FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Thornton, IL Rizzo, JF Cestari, DM AF Thornton, Ivey L. Rizzo, Joseph F. Cestari, Dean M. TI Neuromyelitis Optica: A Review SO SEMINARS IN OPHTHALMOLOGY LA English DT Review DE Devic's disease; Aquaporin 4; anti-NMO Ig G ID MULTIPLE-SCLEROSIS; MARKER; PATHOGENESIS; AQUAPORIN-4; ANTIBODY; MRI; MS C1 [Cestari, Dean M.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Neuroophthalmol Serv, Boston, MA USA. RP Cestari, DM (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM Dean_Cestari@meei.harvard.edu NR 33 TC 2 Z9 2 U1 0 U2 6 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0882-0538 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PD JUL-SEP PY 2011 VL 26 IS 4-5 BP 337 EP 341 DI 10.3109/08820538.2011.588667 PG 5 WC Ophthalmology SC Ophthalmology GA 826VO UT WOS:000295383800016 PM 21958184 ER PT J AU Stacy, RC Rizzo, JF Cestari, DM AF Stacy, Rebecca C. Rizzo, Joseph F. Cestari, Dean M. TI Subtleties in the Histopathology of Giant Cell Arteritis SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE giant cell arteritis; temporal artery biopsy; giant cells; vasculitis; healed arteritis ID CRANIAL ISCHEMIC COMPLICATIONS; LARGE-VESSEL VASCULITIS; TEMPORAL-ARTERY; CORTICOSTEROID TREATMENT; INFLAMMATORY RESPONSE; BIOPSY SPECIMENS; SKIP LESIONS; CLASSIFICATION; ASSOCIATION; MANAGEMENT AB A temporal artery biopsy is typically obtained in cases of suspected giant cell arteritis (GCA). The differentiation between a "positive" versus a "negative" biopsy is sometimes not simple. Degrees of inflammation can vary from obvious, florid accumulations of giant cells to subtle pockets of non-granulomatous inflammation. Areas of normal pathology, or "skip lesions," may be interspersed within inflamed sections of the artery, resulting in a false negative diagnosis. Other features of the biopsy, such as the state of the internal elastic lamina and inflammation of the adjacent, smaller vessels, must also be evaluated and considered as possible signs of disease. Finally, some biopsies have an intermediate histopathologic appearance with mild inflammation and scarring, which may indicate prior treatment with corticosteroids, or "healed" arteritis. Careful examination and clinical correlation is therefore essential to evaluate for these subtleties, which can affect the final diagnosis. C1 [Stacy, Rebecca C.; Rizzo, Joseph F.; Cestari, Dean M.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Stacy, RC (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM Rebecca_Stacy@meei.harvard.edu NR 39 TC 8 Z9 8 U1 1 U2 3 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0882-0538 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PD JUL-SEP PY 2011 VL 26 IS 4-5 BP 342 EP 348 DI 10.3109/08820538.2011.588656 PG 7 WC Ophthalmology SC Ophthalmology GA 826VO UT WOS:000295383800017 PM 21958185 ER PT J AU Santiago, YM Fay, A AF Santiago, Yvette Marie Fay, Aaron TI Wegener's Granulomatosis of the Orbit: A Review of Clinical Features and Updates in Diagnosis and Treatment SO SEMINARS IN OPHTHALMOLOGY LA English DT Review DE cANCA; orbital inflammation; granulomatous inflammation; proteinase 3 (PR3); systemic vasculitis ID ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES; ANCA-ASSOCIATED VASCULITIS; MYCOPHENOLATE-MOFETIL; SYSTEMIC VASCULITIS; OCULAR MANIFESTATIONS; DISEASE-ACTIVITY; RITUXIMAB; THERAPY; CYCLOPHOSPHAMIDE; AUTOANTIBODIES AB Wegener's Granulomatosis (WG) is an uncommon systemic vasculitic disease involving the respiratory system and kidneys. It is the most common antineutrophil cytoplasm antibody (ANCA)-associated vasculitis. Orbital involvement in WG is a rare but potentially devastating disorder leading to visual loss and deformity. Most clinical characteristics of this disease are non-specific, making clinical diagnosis nearly impossible. We reviewed the features of WG involving the orbit including radiologic, serologic, and histopathologic findings. Advances in treatment are likewise discussed. C1 [Santiago, Yvette Marie; Fay, Aaron] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Santiago, Yvette Marie; Fay, Aaron] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Fay, A (reprint author), 243 Charles St, Boston, MA 02114 USA. EM Aaron_fay@meei.harvard.edu NR 56 TC 8 Z9 9 U1 0 U2 4 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0882-0538 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PD JUL-SEP PY 2011 VL 26 IS 4-5 BP 349 EP 355 DI 10.3109/08820538.2011.588662 PG 7 WC Ophthalmology SC Ophthalmology GA 826VO UT WOS:000295383800018 PM 21958186 ER PT J AU Suit, H AF Suit, Herman TI A personal philosophy of a radiation oncologist SO RADIOTHERAPY AND ONCOLOGY LA English DT Article DE Genetic; Heterogeneity; Luck; Age at personality maturity; Physician primary concern AB All humans are of one species and are near identical genetically, viz. >99.5%. Also note, the Chimp is >96% genetically identical to humans. There has been extremely rapid increase in information and knowledge and this is accelerating. Several points: time is absolutely equalitarian. There is and has not been an unnatural event in this universe. Luck is the dominant factor in an individual's success in life. At birth, the infant has zero choice of genes, parents, siblings, relatives, era and site of birth. In addition, the young child has essentially no choice in school [if any], health, etc. The key to advancing knowledge is asking decisive questions, proceeding to investigate and generate answers to the question posed and publishing the investigation, data and interpretation. The number 1 interest and concern of the physician is the care of the individual patient. The potential of "humanized experimental animals" for selected Phase III clinical trial within 2-3 decades is judged feasible. Physicians should view our current best treatment as obsolete and use this as a provocation for active effort to develop superior management strategies. (c) 2011 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 100 (2011) 10-14 C1 [Suit, Herman] Harvard Univ, Dept Radiat Oncol, Sch Med, Boston, MA 02114 USA. RP Suit, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. EM hsuit@partners.org NR 25 TC 0 Z9 0 U1 0 U2 1 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 JUL PY 2011 VL 100 IS 1 BP 10 EP 14 DI 10.1016/j.radonc.2011.05.001 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 825AL UT WOS:000295243200003 PM 21665303 ER PT J AU Ghoshal, G Barabasi, AL AF Ghoshal, Gourab Barabasi, Albert-Laszlo TI Ranking stability and super-stable nodes in complex networks SO NATURE COMMUNICATIONS LA English DT Article ID PROTEIN-INTERACTION NETWORKS; COMMUNITY STRUCTURE; WEB; PAGERANK; INTERNET; IDENTIFICATION; GRAPHS; ATTACK AB Pagerank, a network-based diffusion algorithm, has emerged as the leading method to rank web content, ecological species and even scientists. Despite its wide use, it remains unknown how the structure of the network on which it operates affects its performance. Here we show that for random networks the ranking provided by pagerank is sensitive to perturbations in the network topology, making it unreliable for incomplete or noisy systems. In contrast, in scale-free networks we predict analytically the emergence of super-stable nodes whose ranking is exceptionally stable to perturbations. We calculate the dependence of the number of super-stable nodes on network characteristics and demonstrate their presence in real networks, in agreement with the analytical predictions. These results not only deepen our understanding of the interplay between network topology and dynamical processes but also have implications in all areas where ranking has a role, from science to marketing. C1 [Ghoshal, Gourab; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Phys Biol & Comp Sci, Ctr Complex Network Res, Boston, MA 02115 USA. [Ghoshal, Gourab; Barabasi, Albert-Laszlo] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Ghoshal, Gourab; Barabasi, Albert-Laszlo] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. [Ghoshal, Gourab] MIT, Media Lab, Cambridge, MA 02139 USA. RP Barabasi, AL (reprint author), Northeastern Univ, Dept Phys Biol & Comp Sci, Ctr Complex Network Res, Boston, MA 02115 USA. EM alb@neu.edu FU Network Science Collaborative Technology Alliance; US Army Research Laboratory [W911NF-09-2-0053]; Office of Naval Research [N000141010968]; Defense Threat Reduction Agency [WMD BRBAA07-J-2-0035, BRBAA08-Per4-C-2-0033]; James S. McDonnell Foundation 21st Century Initiative in Studying Complex Systems FX We thank G. Bianconi and J.P. Bagrow for useful discussions. This work was supported by the Network Science Collaborative Technology Alliance sponsored by the US Army Research Laboratory under Agreement Number W911NF-09-2-0053; the Office of Naval Research under Agreement Number N000141010968; the Defense Threat Reduction Agency awards WMD BRBAA07-J-2-0035 and BRBAA08-Per4-C-2-0033; and the James S. McDonnell Foundation 21st Century Initiative in Studying Complex Systems. NR 46 TC 44 Z9 46 U1 9 U2 51 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD JUL PY 2011 VL 2 AR 394 DI 10.1038/ncomms1396 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 819DJ UT WOS:000294805300021 PM 21772265 ER PT J AU Nery, FC Armata, IA Farley, JE Cho, JA Yaqub, U Chen, P da Hora, CC Wang, QY Tagaya, M Klein, C Tannous, B Caldwell, KA Caldwell, GA Lencer, WI Ye, YH Breakefield, XO AF Nery, Flavia C. Armata, Ioanna A. Farley, Jonathan E. Cho, Jin A. Yaqub, Uzma Chen, Pan da Hora, Cintia Carla Wang, Qiuyan Tagaya, Mitsuo Klein, Christine Tannous, Bakhos Caldwell, Kim A. Caldwell, Guy A. Lencer, Wayne I. Ye, Yihong Breakefield, Xandra O. TI TorsinA participates in endoplasmic reticulum-associated degradation SO NATURE COMMUNICATIONS LA English DT Article ID DYSTONIA-ASSOCIATED PROTEIN; VALOSIN-CONTAINING PROTEIN; ER-ASSOCIATED DEGRADATION; DELTA-E-TORSINA; NUCLEAR-ENVELOPE; DYT1 DYSTONIA; CHOLERA-TOXIN; RETRO-TRANSLOCATION; SECRETORY PATHWAY; MOUSE MODEL AB TorsinA is an AAA+ ATPase located within the lumen of the endoplasmic reticulum and nuclear envelope, with a mutant form causing early onset torsion dystonia (DYT1). Here we report a new function for torsinA in endoplasmic reticulum-associated degradation (ERAD). Retro-translocation and proteosomal degradation of a mutant cystic fibrosis transmembrane conductance regulator (CFTR Delta F508) was inhibited by downregulation of torsinA or overexpression of mutant torsinA, and facilitated by increased torsinA. Retro-translocation of cholera toxin was also decreased by downregulation of torsinA. TorsinA associates with proteins implicated in ERAD, including Derlin-1, VIMP and p97. Further, torsinA reduces endoplasmic reticulum stress in nematodes overexpressing CFTR Delta F508, and fibroblasts from DYT1 dystonia patients are more sensitive than controls to endoplasmic reticulum stress and less able to degrade mutant CFTR. Therefore, compromised ERAD function in the cells of DYT1 patients may increase sensitivity to endoplasmic reticulum stress with consequent alterations in neuronal function contributing to the disease state. C1 [Nery, Flavia C.; Armata, Ioanna A.; Farley, Jonathan E.; Yaqub, Uzma; da Hora, Cintia Carla; Tannous, Bakhos; Breakefield, Xandra O.] Harvard Univ, Sch Med, Ctr Neurosci, Dept Neurol, Boston, MA 02114 USA. [Nery, Flavia C.; Armata, Ioanna A.; Farley, Jonathan E.; Yaqub, Uzma; da Hora, Cintia Carla; Tannous, Bakhos; Breakefield, Xandra O.] Harvard Univ, Sch Med, Ctr Mol Imaging Res, Dept Radiol,Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nery, Flavia C.; Armata, Ioanna A.; Farley, Jonathan E.; Yaqub, Uzma; da Hora, Cintia Carla; Tannous, Bakhos; Breakefield, Xandra O.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02114 USA. [Cho, Jin A.; Lencer, Wayne I.] Harvard Univ, Sch Med, Gastrointestinal Cell Biol & Harvard Digest Dis C, Childrens Hosp, Boston, MA 02115 USA. [Chen, Pan; Caldwell, Kim A.; Caldwell, Guy A.] Univ Alabama, Dept Biol Sci, Tuscaloosa, AL 35487 USA. [Chen, Pan; Caldwell, Kim A.; Caldwell, Guy A.] Univ Alabama, Dept Tuscaloosa, Tuscaloosa, AL 35487 USA. [Chen, Pan; Caldwell, Kim A.; Caldwell, Guy A.] Univ Alabama, Ctr Neurodegenerat & Expt Therapeut, Dept Neurol, Tuscaloosa, AL 35487 USA. [Chen, Pan; Caldwell, Kim A.; Caldwell, Guy A.] Univ Alabama, Ctr Neurodegenerat & Expt Therapeut, Dept Neurobiol, Tuscaloosa, AL 35487 USA. [Wang, Qiuyan; Ye, Yihong] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Tagaya, Mitsuo] Tokyo Univ Pharm & Life Sci, Sch Sci, Tokyo 1920392, Japan. [Klein, Christine] Med Univ Lubeck, Sect Clin & Mol Neurogenet, D-23538 Lubeck, Germany. RP Breakefield, XO (reprint author), Harvard Univ, Sch Med, Ctr Neurosci, Dept Neurol, Boston, MA 02114 USA. EM breakefield@hms.harvard.edu FU NINDS [NS037409, P30NS045776]; Dystonia Medical Research Foundation; NSF; QRxPharma; Volkswagen Foundation; Hermann and Lilly Schilling Foundation; Crohn's & Colitis Foundation of America [3042]; [HD007466-11]; [DK083894]; [DK48106]; [DK0484424] FX We thank Nathan Roberts (Dystonia Support Group of Alabama), Nathan Spielberg, Igor Bagayev and Xuan Zhang for help with experiments; Suzanne McDavitt for skilled editorial assistance; Trisha Multhaupt-Buell for IRB submissions; Dr Phyllis Hanson (Washington University) for torsinA constructs; Dr Pedro Gonzalez-Allegre (University of Iowa) for torsinA antibodies; Drs Dinah Sah and Pei Ge (Alnylam Pharmaceuticals) for siRNAs for torsinA; and the Imaging Core of the Harvard Digestive Disease Center DK034854 (W.I.L.) for assistance with confocal imaging. Adenovirus vectors were provided by the Vector Core at the University of Pennsylvania School of Medicine; AAV vectors were provided by Dr Miguel Sena-Esteves (UMass Memorial Medical. Center.). This work was supported by: NINDS NS037409 (XOB); the Dystonia Medical Research Foundation (F.N.); NINDS P30NS045776 and NSF CAREER Award (K.A.C.); QRxPharma (K.A.C. and G.A.C.); Volkswagen Foundation. and Hermann and Lilly Schilling Foundation. (C.K.); HD007466-11, DK083894 and Crohn's & Colitis Foundation of America 3042 (J.A.C.); and DK48106 and DK0484424 (W.I.L.). NR 60 TC 44 Z9 44 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD JUL PY 2011 VL 2 AR 393 DI 10.1038/ncomms1383 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 819DJ UT WOS:000294805300020 PM 21750546 ER PT J AU Orhan, G Wuttke, TV Nies, AT Schwab, M Lerche, H AF Orhan, Goekce Wuttke, Thomas V. Nies, Anne T. Schwab, Matthias Lerche, Holger TI The KCNQ/K(V)7 potassium channel opener Retigabine as add-on therapy for partial epilepsy. Pharmacological and clinical data SO PSYCHOPHARMAKOTHERAPIE LA German DT Article DE Epilepsy; potassium channel; pharmacotherapy; antiepileptic drug; retigabine ID CORTEX HIPPOCAMPAL SLICES; ANTICONVULSANT RETIGABINE; PHARMACOKINETIC INTERACTION; DIFFERENT PATTERNS; N-GLUCURONIDATION; HEALTHY-SUBJECTS; DRUG RETIGABINE; HUMAN LIVER; D-23129; ACTIVATION AB The KCNQ/K(V)7 potassium channel opener Retigabine as add-on therapy for partial epilepsy. Pharmacological and clinical data This review summarizes the pharmacological, preclinical and clinical data on the new anticonvulsant compound retigabine (RGB) and discusses the impact of this drug for patients with refractory partial epilepsy. Retigabine increases the activity of voltage-gated KCNQ/K(V)7 channels and thus exhibits a novel mechanism of action as compared to available anticonvulsive drugs. Retigabine has been investigated in three multicenter, randomized, double-blind and placebo-controlled clinical phase 11 and III trials in adults with >= 4 partialonset seizures per month and showed efficacy in pharmacoresistant epilepsy. In march 2011, Retigabine received approval in Europe as Trobalt (R). C1 [Orhan, Goekce; Lerche, Holger] Univ Tubingen, Hertie Inst Klin Hirnforsch, Abt Neurol Schwerpunkt Epileptol, D-72076 Tubingen, Germany. [Wuttke, Thomas V.] Harvard Univ, Sch Med, Dept Neurosurg, MGH HMS Ctr Nervous Syst Repair, Boston, MA 02114 USA. [Wuttke, Thomas V.] Harvard Univ, Sch Med, Dept Neurol, MGH HMS Ctr Nervous Syst Repair, Boston, MA 02114 USA. [Wuttke, Thomas V.] Harvard Univ, Program Neurosci, Sch Med, Boston, MA 02114 USA. [Wuttke, Thomas V.] Massachusetts Gen Hosp, Nayef Al Rodhan Labs, Boston, MA 02114 USA. [Nies, Anne T.; Schwab, Matthias] Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-70376 Stuttgart, Germany. [Schwab, Matthias] Univ Klinikum Tubingen, Klin Pharmakol Abt, Inst Expt & Klin Pharmakol & Toxikol, D-72076 Tubingen, Germany. RP Orhan, G (reprint author), Univ Tubingen, Hertie Inst Klin Hirnforsch, Abt Neurol Schwerpunkt Epileptol, Hoppe Seyler Str 3, D-72076 Tubingen, Germany. EM holger.lerche@uni-tuebingen.de NR 45 TC 1 Z9 1 U1 4 U2 9 PU WISSENSCHAFTLICHE VERLAGSGESELLSCHAFT STUTTGART PI STUTTGART PA BIRKENWALDSTRASSE 44, POSTFACH 10 10 61, 70009 STUTTGART, GERMANY SN 0944-6877 J9 PSYCHOPHARMAKOTHERAP JI Psychopharmakotherapie PD JUL-AUG PY 2011 VL 18 IS 4 BP 148 EP + PG 8 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 815OD UT WOS:000294534000002 ER PT J AU Katznelson, L Atkinson, JLD Cook, DM Ezzat, SZ Hamrahian, AH Miller, KK AF Katznelson, Laurence Atkinson, John L. D. Cook, David M. Ezzat, Shereen Z. Hamrahian, Amir H. Miller, Karen K. TI AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS MEDICAL GUIDELINES FOR CLINICAL PRACTICE FOR THE DIAGNOSIS AND TREATMENT OF ACROMEGALY-2011 UPDATE: EXECUTIVE SUMMARY SO ENDOCRINE PRACTICE LA English DT Article C1 [Katznelson, Laurence] Stanford Univ, Dept Med, Stanford, CA 94305 USA. [Katznelson, Laurence] Stanford Univ, Dept Neurosurg, Stanford, CA 94305 USA. [Atkinson, John L. D.] Mayo Clin, Dept Neurosurg, Rochester, MN USA. [Cook, David M.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Ezzat, Shereen Z.] Univ Toronto, Toronto Gen Hosp, Dept Med & Endocrinol, Toronto, ON M5G 1L7, Canada. [Hamrahian, Amir H.] Cleveland Clin, Dept Diabet Endocrinol & Metab, Cleveland, OH 44106 USA. [Miller, Karen K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroendocrine Unit,Dept Med, Boston, MA USA. RP Katznelson, L (reprint author), Stanford Univ, Dept Med, Stanford, CA 94305 USA. FU Novartis AG; Indevus Pharmaceuticals; Eli Lilly and Company FX Dr. Laurence Katznelson reports that he has received speakers' bureau honoraria from IPSEN and advisory board honoraria and research grant support from Novartis AG.; Dr. David M. Cook reports that he has received speaker honoraria from Pfizer Inc., research grant support from Indevus Pharmaceuticals, and speaker honoraria and research grant support from Eli Lilly and Company. NR 6 TC 35 Z9 36 U1 0 U2 1 PU AMER ASSOC CLINICAL ENDOCRINOLOGISTS PI JACKSONVILLE PA 245 RIVERSIDE AVENUE, STE 200, JACKSONVILLE, FL 32202 USA SN 1530-891X J9 ENDOCR PRACT JI Endocr. Pract. PD JUL-AUG PY 2011 VL 17 IS 4 BP 636 EP 646 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 812FH UT WOS:000294276000014 PM 21846619 ER PT J AU Kannan, S Khanna, I Kaur, M Radin, M AF Kannan, Subramanian Khanna, Ila Kaur, Manmeet Radin, Michael TI What is the diagnosis? The patient was clinically diagnosed with familial lipodystrophy associated with the metabolic syndrome. Genetic studies confirmed the presence of type 2 familial partial lipodystrophy syndrome of the Dunnigan variety SO ENDOCRINE PRACTICE LA English DT Editorial Material C1 [Kannan, Subramanian; Khanna, Ila] Univ Connecticut, Dept Internal Med, Farmington, CT USA. [Kaur, Manmeet; Radin, Michael] Hosp Cent Connecticut, Joslin Diabet Ctr Affiliate, New Britain, CT USA. RP Kannan, S (reprint author), 263 Farmington Ave,L2104, Farmington, CT 06030 USA. NR 3 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CLINICAL ENDOCRINOLOGISTS PI JACKSONVILLE PA 245 RIVERSIDE AVENUE, STE 200, JACKSONVILLE, FL 32202 USA SN 1530-891X J9 ENDOCR PRACT JI Endocr. Pract. PD JUL-AUG PY 2011 VL 17 IS 4 BP 665 EP 665 DI 10.4158/EP10396.VV PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 812FH UT WOS:000294276000023 PM 21454231 ER PT J AU Souter, I Dimitriadis, I Smith, K Ehrlich, S Berry, K Hauser, R AF Souter, I. Dimitriadis, I. Smith, K. Ehrlich, S. Berry, K. Hauser, R. TI Urinary bisphenol A (BPA) concentrations and ovarian reserve in women undergoing infertility treatments SO HUMAN REPRODUCTION LA English DT Meeting Abstract CT 27th Annual Meeting of the European-Society-of-Human-Reproduction-and-Embryology CY JUL 03-06, 2011 CL Stockholm, SWEDEN SP European Soc Human Reprod & Embryol C1 [Souter, I.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. [Dimitriadis, I.] Harvard Univ, Massachusetts Gen Hosp, Sch Publ Hlth, Cambridge, MA 02138 USA. [Smith, K.; Ehrlich, S.; Berry, K.; Hauser, R.] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. RI Ehrlich , Shelley/L-6991-2015 NR 0 TC 1 Z9 1 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD JUL PY 2011 VL 26 SU 1 BP I6 EP I6 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 814KO UT WOS:000294450500014 ER PT J AU Berin, I McLellan, ST Macklin, EA Toth, TL Wright, DL AF Berin, Inna McLellan, Sarah T. Macklin, Eric A. Toth, Thomas L. Wright, Diane L. TI Frozen-thawed embryo transfer cycles: clinical outcomes of single and double blastocyst transfers SO JOURNAL OF ASSISTED REPRODUCTION AND GENETICS LA English DT Article DE Frozen blastocyst transfer; Frozen cycle outcome; IVF; Multiple pregnancy; Number of embryos to transfer ID IN-VITRO FERTILIZATION; IMPLANTATION; CONCEPTION AB Purpose To evaluate clinical outcomes of frozen-thawed embryo transfer cycles when one or two blastocysts are transferred. Methods Retrospective chart review Results Two hundred forty-three frozen blastocyst transfer (FBT) cycles were analyzed. Clinical pregnancy rate (50.4% vs. 34.7%), live birth rate (45.8% vs. 30.6%), and twin live birth rate (19.3% vs. 0) were significantly higher in the double versus single FBT group, respectively (p < 0.05). Prior fresh cycle success with same-cohort embryos did not predict outcome of FBT cycle. When the fresh cycle was unsuccessful, there still was a significant increase in twinning when two frozen-thawed blastocysts were transferred. Conclusions Transferring two blastocysts during an FBT cycle resulted in higher live birth and twin live birth rates. Single FBT provided acceptable pregnancy rates for couples seeking to avoid a multiple pregnancy or for those having a single blastocyst stored. Interestingly, the outcome of fresh cycle with same-cohort embryos did not influence the outcome of frozen-thawed cycle. C1 [Berin, Inna; McLellan, Sarah T.; Toth, Thomas L.; Wright, Diane L.] Harvard Univ, Sch Med, Div Reprod Med, Vincent Obstet & Gynecol Serv, Boston, MA 02114 USA. [Berin, Inna; McLellan, Sarah T.; Toth, Thomas L.; Wright, Diane L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, IVF, Boston, MA 02114 USA. [Macklin, Eric A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Berin, I (reprint author), Harvard Univ, Sch Med, Div Reprod Med, Vincent Obstet & Gynecol Serv, 55 Fruit St,Yawkey 10A, Boston, MA 02114 USA. EM inna_berin@yahoo.com RI Macklin, Eric/E-2955-2013 OI Macklin, Eric/0000-0003-1618-3502 NR 20 TC 9 Z9 11 U1 0 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1058-0468 J9 J ASSIST REPROD GEN JI J. Assist. Reprod. Genet. PD JUL PY 2011 VL 28 IS 7 BP 575 EP 581 DI 10.1007/s10815-011-9551-7 PG 7 WC Genetics & Heredity; Obstetrics & Gynecology; Reproductive Biology SC Genetics & Heredity; Obstetrics & Gynecology; Reproductive Biology GA 813FZ UT WOS:000294353500003 PM 21373800 ER PT J AU Pizer, SD Prentice, JC AF Pizer, Steven D. Prentice, Julia C. TI Time is money: Outpatient waiting times and health insurance choices of elderly veterans in the United States SO JOURNAL OF HEALTH ECONOMICS LA English DT Article DE Outpatient waiting times; Insurance choice; Medicare ID CARE SERVICES; MEDICARE; ACCESS; BENEFITS; QUALITY; DEMAND; DESIGN; MARKET; IMPACT; COSTS AB Growth in the number of days between an appointment request and the actual appointment reduces demand. Although such waiting times are relatively low in the US, current policy initiatives could cause them to increase. We estimate multiple-equation models of physician utilization and insurance plan choice for Medicare-eligible veterans. We find that a 10% increase in VA waiting times increases demand for Medigap insurance by 5%, implying that a representative patient would be indifferent between waiting an average of 5 more days for VA appointments and paying $300 more in annual premium. Published by Elsevier B.V. C1 [Pizer, Steven D.; Prentice, Julia C.] US Dept Vet Affairs, Boston, MA 02130 USA. [Pizer, Steven D.; Prentice, Julia C.] Boston Univ, Boston, MA 02130 USA. RP Pizer, SD (reprint author), US Dept Vet Affairs, 150 S Huntington Ave,Mail Stop 152H, Boston, MA 02130 USA. EM pizer@bu.edu FU Health Services Research and Development Service of the U.S. Department of Veterans Affairs [IAD 06-112]; Changes in Health Care Financing and Organization (HCFO) Initiative of the Robert Wood Johnson Foundation [62967] FX This research was supported by grants from the Health Services Research and Development Service of the U.S. Department of Veterans Affairs (Grant No. IAD 06-112) and from the Changes in Health Care Financing and Organization (HCFO) Initiative of the Robert Wood Johnson Foundation (Grant No. 62967). The views expressed are those of the authors and do not necessarily reflect the official positions of the U.S. Department of Veterans Affairs, the Robert Wood Johnson Foundation, or Boston University. The authors would like to thank Tom McGuire and participants in the BU/Harvard/MIT Health Economics Seminar Series as well as two anonymous reviewers for many helpful comments. NR 34 TC 7 Z9 7 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-6296 J9 J HEALTH ECON JI J. Health Econ. PD JUL PY 2011 VL 30 IS 4 BP 626 EP 636 DI 10.1016/j.jhealeco.2011.05.004 PG 11 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 813TQ UT WOS:000294393500003 PM 21641062 ER PT J AU Howard, TE AF Howard, T. E. TI Factor VIII gene haplotype and inhibitor development SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 [Howard, T. E.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Pathol, Los Angeles, CA USA. [Howard, T. E.] Vet Affairs Greater Los Angeles Healthcare Syst, Lab Med, Los Angeles, CA USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1538-7933 EI 1538-7836 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD JUL PY 2011 VL 9 SU 2 SI SI BP 1 EP 1 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 800DU UT WOS:000293340800002 ER PT J AU Siller-Matula, JM Merhi, Y Tanguay, JF Duerschmied, D McGinness, KE Pendergrast, SP Wagner, DD Schaub, RG Jilma, B AF Siller-Matula, J. M. Merhi, Y. Tanguay, J-F Duerschmied, D. McGinness, K. E. Pendergrast, S. P. Wagner, D. D. Schaub, R. G. Jilma, B. TI ARC15105 a potent antagonist of von Willebrand factor (VWF) platelet activation and adhesion SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 [Siller-Matula, J. M.] Med Univ Vienna, Dept Cardiol, Vienna, Austria. [Merhi, Y.; Tanguay, J-F] Univ Montreal, Montreal, PQ H3C 3J7, Canada. [Merhi, Y.; Tanguay, J-F] Montreal Heart Inst, Montreal, PQ, Canada. [Duerschmied, D.; Wagner, D. D.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Duerschmied, D.; Wagner, D. D.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Duerschmied, D.] Univ Med Ctr Freiburg, Dept Cardiol & Angiol, Freiburg, Germany. [McGinness, K. E.; Pendergrast, S. P.; Schaub, R. G.] Archemix Corp, Cambridge, England. [Jilma, B.] Med Univ Vienna, Dept Clin Pharmacol, Vienna, Austria. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1538-7933 EI 1538-7836 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD JUL PY 2011 VL 9 SU 2 SI SI BP 17 EP 18 PG 2 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 800DU UT WOS:000293340800058 ER PT J AU De Meyer, SF Fuchs, TA Suidan, GL Brill, A Schatzberg, D Monestier, M Napirei, M Mannherz, HG Wagner, DD AF De Meyer, S. F. Fuchs, T. A. Suidan, G. L. Brill, A. Schatzberg, D. Monestier, M. Napirei, M. Mannherz, H. G. Wagner, D. D. TI Extracellular chromatin is an important mediator of ischemic stroke SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 [De Meyer, S. F.; Fuchs, T. A.; Suidan, G. L.; Brill, A.; Schatzberg, D.; Wagner, D. D.] Harvard Univ, Sch Med, Immune Dis Inst, Cambridge, MA 02138 USA. [Monestier, M.] Temple Univ, Sch Med, Dept Microbiol & Immunol, Philadelphia, PA 19122 USA. [Napirei, M.; Mannherz, H. G.] Ruhr Univ Bochum, Fak Med, Abt Anat & Mol Embryol, Bochum, Germany. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1538-7933 EI 1538-7836 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD JUL PY 2011 VL 9 SU 2 SI SI BP 40 EP 40 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 800DU UT WOS:000293340800123 ER PT J AU Bhide, P AF Bhide, Pradeep TI Prenatal Cocaine Exposure and Embryonic Cortical Development SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Meeting Abstract CT 35th Annual Meeting of the Neurobehavioral-Teratology-Society/51st Annual Meeting of the Teratology-Society/24th Annual Meeting of the Organization-of-Teratology-Information-Specialists CY JUN 25-29, 2011 CL Coronado, CA SP Neurobehav Teratol Soc, Teratol Soc, Org Teratol Informat Specialists C1 [Bhide, Pradeep] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bhide, Pradeep] Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD JUL-AUG PY 2011 VL 33 IS 4 BP 503 EP 504 DI 10.1016/j.ntt.2011.05.044 PG 2 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 815LU UT WOS:000294527900041 ER PT J AU Zhu, JM Spencer, T Biederman, J Bhide, P AF Zhu, Jinmin Spencer, Thomas Biederman, Joseph Bhide, Pradeep TI Prenatal Nicotine Exposure Mouse Model of ADHD SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Meeting Abstract CT 35th Annual Meeting of the Neurobehavioral-Teratology-Society/51st Annual Meeting of the Teratology-Society/24th Annual Meeting of the Organization-of-Teratology-Information-Specialists CY JUN 25-29, 2011 CL Coronado, CA SP Neurobehav Teratol Soc, Teratol Soc, Org Teratol Informat Specialists C1 [Zhu, Jinmin; Bhide, Pradeep] Massachusetts Gen Hosp, Ctr Neurosci, Boston, MA 02129 USA. [Zhu, Jinmin; Bhide, Pradeep] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02129 USA. [Spencer, Thomas; Biederman, Joseph] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02129 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD JUL-AUG PY 2011 VL 33 IS 4 BP 507 EP 507 DI 10.1016/j.ntt.2011.05.056 PG 1 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 815LU UT WOS:000294527900053 ER PT J AU Erten-Lyons, D Wilmot, B Anur, P McWeeney, S Westaway, SK Silbert, L Kramer, P Kaye, J AF Erten-Lyons, Deniz Wilmot, Beth Anur, Pavana McWeeney, Shannon Westaway, Shawn K. Silbert, Lisa Kramer, Patricia Kaye, Jeffrey CA Alzheimer's Dis Neuroimaging TI Microcephaly Genes and Risk of Late-onset Alzheimer Disease SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Article DE Alzheimer disease; microcephaly genes; cognitive reserve ID ONGOING ADAPTIVE EVOLUTION; BRAIN SIZE; MOLECULAR EVOLUTION; HEAD CIRCUMFERENCE; MAJOR DETERMINANT; OLDEST-OLD; ASPM GENE; ASSOCIATION; POPULATION; DEMENTIA AB Brain development in the early stages of life has been suggested to be one of the factors that may influence an individual's risk of Alzheimer disease (AD) later in life. Four microcephaly genes, which regulate brain development in utero and have been suggested to play a role in the evolution of the human brain, were selected as candidate genes that may modulate the risk of AD. We examined the association between single nucleotide polymorphisms tagging common sequence variations in these genes and risk of AD in two case-control samples. We found that the G allele of rs2442607 in microcephalin 1 was associated with an increased risk of AD (under an additive genetic model, P = 0.01; odds ratio = 3.41; confidence interval, 1.77-6.57). However, this association was not replicated using another case-control sample research participants from the Alzheimer Disease Neuroimaging Initiative. We conclude that the common variations we measured in the 4 microcephaly genes do not affect the risk of AD or that their effect size is small. C1 [Erten-Lyons, Deniz; Kaye, Jeffrey] Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Portland, OR 97201 USA. [Erten-Lyons, Deniz; Westaway, Shawn K.; Silbert, Lisa; Kramer, Patricia; Kaye, Jeffrey] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Wilmot, Beth; Anur, Pavana; McWeeney, Shannon] Oregon Hlth & Sci Univ, Oregon Clin & Translat Res Ctr, Portland, OR 97201 USA. [Wilmot, Beth; McWeeney, Shannon] Oregon Hlth & Sci Univ, Div Bioinformat & Computat Biol, Dept Med Informat & Clin Epidemiol, Portland, OR 97201 USA. [McWeeney, Shannon] Oregon Hlth & Sci Univ, Dept Publ Hlth & Preventat Med, Div Biostat, Portland, OR 97201 USA. RP Erten-Lyons, D (reprint author), NIA, Layton Aging & Alzheimers Dis Ctr, 3181 SW Sam Jackson Pk Rd,CR 131, Portland, OR 97239 USA. EM ertenlyo@ohsu.edu RI Scharre, Douglas/E-4030-2011; OI Kaye, Jeffrey/0000-0002-9971-3478; McWeeney, Shannon/0000-0001-8333-6607; Silbert, Lisa/0000-0002-4525-0068 FU Office of Research and Development, Department of Veterans Affairs, National Institutes of Health [AG08017, MO1 RR000334, UL1 RR024140]; Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]; National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering; Northern California Institute for Research and Education; NIH [P30 AG010129, K01 AG030514]; Dana Foundation FX Supported by Merit Review Grant and Research Career Development Award, Office of Research and Development, Department of Veterans Affairs, National Institutes of Health (AG08017, MO1 RR000334, UL1 RR024140), Alzheimer Tax Check-off Grant. 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 nonprofit partners the Alzheimer's Association and Alzheimer's Drug Discovery Foundation, with participation from the US Food and Drug Administration. Private sector contributions to ADNI are facilitated by the Foundation for the National Institutes of Health (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 34 TC 0 Z9 1 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-0341 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PD JUL-SEP PY 2011 VL 25 IS 3 BP 276 EP 282 DI 10.1097/WAD.0b013e31820a1d32 PG 7 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA 811JW UT WOS:000294206600013 PM 21297427 ER PT J AU Pollack, MH Hoge, EA Worthington, JJ Moshier, SJ Wechsler, RS Brandes, M Simon, NM AF Pollack, Mark H. Hoge, Elizabeth A. Worthington, John J. Moshier, Samantha J. Wechsler, Rachel S. Brandes, Mina Simon, Naomi M. TI Eszopiclone for the Treatment of Posttraumatic Stress Disorder and Associated Insomnia: A Randomized, Double-Blind, Placebo-Controlled Trial SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID SEXUAL ASSAULT SURVIVORS; COMBAT-RELATED PTSD; SLEEP DISTURBANCES; CLINICAL-TRIAL; NIGHTMARES; VETERANS; ANTIDEPRESSANTS; COMORBIDITY; EXTINCTION; DEPRESSION AB Objective: The development of novel strategies for the treatment of posttraumatic stress disorder (PTSD) represents a critical public health need. We present the first prospective, randomized, double-blind, placebo-controlled trial of a non-benzodiazepine hypnotic agent for the treatment of PTSD and associated insomnia. Method: Twenty-four patients with PTSD by DSM-IV criteria and sleep disturbance were treated in a randomized, double-blind, placebo-controlled crossover study of 3 weeks of eszopiclone 3 mg at bedtime compared to placebo. The primary outcome measures were changes in scores on the Short PTSD Rating Interview (SPRINT) and the Pittsburgh Sleep Quality Index (PSQI). The data were collected from April 2006 to June 2008. Results: Three weeks of eszopiclone pharmacotherapy was associated with significantly greater improvement than placebo on PTSD symptom measures including the SPRINT (P = .032) and the Clinician-Administered PTSD Scale (P = .003), as well as on measures of sleep including the PSQI (P = .011) and sleep latency (P = .044). Greater improvement with eszopiclone on PTSD measures was present even when specific sleep-related items were excluded. Adverse events were consistent with the known profile of the drug. Conclusions: This study provides initial evidence that pharmacotherapy with eszopiclone may be associated with short-term improvement in overall PTSD severity as well as associated sleep disturbance. Longer, more definitive study of eszopiclone in PTSD is warranted. Trial Registration: clinicaltrials.gov Identifier: NCT00120250 J Clin Psychiatry 2011;72(7):892-897 (C) Copyright 2011 Physicians Postgraduate Press, Inc. C1 [Pollack, Mark H.] Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Pollack, MH (reprint author), Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, 1 Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM mpollack@partners.org RI Hoge, Elizabeth/H-5879-2012 OI Hoge, Elizabeth/0000-0002-5513-2292 FU Sepracor, Inc, Marlborough, Massachusetts; Sepracor; Bristol-Myers Squibb; Forest; GlaxoSmithKline; Eli Lilly; National Center for Complementary and Alternative Medicine; National Institute on Drug Abuse; National Institute of Mental Health (NIMH); AstraZeneca; Pfizer; Cephalon; Janssen; Mind and Life Institute; National Institutes of Health; UCB Pharma; Abbott; Alkermes; Aspect Medical Systems; Johnson Johnson; Lichtwer Pharma; Lorex; Novartis; Organon; PamLab; Pharmavite; Roche; sanofi-aventis; Solvay, Inc; Wyeth-Ayerst; NARSAD; NIMH FX Dr Pollack has served as a consultant to, received research support from and participated in continuing medical education (CME) activities sponsored by Sepracor. In addition, over the last 12 months he has received research support from Bristol-Myers Squibb, Forest, GlaxoSmithKline, Eli Lilly, the National Center for Complementary and Alternative Medicine, the National Institute on Drug Abuse, and the National Institute of Mental Health (NIMH). He has served on the advisory boards and/or provided consultation to Brain Cells, Eli Lilly, Medavante, Mindsite, Pfizer and Targia. He has participated in CME activities supported by AstraZeneca and Pfizer. He also holds equity in Medavante, Mensante Corporation, Mindsite, and Targia and receives copyright royalties for the SIGH-A and SAFER. Dr Hoge has received research grants from or has participated in research trials sponsored by AstraZeneca, Bristol-Myers Squibb, Cephalon, Forest, GlaxoSmithKline, Janssen, Eli Lilly, the Mind and Life Institute, the National Institutes of Health, Pfizer, UCB Pharma, and Sepracor. Dr Worthington has received grant/research support from Abbott, Alkermes, Aspect Medical Systems, AstraZeneca, Bristol-Myers Squibb, Cephalon, Eli Lilly, Forest, GlaxoSmithKline, Johnson & Johnson, Lichtwer Pharma, Lorex, Novartis, Organon, PamLab, Pfizer, Pharmavite, Roche, sanofi-aventis, Sepracor, Solvay, Inc, UCB Pharma, and Wyeth-Ayerst. He has also served on speakers bureaus for Bristol-Myers Squibb, Eli Lily, Forest, GlaxoSmithKline, Pfizer, sanofi-aventis, and Wyeth-Ayerst. Dr Brandes has participated in research trials sponsored by Forest, Eli Lilly, National Institutes of Health, and Sepracor. Dr Simon has received research support from AstraZeneca, Cephalon, Forest, GlaxoSmithKline, Janssen, Eli Lilly, NARSAD, NIMH, Pfizer, UCB-Pharma, and Sepracor; and has participated in CME presentations for MGH Psychiatry Academy and AstraZeneca. Mss Moshier and Wechsler have no financial disclosures or conflicts of interest to report.; This study was funded through an investigator-initiated grant by Sepracor, Inc, Marlborough, Massachusetts. NR 50 TC 31 Z9 31 U1 1 U2 7 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 JUL PY 2011 VL 72 IS 7 BP 892 EP 897 DI 10.4088/JCP.09m05607gry PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 804UD UT WOS:000293678600002 PM 21367352 ER PT J AU Surman, CBH Roth, T AF Surman, Craig B. H. Roth, Thomas TI Impact of Stimulant Pharmacotherapy on Sleep Quality: Post Hoc Analyses of 2 Large, Double-Blind, Randomized, Placebo-Controlled Trials SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; LISDEXAMFETAMINE DIMESYLATE; ADULT ADHD; INDEX AB Background: Sleep disturbances may cause distress among individuals with attention-deficit/hyperactivity disorder (ADHD), but few studies have examined the impact of stimulant pharmacotherapy for ADHD on sleep in adults. Method: These post hoc analyses included sleep data collected with the Pittsburgh Sleep Quality Index (PSQI), a self-rated questionnaire, from 831 adults with DSM-IV-TR defined ADHD in 2 large, randomized, double-blind, placebo-controlled, forced dose titration studies of lisdexamfetamine (N = 420; conducted from May 25, 2006, to November 16, 2006) and triple-bead mixed amphetamine salts (MAS) (N = 411; conducted from April 25, 2005, to November 4, 2005). Change from baseline to endpoint in PSQI clinically meaningful change categories (ie, "decrease:" "no change," or "increase") was analyzed by treatment group in each study using the chi(2) test. The Cochran-Mantel-Haenszel method was used (1) to determine whether there was a statistically significant difference in Clinical Global Impressions-Improvement (CGI-I) score of 1 or 2 (improved) versus >2 (not improved) relative to a decrease or an increase in PSQI and (2) to analyze shifts from good sleep at baseline (PSQI <= 5) to poor sleep at endpoint (PSQI > 5). Results: Impaired sleep (PSQI score > 5) relative to baseline was demonstrated in 8.3% and 9.7% of the treatment and placebo groups, respectively (P = .18), in the MAS study and 7.7% and 8.2%, respectively (P = .03), in the lisdexamfetamine study. Clinically meaningful change in baseline to endpoint PSQI was not statistically significantly different between treatment and placebo groups in either study. A significant difference in CGI-I 1 and 2 relative to an increase or decrease in PSQI was found in both the triple-bead MAS (P < .0001) and the lisdexamfetamine (P = .0008) trials. More subjects with improved CGI-I rating of 1 or 2 had improvement in PSQI than had worsening. Conclusions: Approximately one-third of subjects receiving treatment or placebo had clinically meaningful sleep improvement, emphasizing that change in sleep quality during treatment may not necessarily be related to stimulant therapy. When managing complaints of sleep difficulties in ADHD subjects, clinicians should undertake a broad assessment and consider underlying conditions that may contribute to sleep disruption. Trial Registration: clinicaltrials.gov Identifiers: NCT00334880 and NCT00152022 J Clin Psychiatry 2011;72(7):903-908 (C) Copyright 2011 Physicians Postgraduate Press, Inc. C1 [Surman, Craig B. H.] Massachusetts Gen Hosp, Clin & Res Program Adult ADHD, Boston, MA 02114 USA. [Roth, Thomas] Henry Ford Hosp, Sleep Ctr, Detroit, MI 48202 USA. RP Surman, CBH (reprint author), Massachusetts Gen Hosp, Clin & Res Program Adult ADHD, Ste 2000,185 Alewife Brook Pkwy, Cambridge, MA 02138 USA. EM csurman@partners.org FU Abbott; Alza; Cephalon; Eli Lilly; Hilda; Preston Davis Foundation; McNeil; Merck; New River; National Institutes of Health; Organon; Pfizer; Shire; Takeda; Janssen-Ortho; Novartis; Aventis; GlaxoSmithKline; Neurocrine; Sanofi; Schering-Plough; Sepracor; Somaxon; Syrex; TransOral; Ventus; Wyeth; Xenoport; Shire Development Inc, Wayne, Pennsylvania; Shire Development Inc FX Dr Surman has received research support from Abbott, Alza, Cephalon, Eli Lilly, Hilda and Preston Davis Foundation, McNeil, Merck, New River, National Institutes of Health, Organon, Pfizer, Shire, and Takeda; has received support from Janssen-Ortho, McNeil, Novartis, and Shire for speaking and other educational activities; and has been a consultant/advisor for McNeil, Shire, and Takeda. Dr Surman has also received honoraria from Reed Medical Education (a logistics collaborator for the MGH Psychiatry Academy). Commercial entities supporting the MGH Psychiatry Academy are listed on the Academy's Web site, http://www.mghcme.org.; Dr Roth has received research support from Aventis, Cephalon, GlaxoSmithKline, Merck, Neurocrine, Pfizer, Sanofi, Schering-Plough, Sepracor, Somaxon, Syrex, Takeda, TransOral, Ventus, Wyeth, and Xenoport; has been a speaker for Cephalon, Sanofi, and Sepracor; and in the past year has been a consultant/advisor for Abbott, Cephalon, Eisai, Eli Lilly, Intec, Merck, Ocera, Pfizer, Sanofi, Sepracor, Shire, Somaxon, Steady Sleep Rx, Takeda, and Transcept.; Clinical research was funded by Shire Development Inc, Wayne, Pennsylvania.; Authors directed writing assistance from William Perlman, PhD, of Excerpts Medica. Editorial assistance in formatting, proofreading, editing/copyediting, and fact-checking was also provided by Walter Sella, MD, MBA, of Excerpta Medica, and Liz LaFlamme, PhD, and Maryann Travaglini, PharmD, of Complete Healthcare Communications, Inc. Excerpta Medica and Complete Healthcare Communications, Inc were funded by Shire Development Inc for support in writing and editing this manuscript. Thomas Babcock, DO, and Ben Adeyi, MS, from Shire Development Inc, also reviewed and edited the manuscript for scientific accuracy. Gary Chen, PhD, from Shire Development Inc, was involved with statistical programming. The acknowledged individuals report no additional potential conflicts of interest. NR 18 TC 12 Z9 12 U1 0 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JUL PY 2011 VL 72 IS 7 BP 903 EP 908 DI 10.4088/JCP.11m06838 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 804UD UT WOS:000293678600004 PM 21824454 ER PT J AU Fava, M Asnis, GM Shrivastava, RK Lydiard, B Bastani, B Sheehan, DV Roth, T AF Fava, Maurizio Asnis, Gregory M. Shrivastava, Ram K. Lydiard, Bruce Bastani, Bijan Sheehan, David V. Roth, Thomas TI Improved Insomnia Symptoms and Sleep-Related Next-Day Functioning in Patients With Comorbid Major Depressive Disorder and Insomnia Following Concomitant Zolpidem Extended-Release 12.5 mg and Escitalopram Treatment: A Randomized Controlled Trial SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; GENERALIZED ANXIETY DISORDER; DOUBLE-BLIND; DSM-IV; ANTIDEPRESSANT TREATMENT; HEALTHY WOMEN; EFFICACY; SAFETY; CONSEQUENCES; MULTICENTER AB Objective: This investigation was performed to assess the efficacy and safety of zolpidem extended-release in patients with insomnia associated with major depressive disorder (MDD). Method: Patients (N = 385) received open-label escitalopram 10 mg/d and were randomized to concomitant zolpidem extended-release 12.5 mg/night or placebo for 8 weeks (phase 1) in a randomized, parallel-group, multicenter trial. Responders (>= 50% in 17-item Hamilton Depression Rating Scale [HDRS(17)] score) continued 16 weeks of double-blind treatment (phase 2); escitalopram only was given during a 2-week run-out period. The study was conducted between February 2006 and June 2007. The primary efficacy measure was change from baseline in subjective total sleep time. Secondary efficacy measures included subjective sleep-onset latency, number of awakenings, wake time after sleep onset, sleep quality, sleep-related next-day functioning, HDRS(17), Sleep Impact Scale score, Patient and Clinical Global Impressions of Insomnia Treatment, the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire, and the Quality of Life Enjoyment and Satisfaction Questionnaire. Adverse events were recorded throughout the study; sleep measures were also evaluated during the run-out period. Results: Throughout phase 1, zolpidem extended-release led to significantly greater improvements in total sleep time (P < .0001), wake time after sleep onset, sleep onset latency, number of awakenings, and sleep quality (P <= .0003), and some measures of sleep-related next-day functioning but not in depressive symptoms or quality of life. During phase 2, improvements with the zolpidem extended-release/escitalopram group occurred for total sleep time (significant [P < .05] at weeks 12 and 16), as well as for a few other secondary efficacy measures but not in depressive symptoms or quality of life. The most common adverse events associated with combination treatment included nausea, somnolence, dry mouth, dizziness, fatigue, and amnesia. Conclusions: Zolpidem extended-release administered concomitantly with escitalopram for up to 24 weeks was well tolerated and improved insomnia and some sleep-related next-day symptoms and next-day functioning in patients with MDD but did not significantly augment the antidepressant response of escitalopram. Trial Registration: clinicaltrials.gov Identifier: NCT00296179 J Clin Psychiatry 2011;72(7):914-928 (C) Copyright 2010 Physicians Postgraduate Press, Inc. C1 [Fava, Maurizio] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Asnis, Gregory M.] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Psychiat, Bronx, NY USA. [Shrivastava, Ram K.] Eastside Comprehens Med Ctr, New York, NY USA. [Lydiard, Bruce] S E Hlth Consultants, Charleston, SC USA. [Bastani, Bijan] NorthCoast Clin Trials Inc, Beachwood, OH USA. [Sheehan, David V.] Univ S Florida, Depress & Anxiety Disorders Res Inst, Tampa, FL USA. [Roth, Thomas] Henry Ford Hosp, Sleep Disorders Ctr, Detroit, MI 48202 USA. RP Fava, M (reprint author), Massachusetts Gen Hosp, MGH Clin Trials Network & Inst, 55 Fruit St,Bulfinch 351, Boston, MA 02114 USA. EM MFava@Partners.org FU Abbott; Alkermes; Aspect Medical Systems; AstraZeneca; BioResearch; BrainCells; Bristol-Myers Squibb; Cephalon; Clinical Trial Solutions, LLC; Eli Lilly; Forest; Ganeden; GlaxoSmithKline; Johnson Johnson; Lichtwer Pharma GmbH; Lorex; NARSAD; National Center for Complementary and Alternative Medicine; National Institute on Drug Abuse; National Institute of Mental Health; Novartis; Organon; PamLab; Pfizer; Pfizer, Pharmavite; Roche; sanofi-aventis; Shire; Solvay; Synthelabo; Ad Hoc Committee Treatment Drug & Assessment Research Review; Alexa; Alza; American Medical Association; American Psychiatric Association Task Force on Treatments of Psychotic Disorders; American Psychiatric Association Working Group; Anclote Foundation; Anxiety Disorders Resource Center; Anxiety Drug Efficacy Case-US Food and Drug Administration; Applied Health Outcomes/XCENDA; Avera; Boehringer Ingelheim; Boots; Burroughs Wellcome; Charter Hospitals; Ciba Geigy; Committee (RRC) of NIMH; Connecticut & Ohio Academies of Family Physicians; Cortex Pharmaceuticals; Council on Anxiety Disorders; CPC Coliseum Medical Center; Cypress Bioscience; Dista Products Company; Division of Drugs and Technology-American Medical Association; Eisai; Excerpta Medica Asia; Faxmed; Glaxo; Glaxo Wellcome; Hospital Corporation of America; Humana; ICI; INC Research; International Clinical Research; International Society for CNS Drug Development; Janssen; Jazz; Kali-Duphar; Labopharm; Layton Bioscience; Lilly Research Laboratories; Lundbeck Denmark; Marion Merrill Dow; McNeil; Mead Johnson; Medical Outcome Systems; MediciNova; Merck Sharp Dohme; National Anxiety Awareness Program; National Anxiety Foundation; National Depressive and Manic Depressive Association; National Institute of Health; Novo Nordisk; Orion; Parexel; Parke-Davis; Pharmacia; Pharmacia Upjohn; Philadelphia College of Pharmacy Science; Pierre Fabre France; Quintiles; Rhone Laboratories; Rhone-Poulenc Rorer Pharmaceuticals; Roerig; Sandoz; Sanofi-Synthelabo Recherche; Schering; Sepracor; SmithKline Beecham; Takeda; Tampa General Hospital; USF Psychiatry Center-USF College of Medicine; TAP; Targacept; TGH-University Psychiatry Center; Tikvah; Titan; United Bioscience; Upjohn Company; US Congress-House of Representatives Committee; USF Friends of Research in Psychiatry-Board of Trustees; Warner Chilcott; World Health Organization; Worldwide Clinical Trials; Wyeth-Ayerst; ZARS; Zeneca; Aventis; Neurocrine; Sanofi; Schering-Plough; Somaxon; Syrex; TransOral; Wyeth; Xenoport; sanofi-aventis US FX Dr Fava has received research support from Abbott, Alkermes, Aspect Medical Systems, AstraZeneca, BioResearch, BrainCells, Bristol-Myers Squibb, Cephalon, Clinical Trial Solutions, LLC, Eli Lilly, Forest, Ganeden, GlaxoSmithKline, Johnson & Johnson, Lichtwer Pharma GmbH, Lorex, NARSAD, the National Center for Complementary and Alternative Medicine, the National Institute on Drug Abuse, the National Institute of Mental Health, Novartis, Organon, PamLab, Pfizer, Pharmavite, Roche, sanofi-aventis, Shire, Solvay, Synthelabo, and Wyeth-Ayerst; has been an advisor/consultant for Abbott, Amarin, Aspect Medical Systems, AstraZeneca, Auspex, Bayer AG, Best Practice Project Management, BioMarin, Biovail, BrainCells, Bristol-Myers Squibb, Cephalon, Clinical Trial Solutions, LLC, CNS Response, Compellis, Cypress, Dov, Eisai, Eli Lilly, EPIX, Euthymics Bioscience, Fabre-Kramer, Forest, GlaxoSmithKline, Grunenthal GmbH, Janssen, Jazz, Johnson & Johnson, Knoll, Labopharm, Lorex, Lundbeck, MedAvante, Merck, Methylation Sciences, Neuronetics, Novartis, Nutrition 21, Organon, PamLab, Pfizer, PharmaStar, Pharmavite, Precision Human Biolaboratory, PsychoGenics, Psylin Neurosciences, Ridge Diagnostics, Roche, sanofi-aventis, Sepracor, Schering-Plough, Solvay, Somaxon, Somerset, Synthelabo, Takeda, Tetragenex, TransForm, Transcept, Vanda, and Wyeth-Ayerst; has had speaking/publishing affiliations with Adamed, Advanced Meeting Partners, the American Psychiatric Association, American Society of Clinical Psychopharmacology, 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, and Wyeth-Ayerst; has equity holdings in Compellis; has patent applications for SPCD and for a combination of azapirones and bupropion in MDD; and has received copyright royalties for the MGH-CPFQ, SFI, ATRQ, DESS, and SAFER. Dr. Asnis has received grant/research support from AstraZeneca, GlaxoSmithKline, Pfizer, and sanofi-aventis; and has been a consultant to and served on the speakers/advisory board for sanofi-aventis.; Dr Sheehan has received grant funding support, been affiliated with, or received honoraria and travel expenses related to lectures/presentations or consultant activities from Abbott, Ad Hoc Committee Treatment Drug & Assessment Research Review, Alexa, Alza, American Medical Association, American Psychiatric Association Task Force on Treatments of Psychotic Disorders, American Psychiatric Association Working Group to Revise DSM-III Anxiety Disorders Section, Anclote Foundation, Anxiety Disorders Resource Center, Anxiety Drug Efficacy Case-US Food and Drug Administration, Applied Health Outcomes/XCENDA, AstraZeneca, Avera, Boehringer Ingelheim, Boots, Bristol-Myers Squibb, Burroughs Wellcome, Cephalon, Charter Hospitals, Ciba Geigy, Committee (RRC) of NIMH on Anxiety and Phobic Disorder Projects, Connecticut & Ohio Academies of Family Physicians, Cortex Pharmaceuticals, Council on Anxiety Disorders, CPC Coliseum Medical Center, Cypress Bioscience, Dista Products Company, Division of Drugs and Technology-American Medical Association, Eisai, Eli Lilly, Excerpta Medica Asia, Faxmed, Forest, Glaxo, GlaxoSmithKline, Glaxo Wellcome, Hospital Corporation of America, Humana, ICI, INC Research, International Clinical Research, International Society for CNS Drug Development, Janssen, Jazz, Kali-Duphar, Labopharm, Layton Bioscience, Lilly Research Laboratories, Lundbeck Denmark, Marion Merrill Dow, McNei, Mead Johnson, Medical Outcome Systems, MediciNova, Merck Sharp & Dohme, National Anxiety Awareness Program, National Anxiety Foundation, National Depressive and Manic Depressive Association, National Institute on Drug Abuse, National Institute of Health, Novartis, Novo Nordisk, Organon, Orion, Parexel, Parke-Davis, Pfizer, Pharmacia, Pharmacia & Upjohn, Philadelphia College of Pharmacy & Science, Pierre Fabre France, Quintiles, Rhone Laboratories, Rhone-Poulenc Rorer Pharmaceuticals, Roche, Roerig, Sandoz, sanofi-aventis, Sanofi-Synthelabo Recherche, Schering, Sepracor, Shire, SmithKline Beecham, Solvay, Takeda, Tampa General Hospital, USF Psychiatry Center-USF College of Medicine, TAP, Targacept, TGH-University Psychiatry Center, Tikvah, Titan, United Bioscience, The Upjohn Company, US Congress-House of Representatives Committee, USF Friends of Research in Psychiatry-Board of Trustees, Warner Chilcott, World Health Organization, Worldwide Clinical Trials, Wyeth-Ayerst, ZARS, and Zeneca. Dr Roth has been a consultant for Abbott, Accadia, Acogolix, Acorda, Actelion, Addrenex, Alchemers, Alza, Ancel, Arena, AstraZeneca, Aventis, AVER, Bayer, Bristol-Myers Squibb, BTG, Cephalon, Cypress, Dove, Eisai, Elan, Eli Lilly, Evotec, Forest, GlaxoSmithKline, Hypnion, Impax, Intec, Intra-Cellular, Jazz, Johnson & Johnson, King, Lundbeck, McNeil, MediciNova, Merck, Neurim, Neurocrine, Neurogen, Novartis, Orexo, Organon, Otsuka, Prestwick, Procter and Gamble, Pfizer, Purdue, Resteva, Roche, Sanofi, Schering-Plough, Sepracor, Servier, Shire, Somaxon, Syrex, Takeda, TransOral, Vanda, Vivometrics, Wyeth, Yamanuchi, and Xenoport; has received grant/research support from Aventis, Cephalon, GlaxoSmithKline, Neurocrine, Pfizer, Sanofi, Schering-Plough, Sepracor, Somaxon, Syrex, Takeda, TransOral, Wyeth, and Xenoport; and has been a member of the speakers/advisory boards for Cephalon, Sanofi, and Takeda. Drs Shrivastava, Lydiard, and Bastani have no financial or other relationship to report relevant to the subject of this article.; Funding for this trial was provided by sanofi-aventis US. The authors of this article were fully responsible for the content and editorial decisions and received no financial support or other form of compensation related to the development of this article. NR 47 TC 31 Z9 31 U1 1 U2 5 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 JUL PY 2011 VL 72 IS 7 BP 914 EP 928 DI 10.4088/JCP.09m05571gry PG 15 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 804UD UT WOS:000293678600006 PM 21208597 ER PT J AU Posternak, MA Baer, L Nierenberg, AA Fava, M AF Posternak, Michael A. Baer, Lee Nierenberg, Andrew A. Fava, Maurizio TI Response Rates to Fluoxetine in Subjects Who Initially Show No Improvement SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID MAJOR DEPRESSION; DURATION; TRIAL AB Objective: This study sought to investigate the likelihood that subjects will respond to continued antidepressant therapy when little or no benefit has yet been observed. Method: Six hundred twenty-seven subjects diagnosed with DSM-IV major depressive disorder were recruited in a 12-week open-label trial with fluoxetine, which was designed as a preliminary phase to a subsequent 52-week continuation trial, which was conducted in 1997-2003. For each week of the study, a calculation was made for all subjects who had heretofore demonstrated little or no improvement as to the likelihood of converting to a positive response in subsequent weeks as measured by the Clinical Global Impressions scale, the primary outcome measure. In order to compare our findings with prior research, we focused primarily on outcomes at weeks 6, 8, and 12. Results: The likelihood of converting to a positive response decreased the longer subjects remained unimproved. When week 6 was used as the end point, the likelihood of converting to a positive response for unimproved subjects at week 1 was 36% (n = 302); the respective conversion rates for weeks 2-5 were 29% (n = 208) at week 2, 18% (n = 151) at week 3, 17% (n = 120) at week 4, and 9% (n = 91) at week 5. When week 8 was used as the end point, the likelihood of converting to a positive response for unimproved subjects at week 4 was 23% (n = 118) and, at week 6, was 10% (n = 61). Finally, when week 12 was used as the end point, the likelihood of unimproved subjects at weeks 4, 6, and 8 converting to a positive response at week 12 was 50% (n = 117), 33% (n = 60), and 30% (n = 46), respectively. Conclusions: The study adds to a small, but growing literature that gives clinicians some guidelines to help decide whether to continue an antidepressant trial when little or no benefit has yet been observed. Trial Registration: clinicaltrials.gov Identifier: NCT00427128 J Clin Psychiatry 2011;72(7):949-954 (C) Copyright 2011 Physicians Postgraduate Press, Inc. C1 [Posternak, Michael A.] Comprehens Psychiat Associates, Wellesley, MA 02481 USA. [Baer, Lee; Nierenberg, Andrew A.; Fava, Maurizio] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Posternak, MA (reprint author), Comprehens Psychiat Associates, 372 Washington St, Wellesley, MA 02481 USA. EM maposternak@yahoo.com FU AstraZeneca; li Lilly; Janssen; Bristol-Myers Squibb; Abbott; Alkermes; Aspect Medical Systems; BioResearch; BrainCells; Cephalon; CeNeRx BioPharma; Clinical Trials Solutions; Clintara; Covidien; Eli Lilly; EnVivo; Euthymics Bioscience; Forest; Ganeden Biotech; GlaxoSmithKline; Icon Clinical Research; i3 Innovus/Ingenix; Johnson & Johnson Pharmaceutical Research Development; Lichtwer Pharma GmbH; Lorex; National Alliance for Research on Schizophrenia & Depression (NARSAD); National Center for Complementary and Alternative Medicine; National Institute of Drug Abuse; National Institute of Mental Health; Novartis AG; Organon; Pam Lab; Pfizer; Pharmavite; Photothera; Roche; RCT Logic; Sanofi-Aventis; Shire; Solvay; Synthelabo; Wyeth-Ayerst; Wyeth-Ayerst; has received advisory/consulting fees from Abbott; Affectis AG; Amarin Pharma; Auspex; Bayer AG; Best Practice Project Management; BioMarin; Biovail; CNS Response; Compellis; Cypress; DiagnoSearch Life Sciences (P); Dainippon Sumitomo Pharma; Dov; Edgemont; Eisai; ePharmaSolutions; EPIX; Fabre-Kramer; GenOmind; Grunenthal GmbH; i3 Innovus/Ingenis; Jazz; Knoll; Labopharm; Lundbeck; MedAvante; Merck; MSI Methylation Sciences; Naurex; Neuronetics; Next Wave; Nutrition 21; Orexigen Therapeutics; Organon Otsuka; PamLab; PharmaStar; PharmoRx Therapeutics; Precision Human Biolaboratory; Prexa Pharmaceuticals; Puretech Ventures; PsychoGenics; Psylin Neurosciences; Rexahn; Ridge Diagnostics; Sepracor; Servier Laboratories; Schering-Plough; Somaxon; Somerset; Sunovion; Supernus; Takeda; Tal Medical; Tetragenex; TransForm; Transcept; Vanda; Adamed; Advanced Meeting Partners; American Psychiatric Association; American Society of Clinical Psychopharmacology; Belvoir Media Group; Boehringer Ingelheim GmbH; CME Institute/Physicians Postgraduate Press; Imedex; Massachusetts General Hospital (MGH) Psychiatry Academy/Primedia; MGH Psychiatry Academy/Reed Elsevier; United BioSource; National Institute of Mental Health [R10-MH56058] FX Dr Nierenberg is a full-time employee of Massachusetts General Hospital (MGH). In the past 12 months (as of March 3, 2009), he has served as a consultant to the American Psychiatric Association (only travel expenses paid), Appliance Computing (Mindsite), and Brandeise University. Through the MGH Clinical Trials Network and Institute, he has consulted for Brain Cells, Dianippon Sumitomo/Sepracor, Novartis, PGx Health, Shire, Schering-Plough, Targacept, and Takeda/Lundbeck. Through MGH, he is named for copyrights to the Clinical Positive Affect Scale and the MGH Structured Clinical Interview for the Montgomery-Asberg Depression Rating Scale exclusively licensed to the MGH Clinical Trials Network and Institute and has a patent extension application for the combination of buspirone, bupropion, and melatonin for the treatment of depression. Dr Nierenberg has received honoraria from Belvior Publishing, University of Texas Southwestern Dallas, Hillside Hospital, American Drug Utilization Review, American Society for Clinical Psychopharmacology, Baystate Medical Center, Columbia University, IMEDEX, JM Consulting, New York State, MBL Publishing, Physicians Postgraduate Press, SUNY Buffalo, University of Wisconsin, and the University of Pisa; has been a presenter for the MGH Psychiatry Academy, the education programs of which were supported through independent Medical Education grants from, in 2008, AstraZeneca, Eli Lilly, and Janssen, and, in 2009, AstraZeneca, Eli Lilly, and Bristol-Myers Squibb; is on the advisory boards of Appliance Computing, Brain Cells, Eli Lilly, Takeda/Lundbeck, and Targacept; and owns stock options in Appliance Computing and Brain Cells.; Dr Fava has received research support from Abbott, Alkermes, Aspect Medical Systems, AstraZeneca, BioResearch, BrainCells, Bristol-Myers Squibb, Cephalon, CeNeRx BioPharma, Clinical Trials Solutions, Clintara, Covidien, Eli Lilly, EnVivo, Euthymics Bioscience, Forest, Ganeden Biotech, GlaxoSmithKline, Icon Clinical Research, i3 Innovus/Ingenix, Johnson & Johnson Pharmaceutical Research & Development, Lichtwer Pharma GmbH, Lorex, National Alliance for Research on Schizophrenia & Depression (NARSAD), National Center for Complementary and Alternative Medicine, National Institute of Drug Abuse, National Institute of Mental Health, Novartis AG, Organon, Pam Lab, Pfizer, Pharmavite, Photothera, Roche, RCT Logic, Sanofi-Aventis, Shire, Solvay, Synthelabo, and Wyeth-Ayerst; has received advisory/consulting fees from Abbott, Affectis AG; Alkermes, Amarin Pharma, Aspect Medical Systems, AstraZeneca, Auspex, Bayer AG, Best Practice Project Management, BioMarin, Biovail, BrainCells, Bristol-Myers Squibb, CeNeRx BioPharma, Cephalon, Clinical Trials Solutions, CNS Response, Compellis, Cypress, DiagnoSearch Life Sciences (P), Dainippon Sumitomo Pharma, Dov, Edgemont, Eisai, Eli Lilly, ePharmaSolutions, EPIX, Euthymics Bioscience, Fabre-Kramer, Forest, GenOmind, GlaxoSmithKline, Grunenthal GmbH, i3 Innovus/Ingenis, Janssen, Jazz, Johnson & Johnson Pharmaceutical Research & Development, Knoll, Labopharm, Lorex, Lundbeck, MedAvante, Merck, MSI Methylation Sciences, Naurex, Neuronetics, Next Wave, Novartis AG, Nutrition 21, Orexigen Therapeutics, Organon Otsuka, PamLab, Pfizer, PharmaStar, Pharmavite, PharmoRx Therapeutics, Precision Human Biolaboratory, Prexa Pharmaceuticals, Puretech Ventures, PsychoGenics, Psylin Neurosciences, Rexahn, Ridge Diagnostics, Roche, RCT Logic, Sanofi-Aventis, Sepracor, Servier Laboratories, Schering-Plough, Solvay, Somaxon, Somerset, Sunovion, Supernus, Synthelabo, Takeda Tal Medical, Tetragenex, TransForm, Transcept, and Vanda; has received speaking/publishing fees from Adamed, Advanced Meeting Partners, American Psychiatric Association, American Society of Clinical Psychopharmacology, AstraZeneca, Belvoir Media Group, Boehringer Ingelheim GmbH, Bristol-Myers Squibb, Cephalon, CME Institute/Physicians Postgraduate Press, Eli Lilly, Forest, GlaxoSmithKline, Imedex, Massachusetts General Hospital (MGH) Psychiatry Academy/Primedia, MGH Psychiatry Academy/Reed Elsevier, Novartis AG, Organon, Pfizer, PharmaStar, United BioSource, and Wyeth-Ayerst; has equity holdings in Compellis; receives copyright royalties for the MGH Cognitive & Physical Functioning Questionnaire, Sexual Functioning Inventory, Antidepressant Treatment Response Questionnaire, Discontinuation-Emergent Signs & Symptoms, and SAFER; and has a patent application for a combination of azapirones and bupropion in major depressive disorder. Dr Fava also has a patent for Sequential Parallel Comparison Design (SPCD) and a patent for research and licensing of SPCD with RCT Logic; Lippincott, Williams & Wilkins; and World Scientific Publishing.; This study was supported in part by a National Institute of Mental Health grant R10-MH56058 to Dr Fava and to Patrick J. McGrath, MD. NR 13 TC 6 Z9 6 U1 0 U2 1 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 JUL PY 2011 VL 72 IS 7 BP 949 EP 954 DI 10.4088/JCP.10m06098 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 804UD UT WOS:000293678600010 PM 21672502 ER PT J AU Suri, R Hellemann, G Stowe, ZN Cohen, LS Aquino, A Altshuler, LL AF Suri, Rita Hellemann, Gerhard Stowe, Zachary N. Cohen, Lee S. Aquino, Ana Altshuler, Lori L. TI A Prospective, Naturalistic, Blinded Study of Early Neurobehavioral Outcomes for Infants Following Prenatal Antidepressant Exposure SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID BEHAVIORAL-ASSESSMENT SCALE; MAJOR DEPRESSION; IN-UTERO; PREGNANCY; CHILDREN; WOMEN; PERFORMANCE; SYMPTOMS; COHORT; BIRTH AB Objective: This study examined the potential effects of antidepressant exposure in pregnancy on early infant neurobehavioral outcomes. Method: In this prospective, naturalistic study, neurobehavioral assessments using the Brazelton Neonatal Behavioral Assessment Scale (BNBAS) were completed by blinded raters between March 2001 and August 2005 on 64 infants who were born to mothers in 1 of 3 categories: (1) women with a history of DSM-IV-diagnosed major depressive disorder (MDD) who were treated with antidepressants during pregnancy, (2) women with a history of DSM-IV-diagnosed MDD who discontinued or chose not to be treated with antidepressants during pregnancy, and (3) a nonpsychiatric control group. Summary scores for the BNBAS were obtained within the first week of life and at 6 to 8 weeks of age. Results: No significant differences were observed between groups at either the first week after delivery or at 6 to 8 weeks of age on any of the summary scores for the 7 major clusters of the BNBAS. Conclusions: Antidepressant exposure during pregnancy does not appear to have major adverse effects on indices of early infant neurobehavioral development during the first 2 months of life as assessed by the BNBAS. While this finding is encouraging, further studies with larger samples and longer follow-up are needed. J Clin Psychiatry 2011;72(7):1002-1007 (C) Copyright 2011 Physicians Postgraduate Press, Inc. C1 [Suri, Rita; Hellemann, Gerhard; Aquino, Ana; Altshuler, Lori L.] Univ Calif Los Angeles, Dept Psychiat, Mood Disorders Res Program, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. [Stowe, Zachary N.] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA USA. [Stowe, Zachary N.] Emory Univ, Dept Gynecol & Obstet, Sch Med, Atlanta, GA USA. [Cohen, Lee S.] Massachusetts Gen Hosp, Dept Psychiat, Perinatal & Reprod Psychiat Program, Boston, MA 02114 USA. RP Suri, R (reprint author), Univ Calif Los Angeles, Dept Psychiat, Mood Disorders Res Program, Semel Inst Neurosci & Human Behav, 300 Med Plaza,Ste 1544, Los Angeles, CA 90095 USA. EM rsuri@mednet.ucla.edu FU National Institutes of Health (NIH); GlaxoSmithKline; Wyeth; AstraZeneca; Bayer HealthCare; Bristol-Myers Squibb; Forest; National Institute on Aging; National Institute of Mental Health; Pfizer; National Institute of Child Health and Human Development [K23-HD001304] FX Dr Suri has received research support from the National Institutes of Health (NIH). Dr Stowe has received research support from GlaxoSmithKline, the NIH, and Wyeth; served on advisory boards for Wyeth, Bristol-Myers Squibb, and GlaxoSmithKline; and received speakers' honoraria from Eli Lilly, GlaxoSmithKline, Pfizer, and Wyeth. Dr Cohen has received research support from AstraZeneca, Bayer HealthCare, Bristol-Myers Squibb, Forest, GlaxoSmithKline, the National Institute on Aging, the NIH, the National Institute of Mental Health, and Pfizer and served on advisory boards for Eli Lilly and Noven. Dr Altshuler has received research support from the NIH and served on advisory boards for Forest and Sepracor. Dr Hellemann and Ms Aquino have no financial or other relationships relevant to the subject of this article.; Supported by grant K23-HD001304 (to Dr Suri) from the National Institute of Child Health and Human Development. NR 25 TC 16 Z9 16 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 JUL PY 2011 VL 72 IS 7 BP 1002 EP 1007 DI 10.4088/JCP.10m06135 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 804UD UT WOS:000293678600018 PM 21672498 ER PT J AU Nierenberg, AA AF Nierenberg, Andrew A. TI Keeping 'Em Honest: The Current Crisis of Confidence in Antidepressants Reply SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Letter C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Nierenberg, AA (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. EM anierenberg@partners.org NR 1 TC 0 Z9 0 U1 0 U2 0 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 JUL PY 2011 VL 72 IS 7 BP 1015 EP 1016 DI 10.4088/JCP.11lr07111a PG 2 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 804UD UT WOS:000293678600021 ER PT J AU Boockvar, KS Santos, SL Kushniruk, A Johnson, C Nebeker, JR AF Boockvar, Kenneth S. Santos, Susan L. Kushniruk, Andre Johnson, Christopher Nebeker, Jonathan R. TI Medication Reconciliation: Barriers and Facilitators from the Perspectives of Resident Physicians and Pharmacists SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID ADVERSE DRUG EVENTS AB BACKGROUND: Medication reconciliation can prevent medication errors and harm when patients transition between hospital and other care settings. Though a Joint Commission hospital Patient Safety Goal since 2006, organizations continue to have difficulty implementing the process. OBJECTIVE: To determine factors that influence performance of medication reconciliation in a hospital setting with a computerized medication reconciliation tool. DESIGN: Cognitive task analysis (CTA) and focus group interviews. SETTING: Urban, academic, tertiary-care Veterans Affairs medical center. PARTICIPANTS: Internal medicine house staff physicians (n = 23) and inpatient staff pharmacists (n = 12). MEASUREMENTS: CTA participants verbalized their thoughts while they completed medication reconciliation with the computerized tool. Focus group participants described medication reconciliation's purpose and effectiveness, how they completed the task, and its barriers and facilitators. Interviews were recorded and analyzed using social science methods for analyzing qualitative data. RESULTS: Participants agreed that a central goal of medication reconciliation is to prevent prescribing errors, but disagreed about whether it achieves this goal. Computerization facilitated the task, but participants said that computers and patients can be unreliable sources of information. Participants varied in how they sequenced components of the task. When time was limited, physicians considered other responsibilities higher priority. Both physicians and pharmacists expressed low self-efficacy, ie, low perceived capability to achieve the objectives of the process. CONCLUSION: Key barriers to medication reconciliation are unreliable sources of medication information and tasks that compete for providers' time and attention that they consider higher priority. Addressing these barriers while increasing providers' self-efficacy might improve medication reconciliation and its outcomes. Journal of Hospital Medicine 2011;6:329-337. (C) 2011 Society of Hospital Medicine C1 [Boockvar, Kenneth S.] James J Peters VA Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY 10468 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. [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. [Kushniruk, Andre] Univ Victoria, Sch Hlth Informat Sci, Victoria, BC, Canada. [Johnson, Christopher] Texas A&M Hlth Sci Ctr, Dept Hlth Policy & Management, College Stn, TX USA. [Johnson, Christopher] VA S Cent Mental Illness Res Educ & Clin Ctr, Houston, TX USA. [Johnson, Christopher] Michael E Debakey VA Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. [Nebeker, Jonathan R.] Univ Utah, Salt Lake City, UT USA. [Nebeker, Jonathan R.] VA Geriatr Res Educ & Clin Ctr, Salt Lake City, UT USA. RP Boockvar, KS (reprint author), James J Peters VA Med Ctr, Geriatr Res Educ & Clin Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM kenneth.boockvar@mssm.edu OI Boockvar, Kenneth/0000-0003-1165-5558 FU VA Health Services Research and Development Service; Greenwall Foundation FX This work was supported by VA Health Services Research and Development Service. Dr. Boockvar is also supported by the Greenwall Foundation. The authors have no conflicts of interest to disclose. NR 20 TC 21 Z9 22 U1 0 U2 8 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 JUL-AUG PY 2011 VL 6 IS 6 BP 329 EP 337 DI 10.1002/jhm.891 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 810RA UT WOS:000294143600003 PM 21834114 ER PT J AU Farber, JI Korc-Grodzicki, B Du, QL Leipzig, RM Siu, AL AF Farber, Jeffrey I. Korc-Grodzicki, Beartriz Du, Qingling Leipzig, Rosanne M. Siu, Albert L. TI Operational and Quality Outcomes of a Mobile Acute Care for the Elderly Service SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; OLDER PATIENTS; FUNCTIONAL OUTCOMES; MEDICAL UNIT; INTERVENTION; COSTS AB BACKGROUND: The traditional acute care for the elderly (ACE) unit has demonstrated improved functional outcomes without increased costs or changes in length of stay (LOS). It is, however, limited in scope to patients cared for on a fixed geographical unit. OBJECTIVE: To compare operational and quality outcomes for patients cared for on a mobile ACE (MACE) service to those cared for on a unit-based ACE service and matched controls on other general medical services. DESIGN: Retrospective cohort study with propensity-score matching. SETTING: An urban academic medical center. PATIENTS: A total of 8094 hospitalized adults >64 years old admitted to an ACE, MACE, and general medical services from July 2006 to June 2009. INTERVENTION: An interdisciplinary MACE service composed of a geriatrician-hospitalist, fellow, nurse coordinator, and social worker. MEASUREMENTS: LOS, total cost, 7- and 30-day readmission rates, and in-hospital mortality. RESULTS: Mean LOS and total cost were significantly lower for patients in the MACE service compared with the ACE unit service (5.8 vs 7.9 days, P < 0.001, and $10,315 vs $13,187, P = 0.002) and compared with propensity-score matched controls during the second year of operation (5.6 vs 7.2 days, P < 0.001, and $10,693 vs $15,636, P < 0.001). In-hospital mortality and 7- and 30-day readmission rates were similar in all groups. CONCLUSIONS: A mobile ACE service may result in reduced LOS and lower costs with no change in in-hospital mortality or 7- or 30-day readmission rates when compared with standard medical service and a traditional unit-based ACE service. Journal of Hospital Medicine 2011;6:358-363. (C) 2011 Society of Hospital Medicine C1 [Farber, Jeffrey I.; Du, Qingling; Leipzig, Rosanne M.; Siu, Albert L.] Mt Sinai Sch Med, Brookdale Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Korc-Grodzicki, Beartriz] Mem Sloan Kettering Canc Ctr, Dept Med, Geriatr Serv, New York, NY 10021 USA. [Siu, Albert L.] Geriatr Res Educ & Clin Ctr, James J Peters VA Med Ctr, New York, NY USA. RP Farber, JI (reprint author), Mt Sinai Sch Med, Brookdale Dept Geriatr & Palliat Med, 1 Gustave L Levy Pl,Box 1070, New York, NY 10029 USA. EM jeffrey.farber@mssm.edu OI Korc-Grodzicki, Beatriz/0000-0003-0673-4606 FU Health Resources and Services Administration, US Department of Health and Human Services; National Institute on Aging; John A. Hartford Foundation FX Dr. Farber received grant support from a Geriatric Academic Career Award from the Health Resources and Services Administration, US Department of Health and Human Services. Dr. Sin received grant support from the National Institute on Aging Midcareer Investigator Award in Patient-Oriented Research.; Dr. Kore-Grodzicki received grant support from the John A. Hartford Foundation. NR 13 TC 5 Z9 5 U1 0 U2 5 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 JUL-AUG PY 2011 VL 6 IS 6 BP 358 EP 363 DI 10.1002/jhm.878 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 810RA UT WOS:000294143600007 PM 21834119 ER PT J AU Grant, JS Keltner, NL Eagerton, G AF Grant, Joan S. Keltner, Norman L. Eagerton, Greg TI Simulation to Enhance Care of Patients with Psychiatric and Behavioral Issues Use in Clinical Settings SO JOURNAL OF PSYCHOSOCIAL NURSING AND MENTAL HEALTH SERVICES LA English DT Article ID STANDARDIZED PATIENTS; EDUCATION; SKILLS AB Nurses with a medical-surgical clinical focus often care for patients with psychiatric and behavioral issues in acute care hospitals. This article describes how hospital staff and nursing and theater department faculty joined forces to develop realistic simulated psychiatric scenarios for use by practicing nurses. C1 [Grant, Joan S.; Keltner, Norman L.] Univ Alabama, Birmingham Sch Nursing, Birmingham, AL 35205 USA. [Eagerton, Greg] Birmingham Vet Affairs Med Ctr, Patient Care Nursing Serv, Birmingham, AL USA. RP Keltner, NL (reprint author), Univ Alabama, Birmingham Sch Nursing, NB Room 302,1530 3rd Ave S, Birmingham, AL 35205 USA. EM nkeltner@uab.edu OI Grant, Joan/0000-0001-6000-4060 NR 24 TC 3 Z9 3 U1 2 U2 4 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0279-3695 J9 J PSYCHOSOC NURS MEN JI J. Psychosoc. Nurs. Ment. Health Serv. PD JUL PY 2011 VL 49 IS 7 BP 43 EP 49 DI 10.3928/02793695-20110609-01 PG 7 WC Nursing SC Nursing GA 811ZV UT WOS:000294258400011 PM 21702427 ER PT J AU Singh, JA Taylor, WJ Simon, LS Khanna, PP Stamp, LK McQueen, FM Neogi, T Gaffo, AL Becker, MA MacDonald, PA Dabbous, O Strand, V Dalbeth, ND Aletaha, D Edwards, NL Schumacher, HR AF Singh, Jasvinder A. Taylor, Will J. Simon, Lee S. Khanna, Puja P. Stamp, Lisa K. McQueen, Fiona M. Neogi, Tuhina Gaffo, Angelo L. Becker, Michael A. MacDonald, Patricia A. Dabbous, Omar Strand, Vibeke Dalbeth, Nicola D. Aletaha, Daniel Edwards, N. Lawrence Schumacher, H. Ralph, Jr. TI Patient-reported Outcomes in Chronic Gout: A Report from OMERACT 10 SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE PATIENT-REPORTED OUTCOMES; CHRONIC GOUT; VALIDATION; PAIN; PATIENT GLOBAL; FUNCTIONAL LIMITATION ID QUESTIONNAIRE DISABILITY INDEX; QUALITY-OF-LIFE; SERUM URATE; HYPERURICEMIA; ALLOPURINOL; FEBUXOSTAT AB Objective. To summarize the endorsement of measures of patient-reported outcome (PRO) domains in chronic gout at the 2010 Outcome Measures in Rheumatology Meeting (OMERACT 10). Methods. During the OMERACT 10 gout workshop, validation data were