carbon intake into fatty acids for storage. AMPK functions as a central metabolic switch that governs glucose and lipid metabolism. Recent interest has focused on the potential of targeting metabolic pathways that may be altered during prostate tumorigenesis and progression. Several small molecule inhibitors of FASN have now been described or in development for therapeutic use; in addition, drugs that directly or indirectly induce AMPK activation have potential benefit in prostate cancer prevention and treatment. Copyright (C) 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. C1 [Zadra, Giorgia; Loda, Massimo] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Flavin, Richard; Loda, Massimo] Harvard Univ, Sch Med, Ctr Mol Oncol Pathol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Flavin, Richard] Natl Univ Ireland, Dept Pathol, Galway, Ireland. [Loda, Massimo] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Loda, Massimo] Broad Inst, Cambridge, MA USA. RP Loda, M (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM massimo_loda@dfci.harvard.edu FU Prostate Cancer Foundation; National Cancer Institute [R01CA131945, P01CA89021, P50CA90381]; Linda and Arthur Gelb Center for Translational Research FX We thank Michael Cichanowski for his graphic assistance. This work was supported by the Prostate Cancer Foundation, the National Cancer Institute (Grant Nos R01CA131945, P01CA89021 and P50CA90381) and the Linda and Arthur Gelb Center for Translational Research. NR 131 TC 73 Z9 76 U1 3 U2 20 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0022-3417 J9 J PATHOL JI J. Pathol. PD JAN PY 2011 VL 223 IS 2 SI SI BP 283 EP 294 DI 10.1002/path.2809 PG 12 WC Oncology; Pathology SC Oncology; Pathology GA 697YB UT WOS:000285554600017 PM 21125681 ER PT J AU Bombonati, A Sgroi, DC AF Bombonati, Alessandro Sgroi, Dennis C. TI The molecular pathology of breast cancer progression SO JOURNAL OF PATHOLOGY LA English DT Review DE flat epithelial atypia; atypical ductal hyperplasia; ductal carcinoma in situ; breast cancer progression; genetics; transcriptomics; epigenetics; tumour environment ID COMPARATIVE GENOMIC HYBRIDIZATION; CARCINOMA IN-SITU; TERM FOLLOW-UP; ATYPICAL DUCTAL HYPERPLASIA; GENE-EXPRESSION PROFILES; ESTROGEN-RECEPTOR STATUS; ADULT HUMAN BREAST; STEM-CELLS; LOBULAR CARCINOMA; HISTOLOGICAL GRADE AB The current model of human breast cancer progression proposes a linear multi-step process which initiates as flat epithelial atypia (FEA), progresses to atypical ductal hyperplasia (ADH), evolves into DCIS and culminates in the potentially lethal stage of invasive ductal carcinoma. For several decades a major challenge to human breast cancer research has been the identification of the molecular alterations associated with the different stages of breast cancer progression. Until recently, progress in attaining this goal has been hampered by technical limitations associated with applying advanced molecular technologies to the microscopic preinvasive stages of breast tumorigenesis. Recent advances in comprehensive, high-throughput genetic, transcriptomic and epigenetic technologies in combination with advanced microdissection and ex vivo isolation techniques have provided for a more complete understanding of the complex molecular genetic and molecular biological inter-relationships of the different stages of human breast cancer evolution. Here we review the molecular biological data suggesting that breast cancer develops and evolves along two distinct molecular genetic pathways. We also briefly review gene expression and epigenetic data that support the view of the tumour microenvironment as an important co-conspirator rather than a passive bystander during human breast tumorigenesis. Copyright (C) 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. C1 [Bombonati, Alessandro; Sgroi, Dennis C.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp,Res Unit, Boston, MA 02115 USA. [Sgroi, Dennis C.] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. RP Sgroi, DC (reprint author), MGH E, Mol Pathol Res, 149 13th St, Charlestown, MA 02129 USA. EM dsgroi@partners.org FU Department of Defense [W81XWH-04-1-0606]; Susan G Komen Breast Cancer Foundation [BCTR0402932]; Avon Foundation; [NIH RO1-1CA112021-02] FX We extend special thanks to many collaborators for thoughtful discussions over the years and to Michelle Forrestall for graphic design assistance. We apologize to all investigators whose research could not be appropriately cited owing to space limitations. DCS is supported in part by Grant No. NIH RO1-1CA112021-02, the Department of Defense Grant No. W81XWH-04-1-0606, Susan G Komen Breast Cancer Foundation Grant No. BCTR0402932 and the Avon Foundation. NR 121 TC 108 Z9 113 U1 4 U2 28 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3417 J9 J PATHOL JI J. Pathol. PD JAN PY 2011 VL 223 IS 2 SI SI BP 307 EP 317 DI 10.1002/path.2808 PG 11 WC Oncology; Pathology SC Oncology; Pathology GA 697YB UT WOS:000285554600019 PM 21125683 ER PT J AU Turner, CG Klein, JD Steigman, SA Armant, M Nicksa, GA Zurakowski, D Ritz, J Fauza, DO AF Turner, Christopher G. Klein, Justin D. Steigman, Shaun A. Armant, Myriam Nicksa, Grace A. Zurakowski, David Ritz, Jerome Fauza, Dario O. TI Preclinical regulatory validation of an engineered diaphragmatic tendon made with amniotic mesenchymal stem cells SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article DE Congenital diaphragmatic hernia; Tissue engineering; Amniotic mesenchymal stem cells ID HERNIA REPAIR; MANAGEMENT; RECURRENCE AB Purpose: Under a Food and Drug Administration directive, we examined definite long-term safety and efficacy aspects of an engineered diaphragmatic tendon graft as a regulatory prerequisite for clinical trials. Methods: Newborn lambs (N = 27) underwent partial diaphragmatic replacement with a Teflon patch, a composite acellular bioprosthesis, or the same bioprosthesis seeded with autologous amniotic mesenchymal stem cells processed under Good Manufacturing Practice guidelines. Multiple safety and efficacy analyses were performed at different time points up to 14 months of age (ovine adulthood). Results: There was no mortality. None of the blood tests or full body autopsy specimens showed any abnormality. There was a significantly higher failure rate in animals that received an acellular bioprosthetic graft vs an engineered graft, with no significant differences between Teflon and acellular bioprosthetic implants. Tensile strength and total collagen levels were significantly higher in engineered grafts than in acellular bioprosthetic grafts. On histology, lysozyme and myeloperoxidase stainings were unremarkable in all grafts. Conclusions: Diaphragmatic repair with a clinically viable autologous tendon engineered with amniotic mesenchymal stem cells leads to improved outcomes when compared with an equivalent acellular bioprosthesis, with no local or systemic adverse effects. Clinical trials of engineered diaphragmatic repair appear practicable within regulatory guidelines. (C) 2011 Elsevier Inc. All rights reserved. C1 [Turner, Christopher G.; Klein, Justin D.; Steigman, Shaun A.; Nicksa, Grace A.; Zurakowski, David; Fauza, Dario O.] Childrens Hosp Boston, Dept Surg, Boston, MA 02115 USA. [Armant, Myriam; Ritz, Jerome] Harvard Univ, Sch Med, Ctr Human Cell Therapy, CBR Inst Biomed Res, Boston, MA 02115 USA. RP Fauza, DO (reprint author), Childrens Hosp Boston, Dept Surg, Boston, MA 02115 USA. EM dario.fauza@childrens.harvard.edu OI Ritz, Jerome/0000-0001-5526-4669 NR 24 TC 29 Z9 30 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD JAN PY 2011 VL 46 IS 1 BP 57 EP 61 DI 10.1016/j.jpedsurg.2010.09.063 PG 5 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 706CL UT WOS:000286194200018 PM 21238640 ER PT J AU Raval, MV Dillon, PW Bruny, JL Ko, CY Hall, BL Moss, RL Oldham, KT Richards, KE Vinocur, CD Ziegler, MM AF Raval, Mehul V. Dillon, Peter W. Bruny, Jennifer L. Ko, Clifford Y. Hall, Bruce L. Moss, R. Lawrence Oldham, Keith T. Richards, Karen E. Vinocur, Charles D. Ziegler, Moritz M. CA ACS NSQIP Pediat Steering Comm TI Pediatric American College of Surgeons National Surgical Quality Improvement Program: feasibility of a novel, prospective assessment of surgical outcomes SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article DE ACS NSQIP; Pediatric surgery; Outcomes; Quality assessment ID PRIVATE-SECTOR; NSQIP; CARE AB Purpose: The American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) provides validated assessment of surgical outcomes. This study reports initiation of an ACS NSQIP Pediatric at 4 children's hospitals. Methods: From October 2008 to June 2009, 121 data variables were prospectively collected for 3315 patients, including 30-day outcomes and tailoring the ACS NSQIP methodology to children's surgical specialties. Results: Three hundred seven postoperative complications/occurrences were detected in 231 patients representing 7.0% of the study population. Of the patients with complications, 175 (75.7%) had 1, 39 (16.9%) had 2, and 17 (7.4%) had 3 or more complications. There were 13 deaths (0.39%) and 14 intraoperative occurrences (0.42%) detected. The most common complications were infection, 105 (34%) (SSI, 54; sepsis, 31; pneumonia, 13; urinary tract infection, 7); airway/respiratory events, 27 (9%); wound disruption, 18 (6%); neurologic events, 8 (3%) (nerve injury, 4; stroke/vascular event, 2; hemorrhage, 2); deep vein thrombosis, 3 (<1%); renal failure, 3 (<1%); and cardiac events, 3 (<1%). Current sampling captures 17.5% of cases across institutions with unadjusted complication rates ranging from 6.8% to 10.2%. Completeness of data collection for all variables exceeded 95% with 98% interrater reliability and 87% of patients having full 30-day follow-up. Conclusion: These data represent the first multiinstitutional prospective assessment of specialty-specific surgical outcomes in children. The ACS NSQIP Pediatric is poised for institutional expansion and future development of risk-adjusted models. (C) 2011 Elsevier Inc. All rights reserved. C1 [Raval, Mehul V.; Ko, Clifford Y.; Hall, Bruce L.; Richards, Karen E.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL 60611 USA. [Raval, Mehul V.] Northwestern Univ, Dept Surg, Feinberg Sch Med, Chicago, IL 60611 USA. [Dillon, Peter W.] Penn State Univ, Dept Surg, Sch Med, Div Pediat Surg, Hershey, PA USA. [Bruny, Jennifer L.; Ziegler, Moritz M.] Univ Colorado, Dept Pediat Surg, Childrens Hosp, Denver, CO 80202 USA. [Ko, Clifford Y.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Hall, Bruce L.] Washington Univ, Dept Surg, John Cochran Vet Affairs Med Ctr, St Louis, MO USA. [Hall, Bruce L.] Washington Univ, Ctr Hlth Policy, Barnes Jewish Hosp, St Louis, MO USA. [Hall, Bruce L.] Washington Univ, John M Olin Sch Business, St Louis, MO 63130 USA. [Moss, R. Lawrence] Yale Univ, Yale New Haven Childrens Hosp, Dept Surg, New Haven, CT USA. [Oldham, Keith T.] Med Coll Wisconsin, Dept Surg, Milwaukee, WI 53226 USA. [Vinocur, Charles D.] Thomas Jefferson Univ, Div Pediat Surg, AI DuPont Hosp Children, Wilmington, DE USA. RP Raval, MV (reprint author), Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL 60611 USA. EM m-raval@md.northwestern.edu OI Vinocur, Charles/0000-0001-9650-1122; Raval, Mehul/0000-0002-1527-2661 FU John Gray Research Fellowship; Daniel F. and Ada L. Rice Foundation FX MVR participates in the American College of Surgeons Clinical Scholars in Residence Program. MVR is supported by the John Gray Research Fellowship and the Daniel F. and Ada L. Rice Foundation. The authors would like to thank the ACS NSQIP staff and the tremendous efforts toward high-quality, accurate data collection by the ACS NSQIP SCRs. NR 10 TC 58 Z9 58 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD JAN PY 2011 VL 46 IS 1 BP 115 EP 121 DI 10.1016/j.jpedsurg.2010.09.073 PG 7 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 706CL UT WOS:000286194200029 PM 21238651 ER PT J AU Ryan, DP Doody, DP AF Ryan, Daniel P. Doody, Daniel P. TI Restorative proctocolectomy with and without protective ileostomy in a pediatric population SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article DE Restorative proctocolectomy; Ileostomy; Ileoanal pouches; S-pouch; J-pouch; Pediatrics ID POUCH-ANAL ANASTOMOSIS; TEMPORARY LOOP ILEOSTOMY; ULCERATIVE-COLITIS; ILEOANAL ANASTOMOSIS; MUCOSAL PROCTECTOMY; ILEAL RESERVOIR; TOTAL COLECTOMY; COMPLICATIONS; POLYPOSIS; CHILDREN AB Purpose: This study aim was to review outcomes of pediatric patients after restorative proctocolectomy with or without a protective ileostomy in the treatment of ulcerative colitis and polyposis syndromes. Methods: All patients who underwent rectal mucosectomy with ileal pouch reservoir and hand-sewn ileal pouch anal anastomosis (IPAA) during 19-year period were reviewed retrospectively. Results: Eighty-three patients with ulcerative colitis and 7 patients with polyposis syndromes (ages 2.0-21.8 years) were reviewed. Sixty-eight patients underwent IPAA without diverting ileostomy. Fifty-six patients underwent restorative proctocolectomy as single-stage procedures, and 12 had abdominal colectomy and subsequent definitive IPAA without diverting ileostomy. Nineteen patients had IPAA with diverting ileostomy and subsequent closure of ileostomy. Three-stage procedures were performed in 3 cases. An ileal pouch leak or pelvic abscess occurred in 2 patients. Surgical pouch revision for retraction, efferent limb syndrome, prolapse, pouchitis, or perirectal infections occurred in 19 (6/62 J-pouch, 13/28 S-pouch). Fourteen patients (5/22 with diversion, 9/68 without diversion) developed small bowel obstruction. Overall, daytime and nighttime continence was excellent with rare nocturnal evacuations. Conclusions: Restorative proctocolectomy without protective ileostomy is not associated with an increased morbidity, even in patients with active colitis, and may be appropriate most patients. (C) 2011 Elsevier Inc. All rights reserved. C1 [Ryan, Daniel P.; Doody, Daniel P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA 02114 USA. RP Ryan, DP (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA 02114 USA. EM dryan@partners.org NR 16 TC 8 Z9 9 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD JAN PY 2011 VL 46 IS 1 BP 200 EP 203 DI 10.1016/j.jpedsurg.2010.09.085 PG 4 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 706CL UT WOS:000286194200045 PM 21238667 ER PT J AU Zuckerman, KE Cai, X Perrin, JM Donelan, K AF Zuckerman, Katharine E. Cai, Xin Perrin, James M. Donelan, Karen TI Incomplete Specialty Referral among Children in Community Health Centers SO JOURNAL OF PEDIATRICS LA English DT Article ID PRIMARY-CARE; COMMUNICATION; ACCESS; CONSULTATION; COMPLETION; SERVICES; NEEDS AB Objective To assess rates of incomplete specialty referral (referral not resulting in a specialist visit) and risk factors for incomplete referral in pediatric community health care centers. Study design In this cross-sectional study, we used referral records and electronic health records to calculate rate of incomplete referral in 577 children referred from two health care centers in underserved communities to any of 19 pediatric specialties at an affiliated tertiary care center, over 7 months in 2008-2009. We used logistic regression to test the association of incomplete referral with child/family sociodemographic and health care system factors. Results Of the children, 30.2% had an incomplete referral. Incomplete referral rates were similar at the two health care centers, but varied from 10% to 73% according to specialty clinic type. In multivariate analysis, sociodemographic factors of older child age, public insurance status, and no chronic health conditions correlated with incomplete referral, as did health care system factors of surgical specialty clinic type, low patient volume, longer wait for visit, and appointment rescheduling. Conclusion Almost one-third of children referred to specialists were unable to complete the referral in a timely manner. To improve specialty access, health care organizations and policymakers should target support to families with high-risk children and remediate problematic health care system features. (J Pediatr 2011;158:142-8). C1 [Zuckerman, Katharine E.] Oregon Hlth & Sci Univ, Child & Adolescent Hlth Measurement Initiat, Portland, OR 97239 USA. [Zuckerman, Katharine E.] Oregon Hlth & Sci Univ, Div Gen Pediat, Portland, OR 97239 USA. [Cai, Xin] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Perrin, James M.] MassGen Hosp Children, Ctr Child & Adolescent Hlth Policy, Dept Pediat, Boston, MA USA. [Donelan, Karen] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mongan Inst Hlth Policy, Boston, MA USA. RP Zuckerman, KE (reprint author), Oregon Hlth & Sci Univ, Child & Adolescent Hlth Measurement Initiat, Mail Code CDRC-P,707 SW Gaines St, Portland, OR 97239 USA. EM zuckerma@ohsu.edu OI Cai, Xin/0000-0001-5238-6193 FU CRICO-Risk Management Foundation; Health Resources and Services Administration, Department of Health and Human Services [T32 HP10018] FX Supported by a grant from the CRICO-Risk Management Foundation, a National Research Service Award (T32 HP10018) from the Health Resources and Services Administration, Department of Health and Human Services, to the Harvard Pediatric Health Services Research Fellowship (K.Z.). The authors declare no conflicts of interest. NR 23 TC 11 Z9 11 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 J9 J PEDIATR-US JI J. Pediatr. PD JAN PY 2011 VL 158 IS 1 BP 142 EP 148 DI 10.1016/j.jpeds.2010.07.012 PG 7 WC Pediatrics SC Pediatrics GA 692OG UT WOS:000285161500030 PM 20801461 ER PT J AU Rosenbaum, JL Smith, JR Zollfrank, R AF Rosenbaum, Joan L. Smith, Joan Renaud Zollfrank, Reverend TI Neonatal End-of-Life Spiritual Support Care SO JOURNAL OF PERINATAL & NEONATAL NURSING LA English DT Article DE bereavement; end of life; grief; healthcare teams; interdisciplinary; neonatal; spirituality ID PALLIATIVE CARE; RELIGION; QUALITY; PARENTS; BELIEFS; INFANT; DEATH; UNIT AB The death of an infant is a profound loss that may complicate, disrupt, or end relationships between parents; and lead to maladaptive grieving, long-term decreased quality of life, and symptoms related to psychological morbidity. Facing neonatal loss is frequently experienced as traumatic assault on parents' spiritual and existential world of meaning. This article highlights the importance of supporting parents through loss by providing comprehensive care that focuses not only on the neonate's physical needs, but also addresses parents' and families' spiritual, religious, and existential needs. Our objective is to increase practitioners' awareness of spiritual and existential distress and to provide strategies to address such needs, particularly at the end of life. C1 [Rosenbaum, Joan L.] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. [Smith, Joan Renaud] St Louis Childrens Hosp, Div Nursing & Newborn Intens Care, St Louis, MO 63178 USA. [Zollfrank, Reverend] Massachusetts Gen Hosp, Chaplaincy Dept, Boston, MA 02114 USA. RP Rosenbaum, JL (reprint author), 4942 Parkview Pl, St Louis, MO 63110 USA. EM rosenbaum@kids.wustl.edu NR 41 TC 11 Z9 11 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-2190 J9 J PERINAT NEONAT NUR JI J. Perinat. Neonatal Nurs. PD JAN-MAR PY 2011 VL 25 IS 1 BP 61 EP 69 DI 10.1097/JPN.0b013e318209e1d2 PG 9 WC Nursing; Obstetrics & Gynecology; Pediatrics SC Nursing; Obstetrics & Gynecology; Pediatrics GA 719WT UT WOS:000287242900012 PM 21311271 ER PT J AU Reise, SP Horan, WP Blanchard, JJ AF Reise, Steven P. Horan, William P. Blanchard, Jack J. TI The Challenges of Fitting an Item Response Theory Model to the Social Anhedonia Scale SO JOURNAL OF PERSONALITY ASSESSMENT LA English DT Article ID PSYCHOMETRICALLY IDENTIFIED SCHIZOTYPY; SCHIZOPHRENIA; ANXIETY; DISORDERS; SYMPTOMS; VALIDITY; BIFACTOR; LIFE AB This study explored the application of latent variable measurement models to the Social Anhedonia Scale (SAS; Eckblad, Chapman, Chapman, Mishlove, 1982), a widely used and influential measure in schizophrenia-related research. Specifically, we applied unidimensional and bifactor item response theory (IRT) models to data from a community sample of young adults (n = 2,227). Ordinal factor analyses revealed that identifying a coherent latent structure in the 40-item SAS data was challenging due to (a) the presence of multiple small content clusters (e.g., doublets); (b) modest relations between those clusters, which, in turn, implies a general factor of only modest strength; (c) items that shared little variance with the majority of items; and (d) cross-loadings in bifactor solutions. Consequently, we conclude that SAS responses cannot be modeled accurately by either unidimensional or bifactor IRT models. Although the application of a bifactor model to a reduced 17-item set met with better success, significant psychometric and substantive problems remained. Results highlight the challenges of applying latent variable models to scales that were not originally designed to fit these models. C1 [Reise, Steven P.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. [Horan, William P.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Horan, William P.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Blanchard, Jack J.] Univ Maryland, Dept Psychol, College Pk, MD 20742 USA. RP Reise, SP (reprint author), Univ Calif Los Angeles, Dept Psychol, Franz Hall, Los Angeles, CA 90095 USA. EM reise@psych.ucla.edu FU NIMH NIH HHS [R01 MH082839-03, K02 MH079231, K02 MH079231-05, K02MH079231, R01 MH051240, R01 MH051240-11, R01 MH082782, R01 MH082782-03, R01 MH082839, R01MH082839, R01MH51240, R01MH82782] NR 45 TC 12 Z9 13 U1 1 U2 11 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0022-3891 J9 J PERS ASSESS JI J. Pers. Assess. PY 2011 VL 93 IS 3 BP 213 EP 224 AR PII 936745431 DI 10.1080/00223891.2011.558868 PG 12 WC Psychology, Clinical; Psychology, Social SC Psychology GA 754EW UT WOS:000289837900002 PM 21516580 ER PT J AU Anderson, KS Sibani, S Wallstrom, G Qiu, J Mendoza, EA Raphael, J Hainsworth, E Montor, WR Wong, J Park, JG Lokko, N Logvinenko, T Ramachandran, N Godwin, AK Marks, J Engstrom, P LaBaer, J AF Anderson, Karen S. Sibani, Sahar Wallstrom, Garrick Qiu, Ji Mendoza, Eliseo A. Raphael, Jacob Hainsworth, Eugenie Montor, Wagner R. Wong, Jessica Park, Jin G. Lokko, Naa Logvinenko, Tanya Ramachandran, Niroshan Godwin, Andrew K. Marks, Jeffrey Engstrom, Paul LaBaer, Joshua TI Protein Microarray Signature of Autoantibody Biomarkers for the Early Detection of Breast Cancer SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE breast cancer; autoantibodies; biomarker; proteomics; protein microarrays ID HUMORAL IMMUNE-RESPONSE; PROSTATE-CANCER; TUMOR-ANTIGENS; MAMMOGRAPHIC DENSITY; POSTMENOPAUSAL WOMEN; CDNA LIBRARIES; CELL CARCINOMA; OVARIAN-CANCER; HORMONE-LEVELS; YOUNGER WOMEN AB Cancer patients spontaneously generate autoantibodies (AAb) to tumor-derived proteins. To detect AAb, we have probed novel high-density custom protein microarrays (NAPPA) expressing 4988 candidate tumor antigens with sera from patients with early stage breast cancer (IBC), and bound IgG was measured. We used a three-phase serial screening approach. First, a prescreen was performed to eliminate uninformative antigens. Sera from stage I-III IBC (n = 53) and healthy women (n = 53) were screened for AAb to all 4988 protein antigens. Antigens were selected if the 95th percentile of signal of cases and controls were significantly different (p < 0.05) and if the number of cases with signals above the 95th percentile of controls was significant (p < 0.05). These 761 antigens were screened using an independent set of IBC sera (n = 51) and sera from women with benign breast disease (BBD) (n = 39). From these, 119 antigens had a partial area under the ROC curve (p < 0.05), with sensitivities ranging from 9-40% at > 91% specificity. Twenty-eight of these antigens were confirmed using an independent serum cohort (n = 51 cases/38 controls, p < 0.05). Using all 28 AAb, a classifier was identified with a sensitivity of 80.8% and a specificity of 61.6% (AUC = 0.756). These are potential biomarkers for the early detection of breast cancer. C1 [Anderson, Karen S.; Wong, Jessica; Lokko, Naa] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. [Anderson, Karen S.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Sibani, Sahar; Raphael, Jacob; Hainsworth, Eugenie; Montor, Wagner R.; Logvinenko, Tanya; Ramachandran, Niroshan] Harvard Univ, Sch Med, Harvard Inst Prote, Boston, MA USA. [Wallstrom, Garrick; Qiu, Ji; Mendoza, Eliseo A.; Park, Jin G.; LaBaer, Joshua] Arizona State Univ, Biodesign Inst, Ctr Personalized Diagnost, Tempe, AZ USA. [Godwin, Andrew K.] Fox Chase Canc Ctr, Womens Canc Program, Philadelphia, PA 19111 USA. [Marks, Jeffrey] Duke Univ, Sch Med, Durham, NC USA. [Engstrom, Paul] Fox Chase Canc Ctr, Canc Prevent & Control Program, Philadelphia, PA 19111 USA. RP Anderson, KS (reprint author), Dana Farber Canc Inst, Canc Vaccine Ctr, H1M416,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM kanderson@partners.org; jlabaer@asu.edu RI Montor, Wagner/J-2568-2012 OI Montor, Wagner/0000-0003-3746-9366 FU Early Detection Research Network [5U01CA117374]; [P30 CA006927] FX This study was supported by a research grant from the Early Detection Research Network 5U01CA117374 (K.S.A. and J.L.). We thank Yanhui Hu for bioinformatic support. We acknowledge the Biosample Repository at FCCC and their Institutional Core Grant (P30 CA006927). NR 76 TC 108 Z9 113 U1 2 U2 44 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD JAN PY 2011 VL 10 IS 1 BP 85 EP 96 DI 10.1021/pr100686b PG 12 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 701IQ UT WOS:000285812000010 PM 20977275 ER PT J AU DeBattista, C Kinrys, G Hoffman, D Goldstein, C Zajecka, J Kocsis, J Teicher, M Potkin, S Preda, A Multani, G Brandt, L Schiller, M Iosifescu, D Fava, M AF DeBattista, Charles Kinrys, Gustavo Hoffman, Daniel Goldstein, Corey Zajecka, John Kocsis, James Teicher, Martin Potkin, Steven Preda, Adrian Multani, Gurmeet Brandt, Len Schiller, Mark Iosifescu, Dan Fava, Maurizio TI The use of referenced-EEG (rEEG) in assisting medication selection for the treatment of depression SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Resistant depression; Biomarkers; Antidepressants; QEEG; rEEG; Response prediction ID STAR-ASTERISK-D; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; CLINICAL-PRACTICE; BREAST-CANCER; ANTIDEPRESSANTS; METHYLPHENIDATE; DISORDERS; OUTCOMES; ILLNESS AB Objective: To evaluate the efficacy of rEEG (R)-guided pharmacotherapy for the treatment of depression in those circumstances where rEEG and STAR*D provided different recommendations. Materials and methods: This was a randomized, single-blind, parallel group, 12 center, US study of rEEG-guided pharmacotherapy vs. the most effective treatment regimens reported in the NIH sponsored START study. Relatively treatment-resistant subjects >= 18 years who failed one or more antidepressants were required to have a QIDS-16-SR score >= 13 and a MADRS score >= 26 at baseline. All subjects underwent a washout of all current medications (with some protocol-specified exceptions) for at least five half-lives before receiving a QEEG and rEEG report. Subjects randomized to rEEG were assigned a regimen based on the rEEG report Control subjects who had failed only SSRI's in their current episode were randomized to receive venlafaxine XR. Control subjects who had failed antidepressants from >= 2 classes of antidepressants were randomized to receive a regimen from Steps 2-4 of the STAR*D study. Treatment lasted 12 weeks. The primary outcome measures were change from baseline for self-rated QIDS-5R16 and Q-LES-Q-SF. Results: A total of 114 subjects were randomized and 89 subjects were evaluable. rEEG-guided pharmacotherapy exhibited significantly greater improvement for both primary endpoints, QIDS-SR16 (-6.8 vs. -4.5, p < 0.0002) and Q-LES-Q-SF (18.0 vs. 8.9, p < 0.0002) compared to control, respectively, as well as statistical superiority in 9 out of 12 secondary endpoints. Conclusions: These results warrant additional studies to determine the role of rEEG-guided psychopharmacology in the treatment of depression. If these results were confirmed, rEEG-guided pharmacotherapy would represent an easy, relatively inexpensive, predictive, objective office procedure that builds upon clinical judgment to guide antidepressant medication choice. (C) 2010 Published by Elsevier Ltd. C1 [DeBattista, Charles] Stanford Univ, Dept Psychiat & Behav Sci, Sch Med, Stanford, CA 94305 USA. [Kinrys, Gustavo] Harvard Univ, Sch Med, Depress & Anxiety Disorders Res Program, Dept Psychiat, Cambridge, MA 02139 USA. [Hoffman, Daniel] CNS Response Inc, Aliso Viejo, CA 92656 USA. [Goldstein, Corey; Zajecka, John] Rush Univ, Med Ctr, Dept Psychiat, Chicago, IL 60612 USA. [Kocsis, James] New York Presbyterian Hosp, Payne Whitney Clin, New York, NY 10021 USA. [Teicher, Martin] Harvard Univ, Sch Med, Dept Psychiat, Dev Biopsychiat Res Program,McLean Hosp, Belmont, MA 02478 USA. [Potkin, Steven; Preda, Adrian] UCI Sch Med, Dept Psychiat & Human Behav, Orange, CA 92868 USA. [Multani, Gurmeet] Shanti Clin Trials, Colton, CA 92324 USA. [Schiller, Mark] Mind Therapy Clin, San Francisco, CA USA. [Iosifescu, Dan; Fava, Maurizio] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP DeBattista, C (reprint author), Stanford Univ, Dept Psychiat & Behav Sci, Sch Med, 401 Quarry Rd, Stanford, CA 94305 USA. EM debattista@stanford.edu RI Preda, Adrian /K-8889-2013; OI Preda, Adrian /0000-0003-3373-2438; Potkin, Steven/0000-0003-1028-1013 FU CNS Response, Inc.; GSK; Wyeth; Lilly; Cephalon; Cyberonics; Neuronetics; Novaritis; AstraZeneca; Forest; CNS Response; Medtronics; Boerhinger; ANS; Pfizer; Neuropace; Brain Resources; BMS; Corcept; Bristol-Myers Squibb Company; Elan Pharmaceuticals; Forest Pharmaceuticals Inc.; GlaxoSmithkline; Sanofi/Synthelabo; Sepracor Inc.; Pfizer Inc; UCB Pharma; Wyeth-Ayerst Laboratories; NIMH; NIDA; NARSAD; Tourette's Syndrome Association; Scottish Rite Schizophrenia Research Program; ADAMHA; USPHS; LiteBook; BioBehavioral Diagnostic Co.; Kodak; Wyeth-Ayerst; OPTAx Systems Inc.; Sepracor; SunBox; Ambulatory Monitoring Inc.; Copley Pharmaceuticals; Glaxo-Welcome; Sandoz; Mead Johnson; MDCI; Watson Pharmaceuticals; Sention; Abbott Laboratories; Alkermes; Aspect Medical Systems; BioResearch; Brain Cells, Inc.; Clinical Trial Solutions, LLC; Ganeden; J & J Pharmaceuticals; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; NCCAM; Novartis; Organon Inc.; PamLab, LLC; Pharmavite; Roche; Shire; Solvay Pharmaceuticals, Inc.; Synthelabo; Burroughs Wellcome Trust; Pritzker Consortium; Sanofi Aventis; Boehringer-Ingelheim; Bristol-Myers Squibb/Otsuka; Eli Lilly; McNeil; PamLab; Takeda; Forest Laboratories; Janssen Pharmaceutica; AstraZeneca AB; Bioline; Bristol-Myers Squibb; Ceregene; Cortex; Dainippon-Sumitomo; Elan Corporation plc; Eli Lilly and Company; Minster Pharmaceuticals; Novartis Pharmaceuticals Corporation; Schering Plough/Merck; Otsuka Pharmaceuticals; Pfizer Pharmaceuticals; Solvay Pharmaceuticals; Roche Laboratories; Wyeth Research; Vanda; American Psychiatric Association; Alzheimer's Association; Brigham and Women's Hospital; Harvard Massachusetts General Hospital; ISCTM; NIH (NIAAA); NIH (NIBIB); NIH (NCRR); University of California, San Francisco; University of Southern California FX Financial support and referenced-EEGs for this trial were provided by CNS Response, Inc. The study design was created by a scientific advisory board made up of academic leaders, some of which were investigators and some not, retained by CNS Response, Inc. The written study protocol, data collection, data validation, and site monitoring were done by CNS Response, Inc. The statistical analyses were conducted by an independent company paid for by CNS Response, Inc.; Dr. DeBattista has received research support in the last 5 years from: GSK, Wyeth, Lilly, Cephalon, Cyberonics, Neuronetics, Novaritis, AstraZeneca, Forest, CNS Response, Medtronics, Boerhinger, ANS, Pfizer, Neuropace, Brain Resources. Dr. DeBattista has received support as a speaker/consultant in the last 5 years from: Lilly, GSK, Pfizer, Cephalon, Wyeth, BMS, AstraZeneca, Cyberonics, Corcept, Forest. Dr. DeBattista is a stock holder in: Corcept Therapeutics.; Dr. Kinrys has received research support from: Astra-Zeneca, Bristol-Myers Squibb Company, Cephalon, Elan Pharmaceuticals, Eli Lilly & Company, Forest Pharmaceuticals Inc., GlaxoSmithkline, Sanofi/Synthelabo, Sepracor Inc., Pfizer Inc, UCB Pharma, Wyeth-Ayerst Laboratories. Dr. Kinrys has served as an Advisor and/or Consultant to: Astra-Zeneca, Cephalon, Eli Lilly & Company, Forest Pharmaceuticals Inc., GlaxoSmithkline, Janssen Pharmaceutica, Pfizer Inc, Sepracor Inc., UCB Pharma, Wyeth-Ayerst Laboratories. Dr. Kinrys has received speaking support from: Astra-Zeneca, Forest Pharmaceuticals Inc., GlaxoSmithkline, Sepracor Inc., Wyeth-Ayerst Laboratories.; Dr. Martin H. Teicher has received (throughout his lifetime) research support from: NIMH, NIDA, NARSAD, Tourette's Syndrome Association, Scottish Rite Schizophrenia Research Program, ADAMHA, USPHS, LiteBook, CNS Response, BioBehavioral Diagnostic Co., Kodak, GlaxoSmithKline, Wyeth-Ayerst, OPTAx Systems Inc., Sepracor, SunBox, Ambulatory Monitoring Inc., Copley Pharmaceuticals, Glaxo-Welcome, Sandoz and Mead Johnson. Dr Martin H. Teicher has spoken with support from the following companies: BioBehavioral Diagnostic Co., Bristol-Myers Squib, Glaxo-Welcome, Optax Systems Inc., Upjohn, Cell-tech, Cephalon, J & J Pharmaceuticals and Eli Lilly. Dr. Martin H. Teicher has served on the Scientific Advisory Board of the following companies: OPTAx Systems Inc. and BioBehavioral Diagnostic Co. and has received consulting fees from these companies. He has also received consulting fees from MDCI, Copley Pharmaceuticals, Watson Pharmaceuticals, Sention, Sepracor and Ambulatory Monitoring Inc. Dr. Martin H. Teicher holds 13 US Patents and has received patent royalties for inventions licensed through McLean Hospital to Sepracor, Optax Systems Inc, and BioBehavioral Diagnostic Co.; Dr. Maurizio Fava has received research support (over his lifetime) from the following companies: Abbott Laboratories, Alkermes, Aspect Medical Systems, Astra-Zeneca, BioResearch, Brain Cells, Inc., Bristol-Myers Squibb Company, Cephalon, Clinical Trial Solutions, LLC, Eli Lilly & Company, Forest Pharmaceuticals Inc., Ganeden, GlaxoSmithKline, J & J Pharmaceuticals, Lichtwer Pharma GmbH, Lorex Pharmaceuticals, NARSAD, NCCAM, NIDA, NIMH, Novartis, Organon Inc., PamLab, LLC, Pfizer Inc, Pharmavite, Roche, Sanofi-Aventis, Shire, Solvay Pharmaceuticals, Inc., Synthelabo, Wyeth-Ayerst Laboratories. Dr. Maurizio Fava has consulted (over his lifetime) to the following companies: Abbott Laboratories, Amarin, Aspect Medical Systems, Astra-Zeneca, Auspex Pharmaceuticals, Bayer AG, Best Practice Project Management, Inc, Bio-Marin Pharmaceuticals, Inc., Biovail Pharmaceuticals, Inc., BrainCells, Inc, Bristol-Myers Squibb Company, Cephalon, Clinical Trials Solutions, LLC, CNS Response, Compellis, Cypress Pharmaceuticals, Dov Pharmaceuticals, Eisai, Inc., Eli Lilly & Company, EPIX Pharmaceuticals, Euthymics Bioscience, Inc., Fabre-Kramer, Pharmaceuticals, Inc., Forest Pharmaceuticals Inc., GlaxoSmithKline, Grunenthal GmBH, Janssen Pharmaceutica, Jazz Pharmaceuticals, J & J Pharmaceuticals, Knoll Pharmaceutical Company, Labopharm, Lorex Pharmaceuticals, Lundbeck, MedAvante Inc., Merck, Methylation Sciences, Neuronetics, Novartis, Nutrition 21, Organon Inc., PamLab, LLC, Pfizer Inc, PharmaStar, Pharmavite, Precision Human Biolaboratory, PsychoGenics, Psylin Neurosciences, Inc., Ridge Diagnostics, Inc., Roche, Sanofi-Aventis, Sepracor, Schering-Plough, Solvay Pharmaceuticals, Inc., Somaxon, Somerset Pharmaceuticals, Synthelabo, Takeda, Tetragenex, TransForm Pharmaceuticals, Inc., Transcept Pharmaceuticals, Vanda Pharmaceuticals Inc, Wyeth-Ayerst Laboratories. Dr. Maurizio Fava has spoken/published (over his lifetime) with support from the following companies: Adamed, Co., Advanced Meeting Partners, American Psychiatric Association, American Society of Clinical Psychopharmacology, Astra-Zeneca, Belvoir, Boehringer-Ingelheim, Bristol-Myers Squibb Company, Cephalon, Eli Lilly & Company, Forest Pharmaceuticals Inc., GlaxoSmithKline, Imedex, Novartis, Organon Inc., Pfizer Inc, PharmaStar, MGH Psychiatry Academy/Primedia, MGH Psychiatry Academy/Reed-Elsevier, UBC, Wyeth-Ayerst Laboratories. Dr. Maurizio Fava has equity in the following company: Compellis. Dr. Maurizio Fava has the following rolyalties/patents: patent applications for SPCD and for a combination of azapirones and bupropion in MDD, copyright royalties for the MGH CPFQ, SFI, ATRQ, DESS, and SAFER.; Dr. James H. Kocsis has received research support from: NIMH, NIDA, Burroughs Wellcome Trust, Pritzker Consortium, Astra-Zeneca, Sanofi Aventis, Forest, Novartis, CNS Response, Roche. Dr. James H. Kocsis has spoken with support from: Pfizer, Wyeth, Astra-Zeneca. Dr. James H. Kocsis has served on an advisory board for: Pfizer and Wyeth.; Dr. Corey Goldstein has received research support from: Astra-Zeneca, Boehringer-Ingelheim, Bristol-Myers Squibb/Otsuka, CNS Response, Inc., Cyberonics, Eli Lilly, GlaxoSmithKline, McNeil, National Institute of Mental Health, Novartis, PamLab, Pfizer, Takeda. Dr. Corey Goldstein has spoken with support from: Astra-Zeneca, Eli Lilly.; Dr. Hoffman is an employee of CNS Response, Inc. and holds stock in the company. Over his lifetime, Dr. Hoffman has spoken with support from: Wyeth, Forest Laboratories, Cephalon, Eli Lilly, Pfizer, GlaxoSmithKline.; Dr. Iosifescu has received research support from Aspect Medical Systems, Forest Laboratories and Janssen Pharmaceutica. Dr. Iosifescu has been a consultant for Forest Laboratories, Gerson Lehrman Group and Pfizer, Inc. Dr. Iosifescu has been a speaker for Eli Lilly & Co., Forest Laboratories, Pfizer, Inc and Reed-Elsevier.; Dr. Steven Potkin received grant support, funding, or has been a paid consultant to the following companies in the past year that conduct scientific or medical research and/or make medication related to Psychiatric and Neurodegenerative disorders: AstraZeneca AB, Bioline, Bristol-Myers Squibb, Ceregene, Cortex, Dainippon-Sumitomo, Elan Corporation plc, Eli Lilly and Company, Forest Laboratories, Janssen Pharmaceutica, Minster Pharmaceuticals, Novartis Pharmaceuticals Corporation, Schering Plough/Merck, Otsuka Pharmaceuticals, Pfizer Pharmaceuticals, Solvay Pharmaceuticals, Roche Laboratories, Wyeth Research, and Vanda. Dr. Steven Potkin has received grant support, funding or has been a consultant to the following funding agencies, universities and university affiliates, as well as professional organizations that conduct medical or scientific research related to Psychiatric and Neurodegenerative disorders: American Psychiatric Association, Alzheimer's Association, Brigham and Women's Hospital, Harvard Massachusetts General Hospital, ISCTM, NIH (NIAAA, NIBIB, NCRR), the University of California, San Francisco and the University of Southern California. NR 48 TC 19 Z9 19 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD JAN PY 2011 VL 45 IS 1 BP 64 EP 75 DI 10.1016/j.jpsychires.2010.05.009 PG 12 WC Psychiatry SC Psychiatry GA 717VJ UT WOS:000287075200011 PM 20598710 ER PT J AU Lucas, MR AF Lucas, Michele R. TI A Private Caregiver ListServ: Maximum Benefit for Minimum Cost SO JOURNAL OF PSYCHOSOCIAL ONCOLOGY LA English DT Article DE caregivers; brain tumors; peer support; psychosocial intervention; support group ID FAMILY CAREGIVERS; SUPPORT; CANCER; INTERNET; ONLINE; LIFE AB A private ListServ was created as a psychosocial intervention for the caregivers of the brain tumor patients in a large metropolitan cancer center. Caring for someone with a brain tumor can be quite challenging, and the day-to-day responsibilities restrict the amount of discretionary time allotted the caregiver. Consequently, they can become isolated and overwhelmed. It was conceived that, for convenience sake, a ListServ might be the solution to best serve this population. The hope being that sharing with their peers would lessen the isolation and validate their own experience, decreasing their fear and anxiety. This was all possible for less than a dollar a day. C1 Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol, Boston, MA 02114 USA. RP Lucas, MR (reprint author), Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol, 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. EM mrlucas@partners.org NR 13 TC 2 Z9 2 U1 0 U2 1 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0734-7332 J9 J PSYCHOSOC ONCOL JI J. Psychosoc. Oncol. PY 2011 VL 29 IS 2 BP 168 EP 174 AR PII 934227853 DI 10.1080/07347332.2010.548442 PG 7 WC Psychology, Social SC Psychology GA 733JW UT WOS:000288260000004 PM 21391069 ER PT J AU Henrikson, NB Davison, BJ Berry, DL AF Henrikson, Nora B. Davison, B. Joyce Berry, Donna L. TI Measuring Decisional Control Preferences in Men Newly Diagnosed with Prostate Cancer SO JOURNAL OF PSYCHOSOCIAL ONCOLOGY LA English DT Article DE prostate cancer; qualitative; measurement; multidisciplinary care; measurement Interview ID BREAST-CANCER; PATIENT PARTICIPATION; WOMEN; INFORMATION; INVOLVEMENT; SUPPORT; INSTRUMENTS; ENCOUNTER; ONCOLOGY; HEALTH AB The Control Preferences Scale is widely used in decision research to measure patient preferences for participation in treatment decision making with health care providers. Following anecdotal reports of confusion with the scale the authors conducted an exploratory interview study to examine perceptions of the meaning and applicability of the Control Preferences Scale for men with localized prostate cancer seeking treatment in a multidisciplinary urology clinic. The preliminary data suggest potential validity challenges when the Control Preferences Scale is used in a multidisciplinary prostate cancer care setting, including the clinical context of localized prostate cancer and the meaning of shared decision making. C1 [Henrikson, Nora B.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA 98101 USA. [Davison, B. Joyce] Univ Saskatchewan, Saskatoon, SK, Canada. [Berry, Donna L.] Dana Farber Canc Inst, Phyllis F Cantor Ctr Res Nursing & Patient Care S, Boston, MA 02115 USA. RP Henrikson, NB (reprint author), Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, 1730 Minor Ave,Suite 1600, Seattle, WA 98101 USA. EM henrikson.n@ghc.org FU NCATS NIH HHS [UL1 TR000423]; NCRR NIH HHS [TL1 RR025016-01, TL1 RR025016]; NINR NIH HHS [R01 NR009692, R01 NR009692-01A1] NR 37 TC 8 Z9 8 U1 5 U2 9 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0734-7332 J9 J PSYCHOSOC ONCOL JI J. Psychosoc. Oncol. PY 2011 VL 29 IS 6 BP 606 EP 618 DI 10.1080/07347332.2011.615383 PG 13 WC Psychology, Social SC Psychology GA 888MU UT WOS:000300008700002 PM 22035534 ER PT J AU Trevino, KM Archambault, E Schuster, JL Hilgeman, MM Moye, J AF Trevino, Kelly M. Archambault, Elizabeth Schuster, Jennifer L. Hilgeman, Michelle M. Moye, Jennifer TI Religiosity and Spirituality in Military Veteran Cancer Survivors: A Qualitative Perspective SO JOURNAL OF PSYCHOSOCIAL ONCOLOGY LA English DT Article DE religiosity; spirituality; veteran; qualitative; cancer survivor ID BREAST-CANCER; OF-LIFE; PROSTATE-CANCER; SERIOUS ILLNESS; HEALTH; SUPPORT; PRAYER; PERCEPTIONS; SCALE; CARE AB Religiosity/spirituality (R/S) is often involved in coping with cancer. Qualitative research effectively captures the individuality of R/S constructs. Fourteen military veteran cancer survivors participated in focus groups. R/S questions included "How have your religious/spiritual beliefs affected how you cope with your cancer" and "How have your religious/spiritual beliefs changed as a result of your experience with cancer?" Five primary themes emerged: impact of cancer on R/S, meaning-making, prayer, religious/spiritual role of others, and facing death. Consistency and individuality characterized the role of R/S in cancer survivorship across themes. Implications for future research are discussed. C1 [Trevino, Kelly M.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Schuster, Jennifer L.] Harvard Univ, Natl Ctr PTSD, VA Boston Healthcare Syst, Sch Med, Boston, MA USA. [Hilgeman, Michelle M.] Tuscaloosa VA Med Ctr, Res Serv, Tuscaloosa, AL USA. [Hilgeman, Michelle M.] Tuscaloosa VA Med Ctr, Dev Serv, Tuscaloosa, AL USA. RP Trevino, KM (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,SM 271, Boston, MA 02215 USA. EM trevino.kelly@gmail.com OI Moye, Jennifer/0000-0002-3434-347X FU RRD VA [I01 RX000104] NR 41 TC 4 Z9 4 U1 1 U2 9 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0734-7332 J9 J PSYCHOSOC ONCOL JI J. Psychosoc. Oncol. PY 2011 VL 29 IS 6 BP 619 EP 635 DI 10.1080/07347332.2011.615380 PG 17 WC Psychology, Social SC Psychology GA 888MU UT WOS:000300008700003 PM 22035535 ER PT J AU Cooper, RA Nowak, CJ AF Cooper, Rory A. Nowak, Christopher J. TI Paralympics and veterans SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Editorial Material C1 [Cooper, Rory A.] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA 15213 USA. [Nowak, Christopher J.] VA Paralymp Program, Washington, DC USA. RP Cooper, RA (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA 15213 USA. EM rcooper@pitt.edu NR 2 TC 0 Z9 0 U1 1 U2 9 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2011 VL 48 IS 10 BP XI EP XIII DI 10.1682/JRRD.2011.11.0209 PG 3 WC Rehabilitation SC Rehabilitation GA V28XL UT WOS:000208713400002 PM 22234671 ER PT J AU Henzel, MK Bogie, KM Guihan, M Ho, CH AF Henzel, M. Kristi Bogie, Kath M. Guihan, Marylou Ho, Chester H. TI Pressure ulcer management and research priorities for patients with spinal cord injury: Consensus opinion from SCI QUERI Expert Panel on Pressure Ulcer Research Implementation SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Editorial Material ID DEEP TISSUE-INJURY; RISK-FACTORS; SKELETAL-MUSCLE; NURSING-HOME; HETEROTOPIC OSSIFICATION; EPIDERMAL EQUIVALENTS; VETERANS; PREVENTION; INTERFACE; SYSTEM C1 [Henzel, M. Kristi; Ho, Chester H.] Louis Stokes Cleveland VA Med Ctr, Spinal Cord Injury Serv, Cleveland, OH USA. [Bogie, Kath M.] Louis Stokes Cleveland VA Med Ctr, Cleveland Adv Platform Technol Ctr, Cleveland, OH USA. [Bogie, Kath M.] Louis Stokes Cleveland VA Med Ctr, Funct Elect Stimulat Ctr, Cleveland, OH USA. [Bogie, Kath M.] Case Western Reserve Univ, Dept Orthopaed, Cleveland, OH 44106 USA. [Guihan, Marylou] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, SCI QUERI, Hines, IL 60141 USA. [Guihan, Marylou] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Ctr Management Complex Chron Care, Hines, IL 60141 USA. [Guihan, Marylou] Northwestern Univ, Inst Healthcare Studies, Feinberg Sch Med, Chicago, IL 60611 USA. Case Western Reserve Univ, Dept Phys Med & Rehabil, Cleveland, OH 44106 USA. RP Henzel, MK (reprint author), Louis Stokes Cleveland VA Med Ctr, Spinal Cord Injury Serv, Cleveland, OH USA. EM kmb3@case.edu NR 114 TC 23 Z9 23 U1 2 U2 10 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2011 VL 48 IS 3 BP XI EP XXXI DI 10.1682/JRRD.2011.01.0011 PG 21 WC Rehabilitation SC Rehabilitation GA 749TS UT WOS:000289493900002 PM 21480093 ER PT J AU Cameron, MH Poel, AJ Haselkorn, JK Linke, A Bourdette, D AF Cameron, Michelle H. Poel, Amy J. Haselkorn, Jodie K. Linke, Alex Bourdette, Dennis TI Falls requiring medical attention among veterans with multiple sclerosis: A cohort study SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE accidental falls; cohort study; disability; epidemiology; medical records; multiple sclerosis; risk; sex; veterans; wounds and injuries ID OLDER-ADULTS; ACCIDENTAL FALLS; PEOPLE; EPIDEMIOLOGY; REGISTRY; COSTS; RISK AB The purpose of this study was to estimate the relative risk of an injurious fall requiring medical attention in veterans with multiple sclerosis (MS) compared with veterans without MS after controlling for sex, age, and healthcare use. The sample included 195,417 veterans treated at Veterans Health Administration (VHA) facilities in the Northwest United States in fiscal year 2008. We obtained information regarding MS diagnosis, injurious falls (operationalized as International Classification of Diseases-9th Revision-Clinical Modification codes E880-E888), and demographic and healthcare use data from the VHA Consumer Health Information Performance Set database. Using logistic regression, we determined the adjusted odds ratio (OR) of an injurious fall to be three times higher in female veterans with MS than in female veterans without MS (OR = 3.0, 95% confidence interval [Cl] = 1.6-5.5). The adjusted OR of an injurious fall for men with MS was also higher than for men without MS, but this difference was not statistically significant (OR = 1.2, 95% CI = 0.8-2.1). We recommend further studies evaluating the medical, social, and economic consequences of injurious falls, as well as interventions to prevent injurious falls, to improve the independence and quality of life of veterans and others living with MS. C1 [Cameron, Michelle H.; Bourdette, Dennis] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Cameron, Michelle H.; Bourdette, Dennis] Portland Dept Vet Affairs VA Med Ctr VAMC, Neurol Serv, Portland, OR USA. [Cameron, Michelle H.; Bourdette, Dennis] Portland Dept Vet Affairs VA Med Ctr VAMC, Multiple Sclerosis Ctr Excellence W, Portland, OR USA. [Poel, Amy J.; Haselkorn, Jodie K.] VA Puget Sound Hlth Care Syst, Multiple Sclerosis Ctr Excellence W, Seattle, WA USA. [Poel, Amy J.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Haselkorn, Jodie K.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Linke, Alex] Portland VA Med Ctr, Behav Hlth & Clin Neurosci Div, Portland, OR USA. RP Cameron, MH (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, 3181 SW Sam Jackson Pk Rd,CR120, Portland, OR 97239 USA. EM cameromi@ohsu.edu FU National Multiple Sclerosis Society; VA Rehabilitation Research and Development Service FX This material was based on work supported by a Sylvia Lawry Physician Fellowship from the National Multiple Sclerosis Society and by a Career Development Award (Dr. Cameron) from the VA Rehabilitation Research and Development Service. NR 42 TC 22 Z9 22 U1 0 U2 3 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2011 VL 48 IS 1 BP 13 EP 20 DI 10.1682/JRRD.2009.12.0192 PG 8 WC Rehabilitation SC Rehabilitation GA 719SG UT WOS:000287228700002 PM 21328159 ER PT J AU Walter, JS Wurster, RD Zhu, QL Laghi, F AF Walter, James S. Wurster, Robert D. Zhu, Qianlong Laghi, Franco TI Respiratory muscle pacing with chronically implanted intramuscular Permaloc electrodes: A feasibility study SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE animal model; electrical stimulation; feasibility study; functional electrical stimulation; intramuscular electrodes; muscle pacing; respiration; respiratory distress; spinal cord injury; tidal volume ID SPINAL-CORD-INJURY; FUNCTIONAL ELECTRICAL-STIMULATION; PROVIDE ARTIFICIAL-VENTILATION; ABDOMINAL-MUSCLES; INSPIRATORY INTERCOSTAL; DIAPHRAGM; COUGH; TETRAPLEGIA; NERVE AB We tested the feasibility of stimulating upper-intercostal and abdominal muscles plus the diaphragm by using chronically implanted intramuscular electrodes. During two survival surgeries with six dogs, intramuscular electrodes were implanted bilaterally in the three respiratory muscles. Standard stimulation of the diaphragm was conducted. The dorsolateral and ventrolateral abdominal wall areas were stimulated with a 25 mA current. The second to fourth intercostal spaces were stimulated to elicit the largest tidal volume associated with the least coactivation of the serratus and latissimus muscles. Lone diaphragm and upper-intercostal muscle pacing produced inhaled tidal volumes (mean +/- standard error of the mean) of 293 +/- 36 mL and 59 +/- 17 mL, respectively. Lone abdominal muscle pacing produced an exhaled volume of 55 +/- 17 mL. Combined pacing of diaphragm and intercostal muscles increased the inhaled volume to 389 +/- 39 mL. The addition of abdominal pacing following the combined stimulation of diaphragm and intercostals increased the exhaled volume to 472 +/- 54 mL. During autopsy, dislodgement of the electrodes overlying the ribs was a concern and probably resulted from loose animal jackets. Chronic intramuscular Permaloc electrodes can be implanted in several respiratory muscles and increase tidal volumes more than diaphragm stimulation alone. C1 [Walter, James S.; Wurster, Robert D.; Zhu, Qianlong] Edward Hines Jr Dept Vet Affairs VA Hosp, Res Serv, Hines, IL USA. [Walter, James S.] Loyola Univ, Med Ctr, Dept Urol, Maywood, IL 60153 USA. [Wurster, Robert D.] Loyola Univ, Med Ctr, Dept Neurol Surg & Physiol, Maywood, IL 60153 USA. [Laghi, Franco] Loyola Univ, Med Ctr, Div Pulm & Crit Care Med, Maywood, IL 60153 USA. [Laghi, Franco] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Pulm & Crit Care Med Sect, Hines, IL 60141 USA. RP Walter, JS (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Res Serv 151, Roosevelt & 1st Ave, Hines, IL 60141 USA. EM James.Walter@va.gov FU VA's Office of Research and Development, Rehabilitation Research and Development Service [B3008P] FX This material was based on work supported by the VA's Office of Research and Development, Rehabilitation Research and Development Service (grant B3008P). Synapse Biomedical, Inc, provided electrodes, stimulators, and technical assistance under a Material, Cooperative, Research and Development Agreement between the company and the VA. NR 21 TC 5 Z9 6 U1 0 U2 2 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2011 VL 48 IS 2 BP 103 EP 114 DI 10.1682/JRRD.2010.05.0086 PG 12 WC Rehabilitation SC Rehabilitation GA 733BQ UT WOS:000288235800003 PM 21480085 ER PT J AU Liu, CF Collins, MP Souza, PE Yueh, B AF Liu, Chuan-Fen Collins, Margaret P. Souza, Pamela E. Yueh, Bevan TI Long-term cost-effectiveness of screening strategies for hearing loss SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE audiology; aural rehabilitation; cost-effectiveness; healthcare cost; health services; hearing aid; hearing loss; hearing loss screening; preventive care; veterans ID RANDOMIZED-TRIAL; AUDITORY IMPAIRMENT; OLDER-ADULTS; PRIMARY-CARE; HEALTH; AMPLIFICATION; HANDICAP AB Routine hearing screening can identify patients who are motivated to seek out and adhere to treatment, but little information exists on the cost-effectiveness of hearing screening in a general population of older veterans. We compared the cost-effectiveness of three screening strategies (tone-emitting otoscope, hearing handicap questionnaire, and both together) against no screening (control group) in 2,251 older veterans. The effectiveness measure for each group was the proportion of hearing aid use 1 year after screening. The audiology cost measure included costs of hearing loss screening and audiology care for 1 year after screening. Incremental cost-effectiveness was the audiology cost of additional hearing aid use for each screening group compared with the control group. The mean total audiology cost per patient was $77.04, $122.70, $121.37, and $157.08 for the control, otoscope, questionnaire, and dual screening groups, respectively. The tone-emitting otoscope appears to be the most cost-effective approach for hearing loss screening, with a significant increase in hearing aid use 1 year after screening (2.8%) and an insignificant incremental cost-effectiveness of $1,439.00 per additional hearing aid user compared with the control group. For this population of older veterans, screening for hearing loss with the tone-emitting otoscope is cost-effective. C1 [Liu, Chuan-Fen; Collins, Margaret P.; Yueh, Bevan] Dept Vet Affairs VA Puget Sound Hlth Care Syst, Ctr Excellence Hlth Serv Res & Dev, Seattle, WA USA. [Liu, Chuan-Fen] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Souza, Pamela E.] Univ Washington, Dept Speech & Hearing Sci, Seattle, WA 98195 USA. [Yueh, Bevan] Univ Washington, Dept Otolaryngol & Head & Neck Surg, Seattle, WA 98195 USA. [Yueh, Bevan] VA Puget Sound Hlth Care Syst, Surg & Perioperat Care Serv, Seattle, WA 98101 USA. RP Liu, CF (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Serv 152, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM fliu@u.washington.edu OI Yueh, Bevan/0000-0003-1380-1053 FU Health Services Research and Development Service of the Veterans Health Administration [I1R 99-377] FX This work was supported by the Health Services Research and Development Service of the Veterans Health Administration (grant I1R 99-377). NR 35 TC 7 Z9 7 U1 1 U2 9 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 EI 1938-1352 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2011 VL 48 IS 3 BP 235 EP 243 DI 10.1682/JRRD.2010.03.0041 PG 9 WC Rehabilitation SC Rehabilitation GA 749TS UT WOS:000289493900007 PM 21480098 ER PT J AU Burgar, CG Lum, PS Scremin, AME Garber, SL Van der Loos, HFM Kenney, D Shor, P AF Burgar, Charles G. Lum, Peter S. Scremin, A. M. Erika Garber, Susan L. Van der Loos, H. F. Machiel Kenney, Deborah Shor, Peggy TI Robot-assisted upper-limb therapy in acute rehabilitation setting following stroke: Department of Veterans Affairs multisite clinical trial SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE acute; arm; bilateral; dose-response; hemiparesis; intensity; rehabilitation; robotics; stroke; therapy ID CONSTRAINT-INDUCED MOVEMENT; UPPER-EXTREMITY FUNCTION; FUGL-MEYER ASSESSMENT; MOTOR FUNCTION-TEST; RECOVERY; POSTSTROKE; RELIABILITY; ARM; STIMULATION; FORELIMB AB This randomized, controlled, multisite Department of Veterans Affairs clinical trial assessed robot-assisted (RA) upper-limb therapy with the Mirror Image Movement Enabler (MIME) in the acute stroke rehabilitation setting. Hemiparetic subjects (n = 54) received RA therapy using MIME for either up to 15 hours (low-dose) or 30 hours (high-dose) or received up to 15 hours of additional conventional therapy in addition to usual care (control). The primary outcome measure was the Fugl-Meyer Assessment (FMA). The secondary outcome measures were the Functional Independence Measure (FIM), Wolf Motor Function Test, Motor Power, and Ashworth scores at intake, discharge, and 6-month follow-up. Mean duration of study treatment was 8.6, 15.8, and 9.4 hours for the low-dose, high-dose, and control groups, respectively. Gains in the primary outcome measure were not significantly different between groups at follow-up. Significant correlations were found at discharge between FMA gains and the dose and intensity of RA. Intensity also correlated with FMA gain at 6 months. The high-dose group had greater FIM gains than controls at discharge and greater tone but no difference in FIM changes compared with low-dose subjects at 6 months. As used during acute rehabilitation, motor-control changes at follow-up were no less with MIME than with additional conventional therapy. Intensity of training with MIME was positively correlated with motor-control gains. C1 [Burgar, Charles G.] Cent Texas Vet Hlth Care Syst, Temple, TX 76504 USA. [Burgar, Charles G.] Rice Univ, Dept Mech Engn & Mat Sci, Houston, TX 77251 USA. [Lum, Peter S.] Catholic Univ Amer, Washington DC Dept Vet Affairs VA Med Ctr, Washington, DC 20064 USA. [Lum, Peter S.] Catholic Univ Amer, Dept Biomed Engn, Washington, DC 20064 USA. [Scremin, A. M. Erika] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Scremin, A. M. Erika] Univ Calif Los Angeles, Los Angeles, CA USA. [Garber, Susan L.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Garber, Susan L.] Baylor Coll Med, Houston, TX 77030 USA. [Van der Loos, H. F. Machiel; Kenney, Deborah; Shor, Peggy] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Van der Loos, H. F. Machiel] Stanford Univ, Dept Mech Engn, Stanford, CA 94305 USA. RP Burgar, CG (reprint author), Cent Texas Vet Hlth Care Syst, 1901 Vet Mem Dr, Temple, TX 76504 USA. EM Charles.Burgar1@va.gov RI Van der Loos, Hendrik/A-3693-2012; OI Kenney, Deborah/0000-0003-0795-1901 FU VA Rehabilitation Research and Development Service [B2695I] FX This material was based on work supported by the VA Rehabilitation Research and Development Service (grant B2695I). NR 43 TC 52 Z9 58 U1 3 U2 30 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2011 VL 48 IS 4 BP 445 EP 458 DI 10.1682/JRRD.2010.04.0062 PG 14 WC Rehabilitation SC Rehabilitation GA 774GB UT WOS:000291372200011 PM 21674393 ER PT J AU Folmer, RL McMillan, GP Austin, DF Henry, JA AF Folmer, Robert L. McMillan, Garnett P. Austin, Donald F. Henry, James A. TI Audiometric thresholds and prevalence of tinnitus among male veterans in the United States: Data from the National Health and Nutrition Examination Survey, 1999-2006 SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE audiometry; epidemiology; hearing loss; NHANES; noise exposure; prevalence; rehabilitation; thresholds; tinnitus; veterans ID HEARING-LOSS PREVENTION; NOISE EXPOSURE; BEAVER DAM; INTERVENTION; PROTECTION; WISCONSIN; COHORT; ADULTS; YOUTH; NEED AB Hearing loss and tinnitus are the two most prevalent service-connected disabilities among U.S. veterans. The number of veterans receiving compensation and services from the Department of Veterans Affairs (VA) for these conditions continues to increase annually. However, the majority of veterans in the United States do not use VA medical centers or clinics for healthcare and do not receive VA compensation payments. Therefore, the prevalence of hearing loss and tinnitus among U.S. veterans is unknown. This study used National Health and Nutrition Examination Survey data to estimate the prevalence of these auditory conditions among male veterans. Between 1999 and 2006, pure tone audiometric data collected from 845 male veterans were compared with pure tone thresholds collected from 2,086 male nonveterans. We used questionnaire data collected between 1999 and 2004 to calculate and compare the prevalence of tinnitus for 2,174 veterans and 4,995 nonveterans. In general, pure tone thresholds did not differ significantly between veterans and nonveterans for most frequencies tested (500-8,000 Hz). The overall prevalence of tinnitus was greater for veterans than that for nonveterans (p < 0.001), with statistically significant differences in the 50 to 59 and 60 to 69 age groups. C1 [Folmer, Robert L.; McMillan, Garnett P.; Austin, Donald F.; Henry, James A.] Portland Dept Vet Affairs Med Ctr, Natl Ctr Rehabilitat Auditory Res, Portland, OR USA. [Folmer, Robert L.; Henry, James A.] Oregon Hlth & Sci Univ, Dept Otolaryngol, Portland, OR 97201 USA. [McMillan, Garnett P.; Austin, Donald F.] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. RP Folmer, RL (reprint author), Portland VA Med Ctr, Natl Ctr Rehabilitat Auditory Res, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM Robert.Folmer@va.gov FU VA Rehabilitation Research & Development Center of Excellence [C4844C] FX This material was based on work supported by a VA Rehabilitation Research & Development Center of Excellence grant C4844C to the National Center for Rehabilitative Auditory Research (located at the Portland VAMC) in Portland, Oregon. NR 27 TC 13 Z9 14 U1 0 U2 2 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2011 VL 48 IS 5 BP 503 EP 515 DI 10.1682/JRRD.2010.07.0138 PG 13 WC Rehabilitation SC Rehabilitation GA 783GJ UT WOS:000292069200006 PM 21674401 ER PT J AU Lew, HL Kraft, M Pogoda, TK Amick, MM Woods, P Cifu, DX AF Lew, Henry L. Kraft, Malissa Pogoda, Terri K. Amick, Melissa M. Woods, Patricia Cifu, David X. TI Prevalence and characteristics of driving difficulties in Operation Iraqi Freedom/Operation Enduring Freedom combat returnees SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE automobiles; combat; concussion; deployment; driving; OIF/OEF; posttraumatic stress disorder; road rage; traumatic brain injury; veterans ID POSTTRAUMATIC-STRESS-DISORDER; TRAUMATIC BRAIN-INJURY; MOTOR-VEHICLE ACCIDENT; MENTAL-HEALTH PROBLEMS; WAR VETERANS; POSTCONCUSSIVE SYMPTOMS; SLEEP DISTURBANCE; FOLLOW-UP; GULF-WAR; AFGHANISTAN AB We studied the prevalence and characteristics of self-reported driving difficulties and examined their association with traumatic brain injury (TBI) and/or posttraumatic stress disorder (PTSD) in Operation Iraqi Freedom/Operation Enduring Freedom (OIF/OEF) veterans who were seen at a Department of Veterans Affairs outpatient polytrauma clinic. In this study, we used a brief driving questionnaire and chart reviews to assess the prevalence and characteristics of driving difficulties in the following four groups of patients: TBI only, PTSD only, TBI + PTSD, and Neither (neither TBI nor PTSD). Compared with before deployment, 93% of OIF/OEF veterans seen in the polytrauma clinic reported more difficulties with driving in at least one domain, with the most common areas of difficulty being (1) problems with anger or impatience (82%), (2) general driving difficulties (65%), and (3) experiences with near misses (57%). Patients with PTSD (with or without TBI) reported the most significant driving impairments, whereas respondents with a history of only TBI endorsed driving difficulties similar to veterans without either diagnosis. Qualitative analysis of veterans' comments also revealed similar patterns. Self-reported driving problems were common among OIF/OEF returnees. Respondents who had a diagnosis of PTSD (with or without TBI) reported the most severe driving difficulties since returning from deployment. The association between PTSD and driving problems warrants further investigation. C1 [Lew, Henry L.] DVBIC, Richmond, VA USA. [Lew, Henry L.] Univ Manoa, Honolulu, HI USA. [Kraft, Malissa; Pogoda, Terri K.; Amick, Melissa M.; Woods, Patricia] VA Boston Healthcare Syst, Polytrauma & Traumat Brain Injury Res Ctr, Dept Vet Affairs, Boston, MA USA. [Pogoda, Terri K.] VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, Boston, MA USA. [Pogoda, Terri K.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Amick, Melissa M.] DVBIC, Boston, MA USA. [Cifu, David X.] Hunter Holmes McGuire VA Med Ctr, Phys Med & Rehabil Serv, Richmond, VA USA. RP Lew, HL (reprint author), Univ Hawaii Manoa, 1410 Lower Campus Rd, Honolulu, HI 96822 USA. EM hlew@dvbic.org RI Schueter, nicos/A-3625-2014 FU VA Merit Review Grant [B5009R] FX This material was based on work supported by VA Merit Review Grant B5009R. NR 59 TC 15 Z9 15 U1 1 U2 4 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2011 VL 48 IS 8 BP 913 EP 925 DI 10.1682/JRRD.2010.08.0140 PG 13 WC Rehabilitation SC Rehabilitation GA 847DM UT WOS:000296952100004 PM 22068370 ER PT J AU Koontz, AM Lin, YS Kankipati, P Boninger, ML Cooper, RA AF Koontz, Alicia M. Lin, Yen-Sheng Kankipati, Padmaja Boninger, Michael L. Cooper, Rory A. TI Development of custom measurement system for biomechanical evaluation of independent wheelchair transfers SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE activities of daily living; assessment; forces; kinematics; kinetics; range of motion; reliability; spinal cord injury; three-dimensional motion analysis; upper limb ID SPINAL-CORD-INJURY; SITTING PIVOT TRANSFERS; SHOULDER KINEMATICS; UPPER EXTREMITY; INDIVIDUALS; MOVEMENT; MOTION; USERS; IMPINGEMENT; DISABILITY AB This study describes a new custom measurement system designed to investigate the biomechanics of sitting-pivot wheelchair transfers and assesses the reliability of selected biomechanical variables. Variables assessed include horizontal and vertical reaction forces underneath both hands and three-dimensional trunk, shoulder, and elbow range of motion. We examined the reliability of these measures between 5 consecutive transfer trials for 5 subjects with spinal cord injury and 12 non-disabled subjects while they performed a self-selected sitting pivot transfer from a wheelchair to a level bench. A majority of the biomechanical variables demonstrated moderate to excellent reliability (r > 0.6). The transfer measurement system recorded reliable and valid biomechanical data for future studies of sitting-pivot wheelchair transfers. We recommend a minimum of five transfer trials to obtain a reliable measure of transfer technique for future studies. C1 [Koontz, Alicia M.; Boninger, Michael L.; Cooper, Rory A.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. [Koontz, Alicia M.; Lin, Yen-Sheng; Kankipati, Padmaja; Boninger, Michael L.; Cooper, Rory A.] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. [Boninger, Michael L.; Cooper, Rory A.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. [Koontz, Alicia M.; Lin, Yen-Sheng; Kankipati, Padmaja; Boninger, Michael L.; Cooper, Rory A.] Dept Vet Affairs Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA USA. RP Koontz, AM (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs 151R1 H, 7180 Highland Dr,151R1-H, Pittsburgh, PA 15206 USA. EM akoontz@pitt.edu OI Boninger, Michael/0000-0001-6966-919X FU VA Rehabilitation Research and Development Service [E3589V, B3079R, A4489R]; National Institute on Disability and Rehabilitation Research (NIDRR) [H133A011107]; National Institutes of Health Center for Injury Research Control [NIH R49/CCR310285-06] FX This material was based on work supported by the VA Rehabilitation Research and Development Service (grants E3589V, B3079R, and A4489R); the National Institute on Disability and Rehabilitation Research (grant NIDRR H133A011107); and the National Institutes of Health Center for Injury Research Control (grant NIH R49/CCR310285-06). NR 28 TC 8 Z9 8 U1 1 U2 5 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2011 VL 48 IS 8 BP 1015 EP 1028 DI 10.1682/JRRD.2010.09.0169 PG 14 WC Rehabilitation SC Rehabilitation GA 847DM UT WOS:000296952100010 PM 22068376 ER PT J AU Karmarkar, AM Cooper, RA Wang, HW Kelleher, A Cooper, R AF Karmarkar, Amol M. Cooper, Rory A. Wang, Hongwu Kelleher, Annmarie Cooper, Rosemarie TI Analyzing wheelchair mobility patterns of community-dwelling older adults SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE community participation; data logger; environment; manual wheelchair use; National Veterans Wheelchair Games; older adults; physical activity; power wheelchair use; wheelchair mobility; wheelchair provision ID PHYSICAL-ACTIVITY; OBJECTIVE ASSESSMENT; PROPULSION; USERS; BIOMECHANICS AB This study determined and compared wheelchair mobility patterns for older adults during an organized sporting event and within their community. In July 2008, 39 veterans participating in the 28th National Veterans Wheelchair Games (Omaha, Nebraska) completed the study. Of these, 26 were manual wheelchair and 13 were power wheelchair users. We collected wheelchair-related mobility data using wheelchair data-logging devices. Participants were significantly more active using manual wheelchairs during the games than when using their wheelchairs in their homes in terms of distance traveled (4,466.2 vs 1,367.4 m, p < 0.001) and average speed of propulsion (0.76 vs 0.64 m/s, p < 0.001). The trend was the same for power wheelchair users, with respect to distance (7,306.2 vs 3,450.5 m, p = 0.004) and average speed (0.9 vs 0.7 m/s, p = 0.002). This study demonstrates an objective method of evaluating wheelchair use in community-dwelling older adults. C1 [Cooper, Rory A.; Wang, Hongwu; Kelleher, Annmarie; Cooper, Rosemarie] Pittsburgh Healthcare Syst, Human Engn Res Labs, Dept Vet Affairs, Pittsburgh, PA USA. [Cooper, Rory A.; Wang, Hongwu; Kelleher, Annmarie; Cooper, Rosemarie] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. [Karmarkar, Amol M.] Univ Texas Med Branch, Div Rehabil Sci, Galveston, TX USA. RP Cooper, RA (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, 7180 Highland Dr,Bldg 4,2nd Fl,151R1-HD, Pittsburgh, PA 15206 USA. EM rcooper@pitt.edu RI Wang, Hongwu/J-6133-2013; Karmarkar, Amol/E-6030-2011 OI Wang, Hongwu/0000-0002-6567-9144; Karmarkar, Amol/0000-0001-8355-1585 FU VA Center for Excellence in Wheelchairs and Associated Rehabilitation Engineering [B3142C]; Engineering Research Center on Quality of Life Technology [EEC 0540865]; PVA; Keystone PVA FX This material was based on work supported by the VA Center for Excellence in Wheelchairs and Associated Rehabilitation Engineering (grant B3142C) and Engineering Research Center on Quality of Life Technology (grant EEC 0540865). We would like to thank the PVA and Keystone PVA for their sponsorship of research conducted during the NVWG. NR 23 TC 4 Z9 4 U1 0 U2 4 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2011 VL 48 IS 9 BP 1077 EP 1086 DI 10.1682/JRRD.2009.10.0177 PG 10 WC Rehabilitation SC Rehabilitation GA 859RC UT WOS:000297892500004 PM 22234712 ER PT J AU Rae-Grant, AD Turner, AP Sloan, A Miller, D Hunziker, J Haselkorn, JK AF Rae-Grant, Alex D. Turner, Aaron P. Sloan, Alicia Miller, Deborah Hunziker, James Haselkorn, Jodie K. TI Self-management in neurological disorders: Systematic review of the literature and potential interventions in multiple sclerosis care SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Review DE chronic illness; headache; multiple sclerosis; neurological; Parkinson disease; self-care; self-management; stroke; systematic review; traumatic brain injury ID RANDOMIZED CONTROLLED-TRIAL; INTERNET-BASED TREATMENT; IMPROVING PRIMARY-CARE; CHRONIC ILLNESS; DISEASE MANAGEMENT; EXERCISE PROGRAM; CLINICAL-TRIAL; PATIENT; PEOPLE; MIGRAINE AB Our objective was to review the current body of evidence supporting the efficacy of self-management programs in individuals with multiple sclerosis (MS) and other chronic neurological conditions. We reviewed published literature using standardized search terms; examined self-management interventions in a variety of chronic neurological disorders, including MS; and classified studies using the evidence classification established by the American Academy of Neurology. We reviewed 527 abstracts, of which 39 met our inclusion criteria for evaluation. Of the 39 studies, 3 provided class I evidence assessing the efficacy of self-management interventions: a randomized controlled trial of a telephone counseling program for health promotion in MS, a home-based exercise program for reducing falls in people with Parkinson disease, and the comparison of a fitness center program versus a home-based exercise program for people with traumatic brain injury. The remaining studies provided additional support for self-management interventions with a lesser degree of methodologic rigor (class II, class III, or class IV evidence). We concluded that self-management strategies are applicable to chronic neurological diseases, but a need exists for more rigorous studies in this area. We provide recommendations for future intervention study methodologies with a specific emphasis on MS care. C1 [Turner, Aaron P.; Sloan, Alicia; Hunziker, James; Haselkorn, Jodie K.] Puget Sound Hlth Care Syst, Dept Vet Affairs, Multiple Sclerosis Ctr Excellence W, Seattle, WA USA. [Rae-Grant, Alex D.; Miller, Deborah] Cleveland Clin, Mellen Ctr Multiple Sclerosis Treatment & Res, Cleveland, OH 44106 USA. [Turner, Aaron P.; Haselkorn, Jodie K.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Haselkorn, Jodie K.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Turner, AP (reprint author), VA Puget Sound Hlth Care Syst, Rehabil Care Serv, S-117-RCS,1660 S Columbian Way, Seattle, WA 98108 USA. EM Aaron.Turner@va.gov OI sloan, alicia/0000-0003-4891-3266; Turner, Aaron/0000-0001-6897-8003 FU Department of Veterans Affairs (VA) [B4927W]; VA MS Center of Excellence West FX This material was based on work supported by a Department of Veterans Affairs (VA) Rehabilitation Research and Development Service Career Development Award (grant B4927W to Dr. Turner). Additional support was provided by the VA MS Center of Excellence West. NR 39 TC 10 Z9 10 U1 1 U2 12 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2011 VL 48 IS 9 BP 1087 EP 1099 DI 10.1682/JRRD.2010.08.0159 PG 13 WC Rehabilitation SC Rehabilitation GA 859RC UT WOS:000297892500005 PM 22234713 ER PT J AU Denneson, LM Corson, K Dobscha, SK AF Denneson, Lauren M. Corson, Kathryn Dobscha, Steven K. TI Complementary and alternative medicine use among veterans with chronic noncancer pain SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE acupuncture; aged; alternative therapies; chiropractic; chronic pain; complementary therapies; delivery of healthcare; herbal medicine; massage therapy; veterans ID LOW-BACK-PAIN; PRIMARY-CARE; COLLABORATIVE CARE; MILITARY VETERANS; RANDOMIZED-TRIAL; UNITED-STATES; PREVALENCE; MANAGEMENT; THERAPIES; SEVERITY AB We describe prior use and willingness to try complementary and alternative medicine (CAM) among 401 veterans experiencing chronic noncancer pain and explore differences between CAM users and nonusers. Participants in a randomized controlled trial, of a collaborative intervention for chronic pain from five Department of Veterans Affairs (VA) primary care clinics self-reported prior use and willingness to try chiropractic care, massage therapy, herbal medicines, and acupuncture. Prior CAM users were compared with nonusers on demographic characteristics, pain-related clinical characteristics, disease burden, and treatment satisfaction. A majority of veterans (n = 327, 82%) reported prior use of at least one CAM modality, and nearly all (n = 399, 99%) were willing to try CAM treatment for pain. Chiropractic care was the least preferred option, whereas massage therapy was the most preferred (75% and 96%, respectively). CAM users were less likely to have service-connection disabilities (54% vs 68%; chi square = 4.64, p = 0.03) and reported having spent a larger percentage of their lives in pain (26% vs 20%; Z = 1.40, p = 0.04) than nonusers. We detected few differences between veterans who had tried CAM and those who had not, suggesting that CAM may have broad appeal among veterans with chronic pain. Implications for VA policy and practice and for clinicians treating veterans with chronic pain are discussed. C1 [Denneson, Lauren M.] Portland Dept Vet Affairs Med Ctr, Portland Ctr Study Chron Comorbid Phys & Mental D, Portland, OR USA. Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. RP Denneson, LM (reprint author), Portland VA Med Ctr, POB 1034,P3DEP PC, Portland, OR 97207 USA. EM lauren.denneson@va.gov FU VA Veterans Health Administration and Health Services Research and Development Service [PMI 03-195, REA 06-174] FX This material is based on work supported in part by the VA Veterans Health Administration and Health Services Research and Development Service (grants PMI 03-195 and REA 06-174). NR 48 TC 22 Z9 22 U1 7 U2 17 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2011 VL 48 IS 9 BP 1119 EP 1127 DI 10.1682/JRRD.2010.12.0243 PG 9 WC Rehabilitation SC Rehabilitation GA 859RC UT WOS:000297892500008 PM 22234716 ER PT J AU Velozo, CA Woodbury, ML AF Velozo, Craig A. Woodbury, Michelle L. TI Translating measurement findings into rehabilitation practice: An example using Fugl-Meyer Assessment-Upper Extremity with patients following stroke SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE assessment; clinical goal setting; Fugl-Meyer Assessment; item response theory; measurement; occupational therapy; Rasch analysis; rehabilitation; stroke; upper limb AB Standardized assessments are critical for advancing clinical rehabilitation, yet assessment scores often provide little information for rehabilitation treatment planning. A keyform recovery map is an innovative way for a therapist to record patient responses to standardized assessment items. The form enables a therapist to view the specific items that a patient can or cannot perform. This information can assist a therapist in tailoring treatments to a patient's individual ability level. We demonstrate how a keyform recovery map can be used to inform clinical treatment planning for individuals with stroke-related upper-limb motor impairment. A keyform map of poststroke upper-limb 'recovery defined by items of the Fugl-Meyer Assessment-Upper Extremity (FMA-UE) was generated by a previously published Rasch analysis. Three individuals with stroke enrolled in a separate research study were randomly selected from each of the three impairment strata of the FMAUE. Their performance on each item was displayed on the FMA-UE keyform. The forms directly connected qualitative descriptions of patients' motor ability to assessment measures, thereby suggesting appropriate shorter and longer term rehabilitation goals. This study demonstrates how measurement theory can be used to translate a standardized assessment into a useful, evidence-based tool for making clinical practice decisions. C1 [Velozo, Craig A.] Malcom Randall Dept Vet Affairs VA Med Ctr, Rehabil Outcomes Res Ctr, Gainesville, FL USA. [Velozo, Craig A.] Malcom Randall Dept Vet Affairs VA Med Ctr, Brain Rehabil Res Ctr, Gainesville, FL USA. [Velozo, Craig A.] Univ Florida, Dept Occupat Therapy, Coll Publ Hlth & Hlth Profess, Gainesville, FL 32610 USA. [Woodbury, Michelle L.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Woodbury, Michelle L.] Med Univ S Carolina, Dept Hlth Sci & Res, Charleston, SC 29425 USA. RP Velozo, CA (reprint author), Univ Florida, Dept Occupat Therapy, Coll Publ Hlth & Hlth Profess, PO 100164, Gainesville, FL 32610 USA. EM cvelozo@phhp.ufl.edu FU Department of Veterans Affairs; Veterans Health Administration; Office of Research and Development; Rehabilitation Research and Development Service; Career Development-2 Award [B6332W] FX This material is based on work supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Rehabilitation Research and Development Service, Career Development-2 Award (project B6332W), principal investigator Michelle L. Woodbury. NR 34 TC 16 Z9 16 U1 0 U2 11 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2011 VL 48 IS 10 BP 1211 EP 1221 DI 10.1682/JRRD.2010.10.0203 PG 11 WC Rehabilitation SC Rehabilitation GA V28XL UT WOS:000208713400008 PM 22234665 ER PT J AU Singh, JA Beg, S Lopez-Olivo, MA AF Singh, Jasvinder A. Beg, Saba Lopez-Olivo, Maria Angeles TI Tocilizumab for Rheumatoid Arthritis: A Cochrane Systematic Review SO JOURNAL OF RHEUMATOLOGY LA English DT Review DE TOCILIZUMAB; RHEUMATOID; ARTHRITIS; BENEFIT; SAFETY ID COLLEGE-OF-RHEUMATOLOGY; INTERLEUKIN-6 RECEPTOR INHIBITION; PLACEBO-CONTROLLED TRIAL; DISEASE-ACTIVITY SCORE; DOUBLE-BLIND; RESPONSE CRITERIA; INADEQUATE RESPONSE; CLINICAL-TRIALS; METHOTREXATE; MULTICENTER AB Objective. To compare the benefit and safety of tocilizumab to placebo in patients with rheumatoid arthritis (RA). Methods. We searched multiple databases for published randomized or controlled clinical trials comparing benefit and safety of tocilizumab to placebo, disease-modifying antirheumatic drugs (DMARD), or other biologics. For dichotomous outcomes, we calculated the relative risk, and for continuous outcomes, the mean difference. Results. Eight randomized controlled trials were included in this systematic review, with 3334 participants, 2233 treated with tocilizumab and 1101 controls. The US and Canadian approved dose of tocilizumab, 8 mg/kg every 4 weeks, was given to 1561 participants. In patients taking concomitant methotrexate, compared to placebo, patients treated with approved dose of tocilizumab were substantially and statistically significantly more likely than placebo to achieve the American College of Rheumatology 50 (absolute percentage, 38.8% vs 9.6%, respectively; RR 3.2, 95% CI 2.7, 3.7); Disease Activity Score remission (30.5% vs 2.7%; RR 8.7,95% CI 6.3, 11.8); and a clinically meaningful decrease in Health Assessment Questionnaire (HAQ)/Modified HAQ scores (60.5% vs 34%; RR 1.8, 95% CI 1.6, 1.9). There were no substantive statistically significant differences in serious adverse effects (0.8% vs 0.7%; RR 1.2, 95% CI 0.8, 1.6) or withdrawals due to adverse events (4.9% vs 3.7%; RR 1.4, 95% CI 0.9, 2.1); however, tocilizumab-treated patients were significantly more likely to have any adverse event (74% vs 65%; RR 1.05, 95% CI 1.03, 1.07); elevation in the ratio of low-density lipoprotein to high-density lipoprotein cholesterol (HDL; 20% vs 12%; RR 1.7,95% CI 1.2, 2.2); and increase in the ratio of total to HDL cholesterol (12% vs 7%; RR 1.7.95% CI 1.2, 2.6); and they were less likely to withdraw from treatment for any reason (8.1% vs 14.9%; RR 0.6, 95% CI 0.5, 0.8). Conclusion. At the approved dose of 8 mg/kg every 4 weeks, tocilizumab in combination with methotrexate/DMARD is beneficial in decreasing RA disease activity and improving function. Tocilizumab treatment was associated with a significant increase in cholesterol levels and occurrence of any adverse event, but not serious adverse events. Larger safety studies are needed to address these safety concerns. (First Release Oct 15 2010; J Rheumatol 2011;38:10-20; doi:10.3899/jrheum.100717) C1 [Singh, Jasvinder A.] Univ Alabama, Med Serv, Birmingham Vet Affairs Med Ctr, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Univ Alabama, Div Epidemiol, Sch Publ Hlth, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Birmingham Vet Affairs Med Ctr, Ctr Surg Med Acute Care Res & Transit, Birmingham, AL USA. [Singh, Jasvinder A.] Mayo Clin, Sch Med, Dept Hlth Sci Res, Rochester, MN USA. [Singh, Jasvinder A.] Mayo Clin, Sch Med, Dept Orthoped Surg, Rochester, MN USA. [Lopez-Olivo, Maria Angeles] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Singh, Jasvinder A.; Beg, Saba] Vet Affairs Med Ctr, Med Serv, Minneapolis, MN 55417 USA. RP Singh, JA (reprint author), Univ Alabama, Med Serv, Birmingham Vet Affairs Med Ctr, 820 Fac Off Tower,Room 805B, Birmingham, AL 35294 USA. EM jasvinder.md@gmail.com OI singh, jasvinder/0000-0003-3485-0006 FU National Institutes of Health [I KL2 RR024151-01] FX Supported by the National Institutes of Health Clinical Translational Science Award I KL2 RR024151-01 (Mayo Clinic Center for Clinical and Translational Research). NR 45 TC 51 Z9 57 U1 0 U2 1 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JAN PY 2011 VL 38 IS 1 BP 10 EP 20 DI 10.3899/jrheum.100717 PG 11 WC Rheumatology SC Rheumatology GA 709MZ UT WOS:000286446100005 PM 20952462 ER PT J AU Maserejian, N Parish, S Shifren, J Huang, L Gerstenberger, E Rosen, R AF Maserejian, N. Parish, S. Shifren, J. Huang, L. Gerstenberger, E. Rosen, R. TI TREATMENT SEEKING AND HEALTHCARE UTILIZATION IN PREMENOPAUSAL WOMEN WITH CLINICALLY DIAGNOSED HYPOACTIVE SEXUAL DESIRE DISORDER SO JOURNAL OF SEXUAL MEDICINE LA English DT Meeting Abstract C1 [Maserejian, N.; Huang, L.; Gerstenberger, E.; Rosen, R.] New England Res Inst Inc, Watertown, MA USA. [Parish, S.] Albert Einstein Coll Med, Dept Med, New York, NY USA. [Parish, S.] Montefiore Med Ctr, Bronx, NY 10467 USA. [Shifren, J.] Massachusetts Gen Hosp, Vincent OB GYN Serv, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1743-6095 J9 J SEX MED JI J. Sex. Med. PD JAN PY 2011 VL 8 SU 1 BP 15 EP 15 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 702WL UT WOS:000285926500038 ER PT J AU Whatley, AN Fowler, RL Warner, JJP Higgins, LD AF Whatley, Adam N. Fowler, Rachel L. Warner, Jon J. P. Higgins, Laurence D. TI Postoperative rupture of the anterolateral deltoid muscle following reverse total shoulder arthroplasty in patients who have undergone open rotator cuff repair SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article DE Deltoid rupture; reverse; arthroplasty; rotator cuff; mini-open approach; anterolateral deltoid ID SPONTANEOUS DETACHMENT; PROSTHESIS; ORIGIN; TEARS; DEFICIENCY; ARTHRITIS; REVISION; FRACTURE; SURGERY AB Background: Postoperative ruptures of the antero-lateral deltoid in patients with reverse total shoulder arthroplasty utilizing the delto-pectoral approach following failed mini-open or open rotator cuff repairs have not been reported in the English literature. The incidence of this complication is unknown. Materials and methods: A retrospective review of 199 patients who underwent reverse total shoulder arthroplasty utilizing a deltopectoral approach was performed. These procedures were performed by 2 surgeons in 2 hospitals. There were 3 patients who had postoperative rupture of the deltoid. These ruptures occurred without any history of trauma to the patient. In all 3 patients, past surgical history was significant for a rotator cuff repair utilizing a mini-open or mini-open modified to open approach. Successful repair of the deltoid was achieved using a transosseous suture repair in all 3 patients. Results: At most current follow-up (all >12 months), average forward elevation was 120 degrees. A small residual anterior deltoid defect was present in all 3 patients, but pain was quantified as 0-4 out of 10 and radiographs demonstrated satisfactory position of the reverse arthroplasty implants. Conclusion: Postoperative ruptures of the antero-lateral deltoid can occur in patients who have undergone reverse total shoulder arthroplasty, utilizing the delto-pectoral approach following failed mini-open or open rotator cuff repairs. A supero-lateral approach during reverse total shoulder arthroplasty could be useful in assessing and possibly reinforcing a deltoid origin previously damaged or repaired during mini-open or open rotator cuff repair. Level of evidence: Level IV, Case Series, Treatment Study. (C) 2011 Journal of Shoulder and Elbow Surgery Board of Trustees. C1 [Higgins, Laurence D.] Brigham & Womens Hosp, Harvard Shoulder Serv, Boston, MA 02155 USA. [Fowler, Rachel L.; Warner, Jon J. P.] Massachusetts Gen Hosp, Harvard Shoulder Serv, Boston, MA 02114 USA. RP Higgins, LD (reprint author), Brigham & Womens Hosp, Harvard Shoulder Serv, 75 Francis St, Boston, MA 02155 USA. NR 45 TC 11 Z9 11 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD JAN PY 2011 VL 20 IS 1 BP 114 EP 122 DI 10.1016/j.jse.2010.04.049 PG 9 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 703MR UT WOS:000285982600025 PM 20800511 ER PT J AU Dichter, ME Rhodes, KV AF Dichter, Melissa E. Rhodes, Karin V. TI Intimate Partner Violence Survivors' Unmet Social Service Needs SO JOURNAL OF SOCIAL SERVICE RESEARCH LA English DT Article DE Intimate partner violence; domestic violence; service needs ID DOMESTIC VIOLENCE; WOMEN; SHELTER; HEALTH; ABUSE; RISK; POPULATION; PREGNANCY; PROGRAM; SEEKING AB Women who have experienced intimate partner violence (IPV) victimization are at risk for physical and mental health problems, as well as social and economic challenges. In this cross-sectional study, 173 adult, English-speaking women who had experienced police response to IPV completed a self-report questionnaire about their use of, interest in, and need for various social services and whether or not each type of service helped (or would help) them to feel safer. More than three quarters of the participants reported a current need for health and economic support services. There was less interest in traditional IPV resources: law enforcement and domestic violence counseling or shelter. Expanding services to meet survivors' needs for health care and economic independence may facilitate long-term safety. Recommendations for further research in this area are provided. C1 [Dichter, Melissa E.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. [Rhodes, Karin V.] Univ Penn, Dept Emergency Med, Philadelphia, PA 19104 USA. [Rhodes, Karin V.] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19104 USA. RP Dichter, ME (reprint author), Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, 3900 Woodland Ave, Philadelphia, PA 19104 USA. EM mdichter@sp2.upenn.edu NR 40 TC 7 Z9 7 U1 4 U2 18 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0148-8376 J9 J SOC SERV RES JI J. Soc. Serv. Res. PY 2011 VL 37 IS 5 BP 481 EP 489 DI 10.1080/01488376.2011.587747 PG 9 WC Social Work SC Social Work GA 888OS UT WOS:000300013900003 ER PT J AU Rosen, D Goodkind, S Smith, ML AF Rosen, Daniel Goodkind, Sara Smith, Mary Lindsey TI Using Photovoice to Identify Service Needs of Older African American Methadone Clients SO JOURNAL OF SOCIAL SERVICE RESEARCH LA English DT Article DE Substance abuse; substance abuse treatment; aging; methadone maintenance treatment; African Americans; photovoice ID SUBSTANCE-ABUSE TREATMENT; INJECTION-DRUG USERS; 33-YEAR FOLLOW-UP; HEROIN USERS; MAINTENANCE; HEALTH; ADULTS; STRATEGY; PROGRAMS; GENDER AB This article presents findings from a photovoice project designed to identify service needs of older-adult African American methadone clients, as well as their current barriers to and supports for abstinence. The project involved 10 participants (aged 53 to 63 years old) recruited from a methadone maintenance program in a large Northeastern U.S. city. Thematic analysis techniques were used to analyze participants' narratives of their pictures. Transportation emerged as a significant challenge to accessing services, and caregiving was a motivation for remaining abstinent. Future research should use similar participatory methods and engage a broader group of aging people struggling with substance abuse. C1 [Rosen, Daniel; Goodkind, Sara] Univ Pittsburgh, Sch Social Work, Pittsburgh, PA 15260 USA. [Smith, Mary Lindsey] VA Pittsburgh Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA USA. RP Rosen, D (reprint author), Univ Pittsburgh, Sch Social Work, 2117 Cathedral Learning, Pittsburgh, PA 15260 USA. EM dar15@pitt.edu NR 36 TC 4 Z9 4 U1 2 U2 6 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0148-8376 J9 J SOC SERV RES JI J. Soc. Serv. Res. PY 2011 VL 37 IS 5 BP 526 EP 538 DI 10.1080/01488376.2011.607369 PG 13 WC Social Work SC Social Work GA 888OS UT WOS:000300013900007 ER PT J AU Weaver, FM Smith, B LaVela, SL Evans, CT Ullrich, P Miskevics, S Goldstein, B Strayer, J Burns, SP AF Weaver, Frances M. Smith, Bridget LaVela, Sherri L. Evans, Charlesnika T. Ullrich, Philip Miskevics, Scott Goldstein, Barry Strayer, Jonathan Burns, Stephen P. TI Smoking behavior and delivery of evidence-based care for veterans with spinal cord injuries and disorders SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Article DE Tobacco cessation; Spinal cord injury; Evidence-based care ID NATIONAL-SURVEY; PAIN; CESSATION; SMOKERS; RISK; PREVALENCE; TOBACCO; QUIT; NONVETERANS; DEPENDENCE AB Objective: Little is known about those veterans with spinal cord injuries and disorders (SCI/D) who smoke cigarettes. This study identified the factors associated with smoking in this population, motivations for smoking, and the readiness for smoking cessation. Current practices for the delivery of evidence-based tobacco cessation were also examined. Design: Methods included surveys of veterans with SCI/D, medical record reviews of current smokers, and telephone interviews with SCI/D providers. Setting: Six Veterans Health Administration facilities with SCI centers and one SCI clinic. Participants: Survey data were analyzed for 1210 veterans, 256 medical records were reviewed, and 15 providers served as key informants. Interventions: Observational study. Outcome measures: Veterans self-reported smoking status, quit attempts, methods and care received, motivation for smoking, and health care conditions. Medical record review and informant interviews examined the tobacco cessation care provided. Results: Whereas 22% of the respondents were current smokers; 51% were past smokers. Current smokers more often reported respiratory illnesses and/or symptoms, alcohol use, pain, and depression than past or never smokers, and approximately half made quit attempts in the past year. Smokers received referral to counseling (57%) and/or prescription for medication/nicotine replacement (23%). Key informants identified difficulty of providing follow-up and patients' unwillingness to consider quitting as barriers. Conclusion: Veterans with SCI/D who smoke also had other health problems. Providers offer counseling and medication, but often have difficulty following patients to arrange/provide support. Identifying other support methods such as telehealth, considering the use of combination cessation therapies, and addressing other health concerns (e.g. depression) may affect tobacco cessation in this population. C1 [Weaver, Frances M.; Smith, Bridget; LaVela, Sherri L.; Evans, Charlesnika T.; Miskevics, Scott] Hines VA Hosp, Ctr Management Complex Chron Care, Hines, IL 60141 USA. [Weaver, Frances M.; Smith, Bridget; LaVela, Sherri L.; Evans, Charlesnika T.; Miskevics, Scott] Hines VA Hosp, Spinal Cord Injury Qual Enhancement Res Initiat, Hines, IL 60141 USA. [Weaver, Frances M.; Smith, Bridget] Loyola Univ, Program Hlth Serv Res, Dept Med, Maywood, IL 60153 USA. [LaVela, Sherri L.; Evans, Charlesnika T.] Northwestern Univ, Inst Healthcare Studies, Feinberg Sch Med, Chicago, IL 60611 USA. [Ullrich, Philip; Goldstein, Barry; Burns, Stephen P.] VA Puget Sound Healthcare Syst, Spinal Cord Injury Qual Enhancement Res Initiat, Seattle, WA USA. [Goldstein, Barry; Burns, Stephen P.] Univ Washington, Harborview Injury Prevent & Res Ctr, Seattle, WA 98195 USA. [Goldstein, Barry; Burns, Stephen P.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Strayer, Jonathan] Dayton VAMC, Dayton, OH USA. RP Weaver, FM (reprint author), Hines VA Hosp, Ctr Management Complex Chron Care, Hines, IL 60141 USA. EM Frances.Weaver@va.gov NR 55 TC 13 Z9 13 U1 2 U2 3 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 1079-0268 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PD JAN PY 2011 VL 34 IS 1 BP 35 EP 45 DI 10.1179/107902610X12911165975061 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA 734UG UT WOS:000288364400008 PM 21528625 ER PT J AU Gros, DF Veronee, K Strachan, M Ruggiero, KJ Acierno, R AF Gros, Daniel F. Veronee, Kimberly Strachan, Martha Ruggiero, Kenneth J. Acierno, Ron TI Managing suicidality in home-based telehealth SO JOURNAL OF TELEMEDICINE AND TELECARE LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; COGNITIVE-BEHAVIORAL THERAPY; PTSD; VIDEOCONFERENCE; TELEPSYCHIATRY AB We describe the case of a US veteran from the war in Afghanistan with post-traumatic stress disorder (PTSD). The patient was undergoing treatment at home via telehealth as part of a research trial. In week six, he presented with severe suicidal ideation and required emergency hospitalization. Through a series of immediate enhanced communications (i.e. by videoconference) between the patient, patient's family, treatment team and local resources, the patient's symptoms were assessed to identify suicidality and an intervention was successfully carried out, involving the development of a safety plan and eventual transportation to an inpatient unit at the local Veterans Administration Medical Center, where he was hospitalized for three days. This demonstrates the value of telehealth in identifying and treating severe psychiatric symptoms in addition to supporting the safety of these procedures to address suicidality. C1 [Gros, Daniel F.] Ralph H Johnson VAMC, Mental Hlth Serv 116, Charleston, SC 29401 USA. [Gros, Daniel F.; Veronee, Kimberly; Strachan, Martha; Ruggiero, Kenneth J.; Acierno, Ron] Med Univ S Carolina, Charleston, SC 29425 USA. RP Gros, DF (reprint author), Ralph H Johnson VAMC, Mental Hlth Serv 116, 109 Bee St, Charleston, SC 29401 USA. EM grosd@musc.edu RI Schueter, nicos/A-3625-2014 FU Department of Defense [W81XWH-07-PTSD-IIRA]; Ralph H Johnson VAMC [REA08-261] FX The work was supported by the Department of Defense (grant W81XWH-07-PTSD-IIRA) and the Ralph H Johnson VAMC Research Enhancement Award Program (REA08-261). The views expressed in this article do not necessarily reflect those of the Department of VA or the US Government. NR 19 TC 22 Z9 22 U1 2 U2 7 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 1357-633X J9 J TELEMED TELECARE JI J. Telemed. Telecare PY 2011 VL 17 IS 6 BP 332 EP 335 DI 10.1258/jtt.2011.101207 PG 4 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 824IZ UT WOS:000295196900012 PM 21844180 ER PT J AU Saifu, HN Shamouelian, A Davis, LG Santana-Rios, E Goetz, MB Asch, SM Sun, BC AF Saifu, Hemen N. Shamouelian, Albert Davis, Lisa G. Santana-Rios, Elizabeth Goetz, Matthew Bidwell Asch, Steven M. Sun, Benjamin C. TI Impact of a kiosk educational module on HIV screening rates and patient knowledge SO JOURNAL OF TELEMEDICINE AND TELECARE LA English DT Article ID EMERGENCY-DEPARTMENT; ADULTS AB We assessed the effect of a kiosk educational module on HIV screening rates and patient knowledge about HIV testing. The evaluation was performed in a walk-in clinic offering routine HIV screening. During alternating two-week periods, patients were referred either to view a kiosk-based, educational module prior to receiving usual care, or the kiosk module was turned off and no alterations to care processes were made. The primary outcome was HIV testing rate. The secondary outcome was knowledge about HIV rapid screening, as measured with a questionnaire. There were 71 patients in the kiosk periods and 79 patients in the usual-care periods. The overall HIV testing rate was 41%. The kiosk period was not associated with greater odds of HIV testing (OR 0.7; 95% CI: 0.4-1.4). In 44 patients who completed the knowledge survey, the kiosk group was strongly associated with increased knowledge (predicted increase in knowledge score: 1.3; 95% CI: 036-2.1). The brief kiosk educational module did not improve HIV screening rates, but it increased overall patient knowledge about HIV testing. C1 [Saifu, Hemen N.; Shamouelian, Albert; Davis, Lisa G.; Santana-Rios, Elizabeth; Goetz, Matthew Bidwell; Asch, Steven M.; Sun, Benjamin C.] VA Greater Los Angeles Hlth Syst, Dept Med, Los Angeles, CA USA. [Goetz, Matthew Bidwell; Asch, Steven M.; Sun, Benjamin C.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. RP Saifu, HN (reprint author), W Los Angeles Vet Affairs Med Ctr, Off 3246,Mail Stop 111G,Bldg 500,Wing 3E,11301 Wi, Los Angeles, CA 90073 USA. EM Hemen.Saifu@va.gov OI Goetz, Matthew/0000-0003-4542-992X FU Veterans Affairs HIV/Hepatitis QUERI and a Veterans Affairs [HSRD RRP 08-255]; WLAVA FX The work was supported by the Veterans Affairs HIV/Hepatitis QUERI and a Veterans Affairs grant (HSRD RRP 08-255). We thank the WLAVA walk-in clinic nursing staff and the research assistant staff for supporting the study. NR 11 TC 4 Z9 4 U1 0 U2 1 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 1357-633X J9 J TELEMED TELECARE JI J. Telemed. Telecare PY 2011 VL 17 IS 8 BP 446 EP 450 DI 10.1258/jtt.2011.110415 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 873QZ UT WOS:000298899400009 PM 21967998 ER PT J AU Zanartu, M Mehta, DD Ho, JC Wodicka, GR Hillman, RE AF Zanartu, Matias Mehta, Daryush D. Ho, Julio C. Wodicka, George R. Hillman, Robert E. TI Observation and analysis of in vivo vocal fold tissue instabilities produced by nonlinear source-filter coupling: A case study SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID EXCISED LARYNX EXPERIMENTS; REGISTER TRANSITIONS; VOICE INSTABILITIES; FALSETTO REGISTERS; PHYSICAL MODEL; TRACT; PHONATION; VIBRATION; VIDEOKYMOGRAPHY; SEGMENTATION AB Different source-related factors can lead to vocal fold instabilities and bifurcations referred to as voice breaks. Nonlinear coupling in phonation suggests that changes in acoustic loading can also be responsible for this unstable behavior. However, no in vivo visualization of tissue motion during these acoustically induced instabilities has been reported. Simultaneous recordings of laryngeal high-speed videoendoscopy, acoustics, aerodynamics, electroglottography, and neck skin acceleration are obtained from a participant consistently exhibiting voice breaks during pitch glide maneuvers. Results suggest that acoustically induced and source-induced instabilities can be distinguished at the tissue level. Differences in vibratory patterns are described through kymography and phono-vibrography; measures of glottal area, open/speed quotient, and amplitude/phase asymmetry; and empirical orthogonal function decomposition. Acoustically induced tissue instabilities appear abruptly and exhibit irregular vocal fold motion after the bifurcation point, whereas source-induced ones show a smoother transition. These observations are also reflected in the acoustic and acceleration signals. Added aperiodicity is observed after the acoustically induced break, and harmonic changes appear prior to the bifurcation for the source-induced break. Both types of breaks appear to be subcritical bifurcations due to the presence of hysteresis and amplitude changes after the frequency jumps. These results are consistent with previous studies and the nonlinear source-filter coupling theory. (C) 2011 Acoustical Society of America. [DOI: 10.1121/1.3514536] C1 [Zanartu, Matias; Wodicka, George R.] Purdue Univ, Sch Elect & Comp Engn, W Lafayette, IN 47907 USA. [Mehta, Daryush D.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Ho, Julio C.; Wodicka, George R.] Purdue Univ, Weldon Sch Biomed Engn, W Lafayette, IN 47907 USA. [Hillman, Robert E.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. [Hillman, Robert E.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Hillman, Robert E.] Harvard Mit Div Hlth Sci & Technol, Boston, MA 02114 USA. RP Zanartu, M (reprint author), Purdue Univ, Sch Elect & Comp Engn, W Lafayette, IN 47907 USA. EM mzanartu@purdue.edu RI Zanartu, Matias/I-3133-2012; researchers, ac3e/N-2008-2016 OI Zanartu, Matias/0000-0001-5581-4392; FU NIH National Institute on Deafness and Other Communication Disorders [T32 DC00038, R01 DC007640]; Institute of Laryngology and Voice Restoration; National Science Foundation (NSF) [CBET-0828903] FX This work was supported by grants from the NIH National Institute on Deafness and Other Communication Disorders (Grant Nos. T32 DC00038 and R01 DC007640), the Institute of Laryngology and Voice Restoration, and the National Science Foundation (NSF, Grant No. CBET-0828903). The contents of this work are solely the responsibility of the authors and do not necessarily represent the official views of the NIH or the NSF. NR 47 TC 19 Z9 19 U1 0 U2 4 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD JAN PY 2011 VL 129 IS 1 BP 326 EP 339 DI 10.1121/1.3514536 PG 14 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 716DE UT WOS:000286944600040 PM 21303014 ER PT J AU Wilens, TE AF Wilens, Timothy E. TI A Sobering Fact: ADHD Leads to Substance Abuse SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Editorial Material ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; COMORBIDITY; PREVALENCE; ADULTS C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Wilens, TE (reprint author), Massachusetts Gen Hosp, 55 Fruit St,YAW 6A, Boston, MA 02114 USA. EM twilens@partners.org NR 11 TC 10 Z9 10 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JAN PY 2011 VL 50 IS 1 BP 6 EP 8 DI 10.1016/j.jaac.2010.10.002 PG 3 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 700WX UT WOS:000285776100002 PM 21156265 ER PT J AU Wilens, TE Gault, LM Childress, A Kratochvil, CJ Bensman, L Hall, CM Olson, E Robieson, WZ Garimella, TS Abi-Saab, WM Apostol, G Saltarelli, MD AF Wilens, Timothy E. Gault, Laura M. Childress, Ann Kratochvil, Christopher J. Bensman, Lindsey Hall, Coleen M. Olson, Evelyn Robieson, Weining Z. Garimella, Tushar S. Abi-Saab, Walid M. Apostol, George Saltarelli, Mario D. TI Safety and Efficacy of ABT-089 in Pediatric Attention-Deficit/Hyperactivity Disorder: Results from Two Randomized Placebo-Controlled Clinical Trials SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE ADHD; pharmacologic treatment; alpha 4 beta 2; neuronal nicotinic receptor ID DEFICIT HYPERACTIVITY DISORDER; RECEPTOR AGONISTS; CHRONIC NICOTINE; RAT-BRAIN; CHILDREN; ADULTS; EXPRESSION; ATOMOXETINE; ADOLESCENT; SUBUNITS AB Objective: To assess the safety and efficacy of ABT-089, a novel alpha(4)beta(2) neuronal nicotinic receptor partial agonist, vs. placebo in children with attention-deficit/hyperactivity disorder (ADHD). Method: Two multicenter, randomized, double-blind, placebo-controlled, parallel-group studies of children 6 through 12 years of age were conducted. Study 1 (n = 274) assessed six treatment groups over 8 weeks: 4 once-daily (QD) ABT-089 doses (0.085-0.700 mg/kg), QD atomoxetine, and placebo. Study 2 (n = 119) assessed three treatment groups over 6 weeks: 2 QD ABT-089 doses (0.7 mg/kg, 1.4 mg/kg) and placebo. The primary efficacy variable was the investigator-administered Attention-Deficit/Hyperactivity Disorder Rating Scale-IV: Home Version (ADHD-RS-IV [HV]) Total Score. Safety was assessed by adverse event (AE) monitoring, laboratory tests, vital signs, physical examinations, and electrocardiogram measures. Results: There was no statistically significant difference between ABT-089 and placebo in mean change from baseline to final evaluation of ADHD-RS-IV (HV) Total Score or other outcome measures at any dose in either study. In Study 1, atomoxetine showed statistically significant improvement for the primary and most secondary endpoints. ABT-089 was generally safe and well tolerated, with no statistically significant difference between any ABT-089 dose and placebo in the overall incidence of any specific AE, and no clinically significant changes in other safety measures. Conclusions: ABT-089 did not show efficacy on the primary efficacy variable, the ADHD-RS-IV (MV) Total Score, or other measures of ADHD symptomatology in children with ADHD, and had a safety profile similar to placebo. These results contrast with published reports of efficacy of nicotinic modulators in adults with ADHD. J. Am. Acad. Child Adolesc. Psychiatry, 2011;50(1):73-84. Clinical Trial Registry Information- M06-888 (Study 1): A Safety and Efficacy Study of ABT-089 in Children With Attention-Deficit/Hyperactivity Disorder (ADHD), URL: http://clinicaltrials.gov, unique identifier: NCT00528697. M10-345 (Study 2): Safety and Tolerability Study of ABT-089 in Children With Attention-Deficit/Hyperactivity Disorder (ADHD), URL: http://clinicaltrials.gov, unique identifier: NCT00640419. C1 [Wilens, Timothy E.] Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. [Gault, Laura M.; Bensman, Lindsey; Hall, Coleen M.; Olson, Evelyn; Robieson, Weining Z.; Garimella, Tushar S.; Saltarelli, Mario D.] Abbott, Abbott Pk, IL USA. [Abi-Saab, Walid M.; Apostol, George] Novartis Pharma AG, Basel, Switzerland. [Childress, Ann] Ctr Psychiat & Behav Med Inc, Las Vegas, NV USA. [Kratochvil, Christopher J.] Univ Nebraska Med Ctr, Omaha, NE USA. RP Wilens, TE (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, 55 Fruit St,YAW 6A, Boston, MA 02114 USA. EM twilens@partners.org FU Abbott; McNeil; Eli Lilly and Co.; National Institutes of Health - National Institute on Drug Abuse; Merck; Shire; Bristol-Myers Squibb; Johnson and Johnson; McNeil Pediatrics; Division of Ortho-McNeil-Janssen Pharmaceuticals; Next Wave Pharmaceuticals; Novartis; Sepracor; National Institute of Mental Health; Somerset; Abbott Laboratories; Guilford Press FX Dr. Wilens receives research support from Abbott, McNeil, Eli Lilly and Co., the National Institutes of Health - National Institute on Drug Abuse, Merck, and Shire. He has served on the speakers' bureau for Eli Lilly and Co., McNeil, Novartis, and Shire. He has served as a consultant for Abbott, AstraZeneca, McNeil, Eli Lilly and Co., the National Institutes of Health, National Institute on Drug Abuse, Novartis, Merck, and Shire. He receives royalties from Guilford Press. Dr. Childress has served as a consultant for and on the advisory boards for Novartis and Shire. She receives research support from Abbott, AstraZeneca, Bristol-Myers Squibb, Eli Lilly and Co., Johnson and Johnson, McNeil Pediatrics, Division of Ortho-McNeil-Janssen Pharmaceuticals, Next Wave Pharmaceuticals, Novartis, Sepracor, and Shire. She serves on the speakers' bureau for Bristol-Myers Squibb, Novartis, and Shire. Dr. Kratochvil receives research support from the National Institute of Mental Health, Eli Lilly and Co., Abbott, and Somerset. He serves as a consultant for Eli Lilly and Co., Abbott, Neuroscience Education Institute, MedAvante, AstraZeneca, and Pfizer. He is the Editor of the Brown University Child and Adolescent Psychopharmacology Update, and member of the REACH Institute Primary Pediatric Psychopharmacology Steering Committee. He receives study drug for an National Institute of Mental Health-funded study from Eli Lilly and Co., and Abbott Laboratories. Drs. Gault, Robieson, Garimella, and Saltarelli, and Ms. Bensman, Ms. Hall, and Ms. Olson are employees of Abbott, and hold Abbott stock options and/or stock. Dr. Saltarelli is an Abbott patent holder. Drs. Abi-Saab and Apostol were employees of Abbott when the studies were performed, and hold Abbott stock. Dr. Abi-Saab is an Abbott patent holder. NR 43 TC 21 Z9 21 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JAN PY 2011 VL 50 IS 1 BP 73 EP 84 DI 10.1016/j.jaac.2010.10.001 PG 12 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 700WX UT WOS:000285776100009 PM 21156272 ER PT J AU Boyce, JA Assa'ad, A Burks, AW Jones, SM Sampson, HA Wood, RA Plaut, M Cooper, SF Fenton, MJ Arshad, SH Bahna, SL Beck, LA Byrd-Bredbenner, C Camargo, CA Eichenfield, L Furuta, GT Hanifin, JM Jones, C Kraft, M Levy, BD Lieberman, P Luccioli, S McCall, KM Schneider, LC Simon, RA Simons, FER Teach, SJ Yawn, BP Schwaninger, JM AF Boyce, Joshua A. Assa'ad, Amal Burks, A. Wesley Jones, Stacie M. Sampson, Hugh A. Wood, Robert A. Plaut, Marshall Cooper, Susan F. Fenton, Matthew J. Arshad, S. Hasan Bahna, Sami L. Beck, Lisa A. Byrd-Bredbenner, Carol Camargo, Carlos A., Jr. Eichenfield, Lawrence Furuta, Glenn T. Hanifin, Jon M. Jones, Carol Kraft, Monica Levy, Bruce D. Lieberman, Phil Luccioli, Stefano McCall, Kathleen M. Schneider, Lynda C. Simon, Ronald A. Simons, F. Estelle R. Teach, Stephen J. Yawn, Barbara P. Schwaninger, Julie M. TI Guidelines for the Diagnosis and Management of Food Allergy in the United States: Summary of the NIAID-Sponsored Expert Panel Report SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article AB This document is a summary report of the Guidelines for the Diagnosis and Management of Food Allergy in the United States. The full guidelines can be found online at http://www.jacionline.org C1 [Plaut, Marshall; Cooper, Susan F.; Fenton, Matthew J.; Schwaninger, Julie M.] NIAID, Div Allergy Immunol & Transplantat, NIH, Bethesda, MD 20892 USA. [Boyce, Joshua A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Rheumatol Immunol & Allergy, Cambridge, MA 02138 USA. [Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Emergency Med, Dept Med,Div Rheumatol Allergy & Immunol, Cambridge, MA 02138 USA. [Levy, Bruce D.] Brigham & Womens Hosp, Partners Asthma Ctr, Pulm & Crit Med Div, Boston, MA 02115 USA. [Levy, Bruce D.] Harvard Univ, Sch Med, Boston, MA USA. [Assa'ad, Amal] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Div Allergy & Immunol, Cincinnati, OH 45221 USA. [Burks, A. Wesley] Duke Univ, Med Ctr, Dept Pediat, Div Allergy & Immunol, Durham, NC 27710 USA. [Kraft, Monica] Duke Univ, Med Ctr, Dept Med, Div Pulm Allergy & Crit Care Med, Durham, NC 27710 USA. [Jones, Stacie M.] Univ Arkansas Med Sci, Arkansas Childrens Hosp, Dept Pediat, Div Allergy & Immunol, Little Rock, AR 72205 USA. [Sampson, Hugh A.] Mt Sinai Sch Med, Elliot & Roslyn Jaffe Food Allergy Inst, Dept Pediat, Div Allergy & Immunol, New York, NY USA. [Wood, Robert A.] Johns Hopkins Univ, Sch Med, Dept Pediat, Div Allergy & Immunol, Baltimore, MD 21205 USA. [Arshad, S. Hasan] Univ Southampton, Sch Med, Southampton SO9 5NH, Hants, England. [Arshad, S. Hasan] Southampton Univ Hosp NHS Trust, Southampton, Hants, England. [Bahna, Sami L.] Louisiana State Univ, Hlth Sci Ctr, Dept Pediat, Allergy & Immunol Sect, Baton Rouge, LA 70803 USA. [Beck, Lisa A.] Univ Rochester, Dept Dermatol, Med Ctr, Rochester, NY 14627 USA. [Byrd-Bredbenner, Carol] Rutgers State Univ, Dept Nutr Sci, New Brunswick, NJ 08903 USA. [Eichenfield, Lawrence] Rady Childrens Hosp, Div Pediat & Adolescent Dermatol, San Diego, CA USA. [Eichenfield, Lawrence] Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA. [Eichenfield, Lawrence] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. [Furuta, Glenn T.] Childrens Hosp Denver, Digest Hlth Inst, Sect Pediat Gastroenterol Hepatol & Nutr, Aurora, CO USA. [Furuta, Glenn T.] Natl Jewish Hlth, Dept Pediat, Denver, CO USA. [Furuta, Glenn T.] Univ Colorado, Dept Pediat, Denver Sch Med, Aurora, CO USA. [Hanifin, Jon M.] Oregon Hlth & Sci Univ, Dept Dermatol, Portland, OR 97201 USA. [Jones, Carol] Allergy & Asthma Network Mothers Asthmat, Mclean, VA USA. [Lieberman, Phil] Univ Tennessee, Coll Med, Div Allergy & Immunol, Dept Med, Knoxville, TN 37996 USA. [Luccioli, Stefano] US FDA, Off Food Addit Safety, College Pk, MD USA. [McCall, Kathleen M.] Childrens Hosp Orange Cty, Orange, CA USA. [Schneider, Lynda C.] Childrens Hosp Boston, Div Immunol, Boston, MA USA. [Simon, Ronald A.] Scripps Clin, Div Allergy Asthma & Immunol, San Diego, CA USA. [Simons, F. Estelle R.] Univ Manitoba, Fac Med, Dept Pediat, Winnipeg, MB R3T 2N2, Canada. [Simons, F. Estelle R.] Univ Manitoba, Fac Med, Dept Child Hlth & Immunol, Winnipeg, MB R3T 2N2, Canada. [Teach, Stephen J.] Childrens Natl Med Ctr, Div Emergency Med, Washington, DC 20010 USA. [Yawn, Barbara P.] Olmsted Med Ctr, Dept Res, Rochester, MN USA. [Yawn, Barbara P.] Univ Minnesota, Sch Med, Dept Family & Community Hlth, Minneapolis, MN 55455 USA. RP Fenton, MJ (reprint author), NIAID, Div Allergy Immunol & Transplantat, NIH, 6610 Rockledge Dr,Room 3105, Bethesda, MD 20892 USA. EM fentonm@niaid.nih.gov RI Byrd-Bredbenner, Carol/F-8064-2015 OI Byrd-Bredbenner, Carol/0000-0002-8010-3987 FU National Institutes of Health; GlaxoSmithKline; Food Allergy and Anaphylaxis Network; Gerber; Mead Johnson; Dyax Corp; National Peanut Board; Food Allergy Initiative; National Institutes of Health (Division of Receipt and Referral, National Institute of Allergy and Infectious Diseases, National Center for Complementary and Alternative Medicine); Phadia AB; Genentech; National Institutes of Health (National Institute of Allergy and Infectious Diseases); National Institutes of Health and the National Institute of Health Research, UK; American Academy of Allergy, Asthma, and Immunology; National Eczema Association; US Department of Agriculture; Canned Food Alliance; New Jersey Department of Health and Senior Services; variety of government agencies; not-for-profit research foundations; Dey; Novartis; variety of not-for-profit foundations; Astellas; Ferndale; Johnson Johnson; Sinclair; Stiefel; Therapeutics Inc.; American Gastrointestinal Association; ALZA; Astellas Pharma US, Inc; Asubio Pharmaceuticals, Inc; Centocor, Inc; Corgentech; Nucryst Pharmaceuticals; Seattle Genetics; Shionogi USA; variety of not-for-profit research foundations; AllerGen; Canadian Allergy, Asthma and Immunology Foundation/Anaphylaxis Canada; Canadian Institutes of Health Research; AstraZeneca Foundation; Aventis; Child Health Center Board; CNMC Research Advisory Council; National Association of Chain Drug Stores Foundation; National Institutes of Health (National Institute of Allergy and Infectious Diseases; National Heart, Lung, and Blood Institute); Novartis/Genentech; Robert Woods Johnson Foundation; US Centers for Disease Control and Prevention; US Public Health Service; Washington, DC, Department of Health FX J.A. Boyce has served on the Advisory Board of GlaxoSmithKline. He has served as a consultant and/or speaker for Altana, GlaxoSmithKline, and Merck. He has received funding/grant support from the National Institutes of Health.; Dr Assa'ad has received funding/grant support from GlaxoSmithKline.; Dr Burks has received funding/grant support from the Food Allergy and Anaphylaxis Network, Gerber, Mead Johnson, and the National Institutes of Health.; S.M. Jones has served as a speaker and grant reviewer and has served on the medical advisory committee for the Food Allergy and Anaphylaxis Network.She has received funding/grant support from Dyax Corp, the Food Allergy and Anaphylaxis Network, Mead Johnson, the National Peanut Board, and the National Institutes of Health.; H.A. Sampson holds, or is listed as an inventor on, multiple US patents related to food allergy. He owns stock in Allertein Therapeutics. He is the immediate past president of the American Academy of Allergy, Asthma, and Immunology. He has served as a consultant for Allertein Therapeutics, the American Academy of Allergy, Asthma, and Immunology, the Food Allergy Initiative, and Schering Plough. He has received funding/grant support for research projects from the Food Allergy Initiative, the National Institutes of Health (Division of Receipt and Referral, National Institute of Allergy and Infectious Diseases, National Center for Complementary and Alternative Medicine), and Phadia AB. He is a co-owner of Herbal Spring, LLC.; R.A. Wood has served as a speaker/advisory board member for GlaxoSmithKline, Merck, and Dey. He has received funding/grant support from Genentech and the National Institutes of Health (National Institute of Allergy and Infectious Diseases).; S.H. Arshad has received funding/grant support from the National Institutes of Health and the National Institute of Health Research, UK.; S.L. Bahna has received funding/grant support from Genentech.; L.A. Beck has received funding/grant support from the American Academy of Allergy, Asthma, and Immunology, the National Eczema Association, and the National Institutes of Health.; C. Byrd-Bredbenner owns stock in Johnson & Johnson. She has received funding/grant support from the US Department of Agriculture, the Canned Food Alliance, and the New Jersey Department of Health and Senior Services.; C.A. Camargo Jr has consulted for Dey and Novartis. He has received funding/grant support from a variety of government agencies and not-for-profit research foundations, as well as Dey and Novartis.; L. Eichenfield has received funding/grant support from a variety of not-for-profit foundations, as well as Astellas, Ferndale, Johnson & Johnson, Novartis, Sinclair, Stiefel, and Therapeutics Inc.; G.T. Furuta has served as a consultant and/or speaker to Ception Therapeutics and TAP. He has received funding/grant support from the American Gastrointestinal Association and the National Institutes of Health.; J.M. Hanifin has served as served as a consultant for ALZA, Anesiva, Inc, Barrier Therapeutics, Inc, Milliken & Company, Nordic Biotech, Novartis Pharmaceuticals Corporation, Shionogi USA, Taisho Pharmaceutical R&D, Inc, Teikoku Pharma USA, Inc, UCB, York Pharma, ZARS, Inc, and ZymoGenetics. He has served as an investigator or received research funding from ALZA, Astellas Pharma US, Inc, Asubio Pharmaceuticals, Inc, Centocor, Inc, Corgentech, Novartis, Nucryst Pharmaceuticals, Seattle Genetics, and Shionogi USA.; M. Kraft has served as a consultant and/or speaker for Astra-Zeneca, Genentech, GlaxoSmithKline, Merck, Novartis, and Sepracor. She has received funding/grant support from Genentech, GlaxoSmithKline, the National Institutes of Health and Novartis.; L.C. Schneider has served as a consultant/clinical advisor for the Food Allergy Initiative. She has received funding/grant support from a variety of not-for-profit research foundations, as well as Novartis and the National Institutes of Health.; F.E.R. Simons holds a patent on "Fast-disintegrating epinephrine tablets for sublingual administration." She is a past-president of the American Academy of Allergy, Asthma, and Immunology and of the Canadian Society of Allergy and Clinical Immunology. She is a member of the advisory boards of Dey, Intelliject, and ALK-Abello. She has received funding/grant support from AllerGen, the Canadian Allergy, Asthma and Immunology Foundation/Anaphylaxis Canada, and the Canadian Institutes of Health Research.; S.J. Teach has served as a speaker for AstraZeneca. He has received funding/grant support from the AstraZeneca Foundation, Aventis, the Child Health Center Board, the CNMC Research Advisory Council, the National Association of Chain Drug Stores Foundation, the National Institutes of Health (National Institute of Allergy and Infectious Diseases; National Heart, Lung, and Blood Institute), Novartis/Genentech, the Robert Woods Johnson Foundation, the US Centers for Disease Control and Prevention, the US Public Health Service, and the Washington, DC, Department of Health. NR 0 TC 13 Z9 13 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD JAN PY 2011 VL 64 IS 1 BP 175 EP 192 DI 10.1016/j.jaad.2010.11.020 PG 18 WC Dermatology SC Dermatology GA 701XF UT WOS:000285857800021 PM 21167411 ER PT J AU Bullock, CM Beckson, M AF Bullock, Clayton M. Beckson, Mace TI Male Victims of Sexual Assault: Phenomenology, Psychology, Physiology SO JOURNAL OF THE AMERICAN ACADEMY OF PSYCHIATRY AND THE LAW LA English DT Article ID MALE RAPE VICTIMS; SPINAL-CORD; MEN; EJACULATION; ELECTROEJACULATION; ANXIETY; SERVICE; STIMULATION; MOLESTATION; DYSFUNCTION AB Myths, stereotypes, and unfounded beliefs about male sexuality, in particular male homosexuality, are widespread in legal and medical communities, as well as among agencies providing services to sexual assault victims. These include perceptions that men in noninstitutionalized settings are rarely sexually assaulted, that male victims are responsible for their assaults, that male sexual assault victims are less traumatized by the experience than their female counterparts, and that ejaculation is an indicator of a positive erotic experience. As a result of the prevalence of such beliefs, there is an underreporting of sexual assaults by male victims; a lack of appropriate services for male victims; and, effectively, no legal redress for male sexual assault victims. By comparison, male sexual assault victims have fewer resources and greater stigma than do female sexual assault victims. Many male victims, either because of physiological effects of anal rape or direct stimulation by their assailants, have an erection, ejaculate, or both during the assault. This is incorrectly understood by assailant, victim, the justice system, and the medical community as signifying consent by the victim. Studies of male sexual physiology suggest that involuntary erections or ejaculations can occur in the context of nonconsensual, receptive anal sex. Erections and ejaculations are only partially under voluntary control and are known to occur during times of extreme duress in the absence of sexual pleasure. Particularly within the criminal justice system, this misconception, in addition to other unfounded beliefs, has made the courts unwilling to provide legal remedy to male victims of sexual assault, especially when the victim experienced an erection or an ejaculation during the assault. Attorneys and forensic psychiatrists must be better informed about the physiology of these phenomena to formulate evidence-based opinions. C1 [Bullock, Clayton M.] S Market Mental Hlth Clin, Dept Publ Hlth, San Francisco, CA 94107 USA. [Beckson, Mace] Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA 90024 USA. [Beckson, Mace] VA Greater Los Angeles Healthcare Syst, Psychiat Intens Care Unit, Los Angeles, CA USA. RP Bullock, CM (reprint author), S Market Mental Hlth Clin, Dept Publ Hlth, 760 Harrison St, San Francisco, CA 94107 USA. EM c-bullock@sbcglobal.net NR 56 TC 16 Z9 16 U1 2 U2 29 PU AMER ACAD PSYCHIATRY & LAW PI BLOOMFIELD PA ONE REGENCY DR, PO BOX 30, BLOOMFIELD, CT 06002 USA SN 1093-6793 J9 J AM ACAD PSYCHIATRY JI J. Am. Acad. Psychiatry Law PY 2011 VL 39 IS 2 BP 197 EP 205 PG 9 WC Law; Psychiatry SC Government & Law; Psychiatry GA 782NK UT WOS:000292016200010 PM 21653264 ER PT J AU Kivisto, AJ Moore, TM Fite, PA Seidner, BG AF Kivisto, Aaron J. Moore, Todd M. Fite, Paula A. Seidner, Bruce G. TI Future Orientation and Competence to Stand Trial: The Fragility of Competence SO JOURNAL OF THE AMERICAN ACADEMY OF PSYCHIATRY AND THE LAW LA English DT Article ID YOUTH SCREENING INSTRUMENT; ADOLESCENT DECISION-MAKING; ADJUDICATIVE COMPETENCE; PSYCHOMETRIC PROPERTIES; CRIMINAL ADJUDICATION; ASSESSMENT-TOOL; DEFENDANTS; JUVENILES; JUDGMENT; ADULTS AB The current study examined the direct, indirect, and interactive effects of age, intellectual ability, psychiatric symptomatology, and future orientation on juvenile adjudicative competence utilizing a secondary sample of 927 youth from the MacArthur Juvenile Adjudicative Competence Study. Consistent with previous research, age, intellectual ability, and future orientation were found to be positively associated with competence, and psychiatric symptomatology was weakly negatively related to competence. Tests of indirect effects revealed that the development of an orientation toward future consequences partially explains the relationship between age and the capacity to reason about legal decision-making. Further, tests of invariance revealed that the competence of immature adolescents is particularly "fragile," in that smaller deficits in cognitive abilities appear to pose greater problems in youths regarding their adjudicative competence than in their more mature peers. Findings are discussed in regard to forensic practice as well as for future research. C1 [Kivisto, Aaron J.] Univ Tennessee, Dept Psychol, Knoxville, TN 37996 USA. [Kivisto, Aaron J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kivisto, AJ (reprint author), Univ Tennessee, Dept Psychol, Austin Peay Bldg 227, Knoxville, TN 37996 USA. EM akivisto@utk.edu RI Kivisto, Aaron/O-6860-2015 OI Kivisto, Aaron/0000-0002-2243-1384 NR 48 TC 2 Z9 2 U1 0 U2 3 PU AMER ACAD PSYCHIATRY & LAW PI BLOOMFIELD PA ONE REGENCY DR, PO BOX 30, BLOOMFIELD, CT 06002 USA SN 1093-6793 J9 J AM ACAD PSYCHIATRY JI J. Am. Acad. Psychiatry Law PY 2011 VL 39 IS 3 BP 316 EP 326 PG 11 WC Law; Psychiatry SC Government & Law; Psychiatry GA 831CP UT WOS:000295706600005 PM 21908747 ER PT J AU Recupero, PR Price, M Garvey, KA Daly, B Xavier, SL AF Recupero, Patricia R. Price, Marilyn Garvey, Keelin A. Daly, Brian Xavier, Sarah L. TI Restraint and Seclusion in Psychiatric Treatment Settings: Regulation, Case Law, and Risk Management SO JOURNAL OF THE AMERICAN ACADEMY OF PSYCHIATRY AND THE LAW LA English DT Article ID SPECIAL SECTION; INPATIENT UNIT; REDUCTION; ELIMINATION; CHILD AB Changing federal regulations, civil rights and malpractice cases, and new treatment methods have influenced the use of restraint and seclusion (R&S) in inpatient psychiatric treatment settings, such that restraint and seclusion today are among the most highly regulated practices in psychiatry. Despite increased pressure from regulatory bodies and litigation, the use of R&S remains controversial and risky. These procedures can compromise safety if performed incorrectly or monitored inadequately, but intervention by restraint or seclusion may be necessary to maintain safety on the treatment unit, especially during emergencies. Case law and medical research have demonstrated the importance of a patient-focused, treatment-oriented approach toward risk management. Analysis of specific clinical scenarios can help to develop risk mitigation strategies that are therapeutically conceptualized rather than driven by regulation. Insights drawn from clinical cases that have resulted in litigation can offer an opportunity to develop an approach oriented to patient care from a clinical or risk management perspective. In this article, we seek to provide a foundation for evaluation of current protocols, an analysis of adverse R&S events, and strategies to minimize risk. C1 [Recupero, Patricia R.] Butler Hosp, Providence, RI 02906 USA. [Recupero, Patricia R.] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. [Price, Marilyn] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Price, Marilyn] Massachusetts Gen Hosp, Law & Psychiat Serv, Boston, MA 02114 USA. [Garvey, Keelin A.] Massachusetts Dept Correct, Bridgewater, MA USA. [Daly, Brian] Univ Michigan, Sch Med, Ann Arbor, MI USA. RP Recupero, PR (reprint author), Butler Hosp, 345 Blackstone Blvd, Providence, RI 02906 USA. EM patricia_recupero@brown.edu NR 42 TC 8 Z9 8 U1 3 U2 8 PU AMER ACAD PSYCHIATRY & LAW PI BLOOMFIELD PA ONE REGENCY DR, PO BOX 30, BLOOMFIELD, CT 06002 USA SN 1093-6793 J9 J AM ACAD PSYCHIATRY JI J. Am. Acad. Psychiatry Law PY 2011 VL 39 IS 4 BP 465 EP 476 PG 12 WC Law; Psychiatry SC Government & Law; Psychiatry GA 881DV UT WOS:000299461600003 PM 22159974 ER PT J AU Wortzel, HS Kraus, MF Filley, CM Anderson, CA Arciniegas, DB AF Wortzel, Hal S. Kraus, Marilyn F. Filley, Christopher M. Anderson, C. Alan Arciniegas, David B. TI Diffusion Tensor Imaging in Mild Traumatic Brain Injury Litigation SO JOURNAL OF THE AMERICAN ACADEMY OF PSYCHIATRY AND THE LAW LA English DT Article ID WHITE-MATTER INTEGRITY; INDUCED AXONAL INJURY; CLINICAL-PRACTICE; CORPUS-CALLOSUM; YOUNG-ADULTS; HEAD TRAUMA; ABNORMALITIES; MODERATE; DTI; ADOLESCENTS AB A growing body of literature addresses the application of diffusion tensor imaging (DTI) to traumatic brain injury (TBI). Most TBIs are of mild severity, and their diagnosis and prognosis are often challenging. These challenges may be exacerbated in medicolegal contexts, where plaintiffs seek to present objective evidence that supports a clinical diagnosis of mild (m)TBI. Because DTI permits quantification of white matter integrity and because TBI frequently involves white matter injury, DTI represents a conceptually appealing method of demonstrating white matter pathology attributable to mTBI. However, alterations in white matter integrity are not specific to TBI, and their presence does not necessarily confirm a diagnosis of mTBI. Guided by rules of evidence shaped by Daubert v. Merrell Dow Pharmaceuticals, Inc., we reviewed and analyzed the literature describing DTI findings in mTBI and related neuropsychiatric disorders. Based on this review, we suggest that expert testimony regarding DTI findings will seldom be appropriate in legal proceedings focused on mTBI. C1 [Wortzel, Hal S.] Univ Colorado, Sch Med, Denver VA Med Ctr, VISN 19,MIRECC, Denver, CO USA. [Wortzel, Hal S.] Univ Colorado, Sch Med, Dept Psychiat, Denver, CO USA. [Kraus, Marilyn F.] Walter Reed Natl Mil Med Ctr, Neurobehav Traumat Brain Injury Consult Serv, Bethesda, MD USA. [Filley, Christopher M.] Univ Colorado, Sch Med, Dept Neurol, Behav Neurol Sect, Denver, CO USA. [Anderson, C. Alan] Univ Colorado, Sch Med, Neurobehavioral Disorders Program, Dept Psychiat, Denver, CO USA. [Anderson, C. Alan] Denver VA Med Ctr, Neurol Serv, Denver, CO USA. RP Wortzel, HS (reprint author), VISN 19 MIRECC, 1055 Clermont St, Denver, CO 80220 USA. EM wortzel@ucdenver.edu NR 57 TC 14 Z9 15 U1 2 U2 5 PU AMER ACAD PSYCHIATRY & LAW PI BLOOMFIELD PA ONE REGENCY DR, PO BOX 30, BLOOMFIELD, CT 06002 USA SN 1093-6793 J9 J AM ACAD PSYCHIATRY JI J. Am. Acad. Psychiatry Law PY 2011 VL 39 IS 4 BP 511 EP 523 PG 13 WC Law; Psychiatry SC Government & Law; Psychiatry GA 881DV UT WOS:000299461600008 PM 22159979 ER PT J AU Patel, NK Parchman, ML AF Patel, Neela K. Parchman, Michael L. TI The Chronic Care Model and Exercise Discussions during Primary Care Diabetes Encounters SO JOURNAL OF THE AMERICAN BOARD OF FAMILY MEDICINE LA English DT Article DE Chronic Care Model; Diabetes; Exercise; Patient Education ID SELF-MANAGEMENT BEHAVIORS; PHYSICAL-ACTIVITY ADVICE; CHRONIC ILLNESS CARE; GLUCOSE CONTROL; QUALITY IMPROVEMENT; PREVENTIVE SERVICES; PATIENT; IMPLEMENTATION; ATTRIBUTES; CLINICS AB Background: Discussing self-care activities like exercise is challenging with the many competing demands during primary care encounters. Our objective was to study the relationship between the Chronic Care Model (CCM) score in the clinic and time spent by the physicians discussing exercise during encounters with diabetic patients. Methods: Consecutive patients with diabetes across 20 primary care clinics in South Texas were included. Time spent discussing exercise was determined using the Davis Observation Code on audio recordings of the visits. Clinicians completed the Assessment of Chronic Illness Care survey, a validated measure of the extent to which care delivered is consistent with the CCM. Data were analyzed using hierarchical linear models. Results: A total of 162 transcribed recordings were analyzed. Age, the number of problems addressed, stage of change (SOC), and overall length of the visit were associated with time spent discussing exercise. There was a significant relationship between clinic CCM score and time spent by physicians advising about exercise, independent of SOC for exercise (P < .01). Also, a discussion about exercise was more likely to occur with patients who were in the contemplation SOC for exercise. Conclusions: Discussions of exercise may be 18 to 33 seconds longer in clinics with full implementation of the CCM compared with those with basic implementation. Facilitating more complete CCM implementation in clinics with a basic level of CCM that serve a population of patients who are sedentary may realize the most benefit. (J Am Board Fam Med 2011;24:26-32.) C1 [Patel, Neela K.; Parchman, Michael L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Family & Community Med, San Antonio, TX 78229 USA. [Parchman, Michael L.] S Texas Vet Hlth Care Syst, Verdict Hlth Serv Res Program, San Antonio, TX USA. RP Patel, NK (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Family & Community Med, MC 7795,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM Pateln4@uthscsa.edu OI Parchman, Michael/0000-0001-7129-2889 FU Agency for Healthcare Research and Quality (AHRQ) [K08 HS013008-03]; Bureau of Health Professions; John A Hartford Foundation Center for Excellence in Geriatrics Education; Department of Veterans Affairs; Health Resources and Services Administration Department of Health and Human Services [D01 HP08795] FX The research reported was supported by the Agency for Healthcare Research and Quality (AHRQ K08 HS013008-03) and the Bureau of Health Professions; Health Resources and Services Administration Department of Health and Human Services grant D01 HP08795; The John A Hartford Foundation Center for Excellence in Geriatrics Education; and by the Department of Veterans Affairs. NR 39 TC 6 Z9 6 U1 1 U2 3 PU AMER BOARD FAMILY MEDICINE PI LEXINGTON PA 2228 YOUNG DR, LEXINGTON, KY 40505 USA SN 1557-2625 J9 J AM BOARD FAM MED JI J. Am. Board Fam. Med. PD JAN-FEB PY 2011 VL 24 IS 1 BP 26 EP 32 DI 10.3122/jabfm.2011.01.100137 PG 7 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 702TZ UT WOS:000285920100005 PM 21209341 ER PT J AU Raval, MV Dillon, PW Bruny, JL Ko, CY Hall, BL Moss, RL Oldham, KT Richards, KE Vinocur, CD Ziegler, MM AF Raval, Mehul V. Dillon, Peter W. Bruny, Jennifer L. Ko, Clifford Y. Hall, Bruce L. Moss, R. Lawrence Oldham, Keith T. Richards, Karen E. Vinocur, Charles D. Ziegler, Moritz M. CA ACS NSQIP Pediat Steering Comm TI American College of Surgeons National Surgical Quality Improvement Program Pediatric: A Phase 1 Report SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID OUTCOMES; RISK; MORBIDITY; HOSPITALS; VARIABLES; MORTALITY AB BACKGROUND: There has been a long-standing desire to implement a multi-institutional, multispecialty program to address surgical quality improvement for children. This report documents results of the initial phase of the American College of Surgeons National Surgical Quality Improvement Program Pediatric. STUDY DESIGN: From October 2008 to December 2009, patients from 4 pediatric referral centers were sampled using American College of Surgeons National Surgical Quality Improvement Program methodology tailored to children. RESULTS: A total of 7,287 patients were sampled, representing general/thoracic surgery (n = 2,237; 30.7%), otolaryngology (n = 1,687; 23.2%), orthopaedic surgery (n = 1,367; 18.8%), urology (n = 893; 12.3%), neurosurgery (n = 697; 9.6%), and plastic surgery (n = 406; 5.6%). Overall mortality rate detected was 0.3% and 287(3.9%) patients had postoperative occurrences. After accounting for demographic, preoperative, and operative factors, occurrences were 4 times more likely in those undergoing inpatient versus outpatient procedures (odds ratio [OR] = 4.71; 95% CI, 3.01-7.35). Other factors associated with higher likelihood of postoperative occurrences included nutritional/immune history, such as preoperative weight loss/chronic steroid use (OR = 1.49; 95% CI, 1.03-2.15), as well as physiologic compromise, such as sepsis/inotrope use before surgery (OR = 1.68; 95% Cl, 1.10-1.95). Operative factors associated with occurrences included multiple procedures under the same anesthetic (OR = 1.58; 95% CI, 1.21-2.06) and American Society of Anesthesiologists classification category 4/5 versus 1 (OR = 5.74; 95% Cl, 2.94-11.24). Specialty complication rates varied from 1.5% for otolaryngology to 9.0% for neurosurgery (p < 0.001), with specific procedural groupings within each specialty accounting for the majority of complications. Although infectious complications were the predominant outcomes identified across all specialties, distribution of complications varied by specialty. CONCLUSIONS: Based on this initial phase of development, the highly anticipated American College of Surgeons National Surgical Quality Improvement Program Pediatric has the potential to identify outcomes of children's surgical care that can be targeted for quality improvement efforts. (J Am Coll Sorg 2011;212:1-11. (C) 2010 by the American College of Surgeons) C1 [Raval, Mehul V.; Ko, Clifford Y.; Hall, Bruce L.; Richards, Karen E.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL 60611 USA. [Raval, Mehul V.] Northwestern Univ, Feinberg Sch Med, Dept Surg, Chicago, IL 60611 USA. [Dillon, Peter W.] Penn State Univ, Sch Med, Dept Surg, Div Pediat Surg, Hershey, PA USA. [Bruny, Jennifer L.; Ziegler, Moritz M.] Univ Colorado, Childrens Hosp, Dept Pediat Surg, Denver, CO 80202 USA. [Ko, Clifford Y.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Hall, Bruce L.] Washington Univ, John Cochran Vet Affairs Med Ctr, Dept Surg, St Louis, MO USA. [Hall, Bruce L.] Barnes Jewish Hosp, Ctr Hlth Policy, St Louis, MO 63110 USA. [Hall, Bruce L.] Washington Univ, John M Olin Sch Business, St Louis, MO 63130 USA. [Moss, R. Lawrence] Yale Univ, Yale New Haven Childrens Hosp, Dept Surg, New Haven, CT USA. [Oldham, Keith T.] Med Coll Wisconsin, Dept Surg, Milwaukee, WI 53226 USA. [Vinocur, Charles D.] Thomas Jefferson Univ, Div Pediat Surg, AI DuPont Hosp Children, Wilmington, DE USA. RP Raval, MV (reprint author), Amer Coll Surg, Div Res & Optimal Patient Care, 633 N St Clair St,22nd Floor, Chicago, IL 60611 USA. EM m-raval@md.northwestern.edu OI Vinocur, Charles/0000-0001-9650-1122; Raval, Mehul/0000-0002-1527-2661 FU John Gray Research Fellowship; Daniel F and Ada L Rice Foundation FX Dr Raval is supported by the John Gray Research Fellowship and the Daniel F and Ada L Rice Foundation. NR 16 TC 58 Z9 58 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD JAN PY 2011 VL 212 IS 1 BP 1 EP 11 DI 10.1016/j.jamcollsurg.2010.08.013 PG 11 WC Surgery SC Surgery GA 705LE UT WOS:000286129100001 PM 21036076 ER PT J AU Ingraham, AM Cohen, ME Raval, MV Ko, CY Nathens, AB AF Ingraham, Angela M. Cohen, Mark E. Raval, Mehul V. Ko, Clifford Y. Nathens, Avery B. TI Comparison of Hospital Performance in Emergency Versus Elective General Surgery Operations at 198 Hospitals SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID SURGICAL CARE; ADVERSE OUTCOMES; RISK-FACTORS; QUALITY; NSQIP AB BACKGROUND: Surgical quality improvement has focused on elective general surgery (ELGS) outcomes despite the substantial risk associated with emergency general surgery (EMGS) procedures. Furthermore, any differences in the quality of care provided to EMGS versus ELGS patients are not well described. We compared risk factors and risk-adjusted outcomes associated with EMGS and ELGS procedures to assess whether hospitals have comparable outcomes across these procedures. STUDY DESIGN: Using American College of Surgeons National Surgical Quality Improvement Program data (2005 to 2008), regression models were constructed for 30-day overall morbidity, serious morbidity, and mortality among all patients, EMGS patients, and ELGS patients. Observed-to-expected (O/E) ratios were calculated from models based on EMGS or ELGS patients. Association of hospital performance after EMGS versus ELGS procedures was assessed by evaluating correlations of O/E ratios; agreement in outlier status (hospitals where O/E confidence intervals [CI] do not overlap 1.0) was evaluated with weighted kappa. RESULTS: Of 473,619 procedures, 67,445 (14.2%) patients underwent an EMGS procedure. EMGS patients were more likely to experience any morbidity (odds ratio [OR] 1.20; 95% CI 1.16 to 1.23), serious morbidity (OR 1.26; 95% CI 1.21 to 1.30), and mortality (OR 1.39; 95% CI 1.30 to 1.48). Correlation between O/E ratios for EMGS and ELGS were moderate to low (overall morbidity = 0.48, p < 0.0001; serious morbidity = 0.41, p < 0.0001, mortality = 0.18, p = 0.01). Outlier status was not consistent across EMGS and ELGS, with only slight agreement (overall morbidity = 0.18, p < 0.0001; serious morbidity = 0.16, p = 0.001, mortality = 0.19, p = 0.01). CONCLUSIONS: EMGS patients are at substantially greater risk than ELGS patients for adverse events. Hospitals do not appear to have highly consistent performance across EMGS and ELGS outcomes. Processes of care that afford improved outcomes to EMGS patients need to be identified and disseminated. (J Am Coll Surg 2011;212:20-28. (C) 2010 by the American College of Surgeons) C1 [Ingraham, Angela M.] Univ Cincinnati, Coll Med, Dept Surg, Cincinnati, OH 45267 USA. [Ingraham, Angela M.; Cohen, Mark E.; Raval, Mehul V.; Ko, Clifford Y.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL USA. [Raval, Mehul V.] Northwestern Univ, Feinberg Sch Med, Dept Surg, Chicago, IL 60611 USA. [Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA. [Nathens, Avery B.] St Michaels Hosp, Li Ka Shing Knowledge Inst, Keenan Res Ctr, Div Surg & Trauma, Toronto, ON M5B 1W8, Canada. RP Ingraham, AM (reprint author), Univ Cincinnati, Coll Med, Dept Surg, 231 Albert Sabin Way,Room 1586, Cincinnati, OH 45267 USA. OI Raval, Mehul/0000-0002-1527-2661 FU Clinical Scholar in Residence Program at the American College of Surgeons; John Gray Research Fellowship; Daniel F and Ada L Rice Foundation; Canada Research Chair in Systems of Trauma Care FX Drs Ingraham and Raval are supported by the Clinical Scholar in Residence Program at the American College of Surgeons. Dr Raval is also supported by the John Gray Research Fellowship and the Daniel F and Ada L Rice Foundation. Dr Nathens is supported by a Canada Research Chair in Systems of Trauma Care. NR 22 TC 38 Z9 38 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD JAN PY 2011 VL 212 IS 1 BP 20 EP 28A DI 10.1016/j.jamcollsurg.2010.09.026 PG 10 WC Surgery SC Surgery GA 705LE UT WOS:000286129100003 PM 21184955 ER PT J AU Boruta, DM Growdon, WB Schorge, JO AF Boruta, David M., II Growdon, Whitfield B. Schorge, John O. TI Single-Incision Laparoscopic Staging for Endometrial Cancer SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Editorial Material ID LESS C1 [Boruta, David M., II] Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv, Yawkey Ctr,Div Gynecol Oncol, Gillette Ctr Gynecol Oncol,Dept Obstet Gynecol &, Boston, MA 02114 USA. RP Boruta, DM (reprint author), Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv, Yawkey Ctr,Div Gynecol Oncol, Gillette Ctr Gynecol Oncol,Dept Obstet Gynecol &, Suite 9E,55 Fruit St, Boston, MA 02114 USA. EM dboruta@partners.org NR 12 TC 14 Z9 14 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD JAN PY 2011 VL 212 IS 1 BP E1 EP E5 DI 10.1016/j.jamcollsurg.2010.09.018 PG 5 WC Surgery SC Surgery GA 705LE UT WOS:000286129100024 PM 21184954 ER PT J AU Burke, LE Wang, J Sevick, MA AF Burke, Lora E. Wang, Jing Sevick, Mary Ann TI Self-Monitoring in Weight Loss: A Systematic Review of the Literature SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID LOSS PROGRAM; PHYSICAL-ACTIVITY; RANDOMIZED-TRIAL; LOSS MAINTENANCE; PAPER DIARIES; EXERCISE; INTERVENTION; EXPERIENCES; PREVENTION; COMPONENT AB Self-monitoring is the centerpiece of behavioral weight loss intervention programs This article presents a systematic review of the literature on three components of self-monitoring in behavioral weight loss studies diet, exercise, and self weighing This review included articles that were published between 1993 and 2009 that reported on the relationship between weight loss and these self-monitoring strategies Of the 22 studies identified, 15 focused on dietary self-monitoring, one on self-monitoring exercise, and six on self weighing A wide array of methods was used to perform self-monitoring, the paper diary was used most often Adherence to self-monitoring was reported most frequently as the number of diaries completed or the frequency of log ins or reported weights The use of technology, which included the Internet, personal digital assistants, and electronic digital scales were reported in five studies Descriptive designs were used in the earlier studies whereas more recent reports involved prospective studies and randomized trials that examined the effect of self-monitoring on weight loss A significant association between self-monitoring and weight loss was consistently found, however, the level of evidence was weak because of methodologic limitations The most significant limitations of the reviewed studies were the homogenous samples and reliance on self-report In all but two studies, the samples were predominantly white and women This review highlights the need for studies in more diverse populations, for objective measures of adherence to self-monitoring, and for studies that establish the required dose of self-monitoring for successful outcomes J Am Diet Assoc 2011,111 92 102 C1 [Burke, Lora E.; Wang, Jing] Univ Pittsburgh, Sch Nursing, Pittsburgh, PA 15261 USA. [Burke, Lora E.; Wang, Jing] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. [Sevick, Mary Ann] Univ Pittsburgh, Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA 15261 USA. [Sevick, Mary Ann] Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA 15261 USA. RP Burke, LE (reprint author), Univ Pittsburgh, Sch Nursing, 415 Victoria Bldg,3500 Victoria St, Pittsburgh, PA 15261 USA. FU National Institutes of Health/National Institute of Nursing [K24-NR010742] FX The first and second authors are partially supported by National Institutes of Health/National Institute of Nursing Research grant no K24-NR010742 NR 42 TC 246 Z9 246 U1 8 U2 55 PU AMER DIETETIC ASSOC PI CHICAGO PA 120 S RIVERSIDE PLZ, STE 2000, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD JAN PY 2011 VL 111 IS 1 BP 92 EP 102 DI 10.1016/j.jada.2010.10.008 PG 11 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 703CF UT WOS:000285951000014 PM 21185970 ER PT J AU Boucher, JL Evert, A Daly, A Kulkarni, K Rizzotto, JA Burton, K Bradshaw, BG AF Boucher, Jackie L. Evert, Alison Daly, Anne Kulkarni, Karmeen Rizzotto, Jo Anne Burton, Kathryn Bradshaw, Beverly G. TI American Dietetic Association Revised Standards of Practice and Standards of Professional Performance for Registered Dietitians (Generalist, Specialty, and Advanced) in Diabetes Care SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID PRACTICE FRAMEWORK; NUTRITION CARE; MANAGEMENT; COMPLICATIONS; SCOPE; COMPETENCE; PREVENTION; BEHAVIORS; DELIVERY; THERAPY C1 [Boucher, Jackie L.] Minneapolis Heart Inst Fdn, Minneapolis, MN USA. [Evert, Alison] Univ Washington, Med Ctr, Diabet Care Ctr, Seattle, WA 98195 USA. [Daly, Anne] Springfield Diabet & Endocrine Ctr, Springfield, IL USA. [Kulkarni, Karmeen] Abbott Diabet Care, Salt Lake City, UT USA. [Rizzotto, Jo Anne] Joslin Diabet Ctr, Boston, MA 02215 USA. [Burton, Kathryn] Univ Cincinnati, Cincinnati, OH USA. [Bradshaw, Beverly G.] Univ Utah, Div Nutr, Salt Lake City, UT USA. RP Boucher, JL (reprint author), Care Of Byrne C, Amer Dietet Assoc, 120 S Riverside Plaza,Suite 2000, Chicago, IL 60606 USA. NR 47 TC 12 Z9 12 U1 0 U2 2 PU AMER DIETETIC ASSOC PI CHICAGO PA 120 S RIVERSIDE PLZ, STE 2000, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD JAN PY 2011 VL 111 IS 1 BP 156 EP 166 DI 10.1016/j.jada.2010.10.053 PG 11 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 703CF UT WOS:000285951000023 PM 21185979 ER PT J AU Garrido, MM Kane, RL Kaas, M Kane, RA AF Garrido, Melissa M. Kane, Robert L. Kaas, Merrie Kane, Rosalie A. TI Use of Mental Health Care by Community-Dwelling Older Adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE perceived need; mental health care; attitudes; depression; anxiety ID ELDERLY-PATIENTS; PERCEIVED NEED; UNITED-STATES; ANXIETY DISORDER; HELP-SEEKING; LATE-LIFE; DEPRESSION; SAMPLE; DETERMINANTS; COMORBIDITY AB OBJECTIVES To examine relationships between perceived need for care, illness characteristics, attitudes toward care, and probability that older adults will use mental health care (MHC). DESIGN Secondary data analysis. SETTING The Collaborative Psychiatric Epidemiology Surveys (2001-2003). PARTICIPANTS One thousand six hundred eighty-one community-dwelling adults aged 65 and older. MEASUREMENTS Self-reported MHC use and perceived need for care in the previous 12 months, previous year and history of mental illness, history of physical illness, attitudes toward care, and sociodemographic characteristics. RESULTS Of the entire sample, 6.5% had received some type of MHC in the previous year, although 65.9% of those with major depressive disorder (MDD) and 72.5% with anxiety did not receive MHC. In respondents with previous-year depression or anxiety, use was less likely for those with low World Health Organization Disability Assessment Scale (WHO-DAS) self-care ability. Use was more likely for those with more chronic physical conditions and worse WHO-DAS cognitive capacity. Seventeen percent of those with perceived need for MHC did not receive it. In respondents with perceived need, subthreshold generalized anxiety disorder was associated with lower likelihood of use. Use was more likely for older respondents and those with more household members, at least a high school education, and better self-care ability. Forty-one percent of those who perceived a need for care but did not use it met previous-year diagnostic criteria for anxiety, and 17% met criteria for MDD. CONCLUSION Understanding the perceptions that underlie individuals' health care-seeking behavior is an important step toward reducing underuse of MHC by older adults. C1 [Garrido, Melissa M.] James J Peters VA Med Ctr, GRECC, Bronx, NY 10468 USA. [Garrido, Melissa M.] James J Peters VA Med Ctr, Res Enhancement Award Program, Bronx, NY 10468 USA. [Garrido, Melissa M.] Mt Sinai Sch Med, Brookdale Dept Geriatr & Palliat Med, New York, NY USA. [Garrido, Melissa M.] Rutgers State Univ, Inst Hlth Hlth Care Policy & Aging Res, New Brunswick, NJ 08903 USA. [Kane, Robert L.; Kane, Rosalie A.] Univ Minnesota Twin Cities, Div Hlth Policy & Management, Minneapolis, MN USA. [Kaas, Merrie] Univ Minnesota Twin Cities, Sch Nursing, Minneapolis, MN USA. RP Garrido, MM (reprint author), James J Peters VA Med Ctr, GRECC, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM melissa.garrido@mssm.edu OI Garrido, Melissa/0000-0002-8986-3536 FU National Research Service Award at University of Minnesota-Twin Cities [T32 HS-000036]; National Institute of Mental Health at Rutgers University [T32 MH16242-29] FX Robert Kane consults for United Healthgroup, SCAN Health Plan, Medtronic, Lewin and Associates, and Cleveland Clinic. Melissa Garrido was supported by a National Research Service Award predoctoral training grant at the University of Minnesota-Twin Cities (T32 HS-000036) and a National Institute of Mental Health postdoctoral training grant at Rutgers University (T32 MH16242-29). NR 40 TC 19 Z9 19 U1 1 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JAN PY 2011 VL 59 IS 1 BP 50 EP 56 DI 10.1111/j.1532-5415.2010.03220.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 706HG UT WOS:000286208200008 PM 21198461 ER PT J AU Picard, MH Adams, D Bierig, SM Dent, JM Douglas, PS Gillam, LD Keller, AM Malenka, DJ Masoudi, FA McCulloch, M Pellikka, PA Peters, PJ Stainback, RF Strachan, GM Zoghbi, WA AF Picard, Michael H. Adams, David Bierig, S. Michelle Dent, John M. Douglas, Pamela S. Gillam, Linda D. Keller, Andrew M. Malenka, David J. Masoudi, Frederick A. McCulloch, Marti Pellikka, Patricia A. Peters, Priscilla J. Stainback, Raymond F. Strachan, G. Monet Zoghbi, William A. TI American Society of Echocardiography Recommendations for Quality Echocardiography Laboratory Operations SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article DE Echocardiography; Quality; Echocardiography laboratory operations ID APPROPRIATENESS CRITERIA; STRESS ECHOCARDIOGRAPHY; EUROPEAN-ASSOCIATION; STANDARDS COMMITTEE; OF-ECHOCARDIOGRAPHY; WRITING GROUP; TASK-FORCE; GUIDELINES; CARDIOLOGY; STATEMENT C1 [Picard, Michael H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Adams, David; Douglas, Pamela S.] Duke Univ, Med Ctr, Durham, NC USA. [Bierig, S. Michelle] St Anthonys Med Ctr, St Louis, MO USA. [Dent, John M.] Univ Virginia Hlth Syst, Charlottesville, VA USA. [Gillam, Linda D.] Columbia Univ, New York, NY USA. [Keller, Andrew M.] Danbury Hosp, Danbury, CT USA. [Malenka, David J.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Masoudi, Frederick A.] Denver Hlth Med Ctr, Denver, CO USA. [McCulloch, Marti; Zoghbi, William A.] Methodist DeBakey Heart & Vasc Ctr, Houston, TX USA. [Pellikka, Patricia A.] Mayo Clin, Rochester, MN USA. [Peters, Priscilla J.] Cooper Univ Hosp, Pennsauken, NJ USA. [Stainback, Raymond F.] St Lukes Episcopal Hosp, Texas Heart Inst, Houston, TX USA. [Strachan, G. Monet] Univ Calif San Diego, San Diego, CA 92103 USA. RP Picard, MH (reprint author), Amer Soc Echocardiog, 2100 Gateway Ctr Blvd,Suite 310, Morrisville, NC 27560 USA. EM ase@asecho.org OI Stainback, Raymond/0000-0002-2089-6508; Picard, Michael/0000-0002-9264-3243 FU St. Jude Medical Foundation; National Heart, Lung, and Blood Institute; Agency for Healthcare Research and Quality FX The following authors reported no actual or potential conflicts of interest in relation to this document: Michael H. Picard, MD, FASE; S. Michelle Bierig, RDCS, MPH, FASE; John M. Dent, MD, FASE; Pamela S. Douglas, MD, FASE; Linda D. Gillam, MD, FASE; Andrew M. Keller, MD, FASE; Priscilla J. Peters, RDCS, FASE; Raymond F. Stainback, MD, FASE; and William A. Zoghbi, MD, FASE. The following authors reported a relationship with one or more commercial interests: David Adams, RDCS, FASE, serves as a consultant for Philips, Siemens, and GE. David J. Malenka, MD, FASE, received grant support from St. Jude Medical Foundation. Frederick A. Masoudi, MD, MSPH, received grant support from the National Heart, Lung, and Blood Institute and the Agency for Healthcare Research and Quality. Marti McCulloch, RDCS, FASE, is a speaker for Lantheus and an advisor and consultant for Siemens and GE. Patricia A. Pellikka, MD, FASE, served as a consultant for Novartis. G. Monet Strachan, RDCS, FASE, received a per diem from Lantheus. NR 24 TC 130 Z9 131 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD JAN PY 2011 VL 24 IS 1 BP 1 EP 10 DI 10.1016/j.echo.2010.11.006 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 697GG UT WOS:000285500500003 PM 21172594 ER PT J AU Anderson, S Eldadah, B Halter, JB Hazzard, WR Himmelfarb, J Horne, FM Kimmel, PL Molitoris, BA Murthy, M O'Hare, AM Schmader, KE High, KP AF Anderson, Sharon Eldadah, Basil Halter, Jeffrey B. Hazzard, William R. Himmelfarb, Jonathan Horne, Frances McFarland Kimmel, Paul L. Molitoris, Bruce A. Murthy, Mahadev O'Hare, Ann M. Schmader, Kenneth E. High, Kevin P. TI Acute Kidney Injury in Older Adults SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID ACUTE-RENAL-FAILURE; PERCUTANEOUS CORONARY INTERVENTION; CRITICALLY-ILL PATIENTS; ISCHEMIA-REPERFUSION INJURY; LONG-TERM MORTALITY; ACUTE LUNG INJURY; QUALITY-OF-LIFE; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; GELATINASE-ASSOCIATED LIPOCALIN; ACUTE TUBULAR-NECROSIS AB Aging kidneys undergo structural and functional changes that decrease autoregulatory capacity and increase susceptibility to acute injury. Acute kidney injury associates with duration and location of hospitalization, mortality risk, progression to chronic kidney disease, and functional status in daily living. Definition and diagnosis of acute kidney injury are based on changes in creatinine, which is an inadequate marker and might identify patients when it is too late. The incidence of acute kidney injury is rising and increases with advancing age, yet clinical studies have been slow to address geriatric issues or the heterogeneity in etiologies, outcomes, or patient preferences among the elderly. Here we examine some of the current literature, identify knowledge gaps, and suggest potential research questions regarding acute kidney injury in older adults. Answering these questions will facilitate the integration of geriatric issues into future mechanistic and clinical studies that affect management and care of acute kidney injury. C1 [High, Kevin P.] Wake Forest Univ, Bowman Gray Sch Med, Infect Dis Sect, Dept Internal Med, Winston Salem, NC 27157 USA. [Anderson, Sharon] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Anderson, Sharon] Portland VA Med Ctr, Portland, OR USA. [Eldadah, Basil; Murthy, Mahadev] NIA, Bethesda, MD 20892 USA. [Halter, Jeffrey B.] Univ Michigan, Sch Med, Ann Arbor, MI USA. [Hazzard, William R.; O'Hare, Ann M.] Univ Washington, Sch Med, Seattle, WA USA. [Hazzard, William R.; Himmelfarb, Jonathan] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Horne, Frances McFarland] Assoc Specialty Prof, Washington, DC USA. [Kimmel, Paul L.] NIDDK, Bethesda, MD USA. [Molitoris, Bruce A.] Indiana Univ, Sch Med, Indianapolis, IN USA. [Schmader, Kenneth E.] Duke Univ, Durham, NC USA. [Schmader, Kenneth E.] Durham VA Med Ctr, Geriatr Res Educ & Clin Ctr, Durham, NC USA. RP High, KP (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Infect Dis Sect, Dept Internal Med, 100 Med Ctr Blvd, Winston Salem, NC 27157 USA. EM khigh@wfubmc.edu FU Association of Specialty Professors; American Society of Nephrology; American Geriatrics Society; National Institute on Aging; National Institute of Diabetes and Digestive and Kidney Diseases; John A. Hartford Foundation FX For those who attended a workshop on May 10-11, 2010 sponsored by the Association of Specialty Professors, the American Society of Nephrology, the American Geriatrics Society, the National Institute on Aging, and the National Institute of Diabetes and Digestive and Kidney Diseases.; This workshop was supported by a generous grant from the John A. Hartford Foundation to A.S.P. We are grateful to Charles Clayton and Erika Tarver for assistance with organizing the workshop. For a full list of moderators and attendees of the conference, please visit http://www.im.org/CareerDevelopment/ GrantsandScholarships/IGP/Expanding ResearchEfforts/Pages/WorkshoponAcute KidneyInjuryinOlderAdults.aspx. NR 173 TC 54 Z9 59 U1 1 U2 6 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JAN PY 2011 VL 22 IS 1 BP 28 EP 38 DI 10.1681/ASN.2010090934 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 730PN UT WOS:000288046500009 PM 21209252 ER PT J AU Bouley, R Lu, HAJ Nunes, P Da Silva, N McLaughlin, M Chen, Y Brown, D AF Bouley, Richard Lu, Hua A. J. Nunes, Paula Da Silva, Nicolas McLaughlin, Margaret Chen, Ying Brown, Dennis TI Calcitonin Has a Vasopressin-like Effect on Aquaporin-2 Trafficking and Urinary Concentration SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID NEPHROGENIC DIABETES-INSIPIDUS; RENAL EPITHELIAL-CELLS; PLASMA OXYTOCIN LEVEL; SALMON-CALCITONIN; ADENYLATE-CYCLASE; WATER CHANNEL; LLC-PK1 CELLS; COLLECTING DUCT; PARATHYROID HORMONE; INTERCALATED CELLS AB The most common cause of hereditary nephrogenic diabetes insipidus is a nonfunctional vasopressin (VP) receptor type 2 (V2R). Calcitonin, another ligand of G-protein-coupled receptors, has a VP-like effect on electrolytes and water reabsorption, suggesting that it may affect AQP2 trafficking. Here, calcitonin increased intracellular cAMP and stimulated the membrane accumulation of AQP2 in LLC-PK1 cells. Pharmacologic inhibition of protein kinase A (PKA) and deficiency of a critical PKA phosphorylation site on AQP2 both prevented calcitonin-induced membrane accumulation of AQP2. Fluorescence assays showed that calcitonin led to a 70% increase in exocytosis and a 20% decrease in endocytosis of AQP2. Immunostaining of rat kidney slices demonstrated that calcitonin induced a significant redistribution of AQP2 to the apical membrane of principal cells in cortical collecting ducts and connecting segments but not in the inner stripe or inner medulla. Calcitonin-treated VP-deficient Brattleboro rats had a reduced urine flow and two-fold higher urine osmolality during the first 12 hours of treatment compared with control groups. Although this VP-like effect of calcitonin diminished over the following 72 hours, the tachyphylaxis was reversible. Taken together, these data show that calcitonin induces cAMP-dependent AQP2 trafficking in cortical collecting and connecting tubules in parallel with an increase in urine concentration. This suggests that calcitonin has a potential therapeutic use in nephrogenic diabetes insipidus. C1 [Bouley, Richard] Massachusetts Gen Hosp, Ctr Syst Biol, Program Membrane Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Nephrol, Simches Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Bouley, R (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Program Membrane Biol, Room 8202,185 Cambridge St, Boston, MA 02114 USA. EM Bouley.Richard@mgh.harvard.edu RI Nunes-Hasler, Paula/N-4337-2015 OI Nunes-Hasler, Paula/0000-0002-4598-685X FU National Institutes of Health [POIDK38452]; National Kidney Foundation; Natural Sciences and Engineering Research Council of Canada; NIDDK, National Institutes of Health [K08 DK-075940-01]; Boston Area Diabetes and Endocrinology Research Center [DK57521]; Center for the Study of Inflammatory Bowel Disease [DK43341] FX This work was supported by National Institutes of Health grant POIDK38452 (DB). R. Bouley received an investigator award from the National Kidney Foundation. P. Nunes was supported by a Doctoral Level Postgraduate Scholarship from the Natural Sciences and Engineering Research Council of Canada, and H. A. J. Lu was supported by NIDDK, National Institutes of Health Grant K08 DK-075940-01. The Microscopy Core facility of the Massachusetts General Hospital Program in Membrane Biology receives additional support from the Boston Area Diabetes and Endocrinology Research Center (grant DK57521) and the Center for the Study of Inflammatory Bowel Disease (grant DK43341). This work had been partially presented at the American Society of Nephrology meeting 2009. NR 82 TC 19 Z9 24 U1 0 U2 6 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JAN PY 2011 VL 22 IS 1 BP 59 EP 72 DI 10.1681/ASN.2009121267 PG 14 WC Urology & Nephrology SC Urology & Nephrology GA 730PN UT WOS:000288046500013 PM 21071524 ER PT J AU Peralta, CA Katz, R Sarnak, MJ Lx, J Fried, LF De Boer, I Palmas, W Siscovick, D Levey, AS Shlipak, MG AF Peralta, Carmen A. Katz, Ronit Sarnak, Mark J. Lx, Joachim Fried, Linda F. De Boer, Ian Palmas, Walter Siscovick, David Levey, Andrew S. Shlipak, Michael G. TI Cystatin C Identifies Chronic Kidney Disease Patients at Higher Risk for Complications SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID GLOMERULAR-FILTRATION-RATE; CARDIOVASCULAR EVENTS; SERUM CREATININE; ELDERLY PERSONS; POOLED ANALYSIS; RENAL-FUNCTION; HEART-FAILURE; ATHEROSCLEROSIS; MORTALITY; MARKER AB Although cystatin C is a stronger predictor of clinical outcomes associated with CKD than creatinine, the clinical role for cystatin C is unclear. We included 11,909 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) and the Cardiovascular Health Study (CHS) and assessed risks for death, cardiovascular events, heart failure, and ESRD among persons categorized into mutually exclusive groups on the basis of the biomarkers that supported a diagnosis of CKD (eGFR < 60 ml/min per 1.73 m(2)): creatinine only, cystatin C only, both, or neither. We used CKD-EPI equations to estimate GFR from these biomarkers. In MESA, 9% had CKD by the creatinine-based equation only, 2% had CKD by the cystatin C-based equation only, and 4% had CKD by both equations; in CHS, these percentages were 12, 4, and 13%, respectively. Compared with those without CKD, the adjusted hazard ratios (HR) for mortality in MESA were: 0.80 (95% CI 0.50 to 1.26) for CKD by creatinine only; 3.23 (95% CI 1.84 to 5.67) for CKD by cystatin C only; and 1.93 (95% CI 1.27 to 2.92) for CKD by both; in CHS, the adjusted HR were 1.09 (95% CI 0.98 to 1.21), 1.78 (95% CI 1.53 to 2.08), and 1.74(95% CI 1.58 to 1.93), respectively. The pattern was similar for cardiovascular disease (CVD), heart failure, and kidney failure outcomes. In conclusion, among adults diagnosed with CKD using the creatinine-based CKD-EPI equation, the adverse prognosis is limited to the subset who also have CKD according to the cystatin C-based equation. Cystatin C may have a role in identifying persons with CKD who have the highest risk for complications. C1 [Peralta, Carmen A.; Shlipak, Michael G.] San Francisco VA Med Ctr, San Francisco, CA USA. [Peralta, Carmen A.; Shlipak, Michael G.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Katz, Ronit; Siscovick, David] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Katz, Ronit] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. [Sarnak, Mark J.; Levey, Andrew S.] Tufts Univ New England Med Ctr, Dept Med, Boston, MA USA. [Lx, Joachim] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. [Fried, Linda F.] Pittsburgh Vet Affairs Med Ctr, Pittsburgh, PA USA. [De Boer, Ian; Siscovick, David] Univ Washington, Dept Med, Seattle, WA USA. [Palmas, Walter] Columbia Univ, Dept Med, New York, NY USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Peralta, CA (reprint author), 4150 Clement St,111A1, San Francisco, CA 94121 USA. EM carmenalicia.peralta@ucsf.edu FU National Heart, Lung, and Blood Institute [N01-HC-95159 through N01-HC-95165, N01-HC-95169, U01 HL080295]; National Institute of Neurologic Disorders and Stroke; NIDDK [1K23DK082793-01, R01DK 066488]; [N01-HC-85079 through N01-HC-85086]; [N01-HC-35129]; [N01 HC-15103]; [N01 HC-55222]; [N01-HC-75150]; [N01-HC-45133] FX This work was supported by contracts N01-HC-95159 through N01-HC-95165 and N01-HC-95169 from the National Heart, Lung, and Blood Institute for MESA. The authors thank the other investigators, the staff, and the participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org.; For CHS, the research reported in this article was supported by contract numbers N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, and N01-HC-45133; grant number U01 HL080295 from the National Heart, Lung, and Blood Institute; with additional contributions from the National Institute of Neurologic Disorders and Stroke. A full list of principal CHS investigators and institutions can be found at http://www.chs-nhlbi.org/pi.htm.; This work was also funded by the NIDDK (1K23DK082793-01 to C.P.) and R01DK 066488 (to M.S.). NR 31 TC 88 Z9 96 U1 0 U2 10 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JAN PY 2011 VL 22 IS 1 BP 147 EP 155 DI 10.1681/ASN.2010050483 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 730PN UT WOS:000288046500021 PM 21164029 ER PT J AU Farris, AB Adams, CD Brousaides, N Della Pelle, PA Collins, AB Moradi, E Smith, RN Grimm, PC Colvin, RB AF Farris, Alton B. Adams, Catherine D. Brousaides, Nicole Della Pelle, Patricia A. Collins, A. Bernard Moradi, Ellie Smith, R. Neal Grimm, Paul C. Colvin, Robert B. TI Morphometric and Visual Evaluation of Fibrosis in Renal Biopsies SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID GLOMERULAR-FILTRATION-RATE; COMPUTERIZED IMAGE-ANALYSIS; INTERSTITIAL FIBROSIS; MESENCHYMAL TRANSITION; OXFORD CLASSIFICATION; ALLOGRAFT REJECTION; PROTOCOL BIOPSIES; SERUM CREATININE; KIDNEY FIBROSIS; NEPHROPATHY AB Interstitial fibrosis is an outcome measure of increasing importance in clinical trials of both renal transplantation and native disease, but data on the comparative advantages of fibrosis measurement methods are limited. We compared four morphometric techniques and contrasted these with two visual fibrosis-scoring methods on trichrome-stained slides. Two morphometric methods included whole-slide digital images: collagen III immunohistochemistry and a new technique using trichrome and periodic acid-Schiff subtraction morphometry; the other two methods included Sirius Red with and without polarization on multiple digital fields. We evaluated 10 serial sections from 15 renal biopsies with a range of fibrosis extent and diagnoses on duplicate sections with each method on separate days. Three pathologists performed visual scoring on whole-slide images. Visual and morphometric techniques had good to excellent interassay reproducibility (R(2) = 0.62 to 0.96) and interobserver reproducibility (R(2) = 0.75 to 0.99, all P < 0.001). Morphometry showed less variation between observers than visual assessment (mean of 1% to 5% versus 11% to 13%). Collagen III, Sirius Red unpolarized, and visual scores had the strongest correlations (R(2) = 0.78 to 0.89), the greatest dynamic range, and the best correlation with estimated GFR (R(2) = 0.38 to 0.50, P < 0.01 to 0.001). Considering efficiency, reproducibility, and functional correlation, two current techniques stand out as potentially the best for clinical trials: collagen III morphometry and visual assessment of trichrome-stained slides. C1 [Farris, Alton B.; Adams, Catherine D.; Brousaides, Nicole; Della Pelle, Patricia A.; Collins, A. Bernard; Smith, R. Neal; Colvin, Robert B.] Massachusetts Gen Hosp, Pathol Serv, Boston, MA 02114 USA. [Farris, Alton B.; Adams, Catherine D.; Brousaides, Nicole; Della Pelle, Patricia A.; Collins, A. Bernard; Smith, R. Neal; Colvin, Robert B.] Harvard Univ, Sch Med, Boston, MA USA. [Moradi, Ellie; Grimm, Paul C.] Stanford Univ, Sch Med, Div Pediat Nephrol, Stanford, CA USA. [Farris, Alton B.] Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. RP Farris, AB (reprint author), Emory Univ Hosp, 1364 Clifton Rd NE,Room H-188, Atlanta, GA 30322 USA. EM abfarri@emory.edu FU National Institutes of Health [U01-AI-63623, U01-AI-077816, U01-AI-070107] FX This work has been supported by grants from the National Institutes of Health (U01-AI-63623, U01-AI-077816, U01-AI-070107). NR 45 TC 66 Z9 75 U1 0 U2 5 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JAN PY 2011 VL 22 IS 1 BP 176 EP 186 DI 10.1681/ASN.2009091005 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 730PN UT WOS:000288046500024 PM 21115619 ER PT J AU Vasterling, JJ Proctor, SP AF Vasterling, Jennifer J. Proctor, Susan P. TI Understanding the Neuropsychological Consequences of Deployment Stress: A Public Health Framework SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Review DE Deployment; Stress; Neuropsychological functioning; Public health; Epidemiology; Veterans; Military personnel ID PERSIAN-GULF-WAR; TWINS DISCORDANT; MENTAL-HEALTH; IRAQ-WAR; VETERANS; DISORDER; PTSD; MEMORY; SYMPTOMS; SOLDIERS AB Complaints of neuropsychological dysfunction have emerged among subsets of military personnel after almost every major deployment involving western nations in recent history. Although deployments have been characterized by a range of neural risk factors, psychological stress is common to most prolonged deployments. This review uses a public health framework to address associations between deployment-related stress and neuropsychological performance. Specifically, the review covers mechanisms by which deployment-related psychological stress may affect neuropsychological functioning, considers the advantages and disadvantages of approaching the question from a public health perspective, and discusses how epidemiological research may sort out questions regarding course, cause, and effect. (JINS, 2011, 17,1-6) C1 [Vasterling, Jennifer J.] VA Boston Healthcare Syst, Psychol Serv, Boston, MA 02130 USA. [Vasterling, Jennifer J.] VA Boston Healthcare Syst, PTSD, VA Natl Ctr, Boston, MA 02130 USA. [Vasterling, Jennifer J.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Proctor, Susan P.] USA, Environm Med Res Inst, Mil Performance Div, Natick, MA 01760 USA. [Proctor, Susan P.] VA Boston Healthcare Syst, Res Serv, Boston, MA 02130 USA. [Proctor, Susan P.] Boston Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA. RP Vasterling, JJ (reprint author), VA Boston Healthcare Syst, Psychol Serv, Psychol 116,150 S Huntington Ave, Boston, MA 02130 USA. EM jennifer.vasterling@va.gov NR 43 TC 7 Z9 7 U1 1 U2 4 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1355-6177 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD JAN PY 2011 VL 17 IS 1 BP 1 EP 6 DI 10.1017/S1355617710001116 PG 6 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 702KX UT WOS:000285894700001 PM 21083962 ER PT J AU Burstein, HJ AF Burstein, Harold J. TI Beaten at the Alamo by the Europeans SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Editorial Material C1 [Burstein, Harold J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Burstein, Harold J.] Dana Farber Canc Inst, Boston, MA USA. [Burstein, Harold J.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Burstein, HJ (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 3 TC 4 Z9 4 U1 0 U2 0 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD JAN PY 2011 VL 9 IS 1 BP 1 EP 1 PG 1 WC Oncology SC Oncology GA 719PN UT WOS:000287217200001 PM 21233239 ER PT J AU Greenberg, PL Attar, E Bennett, JM Bloomfield, CD De Castro, CM Deeg, HJ Foran, JM Gaensler, K Garcia-Manero, G Gore, SD Head, D Komrokji, R Maness, LJ Millenson, M Nimer, SD O'Donnell, MR Schroeder, MA Shami, PJ Stone, RM Thompson, JE Westervelt, P AF Greenberg, Peter L. Attar, Eyal Bennett, John M. Bloomfield, Clara D. De Castro, Carlos M. Deeg, H. Joachim Foran, James M. Gaensler, Karin Garcia-Manero, Guillermo Gore, Steven D. Head, David Komrokji, Rami Maness, Lori J. Millenson, Michael Nimer, Stephen D. O'Donnell, Margaret R. Schroeder, Mark A. Shami, Paul J. Stone, Richard M. Thompson, James E. Westervelt, Peter TI Myelodysplastic Syndromes SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review DE NCCN Clinical Practice Guidelines; NCCN Guidelines; myelodysplastic syndromes; chronic myelomonocytic leukemia; refractory anemia; cytopenias; treatment ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; COLONY-STIMULATING FACTOR; WORLD-HEALTH-ORGANIZATION; ACUTE MYELOID-LEUKEMIA; QUALITY-OF-LIFE; CHRONIC MYELOMONOCYTIC LEUKEMIA; TRANSFUSIONAL IRON OVERLOAD; FACTOR RECEPTOR-BETA; ACUTE MYELOGENOUS LEUKEMIA C1 [Greenberg, Peter L.] Stanford Comprehens Canc Ctr, Stanford, CA USA. [Attar, Eyal] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Bloomfield, Clara D.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Deeg, H. Joachim] Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Foran, James M.] Univ Alabama, Ctr Comprehens Canc, Birmingham, W Midlands, England. [Garcia-Manero, Guillermo] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Gore, Steven D.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Sidney, BC, Canada. [Head, David] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Maness, Lori J.] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. [Nimer, Stephen D.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [O'Donnell, Margaret R.] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Schroeder, Mark A.; Westervelt, Peter] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Schroeder, Mark A.; Westervelt, Peter] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Shami, Paul J.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Thompson, James E.] Roswell Pk Canc Inst, Buffalo, NY USA. RP Greenberg, PL (reprint author), Stanford Comprehens Canc Ctr, Stanford, CA USA. FU NCI NIH HHS [K24 CA111717] NR 130 TC 93 Z9 101 U1 2 U2 11 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD JAN PY 2011 VL 9 IS 1 BP 30 EP 56 PG 27 WC Oncology SC Oncology GA 719PN UT WOS:000287217200005 PM 21233243 ER PT J AU Steensma, DP AF Steensma, David P. TI The Role of Iron Chelation Therapy for Patients With Myelodysplastic Syndromes SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article DE Myelodysplastic syndromes; MDS; iron overload; transfusional hemosiderosis; deferasirox; iron chelation therapy ID STEM-CELL TRANSPLANTATION; SERUM FERRITIN; CONSENSUS STATEMENT; OVERLOADED PATIENTS; OXIDATIVE STRESS; SYNDROMES MDS; DEFERASIROX; SURVIVAL; GUIDELINES; IMPACT AB The appropriate role of iron chelation therapy in the management of patients with myelodysplastic syndromes (MDS) is currently controversial. Some investigators interpret data to indicate that careful attention to iron parameters, with early initiation of iron chelation in patients with evidence suggesting transfusion-associated iron overload, is an important component of high-quality MDS patient care. Other physicians are more skeptical, noting that chelation can be cumbersome or costly, has associated risks, and has not yet been shown to reduce morbidity or mortality in the MDS setting. This article reviews the extent to which iron chelation therapy might be either an important clinical intervention in MDS or a distraction from more pressing clinical concerns. (JNCCN 2011;9:65-75) C1 [Steensma, David P.] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. [Steensma, David P.] Harvard Univ, Sch Med, Boston, MA USA. RP Steensma, DP (reprint author), Dana Farber Canc Inst, Div Hematol Malignancies, 44 Binney St,Suite D1B30,Mayer 1B21, Boston, MA 02115 USA. EM david_steensma@dfci.harvard.edu OI Steensma, David/0000-0001-5130-9284 NR 55 TC 9 Z9 9 U1 1 U2 2 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD JAN PY 2011 VL 9 IS 1 BP 65 EP 74 PG 10 WC Oncology SC Oncology GA 719PN UT WOS:000287217200007 PM 21233245 ER PT J AU Morgan, RJ Alvarez, RD Armstrong, DK Boston, B Burger, RA Chen, LM Copeland, L Crispens, MA Gershenson, D Gray, HJ Grigsby, PW Hakam, A Havrilesky, LJ Johnston, C Lele, S Matulonis, UA O'Malley, DM Penson, RT Remmenga, SW Sabbatini, P Schilder, RJ Schink, JC Teng, N Werner, TL AF Morgan, Robert J., Jr. Alvarez, Ronald D. Armstrong, Deborah K. Boston, Barry Burger, Robert A. Chen, Lee-May Copeland, Larry Crispens, Marta Ann Gershenson, David Gray, Heidi J. Grigsby, Perry W. Hakam, Ardeshir Havrilesky, Laura J. Johnston, Carolyn Lele, Shashikant Matulonis, Ursula A. O'Malley, David M. Penson, Richard T. Remmenga, Steven W. Sabbatini, Paul Schilder, Russell J. Schink, Julian C. Teng, Nelson Werner, Theresa L. TI Epithelial Ovarian Cancer SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review DE NCCN Clinical Practice Guidelines; NCCN Guidelines; treatment guidelines; ovarian cancer; staging; surgery; epithelial carcinoma; gynecologic malignancy; chemotherapy; chemosensitivity assay; minimally invasive surgery; in vitro chemosensitivity testing; laparoscopy ID GYNECOLOGIC-ONCOLOGY-GROUP; PHASE-II TRIAL; PEGYLATED LIPOSOMAL DOXORUBICIN; PLATINUM-RESISTANT OVARIAN; PRIMARY PERITONEAL CANCER; TERM-FOLLOW-UP; SECONDARY CYTOREDUCTIVE SURGERY; TUBAL INTRAEPITHELIAL CARCINOMA; COMBINED EXPLORATORY ANALYSIS; PELVIC SEROUS CARCINOMA C1 [Morgan, Robert J., Jr.] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Alvarez, Ronald D.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Armstrong, Deborah K.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Sidney, BC, Canada. [Boston, Barry] Univ Tennessee, Inst Canc, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Burger, Robert A.; Schilder, Russell J.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Chen, Lee-May] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Copeland, Larry; O'Malley, David M.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Copeland, Larry; O'Malley, David M.] Solove Res Inst, Columbus, OH USA. [Crispens, Marta Ann] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Gershenson, David] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Grigsby, Perry W.] Univ Washington, Sch Med, Seattle, WA 98195 USA. [Grigsby, Perry W.] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Johnston, Carolyn] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Lele, Shashikant] Roswell Pk Canc Inst, Buffalo, NY USA. [Matulonis, Ursula A.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Penson, Richard T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Remmenga, Steven W.] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. [Sabbatini, Paul] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Schink, Julian C.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Teng, Nelson] Stanford Comprehens Canc Ctr, Stanford, CA USA. [Werner, Theresa L.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. RP Morgan, RJ (reprint author), City Hope Comprehens Canc Ctr, Duarte, CA USA. RI OMalley, David/E-3789-2011 NR 152 TC 48 Z9 50 U1 4 U2 13 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD JAN PY 2011 VL 9 IS 1 BP 82 EP 113 PG 32 WC Oncology SC Oncology GA 719PN UT WOS:000287217200008 PM 21233246 ER PT J AU Brahmer, JR Dahlberg, SE Gray, RJ Schiller, JH Perry, MC Sandler, A Johnson, DH AF Brahmer, Julie R. Dahlberg, Suzanne E. Gray, Robert J. Schiller, Joan H. Perry, Michael C. Sandler, Alan Johnson, David H. TI Sex Differences in Outcome with Bevacizumab Therapy Analysis of Patients with Advanced-Stage Non-small Cell Lung Cancer Treated with or without Bevacizumab in Combination with Paclitaxel and Carboplatin in the Eastern Cooperative Oncology Group Trial 4599 SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Non-small cell lung cancer; Sex differences; Bevacizumab ID PHASE-III TRIAL; 1ST-LINE THERAPY; SOLID TUMORS; SURVIVAL; PACLITAXEL; PHARMACOKINETICS; CHEMOTHERAPY; GEMCITABINE; CARBOPLATIN; ANTIBODY AB Introduction: E4599 compared carboplatin and paclitaxel with (PCB) or without (PC) bevacizumab in patients with advanced-stage non-small cell lung cancer. Bevacizumab improved overall survival. However, an unplanned subset analysis did not show a survival benefit for females treated with bevacizumab. Methods: Known prognostic factors and toxicities were compared by sex. Proportional hazards models of survival with multiple factor combinations were used to adjust for treatment effect. Results: The analysis includes 850 patients. The median survival was 8.7 months (PC) versus 11.7 months (PCB) for males (p = 0.001) and 13.1 months (PC) versus 13.3 months (PCB) for females (p = 0.87). Progression-free survival and response rate on the PCB arm were 6.3 months and 29% for males and 6.2 months and 41% for females (p > 0.05). Progression-free survival and response rate on the PC arm were 4.3 months and 16% for males and 5.3 months and 14% for females (p > 0.05). No significant demographic differences were seen between the two arms for males, whereas fewer females on the PCB arm had liver metastasis (PCB 11.7% versus PC 23.2%, p = 0.003). Adverse events with a sex difference on the PCB arm included severe hypertension (males: 4.2%, females: 9.9%, p = 0.02), constipation (males: 1.4%, females: 4.7%, p = 0.05), and abdominal pain (males: 0.9%, females: 5.2%, p = 0.01). In the proportional hazards model adjusting for the other factors, the test for a sex by treatment interaction was not significant (p = 0.09). Conclusions: Multiple factors may contribute to the apparent sex-specific differences in efficacy of bevacizumab noted in this study. C1 [Brahmer, Julie R.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD 21231 USA. [Dahlberg, Suzanne E.; Gray, Robert J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Schiller, Joan H.; Johnson, David H.] Univ Texas SW, Dallas, TX USA. [Perry, Michael C.] Univ Missouri, Ellis Fischel Canc Ctr, Columbia, MO USA. [Sandler, Alan] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Brahmer, JR (reprint author), Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Bunting Blaustein Canc Res Bldg,Room G-94,1650 Or, Baltimore, MD 21231 USA. EM brahmju@jhmi.edu FU National Cancer Institute, National Institutes of Health [CA23318, CA66636, CA21115, CA16116, CA21076, CA49957]; Department of Health and Human Services FX Supported in part by Public Health Service Grants CA23318, CA66636, CA21115, CA16116, CA21076, and CA49957, National Cancer Institute, National Institutes of Health, and the Department of Health and Human Services. NR 22 TC 16 Z9 18 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JAN PY 2011 VL 6 IS 1 BP 103 EP 108 DI 10.1097/JTO.0b013e3181fa8efd PG 6 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 698IP UT WOS:000285587800018 PM 21079521 ER PT J AU Ortiz, TM Cohen, DW Kent, MS Janne, PA Costa, DB AF Ortiz, Taylor M. Cohen, David W. Kent, Michael S. Jaenne, Pasi A. Costa, Daniel B. TI KRAS Mutation Analysis Helps to Differentiate Between Pulmonary Metastasis from Colon Adenocarcinoma In Situ and Primary Lung Adenocarcinoma SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article ID COLORECTAL-CANCER C1 [Ortiz, Taylor M.; Jaenne, Pasi A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02215 USA. [Cohen, David W.; Kent, Michael S.; Costa, Daniel B.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Costa, Daniel B.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Surg,Div Hematol Oncol, Boston, MA 02215 USA. [Cohen, David W.; Kent, Michael S.; Costa, Daniel B.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. RP Costa, DB (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Surg,Div Hematol Oncol, 330 Brookline Ave, Boston, MA 02215 USA. EM dbcosta@bidmc.harvard.edu OI Costa, Daniel/0000-0002-0689-395X FU National Institutes of Health [T32-CA09172-35, 2PA50-CA090578-08]; American Society of Clinical Oncology Cancer Foundation [CDA-15431] FX Supported, in part, by grants from the National Institutes of Health T32-CA09172-35 (to T.M.O.) and 2PA50-CA090578-08 (to D.B.C., P.A.J.); and a Career Development Award by the American Society of Clinical Oncology Cancer Foundation CDA-15431 (to D.B.C.). NR 5 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JAN PY 2011 VL 6 IS 1 BP 220 EP 222 DI 10.1097/JTO.0b013e3181f8a164 PG 3 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 698IP UT WOS:000285587800038 PM 21178719 ER PT J AU Buchanan, LH Counter, SA Ortega, F AF Buchanan, Leo H. Counter, S. Allen Ortega, Fernando TI ENVIRONMENTAL LEAD EXPOSURE AND OTOACOUSTIC EMISSIONS IN ANDEAN CHILDREN SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES LA English DT Article ID AUDITORY BRAIN-STEM; BLOOD LEAD; INDUCED OTOTOXICITY; HEARING THRESHOLDS; EVOKED-POTENTIALS; MONKEYS; WORKERS; ADULTS; NEUROTOXICITY; INTOXICATION AB Studies relating sensory hearing impairment to lead (Pb) exposure in children have presented inconsistent results. The objective of this study was to measure distortion product otoacoustic emissions (DPOAE), sounds emanating from the outer hair cells of the inner ear, in Pb-exposed children to determine the effects of Pb poisoning on the inner ear. DPOAE were recorded for 9 f(2) frequencies from 1187 to 7625 Hz on 102 ears of 53 Pb-exposed children (aged 6-16 yr) residing in Pb-contaminated environments in the Andes Mountains of Ecuador where Pb glazing of ceramics is the primary livelihood. Blood lead (PbB) levels ranged from 4.2 to 94.3 mu g/dl (mean: 37.7; SD: 25.7; median: 36.4). The median PbB level was markedly higher than the Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) 10-mu g/dl action level. Spearman rho correlation analyses of the relation between PbB level and DPOAE amplitude and between PbB level and DPOAE signal-to-noise ratio revealed no significant associations at any of the f(2) frequencies tested. In addition, no significant correlation (Spearman rho) between PbB level and hearing sensitivity for 6 pure-tone test frequencies from 1000 to 8000 Hz was found. Although the study group was found to have abnormally elevated PbB levels, in contrast to some earlier reports, the results of the current study showed no consistent Pb-induced sensory effects on the cochlea of Pb-intoxicated children. C1 [Buchanan, Leo H.] Univ Massachusetts, Dept Pediat, Sch Med, Eunice Kennedy Shriver Ctr, Waltham, MA 02452 USA. [Buchanan, Leo H.] Harvard Univ Hlth Serv, Dept Otolaryngol, Cambridge, MA USA. [Counter, S. Allen] Harvard Univ, Sch Med, Dept Neurol, Biol Labs, Cambridge, MA 02138 USA. [Counter, S. Allen] Massachusetts Gen Hosp, Dept Neurophysiol, Boston, MA 02114 USA. [Ortega, Fernando] Univ San Francisco Quito, Integrated Community Dev Dept, Coll Hlth Sci, Quito, Ecuador. RP Buchanan, LH (reprint author), Univ Massachusetts, Dept Pediat, Sch Med, Eunice Kennedy Shriver Ctr, 200 Trapelo Rd, Waltham, MA 02452 USA. EM Leo.Buchanan@umassmed.edu FU Administration of Universidad San Francisco de Quito; Fundacion Capacitar of Ecuador; Harvard University Biological Laboratories; David Rockefeller Center of Latin American Studies at Harvard University; University of Massachusetts Medical School/Shriver Center; Harvard University FX The authors thank the Administration of Universidad San Francisco de Quito and the Fundacion Capacitar of Ecuador for support of this project. We are grateful to Harvard University Biological Laboratories, the David Rockefeller Center of Latin American Studies at Harvard University, the University of Massachusetts Medical School/Shriver Center, and Dr. Jeremy Bloxham of Harvard University for support. We are thankful to Anthony B. Jacobs for excellent technical assistance, and to the Boston Children's Hospital Department of Laboratory Medicine and the Channing Trace Metals Laboratory of the Harvard School of Public Health for laboratory support. NR 54 TC 20 Z9 21 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1528-7394 J9 J TOXICOL ENV HEAL A JI J. Toxicol. Env. Health Part A PY 2011 VL 74 IS 19 BP 1280 EP 1293 DI 10.1080/15287394.2011.587106 PG 14 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 865PA UT WOS:000298321600003 PM 21830857 ER PT J AU Dutra, L Grubbs, K Greene, C Trego, LL McCartin, TL Kloezeman, K AF Dutra, Lissa Grubbs, Kathleen Greene, Carolyn Trego, Lori L. McCartin, Tamarin L. Kloezeman, Karen TI Women at War: Implications for Mental Health SO JOURNAL OF TRAUMA & DISSOCIATION LA English DT Article DE posttraumatic stress disorder; combat; veterans; parenting; attachment ID POSTTRAUMATIC-STRESS-DISORDER; SEXUAL ASSAULT; VETERANS; PTSD; SYMPTOMS; MILITARY; DEPRESSION; COMBAT; RISK; IRAQ AB Few studies have investigated the impact of deployment stressors on the mental health outcomes of women deployed to Iraq in support of Operation Iraqi Freedom. This pilot study examined exposure to combat experiences and military sexual harassment in a sample of 54 active duty women and assessed the impact of these stressors on post-deployment posttraumatic stress disorder (PTSD) symptoms and depressive symptoms. Within 3 months of returning from deployment to Iraq, participants completed (a) the Combat Experiences Scale and the Sexual Harassment Scale of the Deployment Risk and Resilience Inventory, (b) the Primary Care PTSD Screen, and (c) an abbreviated version of the Center for Epidemiological Studies-Depression scale. Approximately three quarters of the sample endorsed exposure to combat experiences, and more than half of the sample reported experiencing deployment-related sexual harassment, with nearly half of the sample endorsing both stressors. Approximately one third of the sample endorsed clinical or subclinical levels of PTSD symptoms, with 11% screening positive for PTSD and 9% to 14% of the sample endorsing depressive symptoms. Regression analyses revealed that combat experiences and sexual harassment jointly accounted for significant variance in post-deployment PTSD symptoms, whereas military sexual harassment was identified as the only unique significant predictor of these symptoms. Findings from the present study lend support to research demonstrating that military sexual trauma may be more highly associated with post-deployment PTSD symptoms than combat exposure among female service members and veterans. C1 [Dutra, Lissa] VA Boston Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, Womens Hlth Sci Div, Boston, MA USA. [Grubbs, Kathleen; Kloezeman, Karen] Univ Hawaii, Dept Psychol, Honolulu, HI 96822 USA. [Grubbs, Kathleen; Greene, Carolyn; Kloezeman, Karen] Pacific Islands VA Hlth Care Syst, Natl Ctr Posttraumat Stress Disorder, Pacific Islands Div, Honolulu, HI USA. [Greene, Carolyn] VA Palo Alto Hlth Care Syst, Natl Ctr Posttraumat Stress Disorder, Educ Div, Palo Alto, CA USA. [Trego, Lori L.] Tripler Army Med Ctr, Nursing Res Serv, Tripler, HI USA. [McCartin, Tamarin L.] Tripler Army Med Ctr, Dept Obstet & Gynecol, Tripler, HI USA. RP Dutra, L (reprint author), Natl Ctr Posttraumat Stress Disorder 116B 5, Womens Hlth Sci Div, 150 S Huntington Ave, Boston, MA 02130 USA. EM lissamdutra@gmail.com RI Schueter, nicos/A-3625-2014 NR 25 TC 32 Z9 32 U1 1 U2 17 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1529-9732 J9 J TRAUMA DISSOCIATIO JI J. Trauma Dissociation PY 2011 VL 12 IS 1 BP 25 EP 37 DI 10.1080/15299732.2010.496141 PG 13 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 733LG UT WOS:000288263600003 PM 21240736 ER PT J AU Luterek, JA Bittinger, JN Simpson, TL AF Luterek, Jane A. Bittinger, Joyce N. Simpson, Tracy L. TI Posttraumatic Sequelae Associated with Military Sexual Trauma in Female Veterans Enrolled in VA Outpatient Mental Health Clinics SO JOURNAL OF TRAUMA & DISSOCIATION LA English DT Article DE military sexual trauma; sexual assault; posttraumatic stress disorder; complex posttraumatic stress disorder; disorders of extreme stress not otherwise specified ID MALE VIETNAM VETERANS; STRESS-DISORDER; EXTREME STRESS; WOMEN VETERANS; STRUCTURED INTERVIEW; NATIONAL SAMPLE; PHYSICAL ABUSE; COMPLEX PTSD; ASSAULT; PREVALENCE AB The purpose of this study was to explore the relationship between military sexual assault (MSA) and posttraumatic stress disorder (PTSD) and other symptoms associated with trauma, referred to as disorders of extreme stress not otherwise specified (DESNOS) or complex PTSD within a Veterans Affairs (VA) Medical Center outpatient mental health treatment-seeking sample. The present results focus on female Veterans only because of the low rates of endorsement of MSA among male Veterans resulting in a sample too small to use in analyses. Compared with those who did not endorse MSA, those who did reported greater frequency of other potentially traumatic events; PTSD symptoms; and symptoms characteristic of DESNOS, such as difficulties with interpersonal relationships, emotion regulation, dissociation, somatization, and self-perception. When childhood and other adulthood interpersonal trauma were both taken into account, MSA continued to contribute unique variance in predicting PTSD and DESNOS symptoms. VA patients reporting MSA may represent notably heterogeneous groups that include more complex posttraumatic reactions. Treatment interventions focused on complex PTSD may be warranted for a subset of female veterans who endorse MSA. C1 [Luterek, Jane A.; Simpson, Tracy L.] VA Puget Sound Hlth Care Syst, Mental Hlth Serv, Seattle, WA 98108 USA. [Luterek, Jane A.; Simpson, Tracy L.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Bittinger, Joyce N.] Univ Washington, Dept Psychol, Seattle, WA 98195 USA. RP Luterek, JA (reprint author), VA Puget Sound Hlth Care Syst, Mental Hlth Serv, 1660 S Columbian Way,S-116 WTRC, Seattle, WA 98108 USA. EM Jane.Luterek@va.gov RI Schueter, nicos/A-3625-2014 NR 34 TC 16 Z9 16 U1 0 U2 12 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1529-9732 J9 J TRAUMA DISSOCIATIO JI J. Trauma Dissociation PY 2011 VL 12 IS 3 SI SI BP 261 EP 274 AR PII 937015763 DI 10.1080/15299732.2011.551504 PG 14 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 756ZP UT WOS:000290053600005 PM 21534095 ER PT J AU Smith, BN Shipherd, JC Schuster, JL Vogt, DS King, LA King, DW AF Smith, Brian N. Shipherd, Jillian C. Schuster, Jennifer L. Vogt, Dawne S. King, Lynda A. King, Daniel W. TI Posttraumatic Stress Symptomatology as a Mediator of the Association Between Military Sexual Trauma and Post-Deployment Physical Health in Women SO JOURNAL OF TRAUMA & DISSOCIATION LA English DT Article DE posttraumatic stress symptomatology; posttraumatic stress disorder; physical health; women's health; military sexual trauma; Gulf War; sexual assault; sexual harassment ID GULF-WAR VETERANS; INTIMATE PARTNER VIOLENCE; COMORBID CHRONIC PAIN; CHILDHOOD MALTREATMENT; PERCEIVED HEALTH; FEMALE VETERANS; PRIMARY-CARE; I VETERANS; DISORDER; PTSD AB This study examined posttraumatic stress symptomatology (PSS) as a mediator of the association between military sexual trauma and post-deployment physical health. Relationships were examined in a sample of 83 female veterans of the first Gulf War (1990-1991) approximately 10 years post-deployment. Participants reported on the frequency of sexual harassment and sexual assault experienced during deployment. Physical health was measured using participants' self-reports of pre-deployment and post-deployment symptoms within 7 body systems. Sexual harassment exposure was not found to be associated with PSS-mediated associations with physical health symptoms. However, sexual assault during deployment was found to be associated with PSS and 4 of the 7 health symptom clusters assessed: gastrointestinal, genitourinary, musculoskeletal, and neurological symptoms. Furthermore, PSS was found to be a significant mediator of the sexual assault-physical health relationship in each of these domains, with the indirect path accounting for 74% to 100% of the relationship. The findings from the current study indicate that sexual assault has detrimental associations with physical health and that PSS plays a primary role in that relationship. C1 [Smith, Brian N.; Shipherd, Jillian C.; Schuster, Jennifer L.; Vogt, Dawne S.; King, Lynda A.] VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA USA. [Smith, Brian N.; Shipherd, Jillian C.; Vogt, Dawne S.] Boston Univ, Sch Med, Boston, MA 02118 USA. [King, Lynda A.; King, Daniel W.] Boston Univ, Dept Psychiat, Boston, MA 02118 USA. [King, Lynda A.; King, Daniel W.] Boston Univ, Dept Psychol, Boston, MA 02118 USA. [King, Daniel W.] VA Boston Healthcare Syst, Natl Ctr PTSD, Behav Sci Div, Boston, MA USA. RP Smith, BN (reprint author), VA Boston Healthcare Syst 116B 3, Womens Hlth Sci Div, Natl Ctr PTSD, 150 S Huntington Ave, Boston, MA 02130 USA. EM Brian.Smith12@va.gov RI Schueter, nicos/A-3625-2014 NR 57 TC 21 Z9 21 U1 3 U2 12 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1529-9732 J9 J TRAUMA DISSOCIATIO JI J. Trauma Dissociation PY 2011 VL 12 IS 3 SI SI BP 275 EP 289 AR PII 937012883 DI 10.1080/15299732.2011.551508 PG 15 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 756ZP UT WOS:000290053600006 PM 21534096 ER PT J AU Crawford, RS Albadawi, H Atkins, MD Jones, JJ Conrad, MF Austen, WG Fink, MP Watkins, MT AF Crawford, Robert S. Albadawi, Hassan Atkins, Marvin D. Jones, John J. Conrad, Mark F. Austen, William G., Jr. Fink, Mitchell P. Watkins, Michael T. TI Postischemic Treatment With Ethyl Pyruvate Prevents Adenosine Triphosphate Depletion, Ameliorates Inflammation, and Decreases Thrombosis in a Murine Model of Hind-Limb Ischemia and Reperfusion SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article DE Ischemia-reperfusion; Inflammation; Skeletal muscle; cytokines ID SKELETAL-MUSCLE ISCHEMIA; OXIDATIVE STRESS; LIMB ISCHEMIA; KAPPA-B; INJURY; CELLS; PATHOPHYSIOLOGY; EXPRESSION; CHEMOKINES; SEVERITY AB Introduction: Experiments were designed to investigate the effects of ethyl pyruvate (EP) in a murine model of hind-limb ischemia-reperfusion (IR) injury. Methods: C57BL6 mice underwent 90 minutes of unilateral ischemia followed by 24 hours of reperfusion using two treatment protocols. For the preischemic treatment (pre-I) protocol, mice (n = 6) were given 300 mg/kg EP before ischemia, followed by 150 mg/kg of EP just before reperfusion and at 6 hours and 12 hours after reperfusion. In a postischemic treatment (post-I) protocol, mice (n = 7) were treated with 300 mg/kg EP at the end of the ischemic period, then 15 minutes later, and 2 hours after reperfusion and 150 mg/kg of EP at 4 hours, 6 hours, 10 hours, 16 hours, and 22 hours after reperfusion. Controls mice for both protocols were treated with lactated Ringers alone at time intervals identical to EP. Skeletal muscle levels of adenosine triphosphate (ATP), interleukin-1 beta, keratinocyte chemoattractant protein, and thrombin antithrombin-3 complex were measured. Skeletal muscle architectural integrity was assessed microscopically. Results: ATP levels were higher in mice treated with EP compared with controls under the both treatment protocols (p = 0.02). Interleukin-1 beta, keratinocyte chemoattractant protein, thrombin antithrombin-3 complex (p < 0.05), and the percentage of injured fibers (p < 0.0001) were significantly decreased in treated versus control mice under the both protocols. Conclusion: Muscle fiber injury and markers of tissue thrombosis and inflammation were reduced, and ATP was preserved with EP in pre-I and post-I protocols. Further investigation of the efficacy of EP to modulate IR injury in a larger animal model of IR injury is warranted. C1 [Crawford, Robert S.; Albadawi, Hassan; Atkins, Marvin D.; Jones, John J.; Conrad, Mark F.; Watkins, Michael T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc & Endovasc Surg,Dept Surg, Boston, MA USA. [Fink, Mitchell P.] Univ Pittsburgh, Dept Crit Care Med, Pittsburgh, PA USA. [Fink, Mitchell P.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA. [Fink, Mitchell P.] Univ Pittsburgh, Dept Pharmacol, Pittsburgh, PA 15261 USA. [Austen, William G., Jr.] Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, Boston, MA 02114 USA. RP Watkins, MT (reprint author), 15 Parkman St,WAC 440, Boston, MA 02114 USA. EM mtwatkins@partners.org FU National Institutes of Health [1R01AR055843]; American Diabetes Association; Pacific Vascular Research Foundation; Department of Surgery, Division of Vascular and Endovascular Surgery, Massachusetts General Hospital FX Supported by the National Institutes of Health grant 1R01AR055843, the American Diabetes Association, the Pacific Vascular Research Foundation, and the Department of Surgery, Division of Vascular and Endovascular Surgery, Massachusetts General Hospital. Dr. Watkins is the Isenberg Scholar in Academic Surgery at the Massachusetts General Hospital. NR 33 TC 13 Z9 14 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5282 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD JAN PY 2011 VL 70 IS 1 BP 103 EP 110 DI 10.1097/TA.0b013e3182031ccb PG 8 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 707WD UT WOS:000286320300019 PM 21217488 ER PT J AU Lador, R Ben-Galim, P Hipp, JA AF Lador, Ran Ben-Galim, Peleg Hipp, John A. TI Motion Within the Unstable Cervical Spine During Patient Maneuvering: The Neck Pivot-Shift Phenomenon SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article ID INTERVERTEBRAL MOTION; INJURIES; IMMOBILIZATION; STABILIZATION; INSTABILITY; INTUBATION; COLLAR AB Background: Cervical extrication collars are applied to millions of blunt trauma victims despite the lack of any evidence that a collar can protect against secondary injuries to the cervical spine. Cadaver studies support that in the presence of a dissociative injury, substantial motion can occur within the occipitocervical spine with collar application or during patient transfers. Little is known about the biomechanics of cervical stabilization; hence, it is difficult to develop and test improved immobilization strategies. Materials: Severe unstable injuries were created in seven fresh whole human cadavers. Rigid collars were applied with the body in a neutral position. Computed tomographic examinations were obtained before and after tilting the body or backboard as would be done during patient transport or to inspect the back. Relative displacements between vertebrae at the site of the injury were measured from the Computed tomographic examinations. The overall relative alignment between body and collar was assessed to understand the mechanisms that may facilitate motion at the injury site. Results: Intervertebral motion averaged 7.7 mm +/- 6.8 mm in the axial plain and 2.9 mm +/- 2.5 mm in the cranial-caudal direction. The rigid collars appeared to create pivot points where the collar contacts the head in the region under the ear and where the collar contacts the shoulders. Discussion: Rigid cervical collars appear to create pivot points that shift the center of rotation lateral to the spine and contribute to the intervertebral motions that were measured. Immobilization strategies that avoid these neck pivot-shift phenomena may help to reduce secondary injuries to the cervical spine. The whole cadaver model with simulation of patient maneuvers may provide an effective test method for cervical immobilization. C1 [Hipp, John A.] Baylor Coll Med, Dept Orthoped Surg, Houston, TX 77030 USA. Michael E DeBakey Vet Adm Med Ctr, Spine Res Lab, Houston, TX USA. RP Hipp, JA (reprint author), Baylor Coll Med, Dept Orthoped Surg, 6620 Main St,11th Floor, Houston, TX 77030 USA. EM jhipp@bcm.edu NR 26 TC 10 Z9 11 U1 3 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5282 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD JAN PY 2011 VL 70 IS 1 BP 247 EP 250 DI 10.1097/TA.0b013e3181fd0ebf PG 4 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 707WD UT WOS:000286320300046 PM 21217496 ER PT J AU Choueiri, TK Xie, WL Kollmannsberger, C North, S Knox, JJ Lampard, JG McDermott, DF Rini, BI Heng, DYC AF Choueiri, Toni K. Xie, Wanling Kollmannsberger, Christian North, Scott Knox, Jennifer J. Lampard, J. Geoffrey McDermott, David F. Rini, Brian I. Heng, Daniel Y. C. TI The Impact of Cytoreductive Nephrectomy on Survival of Patients With Metastatic Renal Cell Carcinoma Receiving Vascular Endothelial Growth Factor Targeted Therapy SO JOURNAL OF UROLOGY LA English DT Article DE neoplasm metastasis; carcinoma, renal cell; prognosis; nephrectomy; survival ID INTERFERON-ALPHA; CANCER; SUNITINIB AB Purpose: Vascular endothelial growth factor targeted therapy is a standard of care in patients with metastatic renal cell carcinoma. The role of cytoreductive nephrectomy in the era of novel agents remains poorly defined. Materials and Methods: We retrospectively reviewed baseline characteristics and outcomes of 314 patients with anti-vascular endothelial growth factor therapy naive, metastatic renal cell carcinoma from United States and Canadian cancer centers to study the impact of cytoreductive nephrectomy on overall survival. Results: Patients who underwent cytoreductive nephrectomy (201) were younger (p < 0.01), and more likely to have a better Karnofsky performance status (p < 0.01), more than 1 site of metastasis (p = 0.04) and lower corrected calcium levels (p < 0.01) compared to those who did not undergo cytoreductive nephrectomy (113). On univariable analysis cytoreductive nephrectomy was associated with a median overall survival of 19.8 months compared to 9.4 months for patients who did not undergo cytoreductive nephrectomy (HR 0.44; 95% CI 0.32, 0.59; p < 0.01). On multivariable analysis and adjusting for established prognostic risk factors the overall survival difference persisted (adjusted HR 0.68; 95% CI 0.46, 0.99; p < 0.04) in favor of the cytoreductive nephrectomy group. In subgroup analyses stratified for favorable/intermediate/poor risk criteria, patients in the poor risk group had a marginal benefit (p = 0.06). Similarly patients with Karnofsky performance status less than 80% also had a marginal survival benefit (p = 0.08). Conclusions: In this retrospective study cytoreductive nephrectomy was independently associated with a prolonged overall survival of patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor targeted agents, although the benefit is marginal in those patients with poor risk features. C1 [Choueiri, Toni K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Kidney Canc Ctr,Dana Farber Canc Inst, Boston, MA 02115 USA. [McDermott, David F.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Kollmannsberger, Christian] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [North, Scott] Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. [Lampard, J. Geoffrey] Univ Calgary, Calgary, AB, Canada. [Knox, Jennifer J.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Rini, Brian I.] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. RP Choueiri, TK (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Kidney Canc Ctr,Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM Toni_Choueiri@dfci.harvard.edu NR 26 TC 135 Z9 137 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JAN PY 2011 VL 185 IS 1 BP 60 EP 66 DI 10.1016/j.juro.2010.09.012 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 692GS UT WOS:000285141900015 PM 21074201 ER PT J AU Hoffman, KE Nguyen, PL Chen, MH Chen, RC Choueiri, TK Hu, JC Kuban, DA D'Amico, AV AF Hoffman, Karen E. Nguyen, Paul L. Chen, Ming-Hui Chen, Ronald C. Choueiri, Toni K. Hu, Jim C. Kuban, Deborah A. D'Amico, Anthony V. TI Recommendations for Post-Prostatectomy Radiation Therapy in the United States Before and After the Presentation of Randomized Trials SO JOURNAL OF UROLOGY LA English DT Article DE prostatic neoplasms; prostatectomy; radiotherapy ID TERM-FOLLOW-UP; PROSTATE-CANCER; RADICAL PROSTATECTOMY; ADJUVANT RADIOTHERAPY; POSTOPERATIVE RADIOTHERAPY; BIOCHEMICAL RECURRENCE; CLINICAL-TRIAL; INSTITUTE; REGISTRY; SURGERY AB Purpose: The EORTC 22911 and the SWOG 8794 studies, presented in 2004 and 2005, showed that adjuvant radiation therapy after prostatectomy improved biochemical disease-free survival in men with adverse pathological features. In this study we evaluated the use of post-prostatectomy radiation therapy following the presentation of these results, and the impact of margin involvement, pathological tumor stage, Gleason score and sociodemographic factors on post-prostatectomy radiation therapy recommendations. Materials and Methods: The SEER cancer registry was used to identify 21,917 men who underwent radical prostatectomy for N0M0 prostate cancer with adverse pathological features (pT3 or margin positive pT2 disease) from 2000 through 2007. Results: After adjusting for age, diagnosis year, race, SEER region and county education level in a multivariable regression model, decreasing age, margin involvement and Gleason 8 to 10 cancer were associated with receiving post-prostatectomy radiation therapy (all p < 0.001). Men with pT3a (AOR 2.95, CI 2.64-3.29) and pT3b disease (AOR 6.77, CI 5.75-7.97) were more likely to receive post-prostatectomy radiation therapy than those with pT2 disease. The use of post-prostatectomy radiation therapy did not increase after the presentation of study results (p = 0.166). Conclusions: While men with involved margins and more aggressive pathological disease features were more likely to receive post-prostatectomy radiation therapy, recommendations for post-prostatectomy radiation did not increase after the initial reports from the randomized trials, perhaps because these studies initially reported improved biochemical disease-free survival but not overall survival. Whether the recent report of a survival benefit from adjuvant radiation therapy in the SWOG trial will impact patterns of care requires further followup. C1 [Hoffman, Karen E.; Kuban, Deborah A.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. [Nguyen, Paul L.; D'Amico, Anthony V.] Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Choueiri, Toni K.; Hu, Jim C.] Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. [Hu, Jim C.] Brigham & Womens Hosp, Div Urol Surg, Boston, MA 02115 USA. [Chen, Ming-Hui] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. [Chen, Ronald C.] Univ N Carolina, Dept Radiat Oncol, Chapel Hill, NC USA. RP Hoffman, KE (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, 1515 Holcombe Blvd,Unit 1202, Houston, TX 77030 USA. EM khoffman1@mdanderson.org NR 29 TC 46 Z9 46 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JAN PY 2011 VL 185 IS 1 BP 116 EP 120 DI 10.1016/j.juro.2010.08.086 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 692GS UT WOS:000285141900035 PM 21074194 ER PT J AU Kauffman, EC Kim, HH Tanrikut, C Goldstein, M AF Kauffman, Eric C. Kim, Howard H. Tanrikut, Cigdem Goldstein, Marc TI Microsurgical Spermatocelectomy: Technique and Outcomes of a Novel Surgical Approach SO JOURNAL OF UROLOGY LA English DT Article DE testis; spermatocele; microsurgery; sperm count; epididymis ID HYDROCELECTOMY; COMPLICATIONS; SURGERY AB Purpose: A microsurgical approach to spermatocelectomy theoretically minimizes the risk of injury to the epididymis and testicular blood supply. We present the technique of microsurgical spermatocelectomy and report our perioperative and recurrence outcomes. Materials and Methods: In a 15-year period 23 men with a total of 36 epididymal cystic masses underwent microsurgical resection with confirmation of spermatocele diagnosis by intraoperative identification of sperm in the cyst fluid. We reviewed pathology reports for resected epididymal tissue in the spermatocele specimen. Postoperative outcome measures included complications, sperm count changes, improvement in pain and fertility, and cyst recurrence. Results: Mean spermatocele size was 5.0 cm (range 1 to 15). Common indications for surgery included pain in 35% of cases, infertility in 30% and the 2 conditions in 13%. A total of 13 patients (57%) underwent simultaneous procedures for concomitant varicocele and/or hydrocele with a mean overall surgical time of 152 minutes. A single scrotal hematoma managed conservatively was the only postoperative complication. There was no case of infection. Avoidance of inadvertent epididymal resection was shown by absent epididymal tissue in each of the 36 spermatocele pathology specimens. Also, no patient with preoperative and postoperative semen analyses available experienced a decreased sperm count, confirming the avoidance of iatrogenic epididymal tubule obstruction. At a mean followup of 17.3 months no man had cyst recurrence or testicular atrophy and all with preoperative pain reported improvement. One patient with preoperative infertility achieved pregnancy 12 months after surgery. Conclusions: Microsurgical spermatocelectomy is safe and effective with a minimal risk of epididymal injury, testicular atrophy and recurrence. C1 [Kauffman, Eric C.; Kim, Howard H.; Goldstein, Marc] Cornell Univ, Dept Urol, Weill Cornell Med Coll, New York, NY 10065 USA. [Kauffman, Eric C.; Kim, Howard H.; Goldstein, Marc] Cornell Univ, Ctr Male Reprod Med & Microsurg, Weill Cornell Med Coll, New York, NY 10065 USA. [Goldstein, Marc] Populat Council, Ctr Biomed Res, New York, NY 10021 USA. [Tanrikut, Cigdem] Massachusetts Gen Hosp, Massachusetts Gen Hosp Fertil Ctr, Boston, MA 02114 USA. RP Goldstein, M (reprint author), Cornell Univ, Dept Urol, Weill Cornell Med Coll, 525 E 68th St,Starr 900, New York, NY 10065 USA. EM mgoldst@med.cornell.edu FU Therologit FX Financial interest and/or other relationship with Therologit. NR 12 TC 3 Z9 3 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JAN PY 2011 VL 185 IS 1 BP 238 EP 242 DI 10.1016/j.juro.2010.09.017 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 692GS UT WOS:000285141900086 PM 21074792 ER PT J AU Suh, WM Yeh, RW Watkins, MT Palacios, IF AF Suh, William M. Yeh, Robert W. Watkins, Michael T. Palacios, Igor F. TI Inadvertent femoral endarterectomy: a complication from a suture-based vascular closure device SO JOURNAL OF VASCULAR ACCESS LA English DT Letter C1 [Suh, William M.; Yeh, Robert W.; Palacios, Igor F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02163 USA. [Watkins, Michael T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc & Endovasc Surg, Boston, MA USA. RP Suh, WM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02163 USA. EM ipalacios@partners.org NR 3 TC 0 Z9 0 U1 0 U2 0 PU WICHTIG EDITORE PI MILAN PA 72/74 VIA FRIULI, 20135 MILAN, ITALY SN 1129-7298 J9 J VASC ACCESS JI J. Vasc. Access PD JAN-MAR PY 2011 VL 12 IS 1 BP 71 EP 72 DI 10.5301/JVA.2010.6016 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 763JE UT WOS:000290551800014 PM 21077045 ER PT J AU Yu, LY Hales, CA AF Yu, Lunyin Hales, Charles A. TI Hypoxia Does neither Stimulate Pulmonary Artery Endothelial Cell Proliferation in Mice and Rats with Pulmonary Hypertension and Vascular Remodeling nor in Human Pulmonary Artery Endothelial Cells SO JOURNAL OF VASCULAR RESEARCH LA English DT Article DE Pulmonary artery endothelial cell; Proliferation; Hypoxia; Mice; Rats ID PROGENITOR CELLS; MOLECULAR-WEIGHT; PROTEIN-KINASE; GROWTH-FACTOR; GUINEA-PIG; HEPARIN; TRANSPLANTATION; MIGRATION; DISEASE; ACTIVATION AB Background: Hypoxia results in pulmonary hypertension and vascular remodeling due to induction of pulmonary artery cell proliferation. Besides pulmonary artery smooth muscle cells, pulmonary artery endothelial cells (PAECs) are also involved in the development of pulmonary hypertension, but the effect of hypoxia on PAEC proliferation has not been completely understood. Methods: We investigated PAEC proliferation in mice and rats with hypoxia-induced pulmonary hypertension and vascular remodeling as well as in human PAECs under hypoxia. Results and Conclusion: We did not find significant PAEC proliferation in chronically hypoxic rats or mice. There was a slight decrease in proliferation in mice and rats with pulmonary hypertension and vascular remodeling. We also did not find significant human PAEC proliferation and cell cycle progression under different levels of oxygen (1, 2, 3, 5 and 10%) for one day, although the same conditions of hypoxia induced significant proliferation and cell cycle progression in pulmonary artery smooth muscle cells and pulmonary artery fibroblasts. Exposure to hypoxia for 7 days also did not increase PAEC proliferation. These results demonstrated that hypoxia alone is not a stimulus to PAEC proliferation in vivo and in vitro. The present study provides a novel role for PAECs in hypoxia-induced pulmonary hypertension and vascular remodeling. Copyright (C) 2011 S. Karger AG, Basel C1 [Yu, Lunyin; Hales, Charles A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit,Dept Med, Boston, MA 02114 USA. RP Yu, LY (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit,Dept Med, 55 Fruit St,Bulfinch 148, Boston, MA 02114 USA. EM lyu3@partners.org FU ATS/Pulmonary Hypertension Research Grant [PH-08-010]; NIH [HL39150]; Susannah Wood Foundation FX This work was supported by ATS/Pulmonary Hypertension Research Grant PH-08-010 (L.Y.) and NIH grant HL39150 (C.A.H.) as well as by the Susannah Wood Foundation. NR 48 TC 17 Z9 17 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-1172 J9 J VASC RES JI J. Vasc. Res. PY 2011 VL 48 IS 6 BP 465 EP 475 DI 10.1159/000327005 PG 11 WC Physiology; Peripheral Vascular Disease SC Physiology; Cardiovascular System & Cardiology GA 834UT UT WOS:000295990300002 PM 21691120 ER PT J AU Bath, J Lawrence, P Chandra, A O'Connell, J Uijtdehaage, S Jimenez, JC Davis, G Hiatt, J AF Bath, Jonathan Lawrence, Peter Chandra, Ankur O'Connell, Jessica Uijtdehaage, Sebastian Jimenez, Juan Carlos Davis, Gavin Hiatt, Jonathan TI Standardization is superior to traditional methods of teaching open vascular simulation SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID ORTHOPEDIC-SURGERY RESIDENTS; 80-HOUR WORK WEEK; OPERATIVE EXPERIENCE; GENERAL-SURGERY; SURGICAL TRAINEES; SKILL RETENTION; TECHNICAL SKILL; PERFORMANCE; IMPACT; IMPROVE AB Objectives: Standardizing surgical skills teaching has been proposed as a method to rapidly attain technical competence. This study compared acquisition of vascular skills by standardized vs traditional teaching methods. Methods: The study randomized 18 first-year surgical residents to a standardized or traditional group. Participants were taught technical aspects of vascular anastomosis using femoral anastomosis simulation (Limbs & Things, Savannah, Ga), supplemented with factual information. One expert instructor taught a standardized anastomosis technique using the same method each time to one group over four sessions, while, similar to current vascular training, four different expert instructors each taught one session to the other (traditional) group. Knowledge and technical skill were assessed at study completion by an independent vascular expert using Objective Structured Assessment of Technical Skill (OSATS) performance metrics. Participants also provided a written evaluation of the study experience. Results: The standardized group had significantly higher mean overall technical (95.7% vs 75.8%; P=.038) and global skill scores (83.4% vs 67%; P=.006). Tissue handling, efficiency of motion, overall technical skill, and flow of operation were rated significantly higher in the standardized group (mean range, 88%-96% vs 67.6%-77.6%; P<.05). The standardized group trended to better cognitive knowledge (mean, 68.8% vs 60.7%; P=.182), creation of a secure knot at the toe of the anastomosis, fashioning an appropriate arteriotomy, better double-ended suture placement at the heel of the anastomosis (100% vs 62.7%; P=.07), and accurate suture placement (70% vs 25%; P=.153). Seventy-two percent of participant evaluations suggested a preference for a standardized approach. Conclusions: This study demonstrates the feasibility of open vascular simulation to assess the effect of differing teaching methods on performance outcome. Findings from this report suggest that for simulation training, standardized may be more effective than traditional methods of teaching. Transferability of simulator-acquired skills to the clinical setting will be required before open simulation can be unequivocally recommended as a major component of resident technical skill training. (J Vase Surg 2011;53:229-35.) C1 [Bath, Jonathan; Lawrence, Peter; Chandra, Ankur; O'Connell, Jessica; Jimenez, Juan Carlos] Univ Calif Los Angeles, Dept Vasc Surg, Los Angeles, CA USA. [Uijtdehaage, Sebastian] Univ Calif Los Angeles, Ctr Educ Dev & Res, Los Angeles, CA USA. [Davis, Gavin; Hiatt, Jonathan] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [O'Connell, Jessica] W Los Angeles Vet Affairs Hosp, Los Angeles, CA USA. RP Bath, J (reprint author), UCLA Surg Vasc, Box 956908,Ste 510-6,200 Med Plaza, Los Angeles, CA 90095 USA. EM jbath@mednet.ucla.edu OI Uijtdehaage, Sebastian/0000-0001-8598-4683 NR 38 TC 12 Z9 13 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JAN PY 2011 VL 53 IS 1 BP 229 EP 235 DI 10.1016/j.jvs.2010.07.064 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 704WB UT WOS:000286085200037 PM 21115317 ER PT J AU Singh, R Gaiha, G Werner, L McKim, K Mlisana, K Luban, J Walker, BD Karim, SSA Brass, AL Ndung'u, T AF Singh, Ravesh Gaiha, Gaurav Werner, Lise McKim, Kevin Mlisana, Koleka Luban, Jeremy Walker, Bruce D. Karim, Salim S. Abdool Brass, Abraham L. Ndung'u, Thumbi CA CAPRISA 002 Acute Infection Study Team TI Association of TRIM22 with the Type 1 Interferon Response and Viral Control during Primary HIV-1 Infection SO JOURNAL OF VIROLOGY LA English DT Article ID RESTRICTION FACTOR TRIM5-ALPHA; MONOCYTE-DERIVED MACROPHAGES; TRIPARTITE MOTIF PROTEINS; I INTERFERON; RETROVIRAL RESTRICTION; FAMILY PROTEINS; T-CELL; EXPRESSION; VIRUS; SUSCEPTIBILITY AB Type 1 interferons (IFNs) induce the expression of the tripartite interaction motif (TRIM) family of E3 ligases, but the contribution of these antiviral factors to HIV pathogenesis is not completely understood. We hypothesized that the increased expression of select type 1 IFN and TRIM isoforms is associated with a significantly lower likelihood of HIV-1 acquisition and viral control during primary HIV-1 infection. We measured IFN-alpha, IFN-beta, myxovirus resistance protein A (MxA), human TRIM5 alpha (huTRIM5 alpha), and TRIM22 mRNA levels in peripheral blood mononuclear cells (PBMCs) of high-risk, HIV-1-uninfected participants and HIV-1-positive study participants. Samples were available for 32 uninfected subjects and 28 infected persons, all within 1 year of infection. HIV-1-positive participants had higher levels of IFN-beta (P = 0.0005), MxA (P = 0.007), and TRIM22 (P = 0.01) and lower levels of huTRIM5 alpha (P < 0.001) than did HIV-1-negative participants. TRIM22 but not huTRIM5 alpha correlated positively with type 1 IFN (IFN-alpha, IFN-beta, and MxA) (all P < 0.0001). In a multivariate model, increased MxA expression showed a significant positive association with viral load (P = 0.0418). Furthermore, TRIM22 but not huTRIM5 alpha, IFN-alpha, IFN-beta, or MxA showed a negative correlation with plasma viral load (P = 0.0307) and a positive correlation with CD4(+) T-cell counts (P = 0.0281). In vitro studies revealed that HIV infection induced TRIM22 expression in PBMCs obtained from HIV-negative donors. Stable TRIM22 knockdown resulted in increased HIV-1 particle release and replication in Jurkat reporter cells. Collectively, these data suggest concordance between type 1 IFN and TRIM22 but not huTRIM5 alpha expression in PBMCs and that TRIM22 likely acts as an antiviral effector in vivo. C1 [Singh, Ravesh; Walker, Bruce D.; Ndung'u, Thumbi] Univ KwaZulu Natal, Doris Duke Med Res Inst, Nelson R Mandela Sch Med, HIV Pathogenesis Programme, ZA-4001 Durban, South Africa. [Gaiha, Gaurav; McKim, Kevin; Walker, Bruce D.; Brass, Abraham L.; Ndung'u, Thumbi] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA USA. [Gaiha, Gaurav; McKim, Kevin; Walker, Bruce D.; Brass, Abraham L.; Ndung'u, Thumbi] Harvard Univ, Boston, MA 02115 USA. [Werner, Lise; Mlisana, Koleka; Karim, Salim S. Abdool; Ndung'u, Thumbi] Univ KwaZulu Natal, Ctr AIDS Programme Res S Africa CAPRISA, ZA-4001 Durban, South Africa. [Luban, Jeremy] Univ Geneva, Dept Microbiol, Geneva, Switzerland. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Ndung'u, T (reprint author), Univ KwaZulu Natal, Doris Duke Med Res Inst, Nelson R Mandela Sch Med, HIV Pathogenesis Programme, Private Bag X7, ZA-4001 Durban, South Africa. EM ndungu@ukzn.ac.za RI Abdool Karim, Salim Safurdeen/N-5947-2013; OI Abdool Karim, Salim Safurdeen/0000-0002-4986-2133; , Carolyn/0000-0003-0125-1226; , Lynn/0000-0003-3961-7828; Hide, Winston/0000-0002-8621-3271; Mlisana, Koleka/0000-0002-8436-3268; Ndung'u, Thumbi/0000-0003-2962-3992 FU National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), U.S. Department of Health and Human Services [U19 AI 51794]; Switzerland South African Joint Research Programme (SSAJRP); Hasso Plattner Foundation; South African DST/NRF Research Chair in Systems Biology of HIV/AIDS; NIAID [R01AI059159]; SNF [3100AO-128655]; KwaZulu-Natal Research Institute FX The CAPRISA 002 study was supported by the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), U.S. Department of Health and Human Services (grant U19 AI 51794). This study was funded by grants from the Switzerland South African Joint Research Programme (SSAJRP) (J.L. and T.N.), the Hasso Plattner Foundation and the South African DST/NRF Research Chair in Systems Biology of HIV/AIDS (T.N.), the NIAID (grant R01AI059159), and grant 3100AO-128655 from the SNF (J.L.). R. S. was a recipient of a KwaZulu-Natal Research Institute for TB and HIV (K-RITH) travel award. NR 46 TC 38 Z9 41 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2011 VL 85 IS 1 BP 208 EP 216 DI 10.1128/JVI.01810-10 PG 9 WC Virology SC Virology GA 691QL UT WOS:000285095800018 PM 20980524 ER PT J AU Meyer, C Grey, F Kreklywich, CN Andoh, TF Tirabassi, RS Orloff, SL Streblow, DN AF Meyer, Christine Grey, Finn Kreklywich, Craig N. Andoh, Takeshi F. Tirabassi, Rebecca S. Orloff, Susan L. Streblow, Daniel N. TI Cytomegalovirus MicroRNA Expression Is Tissue Specific and Is Associated with Persistence SO JOURNAL OF VIROLOGY LA English DT Article ID VIRUS-ENCODED MICRORNAS; EPSTEIN-BARR-VIRUS; SARCOMA-ASSOCIATED HERPESVIRUS; TRANSPLANT VASCULAR SCLEROSIS; RAT CYTOMEGALOVIRUS; GENE-EXPRESSION; SMALL RNAS; ALLOGRAFT ARTERIOSCLEROSIS; HEART-TRANSPLANTS; CHRONIC REJECTION AB MicroRNAs (miRNAs) are a class of small noncoding RNAs involved in posttranscriptional regulation. miRNAs are utilized in organisms ranging from plants to higher mammals, and data have shown that DNA viruses also use this method for host and viral gene regulation. Here, we report the sequencing of the small RNAs in rat cytomegalovirus (RCMV)-infected fibroblasts and persistently infected salivary glands. We identified 24 unique miRNAs that mapped to hairpin structures found within the viral genome. While most miRNAs were detected in both samples, four were detected exclusively in the infected fibroblasts and two were specific for the infected salivary glands. The RCMV miRNAs are distributed across the viral genome on both the positive and negative strands, with clusters of miRNAs at a number of locations, including near viral genes r1 and r111. The RCMV miRNAs have a genomic positional orientation similar to that of the miRNAs described for mouse cytomegalovirus, but they do not share any substantial sequence conservation. Similar to other reported miRNAs, the RCMV miRNAs had considerable variation at their 3' and 5' ends. Interestingly, we found a number of specific examples of differential isoform usage between the fibroblast and salivary gland samples. We determined by real-time PCR that expression of the RCMV miRNA miR-r111.1-2 is highly expressed in the salivary glands and that miR-R87-1 is expressed in most tissues during the acute infection phase. Our study identified the miRNAs expressed by RCMV in vitro and in vivo and demonstrated that expression is tissue specific and associated with a stage of viral infection. C1 [Meyer, Christine; Kreklywich, Craig N.; Andoh, Takeshi F.; Orloff, Susan L.; Streblow, Daniel N.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97239 USA. [Meyer, Christine; Kreklywich, Craig N.; Andoh, Takeshi F.; Orloff, Susan L.; Streblow, Daniel N.] Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Portland, OR 97239 USA. [Kreklywich, Craig N.; Andoh, Takeshi F.; Orloff, Susan L.] Oregon Hlth & Sci Univ, Dept Surg, Portland, OR 97239 USA. [Kreklywich, Craig N.; Andoh, Takeshi F.; Orloff, Susan L.; Streblow, Daniel N.] Portland VA Med Ctr, Portland, OR 97239 USA. [Grey, Finn] Univ Edinburgh, Roslin Inst, Edinburgh, Midlothian, Scotland. [Grey, Finn] Univ Edinburgh, Royal Sch Vet Studies, Edinburgh, Midlothian, Scotland. [Tirabassi, Rebecca S.] Univ Wisconsin, Madison, WI USA. RP Streblow, DN (reprint author), Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, 505 SW 185th Ave, Beaverton, OR 97006 USA. EM streblow@ohsu.edu FU National Institutes of Health [HL083194, HL085451] FX This work was supported by research grants from the National Institutes of Health to D. N. Streblow (HL083194) and S. L. Orloff (HL085451). NR 68 TC 22 Z9 22 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2011 VL 85 IS 1 BP 378 EP 389 DI 10.1128/JVI.01900-10 PG 12 WC Virology SC Virology GA 691QL UT WOS:000285095800034 PM 20980502 ER PT J AU Weinfurter, JT May, GE Soma, T Hessell, AJ Leon, EJ MacNair, CE Piaskowski, SM Weisgrau, K Furlott, J Maness, NJ Reed, J Wilson, NA Rakasz, EG Burton, DR Friedrich, TC AF Weinfurter, Jason T. May, Gemma E. Soma, Taeko Hessell, Ann J. Leon, Enrique J. MacNair, Caitlin E. Piaskowski, Shari M. Weisgrau, Kim Furlott, Jessica Maness, Nicholas J. Reed, Jason Wilson, Nancy A. Rakasz, Eva G. Burton, Dennis R. Friedrich, Thomas C. TI Macaque Long-Term Nonprogressors Resist Superinfection with Multiple CD8(+) T Cell Escape Variants of Simian Immunodeficiency Virus SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-1/SIV CHIMERIC VIRUS; CLASS-I ALLELES; NEUTRALIZING ANTIBODIES; DISEASE PROGRESSION; HIV-INFECTION; MAMU-B-ASTERISK-08-POSITIVE MACAQUES; SIVMAC239 REPLICATION; LYMPHOCYTE RESPONSES; IMMUNE-RESPONSES; DOSE CHALLENGE AB Human immunodeficiency virus (HIV)-positive individuals can be superinfected with different virus strains. Individuals who control an initial HIV infection are therefore still at risk for subsequent infection with divergent viruses, but the barriers to such superinfection remain unclear. Here we tested long-term nonprogressors' (LTNPs') susceptibility to superinfection using Indian rhesus macaques that express the major histocompatibility complex class I (MHC-I) allele Mamu-B*17, which is associated with control of the pathogenic AIDS virus SIVmac239. The Mamu-B*17-restricted CD8(+) T cell repertoire is focused almost entirely on 5 epitopes. We engineered a series of SIVmac239 variants bearing mutations in 3, 4, or all 5 of these epitopes and used them to serially challenge 2 Mamu-B*17-positive LTNPs. None of the escape variants caused breakthrough replication in LTNPs, although they readily infected Mamu-B*17-negative naive macaques. In vitro competing coculture assays and examination of viral evolution in hosts lacking Mamu-B*17 suggested that the mutant viruses had negligible defects in replicative fitness. Both LTNPs maintained robust immune responses, including simian immunodeficiency virus (SIV)-specific CD8(+) and CD4(+) T cells and neutralizing antibodies. Our results suggest that escape mutations in epitopes bound by "protective" MHC-I molecules may not be sufficient to establish superinfection in LTNPs. C1 [Weinfurter, Jason T.; Friedrich, Thomas C.] Univ Wisconsin, Sch Vet Med, Dept Pathobiol Sci, Madison, WI 53706 USA. [Weinfurter, Jason T.; May, Gemma E.; Soma, Taeko; Leon, Enrique J.; MacNair, Caitlin E.; Weisgrau, Kim; Furlott, Jessica; Reed, Jason; Wilson, Nancy A.; Rakasz, Eva G.; Friedrich, Thomas C.] Wisconsin Natl Primate Res Ctr, Madison, WI 53715 USA. [Hessell, Ann J.; Burton, Dennis R.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. [Hessell, Ann J.; Burton, Dennis R.] Scripps Res Inst, Int AIDS Vaccine Initiat, Neutralizing Antibody Ctr, La Jolla, CA 92037 USA. [Piaskowski, Shari M.; Maness, Nicholas J.; Wilson, Nancy A.] Univ Wisconsin, Dept Pathol & Lab Med, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Burton, Dennis R.] Massachusetts Gen Hosp, Ragon Inst, MIT, Boston, MA 02114 USA. [Burton, Dennis R.] Harvard Univ, Boston, MA 02114 USA. RP Friedrich, TC (reprint author), Univ Wisconsin, AIDS Vaccine Res Lab, 555 Sci Dr, Madison, WI 53711 USA. EM thomasf@primate.wisc.edu OI Weinfurter, Jason/0000-0001-8076-2598; Friedrich, Thomas/0000-0001-9831-6895 FU National Institute for Allergy and Infectious Disease (NIAID) [AI 068586, AI 055332, AI 033292]; National Center for Research Resources (NCRR) [P51 RR000167]; Research Facilities Improvement Program [RR15459-01, RR020141-01] FX This work was supported by National Institute for Allergy and Infectious Disease (NIAID) grants AI 068586 to T.C.F. and AI 055332 and AI 033292 to D.R.B. and in part by grant P51 RR000167 from the National Center for Research Resources (NCRR) to the WNPRC. This research was conducted in part at a facility constructed with support from Research Facilities Improvement Program grants RR15459-01 and RR020141-01. NR 60 TC 9 Z9 9 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2011 VL 85 IS 1 BP 530 EP 541 DI 10.1128/JVI.01025-10 PG 12 WC Virology SC Virology GA 691QL UT WOS:000285095800048 PM 20962091 ER PT J AU Chevalier, MF Julg, B Pyo, A Flanders, M Ranasinghe, S Soghoian, DZ Kwon, DS Rychert, J Lian, J Muller, MI Cutler, S McAndrew, E Jessen, H Pereyra, F Rosenberg, ES Altfeld, M Walker, BD Streeck, H AF Chevalier, Mathieu F. Juelg, Boris Pyo, Augustine Flanders, Michael Ranasinghe, Srinika Soghoian, Damien Z. Kwon, Douglas S. Rychert, Jenna Lian, Jeffrey Muller, Matthias I. Cutler, Sam McAndrew, Elizabeth Jessen, Heiko Pereyra, Florencia Rosenberg, Eric S. Altfeld, Marcus Walker, Bruce D. Streeck, Hendrik TI HIV-1-Specific Interleukin-21(+) CD4(+) T Cell Responses Contribute to Durable Viral Control through the Modulation of HIV-Specific CD8(+) T Cell Function SO JOURNAL OF VIROLOGY LA English DT Article ID ACUTE INFECTION; MEMORY; IL-21; PROLIFERATION; VACCINE; VIRUS AB Functional defects in cytotoxic CD8(+) T cell responses arise in chronic human viral infections, but the mechanisms involved are not well understood. In mice, CD4 cell-mediated interleukin-21 (IL-21) production is necessary for the maintenance of CD8(+) T cell function and control of persistent viral infections. To investigate the potential role of IL-21 in a chronic human viral infection, we studied the rare subset of HIV-1 controllers, who are able to spontaneously control HIV-1 replication without treatment. HIV-specific triggering of IL-21 by CD4(+) T cells was significantly enriched in these persons (P = 0.0007), while isolated loss of IL-21-secreting CD4(+) T cells was characteristic for subjects with persistent viremia and progressive disease. IL-21 responses were mediated by recognition of discrete epitopes largely in the Gag protein, and expansion of IL-21(+) CD4(+) T cells in acute infection resulted in lower viral set points (P = 0.002). Moreover, IL-21 production by CD4(+) T cells of HIV controllers enhanced perforin production by HIV-1-specific CD8(+) T cells from chronic progressors even in late stages of disease, and HIV-1-specific effector CD8(+) T cells showed an enhanced ability to efficiently inhibit viral replication in vitro after IL-21 binding. These data suggest that HIV-1-specific IL-21(+) CD4(+) T cell responses might contribute to the control of viral replication in humans and are likely to be of great importance for vaccine design. C1 [Chevalier, Mathieu F.; Juelg, Boris; Pyo, Augustine; Flanders, Michael; Ranasinghe, Srinika; Soghoian, Damien Z.; Kwon, Douglas S.; Lian, Jeffrey; Muller, Matthias I.; Cutler, Sam; McAndrew, Elizabeth; Pereyra, Florencia; Altfeld, Marcus; Walker, Bruce D.; Streeck, Hendrik] Massachusetts Gen Hosp, MGH MIT & Harvard, Ragon Inst, Boston, MA 02129 USA. [Chevalier, Mathieu F.; Juelg, Boris; Pyo, Augustine; Flanders, Michael; Ranasinghe, Srinika; Soghoian, Damien Z.; Kwon, Douglas S.; Lian, Jeffrey; Muller, Matthias I.; Cutler, Sam; McAndrew, Elizabeth; Pereyra, Florencia; Altfeld, Marcus; Walker, Bruce D.; Streeck, Hendrik] Harvard Univ, Sch Med, Boston, MA 02129 USA. [Rychert, Jenna; Rosenberg, Eric S.] Massachusetts Gen Hosp, Dept Pathol, Infect Dis Unit, Boston, MA 02129 USA. [Jessen, Heiko] Jessen Jessen Stein, HIV Clin, Berlin, Germany. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Streeck, H (reprint author), Massachusetts Gen Hosp, MGH MIT & Harvard, Ragon Inst, Boston, MA 02129 USA. EM hstreeck@partners.org OI Chevalier, Mathieu/0000-0002-5601-2217 FU Bill and Melinda Gates Foundation; Susan and Philip T. Ragon Foundation; [NIH 1R01AI091450-01] FX This study was funded by grant NIH 1R01AI091450-01, the Bill and Melinda Gates Foundation, and the Susan and Philip T. Ragon Foundation. NR 25 TC 106 Z9 109 U1 2 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2011 VL 85 IS 2 BP 733 EP 741 DI 10.1128/JVI.02030-10 PG 9 WC Virology SC Virology GA 697XY UT WOS:000285554300009 PM 21047960 ER PT J AU Farivar, R Thompson, B Mansouri, B Hess, RF AF Farivar, Reza Thompson, Benjamin Mansouri, Behzad Hess, Robert F. TI Interocular suppression in strabismic amblyopia results in an attenuated and delayed hemodynamic response function in early visual cortex SO JOURNAL OF VISION LA English DT Article DE functional imaging; visual cortex; visual development; hemodynamic modulation; hemodynamic response ID BINOCULAR VIEWING CONDITIONS; CONTRAST; FMRI; PSYCHOPHYSICS; DEFICIT; HUMANS; ACTIVATION; ADULTS; BOLD; V1 AB Factors such as strabismus or anisometropia during infancy can disrupt normal visual development and result in amblyopia, characterized by reduced visual function in an otherwise healthy eye and often associated with persistent suppression of inputs from the amblyopic eye by those from the dominant eye. It has become evident from fMRI studies that the cortical response to stimulation of the amblyopic eye is also affected. We were interested to compare the hemodynamic response function (HRF) of early visual cortex to amblyopic vs. dominant eye stimulation. In the first experiment, we found that stimulation of the amblyopic eye resulted in a signal that was both attenuated and delayed in its time to peak. We postulated that this delay may be due to suppressive effects of the dominant eye and, in our second experiment, measured the cortical response of amblyopic eye stimulation under two conditions-where the dominant eye was open and seeing a static pattern (high suppression) or where the dominant eye was patched and closed (low suppression). We found that the HRF in response to amblyopic eye stimulation depended on whether the dominant eye was open. This effect was manifested as both a delayed HRF under the suppressed condition and an amplitude reduction. C1 [Farivar, Reza] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Farivar, Reza] Harvard Univ, Sch Med, Boston, MA USA. [Thompson, Benjamin] Univ Auckland, Dept Optometry & Vis Sci, Auckland 1, New Zealand. [Mansouri, Behzad] Univ Manitoba, Dept Internal Med, Div Neurol, Winnipeg, MB, Canada. [Hess, Robert F.] McGill Univ, McGill Vis Res Ctr, Montreal, PQ, Canada. RP Farivar, R (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St, Charlestown, MA USA. EM farivar@nmr.mgh.harvard.edu RI Hess, Robert/A-5624-2008 FU Canadian Institutes of Health Research [MOP-53346] FX This research was supported by an operating grant from the Canadian Institutes of Health Research (MOP-53346) to Robert F. Hess. NR 43 TC 7 Z9 8 U1 2 U2 4 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 1534-7362 J9 J VISION JI J. Vision PY 2011 VL 11 IS 14 AR 16 DI 10.1167/11.14.16 PG 12 WC Ophthalmology SC Ophthalmology GA 869YC UT WOS:000298635300016 ER PT J AU Livne, T Sagi, D AF Livne, Tomer Sagi, Dov TI Multiple levels of orientation anisotropy in crowding with Gabor flankers SO JOURNAL OF VISION LA English DT Article DE crowding; orientation relations; Gabor patches; anisotropy ID ATTENTIONAL RESOLUTION; SPATIAL INTERACTION; PERIPHERAL-VISION; LATERAL MASKING; SHAPE AB Using oriented Gabor patches, we found that for nearly cardinal target orientations, oblique flankers' orientations induced more interference than did cardinal flankers' orientations. This pattern was observed both at the local and global levels of flankers' orientation. With respect to the global orientation (flankers' global arrangement around the target), there was no difference between the effects of the two cardinal orientations, and both induced the same amount of interference. With respect to the local orientation (Gabors' orientation), in accordance with previous reports, a difference was found between the effects of the two cardinal orientations-a considerable amount of interference with flankers equal in orientation to the target (although less than with the oblique flankers) and almost no interference from flankers orthogonal to the target. Crowding was also affected by an anisotropy based on the target-fixation axis (radial, tangential, and diagonal) and by the flankers' relations. The magnitude of these latter factors was small relative to that of the former ones. The multiple factors that affected crowding, as well as the similarities and the differences between the effects at the two orientation levels, suggest that crowding is determined by multiple sources of interference operating at several levels of representation. C1 [Sagi, Dov] Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel. [Livne, Tomer] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. RP Sagi, D (reprint author), Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel. EM dov.sagi@weizmann.ac.il FU Basic Research Foundation FX This work was supported by the Basic Research Foundation administered by the Israel Academy of Sciences and Humanities. NR 21 TC 12 Z9 12 U1 1 U2 7 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 1534-7362 J9 J VISION JI J. Vision PY 2011 VL 11 IS 13 AR 18 DI 10.1167/11.13.18 PG 10 WC Ophthalmology SC Ophthalmology GA 858OE UT WOS:000297809200019 PM 22101017 ER PT J AU Richler, JJ Cheung, OS Gauthier, I AF Richler, Jennifer J. Cheung, Olivia S. Gauthier, Isabel TI Beliefs alter holistic face processing ... if response bias is not taken into account SO JOURNAL OF VISION LA English DT Article DE face recognition; holistic processing ID ACQUIRED PROSOPAGNOSIA; EXPERTISE HYPOTHESIS; SPATIAL-FREQUENCIES; INDIVIDUAL FACES; PERCEPTION; RECOGNITION; CHILDREN; OBJECTS; INTERFERENCE; CORTEX AB The composite paradigm is widely used to quantify holistic processing (HP) of faces, but there is debate regarding the appropriate design (partial vs. complete) and measures in this task. Here, we argue that some operational definitions of HP are problematic because they are sensitive to top-down influences, even though the underlying concept is assumed to be cognitively impenetrable. In Experiment 1, we told one group of participants that the target face half would remain the same on 75% of trials and another group that it would change on 75% of trials. The true proportion of same/different trials was 50%-groups only differed in their beliefs about the target halves. In Experiment 2, we manipulated the actual proportion of same/different trials in the experiment (75% of trials were the same for one group; 75% of trials were different for another group) but did not give explicit instructions about proportions. In both experiments, these manipulations influenced response biases that altered partial design measures of HP while the complete design measure was unaffected. We argue that the partial design should be abandoned because it has poor construct validity. C1 [Richler, Jennifer J.; Gauthier, Isabel] Vanderbilt Univ, Dept Psychol, Nashville, TN 37240 USA. [Cheung, Olivia S.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr, Cambridge, MA 02138 USA. RP Richler, JJ (reprint author), Vanderbilt Univ, Dept Psychol, 111 21st Ave S,Wilson Hall, Nashville, TN 37240 USA. EM jennifer.j.richler@vanderbilt.edu OI Gauthier, Isabel/0000-0002-6249-4769 FU JSMF; NSF [SBE-0542013]; Vanderbilt Vision Research Center [P30-EY008126]; National Eye Institute [2 R01 EY013441-06A2] FX This work was supported by grants from the JSMF and NSF (SBE-0542013), the Vanderbilt Vision Research Center (P30-EY008126), and the National Eye Institute (2 R01 EY013441-06A2). We thank Magen Speegle, Yoseph Beki, and Alex Desire for data collection. NR 39 TC 15 Z9 15 U1 2 U2 29 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 1534-7362 J9 J VISION JI J. Vision PY 2011 VL 11 IS 13 AR 17 DI 10.1167/11.13.17 PG 13 WC Ophthalmology SC Ophthalmology GA 858OE UT WOS:000297809200018 PM 22101018 ER PT J AU Stepp, CE Heaton, JT Braden, MN Jette, ME Stadelman-Cohen, TK Hillman, RE AF Stepp, Cara E. Heaton, James T. Braden, Maia N. Jette, Marie E. Stadelman-Cohen, Tara K. Hillman, Robert E. TI Comparison of Neck Tension Palpation Rating Systems With Surface Electromyographic and Acoustic Measures in Vocal Hyperfunction SO JOURNAL OF VOICE LA English DT Article DE Voice; Muscle tension; Laryngeal palpation; Surface electromyography; Acoustic measures ID MANUAL CIRCUMLARYNGEAL THERAPY; VOICE DISORDERS; PERCEPTUAL EVALUATION; FUNCTIONAL DYSPHONIA; MUSCULAR TENSION; RELIABILITY; MANAGEMENT; REDUCTION; EMG AB The purpose of this study was to evaluate current neck tension palpation rating systems to determine interrater reliability and possible correlation with necksurface electromyography (sEMG, collected from three electrode recording locations) and to measure the third formant for /a/ during various vocal behaviors. This prospective study examined the neck muscle tension of 16 participants before and after a single session of voice therapy. Interrater reliability and relationships between palpation ratings and objective measures of sEMG (anterior neck) and the third formant for /a/ were assessed using Pearson's correlations (r). Interrater reliability was relatively low as measured by Pearson's correlations, although Wilcoxon signed-rank test results were similar as those in a previous study. Correlations between palpation ratings and sEMG and between ratings of laryngeal height and the third formant for /a/ were generally low. Correlations increased between anterior neck sEMG and ratings of suprahyoid muscle tension when examined in a reduced set of individuals with higher interrater reliability. Palpation rating scales do not reliably capture changes that may occur in neck muscle tension of typical voice therapy patients over one session. Consequently, little can be concluded from correlations between sEMG and palpation ratings. C1 [Stepp, Cara E.; Hillman, Robert E.] Harvard MIT, Div Hlth Sci & Technol, Cambridge, MA USA. [Stepp, Cara E.; Heaton, James T.; Braden, Maia N.; Jette, Marie E.; Stadelman-Cohen, Tara K.; Hillman, Robert E.] Massachusetts Gen Hosp, MGH Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. [Heaton, James T.; Hillman, Robert E.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Stepp, CE (reprint author), Univ Washington, Box 352350, Seattle, WA 98195 USA. EM cstepp@alum.mit.edu OI Jette, Marie/0000-0003-4705-1289 FU NIDCD NIH HHS [T32 DC000038, T32 DC000038-18] NR 24 TC 11 Z9 12 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0892-1997 J9 J VOICE JI J. Voice PD JAN PY 2011 VL 25 IS 1 BP 67 EP 75 DI 10.1016/j.jvoice.2009.08.001 PG 9 WC Otorhinolaryngology SC Otorhinolaryngology GA 712DF UT WOS:000286644200010 PM 20347260 ER PT J AU Iezzoni, LI Park, ER Kilbridge, KL AF Iezzoni, Lisa I. Park, Elyse R. Kilbridge, Kerry L. TI Implications of Mobility Impairment on the Diagnosis and Treatment of Breast Cancer SO JOURNAL OF WOMENS HEALTH LA English DT Article ID PREVENTIVE SERVICES; WEIGHT-GAIN; POSTMENOPAUSAL WOMEN; POSTPOLIO SEQUELAE; ADJUVANT TREATMENT; HEALTH-CARE; DISABILITIES; ACCESS; CARCINOMA AB Background: Among women with chronic, preexisting mobility impairments, we sought to explore how their mobility difficulties affected the diagnosis and treatment of early-stage breast cancer Methods: This is a qualitative analysis of transcripts from in-depth in-person or telephone interviews with 20 English-speaking women who had early-stage breast cancer, were <60 years of age, and had chronic difficulty walking or used wheeled mobility aids at the time of their breast cancer diagnoses Results: Nine women were disabled by polio as children or had postpolio syndrome, 3 had cerebral palsy, 3 had spinal cord injury, and 5 had other conditions. Most women reported difficulty obtaining mammograms, primarily because of inaccessible equipment, positioning problems, and difficulties with uncontrollable movements. Many women made decisions about surgical approach and chemotherapy by explicitly considering how various therapies would affect their arms, which are essential to their mobility (they use ambulation aids, self-propel manual wheelchairs, or otherwise rely on their arms for mobility or safety). Managing at home after surgery posed major mobility challenges, especially for women who lived alone. Several women reported feeling they suffered more chemotherapy side effects than do women without mobility problems. Weight gains with endocrine therapy compromised the mobility of several women. Conclusions: Increasing numbers of American women are living with mobility disabilities and entering age ranges with increased risks of breast cancer. Mobility impairments can affect women at every point during early-stage breast cancer diagnosis, therapy, and recovery. Clinicians must consider women's mobility functioning in making therapeutic recommendations to women with impaired mobility who develop breast cancer. C1 [Iezzoni, Lisa I.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Iezzoni, Lisa I.; Kilbridge, Kerry L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Park, Elyse R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. [Kilbridge, Kerry L.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Kilbridge, Kerry L.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. RP Iezzoni, LI (reprint author), Massachusetts Gen Hosp, Mongan Inst Hlth Policy, 50 Staniford St,Room 901B, Boston, MA 02114 USA. EM liezzoni@partners.org FU National Cancer Institute [NCI R21 CA122130] FX This work was supported by National Cancer Institute grant NCI R21 CA122130. NR 41 TC 14 Z9 14 U1 1 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD JAN PY 2011 VL 20 IS 1 BP 45 EP 52 DI 10.1089/jwh.2009.1831 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 709NH UT WOS:000286446900006 PM 21034276 ER PT J AU Gale, JT Martinez-Rubio, C Sheth, SA Eskandar, EN AF Gale, John T. Martinez-Rubio, Clarissa Sheth, Sameer A. Eskandar, Emad N. TI Intra-Operative Behavioral Tasks in Awake Humans Undergoing Deep Brain Stimulation Surgery SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Medicine; Issue 47; Intra-Operative Physiology; Cognitive Neuroscience; Behavioral Neuroscience; Subthalamic Nucleus; Single-Unit Activity; Parkinson Disease; Deep Brain Stimulation AB Deep brain stimulation (DBS) is a surgical procedure that directs chronic, high frequency electrical stimulation to specific targets in the brain through implanted electrodes. Deep brain stimulation was first implemented as a therapeutic modality by Benabid et al. in the late 1980s, when he used this technique to stimulate the ventral intermediate nucleus of the thalamus for the treatment of tremor (1). Currently, the procedure is used to treat patients who fail to respond adequately to medical management for diseases such as Parkinson's, dystonia, and essential tremor. The efficacy of this procedure for the treatment of Parkinson's disease has been demonstrated in well-powered, randomized controlled trials (2). Presently, the U. S. Food and Drug Administration has approved DBS as a treatment for patients with medically refractory essential tremor, Parkinson's disease, and dystonia. Additionally, DBS is currently being evaluated for the treatment of other psychiatric and neurological disorders, such as obsessive compulsive disorder, major depressive disorder, and epilepsy. DBS has not only been shown to help people by improving their quality of life, it also provides researchers with the unique opportunity to study and understand the human brain. Microelectrode recordings are routinely performed during DBS surgery in order to enhance the precision of anatomical targeting. Firing patterns of individual neurons can therefore be recorded while the subject performs a behavioral task. Early studies using these data focused on descriptive aspects, including firing and burst rates, and frequency modulation (3). More recent studies have focused on cognitive aspects of behavior in relation to neuronal activity (4,5). This article will provide a description of the intra-operative methods used to perform behavioral tasks and record neuronal data with awake patients during DBS cases. Our exposition of the process of acquiring electrophysiological data will illuminate the current scope and limitations of intra-operative human experiments. C1 [Gale, John T.; Martinez-Rubio, Clarissa; Sheth, Sameer A.; Eskandar, Emad N.] Harvard Univ, Sch Med, Nayef Al Rodhan Labs Cellular Neurosurg & Neurosu, Cambridge, MA 02138 USA. [Gale, John T.; Martinez-Rubio, Clarissa; Sheth, Sameer A.; Eskandar, Emad N.