presented for key PRO domains including pain [pain by visual analog scale (VAS)], patient global (patient global VAS), activity limitation [Health Assessment Questionnaire-Disability Index (HAQ-DI)], and a disease-specific measure, the Gout Assessment Questionnaire version 2.0 (GAQ v2.0). Data were presented on all 3 aspects of the OMERACT filters of truth, discrimination, and feasibility. One PRO, health-related quality of life measurement with the Medical Outcomes Study Short-form 36 (SF-36), was previously endorsed at OMERACT 9. Results. One measure for each of the 3 PRO of pain, patient global, and activity limitation was endorsed by > 70% of the OMERACT delegates to have appropriate validation data. Specifically, pain measurement by VAS was endorsed by 85%, patient global assessment by VAS by 73%, and activity limitation by HAQ-DI by 71%. GAQ v2.0 received 30% vote and was not endorsed due to several concerns including low internal consistency and lack of familiarity with the measure. More validation studies are needed for this measure. Conclusion. With the endorsement of one measure each for pain, patient global, SF-36, and activity limitation, all 4 PRO for chronic gout have been endorsed. Future validation studies are needed for the disease-specific measure, GAQ v2.0. Validation for PRO for acute gout will be the focus of the next validation exercise for the OMERACT gout group. (J Rheumatol 2011;38:1452-7; doi:10.3899/jrheum.110271) C1 [Singh, Jasvinder A.] Birmingham Vet Affairs VA Med Ctr, Med Serv, Birmingham, AL USA. [Singh, Jasvinder A.; Gaffo, Angelo L.] Univ Birmingham, Dept Med, Div Rheumatol, Birmingham, AL USA. [Singh, Jasvinder A.; Gaffo, Angelo L.] Univ Birmingham, Div Epidemiol, Birmingham, AL USA. [Singh, Jasvinder A.] Birmingham VA 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. [Taylor, Will J.] Univ Otago, Dept Med, Wellington, New Zealand. [Simon, Lee S.] SDG LLC, Cambridge, MA USA. [Khanna, Puja P.] Univ Calif Los Angeles, David Geffen Sch Med, Div Rheumatol, Los Angeles, CA 90095 USA. Univ Otago, Dept Med, Christchurch, New Zealand. [Stamp, Lisa K.; McQueen, Fiona M.] Univ Auckland, Fac Med & Hlth Sci, Dept Mol Med & Pathol, Auckland 1, New Zealand. [Neogi, Tuhina] Boston Univ, Sch Med, Clin Epidemiol Res & Training Unit, Boston, MA 02118 USA. [Becker, Michael A.] Univ Chicago, Rheumatol Sect, Chicago, IL 60637 USA. [MacDonald, Patricia A.] Takeda Global Res & Dev Ctr Inc, Deerfield, IL USA. [Dabbous, Omar] Takeda Pharmaceut Int Inc, Deerfield, IL USA. [Strand, Vibeke] Stanford Univ, Palo Alto, CA 94304 USA. [Dalbeth, Nicola D.] Univ Auckland, Dept Med, Auckland 1, New Zealand. [Aletaha, Daniel] Med Univ, Div Rheumatol, Vienna, Austria. [Edwards, N. Lawrence] Univ Florida, Dept Med, Gainesville, FL USA. [Schumacher, H. Ralph, Jr.] Univ Penn, Div Rheumatol, Philadelphia, PA 19104 USA. [Schumacher, H. Ralph, Jr.] VA Med Ctr, Philadelphia, PA USA. RP Singh, JA (reprint author), Univ Alabama Birmingham, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. EM jasvinder.md@gmail.com OI singh, jasvinder/0000-0003-3485-0006; Neogi, Tuhina/0000-0002-9515-1711 FU National Institutes of Health (NIH) [1 KL2 RR024151-01, AR0557127, P60 AR047785]; NIH/NIAMS [UO1 AR057936]; American College of Rheumatology; Allergan; Takeda; Savient; Wyeth; Amgen; URL pharmaceuticals; Novartis; Regeneron; Pfizer FX Supported by a National Institutes of Health (NIH) Clinical Translational Science Award 1 KL2 RR024151-01 (Mayo Clinic Center for Clinical and Translational Research) to Dr. Singh, and by resources and facilities at the Birmingham VA Medical Center, Alabama, USA. Dr. Neogi was supported by awards from the NIH K23 (AR0557127) and P60 AR047785. Dr. Khanna was supported by research grants from the NIH/NIAMS (UO1 AR057936) and an American College of Rheumatology REF Clinical Investigator Award. Data were obtained from Savient Pharmaceuticals and Takeda Global Research and Development. Dr. Singh has received speaker honoraria from Abbott; research and travel grants from Allergan, Takeda, Savient, Wyeth and Amgen; and consultant fees from Savient, URL pharmaceuticals, and Novartis. Ms MacDonald is an employee of Takeda Global Research and Development. Dr. Dabbous is an employee of Takeda Pharmaceuticals International Inc. Dr. Schumacher has received consulting fees from Takeda, Savient, Regeneron, Novartis, and Pfizer. Dr. Becker has been a consultant for Takeda, Savient, BioCryst, URL/Pharma, Ardea, and Regeneron. Dr. Strand served as a consultant to Savient and Takeda Pharmaceuticals. Dr. Edwards has received consultant fees from Takeda and Savient. Views expressed in this article are the authors' and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government. NR 22 TC 34 Z9 35 U1 3 U2 7 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 JUL PY 2011 VL 38 IS 7 BP 1452 EP 1457 DI 10.3899/jrheum.110271 PG 6 WC Rheumatology SC Rheumatology GA 796HE UT WOS:000293041600036 PM 21724715 ER PT J AU Dalbeth, N McQueen, FM Singh, JA MacDonald, PA Edwards, NL Schumacher, HR Simon, LS Stamp, LK Neogi, T Gaffo, AL Khanna, PP Becker, MA Taylor, WJ AF Dalbeth, Nicola McQueen, Fiona M. Singh, Jasvinder A. MacDonald, Patricia A. Edwards, N. Lawrence Schumacher, H. Ralph, Jr. Simon, Lee S. Stamp, Lisa K. Neogi, Tuhina Gaffo, Angelo L. Khanna, Puja P. Becker, Michael A. Taylor, William J. TI Tophus Measurement as an Outcome Measure for Clinical Trials of Chronic Gout: Progress and Research Priorities SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE GOUT; TOPHUS; OUTCOME MEASURE ID QUANTITATIVE-ANALYSIS; PHYSICAL MEASUREMENT; COMPUTED-TOMOGRAPHY; ALLOPURINOL; FEBUXOSTAT; URATE; HYPERURICEMIA; DOMAINS AB Despite the recognition that tophus regression is an important outcome measure in clinical trials of chronic gout, there is no agreed upon method of tophus measurement. A number of methods have been used in clinical trials of chronic gout, from simple physical measurement techniques to more complex advanced imaging methods. This article summarizes methods of tophus measurement and discusses their properties. Physical measurement using Vernier calipers meets most aspects of the Outcome Measures in Rheumatology (OMERACT) filter. Rigorous testing of the complex methods, particularly with respect to reliability and sensitivity to change, is needed to determine the appropriate use of these methods. Further information is also required regarding which method of physical measurement is best for use in future clinical trials. The need to develop and test a patient-reported outcome measure of tophus burden is also highlighted. (J Rheumatol 2011;38:1458-61; doi:10.3899/jrheum.110272) C1 [Dalbeth, Nicola; McQueen, Fiona M.] Univ Auckland, Fac Med & Hlth Sci, Auckland 1, New Zealand. [Singh, Jasvinder A.; Gaffo, Angelo L.] Birmingham Vet Affairs VA Med Ctr, Birmingham, AL USA. [Singh, Jasvinder A.; Gaffo, Angelo L.] Univ Alabama, Birmingham, AL USA. [MacDonald, Patricia A.] Takeda Global Res & Dev, Clin Sci, Deerfield, IL USA. [Edwards, N. Lawrence] Univ Florida, Dept Med, Gainesville, FL USA. [Schumacher, H. Ralph, Jr.] Univ Penn, Philadelphia, PA 19104 USA. [Schumacher, H. Ralph, Jr.] VA Med Ctr, Philadelphia, PA USA. [Simon, Lee S.] SDG LLC, Med, Cambridge, MA USA. [Stamp, Lisa K.] Univ Otago, Dept Med, Christchurch, New Zealand. [Neogi, Tuhina] Boston Univ, Sch Med, Boston, MA 02118 USA. [Khanna, Puja P.] Univ Calif Los Angeles, David Geffen Sch Med, Div Rheumatol, Los Angeles, CA 90095 USA. [Becker, Michael A.] Univ Chicago, Rheumatol Sect, Chicago, IL 60637 USA. [Taylor, William J.] Univ Otago, Dept Med, Wellington, New Zealand. RP Dalbeth, N (reprint author), Univ Auckland, Fac Med & Hlth Sci, Auckland 1, New Zealand. EM n.dalbeth@auckland.ac.nz OI singh, jasvinder/0000-0003-3485-0006; Neogi, Tuhina/0000-0002-9515-1711 FU American College of Rheumatology REF; NIAMS [5K23AR55127]; Takeda; Novartis; Allergan; Savient; Wyeth; Amgen; URL Pharmaceuticals; BioCryst; Ardea; Regeneron FX Supported by resources and use of facilities at the Birmingham VA Medical Center, Alabama, USA (Dr. Singh). Dr. Khanna is the recipient of an American College of Rheumatology REF Clinical Investigator Award (Quality of Life and Healthcare Utilization in Chronic Gout). Dr. Neogi is supported by NIAMS 5K23AR55127. Dr. Dalbeth has received consultant fees from Takeda and Novartis. Dr. Singh has received speaker honoraria from Abbott; research and travel grants from Allergan, Takeda, Savient, Wyeth, and Amgen; and consultant fees from Savient, URL Pharmaceuticals, and Novartis. Dr. Simon has served on the Board of Directors for Savient Pharmaceuticals and as a consultant for Takeda. Ms MacDonald is an employee of Takeda. Dr. Becker has received consultant fees from Takeda, Savient, BioCryst, URL Pharmaceuticals, Ardea, and Regeneron. NR 17 TC 14 Z9 15 U1 0 U2 3 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 JUL PY 2011 VL 38 IS 7 BP 1458 EP 1461 DI 10.3899/jrheum.110272 PG 4 WC Rheumatology SC Rheumatology GA 796HE UT WOS:000293041600037 PM 21724716 ER PT J AU Stamp, LK Khanna, PP Dalbeth, N Boers, M Maksymowych, WP Schumacher, HR Becker, MA MacDonald, PA Edwards, NL Singh, JA Simon, LS McQueen, FM Neogi, T Gaffo, AL Strand, V Taylor, WJ AF Stamp, Lisa K. Khanna, Puja P. Dalbeth, Nicola Boers, Maarten Maksymowych, Walter P. Schumacher, H. Ralph, Jr. Becker, Michael A. MacDonald, Patricia A. Edwards, N. Lawrence Singh, Jasvinder A. Simon, Lee S. McQueen, Fiona M. Neogi, Tuhina Gaffo, Angelo L. Strand, Vibeke Taylor, William J. TI Serum Urate in Chronic Gout - Will It Be the First Validated Soluble Biomarker in Rheumatology? SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE SERUM URATE; GOUT; BIOMARKER ID NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; URIC-ACID LEVEL; RISK-FACTORS; HYPERURICEMIA; POPULATION; CONSUMPTION; DISEASE; CONSTITUENTS; ALLOPURINOL AB Objective. To summarize evidence for and endorsement of serum urate (SU) as having fulfilled the OMERACT filter as a soluble biomarker in chronic gout at the 2010 Outcome Measures in Rheumatology Meeting (OMERACT 10). Methods. Data were presented to support the use of SU as a soluble biomarker in chronic gout and specifically the ability to utilize it to predict future patient-reported outcomes. Results. SU was accepted as having fulfilled the OMERACT filter by 78% of voters. However, consensus was not obtained regarding its use as a soluble biomarker in chronic gout. Although the majority of the criteria for a soluble biomarker were fulfilled, the key criterion of association of the biomarker with outcomes was not agreed upon. It was agreed that the appropriate choice of endpoint must be linked to its clinical importance to the individual with the disorder and its temporal relationship to the intervention. Appropriate outcomes in chronic gout may therefore include gout flares, reduction in tophi, and patient-reported outcomes. Conclusion. SU is a critical outcome measure. It has the potential to fulfil criteria for a soluble biomarker. Further analyses of existing data from randomized controlled trials will be required to determine whether SU can predict future important outcomes, in particular disability. (J Rheumatol 2011;38:1462-6; doi:10.3899/jrheum.110273) C1 [Stamp, Lisa K.] Univ Otago, Dept Med, Christchurch, New Zealand. [Khanna, Puja P.] Univ Calif Los Angeles, David Geffen Sch Med, Div Rheumatol, Los Angeles, CA 90095 USA. [Dalbeth, Nicola; McQueen, Fiona M.] Univ Auckland, Fac Med & Hlth Sci, Auckland 1, New Zealand. [Boers, Maarten] Vrije Univ Amsterdam Med Ctr, Dept Epidemiol & Biostat, Amsterdam, Netherlands. [Maksymowych, Walter P.] Univ Alberta, Dept Med, Edmonton, AB, Canada. [Schumacher, H. Ralph, Jr.] Univ Penn, Philadelphia, PA 19104 USA. [Schumacher, H. Ralph, Jr.] Vet Affairs VA Med Ctr, Philadelphia, PA USA. [Becker, Michael A.] Univ Chicago, Rheumatol Sect, Chicago, IL 60637 USA. [MacDonald, Patricia A.] Takeda Global Res & Dev, Deerfield, IL USA. [Edwards, N. Lawrence] Univ Florida, Dept Med, Gainesville, FL USA. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL USA. [Singh, Jasvinder A.; Gaffo, Angelo L.] Univ Alabama, Dept Med, Div Rheumatol, Birmingham, AL 35294 USA. [Singh, Jasvinder A.; Gaffo, Angelo L.] Univ Alabama, Div Epidemiol, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Birmingham VA 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. [Simon, Lee S.] SDG LLC, Cambridge, MA USA. [Neogi, Tuhina] Boston Univ, Sch Med, Boston, MA 02118 USA. [Strand, Vibeke] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. [Taylor, William J.] Univ Otago, Wellington, New Zealand. RP Stamp, LK (reprint author), Univ Otago, Dept Med, Christchurch, New Zealand. EM lisa.stamp@cdhb.govt.nz OI singh, jasvinder/0000-0003-3485-0006; Neogi, Tuhina/0000-0002-9515-1711 FU National Institutes of Health (NIH) [1 KL2 RR024151-01, K23 (AR0557127), P60 AR047785]; NIH/NIAMS [UO1 AR057936]; American College of Rheumatology REF; Takeda; Savient; Regeneron; Novartis; Pfizer; Allergan; Wyeth; Amgen; URL Pharmaceuticals FX Supported by National Institutes of Health (NIH) Clinical Translational Science Award 1 KL2 RR024151-01 (Mayo Clinic Center for Clinical and Translational Research) to Dr. Singh; and resources and use of facilities at the Birmingham VA Medical Center, Alabama, USA. Dr. Neogi was supported by awards from the NIH K23 (AR0557127) and P60 AR047785. Dr. Khanna was supported by research grants from the NIH/NIAMS (UO1 AR057936) and an American College of Rheumatology REF Clinical Investigator Award. Data were obtained from the Savient Pharmaceuticals and the Takeda Global Research and Development. Dr. Schumacher has received consulting fees from Takeda, Savient, Regeneron, Novartis, and Pfizer. Dr. Becker has been a consultant for Takeda, Savient, BioCryst, URL Pharmaceuticals, Ardea, and Regeneron. Ms MacDonald is an employee of Takeda Global Research and Development. Dr. Edwards has received consultant fees from Takeda and Savient. Dr. Singh has received speaker honoraria from Abbott; research and travel grants from Allergan, Takeda, Savient, Wyeth and Amgen; and consultant fees from Savient, URL Pharmaceuticals, and Novartis. Dr. Simon has served on the Board of Directors for Savient Pharmaceuticals and as a consultant for Takeda. Dr. Strand has served as a consultant to Savient and Takeda Pharmaceuticals. NR 40 TC 8 Z9 8 U1 0 U2 6 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 JUL PY 2011 VL 38 IS 7 BP 1462 EP 1466 DI 10.3899/jrheum.110273 PG 5 WC Rheumatology SC Rheumatology GA 796HE UT WOS:000293041600038 PM 21724717 ER PT J AU Taylor, WJ Singh, JA Saag, KG Dalbeth, N MacDonald, PA Edwards, NL Simon, LS Stamp, LK Neogi, T Gaffo, AL Khanna, PP Becker, MA Schumacher, HR AF Taylor, William J. Singh, Jasvinder A. Saag, Kenneth G. Dalbeth, Nicola MacDonald, Patricia A. Edwards, N. Lawrence Simon, Lee S. Stamp, Lisa K. Neogi, Tuhina Gaffo, Angelo L. Khanna, Puja P. Becker, Michael A. Schumacher, H. Ralph, Jr. TI Bringing It All Together: A Novel Approach to the Development of Response Criteria for Chronic Gout Clinical Trials SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE GOUT; RESPONSE CRITERIA; MULTICRITERIA DECISION-MAKING AB Objective. To review a novel approach for constructing composite response criteria for use in chronic gout clinical trials that implements a method of multicriteria decision-making. Methods. Preliminary work with paper patient profiles led to a restricted set of core-set domains that were examined using 1000Minds (TM) by rheumatologists with an interest in gout, and (separately) by OMERACT registrants prior to OMERACT 10. These results and the 1000Minds approach were discussed during OMERACT 10 to help guide next steps in developing composite response criteria. Results. There were differences in how individual indicators of response were weighted between gout experts and OMERACT registrants. Gout experts placed more weight upon changes in uric acid levels, whereas OMERACT registrants placed more weight upon reducing flares. Discussion highlighted the need for a "pain" domain to be included, for "worsening" to be an additional level within each indicator, for a group process to determine the decision-making within a 1000Minds exercise, and for the value of patient involvement. Conclusion. Although there was not unanimous support for the 1000Minds approach to inform the construction of composite response criteria, there is sufficient interest to justify ongoing development of this methodology and its application to real clinical trial data. (J Rheumatol 2011;38:1467-70; doi:10.3899/jrheum.110274) C1 [Taylor, William J.] Univ Otago, Dept Med, Wellington, New Zealand. [Singh, Jasvinder A.; Saag, Kenneth G.; Gaffo, Angelo L.] Birmingham Vet Affairs VA Med Ctr, Birmingham, AL USA. [Singh, Jasvinder A.; Saag, Kenneth G.; Gaffo, Angelo L.] Univ Alabama, Birmingham, AL USA. [Dalbeth, Nicola] Univ Auckland, Fac Med & Hlth Sci, Auckland 1, New Zealand. [MacDonald, Patricia A.] Takeda Global Res & Dev, Deerfield, IL USA. [Edwards, N. Lawrence] Univ Florida, Dept Med, Gainesville, FL USA. [Simon, Lee S.] SDG LLC, Cambridge, MA USA. [Stamp, Lisa K.] Univ Otago, Dept Med, Christchurch, New Zealand. [Neogi, Tuhina] Boston Univ, Sch Med, Boston, MA 02118 USA. [Khanna, Puja P.] Univ Calif Los Angeles, David Geffen Sch Med, Div Rheumatol, Los Angeles, CA 90095 USA. [Becker, Michael A.] Univ Chicago, Rheumatol Sect, Chicago, IL 60637 USA. [Schumacher, H. Ralph, Jr.] Univ Penn, Philadelphia, PA 19104 USA. [Schumacher, H. Ralph, Jr.] VA Med Ctr, Philadelphia, PA USA. RP Taylor, WJ (reprint author), Univ Otago, Dept Med, Wellington, New Zealand. EM will.taylor@otago.ac.nz OI singh, jasvinder/0000-0003-3485-0006; Neogi, Tuhina/0000-0002-9515-1711 FU University of Otago; University of Pennsylvania; American College of Rheumatology REF; NIAMS [5K23AR55127]; Allergan; Takeda; Savient; Wyeth; Amgen; URL Pharmaceuticals; Novartis; Takeda, Savient, Regeneron; Pfizer FX Partially supported by a University of Otago Matched Funding Summer Scholarship and ACR-EULAR Grant through the University of Pennsylvania; also supported with resources and use of facilities at Birmingham VA Medical Center (Dr. Singh). Dr. Khanna is the recipient of an American College of Rheumatology REF Clinical Investigator Award (Quality of Life and Healthcare Utilization in Chronic Gout) and Co-Investigator on NIH/NIAMS 1 AR057936 (Development and Initial Validation of PROMIS G1 Distress Scale), Khanna, D; Spiegel B, co-principal investigators. Dr. Neogi is a recipient of NIAMS 5K23AR55127. Dr. Singh has received speaker honoraria from Abbott; research and travel grants from Allergan, Takeda, Savient, Wyeth, and Amgen; and consultant fees from Savient, URL Pharmaceuticals, and Novartis. Dr. Saag has received honoraria from Novartis, Amgen, and Lilly, has conducted clinical trials with Takeda, Novartis, and Regeneron, and serves on the Board of Directors of the Gout and Uric Acid Society. Ms MacDonald is an employee of Takeda Global Research and Development. Dr. Edwards has received consultant fees from Takeda and Savient. Dr. Simon has served on the Board of Directors for Savient Pharmaceuticals, and as a consultant for Takeda. Dr. Becker has been a consultant for Takeda, Savient, BioCryst, URL/Pharma, Ardea, and Regeneron. Dr. Schumacher has received consulting fees from Takeda, Savient, Regeneron, Novartis, and Pfizer. NR 15 TC 9 Z9 9 U1 0 U2 3 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 JUL PY 2011 VL 38 IS 7 BP 1467 EP 1470 DI 10.3899/jrheum.110274 PG 4 WC Rheumatology SC Rheumatology GA 796HE UT WOS:000293041600039 PM 21724718 ER PT J AU Singh, JA Kundukulam, J Riddle, DL Strand, V Tugwell, P AF Singh, Jasvinder A. Kundukulam, Joseph Riddle, Daniel L. Strand, Vibeke Tugwell, Peter TI Early Postoperative Mortality Following Joint Arthroplasty: A Systematic Review SO JOURNAL OF RHEUMATOLOGY LA English DT Review DE MORTALITY; TOTAL KNEE ARTHROPLASTY; TOTAL HIP ARTHROPLASTY; SHORT-TERM MORTALITY ID TOTAL KNEE ARTHROPLASTY; TOTAL HIP-ARTHROPLASTY; QUALITY-OF-LIFE; UNITED-STATES; REVISION HIP; OUTCOMES; SURGEON; REPLACEMENT; ASSOCIATION; VOLUME AB Objective. To perform a systematic review of 30- and 90-day mortality rates in patients undergoing hip or knee arthroplasties. Methods. Five databases were searched for English-language studies of mortality in hip or knee arthroplasties and the following data were extracted: patient characteristics (age, sex, ethnicity), arthroplasty characteristics (unilateral vs bilateral, hip vs knee), system factors (hospital volume and surgeon volume), year of study, etc. Mortality rates were compared across variable categories; proportions were compared using relative risk ratios and 95% confidence intervals. Results. Out of 650 titles and abstracts, 80 studies qualified for analysis. Of these, 35%, 34%, and 31% of studies provided 30-, 90-, and > 90-day mortality rates. Overall 30-day mortality rates across all types of arthroplasties were 0.3%; 90-day, 0.7%. For those reports with specific rates, 30-day mortality was significantly higher in men than women [1.8% vs 0.4%, respectively; relative risk (RR) 3.93, 95% Cl 3.30-4.68] and in bilateral versus unilateral procedures (0.5% vs 0.3%; RR 1.6, 95% CI 1.49-1.72), but no differences were noted by the underlying diagnosis of osteoarthritis (OA) versus rheumatoid arthritis (0.4% vs 0.3%; RR 0.77, 95% CI 0.48-1.24). 90-day mortality showed nonsignificant trends favoring women, OA as the underlying diagnosis, and unilateral procedures. Conclusion. Several demographic and surgical factors were associated with higher 30-day mortality rates following knee and hip arthroplasties. More studies are needed to examine the effect of body mass index, comorbidities, and other modifiable factors, in order to identify interventions to lower mortality rates following arthroplasty procedures. (J Rheumatol 2011;38:1507-13; doi:10.3899/jrheum.110280) C1 [Singh, Jasvinder A.; Kundukulam, Joseph] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Birmingham Vet Affairs VA Med Ctr, Med Serv, Birmingham, AL USA. [Singh, Jasvinder A.] Birmingham Vet Affairs VA Med Ctr, Ctr Surg Med Acute Care Res & Transit, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama, Div Epidemiol, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Mayo Clin, Sch Med, Dept Orthoped Surg, Rochester, MN USA. [Riddle, Daniel L.] Virginia Commonwealth Univ, Dept Phys Therapy, Richmond, VA USA. [Riddle, Daniel L.] Virginia Commonwealth Univ, Dept Orthoped Surg, Richmond, VA USA. [Strand, Vibeke] Stanford Univ, Sch Med, Div Immunol Rheumatol, Palo Alto, CA 94304 USA. [Tugwell, Peter] Ottawa Hosp, Dept Med, Inst Populat Hlth, Ctr Global Hlth, Ottawa, ON, Canada. RP Singh, JA (reprint author), Univ Alabama, Dept Med, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. EM Jasvinder.md@gmail.com OI singh, jasvinder/0000-0003-3485-0006; Tugwell, Peter/0000-0001-5062-0556 FU National Institute of Health (NIH) [1 KL2 RR024151-01, T35 HL007473]; Allergan; Takeda; Savient; Wyeth; Amgen; URL Pharmaceuticals; Novartis FX Dr. Singh was supported by National Institute of Health (NIH) Clinical Translational Science Award 1 KL2 RR024151-01 (Mayo Clinic Center for Clinical and Translational Research). Dr. Singh has received speaker honoraria from Abbott; research and travel grants from Allergan, Takeda, Savient, Wyeth, and Amgen; and consultant fees from Savient, URL Pharmaceuticals, and Novartis. J. Kundukulam was supported by NIH Short Term Training Grant T35 HL007473. NR 10 TC 34 Z9 34 U1 1 U2 4 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 JUL PY 2011 VL 38 IS 7 BP 1507 EP 1513 DI 10.3899/jrheum.110280 PG 7 WC Rheumatology SC Rheumatology GA 796HE UT WOS:000293041600045 PM 21724724 ER PT J AU Burns, JA Kim, KH deBoer, JF Anderson, RR Zeitels, SM AF Burns, James A. Kim, Ki Hean deBoer, Johannes F. Anderson, R. Rox Zeitels, Steven M. TI Polarization-Sensitive Optical Coherence Tomography Imaging of Benign and Malignant Laryngeal Lesions: An In Vivo Study SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article DE optical coherence tomography; larynx; glottis; vocal fold; polarization-sensitive optical coherence tomography; OCT; PS-OCT ID HUMAN VOCAL FOLDS; COLLAGEN; CANCER; BIREFRINGENCE AB Objective. Optical coherence tomography (OCT), an imaging technology that provides cross-sectional subsurface tissue structure images using back-scattered light, is a promising noninvasive imaging modality for in vivo assessment of vocal fold layered microstructure. Polarization-sensitive OCT (PS-OCT) augments conventional OCT by detecting changes in the polarization state of reflected light. This study imaged various benign and malignant laryngeal pathologies in patients undergoing direct laryngoscopy under general anesthesia to determine whether PS-OCT would provide useful additional information about vocal fold microstructure and glottic surface pathology. Study Design. Prospective clinical trial. Setting. Tertiary care center. Subjects and Methods. Twenty-three patients who were undergoing microlaryngoscopy under general anesthesia for benign (n = 18) and malignant (n = 5) glottic disease were imaged bilaterally with OCT and PS-OCT (n = 46 vocal folds). Intraoperative microphotography guided placement of the imaging probe. Normal-appearing glottic tissue was also imaged if present. When clinically indicated, biopsy or complete removal of the lesion established histologic confirmation. Results. PS-OCT provided high-quality, vertical, cross-sectional images up to 1.2-mm deep that complemented microlaryngoscopy and conventional OCT for vocal fold pathologies. Scar tissue was visualized by PS-OCT, characterized by a birefringence pattern more intense than that of normal glottic tissue. Cancer typically showed disruption or absence of both layered structure and birefringence. Conclusion. Combining PS-OCT with OCT during human vocal cord imaging provides useful information in characterizing vocal cord lesions, particularly scar tissue. C1 [Burns, James A.; Zeitels, Steven M.] Harvard Univ, Sch Med, Ctr Laryngeal Surg & Voice Rehabil, Massachusetts Gen Hosp,Dept Surg, Boston, MA 02114 USA. [Kim, Ki Hean] Pohang Univ Sci & Technol, Dept Mech Engn & Integrat Biosci & Biotechnol, Pohang, Gyeongbuk, South Korea. [deBoer, Johannes F.] Vrije Univ Amsterdam, Dept Phys, Amsterdam, Netherlands. [Anderson, R. Rox] Harvard Univ, Sch Med, Wellman Ctr Photomed, Massachusetts Gen Hosp,Dept Dermatol, Boston, MA 02114 USA. RP Burns, JA (reprint author), Harvard Univ, Sch Med, Ctr Laryngeal Surg & Voice Rehabil, Massachusetts Gen Hosp,Dept Surg, 1 Bowdoin Sq,11th Floor, Boston, MA 02114 USA. EM burns.james@mgh.harvard.edu RI de Boer, Johannes/B-7590-2012 OI de Boer, Johannes/0000-0003-1253-4950 NR 25 TC 20 Z9 20 U1 2 U2 11 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 JUL PY 2011 VL 145 IS 1 BP 91 EP 99 DI 10.1177/0194599811403078 PG 9 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 808SP UT WOS:000293999000016 PM 21493273 ER PT J AU Platt, MP Soler, ZM Kao, SY Metson, R Stankovic, KM AF Platt, Michael P. Soler, Zachary M. Kao, Shyan-Yuan Metson, Ralph Stankovic, Konstantina M. TI Topographic Gene Expression in the Sinonasal Cavity of Patients with Chronic Sinusitis with Polyps SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article DE sinonasal polyposis; nasal polyp; chronic rhinosinusitis; sinusitis; periostin; met proto-oncogene; prolactin-inducible protein; zinc alpha 2-glycoprotein; protein phosphatase 1 ID NASAL EPITHELIAL-CELLS; MUCOSAL INFLAMMATION; CONNECTIVE TISSUES; MET; CANCER; AIRWAY; ASTHMA AB Objective. To determine whether variations in gene expression exist at multiple subsites along the sinonasal tract in patients with chronic sinusitis with polyps and in healthy controls. Study Design. Prospective, controlled study. Setting. Academic medical center. Subjects and Methods. Tissue expression levels of 5 genes, previously found to be characteristic of ethmoid polyps, were measured using real-time quantitative polymerase chain reaction in 100 sinonasal tissue samples. Specimens harvested from 5 regions-the ethmoid sinus, septum, inferior turbinate, middle turbinate, and lateral nasal wall-in 10 patients with chronic sinusitis and ethmoid polyps were compared to tissue from similar regions in 10 control patients without sinusitis. Western blot analysis was performed to validate differential gene expression at the protein level. Results. Gene expression levels of ethmoid polyps differed significantly from those of healthy ethmoid mucosa, as well as tissue from 4 surrounding anatomical sites in both patients with chronic sinusitis and controls. Alterations specific to the polyp tissue included downregulated genes, prolactin-induced protein (fold change 377.2 +/- 169.0, P < .0001), and zinc alpha 2-glycoprotein (fold change 72.1 +/- 26.5, P < .0001), as well as upregulated genes, met proto-oncogene (fold change 2.5 +/- 0.7, P = .029), and periostin (fold change 7.5 +/- 3.4, P = .003). No significant differences in gene expression was found for neurabin 2 (fold change 1.0, P = .99). Conclusion. The transcriptional pattern of ethmoid polyps appears to be unique compared with other subsites in the sinonasal cavity of patients with chronic sinusitis. Care must be taken when collecting specimens for molecular studies of the sinonasal tract to differentiate polyp from nonpolyp tissue in chronic sinusitis. C1 [Soler, Zachary M.; Kao, Shyan-Yuan; Metson, Ralph; Stankovic, Konstantina M.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Platt, Michael P.; Soler, Zachary M.; Metson, Ralph; Stankovic, Konstantina M.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Platt, Michael P.] Boston Univ, Dept Otolaryngol Head & Neck Surg, Boston, MA 02215 USA. RP Stankovic, KM (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM konstantina_stankovic@meei.harvard.edu FU Massachusetts Eye and Ear Infirmary Research Foundation; NIH-NIDCD [K08DC010419-01]; Massachusetts Life Sciences Center; Boston Foundation; Harvard Medical School FX This project was funded by the Massachusetts Eye and Ear Infirmary Research Foundation. KMS is supported by grants from NIH-NIDCD K08DC010419-01, Massachusetts Life Sciences Center, the Boston Foundation, and the Shore Fellowship at Harvard Medical School. NR 24 TC 8 Z9 9 U1 0 U2 2 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 JUL PY 2011 VL 145 IS 1 BP 171 EP 175 DI 10.1177/0194599811402030 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 808SP UT WOS:000293999000027 PM 21493287 ER PT J AU Tamers, SL Beresford, SAA Cheadle, AD Zheng, YY Bishop, SK Thompson, B AF Tamers, Sara L. Beresford, Shirley A. A. Cheadle, Allen D. Zheng, Yingye Bishop, Sonia K. Thompson, Beti TI The association between worksite social support, diet, physical activity and body mass index SO PREVENTIVE MEDICINE LA English DT Article DE Worksite; Social support; Diet; Physical activity; Body mass index; Obesity; Health promotion; Lifestyle risk factors; Occupational health; Wellness interventions ID VEGETABLE CONSUMPTION; FRUIT; INITIATIVES; ENVIRONMENT; PREVENTION; OBESITY; IMPACT; TRIAL AB Objective: Social support may be associated with improved diet and physical activity determinants of overweight and obesity. Wellness programs increasingly target worksites. The aim was to evaluate the relationship between worksite social support and dietary behaviors, physical activity, and body mass index (BMI). Method: Baseline data were obtained on 2878 employees from 2005 to 2007 from 34 worksites through Promoting Activity and Changes in Eating, a group-randomized weight reduction intervention in Greater Seattle. Worksite social support, diet, physical activity. and BMI were assessed via self-reported questionnaire. Principal component analysis was applied to workgroup questions. To adjust for design effects, random effects models were employed. Results: No associations were found with worksite social support and BMI, or with many obesogenic behaviors. However, individuals with higher worksite social support had 14.3% higher (95% Cl: 5.6%-23.7%) mean physical activity score and 4% higher (95% Cl: 1%-7%) mean fruit and vegetable intake compared to individuals with one-unit lower support. Conclusion: Our findings do not support a conclusive relationship between higher worksite social support and obesogenic behaviors, with the exception of physical activity and fruit and vegetable intake. Future studies are needed to confirm these relationships and evaluate how worksite social support impacts trial outcomes. (C) 2011 Elsevier Inc. All rights reserved. C1 [Tamers, Sara L.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Tamers, Sara L.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Tamers, Sara L.; Cheadle, Allen D.; Thompson, Beti] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Tamers, Sara L.; Beresford, Shirley A. A.; Zheng, Yingye; Bishop, Sonia K.; Thompson, Beti] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA. [Beresford, Shirley A. A.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Cheadle, Allen D.] Univ Washington, Hlth Promot Res Ctr, Seattle, WA 98195 USA. [Zheng, Yingye] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. RP Tamers, SL (reprint author), Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, 677 Huntington Ave, Boston, MA 02115 USA. EM sara_tamers@dfci.harvard.edu RI Sriwisit, Sukhumaphorn/G-1405-2011 FU University of Washington's Department of Health Services; NCI's Biobehavioral Cancer Prevention and Control [R25 CA92408]; National Heart, Lung, and Blood Institute [R01 HL079491]; NIH/NCI Harvard Education [R25 CA057713] FX The author wishes to acknowledge the training and support of the University of Washington's Department of Health Services as well as the NCI's Biobehavioral Cancer Prevention and Control Fellowship Grant (R25 CA92408; PI: Donald Patrick, PhD), the National Heart, Lung, and Blood Institute Grant (R01 HL079491; PI: Shirley Beresford, PhD) and the NIH/NCI Harvard Education Program in Cancer Prevention and Control (R25 CA057713; PI: Glorian Sorensen, PhD). NR 20 TC 21 Z9 22 U1 2 U2 23 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 JUL-AUG PY 2011 VL 53 IS 1-2 BP 53 EP 56 DI 10.1016/j.ypmed.2011.04.012 PG 4 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 807ZC UT WOS:000293940600011 PM 21570422 ER PT J AU Sullivan, SD Welt, C Sherman, S AF Sullivan, Shannon D. Welt, Corrine Sherman, Stephanie TI FMR1 and the Continuum of Primary Ovarian Insufficiency SO SEMINARS IN REPRODUCTIVE MEDICINE LA English DT Article DE Primary ovarian insufficiency; premature ovarian failure; fragile X syndrome; Fragile X Mental Retardation 1 (FMR1) gene ID FRAGILE-X-SYNDROME; FEMALE PREMUTATION CARRIERS; CEREBELLAR-TREMOR/ATAXIA-SYNDROME; RNA-MEDIATED NEURODEGENERATION; BONE-MINERAL DENSITY; CGG REPEAT NUMBER; CHROMOSOME INACTIVATION; MESSENGER-RNA; FULL MUTATION; NATURAL MENOPAUSE AB Spontaneous 46,XX primary ovarian insufficiency (POI) is a term that describes ovarian dysfunction resulting in a range of abnormalities, from infertility to early menopause as the end stage (overt POI). The most common known genetic cause of 46,XX POI is the expansion of a CGG repeat to 55 to 199 copies in the 5' untranslated region in the X-linked FMR1 gene. This "premutation" is associated with overt POI (FXPOI) in similar to 20% of carrier women. Greater than 200 CGG copies results in methylation of the CGG repeats and subsequent silencing of the FMR1 gene, causing fragile X syndrome. This "full" mutation is not associated with FXPOI. Even in the absence of overt FXPOI, women who carry the premutation may exhibit ovarian dysfunction along a continuum of severity. Evidence also suggests that the severity of FXPOI depends on the CGG repeat length, background modifier genes, and environmental factors (e.g., smoking). This review explores the range of ovarian dysfunction, the mechanisms behind the dysfunction, and the reasons for the variability in presentation in women who carry the FMR1 premutation. Understanding the mechanisms responsible for development of FXPOI is paramount to providing these women with the best overall health care. C1 [Sullivan, Shannon D.] Washington Hosp Ctr, Dept Endocrinol, Washington, DC 20010 USA. [Welt, Corrine] Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. [Sherman, Stephanie] Emory Univ, Dept Human Genet, Atlanta, GA 30322 USA. RP Sullivan, SD (reprint author), Washington Hosp Ctr, Dept Endocrinol, 110 Irving St NW,Suite 217-72, Washington, DC 20010 USA. EM Shannon.D.Sullivan@Medstar.net OI Welt, Corrine/0000-0002-8219-5504 NR 69 TC 65 Z9 66 U1 1 U2 7 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1526-8004 J9 SEMIN REPROD MED JI Semin. Reprod. Med. PD JUL PY 2011 VL 29 IS 4 BP 299 EP 307 DI 10.1055/s-0031-1280915 PG 9 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 810PQ UT WOS:000294138600004 PM 21969264 ER PT J AU Marino, R Misra, M AF Marino, Rose Misra, Madhusmita TI Bone Health in Primary Ovarian Insufficiency SO SEMINARS IN REPRODUCTIVE MEDICINE LA English DT Article DE Bone density; bone microarchitecture; bone turnover; estrogen; androgens; bisphosphonates ID TOTAL-BODY IRRADIATION; PREMENOPAUSAL BREAST-CANCER; HORMONE REPLACEMENT THERAPY; ADJUVANT ENDOCRINE THERAPY; RANDOMIZED CLINICAL-TRIAL; LATE POSTMENOPAUSAL WOMEN; VERTEBRAL FRACTURE RISK; MINERAL DENSITY; TURNER-SYNDROME; MARROW-TRANSPLANTATION AB The etiology of primary ovarian insufficiency (POI) may be genetic, autoimmune, or iatrogenic. Genetic conditions include 45,X, 46,XX and 46,XY POI, and POI associated with galactosemia and FMR premutations. Women with autoimmune polyglandular syndromes 1 and 2 may develop autoimmune POI, as may those who receive chemotherapy or radiotherapy. Hypogonadism in POI can result in reduced rates of bone mass accrual in adolescents and young women, and low bone density for age in older women. Measures to optimize bone density in women with POI include attention to lifestyle measures and hormone replacement. Resistance training and adequate calcium and vitamin D supplementation are essential, as is replacement of estrogen/progestin. Estrogen/progestin replacement may be problematic in women with estrogen-sensitive breast cancer who developed POI in the course of therapy for cancer. In these instances, bisphosphonates are an option. In particular, zoledronic acid has been used successfully in conjunction with chemotherapy, tamoxifen, and aromatase inhibitors. C1 [Misra, Madhusmita] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Marino, Rose; Misra, Madhusmita] Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. 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 NR 90 TC 3 Z9 4 U1 1 U2 4 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1526-8004 EI 1526-4564 J9 SEMIN REPROD MED JI Semin. Reprod. Med. PD JUL PY 2011 VL 29 IS 4 BP 317 EP 327 DI 10.1055/s-0031-1280917 PG 11 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 810PQ UT WOS:000294138600006 PM 21969266 ER PT J AU Collins, J McCloskey, C Titchner, R Goodpaster, B Hoffman, M Hauser, D Wilson, M Eid, G AF Collins, Joy McCloskey, Carol Titchner, Rebecca Goodpaster, Bret Hoffman, Marcus Hauser, Debra Wilson, Mark Eid, George TI Preoperative weight loss in high-risk superobese bariatric patients: a computed tomography-based analysis SO SURGERY FOR OBESITY AND RELATED DISEASES LA English DT Article DE Morbid obesity; Gastric bypass; Bariatric surgery; Low-calorie diet; LCD; High risk ID GASTRIC BYPASS-SURGERY; OBESITY; FAT; OUTCOMES; LIVER; DIET AB Background: Superobesity, through organomegaly, excessive adiposity, and associated severe co-morbidities, is a recognized risk factor for bariatric surgery. Our study examined the utility of preoperative weight loss with a liquid low-calorie diet (LCD) as a method of risk reduction. Methods: All patients with a body mass index (BMI) > 50 kg/m(2) were instructed to consume a LCD (800 kcal/d) with the goal of losing >= 10% of their body weight. The co-morbidities were monitored. The abdominal wall depth and cross-sectional areas of subcutaneous adipose tissue (SAT) at 12 and 20 cm below the costal margin, visceral adipose tissue (VAT), and liver volume were measured, using computed tomography, at baseline and after completion of the LCD. Laparoscopic gastric bypass was performed in all patients. Results: The study included 30 patients (27 men and 3 women) with a mean age of 53 years (range 34-53). The mean BMI was reduced from 56 kg/m(2) (range 50-69) at baseline to 49 kg/m(2) (range 43-60) after an average of 9 weeks of the LCD. The VAT decreased from a mean of 388 cm(2) to 342 cm(2). The abdominal wall depth decreased from 3.6 to 3.2 cm at 12 cm below the costal margin and from 3.7 to 3.4 cm at 20 cm. The mean SAT at both 12 and 20 cm below the costal margin had decreased from 577 cm(2) and 687 cm(2) to 509 cm(2) and 614 cm(2), respectively. The liver volume was reduced by 18%. All co-morbidities were well controlled at LCD completion. No patient died, and 2 minor complications occurred postoperatively. Conclusion: The results of our study have shown that preoperative LCD is a safe and effective tool leading to a significant decrease in liver volume and abdominal wall depth, as well as a reduction in both VAT and SAT. Its use might contribute to improved short-term surgical outcomes in high-risk superobese patients. (Surg Obes Relat Dis 2011;7:480-485.) Published by Elsevier Inc. on behalf of American Society for Metabolic and Bariatric Surgery. C1 [McCloskey, Carol; Hoffman, Marcus; Eid, George] Univ Pittsburgh Med Ctr, Div Minimally Invas Surg, Pittsburgh, PA 15213 USA. [Collins, Joy] Childrens Hosp Philadelphia, Div Gen & Thorac Surg, Philadelphia, PA 19104 USA. [Titchner, Rebecca; Hauser, Debra; Wilson, Mark; Eid, George] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Goodpaster, Bret] Univ Pittsburgh, Dept Med, Div Endocrinol & Metab, Pittsburgh, PA USA. RP Eid, G (reprint author), Univ Pittsburgh Med Ctr, Div Minimally Invas Surg, 300 Halket St, Pittsburgh, PA 15213 USA. EM eidgm@upmc.edu NR 17 TC 22 Z9 23 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1550-7289 J9 SURG OBES RELAT DIS JI Surg. Obes. Relat. Dis. PD JUL-AUG PY 2011 VL 7 IS 4 BP 480 EP 485 DI 10.1016/j.soard.2010.09.026 PG 6 WC Surgery SC Surgery GA 811HC UT WOS:000294196300007 PM 21185789 ER PT J AU Fishman, JA AF Fishman, J. A. TI New Technologies for Infectious Screening of Organ Donors SO TRANSPLANTATION PROCEEDINGS LA English DT Article ID TRANSPLANT RECIPIENTS AB Viral, bacterial, parasitic, prion, and fungal infections, although uncommon, have been transmitted via organ and tissue allografts. Improved screening techniques for infectious diseases in organ donors have helped to reduce disease transmission. Reports of clusters of donor-derived infections illustrate the need to improve the screening of tissue and organ donors. Available microbiologic assays, including molecular tests, are generally designed for use as diagnostic tools in individuals believed to have a specific infection based on clinical or epidemiological criteria. These assays are frequently unsuitable in the screening of deceased organ donors. Nucleic acid testing may reduce the risk of disease transmission by detecting early-stage infection, including those from human immunodeficiency virus, hepatitis B virus, and hepatitis C virus in the "window" period before antibody seroconversion can be documented. Screening of organ donors for potential pathogens cannot completely exclude the risk of disease transmission. The process of donor screening must continue to evolve with advances in diagnostic technologies for infectious diseases. C1 [Fishman, J. A.] Massachusetts Gen Hosp, Transplant Infect Dis & Compromised Host Program, Div Infect Dis, Boston, MA 02114 USA. [Fishman, J. A.] Massachusetts Gen Hosp, Transplant Ctr, Boston, MA 02114 USA. [Fishman, J. A.] Harvard Univ, Sch Med, Boston, MA USA. RP Fishman, JA (reprint author), Massachusetts Gen Hosp, MGH Transplant Ctr, 55 Fruit St,WH510A, Boston, MA 02114 USA. EM jfishman@partners.org NR 9 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0041-1345 J9 TRANSPL P JI Transplant. Proc. PD JUL-AUG PY 2011 VL 43 IS 6 BP 2443 EP 2445 DI 10.1016/j.transproceed.2011.06.019 PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 810CC UT WOS:000294102000075 PM 21839288 ER PT J AU Kotton, CN AF Kotton, C. N. TI Transplant Tourism and Donor-Derived Parasitic Infections SO TRANSPLANTATION PROCEEDINGS LA English DT Article ID KIDNEY-TRANSPLANTATION; RENAL-TRANSPLANTATION; UNITED-STATES; OVERSEAS; INDIA AB Transplant tourism, travel with the intent of receiving or donating a transplanted organ, has grown immensely in the past decade but is not without risks. Solid organ donors are potential carriers of infection and rates of infection are high in transplant recipients. Returning transplant recipients should be screened for blood-borne pathogens, including human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV), as well as bacteremia, urinary tract infections, and other endemic pathogens (malaria, tuberculosis, Chagas disease, and so on). Efforts should be made to optimize posttransplantation prophylaxis against infection. Although donor-derived parasitic infections are rare, rates of morbidity and mortality are high. Increases in world travel and migration will likely contribute to increases in donor-derived parasitic infection. Appropriate epidemiological screening and diagnostic testing, including blood smears, serology, and stool assays, may help reduce the risk of such transmission. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. RP Kotton, CN (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, 55 Fruit St,Cox 5, Boston, MA 02114 USA. EM ckotton@partners.org FU Clafin Distinguished Scholar Award FX Supported by the Clafin Distinguished Scholar Award. NR 12 TC 9 Z9 9 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0041-1345 J9 TRANSPL P JI Transplant. Proc. PD JUL-AUG PY 2011 VL 43 IS 6 BP 2448 EP 2449 DI 10.1016/j.transproceed.2011.06.022 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 810CC UT WOS:000294102000077 PM 21839290 ER PT J AU Clark, A Herman, J Schlozman, SC Beresin, EV AF Clark, Andrew Herman, John Schlozman, Steven C. Beresin, Eugene V. TI False Accusations Against Residents: A Training Program's Perspective SO ACADEMIC PSYCHIATRY LA English DT Editorial Material C1 [Clark, Andrew; Herman, John; Schlozman, Steven C.; Beresin, Eugene V.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Clark, A (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM abclark@bics.bwh.harvard.edu NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1042-9670 J9 ACAD PSYCHIATR JI Acad. Psych. PD JUL-AUG PY 2011 VL 35 IS 4 BP 215 EP 216 PG 2 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 799EB UT WOS:000293265300001 PM 21804036 ER PT J AU Gorrindo, T Baer, L Sanders, KM Birnbaum, RJ Fromson, JA Sutton-Skinner, KM Romeo, SA Beresin, EV AF Gorrindo, Tristan Baer, Lee Sanders, Kathy M. Birnbaum, Robert J. Fromson, John A. Sutton-Skinner, Kelly M. Romeo, Sarah A. Beresin, Eugene V. TI Web-Based Simulation in Psychiatry Residency Training: A Pilot Study SO ACADEMIC PSYCHIATRY LA English DT Article ID VIRTUAL-REALITY; STANDARDIZED PATIENTS; MANAGEMENT; EDUCATION; PATIENT AB Background: Medical specialties, including surgery, obstetrics, anesthesia, critical care, and trauma, have adopted simulation technology for measuring clinical competency as a routine part of their residency training programs; yet, simulation technologies have rarely been adapted or used for psychiatry training. Objective: The authors describe the development of a web-based computer simulation tool intended to assess physician competence in obtaining informed consent before prescribing antipsychotic medication to a simulated patient with symptoms of psychosis. Method: Eighteen residents participated in a pilot study of the Computer Simulation Assessment Tool (CSAT). Outcome measures included physician performance on required elements, pre-and post-test measures of physician confidence in obtaining informed consent, and levels of system usability. Results: Data suggested that the CSAT increased physician confidence in obtaining informed consent and that it was easy to use. Conclusions: The CSAT was an effective educational tool in simulating patient-physician interactions, and it may serve as a model for use of other web-based simulations to augment traditional teaching methods in residency education. C1 [Gorrindo, Tristan] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. McLean Hosp, Belmont, MA 02178 USA. RP Gorrindo, T (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. EM tristan.gorrindo@mgh.harvard.edu NR 26 TC 14 Z9 15 U1 1 U2 8 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1042-9670 J9 ACAD PSYCHIATR JI Acad. Psych. PD JUL-AUG PY 2011 VL 35 IS 4 BP 232 EP 237 PG 6 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 799EB UT WOS:000293265300005 PM 21804041 ER PT J AU Sperling, RA Jack, CR Black, SE Frosch, MP Greenberg, SM Hyman, BT Scheitens, P Carrillo, MC Thies, W Bednar, MM Black, RS Brashear, HR Grundman, M Siemers, ER Feldman, HH Schindler, RJ AF Sperling, Reisa A. Jack, Clifford R., Jr. Black, Sandra E. Frosch, Matthew P. Greenberg, Steven M. Hyman, Bradley T. Scheitens, Philip Carrillo, Maria C. Thies, William Bednar, Martin M. Black, Ronald S. Brashear, H. Robert Grundman, Michael Siemers, Eric R. Feldman, Howard H. Schindler, Rachel J. TI Amyloid-related imaging abnormalities in amyloid-modifying therapeutic trials: Recommendations from the Alzheimer's Association Research Roundtable Workgroup SO ALZHEIMERS & DEMENTIA LA English DT Article DE MRI; Amyloid; Therapeutic trials; Vasogenic edema; Microhemorrhage ID REVERSIBLE POSTERIOR LEUKOENCEPHALOPATHY; RECURRENT INTRACEREBRAL HEMORRHAGE; ASYMPTOMATIC CEREBRAL MICROBLEEDS; TRANSGENIC MOUSE MODELS; FLUID DRAINAGE PATHWAYS; DISEASE-LIKE PATHOLOGY; A-BETA IMMUNOTHERAPY; PRECURSOR-PROTEIN; VASOGENIC EDEMA; RISK-FACTORS AB Amyloid imaging related abnormalities (ARIA) have now been reported in clinical trials with multiple therapeutic avenues to lower amyloid-beta burden in Alzheimer's disease (AD). In response to concerns raised by the Food and Drug Administration, the Alzheimer's Association Research Roundtable convened a working group to review the publicly available trial data, attempts at developing animal models, and the literature on the natural history and pathology of related conditions. The spectrum of ARIA includes signal hyperintensities on fluid attenuation inversion recoverysequences thought to represent "vasogenic edema" and/or sulcal effusion (ARIA-E), as well as signal hypointensities on GRE/T2* thought to represent hemosiderin deposits (ARIA-H), including microhemorrhage and superficial siderosis. The etiology of ARIA remains unclear but the prevailing data support vascular amyloid as a common pathophysiological mechanism leading to increased vascular permeability. The workgroup proposes recommendations for the detection and monitoring of ARIA in ongoing AD clinical trials, as well as directions for future research. (C) 2011 The Alzheimer's Association. All rights reserved. C1 [Sperling, Reisa A.] Brigham & Womens Hosp, Dept Neurol, Ctr Alzheimer Res & Treatment, Boston, MA 02115 USA. [Jack, Clifford R., Jr.] Mayo Clin Minnesota, Dept Radiol, Rochester, MN USA. [Black, Sandra E.] Univ Toronto, Sunnybrook Hlth Sci Ctr, Dept Med, Div Neurol, Toronto, ON, Canada. [Frosch, Matthew P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, CS Kubik Lab Neuropathol, Boston, MA USA. [Greenberg, Steven M.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp,Stroke Res Ctr, Boston, MA 02115 USA. [Scheitens, Philip] Vrije Univ Amsterdam Med Ctr, Alzheimer Ctr, Dept Neurol, Amsterdam, Netherlands. [Carrillo, Maria C.; Thies, William] Alzheimers Assoc, Chicago, IL USA. [Bednar, Martin M.] Pfizer Inc, Groton, CT 06340 USA. [Black, Ronald S.] Pfizer Inc, Collegeville, PA USA. [Brashear, H. Robert] Janssen Alzheimer Immunotherapy, San Francisco, CA USA. [Grundman, Michael] Global R&D Partners, San Diego, CA USA. [Siemers, Eric R.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Feldman, Howard H.] Bristol Myers Squibb Co, Global Clin Res Neurosci, Wallingford, CT 06492 USA. [Feldman, Howard H.] Yale Univ, Dept Neurol, New Haven, CT USA. [Schindler, Rachel J.] Pfizer Inc, New York, NY USA. RP Sperling, RA (reprint author), Brigham & Womens Hosp, Dept Neurol, Ctr Alzheimer Res & Treatment, 75 Francis St, Boston, MA 02115 USA. EM reisa@rics.bwh.harvard.edu RI Jack, Clifford/F-2508-2010; OI Jack, Clifford/0000-0001-7916-622X; Black, Sandra/0000-0001-7093-8289; Feldman, Howard/0000-0002-9258-4538 FU Pfizer; Allon; Baxter, Inc.; Roche; GlaxoSmithKline; Novartis Pharmaceuticals; Myriad Pharmaceuticals; Sanofi-Aventis; Boehringer Ingelheim; Novo Nordisk; AstraZeneca FX Dr. R.A.S. has served as a site investigator for Avid, Bristol-Myers Squibb, Elan, Janssen, Pfizer, and Wyeth, and as a consultant to Avid (unpaid), Bayer, Bristol-Myers Squibb, Elan, Eisai, Janssen, Pfizer, Roche, and Wyeth. Dr. C.R.J. Jr. serves as a consultant for Janssen, Lilly, GE, Johnson and Johnson, Eisai, and Elan, and is an investigator in clinical trials sponsored by Pfizer, Allon, and Baxter, Inc. Dr. S.E.B. has received contract research funds to the Cognitive Neurology and Stroke Research Units from Roche, GlaxoSmithKline, Novartis Pharmaceuticals, Myriad Pharmaceuticals, Pfizer, Sanofi-Aventis, Boehringer Ingelheim, Novo Nordisk, and AstraZeneca. In addition, she has received speaker's honoraria for CME from Janssen-Ortho, Novartis Pharmaceutical, Lundbeck, Pfizer, Eisai, and Myriad Pharmaceuticals, and honoraria for ad hoc consulting from Pfizer, Janssen-Ortho, Novartis Pharmaceuticals, Lundbeck, Myriad Pharmaceuticals, GlaxoSmithKline, Schering-Plough, Elan, Wyeth Pharmaceuticals, Bristol-Myers Squibb, and Eisai. Dr. S.M.G. serves as a consultant for Hoffman-La Roche, Janssen Alzheimer Immunotherapy, and Bristol-Myers Squibb Company, and has received honoraria from Medtronic and Pfizer. Dr. B.T.H. has consulted with several pharmaceutical and biotechnology companies: EMD Serrano, Janssen, Takeda, BMS, Neurophage, Pfizer, Quanterix, foldrx, Elan, and Link. Dr. P.S. serves as a consultant to Roche AG, Novartis AG, Genentech, Danone Research, Lundbeck, GE Healthcare, and Avid. Drs. M.M.B. and R.J.S. are employed by Pfizer. Dr. R.S.B. is a full-time employee of Pfizer and owns stock in the company. Dr. H.R.B. is employed by Johnson and Johnson. Dr. M.G. has consulted for Janssen Alzheimer Immunotherapy, Johnson and Johnson, Elan Pharmaceuticals, and Avid Radiopharmaceuticals. Dr. E.R.S. is a full-time employee and stockholder at Eli Lilly. Dr. H.H.F. is a full-time employee and holds stock with Bristol-Myers Squibb. Drs. M.C.C. and W.T. are employees of the Alzheimer's Association and report no conflicts. NR 102 TC 175 Z9 177 U1 5 U2 27 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD JUL PY 2011 VL 7 IS 4 BP 367 EP 385 DI 10.1016/j.jalz.2011.05.2351 PG 19 WC Clinical Neurology SC Neurosciences & Neurology GA 802DT UT WOS:000293490200002 PM 21784348 ER PT J AU Mattsson, N Andreasson, U Persson, S Arai, H Batish, SD Bernardini, S Bocchio-Chiavetto, L Blankenstein, MA Carrillo, MC Chalbot, S Coart, E Chiasserini, D Cutler, N Dahlfors, G Duller, S Fagan, AM Forlenza, O Frisoni, GB Galasko, D Galimberti, D Hampel, H Handberg, A Heneka, MT Herskovits, AZ Herukka, SK Holtzman, DM Humpel, C Hyman, BT Iqbal, K Jucker, M Kaeser, SA Kaiser, E Kapaki, E Kidd, D Klivenyi, P Knudsen, CS Kummer, MP Lui, J Llado, A Lewczuk, P Li, QX Martins, R Masters, C McAuliffe, J Mercken, M Moghekar, A Molinuevo, JL Montine, TJ Nowatzke, W O'Brien, R Otto, M Paraskevas, GP Parnetti, L Petersen, RC Prvulovic, D de Reus, HPM Rissman, RA Scarpini, E Stefani, A Soininen, H Schroder, J Shaw, LM Skinningsrud, A Skrogstad, B Spreer, A Talib, L Teunissen, C Trojanowski, JQ Tumani, H Umek, RM Van Broeck, B Vanderstichele, H Vecsei, L Verbeek, MM Windisch, M Zhang, J Zetterberg, H Blennow, K AF Mattsson, Niklas Andreasson, Ulf Persson, Staffan Arai, Hiroyuki Batish, Sat Dev Bernardini, Sergio Bocchio-Chiavetto, Luisella Blankenstein, Marinus A. Carrillo, Maria C. Chalbot, Sonia Coart, Els Chiasserini, Davide Cutler, Neal Dahlfors, Gunilla Duller, Stefan Fagan, Anne M. Forlenza, Orestes Frisoni, Giovanni B. Galasko, Douglas Galimberti, Daniela Hampel, Harald Handberg, Aase Heneka, Michael T. Herskovits, Adrianna Z. Herukka, Sanna-Kaisa Holtzman, David M. Humpel, Christian Hyman, Bradley T. Iqbal, Khalid Jucker, Mathias Kaeser, Stephan A. Kaiser, Elmar Kapaki, Elisabeth Kidd, Daniel Klivenyi, Peter Knudsen, Cindy S. Kummer, Markus P. Lui, James Llado, Albert Lewczuk, Piotr Li, Qiao-Xin Martins, Ralph Masters, Colin McAuliffe, John Mercken, Marc Moghekar, Abhay Luis Molinuevo, Jose Montine, Thomas J. Nowatzke, William O'Brien, Richard Otto, Markus Paraskevas, George P. Parnetti, Lucilla Petersen, Ronald C. Prvulovic, David de Reus, Herman P. M. Rissman, Robert A. Scarpini, Elio Stefani, Alessandro Soininen, Hilkka Schroeder, Johannes Shaw, Leslie M. Skinningsrud, Anders Skrogstad, Brith Spreer, Annette Talib, Leda Teunissen, Charlotte Trojanowski, John Q. Tumani, Hayrettin Umek, Robert M. Van Broeck, Bianca Vanderstichele, Hugo Vecsei, Laszlo Verbeek, Marcel M. Windisch, Manfred Zhang, Jing Zetterberg, Henrik Blennow, Kaj TI The Alzheimer's Association external quality control program for cerebrospinal fluid biomarkers SO ALZHEIMERS & DEMENTIA LA English DT Article DE Alzheimer's disease; Cerebrospinal fluid; Biomarkers; External assurance; External control; Proficiency testing ID MILD COGNITIVE IMPAIRMENT; AMYLOID-BETA PEPTIDES; TAU-PROTEINS; PHOSPHORYLATED TAU; XMAP TECHNOLOGY; CSF BIOMARKERS; DISEASE; PREDICTION; MARKERS; BETA-AMYLOID((1-42)) AB Background: The cerebrospinal fluid (CSF) biomarkers amyloid beta (A beta)-42, total-tau (T-tau), and phosphorylated-tau (P-tau) demonstrate good diagnostic accuracy for Alzheimer's disease (AD). However, there are large variations in biomarker measurements between studies, and between and within laboratories. The Alzheimer's Association has initiated a global quality control program to estimate and monitor variability of measurements, quantify batch-to-batch assay variations, and identify sources of variability. In this article, we present the results from the first two rounds of the program. Methods: The program is open for laboratories using commercially available kits for A beta, T-tau, or P-tau. CSF samples (aliquots of pooled CSF) are sent for analysis several times a year from the Clinical Neurochemistry Laboratory at the Molndal campus of the University of Gothenburg, Sweden. Each round consists of three quality control samples. Results: Forty laboratories participated. Twenty-six used INNOTEST enzyme-linked immunosorbent assay kits, 14 used Luminex xMAP with the INNO-BIA AlzBio3 kit (both measure A beta-(1-42), P-tau(181P), and T-tau), and 5 used Mesa Scale Discovery with the A beta triplex (A beta N-42, A beta N-40, and A beta N-38) or T-tau kits. The total coefficients of variation between the laboratories were 13% to 36%. Five laboratories analyzed the samples six times on different occasions. Within-laboratory precisions differed considerably between biomarkers within individual laboratories. Conclusions: Measurements of CSF AD biomarkers show large between-laboratory variability, likely caused by factors related to analytical procedures and the analytical kits. Standardization of laboratory procedures and efforts by kit vendors to increase kit performance might lower variability, and will likely increase the usefulness of CSF AD biomarkers. (C) 2011 The Alzheimer's Association. All rights reserved. C1 [Mattsson, Niklas; Andreasson, Ulf; Persson, Staffan; Zetterberg, Henrik; Blennow, Kaj] Univ Gothenburg, Sahlgrenska Univ Hosp, Clin Neurochem Lab,Inst Neurosci & Physiol, Dept Psychiat & Neurochem,Sahlgrenska Acad, Molndal, Sweden. [Arai, Hiroyuki] Tohoku Univ, Inst Dev Aging & Canc, Dept Geriatr & Gerontol, Sendai, Miyagi 980, Japan. [Batish, Sat Dev; McAuliffe, John] Athena Diagnost Inc, Worcester, MA USA. [Bernardini, Sergio] Univ Roma Tor Vergata, Dept Biochim Clin, Rome, Italy. [Bocchio-Chiavetto, Luisella; Frisoni, Giovanni B.] IRCCS Ctr S Giovanni di Dio Fatebenefratelli, Brescia, Italy. [Blankenstein, Marinus A.; Teunissen, Charlotte] Vrije Univ Amsterdam Med Ctr, Dept Clin Chem, Amsterdam, Netherlands. [Carrillo, Maria C.] Alzheimers Assoc, Chicago, IL USA. [Chalbot, Sonia; Iqbal, Khalid] New York State Inst Basic Res Dev Disabil, Dept Neurochem, Staten Isl, NY USA. [Coart, Els; Vanderstichele, Hugo] Innogenetics, Ghent, Belgium. [Chiasserini, Davide; Parnetti, Lucilla] Univ Perugia, Ctr Memory Disturbances, Lab Clin Neurochem, Neurol Sect, I-06100 Perugia, Italy. [Cutler, Neal; Nowatzke, William] Worldwide Clin Trials, King Of Prussia, PA USA. [Dahlfors, Gunilla] Karolinska Univ Hosp, Karolinska Univ Lab, Dept Clin Chem, Stockholm, Sweden. [Duller, Stefan; Windisch, Manfred] JSW Life Sci GmbH, Grambach, Austria. [Fagan, Anne M.; Holtzman, David M.] Washington Univ, Sch Med, Dept Neurol, Alzheimers Dis Res Ctr,Hope Ctr Neurol Disorders, St Louis, MO 63110 USA. [Forlenza, Orestes; Talib, Leda] Univ Sao Paulo, Fac Med, Lab Neurosci LIM 27, Dept Psychiat, Sao Paulo, Brazil. [Forlenza, Orestes; Talib, Leda] Univ Sao Paulo, Fac Med, Lab Neurosci LIM 27, Inst Psychiat, Sao Paulo, Brazil. [Galasko, Douglas; Rissman, Robert A.] Univ Calif San Diego, Sch Med, Dept Neurosci, La Jolla, CA 92093 USA. [Galimberti, Daniela; Scarpini, Elio] Univ Milan, Dept Neurol Sci, Milan, Italy. [Hampel, Harald; Prvulovic, David] Goethe Univ Frankfurt, Dept Psychiat Psychosomat Med & Psychotherapy, Frankfurt, Germany. [Handberg, Aase; Knudsen, Cindy S.] Aarhus Univ Hosp, Aarhus Hosp, Dept Clin Biochem, DK-8000 Aarhus, Denmark. [Heneka, Michael T.; Kummer, Markus P.] Univ Bonn, Klin Neurowissensch, Neurol Klin & Poliklin, D-5300 Bonn, Germany. [Herskovits, Adrianna Z.; Hyman, Bradley T.] Harvard Univ, MassGen Inst Neurodegenerat Dis, Massachusetts Gen Hosp, Sch Med,Massachusetts Alzheimer Dis Res Ctr, Charlestown, MA USA. [Herukka, Sanna-Kaisa; Soininen, Hilkka] Univ Eastern Finland, Kuopio Univ Hosp, Dept Neurol, Kuopio, Finland. [Humpel, Christian] Innsbruck Med Univ, Lab Psychiat & Expt Alzheimers Res, Innsbruck, Austria. [Jucker, Mathias; Kaeser, Stephan A.] Univ Tubingen, Dept Cellular Neurol, Hertie Inst Clin Brain Res, Tubingen, Germany. [Jucker, Mathias; Kaeser, Stephan A.] DZNE German Ctr Neurodegenerat Dis, Tubingen, Germany. [Kaiser, Elmar; Schroeder, Johannes] Univ Heidelberg, Sect Geriatr Psychiat, Heidelberg, Germany. [Kapaki, Elisabeth; Paraskevas, George P.] Univ Athens, Eginit Hosp, Dept Neurol 1, Athens 11528, Greece. [Kidd, Daniel] Janssen Alzheimer Immunotherapy Res & Dev, San Francisco, CA USA. [Klivenyi, Peter; Vecsei, Laszlo] Univ Szeged, Dept Neurol, Szeged, Hungary. [Lui, James; Martins, Ralph] Edith Cowan Univ, Ctr Excellence Alzheimers Dis Res & Care, Sch Exercise Biomed & Hlth Sci, Perth, WA, Australia. [Llado, Albert; Luis Molinuevo, Jose] Hosp Clin Barcelona, Alzheimers Dis & Other Cognit Disorders Unit, Neurol Serv, Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain. [Lewczuk, Piotr] Univ Klinikum Erlangen, Dept Psychiat & Psychotherapy, Erlangen, Germany. [Li, Qiao-Xin; Masters, Colin] Univ Melbourne, Neuropathol Res Grp, Mental Hlth Res Inst, Melbourne, Vic, Australia. [Mercken, Marc; Van Broeck, Bianca] J&J, Janssen Pharmaceut, Beerse, Belgium. [Moghekar, Abhay; O'Brien, Richard] Johns Hopkins Sch Med, Dept Neurol, Baltimore, MD USA. [Montine, Thomas J.; Zhang, Jing] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Otto, Markus; Tumani, Hayrettin] Univ Ulm, Dept Neurol, D-7900 Ulm, Germany. [Petersen, Ronald C.] Mayo Clin, Alzheimers Dis Res Ctr, Rochester, MN USA. [de Reus, Herman P. M.; Verbeek, Marcel M.] Radboud Univ Nijmegen, Dept Neurol, Alzheimer Ctr Nijmegen, Donders Inst Brain Cognit & Behav,Med Ctr, NL-6525 ED Nijmegen, Netherlands. [de Reus, Herman P. M.; Verbeek, Marcel M.] Radboud Univ Nijmegen, Dept Lab Med, Alzheimer Ctr Nijmegen, Donders Inst Brain Cognit & Behav,Med Ctr, NL-6525 ED Nijmegen, Netherlands. [Stefani, Alessandro] IRCCS Fdn S Lucia, Rome, Italy. [Shaw, Leslie M.; Trojanowski, John Q.] Univ Penn, Med Ctr, ADNI Biomarker Core, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Skinningsrud, Anders; Skrogstad, Brith] Akershus Univ Hosp, Ctr Lab Med, Dept Clin Biochem, Oslo, Norway. [Spreer, Annette] Univ Gottingen, Dept Neurol, D-3400 Gottingen, Germany. [Umek, Robert M.] Meso Scale Discovery, Gaithersburg, MD USA. RP Mattsson, N (reprint author), Univ Gothenburg, Sahlgrenska Univ Hosp, Clin Neurochem Lab,Inst Neurosci & Physiol, Dept Psychiat & Neurochem,Sahlgrenska Acad, Molndal, Sweden. EM niklas.mattsson@neuro.gu.se RI Handberg, Aase/G-6744-2011; Bocchio Chiavetto, Luisella/D-3884-2012; Forlenza, Orestes/B-8848-2013; Otto, Markus/F-4304-2015; Verbeek, Marcel/D-1971-2010; Frisoni, Giovanni B/K-1360-2016; Vecsei, Laszlo/B-2066-2010; Chiasserini, Davide/K-7074-2016; OI Blankenstein, Marinus/0000-0003-1186-0770; Kummer, Markus/0000-0002-0993-2918; Bocchio Chiavetto, Luisella/0000-0002-9801-603X; Otto, Markus/0000-0003-4273-4267; Frisoni, Giovanni B/0000-0002-6419-1753; Vecsei, Laszlo/0000-0001-8037-3672; Chiasserini, Davide/0000-0002-1169-3258; galimberti, daniela/0000-0002-9284-5953; Molinuevo, Jose Luis/0000-0003-0485-6001; STEFANI, ALESSANDRO/0000-0002-1806-8922; scarpini, elio/0000-0002-6395-2119 FU Alzheimer's Association FX A generous grant from the Alzheimer's Association supported this study. NR 30 TC 176 Z9 178 U1 3 U2 32 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD JUL PY 2011 VL 7 IS 4 BP 386 EP 395 DI 10.1016/j.jalz.2011.05.2243 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 802DT UT WOS:000293490200003 PM 21784349 ER PT J AU Breitner, JC Baker, LD Montine, TJ Meinert, CL Lyketsos, CG Ashe, KH Brandt, J Craft, S Evans, DE Green, RC Ismail, MS Martin, BK Mullan, MJ Sabbagh, M Tariot, PN AF Breitner, John C. Baker, Laura D. Montine, Thomas J. Meinert, Curtis L. Lyketsos, Constantine G. Ashe, Karen H. Brandt, Jason Craft, Suzanne Evans, Denis E. Green, Robert C. Ismail, M. Saleem Martin, Barbara K. Mullan, Michael J. Sabbagh, Marwan Tariot, Pierre N. CA ADAPT Res Grp TI Extended results of the Alzheimer's disease anti-inflammatory prevention trial SO ALZHEIMERS & DEMENTIA LA English DT Article DE Alzheimer's disease; Randomized controlled trial; Nonsteroidal anti-inflammatory drugs; Follow-up; Biomarkers; Hypothesis ID RANDOMIZED CONTROLLED-TRIAL; MILD COGNITIVE IMPAIRMENT; MINI-MENTAL STATE; SYNAPTIC PLASTICITY; DRUGS; CELECOXIB; NAPROXEN; NSAIDS; RISK; CYCLOOXYGENASE AB Background: Epidemiologic evidence suggests that nonsteroidal anti-inflammatory drugs (NSAIDs) delay onset of Alzheimer's dementia (AD), but randomized trials show no benefit from NSAIDs in patients with symptomatic AD. The Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT) randomized 2528 elderly persons to naproxen or celecoxib versus placebo for 2 years (standard deviation = 11 months) before treatments were terminated. During the treatment interval, 32 cases of AD revealed increased rates in both NSAID-assigned groups. Methods: We continued the double-masked ADAPT protocol for 2 additional years to investigate incidence of AD (primary outcome). We then collected cerebrospinal fluid (CSF) from 117 volunteer participants to assess their ratio of CSF tau to A beta(1-42). Results: Including 40 new events observed during follow-up of 2071 randomized individuals (92% of participants at treatment cessation), there were 72 AD cases. Overall, NSAID-related harm was no longer evident, but secondary analyses showed that increased risk remained notable in the first 2.5 years of observations, especially in 54 persons enrolled with cognitive impairment-no dementia (CIND). These same analyses showed later reduction in AD incidence among asymptomatic enrollees who were given naproxen. CSF biomarker assays suggested that the latter result reflected reduced Alzheimer-type neurodegeneration. Conclusions: These data suggest a revision of the original ADAPT hypothesis that NSAIDs reduce AD risk, as follows: NSAIDs have an adverse effect in later stages of AD pathogenesis, whereas asymptomatic individuals treated with conventional NSAIDs such as naproxen experience reduced AD incidence, but only after 2 to 3 years. Thus, treatment effects differ at various stages of disease. This hypothesis is consistent with data from both trials and epidemiological studies. (C) 2011 The Alzheimer's Association. All rights reserved. C1 [Breitner, John C.] Douglas Mental Hlth Univ Inst Res Ctr, Ctr Studies Prevent Alzheimers Dis, Montreal, PQ, Canada. [Breitner, John C.] McGill Univ, Dept Psychiat, Montreal, PQ, Canada. [Breitner, John C.; Baker, Laura D.; Craft, Suzanne] VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. [Baker, Laura D.; Craft, Suzanne] Univ Washington, Med Ctr, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Montine, Thomas J.] Univ Washington, Med Ctr, Dept Pathol, Div Neuropathol, Seattle, WA 98195 USA. [Meinert, Curtis L.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Meinert, Curtis L.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. [Lyketsos, Constantine G.; Brandt, Jason] Johns Hopkins Med Inst, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Lyketsos, Constantine G.; Brandt, Jason] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Ashe, Karen H.] Minneapolis VA Med Ctr, Ctr Geriatr Res Educ & Clin, Minneapolis, MN USA. [Ashe, Karen H.] Univ Minnesota, Sch Med, N Bud Grossman Ctr Memory Res & Care, Dept Neurol, Minneapolis, MN 55455 USA. [Ashe, Karen H.] Univ Minnesota, Sch Med, N Bud Grossman Ctr Memory Res & Care, Dept Neurosci, Minneapolis, MN 55455 USA. [Evans, Denis E.] Rush Univ, Med Ctr, Rush Inst Healthy Aging, Chicago, IL 60612 USA. [Green, Robert C.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Green, Robert C.] Boston Univ, Sch Med, Dept Genet, Boston, MA 02118 USA. [Green, Robert C.] Boston Univ, Sch Med, Dept Epidemiol, Boston, MA 02118 USA. [Ismail, M. Saleem] Univ Rochester, Dept Psychiat, Rochester, NY USA. [Martin, Barbara K.] Lancaster Heart & Stroke Fdn, Lancaster, PA USA. [Mullan, Michael J.] Roskamp Inst, Sarasota, FL USA. [Sabbagh, Marwan] Banner Sun Hlth Res Inst, Cleo Roberts Ctr, Sun City, AZ USA. [Tariot, Pierre N.] Banner Alzheimers Inst, Memory Disorders Ctr, Phoenix, AZ USA. RP Breitner, JC (reprint author), Douglas Mental Hlth Univ Inst Res Ctr, Ctr Studies Prevent Alzheimers Dis, Montreal, PQ, Canada. EM john.breitner@mcgill.ca OI Brandt, Jason/0000-0001-7381-6244; Mullan, Michael/0000-0002-1473-7527 FU U.S. Department of Veterans Affairs Puget Sound Health Care System, Seattle, Washington by NIH [U01-AG-15477, R01-AG-24010, P50-AG-05136]; N. Bud Grossman Center for Memory Research and Care, Minneapolis, MN; McGill University FX This work was supported by the U.S. Department of Veterans Affairs Puget Sound Health Care System, Seattle, Washington, by NIH grants U01-AG-15477, R01-AG-24010, and P50-AG-05136, and by the N. Bud Grossman Center for Memory Research and Care, Minneapolis, MN, and McGill University. Celecoxib and matching placebo were provided by Pfizer, Inc. Naproxen sodium and its placebo were provided by Bayer Consumer Healthcare. No funding or supporting agency had any role in the design or conduct of the study; collection, management, or interpretation of the data; or preparation of the manuscript. Courtesy copies of the manuscript have been provided to the funding agency and to Pfizer, Inc., and Bayer Consumer Heathcare. Data management, descriptive statistics, and primary analyses for ADAPT were provided by the ADAPT Coordinating Center under direction of Drs. Meinert and Martin. The planned and ad hoc secondary analyses, as well as derivation of additional descriptive statistics, were performed by Dr. Baker. Each of these parties verified the analytical results of the others. The authors are deeply indebted to Ms. Jane Anau for her superb technical assistance, to the outstanding staff of the ADAPT field sites and Coordinating Center and, especially, to the ADAPT participant cohort for their persistent commitment and generosity of time and effort. NR 38 TC 144 Z9 151 U1 5 U2 34 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD JUL PY 2011 VL 7 IS 4 BP 402 EP 411 DI 10.1016/j.jalz.2010.12.014 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 802DT UT WOS:000293490200005 PM 21784351 ER PT J AU Johnson, SC La Rue, A Hermann, BP Xu, GF Koscik, RL Jonaitis, EM Bendlin, BB Hogan, KJ Roses, AD Saunders, AM Lutz, MW Asthana, S Green, RC Sager, MA AF Johnson, Sterling C. La Rue, Asenath Hermann, Bruce P. Xu, Guofan Koscik, Rebecca L. Jonaitis, Erin M. Bendlin, Barbara B. Hogan, Kirk J. Roses, Allen D. Saunders, Ann M. Lutz, Michael W. Asthana, Sanjay Green, Robert C. Sager, Mark A. TI The effect of TOMM40 poly-T length on gray matter volume and cognition in middle-aged persons with APOE epsilon 3/epsilon 3 genotype SO ALZHEIMERS & DEMENTIA LA English DT Article DE Alzheimer's disease; Posterior cingulate; Risk factors; Genetics; APOE; TOMM40 ID ONSET ALZHEIMERS-DISEASE; APOLIPOPROTEIN-E; FAMILY-HISTORY; PARENTAL HISTORY; HIPPOCAMPAL ATROPHY; QUANTITATIVE TRAIT; E4 ALLELE; MEMORY; ASSOCIATION; IMPAIRMENT AB Objective: Apolipoprotein E (APOE) genotypes are associated with variable risk of developing late-onset Alzheimer's disease (LOAD), with APOE epsilon 4 (APOE epsilon 4) having higher risk. A variable poly-T length polymorphism at rs10524523, within intron 6 of the translocase of the outer mitochondria] membrane (TOMM40) gene, has been shown to influence age of onset in LOAD, with very long (VL) poly-T length associated with earlier disease onset, and short poly-T length associated with later onset. In this study, we tested the hypothesis that brain and cognitive changes suggestive of presymptomatic LOAD may be associated with this TOMM40 polymorphism. Methods: Among healthy APOE epsilon 3 homozygous adults (N = 117; mean age, 55 years), we compared those who were homozygous for VL/VL (n = 35) TOMM40 poly-T lengths (who were presumably at higher risk) with those homozygous for short (S/S; n = 38) poly-T lengths, as well as those with heterozygous (S/VL; n = 44) poly-T length polymorphisms, on measures of learning and memory and on structural brain imaging. Results: The VL/VL group showed lower performance than the S/S TOMM40 group on primacy retrieval from a verbal list learning task, a finding which is also seen in early Alzheimer's disease. A dose-dependent increase in the VL TOMM40 polymorphism (from no VL alleles, to S/VL heterozygous, to VL/VL homozygous) was associated with decreasing gray matter volume in the ventral posterior cingulate and medial ventral precuneus, a region of the brain affected early in LOAD. Conclusions: These findings among APOE epsilon 3/epsilon 3 late middle-aged adults suggest that a subgroup with VL TOMM40 poly-T lengths may be experiencing incipient LOAD-related cognitive and brain changes. (C) 2011 The Alzheimer's Association. All rights reserved. C1 [Johnson, Sterling C.; La Rue, Asenath; Hermann, Bruce P.; Koscik, Rebecca L.; Jonaitis, Erin M.; Hogan, Kirk J.; Asthana, Sanjay; Sager, Mark A.] Univ Wisconsin, Sch Med & Publ Hlth, Wisconsin Alzheimers Inst, Madison, WI 53706 USA. [Johnson, Sterling C.; Xu, Guofan; Bendlin, Barbara B.; Asthana, Sanjay] William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI USA. [Johnson, Sterling C.; La Rue, Asenath; Hermann, Bruce P.; Xu, Guofan; Bendlin, Barbara B.; Asthana, Sanjay; Sager, Mark A.] Univ Wisconsin, Sch Med & Publ Hlth, Wisconsin Alzheimers Dis Res Ctr, Madison, WI USA. [Roses, Allen D.; Saunders, Ann M.; Lutz, Michael W.] Duke Univ, Deane Drug Discovery Inst, Durham, NC USA. [Green, Robert C.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Green, Robert C.] Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA. RP Johnson, SC (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Wisconsin Alzheimers Inst, Madison, WI 53706 USA. EM scjohnson@wisc.edu FU NIH [R01 AG027161, R01 AG021155, P50 AG033514]; Alzheimer's Disease Research Center; Clinical and Translational Science Award [UL1RR025011]; Helen Bader Foundation; Northwestern Mutual Foundation; Extendicare Foundation; Veterans Administration; [RC1AG035635-01] FX This study was supported by grants for the NIH: R01 AG027161; R01 AG021155; P50 AG033514 Alzheimer's Disease Research Center; and UL1RR025011 Clinical and Translational Science Award. Dr. Roses and Dr. Lutz are supported in part by RC1AG035635-01. Portions of this research were supported by the Helen Bader Foundation, Northwestern Mutual Foundation, Extendicare Foundation, and from the Veterans Administration including facilities and resources at the Geriatric Research Education and Clinical Center of the William S. Middleton Memorial Veterans Hospital, Madison, WI. NR 40 TC 40 Z9 40 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD JUL PY 2011 VL 7 IS 4 BP 456 EP 465 DI 10.1016/j.jalz.2010.11.012 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 802DT UT WOS:000293490200011 PM 21784354 ER PT J AU Jack, CR Barkhof, F Bernstein, MA Cantillon, M Cole, PE DeCarli, C Dubois, B Duchesne, S Fox, NC Frisoni, GB Hampel, H Hill, DLG Johnson, K Mangin, JF Scheltens, P Schwarz, AJ Sperling, R Suhy, J Thompson, PM Weiner, M Foster, NL AF Jack, Clifford R., Jr. Barkhof, Frederik Bernstein, Matt A. Cantillon, Marc Cole, Patricia E. DeCarli, Charles Dubois, Bruno Duchesne, Simon Fox, Nick C. Frisoni, Giovanni B. Hampel, Harald Hill, Derek L. G. Johnson, Keith Mangin, Jean-Francois Scheltens, Philip Schwarz, Adam J. Sperling, Reisa Suhy, Joyce Thompson, Paul M. Weiner, Michael Foster, Norman L. TI Steps to standardization and validation of hippocampal volumetry as a biomarker in clinical trials and diagnostic criterion for Alzheimer's disease SO ALZHEIMERS & DEMENTIA LA English DT Article DE Alzheimer's disease; Biomarkers; Magnetic resonance imaging; Hippocampus; Biomarker standards ID MILD COGNITIVE IMPAIRMENT; MEDIAL TEMPORAL ATROPHY; BRAIN ATROPHY; MRI MEASURES; PROBABLE AD; DEMENTIA; SEGMENTATION; PROGRESSION; CLASSIFICATION; PREDICTORS AB Background: The promise of Alzheimer's disease biomarkers has led to their incorporation in new diagnostic criteria and in therapeutic trials; however, significant barriers exist to widespread use. Chief among these is the lack of internationally accepted standards for quantitative metrics. Hippocampal volumetry is the most widely studied quantitative magnetic resonance imaging measure in Alzheimer's disease and thus represents the most rational target for an initial effort at standardization. Methods and Results: The authors of this position paper propose a path toward this goal. The steps include the following: ( I) Establish and empower an oversight board to manage and assess the effort, (2) adopt the standardized definition of anatomic hippocampal boundaries on magnetic resonance imaging arising from the European Alzheimer's Disease Centers Alzheimer's Disease Neuroimaging Initiative hippocampal harmonization effort as a reference standard, (3) establish a scientifically appropriate, publicly available reference standard data set based on manual delineation of the hippocampus in an appropriate sample of subjects (Alzheimer's Disease Neuroimaging Initiative), and (4) define minimum technical and prognostic performance metrics for validation of new measurement techniques using the reference standard data set as a benchmark. Conclusions: Although manual delineation of the hippocampus is the best available reference standard, practical application of hippocampal volumetry will require automated methods. Our intent was to establish a mechanism for credentialing automated software applications to achieve internationally recognized accuracy and prognostic performance standards that lead to the systematic evaluation and then widespread acceptance and use of hippocampal volumetry. The standardization and assay validation process outlined for hippocampal volumetry was envisioned as a template that could be applied to other imaging biomarkers. (C) 2011 The Alzheimer's Association. All rights reserved. C1 [Jack, Clifford R., Jr.; Bernstein, Matt A.] Mayo Clin, Dept Radiol, Rochester, MN 55905 USA. [Cantillon, Marc] Crit Path Inst, Coalit Major Dis, Rockville, MD USA. [Cole, Patricia E.] Imagepace, Cincinnati, OH USA. [DeCarli, Charles] Univ Calif Davis, Dept Neurol, Sacramento, CA 95817 USA. [DeCarli, Charles] Univ Calif Davis, Ctr Neurosci, Sacramento, CA 95817 USA. [Dubois, Bruno] Univ Paris 06, Dept Neurol, Salpetriere Hosp, Paris, France. [Duchesne, Simon] Ctr Rech Univ Laval Robert Giffard, Dept Radiol, Quebec City, PQ, Canada. [Duchesne, Simon] Univ Laval, Dept Radiol, Quebec City, PQ, Canada. [Fox, Nick C.] UCL Inst Neurol, Dementia Res Ctr, London, England. [Frisoni, Giovanni B.] IRCCS San Giovanni di Dio FBF, Lab Epidemiol & Neuroimaging, Brescia, Italy. [Hampel, Harald] Goethe Univ Frankfurt, Dept Psychiat Psychosomat Med & Psychotherapy, Frankfurt, Germany. [Hill, Derek L. G.] UCL, Dept Med Phys & Bioengn, Ctr Med Image Comp, London, England. [Hill, Derek L. G.] IXICO Ltd, London Biosci Innovat Ctr, London, England. [Johnson, Keith] Harvard Univ, Brigham & Womens Hosp, Dept Neurol, Sch Med,Ctr Alzheimer Res & Treatment, Boston, MA 02115 USA. [Johnson, Keith] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Mol Imaging, Boston, MA USA. [Mangin, Jean-Francois] CEA, I2BM, Saclay, France. [Schwarz, Adam J.] Eli Lilly & Co, Translat Med, Indianapolis, IN 46285 USA. [Sperling, Reisa] Harvard Univ, Brigham & Womens Hosp, Dept Neurol, Sch Med, Boston, MA 02115 USA. [Suhy, Joyce] Synarc Inc, Div Neurol, San Francisco, CA USA. [Thompson, Paul M.] Univ Calif Los Angeles, Sch Med, Dept Neurol, Lab Neuro Imaging, Los Angeles, CA 90024 USA. [Weiner, Michael] VA Med Ctr, Ctr Imaging Neurodegenerat Dis, Dept Vet Affairs, San Francisco, CA USA. [Weiner, Michael] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Foster, Norman L.] Univ Utah, Dept Neurol, Ctr Alzheimers Care Imaging & Res, Salt Lake City, UT USA. RP Jack, CR (reprint author), Mayo Clin, Dept Radiol, Rochester, MN 55905 USA. EM Jack.Clifford@mayo.edu RI Jack, Clifford/F-2508-2010; Fox, Nick/B-1319-2009; Frisoni, Giovanni B/K-1360-2016; Duchesne, Simon/O-4852-2016; OI Jack, Clifford/0000-0001-7916-622X; Fox, Nick/0000-0002-6660-657X; Frisoni, Giovanni B/0000-0002-6419-1753; Duchesne, Simon/0000-0002-6326-0745; Bernstein, Matt/0000-0003-3770-0441 FU Pfizer; Allon; Baxter, Inc.; NIA [R01 -AG11378, P50-AG16574, R21-AG38736, U01 AG024904-01]; Mayo Foundation; Pfizer Inc.; Baxter Allon; Medical Research Council (MRC) [00801306, G0601846]; National Institutes of Health (NIH) [U01 AG024904]; Alzheimer Alzheimer Research Trust [ART/RF/2007/1]; Engineering and Physical Sciences Research Council (EPSRC) [GR/S48844/01]; Wyeth Int'l; Lilly Int'l; Lundbeck Italia; AA; VUmc Fonds; Elan/Wyeth; Forest; University of California; Davis, Tel-Aviv University Medical School; Colloquium Paris; Ipsen; Wenner-Gren Foundations; Social Security Administration; Korean Neurological Association; National Institutes of Health; Washington University at St. Louis; Banner Alzheimer's Institute; Merck; Avid FX C.R.J., Jr. serves as a consultant for Janssen, Lilly, General Electric (GE), Johnson and Johnson, Eisai, and Elan. He is an investigator in clinical trials sponsored by Pfizer, Allon and Baxter, Inc. He receives research funding from the NIA (R01 -AG11378 [PI], P50-AG16574 [Co-I], R21-AG38736 [Co-I], and U01 AG024904-01 [Co-I]), and the Alexander Family Alzheimer's Disease Research Professorship of the Mayo Foundation. He owns stock in Johnson and Johnson. F.B. has received compensation for consulting from Roche, Lundbeck, Janssen Alz Immunotherapy, and GE Medical Systems; M.A.B. receives research contract funding from Pfizer Inc., and Baxter Allon; M.C. is an employee of Coalition Against Major Diseases. P.E.C. reports no conflicts; C.D.C. reports no conflicts; BD. has served on the advisory boards of GE healthcare and Eisai/Pfizer; S.D. reports no conflicts; N.C.F. served on the scientific advisory boards of Alzheimer's Research Forum, Alzheimer's Society and Alzheimer's Research Trust, and editorial boards of Alzheimer's Disease and Associated Disorders; Neurodegenerative Diseases and BioMed Central Alzheimer's Research and Therapy. He holds a patent for QA Box that may accrue revenue. In the last 5 years, his research group has received payment for consultancy or for conducting studies from Abbott Laboratories, Elan Pharmaceuticals, Eisai, Eli Lilly, GE Healthcare, Information extraction from imaging company (IXICO), Lundbeck, Pfizer Inc, Sanofi-Aventis, and Wyeth Pharmaceuticals. He receives research support from Medical Research Council (MRC) (00801306 [PI], G0601846 [PI]), National Institutes of Health (NIH) (U01 AG024904 [Co-investigator{sub contract)]), Alzheimer Alzheimer Research Trust (ART/RF/2007/1 [PIA National Institute for Health Research (NIHR) (Senior Investigator), and Engineering and Physical Sciences Research Council (EPSRC) (GR/S48844/01 [PI]); serves/has served on the advisory boards for Lilly, Bristol-Myers Squibb, Bayer, Lundbeck, Elan, Astra Zeneca, Pfizer, Taurx, and Wyeth. He is a member of the editorial boards of Lancet Neurology, Aging Clinical & Experimental Research, Alzheimer's Disease & Associated Disorders, and Neurodegenerative Diseases. He serves as the Imaging Selection Editor of Neurobiology of Aging. He has received grants from Wyeth Int'l, Lilly Int'l, Lundbeck Italia, and the AA; H.H. disclosed no conflicts; D.L.G.H. is an employee and stock holder in IXICO Ltd; K.J. reports no conflicts; J.