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Gale, JT (reprint author), Harvard Univ, Sch Med, Nayef Al Rodhan Labs Cellular Neurosurg & Neurosu, Cambridge, MA 02138 USA. EM galej@ccf.org NR 5 TC 2 Z9 2 U1 0 U2 1 PU JOURNAL OF VISUALIZED EXPERIMENTS PI CAMBRIDGE PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA SN 1940-087X J9 JOVE-J VIS EXP JI J. Vis. Exp. PD JAN PY 2011 IS 47 AR UNSP e2156 DI 10.3791/2156 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V36LF UT WOS:000209212800004 ER PT J AU Ellison, DH AF Ellison, David H. TI Through a glass darkly: salt transport by the distal tubule SO KIDNEY INTERNATIONAL LA English DT Editorial Material ID NA-CL COTRANSPORTER; SODIUM-CHLORIDE COTRANSPORTER; ANGIOTENSIN-II; CONVOLUTED TUBULE; BLOOD-PRESSURE; RAT-KIDNEY; VASOPRESSIN; EXPRESSION; RECEPTOR; WNK4 AB The distal convoluted tubule (DCT) plays a central role in blood pressure and potassium homeostasis, as evidenced by diseases that occur when its function is modified. The paper by van der Lubbe and colleagues makes clear that angiotensin II itself increases the activity and abundance of the thiazide-sensitive Na-Cl cotransporter (NCC), independent of changes in circulating aldosterone. This Commentary provides additional perspective on that work. Kidney International (2011) 79, 5-8. doi: 10.1038/ki.2010.400 C1 [Ellison, David H.] Oregon Hlth & Sci Univ, Div Nephrol & Hypertens, Portland, OR 97239 USA. [Ellison, David H.] Portland VA Med Ctr, Portland, OR USA. RP Ellison, DH (reprint author), Oregon Hlth & Sci Univ, Div Nephrol & Hypertens, PP262,3181 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM ellisond@ohsu.edu OI Ellison, David/0000-0003-2915-265X FU NIDDK NIH HHS [R01 DK051496-13, R01 DK051496] NR 34 TC 4 Z9 4 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JAN PY 2011 VL 79 IS 1 BP 5 EP 8 DI 10.1038/ki.2010.400 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 694XC UT WOS:000285334100001 PM 21157456 ER PT J AU Tamura, MK Yaffe, K AF Tamura, Manjula Kurella Yaffe, Kristine TI Dementia and cognitive impairment in ESRD: diagnostic and therapeutic strategies SO KIDNEY INTERNATIONAL LA English DT Review DE aging; cognitive impairment; dementia; ESRD ID CHRONIC KIDNEY-DISEASE; MINI-MENTAL-STATE; CHRONIC-HEMODIALYSIS TREATMENT; SILENT CEREBRAL INFARCTION; QUALITY-OF-LIFE; DIALYSIS PATIENTS; CYSTATIN-C; ALZHEIMERS-DISEASE; OLDER-ADULTS; IMPROVES BRAIN AB Cognitive impairment, including dementia, is a common but poorly recognized problem among patients with end-stage renal disease (ESRD), affecting 16-38% of patients. Dementia is associated with high risks of death, dialysis withdrawal, hospitalization, and disability among patients with ESRD; thus, recognizing and effectively managing cognitive impairment may improve clinical care. Dementia screening strategies should take into account patient factors, the time available, the timing of assessments relative to dialysis treatments, and the implications of a positive screen for subsequent management (for example, transplantation). Additional diagnostic testing in patients with cognitive impairment, including neuroimaging, is largely based on the clinical evaluation. There is limited data on the efficacy and safety of pharmacotherapy for dementia in the setting of ESRD; therefore, decisions about the use of these medications should be individualized. Management of behavioral symptoms, evaluation of patient safety, and advance care planning are important components of dementia management. Prevention strategies targeting vascular risk factor modification, and physical and cognitive activity have shown promise in the general population and may be reasonably extrapolated to the ESRD population. Modification of ESRD-associated factors such as anemia and dialysis dose or frequency require further study before they can be recommended for treatment or prevention of cognitive impairment. Kidney International (2011) 79, 14-22; doi: 10.1038/ki.2010.336; published online 22 September 2010 C1 [Tamura, Manjula Kurella] Stanford Univ, Div Nephrol, Dept Med, Sch Med, Palo Alto, CA 94304 USA. [Tamura, Manjula Kurella] VA Palo Alto Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Palo Alto, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. RP Tamura, MK (reprint author), Stanford Univ, Div Nephrol, Dept Med, Sch Med, 780 Welch Rd,Suite 106, Palo Alto, CA 94304 USA. EM mktamura@stanford.edu RI Kurella Tamura, Manjula/C-8284-2014 OI Kurella Tamura, Manjula/0000-0001-5227-2479 FU National Institute of Aging [K23AG028952]; Satellite Research; Amgen; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK069406] FX MKT receives support from the National Institute of Aging (K23AG028952) and from a Norman S. Coplon grant from Satellite Research. She has previously received funding support from Amgen. KY is supported by R01DK069406 from the National Institute of Diabetes and Digestive and Kidney Diseases. She serves on a data safety monitoring board for Pfizer and Medivation, and as a consultant to Novartis. NR 71 TC 39 Z9 42 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 EI 1523-1755 J9 KIDNEY INT JI Kidney Int. PD JAN PY 2011 VL 79 IS 1 BP 14 EP 22 DI 10.1038/ki.2010.336 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 694XC UT WOS:000285334100004 ER PT J AU Wesseling-Perry, K Pereira, RC Sahney, S Gales, B Wang, HJ Elashoff, R Juppner, H Salusky, IB AF Wesseling-Perry, Katherine Pereira, Renata C. Sahney, Shobha Gales, Barbara Wang, He-Jing Elashoff, Robert Jueppner, Harald Salusky, Isidro B. TI Calcitriol and doxercalciferol are equivalent in controlling bone turnover, suppressing parathyroid hormone, and increasing fibroblast growth factor-23 in secondary hyperparathyroidism SO KIDNEY INTERNATIONAL LA English DT Article DE bone; children; chronic dialysis; FGF-23; parathyroid hormone ID CHRONIC KIDNEY-DISEASE; CORONARY-ARTERY CALCIFICATION; VITAMIN-D ANALOGS; HEMODIALYSIS-PATIENTS; RENAL OSTEODYSTROPHY; DIALYSIS PATIENTS; SEVELAMER HYDROCHLORIDE; PERITONEAL-DIALYSIS; MINERAL METABOLISM; CALCIUM-CARBONATE AB We compared the effects of calcitriol and doxercalciferol, in combination with either calcium carbonate or sevelamer, on bone, mineral, and fibroblast growth factor-23 (FGF-23) metabolism in patients with secondary hyperparathyroidism. A total of 60 pediatric patients treated with peritoneal dialysis were randomized to 8 months of therapy with either oral calcitriol or doxercalciferol, combined with either calcium carbonate or sevelamer. Bone formation rates decreased during therapy and final values were within the normal range in 72% of patients. A greater improvement in eroded surface was found in patients treated with doxercalciferol than in those given calcitriol. On initial bone biopsy, a mineralization defect was identified in the majority of patients which did not normalize with therapy. Serum phosphate concentrations were controlled equally well by both binders, but serum calcium levels increased during treatment with calcium carbonate, and serum parathyroid hormone levels were decreased by 35% in all groups. Baseline plasma FGF-23 values were significantly elevated and rose over fourfold with calcitriol and doxercalciferol, irrespective of phosphate binder. Thus, doxercalciferol is as effective as calcitriol in controlling serum parathyroid hormone levels and suppressing the bone formation rate. Sevelamer allows the use of higher doses of vitamin D. Implications of these changes on bone and cardiovascular biology remain to be established. Kidney International (2011) 79, 112-119; doi: 10.1038/ki.2010.352; published online 22 September 2010 C1 [Wesseling-Perry, Katherine; Pereira, Renata C.; Gales, Barbara; Salusky, Isidro B.] Univ Calif Los Angeles, David Geffen Sch Med, Div Pediat Nephrol, Los Angeles, CA 90095 USA. [Sahney, Shobha] Loma Linda Univ, Dept Pediat, Loma Linda, CA 92350 USA. [Wang, He-Jing; Elashoff, Robert] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biomath, Los Angeles, CA 90095 USA. [Jueppner, Harald] Harvard Univ, Sch Med, Endocrine Unit, Boston, MA USA. [Jueppner, Harald] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Wesseling-Perry, K (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Pediat Nephrol, A2-383 MDCC,650 Charles Young, Los Angeles, CA 90095 USA. EM kwesseling@mednet.ucla.edu FU USPHS [DK-67563, DK-35423, DK-51081, DK-073039, RR-00865]; Casey Lee Ball Foundation FX This work was supported, in part, by USPHS Grants DK-67563, DK-35423, DK-51081, DK-073039, and RR-00865 and funds from the Casey Lee Ball Foundation. Bone Care International kindly provided doxercalciferol (Hectorol) and unrestricted support for this study. NR 52 TC 70 Z9 71 U1 0 U2 13 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JAN PY 2011 VL 79 IS 1 BP 112 EP 119 DI 10.1038/ki.2010.352 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 694XC UT WOS:000285334100013 PM 20861820 ER PT J AU Young, BA AF Young, Bessie A. TI Prevention of sudden cardiac arrest in dialysis patients: can we do more to improve outcomes? SO KIDNEY INTERNATIONAL LA English DT Editorial Material ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS; HEMODIALYSIS-PATIENTS; DEATH; SURVIVAL; PREDICTORS; CHALLENGE; DESIGN; RISK AB Sudden cardiac arrest (SCA) is a leading cause of cardiac-associated mortality in dialysis patients. Risk factors unique to hemodialysis patients include abnormal electrolytes, large-volume ultrafiltration, and prior history of cardiac disease. Few randomized controlled trials of standard cardiac interventions have been completed in dialysis patients. Observational studies suggest that modification of the dialysis prescription may be one place to intervene. Prospective research is needed to determine mechanisms of SCA in hemodialysis patients. Kidney International (2011) 79, 147-149. doi:10.1038/ki.2010.433 C1 [Young, Bessie A.] Seattle VA Puget Sound Healthcare Syst, Epidemiol Res & Informat Ctr, Seattle, WA USA. [Young, Bessie A.] Univ Washington, Kidney Res Inst, Div Nephrol, Seattle, WA 98195 USA. RP Young, BA (reprint author), VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, 1660 S Columbian Way,152-E, Seattle, WA 98108 USA. EM youngb@u.washington.edu FU NIDDK NIH HHS [R01 DK079745] NR 22 TC 2 Z9 2 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JAN PY 2011 VL 79 IS 2 BP 147 EP 149 DI 10.1038/ki.2010.433 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 700IV UT WOS:000285732900002 PM 21191388 ER PT J AU Yue, B Varadarajan, KM Ai, ST Tang, TT Rubash, HE Li, GA AF Yue, Bing Varadarajan, Kartik M. Ai, Songtao Tang, Tingting Rubash, Harry E. Li, Guoan TI Gender differences in the knees of Chinese population SO KNEE SURGERY SPORTS TRAUMATOLOGY ARTHROSCOPY LA English DT Article DE Knee; Gender differences; Geometry; Total knee arthroplasty ID ANTHROPOMETRIC MEASUREMENTS; 3-DIMENSIONAL MORPHOMETRY; ANATOMIC VARIATIONS; DISTAL FEMUR; FEMALE KNEE; ARTHROPLASTY; KINEMATICS; DESIGN; MOVEMENT; GEOMETRY AB The goal of this study was to characterize the geometry of the distal femur and proximal tibia in the Chinese population. Three-dimensional models of twenty female and twenty male knees were constructed using CT images. The morphologic measurements of the distal femur included mediolateral (ML) and anteroposterior dimension of medial and lateral condyles (MAP, LAP), femoral aspect ratio (ML/LAP), medial and lateral condylar width, intercondylar notch width, notch width index (NWI), and trochlear groove orientation. The sagittal profiles of the medial and lateral femoral condyles and tibial plateaus were also characterized. The results showed that the size of the distal femur of the females was significantly smaller than that of the males. Furthermore, when normalized by LAP, the females had a significantly narrower distal femur (ML), and a shorter MAP compared to the males. In the sagittal plane, the radius of the lateral distal circle of the femur was significantly smaller than that of the medial condyle in both genders. There were no significant gender differences in the proximal tibial geometry. The data of the present study may enable suitable modification of total knee prosthesis sizing/geometry for Asia-Pacific patients. C1 [Yue, Bing; Varadarajan, Kartik M.; Rubash, Harry E.; Li, Guoan] Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab, Boston, MA 02114 USA. [Yue, Bing; Varadarajan, Kartik M.; Rubash, Harry E.; Li, Guoan] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Yue, Bing; Ai, Songtao; Tang, Tingting] Shanghai Jiao Tong Univ, Shanghai Key Lab Orthopaed Implant, Dept Orthopaed Surg, Sch Med,Shanghai Peoples Hosp 9, Shanghai 200030, Peoples R China. [Varadarajan, Kartik M.] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. RP Li, GA (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@partners.org RI Tang, Tingting/B-1361-2013; OI yan, wei/0000-0001-5575-7017 FU Department of Orthopaedics, MGH; Program for Shanghai Key Laboratory of Orthopaedic Implant [08DZ2230330]; Shanghai Municipal Education Commission [J50206]; National Natural Science Foundation of China [30901517] FX This study was supported by an AEF grant of Department of Orthopaedics, MGH, the Program for Shanghai Key Laboratory of Orthopaedic Implant (08DZ2230330), Fund for Key Disciplines of Shanghai Municipal Education Commission (J50206), and National Natural Science Foundation of China (30901517). NR 29 TC 23 Z9 25 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0942-2056 J9 KNEE SURG SPORT TR A JI Knee Surg. Sports Traumatol. Arthrosc. PD JAN PY 2011 VL 19 IS 1 BP 80 EP 88 DI 10.1007/s00167-010-1139-8 PG 9 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 710RP UT WOS:000286529200012 PM 20407755 ER PT B AU Gordon, CR Siemionow, MZ AF Gordon, Chad R. Siemionow, Maria Z. BE Siemionow, MZ TI Timeline and Evolution of Face Transplant Cadaver Models SO KNOW-HOW OF FACE TRANSPLANTATION LA English DT Article; Book Chapter ID FACIAL ALLOGRAFT TRANSPLANTATION; COMPOSITE TISSUE ALLOTRANSPLANTATION; HUMANS; OUTCOMES AB The first worldwide IRB-approved protocol for facial transplantation was obtained by Dr. Siemionow and colleagues at the Cleveland Clinic in 2004. To date, the most complex near-total face transplant remains the one performed in December, 2008 at the Cleveland Clinic (Cleveland, OH). The purpose of this chapter is to describe in detail the strategic evolution of our team's tailored, cadaver dissection model in preparation for its first clinical application. C1 [Gordon, Chad R.] Massachusetts Gen Hosp, Dept Surg, Div Plast & Reconstruct Surg, Boston, MA 02114 USA. [Siemionow, Maria Z.] Cleveland Clin, Dept Plast Surg, Cleveland, OH 44106 USA. RP Gordon, CR (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Plast & Reconstruct Surg, Boston, MA 02114 USA. EM cgordon5@partners.org NR 23 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL RD FARNCOMBE, GODALMING GU7 1NH, SURREY, ENGLAND BN 978-0-85729-252-0 PY 2011 BP 73 EP 79 DI 10.1007/978-0-85729-253-7_7 D2 10.1007/978-0-85729-253-7 PG 7 WC Surgery SC Surgery GA BWB43 UT WOS:000293368900007 ER PT J AU Issadore, D Shao, HL Chung, J Newton, A Pittet, M Weissleder, R Lee, H AF Issadore, David Shao, Huilin Chung, Jaehoon Newton, Andita Pittet, Mikael Weissleder, Ralph Lee, Hakho TI Self-assembled magnetic filter for highly efficient immunomagnetic separation SO LAB ON A CHIP LA English DT Article ID CIRCULATING TUMOR-CELLS; FLOW; MANIPULATION; TECHNOLOGY; CANCER; BLOOD AB We have developed a compact and inexpensive microfluidic chip, the self-assembled magnetic filter, to efficiently remove magnetically tagged cells from suspension. The self-assembled magnetic filter consists of a microfluidic channel built directly above a self-assembled NdFeB magnet. Micrometre-sized grains of NdFeB assemble to form alternating magnetic dipoles, creating a magnetic field with a very strong magnitude B (from the material) and field gradient del B (from the configuration) in the microfluidic channel. The magnetic force imparted on magnetic beads is measured to be comparable to state-of-the-art microfabricated magnets, allowing for efficient separations to be performed in a compact, simple device. The efficiency of the magnetic filter is characterized by sorting non-magnetic (polystyrene) beads from magnetic beads (iron oxide). The filter enriches the population of non-magnetic beads to magnetic beads by a factor of >10(5) with a recovery rate of 90% at 1 mL h(-1). The utility of the magnetic filter is demonstrated with a microfluidic device that sorts tumor cells from leukocytes using negative immunomagnetic selection, and concentrates the tumor cells on an integrated membrane filter for optical detection. C1 [Issadore, David; Shao, Huilin; Chung, Jaehoon; Newton, Andita; Pittet, Mikael; Weissleder, Ralph; Lee, Hakho] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Lee, H (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St,CPZN 5206, Boston, MA 02114 USA. EM hlee@mgh.harvard.edu RI Issadore, David/L-8451-2014 FU National Institute of Health [2R01-EB004626, U01-HL080731, U54-CA119349, T32-CA79443] FX The authors gratefully thank R. M. Westervelt (Harvard) for many helpful comments and generous support for the device fabrication through the Center for Nanoscale Systems at Harvard, V. Cortez-Retamozo (MGH) for her help with flow cytometry and for valuable suggestions. We thank Magnequench for its generous support, through the use of their NdFeB magnetic powder. This work is supported in part by National Institute of Health Grants 2R01-EB004626, U01-HL080731, U54-CA119349 and T32-CA79443. NR 27 TC 31 Z9 31 U1 5 U2 44 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 PY 2011 VL 11 IS 1 BP 147 EP 151 DI 10.1039/c0lc00149j PG 5 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA 691SS UT WOS:000285101700021 PM 20949198 ER PT J AU Hoganson, DM Pryor, HI Bassett, EK Spool, ID Vacanti, JP AF Hoganson, David M. Pryor, Howard I., II Bassett, Erik K. Spool, Ira D. Vacanti, Joseph P. TI Lung assist device technology with physiologic blood flow developed on a tissue engineered scaffold platform SO LAB ON A CHIP LA English DT Article ID SHEAR-STRESS; MEMBRANE-OXYGENATOR; ANEURYSM MODELS; TRANSPLANTATION; FABRICATION; DYNAMICS; CHANNELS; DESIGN; SYSTEM; IMPACT AB There is no technology available to support failing lung function for patients outside the hospital. An implantable lung assist device would augment lung function as a bridge to transplant or possible destination therapy. Utilizing biomimetic design principles, a microfluidic vascular network was developed for blood inflow from the pulmonary artery and blood return to the left atrium. Computational fluid dynamics analysis was used to optimize blood flow within the vascular network. A micro milled variable depth mold with 3D features was created to achieve both physiologic blood flow and shear stress. Gas exchange occurs across a thin silicone membrane between the vascular network and adjacent alveolar chamber with flowing oxygen. The device had a surface area of 23.1 cm(2) and respiratory membrane thickness of 8.7 +/- 1.2 mu m. Carbon dioxide transfer within the device was 156 ml min(-1) m(-2) and the oxygen transfer was 34 ml min(-1) m(-2). A lung assist device based on tissue engineering architecture achieves gas exchange comparable to hollow fiber oxygenators yet does so while maintaining physiologic blood flow. This device may be scaled up to create an implantable ambulatory lung assist device. C1 [Hoganson, David M.; Pryor, Howard I., II; Bassett, Erik K.; Spool, Ira D.; Vacanti, Joseph P.] Massachusetts Gen Hosp, Dept Surg, Ctr Regenerat Med, Boston, MA 02114 USA. RP Vacanti, JP (reprint author), Massachusetts Gen Hosp, Dept Surg, Ctr Regenerat Med, 55 Fruit St,Warren 1151, Boston, MA 02114 USA. OI Hoganson, David/0000-0002-8141-7793 FU NIH [F32 DK076349-01, T32 DK07754-09] FX The authors gratefully acknowledge support from the NIH (F32 DK076349-01, DMH and T32 DK07754-09, HIP). The authors would like to thank Microlution Inc. for their generous contribution of machining the vascular mold for this project; Joel Spencer and Charles Lin of the Wellman Center for Photo-medicine for the confocal imaging; Ali Hart and Elisabeth O'Doherty for their technical assistance; Jessica Melin and the Stanford Microfluidics Foundry for fabricating the microfluidic mold for the alveolar chamber and Dr Warren Zapol for use of the blood gas analyzer. NR 36 TC 35 Z9 35 U1 2 U2 24 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1473-0197 J9 LAB CHIP JI Lab Chip PY 2011 VL 11 IS 4 BP 700 EP 707 DI 10.1039/c0lc00158a PG 8 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA 713VO UT WOS:000286765700018 PM 21152606 ER PT J AU Watkins, NN Sridhar, S Cheng, XH Chen, GD Toner, M Rodriguez, W Bashir, R AF Watkins, Nicholas N. Sridhar, Supriya Cheng, Xuanhong Chen, Grace D. Toner, Mehmet Rodriguez, William Bashir, Rashid TI A microfabricated electrical differential counter for the selective enumeration of CD4+T lymphocytes SO LAB ON A CHIP LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; PLATFORM IMAGE CYTOMETER; RESOURCE-POOR SETTINGS; HIV-INFECTED SUBJECTS; IMPEDANCE SPECTROSCOPY; CD4(+) CELLS; CHIP; MICROCHIP; MICROFLUIDICS; BIOSENSOR AB We have developed a microfabricated biochip that enumerates CD4+ T lymphocytes from leukocyte populations obtained from human blood samples using electrical impedance sensing and immunoaffinity chromatography. T cell counts are found by obtaining the difference between the number of leukocytes before and after depleting CD4+ T cells with immobilized antibodies in a capture chamber. This differential counting technique has been validated to analyze physiological concentrations of leukocytes with an accuracy of similar to 9 cells per mu L by passivating the capture chamber with bovine serum albumin. In addition, the counter provided T cell counts which correlated closely with an optical control (R-2 = 0.997) for CD4 cell concentrations ranging from approximately 100 to 700 cells per mL. We believe that this approach can be a promising method for bringing quantitative HIV/AIDS diagnostics to resource-poor regions in the world. C1 [Watkins, Nicholas N.; Sridhar, Supriya; Bashir, Rashid] Univ Illinois, Micro & Nanotechnol Lab, Dept Elect & Comp Engn, Urbana, IL 61801 USA. [Cheng, Xuanhong] Lehigh Univ, Dept Mat Sci & Engn, Bethlehem, PA 18015 USA. [Cheng, Xuanhong] Lehigh Univ, Program Bioengn, Bethlehem, PA 18015 USA. [Chen, Grace D.; Toner, Mehmet] Harvard Univ, Surg Serv & Bio MEMS Resource Ctr, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Chen, Grace D.; Toner, Mehmet] Shiners Hosp Children, Boston, MA 02114 USA. [Rodriguez, William] Harvard Univ, Partners AIDS Res Ctr, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. [Rodriguez, William] Harvard Univ, Div AIDS, Sch Med, Boston, MA 02115 USA. [Rodriguez, William] Brigham & Womens Hosp, Boston, MA 02115 USA. [Bashir, Rashid] Univ Illinois, Dept Bioengn, Urbana, IL 61801 USA. RP Rodriguez, W (reprint author), Daktari Diagnost Inc, Cambridge, MA 02139 USA. EM wrodriguez@daktaridx.com; rbashir@illinois.edu FU United States Department of Homeland Security; NSF NSEC at OSU [EEC-0914790]; University of Illinois at Urbana-Champaign FX The authors would like to thank Adil Ghafoor (Purdue University) for his help in image analysis. Partial support was provided by the United States Department of Homeland Security graduate student fellowship (NNW), by the NSF NSEC at OSU EEC-0914790, and by the University of Illinois at Urbana-Champaign. The devices were fabricated and tested at the Micro-and Nanotechnology laboratory (www.mntl.illinois.edu). NR 37 TC 38 Z9 38 U1 1 U2 25 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1473-0197 J9 LAB CHIP JI Lab Chip PY 2011 VL 11 IS 8 BP 1437 EP 1447 DI 10.1039/c0lc00556h PG 11 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA 741ZT UT WOS:000288908400005 PM 21283908 ER PT J AU Issadore, D Min, C Liong, M Chung, J Weissleder, R Lee, H AF Issadore, David Min, Changwook Liong, Monty Chung, Jaehoon Weissleder, Ralph Lee, Hakho TI Miniature magnetic resonance system for point-of-care diagnostics SO LAB ON A CHIP LA English DT Article ID GLOBAL HEALTH; RELAXATION; BIOSENSOR; CELLS AB We have developed a next generation, miniaturized platform to diagnose disease at the point-of-care using diagnostic magnetic resonance (DMR-3). Utilizing a rapidly growing library of functionalized magnetic nanoparticles, DMR has previously been demonstrated as a versatile tool to quantitatively and rapidly detect disease biomarkers in unprocessed biological samples. A major hurdle for bringing DMR to the point-of-care has been its sensitivity to temperature variation. As an alternative to costly and bulky mechanisms to control temperature, we have implemented an automated feedback system to track and compensate for the temperature drift, which enables reliable and robust DMR measurements in realistic clinical environments (4-50 degrees C). Furthermore, the new system interfaces with a mobile device to facilitate system control and data sharing over wireless networks. With such features, the DMR-3 platform can function as a self-contained laboratory even in resource-limited, remote settings. The clinical potential of the new system is demonstrated by detecting trace amounts of proteins and as few as 10 bacteria (Staphylococcus aureus) in a short time frame (< 30 min). C1 [Issadore, David; Min, Changwook; Liong, Monty; Chung, Jaehoon; Weissleder, Ralph; Lee, Hakho] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Lee, H (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA. EM hlee@mgh.harvard.edu RI Issadore, David/L-8451-2014 FU National Institutes of Health [2R01-EB004626, HHSN268201000044C, U54-CA119349, T32-CA79443] FX The authors gratefully thank J. MacArthur (Harvard) for his help in the implementation of DMR electronics; N. Sergeyev for CLIO synthesis; H. Shao, M. Fernandez-Suarez and S. Fortune for helpful discussions. This work is supported in part by National Institutes of Health Grants 2R01-EB004626, HHSN268201000044C, U54-CA119349, and T32-CA79443. NR 22 TC 59 Z9 59 U1 5 U2 42 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1473-0197 J9 LAB CHIP JI Lab Chip PY 2011 VL 11 IS 13 BP 2282 EP 2287 DI 10.1039/c1lc20177h PG 6 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA 776RQ UT WOS:000291555500021 PM 21547317 ER PT J AU Sharma, T Hu, Y Stoller, M Feldman, M Ruoff, RS Ferrari, M Zhang, XJ AF Sharma, Tushar Hu, Ye Stoller, Meryl Feldman, Marc Ruoff, Rodney S. Ferrari, Mauro Zhang, Xiaojing TI Mesoporous silica as a membrane for ultra-thin implantable direct glucose fuel cells SO LAB ON A CHIP LA English DT Article ID MINIATURE BIOFUEL CELL; PRESSURE SENSOR; POWER; NANOPARTICLES; PERFORMANCE; ELECTRODES; STABILITY; BIOSENSOR; CATHETER; PROTEIN AB The design, fabrication and characterization of an inorganic catalyst based direct glucose fuel cell using mesoporous silica coating as a functional membrane is reported. The desired use of mesoporous silica based direct glucose fuel cell is for a blood vessel implantable device. Blood vessel implantable direct glucose fuel cells have access to higher continuous glucose concentrations. However, reduction in the implant thickness is required for application in the venous system as part of a stent. We report development of an implantable device with a platinum thin-film (thickness: 25 nm) deposited on silicon substrate (500 mu m) to serve as the anode, and graphene pressed on a stainless steel mesh (175 mu m) to serve as the cathode. Control experiments involved the use of a surfactant-coated polypropylene membrane (50 mu m) with activated carbon (198 mu m) electrodes. We demonstrate that a mesoporous silica thin film (270 nm) is capable of replacing the conventional polymer based membranes with an improvement in the power generated over conventional direct glucose fuel cells. C1 [Sharma, Tushar; Zhang, Xiaojing] Univ Texas Austin, Dept Biomed Engn, Austin, TX 78712 USA. [Hu, Ye; Ferrari, Mauro] Methodist Hosp, Res Inst, Houston, TX 77030 USA. [Stoller, Meryl; Ruoff, Rodney S.] Univ Texas Austin, Mat Sci & Engn Program, Austin, TX 78712 USA. [Feldman, Marc] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Feldman, Marc] S Texas Vet Adm Hlth Care Syst, San Antonio, TX USA. RP Zhang, XJ (reprint author), Univ Texas Austin, Dept Biomed Engn, Austin, TX 78712 USA. EM john.zhang@engr.utexas.edu RI Ferreira, Fernanda /D-3963-2012; Sharma, Tushar/D-8320-2012; Ruoff, Rodney/K-3879-2015 FU University of Texas at Austin; NASA [NNJ06HE06A]; State of Texas Emerging Technology Fund; Veterans Administration (VA) Merit Grant FX This research was performed at the Biomedical Engineering Department, the Mechanical Engineering Department and the Microelectronics Research Center (MRC) at UT Austin, a member of the National Nanofabrication Infrastructure Network (NNIN). We are grateful to The University of Texas at Austin for a Special Research Grant (SRG) to partly support this research. The authors at the Department of Nanomedicine and Biomedical Engineering (nBME) acknowledge the grant support from the following agencies: NASA (NNJ06HE06A) and the State of Texas Emerging Technology Fund. We thank Dr Sanjay Banerjee for providing the platinum electrode materials. MS and RSR appreciate support (startup funds) from The University of Texas at Austin. We also thank Drs Porterfield and Hacker, and Danny Escobedo for the invaluable help with the in vivo porcine studies. We are also grateful to the Veterans Administration (VA) Merit Grant for the support with porcine studies. NR 53 TC 29 Z9 29 U1 3 U2 57 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1473-0197 J9 LAB CHIP JI Lab Chip PY 2011 VL 11 IS 14 BP 2460 EP 2465 DI 10.1039/c1lc20119k PG 6 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA 784PF UT WOS:000292168500022 PM 21637881 ER PT J AU Jain, A Munn, LL AF Jain, Abhishek Munn, Lance L. TI Biomimetic postcapillary expansions for enhancing rare blood cell separation on a microfluidic chip SO LAB ON A CHIP LA English DT Article ID CIRCULATING ENDOTHELIAL-CELLS; CANCER-PATIENTS; WHOLE-BLOOD; LEUKOCYTE MARGINATION; SAMPLE PREPARATION; PROGENITOR CELLS; GENE-EXPRESSION; SMALL TUBES; IN-VIVO; FLOW AB Blood cells naturally auto-segregate in postcapillary venules, with the erythrocytes (red blood cells, RBCs) aggregating near the axis of flow and the nucleated cells (NCs)-which include leukocytes, progenitor cells and, in cancer patients, circulating tumor cells-marginating toward the vessel wall. We have used this principle to design a microfluidic device that extracts nucleated cells (NCs) from whole blood. Fabricated using polydimethylsiloxane (PDMS) soft lithography, the biomimetic cell extraction device consists of rectangular microchannels that are 20-400 mm wide, 11 mm deep and up to 2 cm long. The key design feature is the use of repeated expansions/contractions of triangular geometry mimicking postcapillary venules, which enhance margination and optimize the extraction. The device operates on unprocessed whole blood and is able to extract 94 +/- 4.5% of NCs with 45.75 +/- 2.5-fold enrichment in concentration at a rate of 5 nl s(-1). The device eliminates the need to preprocess blood via centrifugation or RBC lysis, and is ready to be implemented as the initial stage of lab-on-a-chip devices that require enriched nucleated cells. The potential downstream applications are numerous, encompassing all preclinical and clinical assays that operate on enriched NC populations and include on-chip flow cytometry (A. Y. Fu et al., Anal. Chem., 2002, 74, 2451-2457; A. Y. Fu et al., Nat. Biotechnol., 1999, 17, 1109-1111), genetic analyses (M. M. Wang et al., Nat. Biotechnol., 2005, 23, 83-87; L. C. Waters et al., Anal. Chem., 1998, 70, 5172-5176) and circulating tumor cell extraction (S. Nagrath et al., Nature, 2007, 450, 1235-1241; S. L. Stott et al., Proc. Natl. Acad. Sci. U. S. A., 2010, 18392-18397; H. K. Lin et al., Clin. Cancer Res., 2010, 16, 5011-5018). C1 [Jain, Abhishek; Munn, Lance L.] Massachusetts Gen Hosp, Steele Lab Tumor Biol, Charlestown, MA 02129 USA. [Jain, Abhishek; Munn, Lance L.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Jain, Abhishek] Boston Univ, Dept Biomed Engn, Boston, MA 02119 USA. RP Munn, LL (reprint author), Massachusetts Gen Hosp, Steele Lab Tumor Biol, 149 13th St, Charlestown, MA 02129 USA. EM ajain@steele.mgh.harvard.edu; munn@steele.mgh.harvard.edu RI Munn, Lance/L-3950-2016; OI Munn, Lance/0000-0003-0698-7232; Jain, Abhishek/0000-0003-2235-5139 FU NIH [R21CA126761] FX Funding was provided by NIH R21CA126761 (LLM). NR 63 TC 22 Z9 22 U1 1 U2 25 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1473-0197 J9 LAB CHIP JI Lab Chip PY 2011 VL 11 IS 17 BP 2941 EP 2947 DI 10.1039/c1lc20401g PG 7 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA 804JW UT WOS:000293651100018 PM 21773633 ER PT J AU Heo, YS Lee, HJ Hassell, BA Irimia, D Toth, TL Elmoazzen, H Toner, M AF Heo, Yun Seok Lee, Ho-Joon Hassell, Bryan A. Irimia, Daniel Toth, Thomas L. Elmoazzen, Heidi Toner, Mehmet TI Controlled loading of cryoprotectants (CPAs) to oocyte with linear and complex CPA profiles on a microfluidic platform SO LAB ON A CHIP LA English DT Article ID MEMBRANE-TRANSPORT PROPERTIES; MICROSCOPE DIFFUSION CHAMBER; UNFERTILIZED MOUSE OVA; TEMPERATURE-DEPENDENCE; PREIMPLANTATION MOUSE; WATER PERMEABILITY; ACTIVATION-ENERGY; OSMOTIC RESPONSES; INDIVIDUAL CELLS; MATURE MOUSE AB Oocyte cryopreservation has become an essential tool in the treatment of infertility by preserving oocytes for women undergoing chemotherapy. However, despite recent advances, pregnancy rates from all cryopreserved oocytes remain low. The inevitable use of the cryoprotectants (CPAs) during preservation affects the viability of the preserved oocytes and pregnancy rates either through CPA toxicity or osmotic injury. Current protocols attempt to reduce CPA toxicity by minimizing CPA concentrations, or by minimizing the volume changes via the step-wise addition of CPAs to the cells. Although the step-wise addition decreases osmotic shock to oocytes, it unfortunately increases toxic injuries due to the long exposure times to CPAs. To address limitations of current protocols and to rationally design protocols that minimize the exposure to CPAs, we developed a microfluidic device for the quantitative measurements of oocyte volume during various CPA loading protocols. We spatially secured a single oocyte on the microfluidic device, created precisely controlled continuous CPA profiles (step-wise, linear and complex) for the addition of CPAs to the oocyte and measured the oocyte volumetric response to each profile. With both linear and complex profiles, we were able to load 1.5 M propanediol to oocytes in less than 15 min and with a volumetric change of less than 10%. Thus, we believe this single oocyte analysis technology will eventually help future advances in assisted reproductive technologies and fertility preservation. C1 [Heo, Yun Seok; Hassell, Bryan A.; Irimia, Daniel; Elmoazzen, Heidi; Toner, Mehmet] Shriners Hosp Children, BioMEMS Resource Ctr, Ctr Engn Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Heo, Yun Seok; Hassell, Bryan A.; Irimia, Daniel; Elmoazzen, Heidi; Toner, Mehmet] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Lee, Ho-Joon] Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. [Toth, Thomas L.] Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv, Boston, MA 02114 USA. RP Toner, M (reprint author), Shriners Hosp Children, BioMEMS Resource Ctr, Ctr Engn Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. EM mtoner@hms.harvard.edu OI Irimia, Daniel/0000-0001-7347-2082 FU National Institutes of Health [EB002503, HD061297]; Massachusetts General Hospital FX This research was partially supported by the National Institutes of Health (EB002503, HD061297) and the Vincent Memorial Hospital Research Fund, Massachusetts General Hospital. NR 33 TC 18 Z9 22 U1 2 U2 27 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1473-0197 J9 LAB CHIP JI Lab Chip PY 2011 VL 11 IS 20 BP 3530 EP 3537 DI 10.1039/c1lc20377k PG 8 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA 825JT UT WOS:000295270100023 PM 21887438 ER PT J AU Kuehne, AJC Gather, MC Eydelnant, IA Yun, SH Weitz, DA Wheeler, AR AF Kuehne, Alexander J. C. Gather, Malte C. Eydelnant, Irwin A. Yun, Seok-Hyun Weitz, David A. Wheeler, Aaron R. TI A switchable digital microfluidic droplet dye-laser SO LAB ON A CHIP LA English DT Article ID CHIP; TECHNOLOGY; INTERFACE; CHANNEL; LIGHT AB Digital microfluidic devices allow the manipulation of droplets between two parallel electrodes. These electrodes can act as mirrors generating a micro-cavity, which can be exploited for a droplet dye-laser. Three representative laser-dyes with emission wavelengths spanning the whole visible spectrum are chosen to show the applicability of this concept. Sub-microlitre droplets of laser-dye solution are moved in and out of a lasing site on-chip to down-convert the UV-excitation light into blue, green and red laser-pulses. C1 [Eydelnant, Irwin A.; Wheeler, Aaron R.] Univ Toronto, Inst Biomat & Biomed Engn, Toronto, ON M5S 3G9, Canada. [Kuehne, Alexander J. C.; Weitz, David A.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Gather, Malte C.; Yun, Seok-Hyun] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Gather, Malte C.; Yun, Seok-Hyun] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Weitz, David A.] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA. [Wheeler, Aaron R.] Univ Toronto, Dept Chem, Toronto, ON M5S 3H6, Canada. RP Wheeler, AR (reprint author), Univ Toronto, Inst Biomat & Biomed Engn, 164 Coll St, Toronto, ON M5S 3G9, Canada. EM aaron.wheeler@utoronto.ca RI Kuehne, Alexander/L-1333-2015; OI Kuehne, Alexander/0000-0003-0142-8001; Wheeler, Aaron/0000-0001-5230-7475; Gather, Malte/0000-0002-4857-5562 FU NSF [DMR-1006546, ECS-0335765, ECCS-0801412]; Harvard MRSEC [DMR-0820484]; Harvard Center for Nanoscale Systems (CNS), a member of the National Nanotechnology Infrastructure Network (NNIN); Wellman Center; Bullock-Wellman Fellowship; natural sciences and engineering research council of Canada FX This work was supported by the NSF (DMR-1006546) and the Harvard MRSEC (DMR-0820484). This work was performed in part at the Harvard Center for Nanoscale Systems (CNS), a member of the National Nanotechnology Infrastructure Network (NNIN), which is supported by the NSF (ECS-0335765) and in part at the Wellman Center with support by the NSF (ECCS-0801412). A.J.C.K. thanks the DAAD for financial support. M. C. G. acknowledges financial support from the Bullock-Wellman Fellowship. I. A. E. thanks the natural sciences and engineering research council of Canada for a graduate fellowship. A. R. W. thanks the Canada Research Chair program for a CRC. NR 22 TC 16 Z9 17 U1 2 U2 29 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1473-0197 J9 LAB CHIP JI Lab Chip PY 2011 VL 11 IS 21 BP 3716 EP 3719 DI 10.1039/c1lc20405j PG 4 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA 831LP UT WOS:000295732500020 PM 21901207 ER PT J AU Leichsenring, F Leibing, E Kruse, J New, AS Leweke, F AF Leichsenring, Falk Leibing, Eric Kruse, Johannes New, Antonia S. Leweke, Frank TI Borderline personality disorder SO LANCET LA English DT Article ID DIALECTICAL BEHAVIOR-THERAPY; POSTTRAUMATIC-STRESS-DISORDER; RANDOMIZED CONTROLLED-TRIAL; DSM-IV CRITERIA; TRANSFERENCE-FOCUSED PSYCHOTHERAPY; SEROTONIN TRANSPORTER GENE; CONTROLLED CLINICAL-TRIAL; PLACEBO-CONTROLLED-TRIAL; CHILDHOOD SEXUAL-ABUSE; DELIBERATE SELF-HARM AB Recent research findings have contributed to an improved understanding and treatment of borderline personality disorder. This disorder is characterised by severe functional impairments, a high risk of suicide, a negative effect on the course of depressive disorders, extensive use of treatment, and high costs to society. The course of this disorder is less stable than expected for personality disorders. The causes are not yet clear, but genetic factors and adverse life events seem to interact to lead to the disorder. Neurobiological research suggests that abnormalities in the frontolimbic networks are associated with many of the symptoms. Data for the effectiveness of pharmacotherapy vary and evidence is not yet robust. Specific forms of psychotherapy seem to be beneficial for at least some of the problems frequently reported in patients with borderline personality disorder. At present, there is no evidence to suggest that one specific form of psychotherapy is more effective than another. Further research is needed on the diagnosis, neurobiology, and treatment of borderline personality disorder. C1 [Leichsenring, Falk; Kruse, Johannes; Leweke, Frank] Univ Giessen, Dept Psychosomat & Psychotherapy, D-35392 Giessen, Germany. [Leibing, Eric] Univ Goettingen, Dept Psychosomat Med & Psychotherapy, Gottingen, Germany. [New, Antonia S.] James J Peters VA Med Ctr, Dept Vet Affairs, Mental Illness Res Educ & Clin Ctr, New York, NY USA. [New, Antonia S.] Mt Sinai Sch Med, New York, NY USA. RP Leichsenring, F (reprint author), Univ Giessen, Dept Psychosomat & Psychotherapy, Ludwigstr 76, D-35392 Giessen, Germany. EM falk.leichsenring@psycho.med.uni-giessen.de RI Leweke, Frank/B-5300-2012 NR 143 TC 207 Z9 210 U1 17 U2 80 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD JAN 1 PY 2011 VL 377 IS 9759 BP 74 EP 84 DI 10.1016/S0140-6736(10)61422-5 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 709MQ UT WOS:000286445200033 PM 21195251 ER PT J AU Reilly, MP Li, MY He, J Ferguson, JF Stylianou, IM Mehta, NN Burnett, MS Devaney, JM Knouff, CW Thompson, JR Horne, BD Stewart, AFR Assimes, TL Wild, PS Allayee, H Nitschke, PL Patel, RS Martinelli, N Girelli, D Quyyumi, AA Anderson, JL Erdmann, J Hall, AS Schunkert, H Quertermous, T Blankenberg, S Hazen, SL Roberts, R Kathiresan, S Samani, NJ Epstein, SE Rader, DJ AF Reilly, Muredach P. Li, Mingyao He, Jing Ferguson, Jane F. Stylianou, Ioannis M. Mehta, Nehal N. Burnett, Mary Susan Devaney, Joseph M. Knouff, Christopher W. Thompson, John R. Horne, Benjamin D. Stewart, Alexandre F. R. Assimes, Themistocles L. Wild, Philipp S. Allayee, Hooman Nitschke, Patrick Linsel Patel, Riyaz S. Martinelli, Nicola Girelli, Domenico Quyyumi, Arshed A. Anderson, Jeffrey L. Erdmann, Jeanette Hall, Alistair S. Schunkert, Heribert Quertermous, Thomas Blankenberg, Stefan Hazen, Stanley L. Roberts, Robert Kathiresan, Sekar Samani, Nilesh J. Epstein, Stephen E. Rader, Daniel J. CA Myocardial Infarction Genetics Con Wellcome Trust Case Control Consor TI Identification of ADAMTS7 as a novel locus for coronary atherosclerosis and association of ABO with myocardial infarction in the presence of coronary atherosclerosis: two genome-wide association studies SO LANCET LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISMS; VON-WILLEBRAND-FACTOR; ARTERY-DISEASE; SUSCEPTIBILITY LOCUS; CHROMOSOME 9P21; COMPLEX TRAITS; METAANALYSIS; LINKAGE; IMPUTATION; EFFICIENT AB Background We tested whether genetic factors distinctly contribute to either development of coronary atherosclerosis or, specifically, to myocardial infarction in existing coronary atherosclerosis. Methods We did two genome-wide association studies (GWAS) with coronary angiographic phenotyping in participants of European ancestry. To identify loci that predispose to angiographic coronary artery disease (CAD), we compared individuals who had this disorder (n=12393) with those who did not (controls, n=7383). To identify loci that predispose to myocardial infarction, we compared patients who had angiographic CAD and myocardial infarction (n=5783) with those who had angiographic CAD but no myocardial infarction (n=3644). Findings In the comparison of patients with angiographic CAD versus controls, we identified a novel locus, ADAMTS7 (p=4.98x10(-13)). In the comparison of patients with angiographic CAD who had myocardial infarction versus those with angiographic CAD but no myocardial infarction, we identified a novel association at the ABO locus (p=7.62x10(-9)). The ABO association was attributable to the glycotransferase-deficient enzyme that encodes the ABO blood group 0 phenotype previously proposed to protect against myocardial infarction. Interpretation Our findings indicate that specific genetic predispositions promote the development of coronary atherosclerosis whereas others lead to myocardial infarction in the presence of coronary atherosclerosis. The relation to specific CAD phenotypes might modify how novel loci are applied in personalised risk assessment and used in the development of novel therapies for CAD. C1 [Reilly, Muredach P.; Ferguson, Jane F.; Mehta, Nehal N.; Rader, Daniel J.] Univ Penn, Cardiovasc Inst, Philadelphia, PA 19104 USA. [Reilly, Muredach P.; Stylianou, Ioannis M.; Mehta, Nehal N.; Rader, Daniel J.] Univ Penn, Sch Med, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA. [Burnett, Mary Susan; Devaney, Joseph M.; Epstein, Stephen E.] Washington Hosp Ctr, MedStar Hlth Res Inst, Cardiovasc Res Inst, Washington, DC 20010 USA. [Knouff, Christopher W.] GlaxoSmithKline Inc, Div Genet, King Of Prussia, PA USA. [Knouff, Christopher W.] GlaxoSmithKline Inc, Drug Discovery, King Of Prussia, PA USA. [Thompson, John R.] Univ Leicester, Dept Hlth Sci, Leicester, Leics, England. [Samani, Nilesh J.] Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England. [Horne, Benjamin D.; Anderson, Jeffrey L.] Intermt Med Ctr, Cardiovasc Dept, Salt Lake City, UT USA. [Horne, Benjamin D.] Univ Utah, Genet Epidemiol Div, Salt Lake City, UT USA. [Anderson, Jeffrey L.] Univ Utah, Div Cardiol, Salt Lake City, UT 84112 USA. [Stewart, Alexandre F. R.; Roberts, Robert] Univ Ottawa, Inst Heart, Dept Med, Ottawa, ON, Canada. [Assimes, Themistocles L.; Quertermous, Thomas] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA. [Wild, Philipp S.; Blankenberg, Stefan] Univ Med Ctr Mainz, Dept Med 2, Mainz, Germany. [Allayee, Hooman] Univ So Calif, Keck Sch Med, Inst Med Genet, Dept Prevent Med, Los Angeles, CA 90033 USA. [Nitschke, Patrick Linsel; Erdmann, Jeanette; Schunkert, Heribert] Univ Lubeck, Med Klin 2, Lubeck, Germany. [Patel, Riyaz S.; Quyyumi, Arshed A.] Emory Univ, Sch Med, Div Cardiol, Atlanta, GA 30322 USA. [Martinelli, Nicola; Girelli, Domenico] Univ Verona, Dept Med, I-37100 Verona, Italy. [Hall, Alistair S.] Univ Leeds, Leeds Inst Genet Hlth & Therapeut, Leeds, W Yorkshire, England. [Hall, Alistair S.] Univ Leeds, Multidisciplinary Cardiovasc Res Ctr, Leeds, W Yorkshire, England. [Hazen, Stanley L.] Cleveland Clin, Ctr Cardiovasc Diagnost & Prevent, Cleveland, OH 44106 USA. [Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Kathiresan, Sekar] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Kathiresan, Sekar] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Kathiresan, Sekar] MIT, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02139 USA. [Kathiresan, Sekar] Harvard Univ, Cambridge, MA 02138 USA. [Samani, Nilesh J.] Glenfield Hosp, Leicester Natl Inst Hlth Res, Biomed Res Unit Cardiovasc Dis, Leicester, Leics, England. RP Reilly, MP (reprint author), Univ Penn, Cardiovasc Inst, 609 BRB 2-3,421 Curie Blvd, Philadelphia, PA 19104 USA. EM muredach@mail.med.upenn.edu RI Erdmann, Jeanette/A-4417-2009; Ferguson, Jane/C-7154-2011; Library, Woodruff Health/A-6096-2012; Stewart, Alexandre/A-5677-2011; Willenborg, Christina/D-2668-2012; Lucas, Gavin/D-4346-2012; He, Jing/E-5316-2012; Tang, Wai Hong/I-1238-2013; Duga, Stefano/F-8173-2014; Breen, Gerome/A-5540-2010; Collier, David/D-1649-2011; Martinelli, Nicola/J-5622-2016; Ramos , Rafel/D-9627-2016; Erdmann, Jeanette/P-7513-2014; OI Ferguson, Jane/0000-0001-6896-1025; Willenborg, Christina/0000-0001-5217-6882; Breen, Gerome/0000-0003-2053-1792; Collier, David/0000-0003-4087-1559; Martinelli, Nicola/0000-0001-6465-5119; Ramos , Rafel/0000-0001-8146-5288; Eyre, Stephen/0000-0002-1251-6974; Ouwehand, Willem/0000-0002-7744-1790; Asselta, Rosanna/0000-0001-5351-0619; Piazza, Alberto/0000-0002-2355-4183; Lango Allen, Hana/0000-0002-7803-8688; Ramos , Rafel/0000-0001-7970-5537; Stewart, Alexandre/0000-0003-2673-9164; Zeggini, Eleftheria/0000-0003-4238-659X; Erdmann, Jeanette/0000-0002-4486-6231; Dunger, Professor David/0000-0002-2566-9304; Wallace, Chris/0000-0001-9755-1703; Marrugat, Jaume/0000-0003-3320-554X FU Cardiovascular Institute of the University of Pennsylvania; MedStar Health Research Institute at Washington Hospital Center; GlaxoSmithKline FX The PennCath and MedStar studies were supported by the Cardiovascular Institute of the University of Pennsylvania, by the MedStar Health Research Institute at Washington Hospital Center and by a research grant from GlaxoSmithKline. The funding and support for the other cohorts contributing to the paper are described in the webappendix. NR 39 TC 227 Z9 235 U1 1 U2 35 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD JAN-FEB PY 2011 VL 377 IS 9763 BP 383 EP 392 DI 10.1016/S0140-6736(10)61996-4 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 721ES UT WOS:000287337000028 PM 21239051 ER PT J AU Kempers, MJE Kuiper, RP Ockeloen, CW Chappuis, PO Hutter, P Rahner, N Schackert, HK Steinke, V Holinski-Feder, E Morak, M Kloor, M Buttner, R Verwiel, ETP van Krieken, JH Nagtegaal, ID Goossens, M van der Post, RS Niessen, RC Sijmons, RH Kluijt, I Hogervorst, FBL Leter, EM Gille, JJP Aalfs, CM Redeker, EJW Hes, FJ Tops, CMJ van Nesselrooij, BPM van Gijn, ME Garcia, EBG Eccles, DM Bunyan, DJ Syngal, S Stoffel, EM Culver, JO Palomares, MR Graham, T Velsher, L Papp, J Olah, E Chan, TL Leung, SY van Kessel, AG Kiemeney, LALM Hoogerbrugge, N Ligtenberg, MJL AF Kempers, Marlies J. E. Kuiper, Roland P. Ockeloen, Charlotte W. Chappuis, Pierre O. Hutter, Pierre Rahner, Nils Schackert, Hans K. Steinke, Verena Holinski-Feder, Elke Morak, Monika Kloor, Matthias Buettner, Reinhard Verwiel, Eugene T. P. van Krieken, J. Han Nagtegaal, Iris D. Goossens, Monique van der Post, Rachel S. Niessen, Renee C. Sijmons, Rolf H. Kluijt, Irma Hogervorst, Frans B. L. Leter, Edward M. Gille, Johan J. P. Aalfs, Cora M. Redeker, Egbert J. W. Hes, Frederik J. Tops, Carli M. J. van Nesselrooij, Bernadette P. M. van Gijn, Marielle E. Garcia, Encarna B. Gomez Eccles, Diana M. Bunyan, David J. Syngal, Sapna Stoffel, Elena M. Culver, Julie O. Palomares, Melanie R. Graham, Tracy Velsher, Lea Papp, Janos Olah, Edith Chan, Tsun L. Leung, Suet Y. van Kessel, Ad Geurts Kiemeney, Lambertus A. L. M. Hoogerbrugge, Nicoline Ligtenberg, Marjolijn J. L. TI Risk of colorectal and endometrial cancers in EPCAM deletion-positive Lynch syndrome: a cohort study SO LANCET ONCOLOGY LA English DT Article ID REPAIR GENE HMSH2; MUTATION CARRIERS; STEM-CELLS; MSH2; FAMILIES; HYPERMETHYLATION; SURVEILLANCE; METHYLATION; MANAGEMENT; TACSTD1 AB Background Lynch syndrome is caused by germline mutations in MSH2, MLH1, MSH6, and PMS2 mismatch-repair genes and leads to a high risk of colorectal and endometrial cancer. We previously showed that constitutional 3' end deletions of EPCAM can cause Lynch syndrome through epigenetic silencing of MSH2 in EPCAM-expressing tissues, resulting in tissue-specific MSH2 deficiency. We aim to establish the risk of cancer associated with such EPCAM deletions. Methods We obtained clinical data for 194 carriers of a 3' end EPCAM deletion from 41 families known to us at the Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands and compared cancer risk with data from a previously described cohort of 473 carriers from 91 families with mutations in MLH1, MSH2, MSH6, or a combined EPCAM MSH2 deletion. Findings 93 of the 194 EPCAM deletion carriers were diagnosed with colorectal cancer; three of the 92 women with EPCAM deletions were diagnosed with endometrial cancer. Carriers of an EPCAM deletion had a 75% (95% CI 65-85) cumulative risk of colorectal cancer before the age of 70 years (mean age at diagnosis 43 years [SD 12]), which did not differ significantly from that of carriers of combined EPCAM MSH2 deletion (69% [95% CI 47-91], p=0.8609) or mutations in MSH2 (77% [64-90], p=0.5892) or MLH1 (79% [68-90], p=0.5492), but was higher than noted for carriers of MSH6 mutation (50% [38-62], p<0.0001). By contrast, women with EPCAM deletions had a 12% [0-27] cumulative risk of endometrial cancer, which was lower than was that noted for carriers of a combined EPCAM MSH2 deletion (55% [20-90], p<0.0001) or of a mutation in MSH2 (51% [33-69], p=0.0006) or MSH6 (34% [20-48], p=0.0309), but did not differ significantly from that noted for MLH1 (33% [15-51], p=0.1193) mutation carriers. This risk seems to be restricted to deletions that extend close to the MSH2 gene promoter. Of 194 carriers of an EPCAM deletion, three had duodenal cancer and four had pancreatic cancer. Interpretation EPCAM deletion carriers have a high risk of colorectal cancer; only those with deletions extending close to the MSH2 promoter have an increased risk of endometrial cancer. These results underscore the effect of mosaic MSH2 deficiency, leading to variable cancer risks, and could form the basis of an optimised protocol for the recognition and targeted prevention of cancer in EPCAM deletion carriers. C1 [Kempers, Marlies J. E.; Kuiper, Roland P.; Ockeloen, Charlotte W.; Verwiel, Eugene T. P.; van Kessel, Ad Geurts; Hoogerbrugge, Nicoline; Ligtenberg, Marjolijn J. L.] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6500 HB Nijmegen, Netherlands. [Kiemeney, Lambertus A. L. M.] Radboud Univ Nijmegen, Med Ctr, Dept Epidemiol Biostat & HTA, NL-6500 HB Nijmegen, Netherlands. [van Krieken, J. Han; Nagtegaal, Iris D.; Goossens, Monique; van der Post, Rachel S.; Ligtenberg, Marjolijn J. L.] Radboud Univ Nijmegen, Med Ctr, Dept Pathol, NL-6500 HB Nijmegen, Netherlands. [Chappuis, Pierre O.] Univ Hosp, Oncogenet & Canc Prevent Unit, Dept Internal Med, Dept Genet Med & Lab,Div Oncol,Div Genet Med, Geneva, Switzerland. [Hutter, Pierre] Hop Valaisans, Inst Cent, Genet Unit, Sion, Switzerland. [Rahner, Nils; Steinke, Verena] Univ Bonn, Inst Human Genet, D-5300 Bonn, Germany. [Buettner, Reinhard] Univ Bonn, Inst Pathol, D-5300 Bonn, Germany. [Holinski-Feder, Elke; Morak, Monika] Univ Munich, Univ Hosp, Ctr Med Genet, Munich, Germany. [Kloor, Matthias] Univ Heidelberg Hosp, Inst Pathol, Dept Appl Tumor Biol, Heidelberg, Germany. [Schackert, Hans K.] Tech Univ Dresden, Dept Surg Res, Dresden, Germany. [Niessen, Renee C.; Sijmons, Rolf H.] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands. [Kluijt, Irma; Hogervorst, Frans B. L.] Netherlands Canc Inst, Family Canc Clin, Amsterdam, Netherlands. [Leter, Edward M.; Gille, Johan J. P.] Vrije Univ Amsterdam, Dept Clin Genet, Med Ctr, Amsterdam, Netherlands. [Aalfs, Cora M.; Redeker, Egbert J. W.] Univ Amsterdam, Acad Med Ctr, Dept Clin Genet, NL-1012 WX Amsterdam, Netherlands. [Hes, Frederik J.; Tops, Carli M. J.] Leiden Univ, Med Ctr, Dept Clin Genet, Leiden, Netherlands. [van Nesselrooij, Bernadette P. M.; van Gijn, Marielle E.] Dept Med Genet, Utrecht, Netherlands. [Garcia, Encarna B. Gomez] Univ Med Ctr, Dept Genet & Cell Biol, Maastricht, Netherlands. [Garcia, Encarna B. Gomez] Res Inst Growth & Dev GROW, Maastricht, Netherlands. [Bunyan, David J.] Salisbury Dist Hosp, Wessex Reg Genet Lab, Salisbury, Wilts, England. [Eccles, Diana M.] Southampton Univ Hosp NHS Trust, Wessex Clin Genet Serv, Southampton, Hants, England. [Syngal, Sapna; Stoffel, Elena M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Culver, Julie O.; Palomares, Melanie R.] City Hope Comprehens Canc Ctr, Div Clin Canc Genet, Duarte, CA USA. [Graham, Tracy; Velsher, Lea] Sunnybrook Hlth Sci Ctr, Odette Canc Ctr, Toronto, ON M4N 3M5, Canada. [Papp, Janos; Olah, Edith] Natl Inst Oncol, Dept Mol Genet, Budapest, Hungary. [Chan, Tsun L.; Leung, Suet Y.] Univ Hong Kong, Queen Mary Hosp, Hereditary Gastrointestinal Canc Genet Diag Lab, Dept Pathol, Pokfulam, Hong Kong, Peoples R China. RP Ligtenberg, MJL (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, POB 9101, NL-6500 HB Nijmegen, Netherlands. EM m.ligtenberg@antrg.umcn.nl RI Leung, Suet Yi/C-4340-2009; Sijmons, Rolf/E-5829-2012; Geurts van Kessel, Ad/A-2810-2010; van Krieken, Joannes/D-4138-2009; Hoogerbrugge, Nicoline/O-1016-2013; Kuiper, Roland/A-9646-2014; Kiemeney, Lambertus/D-3357-2009; Nagtegaal, Iris/A-2448-2014; Ligtenberg, Marjolijn/N-9666-2013; Ockeloen, Charlotte/P-5732-2015; van der Post, Chella/I-2434-2016 OI Sijmons, Rolf/0000-0001-8446-2779; van Krieken, Joannes/0000-0001-6544-1040; Kiemeney, Lambertus/0000-0002-2368-1326; Nagtegaal, Iris/0000-0003-0887-4127; Ligtenberg, Marjolijn/0000-0003-1290-1474; Ockeloen, Charlotte/0000-0003-0329-1520; FU Sacha Swarttouw-Hijmans Foundation; Dutch Cancer Society [2009-4335]; Deutsche Krebshilfe (German Cancer Aid); Hong Kong Cancer Fund; Hungarian Research Grant OTKA; Norwegian EEA Financial Mechanism (Hungarian National Institute of Oncology); US National Cancer Institute [RC4CA153828]; Hungarian Research Grant [NKTH-OTKA K-80745]; Norwegian EEA Financial Mechanism [Hu0115/NA/2008-3/OP-9] FX Funding Sacha Swarttouw-Hijmans Foundation, Dutch Cancer Society, Deutsche Krebshilfe (German Cancer Aid), Hong Kong Cancer Fund, Hungarian Research Grant OTKA, Norwegian EEA Financial Mechanism (Hungarian National Institute of Oncology), and US National Cancer Institute.We thank the families and their counsellors who contributed to this study. The study was supported by unrestricted grants from the the Sacha Swarttouw-Hijmans foundation, the Dutch Cancer Society grant 2009-4335, the Deutsche Krebshilfe (German Cancer Aid), the Hong Kong Cancer Fund, the Hungarian Research Grant NKTH-OTKA K-80745, and the Norwegian EEA Financial Mechanism Hu0115/NA/2008-3/OP-9. The City of Hope Hereditary Cancer Registry is supported in part by award number RC4CA153828 from the US National Cancer Institute. NR 32 TC 79 Z9 85 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD JAN PY 2011 VL 12 IS 1 BP 49 EP 55 DI 10.1016/S1470-2045(10)70265-5 PG 7 WC Oncology SC Oncology GA 708LA UT WOS:000286362100021 PM 21145788 ER PT J AU Tourville, JA Guenther, FH AF Tourville, Jason A. Guenther, Frank H. TI The DIVA model: A neural theory of speech acquisition and production SO LANGUAGE AND COGNITIVE PROCESSES LA English DT Article DE Speech production; DIVA model; Functional magnetic resonance imaging; Motor learning; Computational modeling ID SUPPLEMENTARY MOTOR AREA; VENTRAL PREMOTOR CORTEX; HUMAN AUDITORY-CORTEX; IPSILATERAL CORTICAL CONNECTIONS; VERTICAL-BAR PRODUCTION; CEREBRAL-BLOOD-FLOW; EMOTIONAL PROSODY; FEEDBACK-CONTROL; FUNCTIONAL CONNECTIVITY; RIGHT-HEMISPHERE AB The DIVA model of speech production provides a computationally and neuroanatomically explicit account of the network of brain regions involved in speech acquisition and production. An overview of the model is provided along with descriptions of the computations performed in the different brain regions represented in the model. The latest version of the model, which contains a new right-lateralised feedback control map in ventral premotor cortex, will be described, and experimental results that motivated this new model component will be discussed. Application of the model to the study and treatment of communication disorders will also be briefly described. C1 [Tourville, Jason A.; Guenther, Frank H.] Boston Univ, Dept Cognit & Neural Syst, Boston, MA 02215 USA. [Guenther, Frank H.] Harvard Univ, MIT, Div Hlth Sci & Technol, Boston, MA 02115 USA. [Guenther, Frank H.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. RP Guenther, FH (reprint author), Boston Univ, Dept Cognit & Neural Syst, 677 Beacon St, Boston, MA 02215 USA. EM guenther@cns.bu.edu FU NIDCD NIH HHS [R01 DC002852] NR 178 TC 65 Z9 68 U1 2 U2 31 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0169-0965 EI 1464-0732 J9 LANG COGNITIVE PROC JI Lang. Cogn. Process. PY 2011 VL 26 IS 7 BP 952 EP 981 DI 10.1080/01690960903498424 PG 30 WC Linguistics; Psychology, Experimental SC Linguistics; Psychology GA 878SI UT WOS:000299276400005 PM 23667281 ER PT J AU Paczynski, M Kuperberg, GR AF Paczynski, Martin Kuperberg, Gina R. TI Electrophysiological evidence for use of the animacy hierarchy, but not thematic role assignment, during verb-argument processing SO LANGUAGE AND COGNITIVE PROCESSES LA English DT Article DE Animacy hierarchy; Thematic roles; Event-related potentials; Sentences ID EVENT-RELATED POTENTIALS; SYNTACTIC AMBIGUITY RESOLUTION; LATENT SEMANTIC ANALYSIS; LANGUAGE COMPREHENSION; SENTENCE COMPREHENSION; EYE-MOVEMENTS; RELATIVE CLAUSES; WORLD KNOWLEDGE; WORKING-MEMORY; INFORMATION AB Animacy is known to play an important role in language processing and production, but debate remains as to how it exerts its effects: (1) through links to syntactic ordering, (2) through inherent differences between animate and inanimate entities in their salience/lexico-semantic accessibility, and (3) through links to specific thematic roles. We contrasted these three accounts in two event-related potential (ERP) experiments examining the processing of direct object arguments in simple English sentences. In Experiment 1, we found a larger N400 to animate than inanimate direct object arguments assigned the Patient role, ruling out the second account. In Experiment 2, we found no difference in the N400 evoked by animate direct object arguments assigned the Patient role (prototypically inanimate) and those assigned the Experiencer role (prototypically animate), ruling out the third account. We therefore suggest that animacy may impact processing through a direct link to syntactic linear ordering, at least on postverbal arguments in English. We also examined processing on direct object arguments that violated the animacy-based selection-restriction constraints of their preceding verbs. These violations evoked a robust P600, which was not modulated by thematic role assignment or reversibility, suggesting that the so-called semantic P600 is driven by overall propositional impossibility, rather than thematic role reanalysis. C1 [Paczynski, Martin; Kuperberg, Gina R.] Tufts Univ, Dept Psychol, Neurocognit Lab, Medford, MA 02155 USA. [Kuperberg, Gina R.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. RP Paczynski, M (reprint author), Tufts Univ, Dept Psychol, Neurocognit Lab, 490 Boston Ave, Medford, MA 02155 USA. EM martin.paczynski@tufts.edu FU NIMH NIH HHS [R01 MH071635-06A2, R01 MH071635] NR 79 TC 18 Z9 21 U1 5 U2 16 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0169-0965 J9 LANG COGNITIVE PROC JI Lang. Cogn. Process. PY 2011 VL 26 IS 9 SI SI BP 1402 EP 1456 DI 10.1080/01690965.2011.580143 PG 55 WC Linguistics; Psychology, Experimental SC Linguistics; Psychology GA 878TE UT WOS:000299278800005 PM 22199415 ER PT J AU Henstrom, DK Skilbeck, CJ Weinberg, J Knox, C Cheney, ML Hadlock, TA AF Henstrom, Douglas K. Skilbeck, Christopher J. Weinberg, Julie Knox, Christopher Cheney, Mack L. Hadlock, Tessa A. TI Good Correlation Between Original and Modified House Brackmann Facial Grading Systems SO LARYNGOSCOPE LA English DT Article DE Facial paralysis; facial analysis; House-Brackmann; facial nerve ID NERVE FUNCTION; RELIABILITY; SUNNYBROOK; SYNKINESIS; AGREEMENT; PARALYSIS; MOTION AB Objectives/Hypothesis: Subjective scales of facial function were plagued with reporting variations until the House-Brackmann scale was described in 1985. Despite its utility, weaknesses were identified, including noninclusion of synkinesis phenomena and insensitivity to segmental weakness. Therefore, the scale was recently revised to address these weaknesses. The objective of this investigation was to determine agreement between the original and the updated House-Brackmann scales. Study Design: Prospective clinical trial. Methods: Fifty consecutive new facial paralysis patients underwent standardized facial videography while performing facial movements. Video clips were scored by three independent facial nerve clinicians. The time it took to produce a score for each method was tracked. Interobserver correlations were calculated, and comparisons were made between scores by using the original and modified House-Brackmann scales. Results: Interobserver correlation was high for both House-Brackmann scales. Overall scores were in excellent agreement (difference of 0.1 +/- 0.5, no statistical difference), although the modified scale took substantially longer to calculate (120 seconds +/- 20 seconds vs. 30 seconds +/- 10 seconds, P < .001). Conclusions: We found substantial grading correlation between the original and the newly modified House Brackmann scales. Because of specific zonal and synkinesis scoring, the modified scale took longer to score. C1 [Henstrom, Douglas K.; Weinberg, Julie; Knox, Christopher; Cheney, Mack L.; Hadlock, Tessa A.] Mass Eye & Ear Infirm, Facial Nerve Ctr, Boston, MA USA. [Skilbeck, Christopher J.] Royal Natl Throat Nose & Ear Hosp, London WC1X 8DA, England. RP Hadlock, TA (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Facial Nerve Ctr, 243 Charles St, Boston, MA 02114 USA. EM tessa_hadlock@meei.harvard.edu NR 17 TC 12 Z9 14 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD JAN PY 2011 VL 121 IS 1 BP 47 EP 50 DI 10.1002/lary.21163 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 708YQ UT WOS:000286400600009 PM 21120826 ER PT J AU Shin, JJ Grillo, HC Mathisen, D Katlic, MR Zurakowski, D Kamani, D Randolph, GW AF Shin, Jennifer J. Grillo, Hermes C. Mathisen, Doug Katlic, Mark R. Zurakowski, David Kamani, Dipti Randolph, Gregory W. TI The Surgical Management of Goiter: Part I. Preoperative Evaluation SO LARYNGOSCOPE LA English DT Article DE Goiter; substernal goiter; thyro-megaly; thyroid surgery; thyroid disease management; thyroid neoplasm; recurrent laryngeal nerve injury; thyroidectomy ID UPPER AIRWAY-OBSTRUCTION; THYROID ENLARGEMENT; RADIOIODINE THERAPY; TOXIC GOITER; COMPRESSION; VOLUME; FLOW AB Objectives/Hypothesis: Our overarching objective is to provide a comprehensive analysis of goiter data in two paired articles. This first article focuses on the preoperative evaluation. The following null hypotheses have been tested: 1) there is no correlation between goiter size and preoperative symptoms, 2) there is no correlation between preoperative neck imaging abnormalities and preoperative symptoms, and 3) there are no predictors for goiter recurrence. Sudy Design: A retrospective review of 200 consecutive thyroidectomies meeting inclusion/exclusion criteria for cervical or substernal goiter. Results: The mean specimen size was 10.5 +/- 4.8 cm and 142.9 +/- 113.3 grams. There was a positive correlation between goiter size and preoperative shortness of breath (P = .02). The presence of substernal goiter was significantly correlated with tracheal deviation and tracheal compression (P < .01) on neck imaging. There was strong correlation between preoperative shortness of breath and tracheal compression (P < .001) on neck computed tomography (CT), but not tracheal deviation. The need for revision surgery was significantly associated with female gender (odds ratio 3.0; 95% confidence interval [CI] 1.5, 6.1, and a positive family history of thyroid disease (odds ratio 6.5 [2.4, 17.3]). Conclusions: Goiter size is associated with increasing symptoms. Tracheal compression but not deviation was related to shortness of breath. Females and patients with a positive family history of goiter have an increased risk of goiter recurrence. C1 [Shin, Jennifer J.; Kamani, Dipti; Randolph, Gregory W.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol,Div Thyroid & Parathyroid Su, Boston, MA USA. [Grillo, Hermes C.; Mathisen, Doug] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Thorac Surg, Boston, MA USA. [Katlic, Mark R.] Geisinger Wyoming Valley Med Ctr, Div Thorac Surg, Wilkes Barre, PA USA. [Zurakowski, David] Childrens Hosp Boston, Dept Anesthesia, Boston, MA USA. [Zurakowski, David] Childrens Hosp Boston, Dept Surg, Boston, MA USA. [Randolph, Gregory W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Surg Serv,Dept Surg,Div Surg Oncol, Boston, MA USA. RP Randolph, GW (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM Gregory_Randolph@meei.harvard.edu RI Shin, Jennifer/A-3169-2016 NR 37 TC 10 Z9 11 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD JAN PY 2011 VL 121 IS 1 BP 60 EP 67 DI 10.1002/lary.21084 PG 8 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 708YQ UT WOS:000286400600012 PM 21132771 ER PT J AU Randolph, GW Shin, JJ Grillo, HC Mathisen, D Katlic, MR Kamani, D Zurakowski, D AF Randolph, Gregory W. Shin, Jennifer J. Grillo, Hermes C. Mathisen, Doug Katlic, Mark R. Kamani, Dipti Zurakowski, David TI The Surgical Management of Goiter: Part II. Surgical Treatment and Results SO LARYNGOSCOPE LA English DT Article DE Goiter; substernal goiter; thyromegaly; thyroid surgery; thyroid disease management; thyroid neoplasm; recurrent laryngeal nerve injury; thyroidectomy ID MULTINODULAR GOITER; SUBTOTAL THYROIDECTOMY; SUBSTERNAL GOITER; NONTOXIC GOITER; RISK-FACTORS; DISEASE; COMPLICATIONS; EXPERIENCE; RECURRENCE; SURGERY AB Objectives/Hypothesis: Surgery for goiter embodies a unique challenge. Our objective is to provide a comprehensive analysis of cervical and substernal goiter data in two paired articles. This second article focuses on surgical management. The following null hypotheses regarding goiter excision have been tested: 1) there are no goiter-associated risk factors for difficult intubation; 2) there are no predictive risk factors for recurrent laryngeal nerve injury (RLN) or postoperative hypocalcemia; 3) there is no difference in RLN injury with neural monitoring versus without. Study Design: A retrospective review of 200 consecutive thyroidectomies meeting inclusion/exclusion criteria for cervical or substernal goiter. Results: Temporary RLN paralysis occurred in 1.8% of nerves at risk and was significantly lower with recurrent laryngeal nerve monitoring than without. Permanent hypoparathyroidism occurred in 3% overall. Bilateral cervical goiter emerged as a definitive risk factor for difficult intubation (P = .05, univariate), recurrent laryngeal nerve injury (P = .002), and postoperative hypocalcemia (P = .001). Female patients (P = .04) or patients with positive family history (P = .01) were more likely to need repeat surgery. There were no cases of tracheomalacia, and sternotomy was required in 1%. Conclusions: In this series of patients with extensive goiter, primary and revision surgery were associated with low rate of complications. Surgical complications were associated with bilateral and large goiters suggesting increased caution in these patients. C1 [Randolph, Gregory W.; Shin, Jennifer J.; Kamani, Dipti] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, Boston, MA USA. [Randolph, Gregory W.; Shin, Jennifer J.; Kamani, Dipti] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Div Thyroid & Parathyroid Surg, Boston, MA USA. [Grillo, Hermes C.; Mathisen, Doug] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Thorac Surg, Boston, MA USA. [Katlic, Mark R.] Geisinger Wyoming Valley Med Ctr, Div Thorac Surg, Wilkes Barre, PA USA. [Zurakowski, David] Childrens Hosp Boston, Dept Biostat, Boston, MA USA. [Randolph, Gregory W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Surg Serv,Div Surg Oncol,Dept Surg, Boston, MA USA. RP Randolph, GW (reprint author), Massachusetts Eye & Ear Infirm, Div Thyroid & Parathyroid Surg, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM Gregory_Randolph@meei.harvard.edu RI Shin, Jennifer/A-3169-2016 NR 29 TC 12 Z9 12 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD JAN PY 2011 VL 121 IS 1 BP 68 EP 76 DI 10.1002/lary.21091 PG 9 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 708YQ UT WOS:000286400600013 PM 21154775 ER PT J AU Francis, DO Maynard, C Weymuller, EA Reiber, G Merati, AL Yueh, B AF Francis, David O. Maynard, Charles Weymuller, Ernest A. Reiber, Gayle Merati, Albert L. Yueh, Bevan TI Reevaluation of Gastroesophageal Reflux Disease as a Risk Factor for Laryngeal Cancer SO LARYNGOSCOPE LA English DT Article DE Gastroesophageal reflux disease; extraesophageal reflux; laryngeal cancer; reverse causality ID LARYNGOPHARYNGEAL REFLUX; CARCINOMA; TOBACCO; PEPSIN; CARCINOGENESIS; SMOKING; INJURY; ACID; GERD AB Objectives/Hypothesis: The relationship between gastroesophageal reflux disease (GERD) and laryngeal cancer has not been fully elucidated. This case-control study investigates whether GERD increases the odds of developing these malignancies. Study Design: Case-control study. Methods: Rates of GERD among cases of laryngeal cancer identified in the Veterans Health Administration outpatient care files (year 2000-2006) were compared with controls. Cases (N = 14,449) were frequency matched 1:1 with controls. Multivariate logistic regression was used to determine the association between GERD and cancer. Results: After adjusting for tobacco and/or alcohol use, there was no association between GERD and laryngeal cancer (adjusted odds ratio, 1.01; 95% confidence interval, 0.92-1.12, P =.780). Although an association was found when time from GERD diagnosis to malignancy was less than 3 months, it disappeared when this period was extended further. Conclusions: In this population, there was no increased risk of laryngeal cancer among patients with GERD. However, in subsite analysis, a possible relationship between GERD and glottic cancer was observed. Reverse causality must be considered in future studies assessing the relationship between reflux and laryngeal cancer to limit misclassification bias. C1 [Francis, David O.; Maynard, Charles; Reiber, Gayle] Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. [Francis, David O.; Weymuller, Ernest A.; Merati, Albert L.] Univ Washington, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA. [Yueh, Bevan] Univ Minnesota, Dept Otolaryngol Head & Neck Surg, Minneapolis, MN USA. RP Francis, DO (reprint author), Med Ctr E, Vanderbilt Voice Ctr, South Tower,1215 21st Ave S,Suite 7302, Nashville, TN 37232 USA. EM david.o.francis@vanderbilt.edu RI Maynard, Charles/N-3906-2015; OI Maynard, Charles/0000-0002-1644-7814; Yueh, Bevan/0000-0003-1380-1053 FU U.S. Department of Veterans Affairs Northwest Center of Excellence for Health Services Research and Development; American Academy of Otolaryngology-Head and Neck Surgery Resident Research C.O.R.E. FX This study was supported in part by the U.S. Department of Veterans Affairs Northwest Center of Excellence for Health Services Research and Development and by an American Academy of Otolaryngology-Head and Neck Surgery Resident Research C.O.R.E. grant. The authors have no other funding, financial relationships, or conflicts of interest to disclose. NR 27 TC 11 Z9 12 U1 1 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD JAN PY 2011 VL 121 IS 1 BP 102 EP 105 DI 10.1002/lary.21165 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 708YQ UT WOS:000286400600017 PM 21046549 ER PT J AU Cunningham, MJ Lin, AC AF Cunningham, Michael J. Lin, Aaron C. TI Pediatric Otolaryngology: the Maturation of a Pediatric Surgical Subspecialty SO LARYNGOSCOPE LA English DT Review DE Pediatric otolaryngology; pediatric surgery; pediatric urology; surgical subspecialty ID HISTORY; SURGERY; UROLOGY AB Objectives/Hypothesis: To review the historical development of pediatric otolaryngology as a surgical subspecialty and to compare and contrast this historical development with that of pediatric surgery and pediatric urology. Study Design: Literature search. Methods: A sequential comparison of these three surgical subspecialties was undertaken in terms of their early origins and founding physicians, sections and societies, standardization of training and accreditation, official recognition, and certification. Supportive materials were obtained via a literature search using the PubMed database from 1950 to the present, supplemented by archived material from the libraries of the Massachusetts Eye and Ear Infirmary and the Countway Library of the Harvard Medical School. Results: Pediatric surgery, urology, and otolaryngology have taken somewhat parallel but also disparate paths toward surgical subspecialty establishment. Conclusions: Pediatric otolaryngology, despite its many accomplishments, lags behind its surgical and urologic brethren from both an accreditation and certification standpoint. C1 [Cunningham, Michael J.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol,Dept Otol & Laryngol, Boston, MA 02114 USA. [Lin, Aaron C.] Univ So Calif, Keck Sch Med, Dept Otolaryngol, Los Angeles, CA 90033 USA. RP Cunningham, MJ (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol,Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA. EM michael_cunningham@meei.harvard.edu NR 27 TC 3 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD JAN PY 2011 VL 121 IS 1 BP 194 EP 201 DI 10.1002/lary.20990 PG 8 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 708YQ UT WOS:000286400600033 PM 20564732 ER PT J AU Randolph, GW Dralle, H Abdullah, H Barczynski, M Bellantone, R Brauckhoff, M Carnaille, B Cherenko, S Chiang, FY Dionigi, G Finck, C Hartl, D Kamani, D Lorenz, K Miccolli, P Mihai, R Miyauchi, A Orloff, L Perrier, N Poveda, MD Romanchishen, A Serpell, J Sitges-Serra, A Sloan, T Van Slycke, S Snyder, S Takami, H Volpi, E Woodson, G AF Randolph, Gregory W. Dralle, Henning Abdullah, Hisham Barczynski, Marcin Bellantone, Rocco Brauckhoff, Michael Carnaille, Bruno Cherenko, Sergii Chiang, Fen-Yu Dionigi, Gianlorenzo Finck, Camille Hartl, Dana Kamani, Dipti Lorenz, Kerstin Miccolli, Paolo Mihai, Radu Miyauchi, Akira Orloff, Lisa Perrier, Nancy Poveda, Manuel Duran Romanchishen, Anatoly Serpell, Jonathan Sitges-Serra, Antonio Sloan, Tod Van Slycke, Sam Snyder, Samuel Takami, Hiroshi Volpi, Erivelto Woodson, Gayle CA Int Intraoperative Monitoring St TI Electrophysiologic Recurrent Laryngeal Nerve Monitoring During Thyroid and Parathyroid Surgery: International Standards Guideline Statement SO LARYNGOSCOPE LA English DT Article DE Recurrent laryngeal nerve; nerve monitoring; intraoperative neural monitoring; international standards; guidelines for intraoperative neural monitoring; thyroid surgery; parathyroid surgery; nerve injury; nerve monitoring equipment; neural mapping; nerve identification; anesthesia and nerve monitoring; loss of signal; laryngeal twitch; vagus nerve; electromyography characteristics; vocal cord mobility; latency; amplitude; superior laryngeal nerve ID STIMULATING SURGICAL-INSTRUMENTS; ASSISTED EVOKED ELECTROMYOGRAPHY; ENDOTRACHEAL-TUBE; INTRAOPERATIVE IDENTIFICATION; THYROARYTENOID MUSCLES; CANINE MODEL; INJURY; RISK; PARALYSIS; EXPERIENCE AB Intraoperative neural monitoring (IONM) during thyroid and parathyroid surgery has gained widespread acceptance as an adjunct to the gold standard of visual nerve identification. Despite the increasing use of IONM, review of the literature and clinical experience confirms there is little uniformity in application of and results from nerve monitoring across different centers. We provide a review of the literature and cumulative experience of the multidisciplinary International Neural Monitoring Study Group with IONM spanning nearly 15 years. The study group focused its initial work on formulation of standards in IONM as it relates to important areas: 1) standards of equipment setup/endotracheal tube placement and 2) standards of loss of signal evaluation/intraoperative problem-solving algorithm. The use of standardized methods and reporting will provide greater uniformity in application of IONM. In addition, this report clarifies the limitations of IONM and helps identify areas where additional research is necessary. This guideline is, at its forefront, quality driven; it is intended to improve the quality of neural monitoring, to translate the best available evidence into clinical practice to promote best practices. We hope this work will minimize inappropriate variations in monitoring rather than to dictate practice options. C1 [Randolph, Gregory W.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Div Thyroid & Parathyroid Surg,Massachusetts Eye, Boston, MA USA. [Randolph, Gregory W.] Harvard Univ, Sch Med, Div Surg Oncol, Endocrine Surg Serv,Dept Surg,Massachusetts Gen H, Boston, MA USA. [Dralle, Henning] Univ Halle Wittenberg, Dept Surg, Halle, Germany. [Dralle, Henning] Univ Halle Wittenberg, Dept Gen Visceral & Vasc Surg, Halle, Germany. RP Randolph, GW (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Div Thyroid & Parathyroid Surg, 243 Charles St, Boston, MA 02114 USA. EM Gregory_Randolph@meei.harvard.edu OI dionigi, gianlorenzo/0000-0003-0864-6087 NR 73 TC 181 Z9 189 U1 3 U2 30 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD JAN PY 2011 VL 121 SU 1 BP S1 EP S16 DI 10.1002/lary.21119 PG 16 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 708YT UT WOS:000286400900001 PM 21181860 ER PT S AU Shammas, MA Rao, MY AF Shammas, Masood A. Rao, Manjula Y. BE Murray, GI TI Purification of Diseased Cells from Barrett's Esophagus and Related Lesions by Laser Capture Microdissection SO LASER CAPTURE MICRODISSECTION: METHODS AND PROTOCOLS, SECOND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Laser microdissection; Barrett's esophagus; Esophageal adenocarcinoma; Esophageal metaplasia; Telomere; Telomerase ID TELOMERASE ACTIVITY; ADENOCARCINOMA; HYBRIDIZATION; CARCINOMA; DYSPLASIA AB Barrett's esophageal adenocarcinoma (BEAC) arises from Barrett's esophagus (BE), a premalignant lesion caused by acid reflux (heartburn). Although the cancer is uncommon, its incidence is rapidly rising in western countries. Like most other cancers, BEAC cells also have elevated telomerase activity which maintains telomere length and supports continued proliferation of these cells. It is not clear if telomerase is activated early at premalignant (BE) stage, because reports of telomerase activity in Barrett's and normal esophagi have been controversial. We have shown that detection of telomerase and telomeres becomes easier and much more reliable if purified BE cells are used instead of tissue specimens. This chapter, therefore, emphasizes the importance of laser capture microdissection and provides the method to purify Barrett's esophagus related cells, using this technique. C1 [Shammas, Masood A.] Harvard Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. [Shammas, Masood A.] VA Boston Healthcare Syst, Boston, MA USA. [Rao, Manjula Y.] Univ Washington, Dept Neurol, Ctr Human Dev & Disabil, Seattle, WA 98195 USA. RP Shammas, MA (reprint author), Harvard Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. NR 17 TC 2 Z9 2 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-162-8 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 755 BP 181 EP 187 DI 10.1007/978-1-61779-163-5_14 D2 10.1007/978-1-61779-163-5 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Pathology SC Biochemistry & Molecular Biology; Pathology GA BWE67 UT WOS:000293771800014 PM 21761303 ER PT J AU Ho, SGY Yeung, CK Chan, NPY Shek, SY Kono, T Chan, HHL AF Ho, S. G. Y. Yeung, C. K. Chan, N. P. Y. Shek, S. Y. Kono, T. Chan, H. H. L. TI A Retrospective Analysis of the Management of Acne Post-Inflammatory Hyperpigmentation Using Topical Treatment, Laser Treatment, or Combination Topical and Laser Treatments in Oriental Patients SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE acne PIH; post-inflammatory hyperpigmentation; Asian; oriental; topical; lasers ID FLUOCINOLONE ACETONIDE 0.01-PERCENT; HYDROQUINONE 4-PERCENT; TRETINOIN 0.05-PERCENT; EXOGENOUS OCHRONOSIS; RETINOIC ACID; MELASMA; SKIN; EFFICACY; CREAM; MELANOGENESIS AB Background: Post-inflammatory hyperpigmentation (PIH) is characterized by an acquired increase in pigmentation secondary to an inflammatory process, and is a commonly observed response to cutaneous injury in Fitzpatrick types III-VI patients. Objectives: To determine the effectiveness and safety of using topical treatment, laser treatment, or combination topical and laser treatments to treat acne PIH in Oriental patients. Methods: This is a retrospective study of 34 randomly selected Chinese patients with acne PIH. They were divided into three groups, and treated with topical agents, 595 nm long pulsed dye laser and/or 1064 nm Q-switched Nd:YAG, or combination topical and laser treatments. An independent clinician assessed pre-and post-treatment photographs to determine efficacy and timing to visible and optimum improvement. Results: There was significant global and focal improvement of acne PIH in patients in all three groups. However, no significant difference was found between the groups. An investigator global assessment showed improvement with all treatment modalities, with 70.6% moderate to marked improvement seen in the combination treatment group, compared to 55.6% in the laser only group, and 50% in the topical treatment only group. Visible and optimum improvement was seen by 3 months in majority of patients treated. One patient developed PIH as a result of laser treatment. Conclusion: Topical treatment, laser therapy, and combination topical and laser treatments all appear to be effective management strategies for acne PIH in Fitzpatrick types III and IV skin with little complications. Topical agents may be considered as first-line therapy for acne PIH, taking into consideration its effectiveness, ease of use and cost. Combined topical and laser therapy is also effective, and may be considered as second-line treatment. Lasers Surg. Med. 43: 1-7, 2011. (C) 2011 Wiley-Liss, Inc. C1 [Ho, S. G. Y.; Yeung, C. K.; Chan, N. P. Y.; Shek, S. Y.; Chan, H. H. L.] Univ Hong Kong, Dept Med, Div Dermatol, Hong Kong, Hong Kong, Peoples R China. [Kono, T.] Tokyo Womens Med Sch, Dept Plast & Reconstruct Surg, Tokyo, Japan. [Chan, H. H. L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. RP Chan, HHL (reprint author), 13-F Club Lusitano,16 Ice House St, Hong Kong, Hong Kong, Peoples R China. EM hhlchan@hku.hk RI Chan, Henry Hin Lee/L-2267-2013; Yeung, Chi Keung/L-4795-2013 FU Candela FX Dr. HHL Chan is on the advisory board for Iridex, has conducted and received grants from Candela, and has received free equipment from Syneron. NR 27 TC 7 Z9 7 U1 0 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD JAN PY 2011 VL 43 IS 1 BP 1 EP 7 DI 10.1002/lsm.21010 PG 7 WC Dermatology; Surgery SC Dermatology; Surgery GA 709LU UT WOS:000286440300001 PM 21254136 ER PT J AU Song, W Tai, YT Tian, Z Hideshima, T Chauhan, D Nanjappa, P Exley, MA Anderson, KC Munshi, NC AF Song, W. Tai, Y-T Tian, Z. Hideshima, T. Chauhan, D. Nanjappa, P. Exley, M. A. Anderson, K. C. Munshi, N. C. TI HDAC inhibition by LBH589 affects the phenotype and function of human myeloid dendritic cells SO LEUKEMIA LA English DT Article DE histone deacetylase inhibitor; LBH589; dendritic cells; T cells; invariant NKT cells; NF-kappa B ID HISTONE DEACETYLASE INHIBITORS; T-CELLS; CANCER; RECOGNITION; EXPRESSION; APOPTOSIS; STRATEGY AB LBH589 is a novel pan-histone deacetylase (HDAC) inhibitor that has potent antitumor activity in multiple myeloma and other hematological malignancies. However, its impact on the immune system has not been defined. We here evaluated the effects of LBH589 on human myeloid dendritic cells (DCs) at clinically relevant concentrations. Exposure to LBH589 affected the surface molecule expression on immature and mature DCs, which was associated with DC maturation (CD83 down arrow), antigen presentation (human leukocyte antigen-ABC down arrow) and T-cell co-stimulation (CD40 down arrow and CD86 up arrow). LBH589 decreased both protein and polysaccharide antigen uptake capacities by DCs. Importantly, LBH589 impaired DC function to stimulate antigen-specific immune responses, resulting in the significant reduction of invariant natural killer T-cell (CD1d-restricted) and T-cell (major histocompatibility complex-restricted) activation in innate and adaptive immunity. LBH589 also significantly repressed the production of interleukin (IL)-6, IL-10, IL-12p70, IL-23 and tumor necrosis factor-alpha by Toll-like receptor (TLR) 3 and TLR4-induced DC activation, indicating an important role of HDAC activity in immune regulation and inflammation. RelB, a component of the nuclear factor-kappa B signaling pathway, was the key component regulated by HDAC inhibition in DCs. Together, our preclinical study demonstrates that LBH589 significantly impairs the phenotype and function of DCs, indicating a need for monitoring the immune status in patients receiving HDAC inhibitor therapy. It also provides a rationale to evaluate LBH589 activity for the treatment of inflammation. Leukemia (2011) 25, 161-168; doi: 10.1038/leu.2010.244; published online 19 November 2010 C1 [Song, W.; Tai, Y-T; Tian, Z.; Hideshima, T.; Chauhan, D.; Nanjappa, P.; Anderson, K. C.; Munshi, N. C.] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Exley, M. A.] Harvard Univ, Sch Med, Canc Biol Program,Beth Israel Deaconess Med Ctr, Hematol Oncol Div,Dept Med, Boston, MA 02115 USA. [Munshi, N. C.] Harvard Univ, Sch Med, VA Boston Hlth Care Syst, Boston, MA 02115 USA. RP Munshi, NC (reprint author), Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, 44 Binney St,M1B28, Boston, MA 02115 USA. EM nikhil_munshi@dfci.harvard.edu FU National Institutes of Health [P050-100707, PO1-78378]; Research Service Veterans Health Care FX We thank Novartis Pharmaceutical Inc. (Cambridge, MA, USA) for kindly providing LBH589. We also thank Kirin Brewery Co. Ltd. (Gunma, Japan) for kindly providing alpha-GalCer. This work is supported in part by the National Institutes of Health Grants P050-100707 and PO1-78378 (NCM and KCA), and a Merit Review Award from the Research Service Veterans Health Care (NCM). NR 26 TC 43 Z9 45 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 JAN PY 2011 VL 25 IS 1 BP 161 EP 168 DI 10.1038/leu.2010.244 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA 705ZJ UT WOS:000286179400019 PM 21102427 ER PT B AU Wadleigh, M DeAngelo, DJ AF Wadleigh, Martha DeAngelo, Daniel J. BE Faderl, S Kantarjian, H TI Induction Therapy of Acute Myeloid Leukemia SO LEUKEMIAS: PRINCIPLES AND PRACTICE OF THERAPY LA English DT Article; Book Chapter ID ACUTE MYELOGENOUS LEUKEMIA; COLONY-STIMULATING FACTOR; HIGH-DOSE CYTARABINE; ACUTE NONLYMPHOCYTIC LEUKEMIA; SOUTHWEST-ONCOLOGY-GROUP; SULFONYLHYDRAZINE ALKYLATING AGENT; TIMED-SEQUENTIAL CHEMOTHERAPY; TRIAL COMPARING IDARUBICIN; PHASE-III TRIAL; ANTI-CD33 MONOCLONAL-ANTIBODY C1 [Wadleigh, Martha] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [DeAngelo, Daniel J.] Harvard Univ, Sch Med, Boston, MA USA. [DeAngelo, Daniel J.] Dana Farber Canc Inst, Dept Med Oncol, Adult Leukemia Program, Boston, MA 02115 USA. RP Wadleigh, M (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. NR 97 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-4443-2736-6; 978-1-4051-8235-5 PY 2011 BP 125 EP 137 PG 13 WC Oncology; Hematology SC Oncology; Hematology GA BA6GJ UT WOS:000337135300011 ER PT J AU Imamura, Y Azuma, K Kurata, S Hattori, S Sasada, T Kinoshita, T Okamoto, M Kawayama, T Kaida, H Ishibashi, M Aizawa, H AF Imamura, Yohei Azuma, Koichi Kurata, Seiji Hattori, Satoshi Sasada, Tetsuro Kinoshita, Takashi Okamoto, Masaki Kawayama, Tomotaka Kaida, Hayato Ishibashi, Masatoshi Aizawa, Hisamichi TI Prognostic value of SUVmax measurements obtained by FDG-PET in patients with non-small cell lung cancer receiving chemotherapy SO LUNG CANCER LA English DT Article DE NSCLC; FDG-PET; SUVmax; PFS; OS; Chemotherapy ID POSITRON-EMISSION-TOMOGRAPHY; CISPLATIN PLUS GEMCITABINE; PROGRESSION-FREE; BREAST-CANCER; SURVIVAL; PLATINUM; METAANALYSIS; EXPRESSION; MUTATIONS; GEFITINIB AB [(18)F]Fluorodeoxyglucose (FDG) uptake has been shown to correlate well with tumor proliferation rates. In patients with non-small cell lung cancer (NSCLC) receiving chemotherapy, we analyzed the relationships between the maximum standardized uptake value (SUVmax) obtained by FDG positron emission tomography (FDG-PET) and other clinical factors, and examined whether or not SUVmax could predict progression-free survival (PFS) and/or overall survival (OS). This retrospective study involved 62 consecutive NSCLC patients (35 male and 27 female: median age, 65 years). All patients underwent FDG-PET examination before treatment. As the first-line treatment, the patients received chemotherapy with (n=15) or without (n=47) radiotherapy. Survival curves were obtained by the Kaplan-Meier method, and differences in survival between subgroups were analyzed by the log-rank test and the Cox proportional hazards model. Significant correlations were observed between SUVmax and gender (P=0.006), histology (P<0.001), smoking status (P=0.049), stage (P=0.015), and treatment modality (P=0.008), but not other factors, including age (P=0.402) and performance status (P=0.421). The median SUVmax was 5.1 (25-75th percentile: 3.45-7.0) in patients with adenocarcinoma and 8.3 (25-75th percentile: 6.9-9.9) in those with other types of NSCLC. Adenocarcinomas showed significantly lower SUVmax than the other tumor types (P<0.001). Cox analysis adjusting for possible confounding factors, including gender, smoking status, histology and stage, demonstrated that the hazard ratios increased as the SUVmax increased in terms of both PFS (P=0.008) and OS (P=0.045), indicating that SUVmax predicts outcome independently of other clinical factors, such as histology and stage. Our findings indicate that FDG-PET examination can provide information useful for prognostication in NSCLC. (C) 2010 Elsevier Ireland Ltd. All rights reserved. C1 [Imamura, Yohei; Azuma, Koichi; Kinoshita, Takashi; Okamoto, Masaki; Kawayama, Tomotaka; Aizawa, Hisamichi] Kurume Univ, Sch Med, Dept Internal Med, Div Respirol Neurol & Rheumatol, Fukuoka 8300011, Japan. [Kurata, Seiji; Kaida, Hayato; Ishibashi, Masatoshi] Kurume Univ, Sch Med, Dept Radiol, Kurume, Fukuoka 830, Japan. [Hattori, Satoshi] Kurume Univ, Ctr Biostat, Kurume, Fukuoka 830, Japan. [Sasada, Tetsuro] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. RP Azuma, K (reprint author), Kurume Univ, Sch Med, Dept Internal Med, Div Respirol Neurol & Rheumatol, 67 Asahi Machi, Fukuoka 8300011, Japan. EM azuma@med.kurume-u.ac.jp NR 26 TC 9 Z9 14 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER JI Lung Cancer PD JAN PY 2011 VL 71 IS 1 BP 49 EP 54 DI 10.1016/j.lungcan.2010.04.004 PG 6 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 710TS UT WOS:000286540500008 PM 20430470 ER PT S AU Liu, PK Liu, CH AF Liu, Philip K. Liu, Christina H. BE Modo, M Bulte, JWM TI Gene Targeting MRI: Nucleic Acid-Based Imaging and Applications SO MAGNETIC RESONANCE NEUROIMAGING: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Amphetamine; antisense; cell typing; cerebral ischemia; drug abuse; gene targeting; heart arrest; molecular imaging; MRI; nanoparticles; prognosis; siDNA ID LIVE ANIMALS; BRAIN; TRANSCRIPTS; EXPRESSION; ISCHEMIA; DELIVERY; PROBES AB Gene action plays a role in neural cell migration, learning processes, stress response, drug addiction, cancer, mental health, psychiatric and neurological disorders, as well as neurodegenerative diseases. Studies also show that upregulation of certain gene activities in neurons may contribute to the development of Alzheimer's disease and other progressive cognitive disorders many decades after the alteration itself occurs. Endogenous, environmental stress-related, or drug-induced chemical imbalances in the brain affect the homeostasis of gene activities in neurons in specific brain regions and contribute to the comorbidity of mental illness and substance dependence. On the other hand, altered gene activities are also a necessary part of repair processes after brain injury. Our general well-being is governed by the highly regulated gene activities in our brains. A better understanding of gene activities and their relationship to the progression of neurological disease can help the research and medical communities develop necessary measures for early intervention, as well as plan more appropriate interventions or new therapeutic approaches that can benefit a broad spectrum of patients who will be or have been affected by brain diseases. We developed a non-invasive imaging technique that allows real-time assessment of gene transcription profiles in live brains. This imaging method has the potential to provide first-hand information about the progression of neurological disorders by gene targeting and cell typing, and it could elucidate a surrogate marker for therapeutic efficacy for future planning of treatments for human diseases. We have established a workable and reproducible MRI technique in live rodent brains. C1 [Liu, Philip K.; Liu, Christina H.] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA USA. RP Liu, PK (reprint author), Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA USA. RI Bulte, Jeff/A-3240-2008; OI Bulte, Jeff/0000-0003-1202-1610; Liu, Christina/0000-0002-5723-177X FU NCRR NIH HHS [RR14075]; NIDA NIH HHS [DA024235, DA026108, DA29889, R01 DA026108]; NINDS NIH HHS [NS057556] NR 9 TC 2 Z9 2 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61737-991-8 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 711 BP 363 EP 377 DI 10.1007/978-1-61737-992-5_18 D2 10.1007/978-1-61737-992-5 PG 15 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Chemistry; Radiology, Nuclear Medicine & Medical Imaging GA BTS51 UT WOS:000287980300018 PM 21279612 ER PT B AU Rosenblum, J AF Rosenblum, Jennifer BE Goldstein, MA TI Adolescent Preventive Services SO MASSGENERAL HOSPITAL FOR CHILDREN ADOLESCENT MEDICINE HANDBOOK LA English DT Article; Book Chapter ID CHILDHOOD C1 [Rosenblum, Jennifer] MassGen Hosp Children, Div Adolescent & Young Adult Med, Boston, MA 02114 USA. [Rosenblum, Jennifer] MassGen Hosp Children, Div Adolescent & Young Adult Med 617 643 1201, Boston, MA 02114 USA. RP Rosenblum, J (reprint author), MassGen Hosp Children, Div Adolescent & Young Adult Med, 55 Fruit St,Yawkey 6D, Boston, MA 02114 USA. EM jrosenblum@partners.org NR 8 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-1-4419-6844-9 PY 2011 BP 3 EP 9 DI 10.1007/978-1-4419-6845-6_1 D2 10.1007/978-1-4419-6845-6 PG 7 WC Pediatrics SC Pediatrics GA BRQ06 UT WOS:000283394600001 ER PT B AU Murphy, M AF Murphy, Mariette BE Goldstein, MA TI The Adolescent Patient Interview SO MASSGENERAL HOSPITAL FOR CHILDREN ADOLESCENT MEDICINE HANDBOOK LA English DT Article; Book Chapter C1 MassGen Hosp Children, Div Adolescent & Young Adult Med, Boston, MA 02114 USA. RP Murphy, M (reprint author), MassGen Hosp Children, Div Adolescent & Young Adult Med, 55 Fruit St,Yawkey 6D, Boston, MA 02114 USA. EM mmurphy5@partners.org NR 4 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-1-4419-6844-9 PY 2011 BP 11 EP 16 DI 10.1007/978-1-4419-6845-6_2 D2 10.1007/978-1-4419-6845-6 PG 6 WC Pediatrics SC Pediatrics GA BRQ06 UT WOS:000283394600002 ER PT B AU Sadler, K AF Sadler, Karen BE Goldstein, MA TI Tanner Staging SO MASSGENERAL HOSPITAL FOR CHILDREN ADOLESCENT MEDICINE HANDBOOK LA English DT Article; Book Chapter ID PUBERTAL CHANGES; PATTERN C1 MassGen Hosp Children, Div Adolescent & Young Adult Med, Boston, MA 02114 USA. RP Sadler, K (reprint author), MassGen Hosp Children, Div Adolescent & Young Adult Med, 55 Fruit St,Yawkey 6D, Boston, MA 02114 USA. EM ksadler@partners.org NR 4 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-1-4419-6844-9 PY 2011 BP 17 EP 22 DI 10.1007/978-1-4419-6845-6_3 D2 10.1007/978-1-4419-6845-6 PG 6 WC Pediatrics SC Pediatrics GA BRQ06 UT WOS:000283394600003 ER PT B AU Sadler, K AF Sadler, Karen BE Goldstein, MA TI Normal Adolescent Development SO MASSGENERAL HOSPITAL FOR CHILDREN ADOLESCENT MEDICINE HANDBOOK LA English DT Article; Book Chapter C1 MassGen Hosp Children, Div Adolescent & Young Adult Med, Boston, MA 02114 USA. RP Sadler, K (reprint author), MassGen Hosp Children, Div Adolescent & Young Adult Med, 55 Fruit St,Yawkey 6D, Boston, MA 02114 USA. EM ksadler@partners.org NR 2 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-1-4419-6844-9 PY 2011 BP 23 EP 26 DI 10.1007/978-1-4419-6845-6_4 D2 10.1007/978-1-4419-6845-6 PG 4 WC Pediatrics SC Pediatrics GA BRQ06 UT WOS:000283394600004 ER PT B AU Kroshinsky, D AF Kroshinsky, Daniela BE Goldstein, MA TI Adolescent Dermatology SO MASSGENERAL HOSPITAL FOR CHILDREN ADOLESCENT MEDICINE HANDBOOK LA English DT Article; Book Chapter ID ACNE C1 Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Kroshinsky, D (reprint author), Massachusetts Gen Hosp, Dept Dermatol, 50 Stanford St,Suite 290, Boston, MA 02114 USA. EM dkroskinsky@partners.org NR 3 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-1-4419-6844-9 PY 2011 BP 43 EP 49 DI 10.1007/978-1-4419-6845-6_7 D2 10.1007/978-1-4419-6845-6 PG 7 WC Pediatrics SC Pediatrics GA BRQ06 UT WOS:000283394600007 ER PT B AU Rosenblum, J AF Rosenblum, Jennifer BE Goldstein, MA TI Obesity SO MASSGENERAL HOSPITAL FOR CHILDREN ADOLESCENT MEDICINE HANDBOOK LA English DT Article; Book Chapter C1 MassGen Hosp Children, Div Adolescent & Young Adult Med 617 643 1201, Boston, MA 02114 USA. RP Rosenblum, J (reprint author), MassGen Hosp Children, Div Adolescent & Young Adult Med 617 643 1201, 55 Fruit St,Yawkey 6D, Boston, MA 02114 USA. EM jrosenblum@partners.org NR 4 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-1-4419-6844-9 PY 2011 BP 51 EP 56 DI 10.1007/978-1-4419-6845-6_8 D2 10.1007/978-1-4419-6845-6 PG 6 WC Pediatrics SC Pediatrics GA BRQ06 UT WOS:000283394600008 ER PT B AU Sabharwal, S Israel, E AF Sabharwal, Sabina Israel, Esther BE Goldstein, MA TI Adolescent Nutrition, IBD, IBS SO MASSGENERAL HOSPITAL FOR CHILDREN ADOLESCENT MEDICINE HANDBOOK LA English DT Article; Book Chapter C1 [Sabharwal, Sabina; Israel, Esther] MassGen Hosp Children, Div Pediat Gastroenterol, Boston, MA 02114 USA. RP Sabharwal, S (reprint author), MassGen Hosp Children, Div Pediat Gastroenterol, 175 Cambridge St,5th Floor, Boston, MA 02114 USA. EM ssabharwal@partners.org; eisrael1@partners.org NR 8 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-1-4419-6844-9 PY 2011 BP 57 EP 62 DI 10.1007/978-1-4419-6845-6_9 D2 10.1007/978-1-4419-6845-6 PG 6 WC Pediatrics SC Pediatrics GA BRQ06 UT WOS:000283394600009 ER PT B AU Price, MD Gill, TJ AF Price, Mark D. Gill, Thomas J. BE Goldstein, MA TI Sports Injuries in the Adolescent SO MASSGENERAL HOSPITAL FOR CHILDREN ADOLESCENT MEDICINE HANDBOOK LA English DT Article; Book Chapter ID SHOULDER C1 [Price, Mark D.] Univ Massachusetts, U Mass Mem Med Ctr, Div Sports Med, Worcester, MA 01605 USA. [Gill, Thomas J.] Massachusetts Gen Hosp, Div Sports Med, Boston, MA 02114 USA. [Price, Mark D.] Univ Massachusetts, U Mass Mem Med Ctr, Div Sports Med, Worcegter, MA 01605 USA. RP Price, MD (reprint author), Univ Massachusetts, U Mass Mem Med Ctr, Div Sports Med, Worcester, MA 01605 USA. EM mark.price@umassmemorial.org; tgill@partners.org NR 9 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-1-4419-6844-9 PY 2011 BP 63 EP 74 DI 10.1007/978-1-4419-6845-6_10 D2 10.1007/978-1-4419-6845-6 PG 12 WC Pediatrics SC Pediatrics GA BRQ06 UT WOS:000283394600010 ER PT B AU Bhatt, AB AF Bhatt, Ami B. BE Goldstein, MA TI Cardiac Issues in Adolescence SO MASSGENERAL HOSPITAL FOR CHILDREN ADOLESCENT MEDICINE HANDBOOK LA English DT Article; Book Chapter ID SYNCOPE C1 Massachusetts Gen Hosp, Div Cardiol, Dept Med, Boston, MA 02114 USA. RP Bhatt, AB (reprint author), Massachusetts Gen Hosp, Div Cardiol, Dept Med, 8 Hawthorne Pl,Suite 110, Boston, MA 02114 USA. EM abhatt@partners.org NR 8 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-1-4419-6844-9 PY 2011 BP 75 EP 79 DI 10.1007/978-1-4419-6845-6_11 D2 10.1007/978-1-4419-6845-6 PG 5 WC Pediatrics SC Pediatrics GA BRQ06 UT WOS:000283394600011 ER PT B AU Corrado, S AF Corrado, Stephanie BE Goldstein, MA TI Menstrual Irregularities: Amenorrhea SO MASSGENERAL HOSPITAL FOR CHILDREN ADOLESCENT MEDICINE HANDBOOK LA English DT Article; Book Chapter C1 MassGen Hosp Children, Div Adolescent & Young Adult Med, Boston, MA 02114 USA. RP Corrado, S (reprint author), MassGen Hosp Children, Div Adolescent & Young Adult Med, 55 Fruit St,Yawkey 6D, Boston, MA 02114 USA. EM scorrado@partners.org NR 7 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-1-4419-6844-9 PY 2011 BP 83 EP 89 DI 10.1007/978-1-4419-6845-6_12 D2 10.1007/978-1-4419-6845-6 PG 7 WC Pediatrics SC Pediatrics GA BRQ06 UT WOS:000283394600012 ER PT B AU Goldstein, MA AF Goldstein, Mark A. BE Goldstein, MA TI Menstrual Irregularities: Abnormal Vaginal Bleeding SO MASSGENERAL HOSPITAL FOR CHILDREN ADOLESCENT MEDICINE HANDBOOK LA English DT Article; Book Chapter C1 MassGen Hosp Children, Div Adolescent & Young Adult Med, Boston, MA 02114 USA. RP Goldstein, MA (reprint author), MassGen Hosp Children, Div Adolescent & Young Adult Med, 175 Cambridge St,5th Floor, Boston, MA 02114 USA. EM mgoldstein@partners.org; mgoldstein@partners.org NR 2 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-1-4419-6844-9 PY 2011 BP 91 EP 94 DI 10.1007/978-1-4419-6845-6_13 D2 10.1007/978-1-4419-6845-6 PG 4 WC Pediatrics SC Pediatrics GA BRQ06 UT WOS:000283394600013 ER PT B AU Gupta, N AF Gupta, Nupur BE Goldstein, MA TI Basics of Hormonal Contraception SO MASSGENERAL HOSPITAL FOR CHILDREN ADOLESCENT MEDICINE HANDBOOK LA English DT Article; Book Chapter ID ADOLESCENT C1 MassGen Hosp Children, Div Adolescent & Young Adult Med, Boston, MA 02114 USA. RP Gupta, N (reprint author), MassGen Hosp Children, Div Adolescent & Young Adult Med, 55 Fruit St Yawkey 6D, Boston, MA 02114 USA. EM ngupta3@partners.org NR 6 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-1-4419-6844-9 PY 2011 BP 95 EP 110 DI 10.1007/978-1-4419-6845-6_14 D2 10.1007/978-1-4419-6845-6 PG 16 WC Pediatrics SC Pediatrics GA BRQ06 UT WOS:000283394600014 ER PT B AU Goldstein, MA AF Goldstein, Mark A. BE Goldstein, MA TI Adolescent Pregnancy SO MASSGENERAL HOSPITAL FOR CHILDREN ADOLESCENT MEDICINE HANDBOOK LA English DT Article; Book Chapter C1 MassGen Hosp Children, Div Adolescent & Young Adult Med, Boston, MA 02114 USA. RP Goldstein, MA (reprint author), MassGen Hosp Children, Div Adolescent & Young Adult Med, 175 Cambridge St,5th Floor, Boston, MA 02114 USA. EM mgoldstein@partners.org; mgoldstein@partners.org NR 3 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-1-4419-6844-9 PY 2011 BP 111 EP 113 DI 10.1007/978-1-4419-6845-6_15 D2 10.1007/978-1-4419-6845-6 PG 3 WC Pediatrics SC Pediatrics GA BRQ06 UT WOS:000283394600015 ER PT B AU Rosenblum, J AF Rosenblum, Jennifer BE Goldstein, MA TI Polycystic Ovary Syndrome SO MASSGENERAL HOSPITAL FOR CHILDREN ADOLESCENT MEDICINE HANDBOOK LA English DT Article; Book Chapter C1 [Rosenblum, Jennifer] MassGen Hosp Children, Div Adolescent & Young Adult Med, Boston, MA 02114 USA. [Rosenblum, Jennifer] MassGen Hosp Children, Div Adolescent & Young Adult Med 617 643 1201, Boston, MA 02114 USA. RP Rosenblum, J (reprint author), MassGen Hosp Children, Div Adolescent & Young Adult Med, 55 Fruit St,Yawkey 6D, Boston, MA 02114 USA. EM jrosenblum@partners.org NR 4 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-1-4419-6844-9 PY 2011 BP 115 EP 118 DI 10.1007/978-1-4419-6845-6_16 D2 10.1007/978-1-4419-6845-6 PG 4 WC Pediatrics SC Pediatrics GA BRQ06 UT WOS:000283394600016 ER PT B AU Goldstein, MA AF Goldstein, Mark A. BE Goldstein, MA TI Sexually Transmitted Infections in Adolescents SO MASSGENERAL HOSPITAL FOR CHILDREN ADOLESCENT MEDICINE HANDBOOK LA English DT Article; Book Chapter C1 MassGen Hosp Children, Div Adolescent & Young Adult Med, Boston, MA 02114 USA. RP Goldstein, MA (reprint author), MassGen Hosp Children, Div Adolescent & Young Adult Med, 175 Cambridge St,5th Floor, Boston, MA 02114 USA. EM mgoldstein@partners.org; mgoldstein@partners.org NR 8 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-1-4419-6844-9 PY 2011 BP 119 EP 146 DI 10.1007/978-1-4419-6845-6_17 D2 10.1007/978-1-4419-6845-6 PG 28 WC Pediatrics SC Pediatrics GA BRQ06 UT WOS:000283394600017 ER PT B AU Katz, M Misra, M AF Katz, Michelle Misra, Madhusmita BE Goldstein, MA TI Delayed Puberty, Short Stature, and Tall Stature SO MASSGENERAL HOSPITAL FOR CHILDREN ADOLESCENT MEDICINE HANDBOOK LA English DT Article; Book Chapter C1 [Katz, Michelle; Misra, Madhusmita] MassGen Hosp Children, Div Pediat Endocrinol, Boston, MA 02114 USA. [Misra, Madhusmita] MassGen Hosp Children, Div Endocrinol, Boston, MA 02114 USA. RP Katz, M (reprint author), MassGen Hosp Children, Div Pediat Endocrinol, 175 Cambridge St,5th Floor, Boston, MA 02114 USA. EM mlkatz@partners.org; mmisra@partners.org NR 5 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-1-4419-6844-9 PY 2011 BP 147 EP 152 DI 10.1007/978-1-4419-6845-6_18 D2 10.1007/978-1-4419-6845-6 PG 6 WC Pediatrics SC Pediatrics GA BRQ06 UT WOS:000283394600018 ER PT B AU Goldstein, MA AF Goldstein, Mark A. BE Goldstein, MA TI Adolescent Substance Abuse SO MASSGENERAL HOSPITAL FOR CHILDREN ADOLESCENT MEDICINE HANDBOOK LA English DT Article; Book Chapter C1 MassGen Hosp Children, Div Adolescent & Young Adult Med, Boston, MA 02114 USA. RP Goldstein, MA (reprint author), MassGen Hosp Children, Div Adolescent & Young Adult Med, 175 Cambridge St,5th Floor, Boston, MA 02114 USA. EM mgoldstein@partners.org; mgoldstein@partners.org NR 10 TC 4 Z9 4 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-1-4419-6844-9 PY 2011 BP 155 EP 165 DI 10.1007/978-1-4419-6845-6_19 D2 10.1007/978-1-4419-6845-6 PG 11 WC Pediatrics SC Pediatrics GA BRQ06 UT WOS:000283394600019 ER PT B AU Kurtz, B AF Kurtz, Brian BE Goldstein, MA TI Adolescent Mental Health Disorders SO MASSGENERAL HOSPITAL FOR CHILDREN ADOLESCENT MEDICINE HANDBOOK LA English DT Article; Book Chapter ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; CARE GLAD-PC; MANAGEMENT; DEPRESSION; PREVALENCE; GUIDELINES; EPIDEMIC; ANXIETY C1 Massachusetts Gen Hosp, Child Psychiat Serv, Dept Psychiat, Boston, MA 02114 USA. RP Kurtz, B (reprint author), Massachusetts Gen Hosp, Child Psychiat Serv, Dept Psychiat, 55 Fruit St,Yawkey 6A, Boston, MA 02114 USA. NR 26 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-1-4419-6844-9 PY 2011 BP 167 EP 188 DI 10.1007/978-1-4419-6845-6_20 D2 10.1007/978-1-4419-6845-6 PG 22 WC Pediatrics SC Pediatrics GA BRQ06 UT WOS:000283394600020 ER PT B AU Corrado, S AF Corrado, Stephanie BE Goldstein, MA TI Eating Disorders SO MASSGENERAL HOSPITAL FOR CHILDREN ADOLESCENT MEDICINE HANDBOOK LA English DT Article; Book Chapter ID ANOREXIA-NERVOSA; ADOLESCENTS; WEIGHT C1 MassGen Hosp Children, Div Adolescent & Young Adult Med, Boston, MA 02114 USA. RP Corrado, S (reprint author), MassGen Hosp Children, Div Adolescent & Young Adult Med, 55 Fruit St,Yawkey 6D, Boston, MA 02114 USA. EM scorrado@partners.org NR 11 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-1-4419-6844-9 PY 2011 BP 189 EP 198 DI 10.1007/978-1-4419-6845-6_21 D2 10.1007/978-1-4419-6845-6 PG 10 WC Pediatrics SC Pediatrics GA BRQ06 UT WOS:000283394600021 ER PT B AU Baumer, F Goldstein, MA AF Baumer, Fiona Goldstein, Mark A. BE Goldstein, MA TI Bullying SO MASSGENERAL HOSPITAL FOR CHILDREN ADOLESCENT MEDICINE HANDBOOK LA English DT Article; Book Chapter ID ASSOCIATION; HEALTH C1 [Baumer, Fiona] Childrens Hosp, Dept Med, Boston, MA 02115 USA. [Goldstein, Mark A.] MassGen Hosp Children, Div Adolescent & Young Adult Med, Boston, MA 02114 USA. [Baumer, Fiona] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Baumer, F (reprint author), Childrens Hosp, Dept Med, 300 Longwood Ave, Boston, MA 02115 USA. EM fiona.baumer@childrens.harvard.edu; mgoldstein@partners.org; mgoldstein@partners.org NR 7 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-1-4419-6844-9 PY 2011 BP 205 EP 207 DI 10.1007/978-1-4419-6845-6_23 D2 10.1007/978-1-4419-6845-6 PG 3 WC Pediatrics SC Pediatrics GA BRQ06 UT WOS:000283394600023 ER PT J AU Seed, KD Bodi, KL Kropinski, AM Ackermann, HW Calderwood, SB Qadri, F Camilli, A AF Seed, Kimberley D. Bodi, Kip L. Kropinski, Andrew M. Ackermann, Hans-Wolfgang Calderwood, Stephen B. Qadri, Firdausi Camilli, Andrew TI Evidence of a Dominant Lineage of Vibrio cholerae-Specific Lytic Bacteriophages Shed by Cholera Patients over a 10-Year Period in Dhaka, Bangladesh SO MBIO LA English DT Article ID TRANSFER-RNA GENES; RIBONUCLEOTIDE REDUCTASE; WEB SERVER; SEQUENCE; GENOMES; COLONIZATION; EPIDEMICS; EVOLUTION; MUTANTS; PHAGE AB Lytic bacteriophages are hypothesized to contribute to the seasonality and duration of cholera epidemics in Bangladesh. However, the bacteriophages contributing to this phenomenon have yet to be characterized at a molecular genetic level. In this study, we isolated and sequenced the genomes of 15 bacteriophages from stool samples from cholera patients spanning a 10-year surveillance period in Dhaka, Bangladesh. Our results indicate that a single novel bacteriophage type, designated ICP1 (for the International Centre for Diarrhoeal Disease Research, Bangladesh cholera phage 1) is present in all stool samples from cholera patients, while two other bacteriophage types, one novel (ICP2) and one T7-like (ICP3), are transient. ICP1 is a member of the Myoviridae family and has a 126-kilobase genome comprising 230 open reading frames. Comparative sequence analysis of ICP1 and related isolates from this time period indicates a high level of genetic conservation. The ubiquitous presence of ICP1 in cholera patients and the finding that the O1 antigen of lipopolysaccharide (LPS) serves as the ICP1 receptor suggest that ICP1 is extremely well adapted to predation of human-pathogenic V. cholerae O1. IMPORTANCE The severe diarrheal disease cholera is caused by the bacterium Vibrio cholerae, which can be transmitted to humans from the aquatic environment. Factors that affect V. cholerae in the environment can impact the occurrence of cholera outbreaks; one of these factors is thought to be the presence of bacterial viruses, or bacteriophages. Bacteriophages that prey on V. cholerae in the environment, and potentially in humans, have not been extensively genetically characterized. Here, we isolated and sequenced the genomes of bacteriophages from cholera patient stool samples collected over a 10-year period in Dhaka, Bangladesh, a region that suffers from regular cholera outbreaks. We describe a unique bacteriophage present in all samples, infer its evolution by sequencing multiple isolates from different patients over time, and identify the host receptor that shows that the bacteriophage specifically predates the serogroup of V. cholerae responsible for the majority of disease occurrences. C1 [Seed, Kimberley D.; Bodi, Kip L.; Camilli, Andrew] Tufts Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02111 USA. [Seed, Kimberley D.; Bodi, Kip L.; Camilli, Andrew] Tufts Univ, Sch Med, Dept Mol Biol & Microbiol, Boston, MA 02111 USA. [Kropinski, Andrew M.] Univ Guelph, Lab Foodborne Zoonoses, Publ Hlth Agcy Canada, Guelph, ON N1G 2W1, Canada. [Kropinski, Andrew M.] Univ Guelph, Dept Mol & Cellular Biol, Guelph, ON N1G 2W1, Canada. [Ackermann, Hans-Wolfgang] Univ Laval, Fac Med, Dept Microbiol, Quebec City, PQ G1K 7P4, Canada. [Calderwood, Stephen B.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Calderwood, Stephen B.] Harvard Univ, Sch Med, Boston, MA USA. [Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, Dhaka 1000, Bangladesh. RP Camilli, A (reprint author), Tufts Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02111 USA. EM andrew.camilli@tufts.edu OI Kropinski, Andrew/0000-0002-6871-6799 FU National Institutes of Health [AI055058, AI058935, AI063079] FX This research was supported by National Institutes of Health grants AI055058 (A. C.), AI058935 (S. B. C.), and AI063079 (F. Q.). A. C. is a Howard Hughes Medical Institute investigator. NR 57 TC 19 Z9 19 U1 2 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD JAN-FEB PY 2011 VL 2 IS 1 AR e00334-10 DI 10.1128/mBio.00334-10 PG 9 WC Microbiology SC Microbiology GA 734XK UT WOS:000288375400018 PM 21304168 ER PT B AU Tian, Z Sun, Y Xiao, PG Wu, EX AF Tian, Ze Sun, Ye Xiao, Peigen Wu, Erxi BA Awaad, AS Kaushik, G Govil, JN BF Awaad, AS Kaushik, G Govil, JN TI Recent Advances in Natural Bioactive Cycloartane Triterpenoids SO MECHANISM AND ACTION OF PHYTOCONSTITUENTS SE Recent Progress in Medicinal Plants LA English DT Article; Book Chapter DE Cycloartane; Triterpenoid; Bioactivity ID BREAST-CANCER CELLS; EXTRACT INHIBITS PROLIFERATION; ASTRAGALOSIDE-IV; BLACK COHOSH; IN-VITRO; CIMICIFUGA-RACEMOSA; LYMPHOCYTE-PROLIFERATION; CYTOTOXIC CYCLOARTANES; ISOPROPANOLIC EXTRACT; CARDIAC-FUNCTION AB Cycloartane triterpenoids are broadly distributed in plants. There has been an increase in the interest in the biological activity of these compounds. The current review summarized the diverse bioactivities of cycloartanes, including anti-tumor, anti-virus, antibacterial, anti-inflammation, immune-regulatory, cardiovascular system, nervous system and hepato-protective effects. These compounds posses unique structures and cellular mechanisms of action and might prove to have potential for medical applications. C1 [Tian, Ze] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sun, Ye] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Urol, Boston, MA 02115 USA. [Tian, Ze; Xiao, Peigen] Chinese Acad Med Sci, Inst Med Plant, Beijing 100094, Peoples R China. [Tian, Ze; Xiao, Peigen] Peking Union Med Coll, Beijing 100094, Peoples R China. [Wu, Erxi] N Dakota State Univ, Dept Pharmaceut Sci, Fargo, ND 58105 USA. RP Tian, Z (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM ze_tian@dfci.harvard.edu NR 84 TC 3 Z9 3 U1 0 U2 0 PU STUDIUM PRESS LLC PI HOUSTON PA PO BOX 722200, HOUSTON, TX 77072 USA BN 978-1-933699-21-9 J9 RECENT PROG MED PLAN PY 2011 VL 31 BP 49 EP 63 PG 15 WC Plant Sciences; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA BWV47 UT WOS:000295059400004 ER PT S AU Kharkwal, GB Sharma, SK Huang, YY De Taboada, L McCarthy, T Hamblin, MR AF Kharkwal, Gitika B. Sharma, Sulbha K. Huang, Ying-Ying De Taboada, Luis McCarthy, Thomas Hamblin, Michael R. BE Hamblin, MR Waynant, RW Anders, J TI Effects of 810 nm laser on mouse primary cortical neurons SO MECHANISMS FOR LOW-LIGHT THERAPY VI SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Mechanisms for Low-Light Therapy VI CY JAN 22-23, 2011 CL San Francisco, CA SP SPIE DE low-level laser therapy; cultured cortical neurons; mitochondrial membrane potential; intracellular calcium; ATP; reactive oxygen species; nitric oxide ID HELIUM-NEON LASER; TERM NEUROLOGICAL DEFICITS; TRAUMATIC BRAIN-INJURY; NITRIC-OXIDE; PROMOTES REGENERATION; FUNCTIONAL RECOVERY; ISCHEMIC-STROKE; ATP SYNTHESIS; SPINAL-CORD; IRRADIATION AB In the past four decades numerous studies have reported the efficacy of low level light (laser) therapy (LLLT) as a treatment for diverse diseases and injuries. Recent studies have shown that LLLT can biomodulate processes in the central nervous system and has been extensively studied as a stroke treatment. However there is still a lack of knowledge on the effects of LLLT at the cellular level in neurons. The present study aimed to study the effect of 810 nm laser on several cellular processes in primary cortical neurons cultured from mouse embryonic brains. Neurons were irradiated with light dose of 0.03, 0.3, 3, 10 and 30 J/cm(2) and intracellular levels of reactive oxygen species, nitric oxide and calcium were measured. The changes in mitochondrial function in response to light were studied in terms of adenosine triphosphate (ATP) and mitochondrial membrane potential (MMP). Light induced a significant increase in calcium, ATP and MMP at lower fluences and a decrease at higher fluence. ROS was induced significantly by light at all light doses. Nitric oxide levels also showed an increase on treatment with light. The results of the present study suggest that LLLT at lower fluences is capable of inducing mediators of cell signaling process which in turn may be responsible for the biomodulatory effects of the low level laser. At higher fluences beneficial mediators are reduced but potentially harmful mediators are increased thus offering an explanation for the biphasic dose response. C1 [Hamblin, Michael R.] Massachusetts Gen Hosp, BAR414, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, BAR414, Wellman Ctr Photomed, 40 Blossom St, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu; hamblin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 NR 42 TC 1 Z9 1 U1 0 U2 3 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-8424-6 J9 PROC SPIE PY 2011 VL 7887 AR 788707 DI 10.1117/12.876664 PG 8 WC Engineering, Biomedical; Optics SC Engineering; Optics GA BXY13 UT WOS:000297594100002 ER PT J AU Curtin, E Hickey, G Kamel, G Davidson, AJ Liao, EC AF Curtin, Eugene Hickey, Graham Kamel, George Davidson, Alan J. Liao, Eric C. TI Zebrafish wnt9a is expressed in pharyngeal ectoderm and is required for palate and lower jaw development SO MECHANISMS OF DEVELOPMENT LA English DT Article DE Wnt; wnt9a; wnt9b; Cleft; Lip; Palate; Craniofacial; Neural crest; Vertebrate; Zebrafish ID NEURAL CREST DEVELOPMENT; TRANSCRIPTION FACTOR AP-2; LIP AND/OR PALATE; CLEFT-PALATE; CRANIOFACIAL DEVELOPMENT; REITERATED WNT; GENE; MICE; MORPHOGENESIS; SPECIFICATION AB Wnt activity is critical in craniofacial morphogenesis. Dysregulation of Wnt/beta-catenin signaling results in significant alterations in the facial form, and has been implicated in cleft palate phenotypes in mouse and man. In zebrafish, we show that wnt9a is expressed in the pharyngeal arch, oropharyngeal epithelium that circumscribes the ethmoid plate, and ectodermal cells superficial to the lower jaw structures. Alcian blue staining of morpholino-mediated knockdown of wnt9a results in loss of the ethmoid plate, absence of lateral and posterior parachordals, and significant abrogation of the lower jaw structures. Analysis of cranial neural crest cells in the sox10:eGFP transgenic demonstrates that the wnt9a is required early during pharyngeal development, and confirms that the absence of Alcian blue staining is due to absence of neural crest derived chondrocytes. Molecular analysis of genes regulating cranial neural crest migration and chondrogenic differentiation suggest that wnt9a is dispensable for early cranial neural crest migration, but is required for chondrogenic development of major craniofacial structures. Taken together, these data corroborate the central role for Wnt signaling in vertebrate craniofacial development, and reveal that wnt9a provides the signal from the pharyngeal epithelium to support craniofacial chondrogenic morphogenesis in zebrafish. (C) 2010 Elsevier Ireland Ltd. All rights reserved. C1 [Curtin, Eugene; Hickey, Graham; Kamel, George; Davidson, Alan J.; Liao, Eric C.] Harvard Univ, Ctr Regenerat Med, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Curtin, Eugene; Hickey, Graham; Kamel, George; Liao, Eric C.] Harvard Univ, Div Plast & Reconstruct Surg, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Liao, EC (reprint author), Harvard Univ, Ctr Regenerat Med, Massachusetts Gen Hosp, Sch Med, CPZN 4256,185 Cambridge St, Boston, MA 02114 USA. EM cliao@partners.org FU Shriners Hospital for Children; Plastic Surgery Education Foundation Basic Science Grant; Amelia Peabody Charity; American Surgical Association; March of Dimes FX This work was funded by the generous support of the Shriners Hospital for Children, Plastic Surgery Education Foundation Basic Science Grant, and the Amelia Peabody Charity Grant. E.C.L. is the recipient of the American Surgical Association Research Fellowship and the March of Dimes Basil O'Connor Starter Scholar Award. NR 56 TC 19 Z9 19 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD JAN-FEB PY 2011 VL 128 IS 1-2 BP 104 EP 115 DI 10.1016/j.mod.2010.11.003 PG 12 WC Developmental Biology SC Developmental Biology GA 719TX UT WOS:000287233700010 PM 21093584 ER PT J AU Trivedi, AN Matula, S Miake-Lye, I Glassman, PA Shekelle, P Asch, S AF Trivedi, Amal N. Matula, Sierra Miake-Lye, Isomi Glassman, Peter A. Shekelle, Paul Asch, Steven TI Systematic Review Comparison of the Quality of Medical Care in Veterans Affairs and Non-Veterans Affairs Settings SO MEDICAL CARE LA English DT Review DE veterans; quality of health care; hospitals, veterans; outcomes and process assessment (health care) ID ACUTE MYOCARDIAL-INFARCTION; FACTOR SURVEILLANCE SYSTEM; PRIVATE-SECTOR HOSPITALS; FEE-FOR-SERVICE; HEALTH-CARE; ADJUSTED MORTALITY; ADVANTAGE PROGRAM; DIABETES CARE; NEW-YORK; VA AB Background: The Veterans Health Administration, the nation's largest integrated delivery system, launched an organizational transformation in the mid 1990s to improve the quality of its care. Purpose: To synthesize the evidence comparing the quality of medical and other nonsurgical care in Veterans Affairs (VA) and non-VA settings. Data Sources: MEDLINE database and bibliographies of retrieved studies. Study Selection: Studies comparing the technical quality of nonsurgical care in VA and US non-VA settings published between 1990 and August 2009. Data Extraction: Two physicians independently reviewed 175 unique studies identified using the search strategy and abstracted data related to 6 domains of study quality. Data Synthesis: Thirty-six studies met the inclusion criteria. All 9 general comparative studies showed greater adherence to accepted processes of care or better health outcomes in the VA compared with care delivered outside the VA. Five studies of mortality following an acute coronary event found no clear survival differences between VA and non-VA settings. Three studies of care processes after an acute myocardial infarction found greater rates of evidence-based drug therapy in VA, and 1 found lower use of clinically-appropriate angiography in the VA. Three studies of diabetes care processes demonstrated a performance advantage for the VA. Studies of hospital mortality found similar risk-adjusted mortality rates in VA and non-VA hospitals. Limitations: Most studies used decade-old data, assessed self-reported service use, or included only a few VA or non-VA sites. Conclusions: Studies that assessed recommended processes of care almost always demonstrated that the VA performed better than non-VA comparison groups. Studies that assessed risk-adjusted mortality generally found similar rates for patients in VA and non-VA settings. C1 [Trivedi, Amal N.] Providence VA Med Ctr, Ctr Syst Outcomes & Qual Chron Dis & Rehabil SOQC, Providence, RI 02908 USA. [Trivedi, Amal N.] Brown Univ, Dept Community Hlth, Alpert Med Sch, Providence, RI 02912 USA. [Matula, Sierra; Miake-Lye, Isomi; Glassman, Peter A.; Shekelle, Paul; Asch, Steven] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv, Los Angeles, CA 90095 USA. [Miake-Lye, Isomi; Glassman, Peter A.; Shekelle, Paul; Asch, Steven] Greater Los Angeles VA Med Ctr, Dept Med, Los Angeles, CA USA. [Glassman, Peter A.; Shekelle, Paul; Asch, Steven] RAND Corp, Santa Monica, CA USA. RP Trivedi, AN (reprint author), Providence VA Med Ctr, Ctr Syst Outcomes & Qual Chron Dis & Rehabil SOQC, 830 Chalkstone Ave, Providence, RI 02908 USA. EM amal.trivedi@va.gov FU Robert Wood Johnson Clinical Scholars Program; Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development FX This material is based upon work supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development. Dr. Matula received funding from the Robert Wood Johnson Clinical Scholars Program. NR 53 TC 53 Z9 53 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD JAN PY 2011 VL 49 IS 1 BP 76 EP 88 DI 10.1097/MLR.0b013e3181f53575 PG 13 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 695XW UT WOS:000285407100011 PM 20966778 ER PT J AU Min, LC Reuben, DB Keeler, E Ganz, DA Fung, CH Shekelle, P Roth, CP Wenger, NS AF Min, Lillian C. Reuben, David B. Keeler, Emmett Ganz, David A. Fung, Constance H. Shekelle, Paul Roth, Carol P. Wenger, Neil S. TI Is Patient-Perceived Severity of a Geriatric Condition Related to Better Quality of Care? SO MEDICAL CARE LA English DT Article DE quality of care; urinary incontinence; falls ID CORONARY-ARTERY-DISEASE; URINARY-INCONTINENCE; ELDERLY-PATIENTS; SEX-DIFFERENCES; BLOOD-PRESSURE; OLDER PATIENTS; DIABETES CARE; MANAGED CARE; MEDICAL-CARE; FOLLOW-UP AB Background: Care for falls and urinary incontinence (UI) among older patients is inadequate. One possible explanation is that physicians provide less recommended care to patients who are not as concerned about their falls and UI. Objective: To test whether patient-reported severity for 2 geriatric conditions, falls, and UI, is associated with quality of care. Research Design: Prospective cohort study of elders with falls and/or fear of falling (n = 384) and UI (n = 163). Subjects: Participants in the Assessing Care of Vulnerable Elders-2 Study (2002-2003), which evaluated an intervention to improve the care for falls and UI among older (age, >= 75) ambulatory care patients with falls/fear of falling or UI. Measures: Falls Efficacy Scale (FES) and the Incontinence Quality of Life surveys measured at baseline, quality of care measured by a 13-month medical record abstraction. Results: There was a small difference in falls quality scores across the range of FES, with greater patient-perceived falls severity associated with better odds of passing falls quality indicators (OR: 1.11 [95% CI: 1.02-1.21] per 10-point increment in FES). Greater patient-perceived UI severity (Incontinence Quality of Life score) was not associated with better quality of UI care. Conclusions: Although older persons with greater patient-perceived falls severity receive modestly better quality of care, those with more distressing incontinence do not. For both conditions, however, even the most symptomatic patients received less than half of recommended care. Low patient-perceived severity of condition is not the basis of poor care for falls and UI. C1 [Min, Lillian C.] Univ Michigan, Sch Med, Div Geriatr, Dept Med, Ann Arbor, MI 48109 USA. [Reuben, David B.; Fung, Constance H.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Geriatr, Los Angeles, CA 90095 USA. [Keeler, Emmett; Ganz, David A.; Shekelle, Paul; Wenger, Neil S.] Univ Calif Los Angeles, David Geffen Sch Med, Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA. [Shekelle, Paul; Roth, Carol P.; Wenger, Neil S.] RAND Hlth, Santa Monica, CA USA. [Ganz, David A.; Shekelle, Paul] Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. RP Min, LC (reprint author), Univ Michigan, Sch Med, Div Geriatr, Dept Med, 300 N Ingalls Bldg,Wing E,Room 966, Ann Arbor, MI 48109 USA. EM lmin@med.umich.edu FU AHRQ [R21 HS017621]; NIA-UCLA [K12 AG001004]; U.S. Department of Veterans Affairs, Veterans Health Administration; VA Health Services Research & Development (HSR&D) Service through the VA Greater Los Angeles HSR& D Center of Excellence [VA CD2 08-012-1]; National Institute of Aging [AG028748] FX Dr. Min is supported by the AHRQ (R21 HS017621). Dr. Min was on the UCLA faculty during the writing of this manuscript, supported by NIA-UCLA (K12 AG001004). Dr. Ganz is funded by the U.S. Department of Veterans Affairs, Veterans Health Administration, VA Health Services Research & Development (HSR&D) Service through the VA Greater Los Angeles HSR& D Center of Excellence (Project # VA CD2 08-012-1). This research was also supported by the UCLA Claude Pepper Older Americans Independence Center funded by the National Institute of Aging (AG028748). NR 50 TC 1 Z9 1 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD JAN PY 2011 VL 49 IS 1 BP 101 EP 107 DI 10.1097/MLR.0b013e3181f53523 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 695XW UT WOS:000285407100014 PM 21079526 ER PT J AU Siddiqui, MM McDougal, WS AF Siddiqui, Mohummad Minhaj McDougal, W. Scott TI Urologic Assessment of Decreasing Renal Function SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article DE Renal failure; Renal insufficiency; GFR; Obstructive uropathy ID GLOMERULAR-FILTRATION-RATE; URETERAL OBSTRUCTION; SERUM CREATININE; PREDICTION; MANAGEMENT; CLEARANCE; EQUATION; UROPATHY; FAILURE; KIDNEY AB The discussion of renal failure as it relates to urology is largely a discussion of obstructive uropathy. Obstructive uropathy has been identified in multiple series to account for approximately 10% of all cases of renal failure. On a total population scale, autopsy series have shown the prevalence of hydronephrosis in 3% of men and women who are younger than 65 years and 6% of men older than 65 years. When benign prostatic hypertrophy and renal stone disease are considered, obstructive uropathy is also one of the most common indications for surgery. In this review, the different causes of obstructive renal insufficiency and management options available are discussed. C1 [Siddiqui, Mohummad Minhaj; McDougal, W. Scott] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. RP Siddiqui, MM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Urol, 55 Fruit St GRB 1102, Boston, MA 02114 USA. EM mmsiddiqui@partners.org OI Siddiqui, Mohummad/0000-0002-4484-6820 NR 18 TC 3 Z9 3 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD JAN PY 2011 VL 95 IS 1 BP 161 EP + DI 10.1016/j.mcna.2010.08.031 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 697BA UT WOS:000285486400014 PM 21095419 ER PT J AU Schroy, PC Emmons, K Peters, E Glick, JT Robinson, PA Lydotes, MA Mylvanaman, S Evans, S Chaisson, C Pignone, M Prout, M Davidson, P Heeren, TC AF Schroy, Paul C., III Emmons, Karen Peters, Ellen Glick, Julie T. Robinson, Patricia A. Lydotes, Maria A. Mylvanaman, Shamini Evans, Stephen Chaisson, Christine Pignone, Michael Prout, Marianne Davidson, Peter Heeren, Timothy C. TI The Impact of a Novel Computer-Based Decision Aid on Shared Decision Making for Colorectal Cancer Screening: A Randomized Trial SO MEDICAL DECISION MAKING LA English DT Article DE preferences and quality of life; clinical prediction rules; risk stratification; decision aids; patient decision making; provider decision making; physician-patient communication; shared decision making ID SERVICES TASK-FORCE; PATIENT PREFERENCES; COLON-CANCER; ASYMPTOMATIC ADULTS; CLINICAL GUIDELINES; ADENOMATOUS POLYPS; PRIMARY-CARE; RISK; SURVEILLANCE; PREDICTORS AB Background. Eliciting patients' preferences within a framework of shared decision making (SDM) has been advocated as a strategy for increasing colorectal cancer (CRC) screening adherence. Our objective was to assess the effectiveness of a novel decision aid on SDM in the primary care setting. Methods. An interactive, computer-based decision aid for CRC screening was developed and evaluated within the context of a randomized controlled trial. A total of 665 average-risk patients (mean age, 57 years; 60% female; 63% black, 6% Hispanic) were allocated to 1 of 2 intervention arms (decision aid alone, decision aid plus personalized risk assessment) or a control arm. The interventions were delivered just prior to a scheduled primary care visit. Outcome measures (patient preferences, knowledge, satisfaction with the decision-making process [ SDMP], concordance between patient preference and test ordered, and intentions) were evaluated using prestudy/poststudy visit questionnaires and electronic scheduling. Results. Overall, 95% of patients in the intervention arms identified a preferred screening option based on values placed on individual test features. Mean cumulative knowledge, SDMP, and intention scores were significantly higher for both intervention groups compared with the control group. Concordance between patient preference and test ordered was 59%. Patients who preferred colonoscopy were more likely to have a test ordered than those who preferred an alternative option (83% v. 70%; P < 0.01). Intention scores were significantly higher when the test ordered reflected patient preferences. Conclusions. Our interactive computer-based decision aid facilitates SDM, but overall effectiveness is determined by the extent to which providers comply with patient preferences. C1 [Schroy, Paul C., III; Glick, Julie T.; Robinson, Patricia A.; Lydotes, Maria A.; Mylvanaman, Shamini; Davidson, Peter] Boston Univ Sch Med, Dept Med, Boston, MA USA. [Emmons, Karen] Dana Farber Canc Inst, Boston, MA 02115 USA. [Peters, Ellen] Decis Res, Eugene, OR USA. [Evans, Stephen; Chaisson, Christine] Boston Univ Sch Publ Hlth, Data Coordinating Ctr, Boston, MA USA. [Pignone, Michael] Univ N Carolina, Dept Med, Chapel Hill, NC USA. [Pignone, Michael] Boston Univ Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Heeren, Timothy C.] Boston Univ Sch Publ Hlth, Dept Biostat, Boston, MA USA. RP Schroy, PC (reprint author), Boston Med Ctr, 85 E Concord St,Suite 7715, Boston, MA 02118 USA. EM paul.schroy@bmc.org OI Prout, Marianne/0000-0001-8747-6199; Chaisson, Christine/0000-0002-3207-9257; Heeren, Timothy/0000-0001-5643-3559; Pignone, Michael/0000-0002-6657-7342 FU Agency for Healthcare Research and Quality [R01HS013912] FX We thank Linda Rosen, MSEE, from the Office of Clinical Research, Boston University School of Medicine, and Daniel Newman, MD, from the Department of Medicine, Boston Medical Center, for their technical support and Jingshun Yang, MS, from the Data Coordinating Center, Boston University School of Public Health, for data management services. Funding support: Agency for Healthcare Research and Quality grant R01HS013912 (PCS). NR 52 TC 37 Z9 37 U1 4 U2 13 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD JAN-FEB PY 2011 VL 31 IS 1 BP 93 EP 107 DI 10.1177/0272989X10369007 PG 15 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 717CQ UT WOS:000287021000011 PM 20484090 ER PT J AU Allen, JD Othus, MKD Hart, A Mohllajee, AP Li, Y Bowen, D AF Allen, Jennifer D. Othus, Megan K. D. Hart, Alton, Jr. Mohllajee, Anshu P. Li, Yi Bowen, Deborah TI Do Men Make Informed Decisions about Prostate Cancer Screening? Baseline Results from the "Take the Wheel" Trial SO MEDICAL DECISION MAKING LA English DT Article DE prostate cancer screening; informed decision making; decision aids; worksite interventions; employee health ID RANDOMIZED CONTROLLED-TRIAL; HEALTH INTERVIEW SURVEY; ANTIGEN TEST USE; ASSESSING PERCEPTIONS; AIDS; METAANALYSIS; MORTALITY; EDUCATION; ACCURACY; BREAST AB Background. The efficacy of prostate cancer (CaP) screening with the prostate-specific antigen (PSA) test is debated. Most medical organizations recommend that men make individual, informed decisions about whether to undergo screening. Informed decision making (IDM) requires adequate knowledge about CaP as well as the risks and benefits of screening; confidence in the ability to participate in decision making at a personally desired level (decision self-efficacy); and decision making that reflects one's values and preferences (decisional consistency). Methods. Baseline data from a randomized trial in 12 worksites were analyzed. Men aged 45+ (n = 812) completed surveys documenting screening history, screening preferences and decisions, CaP knowledge, decision self-efficacy, and decisional consistency. Psychosocial and demographic correlates of IDM were also assessed. Results. Approximately half of the sample had a prior PSA test, although only 35% reported having made an explicit screening decision. Across the sample, CaP knowledge was low (mean = 56%), although decision self-efficacy was high (mean = 78%), and the majority of men (81%) made decisions consistent with their stated values. Compared with those who were undecided, men who made an explicit screening decision had significantly higher levels of knowledge, greater decisional self-efficacy, and were more consistent in terms of making a decision in alignment with their values. They tended to be white, have high levels of income and education, and had discussed screening with their health care provider. Conclusions. Many men undergo CaP screening without being fully informed about the decision. These findings support the need for interventions aimed at improving IDM about screening, particularly among men of color, those with lower levels of income and education, and those who have not discussed screening with their provider. C1 [Allen, Jennifer D.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Allen, Jennifer D.] Harvard Univ, Sch Med, Boston, MA USA. [Othus, Megan K. D.; Li, Yi] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Hart, Alton, Jr.] Virginia Commonwealth Univ, Richmond, VA USA. [Bowen, Deborah] Boston Univ, Sch Publ Hlth, Boston, MA USA. RP Allen, JD (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, 44 Binney St, Boston, MA 02115 USA. EM jennifer_allen@dfci.harvard.edu RI Allen, Jennifer/M-2113-2015 FU Centers for Disease Control and Prevention [3U48DP000064-01S1] FX This study was funded by the Centers for Disease Control and Prevention (Grant 3U48DP000064-01S1, SIP 21-04 Community Intervention to Increase IDM for Prostate Cancer). NR 50 TC 9 Z9 9 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD JAN-FEB PY 2011 VL 31 IS 1 BP 108 EP 120 DI 10.1177/0272989X10369002 PG 13 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 717CQ UT WOS:000287021000012 PM 20484092 ER PT J AU Schenker, Y Fernandez, A Sudore, R Schillinger, D AF Schenker, Yael Fernandez, Alicia Sudore, Rebecca Schillinger, Dean TI Interventions to Improve Patient Comprehension in Informed Consent for Medical and Surgical Procedures: A Systematic Review SO MEDICAL DECISION MAKING LA English DT Review DE informed consent; intervention; comprehension; understanding; interpersonal communication ID RANDOMIZED CONTROLLED-TRIAL; INTERACTIVE VIDEO PROGRAM; ELECTROCONVULSIVE-THERAPY; PREANESTHETIC INFORMATION; WRITTEN INFORMATION; CLINICAL DECISIONS; BACK SURGERY; RECALL; FORMS; COLONOSCOPY AB Background. Patient understanding in clinical informed consent is often poor. Little is known about the effectiveness of interventions to improve comprehension or the extent to which such interventions address different elements of understanding in informed consent. Purpose. To systematically review communication interventions to improve patient comprehension in informed consent for medical and surgical procedures. Data Sources. A systematic literature search of English-language articles in MEDLINE (1949-2008) and EMBASE (1974-2008) was performed. In addition, a published bibliography of empirical research on informed consent and the reference lists of all eligible studies were reviewed. Study Selection. Randomized controlled trials and controlled trials with non-random allocation were included if they compared comprehension in informed consent for a medical or surgical procedure. Only studies that used a quantitative, objective measure of understanding were included. All studies addressed informed consent for a needed or recommended procedure in actual patients. Data Extraction. Reviewers independently extracted data using a standardized form. All results were compared, and disagreements were resolved by consensus. Data Synthesis. Forty-four studies were eligible. Intervention categories included written information, audiovisual/multimedia, extended discussions, and test/feedback techniques. The majority of studies assessed patient understanding of procedural risks; other elements included benefits, alternatives, and general knowledge about the procedure. Only 6 of 44 studies assessed all 4 elements of understanding. Interventions were generally effective in improving patient comprehension, especially regarding risks and general knowledge. Limitations. Many studies failed to include adequate description of the study population, and outcome measures varied widely. Conclusions. A wide range of communication interventions improve comprehension in clinical informed consent. Decisions to enhance informed consent should consider the importance of different elements of understanding, beyond procedural risks, as well as feasibility and acceptability of the intervention to clinicians and patients. Conceptual clarity regarding the key elements of informed consent knowledge will help to focus improvements and standardize evaluations. C1 [Schenker, Yael; Fernandez, Alicia; Sudore, Rebecca; Schillinger, Dean] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Schenker, Yael] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Sudore, Rebecca] San Francisco VA Med Ctr, Hlth Serv Res & Dev, San Francisco, CA USA. [Schillinger, Dean] Univ Calif San Francisco, Ctr Vulnerable Populat, San Francisco Gen Hosp, San Francisco, CA 94143 USA. RP Schenker, Y (reprint author), Univ Calif San Francisco, Dept Med, 1001 Potrero Ave,Bldg 10,Ward 3, San Francisco, CA 94143 USA. EM yael.schenker@ucsf.edu FU Department of Health and Human Services, Health Resources and Services Administration [DHHS HRSA D55HP05165]; National Institutes of Health [K23-RR018324-01, UL1 RR02413]; NIA [K-23 AG030344-02]; Pfizer; VA Career Development Award FX Received 13 August 2009 from the Department of Medicine, University of California, San Francisco (YS, AF, RS, DS); Department of Epidemiology, University of California, San Francisco (YS); Health Services Research and Development, San Francisco Veterans Affairs Medical Center, San Francisco, California (RS); and the University of California, San Francisco, Center for Vulnerable Populations at San Francisco General Hospital (DS). Dr. Schenker was supported by the General Internal Medicine Fellowship at the University of California, San Francisco, funded by the Department of Health and Human Services, Health Resources and Services Administration (DHHS HRSA D55HP05165). Dr. Fernandez was supported by a National Institutes of Health Career Development Award (K23-RR018324-01). Dr. Sudore was supported first by an NIA Mentored Clinical Scientist Award K-23 AG030344-02 and then a VA Career Development Award and a Pfizer Fellowship in Clear Health Communication. Dr. Schillinger was supported by a grant from the National Institutes of Health (UL1 RR02413). Revision accepted for publication 16 January 2010. NR 76 TC 85 Z9 85 U1 6 U2 26 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X EI 1552-681X J9 MED DECIS MAKING JI Med. Decis. Mak. PD JAN-FEB PY 2011 VL 31 IS 1 BP 151 EP 173 DI 10.1177/0272989X10364247 PG 23 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 717CQ UT WOS:000287021000016 PM 20357225 ER PT J AU Li, XH Zhang, D Liu, B AF Li, Xinhua Zhang, Da Liu, Bob TI Sensitivity analysis of a geometric calibration method using projection matrices for digital tomosynthesis systems SO MEDICAL PHYSICS LA English DT Article ID CT AB Purpose: To study the sensitivity of a geometric calibration method using projection matrices for digital tomosynthesis systems. Methods: A generic geometric calibration method for tomographic imaging systems has been presented in our previous work. The method involves a scan of a calibration phantom with multiple markers. Their locations in projection images are detected and are associated with their 3D coordinates to compute 3 X 4 projection matrices, which can be used in subsequent image reconstruction. The accuracy of geometric calibration may be affected by errors in the input data of marker positions. The effects of errors may depend on the number of markers and the volume surrounded by them in 3D space. This work analyzed the sensitivity of the calibration method to the above factors. A 6 cm CIRS breast research phantom and a prototype breast tomosynthesis system were used for our tests. A high contrast ring and two small speck groups were reconstructed in various testing cases for comparison. To achieve quantitative assessment, a 15 X 15 point detection mask was adopted for detecting signals and for computing changes between testing cases and the regular geometric calibration. Results: When 3D coordinates and 2D projections of markers were accurate, all tested numbers of markers, 6-44, provided similar high quality reconstructions of the ring and the two speck groups. Errors in marker positions resulted in image degradations and signal changes, which increased with fewer markers and smaller volume surrounded by markers in the 3D object space. Signal changes of small specks were more significant than those of the ring. Errors in marker projections produced drastic image degradations. Coplanar marker placement caused a failure in projection matrix computation. Conclusions: For practical geometric calibration phantom design, ample markers are desired. They need to have a large volumetric coverage in the 3D space and be far from being coplanar. Precise determination of marker projections on detector planes is crucial for accurate geometric calibration and for small object detection using the reconstructed images. (C) 2011 American Association of Physicists in Medicine. [DOI: 10.1118/1.3524221] C1 [Li, Xinhua; Zhang, Da; Liu, Bob] Massachusetts Gen Hosp, Dept Radiol, Div Diagnost Imaging Phys, Boston, MA 02114 USA. RP Li, XH (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Diagnost Imaging Phys, Boston, MA 02114 USA. EM bliu7@bics.bwh.harvard.edu NR 12 TC 6 Z9 6 U1 1 U2 6 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 JAN PY 2011 VL 38 IS 1 BP 202 EP 209 DI 10.1118/1.3524221 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 700UM UT WOS:000285769800021 PM 21361188 ER PT J AU Winey, B Sharp, G Bussiere, M AF Winey, Brian Sharp, Greg Bussiere, Marc TI A fast double template convolution isocenter evaluation algorithm with subpixel accuracy SO MEDICAL PHYSICS LA English DT Article ID LINEAR-ACCELERATOR; RADIOSURGERY AB Purpose: To design a fast Winston Lutz (fWL) algorithm for accurate analysis of radiation isocenter from images without edge detection or center of mass calculations. Methods: An algorithm has been developed to implement the Winston Lutz test for mechanical/radiation isocenter agreement using an electronic portal imaging device (EPID). The algorithm detects the position of the radiation shadow of a tungsten ball within a stereotactic cone. The fWL algorithm employs a double convolution to independently find the position of the sphere and cone centers. Subpixel estimation is used to achieve high accuracy. Results of the algorithm were compared to (1) a human observer with template guidance and (2) an edge detection/center of mass (edCOM) algorithm. Testing was performed with high resolution (0.05mm/px, film) and low resolution (0.78mm/px, EPID) image sets. Results: Sphere and cone center relative positions were calculated with the fWL algorithm for high resolution test images with an accuracy of 0.002 +/- 0.061 mm compared to 0.042 +/- 0.294 mm for the human observer, and 0.003 +/- 0.038 mm for the edCOM algorithm. The fWL algorithm required 0.01 s per image compared to 5 s for the edCOM algorithm and 20 s for the human observer. For lower resolution images the fWL algorithm localized the centers with an accuracy of 0.083 +/- 0.12 mm compared to 0.03 +/- 0.5514 mm for the edCOM algorithm. Conclusions: A fast (subsecond) subpixel algorithm has been developed that can accurately determine the center locations of the ball and cone in Winston Lutz test images without edge detection or COM calculations. (C) 2011 American Association of Physicists in Medicine. [DOI: 10.1118/1.3524227] C1 [Winey, Brian; Sharp, Greg; Bussiere, Marc] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Winey, B (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. EM winey.brian@mgh.harvard.edu NR 5 TC 8 Z9 8 U1 0 U2 3 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 JAN PY 2011 VL 38 IS 1 BP 223 EP 227 DI 10.1118/1.3524227 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 700UM UT WOS:000285769800023 PM 21361190 ER PT J AU Aristophanous, M Rottmann, J Court, LE Berbeco, RI AF Aristophanous, M. Rottmann, J. Court, L. E. Berbeco, R. I. TI EPID-guided 3D dose verification of lung SBRT SO MEDICAL PHYSICS LA English DT Article DE EPID dosimetry; tumor tracking; delivered fluence; treatment verification ID STEREOTACTIC BODY RADIOTHERAPY; RADIATION-THERAPY; MARKER TRACKING; CANCER; MOTION; BEAMS; ALGORITHM; MOSFET; TUMOR; RECONSTRUCTION AB Purpose: To investigate the feasibility of utilizing tumor tracks from electronic portal imaging device (EPID) images taken during treatment to verify the delivered dose. Methods: The proposed method is based on a computation of the delivered fluence by utilizing the planned fluence and the tumor motion track for each field. A phantom study was designed to assess the feasibility of the method. The CIRS dynamic thorax phantom was utilized with a realistic soft resin tumor, modeled after a real patient tumor. The dose calculated with the proposed method was compared to direct measurements taken with 15 metal oxide semiconductor field effect transistors (MOSFETs) inserted in small fissures made in the tumor model. The phantom was irradiated with the tumor static and moved with different range of motions and setup errors. EPID images were recorded throughout all deliveries and the tumor model was tracked post-treatment with in-house developed software. The planned fluence for each field was convolved with the tumor motion tracks to obtain the delivered fluence. Utilizing the delivered fluence from each field, the delivered dose was calculated. The estimated delivered dose was compared to the dose directly measured with the MOSFETs. The feasibility of the proposed method was also demonstrated on a real lung cancer patient, treated with stereotactic body radiotherapy. Results: The calculation of delivered dose with the delivered fluence method was in good agreement with the MOSFET measurements, with average differences ranging from 0.8% to 8.3% depending on the proximity of a dose gradient. For the patient treatment, the planned and delivered dose volume histograms were compared and verified the overall good coverage of the target volume. Conclusions: The delivered fluence method was applied successfully on phantom and clinical data and its accuracy was evaluated. Verifying each treatment fraction may enable correction strategies that can be applied during the course of treatment to ensure the desired dose coverage. (C) 2011 American Association of Physicists in Medicine. [DOI: 10.1118/1.3532821] C1 [Aristophanous, M.] Brigham & Womens Hosp, Dana Farber Canc Ctr, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Aristophanous, M (reprint author), Brigham & Womens Hosp, Dana Farber Canc Ctr, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. EM maristophanous@lroc.harvard.edu NR 26 TC 8 Z9 8 U1 1 U2 10 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 JAN PY 2011 VL 38 IS 1 BP 495 EP 503 DI 10.1118/1.3532821 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 700UM UT WOS:000285769800051 PM 21361218 ER PT J AU Finn, K Chiappa, V Puig, A Hunt, DP AF Finn, Kathleen Chiappa, Victor Puig, Alberto Hunt, Daniel P. TI How to become a better clinical teacher: A collaborative peer observation process SO MEDICAL TEACHER LA English DT Article ID MEDICAL-EDUCATION; ATTENDING PHYSICIANS; PERSPECTIVES; CHALLENGES; ROUNDS AB Background: Peer observation of teaching (PoT) is most commonly done as a way of evaluating educators in lecture or small group teaching. Teaching in the clinical environment is a complex and hectic endeavor that requires nimble and innovative teaching on a daily basis. Most junior faculty start their careers with little formal training in education and with limited opportunity to be observed or to observe more experienced faculty. Aim: Formal PoT would potentially ameliorate these challenges. Methods: This article describes a collaborative peer observation process that a group of 11 clinician educators is using as a longitudinal faculty development program. Results: The process described in this article provides detailed and specific teaching feedback for the observed teaching attending while prompting the observing faculty to reflect on their own teaching style and to borrow effective teaching techniques from the observation. Conclusion: This article provides detailed examples from written feedback obtained during collaborative peer observation to emphasize the richness of this combined experience. C1 [Hunt, Daniel P.] Massachusetts Gen Hosp, Inpatient Clinician Educator Serv, Dept Med, Boston, MA 02114 USA. RP Hunt, DP (reprint author), Massachusetts Gen Hosp, Inpatient Clinician Educator Serv, Dept Med, 50 Staniford St,Suite 503B, Boston, MA 02114 USA. EM dphunt@partners.org NR 26 TC 15 Z9 15 U1 2 U2 17 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0142-159X J9 MED TEACH JI Med. Teach. PY 2011 VL 33 IS 2 BP 151 EP 155 DI 10.3109/0142159X.2010.541534 PG 5 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 715XK UT WOS:000286928300018 PM 21275544 ER PT J AU Wittenberg-Lyles, EM Shaunfield, S Goldsmith, J Sanchez-Reilly, S AF Wittenberg-Lyles, Elaine M. Shaunfield, Sara Goldsmith, Joy Sanchez-Reilly, Sandra TI How we involved bereaved family caregivers in palliative care education SO MEDICAL TEACHER LA English DT Editorial Material ID STUDENTS AB As palliative care coursework continues to proliferate within US medical education, novel curriculum approaches have included the use of cancer survivors and family caregivers. We included bereaved family caregivers in structured clinical teaching. Methods: First year students were exposed to a lecture about death and dying and then met with a bereaved caregiver in small groups of 10-15 for a presentation about the caregiving experience, bereavement, and question and answer period. Substantial pre-planning was involved to recruit caregivers and arrange for classroom space. Results: Participation evoked caregiver anxiety but was resolved with adequate arrangement of the classroom and student introductions. Conclusions: Future implementation of bereaved caregivers in palliative coursework should include an appropriate follow-up phone call as well as recruiting more caregivers than necessary for the curriculum. C1 [Wittenberg-Lyles, Elaine M.] Univ N Texas, Dept Commun Studies, Denton, TX 76203 USA. [Goldsmith, Joy] Young Harris Coll, Dept Commun, Young Harris, GA USA. [Sanchez-Reilly, Sandra] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Wittenberg-Lyles, EM (reprint author), Univ N Texas, Dept Commun Studies, 1155 Union Circle 305268, Denton, TX 76203 USA. EM lyles@unt.edu NR 8 TC 2 Z9 2 U1 0 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0142-159X J9 MED TEACH JI Med. Teach. PY 2011 VL 33 IS 5 BP 351 EP 353 DI 10.3109/0142159X.2011.530318 PG 3 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 754KR UT WOS:000289854000009 PM 21517682 ER PT J AU Certain, LK Guarino, AJ Greenwald, JL AF Certain, Laura K. Guarino, A. J. Greenwald, Jeffrey L. TI Effective multilevel teaching techniques on attending rounds: A pilot survey and systematic review of the literature SO MEDICAL TEACHER LA English DT Review ID MEDICAL-STUDENTS; LEARNING STYLES; WARD ROUNDS AB Background: While numerous authors acknowledge the challenge of teaching simultaneously to medical students, interns, and residents, few offer specific advice on how to meet that challenge, and none have studied which techniques are most effective. Aims: The purpose of this study was to determine whether multilevel teaching is challenging for attendings, whether trainees feel that teaching on rounds is appropriate to their level, and to define multilevel teaching techniques. Methods: We surveyed attendings and trainees on the internal medicine services at two academic medical centers. Results: Attendings were divided about whether teaching to multiple levels posed a challenge. Trainees reported that the teaching they received was usually appropriate to their level of training. The most effective techniques for multilevel teaching were Broadening (asking "what if'' questions), Targeting (directing questions at specific team members), and Novelty (teaching newly published information), while the least effective were techniques that taught advanced material unfamiliar to most or all of the team. A systematic literature review yielded no studies that focused on multilevel teaching techniques. Conclusions: This article is the first to define and evaluate specific techniques for multilevel instruction in a medical setting and identifies certain techniques as more effective at engaging multiple levels of learners simultaneously. C1 [Certain, Laura K.; Greenwald, Jeffrey L.] Massachusetts Gen Hosp, Dept Med, Inpatient Clinician Educ Serv, Boston, MA 02143 USA. [Guarino, A. J.] Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02143 USA. RP Certain, LK (reprint author), Massachusetts Gen Hosp, Dept Med, Inpatient Clinician Educ Serv, Wang 615,55 Fruit St, Boston, MA 02143 USA. EM lcertain@alumni.princeton.edu NR 32 TC 3 Z9 3 U1 0 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0142-159X J9 MED TEACH JI Med. Teach. PY 2011 VL 33 IS 12 BP E644 EP E650 DI 10.3109/0142159X.2011.610844 PG 7 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 873KT UT WOS:000298882900001 PM 22225446 ER PT J AU Smith, DT Kohlwes, RJ AF Smith, Dustin T. Kohlwes, R. Jeffrey TI Teaching strategies used by internal medicine residents on the wards SO MEDICAL TEACHER LA English DT Article ID CLINICAL TEACHERS; HOUR RESTRICTIONS; STUDENTS; FACULTY; ATTITUDES; PROGRAMS; FEEDBACK; PERCEPTIONS; EDUCATION; SKILLS AB Background: Residents serve as teachers to interns and students in most internal medicine residency programs. Aim: The purpose of our study is to explore what internal medicine residents perceive as effective teaching strategies in the inpatient setting and to formulate a guideline for preparing residents to lead their ward teams. Methods: Housestaff identified as excellent teaching residents were recruited from a large internal medicine residency program. Focus groups were formed and interviews were conducted using open-ended questions. Transcripts of the interviews were reviewed, analyzed, and compared for accuracy by two investigators. The transcripts were then coded to categorize data into similar subjects from which recurrent themes in resident teaching were identified. Results: Twenty-two residents participated in four focus group interviews held in 2008. We identified five principal themes for effective teaching by residents: (T)aking advantage of teaching opportunities, (E)mpowering learners, (A)ssuming the role of leader, (C)reating a learning environment, and (H)abituating the practice of teaching. Conclusion: Strategies for effective teaching by residents exist. The TEACH mnemonic is a resident-identified method of instruction. Use of this tool could enable residency programs to create instructional curricula to prepare their residents and interns to take on the roles of team leaders and teachers. C1 [Smith, Dustin T.] Atlanta Vet Affairs Med Ctr, Med Special Dept, Div Hosp Med, Decatur, GA 30033 USA. [Smith, Dustin T.] Morehouse Sch Med, Atlanta, GA USA. [Smith, Dustin T.] Emory Univ, Sch Med, Atlanta, GA USA. [Kohlwes, R. Jeffrey] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Kohlwes, R. Jeffrey] San Francisco VA Med Ctr, San Francisco, CA USA. RP Smith, DT (reprint author), Atlanta Vet Affairs Med Ctr, Med Special Dept, Div Hosp Med, Decatur, GA 30033 USA. EM dustin.smith2@va.gov FU Department of Veterans Affairs FX The authors recognize Dr Miriam Kuppermann and Dr Patricia Cornett and thank them for their contributions in reviewing our manuscript. This study was supported by the Department of Veterans Affairs (Primary Medical Education Program). NR 35 TC 3 Z9 3 U1 1 U2 5 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0142-159X J9 MED TEACH JI Med. Teach. PY 2011 VL 33 IS 12 BP E697 EP E703 DI 10.3109/0142159X.2011.611838 PG 7 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 873KT UT WOS:000298882900008 PM 22225453 ER PT J AU Carneiro, HA Coleman, JJ Restrepo, A Mylonakis, E AF Carneiro, Herman A. Coleman, Jeffrey J. Restrepo, Alejandro Mylonakis, Eleftherios TI Fusarium Infection in Lung Transplant Patients Report of 6 Cases and Review of the Literature SO MEDICINE LA English DT Article ID INVASIVE FUNGAL-INFECTIONS; VITRO ANTIFUNGAL SUSCEPTIBILITY; DESORPTION/IONIZATION MASS-SPECTROMETRY; LIPOSOMAL AMPHOTERICIN-B; SOLANI SPECIES COMPLEX; BETA-D-GLUCAN; HEMATOLOGIC MALIGNANCIES; VORICONAZOLE TREATMENT; OXYSPORUM INFECTION; CLINICAL-EFFICACY AB Fusarium is a fungal pathogen of immunosuppressed lung transplant patients associated with a high mortality in those with severe and persistent neutropenia. The principle portal of entry for Fusarium species is the airways, and lung involvement almost always occurs among lung transplant patients with disseminated infection. In these patients, the immunoprotective mechanisms of the transplanted lungs are impaired, and they are, therefore, more vulnerable to Fusarium infection. As a result, fusariosis occurs in up to 32% of lung transplant patients. We studied fusariosis in 6 patients following lung transplantation who were treated at Massachusetts General Hospital during an 8-year period and reviewed 3 published cases in the literature. Cases were identified by the microbiology laboratory and through discharge summaries. Patients presented with dyspnea, fever, nonproductive cough, hemoptysis, and headache. Blood tests showed elevated white blood cell counts with granulocytosis and elevated inflammatory markers. Cultures of Fusarium were isolated from bronchoalveolar lavage, blood, and sputum specimens. Treatments included amphotericin B, liposomal amphotericin B, caspofungin, voriconazole, and posaconazole, either alone or in combination. Lung involvement occurred in all patients with disseminated disease and it was associated with a poor outcome. The mortality rate in this group of patients was high (67%), and of those who survived, 1 patient was treated with a combination of amphotericin B and voriconazole, 1 patient with amphotericin B, and 1 patient with posaconazole. Recommended empirical treatment includes voriconazole, amphotericin B or liposomal amphotericin B first-line, and posaconazole for refractory disease. High-dose amphotericin B is recommended for treatment of most cases of fusariosis. The echinocandins (for example, caspofungin, micafungin, anidulafungin) are generally avoided because Fusarium species have intrinsic resistance to them. Treatment should ideally be based on the Fusarium isolate, susceptibility testing, and host-specific factors. Prognosis of fusariosis in the immunocompromised is directly related to a patient's immune status. Prevention of Fusarium infection is recommended with aerosolized amphotericin B deoxycholate, which also has activity against other important fungi. C1 [Carneiro, Herman A.; Coleman, Jeffrey J.; Restrepo, Alejandro; Mylonakis, Eleftherios] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. RP Mylonakis, E (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, 55 Fruit St,Gray Jackson 5,Room GRJ-504, Boston, MA 02114 USA. EM emylonakis@partners.org RI Coleman, Jeffrey/E-2981-2015; OI Coleman, Jeffrey/0000-0001-8579-1996 FU NIH [AI075286]; R21 award [R21A1070569] FX This work was supported by a R01 award AI075286 from the NIH and a R21 award R21A1070569 to EM. NR 129 TC 27 Z9 27 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7974 J9 MEDICINE JI Medicine (Baltimore) PD JAN PY 2011 VL 90 IS 1 BP 69 EP 80 DI 10.1097/MD.0b013e318207612d PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 702AV UT WOS:000285867400007 PM 21200188 ER PT J AU Baggish, AL AF Baggish, Aaron L. TI MYOCARDIAL FUNCTION IN ROWERS RESPONSE SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Letter C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Baggish, AL (reprint author), Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD JAN PY 2011 VL 43 IS 1 BP 193 EP 193 DI 10.1249/MSS.0b013e3181f49261 PG 1 WC Sport Sciences SC Sport Sciences GA 695YW UT WOS:000285410000027 ER PT J AU Kurtz, EG Ridker, PM Rose, LM Cook, NR Everett, BM Buring, JE Rexrode, KM AF Kurtz, Emily G. Ridker, Paul M. Rose, Lynda M. Cook, Nancy R. Everett, Brendan M. Buring, Julie E. Rexrode, Kathryn M. TI Oral postmenopausal hormone therapy, C-reactive protein, and cardiovascular outcomes SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE Cardiovascular diseases; Prevention; Risk factors; Hormones; C-reactive protein ID CORONARY-HEART-DISEASE; RANDOMIZED CONTROLLED-TRIAL; APPARENTLY HEALTHY-MEN; LOW-DOSE ASPIRIN; WOMENS HEALTH; REPLACEMENT THERAPY; PRIMARY PREVENTION; TRANSDERMAL ESTRADIOL; RISK; INFLAMMATION AB Objectives: This study examines C-reactive protein (CRP) levels predicting cardiovascular events (CVEs) among hormone therapy (HT) users and nonusers. Methods: CRP levels are higher in women who use oral HT than those in nonusers; however, whether the same CRP cut-points determine increased cardiovascular risk remains unanswered. CRP was measured at baseline in 10,953 HT users and 15,838 nonusers in the Women's Health Study. In HT nonusers and users, Cox proportional hazard models adjusted for age, cardiovascular risk factors, body mass index, and menopause status were constructed using American Heart Association/Centers for Disease Control and Prevention recommended CRP cut-points for low, average, and high cardiovascular risk as well as HT nonuser- and user-derived quantiles of CRP to predict incident CVEs. Results: CVE risk increased with logarithm CRP for both HT users and nonusers. After adjusting for cardiovascular risk factors including lipids, the multivariable relative risk (RR) per log unit of CRP was 1.27 (95% CI, 1.13-1.44) for HT nonusers and 1.22 (95% CI, 1.07-1.40) for HT users. To compare the risk associated with American Heart Association/Centers for Disease Control and Prevention CRP categories across HT use groups, we fit a model in which nonusers with a CRP level lower than 1 mg/L were the reference group. After adjusting for other risk factors including lipids, HT users with a CRP level of 3 mg/L or higher had an RR of 1.93 (1.38-2.69), whereas nonusers had an RR of 1.92 (1.35-2.72). Conclusions: CRP predicts CVE in a linear relationship among both HT users and nonusers. CRP levels of 3 mg/L or higher were associated with increased cardiovascular risk in both nonusers and HT users. C1 [Kurtz, Emily G.] Vanderbilt Univ, Med Ctr, Div Cardiovasc Med, Nashville, TN USA. [Kurtz, Emily G.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Kurtz, Emily G.; Ridker, Paul M.; Rose, Lynda M.; Cook, Nancy R.; Everett, Brendan M.; Buring, Julie E.; Rexrode, Kathryn M.] Brigham & Womens Hosp, Ctr Cardiovasc Dis Prevent, Boston, MA 02115 USA. [Kurtz, Emily G.; Ridker, Paul M.; Rose, Lynda M.; Cook, Nancy R.; Everett, Brendan M.; Buring, Julie E.; Rexrode, Kathryn M.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Ridker, Paul M.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Ridker, Paul M.; Rose, Lynda M.; Everett, Brendan M.] Harvard Univ, Sch Med, Donald W Reynolds Clin Res Ctr Atherosclerosis, Boston, MA USA. [Ridker, Paul M.] Massachusetts Gen Hosp, Div Cardiovasc Med, Boston, MA 02114 USA. [Cook, Nancy R.; Buring, Julie E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Leducq Ctr Mol & Genet Epidemiol, Boston, MA USA. RP Rexrode, KM (reprint author), 900 Commonwealth Ave E, Boston, MA 02215 USA. EM krexrode@partners.org OI Rexrode, Kathryn/0000-0003-3387-8429 FU Donald W. Reynolds Foundation (Las Vegas, NV); Doris Duke Charitable Foundation (New York, NY); National Institutes of Health [2 T32 HL007411-26A1, 9 K30 RR022298-07]; National Heart, Lung, and Blood Institute [HL-43851, CA-47988]; National Cancer Institute FX The research for this article was supported by grants from the Donald W. Reynolds Foundation (Las Vegas, NV) and the Doris Duke Charitable Foundation (New York, NY). Dr. Kurtz is supported by National Institutes of Health grants 2 T32 HL007411-26A1 and 9 K30 RR022298-07. The Women's Health Study is supported by grants HL-43851 and CA-47988 from the National Heart, Lung, and Blood Institute and the National Cancer Institute. NR 29 TC 9 Z9 10 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD JAN PY 2011 VL 18 IS 1 BP 23 EP 29 DI 10.1097/gme.0b013e3181e750dd PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 699SW UT WOS:000285684100010 PM 20647959 ER PT J AU Ruddy, KJ Gelber, S Ginsburg, ES Schapira, L Abusief, ME Meyer, ME Partridge, AH AF Ruddy, Kathryn J. Gelber, Shari Ginsburg, Elizabeth S. Schapira, Lidia Abusief, Mary E. Meyer, Meghan E. Partridge, Ann H. TI Menopausal symptoms and fertility concerns in premenopausal breast cancer survivors: a comparison to age- and gravidity-matched controls SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE Hot flashes; Menopause, premature; Infertility; Anxiety ID QUALITY-OF-LIFE; SURGICAL ADJUVANT BREAST; YOUNG-WOMEN; PREVENTION; TAMOXIFEN; TRIAL AB Objective: Many young breast cancer survivors experience menopausal symptoms and feel concerned about infertility due to oncologic treatment. However, there has been little research to date comparing young survivors' concerns and symptoms with those of young women of the same age and gravidity in the general population. Methods: We surveyed breast cancer survivors with regular menses after adjuvant chemotherapy and compared them with age-matched, gravidity-matched controls as part of a study to evaluate the effects of chemotherapy on ovarian reserve. All survivors were 1 year or more from diagnosis of early-stage breast cancer, without evidence of recurrence. The survey assessed menopausal symptoms and infertility concerns. Results: The study was stopped after a planned interim analysis of the first 20 matched pairs revealed significantly diminished measures of ovarian reserve in survivors compared with controls. Mean age was 37 years for both groups (range, 31-43 y). Eighty percent of survivors and 25% of controls expressed some concern regarding fertility at the time of the survey (P = 0.001). Survivors were more likely to report bothersome menopausal symptoms than were controls (P = 0.05). An exploratory analysis revealed that menopausal symptoms were greatest in the survivors taking tamoxifen. Conclusions: Young women who remained premenopausal after breast cancer chemotherapy expressed greater concern about fertility and reported more menopausal symptoms than did age- and gravidity-matched controls. This may have been due to cancer diagnosis or treatment, or it may reflect other differences between the survivors and controls in this study. Additional research is warranted to determine how to most effectively address fertility concerns and reduce symptom burden in this population. C1 [Ruddy, Kathryn J.; Gelber, Shari; Meyer, Meghan E.; Partridge, Ann H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ginsburg, Elizabeth S.; Abusief, Mary E.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Schapira, Lidia] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ruddy, KJ (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM kruddy@partners.org FU Lance Armstrong Foundation FX Funding for this study was provided by the Lance Armstrong Foundation. NR 14 TC 24 Z9 24 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD JAN PY 2011 VL 18 IS 1 BP 105 EP 108 DI 10.1097/gme.0b013e3181ef39f8 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 699SW UT WOS:000285684100021 PM 21243735 ER PT B AU Nagaya, M Weir, GC AF Nagaya, Masaki Weir, Gordon C. BE SotoGutierrez, A NavarroAlvarez, N Fox, IJ TI Generation of Insulin-Producing Cells from Adult Mouse Intrahepatic Biliary Epithelial Cells In Vitro SO METHODS IN BIOENGINEERING: CELL TRANSPLANTATION SE Artech House Methods in Bioengineering Series LA English DT Article; Book Chapter DE liver; biliary epithelial cell; Adenovirus; insulin; transdifferentiation ID STEM-CELLS; RAT CHOLANGIOCYTES; PRECURSOR CELLS; LIVER; EXPRESSION; SECRETIN; THERAPY; CULTURE; LINEAGE; NEUROD AB There is great hope that transplantation of insulin-producing cells will be a cure-equivalent for type 1 diabetes. However, two major challenges remain: the shortage of available tissue and the need for immunosuppressive drugs. We hypothesize that transdifferentiation of cells from a patient's own liver into pancreatic beta-cells could resolve the first problem. The bile duct epithelium in the liver seems to have considerable promise as a new source of insulin-producing cells. Because intrahepatic biliary epithelial cells (IHBECs) can serve as progenitors in response to certain stimuli and the cells possess beta-cell progenitor transcription genes. The concept is to obtain a small piece of tissue from a diabetic individual by endoscopic surgery, followed by expansion in vitro and then generation of insulin-producing cells for subsequent autologous transplantation. Herein, we present a strategy for the concept and protocols to expand the IHBECs and generate insulin-producing cells from IHBECs by the ectopic expression of critical beta-cell transcription factors. C1 [Weir, Gordon C.] Joslin Diabet Ctr, Div Res, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Weir, GC (reprint author), Joslin Diabet Ctr, Div Res, Sect Islet Transplantat & Cell Biol, 1 Joslin Pl, Boston, MA 02215 USA. EM gordon.weir@joslin.harvard.edu NR 29 TC 0 Z9 0 U1 0 U2 0 PU ARTECH HOUSE PI NORWOOD PA 685 CANTON ST, NORWOOD, MA 02062 USA BN 978-1-60807-015-2 J9 ARTECH HSE METH BIOE JI Art. Hse. Meth. Bioengr. Ser. PY 2011 BP 47 EP 63 PG 17 WC Cell & Tissue Engineering; Engineering, Biomedical; Transplantation SC Cell Biology; Engineering; Transplantation GA BVP19 UT WOS:000292169800004 ER PT B AU Uygun, BE Soto-Gutierrez, A Yagi, H Izamis, ML Uygun, K Yarmush, M AF Uygun, Basak E. Soto-Gutierrez, Alejandro Yagi, Hiroshi Izamis, Maria Louisa Uygun, Korkut Yarmush, Martin BE Uygun, K Lee, CY TI Preparation of a Transplantable Liver Graft by the Recellularization of a Decellularized Whole Organ SO METHODS IN BIOENGINEERING: ORGAN PRESERVATION AND REENGINEERING SE Artech House Methods in Bioengineering Series LA English DT Article; Book Chapter DE whole organ scaffold; liver tissue engineering; decellularization; heterotopic transplantation ID TISSUES AB Here we describe the methods to develop transplantable liver grafts using perfusion decellularized whole organ scaffolds. The methods include perfusion decellularizaton of rat livers using an anionic detergent to obtain an intact decellularized liver matrix (DLM), which retained the structure of major blood vessels. This matrix is then recellularized in a novel bioreactor with adult primary hepatocytes, creating a liver graft that is functional in vitro. Finally, the heterotopic transplantation of these recellularized grafts demonstrating in vivo viability is described. C1 [Uygun, Basak E.; Soto-Gutierrez, Alejandro; Yagi, Hiroshi; Izamis, Maria Louisa; Uygun, Korkut; Yarmush, Martin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA USA. RP Yarmush, M (reprint author), 51 Blossom St, Boston, MA 02114 USA. EM ireis@sbi.org RI Uygun, Basak/I-1792-2012 OI Uygun, Basak/0000-0002-2600-7900 NR 10 TC 0 Z9 0 U1 0 U2 2 PU ARTECH HOUSE PI NORWOOD PA 685 CANTON ST, NORWOOD, MA 02062 USA BN 978-1-60807-013-8 J9 ARTECH HSE METH BIOE JI Art. Hse. Meth. Bioengr. Ser. PY 2011 BP 161 EP 176 PG 16 WC Cell & Tissue Engineering; Engineering, Biomedical; Transplantation SC Cell Biology; Engineering; Transplantation GA BVN87 UT WOS:000292008900009 ER PT B AU Izamis, ML Calhoun, C Tolboom, H Yarmush, M Uygun, K AF Izamis, Maria-Louisa Calhoun, Candice Tolboom, Herman Yarmush, Martin Uygun, Korkut BE Uygun, K Lee, CY TI Ex Vivo Perfusion of Rat Liver Grafts for Hepatocyte Retrieval SO METHODS IN BIOENGINEERING: ORGAN PRESERVATION AND REENGINEERING SE Artech House Methods in Bioengineering Series LA English DT Article; Book Chapter DE liver; ex vivo perfusion; hepatocyte isolation; ischemia; ischemic ID NORMOTHERMIC EXTRACORPOREAL PERFUSION; MACHINE PERFUSION; COLD-STORAGE; PRESERVATION; TRANSPLANTATION AB Herein we describe a technique for enhancing the available hepatocyte pool by recovering cells from ischemically damaged livers. The methodology utilizes an ex vivo liver perfusion (ELP) system, proven capable of storing fresh livers as well as treating ischemically damaged livers to a transplantable state in a rat model. The system comprises an artificial blood supply, or perfusate, that is pumped through a heater and oxygenator prior to entering the vasculature of the liver. The effluent from the organ is captured in the bowl in which the organ sits, coating it and keeping it at 37 degrees C. The pump draws from this bowl, thereby closing the primary circuit. A secondary circuit uses a different pump to pass the effluent into a dialyzer with a cutoff weight of 30 kDa that communicates with a much larger perfusate reservoir. The dialyzer is impermeable to both albumin (66 kDa) and rat erythrocytes (3 microns). This circuit serves the dual purpose of replenishing nutrients and diluting potentially toxic metabolites while retaining the appropriate hematocrit and oncotic pressure within the primary circuit. We have utilized this technique for the isolation of hepatocytes, enabling a tenfold increase from 60-minute warm ischemic rat livers at a viability of 90% after 5 hours of perfusion. C1 [Uygun, Korkut] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Uygun, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 51 Blossom St, Boston, MA 02114 USA. EM uygun.korkut@mgh.harvard.edu; uygun.korkut@mgh.harvard.edu NR 12 TC 0 Z9 0 U1 0 U2 0 PU ARTECH HOUSE PI NORWOOD PA 685 CANTON ST, NORWOOD, MA 02062 USA BN 978-1-60807-013-8 J9 ARTECH HSE METH BIOE JI Art. Hse. Meth. Bioengr. Ser. PY 2011 BP 213 EP 231 PG 19 WC Cell & Tissue Engineering; Engineering, Biomedical; Transplantation SC Cell Biology; Engineering; Transplantation GA BVN87 UT WOS:000292008900012 ER PT S AU Winnay, JN Kahn, CR AF Winnay, Jonathon N. Kahn, C. Ronald BE Conn, PM TI PI 3-KINASE REGULATORY SUBUNITS AS REGULATORS OF THE UNFOLDED PROTEIN RESPONSE SO METHODS IN ENZYMOLOGY: UNFOLDED PROTEIN RESPONSE AND CELLULAR STRESS, VOL 490, PT B SE Methods in Enzymology LA English DT Review; Book Chapter ID BOX-BINDING PROTEIN-1; P85 ALPHA-GENE; ENDOPLASMIC-RETICULUM; ER STRESS; PHOSPHATIDYLINOSITOL 3-KINASE; MESSENGER-RNA; XBP-1; IRE1; DISEASES; INSULIN AB The endoplasmic reticulum (ER) consists of an interconnected, membranous network that is the major site for the synthesis and folding of integral membrane and secretory proteins. Within the ER lumen, protein folding is facilitated by molecular chaperones and a variety of enzymes that ensure that polypeptides obtain their appropriate, tertiary conformation (Dobson, C. M. (2004). Principles of protein folding, misfolding and aggregation. Semin. Cell Dev. Biol. 15, 3-16; Ni, M., and Lee, A. S. (2007). ER chaperones in mammalian development and human diseases. FEBS Lett. 581, 3641-3651.). Physiological conditions that increase protein synthesis or stimuli that disturb the processes by which proteins obtain their native conformation, create an imbalance between the protein-folding demand and capacity of the ER. This results in the accumulation of unfolded or improperly folded proteins in the ER lumen and a state of ER stress. The cellular response, referred to as the unfolded protein response (UPR), results in activation of three linked signal transduction pathways: PKR-like kinase (PERK), inositol requiring 1 alpha (IRE1 alpha), and activating transcription factor 6 alpha (ATF6 alpha) (Ron, D., and Walter, P. (2007). Signal integration in the endoplasmic reticulum unfolded protein response. Nat. Rev. Mol. Cell. Biol. 8, 519-529; Schroder, M., and Kaufman, R. (2005). ER stress and the unfolded protein response. Mutat. Res./Fundam. Mol. Mech. Mutagen. 569,29-63.). Collectively, the combined actions of these signaling cascades serve to reduce ER stress through attenuation of translation to reduce protein synthesis and through activation of transcriptional programs that ultimately serve to increase ER protein-folding capacity. Recently, we and Park et al. have characterized a novel function for the p85 alpha and p85 beta subunits as modulators of the UPR by virtue of their ability to facilitate the nuclear entry of XBP-1s following induction of ER stress (Park, S. W., Zhou, Y., Lee, J., Lu, A., Sun, C., Chung, J., Ueki, K., and Ozcan, U. (2010). Regulatory subunits of PI3K, p85alpha and p85 beta, interact with XBP1 and increase its nuclear translocation. Nat. Med. 16,429-437; Winnay, J. N., Boucher, J., Mori, M. A., Ueki, K., and Kahn, C. R. (2010). A regulatory subunit of phosphoinositide 3-kinase increases the nuclear accumulation of X-box-binding protein-1 to modulate the unfolded protein response. Nat. Med. 16, 438-445.). This chapter describes the recently elucidated role for the regulatory subunits of PI 3-kinase as modulators of the UPR and provides methods to measure UPR pathway activation. C1 [Winnay, Jonathon N.; Kahn, C. Ronald] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab,Res Div, Boston, MA 02115 USA. RP Winnay, JN (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab,Res Div, Boston, MA 02115 USA. FU NIDDK NIH HHS [R01 DK055545, P30 DK036836] NR 28 TC 5 Z9 5 U1 0 U2 4 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-385114-7 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2011 VL 490 BP 147 EP 158 DI 10.1016/B978-0-12-385114-7.00009-X PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BTP02 UT WOS:000287674900009 PM 21266249 ER PT S AU Sharma, R Tsuchiya, M Tannous, BA Bartlett, JD AF Sharma, Ramaswamy Tsuchiya, Masahiro Tannous, Bakhos A. Bartlett, John D. BE Conn, PM TI MEASUREMENT OF FLUORIDE-INDUCED ENDOPLASMIC RETICULUM STRESS USING GAUSSIA LUCIFERASE SO METHODS IN ENZYMOLOGY, VOL 491: UNFOLDED PROTEIN RESPONSE AND CELLULAR STRESS, PT C SE Methods in Enzymology LA English DT Review; Book Chapter ID IN-VIVO; SECRETORY PATHWAY; BIOLUMINESCENCE; EXPRESSION; FLUOROSIS; CULTURE; CELLS AB Endoplasmic reticulum (ER) stress and its consequent activation of the unfolded protein response (UPR) signaling pathway have been implicated in several pathophysiologic disorders as well as in drug resistance to treatment of tumors. Several techniques have been devised that qualitatively and quantitatively demonstrate the presence of ER stress and the activation of the UPR; however, most of these methods cannot be used to measure ER stress in real time. Here we describe the use of cells stably transduced with a secreted reporter, Gaussia luciferase (Gluc), to measure fluoride-induced ER stress. Factors that affect ER homeostasis, such as high-dose fluoride, will cause decreased Gluc secretion that can be measured as a decrease in Gluc activity in the culture medium supernatant. Gluc catalyzes the oxidative decarboxylation of coelenterazine (CTZ) to coeleneteramide, resulting in blue bioluminescence (lambda(max) 485nm). Therefore, Gluc activity can be easily quantified by mixing a small aliquot of the medium supernatant with CTZ and measuring the resulting bioluminescence in a luminometer. Among the various reporters used so far, Gluc is regarded as the most sensitive indicator of ER stress. A second advantage for using Gluc is its ability to function in a wide pH range. This is especially useful for studying fluoride-mediated toxicity as fluoride-induced stress is enhanced under acidic conditions. Since Gluc can be measured in a noninvasive manner, it has been used in several in vitro and in vivo applications. In this chapter, we detail our methodology for using Gluc to monitor fluoride-induced ER stress. C1 [Sharma, Ramaswamy; Bartlett, John D.] Forsyth Inst, Dept Cytokine Biol, Cambridge, MA 02142 USA. [Sharma, Ramaswamy; Bartlett, John D.] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. [Tsuchiya, Masahiro] Tohoku Univ, Div Aging & Geriatr Dent, Sendai, Miyagi 980, Japan. [Tannous, Bakhos A.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Tannous, Bakhos A.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Tannous, Bakhos A.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. RP Sharma, R (reprint author), Forsyth Inst, Dept Cytokine Biol, Cambridge, MA 02142 USA. RI Sharma, Ramaswamy/F-8401-2012; OI Tsuchiya, Masahiro/0000-0002-7000-4547 NR 23 TC 3 Z9 3 U1 0 U2 3 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-385928-0 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2011 VL 491 BP 111 EP 125 DI 10.1016/B978-0-12-385928-0.00007-9 PG 15 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BTW71 UT WOS:000288293700007 PM 21329797 ER PT B AU Schouten, R Saathoff, GB AF Schouten, Ronald Saathoff, Gregory B. BE Budowle, B Schutzer, SE Breeze, RG Keim, PS Morse, SA TI Biosurety in the Post-9/11 Era SO MICROBIAL FORENSICS, 2ND EDITION LA English DT Article; Book Chapter ID UNITED-STATES; VIOLENCE C1 [Schouten, Ronald] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Law & Psychiat Serv, Boston, MA 02115 USA. [Saathoff, Gregory B.] Univ Virginia, Sch Med, Crit Incident Anal Grp, Charlottesville, VA 22908 USA. RP Schouten, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Law & Psychiat Serv, Boston, MA 02115 USA. NR 27 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-382007-5; 978-0-12-382006-8 PY 2011 BP 221 EP 237 DI 10.1016/B978-0-12-382006-8.00014-1 PG 17 WC Biotechnology & Applied Microbiology; Medicine, Legal SC Biotechnology & Applied Microbiology; Legal Medicine GA BIE39 UT WOS:000327881100016 ER PT J AU Kacmarek, RM Villar, J AF Kacmarek, R. M. Villar, J. TI Lung recruitment maneuvers during acute respiratory distress syndrome: is it useful? SO MINERVA ANESTESIOLOGICA LA English DT Article DE Respiratory distress syndrome, adult; Patient selection; Ventilation ID END-EXPIRATORY PRESSURE; MECHANICAL VENTILATION; PROTECTIVE-VENTILATION; ALVEOLAR RECRUITMENT; SUSTAINED INFLATION; CONTROLLED-TRIAL; TIDAL VOLUME; GAS-EXCHANGE; STRATEGY; INJURY AB Although significant advances have been made in approaches to manage the acute respiratory distress syndrome (ARDS), reported overall mortality for ARDS is still high. Recruitment maneuvers (RM) have been recommended by some as potential adjuncts to lung protective ventilator), approaches in ARDS. In this point of view issues surrounding the use of RM in ARDS are addressed. Specifically, the ability of RM to open the lung, the safety of RM, and their affect on outcome are addressed. Finally, a specific approach to performing RM with the use of a decremental PEEP trial is outlined. (Minerva Anestesiol 2011;77:85-9) C1 [Kacmarek, R. M.] Massachusetts Gen Hosp, Boston, MA 01460 USA. [Kacmarek, R. M.] Harvard Univ, Sch Med, Dept Anesthesiol, Boston, MA USA. [Villar, J.] Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain. [Villar, J.] Hosp Univ Dr Negrin, Res Unit, Multidisciplinary Organ Dysfunct Evaluat Res Netw, Las Palmas Gran Canaria, Spain. RP Kacmarek, RM (reprint author), Massachusetts Gen Hosp, Ellison 401,55 Fruit St, Boston, MA 01460 USA. EM rkacmarek@partners.org FU Instituto de Salud Carlos III in Spain [07/0113] FX JV is supported in part by a grant from the Instituto de Salud Carlos III in Spain (#07/0113). NR 25 TC 21 Z9 29 U1 0 U2 4 PU EDIZIONI MINERVA MEDICA PI TURIN PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY SN 0375-9393 J9 MINERVA ANESTESIOL JI Minerva Anestesiol. PD JAN PY 2011 VL 77 IS 1 BP 85 EP 89 PG 5 WC Anesthesiology; Critical Care Medicine SC Anesthesiology; General & Internal Medicine GA 720RA UT WOS:000287296600015 PM 21273969 ER PT J AU Chiu, A Czader, M Cheng, L Hasserjian, RP Wang, M Bhagavathi, S Hyjek, EM Al-Ahmadie, H Knowles, DM Orazi, A AF Chiu, A. Czader, M. Cheng, L. Hasserjian, R. P. Wang, M. Bhagavathi, S. Hyjek, E. M. Al-Ahmadie, H. Knowles, D. M. Orazi, A. TI Clonal X-chromosome inactivation suggests that splenic cord capillary hemangioma is a true neoplasm and not a subtype of splenic hamartoma SO MODERN PATHOLOGY LA English DT Article DE clonality; cord capillary hemangioma; hamartoma; myoid angioendothelioma; sclerosing angiomatoid nodular transformation; spleen ID ANGIOMATOID-NODULAR-TRANSFORMATION; INFLAMMATORY PSEUDOTUMOR; PLASMA-CELLS; RED PULP; SPLEEN; SANT; ASSOCIATION; METHYLATION; FEATURES; LESIONS AB Splenic hamartoma is a rare tumor-like lesion composed of structurally disorganized red pulp elements. It has been hypothesized that two other splenic lesions, cord capillary hemangioma and myoid angioendothelioma, may fall within the spectrum of splenic hamartoma, simply representing morphological variants. In this study, we compared the vascular and stromal composition of cord capillary hemangioma and myoid angioendothelioma with those of classical hamartoma. In addition, we assessed the clonal vs polyclonal nature of the lesions in nine female cases by performing clonality analysis for X-chromosome inactivation at the human androgen receptor locus (HUMARA) on laser-assisted microdissected samples. In 15 of 17 cases, increased reticulin and/or collagen content was observed. The classical hamartoma cases showed a vasculature predominantly composed of CD8+ CD31+ CD34- splenic sinuses, whereas cases of cord capillary hemangioma and myoid angioendothelioma contained many CD8- CD31+ CD34+ cord capillaries, but very little CD8+ vasculature. All cases lacked expression of D2-40 and Epstein Barr virus-encoded RNA. All cases showed a proliferation index of <= 5% by Ki-67. Cases of classical hamartoma lacked significant perisinusoidal expression of collagen IV and low-affinity nerve growth factor receptor. Both markers were variably expressed in the other lesions. Increased CD163-positive histiocytes were found in four cases (three cord capillary hemangiomas and one myoid angioendothelioma). HUMARA analysis was informative in all nine tested cases, of which three cases showed a non-random X-chromosome inactivation pattern, indicating clonality. All three clonal cases were cord capillary hemangiomas. Our study has shown that in spite of considerable morphologic heterogeneity and overlapping features, classical hamartoma and cord capillary hemangioma and myoid angioendothelioma are different in terms of their vascular and stromal composition. Clonality analysis supports a true neoplastic origin for the cord capillary hemangioma. A larger study using additional immunohistochemical and molecular studies is necessary to further evaluate the biological significance of the current findings. Modern Pathology (2011) 24, 108-116; doi:10.1038/modpathol.2010.168; published online 17 September 2010 C1 [Chiu, A.; Knowles, D. M.; Orazi, A.] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY 10065 USA. [Czader, M.; Cheng, L.; Wang, M.; Bhagavathi, S.] Indiana Univ, Sch Med, Dept Pathol & Lab Med, Indianapolis, IN USA. [Hasserjian, R. P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Hyjek, E. M.; Al-Ahmadie, H.] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. RP Orazi, A (reprint author), Weill Cornell Med Coll, Dept Pathol & Lab Med, 525 E 68th St,Room ST 707, New York, NY 10065 USA. EM ato9002@med.cornell.edu NR 42 TC 3 Z9 3 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2011 VL 24 IS 1 BP 108 EP 116 DI 10.1038/modpathol.2010.168 PG 9 WC Pathology SC Pathology GA 702BG UT WOS:000285868900012 PM 20852592 ER PT J AU Huang, Q Shi, JO Feng, AN Fan, XS Zhang, LH Mashimo, H Cohen, D Lauwers, G AF Huang, Qin Shi, Jiong Feng, Anning Fan, Xiangshan Zhang, Lihua Mashimo, Hiroshi Cohen, Daniel Lauwers, Gregory TI Gastric cardiac carcinomas involving the esophagus are more adequately staged as gastric cancers by the 7th edition of the American Joint Commission on Cancer Staging System SO MODERN PATHOLOGY LA English DT Article DE cancer; esophagus; gastroesophageal junction; staging; stomach ID ESOPHAGOGASTRIC JUNCTION; GASTROESOPHAGEAL JUNCTION; TNM SYSTEMS; ADENOCARCINOMA; CLASSIFICATION; SURVIVAL; METASTASES; CHINESE; BENEFIT; NODES AB The aim of this study was to compare the 7th with the 6th edition of the American Joint Commission on Cancer Staging System for prognostic stratification of gastric cardiac carcinomas involving the esophagus. We retrospectively compared differences in pathological stages with patient survival between the 7th and the 6th staging systems in 142 consecutive resection cases of this cancer. Patient median age was 65 years. The male-female ratio was 3.3. The epicenter of all tumors was within 5 cm below the gastroesophageal junction. The median tumor size was 5.0cm. Most tumors (79%) were typical adenocarcinomas and the rest showed uncommon histology types. Using the guidelines for gastric cancer, this group of cancer was better stratified by the 7th than the 6th edition of the staging system, especially for pathological nodal (pN) and overall stage pIIIC. Patients with celiac axis nodal disease had the 5-year survival rate worse than those staged at pN3A and pIIIA. Patients staged at pT3 and pN3B had the 5-year survival rate worse than those at pM1 and pIV. We showed that the overall stage of gastric cardiac carcinomas was better stratified by gastric than by esophageal cancer grouping. We conclude that these tumors are better stratified with the 7th than the 6th edition of the gastric staging system, especially for pIII cancers, and better staged by the new gastric than esophageal cancer staging system. We propose that the staging of these tumors be reverted to gastric grouping and combine pT3 and pN3B into the overall stage pIV. Modern Pathology (2011) 24, 138-146; doi:10.1038/modpathol.2010.183; published online 17 September 2010 C1 [Huang, Qin] Vet Affairs Boston Healthcare Syst, Dept Pathol & Lab Med, W Roxbury, MA 02132 USA. [Huang, Qin; Shi, Jiong; Feng, Anning; Fan, Xiangshan; Zhang, Lihua] Nanjing Drum Tower Hosp, Dept Pathol, Nanjing, Peoples R China. [Huang, Qin; Mashimo, Hiroshi; Cohen, Daniel; Lauwers, Gregory] Harvard Univ, Sch Med, W Roxbury, MA USA. [Mashimo, Hiroshi] Dept Gastroenterol, W Roxbury, MA USA. [Cohen, Daniel] Vet Affairs Boston Healthcare Syst, Dept Thorac Surg, W Roxbury, MA 02132 USA. [Lauwers, Gregory] Massachusetts Gen Hosp, Dept Pathol, W Roxbury, MA USA. RP Huang, Q (reprint author), Vet Affairs Boston Healthcare Syst, Dept Pathol & Lab Med, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM qinhuang2005@gmail.com FU Science and Technology Development Project of the Nanjing City [200601050]; Nanjing Drum Tower Hospital, Nanjing, China FX This project was financed partially by a grant from the Science and Technology Development Project of the Nanjing City (No. 200601050) and a special grant from the Nanjing Drum Tower Hospital, Nanjing, China. NR 32 TC 28 Z9 36 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2011 VL 24 IS 1 BP 138 EP 146 DI 10.1038/modpathol.2010.183 PG 9 WC Pathology SC Pathology GA 702BG UT WOS:000285868900015 PM 20852593 ER PT J AU Madak-Erdogan, Z Lupien, M Stossi, F Brown, M Katzenellenbogen, BS AF Madak-Erdogan, Zeynep Lupien, Mathieu Stossi, Fabio Brown, Myles Katzenellenbogen, Benita S. TI Genomic Collaboration of Estrogen Receptor alpha and Extracellular Signal-Regulated Kinase 2 in Regulating Gene and Proliferation Programs SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID BREAST-CANCER CELLS; ACTIVATED PROTEIN-KINASE; TARGET GENES; MCF-7 CELLS; MAP KINASE; BETA-CELLS; ER-ALPHA; EXPRESSION; TAMOXIFEN; PHOSPHORYLATION AB The nuclear hormone receptor, estrogen receptor alpha (ER alpha), and mitogen-activated protein kinases (MAPKs) play key roles in hormone-dependent cancers, and yet their interplay and the integration of their signaling inputs remain poorly understood. In these studies, we document that estrogen-occupied ER alpha activates and interacts with extracellular signal-regulated kinase 2 (ERK2), a downstream effector in the MAPK pathway, resulting in ERK2 and ER alpha colocalization at chromatin binding sites across the genome of breast cancer cells. This genomic colocalization, predominantly at conserved distal enhancer sites, requires the activation of both ER alpha and ERK2 and enables ERK2 modulation of estrogen-dependent gene expression and proliferation programs. The ERK2 substrate CREB1 was also activated and recruited to ERK2-bound chromatin following estrogen treatment and found to cooperate with ER alpha/ERK2 in regulating gene transcription and cell cycle progression. Our study reveals a novel paradigm with convergence of ERK2 and ER alpha at the chromatin level that positions this kinase to support nuclear receptor activities in crucial and direct ways, a mode of collaboration likely to underlie MAPK regulation of gene expression by other nuclear receptors as well. C1 [Madak-Erdogan, Zeynep; Stossi, Fabio; Katzenellenbogen, Benita S.] Univ Illinois, Dept Mol & Integrat Physiol, Urbana, IL 61801 USA. [Lupien, Mathieu] Dartmouth Med Sch, Norris Cotton Canc Ctr, Lebanon, NH 03756 USA. [Brown, Myles] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Brown, Myles] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Katzenellenbogen, BS (reprint author), Univ Illinois, Dept Mol & Integrat Physiol, 524 Burrill Hall,407 S Goodwin Ave, Urbana, IL 61801 USA. EM katzenel@uiuc.edu OI Brown, Myles/0000-0002-8213-1658; Madak-Erdogan, Zeynep/0000-0003-2607-1643 FU Breast Cancer Research Foundation; National Institutes of Health [R01 CA18119, P01AG024387, T32ES007326, R01DK074967, P01CA8011105]; DF/HCC Breast Cancer [P50C89393]; U.S. Department of Defense Breast Cancer [W81XWH-08-1-0214] FX This study was supported by grants from the Breast Cancer Research Foundation (to B.S.K.), the National Institutes of Health (R01 CA18119 and P01AG024387 to B.S.K.; T32ES007326 to Z.M.E.; R01DK074967, P01CA8011105, and DF/HCC Breast Cancer SPORE Grant P50C89393 to M.B.), and U.S. Department of Defense Breast Cancer Research Program Award (W81XWH-08-1-0214 to M.L.). NR 42 TC 64 Z9 65 U1 1 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 JAN PY 2011 VL 31 IS 1 BP 226 EP 236 DI 10.1128/MCB.00821-10 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 691PP UT WOS:000285093600018 PM 20956553 ER PT J AU Manor, U Disanza, A Grati, M Andrade, L Lin, H Di Fiore, P Scita, G Kachar, B AF Manor, U. Disanza, A. Grati, M. Andrade, L. Lin, H. Di Fiore, P. Scita, G. Kachar, B. TI Regulation of stereocilia length by myosin XVa and whirlin depends on the actin-regulatory protein Eps8. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2011 CL Denver, CO SP Amer Soc Cell Biol (ASCB) C1 [Manor, U.; Grati, M.; Andrade, L.; Kachar, B.] Natl Inst Deafness & Other Commun Disorders, Lab Cell Struct & Dynam, NIH, Bethesda, MD USA. [Disanza, A.; Di Fiore, P.; Scita, G.] Fdn IFOM, FIRC Inst Mol Oncol, Milan, Italy. [Lin, H.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA USA. FU Associazione Italiana per la Ricerca sul Cancro NR 0 TC 0 Z9 0 U1 0 U2 1 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 PY 2011 VL 22 MA 1403 PG 1 WC Cell Biology SC Cell Biology GA 961YM UT WOS:000305505502516 ER PT J AU Manor, U Disanza, A Grati, M Andrade, L Lin, H Di Fiore, P Scita, G Kachar, B AF Manor, U. Disanza, A. Grati, M. Andrade, L. Lin, H. Di Fiore, P. Scita, G. Kachar, B. TI Regulation of stereocilia length by myosin XVa and whirlin depends on the actin-regulatory protein Eps8 SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2011 CL Denver, CO SP Amer Soc Cell Biol (ASCB) C1 [Manor, U.; Grati, M.; Andrade, L.; Kachar, B.] Natl Inst Deafness & Other Commun Disorders, Lab Cell Struct & Dynam, Bethesda, MD USA. [Disanza, A.; Di Fiore, P.; Scita, G.] Fdn IFOM, FIRC Inst Mol Oncol, Milan, Italy. [Lin, H.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA USA. FU Associazione Italiana per la Ricerca sul Cancro NR 0 TC 0 Z9 0 U1 0 U2 1 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 PY 2011 VL 22 MA 14 PG 2 WC Cell Biology SC Cell Biology GA 961YM UT WOS:000305505500015 ER PT J AU Vartanian, R Masri, J Martin, J Cloninger, C Holmes, B Artinian, N Funk, A Ruegg, T Gera, J AF Vartanian, Raffi Masri, Janine Martin, Jheralyn Cloninger, Cheri Holmes, Brent Artinian, Nicholas Funk, Alex Ruegg, Teresa Gera, Joseph TI AP-1 Regulates Cyclin D1 and c-MYC Transcription in an AKT-Dependent Manner in Response to mTOR Inhibition: Role of AIP4/Itch-Mediated JUNB Degradation SO MOLECULAR CANCER RESEARCH LA English DT Article ID ENHANCED SENSITIVITY; MAMMALIAN TARGET; BINDING-PROTEINS; RAPAMYCIN; PHOSPHORYLATION; EXPRESSION; PROMOTER; KINASE; ACTIVATION; PATHWAY AB One mechanism by which AKT kinase-dependent hypersensitivity to mammalian target of rapamycin (mTOR) inhibitors is controlled is by the differential expression of cyclin D1 and c-MYC. Regulation of posttranscriptional processes has been demonstrated to be crucial in governing expression of these determinants in response to rapamycin. Our previous data suggested that cyclin D1 and c-MYC expression might additionally be coordinately regulated in an AKT-dependent manner at the level of transcription. Under conditions of relatively quiescent AKT activity, treatment of cells with rapamycin resulted in upregulation of cyclin D1 and c-MYC nascent transcription, whereas in cells containing active AKT, exposure repressed transcription. Promoter analysis identified AKT-dependent rapamycin responsive elements containing AP-1 transactivation sites. Phosphorylated c-JUN binding to these promoters correlated with activation of transcription whereas JUNB occupancy was associated with promoter repression. Forced overexpression of JunB or a conditionally active JunB-ER allele repressed cyclin D1 and c-MYC promoter activity in quiescent AKT-containing cells following rapamycin exposure. AIP4/Itch-dependent JUNB protein degradation was found to be markedly reduced in active AKT-containing cells compared with cells harboring quiescent AKT. Moreover, silencing AIP4/Itch expression or inhibiting JNK mediated AIP4 activity abrogated the rapamycin-induced effects on cyclin D1 and c-MYC promoter activities. Our findings support a role for the AKT-dependent regulation of AIP4/Itch activity in mediating the differential cyclin D1 and c-MYC transcriptional responses to rapamycin. Mol Cancer Res; 9(1); 115-30. (C) 2010 AACR. C1 [Vartanian, Raffi; Masri, Janine; Martin, Jheralyn; Cloninger, Cheri; Holmes, Brent; Artinian, Nicholas; Funk, Alex; Ruegg, Teresa; Gera, Joseph] Greater Los Angeles VA Healthcare Syst, Dept Res & Dev, Los Angeles, CA 91343 USA. [Vartanian, Raffi; Gera, Joseph] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Gera, Joseph] Univ Calif Los Angeles, Jonnson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. [Gera, Joseph] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA. RP Gera, J (reprint author), Greater Los Angeles VA Healthcare Syst, Dept Res & Dev, 16111 Plummer St 151,Bldg 1,Room C111A, Los Angeles, CA 91343 USA. EM jgera@mednet.ucla.edu FU VA MERIT; NIH [R01CA109312] FX This work was supported, in whole or in part, by VA MERIT and NIH R01CA109312 grants. NR 52 TC 21 Z9 22 U1 1 U2 7 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 JAN PY 2011 VL 9 IS 1 BP 115 EP 130 DI 10.1158/1541-7786.MCR-10-0105 PG 16 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 706LU UT WOS:000286220700010 PM 21135252 ER PT J AU Meixner, A Boldt, K Van Troys, M Askenazi, M Gloeckner, CJ Bauer, M Marto, JA Ampe, C Kinkl, N Ueffing, M AF Meixner, Andrea Boldt, Karsten Van Troys, Marleen Askenazi, Manor Gloeckner, Christian J. Bauer, Matthias Marto, Jarrod A. Ampe, Christophe Kinkl, Norbert Ueffing, Marius TI A QUICK Screen for Lrrk2 Interaction Partners - Leucine-rich Repeat Kinase 2 is Involved in Actin Cytoskeleton Dynamics SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID AUTOSOMAL-DOMINANT PARKINSONISM; DISEASE-ASSOCIATED MUTATIONS; BINDING PROTEINS; NEURONAL MORPHOGENESIS; DOPAMINERGIC-NEURONS; RNA INTERFERENCE; GENE-EXPRESSION; CROSS-LINKING; MOUSE-BRAIN; ROC DOMAIN AB Mutations in human leucine-rich repeat kinase 2 (Lrrk2), a protein of yet unknown function, are linked to Parkinson's disease caused by degeneration of midbrain dopaminergic neurons. The protein comprises several domains including a GTPase and a kinase domain both affected by several pathogenic mutations. To elucidate the molecular interaction network of endogenous Lrrk2 under stoichiometric constraints, we applied QUICK (quantitative immunoprecipitation combined with knockdown) in NIH3T3 cells. The identified interactome reveals actin isoforms as well as actin-associated proteins involved in actin filament assembly, organization, rearrangement, and maintenance, suggesting that the biological function of Lrrk2 is linked to cytoskeletal dynamics. In fact, we demonstrate Lrrk2 de novo binding to F-actin and its ability to modulate its assembly in vitro. When tested in intact cells, knockdown of Lrrk2 causes morphological alterations in NIH3T3 cells. In developing dopaminergic midbrain primary neurons, Lrrk2 knockdown results in shortened neurite processes, indicating a physiological role of Lrrk2 in cytoskeletal organization and dynamics of dopaminergic neurons. Hence, our results demonstrate that molecular interactions as well as the physiological function of Lrrk2 are closely related to the organization of the actin-based cytoskeleton, a crucial feature of neuronal development and neuron function. Molecular & Cellular Proteomics 10: 10.1074/mcp.M110.001172, 1-17, 2011. C1 [Meixner, Andrea; Boldt, Karsten; Gloeckner, Christian J.; Bauer, Matthias; Kinkl, Norbert; Ueffing, Marius] German Res Ctr Environm Hlth GmbH, Helmholtz Zentrum Munchen, Dept Prot Sci, D-85764 Neuherberg, Germany. [Meixner, Andrea] Tech Univ Munich, Inst Human Genet, D-81675 Munich, Germany. [Boldt, Karsten; Gloeckner, Christian J.; Kinkl, Norbert; Ueffing, Marius] Univ Tubingen, Div Expt Ophthalmol, Inst Ophthalm Res, D-72076 Tubingen, Germany. [Van Troys, Marleen; Ampe, Christophe] VIB, Dept Med Prot Res, B-9000 Ghent, Belgium. [Van Troys, Marleen; Ampe, Christophe] Univ Ghent, Dept Biochem, Fac Med & Hlth Sci, B-9000 Ghent, Belgium. [Askenazi, Manor; Marto, Jarrod A.] Boston Univ, Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Askenazi, Manor; Marto, Jarrod A.] Dana Faber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Askenazi, Manor; Marto, Jarrod A.] Dana Farber Canc Inst, Blais Prote Ctr, Boston, MA 02115 USA. [Askenazi, Manor] Hebrew Univ Jerusalem, Dept Biol Chem, IL-91120 Jerusalem, Israel. [Bauer, Matthias] Univ Tubingen, Hertie Inst Clin Brain Res, Dept Neurol, D-72076 Tubingen, Germany. RP Ueffing, M (reprint author), German Res Ctr Environm Hlth GmbH, Helmholtz Zentrum Munchen, Dept Prot Sci, Ingolstadter Landstr 1, D-85764 Neuherberg, Germany. EM marius.ueffing@helmholtz-muenchen.de RI Ampe, Christophe/B-5534-2012; Boldt, Karsten/B-7538-2014; OI Gloeckner, Christian Johannes/0000-0001-6494-6944 FU NGFN2 SMP Proteomics [FKZ: 01GR0449]; NGFN-Plus [FKZ: 01GS08140]; German Federal Ministry of Education and Research (BMBF) [FKZ: 0316865A, FKZ: 0315513A]; Helmholtz Association (Helmholtz Alliance for Mental Health in an Aging Society) (HelMA) [FKZ: HA-215, 3 WP11]; EU [HEALTH-F5-2010-241955]; FWO [G.0441.10]; BOF [01J04806]; Dana-Faber Cancer Institute; National Human Genome Research Institute [P50HG004233] FX This work was supported by the NGFN2 SMP Proteomics (FKZ: 01GR0449, subproject 9), NGFN-Plus (FKZ: 01GS08140, subproject 12), the German Federal Ministry of Education and Research (BMBF: QuantPro, FKZ: 0316865A and DYNAMO, FKZ: 0315513A), the Initiative and Networking Fund of the Helmholtz Association (Helmholtz Alliance for Mental Health in an Aging Society) (HelMA, FKZ: HA-215, topic 3 WP11), the EU grant SYSCILIA (HEALTH-F5-2010-241955), FWO grant G.0441.10 (to CA), BOF-grant 01J04806 (to MVT), the Dana-Faber Cancer Institute (to JAM and MA) and the National Human Genome Research Institute (P50HG004233; to JAM and MA). NR 78 TC 12 Z9 12 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 EI 1535-9484 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD JAN PY 2011 VL 10 IS 1 AR M110.001172 DI 10.1074/mcp.M110.001172 PG 17 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 715XL UT WOS:000286928400006 PM 20876399 ER PT J AU Milane, L Duan, ZF Amiji, M AF Milane, Lara Duan, Zhenfeng Amiji, Mansoor TI Development of EGFR-Targeted Polymer Blend Nanocarriers for Combination Paclitaxel/Lonidamine Delivery To Treat Multi-Drug Resistance in Human Breast and Ovarian Tumor Cells SO MOLECULAR PHARMACEUTICS LA English DT Article DE Multi-drug resistant cancer; hypoxia; Warburg effect; nanoparticle; drug delivery; Ionidamine; paclitaxel; polymeric nanocarriers ID HYPOXIA-INDUCIBLE FACTOR-1; GROWTH-FACTOR RECEPTOR; STRUCTURAL BASIS; DRUG-DELIVERY; CANCER-CELLS; IN-VIVO; POLY(EPSILON-CAPROLACTONE) NANOPARTICLES; P-GLYCOPROTEIN; PEPTIDE LIGAND; LONIDAMINE AB Multi-drug resistant (MDR) cancer is a significant clinical obstacle and is often implicated in cases of recurrent, nonresponsive disease. Targeted nanoparticles were made by synthesizing a poly(oxlactide-co-glycohde)/poly(ethylene glycol)/epidermal growth factor receptor targeting peptide (PLGA/PEG/ EGFR-peptide) construct for incorporation in poly(epsilon-caprolactone) (PCL) nanoparticles. MDR was induced in a panel of nine human breast and ovarian cancer cell lines using hypoxia. EGFR-targeted polymer blend nanoparticles were shown to actively target EGFR overexpressing cell lines, especially upon induction of hypoxia. The nanoparticles were capable of sustained drug release. Combination therapy with lonidamine and paclitaxel significantly improved the therapeutic index of both drugs. Treatment with a nanoparticle dose of 1 mu M paclitaxel/10 mu M lonidamine resulted in less than 10% cell viability for all hypoxic/MDR cell lines and less than 5% cell viability for all normoxic cell lines. Comparatively, treatment with 1 mu M paclitaxel alone was the approximate IC50 value of the MDR cells while treatment with lonidamine alone had very little effect. The PLGA/PEG/EGFR-peptide delivery system actively targets a MDR cell by exploiting the expression of EGFR. This system treats MDR by inhibiting the Warburg effect and promoting mitochondrial binding of pro-apoptotic BcI-2 proteins (lonidamine), while hyperstabilizing microtubules (paclitaxel). This nanocarrier system actively targets a MDR associated phenotype (EGFR receptor overexpression), further enhancing the therapeutic index of both drugs and potentiating the use of Ionidamine/paclitaxel combination therapy in the treatment of MDR cancer. C1 [Milane, Lara; Amiji, Mansoor] Northeastern Univ, Dept Pharmaceut Sci, Sch Pharm, Boston, MA 02115 USA. [Duan, Zhenfeng] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Duan, Zhenfeng] Massachusetts Gen Hosp, Sarcoma Biol Lab, Ctr Sarcoma & Connect Tissue Oncol, Boston, MA 02114 USA. RP Amiji, M (reprint author), Northeastern Univ, Dept Pharmaceut Sci, Sch Pharm, 110 Mugar Life Sci Bldg,360 Huntington Ave, Boston, MA 02115 USA. EM m.amiji@neu.edu RI Amiji, Mansoor/A-4365-2014 OI Amiji, Mansoor/0000-0001-6170-881X FU National Cancer Institute, National Institutes of Health [R01 CA-119617, R01 CA-119617S1, R21 CA-135594] FX This study was supported by the National Cancer Institute, National Institutes of Health, through Grants R01 CA-119617 and R01 CA-119617S1 (ARRA Supplement) and R21 CA-135594. Scanning electron microscopy was performed by William Fowle at the Electron Microscopy Center at Northeastern University. NR 75 TC 61 Z9 62 U1 3 U2 51 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1543-8384 J9 MOL PHARMACEUT JI Mol. Pharm. PD JAN-FEB PY 2011 VL 8 IS 1 BP 185 EP 203 DI 10.1021/mp1002653 PG 19 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 715UZ UT WOS:000286915000019 PM 20942457 ER PT J AU Liu, Y Blackwood, DH Caesar, S de Geus, EJC Farmer, A Ferreira, MAR Ferrier, IN Fraser, C Gordon-Smith, K Green, EK Grozeva, D Gurling, HM Hamshere, ML Heutink, P Holmans, PA Hoogendijk, WJ Hottenga, JJ Jones, L Jones, IR Kirov, G Lin, D McGuffin, P Moskvina, V Nolen, WA Perlis, RH Posthuma, D Scolnick, EM Smit, AB Smit, JH Smoller, JW St Clair, D van Dyck, R Verhage, M Willemsen, G Young, AH Zandbelt, T Boomsma, DI Craddock, N O'Donovan, MC Owen, MJ Penninx, BWJH Purcell, S Sklar, P Sullivan, PF AF Liu, Y. Blackwood, D. H. Caesar, S. de Geus, E. J. C. Farmer, A. Ferreira, M. A. R. Ferrier, I. N. Fraser, C. Gordon-Smith, K. Green, E. K. Grozeva, D. Gurling, H. M. Hamshere, M. L. Heutink, P. Holmans, P. A. Hoogendijk, W. J. Hottenga, J. J. Jones, L. Jones, I. R. Kirov, G. Lin, D. McGuffin, P. Moskvina, V. Nolen, W. A. Perlis, R. H. Posthuma, D. Scolnick, E. M. Smit, A. B. Smit, J. H. Smoller, J. W. St Clair, D. van Dyck, R. Verhage, M. Willemsen, G. Young, A. H. Zandbelt, T. Boomsma, D. I. Craddock, N. O'Donovan, M. C. Owen, M. J. Penninx, B. W. J. H. Purcell, S. Sklar, P. Sullivan, P. F. CA Wellcome Trust Case Control TI Meta-analysis of genome-wide association data of bipolar disorder and major depressive disorder SO MOLECULAR PSYCHIATRY LA English DT Letter ID POPULATION C1 [Liu, Y.; Sullivan, P. F.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27515 USA. [Blackwood, D. H.] Univ Edinburgh, Dept Psychol Med, Edinburgh, Midlothian, Scotland. [Caesar, S.; Gordon-Smith, K.; Jones, L.] Univ Birmingham, Dept Psychol Med, Birmingham, W Midlands, England. [de Geus, E. J. C.; Hottenga, J. J.; Willemsen, G.; Boomsma, D. I.] Vrije Univ Amsterdam, Dept Psychol, Amsterdam, Netherlands. [Farmer, A.; McGuffin, P.] Inst Psychiat, Dept Psychol Med, London SE5 8AF, England. [Ferreira, M. A. R.] Queensland Inst Med Res, Dept Genet, Brisbane, Qld 4006, Australia. [Ferrier, I. N.] Newcastle Univ, Dept Psychol Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Fraser, C.; Green, E. K.; Grozeva, D.; Hamshere, M. L.; Holmans, P. A.; Jones, I. R.; Kirov, G.; Moskvina, V.; Craddock, N.; O'Donovan, M. C.; Owen, M. J.] Cardiff Univ, Dept Psychol Med, Cardiff, S Glam, Wales. [Gurling, H. M.] UCL, Dept Psychol Med, London, England. [Heutink, P.; Hoogendijk, W. J.; Smit, J. H.; van Dyck, R.; Penninx, B. W. J. H.] VU Univ Med Ctr Amsterdam, Dept Psychiat, Amsterdam, Netherlands. [Lin, D.] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. [Nolen, W. A.] Univ Groningen, Univ Med Ctr Groningen, Dept Psychol Med, NL-9713 AV Groningen, Netherlands. [Perlis, R. H.; Smoller, J. W.; Purcell, S.; Sklar, P.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Posthuma, D.; Smit, A. B.; Verhage, M.] Vrije Univ Amsterdam, Dept Genet, Amsterdam, Netherlands. [Scolnick, E. M.] Broad Inst, Dept Genet, Cambridge, MA USA. [St Clair, D.] Univ Aberdeen, Dept Psychol Med, Aberdeen, Scotland. [Young, A. H.] Univ British Columbia, Dept Psychiat, Vancouver, BC, Canada. [Zandbelt, T.] VU Univ Med Ctr Amsterdam, Dept Psychol, Amsterdam, Netherlands. RP Liu, Y (reprint author), Univ N Carolina, Dept Genet, Chapel Hill, NC 27515 USA. EM pfsulliv@med.unc.edu RI Smit, August /E-8410-2011; turton, miranda/F-4682-2011; Ferreira, Manuel/D-3609-2013; Gurling, Hugh/A-5029-2010; McGuffin, Peter/A-1565-2012; Nolen, Willem/E-9006-2014; Holmans, Peter/F-4518-2015; de Geus, Eco/M-9318-2015; OI Escott-Price, Valentina/0000-0003-1784-5483; verhage, matthijs/0000-0002-6085-7503; McGuffin, Peter/0000-0002-9888-2907; Holmans, Peter/0000-0003-0870-9412; de Geus, Eco/0000-0001-6022-2666; O'Donovan, Michael/0000-0001-7073-2379 FU Medical Research Council [G0701007, G1000708]; NIMH NIH HHS [R01 MH074027, R01 MH074027-01A1, R01 MH074027-02] NR 15 TC 78 Z9 79 U1 1 U2 14 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 JAN PY 2011 VL 16 IS 1 BP 2 EP 4 DI 10.1038/mp.2009.107 PG 3 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 697VE UT WOS:000285546400001 PM 20351715 ER PT J AU Voyiaziakis, E Evgrafov, O Li, D Yoon, HJ Tabares, P Samuels, J Wang, Y Riddle, MA Grados, MA Bienvenu, OJ Shugart, YY Liang, KY Greenberg, BD Rasmussen, SA Murphy, DL Wendland, JR McCracken, JT Piacentini, J Rauch, SL Pauls, DL Nestadt, G Fyer, AJ Knowles, JA AF Voyiaziakis, E. Evgrafov, O. Li, D. Yoon, H-J Tabares, P. Samuels, J. Wang, Y. Riddle, M. A. Grados, M. A. Bienvenu, O. J. Shugart, Y. Y. Liang, K-Y Greenberg, B. D. Rasmussen, S. A. Murphy, D. L. Wendland, J. R. McCracken, J. T. Piacentini, J. Rauch, S. L. Pauls, D. L. Nestadt, G. Fyer, A. J. Knowles, J. A. TI Association of SLC6A4 variants with obsessive-compulsive disorder in a large multicenter US family study SO MOLECULAR PSYCHIATRY LA English DT Article DE OCD genetics; family study; affected sib-pair study; molecular haplotype analysis; serotonin transporter; heterogeneity analysis ID SEROTONIN TRANSPORTER GENE; NUMBER-TANDEM-REPEAT; COMPLEX SEGREGATION ANALYSIS; VARIABLE-NUMBER; TRANSMISSION DISEQUILIBRIUM; LINKAGE DISEQUILIBRIUM; POLYMORPHISM 5-HTTLPR; REGION POLYMORPHISM; PEDIATRIC PROBANDS; REGULATORY REGION AB Genetic association studies of SLC6A4 (SERT) and obsessive-compulsive disorder (OCD) have been equivocal. We genotyped 1241 individuals in 278 pedigrees from the OCD Collaborative Genetics Study for 13 single-nucleotide polymorphisms, for the linked polymorphic region (LPR) indel with molecular haplotypes at rs25531, for VNTR polymorphisms in introns 2 and 7 and for a 381-bp deletion 3' to the LPR. We analyzed using the Family-Based Association Test (FBAT) under additive, dominant, recessive and genotypic models, using both OCD and sex-stratified OCD as phenotypes. Two-point FBAT analysis detected association between Int2 (P = 0.0089) and Int7 (P = 0.0187) (genotypic model). Sex-stratified two-point analysis showed strong association in females with Int2 (P < 0.0002), significant after correction for linkage disequilibrium, and multiple marker and model testing (P(Adj) = 0.0069). The SLC6A4 gene is composed of two haplotype blocks (our data and the HapMap); FBAT whole-marker analysis conducted using this structure was not significant. Several noteworthy nonsignificant results have emerged. Unlike Hu et al., we found no evidence for overtransmission of the LPR L(A) allele (genotype relative risk = 1.11, 95% confidence interval: 0.77-1.60); however, rare individual haplotypes containing L(A) with P < 0.05 were observed. Similarly, three individuals (two with OCD/OCPD) carried the rare I425V SLC6A4 variant, but none of them passed it on to their six OCD-affected offspring, suggesting that it is unlikely to be solely responsible for the 'OCD plus syndrome', as reported by Ozaki et al. In conclusion, we found evidence of genetic association at the SLC6A4 locus with OCD. A noteworthy lack of association at the LPR, LPR-rs25531 and rare 425V variants suggests that hypotheses about OCD risk need revision to accommodate these new findings, including a possible gender effect. Molecular Psychiatry (2011) 16, 108-120; doi:10.1038/mp.2009.100; published online 6 October 2009 C1 [Voyiaziakis, E.; Evgrafov, O.; Knowles, J. A.] Univ So Calif, Dept Psychiat & Behav Sci, Keck Sch Med, Los Angeles, CA 90089 USA. [Li, D.] Univ So Calif, Div Biostat, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90089 USA. [Yoon, H-J; Knowles, J. A.] Univ So Calif, Zilkha Neurogenet Inst, Keck Sch Med, Los Angeles, CA 90089 USA. [Tabares, P.; Fyer, A. J.] Columbia Univ, Dept Psychiat, Coll Phys & Surg, New York, NY USA. [Tabares, P.; Fyer, A. J.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Samuels, J.; Wang, Y.; Riddle, M. A.; Grados, M. A.; Bienvenu, O. J.; Nestadt, G.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Shugart, Y. Y.] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Liang, K-Y] Johns Hopkins Univ, Dept Biostat, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. [Greenberg, B. D.; Rasmussen, S. A.] Butler Hosp, Dept Psychiat & Human Behav, Brown Med Sch, Providence, RI 02906 USA. [Murphy, D. L.; Wendland, J. R.] NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. [McCracken, J. T.; Piacentini, J.] Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Rauch, S. L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Rauch, S. L.; Pauls, D. L.] Harvard Univ, Sch Med, Boston, MA USA. [Pauls, D. L.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. RP Voyiaziakis, E (reprint author), Univ So Calif, Dept Psychiat & Behav Sci, Keck Sch Med, MC-2821,1501 San Pablo,ZNI 401, Los Angeles, CA 90089 USA. EM emanuelv@keck.usc.edu RI Piacentini, John/C-4645-2011; Liang, Kung-Yee/F-8299-2011; Wendland, Jens/A-1809-2012; OI Samuels, Jack/0000-0002-6715-7905 FU NIMH [R01 MH50214, K23-MH066284, K23-MH64543, MH079494, MH050214]; NIH/NCRR/OPD-GCRC [RR00052]; Obsessive Compulsive Foundation (OCF); USC, Keck School, Psychiatry; NARSAD; Neurogen; Sepracor; Novartis; Medtronic; Cyberonics; Cephalon; Northstar; Eli Lilly; Bristol Myers; Squibb; Seaside Pharmaceuticals; Aspect; CMREF FX This study is supported by NIMH R01 MH50214 and NIH/NCRR/OPD-GCRC RR00052 (GN). EV is a recipient of a 2006 grant award from the Obsessive Compulsive Foundation (OCF) and a departmental fellowship award (USC, Keck School, Psychiatry). OE received a Young Investigator Award from NARSAD. YYS initiated her contribution to this report while working at JHU, and is currently working at the Genomic Research Branch, NIMH. Part of this work was completed as her outside activity, and as such the views expressed in this article do not necessarily represent the views of the NIMH, NIH, HHS, or the US Government. SAR and DLP are funded by the NIMH. SLR has received honoraria and/or consultation fees from Neurogen, Sepracor, Novartis and Medtronic, and has conducted research funded by Medtronic, Cyberonics, Cephalon and Northstar. JTM has received research support from Eli Lilly, Bristol Myers, Squibb, Seaside Pharmaceuticals, and Aspect. Other relevant NIMH awards: K23-MH066284 (MG) & K23-MH64543 (OJB). JAK is funded by the NIMH, CMREF and NARSAD, and this project was funded by NIMH grants MH079494 & MH050214. He is a member of the scientific advisory boards of SoftGenetics, Inc. & Life Technologies, Inc. and has received compensation from the latter. NR 71 TC 26 Z9 27 U1 3 U2 9 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 JAN PY 2011 VL 16 IS 1 BP 108 EP 120 DI 10.1038/mp.2009.100 PG 13 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 697VE UT WOS:000285546400012 PM 19806148 ER PT J AU Groeneweg, JW White, YAR Kokel, D Peterson, RT Zukerberg, LR Berin, I Rueda, BR Wood, AW AF Groeneweg, Jolijn W. White, Yvonne A. R. Kokel, David Peterson, Randall T. Zukerberg, Lawrence R. Berin, Inna Rueda, Bo R. Wood, Antony W. TI cables1 Is Required for Embryonic Neural Development: Molecular, Cellular, and Behavioral Evidence From the Zebrafish SO MOLECULAR REPRODUCTION AND DEVELOPMENT LA English DT Article ID DEPENDENT KINASE-5 CDK5; IN-VIVO; CHROMOSOME 18Q; ENDOMETRIAL CANCER; GENE; GROWTH; PHOSPHORYLATION; PROTEIN; CELLS; P35 AB In vitro studies have suggested that the Cables1 gene regulates epithelial cell proliferation, whereas other studies suggest a role in promoting neural differentiation. In efforts to clarify the functions of Cables1 in vivo, we conducted gain- and loss-of-function studies targeting its ortholog (cables 1) in the zebrafish embryo. Similar to rodents, zebrafish cables1 mRNA expression is detected most robustly in embryonic neural tissues. Antisense knockdown of cables1 leads to increased numbers of apoptotic cells, particularly in brain tissue, in addition to a distinct behavioral phenotype, characterized by hyperactivity in response to stimulation. Apoptosis and the behavioral abnormality could be rescued by co-expression of a morpholino-resistant cables1 construct. Suppression of p53 expression in cables1 morphants partially rescued both apoptosis and the behavioral phenotype, suggesting that the phenotype of cables1 morphants is due in part to p53-dependent apoptosis. Alterations in the expression patterns of several neural transcription factors were observed in cables1 morphants during early neurulation, suggesting that cables1 is required for early neural differentiation. Ectopic overexpression of cables1 strongly disrupted embryonic morphogenesis, while overexpression of a cables1 mutant lacking the C-terminal cyclin box had little effect, suggesting functional importance of the cyclin box. Lastly, marked reductions in p35, but not Cdk5, were observed in cables1 morphants. Collectively, these data suggest that cables1 is important for neural differentiation during embryogenesis, in a mechanism that likely involves interactions with the Cdk5/p35 kinase pathway. Mol. Reprod. Dev. 78: 22-32, 2011. (c) 2010 Wiley-Liss, Inc. C1 [Groeneweg, Jolijn W.; White, Yvonne A. R.; Berin, Inna; Rueda, Bo R.; Wood, Antony W.] Massachusetts Gen Hosp, MGH Vincent Dept Obstet & Gynecol, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. [Groeneweg, Jolijn W.; White, Yvonne A. R.; Kokel, David; Peterson, Randall T.; Zukerberg, Lawrence R.; Berin, Inna; Rueda, Bo R.; Wood, Antony W.] Harvard Univ, Sch Med, Boston, MA USA. [Kokel, David; Peterson, Randall T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Zukerberg, Lawrence R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Wood, AW (reprint author), 55 Fruit St,THR 933, Boston, MA 02114 USA. EM awwood@partners.org OI kokel, david/0000-0002-1981-1511 FU Vincent Memorial Research Funds; Advanced Medical Research Foundation; US National Institutes of Health [RO1CA098333, R01MH086867, R21MH085205] FX This study was supported by Vincent Memorial Research Funds, the Advanced Medical Research Foundation, and US National Institutes of Health grants RO1CA098333 (B.R.R.), R01MH086867 (R.T.P.) and R21MH085205 (R.T.P.). NR 33 TC 0 Z9 0 U1 1 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1040-452X J9 MOL REPROD DEV JI Mol. Reprod. Dev. PD JAN PY 2011 VL 78 IS 1 BP 22 EP 32 DI 10.1002/mrd.21263 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology SC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology GA 718HE UT WOS:000287110900006 PM 21268180 ER PT S AU Shah, K AF Shah, Khalid BE Shah, K TI Imaging Fate of Stem Cells at a Cellular Resolution in the Brains of Mice SO MOLEUCLAR IMAGING: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Stem cells; glioma; in vivo intravital microscopy ID MAGNETIC-RESONANCE TRACKING; IN-VIVO TRACKING; SPINAL-CORD; THERAPY; TRANSPLANTATION; NANOPARTICLES; MIGRATION; PROTEINS; DELIVERY AB Transplantation of genetically engineered cells into the central nervous system (CNS) offers immense potential for the treatment of several neurological disorders. Monitoring expression levels of transgenes and following changes in cell function and distribution over time is critical in assessing therapeutic efficacy of such cells in vivo. We detail a unique method to visualize the fate of human neural stem cells (NSC) and tumor cells at a cellular resolution in glioma bearing brains in vivo by using intravital-scanning microscopy in real-time. The ability to monitor fate of stem cells in disease models enables studies aimed at evaluating the efficacy of their treatment for CNS disorders. C1 Harvard Univ, Sch Med, Mol Neurotherapy & Imaging Lab, Dept Radiol & Neurol,Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Shah, K (reprint author), Harvard Univ, Sch Med, Mol Neurotherapy & Imaging Lab, Dept Radiol & Neurol,Massachusetts Gen Hosp, Boston, MA 02114 USA. EM kshah@helix.mgh.harvard.edu; kshah@helix.mgh.harvard.edu NR 20 TC 1 Z9 1 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60761-900-0 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 680 BP 91 EP 101 DI 10.1007/978-1-60761-901-7_6 D2 10.1007/978-1-60761-901-7 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BSZ45 UT WOS:000286165600006 PM 21153375 ER PT S AU Jaffer, FA AF Jaffer, Farouc A. BE Shah, K TI Intravital Fluorescence Microscopic Molecular Imaging of Atherosclerosis SO MOLEUCLAR IMAGING: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Atherosclerosis; near-infrared fluorescence; molecular imaging; intravital microscopy; inflammation ID DISEASE AB Atherosclerosis is a lipid deposition and inflammatory disease that results in considerable morbidity and mortality worldwide. Advances in molecular imaging, particularly near-infrared fluorescence imaging, are now enabling the in vivo study of fundamental biological processes that govern atherogenesis and its complications. Here we describe applications of near-infrared fluorescence reporter technology and intravital fluorescence microscopy to elucidate important biological processes in atherosclerosis in vivo. C1 [Jaffer, Farouc A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02163 USA. [Jaffer, Farouc A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiol Div,Ctr Mol Imaging Res, Boston, MA USA. RP Jaffer, FA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02163 USA. OI Jaffer, Farouc/0000-0001-7980-384X FU NHLBI NIH HHS [R01 HL108229-01A1, R01 HL108229] NR 11 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60761-900-0 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 680 BP 131 EP 140 DI 10.1007/978-1-60761-901-7_9 D2 10.1007/978-1-60761-901-7 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BSZ45 UT WOS:000286165600009 PM 21153378 ER PT S AU Shah, K AF Shah, Khalid BE Shah, K TI In Vivo Imaging of the Dynamics of Different Variants of EGFR in Glioblastomas SO MOLEUCLAR IMAGING: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE EGFR; glioma and in vivo imaging ID LIVING MICE; EXPRESSION; GENE AB A number of altered pathways in cancer cells depend on growth factor receptors. The amplification/alteration of the epidermal growth factor receptor (EGER) has been shown to play a significant role in enhancing tumor burden in a number of tumors, including malignant glioblastomas (GBM). To dissect the role of EGER expression in tumor progression in mouse models of cancer and ultimately evaluate targeted therapies, it is necessary to visualize the dynamics of EGER in real time in vivo. Non-invasive imaging based on quantitative and qualitative changes in light emission by fluorescent and bioluminescent markers offers a huge potential to facilitate drug development. Multiple approaches could be used to follow a molecular target or pathway with the fusion of a bioluminescent fluorescent marker. This unit describes a protocol for simultaneously imaging EGFR activity and progression of GBM in a mouse model. Human glioma cells transduced with lentiviral vectors bearing different combinations of fluorescent and bioluminescent proteins either fused to EGFR or expressed alone can be grown as monolayers and maintained over several passages. The unit begins with a method for transducing glioma cells with lentiviral vectors for stable expression of these fluorescent and bioluminescent markers in vitro, followed by transplantation of engineered glioma cells in mice, and, finally, sequential bioluminescent imaging of EGFR expression and GBM progression in mice. The protocol details characterization of engineered glioma cells in culture, surgical preparation, craniotomy, cell implantation, animal recovery, and imaging procedures to study kinetics of EGFR expression and GBM progression. C1 Harvard Univ, Sch Med, Mol Neurotherapy & Imaging Lab, Dept Radiol & Neurol,Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Shah, K (reprint author), Harvard Univ, Sch Med, Mol Neurotherapy & Imaging Lab, Dept Radiol & Neurol,Massachusetts Gen Hosp, Boston, MA 02114 USA. EM kshah@helix.mgh.harvard.edu; kshah@helix.mgh.harvard.edu NR 9 TC 1 Z9 1 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60761-900-0 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 680 BP 153 EP 164 DI 10.1007/978-1-60761-901-7_11 D2 10.1007/978-1-60761-901-7 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BSZ45 UT WOS:000286165600011 PM 21153380 ER PT S AU Kumar, ATN AF Kumar, Anand T. N. BE Shah, K TI Fluorescence Lifetime-Based Optical Molecular Imaging SO MOLEUCLAR IMAGING: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Fluorescence; lifetime; fluorescent proteins; optical tomography; tissue optics ID IN-VIVO; TOMOGRAPHY; MICROSCOPY AB Fluorescence lifetime is a powerful contrast mechanism for in vivo molecular imaging. In this chapter, we describe instrumentation and methods to optimally exploit lifetime contrast using a time domain fluorescence tomography system. The key features of the system are the use of point excitation in free-space using ultrashort laser pulses and non-contact detection using a gated, intensified CCD camera. The surface boundaries of the imaging volume are acquired using a photogrammetric camera integrated with the imaging system, and implemented in theoretical models of light propagation in biological tissue. The time domain data are optimally analyzed using a lifetime-based tomography approach, which is based on extracting a tomographic set of lifetimes and decay amplitudes from the long time decay portion of the time domain data. This approach improves the ability to locate in vivo targets with a resolution better than conventional optical methods. The application of time domain lifetime multiplexing and tomography are illustrated using phantoms and tumor bearing mouse model of breast adenocarcinoma. In the latter application, the time domain approach allows an improved detection of fluorescent protein signals from intact nude mice in the presence of background autofluorescence. This feature has potential applications for longitudinal pre-clinical evaluation of drug treatment response as well as to address fundamental questions related to tumor physiology and metastasis. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Kumar, ATN (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. FU NIA NIH HHS [AG026240] NR 14 TC 3 Z9 3 U1 0 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60761-900-0 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 680 BP 165 EP 180 DI 10.1007/978-1-60761-901-7_12 D2 10.1007/978-1-60761-901-7 PG 16 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BSZ45 UT WOS:000286165600012 PM 21153381 ER PT S AU El Fakhri, G Ouyang, JS AF El Fakhri, Georges Ouyang, Jinsong BE Shah, K TI Dual-Radionuclide Brain SPECT for the Differential Diagnosis of Parkinsonism SO MOLEUCLAR IMAGING: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Parkinsonism; IPD; MSA; CBD; PSP; SPECT; dual-radionuclide; perfusion; neuro-transmission; ANN; MC-JOSEM ID MULTIPLE SYSTEM ATROPHY; CROSSTALK COMPENSATION; CLINICAL-DIAGNOSIS; DISEASE; ACQUISITION; COLLIMATOR; ACCURACY; SCATTER; CAMERA AB Parkinsonism is a neurological syndrome characterized by tremor, bradykinesia, rigidity, and postural instability. The underlying causes of parkinsonism are numerous. It is of paramount importance to make clean distinction among these diseases. However, the differential diagnosis of parkinsonism is challenging. Simultaneous dual-radionuclide brain SPECT allows us to assess both blood perfusion and dopamine transporter function under the identical physiological conditions. This approach has been proven to improve the differential diagnosis of parkinsonism. The simultaneous Tc-99m-ECD/I-123-FP-CIT brain SPECT protocols, which are used for the differential diagnosis of idiopathic Parkinson's disease and multiple system atrophy as well as corticobasal degeneration and progressive supranuclear palsy, are presented. C1 [El Fakhri, Georges; Ouyang, Jinsong] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nucl Med & Mol Imaging,Dept Radiol, Boston, MA 02114 USA. RP El Fakhri, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nucl Med & Mol Imaging,Dept Radiol, Boston, MA 02114 USA. NR 21 TC 1 Z9 1 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60761-900-0 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 680 BP 237 EP 246 DI 10.1007/978-1-60761-901-7_16 D2 10.1007/978-1-60761-901-7 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BSZ45 UT WOS:000286165600016 PM 21153385 ER PT B AU Khalifa, F Beache, GM Gimel'farb, G Suri, JS El-Baz, AS AF Khalifa, Fahmi Beache, Garth M. Gimel'farb, Georgy Suri, Jasjit S. El-Baz, Ayman S. BE ElBaz, AS U, RA Mirmehdi, M Suri, JS TI State-of-the-Art Medical Image Registration Methodologies: A Survey SO MULTI MODALITY STATE-OF-THE-ART MEDICAL IMAGE SEGMENTATION AND REGISTRATION METHODOLOGIES, VOL 1 LA English DT Article; Book Chapter DE image registration; Similarity functions; image transformations; Global registration; Nonrigid registration; Numerical optimization; Image resampling ID RADIAL BASIS FUNCTIONS; SCATTERED DATA INTERPOLATION; COMBINED MUTUAL INFORMATION; FREE-FORM DEFORMATIONS; THIN-PLATE SPLINES; NONRIGID REGISTRATION; MR-IMAGES; ELASTIC REGISTRATION; B-SPLINES; 3-DIMENSIONAL REGISTRATION AB Almost all computer vision applications, from remote sensing and cartography to medical imaging and biometrics, use image registration or alignment techniques that establish spatial correspondence (one-to-one mapping) between two or more images. These images depict either one planar (2-D) or volumetric (3-D) scene or several such scenes and can be taken at different times, from various viewpoints, and/or by multiple sensors. In medical image processing and analysis, the image registration is instrumental for clinical diagnosis and therapy planning, e.g., to follow disease progression and/or response to treatment, or integrate information from different sources/modalities to form more detailed descriptions of anatomical objects-of-interest. The unified registration goal aligning a 2-D or 3-D target (sensed) image with a reference image is reached by specifying a mathematical model of image transformations for and determining model parameters of the desired alignment. Frequently, the parameters provide an optimum of a goal function supported by the parameter space, so that the registration reduces to a certain optimization problem. This chapter overviews the 2-D and the 3-D medical image registration with special reference to the state-of-the-art robust techniques proposed for the last decade and discusses their advantages, drawbacks, and practical implementations. C1 [Khalifa, Fahmi; El-Baz, Ayman S.] Univ Louisville, BioImaging Lab, Dept Bioengn, Louisville, KY 40292 USA. [Beache, Garth M.] Univ Louisville, Dept Diagnost Radiol, Sch Med, Louisville, KY 40202 USA. [Gimel'farb, Georgy] Univ Auckland, Dept Comp Sci, Auckland 1149, New Zealand. [Suri, Jasjit S.] Biomed Technol Inc, Denver, CO USA. [Suri, Jasjit S.] Idaho State Univ, Pocatello, ID 83209 USA. [Beache, Garth M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Beache, Garth M.] Johns Hopkins Sch Med, Baltimore, MD USA. RP El-Baz, AS (reprint author), Univ Louisville, BioImaging Lab, Dept Bioengn, Louisville, KY 40292 USA. EM aselba01@louisville.edu NR 245 TC 14 Z9 14 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-8194-3 PY 2011 BP 235 EP 280 DI 10.1007/978-1-4419-8195-0_9 PG 46 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BVI33 UT WOS:000291615200009 ER PT S AU Kyle, RA Steensma, DP AF Kyle, Robert A. Steensma, David P. BE Moehler, T Goldschmidt, H TI History of Multiple Myeloma SO MULTIPLE MYELOMA SE Recent Results in Cancer Research LA English DT Article; Book Chapter ID LENALIDOMIDE PLUS DEXAMETHASONE; BONE-MARROW-TRANSPLANTATION; PROTEASOME INHIBITOR PS-341; OVERCOMES DRUG-RESISTANCE; BENCE-JONES PROTEINS; COMBINATION CHEMOTHERAPY; ELECTROPHORETIC ANALYSIS; CLINICAL EXPERIENCES; IMPROVED SURVIVAL; MALIGNANT-TUMORS AB Multiple Myeloma has been recognized since Ancient Times. The first well-documented case was reported in 1844 by Samuel Solly. The most commonly recognized case is that of Thomas Alexander McBean, a highly respectable tradesman from London in 1850. Mr. McBean excreted a large amount of protein that was described by Henry Bence Jones in the middle of the 19th century. Jones was a well-known physician and made many contributions to medicine. One of the best known cases of multiple myeloma was that of Dr. Loos that was reported by Otto Kahler. The recognition of plasma cells and subsequently their product, a monoclonal protein has been described in detail. The authors have reviewed the treatment of multiple myeloma including the novel agents, thalidomide, bortezomib and lenalidomide. C1 [Kyle, Robert A.] Mayo Clin, Dept Med, Div Hematol, Rochester, MN 55905 USA. [Steensma, David P.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Kyle, RA (reprint author), Mayo Clin, Dept Med, Div Hematol, 200 1st St SW,Stabile 6-28, Rochester, MN 55905 USA. EM kyle.robert@mayo.edu OI Steensma, David/0000-0001-5130-9284 NR 100 TC 3 Z9 3 U1 2 U2 4 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0080-0015 BN 978-3-540-85771-6 J9 RECENT RESULTS CANC JI Rec. Res. Camcer Res. PY 2011 VL 183 BP 3 EP 23 DI 10.1007/978-3-540-85772-3_1 D2 10.1007/978-3-540-85772-3 PG 21 WC Oncology SC Oncology GA BDG58 UT WOS:000313126100003 PM 21509678 ER PT S AU Deisboeck, TS Stamatakos, GS AF Deisboeck, Thomas S. Stamatakos, Georgios S. BE Deisboeck, TS Stamatakos, GS TI Multiscale Cancer Modeling Preface SO MULTISCALE CANCER MODELING SE Chapman & Hall CRC Mathematical and Computational Biology Series LA English DT Editorial Material; Book Chapter C1 [Deisboeck, Thomas S.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Stamatakos, Georgios S.] Natl Tech Univ Athens, Inst Commun & Comp Syst, Lab Microwaves & Fiber Opt, Silico Oncol Grp, GR-10682 Athens, Greece. RP Deisboeck, TS (reprint author), Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 9 Z9 9 U1 0 U2 0 PU CHAPMAN & HALL/CRC PRESS PI BOCA RATON PA 6000 BROKEN SOUND PKWY, NW, STE 300, BOCA RATON, FL 33487 USA SN 2154-8064 BN 978-1-4398-1442-0; 978-1-4398-1440-6 J9 CH CRC MATH COMP BIO JI Math. Comp. Biol. Ser. PY 2011 BP XIII EP XIV PG 2 WC Oncology; Mathematical & Computational Biology SC Oncology; Mathematical & Computational Biology GA BC8CU UT WOS:000355551800001 ER PT S AU Wang, ZH Bordas, V Sagotsky, J Deisboeck, TS AF Wang, Zhihui Bordas, Veronika Sagotsky, Jonathan Deisboeck, Thomas S. BE Deisboeck, TS Stamatakos, GS TI Simulating Cancer Growth with Agent-Based Models SO MULTISCALE CANCER MODELING SE Chapman & Hall CRC Mathematical and Computational Biology Series LA English DT Article; Book Chapter ID CELLULAR-AUTOMATON MODEL; SOLID TUMOR-GROWTH; FACTOR-RECEPTOR; BRAIN-TUMORS; LUNG-CANCER; IN-VITRO; MULTICELLULAR PATTERNS; NONLINEAR SIMULATION; COMPUTATIONAL MODEL; MATHEMATICAL-MODEL C1 [Wang, Zhihui; Sagotsky, Jonathan; Deisboeck, Thomas S.] Massachusetts Gen Hosp East, Harvard MIT HST Athinoula A Martinos Ctr Biomed I, Charlestown, MA 02129 USA. [Bordas, Veronika] Harvard Univ, Dept Appl Math, Cambridge, MA 02138 USA. RP Wang, ZH (reprint author), Massachusetts Gen Hosp East, Harvard MIT HST Athinoula A Martinos Ctr Biomed I, Charlestown, MA 02129 USA. NR 97 TC 1 Z9 1 U1 0 U2 0 PU CHAPMAN & HALL/CRC PRESS PI BOCA RATON PA 6000 BROKEN SOUND PKWY, NW, STE 300, BOCA RATON, FL 33487 USA SN 2154-8064 BN 978-1-4398-1442-0; 978-1-4398-1440-6 J9 CH CRC MATH COMP BIO JI Math. Comp. Biol. Ser. PY 2011 BP 173 EP 192 PG 20 WC Oncology; Mathematical & Computational Biology SC Oncology; Mathematical & Computational Biology GA BC8CU UT WOS:000355551800010 ER PT B AU McCarthy, JR Weissleder, R AF McCarthy, Jason R. Weissleder, Ralph BE Chen, X TI Multimodal Imaging and Therapy with Magnetofluorescent Nanoparticles SO NANOPLATFORM-BASED MOLECULAR IMAGING LA English DT Article; Book Chapter ID SUPERPARAMAGNETIC IRON-OXIDE; CONTRAST MR-ANGIOGRAPHY; IN-VIVO TRACKING; MAGNETIC NANOPARTICLES; E-SELECTIN; BIOMEDICAL APPLICATIONS; MOLECULAR ANALYSIS; PROSTATE-CANCER; DRUG-DELIVERY; BRAIN-TUMORS C1 [McCarthy, Jason R.; Weissleder, Ralph] Harvard Univ, Sch Med, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. [McCarthy, Jason R.; Weissleder, Ralph] Massachusetts Gen Hosp, Charlestown, MA USA. RP McCarthy, JR (reprint author), Harvard Univ, Sch Med, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. NR 95 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-76703-0; 978-0-470-52115-1 PY 2011 BP 593 EP 613 D2 10.1002/9780470767047 PG 21 WC Nanoscience & Nanotechnology; Radiology, Nuclear Medicine & Medical Imaging SC Science & Technology - Other Topics; Radiology, Nuclear Medicine & Medical Imaging GA BA5SW UT WOS:000336989900025 ER PT B AU Chen, HH Lucas, JA Chen, M AF Chen, H. H. Lucas, J. A. Chen, M. BE Laudon, M Romanowicz, B TI Effect of Carbon Nanotubes on Chinese Hamster Ovarian Cells SO NANOTECHNOLOGY 2011: BIO SENSORS, INSTRUMENTS, MEDICAL, ENVIRONMENT AND ENERGY, NSTI-NANOTECH 2011, VOL 3 LA English DT Proceedings Paper CT NSTI Nanotechnology Conference and Expo CY JUN 13-16, 2011 CL Boston, MA SP Clean Technol & Sustainable Ind Org, European Patent Off, Greenberg Traurig, Innovat & Mat Sci Inst, Jackson Walker LLP, Linde Nanomaterials, Lockheed Martin, Nano Sci & Technol Inst, Nano Tech Japan, NanoEurope Fair & Conf, Nanpolis Suzhou, Suzhou Nanotech Co Ltd, Natl Inst Standards & Technol, Ctr Nanoscale Sci & Technol, Fraunhofer, Res Germany, TechConnect, Technol Innovat Program, Canadian Trade Commiss Serv, Italian Trade Commiss DE carbon nanotubes; ovarian cells; toxicity; biocompatibility ID LIVING MICE; AGENTS; BIODISTRIBUTION AB We investigated the effect of various concentration of PBS buffered single-walled carbon nanotubes' (SWNTs) solutions on Chinese Hamster Ovarian (CHO) cells at multiple time points. Optical imaging on the CHO cell morphology showed that SWNTs accumulate in various parts of the cells, and the corresponding cell morphology provided qualitative information about the state of the cells' health. Cell-Titer-Glo Luminescence measures ATP level to give quantitative measurement of the percentage of cell survival at various SWNTs concentrations. Our results was consistent with previous findings on the acute toxicity of high concentration SWNTs. At low SWNTs concentration (0.05 mg/ml) our data showed a dramatic decrease in the cell survival after longer (2 day) SWNTs exposure. The toxicity of SWNTs even at low concentrations suggests caution in in-vivo use of SWNTs. C1 [Chen, H. H.] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. [Lucas, J. A.] Simmons Coll, Dept Phys, Boston, MA 02115 USA. [Chen, M.] Point Loma Nazarene Univ, Dept Phys & Engn, San Diego, CA USA. RP Chen, HH (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. EM chen.howard@mgh.harvard.edu; jessica.lucas@simmons.edu; MichelleChen@pointloma.edu NR 15 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4398-7138-6 PY 2011 BP 513 EP 516 PG 4 WC Energy & Fuels; Engineering, Environmental; Nanoscience & Nanotechnology; Medicine, Research & Experimental; Materials Science, Biomaterials SC Energy & Fuels; Engineering; Science & Technology - Other Topics; Research & Experimental Medicine; Materials Science GA BG9XC UT WOS:000394061000135 ER PT J AU Williams, DA Thrasher, AJ AF Williams, David A. Thrasher, Adrian J. TI Out of harm's way SO NATURE BIOTECHNOLOGY LA English DT Editorial Material ID ZINC-FINGER NUCLEASES; HUMAN GENOME; INTEGRATION; LOCUS; CELLS C1 [Williams, David A.] Childrens Hosp, Boston, MA 02115 USA. [Williams, David A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Thrasher, Adrian J.] Inst Child Hlth, Mol Immunol Unit, Ctr Immunodeficiency, London, England. RP Williams, DA (reprint author), Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA. EM DAWilliams@childrens.harvard.edu; a.thrasher@ich.ucl.ac.uk FU Wellcome Trust [090233] NR 10 TC 1 Z9 1 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JAN PY 2011 VL 29 IS 1 BP 41 EP 42 DI 10.1038/nbt.1750 PG 2 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 704JQ UT WOS:000286048900018 PM 21221100 ER PT J AU Anders, AK Call, MJ Schulze, MSED Fowler, KD Schubert, DA Seth, NP Sundberg, EJ Wucherpfennig, KW AF Anders, Anne-Kathrin Call, Melissa J. Schulze, Monika-Sarah E. D. Fowler, Kevin D. Schubert, David A. Seth, Nilufer P. Sundberg, Eric J. Wucherpfennig, Kai W. TI HLA-DM captures partially empty HLA-DR molecules for catalyzed removal of peptide SO NATURE IMMUNOLOGY LA English DT Article ID MHC CLASS-II; MAJOR HISTOCOMPATIBILITY COMPLEX; RESTRICTED ANTIGEN PRESENTATION; INVARIANT-CHAIN; CUTTING EDGE; HYDROGEN-BONDS; KINETIC STABILITY; CRYSTAL-STRUCTURE; IN-VIVO; HLA-DR1 AB The mechanisms of HLA-DM-catalyzed peptide exchange remain uncertain. Here we found that all stages of the interaction of HLA-DM with HLA-DR were dependent on the occupancy state of the peptide-binding groove. High-affinity peptides were protected from removal by HLA-DM through two mechanisms: peptide binding induced the dissociation of a long-lived complex of empty HLA-DR and HLA-DM, and high-affinity HLA-DR-peptide complexes bound HLA-DM only very slowly. Nonbinding covalent HLA-DR-peptide complexes were converted into efficient HLA-DM binders after truncation of an N-terminal peptide segment that emptied the P1 pocket and disrupted conserved hydrogen bonds to HLA-DR. HLA-DM thus binds only to HLA-DR conformers in which a critical part of the binding site is already vacant because of spontaneous peptide motion. C1 [Anders, Anne-Kathrin; Call, Melissa J.; Schulze, Monika-Sarah E. D.; Schubert, David A.; Seth, Nilufer P.; Wucherpfennig, Kai W.] Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. [Anders, Anne-Kathrin; Wucherpfennig, Kai W.] Harvard Univ, Sch Med, Program Immunol, Boston, MA USA. [Schulze, Monika-Sarah E. D.] Free Univ Berlin, Fachbereich Biol, D-1000 Berlin, Germany. [Fowler, Kevin D.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Sundberg, Eric J.] Boston Biomed Res Inst, Watertown, MA USA. RP Wucherpfennig, KW (reprint author), Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. EM kai_wucherpfennig@dfci.harvard.edu FU National Institutes of Health [R01 AI057493, NS044914]; Cancer Research Institute FX We thank A. Chakraborty for discussions; H. Ploegh and G. Grotenbreg (Massachusetts Institute of Technology) for the photolabile peptide; J. Fraser (University of Auckland) for human rhinovirus 3C protease; and J. Pyrdol for help with the purification of HLA-DR-peptide complexes. Supported by the National Institutes of Health (R01 AI057493 and NS044914 to K. W. W.) and the Cancer Research Institute (Irvington Institute Fellowship Program, D.A.S.). NR 49 TC 56 Z9 56 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD JAN PY 2011 VL 12 IS 1 BP 54 EP U76 DI 10.1038/ni.1967 PG 9 WC Immunology SC Immunology GA 696TU UT WOS:000285465100013 PM 21131964 ER PT J AU Araldi, E Khatri, R Giaccia, AJ Simon, MC Schipani, E AF Araldi, Elisa Khatri, Richa Giaccia, Amato J. Simon, M. Celeste Schipani, Ernestina TI Lack of HIF-2 alpha in limb bud mesenchyme causes a modest and transient delay of endochondral bone development SO NATURE MEDICINE LA English DT Letter C1 [Araldi, Elisa; Khatri, Richa; Schipani, Ernestina] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Endocrine Unit, Boston, MA 02163 USA. [Giaccia, Amato J.] Stanford Univ, Dept Radiat Oncol, Sch Med, Div Canc & Radiat Biol, Stanford, CA 94305 USA. [Simon, M. Celeste] Univ Penn, Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. RP Araldi, E (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Endocrine Unit, Boston, MA 02163 USA. EM schipani@helix.mgh.harvard.edu FU NIAMS NIH HHS [R01 AR048191, R01 AR048191-09, R01 AR048191-06] NR 5 TC 23 Z9 23 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JAN PY 2011 VL 17 IS 1 BP 25 EP 26 DI 10.1038/nm0111-25 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 703QH UT WOS:000285994000018 PM 21217667 ER PT J AU Ponomarev, ED Veremeyko, T Barteneva, N Krichevsky, AM Weiner, HL AF Ponomarev, Eugene D. Veremeyko, Tatyana Barteneva, Natasha Krichevsky, Anna M. Weiner, Howard L. TI MicroRNA-124 promotes microglia quiescence and suppresses EAE by deactivating macrophages via the C/EBP-alpha-PU.1 pathway SO NATURE MEDICINE LA English DT Article ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MONOCYTE LINEAGE COMMITMENT; NECROSIS-FACTOR RECEPTOR; C/EBP-ALPHA; NEURONAL DIFFERENTIATION; CELLS; PU.1; CNS; PROLIFERATION; EXPRESSION AB MicroRNAs are a family of regulatory molecules involved in many physiological processes, including differentiation and activation of cells of the immune system. We found that brain-specific miR-124 is expressed in microglia but not in peripheral monocytes or macrophages. When overexpressed in macrophages, miR-124 directly inhibited the transcription factor CCAAT/enhancer-binding protein-alpha (C/EBP-alpha) and its downstream target PU.1, resulting in transformation of these cells from an activated phenotype into a quiescent CD45(low), major histocompatibility complex (MHC) class IIlow phenotype resembling resting microglia. During experimental autoimmune encephalomyelitis (EAE), miR-124 was downregulated in activated microglia. Peripheral administration of miR-124 in EAE caused systemic deactivation of macrophages, reduced activation of myelin-specific T cells and marked suppression of disease. Conversely, knockdown of miR-124 in microglia and macrophages resulted in activation of these cells in vitro and in vivo. These findings identify miR-124 both as a key regulator of microglia quiescence in the central nervous system and as a previously unknown modulator of monocyte and macrophage activation. C1 [Ponomarev, Eugene D.; Veremeyko, Tatyana; Krichevsky, Anna M.; Weiner, Howard L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis, Boston, MA 02115 USA. [Barteneva, Natasha] Harvard Univ, Immune Dis Inst, Sch Med, Boston, MA 02115 USA. RP Krichevsky, AM (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis, Boston, MA 02115 USA. EM akrichevsky@rics.bwh.harvard.edu; hweiner@rics.bwh.harvard.edu FU US National Institutes of Health [R01 NS071039-01A1] FX We thank V. Kuchroo and F.J. Quintana for critical discussion of the results and I. Sotnikov for technical assistance with immunohistochemistry. 2D2 mice were kindly provided by V. Kuchroo (Brigham and Women's Hospital, Harvard Medical School). This work was supported in part by US National Institutes of Health grant R01 NS071039-01A1. NR 45 TC 260 Z9 274 U1 2 U2 27 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JAN PY 2011 VL 17 IS 1 BP 64 EP U234 DI 10.1038/nm.2266 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 703QH UT WOS:000285994000037 PM 21131957 ER PT J AU Sander, JD Dahlborg, EJ Goodwin, MJ Cade, L Zhang, F Cifuentes, D Curtin, SJ Blackburn, JS Thibodeau-Beganny, S Qi, YP Pierick, CJ Hoffman, E Maeder, ML Khayter, C Reyon, D Dobbs, D Langenau, DM Stupar, RM Giraldez, AJ Voytas, DF Peterson, RT Yeh, JRJ Joung, JK AF Sander, Jeffry D. Dahlborg, Elizabeth J. Goodwin, Mathew J. Cade, Lindsay Zhang, Feng Cifuentes, Daniel Curtin, Shaun J. Blackburn, Jessica S. Thibodeau-Beganny, Stacey Qi, Yiping Pierick, Christopher J. Hoffman, Ellen Maeder, Morgan L. Khayter, Cyd Reyon, Deepak Dobbs, Drena Langenau, David M. Stupar, Robert M. Giraldez, Antonio J. Voytas, Daniel F. Peterson, Randall T. Yeh, Jing-Ruey J. Joung, J. Keith TI Selection-free zinc-finger-nuclease engineering by context-dependent assembly (CoDA) SO NATURE METHODS LA English DT Article ID TARGETED MUTAGENESIS; DNA RECOGNITION AB Engineered zinc-finger nucleases (ZFNs) enable targeted genome modification. Here we describe context-dependent assembly (CoDA), a platform for engineering ZFNs using only standard cloning techniques or custom DNA synthesis. Using CoDA-generated ZFNs, we rapidly altered 20 genes in Danio rerio, Arabidopsis thaliana and Glycine max. The simplicity and efficacy of CoDA will enable broad adoption of ZFN technology and make possible large-scale projects focused on multigene pathways or genome-wide alterations. C1 [Sander, Jeffry D.; Dahlborg, Elizabeth J.; Goodwin, Mathew J.; Blackburn, Jessica S.; Thibodeau-Beganny, Stacey; Maeder, Morgan L.; Khayter, Cyd; Langenau, David M.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA USA. [Sander, Jeffry D.; Dahlborg, Elizabeth J.; Goodwin, Mathew J.; Blackburn, Jessica S.; Thibodeau-Beganny, Stacey; Maeder, Morgan L.; Khayter, Cyd; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Charlestown, MA USA. [Sander, Jeffry D.; Blackburn, Jessica S.; Langenau, David M.; Joung, J. Keith] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Cade, Lindsay; Peterson, Randall T.; Yeh, Jing-Ruey J.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Zhang, Feng; Qi, Yiping; Pierick, Christopher J.; Voytas, Daniel F.] Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN USA. [Zhang, Feng; Qi, Yiping; Pierick, Christopher J.; Voytas, Daniel F.] Univ Minnesota, Ctr Genome Engn, Minneapolis, MN USA. [Cifuentes, Daniel; Hoffman, Ellen; Giraldez, Antonio J.