-F.M. reports no conflicts; P.S. serves/has served on the advisory boards of Genentech, Novartis, Roche, Danone, Nutricia, Baxter, and Lundbeck. He has been a speaker at symposia organized by Lundbeck, Merz, Danone, Novartis, Roche, and Genentech. For all his activities, he receives no personal compensation.; He serves on the editorial board of Alzheimer's Research & Therapy and Alzheimers Disease and Associated Disorders, is a member of the scientific advisory board of the European Union Joint Programming Initiative and the French National Plan Alzheimer. The Alzheimer Center receives unrestricted funding from various sources through the VUmc Fonds; A.J.S. is an employee and shareholder of Eli Lilly and Company; R.S. has been a consultant for Pfizer, Janssen, Elan, Bristol-Myers-Squibb, Bayer, and Avid (unpaid). She is a site investigator for clinical trials for Bristol-Myers-Squibb, Pfizer, Janssen, and Avid; J.S. is an employee of Synarc; P.M.T. reports no conflicts; M.W. serves/has served on the advisory boards of Elan/Wyeth, Novartis, Banner, Veterans Affairs Central Office, Lilly, Araclon and Insitut Catala de Neurociencies Aplicades, Biogen Idec, and Pfizer. He serves/has served as a consultant for Elan/Wyeth, Novartis, Forest, Ipsen, Daiichi Sankyo, Inc., Astra Zeneca, Araclon, Medivation/Pfizer, TauRx Therapeutics Ltd, Bayer Healthcare, Biogen Idec, Exonhit Therapeutics, Alzheimer's Association (SA), Servier, Synarc, and Pfizer. Funding for his travel has been provided by Elan/Wyeth, AA, Forest, University of California, Davis, Tel-Aviv University Medical School, Colloquium Paris, Ipsen, Wenner-Gren Foundations, Social Security Administration, Korean Neurological Association, National Institutes of Health, Washington University at St. Louis, Banner Alzheimer's Institute, Clinical Trials on Alzheimer's Disease (CTAD), Veterans Affairs Central Office, Beijing Institute of Geriatrics, Innogenetics, New York University, NeuroVigil, Inc., Centre Hospitalier Regional (CHRU)-Hospital Roger Salengro, Siemens, AstraZeneca, Geneva University Hospitals, Lilly, University of California, San Diego ADNI, Paris University, Institut Catala de Neurociencies Aplicades, University of New Mexico School of Medicine, Pfizer, Paul Sabatier University, and Novartis. He serves on the editorial advisory boards of Alzheimer's and Dementia and MRI. He has received honoraria from American Academy of Neurology, Ipsen, NeuroVigil, Inc., and Insitut Catala de Neurociencies Aplicades. He receives research support from Merck and Avid. He owns stock in Synarc and Elan; N.L.F. disclosed no conflicts. NR 95 TC 78 Z9 78 U1 2 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD JUL PY 2011 VL 7 IS 4 BP 474 EP 485 DI 10.1016/j.jalz.2011.04.007 PG 12 WC Clinical Neurology SC Neurosciences & Neurology GA 802DT UT WOS:000293490200013 PM 21784356 ER PT J AU Wang, C Jackson, G Jones, TH Matsumoto, AM Nehra, A Perelman, MA Swerdloff, RS Traish, A Zitzmann, M Cunningham, G AF Wang, Christina Jackson, Graham Jones, T. Hugh Matsumoto, Alvin M. Nehra, Ajay Perelman, Michael A. Swerdloff, Ronald S. Traish, Abdul Zitzmann, Michael Cunningham, Glenn TI Low Testosterone Associated With Obesity and the Metabolic Syndrome Contributes to Sexual Dysfunction and Cardiovascular Disease Risk in Men With Type 2 Diabetes SO DIABETES CARE LA English DT Review ID HORMONE-BINDING GLOBULIN; LOW SERUM TESTOSTERONE; ANDROGEN DEPRIVATION THERAPY; LOOK-AHEAD TRIAL; MIDDLE-AGED MEN; QUALITY-OF-LIFE; ERECTILE DYSFUNCTION; HYPOGONADAL MEN; DOUBLE-BLIND; INSULIN SENSITIVITY C1 [Wang, Christina; Swerdloff, Ronald S.] Harbor UCLA Med Ctr, Dept Med, Div Endocrinol, Torrance, CA 90509 USA. [Wang, Christina; Swerdloff, Ronald S.] Los Angeles Biomed Res Inst, Torrance, CA USA. [Jackson, Graham] London Bridge Hosp, London, England. [Jones, T. Hugh] Univ Sheffield, Barnsley Hosp, Robert Hague Ctr Diabet & Endocrinol, Sch Med, Sheffield, S Yorkshire, England. [Jones, T. Hugh] Univ Sheffield, Sch Med, Dept Metab, Sheffield, S Yorkshire, England. [Matsumoto, Alvin M.] Univ Washington, Sch Med, Ctr Geriatr Res Educ & Clin, VA Puget Sound Hlth Care Syst,Dept Med, Seattle, WA USA. [Nehra, Ajay] Mayo Clin, Dept Urol, Rochester, MN USA. [Perelman, Michael A.] NY Weill Cornell Coll Med, Dept Psychiat, New York, NY USA. [Perelman, Michael A.] NY Weill Cornell Coll Med, Dept Reprod Med, New York, NY USA. [Perelman, Michael A.] NY Weill Cornell Coll Med, Dept Urol, New York, NY USA. [Traish, Abdul] Boston Univ, Sch Med, Dept Urol, Boston, MA 02118 USA. [Zitzmann, Michael] Univ Clin Muenster, Clin Androl Ctr Reprod Med & Androl, Munster, Germany. [Cunningham, Glenn] Baylor Coll Med, Dept Med, St Lukes Baylor Diabet Program, Houston, TX 77030 USA. [Cunningham, Glenn] Baylor Coll Med, Dept Mol & Cellular Biol, St Lukes Baylor Diabet Program, Houston, TX 77030 USA. RP Wang, C (reprint author), Harbor UCLA Med Ctr, Dept Med, Div Endocrinol, Torrance, CA 90509 USA. EM wang@labiomed.org FU GlaxoSmithKline; Repros Therapeutics; Bayer-Schering Pharma; Lilly; Repros; Clarus Therapeutics; Abbott (Solvay) FX C.W. received research support from GlaxoSmithKline and Repros Therapeutics, received research materials from Besins Health Care, and is a consultant to GlaxoSmithKline and Lilly. T.H.J. is a consultant for Prostrakan and Bayer-Schering Pharma and has received research support and lecture honorarium from Bayer-Schering Pharma. R.S.S. is a consultant for Abbott (Solvay), Clams Therapeutics, Endo Pharmaceuticals, GlaxoSmithKline, Lilly, and Repros Therapeutics and has received research support from Lilly, Repros, and Clarus Therapeutics. G.C. is a consultant for Abbott (Solvay), Endo (Indevus), and GlaxoSmithKline; has received research support from Abbott (Solvay) and Repros Therapeutics; and is on the speakers' list for Abbott (Solvay). No other potential conflicts of interest relevant to this article were reported. NR 60 TC 85 Z9 91 U1 0 U2 9 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUL PY 2011 VL 34 IS 7 BP 1669 EP 1675 DI 10.2337/dc10-2339 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 799CN UT WOS:000293261200043 PM 21709300 ER PT J AU Kahn, SE Utzschneider, KM AF Kahn, Steven E. Utzschneider, Kristina M. TI What's Next for Diabetes Prevention? SO DIABETES CARE LA English DT Editorial Material ID IMPAIRED GLUCOSE-TOLERANCE; LIFE-STYLE INTERVENTION; BETA-CELL DYSFUNCTION; ROSIGLITAZONE; METFORMIN; TRIAL; MELLITUS; COMPLICATIONS; REDUCTION C1 [Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. Univ Washington, Seattle, WA 98195 USA. RP Kahn, SE (reprint author), VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. EM skahn@u.washington.edu OI Kahn, Steven/0000-0001-7307-9002 FU NIDDK NIH HHS [P30 DK017047] NR 19 TC 2 Z9 2 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUL PY 2011 VL 34 IS 7 BP 1678 EP 1680 DI 10.2337/dc11-0694 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 799CN UT WOS:000293261200045 PM 21709302 ER PT J AU Dai, TH Tanaka, M Huang, YY Hamblin, MR AF Dai, Tianhong Tanaka, Masamitsu Huang, Ying-Ying Hamblin, Michael R. TI Chitosan preparations for wounds and burns: antimicrobial and wound-healing effects SO EXPERT REVIEW OF ANTI-INFECTIVE THERAPY LA English DT Review DE antimicrobial activity; chitin; chitosan; drug delivery; wound dressing; wound healing; wound infection ID IN-VITRO EVALUATION; MOLECULAR-WEIGHT CHITOSAN; ENDOSCOPIC SINUS SURGERY; N-CARBOXYBUTYL CHITOSAN; GEL FORMULATION; CARBOXYMETHYL CHITOSAN; ANTIBACTERIAL ACTIVITY; ACETATE BANDAGE; VIVO EVALUATION; GROWTH-FACTOR AB Since its discovery approximately 200 years ago, chitosan, as a cationic natural polymer, has been widely used as a topical dressing in wound management owing to its hemostatic, stimulation of healing, antimicrobial, nontoxic, biocompatible and biodegradable properties. This article covers the antimicrobial and wound-healing effects of chitosan, as well as its derivatives and complexes, and its use as a vehicle to deliver biopharmaceuticals, antimicrobials and growth factors into tissue. Studies covering applications of chitosan in wounds and burns can be classified into in vitro, animal and clinical studies. Chitosan preparations are classified into native chitosan, chitosan formulations, complexes and derivatives with other substances. Chitosan can be used to prevent or treat wound and burn infections not only because of its intrinsic antimicrobial properties, but also by virtue of its ability to deliver extrinsic antimicrobial agents to wounds and burns. It can also be used as a slow-release drug-delivery vehicle for growth factors to improve wound healing. The large number of publications in this area suggests that chitosan will continue to be an important agent in the management of wounds and burns. C1 [Dai, Tianhong; Tanaka, Masamitsu; Huang, Ying-Ying; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Dai, Tianhong; Huang, Ying-Ying; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Tanaka, Masamitsu] Natl Def Med Coll, Dept Orthoped Surg, Tokorozawa, Saitama 3598513, Japan. [Huang, Ying-Ying] Guangxi Med Univ, Aesthet & Plast Ctr, Nanning 530022, Peoples R China. [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 Huang, Ying-ying/G-3153-2011; OI Huang, Ying-ying/0000-0003-3066-6981; Hamblin, Michael/0000-0001-6431-4605 FU NIH [R01AI050875]; Center for Integration of Medicine and Innovative Technology [DAMD17-02-2-0006]; CDMRP Program in TBI [W81XWH-09-1-0514]; Air Force Office of Scientific Research [FA9950-04-1-0079]; Bullock Wellman Fellowship; Airlift Research Foundation [109421] FX Research in the Hamblin laboratory is supported by NIH grant R01AI050875, Center for Integration of Medicine and Innovative Technology (DAMD17-02-2-0006), CDMRP Program in TBI (W81XWH-09-1-0514) and Air Force Office of Scientific Research (FA9950-04-1-0079). Tianhong Dai was partly supported by a Bullock Wellman Fellowship and an Airlift Research Foundation Extremity Trauma Research Grant (grant 109421). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 108 TC 142 Z9 147 U1 20 U2 126 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1478-7210 J9 EXPERT REV ANTI-INFE JI Expert Rev. Anti-Infect. Ther. PD JUL PY 2011 VL 9 IS 7 BP 857 EP 879 DI 10.1586/ERI.11.59 PG 23 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 806IE UT WOS:000293798800016 PM 21810057 ER PT J AU Blank, RD AF Blank, Robert D. CA FRAX Position Dev Conf Members TI Official Positions for FRAX (R) Clinical Regarding Prior Fractures SO JOURNAL OF CLINICAL DENSITOMETRY LA English DT Article DE FRAX; past fractures; fracture risk; vertebral morphometry; family history ID EUROPEAN PROSPECTIVE OSTEOPOROSIS; PREVALENT VERTEBRAL FRACTURES; HIP FRACTURE; SUBSEQUENT FRACTURE; BONE-DENSITY; COLLES FRACTURE; LIMB FRACTURES; FAMILY-HISTORY; SPINE FRACTURE; DISTAL FOREARM AB The 2010 Position Development Conference addressed four questions related to the impact of previous fractures on 10-year fracture risk as calculated by FRAX (R). Does the number of past fractures affect future fracture risk? Does the severity of past vertebral fractures affect future fracture risk? Does the site of past fractures affect future fracture risk? Should the family history of fracture be expanded to include additional sites, additional family members, or account for age at fracture? To address these questions, PubMed was searched on the keywords "fracture, epidemiology, osteoporosis." Titles of retrieved articles were reviewed for an indication that risk for future fracture was discussed. Abstracts of these articles were reviewed for an indication that one or more of the questions listed above was discussed. For those that did, the articles were reviewed in greater detail to extract the findings and to find additional past work and citing works that also bore on the questions. The official positions and the supporting literature review are presented here. FRAX (R) underestimates fracture probability in persons with a history of multiple fractures (good, A, W). FRAX (R) may underestimate fracture probability in individuals with prevalent severe vertebral fractures (good, A, W). While there is evidence that hip, vertebral, and humeral fractures appear to confer greater risk of subsequent fracture than fractures at other sites, quantification of this incremental risk in FRAX (R) is not possible (fair, B, W). FRAX (R) may underestimate fracture probability in individuals with a parental history of non-hip fragility fracture (fair, B, W). Limitations of the methodology include performance by a single reviewer, preliminary review of the literature being confined to titles, and secondary review being limited to abstracts. Limitations of the evidence base include publication bias, overrepresentation of persons of European descent in the published studies, and technical differences in the methods used to identify prevalent and incident fractures. Emerging topics for future research include fracture epidemiology in non-European populations and men, the impact of fractures in family members other than parents, and the genetic contribution to fracture risk. C1 [Blank, Robert D.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Div Endocrinol, Madison, WI 53705 USA. [Blank, Robert D.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Blank, RD (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Div Endocrinol, 4142 MFCB,5148,1685 Highland Ave, Madison, WI 53705 USA. EM rdb@medicine.wisc.edu RI Moayyeri, Alireza/N-3332-2014; Stepan, Jan /A-7280-2013 OI Moayyeri, Alireza/0000-0002-9143-2161; Stepan, Jan /0000-0003-1541-8306 FU Office of Research and Development, Biomedical Laboratory R&D Service, Department of Veterans Affairs; National Institutes of Health [R01-AR54753] FX This report is Madison GRECC manuscript 2010-22. RDB gratefully acknowledges research support from the Office of Research and Development, Biomedical Laboratory R&D Service, Department of Veterans Affairs and from the National Institutes of Health R01-AR54753. NR 40 TC 9 Z9 9 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1094-6950 J9 J CLIN DENSITOM JI J. Clin. Densitom. PD JUL-SEP PY 2011 VL 14 IS 3 BP 205 EP 211 DI 10.1016/j.jocd.2011.05.009 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 808PC UT WOS:000293989900006 PM 21810526 ER PT J AU Traeger, L Braun, IM Greer, JA Temel, JS Cashavelly, B Pirl, WF AF Traeger, Lara Braun, Ilana M. Greer, Joseph A. Temel, Jennifer S. Cashavelly, Barbara Pirl, William F. TI Parsing Depression From Fatigue in Patients with Cancer Using the Fatigue Symptom Inventory SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Cancer; depression; fatigue; Fatigue Symptom Inventory; quality of life ID QUALITY-OF-LIFE; STRUCTURED CLINICAL INTERVIEW; FUNCTIONAL IMPAIRMENT; PSYCHIATRIC MORBIDITY; HOSPITAL ANXIETY; VALIDATION; DISORDERS; TRIAL; PREVALENCE; SCALE AB Context. A central aim in the management of cancer-related fatigue (CRF) is to identify treatable causes, such as depression. However, CRF and depression symptoms overlap and frequently co-occur, complicating diagnostic assessment. Objectives. As cancer-related symptoms have been associated with more functional impairment among patients who are depressed, this study tested the ratio of fatigue interference to fatigue severity as a method for identifying depression cases. Patients who reported that interference was greater than severity were expected to show higher rates of depression as measured by self-report instrument or structured interview. Methods. A secondary analysis was conducted using data from patients who were attending a hospital thoracic oncology clinic and who completed the Fatigue Symptom Inventory (FSI) and Hospital Anxiety and Depression Scale (Sample 1, n = 86). Analyses were then replicated in a sample of diverse cancer patients who completed the FSI and a structured clinical interview for depression on presentation to a CRF clinic at the same hospital (Sample 2, n = 39). Results. Receiver operating curve analyses supported use of the FSI interference/severity ratio in distinguishing depression cases and noncases (area under the curve: Sample 1 - 0.84, 95% confidence interval [CI] 0.74-0.94; Sample 2 0.87, 95% CI 0.76-0.99). With sensitivity and specificity weighted equally, the optimal cutoff was >= 1.0 in Sample 1 (sensitivity = 62.5%, specificity 91.4%) and Sample 2 (sensitivity = 90.9%, specificity = 85.7%). Conclusion. A fatigue score pattern in which interference was greater than or equal to severity predicted depression in two patient samples. This ratio may be useful for brief initial screening of depression in the context of fatigue. J Pain Symptom Manage 2011; 42: 52-59. (C) 2011 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. C1 [Traeger, Lara] Massachusetts Gen Hosp, Behav Med Serv, Ctr Psychiat Oncol & Behav Sci, Boston, MA 02114 USA. [Braun, Ilana M.] Dana Farber Canc Inst, Psychosocial Oncol Serv, Boston, MA 02115 USA. [Braun, Ilana M.] Dana Farber Canc Inst, Psychiat Serv, Boston, MA 02115 USA. RP Traeger, L (reprint author), Massachusetts Gen Hosp, Behav Med Serv, Ctr Psychiat Oncol & Behav Sci, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM ltraeger@partners.org NR 47 TC 7 Z9 7 U1 3 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD JUL PY 2011 VL 42 IS 1 BP 52 EP 59 DI 10.1016/j.jpainsymman.2010.10.262 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 802MO UT WOS:000293515900006 PM 21398085 ER PT J AU Widera, EW Rosenfeld, KE Fromme, EK Sulmasy, DP Arnold, RM AF Widera, Eric W. Rosenfeld, Kenneth E. Fromme, Erik K. Sulmasy, Daniel P. Arnold, Robert M. TI Approaching Patients and Family Members Who Hope for a Miracle SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Miracles; divine intervention; religious beliefs; decision making; spiritual support; pastoral care ID TREATMENT PREFERENCES; ADVANCED CANCER; NEAR-DEATH; LIFE; PHYSICIANS; BELIEFS; CARE; FUTILITY; END; ICU AB A clinical problem may arise when caring for patients or their surrogates who prefer continued aggressive care based on the belief that a miracle will occur, despite a clinician's belief that further medical treatment is unlikely to have any meaningful benefit. An evidence-based approach is provided for the clinician by breaking this complex clinical problem into a series of more focused clinical questions and subsequently answering them through a critical appraisal of the existing medical literature. Belief in miracles is found to be common in the United States and is an important determinant of how decisions are made for those with advanced illness. There is a growing amount of evidence that suggests end-of-life outcomes improve with the provision of spiritual support from medical teams, as well as with a proactive approach to medical decision making that values statements given by patients and family members. J Pain Symptom Manage 2011; 42: 119-125. Published by Elsevier Inc. on behalf of the U.S. Cancer Pain Relief Committee. C1 [Widera, Eric W.] Dept Vet Affairs Med Ctr, San Francisco, CA USA. [Widera, Eric W.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Rosenfeld, Kenneth E.] Vet Adm Greater Los Angeles Healthcare Syst, Div Gen Internal Med, Sect Palliat Care, Los Angeles, CA USA. [Fromme, Erik K.] Oregon Hlth & Sci Univ, Dept Med, Div Hematol & Med Oncol, Portland, OR 97201 USA. [Sulmasy, Daniel P.] Univ Chicago, Dept Med, MacLean Ctr Clin Med Eth, Chicago, IL 60637 USA. [Sulmasy, Daniel P.] Univ Chicago, Divin Sch, Chicago, IL 60637 USA. [Arnold, Robert M.] Univ Pittsburgh, Sch Med, Div Gen Internal Med, Sect Palliat Care & Med Eth,Ctr Bioeth & Hlth Law, Pittsburgh, PA USA. RP Widera, EW (reprint author), VA Med Ctr 181G, 4150 Clement St, San Francisco, CA 94121 USA. EM eric.widera@ucsf.edu FU Hartford Foundation FX Dr. Widera is supported by the Hartford Foundation as a Center of Excellence Faculty Scholar. The authors of this manuscript have no conflicts to disclose. NR 21 TC 21 Z9 21 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD JUL PY 2011 VL 42 IS 1 BP 119 EP 125 DI 10.1016/j.jpainsymman.2011.03.008 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 802MO UT WOS:000293515900012 PM 21641763 ER PT J AU Orban, T Bundy, B Becker, DJ DiMeglio, LA Gitelman, SE Goland, R Gottlieb, PA Greenbaum, CJ Marks, JB Monzavi, R Moran, A Raskin, P Rodriguez, H Russell, WE Schatz, D Wherrett, D Wilson, DM Krischer, JP Skyler, JS AF Orban, Tihamer Bundy, Brian Becker, Dorothy J. DiMeglio, Linda A. Gitelman, Stephen E. Goland, Robin Gottlieb, Peter A. Greenbaum, Carla J. Marks, Jennifer B. Monzavi, Roshanak Moran, Antoinette Raskin, Philip Rodriguez, Henry Russell, William E. Schatz, Desmond Wherrett, Diane Wilson, Darrell M. Krischer, Jeffrey P. Skyler, Jay S. CA Type 1 Diabet TrialNet Abatacept S TI Co-stimulation modulation with abatacept in patients with recent-onset type 1 diabetes: a randomised, double-blind, placebo-controlled trial SO LANCET LA English DT Article ID BETA-CELL FUNCTION; MONOCLONAL-ANTIBODY; COSTIMULATION; COMPLICATIONS; PROGRESSION; ARTHRITIS; MELLITUS; BLOCKADE AB Background The immunopathogenesis of type 1 diabetes mellitus is associated with T-cell autoimmunity. To be fully active, immune T cells need a co-stimulatory signal in addition to the main antigen-driven signal. Abatacept modulates co-stimulation and prevents full T-cell activation. We evaluated the effect of abatacept in recent-onset type 1 diabetes. Methods In this multicentre, double-blind, randomised controlled trial, patients aged 6-45 years recently diagnosed with type 1 diabetes were randomly assigned (2:1) to receive abatacept (10 mg/kg, maximum 1000 mg per dose) or placebo infusions intravenously on days 1, 14, 28, and monthly for a total of 27 infusions over 2 years. Computer. generated permuted block randomisation was used, with a block size of 3 and stratified by participating site. Neither patients nor research personnel were aware of treatment assignments. The primary outcome was baseline-adjusted geometric mean 2-h area-under-the-curve (AUC) serum C-peptide concentration after a mixed-meal tolerance test at 2 years' follow-up. Analysis was by intention to treat for all patients for whom data were available. This trial is registered at ClinicalTrials.gov, NCT00505375. Findings 112 patients were assigned to treatment groups (77 abatacept, 35 placebo). Adjusted C-peptide AUC was 59% (95% CI 6.1-112) higher at 2 years with abatacept (n=73, 0.378 nmol/L) than with placebo (n=30, 0.238 nmol/L; p=0.0029). The difference between groups was present throughout the trial, with an estimated 9.6 months' delay (95% CI 3.47-15.6) in C-peptide reduction with abatacept. There were few infusion-related adverse events (36 reactions occurred in 17 [22%] patients on abatacept and 11 reactions in six [17%] on placebo). There was no increase in infections (32 (42%] patients on abatacept vs 15 [43%] on placebo) or neutropenia (seven [9%] vs five [14%]). Interpretation Co-stimulation modulation with abatacept slowed reduction in beta-cell function over 2 years. The beneficial effect suggests that T-cell activation still occurs around the time of clinical diagnosis of type 1 diabetes. Yet, despite continued administration of abatacept over 24 months, the decrease in beta-cell function with abatacept was parallel to that with placebo after 6 months of treatment, causing us to speculate that T-cell activation lessens with time. Further observation will establish whether the beneficial effect continues after cessation of abatacept infusions. C1 [Skyler, Jay S.] Univ Miami, Miller Sch Med, Diabet Res Inst, Miami, FL 33136 USA. [Orban, Tihamer] Joslin Diabet Ctr, Boston, MA 02215 USA. [Bundy, Brian; Krischer, Jeffrey P.] Univ S Florida, Tampa, FL USA. [Becker, Dorothy J.] Univ Pittsburgh, Pittsburgh, PA USA. [DiMeglio, Linda A.; Rodriguez, Henry] Indiana Univ Sch Med, Indianapolis, IN USA. [Gitelman, Stephen E.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Goland, Robin] Columbia Univ, New York, NY USA. [Gottlieb, Peter A.] Univ Colorado, Barbara Davis Ctr Childhood Diabet, Aurora, CO USA. [Greenbaum, Carla J.] Benaroya Res Inst, Seattle, WA USA. [Monzavi, Roshanak] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Moran, Antoinette] Univ Minnesota, Minneapolis, MN USA. [Raskin, Philip] Univ Texas SW Med Sch, Dallas, TX USA. [Russell, William E.] Vanderbilt Univ, Nashville, TN USA. [Schatz, Desmond] Univ Florida, Gainesville, FL USA. [Wherrett, Diane] Univ Toronto, Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Wilson, Darrell M.] Stanford Univ, Stanford, CA 94305 USA. RP Skyler, JS (reprint author), Univ Miami, Miller Sch Med, Diabet Res Inst, Miami, FL 33136 USA. EM jskyler@miami.edu RI Moore, Daniel/A-4924-2008; Skyler, Jay/F-4211-2016; OI Moore, Daniel/0000-0002-6889-9345; DiMeglio, Linda/0000-0002-8033-6078 FU National Institutes of Health (NIH) through the National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Allergy and Infectious Diseases; Eunice Kennedy Shriver National Institute of Child Health and Human Development [U01 DK061010, U01 DK061016, U01 DK061034, U01 DK061036, U01 DK061040, U01 DK061041, U01 DK061042, U01 DK061055, U01 DK061058, U01 DK084565, U01 DK085453, U01 DK085461, U01 DK085463, U01 DK085466, U01 DK085499, U01 DK085505, U01 DK085509, HHSN267200800019C]; National Center for Research Resources [UL1 RR024131, UL1 RR024139, UL1 RR024153, UL1 RR024975, UL1 RR024982, UL1 RR025744, UL1 RR025761, UL1 RR025780, UL1 RR029890, UL1 RR031986]; General Clinical Research Center [M01 RR00400]; Juvenile Diabetes Research Foundation International (JDRF); American Diabetes Association (ADA); Diamyd; Tolerx; Bayhill Therapeutics; Macrogenics; Omni Bio Therapeutics; Aegera; Andromeda Biotech; Biodel; Boehringer Ingelheim; Calibra; CPEX; Generex; Hoffman-LaRoche; Mann Kind; Novo-Nordisk; Osiris Therapeutics; Reata; Eli Lilly; Medtronic; Halozyme; Intuity; Becton-Dickinson; Merck; Mann Kind Corporation; GlaxoSmithKline; Salutria Pharmaceuticals; Veroscience; Roche; Exsulin FX TO reports serving on a data safety monitoring board for Osiris Therapeutics and beings founder of Orban Biotech LLC. DJB reports receiving a grant from Diamyd. SEG reports serving on an advisory board for Genentech. RG reports receiving grants from Diamyd and Tolerx. PAG reports serving on advisory boards for Genentech, Eli Lilly, Sanofi-Aventis, and Tolerx, and reports receiving grants from Bayhill Therapeutics, Diamyd, Macrogenics, Omni Bio Therapeutics, and Tolerx. CJG reports receiving grants from Bayhill Therapeutics, Diamyd, and Tolerx. JBM reports serving on an advisory board for Amgen. AM reports serving on an advisory board for Pfizer and receiving grants from Tolerx, Merck, and Osiris Therapeutics. PR reports serving on advisory boards for Amgen, AstraZeneca, MannKind, and Novo-Nordisk, serving on speakers bureaus for Merck and Novo-Nordisk, and receiving grants from Aegera, Andromeda Biotech, Bayhill Therapeutics, Biodel, Boehringer Ingelheim, Calibra, CPEX, Generex, Hoffman-LaRoche, Mann Kind, Novo-Nordisk, Osiris Therapeutics, and Reata. HR reports serving on an advisory board for Marcadia Biotech, serving as a Consultant to Eli Lilly, Genentech, Bayer, EMD Serono, and Merck, being on the speakers bureau of Eli Lilly and Novo-Nordisk, and receiving grant support from Macrogenics and Eli Lilly. DS reports serving on advisory boards for Eli Lilly and GlaxoSmithKline and receiving a grant from Diamyd. DW reports receiving lecture fees from Eli Lilly and Medtronic. DMW reports serving on an advisory boards for DexCom and Genentech and receiving grants support from Genentech, Diamyd, and Osiris Therapeutics. JSS reports serving on boards for Amylin Pharmaceuticals, DexCom, and Sanofi-Aventis, receiving grants from Bayhill Therapeutics, Halozyme, Intuity, and Osiris Therapeutics, receiving consultancy fees from Becton-Dickinson, Merck, Mann Kind Corporation, GlaxoSmithKline, Salutria Pharmaceuticals, Veroscience, Roche, and Exsulin, and receiving speakers' fees and payment for development of an educational presentation from Novo-Nordisk and holds stock in Amylin Pharmaceuticals and Dexcom. BB, LADM, RM, WER, and JPK declare that they have no conflicts of interest.; The sponsor of the trial was the Type 1 Diabetes TrialNet Study Group. Type 1 Diabetes TrialNet Study Group is a clinical trials network funded by the National Institutes of Health (NIH) through the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Allergy and Infectious Diseases, and The Eunice Kennedy Shriver National Institute of Child Health and Human Development, through the cooperative agreements U01 DK061010, U01 DK061016, U01 DK061034, U01 DK061036, U01 DK061040, U01 DK061041, U01 DK061042, U01 DK061055, U01 DK061058, U01 DK084565, U01 DK085453, U01 DK085461, U01 DK085463, U01 DK085466, U01 DK085499, U01 DK085505, U01 DK085509, and a contract HHSN267200800019C; the National Center for Research Resources, through Clinical Translational Science Awards UL1 RR024131, UL1 RR024139, UL1 RR024153, UL1 RR024975, UL1 RR024982, UL1 RR025744, UL1 RR025761, UL1 RR025780, UL1 RR029890, UL1 RR031986, and General Clinical Research Center Award M01 RR00400; the Juvenile Diabetes Research Foundation International (JDRF); and the American Diabetes Association (ADA). The contents of this Article are solely the responsibility of the authors and do not necessarily represent the official views of the NIH, JDRF, or ADA. Bristol-Myers Squibb provided abatacept. Lifescan Division of Johnson and Johnson provided blood glucose monitoring meters and strips to participants. NR 27 TC 202 Z9 206 U1 2 U2 11 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 JUL-AUG PY 2011 VL 378 IS 9789 BP 412 EP 419 DI 10.1016/S0140-6736(11)60886-6 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 803XM UT WOS:000293615900032 PM 21719096 ER PT J AU Bergerat, A Decano, J Wu, CJ Choi, H Nesvizhskii, AI Moran, AM Ruiz-Opazo, N Steffen, M Herrera, VLM AF Bergerat, Agnes Decano, Julius Wu, Chang-Jiun Choi, Hyungwon Nesvizhskii, Alexey I. Moran, Ann Marie Ruiz-Opazo, Nelson Steffen, Martin Herrera, Victoria L. M. TI Prestroke Proteomic Changes in Cerebral Microvessels in Stroke-Prone, Transgenic(hCETP)-Hyperlipidemic, Dahl Salt-Sensitive Hypertensive Rats SO MOLECULAR MEDICINE LA English DT Article ID BLOOD-BRAIN-BARRIER; SHOTGUN PROTEOMICS; CARBONIC-ANHYDRASE; EXPRESSION; PROTEIN; AQUAPORIN-4; DISEASE; MODEL; ISCHEMIA/REPERFUSION; MICROHEMORRHAGES AB Stroke is the third leading cause of death in the United States with high rates of morbidity among survivors. The search to fill the unequivocal need for new therapeutic approaches would benefit from unbiased proteomic analyses of animal models of spontaneous stroke in the prestroke stage. Since brain microvessels play key roles in neurovascular coupling, we investigated prestroke microvascular proteome changes. Proteomic analysis of cerebral cortical microvessels (cMVs) was done by tandem mass spectrometry comparing two prestroke time points. Metaprotein-pathway analyses of proteomic spectral count data were done to identify risk factor-induced changes, followed by QSPEC-analyses of individual protein changes associated with increased stroke susceptibility. We report 26 cMV proteome profiles from male and female stroke-prone and non-stroke-prone rats at 2 months and 4.5 months of age prior to overt stroke events. We identified 1,934 proteins by two or more peptides. Metaprotein pathway analysis detected age-associated changes in energy metabolism and cell-to-microenvironment interactions, as well as sex-specific changes in energy metabolism and endothelial leukocyte transmigration pathways. Stroke susceptibility was associated independently with multiple protein changes associated with ischemia, angiogenesis or involved in blood brain barrier (BBB) integrity. Immunohistochemical analysis confirmed aquaporin-4 and laminin-alpha 1 induction in cMVs, representative of proteomic changes with >65 Bayes factor (BF), associated with stroke susceptibility. Altogether, proteomic analysis demonstrates significant molecular changes in ischemic cerebral microvasculature in the prestroke stage, which could contribute to the observed model phenotype of microhemorrhages and postischemic hemorrhagic transformation. These pathways comprise putative targets for translational research of much needed novel diagnostic and therapeutic approaches for stroke. (C) 2011 The Feinstein Institute for Medical Research, www.feinsteininstitute.org C1 [Decano, Julius; Moran, Ann Marie; Ruiz-Opazo, Nelson; Herrera, Victoria L. M.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. [Bergerat, Agnes; Steffen, Martin] Boston Univ, Sch Med, Dept Pathol & Lab Med, Boston, MA 02118 USA. [Decano, Julius; Moran, Ann Marie; Ruiz-Opazo, Nelson; Herrera, Victoria L. M.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Wu, Chang-Jiun] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Choi, Hyungwon; Nesvizhskii, Alexey I.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. [Steffen, Martin] Boston Univ, Dept Biomed Engn, Boston, MA 02118 USA. RP Herrera, VLM (reprint author), Boston Univ, Sch Med, Whitaker Cardiovasc Inst, 700 Albany St, Boston, MA 02118 USA. EM steffen@bu.edu; vherrera@bu.edu RI Nesvizhskii, Alexey/A-5410-2012 OI Nesvizhskii, Alexey/0000-0002-2806-7819 FU National Institutes of Health [RO1 AG32649-02]; Whitaker Cardiovascular Institute [T32 HL07224] FX Grant funding from the National Institutes of Health, RO1 AG32649-02 to VLM Herrera; Whitaker Cardiovascular Institute T32 HL07224 to A Bergerat. NR 51 TC 12 Z9 12 U1 0 U2 5 PU FEINSTEIN INST MED RES PI MANHASSET PA 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1076-1551 EI 1528-3658 J9 MOL MED JI Mol. Med. PD JUL-AUG PY 2011 VL 17 IS 7-8 BP 588 EP 598 DI 10.2119/molmed.2010.00228 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 804VH UT WOS:000293681600002 PM 21519634 ER PT J AU Teitelman, AM Tennille, J Bohinski, JM Jemmott, LS Jemmott, JB AF Teitelman, Anne M. Tennille, Julie Bohinski, Julia M. Jemmott, Loretta S. Jemmott, John B., III TI Unwanted Unprotected Sex Condom Coercion by Male Partners and Self-silencing of Condom Negotiation Among Adolescent Girls SO ADVANCES IN NURSING SCIENCE LA English DT Article DE adolescent; coercion; female; HIV; prevention; sexual behavior ID DATING VIOLENCE; REJECTION SENSITIVITY; AFRICAN-AMERICAN; RISK BEHAVIOR; INTERVENTIONS; PREGNANCY; FEMALES; POWER; COMMUNICATION; HEALTH AB This exploratory study used the theory of reasoned action and the theory of gender and power to guide elicitation of partner-related impediments to condom use among 64 adolescent girls living in poor urban areas with high rates of HIV and partner abuse. About 53% indicated that they had experienced unwanted, unprotected vaginal sex and 25% indicated that they were unable to discuss condom use with a partner. Novel qualitative findings related to condom coercion, condom sabotage, and self-silencing of condom negotiation are discussed in the context of connecting partner abuse to interpersonal control over condom use. Implications for intervention design are discussed. C1 [Teitelman, Anne M.] Univ Penn, Sch Nursing, Ctr Hlth Equ Res, Philadelphia, PA 19104 USA. [Tennille, Julie] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19104 USA. [Jemmott, John B., III] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Jemmott, John B., III] Univ Penn, Annenberg Sch Commun, Philadelphia, PA 19104 USA. RP Teitelman, AM (reprint author), Univ Penn, Sch Nursing, Ctr Hlth Equ Res, Fagin Hall 2L,Room 244,418 Curie Blvd, Philadelphia, PA 19104 USA. EM teitelm@nursing.upenn.edu FU NIMH [1K01MII080649-01A1]; University of Pennsylvania: Center for AIDS Research; Institute for Urban Research FX This research was supported by NIMH grant 1K01MII080649-01A1 and University of Pennsylvania: Center for AIDS Research and Institute for Urban Research. The authors thank late Dr Martin Fishbein for suggestions about the wording of the open-ended questions on the brief survey; Dr Patricia Benner, Dr Pat D'Antonio, and Annet Davis-Vogel for reading and commenting on drafts of the article; Lynette Gueits for her role in advising on the development of the focus group guide; the Talking about Relationships Project research team members for logistical support during focus groups and for insightful discussions during the coding process; and the research study participants for the time and thoughtful comments. NR 49 TC 32 Z9 32 U1 1 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0161-9268 EI 1550-5014 J9 ADV NURS SCI JI Adv. Nurs. Sci. PD JUL-SEP PY 2011 VL 34 IS 3 BP 243 EP 259 DI 10.1097/ANS.0b013e31822723a3 PG 17 WC Nursing SC Nursing GA 803PM UT WOS:000293593200009 PM 21822072 ER PT J AU Baker, MA Harries, AD Jeon, CY Hart, JE Kapur, A Lonnroth, K Ottmani, SE Goonesekera, SD Murray, MB AF Baker, Meghan A. Harries, Anthony D. Jeon, Christie Y. Hart, Jessica E. Kapur, Anil Loennroth, Knut Ottmani, Salah-Eddine Goonesekera, Sunali D. Murray, Megan B. TI The impact of diabetes on tuberculosis treatment outcomes: A systematic review SO BMC MEDICINE LA English DT Review ID MULTIDRUG-RESISTANT TUBERCULOSIS; PULMONARY TUBERCULOSIS; PUBLICATION BIAS; SPUTUM SMEAR; RISK-FACTORS; METAANALYSIS; MELLITUS; MORTALITY; DEATH; MANIFESTATIONS AB Background: Multiple studies of tuberculosis treatment have indicated that patients with diabetes mellitus may experience poor outcomes. We performed a systematic review and meta-analysis to quantitatively summarize evidence for the impact of diabetes on tuberculosis outcomes. Methods: We searched PubMed, EMBASE and the World Health Organization Regional Indexes from 1 January 1980 to 31 December 2010 and references of relevant articles for reports of observational studies that included people with diabetes treated for tuberculosis. We reviewed the full text of 742 papers and included 33 studies of which 9 reported culture conversion at two to three months, 12 reported the combined outcome of failure and death, 23 reported death, 4 reported death adjusted for age and other potential confounding factors, 5 reported relapse, and 4 reported drug resistant recurrent tuberculosis. Results: Diabetes is associated with an increased risk of failure and death during tuberculosis treatment. Patients with diabetes have a risk ratio (RR) for the combined outcome of failure and death of 1.69 (95% CI, 1.36 to 2.12). The RR of death during tuberculosis treatment among the 23 unadjusted studies is 1.89 (95% CI, 1.52 to 2.36), and this increased to an effect estimate of 4.95 (95% CI, 2.69 to 9.10) among the 4 studies that adjusted for age and other potential confounding factors. Diabetes is also associated with an increased risk of relapse (RR, 3.89; 95% CI, 2.43 to 6.23). We did not find evidence for an increased risk of tuberculosis recurrence with drug resistant strains among people with diabetes. The studies assessing sputum culture conversion after two to three months of tuberculosis therapy were heterogeneous with relative risks that ranged from 0.79 to 3.25. Conclusions: Diabetes increases the risk of failure and death combined, death, and relapse among patients with tuberculosis. This study highlights a need for increased attention to treatment of tuberculosis in people with diabetes, which may include testing for suspected diabetes, improved glucose control, and increased clinical and therapeutic monitoring. C1 [Baker, Meghan A.; Jeon, Christie Y.; Goonesekera, Sunali D.; Murray, Megan B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Baker, Meghan A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Harries, Anthony D.] Int Union TB & Lung Dis, Paris, France. [Harries, Anthony D.] London Sch Hyg & Trop Med, London WC1, England. [Jeon, Christie Y.] Columbia Univ, Ctr Infect Dis Epidemiol Res, New York, NY USA. [Hart, Jessica E.] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. [Kapur, Anil] World Diabet Fdn, Lyngby, Denmark. [Loennroth, Knut; Ottmani, Salah-Eddine] WHO, Stop TB Dept, CH-1211 Geneva, Switzerland. [Murray, Megan B.] Brigham & Womens Hosp, Div Global Hlth Equ, Boston, MA 02115 USA. RP Murray, MB (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 665 Huntington Ave, Boston, MA 02115 USA. EM mmurray@hsph.harvard.edu RI Lonnroth, Knut/L-2339-2014 OI Lonnroth, Knut/0000-0001-5054-8240 FU World Diabetes Foundation FX This systematic review was supported by a grant from the World Diabetes Foundation. Authors from Harvard University, the International Union Against Tuberculosis and Lung Disease, the World Diabetes Foundation, the World Health Organization, Columbia University, and Brown University contributed to the planning and execution of the systematic review. NR 70 TC 157 Z9 164 U1 1 U2 19 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1741-7015 J9 BMC MED JI BMC Med. PD JUL 1 PY 2011 VL 9 AR 81 DI 10.1186/1741-7015-9-81 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA 807JD UT WOS:000293892000001 PM 21722362 ER PT J AU Sroczynski, G Schnell-Inderst, P Muhlberger, N Lang, K Aidelsburger, P Wasem, J Mittendorf, T Engel, J Hillemanns, P Petry, KU Kramer, A Siebert, U AF Sroczynski, G. Schnell-Inderst, P. Muehlberger, N. Lang, K. Aidelsburger, P. Wasem, J. Mittendorf, T. Engel, J. Hillemanns, P. Petry, K. U. Kraemer, A. Siebert, U. TI Cost-effectiveness of primary HPV screening for cervical cancer in Germany - a decision analysis SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE Human papillomavirus; Screening; Cervical cancer; Decision analysis; Cost benefit analyses; Cost-effectiveness ID HUMAN-PAPILLOMAVIRUS INFECTION; ATYPICAL SQUAMOUS-CELLS; NATURAL-HISTORY; INTRAEPITHELIAL NEOPLASIA; CLINICAL-APPLICATIONS; YOUNG-WOMEN; HEALTH-CARE; MODEL; RISK; LESIONS AB Objectives: To systematically evaluate the long-term effectiveness and cost-effectiveness of HPV-based primary cervical cancer screening in the German health care context using a decision-analysis approach. Methods: A Markov-model for HPV-infection and cervical cancer was developed for the German health care context, and applied to evaluate various screening strategies that differ by screening interval and test algorithms, including HPV-testing alone or in combination with cytology. German clinical, epidemiological, and economic data, and test accuracy data from international meta-analyses were used. Outcomes predicted included the reduction in cervical cancer cases and deaths, life expectancy and discounted incremental cost-effectiveness ratios (ICER). The analysis was performed from the perspective of the healthcare system adopting a 3% annual discount rate for costs and outcomes. Extensive sensitivity analyses were performed. Results: HPV-based screening is more effective than cytology alone. It results in a 71-97% reduction in cervical cancer cases as compared to 53-93% for cytology alone. The ICER range from 2600 Euro/LYG (cytology, 5-year-interval) to 155,500 Euro/LYG (annual HPV-testing starting at age 30 years, cytology age 20-29 years). Annual cytology alone, the current recommended screening strategy in Germany, is dominated by HPV-strategies. Increasing the age at screening initiation from 20 to 25 years does not result in a relevant loss in effectiveness but results in lower costs. Conclusions: Based on our analyses, HPV-based cervical cancer screening is more effective than cytology alone and could be cost-effective if performed at intervals of two years or longer. In the German context, an optimal screening strategy may be biennial HPV screening starting at age 30 years preceded by biennial cytology for women aged 25-29 years. Longer screening intervals may be considered in low-risk women with good screening adherence and in populations with low HPV-incidence. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Siebert, U.] UMIT Univ Hlth Sci Med Informat & Technol, Inst Publ Hlth Med Decis Making & Hlth Technol As, Dept Publ Hlth & Hlth Technol Assessment, A-6060 Hall In Tirol, Austria. [Lang, K.; Aidelsburger, P.] CAREM GmbH, D-82054 Sauerlach, Germany. [Wasem, J.] Univ Duisburg Essen, Inst Hlth Serv Res & Management, D-45127 Essen, Germany. [Mittendorf, T.] Leibniz Univ Hannover, Ctr Hlth Econ, D-30167 Hannover, Germany. [Engel, J.] Univ Munich, IBE Clin Grosshadern, Munich Canc Ctr, Munich Canc Registry, D-81377 Munich, Germany. [Hillemanns, P.] Hannover Med Sch, Dept Obstet & Gynecol, D-30625 Hannover, Germany. [Petry, K. U.] Teaching Hosp Wolfsburg, Hanover Med Sch, Dept Obstet & Gynecol, D-38440 Wolfsburg, Germany. [Kraemer, A.] Univ Bielefeld, Dept Publ Hlth Med, Sch Publ Hlth, D-33615 Bielefeld, Germany. [Siebert, U.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Ctr Hlth Decis Sci, Boston, MA 02115 USA. [Siebert, U.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Siebert, U.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA 02114 USA. [Siebert, U.] ONCOTYROL Ctr Personalized Canc Med, Div Publ Hlth Decis Modelling Hlth Technol Assess, A-6020 Innsbruck, Austria. [Mittendorf, T.] Herescon GmbH Hlth Econ Res & Consulting, D-30167 Hannover, Germany. RP Siebert, U (reprint author), UMIT Univ Hlth Sci Med Informat & Technol, Inst Publ Hlth Med Decis Making & Hlth Technol As, Dept Publ Hlth & Hlth Technol Assessment, Eduard Wallnoefer Ctr 1, A-6060 Hall In Tirol, Austria. EM public-health@umit.at RI Kraemer, Alexander/F-8832-2016; OI Kraemer, Alexander/0000-0003-2774-7860; Wasem, Juergen/0000-0001-9653-168X FU Institute of Quality and Efficiency in Health Care (IQWiG), Germany; Sanofi Pasteur; SPMSD; Qiagen, MTM; German Agency for HTA at the German Institute for Medical Documentation and Information (DAHTA@DIMDI); Institute of the German Federal Ministry of Health [HTA 41-08] FX K.L., P.A., J.E., A.K., J.W. had no conflict of interests. The other authors declared the following relationships in the previous 3 years: (1) the Institution of G.S., P.S., N.M., U.S. received travel suppbrt from Qiagen for scientific meeting attendance in the previous 3 years and is currently being funded by the Institute of Quality and Efficiency in Health Care (IQWiG), Germany, for conducting an evidence-based benefit assessment of HPV-based screening; (2) T.M. received travel funding and honoraria for consultancy (Sanofi Pasteur); J.W. received payment for board membership (SPMSD), K.-U.P. received travel funding (Qiagen, MTM) and payment for advisory board membership (Roche Diagnostics, MTM); PH. received honoraria for lectures (HPV test companies), and was involved in research studies from HPV-related companies. The authors declare no other relationships that may be relevant to the submitted work.; This health technology assessment was commissioned and funded by the German Agency for HTA at the German Institute for Medical Documentation and Information (DAHTA@DIMDI), an Institute of the German Federal Ministry of Health (Grant no. HTA 41-08). The authors had complete and independent control over study design, analysis and interpretation of data, report writing and publication, regardless of results. NR 66 TC 13 Z9 13 U1 0 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD JUL PY 2011 VL 47 IS 11 BP 1633 EP 1646 DI 10.1016/j.ejca.2011.03.006 PG 14 WC Oncology SC Oncology GA 803WI UT WOS:000293612400005 PM 21482103 ER PT J AU La Salvia, E Chemali, Z AF La Salvia, Elizabeth Chemali, Zeina TI A Perspective on Psychosis in Late Life and Deficits in Social Cognition SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article DE late paraphrenia; late-life psychosis; late-life depression; late-onset schizophrenia; social cognition; theory of mind; very late onset schizophrenia-like psychosis ID LATE-ONSET SCHIZOPHRENIA; LATE PARAPHRENIA; FRONTOTEMPORAL DEMENTIA; PERSECUTORY DELUSIONS; DEPRESSIVE SYMPTOMS; SPECTRUM DISORDERS; ALZHEIMERS-DISEASE; PARANOID IDEATION; MAJOR DEPRESSION; ELDERLY-PATIENTS AB The etiology of new psychotic symptoms in late life, including subtle changes in cognition, is a controversial emerging area of study. The development of psychotic symptoms, particularly paranoia, is a common occurrence in late life, and the symptoms of cognitive dysfunction and psychosis are often prominent in dementia, schizophrenia, and mood disorders. This intermixing of symptoms has inescapably led to diagnostic confusion with regard to elderly patients with new-onset psychosis. The complex relationship among different domains of psychopathology makes it difficult to tease apart disorders of affect from psychosis, affect from cognition, and psychosis from cognition. It is therefore potentially useful to modify and expand our approach to how we conceptualize these patients. Emerging evidence suggests that those with dementia, psychotic disorders, and mood disorders suffer from growing cognitive deficits. The article suggests that deficits in social cognition, in particular, may be the unifying deficit that helps to explain why heterogeneous patients may develop paranoia and psychotic symptoms in late life. (HARV REV PSYCHIATRY 2011;19:190-197.) C1 [La Salvia, Elizabeth] Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA. [Chemali, Zeina] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Chemali, Zeina] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [La Salvia, Elizabeth] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP La Salvia, E (reprint author), Beth Israel Deaconess Med Ctr, Dept Psychiat, 330 Brookline Ave, Boston, MA 02215 USA. EM elasalvi@bidmc.harvard.edu NR 50 TC 1 Z9 1 U1 1 U2 5 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD JUL-AUG PY 2011 VL 19 IS 4 BP 190 EP 197 DI 10.3109/10673229.2011.599184 PG 8 WC Psychiatry SC Psychiatry GA 798AD UT WOS:000293171200002 PM 21790267 ER PT J AU Iravanian, S Sovari, AA Lardin, HA Liu, H Xiao, HD Dolmatova, E Jiao, Z Harris, BS Witham, EA Gourdie, RG Duffy, HS Bernstein, KE Dudley, SC AF Iravanian, Shahriar Sovari, Ali A. Lardin, Harvey A. Liu, Hong Xiao, Hong D. Dolmatova, Elena Jiao, Zhe Harris, Brett S. Witham, Emily A. Gourdie, Robert G. Duffy, Heather S. Bernstein, Kenneth E. Dudley, Samuel C., Jr. TI Inhibition of renin-angiotensin system (RAS) reduces ventricular tachycardia risk by altering connexin43 SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Article DE ACE; Angiotensin; Connexin; Arrhythmia; Electrophysiology ID SUDDEN ARRHYTHMIC DEATH; IMPULSE PROPAGATION; RECEPTOR ANTAGONIST; CARDIAC-ARRHYTHMIA; OXIDATIVE STRESS; HEART-FAILURE; FAILING HEART; PHOSPHORYLATION; PROTEIN; MICE AB Renin-angiotensin system (RAS) activation is associated with arrhythmias. We investigated the effects of RAS inhibition in cardiac-specific angiotensin-converting enzyme (ACE) overexpression (ACE 8/8) mice, which exhibit proclivity to ventricular tachycardia (VT) and sudden death because of reduced connexin43 (Cx43). ACE 8/8 mice were treated with an ACE inhibitor (captopril) or an angiotensin receptor type-1 blocker (losartan). Subsequently, electrophysiological studies were performed, and the hearts were extracted for Cx43 quantification using immunoblotting, immunohistochemistry, fluorescent dye spread method, and sodium current quantification using whole cell patch clamping. VT was induced in 12.5% of captopril-treated ACE 8/8 and in 28.6% of losartan-treated mice compared to 87.5% of untreated mice (P<0.01). Losartan and captopril treatment increased total Cx43 2.4-fold (P=0.01) and the Cx43 phosphorylation ratio 2.3-fold (P=0.005). Treatment was associated with a recovery of gap junctional conductance. Survival in treated mice improved to 0.78 at 10 weeks (95% confidence interval 0.64 to 0.92), compared to the expected survival of less than 0.50. In a model of RAS activation, arrhythmic risk was correlated with reduced Cx43 amount and phosphorylation. RAS inhibition resulted in increased total and phosphorylated Cx43, decreased VT inducibility, and improved survival. C1 [Sovari, Ali A.; Lardin, Harvey A.; Liu, Hong; Dudley, Samuel C., Jr.] Univ Illinois, Div Cardiol, Chicago, IL 60612 USA. [Iravanian, Shahriar; Jiao, Zhe] Atlanta Vet Affairs Med Ctr, Div Cardiol, Atlanta, GA 30033 USA. [Iravanian, Shahriar; Jiao, Zhe] Emory Univ, Atlanta, GA 30033 USA. [Xiao, Hong D.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Dolmatova, Elena; Duffy, Heather S.] Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA 02115 USA. [Harris, Brett S.; Gourdie, Robert G.] Med Univ S Carolina, Dept Cell Biol & Anat, Charleston, SC 29425 USA. [Witham, Emily A.] Univ Calif San Diego, Biomed Sci Grad Program, San Diego, CA 92093 USA. [Bernstein, Kenneth E.] Cedars Sinai Med Ctr, Dept Pathol, Los Angeles, CA 90048 USA. [Bernstein, Kenneth E.] Cedars Sinai Med Ctr, Dept Biomed Sci, Los Angeles, CA 90048 USA. RP Sovari, AA (reprint author), Univ Illinois, Div Cardiol, 840 S Wood St,M-C 715, Chicago, IL 60612 USA. EM scdudley@uic.edu OI Bernstein, Kenneth/0000-0001-8097-3272 FU National Institute of Health [R01 HL085558, R01 HL073753, P01 HL058000, DK039777]; American Heart Association (AHA) FX This work was supported by National Institute of Health grants R01 HL085558 (SCD, KEB), R01 HL073753 (SCD), P01 HL058000 (SCD), DK039777 (KEB), American Heart Association (AHA) National Scientist Development Grant (HDX), and AHA postdoctoral fellowship (SI). NR 34 TC 13 Z9 14 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0946-2716 J9 J MOL MED JI J. Mol. Med. PD JUL PY 2011 VL 89 IS 7 BP 677 EP 687 DI 10.1007/s00109-011-0761-3 PG 11 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 804FG UT WOS:000293639100006 PM 21553032 ER PT J AU Toh, WS Spector, M Lee, EH Cao, T AF Toh, Wei Seong Spector, Myron Lee, Eng Hin Cao, Tong TI Biomaterial-Mediated Delivery of Microenvironmental Cues for Repair and Regeneration of Articular Cartilage SO MOLECULAR PHARMACEUTICS LA English DT Review DE biomaterials; delivery systems; cartilage; microenvironment; repair; regenerative medicine; tissue engineering ID MESENCHYMAL STEM-CELLS; AUTOLOGOUS CHONDROCYTE TRANSPLANTATION; COLLAGEN-GAG SCAFFOLDS; AGE-RELATED-CHANGES; IN-VIVO; BONE-MARROW; TISSUE-REPAIR; ENGINEERING CARTILAGE; EXTRACELLULAR-MATRIX; PROGENITOR CELLS AB Articular cartilage injuries are one of the most challenging problems in musculoskeletal medicine due to the poor intrinsic regenerative capacity of this tissue. The lack of efficient treatment modalities motivates research into tissue engineering: combining cells, biomaterials mimicking extracellular matrix (scaffolds) and microenvironmental signaling cues. The, aim of this review is to focus on the use of biomaterials as delivery systems for microenvironmental cues in relation to their applications for treatment of cartilage defects. The latest advances in cartilage tissue engineering and regeneration are critically reviewed to demonstrate an outline of challenges toward biomaterial-based approaches of cartilage regeneration. C1 [Toh, Wei Seong; Spector, Myron] VA Boston Healthcare Syst, Tissue Engn Labs, Boston, MA 02130 USA. [Toh, Wei Seong; Spector, Myron] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. [Lee, Eng Hin] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Orthopaed Surg, Singapore 117510, Singapore. [Cao, Tong] Natl Univ Singapore, Fac Dent, Singapore 119083, Singapore. RP Toh, WS (reprint author), VA Boston Healthcare Syst, Tissue Engn Labs, Mail Stop 151 Res,150 S Huntington Ave, Boston, MA 02130 USA. EM wtoh@partners.org RI Toh, Wei Seong/K-7720-2013; CAO, Tong/B-1008-2008 OI Toh, Wei Seong/0000-0001-9147-6423; CAO, Tong/0000-0002-7994-9627 FU Agency for Science, Technology and Research (A*STAR) Singapore; Department of Veterans Affairs FX W.S.T. is presently supported by A*STAR International Fellowship, Agency for Science, Technology and Research (A*STAR) Singapore. M.S. is supported by a Research Career Scientist Award from the Department of Veterans Affairs. NR 92 TC 25 Z9 27 U1 0 U2 28 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 JUL-AUG PY 2011 VL 8 IS 4 SI SI BP 994 EP 1001 DI 10.1021/mp100437a PG 8 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 799SW UT WOS:000293307400002 PM 21500855 ER PT J AU DeGutis, J DeNicola, C Zink, T McGlinchey, R Milberg, W AF DeGutis, Joseph DeNicola, Christopher Zink, Tyler McGlinchey, Regina Milberg, William TI Training with own-race faces can improve processing of other-race faces: Evidence from developmental prosopagnosia SO NEUROPSYCHOLOGIA LA English DT Article DE Prosopagnosia/developmental; Continental Population Groups; Discrimination learning; Face; Recognition (psychology); Visual perception ID CONGENITAL PROSOPAGNOSIA; RECOGNITION DEFICIT; ATTENTIONAL BLINK; CATEGORIZATION; EXPERTISE; OBJECTS; DISCRIMINATION; PERCEPTION; PLASTICITY; BIAS AB Faces of one's own race are discriminated and recognized more accurately than faces of an other race (other-race effect - ORE). Studies have employed several methods to enhance individuation and recognition of other-race faces and reduce the ORE, including intensive perceptual training with other-race faces and explicitly instructing participants to individuate other-race faces. Unfortunately, intensive perceptual training has shown to be specific to the race trained and the use of explicit individuation strategies, though applicable to all races, can be demanding of attention and difficult to consistently employ. It has not yet been demonstrated that a training procedure can foster the automatic individuation of all other-race faces, not just faces from the race trained. Anecdotal evidence from a training procedure used with developmental prosopagnosics (DPs) in our lab, individuals with lifelong face recognition impairments, suggests that this may be possible. To further test this idea, we had five Caucasian DPs perform ten days of configural face training (i.e. attending to small spacing differences between facial features) with own-race (Caucasian) faces to see if training would generalize to improvements with other-race (Korean) faces. To assess training effects and localize potential effects to parts-based or holistic processing, we used the part-whole task using Caucasian and Korean faces (Tanaka, J. W., Kiefer, M., & Bukach, C. M. (2004). A holistic account of the own-race effect in face recognition: evidence from a cross-cultural study. Cognition, 93(1), B1-9). Results demonstrated that after training, DPs showed a disproportionate improvement in holistic processing of other-race faces compared to own-race faces, reducing their ORE. This suggests that configural training with own-race faces boosted DPs' general configural/holistic attentional resources, which they were able to apply to other-race faces. This provides a novel method to reduce the ORE and supports more of an attentional/social-cognitive model of the ORE rather than a strictly expertise model. Published by Elsevier Ltd. C1 [DeGutis, Joseph; McGlinchey, Regina; Milberg, William] Boston VA Healthcare Syst, GRECC, Jamaica Plain, NY USA. [DeGutis, Joseph] Harvard Univ, Dept Psychol, Vis Sci Lab, Cambridge, MA 02138 USA. [DeNicola, Christopher] Univ Louisville, Dept Psychol & Brain Sci, Louisville, KY 40292 USA. [Zink, Tyler] Boston Univ, Dept Psychol, Boston, MA 02215 USA. RP DeGutis, J (reprint author), Boston VA Healthcare Syst, GRECC, Boston, MA 02130 USA. EM degutis@wjh.harvard.edu FU VA FX We are very grateful to James Tanaka for the use of the part/whole task and his data as well as useful comments on the manuscript. We also thank Lucia Garrido, Sarah Cohan, and Rogelio J. Mercado for helpful comments. This research is supported by a VA Career Development Award granted to Joseph DeGutis. NR 52 TC 10 Z9 10 U1 1 U2 30 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD JUL PY 2011 VL 49 IS 9 BP 2505 EP 2513 DI 10.1016/j.neuropsychologia.2011.04.031 PG 9 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 803WA UT WOS:000293611600025 PM 21570991 ER PT J AU Dodson, CS Spaniol, M O'Connor, MK Deason, RG Ally, BA Budson, AE AF Dodson, Chad S. Spaniol, Maggie O'Connor, Maureen K. Deason, Rebecca G. Ally, Brandon A. Budson, Andrew E. TI Alzheimer's disease and memory-monitoring impairment: Alzheimer's patients show a monitoring deficit that is greater than their accuracy deficit SO NEUROPSYCHOLOGIA LA English DT Article DE Alzheimer's disease; Recognition memory; Source memory; Memory monitoring; Calibration; Confidence; Anosognosia ID MILD COGNITIVE IMPAIRMENT; HEALTHY OLDER-ADULTS; MEDIAL TEMPORAL-LOBE; RECALL-TO-REJECT; FALSE RECOGNITION; EPISODIC MEMORY; TERRORIST ATTACKS; PARIETAL LESIONS; FRONTAL-CORTEX; RESPONSE BIAS AB We assessed the ability of two groups of patients with mild Alzheimer's disease (AD) and two groups of older adults to monitor the likely accuracy of recognition judgments and source identification judgments about who spoke something earlier. Alzheimer's patients showed worse performance on both memory judgments and were less able to monitor with confidence ratings the likely accuracy of both kinds of memory judgments, as compared to a group of older adults who experienced the identical study and test conditions. Critically, however, when memory performance was made comparable between the AD patients and the older adults (e.g., by giving AD patients extra exposures to the study materials), AD patients were still greatly impaired at monitoring the likely accuracy of their recognition and source judgments. This result indicates that the monitoring impairment in AD patients is actually worse than their memory impairment, as otherwise there would have been no differences between the two groups in monitoring performance when there were no differences in accuracy. We discuss the brain correlates of this memory-monitoring deficit and also propose a Remembrance-Evaluation model of memory-monitoring. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Dodson, Chad S.] Univ Virginia, Dept Psychol, Charlottesville, VA 22904 USA. [Spaniol, Maggie; O'Connor, Maureen K.; Deason, Rebecca G.; Budson, Andrew E.] Bedford VA Hosp, Ctr Translat Cognit Neurosci, Geriatr Res Educ Clin Ctr, Bedford, MA USA. [Spaniol, Maggie; O'Connor, Maureen K.; Deason, Rebecca G.; Budson, Andrew E.] VA Boston Healthcare Syst, Boston, MA USA. [Spaniol, Maggie; O'Connor, Maureen K.; Deason, Rebecca G.; Budson, Andrew E.] Boston Univ, Sch Med, Alzheimers Dis Ctr, Boston, MA 02118 USA. [Ally, Brandon A.] Vanderbilt Univ, Dept Neurol, Nashville, TN USA. [Ally, Brandon A.] Vanderbilt Univ, Dept Psychol, Nashville, TN 37240 USA. [Ally, Brandon A.] Vanderbilt Univ, Dept Psychiat, Nashville, TN USA. RP Dodson, CS (reprint author), Univ Virginia, Dept Psychol, POB 400400,102 Gilmer Hall, Charlottesville, VA 22904 USA. EM cdodson@virginia.edu OI Ally, Brandon/0000-0002-6034-7968 FU National Science Foundation [0925145]; National Institute on Aging [R01 AG025815, P30 AG13846] FX This research was supported by National Science Foundation grant 0925145 (CSD) and National Institute on Aging grants R01 AG025815 (AEB) and P30 AG13846 (AEB). This material is also the result of work supported with resources and the use of facilities at the Bedford VA Hospital in Bedford, MA. NR 55 TC 9 Z9 9 U1 1 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD JUL PY 2011 VL 49 IS 9 BP 2609 EP 2618 DI 10.1016/j.neuropsychologia.2011.05.008 PG 10 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 803WA UT WOS:000293611600035 PM 21620877 ER PT J AU Rentz, DM Amariglio, RE Becker, JA Frey, M Olson, LE Frishe, K Carmasin, J Maye, JE Johnson, KA Sperling, RA AF Rentz, Dorene M. Amariglio, Rebecca E. Becker, J. Alex Frey, Meghan Olson, Lauren E. Frishe, Katherine Carmasin, Jeremy Maye, Jacqueline E. Johnson, Keith A. Sperling, Reisa A. TI Face-name associative memory performance is related to amyloid burden in normal elderly SO NEUROPSYCHOLOGIA LA English DT Article DE Preclinical Alzheimer's disease; Early detection; Normal aging; Amyloid imaging ID PITTSBURGH COMPOUND-B; PRECLINICAL ALZHEIMERS-DISEASE; POSITRON-EMISSION-TOMOGRAPHY; SUBSEQUENT COGNITIVE DECLINE; NEUROPSYCHOLOGICAL TESTS; EPISODIC MEMORY; FUNCTIONAL MRI; OLDER PERSONS; PUTTING NAMES; DEFAULT-MODE AB Cerebral amyloid beta (A beta) deposition occurs in a substantial fraction of cognitively normal (CN) older individuals. However, it has been difficult to reliably detect evidence of amyloid-related cognitive alterations in CN using standard neuropsychological measures. We sought to determine whether a highly demanding face-name associative memory exam (FNAME) could detect evidence of A beta-related memory impairment in CN. We studied 45 CN subjects (mean age = 71.7 +/- 8.8) with Clinical Dementia Rating (CDR) scores = 0 and MMSE >= 28, using Positron Emission Tomography with Pittsburgh Compound B (PiB PET). Memory factor scores were derived from a principal components analysis for FNAME name retrieval (FNN), FNAME occupation retrieval (FN-O) and the 6-Trial Selective Reminding Test (SRT). Using multiple linear and logistic regression analyses, we related the memory factor scores to PiB distribution volume ratios (DVR, cerebellar reference) as either a continuous or a dichotomous variable in frontal cortex and a posterior cortical region representing the precuneus, posterior cingulate and lateral parietal cortices (PPCLP), co-varying for age and AMNART IQ (a proxy of cognitive reserve (CR)). A significant inverse relationship for FN-N was found with A beta deposition in frontal (R-2 = 0.29, beta = -2.2, p = 0.02) and PPCLP cortices (R-2 = 0.26, beta = -2.4, p = 0.05). In contrast, neither FN-O nor the SRT were significantly related to A beta deposition. Performance on a demanding test of face-name associative memory was related to A beta burden in brain regions associated with memory systems. Associative memory for faces and names, a common complaint among older adults, may be a sensitive marker of early A beta-related impairment. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Rentz, Dorene M.] Harvard Univ, Brigham & Womens Hosp, Ctr Alzheimer Res & Treatment, Sch Med,Dept Neurol,Div Cognit & Behav Neurol, Boston, MA 02115 USA. [Rentz, Dorene M.; Olson, Lauren E.; Johnson, Keith A.; Sperling, Reisa A.] Harvard Univ, Dept Neurol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. [Becker, J. Alex; Carmasin, Jeremy; Maye, Jacqueline E.; Johnson, Keith A.] Harvard Univ, Dept Radiol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Rentz, DM (reprint author), Harvard Univ, Brigham & Womens Hosp, Ctr Alzheimer Res & Treatment, Sch Med,Dept Neurol,Div Cognit & Behav Neurol, 221 Longwood Ave, Boston, MA 02115 USA. EM drentz@partners.org FU Alzheimer Association [IIRG-08-90934, ZEN-10-174210]; National Institute on Aging [P01-AG036694-01, P50-AG00513421, R01-AG027435, R01-AG027435-S1, R01-AG037497] FX This work was supported by Alzheimer Association grants IIRG-08-90934 (D.R., K.J.) and ZEN-10-174210 (K.J.) and by National Institute on Aging grants P01-AG036694-01 (R.S. and K. J.); P50-AG00513421 (R.S. and K.J.); R01-AG027435 (R.S.); R01-AG027435-S1 (R.S., K.J.), and R01-AG037497 (K.J.) The authors wish to thank the individual research participants without which this work would not be possible. NR 72 TC 53 Z9 54 U1 4 U2 14 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD JUL PY 2011 VL 49 IS 9 BP 2776 EP 2783 DI 10.1016/j.neuropsychologia.2011.06.006 PG 8 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 803WA UT WOS:000293611600052 PM 21689670 ER PT J AU Endesfelder, D McGranahan, N Birkbak, NJ Szallasi, Z Kschischo, M Graham, TA Swanton, C AF Endesfelder, David McGranahan, Nicholas Birkbak, Nicolai J. Szallasi, Zoltan Kschischo, Maik Graham, Trevor A. Swanton, Charles TI A breast cancer meta-analysis of two expression measures of chromosomal instability reveals a relationship with younger age at diagnosis and high risk histopathological variables. SO ONCOTARGET LA English DT Article DE breast cancer; age; chromosomal instability; histopathological parameters ID SIGNATURE; SURVIVAL; CHEMOTHERAPY; RESISTANCE; PROGNOSIS; PROFILES; PATTERNS; TRENDS; TUMORS AB Breast cancer in younger patients often presents with adverse histopathological features, including increased frequency of estrogen receptor negative and lymph node positive disease status. Chromosomal instability (CIN) is increasingly recognised as an important prognostic variable in solid tumours. In a breast cancer meta-analysis of 2423 patients we examine the relationship between clinicopathological parameters and two distinct chromosomal instability gene expression signatures in order to address whether younger age at diagnosis is associated with increased tumour genome instability. We find that CIN, assessed by the two independently derived CIN expression signatures, is significantly associated with increased tumour size, ER negative or HER2 positive disease, higher tumour grade and younger age at diagnosis in ER negative breast cancer. These data support the hypothesis that chromosomal instability may be a defining feature of breast cancer biology and clinical outcome. C1 [Endesfelder, David; McGranahan, Nicholas; Graham, Trevor A.; Swanton, Charles] Canc Res UK London Res Inst, London WC2A 3LY, England. [McGranahan, Nicholas] UCL, Ctr Math & Phys Life Sci & Expt Biol CoMPLEX, London WC1E 6BT, England. [Birkbak, Nicolai J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Birkbak, Nicolai J.; Szallasi, Zoltan] Tech Univ Denmark, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark. [Szallasi, Zoltan] Harvard Univ, Sch Med, Childrens Hosp Informat Program, Harvard MIT Div Hlth Sci & Technol CHIP HST, Boston, MA USA. [Kschischo, Maik] Univ Appl Sci, D-53424 Remagen, Germany. [Swanton, Charles] Royal Marsden Hosp, Breast Unit, Dept Med, Sutton SM2 5PT, Surrey, England. [Swanton, Charles] Royal Marsden Hosp, Drug Dev Unit, Dept Med, Sutton SM2 5PT, Surrey, England. RP Swanton, C (reprint author), Canc Res UK London Res Inst, London WC2A 3LY, England. EM trevor.graham@cancer.org.uk; charles.swanton@cancer.org.uk FU CR-UK; MRC; Inflammatory Breast Cancer UK; NIH [NCI SPORE P50 CA 89393, R21LM008823-01A1]; Breast Cancer Research Foundation FX CS is a Medical Research Council senior clinical research fellow. This work was funded by CR-UK, MRC, Inflammatory Breast Cancer UK, NIH (grants NCI SPORE P50 CA 89393, R21LM008823-01A1) and by the Breast Cancer Research Foundation. NR 36 TC 3 Z9 4 U1 0 U2 1 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD JUL PY 2011 VL 2 IS 7 BP 529 EP 537 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 802KU UT WOS:000293510500003 PM 21709316 ER PT J AU Watson, AJ O'Rourke, J Jethwani, K Cami, A Stern, TA Kvedar, JC Chueh, HC Zai, AH AF Watson, Alice J. O'Rourke, Julia Jethwani, Kamal Cami, Aurel Stern, Theodore A. Kvedar, Joseph C. Chueh, Henry C. Zai, Adrian H. TI Linking Electronic Health Record-Extracted Psychosocial Data in Real-Time to Risk of Readmission for Heart Failure SO PSYCHOSOMATICS LA English DT Article ID RANDOMIZED-TRIAL; HOSPITAL READMISSION; CARE; INTERVENTION; DEATH; REHOSPITALIZATION; DEPRESSION; PREDICTION; OUTCOMES; PROGRAM AB Background: Knowledge of psychosocial characteristics that helps to identify patients at increased risk for readmission for heart failure (HF) may facilitate timely and targeted care. Objective: We hypothesized that certain psychosocial characteristics extracted from the electronic health record (EHR) would he associated with an increased risk for hospital readmission within the next 30 days. Methods: We identified 15 psychosocial predictors of readmission. Eleven of these were extracted from the EHR (six from structured data sources and five from unstructured clinical notes). We then analyzed their association with the likelihood of hospital readmission within the next 30 days among 729 patients admitted for HF. Finally, we developed a multivariable predictive model to recognize individuals at high risk for readmission. Results: We found five characteristics-dementia, depression, adherence, declining/refusal of services, and missed clinical appointments-that were associated with an increased risk for hospital readmission: the first four features were captured from unstructured clinical notes, while the last item was captured from a structured data source. Conclusions: Unstructured clinical notes contain important knowledge on the relationship between psychosocial risk factors and an increased risk of readmission for HE that would otherwise have been missed if only structured data were considered. Gathering this EHR-based knowledge can be automated, thus enabling timely and targeted care. (Psychosomatics 2011; 52:319-327) C1 [O'Rourke, Julia; Chueh, Henry C.; Zai, Adrian H.] Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA 02114 USA. [Watson, Alice J.; Jethwani, Kamal; Kvedar, Joseph C.] Partners Healthcare, Ctr Connected Hlth, Boston, MA USA. [Cami, Aurel] Childrens Hosp, Boston, MA 02115 USA. [Stern, Theodore A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Zai, AH (reprint author), Massachusetts Gen Hosp, Comp Sci Lab, 50 Staniford St,Suite 750, Boston, MA 02114 USA. EM azai@partners.org OI Zai, Adrian/0000-0002-2972-6839 FU Vitality, Inc.; SentiCare; Siemens; National Institutes of Health, National Library of Medicine [5T15LM007092]; McGraw-Hill; Mosby-Elsevier (fur editing textboooks on psychiatry); Partners Healthcare/Siemens Research Council FX Dr. Watson has received grant funding from Vitality, Inc., SentiCare and Siemens. Dr. O'Rourke is funded by the Boston-area research training program in biomedical informatics from the National Institutes of Health, National Library of Medicine. Dr. Jethwani has received grant funding from SentiCare. Dr. Cami is funded by the Boston-area research training program in biomedical informatics from the National Institutes of Health, National Library of Medicine. Dr. Stern is an employee of the Academy of Psychosomatic Medicine (Editor-in-Chief of Psychosomatics), and receives royalties from McGraw-Hill and Mosby-Elsevier (fur editing textboooks on psychiatry). Dr. Kvedar has done consulting work in the last 3 years for Derm LLC, Suture Health Inc. and Healthrageous. Dr. Clutch reports stock ownership in Linked Medical, Inc., a startup company that intends to commercialize Massachusetts General Hospital (MGH)'s Oncall electronic health record. Dr. Zai is the principal investigator of a grant from the Partners Healthcare/Siemens Research Council, which supports this project.; This project was funded by a grant from the Partners Healthcare/Siemens Research Council and by a Boston area research training program in biomedical informatics from the National Institutes of Health, National Library of Medicine (5T15LM007092). NR 36 TC 21 Z9 21 U1 3 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD JUL-AUG PY 2011 VL 52 IS 4 BP 319 EP 327 PG 9 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 802YH UT WOS:000293546400003 PM 21777714 ER PT J AU Singh, AK Cronin, CG Verma, HA Boland, GW Saini, S Mueller, PR Sahani, DV AF Singh, Ajay K. Cronin, Carmel G. Verma, Hetal A. Boland, Giles W. Saini, Sanjay Mueller, Peter R. Sahani, Dushyant V. TI Imaging of Preoperative Liver Transplantation in Adults: What Radiologists Should Know SO RADIOGRAPHICS LA English DT Article ID DONOR LIVER; HEPATOCELLULAR-CARCINOMA; VARIANTS; SURVIVAL; SURGERY; MODEL; ANGIOGRAPHY; VALIDATION; RECURRENCE; CANDIDATES AB Therapeutic strategies for treating patients with liver failure, particularly optimization of liver transplantation, are constantly being refined, with the goal of improving long-term survival with the lowest risk for toxicity in donors and recipients. Optimal planning for liver transplantation requires a multidisciplinary collaboration between the radiologist, hepatologist, clinical oncologist, and transplant surgeon. Radiologists play an essential role in identifying normal and abnormal variant anatomy and other conditions that may be present, a task that is critical for accurate surgical planning. Radiologists also must understand how their findings affect patient preparation. An awareness of the range of indications for liver transplantation, imaging modalities, and current surgical techniques is important to properly evaluate a patient who may undergo liver transplantation. Establishing a pretransplantation definition of the extent of liver disease and thoroughly evaluating the vascular and biliary anatomy are paramount for proper assessment of potential recipients and donors for liver transplantation. (C) RSNA, 2011 radiographics.rsna.org C1 [Singh, Ajay K.; Cronin, Carmel G.; Verma, Hetal A.; Boland, Giles W.; Saini, Sanjay; Mueller, Peter R.; Sahani, Dushyant V.