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. [Curtin, Shaun J.; Stupar, Robert M.] Univ Minnesota, Dept Agron & Plant Genet, St Paul, MN USA. [Maeder, Morgan L.; Langenau, David M.; Joung, J. Keith] Harvard Univ, Sch Med, Biol & Biomed Sci Program, Boston, MA USA. [Reyon, Deepak; Dobbs, Drena] Iowa State Univ, Dept Genet Dev & Cell Biol, Ames, IA USA. [Reyon, Deepak; Dobbs, Drena] Iowa State Univ, Bioinformat & Computat Biol Program, Ames, IA USA. [Peterson, Randall T.; Yeh, Jing-Ruey J.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Peterson, Randall T.] Broad Inst, Cambridge, MA USA. EM jjoung@partners.org RI Qi, Yiping/E-2004-2011; OI Cifuentes Buira, Daniel/0000-0001-5442-4843; Qi, Yiping/0000-0002-9556-6706; Stupar, Robert/0000-0002-8836-2924 FU US National Institutes of Health [R01 GM088040, R01 GM069906, R24 GM078369, R01 CA140188, R01 GM081602, RC2 MH089956, K01 AG031300, K01 AR055619, T32 CA009216]; National Science Foundation [DBI 0923827]; Claflin Distinguished Scholar Award; Minnesota Soybean Research and Promotion Council; Alex's Lemonade Stand; Leukemia Research Foundation FX This work was supported by US National Institutes of Health grants R01 GM088040 (J.K.J. and R.T.P.), R01 GM069906 (J.K.J.), R24 GM078369 (J.K.J.), R01 CA140188 (J.-R.J.Y.), R01 GM081602 (A.J.G.), RC2 MH089956 (A.J.G.), K01 AG031300 (J.-R.J.Y.), K01 AR055619 (D.M.L.) and T32 CA009216 (J.D.S. and J.S.B.); by National Science Foundation grant DBI 0923827 (D.F.V., D.D. and J.K.J.); by the Claflin Distinguished Scholar Award (J.-R.J.Y.); by the Minnesota Soybean Research and Promotion Council (S.J.C. and R.M.S.); and by Alex's Lemonade Stand and the Leukemia Research Foundation (D.M.L.). NR 20 TC 232 Z9 252 U1 5 U2 41 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 JAN PY 2011 VL 8 IS 1 BP 67 EP U94 DI 10.1038/NMETH.1542 PG 4 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 700CZ UT WOS:000285712000024 PM 21151135 ER PT J AU Lo Celso, C Lin, CP Scadden, DT AF Lo Celso, Cristina Lin, Charles P. Scadden, David T. TI In vivo imaging of transplanted hematopoietic stem and progenitor cells in mouse calvarium bone marrow SO NATURE PROTOCOLS LA English DT Article ID GREEN FLUORESCENT PROTEIN; NICHE; ENGRAFTMENT; TRACKING; MICE; MICROENVIRONMENT; RECONSTITUTION; REVEAL AB In vivo imaging of transplanted hematopoietic stem and progenitor cells (HSPCs) was developed to investigate the relationship between HSPCs and components of their microenvironment in the bone marrow. In particular, it allows a direct observation of the behavior of hematopoietic cells during the first few days after transplantation, when the critical events in homing and early engraftment are occurring. By directly imaging these events in living animals, this method permits a detailed assessment of functions previously evaluated by crude assessments of cell counts (homing) or after prolonged periods (engraftment). This protocol offers a new means of investigating the role of cell-intrinsic and cell-extrinsic molecular regulators of hematopoiesis during the early stages of transplantation, and it is the first to allow the study of cell-cell interactions within the bone marrow in three dimensions and in real time. In this paper, we describe how to isolate, label and inject HSPCs, as well as how to perform calvarium intravital microscopy and analyze the resulting images. A typical experiment can be performed and analyzed in similar to 1 week. C1 [Lo Celso, Cristina; Scadden, David T.] Ctr Regenerat Med, Boston, MA USA. [Lo Celso, Cristina; Lin, Charles P.; Scadden, David T.] Harvard Stem Cell Inst, Cambridge, MA USA. [Lo Celso, Cristina] Univ London Imperial Coll Sci Technol & Med, Div Cell & Mol Biol, London, England. [Lin, Charles P.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Lin, Charles P.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Scadden, David T.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. RP Lo Celso, C (reprint author), Ctr Regenerat Med, Boston, MA USA. EM c.lo-celso@imperial.ac.uk OI Lo Celso, Cristina/0000-0002-1163-4207 FU European Molecular Biology Organization; Human Frontier Science Program; Imperial College London; Kay Kendall Leukaemia Foundation; Cancer Research UK; NIH FX We thank F. Ferraro, S. Lane, S. Lymperi, E. Ozcivici, A. Sanchez-Aguilera and M. Spitaler for critical input on the manuscript. C. L. C. was funded by the European Molecular Biology Organization and Human Frontier Science Program and is currently funded by Imperial College London, Kay Kendall Leukaemia Foundation and Cancer Research UK. C. P. L. and D. T. S. are funded by multiple NIH grants. NR 35 TC 40 Z9 40 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PD JAN PY 2011 VL 6 IS 1 BP 1 EP 14 DI 10.1038/nprot.2010.168 PG 14 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 703FY UT WOS:000285965000001 PM 21212779 ER PT J AU Laubach, J Richardson, P AF Laubach, Jacob Richardson, Paul TI HEMATOLOGY Bortezomib and dexamethasone induction for multiple myeloma SO NATURE REVIEWS CLINICAL ONCOLOGY LA English DT Editorial Material ID STEM-CELL TRANSPLANTATION; SURVIVAL; VINCRISTINE; TRIAL AB An important phase III trial involving transplant-eligible patients with multiple myeloma compared bortezomib and dexamethasone (BzD) induction with the previous standard of care. BzD was associated with a higher overall response and a deeper response to therapy that translated to superior responses following high-dose therapy and autologous stem cell transplantation. C1 [Laubach, Jacob; Richardson, Paul] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Laubach, Jacob; Richardson, Paul] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Laubach, Jacob; Richardson, Paul] Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. RP Laubach, J (reprint author), Harvard Univ, Sch Med, 44 Binney St, Boston, MA 02115 USA. EM jacobp_laubach@dfci.harvard.edu NR 10 TC 7 Z9 7 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4774 J9 NAT REV CLIN ONCOL JI Nat. Rev. Clin. Oncol. PD JAN PY 2011 VL 8 IS 1 BP 8 EP 10 DI 10.1038/nrclinonc.2010.206 PG 4 WC Oncology SC Oncology GA 697UC UT WOS:000285542800003 PM 21179054 ER PT J AU Cheok, CF Verma, CS Baselga, J Lane, DP AF Cheok, Chit Fang Verma, Chandra S. Baselga, Jose Lane, David P. TI Translating p53 into the clinic SO NATURE REVIEWS CLINICAL ONCOLOGY LA English DT Review ID WILD-TYPE P53; CHRONIC LYMPHOCYTIC-LEUKEMIA; MDM2 ANTAGONIST NUTLIN-3; STRUCTURE-BASED DESIGN; ACUTE MYELOGENOUS LEUKEMIA; TUMOR-SUPPRESSOR PATHWAY; SMALL-MOLECULE INHIBITOR; CELL-CYCLE ARREST; CANCER-CELLS; LUNG-CANCER AB Mutations in the TP53 gene are a feature of 50% of all reported cancer cases. In the other 50% of cases, the TP53 gene itself is not mutated but the p53 pathway is often partially inactivated. Cancer therapies that target specific mutant genes are proving to be highly active and trials assessing agents that exploit the p53 system are ongoing. Many trials are aimed at stratifying patients on the basis of TP53 status. In another approach, TP53 is delivered as a gene therapy; this is the only currently approved p53-based treatment. The p53 protein is overexpressed in many cancers and p53-based vaccines are undergoing trials. Processed cell-surface p53 is being exploited as a target for protein-drug conjugates, and small-molecule drugs that inhibit the activity of MDM2, the E3 ligase that regulates p53 levels, have been developed by several companies. The first MDM2 inhibitors are being trialed in both hematologic and solid malignancies. Finally, the first agent found to restore the active function of mutant TP53 has just entered the clinic. Here we discuss the basis of these trials and the future of p53-based therapy. C1 [Cheok, Chit Fang; Lane, David P.] ASTAR, Lab P53, Singapore 138648, Singapore. [Verma, Chandra S.] ASTAR, Bioinformat Inst, Singapore 138671, Singapore. [Baselga, Jose] Harvard Univ, Sch Med, Ctr Canc, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Lane, DP (reprint author), ASTAR, Lab P53, 8A Biomed Grove 06-06, Singapore 138648, Singapore. EM dplane@p53lab.a-star.edu.sg NR 144 TC 195 Z9 198 U1 7 U2 47 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4774 J9 NAT REV CLIN ONCOL JI Nat. Rev. Clin. Oncol. PD JAN PY 2011 VL 8 IS 1 BP 25 EP 37 DI 10.1038/nrclinonc.2010.174 PG 13 WC Oncology SC Oncology GA 697UC UT WOS:000285542800006 PM 20975744 ER PT J AU Tritos, NA Byrne, TN Wu, CL Klibanski, A AF Tritos, Nicholas A. Byrne, Thomas N. Wu, Chin-Lee Klibanski, Anne TI A patient with diabetes insipidus, anterior hypopituitarism and pituitary stalk thickening SO NATURE REVIEWS ENDOCRINOLOGY LA English DT Article ID LANGERHANS CELL HISTIOCYTOSIS; CENTRAL-NERVOUS-SYSTEM; ADULT GH DEFICIENCY; RADIOLOGICAL FEATURES; LESIONS; GROWTH; HORMONE; LCH; MANIFESTATIONS; DIAGNOSIS AB Background. A 42-year-old woman presented to the neuroendocrine unit of a hospital with recent-onset polydipsia, polyuria and oligomenorrhea. She had no visual symptoms, head injury or history of malignancy. Investigations. Measurement of serum sodium and osmolality (as well as urine osmolality) after water deprivation, both before and after desmopressin administration. Measurement of basal serum concentrations of pituitary hormones, insulin-like growth factor 1 and thyroid hormone, cosyntropin stimulation testing of adrenal function, and growth-hormone-releasing hormone-arginine stimulation testing. MRI of the pituitary, CT of the chest and abdomen, skeletal surveys, analyses of cerebrospinal fluid, serology and histologic examination of an excised, painful submandibular salivary gland. Diagnosis. Central diabetes insipidus and anterior hypopituitarism secondary to Langerhans cell histiocytosis. Management. Replacement therapies, including desmopressin, levothyroxine, cyclic estrogen with medroxyprogesterone, and growth hormone. The stalk lesion remained stable after 7 years without specific therapy. C1 [Tritos, Nicholas A.; Klibanski, Anne] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Byrne, Thomas N.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Wu, Chin-Lee] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Tritos, NA (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Zero Emerson Pl,Suite 112, Boston, MA 02114 USA. EM ntritos@partners.org NR 27 TC 2 Z9 2 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5029 J9 NAT REV ENDOCRINOL JI Nat. Rev. Endocrinol. PD JAN PY 2011 VL 7 IS 1 BP 54 EP 59 DI 10.1038/nrendo.2010.198 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 694YF UT WOS:000285337100008 PM 21102546 ER PT J AU Kelly, PJ Lauwers, GY AF Kelly, Paul J. Lauwers, Gregory Y. TI CLINICAL GUIDELINES Consensus for the management of patients with gastric polyps SO NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY LA English DT Editorial Material ID SURVEILLANCE; TUMORS AB Gastric polyps are a heterogeneous group of lesions that have differing consequences for patients, particularly in terms of malignant potential. However, there is currently no consensus for the management of patients with these polyps. The British society of gastroenterology has, therefore, published objective management guidelines for patients with these lesions. C1 [Kelly, Paul J.] Royal Grp Hosp, Dept Pathol, Belfast BT12 6BA, Antrim, North Ireland. [Lauwers, Gregory Y.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Kelly, PJ (reprint author), Royal Grp Hosp, Dept Pathol, Grosvenor Rd, Belfast BT12 6BA, Antrim, North Ireland. EM p.kelly@doctors.org.uk NR 10 TC 7 Z9 8 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5045 J9 NAT REV GASTRO HEPAT JI Nat. Rev. Gastroenterol. Hepatol. PD JAN PY 2011 VL 8 IS 1 BP 7 EP 8 DI 10.1038/nrgastro.2010.187 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 703PW UT WOS:000285992300001 PM 21119611 ER PT J AU Ananthakrishnan, AN AF Ananthakrishnan, Ashwin N. TI Clostridium difficile infection: epidemiology, risk factors and management SO NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY LA English DT Review ID INFLAMMATORY-BOWEL-DISEASE; ANTIBIOTIC-ASSOCIATED DIARRHEA; PCR RIBOTYPE 027; INTRAVENOUS IMMUNOGLOBULIN; HYPERVIRULENT STRAIN; TREATMENT STRATEGIES; TOXIN-A; COLITIS; VANCOMYCIN; METRONIDAZOLE AB The epidemiology of Clostridium difficile infection (CDI) has changed over the past decade. There has been a dramatic worldwide increase in its incidence, and new CDI populations are emerging, such as those with community-acquired infection and no previous exposure to antibiotics, children, pregnant women and patients with IBD. Diagnosis of CDI requires identification of C. difficile toxin A or B in diarrheal stool. The accuracy of current diagnostic tests remains inadequate and the optimal diagnostic testing algorithm has not been defined. The first-line agents for CDI treatment are metronidazole and vancomycin, with the latter being the preferred agent in patients with severe disease as it has significantly superior efficacy. The incidence of metronidazole treatment failures has increased, emphasizing the need to find alternative treatment options. Disease recurrence continues to occur in 20-40% of patients and its treatment remains challenging. In patients with CDI who develop fulminant colitis, early surgical consultation is essential. Intravenous immunoglobulin and tigecycline have been used in patients with severe refractory disease but delaying surgery may be associated with worse outcomes. Infection control measures are key to prevent horizontal transmission of infection. Ongoing research into effective treatment protocols and prevention is essential. C1 [Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ananthakrishnan, Ashwin N.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM aananthakrishnan@partners.org NR 90 TC 145 Z9 154 U1 5 U2 34 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5045 J9 NAT REV GASTRO HEPAT JI Nat. Rev. Gastroenterol. Hepatol. PD JAN PY 2011 VL 8 IS 1 BP 17 EP 26 DI 10.1038/nrgastro.2010.190 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 703PW UT WOS:000285992300007 PM 21119612 ER PT J AU Zhou, VW Goren, A Bernstein, BE AF Zhou, Vicky W. Goren, Alon Bernstein, Bradley E. TI Charting histone modifications and the functional organization of mammalian genomes SO NATURE REVIEWS GENETICS LA English DT Review ID EMBRYONIC STEM-CELLS; DNA METHYLATION; CHROMATIN-STRUCTURE; GENE-EXPRESSION; CPG ISLANDS; TRANSCRIPTIONAL COMPETENCE; HEMATOPOIETIC PROGENITORS; DEVELOPMENTAL REGULATORS; ACTIVE PROMOTERS; H3K4 METHYLATION AB A succession of technological advances over the past decade have enabled researchers to chart maps of histone modifications and related chromatin structures with increasing accuracy, comprehensiveness and throughput. The resulting data sets highlight the interplay between chromatin and genome function, dynamic variations in chromatin structure across cellular conditions, and emerging roles for large-scale domains and higher-ordered chromatin organization. Here we review a selection of recent studies that have probed histone modifications and successive layers of chromatin structure in mammalian genomes, the patterns that have been identified and future directions for research. C1 [Zhou, Vicky W.; Goren, Alon; Bernstein, Bradley E.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. [Zhou, Vicky W.; Goren, Alon; Bernstein, Bradley E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Zhou, Vicky W.; Goren, Alon; Bernstein, Bradley E.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Zhou, Vicky W.; Goren, Alon; Bernstein, Bradley E.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Zhou, Vicky W.; Goren, Alon; Bernstein, Bradley E.] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. [Zhou, Vicky W.; Goren, Alon; Bernstein, Bradley E.] MIT, Cambridge, MA 02142 USA. [Zhou, Vicky W.; Goren, Alon; Bernstein, Bradley E.] Broad Inst Harvard, Cambridge, MA 02142 USA. [Zhou, Vicky W.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Bernstein, BE (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. EM Bernstein.Bradley@mgh.harvard.edu RI Sincan, Murat /A-3794-2010 FU National Defense Science and Engineering Graduate Fellowship; National Science Foundation; EMBO; Howard Hughes Medical Institute; National Institutes of Health FX We thank E. Mendenhall, M. Ku, R. Koche and E. Rheinbay for critical reading of the manuscript. We also thank members of the Bernstein laboratory for insightful discussions. V.W.Z. was supported by a National Defense Science and Engineering Graduate Fellowship and a National Science Foundation Graduate Research Fellowship. A.G. was supported by an EMBO long-term postdoctoral fellowship. B.E.B. is an Early Career Scientist of the Howard Hughes Medical Institute. Research in the Bernstein laboratory is supported by funds from the Burroughs Wellcome Fund, Howard Hughes Medical Institute and the National Institutes of Health. NR 117 TC 461 Z9 477 U1 14 U2 103 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0056 J9 NAT REV GENET JI Nat. Rev. Genet. PD JAN PY 2011 VL 12 IS 1 BP 7 EP 18 DI 10.1038/nrg2905 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 695ZA UT WOS:000285410500007 PM 21116306 ER PT J AU Barabasi, AL Gulbahce, N Loscalzo, J AF Barabasi, Albert-Laszlo Gulbahce, Natali Loscalzo, Joseph TI Network medicine: a network-based approach to human disease SO NATURE REVIEWS GENETICS LA English DT Review ID PROTEIN-INTERACTION NETWORK; METABOLIC NETWORKS; COMPLEX NETWORKS; TOPOLOGICAL FEATURES; INTERACTION DATASETS; GENETIC INTERACTIONS; BIOLOGICAL NETWORKS; INTERACTOME NETWORK; COMMUNITY STRUCTURE; MOLECULAR NETWORKS AB Given the functional interdependencies between the molecular components in a human cell, a disease is rarely a consequence of an abnormality in a single gene, but reflects the perturbations of the complex intracellular and intercellular network that links tissue and organ systems. The emerging tools of network medicine offer a platform to explore systematically not only the molecular complexity of a particular disease, leading to the identification of disease modules and pathways, but also the molecular relationships among apparently distinct (patho)phenotypes. Advances in this direction are essential for identifying new disease genes, for uncovering the biological significance of disease-associated mutations identified by genome-wide association studies and full-genome sequencing, and for identifying drug targets and biomarkers for complex diseases. C1 [Barabasi, Albert-Laszlo; Gulbahce, Natali] Northeastern Univ, Ctr Complex Networks Res, Dana Res Ctr 111, Boston, MA 02115 USA. [Barabasi, Albert-Laszlo; Gulbahce, Natali] Northeastern Univ, Dept Phys, Dana Res Ctr 111, Boston, MA 02115 USA. [Barabasi, Albert-Laszlo; Gulbahce, Natali] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. [Barabasi, Albert-Laszlo; Loscalzo, Joseph] Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp, Boston, MA 02115 USA. [Gulbahce, Natali] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA. RP Barabasi, AL (reprint author), Northeastern Univ, Ctr Complex Networks Res, Dana Res Ctr 111, 110 Forsyth St, Boston, MA 02115 USA. EM alb@neu.edu FU US National Institutes of Health (NIH) through Center of Excellence in Genomic Sciences (CEGS); NIH [HL061795, HL81587, HL70819, HL48743] FX We thank Z. Oltvai, A. Sharma, D.-S. Lee and J. Park for useful discussions and suggestions. A.L.B. and N.G. were supported by the US National Institutes of Health (NIH) through the Center of Excellence in Genomic Sciences (CEGS), and J. L. was supported by NIH grants HL061795 (Merit Award), HL81587, HL70819 and HL48743. NR 131 TC 1127 Z9 1177 U1 41 U2 256 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0056 J9 NAT REV GENET JI Nat. Rev. Genet. PD JAN PY 2011 VL 12 IS 1 BP 56 EP 68 DI 10.1038/nrg2918 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 695ZA UT WOS:000285410500011 PM 21164525 ER PT J AU Felsenfeld, AJ Levine, BS Kleeman, CR AF Felsenfeld, A. J. Levine, B. S. Kleeman, C. R. TI Fuller Albright and our current understanding of calcium and phosphorus regulation and primary hyperparathyroidism SO NEFROLOGIA LA English DT Article DE Calcium; Hyperparathyroidism; Hypoparathyroidism; Parathyroid hormone; Phosphorus ID VITAMIN-D DEFICIENCY; OSTEITIS FIBROSA CYSTICA; AFRICAN BANTU INFANTS; PARATHYROID-HORMONE; SERUM PHOSPHORUS; PHOSPHATE; GLANDS; HYPOPARATHYROIDISM; METABOLISM; EXPRESSION AB The major contributions of Fuller Albright to our understanding of calcium and phosphorus regulation and primary hyperparathyroidism are highlighted. Albright was the first investigator to initiate a systematic study of mineral metabolism. With resources limited to the measurement of serum calcium and phosphorus and the infusion of parathyroid extract, Albright used balance studies to establish a framework for our understanding of calcium and phosphorus regulation and primary hyperparathyroidism. Albright was the first to show that the etiology of primary hyperparathyroidism could be from either an adenoma or hyperplasia of the parathyroid glands and stone disease was a separate manifestation of primary hyperparathyroidism. Albright also showed that: 1) a renal threshold for calcium excretion was present in hypoparathyroid patients; 2) correction of hypocalcemia in hypoparathyroid patients with vitamin D had a phosphaturic action; 3) renal failure reduced the intestinal absorption of calcium in primary hyperparathyroidism; 4) the "hungry bone" syndrome developed after parathyroidectomy in severe primary hyperparathyroidism; and 5) a target organ can fail to respond to a hormone. He also suggested that a malignant tumor could be responsible for ectopic hormone production. Finally, our review integrates the observations of Albright with our current knowledge of calcium regulation and disorders. C1 [Felsenfeld, A. J.] VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA. [Felsenfeld, A. J.] Univ Calif Los Angeles, David Geffen Sch Med, Nephrol Sect 111L, W Los Angeles VA Med Ctr, Los Angeles, CA USA. RP Felsenfeld, AJ (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Med, 11301 Wilshire Blvd, Los Angeles, CA USA. EM Arnold.Felsenfeld@va.gov NR 71 TC 0 Z9 0 U1 0 U2 2 PU SOC ESPANOLA NEFROLOGIA DR RAFAEL MATESANZ PI MADRID PA HOSPITAL RAMON Y CAJAL CTR DE COLMENAR, KM 9,100, 28034 MADRID, SPAIN SN 0211-6995 J9 NEFROLOGIA JI Nefrologia PY 2011 VL 31 IS 3 BP 346 EP 357 DI 10.3265/Nefrologia.pre2011.Mar.10774 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 772LG UT WOS:000291234800015 PM 21629339 ER PT J AU O'Seaghdha, CM Fox, CS AF O'Seaghdha, Conall M. Fox, Caroline S. TI Genetics of Chronic Kidney Disease SO NEPHRON CLINICAL PRACTICE LA English DT Article DE Chronic kidney disease; Genetic variation; Genome-wide association studies; Diabetic nephropathy; End-stage renal disease ID STAGE RENAL-DISEASE; MANGANESE SUPEROXIDE-DISMUTASE; TYPE-2 DIABETIC-PATIENTS; GENOME-WIDE ASSOCIATION; INCIDENT DIALYSIS PATIENTS; URINARY ALBUMIN EXCRETION; AFRICAN-AMERICANS; FECHTNER-SYNDROME; IGA NEPHROPATHY; FAMILIAL PREDISPOSITION AB The current review collates what is already known of the genetics of chronic kidney disease (CKD), and focuses on new trends in genome-wide assessment of the inherited component of susceptibility to this condition. Early efforts to identify kidney disease susceptibility genetic loci using linkage and candidate gene strategies proved disappointing. More recently, genome-wide association studies have yielded highly promising results suggesting a number of potential candidate genes and genomic regions that may contribute to the pathogenesis of CKD. Renal failure susceptibility genes identified by these methods, such as MYH9, have yielded novel insights into the pathogenesis of CKD. Genome-wide association studies of CKD are beginning to define the genomic architecture of kidney disease and will impact our understanding of how genetic variation influences susceptibility to this condition. Copyright (C) 2010 S. Karger AG, Basel C1 [O'Seaghdha, Conall M.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [O'Seaghdha, Conall M.] Massachusetts Gen Hosp, Brigham & Womens Hosp, Div Renal, Boston, MA 02114 USA. [O'Seaghdha, Conall M.; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA. RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov NR 88 TC 8 Z9 8 U1 0 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2110 J9 NEPHRON CLIN PRACT JI Nephron. Clin. Pract. PY 2011 VL 118 IS 1 BP C55 EP C63 DI 10.1159/000320905 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 679JD UT WOS:000284156800009 PM 21071974 ER PT J AU Putrino, DF Chen, Z Ghosh, S Brown, EN AF Putrino, David F. Chen, Zhe Ghosh, Soumya Brown, Emery N. TI Motor Cortical Networks for Skilled Movements Have Dynamic Properties That Are Related to Accurate Reaching SO NEURAL PLASTICITY LA English DT Article ID NEURAL SPIKING ACTIVITY; RAY KINEMATIC ANALYSIS; CAT CEREBRAL-CORTEX; INHIBITORY NEURONS; FUNCTIONAL CONNECTIVITY; SPECIALIZED SUBREGIONS; PREFRONTAL CORTEX; PYRAMIDAL NEURONS; SENSORY-MOTOR; INTERNEURONS AB Neurons in the Primary Motor Cortex (MI) are known to form functional ensembles with one another in order to produce voluntary movement. Neural network changes during skill learning are thought to be involved in improved fluency and accuracy of motor tasks. Unforced errors during skilled tasks provide an avenue to study network connections related to motor learning. In order to investigate network activity in MI, microwires were implanted in the MI of cats trained to perform a reaching task. Spike trains from eight groups of simultaneously recorded cells (95 neurons in total) were acquired. A point process generalized linear model (GLM) was developed to assess simultaneously recorded cells for functional connectivity during reaching attempts where unforced errors or no errors were made. Whilst the same groups of neurons were often functionally connected regardless of trial success, functional connectivity between neurons was significantly different at fine time scales when the outcome of task performance changed. Furthermore, connections were shown to be significantly more robust across multiple latencies during successful trials of task performance. The results of this study indicate that reach-related neurons in MI form dynamic spiking dependencies whose temporal features are highly sensitive to unforced movement errors. C1 [Putrino, David F.; Chen, Zhe; Brown, Emery N.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurosci Stat Res Lab, Boston, MA 02114 USA. [Putrino, David F.; Chen, Zhe; Brown, Emery N.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Ghosh, Soumya] Univ Western Australia, Ctr Neuromuscular & Neurol Disorders, QEII Med Ctr, Nedlands, WA 6009, Australia. [Brown, Emery N.] Massachusetts Gen Hosp, Neurosci Stat Res Lab, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Brown, EN (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurosci Stat Res Lab, Boston, MA 02114 USA. EM enb@neurostat.mit.edu OI Putrino, David/0000-0002-2232-3324; Chen, Zhe/0000-0002-6483-6056 FU National Institute of Health (NIH) [DP1-OD003646, R01-DA015644]; Australian Neuromuscular Research Institute FX This work was supported by the National Institute of Health (NIH) under the Grants DP1-OD003646 (E.N.B.) and R01-DA015644 (E.N.B.) and by the Australian Neuromuscular Research Institute. NR 57 TC 1 Z9 1 U1 0 U2 0 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 0792-8483 J9 NEURAL PLAST JI Neural. Plast. PY 2011 AR 413543 DI 10.1155/2011/413543 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 869AE UT WOS:000298567200001 ER PT J AU Muldoon, LL Gahramanov, S Li, X Marshall, DJ Kraemer, DF Neuwelt, EA AF Muldoon, Leslie L. Gahramanov, Seymur Li, Xin Marshall, Deborah J. Kraemer, Dale F. Neuwelt, Edward A. TI Dynamic magnetic resonance imaging assessment of vascular targeting agent effects in rat intracerebral tumor models SO NEURO-ONCOLOGY LA English DT Article DE bevacizumab; blood-brain barrier; dynamic susceptibility-weighted contrast-enhanced magnetic resonance imaging; intetumumab ID RECURRENT GLIOBLASTOMA-MULTIFORME; MONOCLONAL-ANTIBODY; BRAIN-TUMORS; ANTIANGIOGENIC ACTIVITY; IN-VIVO; ANGIOGENESIS; INTEGRINS; VEGF; PERFUSION; SUSCEPTIBILITY AB We used dynamic Mill to evaluate the effects of monoclonal antibodies targeting brain tumor vasculature. Female athymic rats with intracerebral human tumor xenografts were untreated or treated with intetumumab, targeting alpha(v)-integrins, or bevacizumab, targeting vascular endothelial growth factor (n = 4-6 per group). Prior to treatment and at 1, 3, and 7 days after treatment, we performed standard MRI to assess tumor volume, dynamic susceptibility-contrast MRI with the blood-pool iron oxide nanoparticle fcrumoxytol to evaluate relative cerebral blood volume (rCBV), and dynamic contrast-enhanced MRI to assess tumor vascular permeability. Tumor rCBV increased by 27 +/- 13% over 7 days in untreated rats; intetumumab increased tumor rCBV by 65 +/- 10%, whereas bevacizumab reduced tumor rCBV by 31 +/- 10% at 7 days (P<.001 for group and day). Similarly, intetumumab increased brain tumor vascular permeability compared with controls at 3 and 7 days after treatment, whereas bevacizumab decreased tumor permeability within 24 hours (P=.0004 for group, P=.0081 for day). All tumors grew over the 7-day assessment period, but bevacizumab slowed the increase in tumor volume on Mill. We conclude that the vascular targeting agents intetumumab and bevacizumab had diametrically opposite effects on dynamic MRI of tumor vasculature in rat brain tumor models. Targeting av-integrins increased tumor vascular permeability and blood volume, whereas bevacizumab decreased both measures. These findings have implications for chemotherapy delivery and antitumor efficacy. C1 [Muldoon, Leslie L.; Gahramanov, Seymur; Neuwelt, Edward A.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Muldoon, Leslie L.] Oregon Hlth & Sci Univ, Dept Cell & Dev Biol, Portland, OR 97239 USA. [Li, Xin] Oregon Hlth & Sci Univ, Adv Imaging Res Ctr, Portland, OR 97239 USA. [Neuwelt, Edward A.] Oregon Hlth & Sci Univ, Dept Neurosurg, Portland, OR 97239 USA. [Kraemer, Dale F.] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97239 USA. [Kraemer, Dale F.] Oregon Hlth & Sci Univ, Dept Med Informat, Portland, OR 97239 USA. [Kraemer, Dale F.] Oregon Hlth & Sci Univ, Dept Clin Epidemiol, Portland, OR 97239 USA. [Marshall, Deborah J.] Ortho Biotech Oncol R&D, Radnor, PA USA. [Kraemer, Dale F.] Oregon State Univ, Dept Pharm Practice, Portland, OR USA. [Neuwelt, Edward A.] Portland VA Med Ctr, Portland, OR USA. RP Neuwelt, EA (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, 3181 SW Sam Jackson Pk Rd,L603, Portland, OR 97239 USA. EM neuwelte@ohsu.edu FU Centocor Research and Development Inc.; NIH [NS053468, CA137488, NS44687] FX This study was supported by a sponsored research agreement from Centocor Research and Development Inc., and NIH grants NS053468, CA137488, and NS44687 to E.A.N. NR 42 TC 16 Z9 16 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JAN PY 2011 VL 13 IS 1 BP 51 EP 60 DI 10.1093/neuonc/noq150 PG 10 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 708KQ UT WOS:000286361100005 PM 21123368 ER PT J AU Prados, M Cloughesy, T Samant, M Fang, LA Wen, PY Mikkelsen, T Schiff, D Abrey, LE Yung, WKA Paleologos, N Nicholas, MK Jensen, R Vredenburgh, J Das, A Friedman, HS AF Prados, Michael Cloughesy, Timothy Samant, Meghna Fang, Liang Wen, Patrick Y. Mikkelsen, Tom Schiff, David Abrey, Lauren E. Yung, W. K. Alfred Paleologos, Nina Nicholas, Martin K. Jensen, Randy Vredenburgh, James Das, Asha Friedman, Henry S. TI Response as a predictor of survival in patients with recurrent glioblastoma treated with bevacizumab SO NEURO-ONCOLOGY LA English DT Article DE bevacizumab; glioblastoma multiforme (GBM); landmark analysis; objective response; residual survival ID PROGRESSION-FREE SURVIVAL; II CLINICAL-TRIALS; PHASE-II; MALIGNANT GLIOMA; PROGNOSTIC-FACTORS; END-POINT; CRITERIA; IRINOTECAN; CONSORTIUM; THERAPY AB Development of effective therapies for recurrent glioblastoma multiforme (GBM) and reliable, timely evaluation of their benefit are needed. Understanding the relationship between objective response (OR) and survival is important for determining whether OR can provide an early signal of treatment activity in clinical trials. We performed a landmark analysis to evaluate the association between OR and survival at 9, 18, and 26 weeks for 167 patients with recurrent GBM who participated in BRAIN, a phase H trial that evaluated efficacy of bevacizumab alone or in combination with irinotecan, using the Cox regression models adjusted for age, baseline Karnofsky performance score, first vs second relapse, and treatment arm. Hazard ratios (HRs) and P-values for survival between responders and nonresponders were calculated. Additional analyses were performed to test robustness, validity, fit, and accuracy of the models. The relationships between progression-free survival (PFS) and survival and between OR and PFS were also explored. There were 55 responders and 112 nonresponders across the 2 treatment arms in BRAIN. OR status at 9, 18, and 26 weeks was a statistically significant predictor of survival (HR <= 0.52, P<.01). PFS was also a statistically significant predictor of survival at each landmark (HR <= 0.25, P<.0001). The association between OR and PFS was not statistically significant, likely due to inadequate statistical power for the analysis. Clarifying the relationship of OR and survival is important for determining whether OR can be a reliable predictor of the benefit of a therapeutic agent in patients with recurrent GBM. C1 [Prados, Michael] Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA 94143 USA. [Cloughesy, Timothy] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Samant, Meghna; Fang, Liang; Das, Asha] Genentech Inc, San Francisco, CA 94080 USA. [Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Mikkelsen, Tom] Henry Ford Hosp, Hermelin Brain Tumor Ctr, Detroit, MI 48202 USA. [Schiff, David] Univ Virginia, Charlottesville, VA USA. [Abrey, Lauren E.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Yung, W. K. Alfred] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Paleologos, Nina] NorthShore Univ HealthSyst, Evanston, IL USA. [Nicholas, Martin K.] Univ Chicago, Chicago, IL 60637 USA. [Jensen, Randy] Univ Utah Hosp, Huntsman Canc Inst, Salt Lake City, UT USA. [Vredenburgh, James; Friedman, Henry S.] Duke Univ, Med Ctr, Preston Roberta Tisch Brain Tumor Ctr Duke, Durham, NC USA. RP Prados, M (reprint author), Univ Calif San Francisco, Dept Neurosurg, 400 Parnassus Ave,A-808, San Francisco, CA 94143 USA. EM pradosm@neurosurg.ucsf.edu FU Genentech, Inc. FX This work was supported by Genentech, Inc. NR 22 TC 32 Z9 32 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JAN PY 2011 VL 13 IS 1 BP 143 EP 151 DI 10.1093/neuonc/noq151 PG 9 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 708KQ UT WOS:000286361100013 PM 21084434 ER PT S AU Rembach, A Duce, JA O'Sullivan, LA Tanzi, RE Bush, AI AF Rembach, A. Duce, J. A. O'Sullivan, L. A. Tanzi, R. E. Bush, A. I. BE Milardi, D Rizzarelli, E TI Biological Metals: Metallostasis and Alzheimer's Disease SO NEURODEGENERATION: METALLOSTASIS AND PROTEOSTASIS SE RSC Drug Discovery Series LA English DT Article; Book Chapter ID AMYLOID PRECURSOR PROTEIN; A-BETA PEPTIDE; IRON-RESPONSIVE ELEMENT; ALPHA-SECRETASE CLEAVAGE; CYTOCHROME-C-OXIDASE; APP TRANSGENIC MICE; COPPER-BINDING SITE; P70 S6 KINASE; ZN-II-BINDING; SUPEROXIDE-DISMUTASE C1 [Rembach, A.; Duce, J. A.; O'Sullivan, L. A.; Bush, A. I.] Mental Hlth Res Inst, Parkville, Vic 3052, Australia. [Duce, J. A.] Univ Melbourne, Ctr Neurosci, Melbourne, Vic 3010, Australia. [Tanzi, R. E.] Massachusetts Gen Hosp, Genet & Ageing Res Unit, Dept Neurol, Boston, MA 02129 USA. [Tanzi, R. E.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Bush, A. I.] Univ Melbourne, Dept Pathol, Melbourne, Vic 3010, Australia. RP Rembach, A (reprint author), Mental Hlth Res Inst, Parkville, Vic 3052, Australia. RI Bush, Ashley/A-1186-2007 OI Bush, Ashley/0000-0001-8259-9069 NR 214 TC 0 Z9 0 U1 0 U2 0 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, CAMBRIDGE CB4 4WF, CAMBS, ENGLAND SN 2041-3203 BN 978-1-84973-050-1; 978-1-84973-301-4 J9 RSC DRUG DISCOV JI RSC Drug Discov. PY 2011 IS 7 BP 152 EP 173 DI 10.1039/9781849733014-00152 D2 10.1039/9781849733014 PG 22 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental; Neurosciences SC Biochemistry & Molecular Biology; Research & Experimental Medicine; Neurosciences & Neurology GA BA1LK UT WOS:000332691400009 ER PT J AU Ramaswamy, S Seminara, SB Plant, TM AF Ramaswamy, Suresh Seminara, Stephanie B. Plant, Tony M. TI Evidence from the Agonadal Juvenile Male Rhesus Monkey (Macaca mulatta) for the View that the Action of Neurokinin B to Trigger Gonadotropin-Releasing Hormone Release Is Upstream from the Kisspeptin Receptor SO NEUROENDOCRINOLOGY LA English DT Article DE Gonadotropin-releasing hormone; Neurokinin B; Kisspeptin; Monkey; Kisspeptin receptor; KNDy neurons ID ARCUATE NUCLEUS; HYPOGONADOTROPIC HYPOGONADISM; DYNORPHIN-A; MORPHOLOGIC EVIDENCE; RAT HYPOTHALAMUS; MEDIAN-EMINENCE; NEURONS; SECRETION; ACTIVATION; PUBERTY AB Human genetics have revealed that kisspeptin signaling and neurokinin B (NKB) signaling are both required for robust pulsatile gonadotropin-releasing hormone (GnRH) release, and therefore for puberty and maintenance of adult gonadal function. How these two peptides interact to affect GnRH pulse generation remains a mystery. To address the hierarchy of the NKB and kisspeptin signaling pathways that are essential for GnRH release, two experiments were conducted using agonadal, juvenile male monkeys. Pituitary responsiveness to GnRH was first heightened by a pulsatile GnRH infusion to use the in situ pituitary as a bioassay for GnRH release. In the first experiment (n = 3), the kisspeptin receptor (KISS1R) was desensitized by a continuous 99-hour i.v. infusion of kisspeptin-10 (100 mu g/h). During the last 4 h of continuous kisspeptin-10 infusion, desensitization of KISS1R was confirmed by failure of an i.v. bolus of kisspeptin-10 to elicit GnRH release. Desensitization of KISS1R was associated with a markedly blunted GnRH response to senktide. The response to senktide was progressively restored during the 72 h following termination of continuous kisspeptin-10. An analogous design was employed in the second experiment (n = 2) to desensitize the NKB receptor (neurokinin 3 receptor, NK3R) by administration of a continuous 48-hour i.v. infusion of senktide (200 mu g/h). While a bolus of senktide during the last 3 h of continuous senktide administration failed to elicit GnRH release, thus confirming desensitization of NK3R, the ability of kisspeptin to stimulate GnRH was unimpaired. The foregoing findings support the view that NKB stimulation of GnRH release is upstream from KISS1R. Copyright (C) 2011 S. Karger AG, Basel C1 [Plant, Tony M.] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Magee Womens Res Inst B331, Pittsburgh, PA 15213 USA. [Ramaswamy, Suresh; Plant, Tony M.] Magee Womens Res Inst, Pittsburgh, PA USA. [Seminara, Stephanie B.] Massachusetts Gen Hosp, Reprod Endocrinol Unit, Boston, MA 02114 USA. RP Plant, TM (reprint author), Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Magee Womens Res Inst B331, Pittsburgh, PA 15213 USA. EM planttm@mwri.magee.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development as part of the Specialized Cooperative Center [U54 HD 08610, U54 HD 028138]; National Institutes of Health [R01 HD 013254] FX We thank the Primate and Assay Core staff (Ms. Rachel Rosland, Mr. Mike Cicco and Ms. Carolyn Phalin) of the Specialized Cooperative Centers Program in Reproduction and Infertility Research at the University of Pittsburgh Medical School for their expert technical assistance. The work was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development through cooperative agreement U54 HD 08610 (T. M. P.) and U54 HD 028138 (S. B. S.) as part of the Specialized Cooperative Centers Program in Reproduction and Infertility Research, and National Institutes of Health Grant R01 HD 013254 to T.M.P. NR 48 TC 59 Z9 60 U1 2 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PY 2011 VL 94 IS 3 BP 237 EP 245 DI 10.1159/000329045 PG 9 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 846IW UT WOS:000296891500007 PM 21832818 ER PT J AU Misra, M Klibanski, A AF Misra, Madhusmita Klibanski, Anne TI The Neuroendocrine Basis of Anorexia Nervosa and Its Impact on Bone Metabolism SO NEUROENDOCRINOLOGY LA English DT Review DE Anorexia nervosa; Growth hormone; Cortisol; Gonadal steroids; Ghrelin; Leptin; Peptide YY; Adiponectin; Bone density; Bone turnover markers; Bone microarchitecture ID TRABECULAR STRUCTURE-ANALYSIS; HORMONE-RELEASING HORMONE; PANEL VOLUME CT; ADOLESCENT GIRLS; GROWTH-HORMONE; LUTEINIZING-HORMONE; HYPOTHALAMIC AMENORRHEA; SECRETORY DYNAMICS; HEALTHY ADOLESCENTS; MINERAL DENSITY AB Anorexia nervosa (AN) is a condition of profound undernutrition associated with alterations in various neuroendocrine axes, many of which contribute to a marked impairment in bone accrual and low bone mineral density. This review focuses on changes in the hypothalamo-pituitary-gonadal axis, the growth hormone insulin-like growth factor-1 axis, and the hypothalamo-pituitary-adrenal axis in AN, as well as alterations in various appetite-regulating hormones. In addition, the review discusses low bone mineral density and altered bone microarchitecture in AN, the pathophysiology underlying impaired bone metabolism, and possible therapeutic strategies to optimize bone health. Copyright (C) 2011 S. Karger AG, Basel C1 [Misra, Madhusmita; Klibanski, Anne] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Misra, Madhusmita] Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. [Misra, Madhusmita] Harvard Univ, Sch Med, Boston, MA USA. RP Misra, M (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, BUL 457,55 Fruit St, Boston, MA 02114 USA. EM mmisra@partners.org FU NIH [1 UL1 RR025758-01, DK 062249, K23 RR018851] FX This work was supported in part by NIH grants 1 UL1 RR025758-01, DK 062249 and K23 RR018851. NR 76 TC 33 Z9 33 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 EI 1423-0194 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PY 2011 VL 93 IS 2 BP 65 EP 73 DI 10.1159/000323771 PG 9 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 737NG UT WOS:000288574900001 PM 21228564 ER PT J AU Goebel, M Stengel, A Wang, LX Reeve, J Tache, Y AF Goebel, Miriam Stengel, Andreas Wang, Lixin Reeve, Joseph, Jr. Tache, Yvette TI Lipopolysaccharide Increases Plasma Levels of Corticotropin-Releasing Hormone in Rats SO NEUROENDOCRINOLOGY LA English DT Article DE Adrenocorticotropic hormone; Blood; Colon; Gastric emptying; Lipopolysaccharide; RAPID method ID PITUITARY-ADRENAL AXIS; CRF-BINDING-PROTEIN; ARGININE-VASOPRESSIN; MESSENGER-RNA; IMMUNOREACTIVE NEURONS; PERIPHERAL-BLOOD; MOLECULAR-FORMS; T-LYMPHOCYTES; ACTH; CORTICOSTERONE AB Background: Corticotropin-releasing hormone (CRH) is expressed in the brain, immune cells and the gut, where gene expression is upregulated by lipopolysaccharide (LPS) 6 h after injection. Whether these changes are reflected by increased circulating levels of CRH and adrenocorticotropic hormone (ACTH) is unknown. Methods: LPS (100 mu g/kg) was injected intraperitoneally in conscious rats, and blood processed for CRH using the new RAPID (reduced temperatures, acidification, protease inhibition, isotopic exogenous controls and dilution) method compared with EDTA blood with or without plasma methanol extraction. Hormone levels were measured by commercial radioimmunoassay. Results: The RAPID method improved blood recovery of I-125-CRH in vitro compared to EDTA only added to the blood without or with methanol extraction (90.8 +/- 2.0 vs. 66.9 +/- 2.6 and 47.5 +/- 2.0%, respectively; p < 0.001 vs. RAPID). Basal CRH levels from blood processed by the RAPID method were 28.9 +/- 2.8 pg/ml, and by other methods below the radioimmunoassay detection limit (< 10 pg/ml). At 6 h after LPS, CRH plasma levels increased significantly by 2.9 times, and in the proximal colon tended to decrease (-27.6 +/- 5.7%; p > 0.05), while circulating levels were unchanged at 3 or 4 h. ACTH levels rose compared to control rats (135.3 +/- 13.8 vs. 101.4 +/- 6.0 pg/ml; p < 0.05) 30 min after the increase in CRH, while at 3 or 6 h after LPS, the levels were not changed. Conclusion: intraperitoneal LPS induces a delayed rise in plasma CRH levels associated with an elevation in ACTH plasma levels 30 min later, suggesting that under conditions of immune challenge, CRH of peripheral origin may also contribute to pituitary activation, as detected using the RAPID method of blood processing, which improves CRH recovery. Copyright (C) 2010 S. Karger AG, Basel C1 [Tache, Yvette] VA Greater Los Angeles Healthcare Syst, Ctr Neurobiol Stress, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Dept Med,CURE Digest Dis Res Ctr, Los Angeles, CA 90095 USA. RP Tache, Y (reprint author), VA Greater Los Angeles Healthcare Syst, Ctr Neurobiol Stress, CURE Bldg 115,Room 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM ytache@mednet.ucla.edu FU German Research Foundation [GO 1718/1-1, STE 1765/1-1]; Department of Veterans Affairs; NIHDK [57238]; [DK-41301] FX This study was supported by German Research Foundation fellowship grants GO 1718/1-1 (M.G.) and STE 1765/1-1 (A.S.), the VA Research Career Scientist Award, a Department of Veterans Affairs Merit Award (Y.T.), NIHDK 57238 (Y.T.) and Center grant DK-41301 (Animal Core, Y.T.; Peptidomic RIA Proteomic Core, J.R. Jr.). We are grateful to Mrs. Honghui Liang for her excellent technical support and Ms. Eugenia Hu for reviewing the manuscript. NR 57 TC 10 Z9 10 U1 1 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 EI 1423-0194 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PY 2011 VL 93 IS 3 BP 165 EP 173 DI 10.1159/000322590 PG 9 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 747RU UT WOS:000289337900005 PM 21135542 ER PT J AU La Fountaine, MF Wecht, JM Cirnigliaro, CM Kirshblum, SC Spungen, AM Bauman, WA AF La Fountaine, Michael F. Wecht, Jill M. Cirnigliaro, Christopher M. Kirshblum, Steven C. Spungen, Ann M. Bauman, William A. TI QT/RR Coherence Is Associated with Testosterone Levels in Men with Chronic Spinal Cord Injury SO NEUROENDOCRINOLOGY LA English DT Article DE Spinal cord injury; Hypogonadism; Testosterone; QT interval; Autonomic nervous system ID HEART-RATE-VARIABILITY; VENTRICULAR REPOLARIZATION; QT INTERVAL; AUTONOMIC FUNCTION; SPECTRAL-ANALYSIS; FAILURE; CARDIOMYOPATHY; REFRACTORINESS; ABNORMALITIES; DYSFUNCTION AB Aim: To evaluate the effect of hypogonadism on temporal characteristics of ventricular repolarization (VR) and QT/RR coherence in men with spinal cord injury (SCI). Methods: Thirty-four men with SCI (> 1 year postinjury) were studied. After clinical evaluation, 20 subjects were diagnosed as hypogonadal and 14 as eugonadal. QT and RT time, heart rate (HR), and Bazett QTc were determined from a digital electrocardiogram during quiet rest and a cold pressor test (CPT). QT/RR coherence was calculated across three spectral frequencies including mean (Mean Coh; 0-0.2 Hz), low (LF Coh; 0.04-0.15 Hz) and high (HF Coh; 0.15-0.40 Hz). Respiration was collected via impedance pneumography. Results: No statistical differences were observed among demographics. Pairwise comparisons demonstrated a significantly reduced Mean Coh at rest in the hypogonadal group compared to the eugonadal; during the CPT, the hypogonadal group had significantly elevated Mean and HF Coh. No group main effects were observed with analysis of variance. Condition main effects were observed in QT, Mean, LF and HF Coh. Significant group-condition interactions were present in Mean and HF Coh, while trends toward significance were observed on LF Coh, HR, QT and RT. Post-hoc pairwise comparisons revealed that the change from rest to CPT in Mean, LF and HF Coh was significant in the eugonadal group, but not the hypogonadal. Conclusion: Hypogonadism in SCI appears to adversely affect temporal VR characteristics independently of QTc. QT/RR coherence suggests an autonomic synergism with testosterone. These findings may represent a pathologic sequelae that precedes the well-documented hypogonadic effects on QTc. Copyright (C) 2011 S. Karger AG, Basel C1 [La Fountaine, Michael F.; Wecht, Jill M.; Cirnigliaro, Christopher M.; Spungen, Ann M.; Bauman, William A.] James J Peters VA Med Ctr, VA RR & D Ctr Excellence Med Consequences Spinal, Bronx, NY 10468 USA. [La Fountaine, Michael F.; Wecht, Jill M.; Spungen, Ann M.; Bauman, William A.] James J Peters VA Med Ctr, Med Serv, Bronx, NY 10468 USA. [La Fountaine, Michael F.] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Wecht, Jill M.; Spungen, Ann M.; Bauman, William A.] Mt Sinai Sch Med, Dept Rehabil Med, New York, NY USA. [Kirshblum, Steven C.] Kessler Inst Rehabil, W Orange, NJ USA. [Kirshblum, Steven C.] Univ Med & Dent New Jersey, Dept Phys Med & Rehabil, Newark, NJ 07103 USA. RP La Fountaine, MF (reprint author), James J Peters VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Room 1E-02,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM michael.lafountaine@va.gov FU Veteran Affairs Rehabilitation Research and Development Service [B4162C, B3600R]; James J. Peters VA Medical Center FX This research was supported by the Veteran Affairs Rehabilitation Research and Development Service (#B4162C, #B3600R) and the James J. Peters VA Medical Center. NR 35 TC 2 Z9 2 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 EI 1423-0194 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PY 2011 VL 93 IS 3 BP 174 EP 180 DI 10.1159/000323773 PG 7 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 747RU UT WOS:000289337900006 PM 21252493 ER PT J AU Sung, VW Johnson, N Granstaff, US Jones, WJ Meschia, JF Williams, LS Safford, MM AF Sung, Victor W. Johnson, Natasha Granstaff, U. Shanette Jones, William J. Meschia, James F. Williams, Linda S. Safford, Monika M. TI Sensitivity and Specificity of Stroke Symptom Questions to Detect Stroke or Transient Ischemic Attack SO NEUROEPIDEMIOLOGY LA English DT Article DE Stroke assessment; Transient ischemic attack; Stroke symptoms; Screening questionnaire ID PREVALENCE; POPULATION; VALIDATION; RECORDS; WOMEN AB Background/Aims: Undiagnosed stroke is a major public health problem. The Questionnaire for Verifying Stroke-Free Status (QVSS) includes eight items and was originally designed to detect stroke-free individuals. Its six symptom-related questions could potentially be used to screen for undiagnosed stroke or transient ischemic attack (TIA), but the sensitivity and specificity of just the six symptom-related questions are unknown. Methods: A research assistant administered the QVSS to outpatients from Veterans Administration stroke and general medicine clinics. Neurologists, blinded to QVSS scores, interviewed and examined all subjects to determine stroke status. Responses to the six symptom questions of the QVSS were compared against the neurologist-determined stroke/TIA status. Results: The sensitivity of the individual symptom questions ranged from 0.22 to 0.60, and the specificity ranged from 0.79 to 0.95. The sensitivity of any of the six symptom questions was 0.82, and the specificity was 0.62. Conclusion: The six symptom-related questions of the QVSS demonstrate a high sensitivity and moderate specificity for the diagnosis of stroke or TIA compared with neurological exam. Though these findings should be validated in a more representative general population, these questions have potential for meeting the public health objective of detecting clinically unrecognized but symptomatic stroke. Copyright (C) 2011 S. Karger AG, Basel C1 [Sung, Victor W.; Johnson, Natasha; Granstaff, U. Shanette] Univ Alabama Birmingham, Birmingham Vet Adm Med Ctr, Birmingham, AL USA. [Johnson, Natasha] Univ Alabama Birmingham, Dept Neurol, Div Prevent Med, Birmingham, AL 35294 USA. [Safford, Monika M.] Univ Alabama Birmingham, Dept Med, Div Prevent Med, Birmingham, AL 35294 USA. [Jones, William J.] Univ Colorado Denver, Dept Neurol, Aurora, CO USA. [Meschia, James F.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Williams, Linda S.] Indiana Univ Sch Med, Dept Neurol, Regenstrief Inst, Richard L Roudebush Vet Adm Med Ctr, Indianapolis, IN USA. RP Sung, VW (reprint author), Birmingham VA Med Ctr, 700 19th St S, Birmingham, AL 35233 USA. EM victor.sung@va.gov OI Sung, Victor/0000-0003-1024-3404 FU Veterans Administration National Quality Scholars fellowship; [R01 HL080477-01A1A] FX This study was supported by a Veterans Administration National Quality Scholars fellowship grant (Dr. Sung). Dr. Safford was supported by R01 HL080477-01A1A. NR 16 TC 13 Z9 14 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0251-5350 EI 1423-0208 J9 NEUROEPIDEMIOLOGY JI Neuroepidemiology PY 2011 VL 36 IS 2 BP 100 EP 104 DI 10.1159/000323951 PG 5 WC Public, Environmental & Occupational Health; Clinical Neurology SC Public, Environmental & Occupational Health; Neurosciences & Neurology GA 747RS UT WOS:000289337700006 PM 21311197 ER PT J AU Dahodwala, N Karlawish, J Siderowf, A Duda, JE Mandell, DS AF Dahodwala, Nabila Karlawish, Jason Siderowf, Andrew Duda, John E. Mandell, David S. TI Delayed Parkinson's Disease Diagnosis among African-Americans: The Role of Reporting of Disability SO NEUROEPIDEMIOLOGY LA English DT Article DE African-American; Delay; Diagnosis; Health services; Parkinsonism; Race ID OLDER-ADULTS; PREVALENCE; POPULATION; DISPARITIES; AWARENESS; DEFICITS; SECTION; CARE AB Background/Aims: Racial differences in the observed prevalence of Parkinson's disease (PD) may be due to delayed diagnosis among African-Americans. We sought to compare the stage at which African-American and white PD patients present for healthcare, and determine whether perception of disability accounts for racial differences. Methods: Using records of veterans with newly diagnosed PD at the Philadelphia Veterans Affairs Medical Center, we calculated differences in reporting of symptoms as the difference in z-scores on the Unified Parkinson Disease Rating Scale part 2 (disability) and part 3 (motor impairment). Ordinal logistic regression was used to determine predictors of stage at diagnosis. Results: African-American (n = 16) and white (n = 58) veterans with a mean age of 70.1 years were identified. African-Americans presented at a later PD stage than whites (median Hoehn + Yahr stage 2.5 vs. 2.0, p = 0.02) and were more likely to under-report disability relative to motor impairment (81 vs. 40%, p < 0.01). Multivariate analysis showed that under-reporting of disability accounted for much of the effect of race on stage of diagnosis. Conclusions: Under-reporting of disability among African-Americans may account for later stages of PD diagnosis than whites. This study begins to explain the mechanisms underlying observed racial disparities in PD. Copyright (C) 2011 S. Karger AG, Basel C1 [Dahodwala, Nabila; Siderowf, Andrew; Duda, John E.] Univ Penn, Philadelphia VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA 19104 USA. [Dahodwala, Nabila; Karlawish, Jason; Siderowf, Andrew; Mandell, David S.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Dahodwala, Nabila; Siderowf, Andrew; Duda, John E.] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Karlawish, Jason] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Mandell, David S.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. RP Dahodwala, N (reprint author), Parkinsons Dis & Movement Disorders Ctr, 330 S 9th St,2nd Floor, Philadelphia, PA 19107 USA. EM dahodwan@mail.med.upenn.edu RI Mandell, David/H-2730-2012 OI Mandell, David/0000-0001-8240-820X FU Philadelphia VAMC Parkinson's Disease Research, Education and Clinical Center; NIH [K23 AG034236] FX This study was funded by a Pilot Project Award from the Philadelphia VAMC Parkinson's Disease Research, Education and Clinical Center. N.D. is supported by NIH grant K23 AG034236. NR 21 TC 1 Z9 1 U1 1 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0251-5350 J9 NEUROEPIDEMIOLOGY JI Neuroepidemiology PY 2011 VL 36 IS 3 BP 150 EP 154 DI 10.1159/000324935 PG 5 WC Public, Environmental & Occupational Health; Clinical Neurology SC Public, Environmental & Occupational Health; Neurosciences & Neurology GA 769OB UT WOS:000291024800003 PM 21508648 ER PT J AU Peskind, ER Petrie, EC Cross, DJ Pagulayan, K McCraw, K Hoff, D Hart, K Yu, CE Raskind, MA Cook, DG Minoshima, S AF Peskind, Elaine R. Petrie, Eric C. Cross, Donna J. Pagulayan, Kathleen McCraw, Kathleen Hoff, David Hart, Kim Yu, Chang-En Raskind, Murray A. Cook, David G. Minoshima, Satoshi TI Cerebrocerebellar hypometabolism associated with repetitive blast exposure mild traumatic brain injury in 12 Iraq war Veterans with persistent post-concussive symptoms SO NEUROIMAGE LA English DT Article DE Positron emission tomography; Mild traumatic brain injury; Post-concussive symptoms; Cerebellum; Blast; Veterans; Cognition ID POSTTRAUMATIC-STRESS-DISORDER; CEREBRAL GLUCOSE-METABOLISM; APOLIPOPROTEIN-E; VALIDATION; CEREBELLUM; VALIDITY; IMAGES; SCALE; PTSD; CARE AB Disagreement exists regarding the extent to which persistent post-concussive symptoms (PCS) reported by Iraq combat Veterans with repeated episodes of mild traumatic brain injury (mTBI) from explosive blasts represent structural or functional brain damage or an epiphenomenon of comorbid depression or posttraumatic stress disorder (PTSD). Objective assessment of brain function in this population may clarify the issue. To this end, twelve Iraq war Veterans (32.0 +/- 8.5 [mean +/- standard deviation (SD)] years of age) reporting one or more blast exposures meeting American Congress of Rehabilitation Medicine criteria for mTBI and persistent PCS and 12 cognitively normal community volunteers (53.0 +/- 4.6 years of age) without history of head trauma underwent brain fluorodeoxyglucose positron emission tomography (FDG-PET) and neuropsychological assessments and completed PCS and psychiatric symptom rating scales. Compared to controls, Veterans with mTBI (with or without PTSD) exhibited decreased cerebral metabolic rate of glucose in the cerebellum, vermis, pons, and medial temporal lobe. They also exhibited subtle impairments in verbal fluency, cognitive processing speed, attention, and working memory, similar to those reported in the literature for patients with cerebellar lesions. These FDG-PET imaging findings suggest that regional brain hypometabolism may constitute a neurobiological substrate for chronic PCS in Iraq combat Veterans with repetitive blast-trauma mTBI. Given the potential public health implications of these findings, further investigation of brain function in these Veterans appears warranted. Published by Elsevier Inc. C1 [Peskind, Elaine R.; Petrie, Eric C.; Pagulayan, Kathleen; McCraw, Kathleen; Hoff, David; Hart, Kim; Raskind, Murray A.] Vet Affairs Puget Sound Hlth Care Syst, NW Network Mental Illness Res Educ & Clin Ctr MIR, Seattle, WA 98108 USA. [Yu, Chang-En; Cook, David G.] Vet Affairs Puget Sound Hlth Care Syst, GRECC, Seattle, WA 98108 USA. [Peskind, Elaine R.; Petrie, Eric C.; Pagulayan, Kathleen; Raskind, Murray A.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Cross, Donna J.; Minoshima, Satoshi] Univ Washington, Dept Radiol, Seattle, WA 98195 USA. [Yu, Chang-En; Cook, David G.] Univ Washington, Dept Med, Seattle, WA 98195 USA. RP Peskind, ER (reprint author), Vet Affairs Puget Sound Hlth Care Syst, NW Network Mental Illness Res Educ & Clin Ctr MIR, Mail Code S-116-MIRECC,1660 S Columbian Way, Seattle, WA 98108 USA. EM peskind@uw.edu RI Schueter, nicos/A-3625-2014 FU Northwest Network Mental Illness, Research, Education, and Clinical Center (MIRECC); Office of Research and Development Medical Research Service, Department of Veterans Affairs; National Institutes of Health [P50 AG05136, K08 AG023670, R01 NS045254] FX This material is based upon work supported, in part, by the Northwest Network Mental Illness, Research, Education, and Clinical Center (MIRECC) and Office of Research and Development Medical Research Service, Department of Veterans Affairs; by grants P50 AG05136, K08 AG023670, and R01 NS045254 from the National Institutes of Health; and by a grant from an anonymous foundation. NR 47 TC 100 Z9 102 U1 7 U2 20 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 JAN PY 2011 VL 54 SU 1 BP S76 EP S82 DI 10.1016/j.neuroimage.2010.04.008 PG 7 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 813ZF UT WOS:000294408600011 PM 20385245 ER PT J AU Oscar-Berman, M Song, J AF Oscar-Berman, Marlene Song, Janet TI Brain volumetric measures in alcoholics: a comparison of two segmentation methods SO NEUROPSYCHIATRIC DISEASE AND TREATMENT LA English DT Article DE alcoholism; MRI; brain segmentation ID MAGNETIC-RESONANCE IMAGES; HUMAN CEREBRAL-CORTEX; TOPOGRAPHIC PARCELLATION; MORPHOMETRIC-ANALYSIS; WHITE-MATTER; SYSTEM; WOMEN; SCHIZOPHRENIA; RELIABILITY; DEFICITS AB Measures of regional brain volumes, which can be derived from magnetic resonance imaging (MRI) images by dividing a brain into its constituent parts, can be used as structural indicators of many different neuroanatomical diseases and disorders, including alcoholism. Reducing the time and cost required for brain segmentation would greatly facilitate both clinical and research endeavors. In the present study, we compared two segmentation methods to measure brain volumes in alcoholic and nonalcoholic control subjects: 1) an automated system (FreeSurfer) and 2) a semi-automated, supervised system (Cardviews, developed by the Center for Morphometric Analysis [CMA] at Massachusetts General Hospital), which requires extensive staff and oversight. The participants included 32 abstinent alcoholics (19 women) and 37 demographically matched, nonalcoholic controls (17 women). Brain scans were acquired in a 3 Tesla MRI scanner. The FreeSurfer and CMA methods showed good agreement for the lateral ventricles, cerebral white matter, caudate, and thalamus. In general, the larger the brain structure, the closer the agreement between the methods, except for the cerebral cortex, which showed large between-method differences. However, several other discrepancies existed between the FreeSurfer and CMA volume measures of alcoholics' brains. The CMA volumes, but not FreeSurfer, demonstrated that the thalamus, caudate, and putamen were significantly smaller in male alcoholics as compared with male controls. Additionally, the hippocampus was significantly smaller in alcoholic women compared with women controls. In general, correlation between methods was lowest in male alcoholic subjects, who also showed the greatest abnormalities. These results suggest that although many brain structures can be segmented reliably by CMA and FreeSurfer, low correlations between methods in some regions may be due to morphological changes in the brains of alcoholics. C1 [Oscar-Berman, Marlene] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Oscar-Berman, Marlene] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Oscar-Berman, Marlene] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. [Oscar-Berman, Marlene] VA Boston Healthcare Syst, Boston, MA USA. [Song, Janet] MIT, Ctr Excellence Educ, Res Scientist Inst, Cambridge, MA 02139 USA. [Song, Janet] Harvard Univ, Cambridge, MA USA. RP Oscar-Berman, M (reprint author), Boston Univ, Sch Med, Dept Psychiat, Suite L-815,72 E Concord St, Boston, MA 02118 USA. EM oscar@bu.edu FU US Department of Health and Human Services, NIAAA [R01 AA 07112, K05 AA 00219]; Medical Research Service of the US Department of Veterans Affairs FX This research was supported by funds from the US Department of Health and Human Services, NIAAA (R01 AA 07112, K05 AA 00219), and by funds from the Medical Research Service of the US Department of Veterans Affairs. Ms Song thanks the Center for Excellence in Education (CEE), the Research Science Institute (RSI), the Massachusetts General Hospital (MGH), and the Massachusetts Institute of Technology (MIT) for providing the opportunity to conduct this work, as well as the RSI staff, and especially Mr Zach Wissner-Gross, Mr Austin Webb, and Ms Lauren Lisann, for their support. Thanks also to Rob Zondervan for his help. NR 36 TC 8 Z9 8 U1 1 U2 5 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1176-6328 J9 NEUROPSYCH DIS TREAT JI Neuropsychiatr. Dis. Treat. PY 2011 VL 7 BP 65 EP 75 DI 10.2147/NDT.S13405 PG 11 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 821DN UT WOS:000294955100008 PM 21430796 ER PT J AU Arciniegas, DB Kellermeyer, GF Bonifer, NM Anderson-Salvi, KM Anderson, CA AF Arciniegas, David B. Kellermeyer, Gregory F. Bonifer, Nancy M. Anderson-Salvi, Kristin M. Anderson, C. Alan TI Screening for cognitive decline following single known stroke using the Mini-Mental State Examination SO NEUROPSYCHIATRIC DISEASE AND TREATMENT LA English DT Article DE stroke; Mini-Mental State Examination; cognitive decline; Fugl-Meyer evaluation; motor impairment ID MODERATE VASCULAR DEMENTIA; INDUCED MOVEMENT THERAPY; ALZHEIMERS-DISEASE; CEREBROVASCULAR-DISEASE; POSTSTROKE DEMENTIA; 1ST-EVER STROKE; CLINICAL DETERMINANTS; IMPAIRMENT; RECOVERY; BRAIN AB Background: Progressive cognitive decline develops in a nontrivial minority of stroke survivors. Although commonly used to identify cognitive decline in older stroke survivors, the usefulness of the Mini-Mental State Examination (MMSE) as a screening tool for post-stroke cognitive decline across a wider range of ages is not well established. This study therefore investigated the usefulness of the MMSE for this purpose. Methods: Twenty-seven subjects, aged 18-82 years, with a single known remote stroke were assessed using the MMSE. The frequency of cognitive impairment was determined by comparison of MMSE scores with population-based norms. Relationships between cognitive performance, motor impairments, age, gender, handedness, stroke laterality, and time since stroke also were explored. Results: Age-adjusted MMSE scores identified mild cognitive impairment in 22.2% and moderate-to-severe cognitive impairment in 7.4% of subjects. Raw and age-adjusted MMSE scores were inversely correlated with time since stroke, but not with other patient or stroke characteristics. Conclusion: A relationship between time since single known stroke and MMSE performance was observed in this study. The proportion of subjects identified as cognitively impaired in this group by Z-transformation of MMSE scores using previously published normative data for this measure comports well with the rates of late post-stroke cognitive impairment reported by other investigators. These findings suggest that the MMSE, when normatively interpreted, may identify cognitive decline in the late period following single known stroke. Additionally, the lack of a relationship between MMSE and Fugl-Meyer scores suggests that the severity of post-stroke motor impairments is unlikely to serve as a clinically useful indicator of the need for cognitive assessment. A larger study of stroke survivors is needed to inform more fully on the usefulness of normatively interpreted MMSE scores as a method of screening for post-stroke cognitive decline. C1 [Arciniegas, David B.; Kellermeyer, Gregory F.; Bonifer, Nancy M.; Anderson-Salvi, Kristin M.] HealthONE Spalding Rehabil Hosp, Brain Injury Rehabil Unit, Aurora, CO USA. [Arciniegas, David B.; Kellermeyer, Gregory F.; Anderson, C. Alan] Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Neuropsychiat Serv, Denver, CO 80262 USA. [Arciniegas, David B.; Anderson, C. Alan] Univ Colorado, Hlth Sci Ctr, Dept Neurol, Behav Neurol Sect, Denver, CO 80262 USA. [Anderson, C. Alan] Denver Vet Affairs Med Ctr, Neurol Serv, Denver, CO USA. RP Arciniegas, DB (reprint author), UCD Neurobehav Disorders Program, 13001 E 17th Pl, Aurora, CO 80045 USA. EM david.arciniegas@ucdenver.edu FU Spalding Community Foundation; HealthONE Alliance; HealthONE Spalding Rehabilitation Hospital, Aurora, CO FX The authors gratefully acknowledge the support provided for this study by the Spalding Community Foundation, the HealthONE Alliance, and HealthONE Spalding Rehabilitation Hospital, Aurora, CO. NR 61 TC 6 Z9 6 U1 3 U2 12 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1176-6328 J9 NEUROPSYCH DIS TREAT JI Neuropsychiatr. Dis. Treat. PY 2011 VL 7 BP 189 EP 196 DI 10.2147/NDT.S17886 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 821DN UT WOS:000294955100021 PM 21573080 ER PT J AU Leahy, JT Chu-Shore, CJ Fisher, JL AF Leahy, Jennifer T. Chu-Shore, Catherine J. Fisher, Janet L. TI Clobazam as an adjunctive therapy in treating seizures associated with Lennox-Gastaut syndrome SO NEUROPSYCHIATRIC DISEASE AND TREATMENT LA English DT Review DE benzodiazepine; epilepsy; gamma aminobutyric acid; pediatric; pharmacoresistance ID ADD-ON THERAPY; VAGUS NERVE-STIMULATION; CHILDHOOD EPILEPTIC ENCEPHALOPATHY; GABA(A) RECEPTOR SUBTYPES; REFRACTORY EPILEPSY; PEDIATRIC EPILEPSY; KETOGENIC DIET; N-DESMETHYLCLOBAZAM; ANTIEPILEPTIC DRUG; ANTICONVULSANT ACTION AB Lennox-Gastaut syndrome (LGS) is a devastating childhood epilepsy syndrome characterized by the occurrence of multiple types of seizures and cognitive decline. Most children suffer from frequent seizures that are refractory to current medical management. Recent clinical trials have suggested that addition of clobazam may improve the clinical outcome for some LGS patients. Although clobazam has been available for over five decades, it has only recently been approved by the US Food and Drug Administration for this indication. As a 1,5-benzodiazepine, clobazam is structurally related to the widely used 1,4-benzodiazepines, which include diazepam. Clobazam has been shown to modulate GABAergic neurotransmission by positive allosteric modulation of GABA(A) receptors, and to increase expression of transporters for both GABA and glutamate. The active metabolite n-desmethylclobazam (norclobazam) also modulates GABA(A) receptors, and the relative importance of these two compounds in the clinical effectiveness of clobazam remains an open question. Clinical trials involving clobazam as an addon therapy in a variety of pediatric epilepsy populations have found a significant improvement in seizure control. In patients with LGS, clobazam may have greatest efficacy for drop seizures. Longstanding clinical experience suggests that clobazam is a safe and well tolerated antiepileptic drug with infrequent and mild adverse effects. These results suggest that adjunctive treatment with clobazam may be a reasonable option for LGS patients, particularly those who are treatment-resistant. C1 [Fisher, Janet L.] Univ S Carolina, Sch Med, Dept Pharmacol Physiol & Neurosci, Columbia, SC 29208 USA. [Leahy, Jennifer T.; Chu-Shore, Catherine J.] Massachusetts Gen Hosp, Dept Neurol, Program Neurophysiol, Boston, MA 02114 USA. [Leahy, Jennifer T.; Chu-Shore, Catherine J.] Massachusetts Gen Hosp, Dept Neurol, Program Epilepsy, Boston, MA 02114 USA. [Chu-Shore, Catherine J.] Harvard Univ, Sch Med, Boston, MA USA. RP Fisher, JL (reprint author), Univ S Carolina, Sch Med, Dept Pharmacol Physiol & Neurosci, 6439 Garners Ferry Rd, Columbia, SC 29208 USA. EM jfisher@uscmed.sc.edu NR 91 TC 12 Z9 12 U1 0 U2 2 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1176-6328 J9 NEUROPSYCH DIS TREAT JI Neuropsychiatr. Dis. Treat. PY 2011 VL 7 BP 673 EP 681 DI 10.2147/NDT.520173 PG 9 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 861CT UT WOS:000297997300001 PM 22128252 ER PT J AU Boggio, PS Valasek, CA Campanha, C Giglio, ACA Baptista, NI Lapenta, OM Fregni, F AF Boggio, Paulo Sergio Valasek, Claudia Aparecida Campanha, Camila Alem Giglio, Ana Carolina Baptista, Nathalia Ishikawa Lapenta, Olivia Morgan Fregni, Felipe TI Non-invasive brain stimulation to assess and modulate neuroplasticity in Alzheimer's disease SO NEUROPSYCHOLOGICAL REHABILITATION LA English DT Article DE tDCS; TMS; Cognitive rehabilitation ID TRANSCRANIAL MAGNETIC STIMULATION; DORSOLATERAL PREFRONTAL CORTEX; LATENCY AFFERENT INHIBITION; MILD COGNITIVE IMPAIRMENT; RISK-TAKING BEHAVIOR; WORKING-MEMORY TASK; MOTOR CORTEX; LANGUAGE PERFORMANCE; PARKINSONS-DISEASE; FALSE MEMORIES AB Alzheimer's disease (AD) is a neurodegenerative and progressive disease related to a gradual decline in cognitive functions such as memory, attention, perceptual-spatial abilities, language, and executive functions. Recent evidence has suggested that interventions promoting neural plasticity can induce significant cognitive gains especially in subjects at risk of or with mild AD. Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) are non-invasive techniques that can induce significant and long-lasting changes in focal and non-focal neuroplasticity. In this review, we present initial preliminary evidence that TMS and tDCS can enhance performance in cognitive functions typically impaired in AD. Also, we reviewed the initial six studies on AD that presented early findings showing cognitive gains such as in recognition memory and language associated with TMS and tDCS treatment. In addition, we showed that TMS has also been used to assess neuroplasticity changes in AD supporting the notion that cortical excitability is changed in AD due to the neurodegenerative process. Due to the safe profile, cost of these tools, and initial clinical trials results, further studies are warranted in order to replicate and extend the initial findings of rTMS and tDCS as cognitive enhancers in AD. Further trials should explore different targets of stimulation along with different paradigms of stimulation including combination with behavioural interventions. C1 [Boggio, Paulo Sergio; Valasek, Claudia Aparecida; Campanha, Camila; Alem Giglio, Ana Carolina; Baptista, Nathalia Ishikawa; Lapenta, Olivia Morgan] Univ Prebiteriana Mackenzie, Social & Cognit Neurosci Lab, BR-01241001 Sao Paulo, Brazil. [Boggio, Paulo Sergio; Valasek, Claudia Aparecida; Campanha, Camila; Alem Giglio, Ana Carolina; Baptista, Nathalia Ishikawa; Lapenta, Olivia Morgan] Univ Prebiteriana Mackenzie, Dev Disorders Program, Ctr Hlth & Biol Sci, BR-01241001 Sao Paulo, Brazil. [Fregni, Felipe] Spaulding Rehabil Hosp, Lab Neuromodulat, Dept Phys Med & Rehabil, Boston, MA USA. [Fregni, Felipe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Boggio, PS (reprint author), Univ Prebiteriana Mackenzie, Social & Cognit Neurosci Lab, Rua Piaui 181,108 Andar, BR-01241001 Sao Paulo, Brazil. EM psboggio@gmail.com RI Boggio, Paulo/K-6272-2012 OI Boggio, Paulo/0000-0002-6109-0447 FU CNPq [305718/2009-6]; RJG foundation; CAPES-PROSUP - IES Modality I; [FAPESP- 2010/20063-9]; [FAPESP- 2010/14656-7] FX We would like to thank Kayleen Weaver, BA, for her careful proofreading of this manuscript. PSB is supported by a CNPq researcher grant (305718/2009-6); FF is supported by a grant from RJG foundation; CC is supported by a PhD grant (FAPESP- 2010/20063-9); CAV is supported by a Master grant (FAPESP- 2010/14656-7); OML is supported by a Master grant (CAPES-PROSUP - IES Modality I); and ACAG and NIB are supported by student grants (CNPq). NR 76 TC 38 Z9 39 U1 6 U2 31 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0960-2011 J9 NEUROPSYCHOL REHABIL JI Neuropsychol. Rehabil. PY 2011 VL 21 IS 5 SI SI BP 703 EP 716 DI 10.1080/09602011.2011.617943 PG 14 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA 885OS UT WOS:000299789100008 PM 21942868 ER PT J AU Spencer, KM Nestor, PG Valdman, O Niznikiewicz, MA Shenton, ME McCarley, RW AF Spencer, Kevin M. Nestor, Paul G. Valdman, Olga Niznikiewicz, Margaret A. Shenton, Martha E. McCarley, Robert W. TI Enhanced Facilitation of Spatial Attention in Schizophrenia SO NEUROPSYCHOLOGY LA English DT Article DE attention; schizophrenia; orienting; prefrontal cortex ID TRANSCRANIAL MAGNETIC STIMULATION; FRONTAL EYE FIELD; PREFRONTAL CORTEX; VISUAL-ATTENTION; DEFICITS; DISENGAGEMENT; ASYMMETRY; SACCADES; ABNORMALITIES; INHIBITION AB Objective: While attentional functions are usually found to be impaired in schizophrenia, a review of the literature on the orienting of spatial attention in schizophrenia suggested that voluntary attentional orienting in response to a valid cue might be paradoxically enhanced. We tested this hypothesis with orienting tasks involving the cued detection of a laterally presented target stimulus. Method: Subjects were chronic schizophrenia patients (SZ) and matched healthy control subjects (HC). In Experiment 1 (15 SZ, 16 HC), cues were endogenous (arrows) and could be valid (100% predictive) or neutral with respect to the subsequent target position. In Experiment 2 (16 SZ, 16 HC), subjects performed a standard orienting task with unpredictive exogenous cues (brightening of the target boxes). Results: In Experiment 1, SZ showed a larger attentional facilitation effect on reaction time than HC. In Experiment 2, no clear sign of enhanced attentional facilitation was found in SZ. Conclusions: The voluntary, facilitatory shifting of spatial attention may be relatively enhanced in individuals with schizophrenia in comparison to healthy individuals. This effect bears resemblance to other relative enhancements of information processing in schizophrenia such as saccade speed and semantic priming. C1 [Spencer, Kevin M.; Niznikiewicz, Margaret A.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Res Serv, Boston, MA 02130 USA. [Spencer, Kevin M.; Nestor, Paul G.; Valdman, Olga; Niznikiewicz, Margaret A.; Shenton, Martha E.; McCarley, Robert W.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02130 USA. [Nestor, Paul G.] Univ Massachusetts, Mental Hlth Serv, Vet Affairs Boston Healthcare Syst, Dept Psychol, Amherst, MA 01003 USA. [Valdman, Olga] Univ Massachusetts, Sch Med, Amherst, MA 01003 USA. [Shenton, Martha E.] Brigham & Womens Hosp, Mental Hlth Serv, Vet Affairs Boston Healthcare Syst, Psychiat Neuroimaging Lab, Boston, MA 02115 USA. [McCarley, Robert W.] Harvard Univ, Sch Med, Vet Affairs Boston Healthcare Syst, Mental Hlth Serv, Boston, MA 02130 USA. RP Spencer, KM (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst, Res Serv, Res 151C,150 S Huntington Ave, Boston, MA 02130 USA. EM kevin_spencer@hms.harvard.edu RI McCarley, Robert/N-5562-2014; OI McCarley, Robert/0000-0001-5705-7495; Spencer, Kevin/0000-0002-5500-7627 FU Essel Foundation; NIH [F32 MH 13022, R01 MH080187]; U.S. Department of Veterans Affairs Schizophrenia Center FX This work was supported by an Essel Foundation/NARSAD Young Investigator Award (K.M.S.), NIH F32 MH 13022 (K.M.S.), NIH R01 MH080187 (K.M.S.), and a U.S. Department of Veterans Affairs Schizophrenia Center grant (R.W.M.). The authors are grateful to the anonymous reviewers for their insightful comments on this paper. NR 58 TC 21 Z9 22 U1 2 U2 7 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0894-4105 J9 NEUROPSYCHOLOGY JI Neuropsychology PD JAN PY 2011 VL 25 IS 1 BP 76 EP 85 DI 10.1037/a0020779 PG 10 WC Psychology, Clinical; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA 711AQ UT WOS:000286558500008 PM 20919764 ER PT J AU Yildiz, A Vieta, E Leucht, S Baldessarini, RJ AF Yildiz, Ayseguel Vieta, Eduard Leucht, Stefan Baldessarini, Ross J. TI Efficacy of Antimanic Treatments: Meta-analysis of Randomized, Controlled Trials SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE antimanic; antipsychotic; mania; mood stabilizer; placebo ID PLACEBO-CONTROLLED TRIAL; ACUTE BIPOLAR MANIA; RELEASE CARBAMAZEPINE CAPSULES; SODIUM EXTENDED-RELEASE; DOUBLE-BLIND TRIAL; I-DISORDER; DIVALPROEX SODIUM; MIXED EPISODES; ARIPIPRAZOLE MONOTHERAPY; RISPERIDONE MONOTHERAPY AB We conducted meta-analyses of findings from randomized, placebo-controlled, short-term trials for acute mania in manic or mixed states of DSM (III-IV) bipolar I disorder in 56 drug-placebo comparisons of 17 agents from 38 studies involving 10 800 patients. Of drugs tested, 13 (76%) were more effective than placebo: aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperdone, quetiapine, risperidone, tamoxifen, valproate, and ziprasidone. Their pooled effect size for mania improvement (Hedges' g in 48 trials) was 0.42 (confidence interval (CI): 0.36-0.48); pooled responder risk ratio (46 trials) was 1.52 (CI: 1.42-1.62); responder rate difference (RD) was 17% (drug: 48%, placebo: 31%), yielding an estimated number-needed-to-treat of 6 (all p<0.0001). In several direct comparisons, responses to various antipsychotics were somewhat greater or more rapid than lithium, valproate, or carbamazepine; lithium did not differ from valproate, nor did second generation antipsychotics differ from haloperidol. Meta-regression associated higher study site counts, as well as subject number with greater placebo (not drug) response; and higher baseline mania score with greater drug (not placebo) response. Most effective agents had moderate effect-sizes (Hedges' g=0.26-0.46); limited data indicated large effect sizes (Hedges' g=0.51-2.32) for: carbamazepine, cariprazine, haloperidol, risperidone, and tamoxifen. The findings support the efficacy of most clinically used antimanic treatments, but encourage more head-to-head studies and development of agents with even greater efficacy. Neuropsychopharmacology (2011) 36, 375-389; doi:10.1038/npp.2010.192; published online 27 October 2010 C1 [Yildiz, Ayseguel] Dokuz Eylul Univ, Dept Psychiat, TR-35320 Izmir, Turkey. [Yildiz, Ayseguel; Vieta, Eduard; Baldessarini, Ross J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Yildiz, Ayseguel; Vieta, Eduard; Baldessarini, Ross J.] Massachusetts Gen Hosp, McLean Div, Int Consortium Bipolar Disorder Res, Boston, MA 02114 USA. [Yildiz, Ayseguel; Vieta, Eduard; Baldessarini, Ross J.] Massachusetts Gen Hosp, McLean Div, Psychopharmacol Program, Boston, MA 02114 USA. [Vieta, Eduard] Univ Barcelona, Hosp Clin, Inst Clin Neurosci, Bipolar Disorders Program,IDIBAPS,CIBERSAM, Barcelona, Spain. [Leucht, Stefan] Tech Univ Munich, Klinikum Rechts Isar, Klin Psychiat & Psychotherapie TU Munchen, Dept Psychiat & Psychotherapy, D-8000 Munich, Germany. RP Yildiz, A (reprint author), Dokuz Eylul Univ, Dept Psychiat, TR-35320 Izmir, Turkey. EM agul_yildiz@hotmail.com RI Vieta, Eduard/I-6330-2013 OI Vieta, Eduard/0000-0002-0548-0053 FU Actavis-Turkey; Spanish Ministry of Science and Innovation [2007-0358]; Centro de Investigacion Biomedica en Red de Salud Mental (CIBERSAM); Bruce J Anderson Foundation; McLean Private Donors' Research Fund; Actavis; Ali Raif; Astra-Zeneca; Bristol-Myers Squibb; GlaxoSmithKline; Janssen-Cilag; Pfizer; Sanofi-Aventis; Servier Corporations; Eli Lilly; Actelion; Essex; Lundbeck; Sanofi-Aventis Corporations FX Supported in part by educational grants from the Actavis-Turkey (to AY); by the Spanish Ministry of Science and Innovation (PR 2007-0358), Centro de Investigacion Biomedica en Red de Salud Mental (CIBERSAM) (to EV); by a grant from the Bruce J Anderson Foundation and the McLean Private Donors' Research Fund (to RJB). Sponsors had no influence on the conduct, analysis, or reporting of this study. We thank Seren Ozer for contributing to study identification and data extraction. Unpublished information was generously provided by Dr Charles Bowden, Dr Paul Keck Jr, Dr Roger McIntyre, Dr Harrison G Pope Jr, Dr Steven Potkin, Dr Richard Weisler, and their colleagues, as well as representatives of Abbott, Bristol-Myers Squibb, Eli Lilly, Forest, GlaxoSmithKline, Johnson & Johnson, Novartis, and Pfizer Corporations.; Dr Yildiz has received research grants from and/or served as a consultant or speaker for Actavis, Ali Raif, Astra-Zeneca, Bristol-Myers Squibb, GlaxoSmithKline, Janssen-Cilag, Pfizer, Sanofi-Aventis, and Servier Corporations. Dr Vieta has served as a consultant or speaker for Astra-Zeneca, Bristol-Myers Squibb, Eli Lilly, Forest Research Institute, GlaxoSmithKline, Janssen-Cilag, Jazz, Lundbeck, Novartis, Organon, Otsuka, Pfizer, Sanofi-Aventis, and Servier Corporations. Dr Leucht has received research grants from and/or served as a consultant or speaker for Actelion, Astra-Zeneca, Bristol-Myers Squibb, Eli Lilly, Essex, GlaxoSmithKline, Janssen-Cilag, Lundbeck, Pfizer, and Sanofi-Aventis Corporations. Dr Baldessarini has no current sources of potential conflicts of interest to report, and neither he nor any family member has equity relationships with pharmaceutical or biomedical corporations. NR 79 TC 107 Z9 111 U1 6 U2 16 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JAN PY 2011 VL 36 IS 2 BP 375 EP 389 DI 10.1038/npp.2010.192 PG 15 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 694JE UT WOS:000285292200001 PM 20980991 ER PT J AU Maliszewski, M AF Maliszewski, Mike TI Reflections on a Special Relationship with Mircea Eliade SO NEUROQUANTOLOGY LA English DT Article DE Eliade; yoga; meditation; history of religions AB The author summarizes a relationship he had with Mircea Eliade in the 1970s and 1980s. C1 [Maliszewski, Mike] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Maliszewski, Mike] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Maliszewski, M (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ANKA PUBLISHER PI BORNOVA PA 116-11 SOK NO.10 K 2 D 2, BORNOVA, IZMIR 35050, TURKEY SN 1303-5150 J9 NEUROQUANTOLOGY JI NeuroQuantology PY 2011 VL 9 IS 3 BP 545 EP 546 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 861PQ UT WOS:000298032100022 ER PT J AU Schultz, BA Cifu, DX McNamee, S Nichols, M Carne, W AF Schultz, Billie A. Cifu, David X. McNamee, Shane Nichols, Michelle Carne, William TI Assessment and treatment of common persistent sequelae following blast induced mild traumatic brain injury SO NEUROREHABILITATION LA English DT Article DE Blast injury; polytrauma; rehabilitation ID POSTTRAUMATIC-STRESS-DISORDER; HEAD-INJURY; COGNITIVE REHABILITATION; POSTCONCUSSIVE SYMPTOMS; BEHAVIORAL TREATMENT; CLINICAL MANAGEMENT; SERVICE MEMBERS; EYE INJURIES; SLEEP; IRAQ AB The ongoing wars in Iraq and Afghanistan and terrorist activity worldwide have been associated with an increased incidence of blast injuries. While blast injuries share similarities with blunt or penetrating traumatic injuries, there are unique mechanistic elements of blast injury that create increased vulnerability to damage of specific organs. This review highlights the mechanism of blast-related injury, describes the common sequelae of blast exposure that may impact rehabilitation care, and summarizes the intervention strategies for these blast-related sequelae. C1 [Schultz, Billie A.; McNamee, Shane] Hunter Holmes McGuire Vet Med Ctr, Dept Phys Med & Rehabil, Richmond, VA USA. [Schultz, Billie A.; Cifu, David X.; McNamee, Shane; Nichols, Michelle; Carne, William] Virginia Commonwealth Univ, Dept Phys Med & Rehabil, Richmond, VA USA. [Nichols, Michelle; Carne, William] Henry M Jackson Fdn, Hunter Holmes McGuire Vet Med Ctr, Def & Vet Brain Injury Ctr, Richmond, VA USA. [Cifu, David X.] US Dept Vet Affairs, Phys Med & Rehabil Program Off, Washington, DC USA. RP Schultz, BA (reprint author), Hunter Holmes McGuire Vet Med Ctr, Dept Phys Med & Rehabil, Richmond, VA USA. EM schultz.billie@mayo.edu OI Nichols, Michelle/0000-0002-2078-9649 NR 101 TC 18 Z9 18 U1 1 U2 7 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1053-8135 J9 NEUROREHABILITATION JI Neurorehabilitation PY 2011 VL 28 IS 4 BP 309 EP 320 DI 10.3233/NRE-2011-0659 PG 12 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 795VL UT WOS:000293004900001 PM 21725164 ER PT J AU Rahman, M Ogilvy, CS Zipfel, GJ Derdeyn, CP Siddiqui, AH Bulsara, KR Kim, LJ Riina, HA Mocco, J Hoh, BL AF Rahman, Maryam Ogilvy, Christopher S. Zipfel, Gregory J. Derdeyn, Colin P. Siddiqui, Adnan H. Bulsara, Ketan R. Kim, Louis J. Riina, Howard A. Mocco, J. Hoh, Brian L. TI Unruptured Cerebral Aneurysms Do Not Shrink When They Rupture: Multicenter Collaborative Aneurysm Study Group SO NEUROSURGERY LA English DT Article DE Aneurysm size; Cerebral aneurysm; Computed tomographic angiography; Rupture risk; Subarachnoid hemorrhage ID DIGITAL-SUBTRACTION-ANGIOGRAPHY; INTRACRANIAL ANEURYSMS; SUBARACHNOID HEMORRHAGE; ROTATIONAL ANGIOGRAPHY; NATURAL-HISTORY; CT ANGIOGRAPHY; LOCATION; SIZE; DIFFERENCE; DIAGNOSIS AB BACKGROUND: The International Study of Intracranial Aneurysms found that for patients with no previous history of subarachnoid hemorrhage, small (< 7 mm) anterior circulation and posterior circulation aneurysms had a 0% and 2.5% risk of subarachnoid hemorrhage over 5 years, respectively. OBJECTIVE: To determine whether cerebral aneurysms shrink with rupture. METHODS: The clinical databases of 7 sites were screened for patients with imaging of cerebral aneurysms before and after rupture. Inclusion criteria included documented subarachnoid hemorrhage by imaging or lumbar puncture and intracranial imaging before and after cerebral aneurysm rupture. The patients were evaluated for aneurysm maximal height, maximal width, neck diameter, and other measurement parameters. Only a change of >= 2 mm was considered a true change. RESULTS: Data on 13 patients who met inclusion criteria were collected. The median age was 60, and 11 of the 13 patients (84.6%) were female. Only 5 patients had posterior circulation aneurysms. None of the aneurysms had a significant decrease in size. One aneurysm decreased by 1.8 mm in maximum size after rupture (7.7%). Six aneurysms had an increase in maximum size of at least 2 mm after rupture (46.2%) with a mean increase of 3.5 mm (+/- 0.5 mm). CONCLUSION: Unruptured aneurysms do not shrink when they rupture. The large percentage of ruptured small aneurysms in previous studies were likely small before they ruptured. C1 [Rahman, Maryam; Mocco, J.; Hoh, Brian L.] Univ Florida, Dept Neurosurg, Gainesville, FL 32610 USA. [Ogilvy, Christopher S.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Zipfel, Gregory J.; Derdeyn, Colin P.] Washington Univ, Dept Neurosurg, St Louis, MO USA. [Siddiqui, Adnan H.] SUNY Buffalo, Dept Neurosurg, Buffalo, NY 14260 USA. [Bulsara, Ketan R.] Yale Univ, Dept Neurosurg, New Haven, CT USA. [Kim, Louis J.] Univ Washington, Dept Neurosurg, Seattle, WA 98195 USA. [Riina, Howard A.] Weill Cornell Med Coll, Dept Neurosurg, New York, NY USA. RP Rahman, M (reprint author), Univ Florida, Dept Neurosurg, Box 100265, Gainesville, FL 32610 USA. EM maryam.rahman@neurosurgery.ufl.edu RI Kim, Louis/F-1781-2011; OI Derdeyn, Colin/0000-0002-5932-2683 NR 26 TC 40 Z9 40 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 JAN PY 2011 VL 68 IS 1 BP 155 EP 160 DI 10.1227/NEU.0b013e3181ff357c PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 694IE UT WOS:000285288200049 PM 21150760 ER PT J AU Scremin, OU Chialvo, DR Lavarello, S Berra, HH Lucero, MA AF Scremin, Oscar U. Chialvo, Dante R. Lavarello, Simona Berra, Hector H. Lucero, Miguel A. TI The environmental pollutant endosulfan disrupts cerebral cortical function at low doses SO NEUROTOXICOLOGY LA English DT Article DE Organochlorine insecticides; Epilepsy; GABA-A receptors; Electroencephalogram; Evoked potentials; Cerebral cortex; Endosulfan ID SOMATOSENSORY-EVOKED-POTENTIALS; PERSISTENT ORGANIC POLLUTANTS; ORGANOCHLORINE PESTICIDES; CHLORIDE CHANNELS; IMMUNE-RESPONSES; SEMIARID MIDWEST; EXPOSURE; CORTEX; RATS; GABA(A) AB Endosulfan can induce convulsions that could lead to brain damage. The variability and lack of specificity of neurological signs and symptoms in the pre-convulsive stages makes early diagnosis difficult. We sought to determine if electrophysiological exploration of the cerebral cortex could yield objective signs of endosulfan intoxication at levels that do not elicit convulsions. Endosulfan was administered intravenously to Sprague-Dawley adult rats under urethane anesthesia at doses from 0.5 to 4 mg/kg. EEG power and the evoked potentials (EP) to forepaw electrical stimulation were studied over the contralateral (S1CL) and homolateral (S1HL) cortical somatosensory areas and the contralateral visual area (V1CL). At each area, five EP waves were measured. Arterial blood pressure, heart rate and body temperature were also recorded. Endosulfan induced a dose-related increase in EPs at all sites. At S1CL, EP peak amplitude was greater than baseline at 1, 2 and 4 mg/kg for the first negative, second positive and third negative waves, and at 2 and 4 mg/kg for the first and third positive waves. Similar but less marked trends were observed at S1HL and V1CL. A shift of EEG power to higher frequencies (alpha and beta EEG bands) was only present at 4 mg/kg. In conclusion, endosulfan induced a large increase of cortical evoked potentials amplitudes at doses that did not elicit convulsions. These responses could be used as a non-invasive diagnostic tool to detect low-level endosulfan intoxication in humans and to help establish the NOAEL and LOAEL levels of this pollutant. Published by Elsevier Inc. C1 [Scremin, Oscar U.] VA Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA 90073 USA. [Scremin, Oscar U.; Chialvo, Dante R.; Lavarello, Simona; Berra, Hector H.; Lucero, Miguel A.] UNR, Fac Ciencias Med, Inst Toxicol Agr Rosario, RA-3100 Rosario, Santa Fe, Argentina. [Scremin, Oscar U.; Chialvo, Dante R.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90095 USA. [Scremin, Oscar U.; Chialvo, Dante R.] Consejo Nacl Invest Cient & Tecn, RA-1033 Buenos Aires, DF, Argentina. RP Scremin, OU (reprint author), VA Greater Los Angeles Healthcare Syst, Res Serv, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM oscremin@ucla.edu RI Chialvo, Dante/A-4658-2009 OI Chialvo, Dante/0000-0002-1038-3637 FU Capacitacion e Investigacion para la Medicina Argentina-Asociacion Civil FX This work was supported by funds and equipment donations from Capacitacion e Investigacion para la Medicina Argentina-Asociacion Civil, a non-profit academic organization. NR 61 TC 6 Z9 7 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD JAN PY 2011 VL 32 IS 1 BP 31 EP 37 DI 10.1016/j.neuro.2010.12.001 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 716VW UT WOS:000287002600004 PM 21144862 ER PT J AU Anger, JT Nissim, HA Le, TX Smith, AL Lee, U Sarkisian, C Litwin, MS Raz, S Rodriguez, LV Maliski, SL AF Anger, Jennifer T. Nissim, Helen A. Le, Thuy X. Smith, Ariana L. Lee, Una Sarkisian, Catherine Litwin, Mark S. Raz, Shlomo Rodriguez, Larissa V. Maliski, Sally L. TI Women's Experience With Severe Overactive Bladder Symptoms and Treatment: Insight Revealed From Patient Focus Groups SO NEUROUROLOGY AND URODYNAMICS LA English DT Article DE focus groups; grounded theory; qualitative research; urinary incontinence ID QUALITY-OF-LIFE; QUESTIONNAIRE; DISEASE; BLAME; CARE AB Aims: Research has focused on treatment of overactive bladder (OAB) symptoms in women with the goal of cure. The objective of this study was to assess women's perceptions of their OAB symptoms, treatment experience, and outcomes by conducting patient focus groups. Methods: Women seen in our academic center female urology referral clinics were identified by ICD-9 codes for OAB symptoms and recruited to participate in one of five focus groups, totaling 33 patients. Non-clinician moderators conducted the focus group sessions incorporating topics related to patients' perceptions of OAB symptoms, treatments, and outcomes. Data analysis was performed using grounded theory methodology. Results: Qualitative analysis yielded several preliminary themes: impact of OAB on quality of life, strategies to control wetness, medications and side effects, and triggers. The majority of focus group participants reported only a partial response to medication and other physician-recommended treatments for OAB. Therefore, they developed self-reliant personalized strategies to improve their quality of life. These strategies included fluid restriction, preventive toileting, and, most importantly, the use of incontinence pads. Conclusions: The majority of the women who participated in the focus groups reported only a partial response to medical and other treatments for OAB. As a result, they developed personalized self-management strategies to improve their quality of life. Although most studies addressing the treatment of OAB aim at curing the condition, such a strategy may be unrealistic. Applying a chronic care model that uses a patient-centered symptom-management approach to OAB may optimize patient outcomes and improve quality of life. Neurourol. Urodynam. 30:1295-1299, 2011. (C) 2011 Wiley-Liss, Inc. C1 [Anger, Jennifer T.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Anger, Jennifer T.; Le, Thuy X.; Smith, Ariana L.; Lee, Una; Litwin, Mark S.; Raz, Shlomo; Rodriguez, Larissa V.] UCLA Dept Urol, Los Angeles, CA USA. [Le, Thuy X.] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Sarkisian, Catherine] UCLA Dept Med & Geriatr, Los Angeles, CA USA. [Sarkisian, Catherine] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Litwin, Mark S.] UCLA Sch Publ Hlth, Los Angeles, CA USA. [Maliski, Sally L.] UCLA Sch Nursing, Los Angeles, CA USA. RP Anger, JT (reprint author), Cedars Sinai Med Ctr Urol Reconstruct, 99 La Cienega Blvd,Suite 307, Beverly Hills, CA 90211 USA. EM janger@mednet.ucla.edu FU NIDDK [1 K23 DK080227-01]; National Institute on Aging [1 T35 AG 026736] FX Grant sponsor: NIDDK; Grant number: 1 K23 DK080227-01 (JTA); Grant sponsor: National Institute on Aging Medical Student Training in Aging Research Program (MSTAR); Grant number: 1 T35 AG 026736. NR 17 TC 18 Z9 18 U1 2 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0733-2467 J9 NEUROUROL URODYNAM JI Neurourol. Urodyn. PY 2011 VL 30 IS 7 BP 1295 EP 1299 DI 10.1002/nau.21004 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 818CQ UT WOS:000294727800019 PM 21538495 ER PT S AU Ganesan, S Aggarwal, K Paquette, N Silverman, N AF Ganesan, Sandhya Aggarwal, Kamna Paquette, Nicholas Silverman, Neal BE Karin, M TI NF-kappa B/Rel Proteins and the Humoral Immune Responses of Drosophila melanogaster SO NF-KB IN HEALTH AND DISEASE SE Current Topics in Microbiology and Immunology LA English DT Review; Book Chapter ID PEPTIDOGLYCAN-RECOGNITION PROTEIN; ANTIMICROBIAL PEPTIDE GENES; GRAM-POSITIVE BACTERIA; B FACTOR RELISH; LYSINE-TYPE PEPTIDOGLYCAN; REGULATED NUCLEAR IMPORT; TUMOR-SUPPRESSOR CYLD; GENOME-WIDE ANALYSIS; PATTERN-RECOGNITION; TOLL PATHWAY AB Nuclear Factor-kappa B (NF-kappa B)/Rel transcription factors form an integral part of innate immune defenses and are conserved throughout the animal kingdom. Studying the function, mechanism of activation and regulation of these factors is crucial for understanding host responses to microbial infections. The fruit fly Drosophila melanogaster has proved to be a valuable model system to study these evolutionarily conserved NF-kappa B mediated immune responses. Drosophila combats pathogens through humoral and cellular immune responses. These humoral responses are well characterized and are marked by the robust production of a battery of anti-microbial peptides. Two NF-kappa B signaling pathways, the Toll and the IMD pathways, are responsible for the induction of these antimicrobial peptides. Signal transduction in these pathways is strikingly similar to that in mammalian TLR pathways. In this chapter, we discuss in detail the molecular mechanisms of microbial recognition, signal transduction and NF-kappa B regulation, in both the Toll and the IMD pathways. Similarities and differences relative to their mammalian counterparts are discussed, and recent advances in our understanding of the intricate regulatory networks in these NF-kappa B signaling pathways are also highlighted. C1 [Ganesan, Sandhya; Aggarwal, Kamna; Silverman, Neal] Univ Massachusetts, Sch Med, Dept Med, Div Infect Dis, Worcester, MA 01605 USA. [Paquette, Nicholas] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Program Dev Immunol,Dept Pediat, Boston, MA 02114 USA. RP Silverman, N (reprint author), Univ Massachusetts, Sch Med, Dept Med, Div Infect Dis, Worcester, MA 01605 USA. EM neal.silverman@umassmed.edu FU NIAID NIH HHS [R01 AI060025, R01 AI060025-07, R01 AI074958] NR 226 TC 69 Z9 74 U1 0 U2 26 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 978-3-642-16016-5 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2011 VL 349 BP 25 EP 60 DI 10.1007/82_2010_107 D2 10.1007/978-3-642-16017-2 PG 36 WC Immunology; Microbiology SC Immunology; Microbiology GA BVA80 UT WOS:000290916900002 PM 20852987 ER PT S AU Baud, V Derudder, E AF Baud, Veronique Derudder, Emmanuel BE Karin, M TI Control of NF-kappa B Activity by Proteolysis SO NF-KB IN HEALTH AND DISEASE SE Current Topics in Microbiology and Immunology LA English DT Review; Book Chapter ID SCF-BETA-TRCP; T-CELL-ACTIVATION; UBIQUITIN-PROTEASOME PATHWAY; NECROSIS-FACTOR-ALPHA; P105 REQUIRES PHOSPHORYLATION; SIGNAL-INDUCED UBIQUITINATION; CALPAIN-MEDIATED DEGRADATION; EDITING ENZYME A20; CASEIN KINASE-II; IKK-ALPHA AB NF-kappa B transcription factors are critical regulators of many biological processes such as innate and adaptive immune responses, inflammation, cell proliferation and programmed cell death. This versatility necessitates a highly complex and tightly coordinated control of the signaling pathways leading to their activation. Here, we review the role of proteolysis in the regulation of NF-kappa B activity, more specifically the contribution of the well-known ubiquitin-proteasome system and the involvement of proteolytic activity of caspases and calpains. C1 [Baud, Veronique] Univ Paris 05, Inst Cochin, CNRS, UMR 8104, Paris, France. [Baud, Veronique] INSERM, U1016, Paris, France. [Derudder, Emmanuel] Harvard Univ, Childrens Hosp, Sch Med, Program Cellular & Mol Med,Immune Dis Inst, Boston, MA 02115 USA. RP Baud, V (reprint author), Univ Paris 05, Inst Cochin, CNRS, UMR 8104, Paris, France. EM veronique.baud@inserm.fr RI Baud, Veronique/F-7699-2013 OI Baud, Veronique/0000-0002-4090-718X NR 125 TC 11 Z9 12 U1 0 U2 9 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 978-3-642-16016-5 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2011 VL 349 BP 97 EP 114 DI 10.1007/82_2010_101 D2 10.1007/978-3-642-16017-2 PG 18 WC Immunology; Microbiology SC Immunology; Microbiology GA BVA80 UT WOS:000290916900005 PM 21267708 ER PT J AU Cao, QY Zhou, M Wang, XJ Meyer, CA Zhang, Y Chen, Z Li, C Liu, XS AF Cao, Qingyi Zhou, Meng Wang, Xujun Meyer, Cliff A. Zhang, Yong Chen, Zhi Li, Cheng Liu, X. Shirley TI CaSNP: a database for interrogating copy number alterations of cancer genome from SNP array data SO NUCLEIC ACIDS RESEARCH LA English DT Article ID NUCLEOTIDE POLYMORPHISM ARRAYS; BREAST-CANCER; CHROMOSOMAL-ABERRATIONS; HOMOZYGOUS DELETIONS; GENE-EXPRESSION; AMPLIFICATIONS; HETEROZYGOSITY; MICROARRAYS; REPOSITORY; PATHWAYS AB Cancer is known to have abundant copy number alterations (CNAs) that greatly contribute to its pathogenesis and progression. Investigation of CNA regions could potentially help identify oncogenes and tumor suppressor genes and infer cancer mechanisms. Although single-nucleotide polymorphism (SNP) arrays have strengthened our ability to identify CNAs with unprecedented resolution, a comprehensive collection of CNA information from SNP array data is still lacking. We developed a web-based CaSNP (http://cistrome.dfci.harvard.edu/CaSNP/) database for storing and interrogating quantitative CNA data, which curated similar to 11 500 SNP arrays on 34 different cancer types in 104 studies. With a user input of region or gene of interest, CaSNP will return the CNA information summarizing the frequencies of gain/loss and averaged copy number for each study, and provide links to download the data or visualize it in UCSC Genome Browser. CaSNP also displays the heatmap showing copy numbers estimated at each SNP marker around the query region across all studies for a more comprehensive visualization. Finally, we used CaSNP to study the CNA of protein-coding genes as well as LincRNA genes across all cancer SNP arrays, and found putative regions harboring novel oncogenes and tumor suppressors. In summary, CaSNP is a useful tool for cancer CNA association studies, with the potential to facilitate both basic science and translational research on cancer. C1 [Cao, Qingyi; Meyer, Cliff A.; Li, Cheng; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Cao, Qingyi; Chen, Zhi] Zhejiang Univ, Affiliated Hosp 1, State Key Lab Diag & Treatment Infect Dis, Sch Med, Hangzhou 310012, Zhejiang, Peoples R China. [Zhou, Meng; Wang, Xujun; Zhang, Yong] Tongji Univ, Sch Life Sci & Technol, Dept Bioinformat, Shanghai 200092, Peoples R China. RP Liu, XS (reprint author), Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. EM cli@hsph.harvard.edu; xliu@hsph.harvard.edu RI Zhang, Yong/B-4838-2011 OI Zhang, Yong/0000-0001-6316-2734 FU National Institutes of Health [HG004069, GM077122]; Chinese Scholarship Council [2008632067]; State S & T Projects (11th Five Year) of China [2008ZX10002-007]; National Basic Research Program of China (973 Program) [2010CB944904] FX The National Institutes of Health R01 (HG004069 to X. S. L., GM077122 to C. L.); Chinese Scholarship Council (2008632067 to Q. C.); State S & T Projects (11th Five Year) of China (2008ZX10002-007 to Z.C.); National Basic Research Program of China (973 Program No. 2010CB944904 to M.Z., X.W. and Y.Z.). Funding for open access charge: National Basic Research Program of China (973 Program No. 2010CB944904). NR 27 TC 10 Z9 13 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2011 VL 39 SU 1 BP D968 EP D974 DI 10.1093/nar/gkq997 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 701PA UT WOS:000285831700151 PM 20972221 ER PT J AU Milbury, CA Li, J Makrigiorgos, GM AF Milbury, Coren A. Li, Jin Makrigiorgos, G. Mike TI Ice-COLD-PCR enables rapid amplification and robust enrichment for low-abundance unknown DNA mutations SO NUCLEIC ACIDS RESEARCH LA English DT Article ID RESOLUTION MELTING ANALYSIS; CELL LUNG-CANCER; KRAS AB Identifying low-abundance mutations within wild-type DNA is important in several fields of medicine, including cancer, prenatal diagnosis and infectious diseases. However, utilizing the clinical and diagnostic potential of rare mutations is limited by sensitivity of the molecular techniques employed, especially when the type and position of mutations are unknown. We have developed a novel platform that incorporates a synthetic reference sequence within a polymerase chain reaction (PCR) reaction, designed to enhance amplification of unknown mutant sequences during COLD-PCR (CO-amplification at Lower Denaturation temperature). This new platform enables an Improved and Complete Enrichment (ice-COLD-PCR) for all mutation types and eliminates shortcomings of previous formats of COLD-PCR. We evaluated ice-COLD-PCR enrichment in regions of TP53 in serially diluted mutant and wild-type DNA mixtures. Conventional-PCR, COLD-PCR and ice-COLD-PCR amplicons were run in parallel and sequenced to determine final mutation abundance for a range of mutations representing all possible single base changes. Amplification by ice-COLD-PCR enriched all mutation types and allowed identification of mutation abundances down to 1%, and 0.1% by Sanger sequencing or pyrosequencing, respectively, surpassing the capabilities of other forms of PCR. Ice-COLD-PCR will help elucidate the clinical significance of low-abundance mutations and our understanding of cancer origin, evolution, recurrence-risk and treatment diagnostics. C1 [Milbury, Coren A.; Li, Jin; Makrigiorgos, G. Mike] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol,Div Med Phys & Biophys, Boston, MA 02115 USA. [Milbury, Coren A.; Li, Jin; Makrigiorgos, G. Mike] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol,Div DNA Repair & Genome Stabil, Boston, MA 02115 USA. RP Makrigiorgos, GM (reprint author), Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol,Div Med Phys & Biophys, Boston, MA 02115 USA. EM mmakrigiorgos@partners.org FU German Ministry for Research and Education [FKZ 0313940, PTJ-Bio/0313735/Nn07-06, PTJ-Bio/0315271A]; Deutsche Forschungsgemeinschaft [DFG Wi2648, DFG Schi 505/5-1]; European Union [FlpFlex MEST-CT-2004-504990, LSHB-CT-2006-018933]; European Community [MEST-2004-504990] FX German Ministry for Research and Education (FKZ 0313940; PTJ-Bio/0313735/Nn07-06; PTJ-Bio/0315271A); Deutsche Forschungsgemeinschaft (DFG Wi2648, DFG Schi 505/5-1, and Excellence Cluster REBIRTH) the European Union (FlpFlex MEST-CT-2004-504990; Clinigene, LSHB-CT-2006-018933), MIDITRAIN (Molecular Interactions during Infection Training)- A Marie Curie Early Stage Training (EST) of the European Community's Sixth Framework Programme under Contract number MEST-2004-504990. NR 24 TC 53 Z9 57 U1 4 U2 17 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2011 VL 39 IS 1 AR e2 DI 10.1093/nar/gkq899 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 703VD UT WOS:000286008500002 PM 20937629 ER PT J AU Tilden, V Corless, I Dahlin, C Ferrell, B Gibson, R Lentz, J AF Tilden, Virginia Corless, Inge Dahlin, Constance Ferrell, Betty Gibson, Rosemary Lentz, Judy TI Advance care planning as an urgent public health concern SO NURSING OUTLOOK LA English DT Article C1 [Tilden, Virginia] Univ Nebraska Med Ctr, Coll Nursing, Omaha, NE 68198 USA. [Corless, Inge] MGH Inst Hlth Profess, Charlestown, MA USA. [Dahlin, Constance] Massachusetts Gen Hosp, Palliat Care Serv, Boston, MA 02114 USA. [Ferrell, Betty] City Hope Natl Med Ctr, Duarte, CA USA. [Lentz, Judy] Hosp & Palliat Nurses Assoc, Pittsburgh, PA USA. RP Tilden, V (reprint author), Univ Nebraska Med Ctr, Coll Nursing, 985330 Nebraska Med Ctr, Omaha, NE 68198 USA. EM vtilden@unmc.edu OI Corless, Inge/0000-0003-0438-2037 NR 3 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 0029-6554 J9 NURS OUTLOOK JI Nurs. Outlook PD JAN-FEB PY 2011 VL 59 IS 1 BP 55 EP 56 DI 10.1016/j.outlook.2010.12.001 PG 2 WC Nursing SC Nursing GA 719DZ UT WOS:000287181300010 PM 21329007 ER PT J AU Asgari, MM White, E Warton, EM Hararah, MK Friedman, GD Chren, MM AF Asgari, Maryam M. White, Emily Warton, E. Margaret Hararah, Mohammad K. Friedman, Gary D. Chren, Mary-Margaret TI Association of Tea Consumption and Cutaneous Squamous Cell Carcinoma SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID SKIN AB Laboratory and epidemiologic studies suggest a protective effect of tea consumption on risk of cutaneous squamous cell carcinoma (SCC). We designed a case-control study to examine the association between putative protective exposures, including tea consumption, and SCC risk using a large health maintenance organization population. Cases (n = 415) were defined as Kaiser Permanente Northern California (KPNC) members with a pathology-verified SCC in 2004 and controls (n = 415) were age-, gender-, and race-matched members with no previous history of skin cancer. Tea consumption and SCC risk factors were ascertained by questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional logistic regression to estimate the association of SCC with regular use, as well as dose and duration of tea consumption. Risk factor adjusted models included education, smoking, hair and eye color, skin type, family history of skin cancer, and history of freckling, sunburns, sun exposure, and tanning bed use. Adjusted analyses showed no reduction in SCC risk with regular consumption of tea (OR = 1.11, 95% CI: 0.81-1.54). Examining duration, dose, and combined duration and dose exposure variables did not alter findings. We found no evidence that tea consumption was associated with cutaneous SCC risk. C1 [Asgari, Maryam M.; Warton, E. Margaret; Hararah, Mohammad K.; Friedman, Gary D.] Kaiser Permanente No Calif, Div Res, Oakland, CA 94612 USA. [Asgari, Maryam M.; Chren, Mary-Margaret] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [White, Emily] Univ Washington, Dept Epidemiol, Med Ctr, Seattle, WA 98195 USA. [White, Emily] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA. [Friedman, Gary D.] Stanford Univ, Dept Hlth Res & Policy, Sch Med, Stanford, CA 94305 USA. [Chren, Mary-Margaret] San Francisco VA Med Ctr, Hlth Serv Res Enhancement Award Program REAP, San Francisco, CA USA. RP Asgari, MM (reprint author), Kaiser Permanente No Calif, Div Res, 2000 Broadway, Oakland, CA 94612 USA. EM maryam.m.asgari@kp.org RI Asgari, Maryam/O-4947-2016 FU National Institute of Arthritis Musculoskeletal and Skin Diseases [K23 AR 051037, K24 AR 052667]; National Cancer Institute [R01 CA 098838] FX The work was done at Kaiser Permanente Northern California, Division of Research, Oakland, California, USA. This study was supported by the National Institute of Arthritis Musculoskeletal and Skin Diseases (K23 AR 051037 to MA, K24 AR 052667 to MC) and by the National Cancer Institute (R01 CA 098838 to GF). NR 8 TC 7 Z9 7 U1 1 U2 5 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 0163-5581 J9 NUTR CANCER JI Nutr. Cancer PY 2011 VL 63 IS 2 BP 314 EP 318 AR PII 932401769 DI 10.1080/01635581.2011.523496 PG 5 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 723ET UT WOS:000287489900019 PM 21240832 ER PT J AU Boyce, JA Assa'ad, A Burks, AW Jones, SM Sampson, HA Wood, RA Plaut, M Cooper, SF Fenton, MJ Arshad, SH Bahna, SL Beck, LA Byrd-Bredbenner, C Camargo, CA Eichenfield, L Furuta, GT Hanifin, JM Jones, C Kraft, M Levy, BD Lieberman, P Luccioli, S McCall, KM Schneider, LC Simon, RA Simons, FER Teach, SJ Yawn, BP Schwaninger, JM AF Boyce, Joshua A. Assa'ad, Amal Burks, A. Wesley Jones, Stacie M. Sampson, Hugh A. Wood, Robert A. Plaut, Marshall Cooper, Susan F. Fenton, Matthew J. Arshad, S. Hasan Bahna, Sami L. Beck, Lisa A. Byrd-Bredbenner, Carol Camargo, Carlos A., Jr. Eichenfield, Lawrence Furuta, Glenn T. Hanifin, Jon M. Jones, Carol Kraft, Monica Levy, Bruce D. Lieberman, Phil Luccioli, Stefano McCall, Kathleen M. Schneider, Lynda C. Simon, Ronald A. Simons, F. Estelle R. Teach, Stephen J. Yawn, Barbara P. Schwaninger, Julie M. TI Guidelines for the Diagnosis and Management of Food Allergy in the United States: Summary of the NIAID-Sponsored Expert Panel Report SO NUTRITION RESEARCH LA English DT Article C1 [Plaut, Marshall; Cooper, Susan F.; Fenton, Matthew J.; Schwaninger, Julie M.] NIAID, Div Allergy Immunol & Transplantat, NIH, Bethesda, MD 20892 USA. [Boyce, Joshua A.] Harvard Univ, Brigham & Womens Hosp, Massachusetts Gen Hosp, Dept Med,Sch Med,Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Camargo, Carlos A., Jr.] Harvard Univ, Dept Emergency Med, Massachusetts Gen Hosp, Dept Med,Div Rheumatol Allergy & Immunol,Sch Med, Boston, MA 02115 USA. [Levy, Bruce D.] Brigham & Womens Hosp, Pulm & Crit Med Div, Partners Asthma Ctr, Boston, MA 02115 USA. [Assa'ad, Amal] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Div Allergy & Immunol, Cincinnati, OH USA. [Burks, A. Wesley] Duke Univ, Med Ctr, Dept Pediat, Div Allergy & Immunol, Durham, NC 27710 USA. [Kraft, Monica] Duke Univ, Med Ctr, Dept Med, Div Pulm Allergy & Crit Care Med, Durham, NC 27710 USA. [Jones, Stacie M.] Univ Arkansas Med Sci, Arkansas Childrens Hosp, Dept Pediat, Div Allergy & Immunol, Little Rock, AR 72205 USA. [Sampson, Hugh A.] Mt Sinai Sch Med, Dept Pediat, Div Allergy & Immunol, Elliot & Roslyn Jaffe Food Allergy Inst, New York, NY USA. [Wood, Robert A.] Johns Hopkins Univ, Sch Med, Dept Pediat, Div Allergy & Immunol, Baltimore, MD 21205 USA. [Arshad, S. Hasan] Univ Southampton, Sch Med, Southampton, Hants, England. [Arshad, S. Hasan] St Marys Hosp, David Hide Asthma & Allergy Res Ctr, Newport, Wight, England. [Arshad, S. Hasan] Southampton Univ Hosp NHS Trust, Southampton, Hants, England. [Bahna, Sami L.] Louisiana State Univ, Hlth Sci Ctr, Dept Pediat, Allergy & Immunol Sect, Shreveport, LA 71105 USA. [Beck, Lisa A.] Univ Rochester, Dept Dermatol, Med Ctr, Rochester, NY 14627 USA. [Byrd-Bredbenner, Carol] Rutgers State Univ, Dept Nutr Sci, New Brunswick, NJ 08903 USA. [Eichenfield, Lawrence] Rady Childrens Hosp, Div Pediat & Adolescent Dermatol, San Diego, CA USA. [Eichenfield, Lawrence] Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA. [Eichenfield, Lawrence] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. [Furuta, Glenn T.] Childrens Hosp Denver, Digest Hlth Inst, Sect Pediat Gastroenterol Hepatol & Nutr, Aurora, CO USA. [Furuta, Glenn T.] Natl Jewish Hlth, Dept Pediat, Denver, CO USA. [Furuta, Glenn T.] Univ Colorado Denver, Sch Med, Dept Pediat, Aurora, CO USA. [Hanifin, Jon M.] Oregon Hlth & Sci Univ, Dept Dermatol, Portland, OR 97201 USA. [Jones, Carol] Allergy & Asthma Network Mothers Asthmat, Mclean, VA USA. [Lieberman, Phil] Univ Tennessee, Dept Med, Coll Med, Div Allergy & Immunol, Memphis, TN 38104 USA. [Luccioli, Stefano] US FDA, Off Food Addit Safety, College Pk, MD USA. [McCall, Kathleen M.] Childrens Hosp Orange Cty, Orange, CA 92668 USA. [Schneider, Lynda C.] Childrens Hosp Boston, Div Immunol, Boston, MA USA. [Simon, Ronald A.] Scripps Clin, Div Allergy Asthma & Immunol, San Diego, CA USA. [Simons, F. Estelle R.] Univ Manitoba, Fac Med, Dept Pediat, Winnipeg, MB, Canada. [Simons, F. Estelle R.] Univ Manitoba, Fac Med, Dept Child Hlth & Immunol, Winnipeg, MB, Canada. [Teach, Stephen J.] Childrens Natl Med Ctr, Div Emergency Med, Washington, DC 20010 USA. [Yawn, Barbara P.] Olmsted Med Ctr, Dept Res, Rochester, MN USA. [Yawn, Barbara P.] Univ Minnesota, Sch Med, Dept Family & Community Hlth, Minneapolis, MN 55455 USA. RP Fenton, MJ (reprint author), NIAID, Div Allergy Immunol & Transplantat, NIH, 6610 Rockledge Dr,Room 3105, Bethesda, MD 20892 USA. EM fentonm@niaid.nih.gov RI Byrd-Bredbenner, Carol/F-8064-2015 OI Byrd-Bredbenner, Carol/0000-0002-8010-3987 FU National Institutes of Health; GlaxoSmithKline; Food Allergy and Anaphylaxis Network; Gerber; Mead Johnson; Dyax Corp; National Peanut Board; Food Allergy Initiative; National Institutes of Health (Division of Receipt and Referral, National Institute of Allergy and Infectious Diseases, National Center for Complementary and Alternative Medicine); Phadia AB; Genentech; National Institutes of Health (National Institute of Allergy and Infectious Diseases); National Institute of Health Research, UK; American Academy of Allergy, Asthma, and Immunology; National Eczema Association; US Department of Agriculture; Canned Food Alliance; New Jersey Department of Health and Senior Services; variety of government agencies; Dey; Novartis; Astellas; Ferndale; Johnson Johnson; Sinclair; Stiefel; Therapeutics Inc FX J. A. Boyce has served on the Advisory Board of GlaxoStmithKline. He has served as a consultant and/or speaker for Altana, GlaxoSmithKline, and Merck. He has received funding/grant support from the National Institutes of Health.; A. Assa'ad holds, or is listed as an inventor on, US patent application #10/566903, entitled "Genetic markers of food allergy." She has served as a consultant for GlaxoStmithKline and as a speaker for the American College of Allergy, Asthma, and Immunology, the North East Allergy Society, the Virginia Allergy Society, the New England Allergy Society, and the American Academy of Pediatrics. Dr Assa'ad has received funding/grant support from GlaxoSmithKline.; A. W. Burks holds, or is listed as an inventor on, multiple US patents related to food allergy. He owns stock in Allertein and MastCell, Inc, and is a minority stockholder in Daimon Co Probiotics. He has served as a consultant for ActoGeniX NV, McNeil Nutritionals, Mead Johnson, and Novartis. He has served on the speaker's bureau for EpiPen/Dey, LP, and has served on the data monitoring committee for Genentech. He has served on an expert panel for Nutricia. Dr Burks has received funding/grant support from the Food Allergy and Anaphylaxis Network, Gerber, Mead Johnson, and the National Institutes of Health.; S. M. Jones has served as a speaker and grant reviewer and has served on the medical advisory committee for the Food Allergy and Anaphylaxis Network. She has received funding/grant support from Dyax Corp, the Food Allergy and Anaphylaxis Network, Mead Johnson, the National Peanut Board, and the National Institutes of Health.; H. A. Sampson holds, or is listed as an inventor on, multiple US patents related to food allergy. He owns stock in Allertein Therapeutics. He is the immediate past president of the American Academy of Allergy, Asthma, and Immunology. He has served as a consultant for Allertein Therapeutics, the American Academy of Allergy, Asthma, and Immunology, the Food Allergy Initiative, and Schering Plough. He has received funding/grant support for research projects from the Food Allergy Initiative, the National Institutes of Health (Division of Receipt and Referral, National Institute of Allergy and Infectious Diseases, National Center for Complementary and Alternative Medicine), and Phadia AB. He is a co-owner of Herbal Spring, LLC.; R. A. Wood has served as a speaker/advisory board member for GlaxoSmithKline, Merck, and Dey. He has received funding/grant support from Genentech and the National Institutes of Health (National Institute of Allergy and Infectious Diseases).; S. H. Arshad has received funding/grant support from the National Institutes of Health and the National Institute of Health Research, UK.; S. L. Bahna has received funding/grant support from Genentech.; L. A. Beck has received funding/grant support from the American Academy of Allergy, Asthma, and Immunology, the National Eczema Association, and the National Institutes of Health.; C. Byrd-Bredbenner owns stock in Johnson & Johnson. She has received funding/grant support from the US Department of Agriculture, the Canned Food Alliance, and the New Jersey Department of Health and Senior Services.; C. A. Camargo Jr has consulted for Dey and Novartis. He has received funding/grant support from a variety of government agencies and not-for-profit research foundations, as well as Dey and Novartis.; L. Eichenfield has received funding/grant support from a variety of not-for-profit foundations, as well as Astellas, Ferndale, Johnson & Johnson, Novartis, Sinclair, Stiefel, and Therapeutics Inc. NR 1 TC 33 Z9 39 U1 0 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0271-5317 J9 NUTR RES JI Nutr. Res. PD JAN PY 2011 VL 31 IS 1 BP 61 EP 75 DI 10.1016/j.nutres.2011.01.001 PG 15 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 724ZB UT WOS:000287613900010 PM 21310308 ER PT J AU Bredella, MA Torriani, M Ghomi, RH Thomas, BJ Brick, DJ Gerweck, AV Rosen, CJ Klibanski, A Miller, KK AF Bredella, Miriam A. Torriani, Martin Ghomi, Reza Hosseini Thomas, Bijoy J. Brick, Danielle J. Gerweck, Anu V. Rosen, Clifford J. Klibanski, Anne Miller, Karen K. TI Vertebral Bone Marrow Fat Is Positively Associated With Visceral Fat and Inversely Associated With IGF-1 in Obese Women SO OBESITY LA English DT Article ID PROTON MR SPECTROSCOPY; GROWTH-HORMONE; MINERAL DENSITY; PREMENOPAUSAL WOMEN; ADIPOSE-TISSUE; BODY-FAT; OSTEOPOROSIS; ADIPOCYTES; MEN; SENSITIVITY AB Recent studies have demonstrated an important physiologic link between bone and fat. Bone and fat cells arise from the same mesenchymal precursor cell within bone marrow, capable of differentiation into adipocytes or osteoblasts. Increased BMI appears to protect against osteoporosis. However, recent studies have suggested detrimental effects of visceral fat on bone health. Increased visceral fat may also be associated with decreased growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels which are important for maintenance of bone homeostasis. The purpose of our study was to assess the relationship between vertebral bone marrow fat and trabecular bone mineral density (BMD), abdominal fat depots, GH and IGF-1 in premenopausal women with obesity. We studied 47 premenopausal women of various BMI (range: 18-41 kg/m(2), mean 30 +/- 7 kg/m(2)) who underwent vertebral bone marrow fat measurement with proton magnetic resonance spectroscopy (1H-MRS), body composition, and trabecular BMD measurement with computed tomography (CT), and GH and IGF-1 levels. Women with high visceral fat had higher bone marrow fat than women with low visceral fat. There was a positive correlation between bone marrow fat and visceral fat, independent of BMD. There was an inverse association between vertebral bone marrow fat and trabecular BMD. Vertebral bone marrow fat was also inversely associated with IGF-1, independent of visceral fat. Our study showed that vertebral bone marrow fat is positively associated with visceral fat and inversely associated with IGF-1 and BMD. This suggests that the detrimental effect of visceral fat on bone health may be mediated in part by IGF-1 as an important regulator of the fat and bone lineage. C1 [Bredella, Miriam A.; Torriani, Martin; Ghomi, Reza Hosseini; Thomas, Bijoy J.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Brick, Danielle J.; Gerweck, Anu V.; Klibanski, Anne; Miller, Karen K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Rosen, Clifford J.] Maine Med Ctr, Res Inst, Scarborough, ME USA. RP Bredella, MA (reprint author), Massachusetts Gen Hosp, Dept Radiol, 32 Fruit St, Boston, MA 02114 USA. EM mbredella@partners.org OI Hosseini Ghomi, Reza/0000-0003-4369-8237 FU National Institutes of Health [RO1 HL-077674, UL1 RR025758, K23 RR-23090] FX This work was supported in part by National Institutes of Health Grants RO1 HL-077674, UL1 RR025758, and K23 RR-23090. NR 31 TC 98 Z9 102 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD JAN PY 2011 VL 19 IS 1 BP 49 EP 53 DI 10.1038/oby.2010.106 PG 5 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 698ZL UT WOS:000285633600010 PM 20467419 ER PT J AU Chabner, BA AF Chabner, Bruce A. TI The Oncologist Chinese Edition: A Global Mission, A Unifying Bond SO ONCOLOGIST LA English DT Editorial Material C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Cambridge, MA 02138 USA. RP Chabner, BA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Cambridge, MA 02138 USA. RI Inov Farmaceutica, Inct/K-2313-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2011 VL 16 IS 6 BP I EP I DI 10.1634/theoncologist.2011-0153 PG 1 WC Oncology SC Oncology GA 781JZ UT WOS:000291928900001 PM 21697268 ER PT J AU Baselga, J AF Baselga, Jose TI Targeting the Phosphoinositide-3 (PI3) Kinase Pathway in Breast Cancer SO ONCOLOGIST LA English DT Article ID EVEROLIMUS; RESISTANCE; PIK3CA AB The phosphoinositide-3 kinase (PI3K) pathway has been identified as an important target in breast cancer research for a number of years, but is new to most clinicians responsible for the daily challenges of breast cancer management. In fact, the PI3K pathway is probably one of the most important pathways in cancer metabolism and growth. Mutations in the PI3K pathway are frequent in breast cancer, causing resistance to human epidermal growth factor receptor 2-targeted agents and, possibly, to hormonal agents as well. Available agents that affect the PI3K pathway include monoclonal antibodies and tyrosine kinase inhibitors, as well as PI3K inhibitors, Akt inhibitors, rapamycin analogs, and mammalian target of rapamycin (mTOR) catalytic inhibitors. Multiple PI3K inhibitors are currently under development, including pure PI3K inhibitors, compounds that block both PI3K and mTOR (dual inhibitors), pure catalytic mTOR inhibitors, and inhibitors that block Akt. It is likely that these agents will have to be given in combination with other signal inhibitors because anti-mTOR agents and PI3K inhibitors may result in the activation of compensatory feedback loops that would in turn result in decreased efficacy. This article reviews current data related to the PI3K pathway, its role in breast cancer, the frequency with which PI3K is aberrant in breast cancer, and the potential clinical implications of using agents that target the PI3K pathway. The Oncologist 2011; 16(suppl 1): 12-19 C1 Massachusetts Gen Hosp, Massachusetts Gen Hosp Canc Ctr, Boston, MA 02114 USA. RP Baselga, J (reprint author), Massachusetts Gen Hosp, Massachusetts Gen Hosp Canc Ctr, Boston, MA 02114 USA. EM jbaselga@partners.org RI Inov Farmaceutica, Inct/K-2313-2013 NR 19 TC 108 Z9 113 U1 8 U2 34 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PY 2011 VL 16 SU 1 BP 12 EP 19 DI 10.1634/theoncologist.2011-S1-12 PG 8 WC Oncology SC Oncology GA 712JT UT WOS:000286663700003 PM 21278436 ER PT J AU Miksad, RA Lai, KC Dodson, TB Woo, SB Treister, NS Akinyemi, O Bihrle, M Maytal, G August, M Gazelle, GS Swan, JS AF Miksad, Rebecca Anne Lai, Kuan-Chi Dodson, Thomas Benton Woo, Sook-Bin Treister, Nathaniel Simon Akinyemi, Omosalewa Bihrle, Marian Maytal, Guy August, Meredith Gazelle, G. Scott Swan, J. Shannon TI Quality of Life Implications of Bisphosphonate-Associated Osteonecrosis of the Jaw SO ONCOLOGIST LA English DT Article DE Quality of life; Osteonecrosis; Bisphosphonates; Zoledronic acid; Pamidronate; Utility ID BREAST-CANCER PATIENTS; MULTIPLE-MYELOMA PATIENTS; ORAL-HEALTH STATES; ZOLEDRONIC ACID; BONE METASTASES; RISK-FACTORS; PROSTATE-CANCER; COST-EFFECTIVENESS; INTRAVENOUS BISPHOSPHONATES; PREMENOPAUSAL WOMEN AB Purpose. Potentially debilitating, osteonecrosis of the jaw (ONJ) is an emerging complication of bisphosphonates. However, its effect on quality of life (QoL) is unknown. We determined the ONJ-related QoL decline in a cancer patient cohort. Patients and Methods. Thirty-four cancer patients with bisphosphonate-associated ONJ completed a telephone survey (October 2007 through May 2008). The Oral Health Impact Profile 14 (OHIP) retrospectively assessed participant oral health-related QoL before and after ONJ. Standardized ONJ descriptions were developed in a multidisciplinary, iterative process and were evaluated with three frequently used preference-based QoL measurement methods on a 0 (death) to 1 (perfect health) scale: Visual Analogue Scale (VAS), Time Trade-Off (TTO), and EQ-5D. Results. ONJ significantly (p < .001) increased OHIP scores (worse QoL) for additive (3.56-16.53) and weighted (7.0-17.5) methods. Seven individual OHIP items significantly increased (Bonferroni correction p < .0035): pain, eating discomfort, self-consciousness, unsatisfactory diet, interrupted meals, irritability, and decreased life satisfaction. Mean preference-based QoL values significantly decreased (p < .001) with worsening ONJ stage (VAS, TTO, and EQ-5D): no ONJ (0.76, 0.86, 0.82), ONJ stage 1 (0.69, 0.82, 0.78), ONJ stage 2 (0.51, 0.67, 0.55), and ONJ stage 3 (0.37, 0.61, 0.32). As ONJ worsened, EQ-5D domain scores significantly increased (p < .001). Pain/discomfort and anxiety/depression contributed most to declining QoL. Conclusions. ONJ significantly affects QoL, a detriment that increases with worsening ONJ. QoL impairments for ONJ stages 2 and 3 are similar to other treatment side effects that influence decision-making. Bisphosphonate-associated ONJ QoL is an important consideration for patients, clinicians, and policy makers. The Oncologist 2011; 16: 121-132 C1 [Miksad, Rebecca Anne; Lai, Kuan-Chi; Bihrle, Marian] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Miksad, Rebecca Anne; Gazelle, G. Scott; Swan, J. Shannon] Harvard Univ, Sch Med, Boston, MA USA. [Miksad, Rebecca Anne; Lai, Kuan-Chi; Akinyemi, Omosalewa; Bihrle, Marian; Gazelle, G. Scott; Swan, J. Shannon] Inst Technol Assessment, Boston, MA USA. [Miksad, Rebecca Anne; Lai, Kuan-Chi; Dodson, Thomas Benton; Akinyemi, Omosalewa; Bihrle, Marian; Maytal, Guy; August, Meredith; Gazelle, G. Scott; Swan, J. Shannon] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Dodson, Thomas Benton; Woo, Sook-Bin; Treister, Nathaniel Simon; Maytal, Guy; August, Meredith] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Woo, Sook-Bin; Treister, Nathaniel Simon] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Miksad, RA (reprint author), Beth Israel Deaconess Med Ctr, 330 Brookline Ave,Shapiro 9, Boston, MA 02215 USA. EM rmiksad@bidmc.harvard.edu OI Miksad, Rebecca/0000-0003-3194-5122 FU American Society; Dana-Farber Harvard Cancer Center; Program in Cancer Outcomes Research Training [5R25CA 092203-04]; Department of Medicine, Beth Israel Deaconess Medical Center; Beth Israel Deaconess Medical Center-Harvard/MIT Health Sciences and Technology; Pfizer Inc.; Merck Co. FX R. Miksad was supported by the following grants during the conduct of this research: American Society of Clinical Oncology Young Investigator Award, Dana-Farber Harvard Cancer Center Timely Opportunity Award, the Program in Cancer Outcomes Research Training (5R25CA 092203-04) and the Department of Medicine, Beth Israel Deaconess Medical Center, and the Clinical Investigator Training Program: Beth Israel Deaconess Medical Center-Harvard/MIT Health Sciences and Technology, in collaboration with Pfizer Inc. and Merck & Co. Funding sources had no role in study design, data collection, data analysis, data interpretation, writing of this manuscript, or the decision to submit for publication. NR 119 TC 30 Z9 30 U1 1 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD JAN PY 2011 VL 16 IS 1 BP 121 EP 132 DI 10.1634/theoncologist.2010-0183 PG 12 WC Oncology SC Oncology GA 710JB UT WOS:000286506600014 PM 21212433 ER PT J AU Raut, CP Kulke, MH AF Raut, Chandrajit P. Kulke, Matthew H. TI Targeted Therapy in Advanced Well-Differentiated Neuroendocrine Tumors SO ONCOLOGIST LA English DT Article DE Neuroendocrine tumors; Targeted therapy; VEGF; mTOR; Temozolomide; Everolimus; Temsirolimus; Sunitinib; Bevacizumab; Sorafenib; Radionuclide ID ENDOTHELIAL GROWTH-FACTOR; RECEPTOR RADIONUCLIDE THERAPY; ISLET-CELL-CARCINOMA; PHASE-II TRIAL; ENDOCRINE GASTROENTEROPANCREATIC TUMORS; SOMATOSTATIN ANALOG; PROGNOSTIC-FACTORS; ALPHA-INTERFERON; HUMAN ENDOSTATIN; OCTREOTIDE LAR AB Treatments for advanced neuroendocrine tumors were, until recently, rather limited. Salvage surgery and liver-directed therapy both have relatively limited impact, and systemic cytotoxic chemotherapy has minimal efficacy. In the absence of other effective treatments, somatostatin analogs have been used for years to control disease and neuroendocrine symptoms, without cytotoxic intent. Advances in targeted therapy for neuroendocrine tumors have opened several potentially new treatment paradigms in the management of these otherwise relatively drug-resistant neoplasms. Promising results have emerged from studies evaluating radiolabeled somatostatin analogs and inhibitors of the vascular endothelial growth factor and mammalian target of rapamycin pathways. This article reviews several of the more encouraging developments in this field. The Oncologist 2011; 16: 286-295 C1 [Raut, Chandrajit P.