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Singh, AK (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM mghpartners@yahoo.com NR 30 TC 9 Z9 10 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD JUL-AUG PY 2011 VL 31 IS 4 BP 1017 EP 1030 DI 10.1148/rg.314105197 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 794AV UT WOS:000292867000008 PM 21768236 ER PT J AU Blake, MA AF Blake, Michael A. TI Dual-Energy (Spectral) CT: Applications in Abdominal Imaging SO RADIOGRAPHICS LA English DT Editorial Material ID TOMOGRAPHY; ABDOMEN; KVP C1 Massachusetts Gen Hosp, Div Abdominal Imaging, Boston, MA 02114 USA. RP Blake, MA (reprint author), Massachusetts Gen Hosp, Div Abdominal Imaging, Boston, MA 02114 USA. NR 17 TC 1 Z9 1 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD JUL-AUG PY 2011 VL 31 IS 4 BP 1047 EP 1050 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 794AV UT WOS:000292867000010 ER PT J AU Atlas, SJ AF Atlas, Steven J. TI Commentary: Predictive factors influencing clinical outcome with operative management of lumbar spinal stenosis SO SPINE JOURNAL LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Div Gen Med, Med Serv,Med Sch, Boston, MA 02114 USA. RP Atlas, SJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Div Gen Med, Med Serv,Med Sch, 50 Staniford St, Boston, MA 02114 USA. EM satlas@partners.org NR 10 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 1529-9430 J9 SPINE J JI Spine Journal PD JUL PY 2011 VL 11 IS 7 BP 620 EP 621 DI 10.1016/j.spinee.2011.05.003 PG 2 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 803PF UT WOS:000293592500011 PM 21821200 ER PT J AU Zuckerman, KE Nelson, K Bryant, TK Hobrecker, K Perrin, JM Donean, K AF Zuckerman, Katharine E. Nelson, Kerrie Bryant, Tara K. Hobrecker, Karin Perrin, James M. Donean, Karen TI Specialty Referral Communication and Completion in the Community Health Center Setting SO ACADEMIC PEDIATRICS LA English DT Article DE communication; community health centers; medical specialty; pediatrics; referral and consultation ID PRIMARY-CARE; CHILDREN; PATIENT; GENERALIST AB OBJECTIVE: Parent and provider disagreement about children's care at the time of specialty referral may lead to incomplete referral, ie, not attending a specialty visit when referred. This study's objectives were first to assess parent-provider correlation in perspectives on referral necessity, seriousness of child's health problem, and parental understanding of referral among children referred to pediatric specialists, and second to assess whether these perspectives are associated with incomplete referral. METHODS: Two months after specialty referral, parents and primary care providers completed a survey rating referral necessity, seriousness of problem, and parental understanding on a 4-part scale ("definitely yes" to "definitely no"). Parents were surveyed by telephone; providers completed one self-administered survey per referral. Using z tests and Pearson correlation coefficients, we summarized parent-provider agreement about referral necessity, seriousness of problem, and parent understanding. We applied logistic regression to test associations of parent and provider ratings for each variable with incomplete referral. RESULTS: A total of 299 (60.0%) of 498 matched parent and provider surveys were included in the analysis. Parents had low correlation with providers in perspectives of referral necessity and seriousness of problem. Parents reported that referral was necessary more often than providers, and providers under-estimated parents' self-reported understanding of the referral. Nearly 1 in 3 children had incomplete referral, and both parent and provider reports of lower necessity were associated with incomplete referral. CONCLUSIONS: Parents and providers hold divergent perspectives on referral necessity and seriousness of children's health problems; these perspectives may impact rates of incomplete referral. Improving communication around specialty referral might reduce incomplete referral. C1 [Zuckerman, Katharine E.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Nelson, Kerrie] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Bryant, Tara K.] Case Western Reserve Med Sch, Cleveland, OH USA. [Hobrecker, Karin] Massachusetts Gen Hosp, Patient Care Serv, Boston, MA 02114 USA. [Perrin, James M.] MassGen Hosp Children, Ctr Child & Adolescent Hlth Policy, Boston, MA USA. [Donean, Karen] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. RP Zuckerman, KE (reprint author), Child & Adolescent Hlth Measurement Initiat, Div Gen Pediat, 707 SW Gaines St,Mail Code CDRC-P, Portland, OR 97239 USA. EM zuckerma@ohsu.edu FU CRICO-Risk Management Foundation; National Research Service Award [T32 HP10018] FX This study was funded by a grant from the CRICO-Risk Management Foundation to Massachusetts General Hospital (PI = Zuckerman). Dr. Zuckerman's effort was also supported by a National Research Service Award (T32 HP10018) to the Harvard Pediatric Health Services Research Fellowship Program. The authors would like to thank all of the parents and health care providers for their participation. We additionally thank Esteban Barreto, Xin Cai, Gibran Minero, Michelle Connolly, Dianali Rivera, Tara Bryant, and Odeviz Soto for their assistance with data collection. NR 26 TC 6 Z9 6 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1876-2859 J9 ACAD PEDIATR JI Acad. Pediatr. PD JUL-AUG PY 2011 VL 11 IS 4 BP 288 EP 296 PG 9 WC Pediatrics SC Pediatrics GA 797EJ UT WOS:000293107000006 PM 21622041 ER PT J AU Welch, LK Olson, KL Snow, KE Pointer, L Lambert-Kerzner, A Havranek, EP Magid, DJ Ho, PM AF Welch, Lesley K. Olson, Kari L. Snow, Karen E. Pointer, Lauren Lambert-Kerzner, Anne Havranek, Edward P. Magid, David J. Ho, P. Michael TI Systolic Blood Pressure Control After Participation in a Hypertension Intervention Study SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID OUTCOMES; DISEASE AB Objective: To evaluate whether systolic blood pressure (SBP) control is maintained following participation in a multimodal hypertension intervention. Study Design: This was a retrospective cohort of patients completing the Improving Blood Pressure in Colorado study, a randomized trial comparing a multimodal intervention with usual care for patients who had uncontrolled hypertension. Methods: Chart review assessed the first SBP measurement recorded as part of routine care after the study ended. Among patients who had controlled SBP at the final study visit, the proportions who had uncontrolled SBP during follow-up were compared for the intervention and usual care (UC) groups. Kaplan-Meier estimates assessed time to uncontrolled SBP by treatment arm. Results: Of 283 patients completing the Improving Blood Pressure in Colorado study, 51.5% in the intervention and 46.9% in the UC group had controlled SBP at the final study visit. Of patients with controlled SBP, 37.0% and 46.4% of patients in the intervention and UC groups, respectively, had uncontrolled SBP at their initial measurement during follow-up (P = .32). There was no difference in median time to uncontrolled SBP (126 vs 114 days for the intervention and UC groups, respectively; P = .47). Conclusions: SBP control was not maintained in a significant proportion of patients in both groups following hypertension study participation. These findings suggest the need for interventions to focus on longer-term BP control in contrast to the short duration of most hypertension intervention trials. (Am J Manag Care. 2011; 17(7):473-478) C1 [Welch, Lesley K.; Pointer, Lauren; Lambert-Kerzner, Anne; Ho, P. Michael] Denver VA Med Ctr, Denver, CO USA. [Olson, Kari L.] Kaiser Permanente Colorado, Dept Pharm, Aurora, CO USA. [Olson, Kari L.; Lambert-Kerzner, Anne; Havranek, Edward P.; Magid, David J.; Ho, P. Michael] Univ Colorado Denver, Denver, CO USA. [Snow, Karen E.; Havranek, Edward P.] Denver Hlth Med Ctr, Denver, CO USA. [Magid, David J.] Kaiser Permanente Colorado, Inst Hlth, Denver, CO USA. RP Welch, LK (reprint author), 1055 Clermont St, Denver, CO 80220 USA. EM Lesley.welch@va.gov FU American Heart Association [0535086N]; VA Health Services Research and Development Award [05-026] FX This work was funded by an award from the American Heart Association (0535086N).; Dr Ho is supported by a VA Health Services Research and Development Award (05-026) and serves as a consultant for Wellpoint, Inc. He also reports having given lectures for Pfizer in Japan. The authors (LKW, KLO, KES, LP, AL-K, EPH, DJM) report no relationship or financial interest with any entity that would pose a conflict of interest with the subject matter of this article. NR 13 TC 4 Z9 4 U1 0 U2 0 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD JUL PY 2011 VL 17 IS 7 BP 473 EP 478 PG 6 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 801QJ UT WOS:000293455000007 PM 21819167 ER PT J AU Fung, V Brand, RJ Newhouse, JP Hsu, J AF Fung, Vicki Brand, Richard J. Newhouse, Joseph P. Hsu, John TI Using Medicare Data for Comparative Effectiveness Research: Opportunities and Challenges SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Review ID ACUTE MYOCARDIAL-INFARCTION; INSTRUMENTAL-VARIABLES; OUTCOMES RESEARCH; CLINICAL-TRIALS; HEALTH-POLICY; CARE; MORTALITY; SELECTION; QUALITY; REFORM AB Background: With the introduction of Part D drug benefits, Medicare began to collect information on diagnoses, treatments, and clinical events for millions of beneficiaries. These data are a promising resource for comparative effectiveness research (CER) on treatments, benefit designs, and delivery systems. Objective: To explore the data available for researchers and approaches that could be used to enhance the value of Medicare data for CER. Challenges and Opportunities: Using currently available Medicare data for CER is challenging; as with all administrative data, it is not possible to capture every factor that contributes to prescribing decisions and patients are not randomly assigned to treatments. In addition, Part D plan selection and switching may influence treatment decisions and contribute to selection bias. Exploiting certain program aspects could address these limitations. For example, ongoing changes in Medicare or plan policies and the random assignment of beneficiaries with Part D low-income subsidies into plans with different formularies could yield natural experiments. Conclusions: Medicare data provide a rich resource for CER. Leveraging existing program elements, combined with some administrative changes in data availability, could create large data sets for evaluating treatment patterns, spending, and coverage decisions. (Am J Manag Care. 2011; 17(7):489-496) C1 [Fung, Vicki] Midatlantic Permanente Med Grp, Midatlantic Permanente Res Inst, Rockville, MD USA. [Brand, Richard J.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Newhouse, Joseph P.; Hsu, John] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Newhouse, Joseph P.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Newhouse, Joseph P.] Harvard Univ, John F Kennedy Sch Govt, Cambridge, MA 02138 USA. [Hsu, John] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. RP Fung, V (reprint author), Kaiser Permanente, 2101 E Jefferson St, Rockville, MD 20852 USA. EM Vicki.Fung@kp.org FU National Institute on Aging [R01 AG029316]; Commonwealth Fund; Alfred P. Sloan Foundation; National Institutes of Health FX The National Institute on Aging (R01 AG029316), the Commonwealth Fund, and the Alfred P. Sloan Foundation provided funding for the study.; Dr Newhouse reports board membership with Aetna and also reports holding stock in the company. Dr Hsu reports receiving grants from the National Institutes of Health. The other authors (VF, RJB) report no relationship or financial interest with any entity that would pose a conflict of interest with the subject matter of this article. NR 34 TC 5 Z9 5 U1 0 U2 7 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD JUL PY 2011 VL 17 IS 7 BP 489 EP 496 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 801QJ UT WOS:000293455000009 ER PT J AU Zhao, KQ Goldstein, N Yang, HB Cowan, AT Chen, B Zheng, CQ Palmer, JN Kreindler, JL Cohen, NA AF Zhao, Ke-Qing Goldstein, Natalia Yang, Haibin Cowan, Andrew T. Chen, Bei Zheng, Chunquan Palmer, James N. Kreindler, James L. Cohen, Noam A. TI Inherent differences in nasal and tracheal ciliary function in response to Pseudomonas aeruginosa challenge SO AMERICAN JOURNAL OF RHINOLOGY & ALLERGY LA English DT Article ID LIQUID INTERFACE CULTURES; BEAT FREQUENCY; CHRONIC RHINOSINUSITIS; IN-VITRO; AIRWAY; EPITHELIUM; PYOCYANIN; SINUSITIS; TRANSPORT; RHINITIS AB Background: Sinonasal mucosal biofilms are recognized as contributors to the pathogenesis of chronic rhinosinusitis (CRS). Attachment of bacteria to the sinonasal surface is an initial step in biofilm formation. A critical defense against this occurrence is mucociliary clearance (MCC). To ascertain whether the ciliary component of MCC is uniform throughout the airway we compared ciliary beat frequency (CBF) in the murine nasal septum and trachea at baseline and after challenge with Pseudomonas aeruginosa, a common pathogen of CRS. Methods: Murine septal and tracheal air-liquid interface cultures were evaluated for basal and stimulated CBF after exposure to control or conditioned media from Pseudomonas. Additionally, the attachment of Pseudomonas to nasal and tracheal cultures was assessed after pretreatment with control or conditioned media. Results: Basal CBF is significantly slower in primary nasal airway cultures compared with tracheal airway cultures. Tracheal airway cultures show resistance to Pseudomonas secreted ciliotoxins not evident in nasal septal cultures. Furthermore, after challenge with viable Pseudomonas, significantly more bacteria attach to the nasal cultures compared with the tracheal cultures. Conclusion: Using primary murine nasal and tracheal airway cultures we show inherent differences in cilia function and increased susceptibility of the upper airway to attachment by Pseudomonas. Understanding the differences between upper and subglottic airway mucociliary clearance should lead to novel approaches in the management of upper airway infection. (Am J Rhinol Allergy 25, 209-213, 2011; doi: 10.2500/ajra.2011.25.3614) C1 [Zhao, Ke-Qing; Goldstein, Natalia; Chen, Bei; Palmer, James N.; Cohen, Noam A.] Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Philadelphia, PA 19004 USA. [Zhao, Ke-Qing; Zheng, Chunquan] Fudan Univ, Sch Shanghai Med, Eye & Ear Nose & Throat Hosp, Dept Otorhinolaryngol Head & Neck Surg, Shanghai 200433, Peoples R China. [Goldstein, Natalia] Pontificia Univ Catolica Chile, PhD Program Med Sci, Santiago, Chile. [Yang, Haibin] Xiamen Univ, Zhongshan Hosp, Dept Otolaryngol, Xiamen, Fujian, Peoples R China. [Cowan, Andrew T.] Temple Univ, Sch Med, Dept Otorhinolaryngol Head & Neck Surg, Philadelphia, PA 19122 USA. [Kreindler, James L.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Kreindler, James L.] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19004 USA. [Cohen, Noam A.] Philadelphia Vet Affairs Med Ctr, Surg Serv, Philadelphia, PA USA. RP Cohen, NA (reprint author), Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Ravdin Bldg,5th Floor,3400 Spruce St, Philadelphia, PA 19004 USA. EM cohenn@uphs.upenn.edu OI Cohen, Noam/0000-0002-9462-3932 NR 32 TC 11 Z9 11 U1 0 U2 10 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1945-8924 J9 AM J RHINOL ALLERGY JI Am. J. Rhinol. Allergy PD JUL-AUG PY 2011 VL 25 IS 4 BP 209 EP 213 DI 10.2500/ajra.2011.25.3614 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA 797OB UT WOS:000293136100012 PM 21819755 ER PT J AU Hwang, U Aufses, AH Bickell, NA AF Hwang, Ula Aufses, Arthur H., Jr. Bickell, Nina A. TI Factors associated with delays to emergency care for bowel obstruction SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Emergency department; Bowel obstruction; Hand-offs; Delays ID CLOSED MALPRACTICE CLAIMS; NURSE-STAFFING LEVELS; QUALITY; TIME; MANAGEMENT; RISK; PAIN; APPENDICITIS; DIAGNOSES; OUTCOMES AB BACKGROUND: Our objective was to determine factors associated with delays to first treatment for emergency department (ED) patients diagnosed with small-bowel obstruction (SBO). METHODS: This was a retrospective study of ED patients with SBO. Data were collected from medical records, administrative databases, and staffing schedules at an urban, tertiary care medical center from June 1, 2001, to November 30, 2002. Patient-related characteristics and processes of ED and hospital care were evaluated. Outcomes studied were time to first treatment (nasogastric tube or surgery) and risk of surgical resection. RESULTS: A total of 193 patients were diagnosed with confirmed intestinal obstruction. Patients with longer times to first treatment arrived during ED clinician hand-offs (adjusted hazard ratio, .40; 95% confidence interval, .17-.98). Patients with longer times to surgery consult (ref. first quartile) had greater odds of surgical resection (second quartile adjusted odds ratio, 6.91; 95% confidence interval, 1.85-24.80). CONCLUSIONS: Remediable ED and hospital factors were associated with longer times to treatment for patients with bowel obstruction. Published by Elsevier Inc. C1 [Hwang, Ula] Mt Sinai Sch Med, Dept Emergency Med, New York, NY 10029 USA. [Hwang, Ula] Mt Sinai Sch Med, Brookdale Dept Geriatr & Palliat Care, New York, NY 10029 USA. [Hwang, Ula] Mt Sinai Sch Med, Dept Hlth Evidence & Policy, New York, NY 10029 USA. [Aufses, Arthur H., Jr.; Bickell, Nina A.] Mt Sinai Sch Med, Dept Surg, New York, NY 10029 USA. [Aufses, Arthur H., Jr.] Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. [Bickell, Nina A.] James J Peters Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. RP Hwang, U (reprint author), Mt Sinai Sch Med, Dept Emergency Med, 1 Gustave L Levy Pl,Box 1620, New York, NY 10029 USA. EM ula.hwang@mountsinai.org FU Healthcare Research and Quality [R0313464] FX This study was funded by the Agency for Healthcare Research and Quality R0313464 (N.A.B.). NR 29 TC 4 Z9 4 U1 0 U2 2 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD JUL PY 2011 VL 202 IS 1 BP 1 EP 7 DI 10.1016/j.amjsurg.2010.05.003 PG 7 WC Surgery SC Surgery GA 803PR UT WOS:000293593700004 PM 21632032 ER PT J AU Cruzat, A Witkin, D Baniasadi, N Zheng, L Ciolino, JB Jurkunas, UV Chodosh, J Pavan-Langston, D Dana, R Hamrah, P AF Cruzat, Andrea Witkin, Deborah Baniasadi, Neda Zheng, Lixin Ciolino, Joseph B. Jurkunas, Ula V. Chodosh, James Pavan-Langston, Deborah Dana, Reza Hamrah, Pedram TI Inflammation and the Nervous System: The Connection in the Cornea in Patients with Infectious Keratitis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID VIVO-CONFOCAL-MICROSCOPY; DENDRITIC CELL DISTRIBUTION; ANTIGEN-PRESENTING CELLS; MARROW-DERIVED CELLS; DRY EYE; SJOGRENS-SYNDROME; OCULAR SURFACE; SUBSTANCE-P; NERVES; MORPHOLOGY AB PURPOSE. To study the density and morphologic characteristics of epithelial dendritic cells, as correlated to subbasal corneal nerve alterations in acute infectious keratitis (IK) by in vivo confocal microscopy (IVCM). METHODS. IVCM of the central cornea was performed prospectively in 53 eyes with acute bacterial (n = 23), fungal (n = 13), and Acanthamoeba (n = 17) keratitis, and in 20 normal eyes, by using laser in vivo confocal microscopy. Density and morphology of dendritic-shaped cells (DCs) of the central cornea, corneal nerve density, nerve numbers, branching, and tortuosity were assessed and correlated. It should be noted that due to the "in vivo" nature of the study, the exact identity of these DCs cannot be specified, as they could be monocytes or tissue macrophages, but most likely dendritic cells. RESULTS. IVCM revealed the presence of central corneal DCs in all patients and controls. The mean DC density was significantly higher in patients with bacterial (441.1 +/- 320.5 cells/mm(2); P < 0.0001), fungal (608.9 +/- 812.5 cells/mm(2); P < 0.0001), and Acanthamoeba keratitis (1000.2 +/- 1090.3 cells/mm(2); P < 0.0001) compared with controls (49.3 +/- 39.6 cells/mm(2)). DCs had an increased size and dendrites in patients with IK. Corneal nerves were significantly reduced in eyes with IK compared with controls across all subgroups, including nerve density (674.2 +/- 976.1 vs. 3913.9 +/- 507.4 mu m/frame), total nerve numbers (2.7 +/- 3.9 vs. 20.2 +/- 3.3), main trunks (1.5 +/- 2.2 vs. 6.9 +/- 1.1), and branching (1.2 +/- 2.0 vs. 13.5 +/- 3.1; P < 0.0001). A strong association between the diminishment of corneal nerves and the increase of DC density was observed ( r = -0.44; P < 0.0005). CONCLUSIONS. IVCM reveals an increased density and morphologic changes of central epithelial DCs in infectious keratitis. There is a strong and significant correlation between the increase in DC numbers and the decreased subbasal corneal nerves, suggesting a potential interaction between the immune and nervous system in the cornea. (Invest Ophthalmol Vis Sci. 2011;52:5136-5143) DOI:10.1167/iovs.10-7048 C1 [Hamrah, Pedram] Harvard Univ, Ocular Surface Imaging Ctr, Cornea & Refract Surg Serv, Sch Med,Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Cruzat, Andrea; Ciolino, Joseph B.; Jurkunas, Ula V.; Chodosh, James; Pavan-Langston, Deborah; Dana, Reza; Hamrah, Pedram] Harvard Univ, Dept Ophthalmol, Cornea & Refract Surg Serv, Sch Med,Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Hamrah, P (reprint author), Harvard Univ, Ocular Surface Imaging Ctr, Cornea & Refract Surg Serv, Sch Med,Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM pedram_hamrah@meei.harvard.edu OI Cruzat, Andrea/0000-0002-3724-7037 FU NIH [K12-EY016335, K08-EY020575, K24-EY19098]; New England Corneal Transplant Research Fund; Falk Medical Research Foundation; Research to Prevent Blindness, New York, New York FX Supported by NIH K12-EY016335 (PH), NIH K08-EY020575 (PH), NIH K24-EY19098 (RD), New England Corneal Transplant Research Fund (PH), Falk Medical Research Foundation (PH), and an unrestricted grant to the Department of Ophthalmology, Harvard Medical School, from Research to Prevent Blindness, New York, New York. The funding organizations had no role in the design or conduct of this research. NR 56 TC 52 Z9 52 U1 2 U2 8 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUL PY 2011 VL 52 IS 8 BP 5136 EP 5143 DI 10.1167/iovs.10-7048 PG 8 WC Ophthalmology SC Ophthalmology GA 800QC UT WOS:000293377400018 PM 21460259 ER PT J AU Shih, YYI De La Garza, BH Muir, ER Rogers, WE Harrison, JM Kiel, JW Duong, TQ AF Shih, Yen-Yu I. De La Garza, Bryan H. Muir, Eric R. Rogers, William E. Harrison, Joseph M. Kiel, Jeffrey W. Duong, Timothy Q. TI Lamina-Specific Functional MRI of Retinal and Choroidal Responses to Visual Stimuli SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID CEREBRAL-BLOOD-FLOW; DIFFUSE LUMINANCE FLICKER; LASER-DOPPLER FLOWMETRY; BOLD FMRI; OPTIC-NERVE; SOMATOSENSORY STIMULATION; HEMODYNAMIC-RESPONSE; FOREPAW STIMULATION; ANESTHETIZED RATS; OXYGEN-TENSION AB PURPOSE. To demonstrate lamina-specific functional magnetic resonance imaging (MRI) of retinal and choroidal responses to visual stimulation of graded luminance, wavelength, and frequency. MATERIALS AND METHODS. High-resolution (60 X 60 mu m) MRI was achieved using the blood-pool contrast agent, monocrystalline iron oxide nanoparticles (MION) and a high-magnetic-field (11.7 T) scanner to image functional changes in the normal rat retina associated with various visual stimulations. MION functional MRI measured stimulus-evoked blood-volume (BV) changes. Graded luminance, wavelength, and frequency were investigated. Stimulus-evoked fMRI signal changes from the retinal and choroidal vascular layers were analyzed. RESULTS. MRI revealed two distinct laminar signals that corresponded to the retinal and choroidal vascular layers bounding the retina and were separated by the avascular layer in between. The baseline outer layer BV index was 2-4 times greater than the inner layer BV, consistent with higher choroidal vascular density. During visual stimulation, BV responses to flickering light of different luminance, frequency, and wavelength in the inner layer were greater than those in the outer layer. The inner layer responses were dependent on luminance, frequency, and wavelength, whereas the outer layer responses were not, suggesting differential neurovascular coupling between the two vasculatures. CONCLUSIONS. This is the first report of simultaneous resolution of layer-specific functional responses of the retinal and choroid vascular layers to visual stimulation in the retina. This imaging approach could have applications in early detection and longitudinal monitoring of retinal diseases where retinal and choroidal hemodynamics may be differentially perturbed at various stages of the diseases. (Invest Ophthalmol Vis Sci. 2011; 52:5303-5310) DOI: 10.1167/iovs.10-6438 C1 [Shih, Yen-Yu I.; De La Garza, Bryan H.; Muir, Eric R.; Rogers, William E.; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Harrison, Joseph M.; Kiel, Jeffrey W.; 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 Radiol, 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; Muir, Eric/H-8830-2013; OI Shih, Yen-Yu Ian/0000-0001-6529-911X FU NIH/NEI [R01 EY014211, EY018855, R01EY09702]; Department of Veterans Affairs; San Antonio Life Science Institute; American Heart Association [10POST4290091]; San Antonio Area Foundation FX Supported in part by the NIH/NEI (R01 EY014211, EY018855, and R01EY09702), MERIT Award from the Department of Veterans Affairs, and a grant from the San Antonio Life Science Institute to TQD. Y.-Y.I.S. is supported by American Heart Association (10POST4290091) and San Antonio Area Foundation. NR 64 TC 22 Z9 23 U1 0 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUL PY 2011 VL 52 IS 8 BP 5303 EP 5310 DI 10.1167/iovs.10-6438 PG 8 WC Ophthalmology SC Ophthalmology GA 800QC UT WOS:000293377400039 PM 21447679 ER PT J AU Chen, JJ Smaoui, N Hammer, MBH Jiao, XD Riazuddin, SA Harper, S Katsanis, N Riazuddin, S Chaabouni, H Berson, EL Hejtmancik, JF AF Chen, Jianjun Smaoui, Nizar Hammer, Monia Ben Hamed Jiao, Xiaodong Riazuddin, S. Amer Harper, Shyana Katsanis, Nicholas Riazuddin, Sheikh Chaabouni, Habiba Berson, Eliot L. Hejtmancik, J. Fielding TI Molecular Analysis of Bardet-Biedl Syndrome Families: Report of 21 Novel Mutations in 10 Genes SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID BBS GENES; POPULATION; DISEASE; IDENTIFICATION; COMPLEX; LOCUS; INHERITANCE; PROTEINS; OBESITY AB PURPOSE. Bardet-Biedl syndrome (BBS) is genetically heterogeneous with 15 BBS genes currently identified, accounting for approximately 70% of cases. The aim of our study was to define further the spectrum of BBS mutations in a cohort of 44 European-derived American, 8 Tunisian, 1 Arabic, and 2 Pakistani families (55 families in total) with BBS. METHODS. A total of 142 exons of the first 12 BBS-causing genes were screened by dideoxy sequencing. Cases in which no mutations were found were then screened for BBS13, BBS14, BBS15, RPGRIP1L, CC2D2A, NPHP3, TMEM67, and INPP5E. RESULTS. Forty-three mutations, including 8 frameshift mutations, 10 nonsense mutations, 4 splice site mutations, 1 deletion, and 20 potentially or probably pathogenic missense variations, were identified in 46 of the 55 families studied (84%). Of these, 21 (2 frameshift mutations, 4 nonsense mutations, 4 splice site mutations, 1 deletion, and 10 missense variations) were novel. The molecular genetic findings raised the possibility of triallelic inheritance in 7 Caucasian families, 1 Arabian family, and 1 Tunisian patient. No mutations were detected for BBS4, BBS11, BBS13, BBS14, BBS15, RPGRIP1L, CC2D2A, NPHP3, TMEM67, or INPP5E. CONCLUSIONS. This mutational analysis extends the spectrum of known BBS mutations. Identification of 21 novel mutations highlights the genetic heterogeneity of this disorder. Differences in European and Tunisian patients, including the high frequency of the M390R mutation in Europeans, emphasize the population specificity of BBS mutations with potential diagnostic implications. The existence of some BBS cases without mutations in any currently identified BBS genes suggests further genetic heterogeneity. (Invest Ophthalmol Vis Sci. 2011; 52:5317-5324) DOI: 10.1167/iovs.11-7554 C1 [Chen, Jianjun; Jiao, Xiaodong; Hejtmancik, J. Fielding] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Rockville, MD 20852 USA. [Smaoui, Nizar; Hammer, Monia Ben Hamed] NEI, DNA Diagnost Lab, NIH, Rockville, MD 20852 USA. [Riazuddin, S. Amer; Riazuddin, Sheikh] Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore, Pakistan. [Riazuddin, S. Amer] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA. [Harper, Shyana; Berson, Eliot L.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA USA. [Katsanis, Nicholas] Duke Univ, Ctr Human Dis Modeling, Durham, NC USA. [Katsanis, Nicholas] Duke Univ, Dept Cell Biol, Durham, NC USA. [Riazuddin, Sheikh] Allama Iqbal Med Coll, Allama Iqbal Med Res Ctr, Lahore, Pakistan. [Chaabouni, Habiba] Hop Charles Nicolle, Serv Malad Congenitales & Hereditaires, Tunis, Tunisia. RP Hejtmancik, JF (reprint author), NEI, Ophthalm Genet & Visual Funct Branch, NIH, 5635 Fishers Lane, Rockville, MD 20852 USA. EM f3h@helix.nih.gov RI Katsanis, Nicholas/E-1837-2012; OI Katsanis, Nicholas/0000-0002-2480-0171 FU Foundation Fighting Blindness FX Supported in part by a Center Grant from the Foundation Fighting Blindness (ELB). NR 42 TC 17 Z9 18 U1 1 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUL PY 2011 VL 52 IS 8 BP 5317 EP 5324 DI 10.1167/iovs.11-7554 PG 8 WC Ophthalmology SC Ophthalmology GA 800QC UT WOS:000293377400041 PM 21642631 ER PT J AU Morales, SA Telander, D Notterpek, L Wadehra, M Braun, J Gordon, LK AF Morales, Shawn A. Telander, David Notterpek, Lucia Wadehra, Madhuri Braun, Jonathan Gordon, Lynn K. TI Rewiring Integrin-Mediated Signaling and Cellular Response with the Peripheral Myelin Protein 22 and Epithelial Membrane Protein 2 Components of the Tetraspan Web SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID COLLAGEN GEL CONTRACTION; SURFACE EXPRESSION; IN-VITRO; CELLS; ADHESION; EMP2; FIBROBLASTS; ACTIVATION; COMPLEX; GENE AB PURPOSE. Integrin-mediated collagen gel contraction by ARPE-19 is an in vitro model for proliferative vitreoretinopathy (PVR), an aberrant wound healing response after retinal detachment or ocular trauma. Expression of the tetraspan protein epithelial membrane protein 2 (EMP2) controls gel contraction through FAK activation. Peripheral myelin protein 22 (PMP22), another member of the tetraspan web, is closely related to EMP2. The purpose of this study was to determine whether PMP22 also controls the contractile phase associated with PVR. METHODS. Integrin expression, adhesion, and protein expression were assessed, respectively, through flow cytometry, binding to collagen types I and IV, and Western blot analysis. Collagen gel contraction was assessed using an in vitro assay. RESULTS. Overexpression of PMP22 in ARPE-19 cells (ARPE-19/PMP22) resulted in increased collagen adhesion. Gel contraction, however, was reduced by greater than 50% in ARPE-19/PMP22 cells (P < 0.001). In contrast to the FAK activation observed by increasing EMP2 expression, PMP22 overexpression led to increased AKT activation. The decrease in gel contraction by the ARPE-19/PMP22 cells was partially reversed through either PMP22 siRNA or by blockade of AKT. CONCLUSIONS. Relative expression of EMP2 or PMP22 within the tetraspan web drives a cellular response toward a FAK-or AKT-dependent pathway, respectively. EMP2 and PMP22 differentially regulate collagen gel contraction in the ARPE-19 cell line. The implication of this finding adds a new dimension to the concept of the tetraspan web, in which the abundance of individual tetraspan family members differentially regulates signal transduction and the downstream cellular response. (Invest Ophthalmol Vis Sci. 2011; 52: 5465-5472) DOI: 10.1167/iovs.10-6139 C1 [Gordon, Lynn K.] Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, Dept Ophthalmol, Los Angeles, CA 90095 USA. [Wadehra, Madhuri; Braun, Jonathan] Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Telander, David] Univ Calif Davis, Dept Ophthalmol & Vis Sci, Davis, CA 95616 USA. [Notterpek, Lucia] Univ Florida, Dept Neurosci, Sch Med, Gainesville, FL 32610 USA. [Gordon, Lynn K.] Greater Los Angeles VA Healthcare Syst, Dept Surg, Los Angeles, CA USA. RP Gordon, LK (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, Dept Ophthalmol, 100 Stein Plaza, Los Angeles, CA 90095 USA. EM lgordon@ucla.edu FU National Institutes of Health [RO1 EY019909, HD48540]; American Health Assistance Foundation; A. P. Giannini Foundation; Ruzic Foundation FX Supported by National Institutes of Health Grants RO1 EY019909 (LKG, DT) and HD48540 (JB), the American Health Assistance Foundation (LKG), the A. P. Giannini Foundation (SAM), and the Ruzic Foundation (JB). NR 44 TC 1 Z9 1 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUL PY 2011 VL 52 IS 8 BP 5465 EP 5472 DI 10.1167/iovs.10-6139 PG 8 WC Ophthalmology SC Ophthalmology GA 800QC UT WOS:000293377400059 PM 21421883 ER PT J AU Giani, A Luiselli, C Esmaili, DD Salvetti, P Cigada, M Miller, JW Staurenghi, G AF Giani, Andrea Luiselli, Cristiano Esmaili, Daniel D. Salvetti, Paola Cigada, Mario Miller, Joan W. Staurenghi, Giovanni TI Spectral-Domain Optical Coherence Tomography as an Indicator of Fluorescein Angiography Leakage from Choroidal Neovascularization SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID MACULAR DEGENERATION; PHOTODYNAMIC THERAPY; VISUAL-ACUITY; VERTEPORFIN; RANIBIZUMAB; AGREEMENT; TAP; EYE AB PURPOSE. To evaluate spectral-domain optical coherence tomography (SD-OCT) findings that predict angiographic leakage in choroidal neovascularization (CNV). METHODS. SD-OCT and fluorescein angiography (FA) images of 93 eyes of 93 patients were retrospectively analyzed. All patients were previously treated with anti-vascular endothelial growth factor agents for CNV from age-related macular degeneration. FA images were analyzed to assess the presence of leakage. SD-OCT images were analyzed to identify the overall presence of fluid, as well as specific patterns of fluid presentation, including intraretinal cystic spaces (ICS), retinal pigment epithelium detachment (PED), and neurosensory detachment (NSD). The presence of ultrastructural features such as intraretinal hyperreflective flecks and the inherent reflectivity and boundary definition of the subretinal material were evaluated. Both the association and the sensitivity, specificity, and both positive and negative predictive values of SD-OCT findings compared with FA leakage were calculated. RESULTS. A statistically significant association between SD-OCT findings and FA leakage was found for eyes that displayed fluid, NSD, intraretinal flecks, and low reflectivity or undefined boundaries from subretinal material, and not for PED or ICS. Sensitivity and specificity for SD-OCT findings were, respectively: 94% and 27% for fluid; 68% and 88% for NSD; 81% and 83% for intraretinal flecks; 63% and 92% for undefined boundaries of subretinal material; and 94% and 87% for low reflectivity from subretinal material. CONCLUSIONS. The evidence of fluid on SD-OCT is sensitive but nonspecific in identifying FA leaky CNV. The assessment of neurosensory detachment as well as other ultrastructural elements may increase the specificity of analysis. (Invest Ophthalmol Vis Sci. 2011; 52: 5579-5586) DOI: 10.1167/iovs.10-6617 C1 [Staurenghi, Giovanni] Univ Milan, Sch Ophthalmol 2, Sacco Hosp, Eye Clin,Dept Clin Sci Luigi Sacco, I-20100 Milan, Italy. [Giani, Andrea; Esmaili, Daniel D.; Miller, Joan W.