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Surg, Boston, MA 02115 USA. [Kulke, Matthew H.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Raut, CP (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM craut@partners.org NR 70 TC 11 Z9 11 U1 0 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PY 2011 VL 16 IS 3 BP 286 EP 295 DI 10.1634/theoncologist.2010-0313 PG 10 WC Oncology SC Oncology GA 737WU UT WOS:000288601800004 PM 21346024 ER PT J AU Nucera, C Nehs, MA Nagarkatti, SS Sadow, PM Mekel, M Fischer, AH Lin, PS Bollag, GE Lawler, J Hodin, RA Parangi, S AF Nucera, Carmelo Nehs, Matthew A. Nagarkatti, Sushruta S. Sadow, Peter M. Mekel, Michal Fischer, Andrew H. Lin, Paul S. Bollag, Gideon E. Lawler, Jack Hodin, Richard A. Parangi, Sareh TI Targeting BRAF(V600E) with PLX4720 Displays Potent Antimigratory and Anti-invasive Activity in Preclinical Models of Human Thyroid Cancer SO ONCOLOGIST LA English DT Article DE BRAF(V600E) inhibitor; Anaplastic thyroid cancer; Metastasis; Invasion; Orthotopic; Primary human normal thyroid follicular cells; Mutation ID B-RAF; KINASE INHIBITORS; GENE-EXPRESSION; CARCINOMA CELLS; BRAF MUTATIONS; GROWTH-FACTOR; ACTIVATION; RET/PTC; THROMBOSPONDIN-1; PATHWAY AB Purpose. B-Raf(V600E) may play a role in the progression from papillary thyroid cancer to anaplastic thyroid cancer (ATC). We tested the effects of a highly selective B-Raf(V600E) inhibitor, PLX4720, on proliferation, migration, and invasion both in human thyroid cancer cell lines (8505c(B-RafV600E) and TPC-1(RET/PTC-1 and wild-type B-Raf)) and in primary human normal thyroid (NT) follicular cells engineered with or without B-Raf(V600E). Experimental Design. Large-scale genotyping analysis by mass spectrometry was performed in order to analyze > 900 gene mutations. Cell proliferation and migration/invasion were performed upon PLX4720 treatment in 8505c, TPC-1, and NT cells. Orthotopic implantation of either 8505c or TPC-1 cells into the thyroid of severe combined immunodeficient mice was performed. Gene validations were performed by quantitative polymerase chain reaction and immunohistochemistry. Results. We found that PLX4720 reduced in vitro cell proliferation and migration and invasion of 8505c cells, causing early downregulation of genes involved in tumor progression. PLX4720-treated NT cells overexpressing B-Raf(V600E) (heterozygous wild-type B-Raf/B-Raf(V600E)) showed significantly lower cell proliferation, migration, and invasion. PLX4720 treatment did not block cell invasion in TPC-1 cells with wild-type B-Raf, which showed very low and delayed in vivo tumor growth. In vivo, PLX4720 treatment of 8505c orthotopic thyroid tumors inhibited tumor aggressiveness and significantly upregulated the thyroid differentiation markers thyroid transcription factor 1 and paired box gene 8. Conclusions. Here, we have shown that PLX4720preferentially inhibits migration and invasion of B-Raf(V600E) thyroid cancer cells and tumor aggressiveness. Normal thyroid cells were generated to be heterozygous for wild-type B-Raf/B-Raf(V600E), mimicking the condition found in most human thyroid cancers. PLX4720 was effective in reducing cell proliferation, migration, and invasion in this heterozygous model. PLX4720 therapy should be tested and considered for a phase I study for the treatment of patients with B-Raf(V600E) ATC. The Oncologist 2011; 16: 296-309 C1 [Nucera, Carmelo; Nehs, Matthew A.; Nagarkatti, Sushruta S.; Mekel, Michal; Hodin, Richard A.; Parangi, Sareh] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Unit Endocrine Surg,Thyroid Canc Res Lab, Boston, MA 02115 USA. [Sadow, Peter M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. [Nucera, Carmelo; Fischer, Andrew H.] Univ Massachusetts, Dept Pathol, Worcester, MA 01605 USA. [Lin, Paul S.; Bollag, Gideon E.] Plexxikon Inc, Berkeley, CA USA. [Lawler, Jack] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Canc Biol & Angiogenesis,Dept Pathol, Boston, MA 02115 USA. RP Parangi, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Unit Endocrine Surg,Thyroid Canc Res Lab, Wang ACC 460,15 Parkman St, Boston, MA 02115 USA. EM sparangi@partners.org OI Fischer, Andrew/0000-0002-5944-4621 FU Gemelli Medical School (Catholic University, Rome); Italian Ministry of Education (MIUR) (Italy); NIH [5T32 DK007754-10, DK050623, DK047186, CA130895]; ATA; Polsky Fund FX Carmelo Nucera was funded through A. Gemelli Medical School (Catholic University, Rome) grants and Italian Ministry of Education (MIUR) (Italy) grants. Richard A. Hodin was funded by NIH T32 # 5T32 DK007754-10. Other funding included research funds to Sareh Parangi, Jack Lawler, and Richard A. Hodin from NIH DK050623, DK047186, CA130895, CA130895, ATA, and the Polsky Fund. We thank Dr. Yutaka Kawami (Keio University, Tokyo, Japan) for providing HIV-U6 vectors, Dr. Shou-Ching Shih for help with the RT-PCR, and Mark Duquette for technical assistance, as well as the Center for Cancer Genome Discovery (Dana Farber Cancer Institute) and the Center for Systems Biology Mouse Imaging Program (Massachusetts General Hospital). We thank Drs. Efisio Puxeddu and Sonia Moretti (University of Perugia) for RET/PTC-1 analysis of TPC-1 cells. NR 41 TC 46 Z9 47 U1 0 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 PY 2011 VL 16 IS 3 BP 296 EP 309 DI 10.1634/theoncologist.2010-0317 PG 14 WC Oncology SC Oncology GA 737WU UT WOS:000288601800005 PM 21355020 ER PT J AU Kozyreva, ON Chi, D Clark, JW Wang, HJ Theall, KP Ryan, DP Zhu, AX AF Kozyreva, Olga N. Chi, Dorcas Clark, Jeffrey W. Wang, Hejing Theall, Kathy P. Ryan, David P. Zhu, Andrew X. TI A Multicenter Retrospective Study on Clinical Characteristics, Treatment Patterns, and Outcome in Elderly Patients with Hepatocellular Carcinoma SO ONCOLOGIST LA English DT Article DE Hepatocellular carcinoma; Epidemiology; Elderly; Treatment pattern; Survival ID UNITED-STATES; PATIENTS OLDER; RISK-FACTORS; CLINICOPATHOLOGICAL FEATURES; PROGNOSTIC INDICATORS; HEPATIC RESECTION; SURVIVAL ANALYSIS; LIVER-DISEASE; CANCER; MANAGEMENT AB Background. There is a paucity of information on the clinical presentation and outcome of elderly hepatocellular carcinoma (HCC) patients. We performed a multicenter retrospective comparative study to assess the impact of age on potential differences in clinical characteristics, treatment patterns, and outcome in HCC patients. Methods. We retrospectively analyzed HCC patients treated at two U. S. tertiary institutions from 1998 to 2008. Demographics, tumor parameters, etiology and severity of cirrhosis, treatment, and survival from diagnosis were collected and analyzed. After exclusion of transplanted patients, survival analyses were performed using the Kaplan-Meier method with log-rank tests and Cox proportional hazards models. Results. Three hundred thirty-five HCC patients were divided into two groups: "elderly" (95 patients, age >= 70 years) and "younger" (240 patients, aged < 70 years). The male/female (M/F) ratio was 5.8:1 and 1.7:1 in the younger and elderly groups, respectively (p < .0001). Hepatitis C virus (HCV) infection rate was 48.3% in younger and 21.1% in elderly patients (p <. 0001); Child class B and C cirrhosis accounted for 35.8% in younger and 25.3% in elderly patients (p = .063). Compared with younger patients, the elderly received transplant less frequently (19.6% versus 5.3%, p = .0002) and were more likely to receive supportive care only (22.9% versus 36.8%, p = .01). No significant differences between the two age groups were seen in tumor parameters or other treatments received. Overall (p = .47) and HCC-specific survival rates (p = .38) were similar in both age groups. Conclusions. Characteristics that distinguish elderly from younger HCC patients include lower M/F ratio, worse performance status, lower rate of HCV infection, and less advanced underlying cirrhosis. Elderly patients were less likely to have a liver transplant and more likely to receive supportive care only. However, overall and HCC-specific survival were similar between the two groups. The Oncologist 2011; 16: 310-318 C1 [Clark, Jeffrey W.; Ryan, David P.; Zhu, Andrew X.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Kozyreva, Olga N.; Chi, Dorcas; Theall, Kathy P.] Tufts Med Sch, Tufts Med Ctr Canc Ctr, Boston, MA USA. [Wang, Hejing] Univ Calif Los Angeles, Los Angeles, CA USA. RP Zhu, AX (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,LH POB 232, Boston, MA 02114 USA. EM azhu@partners.org NR 33 TC 20 Z9 21 U1 0 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2011 VL 16 IS 3 BP 310 EP 318 DI 10.1634/theoncologist.2010-0223 PG 9 WC Oncology SC Oncology GA 737WU UT WOS:000288601800006 PM 21349948 ER PT J AU Mak, RH Digumarthy, SR Muzikansky, A Engelman, JA Shepard, JAO Choi, NC Sequist, LV AF Mak, Raymond H. Digumarthy, Subba R. Muzikansky, Alona Engelman, Jeffrey A. Shepard, Jo-Anne O. Choi, Noah C. Sequist, Lecia V. TI Role of F-18-Fluorodeoxyglucose Positron Emission Tomography in Predicting Epidermal Growth Factor Receptor Mutations in Non-Small Cell Lung Cancer SO ONCOLOGIST LA English DT Article DE Positron emission tomography; Epidermal growth factor receptor genes; Mutation; Non-small cell lung carcinoma ID PULMONARY LYMPHANGITIC CARCINOMATOSIS; STANDARDIZED UPTAKE VALUES; EGFR MUTATIONS; NORMAL-TISSUES; FDG-PET; GEFITINIB; FLUORODEOXYGLUCOSE; ADENOCARCINOMA; FEATURES; THERAPY AB Purpose. To compare F-18-fluorodeoxyglucose positron emission tomography (FDG-PET) and computed tomography (CT) imaging characteristics in non-small cell lung cancer (NSCLC) with or without epidermal growth factor receptor (EGFR) mutations. Methods. We retrospectively identified NSCLC patients who underwent EGFR mutation testing and pretreatment FDG-PET and CT scans. The maximum standard uptake value (SUVmax) of the primary tumor and any metastases was measured and normalized to the SUV of blood in the pulmonary artery. We compared normalized SUVmax values between EGFR-mutant and wild-type patients and modeled radiographic and clinical predictors of EGFR mutation status. Receiver operator characteristic (ROC) curves were used to identify potential SUV cutoffs predictive of genotype. Results. We included 100 patients (24 EGFR-mutant and 76 wild-type). There was a trend for higher normalized SUVmax in the primary tumors among patients with EGFR-wild-type versus mutant (median, 3.4; range, 0.6-12.8; versus median, 2.9; range, 0.4-5.0; p = .09). Normalized SUVmax of nodal and distant metastases, and CT characteristics were not associated with genotype. On multivariate analysis, low normalized SUVmax of the primary tumor was predictive for EGFR mutation (odds ratio, 0.72; 95% confidence interval, 0.53-0.98; p = .034). ROC curve analyses yielded an area under the curve of 0.62, and identified a potential cutoff of >= 5.0 to distinguish wild-type from mutant tumors. Conclusions. In this retrospective study, high FDG avidity (normalized SUVmax >= 5) correlated with EGFR-wild-type genotype. Although genotyping remains the gold standard, further work to validate FDG-PET as a surrogate for tumor genotype may provide useful information in patients without available tumor tissue. The Oncologist 2011; 16: 319-326 C1 [Mak, Raymond H.] Harvard Radiat Oncol Program, Boston, MA USA. [Digumarthy, Subba R.; Shepard, Jo-Anne O.] Massachusetts Gen Hosp, Ctr Canc, Dept Radiol, Boston, MA USA. [Muzikansky, Alona] Massachusetts Gen Hosp, Ctr Canc, Ctr Biostat, Boston, MA USA. [Engelman, Jeffrey A.; Sequist, Lecia V.] Massachusetts Gen Hosp, Ctr Canc, Ctr Thorac Cancers, Boston, MA USA. [Choi, Noah C.] Massachusetts Gen Hosp, Ctr Canc, Dept Radiat Oncol, Boston, MA USA. [Digumarthy, Subba R.; Engelman, Jeffrey A.; Shepard, Jo-Anne O.; Choi, Noah C.; Sequist, Lecia V.] Harvard Univ, Sch Med, Boston, MA USA. RP Sequist, LV (reprint author), 55 Fruit St,POB 212, Boston, MA 02144 USA. EM LVSequist@partners.org FU NCI NIH HHS [P20 CA090578, P20 CA090578-03] NR 28 TC 25 Z9 27 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 PY 2011 VL 16 IS 3 BP 319 EP 326 DI 10.1634/theoncologist.2010-0300 PG 8 WC Oncology SC Oncology GA 737WU UT WOS:000288601800007 PM 21339258 ER PT J AU Hassett, MJ Rao, SR Brozovic, S Stahl, JE Schwartz, JH Maloney, B Jacobson, JO AF Hassett, Michael J. Rao, Sowmya R. Brozovic, Suzana Stahl, James E. Schwartz, Joel H. Maloney, Betty Jacobson, Joseph O. TI Chemotherapy-Related Hospitalization Among Community Cancer Center Patients SO ONCOLOGIST LA English DT Article DE Chemotherapy; Adverse events; Cancer; Quality improvement ID ADVERSE DRUG-REACTIONS; CLINICAL-TRIALS; ONCOLOGY PRACTICE; BREAST-CANCER; PARTICIPATION; QUALITY; ENROLLMENT; EVENTS; WOMEN; RACE AB Purpose. To describe the frequency, nature, trends, predictors, and outcomes of chemotherapy-related hospitalizations (CRHs) among a nonselected population of cancer patients treated at a community cancer center, and to explore the feasibility of implementing continuous quality improvement methodologies in routine oncology practice. Methods. We conducted a prospective cohort study of consecutive adult cancer patients who received chemo-therapy at a community cancer center January 2003 to December 2006. Demographic, comorbidity, diagnosis, treatment, and laboratory data were collected via medical record abstraction. Hospitalizations were classified as chemotherapy related or unrelated by a multidisciplinary panel. Patients who experienced CRHs were compared with those who did not. Using a randomly sampled subset of cases and controls, we built a logistic regression model to identify independent predictors of CRH. Results. Of 2,068 chemotherapy recipients, 179 (8.7%) experienced 262 CRHs. Most hospitalizations were not chemotherapy related (73.7%). The mean monthly rate of CRH was 1.5%, the median length of stay was 5 days, the most common type of CRH was gastrointestinal (46.1%) followed by infectious (31.4%), and 0.9% of chemotherapy recipients had a fatal CRH. Significant predictors of CRH included having a comorbidity score of 3-4 versus 0 and having a higher creatinine level. Conclusions. Although the vast majority of chemotherapy recipients did not experience a CRH, these events were, unfortunately, not without serious consequences. Care should be taken when offering chemotherapy to patients with multiple comorbid conditions. Systematic efforts to monitor toxicity can lead directly to improvements in quality of care. The Oncologist 2011;16:378-387 C1 [Hassett, Michael J.] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02215 USA. [Rao, Sowmya R.; Stahl, James E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Brozovic, Suzana] N Shore Med Ctr, Salem, MA USA. [Schwartz, Joel H.; Maloney, Betty; Jacobson, Joseph O.] Mass General N Shore Canc Ctr, Peabody, MA USA. RP Hassett, MJ (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, 450 Brookline Ave, Boston, MA 02215 USA. EM michael_hassett@dfci.harvard.edu FU Norman H. Reed Charitable Trust; American Society of Clinical Oncology Career Development FX The Norman H. Reed Charitable Trust provided financial assistance for the study. The American Society of Clinical Oncology Career Development Award provided salary support to Dr. Hassett. The sponsors had no direct influence on the design of the study, analysis of the data, interpretation of the results, or writing of the manuscript. NR 29 TC 15 Z9 17 U1 1 U2 2 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2011 VL 16 IS 3 BP 378 EP 387 DI 10.1634/theoncologist.2010-0354 PG 10 WC Oncology SC Oncology GA 737WU UT WOS:000288601800014 PM 21349949 ER PT J AU Kollmannsberger, C Bjarnason, G Burnett, P Creel, P Davis, M Dawson, N Feldman, D George, S Hershman, J Lechner, T Potter, A Raymond, E Treister, N Wood, L Wu, SH Bukowski, R AF Kollmannsberger, Christian Bjarnason, Georg Burnett, Patrick Creel, Patricia Davis, Mellar Dawson, Nancy Feldman, Darren George, Suzanne Hershman, Jerome Lechner, Thomas Potter, Amy Raymond, Eric Treister, Nathaniel Wood, Laura Wu, Shenhong Bukowski, Ronald TI Sunitinib in Metastatic Renal Cell Carcinoma: Recommendations for Management of Noncardiovascular Toxicities SO ONCOLOGIST LA English DT Article DE Sunitinib; Toxicity; Side effect management; Treatment optimization ID ENDOTHELIAL GROWTH-FACTOR; EVIDENCE-BASED INTERVENTIONS; KINASE INHIBITORS; INTERFERON-ALPHA; TARGETED THERAPY; PUTTING EVIDENCE; FACTOR RECEPTOR; C-KIT; HYPOTHYROIDISM; CANCER AB The multitargeted tyrosine-kinase inhibitor sunitinib has emerged as one of the standards of care for good-and intermediate-risk metastatic renal cell carcinoma. Although generally associated with acceptable toxicity, sunitinib exhibits a novel and distinct toxicity profile that requires monitoring and management. Fatigue, diarrhea, anorexia, oral changes, hand-foot syndrome and other skin toxicity, thyroid dysfunction, myelotoxicity, and hypertension seem to be the most common and clinically relevant toxicities of sunitinib. Drug dosing and treatment duration are correlated with response to treatment and survival. Treatment recommendations for hypertension have been published but, currently, no standard guidelines exist for the management of noncardiovascular side effects. To discuss the optimal management of noncardiovascular side effects, an international, interdisciplinary panel of experts gathered in November 2009. Existing literature on incidence, severity, and underlying mechanisms of side effects as well as on potential treatment options were carefully reviewed and discussed. On the basis of these proceedings and the thorough review of the existing literature, recommendations were made for the monitoring, prevention, and treatment of the most common noncardiovascular side effects and are summarized in this review. The proactive assessment and consistent and timely management of sunitinib-related side effects are critical to ensure optimal treatment benefit by allowing appropriate drug dosing and prolonged treatment periods. The Oncologist 2011;16:543-553 C1 [Kollmannsberger, Christian] Univ British Columbia, Div Med Oncol, British Columbia Canc Agcy, Vancouver Canc Ctr, Vancouver, BC V5Z 4E6, Canada. [Bjarnason, Georg] Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. [Burnett, Patrick] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Creel, Patricia] Duke Univ, Med Ctr, Durham, NC USA. [Davis, Mellar; Wood, Laura; Bukowski, Ronald] Cleveland Clin, Taussig Canc Ctr, Cleveland, OH 44106 USA. [Dawson, Nancy] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. [Feldman, Darren] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [George, Suzanne; Potter, Amy] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hershman, Jerome] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Lechner, Thomas] Pfizer Oncol, New York, NY USA. [Raymond, Eric] Serv Interhosp Cancerol Beaujon Bichat, Clichy, France. [Treister, Nathaniel] Brigham & Womens Hosp, Boston, MA 02115 USA. [Wu, Shenhong] SUNY Stony Brook, Med Ctr, Stony Brook, NY 11794 USA. RP Kollmannsberger, C (reprint author), Univ British Columbia, Div Med Oncol, British Columbia Canc Agcy, Vancouver Canc Ctr, 600 W 10th Ave, Vancouver, BC V5Z 4E6, Canada. EM ckollmannsberger@bccancer.bc.ca OI Bjarnason, Georg Arnold/0000-0001-6903-5357; Feldman, Darren/0000-0003-2424-4635 FU Pfizer Inc.; Pfizer; Novartis; Bayer FX The meeting in Boston on November 19, 2009, at which the data presentation, interpretation, and discussion took place, was supported by Pfizer Inc.; Christian Kollmannsberger: Consultant/advisory role: Pfizer, Novartis, GlaxoSmithKline (advisory boards); Honoraria: Pfizer, Novartis (presentations); Georg Bjarnason: Consultant/advisory role: Pfizer; Honoraria: Pfizer; Research funding/contracted research: Pfizer; Patrick Burnett: Consultant/advisory role: Pfizer; Honoraria: Pfizer; Patricia Creel: Honoraria: Pfizer (advisory board); Mellar Davis: None; Nancy Dawson: Consultant/advisory role: Pfizer (advisory board for the purpose of this manuscript); Honoraria: Pfizer (speakers' bureau); Darren Feldman: Consultant/advisory role: Pfizer (for the meeting on optimizing management of sunitinib-related toxicities); Suzanne George: Consultant/advisory role: Pfizer, Novartis; Research funding/contracted research: Pfizer, Novartis, Bayer; Jerome Hershman: None; Thomas Lechner: Employment/leadership position: Pfizer (employee at the time this manuscript was developed); Amy Potter: Consultant/advisory role: Pfizer (honoraria from Sutent advisory board on one occasion); Eric Raymond: Consultant/advisory role: Pfizer; Research funding/contracted research: Pfizer; Nathaniel Treister: Consultant/advisory role: Pfizer; Laura Wood: Consultant/advisory role: Bayer Pharmaceutical (advisory board); Honoraria: Onyx Pharma, Genentech, Novartis, Pfizer (speakers' bureaus); Shenhong Wu: Consultant/advisory role: Pfizer; Honoraria: Pfizer, Novartis, Onyx; Ronald Bukowski: Consultant/advisory role: Pfizer, GlaxoSmithKline, Novartis, Genentech, Bayer; Honoraria: Pfizer, Novartis, Genentech, Roche. NR 54 TC 35 Z9 38 U1 0 U2 3 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2011 VL 16 IS 5 BP 543 EP 553 DI 10.1634/theoncologist.2010-0263 PG 11 WC Oncology SC Oncology GA 764VG UT WOS:000290661900003 PM 21490127 ER PT J AU Wong, YN Ottesen, RA Hughes, ME Niland, JC Theriault, R Edge, SB Blayney, D Weeks, JC AF Wong, Yu-Ning Ottesen, Rebecca A. Hughes, Melissa E. Niland, Joyce C. Theriault, Richard Edge, Stephen B. Blayney, Douglas Weeks, Jane C. TI Continued Use of Trastuzumab Beyond Disease Progression in the National Comprehensive Cancer Network: Should We Practice Ahead of the Evidence? SO ONCOLOGIST LA English DT Article ID METASTATIC BREAST-CANCER; CHEMOTHERAPY; OUTCOMES; THERAPY; HER2 AB Background. The role of continued trastuzumab after progression in women with human epidermal growth factor receptor (HER)-2(+) metastatic breast cancer is controversial. Controlled clinical trials that establish a benefit from continued trastuzumab have been difficult to complete. Methods. In the National Comprehensive Cancer Center Network (NCCN) Breast Cancer Outcomes Database, we identified women treated with trastuzumab for metastatic or relapsed HER-2(+) breast cancer at eight NCCN centers who subsequently progressed. Patients were eligible for this analysis if they initiated treatment at an NCCN institution between July 1997 and December 2004, received trastuzumab-containing treatment, and progressed while on therapy. We calculated the proportion of patients who received trastuzumab after progression, and in a multivariate analysis assessed the association of patient and provider characteristics with continued trastuzumab therapy. Results. Our final cohort consisted of 218 women who experienced disease progression while on trastuzumab-containing therapy. Of these, 168 (77%) continued trastuzumab. Of these, 36 patients (17%) received therapy as part of a clinical trial. The only factors significantly associated with continuation of trastuzumab beyond progression were the presence of bone metastases and more recent year of development of progressive disease. Conclusions. Prior to the availability of any high-quality evidence supporting this practice, over three quarters of patients treated with trastuzumab for HER-2(+) metastatic breast cancer at eight NCCN centers continued therapy beyond progression. Further work is needed to understand how physicians adopt new treatments when there is ambiguity surrounding their benefit. The Oncologist 2011;16:559-565 C1 [Wong, Yu-Ning] Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA. [Ottesen, Rebecca A.; Niland, Joyce C.] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Hughes, Melissa E.; Weeks, Jane C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Theriault, Richard] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Edge, Stephen B.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Blayney, Douglas] Stanford Univ, Ctr Comprehens Canc, Palo Alto, CA 94304 USA. RP Wong, YN (reprint author), Fox Chase Canc Ctr, Dept Med Oncol, 333 Cottman Ave, Philadelphia, PA 19111 USA. EM Yu-Ning.wong@fccc.edu FU National Cancer Institute [P50 CA089393, P30 CA006927]; Aetna; Blue Cross and Blue Shield of Michigan FX This work was supported in part by grant P50 CA089393 from the National Cancer Institute to Dana-Farber Cancer Institute. Dr. Wong was supported by in part by P30 CA006927.; Yu-Ning Wong: Honoraria: Independence Blue Cross Blue Shield; Research funding/contracted research: Aetna; Rebecca A. Ottesen: None; Melissa E. Hughes: None; Joyce C. Niland: None; Richard Theriault: None; Stephen B. Edge: None; Douglas Blayney: Research funding/contracted research: Blue Cross and Blue Shield of Michigan; Jane C. Weeks: None. NR 24 TC 6 Z9 6 U1 0 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2011 VL 16 IS 5 BP 559 EP 565 DI 10.1634/theoncologist.2010-0360 PG 7 WC Oncology SC Oncology GA 764VG UT WOS:000290661900005 PM 21450786 ER PT J AU McHenry, CR Phitayakorn, R AF McHenry, Christopher R. Phitayakorn, Roy TI Follicular Adenoma and Carcinoma of the Thyroid Gland SO ONCOLOGIST LA English DT Article DE Follicular thyroid carcinoma; Follicular adenoma; Follicular neoplasm ID HURTHLE CELL-CARCINOMA; PROGNOSTIC-FACTORS; BONE METASTASES; MESSENGER-RNA; CANCER; DIAGNOSIS; MUTATIONS; MANAGEMENT; NEOPLASMS; NODULES AB Follicular neoplasms of the thyroid gland include benign follicular adenoma and follicular carcinoma. Currently, a follicular carcinoma cannot be distinguished from a follicular adenoma based on cytologic, sonographic, or clinical features alone. The pathogenesis of follicular carcinoma may be related to iodine deficiency and various oncogene and/or microRNA activation. Advances in molecular testing for genetic mutations may soon allow for preoperative differentiation of follicular carcinoma from follicular adenoma. Until then, a patient with a follicular neoplasm should undergo a diagnostic thyroid lobectomy and isthmusectomy, which is definitive treatment for a benign follicular adenoma or a minimally invasive follicular cancer. Additional therapy is necessary for invasive follicular carcinoma including completion thyroidectomy, postoperative radioactive iodine ablation, whole body scanning, and thyrotropin suppressive doses of thyroid hormone. Less than 10% of patients with follicular carcinoma will have lymph node metastases, and a compartment-oriented neck dissection is reserved for patients with macroscopic disease. Regular follow-up includes history and physical examination, cervical ultrasound and serum TSH, and thyroglobulin and antithyroglobulin antibody levels. Other imaging studies are reserved for patients with an elevated serum thyroglobulin level and a negative cervical ultrasound. Systemic metastases most commonly involve the lung and bone and less commonly the brain, liver, and skin. Microscopic metastases are treated with high doses of radioactive iodine. Isolated macroscopic metastases can be resected with an improvement in survival. The overall ten-year survival for patients with minimally invasive follicular carcinoma is 98% compared with 80% in patients with invasive follicular carcinoma. The Oncologist 2011;16:585-593 C1 [McHenry, Christopher R.] Case Western Reserve Univ, Dept Surg, Metrohlth Med Ctr, Cleveland, OH 44109 USA. [Phitayakorn, Roy] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Div Gen & Gastrointestinal Surg, Boston, MA 02115 USA. RP McHenry, CR (reprint author), Case Western Reserve Univ, Dept Surg, Metrohlth Med Ctr, 2500 MetroHlth Dr,H-917, Cleveland, OH 44109 USA. EM cmchenry@metrohealth.org OI Phitayakorn, Roy/0000-0002-8327-1484 FU Novartis FX Section Editor Herbert Chen discloses research funding received from Novartis. NR 73 TC 24 Z9 29 U1 0 U2 9 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PY 2011 VL 16 IS 5 BP 585 EP 593 DI 10.1634/theoncologist.2010-0405 PG 9 WC Oncology SC Oncology GA 764VG UT WOS:000290661900008 PM 21482585 ER PT J AU Pozzi, S Raje, N AF Pozzi, Samantha Raje, Noopur TI The Role of Bisphosphonates in Multiple Myeloma: Mechanisms, Side Effects, and the Future SO ONCOLOGIST LA English DT Article DE Zoledronic acid; Pamidronate; Bisphosphonates; Myeloma ID DELTA-T-CELLS; PLACEBO-CONTROLLED TRIAL; CLINIC CONSENSUS STATEMENT; SUPPRESSED BONE TURNOVER; SURGEONS POSITION PAPER; FEMORAL-SHAFT FRACTURES; SKELETAL-RELATED EVENTS; TERM-FOLLOW-UP; ZOLEDRONIC ACID; MONOCLONAL GAMMOPATHY AB Zoledronic acid and pamidronate are two potent anti-catabolic nitrogen-containing bisphosphonates (BPs) used extensively in diseases with high bone turnover such as multiple myeloma (MM). In this review we focus on their biology and their current and future use in MM, and highlight some of the most common and emerging side effects. Although the primary target cells for BPs are osteoclasts, new insights suggest other cell types of the bone microenvironment as possible targets, including osteoblasts, endothelial cells, immune cells, and cancer cells. Here, we focus on the current guidelines for the use of BPs in MM and address side effects such as renal toxicity, osteonecrosis of the jaw, and low-energy fractures. Finally, we approach the future of BP use in MM in the context of other bone-targeted agents, evaluating ongoing clinical trials addressing alternate dosing and schedules of BP administration in MM patients. The Oncologist 2011;16:651-662 C1 [Raje, Noopur] Harvard Univ, Div Hematol & Oncol, Massachusetts Gen Hosp, Canc Ctr,Med Sch, Boston, MA 02114 USA. RP Raje, N (reprint author), Harvard Univ, Div Hematol & Oncol, Massachusetts Gen Hosp, Canc Ctr,Med Sch, POB 216,55 Fruit St, Boston, MA 02114 USA. EM nraje@partners.org RI Pozzi, Samantha/A-7617-2012 OI Pozzi, Samantha/0000-0001-7917-1774 FU AstraZeneca; Acetylon FX Research funding/contracted research: AstraZeneca, Acetylon. NR 151 TC 16 Z9 16 U1 0 U2 5 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PY 2011 VL 16 IS 5 BP 651 EP 662 DI 10.1634/theoncologist.2010-0225 PG 12 WC Oncology SC Oncology GA 764VG UT WOS:000290661900015 PM 21493759 ER PT J AU Hong, TS Mamon, H AF Hong, Theodore S. Mamon, Harvey TI Short-Course Versus Standard Chemoradiation in T3 Rectal Cancer SO ONCOLOGIST LA English DT Editorial Material ID PREOPERATIVE RADIOTHERAPY; CIRCUMFERENTIAL MARGIN; RANDOMIZED-TRIAL; POSTOPERATIVE CHEMORADIOTHERAPY; RADIATION-THERAPY; ADJUVANT; SURVIVAL; FLUOROURACIL; CARCINOMA AB A 68-year-old woman with no past medical history presents with rectal bleeding. Colonoscopy reveals amass in the midrectum at approximately 8 cm. Biopsy shows adenocarcinoma. On physical exam, the tip of the mass is barely palpable. A magnetic resonance imaging (MRI) scan of the pelvis demonstrates a tumor with invasion through the muscularis in the midrectum (Fig. 1). There is at least 2 cm between the tip of the mass and the mesorectum. A single 8-mm lymph node is seen in the perirectal space. A medical oncologist, surgical oncologist, and radiation oncologist see the patient and they recommend that the patient receive 6 weeks of infusional 5-fluorouracil (5-FU) and external beam radiation to a dose of 50.4 Gy. After chemoradiation, the oncologists expect the patient to undergo a low anterior resection and, upon recovery, 4 months of 5-FU-based adjuvant chemotherapy. The oncology fellow asks the attending physicians whether short-course radiation therapy is appropriate for this patient. The Oncologist 2011;16:717-721 C1 [Hong, Theodore S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mamon, Harvey] Brigham & Womens Hosp, Boston, MA 02115 USA. [Mamon, Harvey] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Hong, TS (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Inov Farmaceutica, Inct/K-2313-2013 FU Novartis FX Research funding/contracted research: Novartis. NR 22 TC 1 Z9 1 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PY 2011 VL 16 IS 5 BP 717 EP 721 DI 10.1634/theoncologist.2011-0052 PG 5 WC Oncology SC Oncology GA 764VG UT WOS:000290661900022 PM 21586661 ER PT J AU Schapira, L Higgins, MJ AF Schapira, Lidia Higgins, Michaela J. TI All Nodes Lead to Chemo ... SO ONCOLOGIST LA English DT Editorial Material ID EARLY BREAST-CANCER; PATIENTS PREFERENCES; ADJUVANT CHEMOTHERAPY; PREMENOPAUSAL WOMEN; THERAPY; SUPPRESSION; WORTHWHILE; TRIALS AB A 51-year-old woman presents with an abnormal screening mammogram. Core biopsy shows an invasive ductal cancer that stains strongly for estrogen receptor (ER) and progesterone receptor (PR) and does not overexpress human epidermal growth factor receptor 2. She underwent a partial mastectomy and sentinel node biopsy. The invasive tumor measured 2.1 cm in greatest diameter and was grade 1. There was a 0.4 cm metastatic deposit in one of two sentinel lymph nodes (pT1cN1/stage IIA). There was no tumor within 0.2 cm of all margins and no lymphatic or vascular invasion noted. She was evaluated in the breast multidisciplinary clinic by a medical, surgical, and radiation oncologist. The question for our colleagues is what is the optimal adjuvant therapy for this woman and, more specifically, is chemotherapy necessary? The Oncologist 2011;16:722-725 C1 [Schapira, Lidia; Higgins, Michaela J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Schapira, L (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Inov Farmaceutica, Inct/K-2313-2013 NR 16 TC 0 Z9 0 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2011 VL 16 IS 5 BP 722 EP 725 DI 10.1634/theoncologist.2011-0118 PG 4 WC Oncology SC Oncology GA 764VG UT WOS:000290661900023 PM 21586662 ER PT J AU La Vecchia, C Giordano, SH Hortobagyi, GN Chabner, B AF La Vecchia, Carlo Giordano, Sharon H. Hortobagyi, Gabriel N. Chabner, Bruce TI Overweight, Obesity, Diabetes, and Risk of Breast Cancer: Interlocking Pieces of the Puzzle SO ONCOLOGIST LA English DT Editorial Material DE Breast cancer; Diabetes; Overweight; Risk ID WEIGHT CHANGE; BODY-SIZE; MEDICAL CONDITIONS; UNITED-STATES; MELLITUS; INSULIN; WOMEN; GLUCOSE; HEALTH; AGE AB We considered epidemiological data on overweight, diabetes, insulin, and breast cancer. Overweight is inversely related to premenopausal breast cancer, but there is definite evidence that, as compared with normal weight women, the relative risk (RR) for postmenopausal breast cancer is around 1.5 for overweight women and > 2 for obese women, and that the association is stronger in elderly women. Overweight and obesity are strongly related to diabetes. Diabetes is associated with postmenopausal breast cancer, too, with summary RRs from meta-analyses of 1.15-1.20, but not with premenopausal breast cancer (RR, 0.9). There is no consistent evidence that fasting insulin is related to breast cancer risk. Thus, although overweight and obesity are strongly related to postmenopausal breast cancer, diabetes is only moderately related to it. Given the extent of the association, and the likely residual confounding by overweight, inference on causality for the diabetes-breast cancer relation remains open to discussion. The Oncologist 2011;16:726-729 C1 [La Vecchia, Carlo] Univ Milan, Dept Occupat Hlth, Ist Ric Farmacol Mario Negri, I-20156 Milan, Italy. [La Vecchia, Carlo] I PRI, Lyon, France. [Giordano, Sharon H.; Hortobagyi, Gabriel N.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Chabner, Bruce] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP La Vecchia, C (reprint author), Univ Milan, Dept Occupat Hlth, Ist Ric Farmacol Mario Negri, Via Giuseppe La Masa 19, I-20156 Milan, Italy. EM carlo.lavecchia@marionegri.it RI Inov Farmaceutica, Inct/K-2313-2013; OI La Vecchia, Carlo/0000-0003-1441-897X FU Associazione Italiana per la Ricerca sul Cancro (AIRC); American Cancer Society; Cancer Prevention Research Institute of Texas; NIH/NCI; Novartis; Susan G. Komen for the Cure; Bruce Chabner; U.S. Government FX Disclosures: Carlo La Vecchia: Research funding/contracted research: Associazione Italiana per la Ricerca sul Cancro (AIRC n. 10068); Sharon H. Giordano: Research funding/contracted research: American Cancer Society and the Cancer Prevention Research Institute of Texas; Gabriel N. Hortobagyi: Consultant/advisory role: sanofi-aventis, Allergan, Genentech, Merck, Novartis, Tyvex; Research funding/contracted research: NIH/NCI, Novartis, Susan G. Komen for the Cure; Bruce Chabner: Consultant/advisory role: Sanofi, Allergan, Epizyme, PharmaMar, GlaxoSmithKline, Peregrine, Onyx; Honoraria: Eli Lilly; Research funding/contracted research: U.S. Government; Ownership interest: PharmaMar, Gilead, Epizyme, Human Genome Sciences, Onyx. NR 40 TC 60 Z9 61 U1 0 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 PY 2011 VL 16 IS 6 BP 726 EP 729 DI 10.1634/theoncologist.2011-0050 PG 4 WC Oncology SC Oncology GA 781JZ UT WOS:000291928900002 PM 21632448 ER PT J AU Mak, RH Doran, E Muzikansky, A Kang, J Neal, JW Baldini, EH Choi, NC Willers, H Jackman, DM Sequist, LV AF Mak, Raymond H. Doran, Elizabeth Muzikansky, Alona Kang, Josephine Neal, Joel W. Baldini, Elizabeth H. Choi, Noah C. Willers, Henning Jackman, David M. Sequist, Lecia V. TI Outcomes After Combined Modality Therapy for EGFR-Mutant and Wild-Type Locally Advanced NSCLC SO ONCOLOGIST LA English DT Article DE Radiation therapy; Epidermal growth factor receptor; Mutation; Non-small cell lung carcinoma; Neoplasm recurrence; Local; Combined modality therapy ID CELL LUNG-CANCER; GROWTH-FACTOR RECEPTOR; PHASE-III TRIAL; CONCURRENT CHEMORADIOTHERAPY; IONIZING-RADIATION; ONCOLOGY-GROUP; KINASE DOMAIN; GEFITINIB; MUTATIONS; CHEMOTHERAPY AB Background. Epidermal growth factor receptor (EGFR) mutations identify a unique biological subtype of non-small cell lung cancer (NSCLC). Treatment outcomes for EGFR-mutant locally advanced NSCLC patients have not been well described. Methods. We retrospectively examined outcomes after combined modality therapy including thoracic radiation therapy (RT) in 123 patients with locally advanced NSCLC and known EGFR mutation status. Outcomes were compared using Kaplan-Meier analysis, the log-rank test, and multivariate Cox regression models. Results. All 123 patients underwent thoracic RT; 25% had tumors with EGFR mutations and 94% had stage III disease. Overall, 81% received chemotherapy concurrent with RT and 55% underwent surgical resection. With a median follow-up of 27.5 months, the overall survival (OS) rate was significantly higher in patients with EGFR-mutant tumors than in those with wild-type EGFR tumors (2-year estimate: 92.6% versus 69.0%; p = .04). The 2-year relapse-free survival and distant recurrence rates did not differ significantly by genotype. The 2-year locoregional recurrence rate (LRR) was significantly lower in EGFR-mutant than in wild-type EGFR patients (17.8% versus 41.7%; p = .005). EGFR-mutant genotype was associated with a lower risk for LRR on multivariate analysis, but not OS, after adjusting for surgery and other potential confounders. Conclusion. We observed that EGFR-mutant patients with locally advanced NSCLC treated with RT had lower rates of LRR than wild-type EGFR patients, raising the hypothesis that EGFR mutations may confer sensitivity to RT and/or chemotherapy. The association between mutation status and OS after combined modality therapy was less robust. Our data may serve as a useful baseline estimate of outcomes by EGFR genotype for future prospective studies. The Oncologist 2011;16:886-895 C1 [Mak, Raymond H.; Kang, Josephine] Harvard Radiat Oncol Program, Boston, MA USA. [Doran, Elizabeth; Baldini, Elizabeth H.; Jackman, David M.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. [Muzikansky, Alona] Massachusetts Gen Hosp, Ctr Canc, Ctr Biostat, Boston, MA USA. [Choi, Noah C.; Willers, Henning] Massachusetts Gen Hosp, Ctr Canc, Dept Radiat Oncol, Boston, MA USA. [Sequist, Lecia V.] Massachusetts Gen Hosp, Ctr Canc, Ctr Thorac Canc, Boston, MA USA. [Neal, Joel W.] Stanford Canc Ctr, Stanford, CA USA. [Baldini, Elizabeth H.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Baldini, Elizabeth H.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Baldini, Elizabeth H.; Choi, Noah C.; Willers, Henning; Jackman, David M.; Sequist, Lecia V.] Harvard Univ, Sch Med, Boston, MA USA. RP Sequist, LV (reprint author), 55 Fruit St,POB 212, Boston, MA 02144 USA. EM LVSequist@partners.org RI Inov Farmaceutica, Inct/K-2313-2013 FU Genentech; National Cancer Institute, Dana-Farber/Harvard Cancer Center [P50 CA090578] FX Disclosures Raymond H. Mak: None; Elizabeth Doran: None; Alona Muzikansky: None; Josephine Kang: None; Joel W. Neal: Research funding/contracted research: Genentech; Elizabeth H. Baldini: None; Noah C. Choi: None; Henning Willers: None; David M. Jackman: Consultant/advisory role: Foundation Medicine; Lecia V. Sequist: Consultant/advisory role: GlaxoSmithKline, Daiichi-sankyo, Merrimack.; This work was supported in part by the National Cancer Institute, Dana-Farber/Harvard Cancer Center SPORE in Lung Cancer P50 CA090578 (H.W.). NR 36 TC 32 Z9 34 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PY 2011 VL 16 IS 6 BP 886 EP 895 DI 10.1634/theoncologist.2011-0040 PG 10 WC Oncology SC Oncology GA 781JZ UT WOS:000291928900018 PM 21632451 ER PT J AU Sekeres, MA Maciejewski, JP List, AF Steensma, DP Artz, A Swern, AS Scribner, P Huber, J Stone, R AF Sekeres, Mikkael A. Maciejewski, Jaroslaw P. List, Alan F. Steensma, David P. Artz, Andrew Swern, Arlene S. Scribner, Paul Huber, John Stone, Richard TI Perceptions of Disease State, Treatment Outcomes, and Prognosis Among Patients with Myelodysplastic Syndromes: Results from an Internet-Based Survey SO ONCOLOGIST LA English DT Article DE Myelodysplastic syndromes; Health survey; Patient-reported outcomes; Treatment outcome ID QUALITY-OF-LIFE; UNITED-STATES; SCORING SYSTEM; PHASE-III; EFFICACY; CANCER; MDS; EPIDEMIOLOGY; AZACITIDINE; SURVIVAL AB Purpose. Myelodysplastic syndromes (MDSs) are a heterogenous group of clonal hematopoietic disorders affecting approximately 60,000 people in the U. S. Little information is available regarding how aware MDS patients are of their disease severity, prognosis, and treatment outcomes. Methods. This Internet-based survey assessed patient perceptions regarding these factors, determined differences between patients with higher-and lower-risk disease and between those receiving active treatment and supportive care, and assessed patient-reported outcomes. Results. Among 358 patients (median age, 65 years), the median time since MDS diagnosis was 3 years and time from initial hematologic abnormality detection was 6 years. Many patients (55%) did not know their International Prognostic Scoring System score, 42% were unaware of their blast percentage, and 28% were unaware of their cytogenetics. Patients were unlikely to recall having their MDS described as cancer (7%), 37% felt their treatment would improve survival, and 16% felt treatment would be curative. Patients receiving active treatment were more likely to believe their therapy would prolong survival than those receiving supportive care (52% versus 31%; p < .001) or be curative (23% versus 14%; p = .03). Patients with higher-risk disease were more likely to think their therapy would be curative than those with lower-risk disease (26% versus 11%; p = .01). Patients with MDS reported poor physical or mental health on two to three times more days per month than population norms. Conclusion. Patients with MDS have a limited understanding of their disease characteristics, prognosis, and treatment goals. These results may help improve physician-patient communication and identify factors to consider when making treatment decisions. The Oncologist 2011;16:904-911 C1 [Sekeres, Mikkael A.] Cleveland Clin, Taussig Canc Inst, Dept Hematol Oncol & Blood Disorders, Leukemia Program, Cleveland, OH 44195 USA. [Maciejewski, Jaroslaw P.] Cleveland Clin, Taussig Canc Inst, Dept Translat Hematol & Oncol Res, Cleveland, OH 44195 USA. [List, Alan F.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Malignant Hematol, Tampa, FL 33612 USA. [Stone, Richard] Dana Farber Canc Inst, Boston, MA 02115 USA. [Steensma, David P.] Dept Hematol Malignancies, Boston, MA USA. [Artz, Andrew] Univ Chicago Hosp, Chicago, IL 60637 USA. [Swern, Arlene S.] Celgene Corp, Summit, NJ USA. [Scribner, Paul; Huber, John] Aplast Anemia & MDS Int Fdn, Rockville, MD USA. RP Sekeres, MA (reprint author), Cleveland Clin, Taussig Canc Inst, Dept Hematol Oncol & Blood Disorders, Leukemia Program, Desk R35,9500 Euclid Ave, Cleveland, OH 44195 USA. EM sekerem@ccf.org OI Steensma, David/0000-0001-5130-9284 FU Celgene FX Disclosures: Mikkael A. Sekeres: None; Jaroslaw P. Maciejewski: Research funding/contracted research: Celgene; Alan F. List: Consultant/advisory role: Celgene; David P. Steensma: None; Andrew Artz: None; Arlene S. Swern: Employment/leadership position: Celgene; Paul Scribner: None; John Huber: None; Richard Stone: Consultant/advisory role: Merck, Eisai, Genzyme, Celgene; Honoraria: Celgene.; Access to the patient survey by the AAMDS Foundation and the data collection and data entry by RedCar were funded by Celgene. NR 23 TC 26 Z9 26 U1 0 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2011 VL 16 IS 6 BP 904 EP 911 DI 10.1634/theoncologist.2010-0199 PG 8 WC Oncology SC Oncology GA 781JZ UT WOS:000291928900020 PM 21478277 ER PT J AU Cheng, AL Shen, YC Zhu, AX AF Cheng, Ann-Lii Shen, Ying-Chun Zhu, Andrew X. TI Targeting Fibroblast Growth Factor Receptor Signaling in Hepatocellular Carcinoma SO ONCOLOGY LA English DT Review DE Hepatocellular carcinoma; Fibroblast growth factor receptor; Fibrosis; Cirrhosis; Multikinase inhibitor ID TYROSINE KINASE INHIBITOR; ADVANCED SOLID TUMORS; PHASE-I; EXTRACELLULAR-MATRIX; DUAL INHIBITOR; LIVER FIBROSIS; STELLATE CELLS; EXPRESSION; INJURY; BRIVANIB AB Hepatocellular carcinoma (HCC) is the primary type of liver cancer, and both the age-adjusted incidence and mortality of HCC have steadily increased in recent years. Advanced HCC is associated with a very poor survival rate. Despite accumulating data regarding the risk factors for HCC, the mechanisms that contribute to HCC tumorigenesis remain poorly understood. Signaling through the fibroblast growth factor (FGF) family is involved in fibrosis and its progression to cirrhosis of the liver, which is a risk factor for the development of HCC. Furthermore, several alterations in FGF/FGF receptor (FGFR) signaling correlate with the outcomes of HCC patients, suggesting that signaling through this family of proteins contributes to the development or progression of HCC tumors. Currently, there are no established systemic treatments for patients with advanced HCC in whom sorafenib treatment has failed or who were unable to tolerate it. Recently, several multikinase inhibitors that target FGFRs have demonstrated some early evidence of antitumor activity in phase I/II trials. Therefore, this review discusses the molecular implications of FGFR-mediated signaling in HCC and summarizes the clinical evidence for novel FGFR-targeted therapies for HCC currently being studied in clinical trials. Copyright (C) 2012 S. Karger AG, Basel C1 [Cheng, Ann-Lii; Shen, Ying-Chun] Natl Taiwan Univ Hosp, Dept Oncol, Taipei 10016, Taiwan. [Cheng, Ann-Lii] Natl Taiwan Univ Hosp, Dept Internal Med, Taipei 10016, Taiwan. [Cheng, Ann-Lii] Natl Taiwan Univ, Inst Oncol, Taipei 10764, Taiwan. [Shen, Ying-Chun] Natl Taiwan Univ Hosp, Natl Ctr Excellence Clin Trial & Res, Taipei 10016, Taiwan. [Zhu, Andrew X.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. RP Cheng, AL (reprint author), Natl Taiwan Univ Hosp, Dept Oncol, 7 Chung Shan S Rd, Taipei 10016, Taiwan. EM alcheng@ntu.edu.tw OI Cheng, Ann-Lii/0000-0002-9152-6512 FU Novartis Pharmaceuticals FX Financial support for medical editorial assistance was provided by Novartis Pharmaceuticals. NR 48 TC 18 Z9 19 U1 1 U2 7 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-2414 J9 ONCOLOGY-BASEL JI Oncology PY 2011 VL 81 IS 5-6 BP 372 EP 380 DI 10.1159/000335472 PG 9 WC Oncology SC Oncology GA 889UB UT WOS:000300098300014 PM 22269894 ER PT J AU Ganjoo, KN Cranmer, LD Butrynski, JE Rushing, D Adkins, D Okuno, SH Lorente, G Kroll, S Langmuir, VK Chawla, SP AF Ganjoo, Kristen N. Cranmer, Lee D. Butrynski, James E. Rushing, Daniel Adkins, Douglas Okuno, Scott H. Lorente, Gustavo Kroll, Stew Langmuir, Virginia K. Chawla, Sant P. TI A Phase I Study of the Safety and Pharmacokinetics of the Hypoxia-Activated Prodrug TH-302 in Combination with Doxorubicin in Patients with Advanced Soft Tissue Sarcoma SO ONCOLOGY LA English DT Article DE Hypoxia-activated prodrug; TH-302; Phase I clinical trial; Soft tissue sarcoma ID STANDARD-DOSE DOXORUBICIN; CELL LUNG-CANCER; EUROPEAN-ORGANIZATION; PLUS IFOSFAMIDE; SOLID TUMORS; III TRIAL; TIRAPAZAMINE; EXPRESSION AB Purpose: The purpose of this study was to determine the dose-limiting toxicities (DLT), maximum tolerated dose (MTD), safety, pharmacokinetics and preliminary activity of TH-302, a hypoxia-activated prodrug, in combination with doxorubicin in patients with advanced soft tissue sarcoma. Patients and Methods: TH-302 was administered intravenously on days 1 and 8 and doxorubicin 75 mg/m(2) on day 1 (2 h after TH-302) of every 3-week cycle. TH-302 starting dose was 240 mg/m(2) with a classic 3 + 3 dose escalation. Pharmacokinetics were assessed on days 1 and 8 of cycle 1. Tumor assessments were performed after every second cycle. Results: Sixteen patients enrolled. Prophylactic growth factor support was added due to grade 4 neutropenia. The MTD was 300 mg/m(2). DLTs at 340 mg/m(2) were neutropenia-associated infection and grade 4 thrombocytopenia. Common adverse events included fatigue, nausea and skin rash. There was no evidence of pharmacokinetic interaction between TH-302 and doxorubicin. Five of 15 (33%) evaluable patients had a partial response by RECIST (Response Evaluation Criteria in Solid Tumors) criteria. Conclusions: The hematologic toxicity of doxorubicin is increased when combined with TH-302. This can be mitigated by prophylactic growth factor support. Toxicities were manageable and there was evidence of antitumor activity. Copyright (C) 2011 S. Karger AG, Basel C1 [Ganjoo, Kristen N.] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Cranmer, Lee D.] Univ Arizona, Arizona Canc Ctr, Tucson, AZ USA. [Butrynski, James E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rushing, Daniel] Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA. [Adkins, Douglas] Washington Univ, St Louis, MO USA. [Okuno, Scott H.] Mayo Clin, Rochester, MN USA. [Lorente, Gustavo; Kroll, Stew; Langmuir, Virginia K.] Threshold Pharmaceut, Redwood City, CA USA. [Chawla, Sant P.] Sarcoma Oncol Ctr, Santa Monica, CA USA. RP Ganjoo, KN (reprint author), Stanford Univ, Med Ctr, 875 Blake Wilbur Dr, Stanford, CA 94305 USA. EM kganjoo@stanford.edu FU Threshold Pharmaceuticals Inc. FX The research was supported by Threshold Pharmaceuticals Inc. NR 22 TC 29 Z9 29 U1 0 U2 7 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-2414 EI 1423-0232 J9 ONCOLOGY-BASEL JI Oncology PY 2011 VL 80 IS 1-2 BP 50 EP 56 DI 10.1159/000327739 PG 7 WC Oncology SC Oncology GA 779BT UT WOS:000291753800007 PM 21625179 ER PT J AU Zakka, FR Jakobiec, FA Thakker, MM AF Zakka, Fouad R. Jakobiec, Frederick A. Thakker, Manoj M. TI Eyelid Varix With Phlebolith Formation, Thrombus Recanalization, and Early Intravascular Papillary Endothelial Hyperplasia SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article AB An asymptomatic, bluish-gray, movable, raised, and firm left upper eyelid mass had been present for 8 months in an 82-year-old woman. Histopathologic examination revealed a lesion restricted to the dermis and composed in part of a calcific nodule that was circumscribed by an acellular fibrous capsule. An adjacent nodule exhibited proliferating endothelial cells invading a fresh thrombus. Immunohistochemical staining revealed positivity for CD31, CD34, and CD68; D2-40 was negative, ruling out a lymphatic origin. Masson trichrome and elastic staining of deeper sections revealed recanalization of an earlier thrombus; surviving elastic fibers were discovered in the outer wall, establishing a venous source. This is the first reported case of 3 microscopically discernible events (old phlebolith, fresh intravascular endothelial hyperplasia invading a thrombus, and labyrinthine recanalization of a temporally more remote thrombus) in an eyelid varix. The clinical differential diagnosis is reviewed. C1 [Zakka, Fouad R.; Jakobiec, Frederick A.] Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Boston, MA 02114 USA. [Thakker, Manoj M.] Massachusetts Eye & Ear Infirm, Oculoplast Serv, Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Suite 321,243 Charles St, Boston, MA 02114 USA. EM fred_jakobiec@meei.harvard.edu NR 11 TC 2 Z9 2 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD JAN-FEB PY 2011 VL 27 IS 1 BP E8 EP E11 DI 10.1097/IOP.0b013e3181d8e13c PG 4 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 703QT UT WOS:000285996300005 PM 20724862 ER PT J AU Gentile, RC Milman, T Eliott, D Romero, JM McCormick, SA AF Gentile, Ronald C. Milman, Tatyana Eliott, Dean Romero, Juan M. McCormick, Steven A. TI Taut Internal Limiting Membrane Causing Diffuse Diabetic Macular Edema after Vitrectomy: Clinicopathological Correlation SO OPHTHALMOLOGICA LA English DT Article DE Diabetes; Internal limiting membrane, taut; Immunohistochemistry; Macular edema; Pathology; Vitrectomy ID PARS-PLANA VITRECTOMY; POSTERIOR HYALOIDAL TRACTION; GRID LASER PHOTOCOAGULATION; EPIRETINAL MEMBRANE; SURGICAL REMOVAL; VISUAL-ACUITY; ULTRASTRUCTURE; DETACHMENT; EYES AB Aims: To describe 2 cases of diffuse diabetic macular edema (DME) after diabetic vitrectomy caused by a taut internal limiting membrane (ILM), with clinicopathological correlation. Methods: Interventional case series with immunohistochemical analysis. Results: Two patients were referred for unresponsive diffuse DME after pars plana vitrectomy with removal of the posterior hyaloid. Clinically, a taut ILM was noted over the fovea, and its removal resulted in rapid and long-term resolution of the edema, confirmed by optical coherence tomography with visual acuity improvement. Histopathology with immunostaining revealed a segment of ILM with an inner monolayer of cytokeratin-positive (retinal pigment epithelial cells) and/or glial fibrillary acidic protein-positive cells with smooth muscle actin immunoreactivity. Conclusions: A taut ILM can cause diffuse DME after vitrectomy, and its removal can restore the normal foveal contour and improve visual acuity. Tangential tractional forces from contractile cells propagated across the fovea via the ILM appear to be the etiology. Copyright (C) 2011 S. Karger AG, Basel C1 [Gentile, Ronald C.] New York Eye & Ear Infirm, Vitreo Retina Serv, Dept Ophthalmol, New York, NY 10003 USA. [Milman, Tatyana; McCormick, Steven A.] New York Eye & Ear Infirm, Dept Pathol, New York, NY 10003 USA. [Gentile, Ronald C.; McCormick, Steven A.] New York Med Coll, Dept Ophthalmol, Valhalla, NY 10595 USA. [Eliott, Dean] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Gentile, RC (reprint author), New York Eye & Ear Infirm, Vitreo Retina Serv, Dept Ophthalmol, 310 E 14th St, New York, NY 10003 USA. EM rgentile@nyee.edu FU Department of Ophthalmology Research Fund of the New York Eye and Ear Infirmary; Norma Lazar Ophthalmology Research Fund FX This study was supported by the Department of Ophthalmology Research Fund of the New York Eye and Ear Infirmary and the Norma Lazar Ophthalmology Research Fund. Both entities had no role in the study design, data, writing, or decision to submit. NR 30 TC 1 Z9 1 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-3755 J9 OPHTHALMOLOGICA JI Ophthalmologica PY 2011 VL 226 IS 2 BP 64 EP 70 DI 10.1159/000327365 PG 7 WC Ophthalmology SC Ophthalmology GA 771JO UT WOS:000291153200006 PM 21597307 ER PT J AU Tanna, AP Bandi, JR Budenz, DL Feuer, WJ Feldman, RM Herndon, LW Rhee, DJ Whiteside-de Vos, J AF Tanna, Angelo P. Bandi, Jagadeesh R. Budenz, Donald L. Feuer, William J. Feldman, Robert M. Herndon, Leon W. Rhee, Douglas J. Whiteside-de Vos, Julia TI Interobserver Agreement and Intraobserver Reproducibility of the Subjective Determination of Glaucomatous Visual Field Progression SO OPHTHALMOLOGY LA English DT Article ID TRIAL; VARIABILITY AB Purpose: To determine the extent of interobserver agreement and intraobserver reproducibility of the subjective determination of visual field progression with achromatic automated static perimetry in eyes with glaucoma, and to determine the impact of access to Glaucoma Progression Analysis (GPA) data on interobserver agreement. Design: Retrospective, observational case series. Participants: Five glaucoma subspecialists from 5 different academic medical centers. Methods: Five visual field tests from each of 100 eyes of 83 patients being monitored for glaucoma were retrospectively identified and subjectively and independently evaluated by the 5 glaucoma subspecialists. Each set of visual fields was classified regarding progression as "none," "questionable," "probable," or "definite." More than 1 month later, the same expert observers reevaluated the same sets of visual field tests to allow determination of intraobserver reproducibility. A final subjective evaluation regarding progression was performed 3 months later, at which time the expert observers had access to the GPA printout. Main Outcome Measures: The level of interobserver agreement and intraobserver reproducibility was estimated using kappa statistics on the raw classification data and also on dichotomized data in which "none" and "questionable" progression were reclassified together as nonprogressed and "probable" and "definite" were reclassified as progressed. Results: Intraobserver reproducibility was good to excellent (kappa = 0.62-0.78) for the raw data and moderate to good (kappa = 0.58-0.71) for the dichotomized data. Interobserver agreement was moderate (kappa = 0.45; 95% confidence interval [CI], 0.35-0.55) for the raw classification data and also for dichotomized data (kappa = 0.55; 95% CI, 0.46-0.64). Access to the GPA printout did not significantly change the level of interobserver agreement. Conclusions: Five glaucoma experts had good to excellent reproducibility of the determination of visual field progression compared with earlier evaluation of the same field sets. Agreement among the experts with each other was only moderate, and did not improve when each had access to GPA results. C1 [Tanna, Angelo P.] Northwestern Univ, Dept Ophthalmol, Feinberg Sch Med, Chicago, IL 60611 USA. [Feldman, Robert M.] Univ Texas Med Sch Houston, Dept Ophthalmol & Visual Sci, Houston, TX USA. [Herndon, Leon W.] Duke Univ, Ctr Eye, Durham, NC USA. [Rhee, Douglas J.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Whiteside-de Vos, Julia] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Bandi, Jagadeesh R.; Budenz, Donald L.; Feuer, William J.] Univ Miami, Bascom Palmer Eye Inst, Sch Med, Miami, FL 33136 USA. RP Budenz, DL (reprint author), Univ Miami, Bascom Palmer Eye Inst, Sch Med, 900 NW 17th St, Miami, FL 33136 USA. EM dbudenz@med.miami.edu FU National Eye Institute, Bethesda, Maryland [P30 EY-014801]; Research to Prevent Blindness, New York, New York; Carl Zeiss Meditec, Inc., Dublin, California FX Financial Disclosure(s): The authors have made the following disclosures: Angelo P. Tanna - Consultant, Honoraria for lectures - Carl Zeiss Meditec, Inc. Supported in part by research grant P30 EY-014801 awarded by the National Eye Institute, Bethesda, Maryland; by an unrestricted grant from Carl Zeiss Meditec, Inc., Dublin, California; and by an unrestricted grant from Research to Prevent Blindness, New York, New York. NR 17 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD JAN PY 2011 VL 118 IS 1 BP 60 EP 65 DI 10.1016/j.ophtha.2010.04.038 PG 6 WC Ophthalmology SC Ophthalmology GA 701PF UT WOS:000285832500011 PM 20723992 ER PT J AU Heier, JS Brown, D Ciulla, T Abraham, P Bankert, JM Chong, S Daniel, PE Kim, IK AF Heier, Jeffrey S. Brown, David Ciulla, Thomas Abraham, Prema Bankert, Joy M. Chong, Sandy Daniel, Paul E., Jr. Kim, Ivana K. TI Ranibizumab for Choroidal Neovascularization Secondary to Causes Other Than Age-Related Macular Degeneration: A Phase I Clinical Trial SO OPHTHALMOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; INTRAVITREAL RANIBIZUMAB; PATHOLOGICAL MYOPIA; BEVACIZUMAB; EXPRESSION; THERAPY AB Purpose: To investigate the safety and efficacy of ranibizumab for the treatment of choroidal neovascularization (CNV) secondary to causes other than age-related macular degeneration (AMD). Design: Multicenter, randomized, 12-month clinical trial. Participants: Thirty patients with CNV due to causes other than AMD, including pathologic myopia, ocular histoplasmosis, and angioid streaks. Methods: Participants were randomly assigned 1: 1 to monthly intravitreal injections of 0.5 mg ranibizumab or 3 monthly injections followed by dosing as needed (pro re nata [PRN]) at monthly follow-up visits. Main Outcome Measures: Outcome measures included the incidence of ocular and nonocular adverse events, the percentage of patients gaining >= 15 letters of visual acuity (VA) at 6 and 12 months from baseline, the percentage of patients losing >= 15 letters of VA at 6 and 12 months from baseline, and mean change in VA and central retinal thickness (CRT) at 6 and 12 months from baseline. Results: No serious ocular or systemic adverse events related to ranibizumab or the injection procedure were reported. Among patients who received monthly ranibizumab injections, 8 of 12 (66.7%) gained >= 15 letters of VA at both 6 and 12 months, and among patients who received PRN injections, 9 of 14 (64.3%) and 8 of 14 (57.1%) gained >= 15 letters of VA at 6 and 12 months, respectively. No patient in the study lost >= 15 letters of VA. Mean VA improved significantly from baseline by 23.9 +/- 5.4 (P = 0.001) and 21.1 +/- 4.3 letters (P = 0.0003) at 6 months and by 26.9 +/- 5.3 (P = 0.0003) and 19.2 +/- 3.8 letters (P = 0.0002) at 12 months in the monthly and PRN treatment arms, respectively. Mean CRT decreased significantly from baseline by 103.4 +/- 18.9 (P = 0.0005) and 161.1 +/- 43.7 mu m (P = 0.0034) at 6 months and by 109.3 +/- 19.5 (P = 0.0004) and 166.6 +/- 38.4 mu m (P = 0.001) at 12 months in the monthly and PRN treatment groups, respectively. No statistically significant difference was found between treatment groups in change in VA or CRT at any time point. Conclusions: Intravitreal ranibizumab, given as monthly injections or as 3 monthly injections followed by PRN dosing, showed a promising efficacy and safety profile in the treatment of CNV due to causes other than AMD. C1 [Heier, Jeffrey S.; Bankert, Joy M.; Chong, Sandy; Daniel, Paul E., Jr.] Ophthalm Consultants Boston, Boston, MA 02114 USA. [Brown, David] Vitreoretinal Consultants, Houston, TX USA. [Ciulla, Thomas] Midwest Eye Inst, Indianapolis, IN USA. [Abraham, Prema] Black Hills Reg Eye Inst, Rapid City, SD USA. [Kim, Ivana K.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Heier, JS (reprint author), Ophthalm Consultants Boston, 50 Staniford St,Suite 600, Boston, MA 02114 USA. EM jsheier@eyeboston.com FU Genentech, Inc.; Alcon Laboratories; Allergan; Bausch Lomb; CoMentis; Eyemaginations; Fovea; Genentech; Genzyme; Heidelberg Engineering; iScience; Ista Pharmaceuticals; Jerini Ophthalmics; LPath; NeoVista; Neurotech; Notal Vision; Novartis Pharmaceuticals; Optherion; Optimedica; Oraya Therapeutics; Oxigene; Paloma; Pfizer Ophthalmics; Regeneron; Resolvyx Pharmaceuticals; Schering Plough Research Institute; Scyfix; Steba; VisionCare Ophthalmic Technologies; Alimera; Carl Zeiss Meditec; Othera; Pfizer; Glaxo-Smith-Kline; Optko; National Eye Institute/National Institutes of Health; Abraham: Genentech; Alcon; Novartis; Opko Health; Jerini Ophthalmic; Eli Lilly; VRT; Schering Plough FX Financial Disclosure(s): The author(s) have made the following disclosure(s): J. S. Heier: Acucela (C), Alcon Laboratories (C, S), Allergan (C, S), Bausch & Lomb (C), CoMentis (S), Eyemaginations (C), Fovea (C), Genentech (C, S, L), Genzyme (C), Heidelberg Engineering (C, L), iScience (C, S), Ista Pharmaceuticals (C, S), Jerini Ophthalmics (C, S, L), LPath (C), NeoVista (C, S, L), Neurotech (S), Notal Vision (C), Novartis Pharmaceuticals (C, S), Optherion (C), Optimedica (R), Oraya Therapeutics (C), Oxigene (S), Paloma (C, S), Pfizer Ophthalmics (C, S), Regeneron (C, S, L), Resolvyx Pharmaceuticals (C), Schering Plough Research Institute (C), Scyfix (C), Steba (C), VisionCare Ophthalmic Technologies (C, S) D. Brown: Alcon Laboratories (C, S), Alimera (S), Allergan (C, S), Carl Zeiss Meditec (C), CoMentis (S), Eyemaginations (C), Genentech (C, S, L), Heidelberg Engineering (C, L), Jerini Ophthalmics (C, S, L), NeoVista (C, S, L), Neurotech (S), Novartis Pharmaceuticals (C, S), Oraya Therapeutics (C), Othera (S), Oxigene (S), Pfizer Ophthalmics (C, S), Regeneron (C, S, L), Steba (C) T. Ciulla: Neovista (C), Regeneron (C), Pfizer (C), Genentech (S), Regeneron (S), Allergan (S), Alimera (S), Othera (S), Glaxo-Smith-Kline (S), Optko (S), National Eye Institute/National Institutes of Health (S) P. Abraham: Genentech (C, S), Alcon (C, S), Novartis (C, S), Regeneron (S), Allergan (S), Opko Health (S), Jerini Ophthalmic (S), Pfizer (S), Eli Lilly (S), Alimera (S), VRT (S), Schering Plough (S) J. M. Bankert: none This study was funded by Genentech, Inc. The sponsor or funding organization had no role in the design or conduct of this research. Third-party medical writing logistical assistance, but not content sufficient to meet International Committee of Medical Journal Editors' criteria, was provided by Robert Romanelli, PhD, of ApotheCom Associates and was supported by Genentech, Inc. NR 19 TC 22 Z9 22 U1 0 U2 3 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 JAN PY 2011 VL 118 IS 1 BP 111 EP 118 DI 10.1016/j.ophtha.2010.04.016 PG 8 WC Ophthalmology SC Ophthalmology GA 701PF UT WOS:000285832500018 PM 20678799 ER PT J AU Andreoli, MT Andreoli, CM AF Andreoli, Michael T. Andreoli, Christopher M. TI Geriatric Traumatic Open Globe Injuries SO OPHTHALMOLOGY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; CATARACT-SURGERY; OLDER-PEOPLE; RISK-FACTORS; FALLS; ENDOPHTHALMITIS; OUTCOMES; VISION AB Purpose: To characterize the pattern of ocular trauma in the geriatric population. Design: Retrospective, comparative case series. Participants: Eight hundred forty-six consecutive patients comprising 848 open globe injuries, of which 166 injuries occurred in geriatric patients (defined as 65 years old or older at the time of injury), with the remaining patients serving as control subjects. Methods: Charts of open globe injuries (848 in total) treated surgically at the Massachusetts Eye and Ear Infirmary between January 2000 and April 2009 were retrospectively reviewed. Main Outcome Measures: Ocular Trauma Score, age, gender, mechanism of injury, zone of injury, site of injury, time of day, visual acuity at presentation, and best post-repair visual acuity were analyzed. Results: Of 848 open globe injuries, 166 occurred in the geriatric population. The mean patient age in the geriatric group was 79.8 years. Females comprised most (58%) of this subpopulation. The most common mechanisms of injury were fall (65%), blunt trauma (16%), and motor vehicle accident (6%). The geriatric traumas tended to happen in late morning or late at night. There were no cases of endophthalmitis and fewer instances of enucleation in this group. The median raw Ocular Trauma Score was 47 in the geriatric population, compared with 70 in the younger subset (P<0.0001). The injuries more often were in zones II and III in the geriatric population compared with the nongeriatric population (P<0.0001). The geriatric patients were much more likely to have undergone previous intraocular surgery (P<0.0001), which consisted of primarily cataract procedures. Visual acuity at presentation was significantly worse in the geriatric population than the nongeriatric population (P<0.0001). Similarly, the best postoperative visual acuity was worse in the elderly group than the younger group (P<0.0001). Conclusions: The elderly represent a unique, yet neglected ocular trauma population. The pattern of ophthalmic injury and outcome differs greatly between the geriatric and nongeriatric populations. A better understanding of these injuries is necessary to improve prevention and treatment strategies for potentially devastating open globe injuries in this susceptible population. C1 [Andreoli, Michael T.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Andreoli, Michael T.; Andreoli, Christopher M.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Andreoli, Christopher M.] Harvard Vanguard Med Associates, Boston, MA USA. [Andreoli, Christopher M.] Harvard Univ, Sch Med, Boston, MA USA. RP Andreoli, CM (reprint author), 133 Brookline Ave, Boston, MA 02215 USA. EM christopher_andreoli@meei.harvard.edu NR 19 TC 16 Z9 17 U1 0 U2 0 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 JAN PY 2011 VL 118 IS 1 BP 156 EP 159 DI 10.1016/j.ophtha.2010.04.034 PG 4 WC Ophthalmology SC Ophthalmology GA 701PF UT WOS:000285832500023 PM 20709403 ER PT J AU Duszak, RS Duszak, R AF Duszak, Robert S. Duszak, Richard, Jr. TI Malpractice payments by optometrists: An analysis of the national practitioner databank over 18 years SO OPTOMETRY-JOURNAL OF THE AMERICAN OPTOMETRIC ASSOCIATION LA English DT Article DE National Practitioner Data Bank; Optometrist malpractice; Optometrist prescriptive authority ID MEDICAL MALPRACTICE; PHYSICIANS AB PURPOSE: The aim of this analysis was to describe characteristics and trends of malpractice payments by optometrists since the inception of the National Provider Data Bank (NPDB) as they assumed increasing prescriptive authority. METHODS: NPDB data files were analyzed for details of optometrist malpractice payments from 1991 through 2008. Payment amounts, sources, and allegations were all identified and summarized, along with geographic and demographic data. RESULTS: Between 1991 and 2008, a total of 609 optometrist malpractice payments were reported nationally, ranging from $50 to $2,050,000 (median, $57,500; mean, $156,055 +/- 246,556), with 603 (99%) less than $1,000,000. Annual inflation-adjusted mean dollars and frequency of payments increased only nominally over the 18-year interval, from $154,573 to $155,151, and 30 to 40, respectively. More than half of all cases originated in 11 states. Alleged errors in diagnosis accounted for 55% of all cases. CONCLUSION: Malpractice payments on behalf of optometrists are relatively infrequent (on average, less than 34 nationally each year) and usually relatively small (almost half less than $50,000). The frequency of payments and mean payments have increased little over the last 2 decades. Optometry 2011;82:32-37 C1 [Duszak, Robert S.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Duszak, Richard, Jr.] Mid S Imaging & Therapeut, Memphis, TN USA. [Duszak, Richard, Jr.] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. RP Duszak, RS (reprint author), Philadelphia Vet Affairs Med Ctr, 3800 Woodland Ave, Philadelphia, PA 19104 USA. EM bduszak@mac.com RI Duszak, Richard/L-1811-2016 OI Duszak, Richard/0000-0003-0425-3008 NR 27 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1529-1839 J9 OPTOMETRY JI Optometry PD JAN PY 2011 VL 82 IS 1 BP 32 EP 37 DI 10.1016/j.optm.2010.05.009 PG 6 WC Ophthalmology SC Ophthalmology GA 778MM UT WOS:000291708400007 PM 20656562 ER PT J AU Rah, MJ AF Rah, Marjorie J. TI A review of hyaluronan and its ophthalmic applications SO OPTOMETRY-JOURNAL OF THE AMERICAN OPTOMETRIC ASSOCIATION LA English DT Review DE Hyaluronan; Dry eye; Contact lens; Artificial tear ID SODIUM HYALURONATE; PROTEIN ADSORPTION; ACID; MIGRATION; HYDROGELS; EYEDROPS; LENSES; CD44 AB Hyaluronan (HA) is a naturally occurring, biocompatible polysaccharide with unique viscoelastic and hygroscopic properties. Its role as a natural lubricant and its excellent water-retaining properties make it well-suited for use in ophthalmic products. Many reports have been written describing the various uses of HA. The purpose of this report is to review the uses of HA in the anterior segment of the eye, more specifically, its use in the treatment of dry eye syndrome, and in contact lenses and contact lens care systems. Optometry 2011;82:38-43 C1 Massachusetts Eye & Ear Infirm, Contact Lens Serv, Boston, MA 02114 USA. RP Rah, MJ (reprint author), Massachusetts Eye & Ear Infirm, Contact Lens Serv, 243 Charles St, Boston, MA 02114 USA. EM marjie.rah@verizon.net FU Bausch Lomb, Inc. FX This manuscript is supported by Bausch & Lomb, Inc. NR 36 TC 41 Z9 41 U1 5 U2 34 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1529-1839 J9 OPTOMETRY JI Optometry PD JAN PY 2011 VL 82 IS 1 BP 38 EP 43 DI 10.1016/j.optm.2010.08.003 PG 6 WC Ophthalmology SC Ophthalmology GA 778MM UT WOS:000291708400008 PM 21146792 ER PT J AU Cashman, EC Timon, C AF Cashman, Emma Catherine Timon, Conrad TI Otolaryngology and the American Presidency: A Medical Legacy SO ORL-JOURNAL FOR OTO-RHINO-LARYNGOLOGY AND ITS RELATED SPECIALTIES LA English DT Article DE Ulysses S. Grant; Grover Cleveland; Presidency, United States of America; Tumor historical cases ID SQUAMOUS-CELL CARCINOMA; VERRUCOUS CARCINOMA; CANCER; NECK; HEAD; TUMOR AB The various medical histories of eminent members of state have been well documented and explored. Such accounts provide interesting insights into advances in treatment and management of disease. Moreover, historical cases serve as a timely reminder of how the central tenets of good medical practice do not change with time. Two American presidents, Ulysses S. Grant and Grover Cleveland, were afflicted with diseases of the head and neck, and one would subsequently die from his illness. Here we examine their diagnosis, treatment and their disease in the context of modern management. Copyright (C) 2011 S. Karger AG, Basel C1 [Cashman, Emma Catherine] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Timon, Conrad] Royal Victoria Eye & Ear Hosp, Dublin, Ireland. RP Cashman, EC (reprint author), 92 Beacon St, Boston, MA 02108 USA. EM emma_cashman@dfci.harvard.edu NR 30 TC 0 Z9 0 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-1569 J9 ORL-J OTO-RHIN-LARYN JI ORL-J. Oto-Rhino-Laryngol. Relat. Spec. PY 2011 VL 73 IS 2 BP 105 EP 109 DI 10.1159/000324649 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA 744QM UT WOS:000289109400009 PM 21372617 ER PT J AU Wu, JY Kronenberg, HM AF Wu, Joy Y. Kronenberg, Henry M. BE Lorenzo, J Choi, Y Horowitz, M Takayanagi, H TI The Role of Bone Cells in Establishing the Hematopoietic Stem Cell Niche SO OSTEOIMMUNOLOGY: INTERACTIONS OF THE IMMUNE AND SKELETAL SYSTEMS LA English DT Article; Book Chapter ID PROSTAGLANDIN EP2 RECEPTOR; COLONY-STIMULATING FACTOR; PROGENITOR CELLS; SELF-RENEWAL; IN-VIVO; OSTEOBLAST DIFFERENTIATION; MARROW NICHE; BETA-CATENIN; N-CADHERIN; MICROENVIRONMENT C1 [Wu, Joy Y.; Kronenberg, Henry M.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Wu, JY (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 107 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-375671-8 PY 2011 BP 81 EP 99 DI 10.1016/B978-0-12-375670-1.10004-4 PG 19 WC Immunology SC Immunology GA BFC39 UT WOS:000319195900006 ER PT J AU Caplan, L Hines, AE Williams, E Prochazka, AV Saag, KG Cunningham, F Hutt, E AF Caplan, L. Hines, A. E. Williams, E. Prochazka, A. V. Saag, K. G. Cunningham, F. Hutt, E. TI An observational study of glucocorticoid-induced osteoporosis prophylaxis in a national cohort of male veterans with rheumatoid arthritis SO OSTEOPOROSIS INTERNATIONAL LA English DT Article DE Adverse effects; Glucocorticoids; Osteoporosis; Prevention ID CORTICOSTEROID-INDUCED OSTEOPOROSIS; CHRONIC KIDNEY-DISEASE; PRACTICE PATTERNS; HEALTH-CARE; ORAL CORTICOSTEROIDS; FRACTURE RISK; ELDERLY-WOMEN; BONE-DENSITY; PREVENTION; GUIDELINES AB We applied regression techniques to a large cohort of patients to understand why certain patients are prescribed medications to prevent glucocorticoid-induced osteoporosis (GIO). Rates of prescriptions to prevent osteoporosis were low. The presence of drugs and disorders associated with osteoporosis and gastrointestinal conditions actually are associated with a decreased likelihood of receiving osteoporosis-preventing medications. To understand why some patients are prescribed medications to prevent GIO while other patients are not, we examined whether there is an association among osteoporosis-inducing medical conditions or medications and prescriptions for osteoporosis prophylaxis in a large cohort of rheumatoid arthritis patients on chronic glucocorticoids. Department of Veterans' Affairs national administrative databases were used to construct a cohort (n = 9,605) and provide the data for this study. Multivariate logistic regression was performed to determine medical conditions and medications associated with dispensing of GIO-preventive medications, controlling for sociodemographic variables, comorbidities, glucocorticoid dosage, prior fractures, and rheumatoid arthritis severity. A subanalysis examined predictors of early GIO prevention. Subjects were more likely to receive GIO prophylaxis if they were older, African American, treated with multiple antirheumatic disease-modifying drugs, or received greater glucocorticoid exposure. The prescription of certain drug classes (loop diuretics and anticonvulsants) and conditions (malignancy, renal insufficiency, alcohol abuse, and hepatic disease) were associated with lower likelihood of GIO prophylaxis, despite putative links between these agents/conditions and osteoporosis. The presence of gastrointestinal disorders dramatically decreased likelihood of GIO prophylaxis. Few characteristics predicted the dispensing of GIO-preventing medications within 7 days of the initial glucocorticoid start date. Rates of prescriptions to prevent osteoporosis in a cohort of older men with rheumatoid arthritis on chronic glucocorticoids were low. Gastrointestinal disorders and drugs and disorders potentially linked to osteoporosis are associated with diminished odds of being prescribed GIO-preventing medications. C1 [Caplan, L.] Univ Colorado, Denver, CO 80045 USA. [Caplan, L.; Hines, A. E.; Williams, E.; Prochazka, A. V.; Hutt, E.] Denver VA Med Ctr, Denver, CO 80220 USA. [Caplan, L.; Prochazka, A. V.; Hutt, E.] Univ Colorado, Sch Med, Denver, CO 80045 USA. [Saag, K. G.] Univ Alabama, Ctr Educ & Res Therapeut Musculoskeletal Disorder, Birmingham, AL 35294 USA. [Saag, K. G.] Univ Alabama, Sch Med, Birmingham, AL USA. [Cunningham, F.] Vet Affairs Pharm Benefits Management, Hines, IL 60141 USA. RP Caplan, L (reprint author), Univ Colorado, POB 6511,B115, Denver, CO 80045 USA. EM liron.caplan@ucdenver.edu FU VA Health Services Research and Development service; VA HSR&D Career Development Award FX This project was supported by funding from the VA Health Services Research and Development service. Dr. Caplan is supported by a VA HSR&D Career Development Award. NR 52 TC 8 Z9 8 U1 0 U2 6 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD JAN PY 2011 VL 22 IS 1 BP 305 EP 315 DI 10.1007/s00198-010-1201-x PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 703TC UT WOS:000286003200037 PM 20358362 ER PT J AU Misra, D Berry, SD Broe, KE McLean, RR Cupples, LA Tucker, KL Kiel, DP Hannan, MT AF Misra, D. Berry, S. D. Broe, K. E. McLean, R. R. Cupples, L. A. Tucker, K. L. Kiel, D. P. Hannan, M. T. TI Does dietary protein reduce hip fracture risk in elders? The Framingham osteoporosis study SO OSTEOPOROSIS INTERNATIONAL LA English DT Article DE Dietary protein; Elders; Hip fracture; Osteoporosis; Population study; Protein intake ID POSTMENOPAUSAL WOMEN; BONE; STRENGTH; CALCIUM AB Association between dietary protein and fracture risk is unclear. We examined association between energy-adjusted protein intake and hip fracture risk in elders. The risk of hip fracture was reduced in upper quartiles of protein intake when compared with lowest quartile. Studies of the association between dietary protein intake and hip fracture risk are conflicting. Therefore, we examined protein intake and hip fracture risk in a population-based group of elderly men and women. Five hundred seventy-six women and 370 men from the Framingham Osteoporosis Study with no previous history of hip fracture completed Food Frequency Questionnaires. Energy-adjusted protein intake was evaluated as a continuous variable and as quartiles. Incidence rates and hazard ratios were calculated, adjusting for age, BMI, sex, and energy intake. Among 946 participants (mean age 75 years), mean protein intake was found to be 68 gm/d. Increased protein intake was associated with a decreased risk of hip fracture compared to those in the lowest quartile of protein intake (Q2 HR = 0.70, Q3 HR = 0.56, and Q4 HR = 0.63; all p values a parts per thousand yenaEuro parts per thousand 0.044), p for trend was 0.07. When a threshold effect was considered (Q2-4 vs Q1), intakes in the higher quartiles combined were associated with a significantly lower risk for hip fracture (HR = 0.63; p = 0.04). Our results are consistent with reduced risk of hip fracture with higher dietary protein intake. Larger prospective studies are needed to confirm and extend this finding in elderly men and women. C1 [Berry, S. D.; Broe, K. E.; McLean, R. R.; Kiel, D. P.; Hannan, M. T.] Hebrew SeniorLife, Inst Aging Res, Boston, MA 02131 USA. [Misra, D.] Boston Univ Med Ctr, Dept Rheumatol, Boston, MA USA. [Berry, S. D.; McLean, R. R.; Kiel, D. P.; Hannan, M. T.] Harvard Univ, Sch Med, Div Gerontol & Geriatr, BIDMC, Boston, MA USA. [Cupples, L. A.] Boston Univ Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Cupples, L. A.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Tucker, K. L.] Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA USA. [Tucker, K. L.] Northeastern Univ, Dept Hlth Sci, Boston, MA 02115 USA. RP Hannan, MT (reprint author), Hebrew SeniorLife, Inst Aging Res, 1200 Ctr St, Boston, MA 02131 USA. EM devyani.misra@bmc.org; hannan@hrca.harvard.edu RI Tucker, Katherine/A-4545-2010; OI Misra, Devyani/0000-0003-2881-7920; Cupples, L. Adrienne/0000-0003-0273-7965; Kiel, Douglas/0000-0001-8474-0310; Tucker, Katherine/0000-0001-7640-662X FU NHLBI NIH HHS [N01-HC-25195, N01HC25195]; NIA NIH HHS [AR/AG41398, AG14759]; NIAMS NIH HHS [R01 AR053205, R01 AR053205-04] NR 17 TC 23 Z9 25 U1 0 U2 8 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD JAN PY 2011 VL 22 IS 1 BP 345 EP 349 DI 10.1007/s00198-010-1179-4 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 703TC UT WOS:000286003200041 PM 20442986 ER PT J AU Vakharia, KT Lindsay, RW Knox, C Edwards, C Henstrom, D Weinberg, J Hadlock, TA Heaton, JT AF Vakharia, Kalpesh T. Lindsay, Robin W. Knox, Christopher Edwards, Colin Henstrom, Doug Weinberg, Julie Hadlock, Tessa A. Heaton, James T. TI The Effects of Potential Neuroprotective Agents on Rat Facial Function Recovery Following Facial Nerve Injury SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article DE facial paralysis; atorvastatin; sildenafil; darbepoetin; facial nerve crush injury ID NITRIC-OXIDE SYNTHASE; SCIATIC-NERVE; DARBEPOETIN-ALPHA; CRUSH INJURY; ERYTHROPOIETIN PROMOTES; NEURITE OUTGROWTH; IN-VIVO; STROKE; MODEL; REGENERATION AB Objective. To evaluate whether a series of pharmacologic agents with potential neuroprotective effects accelerate and/or improve facial function recovery after facial nerve crush injury. Study Design. Randomized animal study. Setting. Tertiary care facility. Methods. Eighty female Wistar-Hannover rats underwent head restraint implantation and daily conditioning. Animals then underwent unilateral crush injury to the main trunk of the facial nerve and were randomized to receive treatment with atorvastatin (n = 10), sildenafil (n = 10), darbepoetin (n = 20), or a corresponding control agent (n = 40). The return of whisking function was tracked throughout the recovery period. Results. All rats initiated the return of whisking function from nerve crush by day 12. Darbepoetin-treated rats (n = 20) showed significantly improved whisking amplitude and velocity across the recovery period, with several days of significant pairwise differences vs comparable control rats (n = 16) across the first 2 weeks of whisking function return. In contrast, rats treated with sildenafil (n = 10) and atorvastatin (n = 10) did not show significant improvement in whisking function recovery after facial nerve crush compared to controls. By week 8, all darbepoetin-treated animals and comparable nerve crush control animals fully recovered whisking function and were statistically indistinguishable. Conclusion. Among the 3 potentially neuroprotective agents evaluated, only darbepoetin administration resulted in accelerated recovery of whisking parameters after facial nerve crush injury. Further efforts to define the mechanism of action and translate these findings to the use of darbepoetin in the care of patients with traumatic facial paralysis are needed. C1 [Vakharia, Kalpesh T.; Knox, Christopher; Edwards, Colin; Henstrom, Doug; Weinberg, Julie; Hadlock, Tessa A.] Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA. [Lindsay, Robin W.] Natl Naval Med Ctr, Div Otolaryngol Head & Neck Surg, Bethesda, MD USA. [Heaton, James T.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Hadlock, TA (reprint author), Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA. EM tessa_hadlock@meei.harvard.edu FU American Academy of Otolaryngology-Head and Neck Surgery Foundation FX Resident research grant, American Academy of Otolaryngology-Head and Neck Surgery Foundation. NR 30 TC 6 Z9 6 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD JAN PY 2011 VL 144 IS 1 BP 53 EP 59 DI 10.1177/0194599810390892 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 808RR UT WOS:000293996600010 PM 21493387 ER PT J AU Bleier, BS Debnath, I O'Connell, BP Vandergrift, WA Palmer, JN Schlosser, RJ AF Bleier, Benjamin S. Debnath, Indranil O'Connell, Brendan P. Vandergrift, W. Alexander, III Palmer, James N. Schlosser, Rodney J. TI Preliminary Study on the Stability of Beta-2 Transferrin in Extracorporeal Cerebrospinal Fluid SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article DE CSF Leak; Beta-2 Transferrin; protease; encephalocele; cranial base surgery ID BETA-2-TRANSFERRIN; IDENTIFICATION; DIAGNOSIS; FISTULAS; LEAKAGE AB Objective. Detection of beta-2 transferrin in rhinorrhea fluid is a sensitive and specific method for the diagnosis of a cerebrospinal fluid (CSF) leak. Patients may be asked to collect this fluid at home to obtain an adequate volume for detection, and thus the age and storage conditions of these specimens may be variable upon analysis. The purpose of this study is to understand how age, storage temperature, and exposure to mucus affect the ability to detect beta-2 transferrin in CSF. Study Design. Case series with planned data collection. Setting. Tertiary care university hospital. Subjects and Methods. This study consists of 6 patients undergoing endoscopic CSF leak repair. CSF was collected directly from a lumbar drain (n = 4) or from nasal drainage (n = 2). Specimens were stored at 4 degrees C (n = 3) or room temperature (n = 3). Samples were tested for the presence of beta-2 transferrin for up to 7 days using standard immunofixation electrophoresis techniques. Results. Beta-2 transferrin was detected in all specimens through day 7 regardless of storage temperature or collection site (95% exact binomial confidence interval of 0%-46%). Conclusions. Beta-2 transferrin remains detectable in extracorporeal CSF for up to 7 days regardless of storage at room temperature or exposure to nasal mucus. Negative detection in patient specimens up to a week old is therefore not likely to be caused by protein degradation. C1 [Bleier, Benjamin S.] Harvard Univ, Dept Otolaryngol Head & Neck Surg, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. [Debnath, Indranil] Washington Univ, Sch Med, St Louis, MO USA. [O'Connell, Brendan P.; Vandergrift, W. Alexander, III; Schlosser, Rodney J.] Med Univ S Carolina, Charleston, SC 29425 USA. [Palmer, James N.] Hosp Univ Penn, Philadelphia, PA 19104 USA. RP Bleier, BS (reprint author), Harvard Univ, Dept Otolaryngol Head & Neck Surg, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA. EM bleierb@gmail.com NR 9 TC 4 Z9 4 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD JAN PY 2011 VL 144 IS 1 BP 101 EP 103 DI 10.1177/0194599810390887 PG 3 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 808RR UT WOS:000293996600019 PM 21493396 ER PT J AU Riess, H Kelley, JM Bailey, R Konowitz, PM Gray, ST AF Riess, Helen Kelley, John M. Bailey, Robert Konowitz, Paul M. Gray, Stacey Tutt TI Improving Empathy and Relational Skills in Otolaryngology Residents: A Pilot Study SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article DE patient-doctor relationship; empathy; relational skills; patient-doctor communication; otolaryngology AB Physician empathy and relational skills are critical factors predicting quality of care, patient safety, patient satisfaction, and decreasing malpractice claims. Studies indicate that physician empathy declines throughout medical training, yet little is published about methods to enhance empathy, especially in surgical residency training. The Accreditation Council for Graduate Medical Education requires competencies in 6 areas, including interpersonal skills and communication. To address this important problem, the first author developed an innovative empathy-relational skills training protocol focusing on the underlying neurobiological mechanisms of empathy and the interpersonal processes that positively affect the patient-doctor relationship. The authors tested the effectiveness of this protocol in a pilot study with 11 otolaryngology residents. Results showed that a brief series of 3 empathy training sessions can significantly improve physicians' knowledge of the neurobiology and physiology of empathy, as well as their self-reported capacity to empathize with patients. A trend toward increased patient satisfaction was observed. C1 [Riess, Helen; Kelley, John M.; Bailey, Robert] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Kelley, John M.] Endicott Coll, Dept Psychol, Beverly, MA USA. [Konowitz, Paul M.; Gray, Stacey Tutt] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. [Konowitz, Paul M.; Gray, Stacey Tutt] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Riess, H (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Wang ACC Suite 812, Boston, MA 02114 USA. EM hriess@partners.org FU Massachusetts Eye and Ear Infirmary (MEEI); Massachusetts General Hospital (MGH); Arnold P. Gold Foundation; David Judah Fund; Josiah Macy Jr. Foundation; Risk Management Foundation FX Massachusetts Eye and Ear Infirmary (MEEI) and Massachusetts General Hospital (MGH). MEEI and MGH had no role in the study design and conduct; collection, analysis, and interpretation of the data; and writing or approval of the manuscript.; Arnold P. Gold Foundation, David Judah Fund, Josiah Macy Jr. Foundation, and Risk Management Foundation. The foundations had no role in the study design and conduct; collection, analysis, and interpretation of the data; and writing or approval of the manuscript. NR 5 TC 10 Z9 11 U1 0 U2 4 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD JAN PY 2011 VL 144 IS 1 BP 120 EP 122 DI 10.1177/0194599810390897 PG 3 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 808RR UT WOS:000293996600023 PM 21493400 ER PT J AU Quesnel, AM Lee, DJ AF Quesnel, Alicia M. Lee, Daniel J. TI Extensive Osteomas of the Temporal-Parietal-Occipital Skull SO OTOLOGY & NEUROTOLOGY LA English DT Editorial Material ID BONE C1 [Lee, Daniel J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Lee, DJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM daniel_lee@meei.harvard.edu NR 5 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD JAN PY 2011 VL 32 IS 1 BP E3 EP E4 DI 10.1097/MAO.0b013e3181cdd928 PG 2 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 694XE UT WOS:000285334400002 PM 20087243 ER PT J AU Borckardt, JJ Reeves, ST Frohman, H Madan, A Jensen, MP Patterson, D Barth, K Smith, AR Gracely, R George, MS AF Borckardt, Jeffrey J. Reeves, Scott T. Frohman, Heather Madan, Alok Jensen, Mark P. Patterson, David Barth, Kelly Smith, A. Richard Gracely, Richard George, Mark S. TI Fast left prefrontal rTMS acutely suppresses analgesic effects of perceived controllability on the emotional component of pain experience SO PAIN LA English DT Article DE TMS; Pain; Transcranial magnetic stimulation; Control; Prefrontal cortex ID TRANSCRANIAL MAGNETIC STIMULATION; CHRONIC NEUROPATHIC PAIN; DORSAL RAPHE NUCLEUS; MOTOR CORTEX RTMS; STRESSOR CONTROLLABILITY; LEARNED HELPLESSNESS; CORTICAL STIMULATION; PLACEBO; DEPRESSION; RELIEF AB The prefrontal cortex may be a promising target for transcranial magnetic stimulation (TMS) in the management of pain. It is not clear how prefrontal TMS affects pain perception, but previous findings suggest that ventral lateral and medial prefrontal circuits may comprise an important part of a circuit of perceived controllability regarding pain, stress, and learned helplessness. Although the left dorsolateral prefrontal cortex is a common TMS target for treating clinical depression as well as modulating pain, little is known about whether TMS over this area may affect perceived controllability. The present study explored the immediate effects of fast TMS over the left dorsolateral prefrontal cortex on the analgesic effects of perceived pain controllability. Twenty-four healthy volunteers underwent a laboratory pain task designed to manipulate perception of pain controllability. Real TMS, compared with sham, suppressed the analgesic benefits of perceived control on the emotional dimension of pain, but not the sensory/discriminatory dimension. Findings suggest that, at least acutely, fast TMS over the left dorsolateral prefrontal cortex may interrupt the perceived-controllability effect on the emotional dimension of pain experience. Although it is not clear whether this cortical area is directly involved with modulating perceived controllability or whether downstream effects are responsible for the present findings, it appears possible that left dorsolateral prefrontal TMS may produce analgesic effects by acting through a cortical perceived-control circuit regulating limbic and brainstem areas of the pain circuit. (C) 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 [Borckardt, Jeffrey J.; Madan, Alok; Barth, Kelly; George, Mark S.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Borckardt, Jeffrey J.; Reeves, Scott T.; Frohman, Heather; Smith, A. Richard] Med Univ S Carolina, Dept Anesthesiol & Perioperat Med, Charleston, SC 29425 USA. [Jensen, Mark P.; Patterson, David] Univ Washington, Sch Med, Dept Rehabil Med, Seattle, WA 98195 USA. [George, Mark S.] Med Univ S Carolina, Dept Neurol, Charleston, SC 29425 USA. [George, Mark S.] Med Univ S Carolina, Dept Radiol, Charleston, SC 29425 USA. [Gracely, Richard] Univ N Carolina, Sch Dent, Dept Endodont, Ctr Neurosensory Disorders, Chapel Hill, NC USA. [George, Mark S.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Borckardt, JJ (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, 171 Ashley Ave, Charleston, SC 29425 USA. EM borckard@musc.edu FU National Institutes Health (NINDS, NINR, NIDA); South Carolina Translational Research Program; American Society for Gastrointestinal Endoscopy; Obesity Society (Covidien); National Institute for Neurological Disorders and Stroke; NIH; Glaxo-Smith Kline; Jazz Pharmaceuticals; Brainsway; Cephos; Force Protection; NIAMS; NIGMS; NIHCD; NIAMS at NIH; NINDS at NIH FX Dr. Borckardt receives funding from the National Institutes Health (NINDS, NINR, NIDA), the South Carolina Translational Research Program, The American Society for Gastrointestinal Endoscopy, and The Obesity Society (Covidien). The present study was funded by the National Institute for Neurological Disorders and Stroke. Dr. George reports research grants in the past 5 years from NIH, Glaxo-Smith Kline, Jazz Pharmaceuticals, Brainsway, Cephos, and Force Protection. He has been an unpaid advisor to Brainsonix, Brainsway, Neuronetics, Neostim and Neosync (as they make products related to TMS), and a paid advisor to Jazz, Cyberonics, Neuropace, and Puretech ventures. The full amount of his advisory income has never been more than 10% of his university salary. MUSC has 2 patent applications in Dr. George's name on combining TMS with MRI imaging. Dr. Patterson receives funding from NIAMS and NIGMS, Dr. Jensen receives funding from NIHCD, and Dr. Gracely receives funding from NIAMS and NINDS at NIH. NR 54 TC 18 Z9 18 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD JAN PY 2011 VL 152 IS 1 BP 182 EP 187 DI 10.1016/j.pain.2010.10.018 PG 6 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 695ZD UT WOS:000285410800029 PM 21122992 ER PT J AU Wang, SX Zhang, L Ma, YX Chen, LC Tian, YH Mao, JR Martyn, JJA AF Wang, Shuxing Zhang, Lin Ma, Yuxin Chen, Lucy Tian, Yinghong Mao, Jianren Martyn, Jeevendra J. A. TI Nociceptive Behavior Following Hindpaw Burn Injury in Young Rats: Response to Systemic Morphine SO PAIN MEDICINE LA English DT Article DE Burn Injury; Allodynia; Hyperalgesia; NOS; NMDAR; PKB; Akt; GSK-3 beta ID PROTEIN-KINASE-C; NITRIC-OXIDE SYNTHASE; NF-KAPPA-B; FORKHEAD TRANSCRIPTION FACTOR; PERIPHERAL-NERVE INJURY; SERINE-THREONINE KINASE; SPINAL-CORD; NEUROPATHIC PAIN; SECONDARY HYPERALGESIA; THERMAL HYPERALGESIA AB Objective. Develop a burn injury model in young age rats. Background. Management of pain after burn injury in pediatric patients is an unresolved clinical issue. Methods. A burn injury model in young rats of 3-4 weeks old was developed by briefly immersing the dorsal part of the right hindpaw in a hot water bath (85 degrees C) for 12 seconds under pentobarbital anesthesia. Results. Burn injury, but not sham control, induced nociceptive behaviors (mechanical allodynia, thermal hyperalgesia) when examined on post-injury day 2, 4, and 7. In burn-injured rats, there was the upregulated expression of the NR1 subunit of the N-methyl-d-aspartate (NMDA) receptor, Akt1, Akt2, and protein kinase C gamma (PKC gamma), but downregulated expression of neuronal nitric oxide synthase (NOS), inducible NOS, and glycogen synthase kinase-3 beta, within the spinal cord dorsal horn ipsilateral to burn injury. Moreover, intraperitoneal administration of a clinically available NMDA receptor antagonist dextromethorphan (30 mg/kg, once daily x 7 days beginning on day 7 after burn injury) attenuated mechanical allodynia and thermal hyperalgesia in burn-injured rats. Different from our previous finding in adult burn-injured rats; however, burn injury in young rats of this age did not spontaneously shift the morphine antinociceptive response curve to the right within the dose range used in the study when exposed to morphine for the first time, suggesting that the development of intrinsic tolerance to morphine antinociception may be different from adult rats following burn injury. Conclusions. Our data suggest that this model may be used to explore the mechanisms of burn injury-induced nociception in young rats and to differentiate the sequelae from burn injury between adult and young rats under certain experimental conditions. C1 [Wang, Shuxing; Zhang, Lin; Ma, Yuxin; Chen, Lucy; Tian, Yinghong; Mao, Jianren] Harvard Univ, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, MGH Ctr Translat Pain Res,Sch Med, Boston, MA 02114 USA. [Wang, Shuxing; Martyn, Jeevendra J. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wang, Shuxing; Martyn, Jeevendra J. A.] Shriners Hosp Children, Boston, MA USA. RP Mao, JR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, MGH Ctr Translat Pain Res,Sch Med, 15 Parkman St, Boston, MA 02114 USA. EM jmao@partners.org; jmartyn@partners.org FU Shriners Hospital for Children in Boston; NIH [DE18214, DE18538] FX This work was supported by a grant from Shriners Hospital for Children in Boston and NIH RO1 grants DE18214 and DE18538. NR 59 TC 8 Z9 9 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1526-2375 J9 PAIN MED JI Pain Med. PY 2011 VL 12 IS 1 BP 87 EP 98 DI 10.1111/j.1526-4637.2010.01021.x PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 705FN UT WOS:000286114400013 PM 21143761 ER PT J AU Vazquez, R Johnson, DW Ahmed, SU AF Vazquez, Rafael Johnson, Daniel W. Ahmed, Shihab U. TI Epidural Blood Patch for Postdural Puncture Positional Vertigo SO PAIN MEDICINE LA English DT Article DE Epidural Blood Patch; Vertigo AB Study Design. Case report. Objective. To report an unusual case of refractory positional vertigo without headache that developed after the placement of an epidural catheter for postoperative pain and that was treated with an epidural blood patch. Summary of the Background Data. Although it is common practice to use epidural blood patch (EBP) to treat positional headache from postdural puncture (PDP), the literature is limited to one letter to the editor describing PDP positional vertigo treated with EBP. Methods. Description of a clinical case. Results. Here we present a case where the patient presented with the complaint of vertigo without headache and had a characteristic onset with upright position and marked relief when lying down. The patient received an EBP with complete resolution of her symptoms. Conclusions. This case illustrates patient can present with an isolated symptom such as dizziness without headache after PDP. The patient received an EBP with complete resolution of her symptom of postdural dizziness. C1 [Vazquez, Rafael; Johnson, Daniel W.; Ahmed, Shihab U.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Ahmed, SU (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM sahmed@partners.org NR 11 TC 3 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1526-2375 J9 PAIN MED JI Pain Med. PY 2011 VL 12 IS 1 BP 148 EP 151 DI 10.1111/j.1526-4637.2010.00995.x PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 705FN UT WOS:000286114400019 PM 21087409 ER PT J AU Jamison, RN Washington, TA Gulur, P Fanciullo, GJ Arscott, JR McHugo, GJ Baird, JC AF Jamison, Robert N. Washington, Tabitha A. Gulur, Padma Fanciullo, Gilbert J. Arscott, John R. McHugo, Gregory J. Baird, John C. TI Reliability of a Preliminary 3-D Pain Mapping Program SO PAIN MEDICINE LA English DT Article DE Pain Assessment; Pain Mapping; Computer Methods ID LOW-BACK-PAIN; DRAWINGS; CLASSIFICATION; FIBROMYALGIA AB Objective. The objective of this preliminary investigation was to evaluate the test-retest reliability of a new pain assessment method referred to as 3-D pain mapping. Methods. In Study 1, 101 chronic noncancer pain patients from four sites reported their pain using the method on two occasions (separated by approximately 10 days). The patients marked intensity, surface location, and depth of pain on a 3-D computer display of a male or female body. The model body could be rotated in order to mark multiple pain locations. In Study 2, 25 patients from a single site were tested with a revised version of the mapping program used in Study 1. Each patient gave ratings on two occasions separated by approximately 1 week. Results. In Study 1, the intra-class correlations of the 3-D pain mapping measures were moderate to high for maximum pain intensity (0.73), vertical location of the point of maximum pain (0.94), and the number of pain marks (0.84). Correlations were low for the horizontal location of the point of maximum pain (0.56) and for the depth of pain (0.50). In Study 2, using the revised program, intra-class correlations were moderate for pain intensity (0.76), and high for the vertical (0.99) and horizontal (0.98) locations of the point of maximum pain, number of pain marks (0.89), and the depth of pain (0.84). Conclusion. Three-dimensional pain mapping enables patients to report the location and intensity of their pain on all parts of the body, and such ratings are highly reliable. Future studies are needed to determine whether the clinical value of this method can improve the accuracy of pain diagnoses and the quality of pain management. C1 [Jamison, Robert N.] Brigham & Womens Hosp, Pain Management Ctr, Dept Anesthesia, Chestnut Hill, MA 02467 USA. [Jamison, Robert N.] Brigham & Womens Hosp, Dept Psychiat, Chestnut Hill, MA 02467 USA. [Jamison, Robert N.] Harvard Univ, Sch Med, Pain Management Ctr, Chestnut Hill, MA USA. [Washington, Tabitha A.; Fanciullo, Gilbert J.] Dartmouth Hitchcock Med Ctr, Dept Anesthesiol, Lebanon, NH 03766 USA. [Gulur, Padma] Massachusetts Gen Hosp, Dept Anesthesiol, Boston, MA 02114 USA. [McHugo, Gregory J.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Community & Family Med, Hanover, NH 03756 USA. [McHugo, Gregory J.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Psychiat, Hanover, NH 03756 USA. [Baird, John C.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Med, Hanover, NH 03756 USA. [Arscott, John R.; Baird, John C.] Psychol Applicat LLC, S Pomfret, VT USA. RP Jamison, RN (reprint author), Brigham & Womens Hosp, Pain Management Ctr, Dept Anesthesia, 850 Boylston St,Suite 320, Chestnut Hill, MA 02467 USA. EM rjamison@partners.org OI Jamison, Robert/0000-0003-1768-0906 FU National Institute of Mental Health [R43NS061388-01A2] FX The authors wish to thank Carol Santa Maria, Naomi Shin, Li Chen, Kathleen Howard, and Caroline Holcomb. This research was supported in part by Grant # R43NS061388-01A2 from the National Institute of Mental Health (PI: J. C. Baird). NR 19 TC 6 Z9 6 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1526-2375 J9 PAIN MED JI Pain Med. PY 2011 VL 12 IS 3 BP 344 EP 351 DI 10.1111/j.1526-4637.2010.01049.x PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 735MS UT WOS:000288419700005 PM 21276186 ER PT J AU Zhang, Y Wood, MJ Gilligan, C AF Zhang, Yi Wood, Monica J. Gilligan, Christopher TI Spinal Cord Stimulation in a Patient with Spinal Epidural Lipomatosis SO PAIN MEDICINE LA English DT Article DE Spinal Cord Stimulation; Spinal Epidural Lipomatosis; Lower Extremity Pain; Impedance ID SYNDROME SECONDARY; INJECTIONS; PAIN; FAT AB Background and Objective. Spinal cord stimulation is the most commonly used implantable neurostimulation modality for management of pain syndromes. For treatment of lower extremity pain, the spinal cord stimulator lead is typically placed in the thoracic epidural space, at the T10-T12 levels. Typically, satisfactory stimulation can be obtained relatively easily. Anatomical variability in the epidural space, such as epidural scarring, has been reported to prevent successful implantation of spinal cord stimulators. Spinal epidural lipomatosis describes an abnormal overgrowth of adipose tissue in the extradural space. Cases have documented spinal epidural lipomatosis complicating intrathecal baclofen pump implantation or causing repeated failure of epidural analgesia. However, so far, there is no published literature describing how spinal epidural lipomatosis affects spinal cord stimulation. Case Report. We report a case of spinal cord stimulation in a patient with spinal epidural lipomatosis. Very high impedance was encountered during the trial spinal cord stimulator lead placement. Satisfactory stimulation was only obtained after repeated repositioning of the spinal cord stimulator trial lead. Post-procedure thoracic spine magnetic resonance imaging revealed marked thoracic epidural lipomatosis. At the level where satisfactory stimulation was obtained, the thickness of the epidural fat was within normal limits. The patient eventually underwent placement of a laminotomy lead with good coverage and pain relief. Conclusion. Spinal epidural lipomatosis significantly increases the impedance in the epidural space, making effective neurostimulation very difficult to obtain. Physicians should consider the possibility of spinal epidural lipomatosis when very high impedances are encountered during lead placement. C1 [Gilligan, Christopher] Harvard Univ, Massachusetts Gen Hosp, Sch Med,MGH Ctr Pain Med, Dept Anesthesia Crit Care & Pain Med,Div Pain Med, Boston, MA 02114 USA. [Wood, Monica J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Gilligan, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,MGH Ctr Pain Med, Dept Anesthesia Crit Care & Pain Med,Div Pain Med, 15 Parkman St, Boston, MA 02114 USA. EM cgilligan@partners.org NR 21 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1526-2375 J9 PAIN MED JI Pain Med. PY 2011 VL 12 IS 3 BP 377 EP 381 DI 10.1111/j.1526-4637.2011.01057.x PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 735MS UT WOS:000288419700009 PM 21332929 ER PT J AU Nicolaidis, C Chianello, T Gerrity, M AF Nicolaidis, Christina Chianello, Terry Gerrity, Martha TI Development and Preliminary Psychometric Testing of the Centrality of Pain Scale SO PAIN MEDICINE LA English DT Article DE Chronic Pain; Quality of Life; Health Function ID PATIENT HEALTH QUESTIONNAIRE; IMMPACT RECOMMENDATIONS; CLINICAL-TRIALS; PRIME-MD; VALIDATION; VALIDITY; RELIABILITY; DEPRESSION; SEVERITY; UTILITY AB Objective. The objective of the study was to develop and begin to evaluate a new measure of the centrality of pain in patients' lives. Design. The study was designed as a cross-sectional survey and cognitive interviews. Setting. The study was set in an academic general internal medicine clinic. Patients. Sixty-five adult internal medicine patients with chronic nonmalignant pain (CNMP) participated in the study. Outcome Measures. We assessed content validity and clarity of the 10-item Centrality of Pain Scale (COPS) by soliciting feedback from chronic pain experts and by conducting cognitive interviews with patients with CNMP. We assessed internal consistency reliability using Cronbach's alpha. We assessed construct validity by comparing the COPS with other measures of chronic pain morbidity including pain severity, depression, anxiety, physical and mental health function, posttraumatic stress disorder, quality of life, and provider assessment. Results. Health care providers felt the COPS had excellent face validity. Cognitive interviews revealed that patients' understanding of the items matched the intended construct, the scale measured an important concept, and items were easy to understand. The COPS had excellent internal consistency (alpha = 0.9). It was negatively associated with age (r = -0.29; P = 0.02), but not with other demographic characteristics. Higher COPS scores were associated with poorer physical (r = -0.48; P < 0.001) and mental (r = -0.39; P = 0.002) health function, quality of life (r = -0.36; P = 0.004), and provider assessment of stability (r = -0.38; P = 0.004) as well as with greater pain grade (r = 0.55; P < 0.001), and depression (r = 0.63; P < 0.001). In multivariate analyses, age, physical and mental health function, and depression were independently associated with COPS. Conclusions. The COPS has excellent internal consistency and construct validity. Additional studies are needed to further validate the scale. C1 [Nicolaidis, Christina] Oregon Hlth & Sci Univ, Div Gen Med & Geriatr, Dept Med, Portland, OR 97239 USA. [Nicolaidis, Christina] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97239 USA. [Chianello, Terry] Portland State Univ, Sch Social Work, Portland, OR 97207 USA. [Gerrity, Martha] Portland VA Med Ctr, Portland, OR USA. RP Nicolaidis, C (reprint author), Oregon Hlth & Sci Univ, Div Gen Med & Geriatr, Dept Med, L475,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM nicolaid@ohsu.edu FU Oregon Health & Science University Division of General Internal Medicine and Geriatrics; National Institute of Mental Health [K23MH073008] FX This study was funded by the Oregon Health & Science University Division of General Internal Medicine and Geriatrics. The study would not have been possible without the support of Judith L. Bowen, MD, who was serving as the Division Chief at the time the study was being conducted. We would like to thank Ruth Liebowitz, PhD, for help in conceptualizing the Centrality of Pain Scale and the members of the Society of General Internal Medicine Chronic Pain Interest Group, Erik Fromme, MD, MPH, and Ben Morasco, PhD, for reviewing early versions of the scale. We wish to thank medical assistants Cecilia Aflleje, Hope Roach, and Tony Thao for their help in incorporating the study into a busy clinical practice. We would also like to acknowledge Ana Hilde, MPH, and Angie Mejia, MSW, for administrative support. Dr Nicolaidis' time was supported, in part, via a career development award from the National Institute of Mental Health (K23MH073008). NR 20 TC 4 Z9 4 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1526-2375 J9 PAIN MED JI Pain Med. PY 2011 VL 12 IS 4 BP 612 EP 617 DI 10.1111/j.1526-4637.2011.01072.x PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 751OX UT WOS:000289628500008 PM 21392248 ER PT J AU Dragovich, A Trainer, RJ AF Dragovich, Anthony Trainer, Robert J. TI A Report of 3 Soldiers Returned to Full Duty after Lumbar Radiofrequency Facet Denervation in a Theater of War SO PAIN MEDICINE LA English DT Article DE Zygapophysial; Nerve Ablation; Soldiers; Combat; Axial; Low Back Pain ID LOW-BACK-PAIN; DOUBLE-BLIND; JOINT DENERVATION; TRIAL; EFFICACY; NEUROTOMY; SCIATICA AB Objective. To provide the advanced interventional procedure of zygapophysial joint neurotomy to soldiers meeting the diagnostic criteria in a combat environment and thus reduce medical evacuations of soldiers from a theater of war. Design. Retrospective chart review was performed on three consecutive soldiers who received neuroablation of the lumbar ZP joint. Patients received single MBB with 1 cc of 1% lidocaine at the b/l L3-L5 levels considered diagnostic if > 50% analgesia was achieved concordant with duration of anesthetic. Setting. All procedures were co-performed by the two authors at the Ibn Sina hospital in Baghdad, Iraq over a 3-month period. Patients. Three consecutive patients with > 50% pain relief from diagnostic medial branch blocks were treated with radiofrequency ablation of the bilateral L3-L4 medial branch nerves and L5 posterior primary ramus. Interventions. Sensory test stimulation at 50 Hz and motor stimulation at 2 Hz were performed at each level. The nerves were then lesioned at 80 degrees Centigrade for 90 seconds after injection of lidocaine and methylprednisolone. Outcome Measures. Procedure was considered successful if patients were able to wear body armour without significant discomfort (at least 1 hour/day). Results and Conclusions. Medical evacuation from Iraq was prevented and all soldiers returned to rigorous combat duties including the wearing of body armour daily. We believe to be the first to report on the use of RF nerve ablation in a war time setting and with this functional outcome. C1 [Dragovich, Anthony] Beth Israel Deaconness Med Ctr, Dept Pain Med, Boston, MA 02445 USA. [Trainer, Robert J.] Walter Reed Army Med Ctr, Dept Anesthesiol, Washington, DC 20307 USA. RP Trainer, RJ (reprint author), Beth Israel Deaconness Med Ctr, Dept Pain Med, 1 Brookline Ave, Boston, MA 02445 USA. EM rob.trainer@gmail.com NR 15 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1526-2375 J9 PAIN MED JI Pain Med. PY 2011 VL 12 IS 4 BP 679 EP 681 DI 10.1111/j.1526-4637.2010.01041.x PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 751OX UT WOS:000289628500017 PM 21223502 ER PT J AU Kulich, R Loeser, JD AF Kulich, Ronald Loeser, John D. TI The Business of Pain Medicine: The Present Mirrors Antiquity SO PAIN MEDICINE LA English DT Article DE Pain Medicine; Ethics; Historical; Public Policy; Liability ID COST-EFFECTIVENESS; OF-INTEREST; INDUSTRY; GUIDELINES; INNOVATION; REFORM AB The practice of pain medicine is often considered a fledgling field, as are the economic, business, and related ethical issues associated with providing these services. This article first traces the history of pain care and its relationships to industry and business, as well as the impact of government regulations over the ages. The authors challenge the view that the commonly discussed health care issues facing pain medicine are new by tracing the business and regulatory-related antecedents of pain care practice from the first through 21st century. The controversies associated with the practice of delivering pain-related health care services in an ethical manner are discussed with specific reference to the early work of clinicians, health care activists, and policy makers. The early activities of noteworthy individuals such as Pliny the Great, Hua T'o, John Locke, Benjamin Franklin, Oliver Wendell Holmes Sr., William Morton, Henry and William James, Heinrick Dresser, and other recent health care activists are reviewed. Issues of practitioner liability and regulatory restrictions on practice are also discussed in a historical context. The authors conclude that familiar ethical dilemmas commonly arose in past centuries, and history may be repeating itself with respect to the concerns now being discussed within our field. These arguments are reflected against the pain medicine Ethics Charters of the American Academy of Pain Medicine throughout the document. Finally, we outline the challenges for the present and future. With an understanding of these eight historical events as a backdrop, we may be at an opportune time to better address these issues in a manner that could provide the most effective pain care in our society. C1 [Kulich, Ronald] Tufts Sch Med, Craniofacial Pain & Headache Ctr, Boston, MA USA. [Kulich, Ronald] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Pain Med, Boston, MA USA. [Loeser, John D.] Univ Washington, Dept Neurol Surg, Seattle, WA 98195 USA. [Loeser, John D.] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA. RP Kulich, R (reprint author), Tufts Sch Dent Med, Craniofacial Pain & Headache Ctr, 1 Kneeland St, Boston, MA 02111 USA. EM rkulich@partners.org NR 67 TC 8 Z9 8 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1526-2375 J9 PAIN MED JI Pain Med. PY 2011 VL 12 IS 7 BP 1063 EP 1075 DI 10.1111/j.1526-4637.2011.01176.x PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 791WA UT WOS:000292697100013 PM 21699650 ER PT J AU Reid, MC Bennett, DA Chen, WG Eldadah, BA Farrar, JT Ferrell, B Gallagher, RM Hanlon, JT Herr, K Horn, SD Inturrisi, CE Lemtouni, S Lin, YW Michaud, K Morrison, RS Neogi, T Porter, LL Solomon, DH Von Korff, M Weiss, K Witter, J Zacharoff, KL AF Reid, M. Cary Bennett, David A. Chen, Wen G. Eldadah, Basil A. Farrar, John T. Ferrell, Bruce Gallagher, Rollin M. Hanlon, Joseph T. Herr, Keela Horn, Susan D. Inturrisi, Charles E. Lemtouni, Salma Lin, Yu Woody Michaud, Kaleb Morrison, R. Sean Neogi, Tuhina Porter, Linda L. Solomon, Daniel H. Von Korff, Michael Weiss, Karen Witter, James Zacharoff, Kevin L. TI Improving the Pharmacologic Management of Pain in Older Adults: Identifying the Research Gaps and Methods to Address Them SO PAIN MEDICINE LA English DT Review DE Analgesic Use; Chronic Noncancer Pain; Older Adults ID CHRONIC NONCANCER PAIN; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; OBSTRUCTIVE PULMONARY-DISEASE; PERSISTENT NONMALIGNANT PAIN; NURSING-HOME RESIDENTS; NATIONAL-DATA-BANK; MUSCULOSKELETAL PAIN; UNITED-STATES; COGNITIVE IMPAIRMENT; RHEUMATIC-DISEASES AB Objective. There has been a growing recognition of the need for better pharmacologic management of chronic pain among older adults. To address this need, the National Institutes of Health Pain Consortium sponsored an "Expert Panel Discussion on the Pharmacological Management of Chronic Pain in Older Adults" conference in September 2010 to identify research gaps and strategies to address them. Specific emphasis was placed on ascertaining gaps regarding use of opioid and nonsteroidal anti-inflammatory medications because of continued uncertainties regarding their risks and benefits. Design. Eighteen panel members provided oral presentations; each was followed by a multidisciplinary panel discussion. Meeting transcripts and panelists' slide presentations were reviewed to identify the gaps and the types of studies and research methods panelists suggested could best address them. Results. Fifteen gaps were identified in the areas of treatment (e.g., uncertainty regarding the long-term safety and efficacy of commonly prescribed analgesics), epidemiology (e.g., lack of knowledge regarding the course of common pain syndromes), and implementation (e.g., limited understanding of optimal strategies to translate evidence-based pain treatments into practice). Analyses of data from electronic health care databases, observational cohort studies, and ongoing cohort studies (augmented with pain and other relevant outcomes measures) were felt to be practical methods for building an age-appropriate evidence base to improve the pharmacologic management of pain in later life. Conclusion. Addressing the gaps presented in the current report was judged by the panel to have substantial potential to improve the health and wellbeing of older adults with chronic pain. C1 [Reid, M. Cary] Weill Cornell Med Ctr, Div Geriatr & Gerontol, New York, NY 10065 USA. [Bennett, David A.] Rush Univ, Med Ctr, Dept Neurol Sci, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA. [Chen, Wen G.] NIA, Behav & Syst Neurosci Branch, Div Neurosci, Bethesda, MD 20892 USA. [Eldadah, Basil A.] NIA, Div Geriatr & Clin Gerontol, Bethesda, MD 20892 USA. [Farrar, John T.] Univ Penn, Dept Epidemiol, Philadelphia, PA 19104 USA. [Farrar, John T.] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Ferrell, Bruce] UCLA Sch Med, Div Geriatr, Los Angeles, CA USA. Univ Penn, Sch Med, Philadelphia VA Med Ctr, Penn Pain Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Anesthesiol & Crit Care, Philadelphia, PA 19104 USA. [Gallagher, Rollin M.] Univ Pittsburgh, Dept Geriatr Med, Pittsburgh, PA USA. [Hanlon, Joseph T.] VA Pittsburgh Hlth Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Herr, Keela] Univ Iowa, Coll Nursing, John A Hartford Ctr Geriatr Nursing Excellence, Iowa City, IA 52242 USA. [Horn, Susan D.] Inst Clin Outcomes Res, Salt Lake City, UT USA. [Inturrisi, Charles E.] Weill Cornell Med Coll, Dept Pharmacol, New York, NY USA. [Lemtouni, Salma; Weiss, Karen] US FDA, Ctr Drug Evaluat & Res, Washington, DC 20204 USA. [Lin, Yu Woody] Natl Inst Drug Abuse, Div Clin Neurosci & Behav Res, Bethesda, MD USA. [Michaud, Kaleb] Univ Nebraska Med Ctr, Omaha, NE USA. [Michaud, Kaleb] Natl Data Bank Rheumat Dis, Wichita, KS USA. [Morrison, R. Sean] Mt Sinai Sch Med, Brookdale Dept Geriatr & Palliat Med, New York, NY USA. [Neogi, Tuhina] Boston Univ, Sch Med, Sect Clin Epidemiol Res & Training Unit, Boston, MA 02118 USA. [Neogi, Tuhina] Boston Univ, Sch Med, Rheumatol Sect, Boston, MA 02118 USA. [Porter, Linda L.] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. [Solomon, Daniel H.] Harvard Univ, Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Sch Med, Boston, MA 02115 USA. [Solomon, Daniel H.] Brigham & Womens Hosp, Div Rheumatol, Boston, MA 02115 USA. [Von Korff, Michael] Ctr Hlth Studies Grp Hlth Cooperat, Seattle, WA USA. [Witter, James] NIAMSD, Div Skin & Rheumat Dis, Bethesda, MD 20892 USA. [Zacharoff, Kevin L.] Inflexxion Inc, Newton, MA USA. RP Reid, MC (reprint author), Weill Cornell Med Ctr, Div Geriatr & Gerontol, 525 E 68th St,Box 39, New York, NY 10065 USA. EM mcr2004@med.cornell.edu RI Inturrisi, Charles/E-7365-2013; OI Reid, Cary/0000-0001-8117-662X; Neogi, Tuhina/0000-0002-9515-1711 FU Edward R. Roybal Center for Translational Research on Aging, NIA [P30 AG22845]; NIA [P30AG10161, R01AG15819, R01AG17917, P30AG028741, K24AG022345, R01AG030141, R01AG034181]; National Center for Research Resources [UL1RR024134]; National Institute of Aging [P30AG024827, T32AG021885, K07AG033174, R01AG034056, R56AG027017, U01AG012553]; National Institute of Mental Health [R34MH082682]; National Institute of Nursing [R01NR010135]; AHRQ [R01HS017695, R01HS018721, K12HS019461]; VA Health Services [IIR-06-062]; National Cancer Institute [R01CA115363]; National Institute of Nursing Research [T32NR011147]; NIDA [RC2DA028928, R01DA022557]; National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) [RC1AR058601, K23AR055127, K24AR055989] FX The authors would like to acknowledge the participation of all the conference attendees, who are listed in Appendix A. Dr. Reid was supported by an Edward R. Roybal Center for Translational Research on Aging Award (P30 AG22845) provided by the NIA. Dr. Bennett was supported by NIA grants P30AG10161, R01AG15819, and R01AG17917. Dr. Farrar was supported by a grant from the National Center for Research Resources (UL1RR024134). Dr. Hanlon was supported by National Institute of Aging grants (P30AG024827, T32AG021885, K07AG033174, R01AG034056, R56AG027017, U01AG012553), a National Institute of Mental Health grant (R34MH082682), a National Institute of Nursing Research grant (R01NR010135), AHRQ grants (R01HS017695, R01HS018721, K12HS019461), and a VA Health Services Research grant (IIR-06-062). Dr. Herr was supported by grants from the National Cancer Institute (R01CA115363) and National Institute of Nursing Research (T32NR011147). Drs. Horn and Inturrisi were supported by American Recovery and Reinvestment Act (ARRA) grant RC2DA028928 from NIDA. Dr. Michaud was supported by an ARRA grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) (RC1AR058601). Dr. Neogi was supported by a grant from the NIAMS (K23AR055127). Dr. Morrison was supported by grants from the NIA (P30AG028741, K24AG022345, and R01AG030141). Dr. Solomon was supported by a grant from the NIAMS (K24AR055989). Dr. Von Korff was supported by grants from the NIDA (R01DA022557) and the NIA (R01AG034181). NR 106 TC 37 Z9 38 U1 7 U2 19 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1526-2375 J9 PAIN MED JI Pain Med. PY 2011 VL 12 IS 9 BP 1336 EP 1357 DI 10.1111/j.1526-4637.2011.01211.x PG 22 WC Medicine, General & Internal SC General & Internal Medicine GA 822MJ UT WOS:000295051500009 PM 21834914 ER PT J AU Lange, G Janal, MN Maniker, A FitzGibbons, J Fobler, M Cook, D Natelson, BH AF Lange, Gudrun Janal, Malvin N. Maniker, Allen FitzGibbons, Jennifer Fobler, Malusha Cook, Dane Natelson, Benjamin H. TI Safety and Efficacy of Vagus Nerve Stimulation in Fibromyalgia: A Phase I/II Proof of Concept Trial SO PAIN MEDICINE LA English DT Article DE Fibromyalgia; Chronic Pain; Neurology ID DOUBLE-BLIND; MULTICENTER; SURGERY AB Objective. We performed an open-label Phase I/II trial to evaluate the safety and tolerability of vagus nerve stimulation (VNS) in patients with treatment-resistant fibromyalgia (FM) as well as to determine preliminary measures of efficacy in these patients. Methods. Of 14 patients implanted with the VNS stimulator, 12 patients completed the initial 3-month study of VNS; 11 patients returned for follow-up visits 5, 8, and 11 months after start of stimulation. Therapeutic efficacy was assessed with a composite measure requiring improvement in pain, overall wellness, and physical function. Loss of both pain and tenderness criteria for the diagnosis of FM was added as a secondary outcome measure because of results found at the end of 3 months of stimulation. Results. Side effects were similar to those reported in patients treated with VNS for epilepsy or depression and, in addition, dry mouth and fatigue were reported. Two patients did not tolerate stimulation. At 3 months, five patients had attained efficacy criteria; of these, two patients no longer met widespread pain or tenderness criteria for the diagnosis of FM. The therapeutic effect seemed to increase over time in that additional participants attained both criteria at 11 months. Conclusions. Side effects and tolerability were similar to those found in disorders currently treated with VNS. Preliminary outcome measures suggested that VNS may be a useful adjunct treatment for FM patients resistant to conventional therapeutic management, but further research is required to better understand its actual role in the treatment of FM. C1 [Natelson, Benjamin H.] Beth Israel Deaconess Med Ctr, Pain & Fatigue Study Ctr, Dept Pain Med & Palliat Care, New York, NY 10003 USA. [Maniker, Allen] Beth Israel Deaconess Med Ctr, Dept Neurosurg, New York, NY 10003 USA. [Lange, Gudrun; FitzGibbons, Jennifer; Fobler, Malusha] UMDNJ New Jersey Med Sch, Dept Radiol, Newark, NJ USA. [Janal, Malvin N.] UMDNJ New Jersey Med Sch, Dept Psychiat, Newark, NJ USA. [Natelson, Benjamin H.] UMDNJ New Jersey Med Sch, Dept Neurosci, Newark, NJ USA. [Lange, Gudrun; FitzGibbons, Jennifer; Fobler, Malusha] New Jersey Hlth Care Syst, Dept Vet Affairs, E Orange, NJ USA. [Janal, Malvin N.] NYU, Coll Dent, Dept Epidemiol & Hlth Promot, New York, NY USA. [Cook, Dane] Univ Wisconsin, William S Middleton Mem Vet Hosp, Madison, WI USA. [Cook, Dane] Univ Wisconsin, Dept Kinesiol, Madison, WI USA. RP Natelson, BH (reprint author), Beth Israel Deaconess Med Ctr, Pain & Fatigue Study Ctr, Dept Pain Med & Palliat Care, 10 Union Sq E, New York, NY 10003 USA. EM bnatelson@bethisraelny.org FU National Institutes of Health [AR-053732] FX This work was supported by National Institutes of Health # AR-053732. A patent application for the use of VNS in FM is pending for author Gudrun Lange under US Patent Application no. 12/322,741. We thank Dr. Daniel Clauw, a physician expert in FM and FM treatment trials and Dr. Sandra Helmers, an expert in the use of VNS in epilepsy for their help in various aspects of this study. We acknowledge the help of Dr. Adam Perlman in patient recruitment and medical decision making and the help of Ms. Kristin Thorsen, editor of the Fibromyalgia Network News, for publicizing the existence of this clinical "proof of concept" trial to the FM community at large and thus aiding in recruitment of participants. NR 19 TC 11 Z9 11 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1526-2375 J9 PAIN MED JI Pain Med. PY 2011 VL 12 IS 9 BP 1406 EP 1413 DI 10.1111/j.1526-4637.2011.01203.x PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 822MJ UT WOS:000295051500015 PM 21812908 ER PT J AU Corson, K Doak, MN Denneson, L Crutchfield, M Soleck, G Dickinson, KC Gerrity, MS Dobscha, SK AF Corson, Kathryn Doak, Melanie N. Denneson, Lauren Crutchfield, Megan Soleck, Geoffrey Dickinson, Kathryn C. Gerrity, Martha S. Dobscha, Steven K. TI Primary Care Clinician Adherence to Guidelines for the Management of Chronic Musculoskeletal Pain: Results from the Study of the Effectiveness of a Collaborative Approach to Pain SO PAIN MEDICINE LA English DT Article DE Chronic Pain; Pain Management; Quality of Healthcare; Randomized Controlled Trial ID LOW-BACK-PAIN; RANDOMIZED CONTROLLED-TRIAL; 5TH VITAL SIGN; MORRIS DISABILITY QUESTIONNAIRE; GENERAL-PRACTICE; IMPLEMENTATION STRATEGIES; PATIENT OUTCOMES; SCREENING-TEST; UNITED-STATES; DEPRESSION AB Objective. We assessed primary care clinician-provided guideline-concordant care as documented in patients' medical records, predictors of documented guideline-concordant care, and its association with pain-related functioning. Patients were participants in a randomized trial of collaborative care for chronic musculoskeletal pain. The intervention featured patient and primary care clinician education, symptom monitoring and feedback to clinicians by the intervention team. Methods. To assess concordance with the evidence-based treatment guidelines upon which our intervention was based, we developed an 8-item chart review tool, the Pain Process Checklist (PPC). We then reviewed electronic medical records for 365 veteran patients treated by 42 primary care clinicians over 12 months. Intervention status, demographic, and clinical variables were tested as predictors of PPC scores using generalized estimating equations (GEE). GEE was also used to test whether PPC scores predicted treatment response (>= 30% decrease in Roland-Morris Disability Questionnaire score). Results. Rates of documented guideline-concordant care varied widely among PPC items, from 94% of patients having pain addressed to 17% of patients on opioids having side effects addressed. Intervention status was unrelated to item scores, and PPC-7 totals did not differ significantly between intervention and treatment-as-usual patients (61.2%, standard error [SE] = 3.3% vs 55.2%, SE = 2.6%, P = 0.15). In a multivariate model, higher PPC-7 scores were associated with receiving a prescription for opioids (odds ratio [OR] = 1.07, P = 0.007) and lower PPC-7 scores with patient age (10-year difference OR = 0.97, P = 0.004). Finally, intervention patients who received quantitative pain and depression assessments were less likely to respond to treatment (assessed vs not: 18% vs 33%, P = 0.008, and 13% vs 28%, P = 0.001, respectively). Conclusions. As measured by medical record review, additional training and clinician feedback did not increase provision of documented guideline-concordant pain care, and adherence to guidelines by primary care clinicians did not improve clinical outcomes for patients with chronic musculoskeletal pain. C1 [Corson, Kathryn; Denneson, Lauren; Crutchfield, Megan; Soleck, Geoffrey; Dickinson, Kathryn C.; Gerrity, Martha S.; Dobscha, Steven K.] Portland VA Med Ctr, Portland Ctr Study Chron, Portland, OR 97207 USA. [Corson, Kathryn; Dobscha, Steven K.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Doak, Melanie N.; Gerrity, Martha S.] Portland VA Med Ctr, Primary Care Div, Portland, OR 97207 USA. RP Corson, K (reprint author), Portland VA Med Ctr, Portland Ctr Study Chron, POB 1034,P3 DEP PC, Portland, OR 97207 USA. EM kathryn.corson@va.gov RI Duncan, Kirsty/H-1911-2011 FU Oregon Clinical and Translational Research Institute; National Center for Research Resources [UL1RR024140 01]; VA Primary Care Division; Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service [PMI 03-195, RCD04129] FX The authors gratefully acknowledge the assistance of Jean O'Malley MPH for consultation on statistical analyses made possible through support from the Oregon Clinical and Translational Research Institute, grant number UL1RR024140 01 from the National Center for Research Resources. We also thank Kurt Kroenke MD and Mark Sullivan MD PhD who helped to refine our intervention and measurement approaches, and the VA Primary Care Division clinicians for their participation and support.; The research reported here was supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service Projects PMI 03-195 and RCD04129. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. NR 73 TC 14 Z9 14 U1 1 U2 10 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1526-2375 J9 PAIN MED JI Pain Med. PY 2011 VL 12 IS 10 BP 1490 EP 1501 DI 10.1111/j.1526-4637.2011.01231.x PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 839FA UT WOS:000296349600007 PM 21943325 ER PT J AU Macey, TA Morasco, BJ Duckart, JP Dobscha, SK AF Macey, Tara A. Morasco, Benjamin J. Duckart, Jonathan P. Dobscha, Steven K. TI Patterns and Correlates of Prescription Opioid Use in OEF/OIF Veterans with Chronic Noncancer Pain SO PAIN MEDICINE LA English DT Article DE Chronic Pain; Opioids; Veteran; Pain/Drug Therapy ID OPERATIONS ENDURING FREEDOM; MENTAL-HEALTH DISORDERS; MUSCULOSKELETAL PAIN; IRAQI FREEDOM; ASSOCIATION; AFGHANISTAN; MANAGEMENT; SYMPTOMS; INJURIES; EXPOSURE AB Objectives. Little is known about the treatment Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) veterans receive for chronic noncancer pain (CNCP). We sought to describe the prevalence of prescription opioid use, types, and doses of opioids received and to identify correlates of receiving prescription opioids for CNCP among OEF/OIF veterans. Design. Retrospective review of Veterans Affairs (VA) administrative data. Setting. Ambulatory clinics within a VA regional health care network. Patients. OEF/OIF veterans who had at least three elevated pain screening scores within a 12-month period in 2008. Within this group, those prescribed opioids (N = 485) over the next 12 months were compared with those not prescribed opioids (N = 277). In addition, patients receiving opioids short term (<90 days, N = 284) were compared with patients receiving them long term (>= 90 consecutive days, N = 201). Results. Of 762 OEF/OIF veterans with CNCP, 64% were prescribed at least one opioid medication over the 12 months following their index dates. Of those prescribed an opioid, 59% were prescribed opioids short term and 41% were prescribed opioids long term. The average morphine-equivalent opioid dose for short-term users was 23.7 mg (standard deviation [SD] = 20.5) compared with 40.8 mg (SD = 36.1) for long-term users (P < 0.001). Fifty-one percent of long-term opioid users were prescribed short-acting opioids only, and one-third were also prescribed sedative hypnotics. In adjusted analyses, diagnoses of low back pain, migraine headache, posttraumatic stress disorder, and nicotine use disorder were associated with an increased likelihood of receiving an opioid prescription. Conclusion. Prescription opioid use is common among OEF/OIF veterans with CNCP and is associated with several pain diagnoses and medical conditions. C1 [Macey, Tara A.; Morasco, Benjamin J.; Dobscha, Steven K.] Portland VA Med Ctr, Mental Hlth & Clin Neurosci Div, Portland, OR USA. [Macey, Tara A.; Duckart, Jonathan P.; Dobscha, Steven K.] Portland VA Med Ctr, Portland Ctr Study Chron, Portland, OR USA. [Macey, Tara A.; Duckart, Jonathan P.; Dobscha, Steven K.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. RP Dobscha, SK (reprint author), Portland VA Med Ctr P3 MHADM, Mental Hlth & Clin Neurosci Div, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM steven.dobscha@va.gov FU Portland VA Medical Center; National Institute on Drug Abuse [K23DA023467]; VA Health Services Research and Development service [REA 06-174]; Oregon Clinical and Translational Research Institute; National Institutes of Health [Ul1RR024140] FX We appreciate comments from Teresa Hudson, Pharm D., on a prior draft of this manuscript. This material is the result of work supported with resources and the use of facilities at the Portland VA Medical Center. This study was supported in part by award K23DA023467 from the National Institute on Drug Abuse to Dr. Morasco. Jonathan Duckart, MPS, was supported by a Research Enhancement Award Program grant (REA 06-174) from the VA Health Services Research and Development service. The authors appreciate the statistical support provided from the Oregon Clinical and Translational Research Institute, grant number Ul1RR024140 from the National Institutes of Health. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Department of Veterans Affairs. No author reports having any potential conflict of interest with this study. NR 36 TC 21 Z9 21 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1526-2375 J9 PAIN MED JI Pain Med. PY 2011 VL 12 IS 10 BP 1502 EP 1509 DI 10.1111/j.1526-4637.2011.01226.x PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 839FA UT WOS:000296349600008 PM 21899715 ER PT J AU Marcum, ZA Perera, S Donohue, JM Boudreau, RM Newman, AB Ruby, CM Studenski, SA Kwoh, CK Simonsick, EM Bauer, DC Satterfield, S Hanlon, JT AF Marcum, Zachary A. Perera, Subashan Donohue, Julie M. Boudreau, Robert M. Newman, Anne B. Ruby, Christine M. Studenski, Stephanie A. Kwoh, C. Kent Simonsick, Eleanor M. Bauer, Doug C. Satterfield, Suzanne Hanlon, Joseph T. CA Hlth Aging & Body Composition Stud TI Analgesic Use for Knee and Hip Osteoarthritis in Community-Dwelling Elders SO PAIN MEDICINE LA English DT Article DE Aged; Analgesic; Osteoarthritis ID CARDIOVASCULAR-DISEASE INDICATORS; OLDER-ADULTS; BODY-COMPOSITION; HEALTH ABC; PAIN; CARE; RECOMMENDATIONS; MANAGEMENT; PERFORMANCE; ARTHRITIS AB Objective. To examine the prevalence and correlates of non-opioid and opioid analgesic use and descriptively evaluate potential undertreatment in a sample of community-dwelling elders with symptomatic knee and/or hip osteoarthritis (OA). Design. Cross-sectional. Setting. Health, Aging, and Body Composition Study. Patients. Six hundred and fifty-two participants attending the year 6 visit (2002-03) with symptomatic knee and/or hip OA. Outcome Measures. Analgesic use was defined as taking >= 1 non-opioid and/or >= 1 opioid receptor agonist. Non-opioid and opioid doses were standardized across all agents by dividing the daily dose used by the minimum effective analgesic daily dose. Inadequate pain control was defined as severe/extreme OA pain in the past 30 days from a modified Western Ontario and McMaster Universities Osteoarthritis Index. Results. Just over half (51.4%) reported taking at least one non-opioid analgesic and approximately 10% was taking an opioid, most (88.5%) of whom also took a non-opioid. One in five participants (19.3%) had inadequate pain control, 39% of whom were using <1 standardized daily dose of either a non-opioid or opioid analgesic. In adjusted analyses, severe/extreme OA pain was significantly associated with both non-opioid (adjusted odds ratio [AOR] = 2.44; 95% confidence interval [95% CI] = 1.49-3.99) and opioid (AOR = 2.64; 95% CI = 1.26-5.53) use. Conclusions. Although older adults with severe/extreme knee and/or hip OA pain are more likely to take analgesics than those with less severe pain, a sizable proportion takes less than therapeutic doses and thus may be undertreated. Further research is needed to examine barriers to optimal analgesic use. C1 [Marcum, Zachary A.] Univ Pittsburgh, Sch Med, Dept Med Geriatr, Pittsburgh, PA 15213 USA. [Kwoh, C. Kent] Univ Pittsburgh, Sch Med, Dept Med Rheumatol & Clin Immunol, Pittsburgh, PA 15213 USA. [Perera, Subashan] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15213 USA. [Donohue, Julie M.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Hlth Policy & Management, Pittsburgh, PA 15213 USA. [Boudreau, Robert M.; Newman, Anne B.; Hanlon, Joseph T.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA. [Ruby, Christine M.; Hanlon, Joseph T.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15213 USA. [Studenski, Stephanie A.; Kwoh, C. Kent; Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res, Pittsburgh, PA USA. [Studenski, Stephanie A.; Kwoh, C. Kent; Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Simonsick, Eleanor M.] NIA, Intramural Res Program, Baltimore, MD 21224 USA. [Bauer, Doug C.] Univ Calif San Francisco, Sch Med, Dept Med Gen Internal Med, San Francisco, CA USA. [Satterfield, Suzanne] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. RP Marcum, ZA (reprint author), Univ Pittsburgh, Sch Med, Dept Med Geriatr, Kaufmann Med Bldg,Suite 500,3471 5th Ave, Pittsburgh, PA 15213 USA. EM zam12@pitt.edu RI Perera, Subashan/D-7603-2014; Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Boudreau, Robert/0000-0003-0162-5187; Donohue, Julie/0000-0003-2418-6017 FU National Institute on Aging [R01AG027017, P30AG024827, T32 AG021885, K07AG033174, R01AG034056, N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; National Institute of Mental Health [R34 MH082682]; National Institute of Nursing Research [R01 NR010135]; Agency for Healthcare Research and Quality [R01 HS017695]; VA Health Services [IIR-06-062]; NIH, National Institute on Aging FX This study was primarily supported by National Institute on Aging grants and contracts (R01AG027017, P30AG024827, T32 AG021885, K07AG033174, R01AG034056, N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106), a National Institute of Mental Health grant (R34 MH082682), a National Institute of Nursing Research grant (R01 NR010135), an Agency for Healthcare Research and Quality grant (R01 HS017695), and a VA Health Services Research grant (IIR-06-062). This research was also supported in part by the Intramural Research program of the NIH, National Institute on Aging. The authors would like to thank Yihuang Kang and Yan Zheng for their assistance with data programming. NR 35 TC 12 Z9 12 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1526-2375 J9 PAIN MED JI Pain Med. PY 2011 VL 12 IS 11 BP 1628 EP 1636 DI 10.1111/j.1526-4637.2011.01249.x PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 854PO UT WOS:000297506900009 PM 21992521 ER PT J AU Manchikanti, L Caraway, D Parr, AT Fellows, B Hirsch, JA AF Manchikanti, Laxmaiah Caraway, David Parr, Allan T. Fellows, Bert Hirsch, Joshua A. TI Patient Protection and Affordable Care Act of 2010: Reforming the Health Care Reform for the New Decade SO PAIN PHYSICIAN LA English DT Review DE Affordable Care Act; health care costs; health care regulation; health care reform; Patient Centered Outcomes Research Institute; health exchanges; health care subsidies; health insurance premiums; uninsured; Medicare; cost control ID LOW-BACK-PAIN; EVIDENCE-BASED MEDICINE; INTERLAMINAR EPIDURAL INJECTIONS; CLINICAL-PRACTICE GUIDELINE; LUMBAR SURGERY SYNDROME; JOINT NERVE BLOCKS; CONTROLLED DIAGNOSTIC BLOCKS; CHRONIC SPINAL PAIN; SYSTEMATIC REVIEWS; NURSE-PRACTITIONER AB The Patient Protection and Affordable Care Act (the ACA, for short) became law with President Obama's signature on March 23, 2010. It represents the most significant transformation of the American health care system since Medicare and Medicaid. It is argued that it will fundamentally change nearly every aspect of health care, from insurance to the final delivery of care. The length and complexity of the legislation and divisive and heated debates have led to massive confusion about the impact of ACA. It also became one of the centerpieces of 2010 congressional campaigns. Essentials of ACA include: 1) a mandate for individuals and businesses requiring as a matter of law that nearly every American have an approved level of health insurance or pay a penalty; 2) a system of federal subsidies to completely or partially pay for the now required health insurance for about 34 million Americans who are currently uninsured subsidized through Medicaid and exchanges; 3) extensive new requirements on the health insurance industry; and 4) numerous regulations on the practice of medicine. The act is divided into 10 titles. It contains provisions that went into effect starting on June 21, 2010, with the majority of provisions going into effect in 2014 and later. The perceived major impact on practicing physicians in the ACA is related to growing regulatory authority with the Independent Payment Advisory Board (IPAB) and the Patient Centered Outcomes Research Institute (PCORI). In addition to these specifics is a growth of the regulatory regime in association with further discounts in physician reimbursement. With regards to cost controls and projections, many believe that the ACA does not fix the finances of our health care system neither public nor private. It has been suggested that the Congressional Budget Office (CBO) and the administration have used creative accounting to arrive at an alleged deficit reduction; however, if everything is included appropriately and accounted for, we will be facing a significant increase in deficits rather than a reduction. When posed as a global question, polls suggest that public opinion continues to be against the health insurance reform. The newly elected Republican congress is poised to pass a bill aimed at repealing health care reform. However, advocates of the repeal of health care reform have been criticized for not providing a meaningful alternative approach. Those criticisms make clear that it is not sufficient to provide vague arguments against the ACA without addressing core issues embedded in health care reform. It is the opinion of the authors that while some parts of the ACA may be reformed, it is unlikely to be repealed. Indeed, the ACA already is growing roots. Consequently, it will be extremely difficult to repeal. In this manuscript, we look at reducing the regulatory burden on the public and providers and elimination of IPAB and PCORI. The major solution lies in controlling the drug and durable medical supply costs with appropriate negotiating capacity for Medicare, and consequently for other insurers. C1 [Manchikanti, Laxmaiah; Fellows, Bert] Pain Management Ctr Paducah, Paducah, KY USA. [Caraway, David] St Marys Pain Relief Ctr, Huntington, WV USA. [Parr, Allan T.] Premier Pain Ctr, Covington, LA USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA. RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM Drlm@thepainmd.com NR 247 TC 50 Z9 50 U1 1 U2 45 PU AM SOC INTERVENTIONAL PAIN PHYSICIANS PI PADUCAH PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA SN 1533-3159 J9 PAIN PHYSICIAN JI Pain Physician PD JAN-FEB PY 2011 VL 14 IS 1 BP E35 EP E67 PG 33 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA 857IU UT WOS:000297712600003 PM 21267047 ER PT J AU Manchikanti, L Singh, V Caraway, DL Benyamin, RM Hirsch, JA AF Manchikanti, Laxmaiah Singh, Vijay Caraway, David L. Benyamin, Ramsin M. Hirsch, Joshua A. TI Medicare Physician Payment Systems: Impact of 2011 Schedule on Interventional Pain Management SO PAIN PHYSICIAN LA English DT Review DE Health policy; physician payment policy; physician fee schedule; Medicare; sustained growth rate formula; interventional pain management; regulatory reform ID LOW-BACK-PAIN; CAUDAL EPIDURAL INJECTIONS; EVIDENCE-BASED MEDICINE; CHRONIC SPINAL PAIN; FACET JOINT PAIN; LUMBAR SURGERY SYNDROME; MEDIAL BRANCH BLOCKS; TECHNOLOGY-ASSESSMENT-SUBCOMMITTEE; PREVIOUSLY ASYMPTOMATIC SUBJECTS; HEALTH SPENDING PROJECTIONS AB Physicians in the United States have been affected by significant changes in the patterns of medical practice evolving over the last several decades. The recently passed affordable health care law, termed the Patient Protection and Affordable Care Act of 2010 (the ACA, for short) affects physicians more than any other law. Physician services are an integral part of health care. Physicians are paid in the United States for their personal services. This payment also includes the overhead expenses for maintaining an office and providing services. The payment system is highly variable in the private insurance market; however, governmental systems have a formula-based payment, mostly based on the Medicare payment system. Physician services are billed under Part B. Since the inception of the Medicare program in 1965, several methods have been used to determine the amounts paid to physicians for each covered service. Initially, the payment systems compensated physicians on the basis of their charges. In 1975, just over 10 years after the inception of the Medicare program, payments changed so as not to exceed the increase in the Medical Economic Index (MEI). Nevertheless, the policy failed to curb increases in costs, leading to the determination of a yearly change in fees by legislation from 1984 to 1991. In 1992, the fee schedule essentially replaced the prior payment system that was based on the physician's charges, which also failed to live up to expectations for operational success. Then, in 1998, the sustainable growth rate (SGR) system was introduced. In 2009, multiple attempts were made by Congress to repeal the formula rather unsuccessfully. Consequently, the SGR formula continues to hamper physician payments. The mechanism of the SGR includes 3 components that are incorporated into a statutory formula: expenditure targets, growth rate period, and annual adjustments of payment rates for physician services. Further, the relative value of a physician fee schedule is based on 3 components: physician work, practice expense (PE), and malpractice expense that are used to determine a value ranking for each service to which it is applied. On average, the work component represents 53.5% of a service's relative value, the fee component represents 43.6%, and the malpractice component represents 3.9%. The final schedule for physician payment was issued on November 24, 2010. This was based on a total cut of 30.8% with 24.9% of the cut attributed to SGR. However, as usual, with patchwork efficiency, Congress passed a one-year extension of the 0% update, effective through December 2011. Consequently, CMS issued an emergency update of the 2011 Medicare fee schedule, with multiple revisions, resulting in a reduction of the conversion factor of $36.8729 from December 2010 to $33.9764 for 2011. C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA. [Singh, Vijay] Pain Diagnost Associates, Niagara, WI USA. [Caraway, David L.] St Marys Pain Relief Ctr, Huntington, WV USA. [Benyamin, Ramsin M.] Millennium Pain Ctr, Bloomington, IL USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com NR 193 TC 39 Z9 39 U1 0 U2 6 PU AM SOC INTERVENTIONAL PAIN PHYSICIANS PI PADUCAH PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA SN 1533-3159 J9 PAIN PHYSICIAN JI Pain Physician PD JAN-FEB PY 2011 VL 14 IS 1 BP E5 EP E33 PG 29 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA 857IU UT WOS:000297712600002 PM 21267048 ER PT J AU Alexandre, M Pandol, SJ Gorelick, FS Thrower, EC AF Alexandre, Martine Pandol, Stephen J. Gorelick, Fred S. Thrower, Edwin C. TI The Emerging Role of Smoking in the Development of Pancreatitis SO PANCREATOLOGY LA English DT Review DE Acute and chronic pancreatitis; Zymogen activation; Cellular injury; Nicotine; NNK; Tobacco smoking ID CIGARETTE-SMOKING; RISK-FACTOR; NICOTINE EXPOSURE; TOBACCO; ADENOCARCINOMA; LUNG; RATS; CELL; INHALATION; ALCOHOL AB Background/Aims: Cigarette smoking has been linked to many diseases, including pancreatic cancer and more recently, pancreatitis. Methods: Electronic searches of primarily PubMed from 1990 to August 2011 were conducted and only articles published in English were reviewed. Original articles and reviews were selected based on screening of article abstracts and their relevance to tobacco smoking, its components, nicotine and its metabolites, and their effects particularly on the pancreas. Results: Smoking may affect the risk of developing chronic pancreatitis or its progression. Smoking may also affect the risk for developing acute pancreatitis. Its effects in pancreatitis appear to be dose dependent and its effects may be alcohol independent but synergize with alcohol. Conclusion: Specific constituents of cigarette smoke, including nicotine and its metabolites, could mediate effects on the pancreas. Copyright (C) 2011 S. Karger AG, Basel and IAP C1 [Alexandre, Martine; Gorelick, Fred S.; Thrower, Edwin C.] Yale Univ, Sch Med, Dept Internal Med, Sect Digest Dis, New Haven, CT 06510 USA. [Gorelick, Fred S.] Yale Univ, Sch Med, Dept Cell Biol, New Haven, CT 06510 USA. [Alexandre, Martine; Gorelick, Fred S.; Thrower, Edwin C.] Vet Adm Connecticut Healthcare, West Haven, CT USA. [Pandol, Stephen J.] Vet Affairs Greater Los Angeles Hlth Care Syst, So Calif Res Ctr Alcohol Liver & Pancreat Dis, Los Angeles, CA USA. [Pandol, Stephen J.] Univ Calif Los Angeles, Los Angeles, CA USA. RP Thrower, EC (reprint author), VA Healthcare Syst Connecticut, GI Res Lab, Bldg 4,950 Campbell Ave, West Haven, CT 06516 USA. EM edwin.thrower@yale.edu FU National Institutes of Health [RO1 DK54021]; Veterans Administration Merit; Senior Career Development Award; Department of Veterans Affairs; National Institutes of Health/NIAAA Southern California Research Center for Alcoholic Liver and Pancreatic Diseases [P60 AA11999]; National Institutes of Health/NCCAM UCLA Center for Excellence in Pancreatic Diseases [P01AT003960-01] FX The authors would like to acknowledge the following funding sources: National Institutes of Health Grant RO1 (DK54021 to F.S.G.), Veterans Administration Merit and Senior Career Development Award (to F.S.G.), National Institutes of Health Grant R21 (DK69702 to E.C.T.) and National Institutes of Health Grant RO1 supplement (DK54021 supplement to M.A.), Department of Veterans Affairs (to S.J.P.), National Institutes of Health/NIAAA Southern California Research Center for Alcoholic Liver and Pancreatic Diseases (P60 AA11999 to S.J.P.), National Institutes of Health/NCCAM UCLA Center for Excellence in Pancreatic Diseases (P01AT003960-01 to S.J.P.). The authors would like to thank Asad Khan for useful suggestions concerning the manuscript. NR 36 TC 29 Z9 29 U1 1 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-3903 J9 PANCREATOLOGY JI Pancreatology PY 2011 VL 11 IS 5 BP 469 EP 474 DI 10.1159/000332196 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 872ZU UT WOS:000298850900003 PM 21986098 ER PT J AU Khalid, A Dewitt, J Ohori, NP Chen, JH Fasanella, KE Sanders, M McGrath, KM Nikiforova, M AF Khalid, Asif Dewitt, John Ohori, N. Paul Chen, Jey-Hsin Fasanella, Kenneth E. Sanders, Michael McGrath, Kevin M. Nikiforova, Marina TI EUS-FNA Mutational Analysis in Differentiating Autoimmune Pancreatitis and Pancreatic Cancer SO PANCREATOLOGY LA English DT Article DE Pancreatic cancer; Autoimmune pancreatitis; Endoscopic ultrasound; K-ras ID FINE-NEEDLE-ASPIRATION; GUIDED TRUCUT BIOPSY; DIAGNOSIS AB Background/Aims: Autoimmune pancreatitis (AIP) may mimic pancreatic cancer (PC). The detection of DNA mutations in endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) material may improve discrimination between AIP and PC and is the context for this study. Methods: In a retrospective study, archived EUS-FNA material from patients with AIP and PC at two centers was analyzed for KRAS mutations and loss-of-heterozygosity analysis involving 18 microsatellite markers. KRAS status and the fractional allelic loss (number of affected microsatellites divided by informative ones) were compared for AIP and PC. Results: Thirty-two patients with 33 samples were studied. There were 16 patients with AIP (17 samples) and 16 patients with PC. DNA amplification failed in 7 samples. Of 25 patients (26 samples), 14 had AIP (7 male, age 57 +/- 17 years; mean +/- SD) and 11 had PC (7 male, age 65 +/- 14 years; mean +/- SD). Cytology results for AIP were inflammatory = 3, inconclusive = 10, suspicious for malignancy = 2 and for PC were malignant = 5, suspicious for malignancy = 4 and inconclusive = 2, respectively. KRAS mutation was detected in none of the AIP cases and 10/11 PC cases (91%, Pearson chi(2) = 22.16, p < 0.001) or 10/16 PC cases (63%) accounting for PC cases with failed DNA amplification. Mean (+/- SD) fractional allelic loss for the AIP cases (0.16 +/- 0.15) was not significantly different from the PC cases (0.26 +/- 0.19). Conclusions: A KRAS mutation in EUS/FNA material from a pancreatic mass is associated with malignancy and may help discriminate from benign conditions such as AIP. Copyright (C) 2011 S. Karger AG, Basel and IAP C1 [Khalid, Asif; Ohori, N. Paul; Fasanella, Kenneth E.; Sanders, Michael; McGrath, Kevin M.; Nikiforova, Marina] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Khalid, Asif] VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. [Dewitt, John; Chen, Jey-Hsin] Indiana Univ, Med Ctr, Indianapolis, IN USA. RP Khalid, A (reprint author), Div Gastroenterol, M2,PUH 200 Lothrop St, Pittsburgh, PA 15213 USA. EM khalida@upmc.edu RI Fasanella, Kenneth/I-2781-2012 NR 17 TC 10 Z9 12 U1 0 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-3903 J9 PANCREATOLOGY JI Pancreatology PY 2011 VL 11 IS 5 BP 482 EP 486 DI 10.1159/000331505 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 872ZU UT WOS:000298850900005 PM 21997479 ER PT B AU Weintraub, D Hoops, S AF Weintraub, Daniel Hoops, Staci BE Olanow, CW Stocchi, F Lang, AE TI Anxiety Syndromes and Panic Attacks SO PARKINSON'S DISEASE: NON-MOTOR AND NON-DOPAMINERGIC FEATURES LA English DT Article; Book Chapter ID DEEP BRAIN-STIMULATION; OBSESSIVE-COMPULSIVE SYMPTOMS; PARKINSONS-DISEASE PATIENTS; PSYCHIATRIC-SYMPTOMS; SUBTHALAMIC NUCLEUS; PERSONALITY-TRAITS; SOCIAL PHOBIA; RATING-SCALES; DOUBLE-BLIND; DEPRESSION C1 [Weintraub, Daniel; Hoops, Staci] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Vet Affairs Med Ctr, Parkinsons Dis Res Educ & Clin Ctr PADRECC, Philadelphia, PA USA. [Weintraub, Daniel] Vet Affairs Med Ctr, MIRECC, Philadelphia, PA USA. RP Weintraub, D (reprint author), Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. NR 62 TC 1 Z9 1 U1 1 U2 1 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-4443-9795-6; 978-1-4051-9185-2 PY 2011 BP 193 EP 201 D2 10.1002/9781444397970 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA BA6JM UT WOS:000337162400018 ER PT B AU Duda, JE Stern, MB AF Duda, John E. Stern, Matthew B. BE Olanow, CW Stocchi, F Lang, AE TI Olfactory Dysfunction SO PARKINSON'S DISEASE: NON-MOTOR AND NON-DOPAMINERGIC FEATURES LA English DT Article; Book Chapter ID IDIOPATHIC PARKINSONS-DISEASE; SMELL IDENTIFICATION TEST; SNIFF MAGNITUDE TEST; ODOR IDENTIFICATION; LEWY BODIES; NEURODEGENERATIVE DISEASE; BODY PATHOLOGY; DE-NOVO; DIAGNOSIS; BULB C1 [Duda, John E.; Stern, Matthew B.] Univ Penn, Sch Med, Parkinsons Dis Res Educ & Clin Ctr PADRECC, Philadelphia, PA 19104 USA. [Duda, John E.; Stern, Matthew B.] Univ Penn, Sch Med, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Duda, John E.; Stern, Matthew B.] Univ Penn, Sch Med, Dept Neurol, Philadelphia, PA 19104 USA. RP Duda, JE (reprint author), Univ Penn, Sch Med, Parkinsons Dis Res Educ & Clin Ctr PADRECC, Philadelphia, PA 19104 USA. NR 84 TC 1 Z9 1 U1 0 U2 2 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-4443-9795-6; 978-1-4051-9185-2 PY 2011 BP 304 EP 314 D2 10.1002/9781444397970 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA BA6JM UT WOS:000337162400028 ER PT J AU Thompson, AW Liu, HH Hays, RD Katon, WJ Rausch, R Diaz, N Jacob, EL Vassar, SD Vickrey, BG AF Thompson, Alexander W. Liu, Honghu Hays, Ron D. Katon, Wayne J. Rausch, Rebecca Diaz, Natalie Jacob, Erin L. Vassar, Stefanie D. Vickrey, Barbara G. TI Diagnostic accuracy and agreement across three depression assessment measures for Parkinson's disease SO PARKINSONISM & RELATED DISORDERS LA English DT Article DE SCID; PHQ-9; GDS; Geriatric Depression Scale; Patient Health Questionnaire-9 ID SCALE; VALIDITY; SYMPTOMS AB Purpose: To assess diagnostic accuracy of two self-administered depression measures compared to an interviewer-administered measure in subjects with Parkinson's disease (PD), and to analyze clinical and sociodemographic factors associated with disagreement among the three depression assessment tools. Methods: We assessed 214 PD subjects using the Patient Health Questionnaire-9 (PHQ-9), the Geriatric Depression Scale-15 (GDS-15), and the Structured Clinical Interview for the DSM-IV depression module (SCID). Diagnostic accuracy of the PHQ-9 and GDS-15 compared to the SCID was evaluated. Multivariate logistic regression was conducted to analyze factors associated with measure disagreement. We compared item agreement between the PHQ-9 and SCID to test the hypothesis that there would be less agreement between items assessing depression symptoms overlapping with common PD symptoms, compared to items having minimal overlap with PD manifestations. Results: Compared to SCID diagnosis of major depression, PHQ-9 sensitivity is 50% and specificity is 93%; GDS-15 sensitivity is 43% and specificity is 96%. The GDS-15 has 85% sensitivity and 79% specificity and the PHQ-9 has 54% sensitivity and 85% specificity compared to SCID diagnosis of minor or major depression. The PHQ-9 and SCID show more agreement on items unrelated to PD manifestations. Pain was the only factor associated with disagreement between the SCID and PHQ-9. Conclusion: Compared to the PHQ-9, the GDS-15 had higher sensitivity and similar positive predictive value, suggesting it is a superior screening tool in clinical applications for PD. On future depression screening or diagnostic instruments, consideration should be given to excluding depression items overlapping with PD manifestations. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Thompson, Alexander W.] Texas A&M Univ, Coll Med, Texas A&M Hlth Sci Ctr, Dept Psychiat, Temple, TX 76508 USA. [Liu, Honghu] Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA. [Liu, Honghu; Hays, Ron D.] Univ Calif Los Angeles, Dept Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90024 USA. [Liu, Honghu; Hays, Ron D.] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Hays, Ron D.] RAND Corp, Santa Monica, CA USA. [Katon, Wayne J.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Rausch, Rebecca; Vassar, Stefanie D.; Vickrey, Barbara G.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Diaz, Natalie] Harbor UCLA Dept Neurol, Los Angeles, CA USA. [Jacob, Erin L.] Univ Calif Los Angeles, Dept Epidemiol, Los Angeles, CA USA. [Vassar, Stefanie D.; Vickrey, Barbara G.] VA Greater Los Angeles Healthcare Syst, Parkinsons Dis Res Educ & Clin Ctr, Los Angeles, CA USA. RP Thompson, AW (reprint author), Texas A&M Univ, Coll Med, Texas A&M Hlth Sci Ctr, Dept Psychiat, Temple, TX 76508 USA. EM awt@alumni.rice.edu RI Hays, Ronald/D-5629-2013 FU NIEHS [ES10544]; NIH/NINDS [NS038367]; Veteran's Administration through its Southwest Parkinson's Disease Research, Education, and Clinical Center (PADRECC); UCLA Resource Center for Minority Aging Research/Center for Health Improvement in Minority Elderly (RCMAR/CHIME); NIH/NIA [P30AG021684]; UCLA/Drew Project EXPORT; NCMHD; UCLA Older Americans Independence Center, NIH/NIA [P30-AG028748]; [2P20MD000182] FX We appreciate the work of research assistants Michelle Ornelas, Cristina Ruiz, and Nadia Ruiz who collected the bulk of these study data. We would also like to acknowledge Jeff Bronstein and Yvette Bordelon for UPDRS and Hoehn and Yahr data collection, Jurgen Unutzer for depression measure selection, and Beate Ritz for planning and execution of data collection. The PEG study originally identifying the subjects was supported by NIEHS ES10544 (PI: Ritz). The research presented here was supported by NIH/NINDS NS038367 for the UCLA UDALL Parkinson's Disease Center of Excellence and by the Veteran's Administration through its Southwest Parkinson's Disease Research, Education, and Clinical Center (PADRECC). Ron Hays was supported in part by the UCLA Resource Center for Minority Aging Research/Center for Health Improvement in Minority Elderly (RCMAR/CHIME), NIH/NIA Grant Award Number P30AG021684, the UCLA/Drew Project EXPORT, NCMHD, 2P20MD000182, and the UCLA Older Americans Independence Center, NIH/NIA Grant P30-AG028748. NR 29 TC 15 Z9 16 U1 1 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1353-8020 J9 PARKINSONISM RELAT D JI Parkinsonism Relat. Disord. PD JAN PY 2011 VL 17 IS 1 BP 40 EP 45 DI 10.1016/j.parkreldis.2010.10.007 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 722XD UT WOS:000287467700008 PM 21084211 ER PT J AU Bordelon, YM Hays, RD Vassar, SD Diaz, N Bronstein, J Vickrey, BG AF Bordelon, Yvette M. Hays, Ron D. Vassar, Stefanie D. Diaz, Natalie Bronstein, Jeff Vickrey, Barbara G. TI Medication Responsiveness of Motor Symptoms in a Population-Based Study of Parkinson Disease SO PARKINSONS DISEASE LA English DT Article AB We assessed degree of Parkinson disease motor symptom improvement with medication among subjects enrolled in an ongoing, population-based study in Central California. The motor section of the unified Parkinson disease rating scale (UPDRS) was performed on subjects in both OFF and ON medication states, and difference between these scores was used as an indicator of symptomatic benefit. Higher OFF minus ON scores correlated with more severe baseline symptoms. There was equivalent improvement on the motor UPDRS scale for subjects divided according to medication classes used: levodopa alone 7.3 points, levodopa plus other medications 8.5 points, and dopamine agonists but not levodopa 6.1 points. In addition, there was no difference in the magnitude of improvement when subjects were divided according to Parkinson disease subtype, defined as tremor dominant, akinetic-rigid, or mixed. In this community-based sample, these values are within the range of a clinically important difference as defined by previous studies. C1 [Bordelon, Yvette M.; Vassar, Stefanie D.; Bronstein, Jeff; Vickrey, Barbara G.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Hays, Ron D.] Univ Calif Los Angeles, Dept Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA. [Hays, Ron D.] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90095 USA. [Hays, Ron D.] RAND Corp, Santa Monica, CA 90407 USA. [Vassar, Stefanie D.; Bronstein, Jeff; Vickrey, Barbara G.] Parkinsons Dis Res, VA Greater Los Angeles Healthcare Syst, Educ & Clin Ctr, Los Angeles, CA 90073 USA. [Diaz, Natalie] Harbor UCLA Med Ctr, Dept Neurol, Torrance, CA 90502 USA. RP Bordelon, YM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. EM ybordelon@mednet.ucla.edu FU National Institutes of Health/National Institute of Neurological Disorders and Stroke [NS038367]; Veterans Administration through its Southwest Parkinson's Disease Research, Education, and Clinical Center (PADRECC); NIA [P30AG021684, P30-AG028748]; NCMHD [2P20MD000182] FX The research presented here was supported by the National Institutes of Health/National Institute of Neurological Disorders and Stroke for the University of California Los Angeles UDALL Parkinson's Disease Center of Excellence (NS038367) and by the Veterans Administration through its Southwest Parkinson's Disease Research, Education, and Clinical Center (PADRECC). R. D. Hays was also supported in part by NIA (nos. P30AG021684 and P30-AG028748) and NCMHD (no. 2P20MD000182) grants. We thank Cherry Mao, MS, and Aaron Cook, MPH, for technical assistance in paper preparation. NR 12 TC 0 Z9 0 U1 0 U2 0 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2090-8083 J9 PARKINSONS DIS-US JI Parkinsons Dis. PY 2011 AR UNSP 967839 DI 10.4061/2011/967839 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA V29RN UT WOS:000208765600087 ER PT J AU Kleiner-Fisman, G Martine, R Lang, AE Stern, MB AF Kleiner-Fisman, Galit Martine, Rebecca Lang, Anthony E. Stern, Matthew B. TI Development of a Non-Motor Fluctuation Assessment Instrument for Parkinson Disease SO PARKINSONS DISEASE LA English DT Article AB Patients with Parkinson disease are increasingly recognized to suffer from non-motor symptoms in addition to motor symptoms. Many non-motor symptoms fluctuate in parallel with motor symptoms and in relationship to plasma levodopa levels. Though these symptoms are troublesome and result in reduced quality of life to patients and their caregivers, there has not been an objective method of recognizing and quantifying non-motor fluctuations (NMFs). This study sought to develop a patient-based instrument that would accurately capture the experience of patients with NMFs. Patient-based nominal group technique sessions, focus groups, and expert opinion were utilized in developing this questionnaire. C1 [Kleiner-Fisman, Galit] Univ Toronto, Baycrest Hosp, Toronto, ON M6A 2E1, Canada. [Martine, Rebecca; Stern, Matthew B.] Philadelphia VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr PADRECC, Philadelphia, PA 19107 USA. [Lang, Anthony E.] Univ Toronto, Toronto Western Hosp, Toronto, ON M51 2S8, Canada. [Stern, Matthew B.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Kleiner-Fisman, G (reprint author), Univ Toronto, Baycrest Hosp, 3560 Bathurst St, Toronto, ON M6A 2E1, Canada. EM gkleinerfisman@yahoo.com FU Philadelphia VA Medical Center FX The authors thank Dr. A. Siderowf for facilitation of data acquisition at Pennsylvania Hospital. They also wish to thank the clinician expert panel members: Drs. Anderson, Miyasaki, Samuel, Siderowf, Shulman, Stacy, Voon, and Weiner. This study was supported by a competitive pilot project grant from the Philadelphia VA Medical Center. NR 12 TC 2 Z9 2 U1 0 U2 1 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2090-8083 J9 PARKINSONS DIS-US JI Parkinsons Dis. PY 2011 AR UNSP 292719 DI 10.4061/2011/292719 PG 13 WC Clinical Neurology SC Neurosciences & Neurology GA V29RN UT WOS:000208765600021 ER PT S AU Kim, J Bordiuk, OL Ferrante, RJ AF Kim, Jinho Bordiuk, Olivia L. Ferrante, Robert J. BE Brotchie, J Bezard, E Jenner, P TI EXPERIMENTAL MODELS OF HD AND REFLECTION ON THERAPEUTIC STRATEGIES SO PATHOPHYSIOLOGY, PHARMACOLOGY, AND BIOCHEMISTRY OF DYSKINESIA SE International Review of Neurobiology LA English DT Review; Book Chapter ID TRANSGENIC MOUSE MODEL; HUNTINGTONS-DISEASE MICE; NEURONAL INTRANUCLEAR INCLUSIONS; AMYOTROPHIC-LATERAL-SCLEROSIS; TOXIN 3-NITROPROPIONIC ACID; STRIATAL PROJECTION NEURONS; INCREASED OXIDATIVE DAMAGE; PLACEBO-CONTROLLED TRIAL; CYTOCHROME-C RELEASE; KNOCK-IN MOUSE AB Huntington's disease (HD) is an autosomal dominant, progressive, and fatal neurodegenerative disorder caused by an expanded polyglutamine cytosine adenine-guanine repeat in the gene coding for the protein huntingtin. Despite great progress over the past two decades since the identification of the gene mutation, a direct causative pathway from the HD gene mutation to neuronal dysfunction and death has not yet been established. One important advance in understanding the pathogenic mechanisms of this disease has been the development of experimental mouse models that replicate many of the clinical, neuropathological, and molecular events in HD patients. These murine models have played a critical role in providing accurate and experimentally accessible systems to study multiple features of disease pathogenesis and to test potential therapeutic strategies. A better understanding of the pathophysiological mechanisms of disease and how they interrelate has become important in identifying a treatment for HD and in the design of human clinical trials. In this chapter, we review the current state of HD mouse models and their successes in elucidating disease pathogenesis and in developing pharmacotherapies. There is no clinically proven treatment for HD that can halt or ameliorate the inexorable disease progression. As such, a guide to assessing studies in mouse models and salient issues related to translation from mice to humans are included. C1 [Kim, Jinho; Ferrante, Robert J.] Presbyterian Univ Hosp, Dept Neurol Surg, Pittsburgh, PA 15213 USA. [Bordiuk, Olivia L.] New England Vet Adm VISN 1, Geriatr Res Educ & Clin Ctr, Bedford, MA 01730 USA. [Ferrante, Robert J.] Univ Pittsburgh, Pittsburgh, PA 15213 USA. [Ferrante, Robert J.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr 00 GR H, Pittsburgh, PA 15206 USA. [Ferrante, Robert J.] Boston Univ, Dept Psychiat, Sch Med, Boston, MA 02118 USA. [Kim, Jinho] Lab Med & Pathol, Boston, MA 02118 USA. [Bordiuk, Olivia L.] New England Vet Adm VISN 1, Geriatr Res Educ Clin Ctr, Bedford, MA 01730 USA. RP Kim, J (reprint author), Presbyterian Univ Hosp, Dept Neurol Surg, Pittsburgh, PA 15213 USA. RI Hartman, Jessica/N-3210-2016 FU NINDS NIH HHS [NS066912, NS058793, NS045806] NR 324 TC 10 Z9 10 U1 3 U2 13 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7742 BN 978-0-12-381328-2 J9 INT REV NEUROBIOL JI Int. Rev. Neurobiol. PY 2011 VL 98 BP 419 EP 481 DI 10.1016/B978-0-12-381328-2.00016-X PG 63 WC Neurosciences SC Neurosciences & Neurology GA BXA93 UT WOS:000295559600016 PM 21907096 ER PT J AU Rosenfeld, L Rudd, R Emmons, KM Acevedo-Garcia, D Martin, L Buka, S AF Rosenfeld, Lindsay Rudd, Rima Emmons, Karen M. Acevedo-Garcia, Dolores Martin, Laurie Buka, Stephen TI Beyond reading alone: The relationship between aural literacy and asthma management SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE Literacy; Aural literacy; Asthma; Asthma management; Health communications; Provider-patient communication; Oral exchange ID PROVIDER-PATIENT COMMUNICATION; HEALTH LITERACY; SELF-MANAGEMENT; CHRONIC DISEASE; CARE; INFORMATION; DISPARITIES; KNOWLEDGE; EDUCATION; DIALOGUE AB Objectives: To examine the relationship between literacy and asthma management with a focus on the oral exchange. Methods: Study participants, all of whom reported asthma, were drawn from the New England Family Study (NEFS), an examination of links between education and health. NEFS data included reading, oral (speaking), and aural (listening) literacy measures. An additional survey was conducted with this group of study participants related to asthma issues, particularly asthma management. Data analysis focused on bivariate and multivariable logistic regression. Results: In bivariate logistic regression models exploring aural literacy, there was a statistically significant association between those participants with lower aural literacy skills and less successful asthma management (OR: 4.37, 95%CI: 1.11, 17.32). In multivariable logistic regression analyses, controlling for gender, income, and race in separate models (one-at-a-time), there remained a statistically significant association between those participants with lower aural literacy skills and less successful asthma management. Conclusion: Lower aural literacy skills seem to complicate asthma management capabilities. Practice implications: Greater attention to the oral exchange, in particular the listening skills highlighted by aural literacy, as well as other related literacy skills may help us develop strategies for clear communication related to asthma management. (C) 2010 Elsevier Ireland Ltd. All rights reserved. C1 [Rosenfeld, Lindsay] Northeastern Univ, Inst Urban Hlth Res, Bouve Coll Hlth Sci, Boston, MA 02115 USA. [Rosenfeld, Lindsay; Rudd, Rima; Emmons, Karen M.; Acevedo-Garcia, Dolores] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Cambridge, MA 02138 USA. [Emmons, Karen M.] Dana Farber Canc Inst, Boston, MA USA. [Martin, Laurie] RAND Corp, Santa Monica, CA 90406 USA. [Buka, Stephen] Brown Univ, Providence, RI 02912 USA. RP Rosenfeld, L (reprint author), Northeastern Univ, Inst Urban Hlth Res, Bouve Coll Hlth Sci, 360 Huntington Ave,310 Int Village, Boston, MA 02115 USA. EM L.Rosenfeld@neu.edu RI Buka, Stephen/H-7335-2014 OI Buka, Stephen/0000-0002-8578-9308 FU Pathways Linking Education and Health in Middle Adulthood [1 R01 AG023397-01] FX We would like to acknowledge the following people for their time and efforts with this study: NEFS Study Participants and the Research Team: Drs. Stephen Gilman, Ichiro Kawachi, Laura Kubzansky, Eric Loucks, and Ms. Allison Appleton, Ms. Kathleen McGaffigan, Ms. Norma-Jean Pirri, and Ms. Christina Provencal. In addition, we would like to acknowledge the following grant which supported this work: "Pathways Linking Education and Health in Middle Adulthood" # 1 R01 AG023397-01. NR 93 TC 21 Z9 21 U1 2 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD JAN PY 2011 VL 82 IS 1 BP 110 EP 116 DI 10.1016/j.pec.2010.02.023 PG 7 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 717SA UT WOS:000287066500018 PM 20399060 ER PT J AU Tillquist, MN Maddox, TM AF Tillquist, Maggie N. Maddox, Thomas M. TI Cardiac crossroads: deciding between mechanical or bioprosthetic heart valve replacement SO PATIENT PREFERENCE AND ADHERENCE LA English DT Review DE prosthetic heart valves; patient preference; valve type; anticoagulant; structural valve deterioration ID ORAL ANTICOAGULANT TREATMENT; BLEEDING COMPLICATIONS; INCEPTION-COHORT; RANDOMIZED-TRIAL; ELDERLY-PATIENTS; DECISION-MAKING; RISK; OUTCOMES; THERAPY; MANAGEMENT AB Nearly 15 million people in the United States suffer from either aortic or mitral valvular disease. For patients with severe and symptomatic valvular heart disease, valve replacement surgery improves morbidity and mortality outcomes. In 2009, 90,000 valve replacement surgeries were performed in the United States. This review evaluates the advantages and disadvantages of mechanical and bioprosthetic prosthetic heart valves as well as the factors for consideration in deciding the appropriate valve type for an individual patient. Although many caveats exist, the general recommendation is for patients younger than 60 to 65 years to receive mechanical valves due to the valve's longer durability and for patients older than 60 to 65 years to receive a bioprosthetic valve to avoid complications with anticoagulants. Situations that warrant special consideration include patient co-morbidities, the need for anticoagulation, and the potential for pregnancy. Once these characteristics have been considered, patients' values, anxieties, and expectations for their lifestyle and quality of life should be incorporated into final valve selection. Decision aids can be useful in integrating preferences in the valve decision. Finally, future directions in valve technology, anticoagulation, and medical decision-making are discussed. C1 [Maddox, Thomas M.] Univ Colorado, VA Eastern Colorado Hlth Care Syst, Denver VA Med Ctr, Denver, CO 80220 USA. [Maddox, Thomas M.] Univ Colorado, Dept Med Cardiol, Denver, CO 80220 USA. [Tillquist, Maggie N.] Univ Colorado, Sch Med, Denver, CO 80220 USA. RP Maddox, TM (reprint author), Univ Colorado, VA Eastern Colorado Hlth Care Syst, Denver VA Med Ctr, 1055 Clermont St, Denver, CO 80220 USA. EM thomas.maddox@va.gov NR 40 TC 18 Z9 21 U1 1 U2 10 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1177-889X J9 PATIENT PREFER ADHER JI Patient Prefer. Adherence PY 2011 VL 5 BP 91 EP 99 DI 10.2147/PPA.S16420 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 888QJ UT WOS:000300018300001 PM 21448466 ER PT J AU Firth, PG McMillan, KN Haberkern, CM Yaster, M Bender, MA Goodwin, SR AF Firth, Paul G. McMillan, Kristen N. Haberkern, Charles M. Yaster, Myron Bender, Michael A. Goodwin, Salvatore R. TI A survey of perioperative management of sickle cell disease in North America SO PEDIATRIC ANESTHESIA LA English DT Article DE sickle cell disease; hemoglobinopathy; anesthesia; surgery; acute chest syndrome; pain crisis ID NITRIC-OXIDE; PREOPERATIVE TRANSFUSION; CHEMICAL DIFFERENCE; RISK-FACTORS; ANESTHESIA; HEMOGLOBIN; PRECIPITATION; HAEMOGLOBIN; ANEMIA AB P>Background: Children with sickle cell disease frequently undergo surgical procedures that are associated with acute exacerbations of the disease. Current perioperative management practices are unclear. Objectives: We aimed at describing the current management. Methods: We conducted an electronic survey of North American members of the Society for Pediatric Anesthesia, in which we asked about their perioperative management of sickle cell disease. Results: The response rate to valid addresses was 25% (n = 510/2006). In four scenarios, (a patient with mild disease undergoing a minor procedure; a patient with mild disease undergoing a more invasive procedure; a patient with severe disease undergoing a minor procedure; and a patient with severe disease undergoing a more invasive procedure) 80%, 38%, 27%, and 16% of respondents, respectively, would rely on oral fluids to hydrate patients during the preoperative fast, while 13%, 34%, 44%, and 59%, respectively, would use intravenous fluid. For the same four scenarios, 64%, 28%, 33%, and 10%, respectively, would not transfuse patients in an attempt to prevent sickle cell exacerbations, while 17%, 49%, 36%, and 51%, respectively, would transfuse to a hemoglobin concentration of 10 g center dot dl-1. The tendencies to administer preoperative intravenous fluid and to transfuse blood increased with disease severity and procedure invasiveness (P < 0.001). Although 89% felt comfortable managing patients with sickle cell disease, 73% thought an advisory statement on optimal perioperative management was needed. Conclusions: There is a wide variation in the management of children with sickle cell disease. Clinicians differentiate management based on disease severity and procedure type. C1 [Firth, Paul G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [McMillan, Kristen N.; Yaster, Myron] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Bender, Michael A.] Seattle Childrens Hosp, Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Haberkern, Charles M.; Bender, Michael A.] Univ Washington, Seattle, WA 98195 USA. [Goodwin, Salvatore R.] Nemours Childrens Clin, Jacksonville, FL USA. [Goodwin, Salvatore R.] Mayo Clin & Mayo Grad Sch Med, Jacksonville, FL USA. RP Firth, PG (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM pfirth@partners.org NR 24 TC 4 Z9 4 U1 1 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1155-5645 J9 PEDIATR ANESTH JI Pediatr. Anesth. PD JAN PY 2011 VL 21 IS 1 BP 43 EP 49 DI 10.1111/j.1460-9592.2010.03415.x PG 7 WC Anesthesiology; Pediatrics SC Anesthesiology; Pediatrics GA 694NF UT WOS:000285304200007 PM 20880153 ER PT J AU Ma, HB Lovich, MA Peterfreund, RA AF Ma, Haobo Lovich, Mark A. Peterfreund, Robert A. TI Quantitative analysis of continuous intravenous infusions in pediatric anesthesia: safety implications of dead volume, flow rates, and fluid delivery SO PEDIATRIC ANESTHESIA LA English DT Article DE dead volume; drug infusions; propofol; remifentanil; fluid management ID DRUG-DELIVERY; DYNAMICS AB P>Objective: Quantitative characterization of continuous pediatric drug infusions. Background: The dynamics of drug delivery by continuous infusion to pediatric patients have not been systematically examined. This study extends previously described analytic models to propofol and remifentanil delivery, focusing on infants and toddlers. We postulated that infusion system dead volume, and drug and carrier flow rates, significantly influence drug delivery. Methods: We studied effects of patient weight, infusion system dead volume, drug and carrier flow rates, along with drug stock concentration and dose, on propofol and remifentanil delivery to the circulation. We calculated the drug mass available for inadvertent bolus in the dead volume, the volume of fluid supplied by drug infusions, and model-based estimates of the range of lag times to achieve a targeted steady-state rate of drug delivery. Results: The drug mass in the dead volume at steady state increased with dead volume size and drug dose. For infants, this drug mass could exceed 100% of commonly used loading doses. Predicted lag times to steady state depend on patient size, fluid flow rates, and the mixing behavior of the drug entering the main fluid pathway. Neonates have the longest lag times to achieve steady state. Fluid quantities delivered by drug infusions increase with drug flow rate and can represent a large fraction of estimated maintenance fluid requirements. Fluid delivery increases if stock drug concentrations are diluted. These relationships were qualitatively similar for propofol and remifentanil. Conclusions: Traditional studies focus on drug disposition once a drug enters the circulation. Our analysis shows the potential importance of factors influencing drug delivery to the patient's circulation, focusing on propofol and remifentanil administration to small patients. The drug mass available for inadvertent bolus residing in the reservoir of the dead volume at steady state may be large and clinically relevant. Lag times to achieve steady-state delivery are long, depending on the infusion system's architecture and fluid flow rates. By themselves, drug infusions can deliver significant fluid loads to children. These observations have practical and perhaps safety implications for infusions of drugs commonly administered to infants and children. C1 [Ma, Haobo; Peterfreund, Robert A.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Lovich, Mark A.] Caritas St Elizabeths Med Ctr, Dept Anesthesiol & Pain Med, Boston, MA USA. RP Peterfreund, RA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Jackson 439,55 Fruit St, Boston, MA 02114 USA. EM RPeterfreund@Partners.org FU Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital FX We thank Dr. Charles Cote and Dr. Lucinda Everett for helpful comments during the preparation of this manuscript. Supported by institutional funds from the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital. NR 7 TC 11 Z9 12 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1155-5645 J9 PEDIATR ANESTH JI Pediatr. Anesth. PD JAN PY 2011 VL 21 IS 1 BP 78 EP 86 DI 10.1111/j.1460-9592.2010.03475.x PG 9 WC Anesthesiology; Pediatrics SC Anesthesiology; Pediatrics GA 694NF UT WOS:000285304200013 PM 21155930 ER PT J AU Srinivasan, R Song, YL Wiener-Kronish, J Flori, HR AF Srinivasan, Ramya Song, Yuanlin Wiener-Kronish, Jeanine Flori, Heidi R. TI Plasminogen activation inhibitor concentrations in bronchoalveolar lavage fluid distinguishes ventilator-associated pneumonia from colonization in mechanically ventilated pediatric patients SO PEDIATRIC CRITICAL CARE MEDICINE LA English DT Article DE ventilator-associated pneumonia; biological markers; surfactant protein D; plasminogen activation inhibitor; soluble triggering receptor expressed on myeloid cells; receptor for advanced glycation end-products; intensive care unit; pediatric ID GLYCATION END-PRODUCTS; SURFACTANT PROTEIN-A; ACUTE LUNG INJURY; RESPIRATORY-DISTRESS-SYNDROME; PNEUMOCOCCAL PNEUMONIA; MYELOID CELLS; HOST-DEFENSE; RISK-FACTORS; RECEPTOR; DIAGNOSIS AB Objective: To compare the ability of four biomarkers to distinguish between those with ventilator-associated pneumonia (VAP) vs. lower respiratory tract bacterial colonization in mechanically ventilated intensive care unit (ICU) pediatric patients. Design: Prospective, pilot cohort study. Setting: Tertiary care children's hospital, pediatric ICU. Patients: All pediatric ICU patients mechanically ventilated >48 hrs were eligible for enrollment between April 2006 to May 2007. Thirty-three patients were consecutively screened and enrolled after institutional consent process. Interventions: None. Measurements and Main Results: VAP was defined by both Centers for Disease and Prevention/National Nosocomial Infections Surveillance criteria and clinician diagnosis; those not meeting the criteria were considered to be colonized. Plasminogen activation inhibitor (PAI-1), soluble triggering receptor expressed on myeloid cells, receptor for advanced glycation end-products, and surfactant protein D levels were measured in bronchoalveolar lavage samples on average within 24 hrs of suspicion for VAP, i.e., a positive screening endotracheal Gram stain. Sixteen patients were diagnosed with VAP and 17 met the criteria for colonization. PAI-1 was associated with VAP independent of age, sex, race, acute lung injury/acute respiratory distress syndrome, Pediatric Risk of Mortality 3 score, pediatric logistic organ dysfunction score, and duration of intubation. The receiver operating characteristics for PAI-1 showed good discrimination with an area under the curve of 0.82. PAI-1 levels of >= 2.8 ng/mL had a sensitivity of 81.3%, specificity of 76.5%, and positive likelihood ratio of 3.5. Levels of soluble triggering receptor expressed on myeloid cells, receptor for advanced glycation end-products, and surfactant protein D were not significantly associated with VAP. Conclusions: In mechanically ventilated pediatric ICU patients, PAI-1 is independently associated with the diagnosis of VAP. Real-time measurement of PAI-1 levels in bronchoalveolar lavage fluid may be of benefit in the early diagnosis and subsequent treatment of VAP in ICU patients. (Pediatr Crit Care Med 2011; 12:21-27) C1 [Srinivasan, Ramya; Song, Yuanlin] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Wiener-Kronish, Jeanine] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Flori, Heidi R.] Childrens Hosp & Res Ctr Oakland, Oakland, CA USA. RP Srinivasan, R (reprint author), Univ Calif San Francisco, San Francisco, CA 94143 USA. EM rsrinivasan2004@yahoo.com FU SCCOR [HL74005, HL69809]; PCRC [M01-RR01271] FX The research was funded, in part, by SCCOR HL74005 and HL69809, PCRC M01-RR01271, and in-kind donation of Combicath catheters from SRC Medical. NR 37 TC 12 Z9 12 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1529-7535 J9 PEDIATR CRIT CARE ME JI Pediatr. Crit. Care Med. PD JAN PY 2011 VL 12 IS 1 BP 21 EP 27 DI 10.1097/PCC.0b013e3181e2a352 PG 7 WC Critical Care Medicine; Pediatrics SC General & Internal Medicine; Pediatrics GA 703FT UT WOS:000285964500014 PM 20473240 ER PT J AU West, PL McKeown, NJ Hendrickson, RG AF West, Patrick Leight McKeown, Nathanael J. Hendrickson, Robert G. TI Massive Hymenoptera Envenomation in a 3-Year-Old SO PEDIATRIC EMERGENCY CARE LA English DT Article DE Hymenoptera; yellow jacket; massive envenomation; rhabdomyolysis ID AFRICANIZED HONEYBEE STINGS; ACUTE-RENAL-FAILURE; YELLOW JACKET; BEE STINGS; INSECT STINGS; CHILD; HORNET; VENOM AB Background: Envenomation by a large number of hymenopterans can cause significant morbidity and mortality due to venom load. We present the first case of massive Hymenoptera envenomation by native US Hymenoptera. Case: A 3-year-old boy and his family were hiking in Oregon and were attacked by yellow jackets. On emergency department arrival, the child was uncomfortable and vomiting. Vital signs were normal; physical examination showed more than 90 punctate lesions on the head and neck, and 30 below the neck without urticaria. Initial laboratory values were normal except for a white blood cell count of 37,500/mu L and mild hypokalemia, including a normal creatinine kinase. Intravenously administered fluids, ondansetron, midazolam, and morphine were given for symptom control. Generalized edema developed 12 hours later and was treated with intravenously administered dexamethasone and diphenhydramine. His creatinine kinase peaked at 2085 U/L after 32 hours. Forty-eight hours after the incident, the child began to take oral fluids with laboratory values returning to normal. Discussion: Delayed toxic effects of mass envenomation are due to direct toxic effects from the large venom load, with several cases of death reported. All prior cases of mass Hymenoptera envenomation in the United States have involved Africanized "killer" honeybees. Guidelines recommend admitting all pediatric patients sustaining more than 50 stings for 24 hours for laboratory evaluations. Conclusions: Delayed toxic reaction may be caused by native US species of Hymenoptera. Physicians should be aware that endemic US species can cause this reaction and should have a low threshold to admit pediatric patients with more than 50 stings for 24 hours. C1 [West, Patrick Leight; McKeown, Nathanael J.; Hendrickson, Robert G.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [West, Patrick Leight; McKeown, Nathanael J.; Hendrickson, Robert G.] Oregon Poison Ctr, Portland, OR USA. [McKeown, Nathanael J.] Portland VA Med Ctr, Portland, OR USA. RP West, PL (reprint author), 3181 SW Sam Jackson Pk Rd,CB 550, Portland, OR 97239 USA. EM westp@ohsu.edu NR 20 TC 2 Z9 2 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0749-5161 J9 PEDIATR EMERG CARE JI Pediatr. Emerg. Care PD JAN PY 2011 VL 27 IS 1 BP 46 EP 48 DI 10.1097/PEC.0b013e3182045f47 PG 3 WC Emergency Medicine; Pediatrics SC Emergency Medicine; Pediatrics GA 702SO UT WOS:000285916000014 PM 21206257 ER PT J AU Diekema, DS Joffe, S Vandeven, AM Lantos, JD AF Diekema, Douglas S. Joffe, Steven Vandeven, Andrea M. Lantos, John D. TI Bone Marrow Donation Between Siblings Living in Different Families SO PEDIATRICS LA English DT Article ID CELL DONORS; TRANSPLANTATION; OSTEOPETROSIS; ETHICS C1 [Lantos, John D.] Childrens Mercy Hosp, Dept Pediat, Ctr Bioeth, Kansas City, MO 64108 USA. [Diekema, Douglas S.] Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA. [Diekema, Douglas S.] Seattle Childrens Hosp, Treuman Katz Ctr Pediat Bioeth, Seattle, WA USA. [Joffe, Steven] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Joffe, Steven] Childrens Hosp, Dept Med, Boston, MA 02115 USA. [Joffe, Steven] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Vandeven, Andrea M.; Lantos, John D.] Univ Missouri, Dept Pediat, Kansas City, MO 64110 USA. [Vandeven, Andrea M.] Childrens Mercy Hosp, Sect Child Abuse & Neglect, Kansas City, MO 64108 USA. RP Lantos, JD (reprint author), Childrens Mercy Hosp, Dept Pediat, Ctr Bioeth, 2401 Gillham Rd, Kansas City, MO 64108 USA. EM jlantos@cmh.edu OI Joffe, Steven/0000-0002-0667-7384 NR 9 TC 0 Z9 0 U1 1 U2 3 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JAN PY 2011 VL 127 IS 1 BP 158 EP 162 DI 10.1542/peds.2010-2577 PG 5 WC Pediatrics SC Pediatrics GA 700YT UT WOS:000285782200057 PM 21172994 ER PT J AU Camargo, CA Ingham, T Wickens, K Thadhani, R Silvers, KM Epton, MJ Town, GI Pattemore, PK Espinola, JA Crane, J AF Camargo, Carlos A., Jr. Ingham, Tristram Wickens, Kristin Thadhani, Ravi Silvers, Karen M. Epton, Michael J. Town, G. Ian Pattemore, Philip K. Espinola, Janice A. Crane, Julian TI Cord-Blood 25-Hydroxyvitamin D Levels and Risk of Respiratory Infection, Wheezing, and Asthma SO PEDIATRICS LA English DT Article DE vitamin D; 25-hydroxyvitamin D; cord blood; respiratory infection; wheezing; asthma; New Zealand ID VITAMIN-D DEFICIENCY; NEW-ZEALAND; CHILDREN; PREGNANCY; CATHELICIDIN; INFANTS; SCHOOLCHILDREN; PREVALENCE; CHILDHOOD; INFLUENZA AB OBJECTIVE: Higher maternal intake of vitamin D during pregnancy is associated with a lower risk of wheezing in offspring. The relationship between cord-blood levels of 25-hydroxyvitamin D (25[OH]D) and childhood wheezing is unknown. We hypothesized that cord-blood levels would be inversely associated with risk of respiratory infection, wheezing, and asthma. PATIENTS AND METHODS: Cord blood from 922 newborns was tested for 25(OH)D. Parents were asked if their child had a history of respiratory infection at 3 months of age or a history of wheezing at 15 months of age and then annually thereafter. Incident asthma was defined as doctor-diagnosed asthma by the time the child was 5 years old and reported inhaler use or wheezing since the age of 4 years. RESULTS: The median cord-blood level of 25(OH)D was 44 nmol/L (interquartile range: 29-78). Follow-up was 89% at the age of 5 years. Adjusting for the season of birth, 25(OH)D had an inverse association with risk of respiratory infection by 3 months of age (odds ratio: 1.00 [reference] for >= 75 nmol/L, 1.39 for 25-74 nmol/L, and 2.16 [95% confidence interval: 1.35-3.46] for <25 nmol/L). Likewise, cord-blood 25(OH) D levels were inversely associated with risk of wheezing by 15 months, 3 years, and 5 years of age (all P < .05). Additional adjustment for more than 12 potential confounders did not materially change these results. In contrast, we found no association between 25(OH)D levels and incident asthma by the age of 5 years. CONCLUSIONS: Cord-blood levels of 25(OH)D had inverse associations with risk of respiratory infection and childhood wheezing but no association with incident asthma. Pediatrics 2011;127:e180-e187 C1 [Camargo, Carlos A., Jr.; Thadhani, Ravi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr D Receptor Activat Res, Boston, MA 02114 USA. [Camargo, Carlos A., Jr.; Espinola, Janice A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02114 USA. [Ingham, Tristram; Wickens, Kristin; Crane, Julian] Univ Otago, Wellington Sch Med & Hlth Sci, Dept Med, Wellington Asthma Res Grp, Wellington, New Zealand. [Silvers, Karen M.; Epton, Michael J.; Pattemore, Philip K.] Univ Otago, Christchurch Sch Med & Hlth Sci, Dept Paediat, Canterbury Resp Res Grp, Christchurch, New Zealand. [Town, G. Ian] Univ Canterbury, Christchurch 1, New Zealand. RP Camargo, CA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr D Receptor Activat Res, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM ccamargo@partners.org OI Siebers, Robert/0000-0002-6359-3144 FU Health Research Council of New Zealand; David and Cassie Anderson Bequest (Wellington, New Zealand); Massachusetts General Hospital Center for D-Receptor Activation Research (Boston, MA) FX This work was supported by grants from the Health Research Council of New Zealand, the David and Cassie Anderson Bequest (Wellington, New Zealand), and the Massachusetts General Hospital Center for D-Receptor Activation Research (Boston, MA). NR 40 TC 223 Z9 229 U1 3 U2 24 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JAN PY 2011 VL 127 IS 1 BP E180 EP E187 DI 10.1542/peds.2010-0442 PG 8 WC Pediatrics SC Pediatrics GA 700YT UT WOS:000285782200023 PM 21187313 ER PT J AU Henderson, E Testa, MA Hartnick, C AF Henderson, Elisabeth Testa, Marcia A. Hartnick, Christopher TI Prevalence of Noise-Induced Hearing-Threshold Shifts and Hearing Loss Among US Youths SO PEDIATRICS LA English DT Article DE adolescent; audiometry; auditory threshold; cross-sectional studies; hearing loss ID NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; YOUNG-ADULTS; AMPLIFIED MUSIC; MP3 PLAYERS; CHILDREN 6; ADOLESCENTS; CONSERVATION; ABILITY; DAMAGE AB OBJECTIVE: We investigated trends in noise-induced threshold shifts (NITSs), high-frequency hearing loss (HFHL), and low-frequency hearing loss (LFHL). METHODS: A total of 4310 adolescents 12 to 19 years of age completed audiometric testing during National Health and Nutrition Examination Surveys in 1988-1994 and 2005-2006. NITS criteria were audiometric patterns of decreased 3- to 6-kHz thresholds but preserved 0.5- to 1-kHz and 8-kHz thresholds; HFHL and LFHL criteria were high and low pure-tone averages, respectively, of >15 dB HL. RESULTS: There were no significant increases in NITSs (odds ratio [OR]: 0.81 [95% confidence interval [CI]: 0.53-1.22]; P = .29), HFHL (OR: 1.21 [95% CI: 0.87-1.69]; P = .25), or LFHL (OR: 1.37 [95% CI: 0.77-2.45]; P = .28) between survey periods. However, a significant increase in the prevalence of NITSs occurred among female youths (11.6% [95% CI: 9.0%-14.1%] vs 16.7% [95% CI: 13.2%-20.3%]; P < .0001). The overall prevalence of exposure to loud noise or listening to music through headphones in the previous 24 hours increased from 19.8% (95% CI: 17.6%-22.1%) to 34.8% (95% CI: 31.0%-38.5%; P < .0001). In 2005-2006, female youths had a similar prevalence of exposure to recreational noise (23.6% [95% CI: 19.6%-27.6%] vs 27.7% [95% CI: 23.6%-31.8%]; P < .0001) and a lower prevalence of hearing-protection use (3.4% [95% CI: 1.6%-5.3%] vs 10.3% [95% CI: 7.3%-13.2%]; P < .0001) compared with male youths. CONCLUSIONS: Increased exposure to recreational noise and minimal use of hearing protection might have lead to an increase in NITS prevalence among female youths. Pediatrics 2011;127:e39-e46 C1 [Henderson, Elisabeth] Harvard Univ, Peabody Soc, Sch Med, Sch Publ Hlth, Boston, MA 02115 USA. [Testa, Marcia A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Hartnick, Christopher] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, Boston, MA 02115 USA. RP Henderson, E (reprint author), Harvard Univ, Peabody Soc, Sch Med, Sch Publ Hlth, 25 Shattuck St, Boston, MA 02115 USA. EM elisabeth_henderson@hms.harvard.edu RI lee, an chi/G-7503-2011 NR 37 TC 61 Z9 63 U1 5 U2 36 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JAN PY 2011 VL 127 IS 1 BP E39 EP E46 DI 10.1542/peds.2010-0926 PG 8 WC Pediatrics SC Pediatrics GA 700YT UT WOS:000285782200006 PM 21187306 ER PT J AU Staley, BA Vail, EA Thiele, EA AF Staley, Brigid A. Vail, Emily A. Thiele, Elizabeth A. TI Tuberous Sclerosis Complex: Diagnostic Challenges, Presenting Symptoms, and Commonly Missed Signs SO PEDIATRICS LA English DT Article DE tuberous sclerosis complex; diagnosis; epilepsy; seizures; neurocutaneous disorders ID MUTATIONAL ANALYSIS; INFANTILE SPASMS; TSC2; LYMPHANGIOLEIOMYOMATOSIS; RHABDOMYOMA; FEATURES; CRITERIA AB OBJECTIVE: To describe presenting symptoms and signs according to age group in a cohort of 243 patients with tuberous sclerosis complex (TSC) and identify earlier symptoms and signs that did not lead to immediate diagnosis. PATIENTS AND METHODS: We performed a retrospective chart review for 278 patients with TSC who were examined at Children's Hospital Boston in Massachusetts and at the Herscot Center for Tuberous Sclerosis Complex, Massachusetts General Hospital. The presenting symptom or sign was the first symptom or sign to cause suspicion for TSC and lead to diagnosis. Missed symptoms or signs were those that were documented in the patient's chart but did not immediately lead to diagnosis. RESULTS: There were 243 patients for whom there were sufficient data for inclusion in this study. Patients were diagnosed with TSC at ages ranging from birth to 73 years. The average age at diagnosis was 7.5 years. Of the patients, 81% were diagnosed before the age of 10. Diagnosis during adolescence and adulthood was not uncommon. The most common presenting symptoms and signs included new onset of seizures, history of seizures, infantile spasms, family history of TSC, cardiac rhabdomyomas, and hypopigmented macules. Of the patients, 39% reported missed symptoms or signs of TSC, most commonly seizures (including infantile spasms) and dermatologic features. CONCLUSIONS: Many patients had symptoms or signs of TSC that did not lead to immediate diagnosis. Clinicians should be aware of the myriad potential presenting symptoms and signs of TSC. Early diagnosis may reduce morbidity and mortality. Pediatrics 2011;127:e117-e125 C1 [Staley, Brigid A.; Vail, Emily A.; Thiele, Elizabeth A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Thiele, EA (reprint author), Herscot Ctr Tuberous Sclerosis Complex, 175 Cambridge St,Suite 340, Boston, MA 02114 USA. EM ethiele@partners.org FU National Institutes of Health/National Institute of Neurological Disorders and Stroke [P01 NS024279]; National Institutes of Health (NIH) FX This work was supported by National Institutes of Health/National Institute of Neurological Disorders and Stroke grant P01 NS024279.; Funded by the National Institutes of Health (NIH). NR 31 TC 27 Z9 29 U1 1 U2 8 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JAN PY 2011 VL 127 IS 1 BP E117 EP E125 DI 10.1542/peds.2010-0192 PG 9 WC Pediatrics SC Pediatrics GA 700YT UT WOS:000285782200015 PM 21173003 ER PT J AU Goebel, M Stengel, A Wang, LX Tache, Y AF Goebel, Miriam Stengel, Andreas Wang, Lixin Tache, Yvette TI Central nesfatin-1 reduces the nocturnal food intake in mice by reducing meal size and increasing inter-meal intervals SO PEPTIDES LA English DT Article DE Food intake; Hypothalamus; Meal pattern; Mouse; Nesfatin-1; Satiation; Satiety ID REGULATED TRANSCRIPT PEPTIDE; SATIETY MOLECULE NESFATIN-1; EDINGER-WESTPHAL NUCLEUS; BLOOD-BRAIN-BARRIER; RAT-BRAIN; HYPOTHALAMUS; IMMUNOREACTIVITY; NEURONS; SYSTEM; IDENTIFICATION AB Nesfatin-1 is well established to reduce food intake upon brain injection in rats, while in mice its anorexigenic action and brain expression are largely unexplored. We characterized the influence of intracerebroventricular (icy) and peripheral (intraperitoneal, ip, subcutaneous, sc) injection of nesfatin-1 on dark phase ingestive behavior using an automated feeding monitoring system and co-localized NUCB2/nesfatin-1 immunoreactivity in the associated brain areas. Nesfatin-1 (0.3, 1 or 3 mu g/mouse, icy) caused a dose-related reduction of 4-h dark phase food intake by 13%, 27%, and 46% respectively. Nesfatin-1 (3 mu g/mouse, icy) action had a 2-h delayed onset, 82% peak inhibition occurring at 3-4 h post-injection and was long lasting (30% reduction for 12 h period post-injection). Nesfatin-1 (3 mu g/mouse, icv)-treated mice had a 46% lower meal frequency associated with 2-times longer inter-meal intervals and a 35% reduction in meal size compared to vehicle during the 1-4 h post-injection (p<0.05). NUCB2/nesfatin-1-immunopositive neurons were found in hypothalamic (supraoptic, paraventricular, arcuate, dorsomedial, lateral) and brainstem (dorsal vagal complex) feeding regulatory nuclei. When injected peripherally, neither food intake nor feeding microstructure parameters were altered. These results demonstrate that NUCB2/nesfatin-1 is prominently expressed in mouse hypothalamus and medulla and acts in the brain to curtail the dark phase feeding by inducing satiation and satiety indicated by reduced meal size and prolonged inter-meal intervals respectively. The lack of nesfatin-1 effect when injected peripherally at a 23-times higher dose indicates a primarily central site of the anorexigenic action for nesfatin-1 in mice. (C) 2010 Elsevier Inc. All rights reserved. C1 Univ Calif Los Angeles, CURE Digest Dis Res Ctr, Ctr Neurobiol Stress, Dept Med,Digest Dis Div, Los Angeles, CA 90073 USA. Vet Affairs Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90073 USA. RP Tache, Y (reprint author), VA GLA Healthcare Syst, Ctr Neurobiol Stress, CURE Bldg 115,Room 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM ytache@mednet.ucla.edu FU Veterans Administration [R01 NIH DK-33061, DK-41301] FX This work was supported by Veterans Administration Research Career Scientist Award, R01 NIH DK-33061, Center Grant DK-41301 (Animal Core and Supplement Grant, Y.T. and Peptide Biochemistry Core, Joseph R. Reeve, Jr.). We are grateful to Dr. Kym Faull for performing the mass spectral analysis, to Mrs. Honghui Liang for the excellent technical support and thank Ms. Eugenia Hu for reviewing the manuscript. NR 38 TC 51 Z9 54 U1 1 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 JAN PY 2011 VL 32 IS 1 BP 36 EP 43 DI 10.1016/j.peptides.2010.09.027 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 711CC UT WOS:000286562300006 PM 20933030 ER PT J AU Wang, LX Stengel, A Goebel, M Martinez, V Gourcerol, G Rivier, J Tache, Y AF Wang, Lixin Stengel, Andreas Goebel, Miriam Martinez, Vicente Gourcerol, Guillaume Rivier, Jean Tache, Yvette TI Peripheral activation of corticotropin-releasing factor receptor 2 inhibits food intake and alters meal structures in mice SO PEPTIDES LA English DT Article DE Urocortin; Corticotropin-releasing factor receptor; Food intake; Astressin(2)-B; Meal pattern; Mouse ID UROCORTIN-III; FACTOR CRF; MOTOR-ACTIVITY; COLONIC TRANSIT; OBESE MICE; RAT; BRAIN; HORMONE; EXPRESSION; AGONIST AB The orexigenic effect of urocortins (Ucns), namely Ucn 1, Ucn 2 and Ucn 3 through activation of corticotropin-releasing factor (CRF) receptors, has been well characterized after injection into the brain but not in the periphery. We examined the role of CRF receptor subtype 2 (CRF(2)) in the regulation of food intake using intraperitoneal (ip) injection of Ucns and the selective CRF(2) antagonist, astressin(2)-B, and CRF(2) knockout (-/-) mice. Meal structures were monitored using an automated episodic solid food intake monitoring system. Ucn 2 (3, 10 or 30 mu g/kg, ip) induced a rapid in onset, long lasting and dose-dependent decrease (38%, 66% and 86%, respectively at 4 h) of cumulative food intake after an overnight fast in mice. Ucn 3 anorexic effect was 10-times less potent. Astressin(2)-B (30 or 100 mu g/kg) injected ip, but not intracerebroventricularly, blocked the inhibitory effect of ip Ucn 1 and Ucn 2 (10 mu g/kg). Fasted CRF(2-/-) mice did not respond to ip Ucn 1 (10 mu g/kg). Meal microstructure analysis of the 4-h re-feeding response to an overnight fast showed that Ucn 2 (10 mu g/kg, ip) decreased meal size and duration, but increased meal frequency. In mice fed ad libitum, Ucn 2 (30 mu g/kg) injected ip before the dark phase decreased the 4-h nocturnal meal size and duration without influencing meal frequency while the 10 mu g/kg dose had no effect. These data indicate that Ucns, through peripheral CRF(2) receptor-mediated induction of satiation, inhibit the eating response to a fast more potently than the physiological nocturnal feeding in mice. (C) 2010 Elsevier Inc. All rights reserved. C1 [Wang, Lixin; Stengel, Andreas; Goebel, Miriam; Martinez, Vicente; Gourcerol, Guillaume; Tache, Yvette] Univ Calif Los Angeles, David Geffen Sch Med, CURE Digest Dis Res Ctr, Ctr Neurobiol Stress,Dept Med,Digest Dis Div, Los Angeles, CA 90095 USA. [Wang, Lixin; Stengel, Andreas; Goebel, Miriam; Martinez, Vicente; Gourcerol, Guillaume; Tache, Yvette] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Rivier, Jean] Salk Inst Biol Studies, Peptide Biol Labs, La Jolla, CA USA. RP Wang, LX (reprint author), Bldg 115,Rm 117B,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM lixinw@ucla.edu RI Martinez, Vicente/N-1189-2014 FU Digestive Diseases Research Center [DK 41301]; Veterans Administration; NIHDDK [PO1 26741]; German Research Foundation [STE 1765/1-1, GO 1718/1-1]; [R01 NIH DK-33061]; [R01 NIH DDK 57238] FX This work was supported by R01 NIH DK-33061, R01 NIH DDK 57238, Digestive Diseases Research Center DK 41301 (Animal Core and Administrative Supplement Grant) and Veterans Administration Research Career Scientist Award (Y.T), NIHDDK PO1 26741 (J.R.) and German Research Foundation Grants STE 1765/1-1 (A.S.), GO 1718/1-1 (M.G.). J.R. is the Dr. Frederik Paulsen Chair in Neurosciences Professor and Founder of Sentia Medical Sciences Inc. We are grateful to Mrs. Honghui Liang for her excellent technical support and we thank Ms. Eugenia Hu for reviewing the manuscript. NR 42 TC 10 Z9 10 U1 0 U2 4 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 JAN PY 2011 VL 32 IS 1 BP 51 EP 59 DI 10.1016/j.peptides.2010.10.017 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 711CC UT WOS:000286562300008 PM 20969907 ER PT J AU Lembke, V Goebel, M Frommelt, L Inhoff, T Lommel, R Stengel, A Tache, Y Grotzinger, C Bannert, N Wiedenmann, B Klapp, BF Kobelt, P AF Lembke, Vanessa Goebel, Miriam Frommelt, Lisa Inhoff, Tobias Lommel, Reinhardt Stengel, Andreas Tache, Yvette Groetzinger, Carsten Bannert, Norbert Wiedenmann, Bertram Klapp, Burghard F. Kobelt, Peter TI Sulfated cholecystokinin-8 activates phospho-mTOR immunoreactive neurons of the paraventricular nucleus in rats SO PEPTIDES LA English DT Article DE CCK; c-Fos oxytocin; Phospho-mTOR; PVN ID C-FOS EXPRESSION; DORSAL VAGAL COMPLEX; FOOD-INTAKE; PERIPHERAL INJECTION; SOLITARY TRACT; BRAIN-STEM; LEAN MICE; OXYTOCIN; HYPOTHALAMUS; SATIETY AB The serin/threonin-kinase, mammalian target of rapamycin (mTOR) was detected in the arcuate nucleus (ARC) and paraventricular nucleus of the hypothalamus (PVN) and suggested to play a role in the integration of satiety signals. Since cholecystokinin (CCK) plays a role in the short-term inhibition of food intake and induces c-Fos in PVN neurons, the aim was to determine whether intraperitoneally injected CCK-8S affects the neuronal activity in cells immunoreactive for phospho-mTOR in the PVN. Ad libitum fed male Sprague-Dawley rats received 6 or 10 mu g/kg CCK-8S or 0.15 M NaCl ip (n = 4/group). The number of c-Fos-immunoreactive (ir) neurons was assessed in the PVN, ARC and in the nucleus of the solitary tract (NTS). CCK-8S increased the number of c-Fos-ir neurons in the PVN (6 mu g: 103 +/- 13 vs. 10 mu g: 165 +/- 14 neurons/section; p<0.05) compared to vehicle treated rats (4 +/- 1, p<0.05), but not in the ARC. CCK-8S also dose-dependently increased the number of c-Fos neurons in the NTS. Staining for phospho-mTOR and c-Fos in the PVN showed a dose-dependent increase of activated phospho-mTOR neurons (17 +/- 3 vs. 38 +/- 2 neurons/section; p < 0.05), while no activated phospho-mTOR neurons were observed in the vehicle group. Triple staining in the PVN showed activation of phospho-mTOR neurons co-localized with oxytocin, corresponding to 9.8 +/- 3.6% and 19.5 +/- 3.3% of oxytocin neurons respectively. Our observations indicate that peripheral CCK-8S activates phospho-mTOR neurons in the PVN and suggest that phospho-mTOR plays a role in the mediation of CCK-8S's anorexigenic effects. (C) 2010 Elsevier Inc. All rights reserved. C1 [Lembke, Vanessa; Frommelt, Lisa; Lommel, Reinhardt; Stengel, Andreas; Klapp, Burghard F.; Kobelt, Peter] Univ Med Berlin, Dept Med, Div Psychosomat Med & Psychotherapy, Charite, Berlin, Germany. [Goebel, Miriam; Stengel, Andreas; Tache, Yvette] Univ Calif Los Angeles, Dept Med, Div Digest Dis, CURE Digest Dis Res Ctr, Los Angeles, CA 90024 USA. [Goebel, Miriam; Stengel, Andreas; Tache, Yvette] Univ Calif Los Angeles, Ctr Neurobiol Stress, Los Angeles, CA 90024 USA. [Goebel, Miriam; Stengel, Andreas; Tache, Yvette] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Inhoff, Tobias; Groetzinger, Carsten; Wiedenmann, Bertram; Kobelt, Peter] Univ Med Berlin, Dept Med, Div Hepatol Gastroenterol & Endocrinol, Charite, Berlin, Germany. [Bannert, Norbert] Robert Koch Inst, D-1000 Berlin, Germany. RP Kobelt, P (reprint author), Charite Univ Med Berlin, Dept Med, Div Psychosomat Med & Psychotherapy, Campus Mitte,Luisenstr 13 A, D-10117 Berlin, Germany. EM peter.kobelt@charite.de OI Grotzinger, Carsten/0000-0001-9872-3087 FU German Research Foundation [DFG KO 3864/2-1]; Charite-Universitatsmedizin Berlin [UFF 10/45004, 10/45018]; Veterans Administration; [DK-41301] FX This work was supported by grants from the German Research Foundation to P.K. (DFG KO 3864/2-1) and from Charite-Universitatsmedizin Berlin to P.K. (UFF 10/45004 and 10/45018) as well as Veterans Administration Research Career Scientist Award (Y.T.), and Center Grant DK-41301 (Animal Core, Y.T.). NR 37 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 0196-9781 J9 PEPTIDES JI Peptides PD JAN PY 2011 VL 32 IS 1 BP 65 EP 70 DI 10.1016/j.peptides.2010.09.025 PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 711CC UT WOS:000286562300010 PM 20933028 ER PT J AU Glick, HA AF Glick, Henry A. TI Sample Size and Power for Cost-Effectiveness Analysis (Part 1) SO PHARMACOECONOMICS LA English DT Article ID EFFECTIVENESS RATIOS; CLINICAL-TRIALS AB Basic sample size and power formulae for cost-effectiveness analysis have been established in the literature. These formulae are reviewed and the similarities and differences between sample size and power for cost-effectiveness analysis and for the analysis of other continuous variables such as changes in blood pressure or weight are described. The types of sample size and power tables that are commonly calculated for cost-effectiveness analysis are also described and the impact of varying the assumed parameter values on the resulting sample size and power estimates is discussed. Finally, the way in which the data for these calculations may be derived are discussed. C1 [Glick, Henry A.] Univ Penn, Div Gen Internal Med, Philadelphia, PA 19104 USA. [Glick, Henry A.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Glick, HA (reprint author), Univ Penn, Div Gen Internal Med, Room 1211 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM hlthsvrs@mail.med.upenn.edu FU Center for Health Equity Research and Promotion, Philadelphia Veterans Affairs Medical Center FX This article was funded in part by the Center for Health Equity Research and Promotion, Philadelphia Veterans Affairs Medical Center. NR 22 TC 13 Z9 13 U1 0 U2 7 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1170-7690 J9 PHARMACOECONOMICS JI Pharmacoeconomics PY 2011 VL 29 IS 3 BP 189 EP 198 DI 10.2165/11585080-000000000-00000 PG 10 WC Economics; Health Care Sciences & Services; Health Policy & Services; Pharmacology & Pharmacy SC Business & Economics; Health Care Sciences & Services; Pharmacology & Pharmacy GA 730RD UT WOS:000288050900003 PM 21309615 ER PT J AU Glick, HA AF Glick, Henry A. TI Sample Size and Power for Cost-Effectiveness Analysis (Part 2) The Effect of Maximum Willingness to Pay SO PHARMACOECONOMICS LA English DT Article ID LIFE AB Sample size and power for cost-effectiveness analysis depend on assumptions about the difference in cost and effect, the standard deviations of cost and effect, the correlation of the difference in cost and effect, the alpha and beta errors and maximum willingness to pay (W). The first seven of these parameters share much in common in their effect on sample size and power for cost-effectiveness analysis, including that each is associated with a single pattern of power. W, on the other hand, is unique in that, when plotted for positive values, we can potentially observe any of six patterns of power associated with positive values of W. In addition, as W approaches infinity, power need be neither monotonically increasing nor decreasing and it can be multi-modal. In this article, the relationship between W and sample size and power is explained. C1 [Glick, Henry A.] Univ Penn, Div Gen Internal Med, Philadelphia, PA 19104 USA. [Glick, Henry A.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Glick, HA (reprint author), Univ Penn, Div Gen Internal Med, Room 1211 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM hlthsvrs@mail.med.upenn.edu FU Center for Health Equity Research and Promotion, Philadelphia Veterans Affairs Medical Center FX This work was funded in part by the Center for Health Equity Research and Promotion, Philadelphia Veterans Affairs Medical Center. The author has no conflicts of interest that are directly relevant to the content of this article. NR 7 TC 4 Z9 4 U1 0 U2 1 PU ADIS INT LTD PI NORTHCOTE PA 5 THE WAREHOUSE WAY, NORTHCOTE 0627, AUCKLAND, NEW ZEALAND SN 1170-7690 EI 1179-2027 J9 PHARMACOECONOMICS JI Pharmacoeconomics PY 2011 VL 29 IS 4 BP 287 EP 296 PG 10 WC Economics; Health Care Sciences & Services; Health Policy & Services; Pharmacology & Pharmacy SC Business & Economics; Health Care Sciences & Services; Pharmacology & Pharmacy GA 746TV UT WOS:000289271500002 PM 21395349 ER PT J AU Goehler, A Geisler, BP Manne, JM Jahn, B Conrads-Frank, A Schnell-Inderst, P Gazelle, GS Siebert, U AF Goehler, Alexander Geisler, Benjamin P. Manne, Jennifer M. Jahn, Beate Conrads-Frank, Annette Schnell-Inderst, Petra Gazelle, G. Scott Siebert, Uwe TI Decision-Analytic Models to Simulate Health Outcomes and Costs in Heart Failure A Systematic Review SO PHARMACOECONOMICS LA English DT Review ID CARDIAC RESYNCHRONIZATION THERAPY; IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; LEFT-VENTRICULAR DYSFUNCTION; BETA-BLOCKER THERAPY; MYOCARDIAL-INFARCTION; ECONOMIC-EVALUATION; NATRIURETIC PEPTIDE; MANAGEMENT PROGRAMS; DISEASE MANAGEMENT; ASSIST DEVICES AB Chronic heart failure (CHF) is a critical public health issue with increasing effect on the healthcare budgets of developed countries. Various decision-analytic modelling approaches exist to estimate the cost effectiveness of health technologies for CHF. We sought to systematically identify these models and describe their structures. We performed a systematic literature review in MEDLINE/PreMEDLINE, EMBASE, EconLit and the Cost-Effectiveness Analysis Registry using a combination of search terms for CHF and decision-analytic models. The inclusion criterion required 'use of a mathematical model evaluating both costs and health consequences for CHF management strategies'. Studies that were only economic evaluations alongside a clinical trial or that were purely descriptive studies were excluded. We identified 34 modelling studies investigating different interventions including screening (n = 1), diagnostics (n = 1), pharmaceuticals (n = 15), devices (n = 13), disease management programmes (n = 3) and cardiac transplantation (n = 1) in CHF. The identified models primarily focused on middle-aged to elderly patients with stable but progressed heart failure with systolic left ventricular dysfunction. Modelling approaches varied substantially and included 27 Markov models, three discrete-event simulation models and four mathematical equation sets models; 19 studies reported QALYs. Three models were externally validated. In addition to a detailed description of study characteristics, the model structure and output, the manuscript also contains a synthesis and critical appraisal for each of the modelling approaches. Well designed decision models are available for the evaluation of different CHF health technologies. Most models depend on New York Heart Association (NYHA) classes or number of hospitalizations as proxy for disease severity and progression. As the diagnostics and biomarkers evolve, there is the hope for better intermediate endpoints for modelling disease progression as those that are currently in use all have limitations. C1 [Goehler, Alexander; Geisler, Benjamin P.; Gazelle, G. Scott; Siebert, Uwe] Harvard Univ, Sch Med, Inst Technol Assessment, Massachusetts Gen Hosp, Boston, MA 02214 USA. [Goehler, Alexander] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac MR,PET,CT Program,Dept Radiol, Boston, MA 02214 USA. [Goehler, Alexander; Geisler, Benjamin P.; Jahn, Beate; Conrads-Frank, Annette; Schnell-Inderst, Petra; Siebert, Uwe] UMIT Univ Hlth Sci Med Informat & Technol, Dept Publ Hlth Informat Syst & Hlth Technol Asses, Inst Publ Hlth Med Decis Making & Hlth Technol As, Hall In Tirol, Austria. [Goehler, Alexander] Univ Duisburg Essen, Inst Hlth Syst Management, Alfried Krupp von Bohlen & Halbach Fdn, Essen, Germany. [Manne, Jennifer M.] Harvard Univ, Sch Publ Hlth, Dept Populat & Int Hlth, Boston, MA 02214 USA. [Gazelle, G. Scott; Siebert, Uwe] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Ctr Hlth Decis Sci, Boston, MA 02214 USA. RP Goehler, A (reprint author), Harvard Univ, Sch Med, Inst Technol Assessment, Massachusetts Gen Hosp, 165 Cambridge St,Suite 400, Boston, MA 02214 USA. EM alex@mgh-ita.org RI Geisler, Benjamin/A-9244-2010 OI Geisler, Benjamin/0000-0003-1704-6067 FU Competence Network of Heart Failure; Federal Ministry of Education and Research (BMBF), Germany [01GI0205] FX This work was supported by the Competence Network of Heart Failure, funded by the Federal Ministry of Education and Research (BMBF), Germany (funding no. 01GI0205). NR 55 TC 8 Z9 8 U1 3 U2 15 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1170-7690 J9 PHARMACOECONOMICS JI Pharmacoeconomics PY 2011 VL 29 IS 9 BP 753 EP 769 PG 17 WC Economics; Health Care Sciences & Services; Health Policy & Services; Pharmacology & Pharmacy SC Business & Economics; Health Care Sciences & Services; Pharmacology & Pharmacy GA 822ST UT WOS:000295070600003 PM 21557632 ER PT J AU Kaplan, GB Heinrichs, SC Carey, RJ AF Kaplan, Gary B. Heinrichs, Stephen C. Carey, Robert J. TI Treatment of addiction and anxiety using extinction approaches: Neural mechanisms and their treatment implications SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Review DE Exposure therapy; Extinction; Substance use disorder; Addiction; Anxiety; Posttraumatic stress disorder; Classical conditioning; GABA; Glutamate; Dopamine ID POSTTRAUMATIC-STRESS-DISORDER; CUE EXPOSURE TREATMENT; RANDOMIZED CONTROLLED-TRIAL; CONTROLLED CLINICAL-TRIAL; NUCLEUS-ACCUMBENS CORE; D-CYCLOSERINE; FEAR EXTINCTION; ALCOHOL DEPENDENCE; PREFRONTAL CORTEX; SEEKING BEHAVIOR AB Clinical interventions which produce cue and contextual extinction learning can reduce craving and relapse in substance abuse and inhibit conditioned fear responses in anxiety disorders. In both types of disorders, classical conditioning links unconditioned drug or fear responses to associated contextual cues and result in enduring pathological responses to multiple stimuli. Extinction therapy countermeasures seek to reduce conditioned responses using a set of techniques in which patients are repeatedly exposed to conditioned appetitive or aversive stimuli using imaginal imagery, in vivo exposure, or written scripts. Such interventions allow patients to rehearse more adaptive responses to conditioned stimuli. The ultimate goal of these interventions, extinction of the original conditioned response, is a new learning process that results in a decrease in frequency or intensity of conditioned responses to drug or fear cues. This review explores extinction approaches in conditioned drug reward and fear responses. The behavioral, neuroanatomical and neurochemical mechanisms of conditioned reward and fear responses and their extinction are derived from our understanding of the animal literature. Extensive neuroscience research shows that even though many mechanisms differ in conditioned fear and reward, converging prefrontal cortical glutamatergic pathways underlie extinction learning. Efficacy of pharmacological and behavioral treatment approaches in addiction and anxiety disorders may be optimized by enhancing extinction and weakening the bond between the original conditioned stimuli and conditioned responses. Adjunctive pharmacotherapy approaches using agents which alter glutamate or y-aminobutyric acid signaling or epigenetic mechanisms in prefrontal cortical pathways can enhance extinction learning. A comparative study of extinction processes and its neural mechanisms can be translated into more effective behavioral and pharmacological treatment approaches in substance abuse and anxiety. Published by Elsevier Inc. C1 [Kaplan, Gary B.; Heinrichs, Stephen C.] VA Boston Healthcare Syst, Mental Hlth & Res Serv, Boston, MA USA. [Kaplan, Gary B.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Carey, Robert J.] Syracuse VA Med Ctr, Syracuse, NY USA. [Carey, Robert J.] SUNY Upstate Med Univ, Syracuse, NY USA. RP Kaplan, GB (reprint author), VA Boston, 150 S Huntington Ave, Boston, MA 02130 USA. EM gary.kaplan@va.gov FU Department of Veterans Affairs; Department of Defense CDMRP; National Institutes on Drug Abuse FX This work was supported by grants from the Department of Veterans Affairs and the Department of Defense CDMRP Concept Award grants to GBK and from the National Institutes on Drug Abuse to RCC. All authors contributed to and have approved the final draft of the manuscript. We thank Angela Young and Marsha Guy for their expert editing support. NR 62 TC 39 Z9 42 U1 2 U2 20 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD JAN PY 2011 VL 97 IS 3 BP 619 EP 625 DI 10.1016/j.pbb.2010.08.004 PG 7 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 707PR UT WOS:000286299000029 PM 20723558 ER PT J AU Vazquez, G Tondo, L Baldessarini, RJ AF Vazquez, G. Tondo, L. Baldessarini, R. J. TI Comparison of Antidepressant Responses in Patients with Bipolar vs. Unipolar Depression: A Meta-Analytic Review SO PHARMACOPSYCHIATRY LA English DT Article ID DISORDER PATIENTS; II DISORDER; EFFICACY; MONOTHERAPY; SAFETY; VENLAFAXINE; EPISODE; TRIALS; RISKS AB Background: Since there is considerable uncertainty about therapeutic responses to antidepressants among depressed patients diagnosed with bipolar (BP) vs. unipolar (UP) mood disorders, we have reviewed available studies that compared both types of depressed patients. Methods: Extensive computerized literature-searching identified reports of antidepressant studies involving both BP and UP depressed patients. We used random-effects meta-analysis to compare short-term drug responses by patient type, as well as meta-regression modeling for effects of selected covariates. Results: We identified only 10 studies meeting even liberal inclusion criteria, and they varied greatly in size and design quality. The overall difference in antidepressant responses between BP (n=863) and UP (n=2226) disorder patients was not significant (pooled RR = 1.05; CI: 0.96-1.15; p=0.34). Based on meta-regression, we also found no difference in responses based on diagnosis or subtype, subjects/study, % women, average age, or length of treatment based on meta-regression. Risk of manic-switching averaged 2.50 vs. 0.275%/week among BP vs. UP disorder patients, including co-treatment with mood stabilizers in 70% of BP patients. Comments: The findings suggest little difference in antidepressant responses by diagnostic type, sex, or other factors considered, but a substantial risk of mania and hypomania with BP disorders. However, data pertaining to the fundamental question of antidepressant response among BP vs. UP depressed patients were strikingly limited, and support only tentative conclusions. Additional, well-designed, prospective trials of matched BP and UP depression patients and controlled treatment are required. C1 [Vazquez, G.] Univ Palermo, Dept Neurosci, Buenos Aires, DF, Argentina. [Vazquez, G.; Tondo, L.; Baldessarini, R. J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA USA. [Vazquez, G.; Tondo, L.; Baldessarini, R. J.] Harvard Univ, Sch Med, Neurosci Program, Boston, MA USA. [Vazquez, G.; Tondo, L.; Baldessarini, R. J.] Massachusetts Gen Hosp, McLean Hosp Div, Int Consortium Bipolar Disorder Res, Boston, MA 02114 USA. [Tondo, L.] Lucio Bini Mood Disorder Ctr, Cagliari, Sardinia, Italy. RP Baldessarini, RJ (reprint author), McLean Hosp, Mailman Res Ctr 306, 115 Mill St, Belmont, MA 02478 USA. EM rjb@mclean.org FU Bruce J. Anderson Foundation; McLean Hospital FX Partially supported by a grant from the Bruce J. Anderson Foundation and by the McLean Hospital Private Donors' Research Fund for Psychopharmacology (to RJB). NR 45 TC 21 Z9 21 U1 0 U2 2 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0176-3679 J9 PHARMACOPSYCHIATRY JI Pharmacopsychiatry PD JAN PY 2011 VL 44 IS 1 BP 21 EP 26 DI 10.1055/s-0030-1265198 PG 6 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 719EU UT WOS:000287184700003 PM 21031345 ER PT J AU Mroz, P Hamblin, MR AF Mroz, Pawel Hamblin, Michael R. TI The immunosuppressive side of PDT SO PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES LA English DT Review ID ENDOTHELIAL GROWTH-FACTOR; ADJUVANT-ENHANCED ARTHRITIS; SKIN ALLOGRAFT SURVIVAL; PHOTODYNAMIC THERAPY; ANTITUMOR IMMUNITY; APOPTOTIC CELLS; CONTACT HYPERSENSITIVITY; AMINOLEVULINIC-ACID; COMPLEMENT ACTIVATION; DENDRITIC CELLS AB Photodynamic therapy (PDT) is a promising novel therapeutic procedure for the management of a variety of solid tumors and many non-malignant diseases. PDT has been described as having a significant effect on the immune system, which may be either immunostimulatory or, in some circumstances, immunosuppressive. The immunosuppressive effects of PDT have nearly all been concerned with the suppression of the contact hypersensitivity reaction in mice. Here, we review the immunosuppressive aspects of PDT treatment and discuss some additional mechanisms that may be involved. C1 [Mroz, Pawel] Harvard Univ, Massachusetts Gen Hosp, Wellman Ctr Photomed, Sch Med, Boston, MA 02114 USA. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Mroz, Pawel; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02114 USA. RP Mroz, P (reprint author), Harvard Univ, Massachusetts Gen Hosp, Wellman Ctr Photomed, Sch Med, Blossom St,BAR406, Boston, MA 02114 USA. EM pmroz@partners.org OI Hamblin, Michael/0000-0001-6431-4605 FU NIAID NIH HHS [R01 AI050875] NR 77 TC 21 Z9 22 U1 2 U2 11 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1474-905X J9 PHOTOCH PHOTOBIO SCI JI Photochem. Photobiol. Sci. PY 2011 VL 10 IS 5 BP 751 EP 758 DI 10.1039/c0pp00345j PG 8 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA 756EY UT WOS:000289995700011 PM 21437314 ER PT J AU St Denis, TG Aziz, K Waheed, AA Huang, YY Sharma, SK Mroz, P Hamblin, MR AF St Denis, Tyler G. Aziz, Kanza Waheed, Anam A. Huang, Ying-Ying Sharma, Sulbha K. Mroz, Pawel Hamblin, Michael R. TI Combination approaches to potentiate immune response after photodynamic therapy for cancer SO PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES LA English DT Review ID COLONY-STIMULATING FACTOR; LOW-DOSE CYCLOPHOSPHAMIDE; VULVAL INTRAEPITHELIAL NEOPLASIA; TRANSITIONAL CELL-CARCINOMA; REGULATORY T-CELLS; ANTITUMOR IMMUNITY; STREPTOCOCCAL PREPARATION; CORYNEBACTERIUM PARVUM; COMPLEMENT ACTIVATION; LOCALIZED TREATMENT AB Photodynamic therapy (PDT) has been used as a cancer therapy for forty years but has not advanced to a mainstream cancer treatment. Although it has been shown to be an efficient way to destroy local tumors by a combination of non-toxic dyes and harmless visible light, it is its additional effects in mediating the stimulation of the host immune system that gives PDT great potential to become more widely used. Although the stimulation of tumor-specific cytotoxic T-cells that can destroy distant tumor deposits after PDT has been reported in some animal models, it remains the exception rather than the rule. This realization has prompted several investigators to test various combination approaches that could potentiate the immune recognition of tumor antigens that have been released after PDT. This review will cover these combination approaches using immunostimulants including various microbial preparations that activate Toll-like receptors and other receptors for pathogen-associated molecular patterns, cytokines growth factors, and approaches that target regulatory T-cells. We believe that by understanding the methods employed by tumors to evade immune response and neutralizing them, more precise ways of potentiating PDT-induced immunity can be devised. C1 [St Denis, Tyler G.; Aziz, Kanza; Waheed, Anam A.; Huang, Ying-Ying; Sharma, Sulbha K.; Mroz, Pawel; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [St Denis, Tyler G.] John Jay High Sch, Cross River, NY 10518 USA. [Aziz, Kanza; Waheed, Anam A.] Aga Khan Univ, Coll Med, Karachi 75950, Pakistan. [Huang, Ying-Ying; Mroz, Pawel; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Huang, Ying-Ying] Guangxi Med Univ, Aesthet & Plast Ctr, Nanning, Peoples R China. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP St Denis, TG (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 40 Blossom St, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu RI Huang, Ying-ying/G-3153-2011; OI Huang, Ying-ying/0000-0003-3066-6981; Hamblin, Michael/0000-0001-6431-4605 FU US-NIH [R01AI050875, R01CA/AI838801]; Center for Integration of Medicine and Innovative Technology [DAMD17-02-20006]; CDMRP Program in TBI [W81XWH-09-1-0514]; Air Force Office of Scientific Research [FA9950-04-1-0079] FX Research in the Hamblin laboratory is supported by US-NIH (grants R01AI050875 and R01CA/AI838801), Center for Integration of Medicine and Innovative Technology (DAMD17-02-20006), CDMRP Program in TBI (W81XWH-09-1-0514) and Air Force Office of Scientific Research (FA9950-04-1-0079). NR 73 TC 21 Z9 21 U1 2 U2 12 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1474-905X J9 PHOTOCH PHOTOBIO SCI JI Photochem. Photobiol. Sci. PY 2011 VL 10 IS 5 BP 792 EP 801 DI 10.1039/c0pp00326c PG 10 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA 756EY UT WOS:000289995700013 PM 21479313 ER PT J AU Dai, TH Tegos, GP St Denis, TG Anderson, D Sinofsky, E Hamblin, MR AF Dai, Tianhong Tegos, George P. St. Denis, Tyler G. Anderson, Don Sinofsky, Ed Hamblin, Michael R. TI Ultraviolet-C Irradiation for Prevention of Central Venous Catheter-related Infections: An In Vitro Study SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID MICROORGANISMS; INACTIVATION; VANCOMYCIN; BACTERIA; BIOFILMS; LOCK AB Central venous catheters (CVC) are widely used in the United States and are associated with 250 000 to 500 000 CVC-related infections in hospitals annually. We used a catheter made from ultraviolet-C (UVC) transmissive material to test whether delivery of UVC from the lumen would allow inactivation of microorganisms on the outer surface of CVC. When the catheter was exposed to UVC irradiation from a cold cathode fluorescent lamp inside the catheter lumen at a radiant exposure of 3.6 mJ cm(-2), more than 6-log(10) of drug-resistant Gram-positive bacteria adhered to the outer surface of the catheter were inactivated. Three to 7-log(10) of drug-resistant Gram-negative bacteria and 2.80-log(10) of fungi were inactivated at a radiant exposure of 11 mJ cm(-2). UVC irradiation also offered a highly selective inactivation of bacteria over keratinocytes under exactly comparable conditions. After 11 mJ cm(-2) UVC light had been delivered, over 6-log(10) of bacteria were inactivated while the viability loss of the keratinocytes was only about 57%. C1 [Dai, Tianhong; Tegos, George P.; St. Denis, Tyler G.; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Dai, Tianhong; Tegos, George P.; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [St. Denis, Tyler G.] John Jay High Sch, Cross River, NY USA. [Anderson, Don] LumiCare Med Syst Inc, Boston, MA USA. [Sinofsky, Ed] Photoglow Inc, S Yarmouth, MA USA. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu RI Tegos, George/C-8830-2011; OI Hamblin, Michael/0000-0001-6431-4605 FU NIH [R01 AI050875]; Bullock-Wellman Fellowship; Massachusetts Technology Transfer Center FX This work was supported by NIH grant R01 AI050875 to MRH. T.D. was supported by a Bullock-Wellman Fellowship. G.P.T was partly supported by a Massachusetts Technology Transfer Center Award. NR 17 TC 10 Z9 10 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD JAN-FEB PY 2011 VL 87 IS 1 BP 250 EP 255 DI 10.1111/j.1751-1097.2010.00819.x PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 705IM UT WOS:000286122100030 PM 21073470 ER PT J AU Guo, JJ Wang, SC Valerius, O Hall, H Zeng, QN Li, JF Weston, DJ Ellis, BE Chen, JG AF Guo, Jianjun Wang, Shucai Valerius, Oliver Hall, Hardy Zeng, Qingning Li, Jian-Feng Weston, David J. Ellis, Brian E. Chen, Jin-Gui TI Involvement of Arabidopsis RACK1 in Protein Translation and Its Regulation by Abscisic Acid SO PLANT PHYSIOLOGY LA English DT Article ID MESSENGER-RNA TRANSLATION; G-BETA-GAMMA; HETEROTRIMERIC G-PROTEINS; SACCHAROMYCES-CEREVISIAE; GENE-EXPRESSION; SIGNAL-TRANSDUCTION; INSERTIONAL MUTAGENESIS; EUKARYOTIC TRANSLATION; MESOPHYLL PROTOPLASTS; RIBOSOMAL-PROTEINS AB Earlier studies have shown that RACK1 functions as a negative regulator of abscisic acid (ABA) responses in Arabidopsis (Arabidopsis thaliana), but the molecular mechanism of the action of RACK1 in these processes remains elusive. Global gene expression profiling revealed that approximately 40% of the genes affected by ABA treatment were affected in a similar manner by the rack1 mutation, supporting the view that RACK1 is an important regulator of ABA responses. On the other hand, coexpression analysis revealed that more than 80% of the genes coexpressed with RACK1 encode ribosome proteins, implying a close relationship between RACK1's function and the ribosome complex. These results implied that the regulatory role for RACK1 in ABA responses may be partially due to its putative function in protein translation, which is one of the major cellular processes that mammalian and Saccharomyces cerevisiae RACK1 is involved in. Consistently, all three Arabidopsis RACK1 homologous genes, namely RACK1A, RACK1B, and RACK1C, complemented the growth defects of the S. cerevisiae cross pathway control2/rack1 mutant. In addition, RACK1 physically interacts with Arabidopsis Eukaryotic Initiation Factor6 (eIF6), whose mammalian homolog is a key regulator of 80S ribosome assembly. Moreover, rack1 mutants displayed hypersensitivity to anisomycin, an inhibitor of protein translation, and displayed characteristics of impaired 80S functional ribosome assembly and 60S ribosomal subunit biogenesis in a ribosome profiling assay. Gene expression analysis revealed that ABA inhibits the expression of both RACK1 and eIF6. Taken together, these results suggest that RACK1 may be required for normal production of 60S and 80S ribosomes and that its action in these processes may be regulated by ABA. C1 [Guo, Jianjun; Wang, Shucai; Hall, Hardy; Zeng, Qingning; Chen, Jin-Gui] Univ British Columbia, Dept Bot, Vancouver, BC V6T 1Z4, Canada. [Hall, Hardy; Zeng, Qingning; Ellis, Brian E.] Univ British Columbia, Michael Smith Labs, Vancouver, BC V6T 1Z4, Canada. [Guo, Jianjun; Li, Jian-Feng] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Guo, Jianjun; Li, Jian-Feng] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Valerius, Oliver] Univ Gottingen, Dept Mol Microbiol & Genet, Inst Microbiol & Genet, D-37077 Gottingen, Germany. [Weston, David J.; Chen, Jin-Gui] Oak Ridge Natl Lab, Biosci Div, Oak Ridge, TN 37831 USA. RP Chen, JG (reprint author), Univ British Columbia, Dept Bot, Vancouver, BC V6T 1Z4, Canada. EM chenj@ornl.gov RI Chen, Jin-Gui/A-4773-2011; Weston, David/A-9116-2011; Li, Jian-Feng/H-4307-2011; Zeng, Qingning/M-2245-2013 OI Chen, Jin-Gui/0000-0002-1752-4201; Weston, David/0000-0002-4794-9913; FU Natural Sciences and Engineering Research Council of Canada; Canada Foundation for Innovation; British Columbia Ministry of Advanced Education; U.S. Department of Energy [DE-AC05-00OR22725] FX This work was supported by grants from the Natural Sciences and Engineering Research Council of Canada, the Canada Foundation for Innovation, the British Columbia Ministry of Advanced Education, and the Laboratory Directed Research and Development Program of Oak Ridge National Laboratory, managed by UT-Battelle, LLC, for the U.S. Department of Energy under contract number DE-AC05-00OR22725. NR 64 TC 44 Z9 46 U1 3 U2 21 PU AMER SOC PLANT BIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA SN 0032-0889 J9 PLANT PHYSIOL JI Plant Physiol. PD JAN PY 2011 VL 155 IS 1 BP 370 EP 383 DI 10.1104/pp.110.160663 PG 14 WC Plant Sciences SC Plant Sciences GA 701QV UT WOS:000285838300035 PM 21098678 ER PT J AU Lee, CN Belkora, J Chang, Y Moy, B Partridge, A Sepucha, K AF Lee, Clara N. Belkora, Jeff Chang, Yuchiao Moy, Beverly Partridge, Ann Sepucha, Karen TI Are Patients Making High-Quality Decisions about Breast Reconstruction after Mastectomy? SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID INFORMED-CONSENT; CANCER-TREATMENT; PATIENTS RECALL; KNOWLEDGE; WOMEN; IMMEDIATE; REASONS; CHOICE AB Background: Variation in rates of breast reconstruction after mastectomy has raised concerns about the quality of decisions about reconstruction. The authors sought to evaluate patient decision making about reconstruction, using a validated measure of knowledge and preferences related to reconstruction. Methods: A cross-sectional survey of early-stage breast cancer survivors from four university medical centers was conducted. The survey included measures of knowledge about specific reconstruction facts, personal goals and concerns, and involvement in decision making. A multivariable linear regression model of characteristics associated with knowledge and a logistic regression model of factors associated with having reconstruction were developed. Results: A total of 84 patients participated (59 percent response rate). Participants answered 37.9 percent of knowledge questions correctly. Higher education (beta, 15 percent; p = 0.003) and having reconstruction (beta, 21 percent; p < 0.0001) were associated with higher knowledge. The goals "use your own tissue to make a breast" (odds ratio, 1.53; 95 percent CI, 1.15, 2.05) and "wake up after mastectomy with reconstruction underway" (odds ratio, 1.66; 95 percent CI, 1.30, 2.12) were associated with reconstruction. The goal "avoid putting foreign material in your body" was associated with no reconstruction (odds ratio, 0.64; 95 percent CI, 0.48, 0.86). Most patients reported they mainly made the decision or made the decision with the doctor equally (93 percent; 95 percent CI, 85 to 97 percent) and that their degree of involvement was about right (85 percent; 95 percent CI, 75 to 91 percent). Conclusions: Women treated with mastectomy in this study were not well-informed about breast reconstruction. Treatments were associated with patients' goals and concerns, however, and patients were highly involved in their decisions. Knowledge deficits suggest that breast cancer patients would benefit from interventions to support their decision making. (Plast. Reconstr. Surg. 127: 18, 2011.) C1 [Lee, Clara N.] Univ N Carolina, Div Plast & Reconstruct Surg, Lineberger Comprehens Canc Ctr, Sheps Ctr Hlth Serv Res, Chapel Hill, NC 27599 USA. Univ Calif San Francisco, Inst Hlth Policy Studies, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Ctr Canc, Dept Gen Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst, Cambridge, MA 02138 USA. RP Lee, CN (reprint author), Univ N Carolina, Div Plast & Reconstruct Surg, Lineberger Comprehens Canc Ctr, Sheps Ctr Hlth Serv Res, CB 7195, Chapel Hill, NC 27599 USA. EM cnlee@med.unc.edu FU Foundation for Informed Medical Decision Making; National Institutes of Health/Humanities Collections and Reference Resources [1KL2RR025746] FX This study was supported by a grant from the Foundation for Informed Medical Decision Making. Dr. Lee was supported by National Institutes of Health/Humanities Collections and Reference Resources grant 1KL2RR025746. NR 29 TC 21 Z9 21 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD JAN PY 2011 VL 127 IS 1 BP 18 EP 26 DI 10.1097/PRS.0b013e3181f958de PG 9 WC Surgery SC Surgery GA 703PU UT WOS:000285992100006 PM 21200195 ER PT J AU Yannas, IV Orgill, DP Burke, JF AF Yannas, Ioannis V. Orgill, Dennis P. Burke, John F. TI Template for Skin Regeneration SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID INTEGRA ARTIFICIAL SKIN; NERVE REGENERATION; DERMAL SUBSTITUTE; TISSUE DEFECTS; PORCINE MODEL; SCALP DEFECTS; BURN INJURY; RECONSTRUCTION; MATRIX; EXCISION AB Background: Advances in critical care allowed survival of large total body surface burn patients in the 1970s, spawning the development of artificial skin for burn victims. Lack of dermis resulted in severe scarring and contractures. The physicochemical properties that are critical to dermal regeneration have subsequently been described, and a dermal regeneration template has been developed. Methods: The peer-reviewed literature regarding the basic science and clinical use of dermal regeneration template was reviewed, as was our practical experience in using dermal regeneration template. Results: Dermal regeneration template has been effective in treating large areas of skin loss in burn victims and has been shown to have scar reductive and regenerative properties. Its use has been extended to reconstructive burns, including scar revisions and the treatment of burn scar contractures. It has also been useful in treating small areas of exposed bone, tendon, or joints and a variety of acute and chronic wounds. Meticulous wound bed preparation and close monitoring of the dermal regeneration template is critical to successful use. Conclusions: Dermal regeneration template provides a novel element to add to the reconstructive tools used today by plastic surgeons. Further development of these technologies may allow for improved regenerative capacity of these devices to allow optimal aesthetic and functional results of dermal reconstruction. (Plast. Reconstr. Surg. 127 (Suppl.): 60S, 2011.) C1 [Orgill, Dennis P.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Plast Surg, Boston, MA 02115 USA. MIT, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Orgill, DP (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Plast Surg, 75 Francis St, Boston, MA 02115 USA. EM dorgill@partners.org OI Orgill, Dennis/0000-0002-8279-7310 FU Integra LifeSciences FX Dr. Yannas has received royalties from the Massachusetts Institute of Technology relating to the dermal regeneration template technologies manufactured by Integra LifeSciences. He has been a consultant for and owns no shares in Integra LifeSciences. Dr. Orgill has been a consultant for Integra LifeSciences and has been a principal investigator on research grants to the Brigham and Women's Hospital by Integra LifeSciences. He has also received patent royalties from the Massachusetts Institute of Technology related to these technologies. Dr. Burke acknowledges stock interest in Integra LifeSciences. NR 66 TC 34 Z9 37 U1 5 U2 26 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD JAN PY 2011 VL 127 IS 1 SU S BP 60S EP 70S DI 10.1097/PRS.0b013e318200a44d PG 11 WC Surgery SC Surgery GA 705IP UT WOS:000286122400010 PM 21200274 ER PT J AU Veves, A AF Veves, Aristidis TI Discussion: Bioengineered Skin Constructs and Their Use in Wound Healing SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Editorial Material ID DIABETIC FOOT ULCERS; TRIAL C1 [Veves, Aristidis] Harvard Univ, Sch Med, Microcirculat Lab, Boston, MA 02215 USA. [Veves, Aristidis] Harvard Univ, Sch Med, Joslin Beth Israel Deaconess Foot Ctr, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Veves, A (reprint author), Harvard Univ, Sch Med, Microcirculat Lab, Palmer 318,Beth Israel Deaconess Med Ctr W Campus, Boston, MA 02215 USA. EM aveves@bidmc.harvard.edu NR 4 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD JAN PY 2011 VL 127 IS 1 SU S BP 91S EP 92S DI 10.1097/PRS.0b013e3182009d8c PG 2 WC Surgery SC Surgery GA 705IP UT WOS:000286122400013 PM 21200277 ER PT J AU Rao, NL Ziran, BH Lipsky, BA AF Rao, Nalini Ziran, Bruce H. Lipsky, Benjamin A. TI Treating Osteomyelitis: Antibiotics and Surgery SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID INTRAVENOUS ANTIMICROBIAL THERAPY; RNAIII-INHIBITING PEPTIDE; DIABETIC FOOT INFECTIONS; NEEDLE BONE-BIOPSY; STAPHYLOCOCCUS-AUREUS; ORTHOPEDIC INFECTIONS; PRESSURE ULCERS; SOFT-TISSUE; BEADS; DISEASES AB Background: Osteomyelitis is an inflammatory disorder of bone caused by infection leading to necrosis and destruction. It can affect all ages and involve any bone. Osteomyelitis may become chronic and cause persistent morbidity. Despite new imaging techniques, diagnosis can be difficult and often delayed. Because infection can recur years after apparent "cure," "remission" is a more appropriate term. Methods: The study is a nonsystematic review of literature. Results: Osteomyelitis usually requires some antibiotic treatment, usually administered systemically but sometimes supplemented by antibiotic-containing beads or cement. Acute hematogenous osteomyelitis can be treated with antibiotics alone. Chronic osteomyelitis, often accompanied by necrotic bone, usually requires surgical therapy. Unfortunately, evidence for optimal treatment regimens or therapy durations largely based upon expert opinion, case series, and animal models. Antimicrobial therapy is now complicated by the increasing prevalence of antibiotic-resistant organisms, especially methicillin-resistant Staphylococcus aureus. Without surgical resection of infected bone, antibiotic treatment must be prolonged to 6 weeks). Advances in surgical technique have increased the potential for bone (and often limb) salvage and infection remission. Conclusions: Osteomyelitis is best managed by a multidisciplinary team. It requires accurate diagnosis and optimization of host defenses, appropriate anti-infective therapy, and often bone debridement and reconstructive surgery. The antibiotic regimen must target the likely (or optimally proven) causative pathogen, with few adverse effects and reasonable costs. The authors offer practical guidance to the medical and surgical aspects of treating osteomyelitis. (Mast. Reconstr. Surg. 127 (Suppl.): 177S, 2011.) C1 Univ Pittsburgh, Sch Med, Atlanta Med Ctr, Pittsburgh, PA USA. Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. RP Rao, NL (reprint author), 5750 Ctr Ave,Suite 510, Pittsburgh, PA 15206 USA. EM raon@upmc.edu OI Lipsky, Benjamin A./0000-0001-9886-5114 FU Pfizer; Ortho-McNeil/Johnson Johnson; Cubist; Merck FX Dr. Lipsky has been a consultant to and received research funding from Pfizer, Ortho-McNeil/Johnson & Johnson, Cubist, and Merck. The other authors have no financial interest to disclose. NR 58 TC 44 Z9 49 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0032-1052 EI 1529-4242 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD JAN PY 2011 VL 127 IS 1 SU S BP 177S EP 187S DI 10.1097/PRS.0b013e3182001f0f PG 11 WC Surgery SC Surgery GA 705IP UT WOS:000286122400025 PM 21200289 ER PT J AU Abbott, MM Meara, JG AF Abbott, Megan M. Meara, John G. TI A Microcosting Approach for Isolated, Unilateral Cleft Lip Care in the First Year of Life SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID HEALTH-CARE; OROFACIAL CLEFTS; COSTS; CHILDREN; APPENDECTOMY AB Background: The concept of value-based health care underlies many new improvement initiatives in U. S. health care. To determine value, accurate measures of both outcomes and costs are essential, which may then be compared for the same provider or system over time or between providers, to foster improvement. Although outcomes measurement has received a great deal of attention since the quality movement began in the United States, costing methodologies are lacking. Methods: A basic microcosting methodology was used to obtain direct medical costs, including physician compensation, for individuals with isolated, unilateral cleft lip deformity receiving their full course of care from one surgeon. The authors analyzed costs associated with the timeline of care during the first year of life. Results: The median cost for the first year of life was $13,013 (range, $10,426 to $16,115; n = 12). Ninety-one percent of costs were associated with the cleft lip repair, which occurred at a median age of 3.7 months. The majority of these costs stemmed from time in the operating room and the inpatient stay, which accounted for 68 and 19 percent of first-year costs, respectively. Conclusions: Using a microcosting approach, the authors identified specific cost drivers and outlined a distinct timeline of care for patients with isolated cleft lip in the first year of life. This approach may serve as a template for the cost side of the value equation, for which accurate methodologies are needed. When combined with key outcomes measures, it will be possible to measure and improve value at the patient and provider levels. (Plast. Reconstr. Surg. 127: 333, 2011.) C1 [Meara, John G.] Childrens Hosp Boston, Dept Plast & Oral Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Meara, JG (reprint author), Childrens Hosp Boston, Dept Plast & Oral Surg, Boston, MA 02115 USA. EM john.meara@childrens.harvard.edu NR 18 TC 6 Z9 6 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD JAN PY 2011 VL 127 IS 1 BP 333 EP 339 DI 10.1097/PRS.0b013e3181f95af3 PG 7 WC Surgery SC Surgery GA 703PU UT WOS:000285992100045 PM 21200227 ER PT J AU Wray, NR Purcell, SM Visscher, PM AF Wray, Naomi R. Purcell, Shaun M. Visscher, Peter M. TI Synthetic Associations Created by Rare Variants Do Not Explain Most GWAS Results SO PLOS BIOLOGY LA English DT Article ID GENOME-WIDE ASSOCIATION; MISSING HERITABILITY; HUMAN HEIGHT; SCHIZOPHRENIA; FREQUENCIES; SIGNALS C1 [Wray, Naomi R.; Visscher, Peter M.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Purcell, Shaun M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Purcell, Shaun M.] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA USA. RP Wray, NR (reprint author), Queensland Inst Med Res, Brisbane, Qld 4006, Australia. EM Naomi.Wray@qimr.edu.au RI Wray, Naomi/C-8639-2015; OI Wray, Naomi/0000-0001-7421-3357; Visscher, Peter/0000-0002-2143-8760 FU Australian National Health and Medical Research Council [389892, 442915, 496688, 613672, 613601]; Australian Research Council [DP0770096, DP1093900] FX We acknowledge funding from the Australian National Health and Medical Research Council (grants 389892, 442915, 496688, 613672, and 613601) and the Australian Research Council (grants DP0770096 and DP1093900 and Future Fellowship to NRW). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 21 TC 97 Z9 99 U1 0 U2 11 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 JAN PY 2011 VL 9 IS 1 AR e1000579 DI 10.1371/journal.pbio.1000579 PG 11 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 711MF UT WOS:000286595000004 PM 21267061 ER PT J AU Festen, EAM Goyette, P Green, T Boucher, G Beauchamp, C Trynka, G Dubois, PC Lagace, C Stokkers, PCF Hommes, DW Barisani, D Palmieri, O Annese, V van Heel, DA Weersma, RK Daly, MJ Wijmenga, C Rioux, JD AF Festen, Eleonora A. M. Goyette, Philippe Green, Todd Boucher, Gabrielle Beauchamp, Claudine Trynka, Gosia Dubois, Patrick C. Lagace, Caroline Stokkers, Pieter C. F. Hommes, Daan W. Barisani, Donatella Palmieri, Orazio Annese, Vito van Heel, David A. Weersma, Rinse K. Daly, Mark J. Wijmenga, Cisca Rioux, John D. TI A Meta-Analysis of Genome-Wide Association Scans Identifies IL18RAP, PTPN2, TAGAP, and PUS10 As Shared Risk Loci for Crohn's Disease and Celiac Disease SO PLOS GENETICS LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; SUSCEPTIBILITY LOCI; ULCERATIVE-COLITIS; GENETIC-VARIANTS; MULTIPLE; IMPUTATION AB Crohn's disease (CD) and celiac disease (CelD) are chronic intestinal inflammatory diseases, involving genetic and environmental factors in their pathogenesis. The two diseases can co-occur within families, and studies suggest that CelD patients have a higher risk to develop CD than the general population. These observations suggest that CD and CelD may share common genetic risk loci. Two such shared loci, IL18RAP and PTPN2, have already been identified independently in these two diseases. The aim of our study was to explicitly identify shared risk loci for these diseases by combining results from genome-wide association study (GWAS) datasets of CD and CelD. Specifically, GWAS results from CelD (768 cases, 1,422 controls) and CD (3,230 cases, 4,829 controls) were combined in a meta-analysis. Nine independent regions had nominal association p-value <1.0x10(-5) in this meta-analysis and showed evidence of association to the individual diseases in the original scans (p-value <1x10(-2) in CelD and <1x10(-3) in CD). These include the two previously reported shared loci, IL18RAP and PTPN2, with p-values of 3.37x10(-8) and 6.39x10(-9), respectively, in the meta-analysis. The other seven had not been reported as shared loci and thus were tested in additional CelD (3,149 cases and 4,714 controls) and CD (1,835 cases and 1,669 controls) cohorts. Two of these loci, TAGAP and PUS10, showed significant evidence of replication (Bonferroni corrected p-values, <0.0071) in the combined CelD and CD replication cohorts and were firmly established as shared risk loci of genome-wide significance, with overall combined p-values of 1.55x10(-10) and 1.38x10(-11) respectively. Through a meta-analysis of GWAS data from CD and CelD, we have identified four shared risk loci: PTPN2, IL18RAP, TAGAP, and PUS10. The combined analysis of the two datasets provided the power, lacking in the individual GWAS for single diseases, to detect shared loci with a relatively small effect. C1 [Festen, Eleonora A. M.; Weersma, Rinse K.] Univ Groningen, Univ Med Ctr Groningen, Dept Gastroenterol & Hepatol, Groningen, Netherlands. [Festen, Eleonora A. M.; Trynka, Gosia; Wijmenga, Cisca] Univ Med Ctr Groningen, Dept Genet, NL-9713 AV Groningen, Netherlands. [Goyette, Philippe; Boucher, Gabrielle; Beauchamp, Claudine; Lagace, Caroline; Rioux, John D.] Univ Montreal, Res Ctr, Montreal, PQ, Canada. [Goyette, Philippe; Boucher, Gabrielle; Beauchamp, Claudine; Lagace, Caroline; Rioux, John D.] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. [Green, Todd; Daly, Mark J.] Broad Inst, Cambridge, MA USA. [Dubois, Patrick C.; van Heel, David A.] Queen Mary Univ London, Barts & London Sch Med & Dent, Blizard Inst Cell & Mol Sci, Ctr Digest Dis, London, England. [Stokkers, Pieter C. F.] Univ Amsterdam, Acad Med Ctr, Dept Gastroenterol & Hepatol, NL-1105 AZ Amsterdam, Netherlands. [Hommes, Daan W.] Leiden Univ, Med Ctr, Dept Gastroenterol & Hepatol, Leiden, Netherlands. [Barisani, Donatella] Univ Milano Bicocca, Fac Med, Dept Expt Med, Monza, Italy. [Palmieri, Orazio; Annese, Vito] IRCCS, Osped Casa Sollievo della Sofferenza, UO Gastroenterol & Endoscopia Digest, San Giovanni Rotondo, Italy. [Daly, Mark J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA. RP Festen, EAM (reprint author), Univ Groningen, Univ Med Ctr Groningen, Dept Gastroenterol & Hepatol, Groningen, Netherlands. EM R.K.Weersma@int.umcg.nl; john.david.rioux@umontreal.ca RI Wijmenga, Cisca/D-2173-2009; Rioux, John/A-9599-2015; Palmieri, Orazio/J-7697-2012; Festen, Eleonora/S-3557-2016; OI Rioux, John/0000-0001-7560-8326; Palmieri, Orazio/0000-0002-0019-7929; van Heel, David/0000-0002-0637-2265; Trynka, Gosia/0000-0002-6955-9529; Wijmenga, Cisca/0000-0002-5635-1614 FU Celiac Disease Consortium; Innovative Cluster; Dutch Government [BSIK03009]; Netherlands Organization for Scientific Research (NWO) [918.66.620, 92.003.533, 907.00.281]; Wellcome Trust [WT084743MA, 068545/Z/02, 085475]; National Institutes of Allergy and Infectious Diseases [AI065687, AI067152]; National Institute of Diabetes and Digestive and Kidney Diseases [DK064869, DK062432]; Crohn's and Colitis Foundation of America [SRA512]; The Netherlands Organisation for Health Research and Development; Royal Netherlands Academy of Arts and Sciences (KNAW); UK Medical Research Council [G0000934] FX The study was supported by the Celiac Disease Consortium, an Innovative Cluster approved by the Netherlands Genomics Initiative and partially funded by the Dutch Government (BSIK03009); by the Netherlands Organization for Scientific Research (NWO, VICI grant 918.66.620 to CW, AGIKO grant 92.003.533 to EAMF, KF grant 907.00.281 to RKW); by the Wellcome Trust (grant WT084743MA to DAvH); by the National Institutes of Allergy and Infectious Diseases (grant AI065687, AI067152 to JDR); by the National Institute of Diabetes and Digestive and Kidney Diseases (grant DK064869, DK062432 to JDR); and by the Crohn's and Colitis Foundation of America (grant SRA512 to JDR). EAMF is a MD-medical research trainee with financial support from The Netherlands Organisation for Health Research and Development. GT was awarded a Ter Meulen Fund travel grant by the Royal Netherlands Academy of Arts and Sciences (KNAW). PCD is a MRC Clinical Training Fellow (G0700545). The British 1958 Birth Cohort collection was funded by the UK Medical Research Council (grant G0000934) and the Wellcome Trust (grant 068545/Z/02). Funding for the project Wellcome Trust Case-Control Consortium 2 data was provided by the Wellcome Trust under award 085475. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 25 TC 81 Z9 83 U1 0 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD JAN PY 2011 VL 7 IS 1 AR e1001283 DI 10.1371/journal.pgen.1001283 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 712GG UT WOS:000286653500022 PM 21298027 ER PT J AU Rossin, EJ Lage, K Raychaudhuri, S Xavier, RJ Tatar, D Benita, Y Cotsapas, C Daly, MJ AF Rossin, Elizabeth J. Lage, Kasper Raychaudhuri, Soumya Xavier, Ramnik J. Tatar, Diana Benita, Yair Cotsapas, Chris Daly, Mark J. CA Int Inflammatory Bowel Dis Genetic TI Proteins Encoded in Genomic Regions Associated with Immune-Mediated Disease Physically Interact and Suggest Underlying Biology SO PLOS GENETICS LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; MOLECULAR INTERACTION DATABASE; LARGE-SCALE REPLICATION; SUSCEPTIBILITY LOCI; WIDE ASSOCIATION; RHEUMATOID-ARTHRITIS; CROHNS-DISEASE; INTERACTION NETWORK; GENETIC-VARIANTS; CELIAC-DISEASE AB Genome-wide association studies (GWAS) have defined over 150 genomic regions unequivocally containing variation predisposing to immune-mediated disease. Inferring disease biology from these observations, however, hinges on our ability to discover the molecular processes being perturbed by these risk variants. It has previously been observed that different genes harboring causal mutations for the same Mendelian disease often physically interact. We sought to evaluate the degree to which this is true of genes within strongly associated loci in complex disease. Using sets of loci defined in rheumatoid arthritis (RA) and Crohn's disease (CD) GWAS, we build protein-protein interaction (PPI) networks for genes within associated loci and find abundant physical interactions between protein products of associated genes. We apply multiple permutation approaches to show that these networks are more densely connected than chance expectation. To confirm biological relevance, we show that the components of the networks tend to be expressed in similar tissues relevant to the phenotypes in question, suggesting the network indicates common underlying processes perturbed by risk loci. Furthermore, we show that the RA and CD networks have predictive power by demonstrating that proteins in these networks, not encoded in the confirmed list of disease associated loci, are significantly enriched for association to the phenotypes in question in extended GWAS analysis. Finally, we test our method in 3 non-immune traits to assess its applicability to complex traits in general. We find that genes in loci associated to height and lipid levels assemble into significantly connected networks but did not detect excess connectivity among Type 2 Diabetes (T2D) loci beyond chance. Taken together, our results constitute evidence that, for many of the complex diseases studied here, common genetic associations implicate regions encoding proteins that physically interact in a preferential manner, in line with observations in Mendelian disease. C1 [Rossin, Elizabeth J.; Raychaudhuri, Soumya; Xavier, Ramnik J.; Benita, Yair; Cotsapas, Chris; Daly, Mark J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Rossin, Elizabeth J.; Raychaudhuri, Soumya; Xavier, Ramnik J.; Benita, Yair; Cotsapas, Chris; Daly, Mark J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Rossin, Elizabeth J.; Lage, Kasper; Raychaudhuri, Soumya; Xavier, Ramnik J.; Cotsapas, Chris; Daly, Mark J.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Rossin, Elizabeth J.; Lage, Kasper; Xavier, Ramnik J.; Daly, Mark J.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Rossin, Elizabeth J.; Daly, Mark J.] Harvard Univ, Hlth Sci & Technol MD Program, Boston, MA 02115 USA. [Rossin, Elizabeth J.; Daly, Mark J.] Harvard Univ, Harvard Biol & Biomed Sci Program, Boston, MA 02115 USA. [Lage, Kasper; Tatar, Diana] Massachusetts Gen Hosp, Pediat Surg Res Labs, Boston, MA 02114 USA. [Lage, Kasper] Tech Univ Denmark, Dept Syst Biol, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark. [Raychaudhuri, Soumya] Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. RP Rossin, EJ (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. EM mjdaly@chgr.mgh.harvard.edu RI Benita, Yair/E-3094-2012; D'Amato, Mauro/F-2450-2010; Ellinghaus, David/G-4467-2012; Silverberg, Mark/B-4183-2008; Rioux, John/A-9599-2015; Franke, Andre/B-2151-2010; OI Halfvarson, Jonas/0000-0003-0122-7234; Newman, William/0000-0002-6382-4678; D'Amato, Mauro/0000-0003-2743-5197; Rioux, John/0000-0001-7560-8326; Franke, Andre/0000-0003-1530-5811; Laukens, Debby/0000-0002-1984-5850; Gearry, Richard/0000-0002-2298-5141 FU MIT; Harvard; Forskningsradet for Sundhed og Sygdom; NICHD [HD055150-03]; NIH-NIAMS [AR055688]; Center for Study of Inflammatory Bowel Disease; [DK083756]; [DK086502] FX EJR was supported by the MIT IDEA2 Program (http://hst.mit.edu/go/idea2/), Harvard and MIT's Health Sciences and Technology Program, and Harvard's Biological and Biomedical Sciences Program (http://www.hms.harvard.edu/dms/bbs/). KL was supported by a grant from Forskningsradet for Sundhed og Sygdom and NICHD RO1 grant HD055150-03. SR was supported by a K08 NIH-NIAMS career development award (AR055688). RJX, MJD, and CC were supported by DK083756 and DK086502. DT was supported under NICHD RO1 grant HD055150-03. YB was supported by the Center for Study of Inflammatory Bowel Disease. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 64 TC 247 Z9 248 U1 4 U2 15 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD JAN PY 2011 VL 7 IS 1 AR e1001273 DI 10.1371/journal.pgen.1001273 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 712GG UT WOS:000286653500012 PM 21249183 ER PT J AU Ryan, ET AF Ryan, Edward T. TI The Cholera Pandemic, Still with Us after Half a Century: Time to Rethink SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Editorial Material C1 [Ryan, Edward T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ryan, Edward T.] Harvard Univ, Boston, MA 02115 USA. RP Ryan, ET (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM etryan@partners.org NR 3 TC 27 Z9 27 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1935-2727 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD JAN PY 2011 VL 5 IS 1 AR e1003 DI 10.1371/journal.pntd.0001003 PG 2 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 711MP UT WOS:000286596000026 PM 21283611 ER PT J AU Mikell, I Sather, DN Kalams, SA Altfeld, M Alter, G Stamatatos, L AF Mikell, Iliyana Sather, D. Noah Kalams, Spyros A. Altfeld, Marcus Alter, Galit Stamatatos, Leonidas TI Characteristics of the Earliest Cross-Neutralizing Antibody Response to HIV-1 SO PLOS PATHOGENS LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; PROXIMAL EXTERNAL REGION; FOLLICULAR-HELPER-CELLS; SUBTYPE-C INFECTION; MONOCLONAL-ANTIBODIES; DISEASE PROGRESSION; NONNEUTRALIZING ANTIBODIES; HIV-1-INFECTED PATIENTS; ANTI-GP41 ANTIBODIES; GLYCOPROTEIN GP41 AB Recent cross-sectional analyses of HIV-1+ plasmas have indicated that broadly cross-reactive neutralizing antibody responses are developed by 10%-30% of HIV-1+ subjects. The timing of the initial development of such anti-viral responses is unknown. It is also unknown whether the emergence of these responses coincides with the appearance of antibody specificities to a single or multiple regions of the viral envelope glycoprotein (Env). Here we analyzed the cross-neutralizing antibody responses in longitudinal plasmas collected soon after and up to seven years after HIV-1 infection. We find that anti-HIV-1 cross-neutralizing antibody responses first become evident on average at 2.5 years and, in rare cases, as early as 1 year following infection. If cross-neutralizing antibody responses do not develop during the first 2-3 years of infection, they most likely will not do so subsequently. Our results indicate a potential link between the development of cross-neutralizing antibody responses and specific activation markers on T cells, and with plasma viremia levels. The earliest cross-neutralizing antibody response targets a limited number of Env regions, primarily the CD4-binding site and epitopes that are not present on monomeric Env, but on the virion-associated trimeric Env form. In contrast, the neutralizing activities of plasmas from subjects that did not develop cross-neutralizing antibody responses target epitopes on monomeric gp120 other than the CD4-BS. Our study provides information that is not only relevant to better understanding the interaction of the human immune system with HIV but may guide the development of effective immunization protocols. Since antibodies to complex epitopes that are present on the virion-associated envelope spike appear to be key components of earliest cross-neutralizing activities of HIV-1+ plasmas, then emphasis should be made to elicit similar antibodies by vaccination. C1 [Mikell, Iliyana; Sather, D. Noah; Stamatatos, Leonidas] Seattle BioMed, Seattle, WA USA. [Mikell, Iliyana; Stamatatos, Leonidas] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA. [Kalams, Spyros A.] Vanderbilt Univ, Sch Med, Dept Med, Div Infect Dis, Nashville, TN 37212 USA. [Altfeld, Marcus; Alter, Galit] Ragon Inst Massachusetts Gen Hosp MIT & Harvard U, Boston, MA 02114 USA. RP Mikell, I (reprint author), Seattle BioMed, Seattle, WA USA. EM leo.stamatatos@seattlebiomed.org FU NIH [R01 AI081625, U01 A1078407, P01 AI78063]; M. J. Murdock Charitable Trust; J. B. Pendleton Charitable Trust FX This study was funded by NIH grants R01 AI081625 (LS), U01 A1078407 (SAK), P01 AI78063 (SAK). We would also like to acknowledge support by the M. J. Murdock Charitable Trust and the J. B. Pendleton Charitable Trust. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 61 TC 152 Z9 155 U1 1 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD JAN PY 2011 VL 7 IS 1 AR e1001251 DI 10.1371/journal.ppat.1001251 PG 15 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 712GL UT WOS:000286654100008 PM 21249232 ER PT J AU Hoerster, KD Mayer, JA Sallis, JF Pizzi, N Talley, S Pichon, LC Butler, DA AF Hoerster, Katherine D. Mayer, Joni A. Sallis, James F. Pizzi, Nicole Talley, Sandra Pichon, Latrice C. Butler, Dalila A. TI Dog walking: Its association with physical activity guideline adherence and its correlates SO PREVENTIVE MEDICINE LA English DT Article DE Dog walking; Physical activity; Health promotion ID NEIGHBORHOOD ENVIRONMENT; UNITED-STATES; HEALTH; OWNERSHIP; ADULTS; INTERVENTIONS; PROMOTE; BEHAVIOR; SCALE; PETS AB Objective. We examined the prevalence and correlates of dog walking among dog owners, and whether dog walking is associated with meeting the American College of Sports Medicine/American Heart Association physical activity guidelines. Methods. In March 2008, we mailed a survey to dog-owning clients from two San Diego County veterinary clinics. Useable data were obtained from 984 respondents, and 75 of these completed retest surveys. We assessed associations between potential correlates and dog walking (i.e., yes/no dog walking for at least 10 min in past week). Results. Test-retest reliability of measures was generally high. Approximately one-third of the sample (31.5%) were not dog walkers. Proportions of dog walkers versus non-dog walkers meeting United States guidelines were 64.3% and 55.0%, respectively. Dog walking was independently associated with meeting guidelines in a multivariate model (odds ratio = 1.59, p = 0.004). Three variables were independently associated with dog walking in a multivariate model: dog encouragement of dog walking, dog-walking obligation, and dog-walking self-efficacy. Conclusion. Dog walking was associated with meeting physical activity guidelines, making it a viable method for promoting physical activity. Dog-walking obligation and self-efficacy may be important mediators of dog walking and may need to be targeted if interventions are to be successful. Published by Elsevier Inc. C1 [Hoerster, Katherine D.; Mayer, Joni A.; Sallis, James F.; Pizzi, Nicole; Talley, Sandra; Pichon, Latrice C.; Butler, Dalila A.] San Diego State Univ, Sch Publ Hlth, San Diego, CA 92123 USA. [Hoerster, Katherine D.; Sallis, James F.] Univ Calif San Diego, San Diego State Univ, San Diego Joint Doctoral Program Clin Psychol, San Diego, CA 92120 USA. RP Hoerster, KD (reprint author), VA Puget Sound Healthcare Syst, Seattle Div, 1660 S Columbian Way,S-116, Seattle, WA 98108 USA. EM Katherine.Hoerster@va.gov FU San Diego State University Research Foundation FX We thank Debra Rubio, Beth Gordon, Elva Arredondo, Simon Marshall, Thomas McKenzie, Donald Slymen, and the San Diego Veterinary Medical Association. We thank the veterinarian owners and staff of the two participating clinics for their assistance with recruitment and other study procedures. This research was supported by a San Diego State University Research Foundation Research Support Fund awarded to Dr. Mayer. This funding source had no involvement in study design; in the collection, analysis, and interpretation of data; or in the decision to submit this article for publication. NR 39 TC 25 Z9 25 U1 2 U2 21 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD JAN PY 2011 VL 52 IS 1 BP 33 EP 38 DI 10.1016/j.ypmed.2010.10.011 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 707OQ UT WOS:000286296300008 PM 21047528 ER PT B AU Chen, CH Li, JS Hosseini, A Gadikota, HR Kozanek, M Gill, TJ Li, GA AF Chen, Chih-Hui Li, Jing-Sheng Hosseini, Ali Gadikota, Hemanth Reddy Kozanek, Michal Gill, Thomas J. Li, Guoan GP ASME TI TIBIOFEMORAL KINEMATICS OF THE KNEE DURING THE STANCE PHASE OF GAIT AFTER ACL DEFICIENCY SO PROCEEDINGS OF THE ASME SUMMER BIOENGINEERING CONFERENCE 2011, PTS A AND B LA English DT Proceedings Paper CT 13th ASME Summer Bioengineering Conference (SBC) CY JUN 22-25, 2011 CL Farmington, PA SP Amer Soc Mech Engineers, Bioengineer Div ID MOTION C1 [Chen, Chih-Hui; Li, Jing-Sheng; Hosseini, Ali; Gadikota, Hemanth Reddy; Kozanek, Michal; Gill, Thomas J.; Li, Guoan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Bioengn Lab, Boston, MA 02114 USA. RP Chen, CH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Bioengn Lab, Boston, MA 02114 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MECHANICAL ENGINEERS PI NEW YORK PA THREE PARK AVENUE, NEW YORK, NY 10016-5990 USA BN 978-0-7918-5458-7 PY 2011 BP 663 EP 664 PG 2 WC Biophysics; Engineering, Biomedical; Engineering, Mechanical SC Biophysics; Engineering GA BFL60 UT WOS:000320411400331 ER PT J AU Levy, BD Zhang, QY Bonnans, C Primo, V Reilly, JJ Perkins, DL Liang, YR Arnaout, MA Nikolic, B Serhan, CN AF Levy, Bruce D. Zhang, Qing-yin Bonnans, Caroline Primo, Valeria Reilly, John J. Perkins, David L. Liang, Yurong Arnaout, M. Amin Nikolic, Boris Serhan, Charles N. TI The endogenous pro-resolving mediators lipoxin A(4) and resolvin E1 preserve organ function in allograft rejection SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article DE Lipid mediators; Resolution; Transplantation; Allograft rejection ID HUMAN LUNG TRANSPLANTATION; BRONCHIOLITIS OBLITERANS; APOPTOTIC NEUTROPHILS; LIPID MEDIATORS; STABLE ANALOGS; INFLAMMATION; RESOLUTION; INHIBITION; RECEPTOR; INJURY AB Allograft rejection remains a major limitation to successful solid organ transplantation. Here, we investigated the biosynthesis and bioactions of the pro-resolving mediators lipoxin A(4) and resolvin E1 in host responses to organ transplantation. In samples obtained during screening bronchoscopy after human lung transplantation, bronchoalveolar lavage fluid levels of lipoxin A(4) were increased in association with the severity of allograft rejection that was graded independently by clinical pathology. Lipoxin A(4) significantly inhibited calcineurin activation in human neutrophils, and lipoxin A(4) stable analogs prevented acute rejection of vascularized cardiac and renal allografts. Transgenic animals expressing human lipoxin A(4) receptors revealed important sites of action in host tissues for lipoxin A(4)'s protective effects. Resolvin E1 displays counter-regulatory actions for leukocytes, in part, via increased lipoxin A(4) biosynthesis, yet RvE1 administered (1 mu g, iv) to donor (days - 1 and 0) and recipient mice (days - 1, 0 and +4) was even more potent than a lipoxin stable analog (1 mu g, iv) in prolonging renal allograft survival (median survival time=74.0 days with RvE1 and 37.5 days with a LXA(4) analog). Together, these results highlight the potential for pro-resolving mediators in prolonging survival of solid organ transplants. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Levy, Bruce D.; Bonnans, Caroline; Reilly, John J.] Brigham & Womens Hosp, Harvard Inst Med, Dept Internal Med, Boston, MA 02115 USA. [Levy, Bruce D.; Serhan, Charles N.] Brigham & Womens Hosp, Harvard Inst Med, Dept Anesthesiol Perioperat & Pain Med, Ctr Expt Therapeut & Reperfus Injury, Boston, MA 02115 USA. [Zhang, Qing-yin; Primo, Valeria; Arnaout, M. Amin; Nikolic, Boris] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nephrol, Boston, MA USA. [Perkins, David L.] Univ Calif San Diego, Sch Med, Dept Med, San Diego, CA 92103 USA. [Liang, Yurong] Chinese Peoples Liberat Army Gen Hosp, Hosp Hepatobiliary Surg, Beijing, Peoples R China. [Liang, Yurong] Chinese Peoples Liberat Army Gen Hosp, Inst Hepatobiliary Surg, Beijing, Peoples R China. RP Levy, BD (reprint author), Brigham & Womens Hosp, Harvard Inst Med, Dept Internal Med, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM blevy@partners.org; cnserhan@zeus.bwh.harvard.edu RI Reilly, John/H-8755-2012 FU National Kidney Foundation; La Fondation de la Recherche Medicale; [DK067940]; [HL68669]; [DE016191]; [DK48549]; [DK07448] FX This work was supported by DK067940 (BN), HL68669 (BDL), DE016191 (BDL, CNS), DK48549 (MAA) and DK07448 (CNS), by The Patricia Welder Robinson Young Investigator Grant of the National Kidney Foundation (BN) and a fellowship from La Fondation de la Recherche Medicale (CB). NR 44 TC 18 Z9 20 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD JAN-FEB PY 2011 VL 84 IS 1-2 BP 43 EP 50 DI 10.1016/j.plefa.2010.09.002 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA 718ZS UT WOS:000287166300007 PM 20869861 ER PT J AU Whitley, BM Moreira, DM Thomas, JA Aronson, WJ Terris, MK Presti, JC Kane, CJ Amling, CL Freedland, SJ AF Whitley, B. M. Moreira, D. M. Thomas, J-A Aronson, W. J. Terris, M. K. Presti, J. C., Jr. Kane, C. J. Amling, C. L. Freedland, S. J. CA SEARCH Database Study Grp TI Preoperative weight change and risk of adverse outcome following radical prostatectomy: results from the Shared Equal Access Regional Cancer Hospital database SO PROSTATE CANCER AND PROSTATIC DISEASES LA English DT Article DE biochemical recurrence; obesity; radical prostatectomy; weight change ID BODY-MASS INDEX; OBESITY; GROWTH; MEN; MORTALITY; INSULIN; RECURRENCE; CARBOHYDRATE; RESTRICTION; SURVIVAL AB BACKGROUND: We examined the relationship between weight change in the year before radical prostatectomy (RP) and biochemical recurrence (BCR) and adverse pathology. METHODS: We abstracted data from 359 men undergoing RP in the SEARCH (Shared Equal Access Regional Cancer Hospital) database between 2001-2007. Logistic regression and Cox proportional hazards models were used to test the association between weight change in the year before surgery and adverse pathology and BCR, respectively. RESULTS: In all, 152 (42%) men gained weight, 193 (54%) lost weight and 14 (4%) had the same weight. Among weight gainers, median gain was 2.4 kg and among weight losers, median loss was 2.7 kg. As a continuous variable, weight change was not associated with adverse pathology or BCR (all P>0.05). In secondary analysis, on multivariate analysis, men gaining >= 2.5 kg were at higher BCR risk (hazards ratio = 1.65, 95% confidence interval (Cl): 1.03-2.64, P = 0.04) while weight loss >= 2.5 kg was not associated with BCR (hazards ratio = 0.83, 95% CI: 0.54-1.29, P = 0.41). CONCLUSIONS: As a continuous variable, weight change was not associated with outcome. In secondary hypothesis-generating analyses, weight gain >= 2.5 kg in the year before surgery, regardless of final body mass index, was associated with increased BCR following RP. If validated, these data suggest weight gain >= 2.5 kg may promote prostate cancer progression. C1 [Freedland, S. J.] Duke Univ, Sch Med, Div Urol, Duke Prostate Ctr,Dept Pathol, Durham, NC 27710 USA. [Whitley, B. M.; Moreira, D. M.; Thomas, J-A; Freedland, S. J.] Duke Univ, Sch Med, Dept Surg, Duke Prostate Ctr,Div Urol Surg, Durham, NC 27710 USA. [Whitley, B. M.; Moreira, D. M.; Thomas, J-A; Freedland, S. J.] Vet Affairs Med Ctr, Dept Surg, Urol Sect, Durham, NC USA. [Aronson, W. J.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Surg, Urol Sect, Los Angeles, CA USA. [Aronson, W. J.] Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA USA. [Terris, M. K.] Vet Affairs Med Ctr, Dept Surg, Urol Sect, Augusta, GA USA. [Terris, M. K.] Med Coll Georgia, Dept Surg, Div Urol Surg, Augusta, GA 30912 USA. [Presti, J. C., Jr.] Stanford Univ, Sch Med, Dept Urol, Palo Alto, CA 94304 USA. [Presti, J. C., Jr.] Vet Affairs Med Ctr, Dept Surg, Urol Sect, Palo Alto, CA 94304 USA. [Kane, C. J.] Univ Calif San Diego, Med Ctr, Dept Surg, Div Urol, San Diego, CA 92103 USA. [Amling, C. L.] Oregon Hlth & Sci Univ, Dept Surg, Div Urol, Portland, OR 97201 USA. RP Freedland, SJ (reprint author), Duke Univ, Sch Med, Div Urol, Duke Prostate Ctr,Dept Pathol, Box 2626 DUMC, Durham, NC 27710 USA. EM steve.freedland@duke.edu OI Terris, Martha/0000-0002-3843-7270; Moreira, Daniel/0000-0003-4517-244X NR 24 TC 8 Z9 8 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1365-7852 J9 PROSTATE CANCER P D JI Prostate Cancer Prostatic Dis. PY 2011 VL 14 IS 4 BP 361 EP 366 DI 10.1038/pcan.2011.42 PG 6 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 843FN UT WOS:000296657800013 PM 21894174 ER PT S AU Anderson, KS AF Anderson, Karen S. BE Wu, CJ TI Multiplexed Detection of Antibodies Using Programmable Bead Arrays SO PROTEIN MICROARRAY FOR DISEASE ANALYSIS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Bead array; Luminex; Autoantibodies; Biomarkers; ELISA ID ASSEMBLING PROTEIN MICROARRAYS; CANCER; RESPONSES AB The detection of antibodies in sera has broad applications for detection and monitoring of infectious diseases, autoimmunity, and cancer. Proteomic methods of antigen detection, such as protein microarrays, are excellent clinical discovery tools, but due to both cost and specialization of manufacture, these are limited to screening small numbers of sera. Downstream assays for biomarker validation studies require rapid, reproducible, multiplexed assays for the simultaneous screening of fewer (< 100) antigens with hundreds or thousands of sera. Traditional clinical ELISA assays use recombinant proteins, but these are limited by the ability to purify proteins free of cross-reacting contaminants and are limited to one antigen at a time. Here, WC describe the application of coupled in vitro protein production with anti-tag capture onto bead arrays, for the rapid multiplexed detection of antibodies in sera. These assays can be readily adapted for detection of any protein-specific infectious, autoimmune, or cancer-specific antibodies. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. RP Anderson, KS (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Canc Vaccine Ctr, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [U01 CA117374, 5U01CA117374] NR 11 TC 3 Z9 3 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-042-3 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 723 BP 227 EP 238 DI 10.1007/978-1-61779-043-0_15 D2 10.1007/978-1-61779-043-0 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA BUD42 UT WOS:000288923400015 PM 21370069 ER PT S AU Marina, O Duke-Cohan, JS Wu, CJ AF Marina, Ovidiu Duke-Cohan, Jonathan S. Wu, Catherine J. BE Wu, CJ TI A Coprecipitation-Based Validation Methodology for Interactions Identified Using Protein Microarrays SO PROTEIN MICROARRAY FOR DISEASE ANALYSIS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE High-throughput screening; Validation; Coupled transcription/translation in vitro; Coprecipitation; Image processing ID MASS-SPECTROMETRY AB Candidate interactions identified by high-throughput protein microarray screening require rigorous confirmation. Such validation is time-consuming and labor-intensive using conventional techniques. We describe a medium-throughput validation protocol based on coprecipitation of biotin-labeled proteins synthesized in vitro using a rabbit reticulocyte lysate-coupled transcription and translation system. As our experimental system is based on screening for serum antibodies, we also present methods on purifying immunoglobulin from scrum and quantifying the amount of coprecipitated (immunoprecipitated) target protein on Western blot. This technique provides a sensitive confirmatory test allowing for the rapid elimination of false positives prior to more extensive validation and analysis of target interactions in their native environment. C1 [Marina, Ovidiu] William Beaumont Hosp, Dept Radiat Oncol, Royal Oak, MI 48072 USA. [Duke-Cohan, Jonathan S.] Dana Farber Canc Inst, Immunobiol Lab, Dept Med Oncol, Boston, MA 02115 USA. [Wu, Catherine J.] Dana Farber Canc Inst, Div Hematol Neoplasia, Dept Med Oncol, Canc Vaccine Ctr, Boston, MA 02115 USA. RP Marina, O (reprint author), William Beaumont Hosp, Dept Radiat Oncol, Royal Oak, MI 48072 USA. OI Duke-Cohan, Jonathan/0000-0002-9478-9609 FU Howard Hughes Medical Institute; NCI NIH HHS [5R21CA115043-2] NR 13 TC 3 Z9 3 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-042-3 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 723 BP 239 EP 254 DI 10.1007/978-1-61779-043-0_16 D2 10.1007/978-1-61779-043-0 PG 16 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA BUD42 UT WOS:000288923400016 PM 21370070 ER PT S AU DeLuca, DS Marina, O Ray, S Zhang, GL Wu, CJ Brusic, V AF DeLuca, David S. Marina, Ovidiu Ray, Surajit Zhang, Guang Lan Wu, Catherine J. Brusic, Vladimir BE Wu, CJ TI Data Processing and Analysis for Protein Microarrays SO PROTEIN MICROARRAY FOR DISEASE ANALYSIS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Protein microarray; Concentration dependent analysis; Z score; Differential expression analysis; Bioinformatics ID NORMALITY AB Protein microarrays arc a high-throughput technology capable of generating large quantities of proteomics data. They can be used for general research or for clinical diagnostics. Bioinformatics and statistical analysis techniques are required for interpretation and reaching biologically relevant conclusions from raw data. We describe essential algorithms for processing protein microarray data, including spot-finding on slide images, Z score, and significance analysis of microarrays (SAM) calculations, as well as the concentration dependent analysis (CDA). We also describe available tools for protein microarray analysis, and provide a template for a step-by-step approach to performing an analysis centered on the CDA method. We conclude with a discussion of fundamental and practical issues and considerations. C1 [DeLuca, David S.; Wu, Catherine J.] Dana Farber Canc Inst, Canc Vaccine Ctr, Dept Med Oncol, Div Hematol Neoplasia, Boston, MA 02115 USA. [Marina, Ovidiu] William Beaumont Hosp, Dept Radiat Oncol, Royal Oak, MI USA. [Ray, Surajit] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Zhang, Guang Lan] Harvard Univ, Sch Med, Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. RP DeLuca, DS (reprint author), Dana Farber Canc Inst, Canc Vaccine Ctr, Dept Med Oncol, Div Hematol Neoplasia, Boston, MA 02115 USA. FU Howard Hughes Medical Institute; NCI NIH HHS [5R21CA115043-2] NR 24 TC 2 Z9 2 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-042-3 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 723 BP 337 EP 347 DI 10.1007/978-1-61779-043-0_21 D2 10.1007/978-1-61779-043-0 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA BUD42 UT WOS:000288923400021 PM 21370075 ER PT S AU Zhang, GL DeLuca, DS Brusic, V AF Zhang, Guang Lan DeLuca, David S. Brusic, Vladimir BE Wu, CJ TI Database Resources for Proteomics-Based Analysis of Cancer SO PROTEIN MICROARRAY FOR DISEASE ANALYSIS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Database; Proteomics; Protein microarray; Protein expression; Single nucleotide polymorphisms; Mutation; Tumor antigen; Protein-protein interaction; Biological pathway ID GENE-EXPRESSION DATABASE; GENOME ANATOMY PROJECT; MUTATIONS DATABASE; BIOLOGY DATABASE; HIGH-THROUGHPUT; TUMOR-ANTIGENS; 2004 UPDATE; PROTEIN; ARRAYS; IDENTIFICATION AB Biological/bioinformatics databases are essential for medical and biological studies. They integrate and organize biologically related information in a structured format and provide researchers with easy access to a variety of relevant data. This review presents an overview of publicly available databases relevant to proteomics studies in cancer research. They include gene/protein expression databases, gene mutation and single nucleotide polymorphisms databases, tumor antigen databases, protein-protein interaction, and biological pathway databases. Automated information retrieval from these databases enables efficient large-scale proteomics data analysis. C1 [Zhang, Guang Lan] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Canc Vaccine Ctr, Boston, MA 02115 USA. RP Zhang, GL (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Canc Vaccine Ctr, 44 Binney St, Boston, MA 02115 USA. NR 59 TC 6 Z9 6 U1 1 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-042-3 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 723 BP 349 EP 364 DI 10.1007/978-1-61779-043-0_22 D2 10.1007/978-1-61779-043-0 PG 16 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA BUD42 UT WOS:000288923400022 PM 21370076 ER PT S AU Hook, V Kindy, M Hook, G AF Hook, Vivian Kindy, Mark Hook, Gregory BE Dunn, B TI Discovery of the Cysteine Protease Cathepsin B as a Drug Target for Alzheimer's Disease SO PROTEINASES AS DRUG TARGETS SE RSC Drug Discovery Series LA English DT Article; Book Chapter ID AMYLOID PRECURSOR PROTEIN; BETA-SECRETASE ACTIVITY; TRANSGENIC MICE; WILD-TYPE; IN-VIVO; ACTIVE-SITE; PEPTIDE NEUROTRANSMITTERS; CHROMAFFIN CELLS; BACE1; INHIBITORS C1 [Hook, Vivian] Univ Calif San Diego, Dept Neurosci, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA. [Hook, Vivian] Univ Calif San Diego, Dept Pharmacol, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA. [Hook, Vivian] Univ Calif San Diego, Dept Med, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA. [Kindy, Mark] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [Kindy, Mark] Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. [Hook, Gregory] Amer Life Sci Pharmaceut Inc, San Diego, CA 92109 USA. RP Hook, V (reprint author), Univ Calif San Diego, Dept Neurosci, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA. NR 61 TC 0 Z9 0 U1 0 U2 0 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, CAMBRIDGE CB4 4WF, CAMBS, ENGLAND SN 2041-3203 BN 978-1-84973-049-5 J9 RSC DRUG DISCOV JI RSC Drug Discov. PY 2011 IS 18 BP 145 EP 168 D2 10.1039/9781849733151 PG 24 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BA5JG UT WOS:000336722600007 ER PT J AU Adler, DA Possemato, K Mavandadi, S Lerner, D Chang, H Klaus, J Tew, JD Barrett, D Ingram, E Oslin, DW AF Adler, David A. Possemato, Kyle Mavandadi, Shahrzad Lerner, Debra Chang, Hong Klaus, Johanna Tew, James D. Barrett, David Ingram, Erin Oslin, David W. TI Psychiatric Status and Work Performance of Veterans of Operations Enduring Freedom and Iraqi Freedom SO PSYCHIATRIC SERVICES LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; MENTAL-HEALTH PROBLEMS; PRODUCTIVITY LOSS; JOB-PERFORMANCE; CARE MANAGEMENT; DEPRESSION; ASSOCIATION; OUTCOMES; WAR; US AB Objective: This cross-sectional study investigated the relationship between psychiatric diagnosis and impaired work functioning among American service members returning from Operation Iraqi Freedom-Operation Enduring Freedom (OEF-OIF). Methods: Participants were 797 OEF-OIF veterans, of whom 473 were employed. They were referred for further psychiatric assessment by primary care providers at six Veterans Affairs medical centers and underwent a behavioral health interview that assessed psychiatric and health status and work impairment as measured by the Work Limitations Questionnaire (WLQ). The four WLQ subscales (mental-interpersonal demands, time management, output, and physical demands) and an aggregated measure of productivity loss were considered in the analysis. Associations between patient characteristics, psychiatric status, and work impairments were investigated with regression models. Results: Major depressive disorder, posttraumatic stress disorder, and generalized anxiety or panic disorder were significantly associated with impairments in mental-interpersonal demands, time management, and output. Alcohol dependence and illicit drug use were associated with impairments in output and physical demands. On average these productivity losses were four times those found in a previous study of nonveteran employees with no psychiatric disorders. Conclusions: Veterans' ability to maintain gainful employment is a major component of successful reintegration into civilian life, and psychiatric disorders have a negative impact on work performance. This study demonstrated that multiple dimensions of job performance are impaired by psychiatric illness among OEF-OIF veterans. Delivery of empirically supported interventions to treat psychiatric disorders and development of care models that focus on work-specific interventions are needed to help veterans return to civilian life. (Psychiatric Services 62:39-46, 2011) C1 [Tew, James D.] Univ Penn, Philadelphia VA Med Ctr, Sch Med, Philadelphia, PA 19104 USA. [Tew, James D.] Univ Penn, Dept Psychiat, Sch Med, Philadelphia, PA 19104 USA. [Adler, David A.; Lerner, Debra; Chang, Hong] Tufts Med Ctr, Dept Med, Boston, MA USA. [Adler, David A.; Lerner, Debra; Chang, Hong] Tufts Med Ctr, Dept Psychiat, Boston, MA USA. [Possemato, Kyle] Syracuse Univ, Ctr Integrated Healthcare, Syracuse Dept Vet Affairs VA Med Ctr, Syracuse, NY USA. [Possemato, Kyle] Syracuse Univ, Dept Psychol, Syracuse, NY USA. [Barrett, David] Univ Maryland, Dept Psychiat, Baltimore, MD 21201 USA. [Barrett, David] VA Maryland Hlth Care Syst, Baltimore, MD USA. RP Oslin, DW (reprint author), Univ Penn, Philadelphia VA Med Ctr, Sch Med, 3900 Chestnut St, Philadelphia, PA 19104 USA. EM oslin@upenn.edu RI Schueter, nicos/A-3625-2014 FU Mental Illness Research, Education, and Clinical Center (MIRECC); Department of Veterans Affairs Veterans Integrated Service Network 4 (VISN-4); VISN-5 MIRECC; VISN-2 Center for Integrated Healthcare; Tufts Medical Center FX This project was supported by the Mental Illness Research, Education, and Clinical Center (MIRECC), Department of Veterans Affairs Veterans Integrated Service Network 4 (VISN-4), the VISN-5 MIRECC, the VISN-2 Center for Integrated Healthcare, and the Fisher Fund of the Tufts Medical Center. The authors thank the primary care providers who facilitated care for the veterans in this project. NR 35 TC 33 Z9 33 U1 1 U2 16 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD JAN PY 2011 VL 62 IS 1 BP 39 EP 46 DI 10.1176/appi.ps.62.1.39 PG 8 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 702SX UT WOS:000285917200009 PM 21209298 ER PT J AU Dassori, AM Copeland, LA Zeber, JE Miller, AL AF Dassori, Albana M. Copeland, Laurel A. Zeber, John E. Miller, Alexander L. TI Factors in Second-Generation Antipsychotic Switching Patterns in a National Sample of Older Veterans With Schizophrenia SO PSYCHIATRIC SERVICES LA English DT Article ID WEIGHT-GAIN; METABOLIC SYNDROME; DIABETES-MELLITUS; PREVALENCE; CLOZAPINE; DRUGS; INTERVENTION; MEDICATIONS; OLANZAPINE; AFFAIRS AB Objective: A 2004 consensus statement by the American Psychiatric Association and other groups noted that metabolic side effects of second-generation antipsychotics require monitoring. To reduce risk, prescribers may consider factors differentially associated with development of metabolic abnormalities, such as age, gender, and race-ethnicity. As part of a study of older patients with schizophrenia (50-102 years), this study evaluated factors associated with antipsychotic switches and switches that incurred a greater or lesser metabolic risk. Methods: Administrative data were analyzed for a national cohort of 16,103 Veterans Health Administration patients with schizophrenia receiving second-generation antipsychotics. Multinomial logistic regression predicted the likelihood of switches from 2002 to 2003 and again from 2004 to 2005. Results: At baseline nearly half the patients (45%) had a diagnosis of hypertension, a third (34%) had dyslipidemia, and 15% had a diagnosis of obesity. In both periods diabetes was associated with switches to lower-risk antipsychotics, and older patients were likely to experience neutral or no switches. Women were more likely to experience switches to higher-risk antipsychotics in 2004-2005. Conclusions: General medical conditions potentially associated with antipsychotic-related metabolic concerns were common; however, half of these patients were prescribed medication that made them liable to developing metabolic problems. Modest evidence suggests that metabolic considerations became a higher priority during the study. Future research should investigate the differential impact of antipsychotics on metabolic dysregulation for women and elderly patients. Findings underscore the need to monitor metabolic parameters of older patients taking antipsychotics. (Psychiatric Services 62:47-53, 2011) C1 [Dassori, Albana M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX USA. [Dassori, Albana M.] S Texas Vet Hlth Care Syst, Dept Psychiat, San Antonio, TX USA. [Copeland, Laurel A.; Zeber, John E.; Miller, Alexander L.] Scott & White Healthcare, Temple, TX USA. [Copeland, Laurel A.; Zeber, John E.; Miller, Alexander L.] Cent Texas Vet Hlth Care Syst, Ctr Appl Hlth Res, Temple, TX 76502 USA. RP Copeland, LA (reprint author), Cent Texas Vet Hlth Care Syst, Ctr Appl Hlth Res, 2102 Birdcreek Dr, Temple, TX 76502 USA. EM laurel.copeland@va.gov OI Copeland, Laurel/0000-0002-9478-0209 FU Department of Veterans Affairs; Veterans Health Administration; Health Services Research and Development Service (HSRD) [IIR-05-YYY]; PhRMA Foundation; AstraZeneca; Pfizer; Pfizer Organon; Sanofi Aventis FX This research was supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service (HSRD) and HSRD grant IIR-05-YYY. The views expressed are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs.; Dr. Zeber has received grant funding from the PhRMA Foundation. Dr. Miller has received grant funding from AstraZeneca, Pfizer, Pfizer Organon, and Sanofi Aventis. The other authors report no competing interests. NR 25 TC 7 Z9 7 U1 1 U2 3 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 EI 1557-9700 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD JAN PY 2011 VL 62 IS 1 BP 47 EP 53 DI 10.1176/appi.ps.62.1.47 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 702SX UT WOS:000285917200010 PM 21209299 ER PT J AU Sani, G Tondo, L Koukopoulos, A Reginaldi, D Kotzalidis, GD Koukopoulos, AE Manfredi, G Mazzarini, L Pacchiarotti, I Simonetti, A Ambrosi, E Angeletti, G Girardi, P Tatarelli, R AF Sani, Gabriele Tondo, Leonardo Koukopoulos, Athanasios Reginaldi, Daniela Kotzalidis, Giorgio D. Koukopoulos, Alexia E. Manfredi, Giovanni Mazzarini, Lorenzo Pacchiarotti, Isabella Simonetti, Alessio Ambrosi, Elisa Angeletti, Gloria Girardi, Paolo Tatarelli, Roberto TI Suicide in a large population of former psychiatric inpatients SO PSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article DE agitation; antidepressant drugs; bipolar disorder; schizophrenia; suicide ID TERM LITHIUM TREATMENT; MAJOR DEPRESSIVE DISORDER; BIPOLAR DISORDER; UNIPOLAR DEPRESSION; RISK; CLOZAPINE; PREVENTION; BEHAVIOR; METAANALYSIS; ANTIDEPRESSANTS AB Aims: The aim of this study was to identify predictors of completed suicide in a wide sample of psychiatric inpatients receiving retrospective and prospective DSM-IV diagnoses. Methods: We followed up 4441 severe psychiatric patients who were hospitalized for some time during a 35-year period in a private hospital setting. We collected sociodemographic, clinical and temperamental data. Results: Ninety-six patients from the sample committed suicide. There were no sex differences in suicide completion and no differences between major psychiatric disorders, but people who had been hospitalized for anxiety disorders did not commit suicide and people with bipolar disorders were more likely to commit suicide than people with unipolar major depression. Shorter-term treatment with lithium and anticonvulsants, longer-term treatment with antidepressants, history of suicide attempts, suicidal thinking, and single status positively predicted completed suicide. Suicide tended to occur after a mean period of about 14 years of duration of disease. Patients' symptoms during the period preceding suicide were assessed through interviewing patients' physicians or family members. Symptoms occurring in > 10% of cases were, in decreasing order, inner tension, racing/crowded thoughts, aggressive behavior, guilt, psychomotor agitation, persecutory ideation, anxiety, and hallucinations. Surprisingly, cyclothymic temperament was less associated with completed suicide as compared to other temperaments. Conclusions: Suicide is likely to occur in a milieu of agitation, mixed anxiety and depression, and psychosis. Longer-term mood stabilizer treatment may reduce the rate of completed suicide. C1 [Sani, Gabriele; Tondo, Leonardo; Koukopoulos, Athanasios; Reginaldi, Daniela; Koukopoulos, Alexia E.; Manfredi, Giovanni; Simonetti, Alessio; Girardi, Paolo] Ctr Lucio Bini, Rome, Italy. [Sani, Gabriele; Tondo, Leonardo; Koukopoulos, Athanasios; Reginaldi, Daniela; Koukopoulos, Alexia E.; Manfredi, Giovanni; Simonetti, Alessio; Girardi, Paolo] Ctr Lucio Bini, Cagliari, Italy. [Sani, Gabriele; Kotzalidis, Giorgio D.; Koukopoulos, Alexia E.; Manfredi, Giovanni; Mazzarini, Lorenzo; Pacchiarotti, Isabella; Simonetti, Alessio; Ambrosi, Elisa; Angeletti, Gloria; Girardi, Paolo; Tatarelli, Roberto] Univ Roma La Sapienza, Unit Psychiat, Neurosci Mental Hlth & Sensory Funct Dept, St Andrea Hosp,Med Sch 2, I-00189 Rome, Italy. [Tondo, Leonardo] Harvard Univ, Sch Med, Dept Psychiat & Neurosci Program, Boston, MA USA. [Tondo, Leonardo] Massachusetts Gen Hosp, McLean Div, Boston, MA 02114 USA. [Tondo, Leonardo; Mazzarini, Lorenzo; Pacchiarotti, Isabella] Univ Barcelona, Hosp Clin, Clin Inst Neurosci, Bipolar Disorders Program, Catalunya, Spain. RP Kotzalidis, GD (reprint author), Univ Roma La Sapienza, Unit Psychiat, Dept Psychiat,St Andrea Hosp, Sch Med & Psychol,NESMOS Dept Neurosci Mental Hlt, Via Grottarossa 1035-1039, I-00189 Rome, Italy. EM giorgio.kotzalidis@uniroma1.it RI Manfredi, Giovanni/C-2176-2011; OI Tatarelli, Roberto/0000-0003-4396-2632 FU NARSAD; Stanley Foundation FX This paper has not received funds from any agency. The authors do not have an affiliation with or financial interest that might pose a conflict of interest for this paper. However, Leonardo Tondo has received sources of funding from clinical grants from NARSAD and the Stanley Foundation; in the past, Paolo Girardi has received research support from Lilly and Janssen and honoraria from Lilly and Organon, and has also participated on advisory boards for Lilly, Organon, Pfizer, and Schering; and Roberto Tatarelli has participated on advisory boards for Schering, Servier, and Pfizer and received honoraria from Schering, Servier, and Pfizer. Other authors declare no conflict of interest whatsoever. NR 57 TC 36 Z9 36 U1 1 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1323-1316 J9 PSYCHIAT CLIN NEUROS JI Psychiatry Clin. Neurosci. PY 2011 VL 65 IS 3 BP 286 EP 295 DI 10.1111/j.1440-1819.2011.02205.x PG 10 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 753BY UT WOS:000289740400011 PM 21507136 ER PT J AU Uehara-Aoyama, K Nakamura, M Asami, T Yoshida, T Hayano, F Roppongi, T Fujiwara, A Inoue, T Shenton, ME Hirayasu, Y AF Uehara-Aoyama, Kumi Nakamura, Motoaki Asami, Takeshi Yoshida, Takeshi Hayano, Fumi Roppongi, Tomohide Fujiwara, Akiko Inoue, Tomio Shenton, Martha E. Hirayasu, Yoshio TI Sexually dimorphic distribution of orbitofrontal sulcogyral pattern in schizophrenia SO PSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article DE gender; orbitofrontal cortex; schizophrenia; sulcogyral pattern; symptom ID MEDIAL PREFRONTAL CORTEX; GENDER-DIFFERENCES; SEX-DIFFERENCES; MACAQUE MONKEYS; BRAIN; ESTROGEN; VOLUME; MRI; CONNECTIONS AB Aim: The sulcogyral pattern of the orbitofrontal cortex (OFC) is characterized by a remarkable inter-individual variability that likely reflects neurobehavioral traits and genetic aspects of neurodevelopment. The aim of the present study was to evaluate the OFC sulcogyral pattern of patients with schizophrenia (SZ) and healthy controls (HC) to determine group differences in OFC sulcogyral pattern as well as gender differences between groups. Methods: Forty-seven SZ patients (M/F, 23/24) and forty-seven HC (M/F, 17/30), matched on age and gender, were analyzed using magnetic resonance imaging. The sulcogyral pattern was classified into type I, II, or III based on the guidelines set by Chiavaras and Petrides in a previous paper. Chi-squared analysis was used to investigate group and gender differences in the sulcogyral pattern distribution, and categorical regression was used to explore clinical correlations. Results: The distribution of OFC sulcogyral pattern in HC replicated the results found in the previous study (left, chi(2) = 0.02, P = 0.989; right, chi(2) = 0.97, P = 0.616), in that there were no gender differences. Moreover, the distribution in SZ-M was in accordance with that in the previous study (left, chi(2) = 1.59, P = 0.451; right, chi(2) = 0.14, P = 0.933). Additionally, within SZ-M, patients with the type III pattern had a higher total positive and negative syndrome scale score (beta = 0.902, F = 14.75, P = 0.001). In contrast, the distribution in the right hemisphere in the SZ-F group differed significantly from that observed in SZ-M (chi(2) = 6.017, P = 0.046), but did not differ from HC (chi(2) = 2.557, P = 0.110). Conclusion: OFC sulcogyral pattern is altered in SZ-M but not in SZ-F, possibly reflecting gender differences in early neurodevelopment. C1 [Uehara-Aoyama, Kumi; Nakamura, Motoaki; Asami, Takeshi; Yoshida, Takeshi; Hayano, Fumi; Roppongi, Tomohide; Fujiwara, Akiko; Inoue, Tomio; Hirayasu, Yoshio] Yokohama City Univ, Dept Psychiat, Yokohama, Kanagawa 2360004, Japan. [Uehara-Aoyama, Kumi; Nakamura, Motoaki] Kanagawa Psychiat Ctr, Dept Clin Res, Kanagawa, Japan. [Asami, Takeshi; Roppongi, Tomohide; Shenton, Martha E.] Harvard Univ, Sch Med, Psychiat Neuroimaging Lab, Brigham & Womens Hosp,Dept Psychiat, Brockton, MA 02401 USA. [Asami, Takeshi; Roppongi, Tomohide; Shenton, Martha E.] VA Boston Healthcare Syst, Neurosci Lab, Clin Neurosci Div, Brockton, MA USA. [Asami, Takeshi; Roppongi, Tomohide; Shenton, Martha E.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Hirayasu, Y (reprint author), Yokohama City Univ, Dept Psychiat, Yokohama, Kanagawa 2360004, Japan. EM hirayasu@yokohama-cu.ac.jp NR 33 TC 5 Z9 5 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1323-1316 EI 1440-1819 J9 PSYCHIAT CLIN NEUROS JI Psychiatry Clin. Neurosci. PY 2011 VL 65 IS 5 BP 483 EP 489 DI 10.1111/j.1440-1819.2011.02229.x PG 7 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 809AD UT WOS:000294022200011 PM 21851457 ER PT J AU Bovin, MJ Marx, BP AF Bovin, Michelle J. Marx, Brian P. TI The Importance of the Peritraumatic Experience in Defining Traumatic Stress SO PSYCHOLOGICAL BULLETIN LA English DT Article DE PTSD; trauma; peritraumatic emotions; appraisals; peritraumatic behaviors ID MOTOR-VEHICLE ACCIDENT; PTSD SYMPTOM SEVERITY; SEXUAL ASSAULT SURVIVORS; FEMALE CRIME VICTIMS; POSTTRAUMATIC-STRESS; VIETNAM VETERANS; DSM-IV; TONIC IMMOBILITY; DISORDER PTSD; HEART-RATE AB In the Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev., DSM-IV TR; American Psychiatric Association, 2000), posttratimatic stress disorder (PTSD) Criterion A2 stipulates that an individual must experience intense fear, helplessness, or horror during an event that threatened the life or physical integrity of oneself or others to be eligible for the PTSD diagnosis. In considering this criterion, we describe its origins, review studies that have examined its predictive validity, and reflect on the intended purpose of the criterion and how it complements the mission of the DSM. We then assert that the predictive validity of Criterion A2 may not be an appropriate metric for evaluating its worth. We also note that the current Criterion A2 may not fully capture all the salient aspects of the traumatic stress response. To support this claim, we review empirical research showing that individuals adapt to extreme environmental events by responding in a complex and coordinated manner. This complex response set involves an individual's appraisal regarding the degree to which the event taxes his or her resources, as well as a range of other cognitions (e.g., dissociation), felt emotions (e.g., fear), physiological reactions (e.g., heart rate increase), and behaviors (e.g., tonic immobility). We provide evidence that these response components may be associated with the subsequent development of PTSD. We then describe the challenges associated with accurately assessing an individual's traumatic stress response. We conclude with a discussion of the need to consider the individual's immediate response when defining a traumatic stressor. C1 [Bovin, Michelle J.; Marx, Brian P.] Vet Affairs Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Bovin, Michelle J.] Temple Univ, Dept Psychol, Philadelphia, PA 19122 USA. [Marx, Brian P.] Boston Univ, Sch Med, Boston, MA 02215 USA. RP Marx, BP (reprint author), VA Boston Healthcare Syst 116B 4, Natl Ctr PTSD, 150 S Huntington Ave, Boston, MA 02130 USA. EM brian.marx@va.gov NR 215 TC 38 Z9 38 U1 7 U2 20 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0033-2909 J9 PSYCHOL BULL JI Psychol. Bull. PD JAN PY 2011 VL 137 IS 1 BP 47 EP 67 DI 10.1037/a0021353 PG 21 WC Psychology; Psychology, Multidisciplinary SC Psychology GA 707KL UT WOS:000286285100003 PM 21090886 ER PT J AU Barrett, LF AF Barrett, Lisa Feldman TI Bridging Token Identity Theory and Supervenience Theory Through Psychological Construction SO PSYCHOLOGICAL INQUIRY LA English DT Editorial Material ID HUMAN BRAIN; FUNCTIONAL CONNECTIVITY; NATURAL KINDS; EMOTION; NETWORKS; AMYGDALA; FEAR; EXPERIENCE; CORTEX; MIND C1 [Barrett, Lisa Feldman] Northeastern Univ, Dept Psychol, Boston, MA 02115 USA. [Barrett, Lisa Feldman] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Barrett, LF (reprint author), Northeastern Univ, Dept Psychol, 125 Nightingale,360 Huntington Ave, Boston, MA 02115 USA. EM l.barrett@neu.edu FU NIA NIH HHS [R01 AG030311]; NIH HHS [DP1 OD003312, DP1 OD003312-04] NR 83 TC 16 Z9 16 U1 2 U2 9 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1047-840X EI 1532-7965 J9 PSYCHOL INQ JI Psychol. Inq. PY 2011 VL 22 IS 2 BP 115 EP 127 AR PII 938339505 DI 10.1080/1047840X.2011.555216 PG 13 WC Psychology, Multidisciplinary SC Psychology GA 775WZ UT WOS:000291495500005 PM 21785534 ER PT J AU Thomas, JJ Crosby, RD Wonderlich, SA Striegel-Moore, RH Becker, AE AF Thomas, J. J. Crosby, R. D. Wonderlich, S. A. Striegel-Moore, R. H. Becker, A. E. TI A latent profile analysis of the typology of bulimic symptoms in an indigenous Pacific population: evidence of cross-cultural variation in phenomenology SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Classification; eating disorders; Fiji; herbal purgative; latent profile analysis ID EATING-DISORDER PHENOTYPES; ANOREXIA-NERVOSA; EXAMINATION QUESTIONNAIRE; SELF-REPORT; CES-D; WOMEN; ADOLESCENTS; INTERVIEW; SAMPLE; CLASSIFICATION AB Background. Previous efforts to derive empirically based eating disorder (ED) typologies through latent structure modeling have been limited by the ethnic and cultural homogeneity of their study populations and their reliance on DSM-IV ED signs and symptoms as indicator variables. Method. Ethnic Fijian schoolgirls (n=523) responded to a self-report battery assessing ED symptoms, herbal purgative use, co-morbid psychopathology, clinical impairment, cultural orientation, and peer influences. Participants who endorsed self-induced vomiting or herbal purgative use in the past 28 days (n=222) were included in a latent profile analysis (LPA) to identify unique subgroups of bulimic symptomatology. Results. LPA identified a bulimia nervosa (BN)-like class (n=86) characterized by high rates of binge eating and self-induced vomiting, and a herbal purgative class (n=136) characterized primarily by the use of indigenous Fijian herbal purgatives. Both ED classes endorsed greater eating pathology and general psychopathology than non-purging participants, and the herbal purgative class endorsed greater clinical impairment than either the BN-like or nonpurging participants. Cultural orientation did not differ between the two ED classes. Conclusions. Including study populations typically under-represented in mental health research and broadening the scope of relevant signs and symptoms in latent structure models may increase the generalizability of ED nosological schemes to encompass greater cultural diversity. C1 [Thomas, J. J.; Becker, A. E.] Massachusetts Gen Hosp, Eating Disorders Clin & Res Program, Boston, MA 02114 USA. [Thomas, J. J.] McLean Hosp, Klarman Eating Disorders Ctr, Belmont, MA 02478 USA. [Thomas, J. J.; Becker, A. E.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Crosby, R. D.; Wonderlich, S. A.] Univ N Dakota, Sch Med & Hlth Sci, Grand Forks, ND 58201 USA. [Striegel-Moore, R. H.] Montana State Univ, Dept Psychol, Bozeman, MT 59717 USA. [Becker, A. E.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Cambridge, MA 02138 USA. RP Thomas, JJ (reprint author), Massachusetts Gen Hosp, Eating Disorders Clin & Res Program, WAC 816D,15 Parkman St, Boston, MA 02114 USA. EM jjthomas@partners.org OI Crosby, Ross/0000-0001-9131-1629 FU NIMH [K23 MH 068575]; Harvard Research Enabling Grant; Klarman Foundation FX This project was funded by NIMH K23 MH 068575 (A.E.B.), a Harvard Research Enabling Grant (A.E.B.), and a Klarman Foundation Post-Doctoral Fellowship (J.J.T.). NR 47 TC 9 Z9 9 U1 1 U2 7 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD JAN PY 2011 VL 41 IS 1 BP 195 EP 206 DI 10.1017/S0033291710000255 PG 12 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 696ZA UT WOS:000285478700020 PM 20346191 ER PT J AU Boeka, AG Solomon, AC Lokken, K McGuire, BM Bynon, JS AF Boeka, Abbe G. Solomon, Andrea C. Lokken, Kristine McGuire, Brendan M. Bynon, J. Steve TI A biopsychosocial approach to liver transplant evaluation in two patients with Wilson's disease SO PSYCHOLOGY HEALTH & MEDICINE LA English DT Article DE Wilson's disease; cognitive; neuropsychiatric; transplant ID DIAGNOSIS; THERAPY AB Wilson's disease (WD) is characterized by hepatic, neurological, and/or psychiatric disturbances. In some cases, liver transplantation is indicated. Because psychologists and other health care workers play an increasing role in the evaluation of individuals presenting for transplant, an understanding of the heterogeneous phenotype of WD is important for mental health professionals working in medical settings. This article reviews two cases of patients with WD (one probable, one confirmed) presenting for liver transplantation and a biopsychosocial assessment approach is demonstrated. Patients are presented in terms of medical, psychiatric, and psychosocial history, neuropsychological examination results, and the subsequent indications for liver transplantation. Both patients exhibited neurocognitive and psychiatric symptoms. One patient was determined to be a marginally suitable candidate for transplantation, whereas the other was considered at high risk for negative outcome post-transplant. This article demonstrates the importance of considering phenotypic presentation, neurocognitive function, psychiatric status, and psychosocial circumstances in assessing transplant readiness in patients with WD. A comprehensive and integrative biopsychosocial assessment approach is appropriate for evaluating patients with WD presenting for liver transplantation. C1 [Boeka, Abbe G.; Lokken, Kristine] Univ Alabama, Dept Psychiat & Behav Neurobiol, Div Consultat Liason, Birmingham, AL 35294 USA. [Solomon, Andrea C.] Univ Alabama, Dept Neurol, Div Neuropsychol, Birmingham, AL 35294 USA. [Lokken, Kristine] Birmingham VA Med Ctr, Dept Phys Med & Rehabil, Birmingham, AL USA. [McGuire, Brendan M.] Univ Alabama, Dept Med, Div Gastroenterol, Birmingham, AL 35294 USA. [Bynon, J. Steve] Univ Alabama, Dept Surg, Div Transplantat, Birmingham, AL 35294 USA. RP Boeka, AG (reprint author), Univ Alabama, Dept Psychiat & Behav Neurobiol, Div Consultat Liason, Birmingham, AL 35294 USA. EM abbe.boeka@vanderbilt.edu NR 17 TC 0 Z9 0 U1 0 U2 1 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1354-8506 J9 PSYCHOL HEALTH MED JI Psychol. Health Med. PY 2011 VL 16 IS 3 BP 268 EP 275 AR PII 936276882 DI 10.1080/13548506.2010.532561 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 750WY UT WOS:000289580000002 PM 21491335 ER PT J AU Sivasubramanian, M Mimiaga, MJ Mayer, KH Anand, VR Johnson, CV Prabhugate, P Safren, SA AF Sivasubramanian, Murugesan Mimiaga, Matthew J. Mayer, Kenneth H. Anand, Vivek R. Johnson, Carey V. Prabhugate, Priti Safren, Steven A. TI Suicidality, clinical depression, and anxiety disorders are highly prevalent in men who have sex with men in Mumbai, India: Findings from a community-recruited sample SO PSYCHOLOGY HEALTH & MEDICINE LA English DT Article DE men who have sex with men (MSM); Mumbai; India; mental health; suicide; depression; anxiety ID NATIONAL-COMORBIDITY-SURVEY; UNITED-STATES; PSYCHIATRIC-DISORDERS; BISEXUAL ADULTS; HEALTH-PROBLEMS; HIV PREVALENCE; RISK; ORIENTATION; CHENNAI; GAY AB In India men who have sex with men (MSM) are a stigmatized and hidden population, vulnerable to a variety of psychosocial and societal stressors. This population is also much more likely to be HIV-infected compared to the general population. However, little research exists about how psychosocial and societal stressors result in mental health problems. A confidential, quantitative mentalhealth interview was conducted among 150 MSM in Mumbai, India at The Humsafar Trust, the largest non-governmental organization serving MSM in India. The interview collected information on sociodemographics and assessed self-esteem, social support and DSM-IV psychiatric disorders using the Mini International Neuropsychiatric Interview (MINI). Participants' mean age was 25.1 years (SD 5.1); 21% were married to women. Forty-five percent reported current suicidal ideation, with 66% low risk, 19% moderate risk, and 15% high risk for suicide per MINI guidelines. Twenty-nine percent screened in for current major depression and 24% for any anxiety disorder. None of the respondents reported current treatment for any psychiatric disorder. In multivariable models controlling for age, education, income, and sexual identity, participants reporting higher levels of self-esteem and greater levels of satisfaction with the social support they receive from family and friends were at lower risk of suicidality (selfesteem AOR = 0.85, 95% CI: 0.78-0.93; social support AOR 0.76, 95% CI: 0.62-0.93) and major depression (self-esteem AOR = 0.79, 95% CI: 0.71-0.89; social support AOR 0.68, 95% CI: 0.54-0.85). Those who reported greater social support satisfaction were also at lower risk of a clinical diagnosis of an anxiety disorder (AOR = 0.80; 95% CI: 0.65-0.99). MSM in Mumbai have high rates of suicidal ideation, depression, and anxiety. Programs to improve selfesteem and perceived social support may improve these mental health outcomes. Because they are also a high-risk group for HIV, MSM HIV prevention and treatment services may benefit from incorporating mental health services and referrals into their programs. C1 [Mimiaga, Matthew J.; Mayer, Kenneth H.; Johnson, Carey V.; Safren, Steven A.] Fenway Hlth, Fenway Inst, Boston, MA USA. [Sivasubramanian, Murugesan; Anand, Vivek R.; Prabhugate, Priti] Humsafar Trust, Bombay, Maharashtra, India. [Mimiaga, Matthew J.; Safren, Steven A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Mayer, Kenneth H.] Miriam Hosp, Brown Med Sch, Providence, RI 02906 USA. RP Mimiaga, MJ (reprint author), Fenway Hlth, Fenway Inst, Boston, MA USA. EM mmimiaga@fenwayhealth.org FU National Institute of Mental Health, NIH [R01MH76488]; National Institute of Nursing Research FX The study described in this report was supported by NIH Research Grant R01MH76488 by the National Institute of Mental Health and the National Institute of Nursing Research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health or the National Institute of Nursing Research. The authors also want to thank Joanne Zwemer for assistance with the manuscript preparation. NR 43 TC 29 Z9 30 U1 7 U2 15 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1354-8506 J9 PSYCHOL HEALTH MED JI Psychol. Health Med. PY 2011 VL 16 IS 4 BP 450 EP 462 DI 10.1080/13548506.2011.554645 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 883HY UT WOS:000299626100007 PM 21749242 ER PT J AU Foynes, MM Freyd, JJ AF Foynes, Melissa Ming Freyd, Jennifer J. TI The Impact of Skills Training on Responses to the Disclosure of Mistreatment SO PSYCHOLOGY OF VIOLENCE LA English DT Article DE skills training; disclosure; mistreatment; social support AB Objective: Although disclosure of mistreatment can be beneficial, the effects of disclosure are largely contingent on the quality of responses received. An experimental design was used to evaluate a set of skills-training materials (STMs; Foynes & Freyd, 2010) designed to improve supportive responding to the disclosure of mistreatment experiences. Method: Dyads of university students and community members (N = 110) were randomly assigned to condition (experimental or control) and role (discloser or listener). After completing a series of questionnaires, the "discloser" was asked to describe an experience of mistreatment not previously disclosed to the "listener." Dyads completed postdisclosure questionnaires, reviewed a set of STMs regarding either healthy lifestyle improvements (control) or supportive listening techniques (experimental), and completed a quiz. A second experience of mistreatment was disclosed and a final set of questionnaires was completed. Results: Results indicated that listeners in the experimental condition demonstrated significantly fewer unsupportive behaviors than listeners in the control condition. Listeners who started with high levels of unsupportive behaviors benefitted the most from the STMs. Conclusions: The STMs developed for this study are relatively short in length, easy to administer, and informed by disclosers' perceptions of supportive behaviors. Thus, these materials could serve as a preliminary step toward developing more effective ways of providing lay people with education on enhancing supportive listening behaviors. C1 [Foynes, Melissa Ming; Freyd, Jennifer J.] Univ Oregon, Dept Psychol, Eugene, OR 97403 USA. RP Foynes, MM (reprint author), VA Boston Healthcare Syst, Psychol Serv 116B,150 S Huntington Ave, Boston, MA 02130 USA. EM melissa.foynes2@va.gov NR 54 TC 9 Z9 9 U1 1 U2 4 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 2152-0828 J9 PSYCHOL VIOLENCE JI Psychol. Violence PD JAN PY 2011 VL 1 IS 1 BP 66 EP 77 DI 10.1037/a0022021 PG 12 WC Psychology, Clinical; Criminology & Penology; Family Studies SC Psychology; Criminology & Penology; Family Studies GA V27TM UT WOS:000208635500007 ER PT J AU Pedrelli, P Farabaugh, AH Zisook, S Tucker, D Rooney, K Katz, J Clain, AJ Petersen, TJ Fava, M AF Pedrelli, Paola Farabaugh, Amy H. Zisook, Sidney Tucker, Dorothy Rooney, Kate Katz, Judith Clain, Alisabeth J. Petersen, Tim J. Fava, Maurizio TI Gender, Depressive Symptoms and Patterns of Alcohol Use among College Students SO PSYCHOPATHOLOGY LA English DT Article DE Alcohol use; Depressive symptoms; Gender; College students ID OBSESSIVE-COMPULSIVE DRINKING; SUBSTANCE USE; YOUNG-ADULTS; BINGE-DRINKING; NATIONAL-SURVEY; HARVARD-SCHOOL; MENTAL-HEALTH; USE DISORDERS; FOLLOW-UP; ABUSE AB Background: Serious alcohol-related negative consequences are associated with a number of drinking behaviors among college students. Thus, it is critical to identify students who are at greater risk for hazardous drinking. Although some studies have shown that depressive symptoms may be associated with alcohol use in this population, findings are not consistent. The current study extends previous research by investigating the relationship between depressive symptoms, daily alcohol use and compulsive drinking among college students and whether gender moderates these relationships. Sampling and Methods: The participants were 904 college students (495 females; mean age = 20.07 +/- 1.85 years) who filled out questionnaires that focused on drinking behaviors and severity of depressive symptoms. Results: Gender moderated the relationship between depressive symptoms and daily alcohol consumption. In male college students, worse depressive symptoms were associated with increased daily alcohol use and with greater risk for compulsive drinking. In female college students, worse depressive symptoms increased the risk for compulsive drinking, but not for greater daily alcohol use. Conclusions: Results suggest that prevention programs aimed at decreasing harmful alcohol use among college students must take into consideration the role of both gender and depressive symptoms in the development of problematic drinking behaviors. Copyright (C) 2010 S. Karger AG, Basel C1 [Pedrelli, Paola; Farabaugh, Amy H.; Rooney, Kate; Katz, Judith; Clain, Alisabeth J.; Petersen, Tim J.; Fava, Maurizio] Harvard Univ, Depress & Clin Res Program, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Zisook, Sidney] Univ Calif San Diego, San Diego, CA 92103 USA. [Tucker, Dorothy] Vanderbilt Univ, Nashville, TN USA. RP Pedrelli, P (reprint author), Harvard Univ, Depress & Clin Res Program, Massachusetts Gen Hosp, Sch Med, 1 Bowdoin Sq, Boston, MA 02114 USA. EM ppedrelli@partners.org FU Jed Foundation FX The study was supported by the Jed Foundation. NR 41 TC 23 Z9 23 U1 2 U2 9 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0254-4962 J9 PSYCHOPATHOLOGY JI Psychopathology PY 2011 VL 44 IS 1 BP 27 EP 33 DI 10.1159/000315358 PG 7 WC Psychiatry SC Psychiatry GA 679JI UT WOS:000284157300004 PM 20980785 ER PT J AU Markowitz, SM Gonzalez, JS Wilkinson, JL Safren, SA AF Markowitz, Sarah M. Gonzalez, Jeffrey S. Wilkinson, Jesse L. Safren, Steven A. TI A Review of Treating Depression in Diabetes: Emerging Findings SO PSYCHOSOMATICS LA English DT Review ID QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIALS; COMORBIDITY SURVEY REPLICATION; SEROTONIN REUPTAKE INHIBITORS; PLACEBO-CONTROLLED TRIAL; CORONARY-HEART-DISEASE; PRIMARY-CARE PATIENTS; DSM-IV DISORDERS; SELF-MANAGEMENT; GLYCEMIC CONTROL AB Background: Depression in patients with diabetes is associated with poorer adherence and worse health outcomes, however treating depression may help improve these outcomes. Objective: The present systematic review identified published papers to evaluate treatments for depression in patients with diabetes. Results: Seventeen studies that met criteria were identified, indicating that psychosocial interventions, particularly cognitive-behavior therapy, anti-depressant medications, and collaborative care are effective in the treatment of depression in patients with diabetes. Conclusion: Evidence for the efficacy of these interventions in improving glycemic control was mixed. No study targeted adherence to treatment or health behaviors in addition to depression, which may be necessary to maximize improvement in diabetes outcomes such as glycemic control. (Psychosomatics 2011; 52:1-18) C1 [Markowitz, Sarah M.; Wilkinson, Jesse L.; Safren, Steven A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Markowitz, Sarah M.; Safren, Steven A.] Harvard Univ, Sch Med, Boston, MA USA. [Gonzalez, Jeffrey S.] Yeshiva Univ, Ferkauf Grad Sch Psychol, Bronx, NY USA. [Gonzalez, Jeffrey S.] Yeshiva Univ, Albert Einstein Coll Med, Bronx, NY USA. RP Markowitz, SM (reprint author), Wells Coll, Dept Psychol, 170 Main St, Aurora, NY 13026 USA. EM sarah.markowitz@gmail.com FU NIMH [1R01MH078571-01] FX The writing of this manuscript was funded by NIMH project 1R01MH078571-01, awarded to Steven A. Safren, Ph.D. NR 105 TC 80 Z9 81 U1 8 U2 18 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 JAN-FEB PY 2011 VL 52 IS 1 BP 1 EP 18 PG 18 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 725CX UT WOS:000287623900001 PM 21300190 ER PT J AU Huffman, JC Mastromauro, CA Sowden, GL Wittmann, C Rodman, R Januzzi, JL AF Huffman, Jeff C. Mastromauro, Carol A. Sowden, Gillian L. Wittmann, Curtis Rodman, Rachel Januzzi, James L. TI A Collaborative Care Depression Management Program for Cardiac Inpatients: Depression Characteristics and In-Hospital Outcomes SO PSYCHOSOMATICS LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; CORONARY-ARTERY-DISEASE; UNSTABLE ANGINA; HEART-FAILURE; SUICIDAL IDEATION; MAJOR DEPRESSION; RISK-FACTOR; VALIDITY; MORTALITY; TRIAL AB Background: Depression in cardiac patients is common, under-recognized, and independently associated with mortality. Objectives: Our objectives in this initial report from a 6-month longitudinal trial were to determine whether a collaborative care program improves rates of depression treatment by discharge among patients hospitalized with acute cardiovascular disease, and to assess key clinical characteristics of depression in this cohort. Method: This was a prospective, randomized trial comparing collaborative care and usual care interventions for depressed cardiac patients who were admitted to cardiac units in an urban academic medical center. For collaborative care subjects, the care manager performed a multi-component depression intervention in the hospital that included patient education and treatment coordination; usual care subjects' inpatient providers were informed of the depression diagnosis. Results: The mean Patient Health Questionnaire-9 for subjects (N = 175) was 17.6 (SD 3.5; range 11-26), consistent with moderate-severe depression. The majority of subjects had depression for over one month (n = 134; 76.6%) and a prior depressive episode (n = 124; 70.8%); nearly one-half (n = 75; 42.9%) had thoughts that life was not worth living in the preceding 2 weeks. Collaborative care subjects were far more likely to receive adequate depression treatment by discharge (71.9% collaborative care vs. 9.5% usual care; p < 0.001). Conclusion: Depression identified by systematic screening in hospitalized cardiac patients appears was prolonged, and of substantial severity. A collaborative care depression management model appears to vastly increase rates of appropriate treatment by discharge. (Psychosomatics 2011; 52:26-33) C1 [Huffman, Jeff C.; Mastromauro, Carol A.; Wittmann, Curtis; Rodman, Rachel] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Huffman, Jeff C.; Sowden, Gillian L.; Wittmann, Curtis; Januzzi, James L.] Harvard Univ, Sch Med, Boston, MA USA. [Januzzi, James L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Huffman, JC (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St,Blake 11, Boston, MA 02114 USA. EM jhuffman@partners.org FU AHA [0735530T] FX This study was funded by an AHA Scientist Development Grant (0735530T) to Jeff C. Huffman. Portions of this manuscript were presented at the Academy of Psychosomatic Medicine Annual Meeting, Las Vegas, November 2009. NR 29 TC 21 Z9 21 U1 2 U2 6 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 JAN-FEB PY 2011 VL 52 IS 1 BP 26 EP 33 PG 8 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 725CX UT WOS:000287623900003 PM 21300192 ER PT J AU Chouinard, G Chouinard, VA Corruble, E AF Chouinard, Guy Chouinard, Virginie-Anne Corruble, Emmanuelle TI Beyond DSM-IV Bereavement Exclusion Criterion E for Major Depressive Disorder SO PSYCHOTHERAPY AND PSYCHOSOMATICS LA English DT Editorial Material ID STRESSFUL LIFE EVENTS; CONJUGAL BEREAVEMENT; SPOUSAL BEREAVEMENT; SUICIDAL IDEATION; PSYCHOLOGICAL DISTRESS; COMPLICATED GRIEF; POLYMORPHISM; REPLICATION; PREDICTION; DYSPHORIA C1 [Chouinard, Guy] McGill Univ, Ctr Hlth, RVH Allan Mem Inst, Dept Psychiat, Montreal, PQ H3A 1A1, Canada. [Chouinard, Guy] St Antoine Hosp, Dept Psychiat, Paris, France. [Corruble, Emmanuelle] Univ Paris 11, Bicetre Univ Hosp, AP HP, Dept Psychiat,INSERM,U669, Le Kremlin Bicetre, France. [Chouinard, Virginie-Anne] Harvard Univ, Massachusetts Gen Hosp, Sch Med, McLean Adult Psychiat Residency Training Program, Boston, MA USA. RP Chouinard, G (reprint author), McGill Univ, Ctr Hlth, RVH Allan Mem Inst, Dept Psychiat, 1025 Pine Ave W, Montreal, PQ H3A 1A1, Canada. NR 55 TC 5 Z9 5 U1 1 U2 6 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0033-3190 J9 PSYCHOTHER PSYCHOSOM JI Psychother. Psychosom. PY 2011 VL 80 IS 1 BP 4 EP 9 DI 10.1159/000316966 PG 6 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 693ON UT WOS:000285233500002 PM 20975322 ER PT J AU Baldessarini, RJ Vazquez, G Tondo, L AF Baldessarini, Ross J. Vazquez, Gustavo Tondo, Leonardo TI Treatment of Cyclothymic Disorder: Commentary SO PSYCHOTHERAPY AND PSYCHOSOMATICS LA English DT Editorial Material ID MAJOR DEPRESSIVE DISORDER; CYCLING BIPOLAR DISORDER; PSYCHOSOCIAL TREATMENTS; II DISORDER; TEMPERAMENT; THERAPY C1 [Baldessarini, Ross J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Baldessarini, Ross J.] Massachusetts Gen Hosp, Psychopharmacol Program, McLean Div, Boston, MA 02114 USA. [Baldessarini, Ross J.; Vazquez, Gustavo; Tondo, Leonardo] Massachusetts Gen Hosp, McLean Div, Int Consortium Bipolar Disorder Res, Belmont, MA USA. [Vazquez, Gustavo] Univ Palermo, Dept Neurosci, Buenos Aires, DF, Argentina. [Tondo, Leonardo] Lucio Bino Mood Disorders Ctr, Cagliari, Italy. RP Baldessarini, RJ (reprint author), McLean Hosp, Mailman Res Ctr 312, 115 Mill St, Belmont, MA 02467 USA. EM rjb@mclean.org NR 35 TC 15 Z9 15 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0033-3190 J9 PSYCHOTHER PSYCHOSOM JI Psychother. Psychosom. PY 2011 VL 80 IS 3 BP 131 EP 135 DI 10.1159/000322234 PG 5 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 747SD UT WOS:000289338800001 PM 21372620 ER PT J AU Osatuke, K Reid, M Stiles, WB Kasckow, JW Zisook, S Mohamed, S AF Osatuke, Katerine Reid, Mary Stiles, William B. Kasckow, John W. Zisook, Sidney Mohamed, Somaia TI Narrative evolution and assimilation of problematic experiences in a case of pharmacotherapy for schizophrenia SO PSYCHOTHERAPY RESEARCH LA English DT Article DE process research; qualitative research methods; narrative; assimilation ID DEPRESSION RATING-SCALE; CLIENTS ASSIMILATION; INNOVATIVE MOMENTS; MENTAL-ILLNESS; PSYCHOTHERAPY; RECOVERY; DISORDER; VOICES; MODEL; THERAPY AB This case study applied the assimilation model to examine the changing narrative of an outpatient with schizophrenia and symptoms of depression across a successful pharmacotherapy. The assimilation model describes how clients assimilate painful, problematic experiences. Therapeutic progress is understood to reflect increasing assimilation, measured by the Assimilation of Problematic Experiences Scale (APES). The authors used a 15-min semistructured interview (Problematic Experiences Questionnaire) to elicit narrative descriptions of the patient's problems and coping across five interviews throughout his 12-week treatment. They describe how the patient's narrative and APES ratings of his main problems by two clinicians changed in concert through treatment, explain these developments using assimilation concepts, and interpret the results in relation to assimilation and insight in schizophrenia. C1 [Osatuke, Katerine] Vet Hlth Adm, Natl Ctr Org Dev, Cincinnati, OH 45249 USA. [Reid, Mary] Univ Edinburgh, Coll Med, Edinburgh EH8 9YL, Midlothian, Scotland. [Stiles, William B.] Miami Univ, Dept Psychol, Oxford, OH USA. [Kasckow, John W.] Vet Affairs Pittsburgh Healthcare Syst, MIRECC, Pittsburgh, PA USA. [Kasckow, John W.] Vet Affairs Pittsburgh Healthcare Syst, Behav Hlth, Pittsburgh, PA USA. [Kasckow, John W.] Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Pittsburgh, PA 15260 USA. [Zisook, Sidney] Univ Calif San Diego, San Diego, CA 92103 USA. [Mohamed, Somaia] Vet Affairs NE Program Evaluat Ctr, VISN MIRECC 1, West Haven, CT USA. [Mohamed, Somaia] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06520 USA. RP Osatuke, K (reprint author), Vet Hlth Adm, Natl Ctr Org Dev, 11500 Northlake Dr,Suite 230, Cincinnati, OH 45249 USA. EM Katerine.Osatuke@va.gov FU NIMH NIH HHS [MH6398] NR 68 TC 5 Z9 7 U1 2 U2 6 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1050-3307 J9 PSYCHOTHER RES JI Psychother. Res. PY 2011 VL 21 IS 1 BP 41 EP 53 AR PII 926982196 DI 10.1080/10503307.2010.508760 PG 13 WC Psychology, Clinical SC Psychology GA 722BA UT WOS:000287403000005 PM 20845225 ER PT J AU Soulieres, I Mottron, L Giguere, G Larochelle, S AF Soulieres, Isabelle Mottron, Laurent Giguere, Gyslain Larochelle, Serge TI Category induction in autism: Slower, perhaps different, but certainly possible SO QUARTERLY JOURNAL OF EXPERIMENTAL PSYCHOLOGY LA English DT Article DE Autism; Categorization; Discrimination; Perception; Learning; Rules ID SAVANT SYNDROME; NORMAL-CHILDREN; CATEGORIZATION; CLASSIFICATION; INDIVIDUALS; RULE; DISCRIMINATION; INFORMATION; PERCEPTION; MODEL AB Available studies on categorization in autism indicate possibly intact category formation, performed through atypical processes. Category learning was investigated in 16 high-functioning autistic and 16 IQ-matched nonautistic participants, using a category structure that could generate a conflict between the application of a rule and exemplar memory. Same-different and matching-to-sample tasks allowed us to verify discrimination abilities for the stimuli to be used in category learning. Participants were then trained to distinguish between two categories of imaginary animals, using categorization tests early in the training and at the end (160 trials). A recognition test followed, in order to evaluate explicit exemplar memory. Similar discrimination performance was found in control tasks for both groups. For the categorization task, autistic participants did not use any identifiable strategy early in the training, but used strategies similar to those of the nonautistic participants by the end, with the same level of accuracy. Memory for the exemplars was poor in both groups. Our findings confirm that categorization may be successfully performed by autistics, but may necessitate longer exposure to material, as the top-down use of rules may be only secondary to a guessing strategy in autistics. C1 [Soulieres, Isabelle; Mottron, Laurent] CETEDUM, Hop Riviere Prairies, Montreal, PQ H1E 1A4, Canada. [Soulieres, Isabelle] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Mottron, Laurent] Univ Montreal, Dept Psychiat, Montreal, PQ H3C 3J7, Canada. [Giguere, Gyslain] Univ Texas Austin, Austin, TX 78712 USA. [Larochelle, Serge] Univ Montreal, Dept Psychol, Montreal, PQ H3C 3J7, Canada. RP Soulieres, I (reprint author), CETEDUM, Hop Riviere Prairies, 7070 Boul Perras, Montreal, PQ H1E 1A4, Canada. EM isabelle@nmr.mgh.harvard.edu FU Natural Sciences and Engineering Research Council of Canada (NSERC); Fonds pour la Formation de Chercheurs et L'Aide a la Recherche (FCAR); Canadian Institutes of Health Research (CIHR) FX This project was funded by a scholarship from the Natural Sciences and Engineering Research Council of Canada (NSERC) and Fonds pour la Formation de Chercheurs et L'Aide a la Recherche (FCAR; I. S.) and a grant from the Canadian Institutes of Health Research (CIHR; L. M.). We thank Guy Lacroix for providing the stimuli, Lisa-Marie Sauve and Genevieve Martel for assistance, Jean-Philippe Lafrance for help with statistical analyses, and Michelle Dawson for helpful comments. We also thank the participants and their families. NR 39 TC 17 Z9 17 U1 6 U2 18 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 1747-0218 J9 Q J EXP PSYCHOL JI Q. J. Exp. Psychol. PY 2011 VL 64 IS 2 BP 311 EP 327 AR PII 924061189 DI 10.1080/17470218.2010.492994 PG 17 WC Psychology, Biological; Physiology; Psychology; Psychology, Experimental SC Psychology; Physiology GA 714PT UT WOS:000286822200007 PM 20623440 ER PT J AU Baudiffier, V Caplan, D Gaonac'h, D Chesnet, D AF Baudiffier, Vanessa Caplan, David Gaonac'h, Daniel Chesnet, David TI The effect of noun animacy on the processing of unambiguous sentences: Evidence from French relative clauses SO QUARTERLY JOURNAL OF EXPERIMENTAL PSYCHOLOGY LA English DT Article DE Relative clause sentences; Noun animacy; French ID EYE-TRACKING; COMPREHENSION; INTERFERENCE; COMPLEXITY; SUBJECT; MEMORY AB Two experiments, one using self-paced reading and one using eye tracking, investigated the influence of noun animacy on the processing of subject relative (SR) clauses, object relative (OR) clauses, and object relative clauses with stylistic inversion (OR-SI) in French. Each sentence type was presented in two versions: either with an animate relative clause (RC) subject and an inanimate object (AS/IO), or with an inanimate RC subject and an animate object (IS/AO). There was an interaction between the RC structure and noun animacy. The advantage of SR sentences over OR and OR-SI sentences disappeared in AS/IO sentences. The interaction between animacy and structure occurred in self-paced reading times and in total fixation times on the RCs, but not in first-pass reading times. The results are consistent with a late interaction between animacy and structural processing during parsing and provide data relevant to several models of parsing. C1 [Baudiffier, Vanessa] Univ Poitiers, CNRS, Lab Ctr Rech Cognit & Apprentissage, UMR 6234, F-86022 Poitiers, France. [Caplan, David] Harvard Univ, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Chesnet, David] Maison Sci lHomme & Soc, Poitiers, France. RP Baudiffier, V (reprint author), Univ Poitiers, CNRS, Lab Ctr Rech Cognit & Apprentissage, UMR 6234, 5 Rue Theodore Lefevre, F-86022 Poitiers, France. EM vanessa.baudiffier@orange.fr FU National Institute on Deafness and Other Communication Disorders (NIDCD) [DC02146]; la region Poitou-Charentes [03/RPC-R-156] FX David Caplan's work on this paper was supported by a grant from the National Institute on Deafness and Other Communication Disorders (NIDCD; DC02146), and Vanessa Baudiffier's work on this paper was supported by a grant from la region Poitou-Charentes (03/RPC-R-156). NR 20 TC 7 Z9 8 U1 0 U2 5 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 1747-0218 J9 Q J EXP PSYCHOL JI Q. J. Exp. Psychol. PY 2011 VL 64 IS 10 BP 1896 EP 1905 DI 10.1080/17470218.2011.608851 PG 10 WC Psychology, Biological; Physiology; Psychology; Psychology, Experimental SC Psychology; Physiology GA 878TY UT WOS:000299281000003 PM 21895558 ER PT J AU Quentin, M Kropil, P Steiner, S Lanzman, RS Blondin, D Miese, F Choy, G Abbara, S Scherer, A AF Quentin, M. Kroepil, P. Steiner, S. Lanzman, R. S. Blondin, D. Miese, F. Choy, G. Abbara, S. Scherer, A. TI Prevalence and clinical significance of incidental cardiac findings in non-ECG-gated chest CT scans SO RADIOLOGE LA German DT Article DE Chest; Computed tomography; Heart; Incidental findings ID CORONARY-ARTERY CALCIFICATION; AORTIC-VALVE CALCIFICATION; HEART-DISEASE; COMPUTED-TOMOGRAPHY; ECHOCARDIOGRAPHY; CARDIOLOGY; DIAGNOSIS; COMMITTEE; ISCHEMIA; STENOSIS AB The purpose of this study was to evaluate the prevalence and clinical significance of incidental cardiac findings in non-ECG-gated chest CT. Non-ECG-gated chest CT examinations of 300 patients were retrospectively analyzed for incidental cardiac findings. Subsequently, these findings were evaluated for their clinical relevance by a cardiologist. A total of 107 out of 300 examined patients had 174 incidental cardiac findings including coronary calcification (90), aortic/mitral valve calcification (42), iatrogenic changes (23), pericardial effusion (6), dilatation of the heart (4), myocardial changes (3), thrombus in the left ventricle (2), constrictive pericarditis (2) and atrial myxoma (1). Of the cardiac findings 51% were described in the written report and in 53 out of the 107 patients the cardiac findings were unknown. Newly detected incidental findings from 8 patients were rated as clinically significant: pericardial effusion (4), constrictive pericarditis (1), thrombus in the left ventricle (1), atrial myxoma (1) and dilatation of the heart (1). Incidental cardiac findings are frequent in non-ECG-gated chest CT and may have a high clinical relevance. C1 [Quentin, M.; Kroepil, P.; Lanzman, R. S.; Blondin, D.; Miese, F.; Scherer, A.] Univ Dusseldorf, Inst Radiol, D-40225 Dusseldorf, Germany. [Choy, G.; Abbara, S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Imaging Sect, Boston, MA USA. [Steiner, S.] Klinikum Heinrich Heine Univ Dusseldorf, Klin Kardiol Pneumol & Angiol, Dusseldorf, Germany. RP Quentin, M (reprint author), Univ Dusseldorf, Inst Radiol, Moorenstr 5, D-40225 Dusseldorf, Germany. EM michael.quentin@med.uni-duesseldorf.de NR 26 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-832X J9 RADIOLOGE JI Radiologe PD JAN PY 2011 VL 51 IS 1 BP 59 EP 64 DI 10.1007/s00117-010-2071-0 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 708AN UT WOS:000286333000012 PM 20967410 ER PT J AU Kunst, MM Schaefer, PW AF Kunst, Mara M. Schaefer, Pamela W. TI Ischemic Stroke SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article DE Ischemia; Infarction; Stroke imaging; Penumbra; Perfusion ID CAROTID-ARTERY STENOSIS; MAGNETIC-RESONANCE ANGIOGRAPHY; TISSUE-PLASMINOGEN ACTIVATOR; ATTENUATED INVERSION-RECOVERY; ACUTE HEMISPHERIC STROKE; HYPERINTENSE CEREBROSPINAL-FLUID; COMPUTED-TOMOGRAPHY ANGIOGRAPHY; NEPHROGENIC SYSTEMIC FIBROSIS; MECHANICAL EMBOLUS REMOVAL; ENHANCED MR-ANGIOGRAPHY AB The goal of stroke imaging is to appropriately select patients for different types of therapeutic management in order to optimize outcome and minimize potential complications. To accomplish this, the radiologist has to evaluate each case and tailor an imaging protocol to fit the patient's needs and best answer the clinical question. This review outlines the routinely used, current neuroimaging techniques and their role in the evaluation of the acute stroke patient. The ability of computed tomography and magnetic resonance imaging to adequately evaluate the infarcted brain parenchyma, the cerebral vasculature, and the ischemic, but potentially viable tissue, often referred to as the "ischemic penumbra," is compared The authors outline an imaging algorithm that has been employed at their institution, and briefly review endovascular therapies that can be used in specific patients for stroke treatment. C1 [Kunst, Mara M.; Schaefer, Pamela W.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp,Sect Neuroradiol, Boston, MA 02115 USA. RP Kunst, MM (reprint author), Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp,Sect Neuroradiol, 55 Fruit St, Boston, MA 02115 USA. EM marakunst@gmail.com NR 94 TC 9 Z9 9 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD JAN PY 2011 VL 49 IS 1 BP 1 EP + DI 10.1016/j.rcl.2010.07.010 PG 27 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 701VE UT WOS:000285850900002 PM 21111127 ER PT J AU Rana, RS Moonis, G AF Rana, Rich S. Moonis, Gul TI Head and Neck Infection and Inflammation SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article DE Head and neck; Inflammation; Infection; Abscess ID SPACE INFECTIONS; COMPUTERIZED-TOMOGRAPHY; RETROPHARYNGEAL LYMPHADENITIS; PERITONSILLAR ABSCESS; ORBITAL CELLULITIS; ACUTE EPIGLOTTITIS; LEMIERRES-SYNDROME; HONG-KONG; CT; DIAGNOSIS AB This article discusses the imaging manifestations of infectious and inflammatory conditions of the head and neck. Special attention is paid to the sites, routes of spread, and complications of neck infections. Because the clinical signs and symptoms and the complications of these conditions are often determined by the precise anatomic site involved, anatomic considerations are stressed. Familiarity with the fascial layers, spaces of the neck, and the contents of each space is helpful for this discussion. The fascial layers of the neck are important barriers to infection, and once infection is established, the fascial layers play a part in directing its spread. C1 [Rana, Rich S.; Moonis, Gul] Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Radiol, Sch Med, Boston, MA 02215 USA. [Moonis, Gul] Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02114 USA. RP Moonis, G (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Radiol, Sch Med, 330 Brookline Ave,WCCB-90, Boston, MA 02215 USA. EM gmoonis@bidmc.harvard.edu NR 58 TC 16 Z9 20 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 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD JAN PY 2011 VL 49 IS 1 BP 165 EP + DI 10.1016/j.rcl.2010.07.013 PG 20 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 701VE UT WOS:000285850900009 PM 21111134 ER PT J AU Avery, LL Susarla, SM Novelline, RA AF Avery, Laura L. Susarla, Srinivas M. Novelline, Robert A. TI Multidetector and Three-Dimensional CT Evaluation of the Patient With Maxillofacial Injury SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article DE Maxillofacial injury; Facial fractures; Multidetector CT; Facial trauma ID CERVICAL-SPINE INJURY; FRONTAL-SINUS FRACTURES; COMPUTED-TOMOGRAPHY; FACIAL TRAUMA; MANDIBULAR CONDYLE; ORBITAL FRACTURES; MANAGEMENT; DIAGNOSIS; CHILDREN AB Interpretation of images associated with the traumatically injured face is challenging. The complexity of facial anatomy, coupled with the superimposition of numerous bony structures on plain radiographs, poses specific obstacles to accurate interpretation of facial injury. Although plain radiographs can be helpful in cases of isolated injuries, CT is the most useful modality for evaluating facial injury. This article reviews facial anatomy as it pertains to traumatic injury, emphasizes the clinical findings associated with various types of facial injury, and simplifies the diagnosis of facial injury on CT. C1 [Avery, Laura L.; Novelline, Robert A.] Massachusetts Gen Hosp, Dept Radiol, Div Emergency Radiol, Boston, MA 02114 USA. [Susarla, Srinivas M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Avery, LL (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Emergency Radiol, 55 Fruit St,FND210A, Boston, MA 02114 USA. EM lavery@partners.org OI Susarla, Srinivas/0000-0003-0155-8260 NR 54 TC 10 Z9 12 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 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD JAN PY 2011 VL 49 IS 1 BP 183 EP + DI 10.1016/j.rcl.2010.07.014 PG 22 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 701VE UT WOS:000285850900010 PM 21111135 ER PT J AU Fang, QQ Selb, J Carp, SA Boverman, G Miller, EL Brooks, DH Moore, RH Kopans, DB Boas, DA AF Fang, Qianqian Selb, Juliette Carp, Stefan A. Boverman, Gregory Miller, Eric L. Brooks, Dana H. Moore, Richard H. Kopans, Daniel B. Boas, David A. TI Combined Optical and X-ray Tomosynthesis Breast Imaging SO RADIOLOGY LA English DT Article ID DIGITAL TOMOSYNTHESIS; MAMMOGRAPHY; RECONSTRUCTION; TOMOGRAPHY; CANCER; TISSUE; INFORMATION; MEDICINE; CONTRAST; WOMEN AB Purpose: To explore the optical and physiologic properties of normal and lesion-bearing breasts by using a combined optical and digital breast tomosynthesis (DBT) imaging system. Materials and Methods: Institutional review board approval and patient informed consent were obtained for this HIPAA-compliant study. Combined optical and tomosynthesis imaging analysis was performed in 189 breasts from 125 subjects (mean age, 56 years +/- 13 [standard deviation]), including 138 breasts with negative findings and 51 breasts with lesions. Three-dimensional (3D) maps of total hemoglobin concentration (Hb(T)), oxygen saturation (So(2)), and tissue reduced scattering coefficients were interpreted by using the coregistered DBT images. Paired and unpaired t tests were performed between various tissue types to identify significant differences. Results: The estimated average bulk Hb(T) from 138 normal breasts was 19.2 mu mol/L. The corresponding mean So(2) was 0.73, within the range of values in the literature. A linear correlation (R = 0.57, P < .0001) was found between Hb(T) and the fibroglandular volume fraction derived from the 3D DBT scans. Optical reconstructions of normal breasts revealed structures corresponding to chest-wall muscle, fibroglandular, and adipose tissues in the Hb(T), So(2), and scattering images. In 26 malignant tumors of 0.6-2.5 cm in size, Hb(T) was significantly greater than that in the fibroglandular tissue of the same breast (P = .0062). Solid benign lesions (n = 17) and cysts (n = 8) had significantly lower Hb(T) contrast than did the malignant lesions (P = .025 and P = .0033, respectively). Conclusion: The optical and DBT images were structurally consistent. The malignant tumors and benign lesions demonstrated different Hb(T) and scattering contrasts, which can potentially be exploited to reduce the false-positive rate of conventional mammography and unnecessary biopsies. (C) RSNA, 2010 C1 [Fang, Qianqian; Selb, Juliette; Carp, Stefan A.; Boas, David A.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Boverman, Gregory; Brooks, Dana H.] Northeastern Univ, Dept Elect & Comp Engn, Boston, MA 02115 USA. [Miller, Eric L.] Tufts Univ, Dept Elect & Comp Engn, Medford, MA 02155 USA. [Moore, Richard H.; Kopans, Daniel B.] Massachusetts Gen Hosp, Avon Fdn, Comprehens Breast Evaluat Ctr, Boston, MA 02114 USA. RP Fang, QQ (reprint author), Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, 149 13th St, Charlestown, MA 02129 USA. EM fangq@nmr.mgh.harvard.edu RI Miller, Eric/B-2546-2008 OI Miller, Eric/0000-0002-3156-6002 FU USARMY [DAMD17-98-8309]; National Science Foundation [EEC-9986821]; GE Healthcare and Massachusetts General Hospital; National Institutes of Health [R01-CA97305, P41-RR14075, U54-CA105480] FX From the Martinos Center for Biomedical Imaging, Massachusetts General Hospital, 149 13th St, Charlestown, MA 02129 (Q.F., J.S., S.A.C., D.A.B.); Department of Electrical and Computer Engineering, Tufts University, Medford, Mass (E.L.M.); Department of Electrical and Computer Engineering, Northeastern University, Boston, Mass (G.B., D.H.B.); and Avon Foundation Comprehensive Breast Evaluation Center, Massachusetts General Hospital, Boston, Mass (R.H.M., D.B.K.). From the 2007 RSNA Annual Meeting. Received December 8, 2008; revision requested January 7, 2009; final revision received February 4, 2010; accepted March 15; final version accepted August 5. Supported by USARMY BRMC grant DAMD17-98-8309 and the Gordon Center for Subsurface Sensing and Imaging Systems under the Engineering Research Centers Program of the National Science Foundation (award EEC-9986821). D.B.K. supported in part by funds from GE Healthcare and Massachusetts General Hospital. Address correspondence to Q.F. (e-mail: fangq@nmr.mgh.harvard.edu).; This research was supported by the National Institutes of Health (grants R01-CA97305, P41-RR14075, and U54-CA105480 [NTROI]). NR 36 TC 75 Z9 75 U1 1 U2 10 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 JAN PY 2011 VL 258 IS 1 BP 89 EP 97 DI 10.1148/radiol.10082176 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 698ED UT WOS:000285574200011 PM 21062924 ER PT J AU Athar, BS Paganetti, H AF Athar, Basit S. Paganetti, Harald TI Comparison of second cancer risk due to out-of-field doses from 6-MV IMRT and proton therapy based on 6 pediatric patient treatment plans SO RADIOTHERAPY AND ONCOLOGY LA English DT Article DE Proton therapy; IMRT; Second cancer risk; Whole-body phantom; Pediatric radiation oncology ID MALIGNANT NEOPLASMS; RADIATION-THERAPY; CHILDHOOD-CANCER; IRRADIATION; SURVIVORS; PHANTOMS; ORGAN; MODEL; AGE AB Background and purpose: This study compared 6-MV IMRT and proton therapy in terms of organ specific second cancer lifetime attributable risks (LARs) caused by scattered and secondary out-of-field radiation. Materials and methods: Based on simulated organ doses, excess relative and excess absolute risk models were applied to assess organ-specific LARs. Two treatment sites (cranium and central spine) were considered involving six treatment volumes and six patient ages (9-month, 4-year, 8-year, 11-year, 14-year, and adult). Results: The LARs for thyroid cancer from a 6 cm diameter field treating a brain lesion in a 4-year old patient were estimated to be 1.1% and 0.3% in passive proton therapy and IMRT, respectively. However, estimated LARs for bladder cancer, more than 25 cm from the field edge for the same patient and treatment field, were estimated to be 0.2% and 0.02% from IMRT and proton therapy, respectively. Risks for proton beam scanning was found to be an order of magnitude smaller compared to passive proton therapy. Conclusion: In terms of out-of-field risks, IMRT offers advantage close to the primary field and an increasing advantage for passive proton therapy is noticed with increasing distance to the field. Scanning proton beam therapy shows the lowest risks. (C) 2010 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 98 (2011) 87-92 C1 [Athar, Basit S.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Athar, Basit S.] Harvard Univ, Sch Med, Francis H Burr Proton Therapy Ctr, Boston, MA 02114 USA. RP Athar, BS (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 55 Fruit St, Boston, MA 02114 USA. EM Basit.Athar@hamptonproton.org; hpaganetti@parteners.org FU Partners Health Care Inc.; Department of Radiation Oncology at Massachusetts General Hospital (MGH); NIH/NCI [CO6-CA059267] FX This work was supported by institutional funds (ECOR award by Partners Health Care Inc., Ira Spiro award for translational research by the Department of Radiation Oncology at Massachusetts General Hospital (MGH)) and a NIH/NCI grant (CO6-CA059267). NR 29 TC 49 Z9 49 U1 0 U2 12 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD JAN PY 2011 VL 98 IS 1 BP 87 EP 92 DI 10.1016/j.radonc.2010.11.003 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 716SS UT WOS:000286994400015 PM 21159398 ER PT S AU Daniel, C Ploegh, H von Boehmer, H AF Daniel, Carolin Ploegh, Hidde von Boehmer, Harald BE Kassiotis, G Liston, A TI Antigen-Specific Induction of Regulatory T Cells In Vivo and In Vitro SO REGULATORY T CELLS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Foxp3; Regulatory T cells (Tregs); Conversion; Antigen; DEC205; Sortagging ID RETINOIC ACID; IMMUNE TOLERANCE; APOPTOTIC CELLS; FOXP3; GENES; MICE; SUPPRESSION; MECHANISMS; CONVERSION; OCCUPANCY AB The peripheral induction of Foxp3-expressing regulatory T cells outside the thymus is required in order to maintain local homeostasis in distinct microenvironments such as the gut. Extrathymic induction of Treg may also be exploited to prevent unwanted immune responses. Here, we discuss the methodology allowing for the stable de novo generation of Tregs specific for foreign antigens in peripheral lymphoid tissue via subimmunogenic peptide delivery using either peptide contained in fusion antibodies directed against the DEC205 endocytotic receptor on steady-state dendritic cells or the implantation of peptide-delivering osmotic mini-pumps. Furthermore, we also address methods in order to achieve TGF beta-dependent Treg conversion in vitro, thereby mainly focusing on the role of retinoic acid (RA) to enhance TGF beta-dependent conversion into Tregs. C1 [Daniel, Carolin; von Boehmer, Harald] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Ploegh, Hidde] MIT, Whitehead Inst Biomed Res, Dept Biol, Cambridge, MA USA. RP Daniel, C (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. RI Liston, Adrian/G-8606-2013; Daniel, Carolin/M-4624-2014 OI Liston, Adrian/0000-0002-6272-4085; Daniel, Carolin/0000-0003-4698-7069 FU NIAID NIH HHS [AI-53102] NR 30 TC 18 Z9 20 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61737-978-9 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 707 BP 173 EP 185 DI 10.1007/978-1-61737-979-6_11 D2 10.1007/978-1-61737-979-6 PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BUJ02 UT WOS:000289486200011 PM 21287335 ER PT S AU Celli, JP Rizvi, I Blanden, AR Evans, CL Abu-Yousif, AO Spring, BQ Muzikansky, A Pogue, BW Finkelstein, DM Hasan, T AF Celli, Jonathan P. Rizvi, Imran Blanden, Adam R. Evans, Conor L. Abu-Yousif, Adnan O. Spring, Bryan Q. Muzikansky, Alona Pogue, Brian W. Finkelstein, Dianne M. Hasan, Tayyaba BE Achilefu, S Raghavachari, R TI Imaging Enabled Platforms for Development of Therapeutics SO REPORTERS, MARKERS, DYES, NANOPARTICLES, AND MOLECULAR PROBES FOR BIOMEDICAL APPLICATIONS III SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications III CY JAN 24-26, 2011 CL San Francisco, CA SP SPIE DE Photodynamic Therapy; Imaging; 3D Tumor Models; carboplatin; combination treatment; benzoporphyrin derivative monoacid ring A (BPD-MA) ID OVARIAN-CANCER; CHEMOTHERAPY; THERAPY AB Advances in imaging and spectroscopic technologies have enabled the optimization of many therapeutic modalities in cancer and noncancer pathologies either by earlier disease detection or by allowing therapy monitoring. Amongst the therapeutic options benefiting from developments in imaging technologies, photodynamic therapy (PDT) is exceptional. PDT is a photochemistry-based therapeutic approach where a light-sensitive molecule (photosensitizer) is activated with light of appropriate energy (wavelength) to produce reactive molecular species such as free radicals and singlet oxygen. These molecular entities then react with biological targets such as DNA, membranes and other cellular components to impair their function and lead to eventual cell and tissue death. Development of PDT-based imaging also provides a platform for rapid screening of new therapeutics in novel in vitro models prior to expensive and labor-intensive animal studies. In this study we demonstrate how an imaging platform can be used for strategizing a novel combination treatment strategy for multifocal ovarian cancer. Using an in vitro 3D model for micrometastatic ovarian cancer in conjunction with quantitative imaging we examine dose and scheduling strategies for PDT in combination with carboplatin, a chemotherapeutic agent presently in clinical use for management of this deadly form of cancer. C1 [Celli, Jonathan P.; Rizvi, Imran; Blanden, Adam R.; Evans, Conor L.; Abu-Yousif, Adnan O.; Spring, Bryan Q.; Hasan, Tayyaba] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Celli, JP (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, 55 Fruit St, Boston, MA 02114 USA. EM thasan@partners.org NR 12 TC 0 Z9 0 U1 1 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-8447-5 J9 PROC SPIE PY 2011 VL 7910 AR 791002 DI 10.1117/12.877293 PG 8 WC Engineering, Biomedical; Nanoscience & Nanotechnology; Optics SC Engineering; Science & Technology - Other Topics; Optics GA BXZ86 UT WOS:000297729300001 ER PT J AU Roberts, DJ AF Roberts, Drucilla J. BE Gupta, RC TI Placental pathology SO REPRODUCTIVE AND DEVELOPMENTAL TOXICOLOGY LA English DT Article; Book Chapter ID MATERNAL FLOOR INFARCTION; INFLAMMATORY RESPONSE SYNDROME; OF-THE-LITERATURE; BECKWITH-WIEDEMANN-SYNDROME; PARTIAL HYDATIDIFORM MOLE; INTRAUTERINE FETAL-GROWTH; CHORIOCARCINOMA IN-SITU; BIRTH-WEIGHT INFANTS; PERIVILLOUS FIBRIN DEPOSITION; GENE-PRODUCT P57(KIP2) C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Roberts, DJ (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 258 TC 0 Z9 0 U1 1 U2 4 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-382033-4 PY 2011 BP 1087 EP 1105 DI 10.1016/B978-0-12-382032-7.10081-5 PG 19 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA BEX82 UT WOS:000318575300082 ER PT J AU Sanna, KG Eira, JV Alice, C Rachel, PW Katja, J Marja-Leena, M Jukka, R Hanna, E David, P Irma, M AF Sanna, Kuusikko-Gauffin Eira, Jansson-Verkasalo Alice, Carter Rachel, Pollock-Wurman Katja, Jussila Marja-Leena, Mattila Jukka, Rahko Hanna, Ebeling David, Pauls Irma, Moilanen TI Face memory and object recognition in children with high-functioning autism or Asperger syndrome and in their parents SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Asperger syndrome; Autism Spectrum Disorder; Face memory; Children; Object; Recognition; Parent ID SPECTRUM DISORDERS; CLINICAL-IMPLICATIONS; PATTERNS AB Children with Autism Spectrum Disorders (ASDs) have reported to have impairments in face, recognition and face memory, but intact object recognition and object memory. Potential abnormalities, in these fields at the family level of high-functioning children with ASD remains understudied despite, the ever-mounting evidence that ASDs are genetic and highly heritable disorders. Recent studies indicate also that face perception is heritability ability, thus impairments in facial memory may be, inherited from parents with or without ASD symptoms. We studied 45 high-functioning children with, ASD (M = 11.5 years) and 26 of their parents as well as 70 control community children (M = 12.4 years), and 73 of their parents. Three subtests of the Developmental Neuropsychological Evaluation (NEPSY), were administered. Results indicate that younger children with ASD (<11.9 years old) had poorer, facial memory than their control counterparts and that the facial memory improves with age in, children with ASD. Adolescents with ASD (>11.9 years) performed better than their community, counterparts in visual object recognition. Parents of children with ASD share weakness in facial, memory ability and strength in visual object recognition with their children. Thus, families with, HFA/AS may benefit interventions of social cognition and attentional strategy. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Sanna, Kuusikko-Gauffin; Eira, Jansson-Verkasalo; Katja, Jussila; Marja-Leena, Mattila; Jukka, Rahko; Hanna, Ebeling; Irma, Moilanen] Univ Oulu, Oys 90029, Finland. [Eira, Jansson-Verkasalo] Univ Hosp Oulu, Neurocognit Unit, Oys 90029, Finland. [Alice, Carter] Univ Massachusetts, Dept Psychol, Boston, MA 02125 USA. [Rachel, Pollock-Wurman; David, Pauls] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rachel, Pollock-Wurman; David, Pauls] Harvard Univ, Sch Med, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Sanna, Kuusikko-Gauffin; Katja, Jussila; Marja-Leena, Mattila; Jukka, Rahko; Hanna, Ebeling; Irma, Moilanen] Univ Hosp Oulu, Clin Child Psychiat, Oys 90029, Finland. RP Sanna, KG (reprint author), Univ Oulu, POB 26, Oys 90029, Finland. EM sanna.kuusikko-gauffin@oulu.fi NR 28 TC 0 Z9 1 U1 2 U2 16 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1750-9467 J9 RES AUTISM SPECT DIS JI Res. Autism Spectr. Disord. PD JAN-MAR PY 2011 VL 5 IS 1 BP 622 EP 628 DI 10.1016/j.rasd.2010.07.007 PG 7 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA 676XX UT WOS:000283953800071 ER PT J AU Fan, VS Bridevaux, PO McDonell, MB Fihn, SD Besser, LM Au, DH AF Fan, Vincent S. Bridevaux, Pierre-Olivier McDonell, Mary B. Fihn, Stephan D. Besser, Lilah M. Au, David H. TI Regional Variation in Health Status among Chronic Obstructive Pulmonary Disease Patients SO RESPIRATION LA English DT Article DE Chronic obstructive pulmonary disease; Lung disease, obstructive; Health-related quality of life; Regional variation; Geographic differences ID QUALITY-OF-LIFE; VETERANS-AFFAIRS; AIR-POLLUTION; GEOGRAPHIC-VARIATION; COMORBIDITY INDEX; RANDOMIZED-TRIAL; CARE UTILIZATION; ELDERLY PATIENTS; LUNG-DISEASE; COPD AB Background: Little is known about geographic differences in health status among patients with chronic obstructive pulmonary disease (COPD). Objectives: The aim of this study was to examine regional variations in self-reported health status of COPD patients at 7 Veterans Affairs clinics. Methods: The Ambulatory Care Quality Improvement Project was a multicenter, randomized trial conducted from 1997 to 2000 that evaluated a quality improvement intervention in the primary care setting. Four thousand and nine participants with COPD (age 6 45 years) completed the Seattle Obstructive Lung Disease Questionnaire (SOLDQ) and 2,991 also completed the Medical Outcomes Study 36-item short form (SF-36). The unadjusted maximal difference in health status scores is reported as the ratio of the highest and lowest site prevalence. We report the maximal site difference in mean health status scores after adjusting for demographics, comorbidities, utilization, medication use and clinic factors. Results: Subjects were predominantly older (66.5 +/- 9.2 years) Caucasian (83.2%) men (97.9%). After adjustment, the maximal site difference for each health status score was significant (p < 0.01) but larger for the SOLDQ (physical 11.2, emotional 9.7, coping skills 7.6) than for the SF-36 (physical component summary 4.7, mental component summary 2.6). Most of the health status variation was explained by individual or clinic level factors, not clinic site. Conclusions: Our models explained < 30% of variation in health status measures; therefore, future studies should consider additional predictors of health status such as physical performance, social determinants of health, COPD treatment and environmental factors. Despite its limitations, this study suggests a need to consider regional differences in health status when comparing COPD health outcomes in diverse geographic areas. Copyright (C) 2010 S. Karger AG, Basel C1 [Fan, Vincent S.; Bridevaux, Pierre-Olivier; McDonell, Mary B.; Fihn, Stephan D.; Besser, Lilah M.; Au, David H.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, Seattle, WA 98101 USA. [Fan, Vincent S.; Fihn, Stephan D.; Au, David H.] Univ Washington, Dept Med, Seattle, WA USA. [Bridevaux, Pierre-Olivier] Univ Hosp Geneva, Div Pulm Med, Geneva, Switzerland. RP Fan, VS (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM vincent.fan@va.gov FU VA Health Services Research and Development [SDR96-002, IIR99-376]; Department of Veterans Affairs Health Services Research and Development; Swiss National Fund; Societe Academique Vaudoise; Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland FX The Veterans Affairs ACQUIP was funded by VA Health Services Research and Development grants No. SDR96-002 and IIR99-376. Researcher funding: Department of Veterans Affairs Health Services Research and Development Career Development Awards (Drs. D.H. Au and V.S. Fan); grants from the Swiss National Fund, the Societe Academique Vaudoise and the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland (Dr. P.-O. Bridevaux). NR 45 TC 8 Z9 8 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0025-7931 J9 RESPIRATION JI Respiration PY 2011 VL 81 IS 1 BP 9 EP 17 DI 10.1159/000320115 PG 9 WC Respiratory System SC Respiratory System GA 732RU UT WOS:000288207800005 PM 20720400 ER PT J AU Nair, DG Renga, V Lindenberg, R Zhu, L Schlaug, G AF Nair, Dinesh G. Renga, Vijay Lindenberg, Robert Zhu, Lin Schlaug, Gottfried TI Optimizing recovery potential through simultaneous occupational therapy and non-invasive brain-stimulation using tDCS SO RESTORATIVE NEUROLOGY AND NEUROSCIENCE LA English DT Article DE Rehabilitation; stroke recovery; non-invasive brain-stimulation; fMRI; tDCS ID HUMAN MOTOR CORTEX; TRANSCRANIAL MAGNETIC STIMULATION; PAIRED ASSOCIATIVE STIMULATION; LONG-TERM POTENTIATION; CHRONIC STROKE; UNAFFECTED HEMISPHERE; CORTICAL STIMULATION; HORIZONTAL CONNECTIONS; SUBCORTICAL STROKE; EXCITABILITY AB Purpose: It is thought that following a stroke the contralesional motor region exerts an undue inhibitory influence on the lesional motor region which might limit recovery. Pilot studies have shown that suppressing the contralesional motor region with cathodal transcranial Direct Current Stimulation (tDCS) can induce a short lasting functional benefit; greater and longer lasting effects might be achieved with combining tDCS with simultaneous occupational therapy (OT) and applying this intervention for multiple sessions. Methods: We carried out a randomized, double blind, sham controlled study of chronic stroke patients receiving either 5 consecutive days of cathodal tDCS (for 30 minutes) applied to the contralesional motor region and simultaneous OT, or sham tDCS+OT. Results: We showed that cathodal tDCS+OT resulted in significantly more improvement in Range-Of-Motion in multiple joints of the paretic upper extremity and in the Upper-Extremity Fugl-Meyer scores than sham tDCS+OT, and that the effects lasted at least one week post-stimulation. Improvement in motor outcome scores was correlated with decrease in fMRI activation in the contralesional motor region exposed to cathodal stimulation. Conclusions: This suggests that cathodal tDCS combined with OT leads to significant motor improvement after stroke due to a decrease in the inhibitory effect that the contralesional hemisphere exerts onto the lesional hemisphere. C1 [Schlaug, Gottfried] Harvard Univ, BIDMC, Dept Neurol, Neuroimaging & Stroke Recovery Labs,Sch Med, Boston, MA 02215 USA. RP Schlaug, G (reprint author), Harvard Univ, BIDMC, Dept Neurol, Neuroimaging & Stroke Recovery Labs,Sch Med, 330 Brookline Ave, Boston, MA 02215 USA. EM gschlaug@bidmc.harvard.edu RI Zhu, Lin/F-4446-2010; OI Zhu, Lin/0000-0001-6260-2515; Renga, Vijay/0000-0003-2242-2928 FU National Institute of Health [RO1 NS045049, RO1 DC008796]; CIMIT; Mary Crown and William Ellis Family Fund FX This research work was supported by grants from the National Institute of Health (RO1 NS045049, RO1 DC008796), CIMIT, Mary Crown and William Ellis Family Fund. NR 52 TC 63 Z9 69 U1 1 U2 4 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0922-6028 J9 RESTOR NEUROL NEUROS JI Restor. Neurol. Neurosci. PY 2011 VL 29 IS 6 BP 411 EP 420 DI 10.3233/RNN-2011-0612 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 883EO UT WOS:000299617000005 PM 22124031 ER PT J AU Zacharias, N Sailhamer, EA Li, YQ Liu, BL Butt, MU Shuja, F Velmahos, GC de Moya, M Alam, HB AF Zacharias, Nikolaos Sailhamer, Elizabeth A. Li, Yongqing Liu, Baoling Butt, Muhammad U. Shuja, Fahad Velmahos, George C. de Moya, Marc Alam, Hasan B. TI Histone deacetylase inhibitors prevent apoptosis following lethal hemorrhagic shock in rodent kidney cells SO RESUSCITATION LA English DT Article DE Akt; Apoptosis; Hemorrhage; Resuscitation; Survival; Valproic acid; Bad; Bcl-2 ID PROTEIN-KINASE AKT; PHOSPHOINOSITIDE 3-KINASE; SIGNALING SYSTEM; PHOSPHORYLATION; ACETYLATION; SURVIVAL; RESUSCITATION; MECHANISM; RECEPTOR; IRS-1 AB Background: We have previously demonstrated that treatment with histone deacetylase inhibitors (HDACI), such as valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA), can improve survival after hemorrhagic shock in animal models. Hemorrhage results in hypoacetylation of proteins which is reversed by HDACI. These agents are known to acetylate insulin receptor substrate-I (IRS-I), which in turn activates the Akt survival pathway. This study investigated whether HDACI exert their beneficial effects through the Akt survival pathway. Methods: Wistar-Kyoto rats (N = 21) underwent hemorrhage (60% blood loss) and were randomized into 3 groups; no resuscitation (NR), and treatment with VPA or SAHA. Kidneys were harvested at 1, 6, and 24 h after HDACI treatment and analyzed for acetylated histone 3 at lysine 9 residue (Ac-H3K9), phosphorylated Akt (phospho-Akt), BAD and Bcl-2 proteins. Results: Hemorrhaged animals were in severe shock, with mean arterial pressures of 25-30 mm Hg and lactic acid 7-9 mg/ml. Only animals treated with VPA and SAHA survived to the 6- and 24-h timepoints. Treatment with HDACI produced a biologic effect on rat kidney cells inducing acetylation of histone H3K9, which peaked after 1 h of treatment, and was statistically significant in the VPA group (p = 0.01) compared to NR. Phospho-Akt protein increased in the VPA group with a reciprocal decrease in the pro-apoptotic BAD protein in both groups which was statistically significant in the VPA group after 1 h (p = 0.007) and 24 h (p = 0.006) of treatment and in the SAHA group after 24 h of treatment (p = 0.028). Anti-apoptotic Bcl-2 protein markedly increased after 6 (p = 0.04) and 24 h (p = 0.014) of VPA treatment. Bcl-2 also increased in the SAHA group, but failed to reach statistical significance. Conclusion: Treatment with HDACI increases phosphorylation of Akt with a subsequent decrease in the pro-apoptotic BAD protein. The above mechanism facilitates the action of anti-apoptotic protein Bcl-2. HDACI protect kidney cells subjected to hemorrhagic shock in rodents through the Akt survival pathway. (C) 2010 Elsevier Ireland Ltd. All rights reserved. C1 [Zacharias, Nikolaos; Sailhamer, Elizabeth A.; Li, Yongqing; Liu, Baoling; Butt, Muhammad U.; Shuja, Fahad; Velmahos, George C.; de Moya, Marc; Alam, Hasan B.] Harvard Univ, Div Trauma Emergency Surg & Surg Crit Care, Massachusetts Gen Hosp, Sch Med,Dept Surg, Boston, MA 02114 USA. RP Alam, HB (reprint author), Harvard Univ, Div Trauma Emergency Surg & Surg Crit Care, Massachusetts Gen Hosp, Sch Med,Dept Surg, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM hbalam@partners.org FU Office of Naval Research; Polsky family FX Funded by a grant from the Office of Naval Research to Dr. Alam. Additional funds provided through a generous donation by the Polsky family. NR 23 TC 20 Z9 23 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-9572 J9 RESUSCITATION JI Resuscitation PD JAN PY 2011 VL 82 IS 1 BP 105 EP 109 DI 10.1016/j.resuscitation.2010.09.469 PG 5 WC Critical Care Medicine; Emergency Medicine SC General & Internal Medicine; Emergency Medicine GA 713FN UT WOS:000286720500019 PM 21036453 ER PT J AU Hadler, NM AF Hadler, Nortin M. BA Hadler, NM BF Hadler, NM TI ENLIGHTENED AGING SO RETHINKING AGING: GROWING OLD AND LIVING WELL IN AN OVERTREATED SOCIETY LA English DT Article; Book Chapter C1 [Hadler, Nortin M.] Massachusetts Gen Hosp, NIH, Boston, MA 02114 USA. [Hadler, Nortin M.] Clin Res Ctr London, London, England. [Hadler, Nortin M.] Univ N Carolina, Chapel Hill, NC 27515 USA. RP Hadler, NM (reprint author), Massachusetts Gen Hosp, NIH, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV NORTH CAROLINA PRESS PI CHAPEL HILL PA BOX 2288, CHAPEL HILL, NC 27514 USA BN 978-0-80786-923-9 PY 2011 BP 1 EP 8 PG 8 WC Gerontology SC Geriatrics & Gerontology GA BWK03 UT WOS:000294057200002 ER PT J AU Hadler, NM AF Hadler, Nortin M. BA Hadler, NM BF Hadler, NM TI THE GOLDEN YEARS SO RETHINKING AGING: GROWING OLD AND LIVING WELL IN AN OVERTREATED SOCIETY LA English DT Article; Book Chapter C1 [Hadler, Nortin M.] Massachusetts Gen Hosp, NIH, Boston, MA 02114 USA. [Hadler, Nortin M.] Clin Res Ctr London, London, England. [Hadler, Nortin M.] Univ N Carolina, Chapel Hill, NC 27515 USA. RP Hadler, NM (reprint author), Massachusetts Gen Hosp, NIH, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV NORTH CAROLINA PRESS PI CHAPEL HILL PA BOX 2288, CHAPEL HILL, NC 27514 USA BN 978-0-80786-923-9 PY 2011 BP 9 EP 57 PG 49 WC Gerontology SC Geriatrics & Gerontology GA BWK03 UT WOS:000294057200003 ER PT J AU Hadler, NM AF Hadler, Nortin M. BA Hadler, NM BF Hadler, NM TI ROUNDING WITH MURRAY PREFACE SO RETHINKING AGING: GROWING OLD AND LIVING WELL IN AN OVERTREATED SOCIETY LA English DT Editorial Material; Book Chapter C1 [Hadler, Nortin M.] Massachusetts Gen Hosp, NIH, Boston, MA 02114 USA. [Hadler, Nortin M.] Clin Res Ctr London, London, England. [Hadler, Nortin M.] Univ N Carolina, Chapel Hill, NC 27515 USA. RP Hadler, NM (reprint author), Massachusetts Gen Hosp, NIH, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV NORTH CAROLINA PRESS PI CHAPEL HILL PA BOX 2288, CHAPEL HILL, NC 27514 USA BN 978-0-80786-923-9 PY 2011 BP XI EP + PG 35 WC Gerontology SC Geriatrics & Gerontology GA BWK03 UT WOS:000294057200001 ER PT J AU Hadler, NM AF Hadler, Nortin M. BA Hadler, NM BF Hadler, NM TI STAYIN' ALIVE SO RETHINKING AGING: GROWING OLD AND LIVING WELL IN AN OVERTREATED SOCIETY LA English DT Article; Book Chapter C1 [Hadler, Nortin M.] Massachusetts Gen Hosp, NIH, Boston, MA 02114 USA. [Hadler, Nortin M.] Clin Res Ctr London, London, England. [Hadler, Nortin M.] Univ N Carolina, Chapel Hill, NC 27515 USA. RP Hadler, NM (reprint author), Massachusetts Gen Hosp, NIH, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV NORTH CAROLINA PRESS PI CHAPEL HILL PA BOX 2288, CHAPEL HILL, NC 27514 USA BN 978-0-80786-923-9 PY 2011 BP 59 EP 87 PG 29 WC Gerontology SC Geriatrics & Gerontology GA BWK03 UT WOS:000294057200004 ER EF