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv,Dept Ophthalmol, Boston, MA USA. RP Staurenghi, G (reprint author), Univ Milan, Sch Ophthalmol 2, Sacco Hosp, Eye Clin,Dept Clin Sci Luigi Sacco, Via GB Grassi 74, I-20100 Milan, Italy. EM giovanni.staurenghi@unimi.it NR 28 TC 25 Z9 25 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 JUL PY 2011 VL 52 IS 8 BP 5579 EP 5586 DI 10.1167/iovs.10-6617 PG 8 WC Ophthalmology SC Ophthalmology GA 800QC UT WOS:000293377400074 PM 21693602 ER PT J AU Gordon, CR Alghoul, M Goldberg, JS Habal, MB Papay, F AF Gordon, Chad R. Alghoul, Mohammed Goldberg, Jonathan S. Habal, Mutaz B. Papay, Francis TI Diced Cartilage Grafts Wrapped in AlloDerm for Dorsal Nasal Augmentation SO JOURNAL OF CRANIOFACIAL SURGERY LA English DT Article DE Diced cartilage graft; nasal dorsal augmentation; American Delight; AlloDerm; rhinoplasty ID RHINOPLASTY AB Dorsal nasal augmentation is commonly performed for various aesthetic deficiencies and/or reconstructive defects such as the saddle nose deformity. However, the optimal technique for volume augmentation has yet to be identified. The senior author (F.P.) has since developed a new modified technique using wrapped diced cartilage within an AlloDerm. This novel construct provides the plastic surgeon a smooth, convenient, pliable option with similar operative times as compared with other popular techniques. In summary, this technique has been proven to be successful in achieving attractive, safe, and acceptable outcomes in nasal dorsal configuration and overall patient satisfaction. C1 [Gordon, Chad R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, Boston, MA 02114 USA. [Gordon, Chad R.; Alghoul, Mohammed; Goldberg, Jonathan S.; Papay, Francis] Cleveland Clin, Inst Dermatol & Plast Surg, Dept Plast Surg, Cleveland, OH 44106 USA. [Habal, Mutaz B.] Tampa Bay Craniofacial Ctr, Tampa, FL USA. RP Gordon, CR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, 15 Parkman St,WACC 435, Boston, MA 02114 USA. EM cgordon5@partners.org NR 12 TC 18 Z9 18 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1049-2275 J9 J CRANIOFAC SURG JI J. Craniofac. Surg. PD JUL PY 2011 VL 22 IS 4 BP 1196 EP 1199 DI 10.1097/SCS.0b013e31821c0d69 PG 4 WC Surgery SC Surgery GA 796OT UT WOS:000293062100006 PM 21772214 ER PT J AU Hess, R DesRoches, C Donelan, K Norman, L Buerhaus, PI AF Hess, Robert DesRoches, Catherine Donelan, Karen Norman, Linda Buerhaus, Peter I. TI Perceptions of Nurses in Magnet (R) Hospitals, Non-Magnet Hospitals, and Hospitals Pursuing Magnet Status SO JOURNAL OF NURSING ADMINISTRATION LA English DT Article ID ENVIRONMENT AB Objective: The objective of the study was to compare perceptions of RNs employed in Magnet A, in-process (ie, hospitals seeking Magnet recognition), and non-Magnet hospitals using data from the 2010 National Survey of Registered Nurses (NSRN). Background: The NSRN is administered biennially and measures nurses' perceptions about their profession, workplace environment, and professional relationships. Methods: Self-administered mail survey to a national sample of 1,500 RNs was used. Bivariate statistical techniques were used to analyze responses from 518 nurses who indicated their employer's Magnet status and to examine associations between Magnet status and the nurses' perceptions of career satisfaction, the nursing shortage, work environment, opportunities to influence the workplace, and professional relationships. Results: Nurses employed in all 3 groups (Magnet, in-process, and non-Magnet hospitals) were uniformly satisfied with being a nurse, although significantly more Magnet and in-process nurses would recommend nursing as a career than would non-Magnet RNs. Views of workplace safety were similar across groups, with no significant differences in violence, verbal abuse, discrimination, or harassment; however, Magnet nurses reported significantly more musculoskeletal injuries. Magnet and in-process nurses rated opportunities to influence decisions about workplace organization and participate in shared governance and employer-paid continuing education, and relationships with advanced practice nurses and nursing faculty higher than did non-Magnet nurses; relationships with new nurses and physicians were not different across groups. Conclusions: The Magnet program continues to have a positive influence on nurses, their decision making, and their professional relationships. The paucity of other differences suggests that Magnet, in-process, and non-Magnet organizations are increasingly guided by a shared set of principles that define a positive professional environment derived not only by the Magnet program, but also by other professional organizations and forces. C1 [Hess, Robert] Gannett Healthcare Grp, Global Programming, Voorhees, NJ USA. [DesRoches, Catherine; Donelan, Karen] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Norman, Linda] Vanderbilt Univ, Sch Nursing, Nashville, TN 37240 USA. [Buerhaus, Peter I.] Vanderbilt Univ, Med Ctr, Inst Med & Publ Hlth, Ctr Interdisciplinary Hlth Workforce Studies, Nashville, TN USA. RP Hess, R (reprint author), POB 412, Voorhees, NJ 08043 USA. EM rhess@gannetthg.com FU Johnson & Johnson national Campaign for Nursing's Future; Gannett Healthcare Group FX This study was funded by a major grant from the Johnson & Johnson national Campaign for Nursing's Future. Johnson & Johnson played no role in the design and conduct of the study, the analysis and interpretation of results, or the preparation or approval of this manuscript. Financial support for the study was also received from the Gannett Healthcare Group. NR 17 TC 24 Z9 25 U1 1 U2 19 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-0443 J9 J NURS ADMIN JI J. Nurs. Adm. PD JUL-AUG PY 2011 VL 41 IS 7-8 BP 315 EP 323 DI 10.1097/NNA.0b013e31822509e2 PG 9 WC Nursing SC Nursing GA 799EC UT WOS:000293265400007 PM 21799363 ER PT J AU Clark, CM Olender, L Cardoni, C Kenski, D AF Clark, Cynthia M. Olender, Lynda Cardoni, Cari Kenski, Diane TI Fostering Civility in Nursing Education and Practice Nurse Leader Perspectives SO JOURNAL OF NURSING ADMINISTRATION LA English DT Editorial Material ID INCIVILITY; WORKPLACE; STRATEGIES; FACULTY; STAFF C1 [Clark, Cynthia M.; Cardoni, Cari; Kenski, Diane] Boise State Univ, Sch Nursing, Boise, ID 83725 USA. [Olender, Lynda] Seton Hall Univ, S Orange, NJ 07079 USA. [Olender, Lynda] James J Peters VA Med Ctr, Bronx, NY USA. RP Clark, CM (reprint author), Boise State Univ, Sch Nursing, 1910 Univ Dr, Boise, ID 83725 USA. EM cclark@boisestate.edu NR 29 TC 13 Z9 13 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-0443 J9 J NURS ADMIN JI J. Nurs. Adm. PD JUL-AUG PY 2011 VL 41 IS 7-8 BP 324 EP 330 DI 10.1097/NNA.0b013e31822509c4 PG 7 WC Nursing SC Nursing GA 799EC UT WOS:000293265400008 PM 21799364 ER PT J AU Rosado-Rivera, D Radulovic, M Handrakis, JP Cirnigliaro, CM Jensen, AM Kirshblum, S Bauman, WA Wecht, JM AF Rosado-Rivera, Dwindally Radulovic, M. Handrakis, John P. Cirnigliaro, Christopher M. Jensen, A. Marley Kirshblum, Steve Bauman, William A. Wecht, Jill Maria TI Comparison of 24-hour cardiovascular and autonomic function in paraplegia, tetraplegia, and control groups: Implications for cardiovascular risk SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Article DE Paraplegia; Tetraplegia; Autonomic nervous system; Heart rate; Blood pressure; Heart rate variability; Diumal variation; Spinal cord injuries; Cardiovascular risk ID SPINAL-CORD-INJURY; HEART-RATE-VARIABILITY; LOW BLOOD-PRESSURE; CONTINGENT NEGATIVE-VARIATION; SYMPATHETIC-NERVOUS-SYSTEM; VOLUNTARY STATIC EXERCISE; ARTERIAL STIFFNESS; DISEASE RISK; COGNITIVE PERFORMANCE; NON-DIPPERS AB Background: Fluctuations in 24-hour cardiovascular hemodynamics, specifically heart rate (HR) and blood pressure (BP), are thought to reflect autonomic nervous system (ANS) activity. Persons with spinal cord injury (SCI) represent a model of ANS dysfunction, which may affect 24-hour hemodynamics and predispose these individuals to increased cardiovascular disease risk. Objective: To determine 24-hour cardiovascular and ANS function among individuals with tetraplegia (n = 20; TETRA: C4-C8), high paraplegia (n = 10; HP: T2-T5), low paraplegia (n = 9; LP: T7-T12), and non-SCI controls (n = 10). Twenty-four-hour ANS function was assessed by time domain parameters of heart rate variability (HRV); the standard deviation of the 5-minute average R-R intervals (SDANN; milliseconds/ms), and the root-mean square of the standard deviation of the R-R intervals (rMSSD; ms). Subjects wore 24-hour ambulatory monitors to record HR, HRV, and BP. Mixed analysis of variance (ANOVA) revealed significantly lower 24-hour BP in the tetraplegic group; however, BP did not differ between the HP, LP, and control groups. Mixed ANOVA suggested significantly elevated 24-hour HR in the HP and LP groups compared to the TETRA and control groups (P < 0.05); daytime HR was higher in both paraplegic groups compared to the TETRA and control groups (P < 0.01) and nighttime HR was significantly elevated in the LP group compared to the TETRA and control groups (P < 0.01). Twenty-four-hour SDANN was significantly increased in the HP group compared to the LP and TETRA groups (P < 0.05) and rMSSD was significantly lower in the LP compared to the other three groups (P < 0.05). Elevated 24-hour HR in persons with paraplegia, in concert with altered HRV dynamics, may impart significant adverse cardiovascular consequences, which are currently unappreciated. C1 [Rosado-Rivera, Dwindally; Radulovic, M.; Handrakis, John P.; Cirnigliaro, Christopher M.; Jensen, A. Marley; Bauman, William A.; Wecht, Jill Maria] James J Peters VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Bronx, NY 10468 USA. [Rosado-Rivera, Dwindally; Radulovic, M.; Handrakis, John P.; Cirnigliaro, Christopher M.; Jensen, A. Marley; Bauman, William A.; Wecht, Jill Maria] Ctr Excellence, New York, NY USA. [Radulovic, M.; Handrakis, John P.; Cirnigliaro, Christopher M.; Jensen, A. Marley; Bauman, William A.; Wecht, Jill Maria] Med Serv, New York, NY USA. [Radulovic, M.; Handrakis, John P.; Cirnigliaro, Christopher M.; Jensen, A. Marley; Bauman, William A.; Wecht, Jill Maria] Mt Sinai Sch Med, New York, NY USA. [Radulovic, M.; Handrakis, John P.; Cirnigliaro, Christopher M.; Jensen, A. Marley; Bauman, William A.; Wecht, Jill Maria] Dept Med, W Orange, NJ USA. [Radulovic, M.; Handrakis, John P.; Cirnigliaro, Christopher M.; Jensen, A. Marley; Bauman, William A.; Wecht, Jill Maria] Dept Rehabil Med, W Orange, NJ USA. [Handrakis, John P.; Cirnigliaro, Christopher M.; Jensen, A. Marley; Kirshblum, Steve] Kessler Inst Rehabil, W Orange, NJ USA. [Handrakis, John P.] NYIT Sch Hlth Profess, Old Westbury, NY USA. RP Wecht, JM (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 jm.wecht@va.gov FU Veterans Affairs Rehabilitation Research and Development Service [A6161W, B3203R, B4162C] FX We thank Dr Joseph Weir for his support with the statistical analyses. This research was supported by the Veterans Affairs Rehabilitation Research and Development Service (grant no. A6161W, B3203R and B4162C). NR 64 TC 23 Z9 24 U1 1 U2 5 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 JUL PY 2011 VL 34 IS 4 BP 395 EP 403 DI 10.1179/2045772311Y.0000000019 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 804BS UT WOS:000293629500007 PM 21903013 ER PT J AU Hoffman, J Salzman, C Garbaccio, C Burns, SP Crane, D Bombardier, C AF Hoffman, Jeanne Salzman, Cynthia Garbaccio, Chris Burns, Stephen P. Crane, Deborah Bombardier, Charles TI Use of on-demand video to provide patient education on spinal cord injury SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Article DE Patient education; Spinal cord injuries; Media; Print; Digital; Video; Internet; Secondary complications; Prevention; Self-care; Quality of life ID INTERNET USE; HEALTH; PEOPLE AB Background/objective: Persons with chronic spinal cord injury (SCI) have a high lifetime need for ongoing patient education to reduce the risk of serious and costly medical conditions. We have addressed this need through monthly in-person public education programs called SCI Forums. More recently, we began videotaping these programs for streaming on our website to reach a geographically diverse audience of patients, caregivers, and providers. Design/methods: We compared information from the in-person forums to that of the same forums shown streaming on our website during a 1-year period. Results: Both the in-person and Internet versions of the forums received high overall ratings from individuals who completed evaluation forms. Eighty-eight percent of online evaluators and 96% of in-person evaluators reported that they gained new information from the forum; 52 and 64% said they changed their attitude, and 61 and 68% said they would probably change their behavior or take some kind of action based on information they learned. Ninety-one percent of online evaluators reported that video is better than text for presenting this kind of information. Conclusion: Online video is an accessible, effective, and well-accepted way to present ongoing SCI education and can reach a wider geographical audience than in-person presentations. C1 [Hoffman, Jeanne; Salzman, Cynthia; Garbaccio, Chris; Burns, Stephen P.; Crane, Deborah; Bombardier, Charles] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Burns, Stephen P.] VA Puget Sound Hlth Care Syst, Spinal Cord Injury Serv, Seattle, WA USA. RP Hoffman, J (reprint author), Univ Washington, Dept Rehabil, Box 356490, Seattle, WA 98195 USA. EM jeanneh@uw.edu FU Department of Education, National Institute on Disability and Rehabilitation Research, SCI Model Systems at the University of Washington [H133N060033] FX This study was funded by the Department of Education, National Institute on Disability and Rehabilitation Research, SCI Model Systems at the University of Washington H133N060033. NR 15 TC 8 Z9 8 U1 0 U2 1 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 JUL PY 2011 VL 34 IS 4 BP 404 EP 409 DI 10.1179/2045772311Y.0000000015 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 804BS UT WOS:000293629500008 PM 21903014 ER PT J AU Spiro, A Brady, CB AF Spiro, Avron, III Brady, Christopher B. TI Integrating Health into Cognitive Aging: Toward a Preventive Cognitive Neuroscience of Aging SO JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES LA English DT Article DE Alzheimer's disease; Cardiovascular disease; Cognition; Epidemiology; Health ID VASCULAR RISK-FACTORS; CARDIOVASCULAR RISK; ALZHEIMERS-DISEASE; DEMENTIA RISK; OLDER-ADULTS; STROKE; AGE; POPULATION; IMPAIRMENT; PREDICTION AB Objectives. We argue that age is a descriptive, and not explanatory, variable and consequently cannot account for the cognitive changes that often occur with aging. Once age is removed from consideration, other truly causal explanations for "cognitive aging" must be identified. We argue that health and disease represent an important class of explanatory variables for age-related cognitive changes. Methods/Results. We make this argument first by reviewing the prevalence of risk factors, disability, and subclinical and frank disease in the elderly population. We emphasize that the complexity of health effects rivals that of age on cognition while noting that most studies of cognitive aging rarely consider this complexity fully. We then consider in more detail the "vascular hypothesis," which proposes that vascular diseases (e.g., stroke, heart disease) and their risk factors (e.g., hypertension) can explain aspects of cognitive decline in aging through their impact on circulatory and brain functions. Clinical implications of this hypothesis suggest that treatment of vascular risk factors might well reduce the incidence or severity of dementia syndromes. Discussion. We conclude with a brief summary of approaches to further integrate aspects of health and disease into the study of "cognitive aging." C1 [Spiro, Avron, III; Brady, Christopher B.] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [Spiro, Avron, III] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. [Spiro, Avron, III] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Brady, Christopher B.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. [Brady, Christopher B.] Boston Univ, Sch Med, Dept Behav Neurosci, Boston, MA 02215 USA. RP Spiro, A (reprint author), VA Boston Healthcare Syst, MAVERIC 151MAV, 150 S Huntington Ave, Boston, MA 02130 USA. EM aspiro3@bu.edu OI Brady, Christopher/0000-0002-6095-6480; Spiro III, Avron/0000-0003-4080-8621 FU Clinical Science Research and Development Service, U.S. Department of Veterans Affairs; National Institute on Aging [R01-AG014345, R01-AG018436]; Center for Healthcare Evaluation at VA Palo Alto Healthcare System, Menlo Park, CA; Center for Advanced Study in the Behavioral Sciences, Stanford, CA FX This paper was supported in part by Merit Review and Research Career Scientist awards from the Clinical Science Research and Development Service, U.S. Department of Veterans Affairs to the first author and by grants R01-AG014345 and R01-AG018436 from the National Institute on Aging.; We thank Martin L. Albert, MD, PhD, J. Michael Gaziano, MD, MPH, and Pantel Vokonas, MD, for many useful discussions with us on these and related topics over the past few years. A. Spiro would like to thank the Center for Healthcare Evaluation at VA Palo Alto Healthcare System, Menlo Park, CA, and the Center for Advanced Study in the Behavioral Sciences, Stanford, CA, for their support while working on this paper. Versions of this paper have been presented at the conference on Cognition, Health & Aging: Integrating Cross-Disciplinary Perspectives. University Park, PA (October, 2009), at Georgia Institute of Technology (November 2009), and at the Meeting of the Integrative Analysis of Longitudinal Studies, Victoria, BC, Canada (June 2010). NR 83 TC 17 Z9 17 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5014 J9 J GERONTOL B-PSYCHOL JI J. Gerontol. Ser. B-Psychol. Sci. Soc. Sci. PD JUL PY 2011 VL 66 SU 1 BP 17 EP 25 DI 10.1093/geronb/gbr018 PG 9 WC Geriatrics & Gerontology; Gerontology; Psychology; Psychology, Multidisciplinary SC Geriatrics & Gerontology; Psychology GA 798ZS UT WOS:000293252000002 ER PT J AU Lo Re, V Lim, JK Goetz, MB Tate, J Bathulapalli, H Klein, MB Rimland, D Rodriguez-Barradas, MC Butt, AA Gibert, CL Brown, ST Kidwai, F Brandt, C Dorey-Stein, Z Reddy, KR Justice, AC AF Lo Re, Vincent, III Lim, Joseph K. Goetz, Matthew Bidwell Tate, Janet Bathulapalli, Harini Klein, Marina B. Rimland, David Rodriguez-Barradas, Maria C. Butt, Adeel A. Gibert, Cynthia L. Brown, Sheldon T. Kidwai, Farah Brandt, Cynthia Dorey-Stein, Zachariah Reddy, K. Rajender Justice, Amy C. TI Validity of diagnostic codes and liver-related laboratory abnormalities to identify hepatic decompensation events in the Veterans Aging Cohort Study SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE hepatic decompensation; end-stage liver disease; epidemiologic methods; outcomes; validation studies ID HUMAN-IMMUNODEFICIENCY-VIRUS; HEPATOCELLULAR-CARCINOMA; C-VIRUS; DRUG-USERS; FIBROSIS PROGRESSION; COINFECTED PATIENTS; NATURAL-HISTORY; HIV-INFECTION; CIRRHOSIS; MANAGEMENT AB Purpose The absence of validated methods to identify hepatic decompensation in cohort studies has prevented a full understanding of the natural history of chronic liver diseases and impact of medications on this outcome. We determined the ability of diagnostic codes and liver-related laboratory abnormalities to identify hepatic decompensation events within the Veterans Aging Cohort Study (VACS). Methods Medical records of patients with hepatic decompensation codes and/or laboratory abnormalities of liver dysfunction (total bilirubin >= 5.0 g/dL, albumin <= 2.0 g/dL, INR >= 1.7) recorded 1 year before through 6 months after VACS entry were reviewed to identify decompensation events (i.e., ascites, spontaneous bacterial peritonitis, variceal hemorrhage, hepatic encephalopathy, hepatocellular carcinoma) at VACS enrollment. Positive predictive values (PPVs) of diagnostic codes, laboratory abnormalities, and their combinations for confirmed outcomes were determined. Results Among 137 patients with a hepatic decompensation code and 197 with a laboratory abnormality, the diagnosis was confirmed in 57 (PPV, 42%; 95%CI, 33%-50%) and 56 (PPV, 28%; 95%CI, 22%-35%) patients, respectively. The combination of any code plus laboratory abnormality increased PPV (64%; 95%CI, 47%-79%). One inpatient or >= 2 outpatient diagnostic codes for ascites, spontaneous bacterial peritonitis, or variceal hemorrhage had high PPV (91%; 95%CI, 77%-98%) for confirmed hepatic decompensation events. Conclusion An algorithm of 1 inpatient or >= 2 outpatient codes for ascites, peritonitis, or variceal hemorrhage has sufficiently high PPV for hepatic decompensation to enable its use for epidemiologic research in VACS. This algorithm may be applicable to other cohorts. Copyright (C) 2011 John Wiley & Sons, Ltd. C1 [Lo Re, Vincent, III; Dorey-Stein, Zachariah] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Lo Re, Vincent, III; Dorey-Stein, Zachariah] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Lim, Joseph K.; Tate, Janet; Bathulapalli, Harini; Kidwai, Farah; Brandt, Cynthia; Justice, Amy C.] VA Connecticut Healthcare Syst, West Haven, CT USA. [Lim, Joseph K.; Tate, Janet; Bathulapalli, Harini; Kidwai, Farah; Brandt, Cynthia; Justice, Amy C.] Yale Univ, Sch Med, New Haven, CT USA. [Goetz, Matthew Bidwell] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Goetz, Matthew Bidwell] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Klein, Marina B.] McGill Univ, Royal Victoria Hosp, Ctr Hlth, Montreal, PQ H3A 1A1, Canada. [Rimland, David] Atlanta VA Med Ctr, Atlanta, GA USA. [Rimland, David] Emory Univ, Sch Med, Atlanta, GA USA. [Rodriguez-Barradas, Maria C.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Rodriguez-Barradas, Maria C.] Baylor Coll Med, Houston, TX 77030 USA. [Butt, Adeel A.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Butt, Adeel A.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Gibert, Cynthia L.] Washington DC VA Med Ctr, Washington, DC USA. [Gibert, Cynthia L.] George Washington Univ, Med Ctr, Washington, DC 20037 USA. [Brown, Sheldon T.] James J Peters VA Med Ctr, New York, NY USA. [Brown, Sheldon T.] Mt Sinai Sch Med, New York, NY USA. RP Lo Re, V (reprint author), Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, 836 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM vincentl@mail.med.upenn.edu RI Bathulapalli, Harini/B-7451-2015; Lo Re, Vincent/N-7817-2015; OI Goetz, Matthew/0000-0003-4542-992X FU National Institute of Allergy and Infectious Diseases [K01-AI070001]; National Institute on Alcohol Abuse and Alcoholism [U10-AA13566] FX This work was supported by the National Institute of Allergy and Infectious Diseases (grant number K01-AI070001 to Dr. Lo Re) and the National Institute on Alcohol Abuse and Alcoholism (U10-AA13566). The contents do not represent the views of the Department of Veterans Affairs or the United States Government. NR 35 TC 34 Z9 34 U1 2 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD JUL PY 2011 VL 20 IS 7 BP 689 EP 699 DI 10.1002/pds.2148 PG 11 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 800PE UT WOS:000293374600003 PM 21626605 ER PT J AU Lemaitre, RN Tanaka, T Tang, WH Manichaikul, A Foy, M Kabagambe, EK Nettleton, JA King, IB Weng, LC Bhattacharya, S Bandinelli, S Bis, JC Rich, SS Jacobs, DR Cherubini, A McKnight, B Liang, S Gu, XJ Rice, K Laurie, CC Lumley, T Browning, BL Psaty, BM Chen, YDI Friedlander, Y Djousse, L Wu, JHY Siscovick, DS Uitterlinden, AG Arnett, DK Ferrucci, L Fornage, M Tsai, MY Mozaffarian, D Steffen, LM AF Lemaitre, Rozenn N. Tanaka, Toshiko Tang, Weihong Manichaikul, Ani Foy, Millennia Kabagambe, Edmond K. Nettleton, Jennifer A. King, Irena B. Weng, Lu-Chen Bhattacharya, Sayanti Bandinelli, Stefania Bis, Joshua C. Rich, Stephen S. Jacobs, David R., Jr. Cherubini, Antonio McKnight, Barbara Liang, Shuang Gu, Xiangjun Rice, Kenneth Laurie, Cathy C. Lumley, Thomas Browning, Brian L. Psaty, Bruce M. Chen, Yii-Der I. Friedlander, Yechiel Djousse, Luc Wu, Jason H. Y. Siscovick, David S. Uitterlinden, Andre G. Arnett, Donna K. Ferrucci, Luigi Fornage, Myriam Tsai, Michael Y. Mozaffarian, Dariush Steffen, Lyn M. TI Genetic Loci Associated with Plasma Phospholipid n-3 Fatty Acids: A Meta-Analysis of Genome-Wide Association Studies from the CHARGE Consortium SO PLOS GENETICS LA English DT Article ID ALPHA-LINOLENIC ACID; ISCHEMIC-HEART-DISEASE; DOCOSAHEXAENOIC ACID; EICOSAPENTAENOIC ACID; DEPRESSIVE SYMPTOMATOLOGY; MYOCARDIAL-INFARCTION; DIETARY-INTAKE; RISK-FACTOR; FISH-OIL; VARIANTS AB Long-chain n-3 polyunsaturated fatty acids (PUFAs) can derive from diet or from a-linolenic acid (ALA) by elongation and desaturation. We investigated the association of common genetic variation with plasma phospholipid levels of the four major n-3 PUFAs by performing genome-wide association studies in five population-based cohorts comprising 8,866 subjects of European ancestry. Minor alleles of SNPs in FADS1 and FADS2 (desaturases) were associated with higher levels of ALA (p=3x10(-64)) and lower levels of eicosapentaenoic acid (EPA, p=5x10(-58)) and docosapentaenoic acid (DPA, p=4x10(-154)). Minor alleles of SNPs in ELOVL2 (elongase) were associated with higher EPA (p=2x10(-12)) and DPA (p=1x10(-43)) and lower docosahexaenoic acid (DHA, p=1x10(-15)). In addition to genes in the n-3 pathway, we identified a novel association of DPA with several SNPs in GCKR (glucokinase regulator, p=1x10(-8)). We observed a weaker association between ALA and EPA among carriers of the minor allele of a representative SNP in FADS2 (rs1535), suggesting a lower rate of ALA-to-EPA conversion in these subjects. In samples of African, Chinese, and Hispanic ancestry, associations of n-3 PUFAs were similar with a representative SNP in FADS1 but less consistent with a representative SNP in ELOVL2. Our findings show that common variation in n-3 metabolic pathway genes and in GCKR influences plasma phospholipid levels of n-3 PUFAs in populations of European ancestry and, for FADS1, in other ancestries. C1 [Lemaitre, Rozenn N.; Bis, Joshua C.; Psaty, Bruce M.; Siscovick, David S.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Tanaka, Toshiko; Ferrucci, Luigi] NIA, Clin Res Branch, NIH, Baltimore, MD 21224 USA. [Tang, Weihong; Weng, Lu-Chen; Jacobs, David R., Jr.; Steffen, Lyn M.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Manichaikul, Ani] Univ Virginia, Ctr Publ Hlth Genom, Div Biostat & Epidemiol, Charlottesville, VA USA. [Foy, Millennia; Gu, Xiangjun; Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX USA. [Kabagambe, Edmond K.; Arnett, Donna K.] Univ Alabama, Dept Epidemiol, Birmingham, AL USA. [Nettleton, Jennifer A.; Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Div Epidemiol Human Genet & Environm Sci, Houston, TX USA. [King, Irena B.] Univ New Mexico, Dept Internal Med, Albuquerque, NM 87131 USA. [Bhattacharya, Sayanti] Duke Univ, Duke Global Hlth Inst, Durham, NC USA. [Bandinelli, Stefania] ASF, Geriatr Unit, Florence, Italy. [Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA. [Cherubini, Antonio] Univ Perugia, Inst Gerontol & Geriatr, Dept Clin & Expt Med, I-06100 Perugia, Italy. [McKnight, Barbara; Rice, Kenneth; Laurie, Cathy C.] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA. [Liang, Shuang; Tsai, Michael Y.] Univ Minnesota, Lab Med & Pathol, Minneapolis, MN USA. [Lumley, Thomas] Univ Auckland, Dept Stat, Auckland 1, New Zealand. [Browning, Brian L.] Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Chen, Yii-Der I.] Cedars Sinai Med Ctr, Med Genet Res Inst, Los Angeles, CA 90048 USA. [Friedlander, Yechiel] Hebrew Univ Jerusalem Hadassah Hosp & Med Sch, Sch Publ Hlth, Epidemiol Unit, Jerusalem, Israel. [Djousse, Luc] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Aging,Dept Med, Boston, MA 02115 USA. [Djousse, Luc] Boston VA Healthcare Syst, Boston, MA USA. [Wu, Jason H. Y.; Mozaffarian, Dariush] Harvard Univ, Sch Publ Hlth, Dept Epidemiol & Nutr, Boston, MA 02115 USA. [Wu, Jason H. Y.] Univ Western Australia, Sch Med & Pharmacol, Perth, WA 6009, Australia. [Siscovick, David S.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Mozaffarian, Dariush] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc Med, Boston, MA 02115 USA. RP Lemaitre, RN (reprint author), Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. EM rozenl@u.washington.edu RI Manichaikul, Ani/B-7726-2009; Browning, Brian/A-1178-2010; Rice, Kenneth/A-4150-2013; Djousse, Luc/F-5033-2017; OI Browning, Brian/0000-0001-6454-6633; Rice, Kenneth/0000-0001-5779-4495; Djousse, Luc/0000-0002-9902-3047; Kabagambe, Edmond/0000-0002-8993-3186; Manichaikul, Ani/0000-0002-5998-795X; Cherubini, Antonio/0000-0003-0261-9897 FU National Heart, Lung, and Blood Institute (NHLBI); National Human Genome Research Institute [HSN268200625226C, U01-HG-004729, U01-HG-004446, U01-HG-004424]; National Institutes of Health; NIH Roadmap for Medical Research; National Institute of Neurological Disorders and Stroke [HL075366, HL080295, HL087652, HL105756, HL085251]; National Institute on Aging [AG-023269, AG-15928, AG-20098, AG-027058]; National Center for Research Resources [M01RR00425]; National Institute of Diabetes and Digestive and Kidney Diseases [DK063491]; Italian Ministry of Health [ICS110.1/RF97.71]; U.S. National Institute on Aging [263 MD 9164, 263 MD 821336]; National Institute on Aging, National Institutes of Health, Baltimore, Maryland; MESA; National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases [5K01DK082729-02]; [UL1RR025005]; [R01HL071051]; [R01HL071205]; [R01HL071250]; [R01HL071251]; [R01HL071252]; [R01HL071258]; [R01HL071259] FX The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL087641, R01HL59367, and R01HL086694; National Human Genome Research Institute contract U01HG004402; and National Institutes of Health contract HSN268200625226C. Infrastructure was partly supported by Grant Number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research. The Cardiovascular Health Study research reported in this article was supported by the National Heart, Lung, and Blood Institute contract N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133 and grants HL075366, HL080295, HL087652, HL105756, and HL085251 with additional contribution from the National Institute of Neurological Disorders and Stroke. Additional support from the National Institute on Aging was provided through AG-023269, AG-15928, AG-20098, and AG-027058. DNA handling and genotyping was supported in part by the National Center for Research Resources grant M01RR00425 to the Cedars-Sinai General Clinical Research Center Genotyping core and the National Institute of Diabetes and Digestive and Kidney Diseases grant DK063491 to the Southern California Diabetes Endocrinology Research Center. The Coronary Artery Risk Development in Young Adults (CARDIA) study is funded by contracts N01-HC-95095, N01-HC-48047, N01-HC-48048, N01-HC-48049, N01-HC-48050, N01-HC-45134, N01-HC-05187, N01-HC-45205, and N01-HC-45204 from the National Heart, Lung, and Blood Institute to the CARDIA investigators. Genotyping of the CARDIA participants was supported by grants U01-HG-004729, U01-HG-004446, and U01-HG-004424 from the National Human Genome Research Institute and R01-HL-084099 from the National Heart, Lung, and Blood Institute to MF. The InCHIANTI Study baseline (1998-2000) was supported as a "targeted project" (ICS110.1/RF97.71) by the Italian Ministry of Health and in part by the U.S. National Institute on Aging (Contracts: 263 MD 9164 and 263 MD 821336) and was supported in part by the Intramural research program of the National Institute on Aging, National Institutes of Health, Baltimore, Maryland. The Multi-Ethnic Study of Atherosclerosis (MESA) and MESA SHARe were supported by contracts N01-HC-95159 through N01-HC-95169 and RR-024156 from the National Heart, Lung, and Blood Institute. Funding for MESA SHARe genotyping was provided by NHLBI Contract N02HL64278. MESA Family is conducted and supported in collaboration with MESA investigators; support is provided by grants and contracts R01HL071051, R01HL071205, R01HL071250, R01HL071251, R01HL071252, R01HL071258, R01HL071259. 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. JA Nettleton is supported by a K01 from the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases (5K01DK082729-02). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 51 TC 105 Z9 107 U1 1 U2 22 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 JUL PY 2011 VL 7 IS 7 AR e1002193 DI 10.1371/journal.pgen.1002193 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 800DB UT WOS:000293338600041 PM 21829377 ER PT J AU Kontos, EZ Emmons, KM Puleo, E Viswanath, K AF Kontos, Emily Z. Emmons, Karen M. Puleo, Elaine Viswanath, K. TI Determinants and beliefs of health information mavens among a lower-socioeconomic position and minority population SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE Communication inequalities; Health disparities; Health information mavenism ID BEHAVIOR-CHANGE; PEER LEADERS; MARKET MAVEN; COMMUNICATION; DIRECTIONS; EDUCATION; DISPARITIES; DIFFUSION; ENCLAVES AB People of lower-socioeconomic position (SEP) and most racial/ethnic minorities face significant communication challenges which may negatively impact their health. Previous research has shown that these groups rely heavily on interpersonal sources to share and receive health information; however, little is known about these lay sources. The purpose of this paper is to apply the concept of a market maven to the public health sector with the aims of identifying determinants of high health information mavenism among low-SEP and racial/ethnic minority groups and to assess the information they may be sharing based on their own health beliefs. Data for this study were drawn from the baseline survey (n = 325) of a US randomized control intervention study aimed at eliciting an understanding of Internet-related challenges among lower-SEP and minority individuals. Regression models were estimated to distinguish significant determinants of health information mavenism among the sample. Similarly, bivariate and logistic multivariable models were estimated to determine the association between health information mavenism and accurate health beliefs relating to diet, physical activity and smoking. The data illustrate that having a larger social network, being female and being older were important factors associated with higher mavenism scores. Additionally being a moderate consumer of general media as well as fewer years in the US and lower language acculturation were significant predictors of higher mavenism scores. Mavens were more likely than non-mavens to maintain accurate beliefs regarding diet; however, there was no distinction between physical activity and smoking beliefs between mavens and non-mavens. These results offer a unique understanding of health information mavenism which could better leverage word-of-mouth health communication efforts among lower-SEP and minority groups in order to reduce communication inequalities. Moreover, the data indicate that health information mavens may serve as an ideal point of intervention in attempts to modify health beliefs with the goal of reducing health disparities among these populations. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Kontos, Emily Z.; Emmons, Karen M.; Viswanath, K.] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Soc Human Dev & Hlth, Boston, MA 02215 USA. [Puleo, Elaine] Univ Massachusetts, Amherst Sch Publ Hlth & Hlth Sci, Amherst, MA 01003 USA. RP Kontos, EZ (reprint author), Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Soc Human Dev & Hlth, 401 Pk Dr,Room 403F, Boston, MA 02215 USA. EM ekontos@hsph.harvard.edu FU US National Cancer Institute [5R01CA122894]; Harvard Education Program in Cancer Prevention and Control [5R25CA057711] FX This study was made possible with funding from the US National Cancer Institute through the following mechanisms: "Click to Connect: Improving Health Literacy through Computer Literacy", grant #5R01CA122894, and the Harvard Education Program in Cancer Prevention and Control, grant #5R25CA057711. NR 47 TC 15 Z9 16 U1 3 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD JUL PY 2011 VL 73 IS 1 BP 22 EP 32 DI 10.1016/j.socscimed.2011.04.024 PG 11 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 799DK UT WOS:000293263500004 PM 21683493 ER PT J AU Singhal, AB AF Singhal, Aneesh B. TI Diagnostic challenges in RCVS, PACNS, and other cerebral arteriopathies SO CEPHALALGIA LA English DT Editorial Material ID CENTRAL-NERVOUS-SYSTEM; VASOCONSTRICTION SYNDROME; ISCHEMIC-STROKE; CLINICAL-COURSE; YOUNG STROKE; RISK-FACTORS; VASCULITIS; ANGIOPATHY; NIMODIPINE; VASOSPASM C1 [Singhal, Aneesh B.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Singhal, AB (reprint author), Massachusetts Gen Hosp, Dept Neurol, ACC-729-C, Boston, MA 02114 USA. EM asinghal@partners.org FU NINDS NIH HHS [R01 NS 051412] NR 26 TC 14 Z9 14 U1 0 U2 4 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0333-1024 J9 CEPHALALGIA JI Cephalalgia PD JUL PY 2011 VL 31 IS 10 BP 1067 EP 1070 DI 10.1177/0333102411410084 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 796WD UT WOS:000293083300001 PM 21673004 ER PT J AU Thompson, BT Bernard, GR AF Thompson, B. Taylor Bernard, Gordon R. TI ARDS Network (NHLBI) Studies: Successes and Challenges in ARDS Clinical Research SO CRITICAL CARE CLINICS LA English DT Article DE Acute respiratory distress syndrome; ARDS Network; Acute lung injury; Clinical trials; Multicenter ID RESPIRATORY-DISTRESS-SYNDROME; ACUTE LUNG INJURY; PULMONARY-ARTERY; CONTROLLED-TRIAL; CATHETERIZATION; VENTILATION; HEART AB To hasten the development of effective therapy for acute respiratory distress syndrome (ARDS), in 1994, the National Heart, Lung, and Blood Institute initiated a clinical network to carry out multicenter clinical trials of ARDS treatments. The ARDS Network is a clinical research network of approximately 42 hospitals, organized into 12 clinical sites. The goal of the Network is to efficiently test promising agents, devices, or management strategies to improve the care of patients with ARDS. Comprehensive information regarding all completed and ongoing ARDSNet clinical trials is available at www.ardsnet.org, but a brief summary is provided in this article. C1 [Thompson, B. Taylor] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Med Intens Care Unit, Boston, MA 02114 USA. [Bernard, Gordon R.] Vanderbilt Univ, Med Ctr, Sch Med, Nashville, TN 37232 USA. RP Thompson, BT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Med Intens Care Unit, 55 Fruit St,BUL 148, Boston, MA 02114 USA. EM TTHOMPSON1@PARTNERS.ORG FU NHLBI NIH HHS [N01 HR016146] NR 11 TC 10 Z9 11 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-0704 J9 CRIT CARE CLIN JI Crit. Care Clin. PD JUL PY 2011 VL 27 IS 3 BP 459 EP + DI 10.1016/j.ccc.2011.05.011 PG 11 WC Critical Care Medicine SC General & Internal Medicine GA 799SM UT WOS:000293306400004 PM 21742211 ER PT J AU Lansdorp-Vogelaar, I Knudsen, AB Brenner, H AF Lansdorp-Vogelaar, Iris Knudsen, Amy B. Brenner, Hermann TI Cost-effectiveness of Colorectal Cancer Screening SO EPIDEMIOLOGIC REVIEWS LA English DT Article DE colonography; computed tomographic; colonoscopy; colorectal neoplasms; cost-benefit analysis; mass screening; occult blood; sigmoidoscopy ID SERVICES TASK-FORCE; OCCULT BLOOD-TEST; CT COLONOGRAPHY; STOOL DNA; DECISION-ANALYSIS; AVERAGE-RISK; POPULATION; COLONOSCOPY; IMPACT; PREVENTION AB Colorectal cancer is an important public health problem. Several screening methods have been shown to be effective in reducing colorectal cancer mortality. The objective of this review was to assess the cost-effectiveness of the different colorectal cancer screening methods and to determine the preferred method from a cost-effectiveness point of view. Five databases (MEDLINE, EMBASE, the Cost-Effectiveness Analysis Registry, the British National Health Service Economic Evaluation Database, and the lists of technology assessments of the Centers for Medicare and Medicaid Services) were searched for cost-effectiveness analyses published in English between January 1993 and December 2009. Fifty-five publications relating to 32 unique cost-effectiveness models were identified. All studies found that colorectal cancer screening was cost-effective or even cost-saving compared with no screening. However, the studies disagreed as to which screening method was most effective or had the best incremental cost-effectiveness ratio for a given willingness to pay per life-year gained. There was agreement among studies that the newly developed screening tests of stool DNA testing, computed tomographic colonography, and capsule endoscopy were not yet cost-effective compared with the established screening options. C1 [Lansdorp-Vogelaar, Iris] Univ Med Ctr, Dept Publ Hlth, Erasmus MC, NL-3000 CA Rotterdam, Netherlands. [Knudsen, Amy B.] Massachusetts Gen Hosp, Dept Radiol, Inst Technol Assessment, Boston, MA 02114 USA. [Brenner, Hermann] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, D-6900 Heidelberg, Germany. RP Lansdorp-Vogelaar, I (reprint author), Univ Med Ctr, Dept Publ Hlth, Erasmus MC, POB 2040, NL-3000 CA Rotterdam, Netherlands. EM i.vogelaar@erasmusmc.nl RI Brenner, Hermann/B-4627-2017 OI Brenner, Hermann/0000-0002-6129-1572 FU National Cancer Institute at the National Institutes of Health [U01-CA-088204, U01-CA-097426, U01-CA-115953]; German Research Foundation [BR 1704/6-4] FX This work was supported by the National Cancer Institute at the National Institutes of Health (grants U01-CA-088204 to A. B. K., U01-CA-097426 to I. L-V., and U01-CA-115953 to I. L-V.) for the Cancer Intervention and Surveillance Modeling Network. The work of H. B. was supported in part by a grant from the German Research Foundation (grant BR 1704/6-4). NR 72 TC 83 Z9 84 U1 3 U2 20 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0193-936X J9 EPIDEMIOL REV JI Epidemiol. Rev. PD JUL 1 PY 2011 VL 33 IS 1 BP 88 EP 100 DI 10.1093/epirev/mxr004 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 793OP UT WOS:000292833300007 PM 21633092 ER PT J AU Wu, GF Corbo, E Schmidt, M Smith-Garvin, JE Riese, MJ Jordan, MS Laufer, TM Brown, EJ Maltzman, JS AF Wu, Gregory F. Corbo, Evann Schmidt, Michelle Smith-Garvin, Jennifer E. Riese, Matthew J. Jordan, Martha S. Laufer, Terri M. Brown, Eric J. Maltzman, Jonathan S. TI Conditional deletion of SLP-76 in mature T cells abrogates peripheral immune responses SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE Knockout mice; Signal transduction; T cells ID PHOSPHOLIPASE C-GAMMA-1 PLC-GAMMA-1; CONTAINING LEUKOCYTE PROTEIN; HOMEOSTATIC PROLIFERATION; THYMOCYTE DEVELOPMENT; SIGNAL-TRANSDUCTION; MEDIATED ACTIVATION; ADAPTER; MICE; LAT; REQUIREMENT AB The adaptor protein Src homology 2 domain-containing leukocyte-specific protein of 76 kDa (SLP-76) is central to the organization of intracellular signaling downstream of the T-cell receptor (TCR). Evaluation of its role in mature, primary T cells has been hampered by developmental defects that occur in the absence of WT SLP-76 protein in thymocytes. Here, we show that following tamoxifen-regulated conditional deletion of SLP-76, mature, antigen-inexperienced T cells maintain normal TCR surface expression but fail to transduce TCR-generated signals. Conditionally deficient T cells fail to proliferate in response to antigenic stimulation or a lymphopenic environment. Mice with induced deletion of SLP-76 are resistant to induction of the CD4(+) T-cell-mediated autoimmune disease experimental autoimmune encephalomyelitis. Altogether, our findings demonstrate the critical role of SLP-76-mediated signaling in initiating T-cell-directed immune responses both in vitro and in vivo and highlight the ability to analyze signaling processes in mature T cells in the absence of developmental defects. C1 [Corbo, Evann; Schmidt, Michelle; Maltzman, Jonathan S.] Univ Penn, Sch Med, Dept Med, Renal Electrolyte & Hypertens Div, Philadelphia, PA 19104 USA. [Wu, Gregory F.] Univ Penn, Sch Med, Dept Neurol, Philadelphia, PA 19104 USA. [Smith-Garvin, Jennifer E.; Jordan, Martha S.] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Riese, Matthew J.] Univ Penn, Sch Med, Dept Med, Div Hematol Oncol, Philadelphia, PA 19104 USA. [Laufer, Terri M.] Univ Penn, Sch Med, Dept Med, Div Rheumatol, Philadelphia, PA 19104 USA. [Laufer, Terri M.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Brown, Eric J.] Univ Penn, Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. [Brown, Eric J.] Univ Penn, Sch Med, Dept Canc Biol, Philadelphia, PA 19104 USA. RP Maltzman, JS (reprint author), Univ Penn, Sch Med, Dept Med, Renal Electrolyte & Hypertens Div, 754 BRB 2-3,421 Curie Blvd, Philadelphia, PA 19104 USA. EM maltz@mail.med.upenn.edu FU NIH/NIAID [K08 AI055806, R01 AI085160, K01AR52802]; American Society of Nephrology/American Society of Transplantation; National Multiple Sclerosis Society FX We thank F. Costantini and G. Koretzky for providing mouse lines. We thank L. Kovoor for technical assistance. We thank D. Farber for critical review of this manuscript. This work was supported in part by grants from the NIH/NIAID (K08 AI055806 and R01 AI085160 to J. S. M. and K01AR52802 to M. S. J.) and the John Merrill Award from the American Society of Nephrology/American Society of Transplantation (to J. S. M.). G. F. W. and T. M. L. receive support from the National Multiple Sclerosis Society. NR 45 TC 11 Z9 12 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JUL PY 2011 VL 41 IS 7 BP 2064 EP 2073 DI 10.1002/eji.201040809 PG 10 WC Immunology SC Immunology GA 797ME UT WOS:000293131200027 PM 21469089 ER PT J AU Stadtmann, A Brinkhaus, L Mueller, H Rossaint, J Bolomini-Vittori, M Bergmeier, W Van Aken, H Wagner, DD Laudanna, C Ley, K Zarbock, A AF Stadtmann, Anika Brinkhaus, Laura Mueller, Helena Rossaint, Jan Bolomini-Vittori, Matteo Bergmeier, Wolfgang Van Aken, Hugo Wagner, Denisa D. Laudanna, Carlo Ley, Klaus Zarbock, Alexander TI Rap1a activation by CalDAG-GEFI and p38 MAPK is involved in E-selectin-dependent slow leukocyte rolling SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE CalDAG-GEFI; Integrin; p38; Rap1a; Signaling ID INTEGRIN ACTIVATION; ADHESION DEFICIENCY; NEUTROPHIL ARREST; CAIDAG-GEFI; IN-VIVO; PROTEIN; KINASE; SIGNALS; PSGL-1; LFA-1 AB Rolling leukocytes are exposed to different adhesion molecules and chemokines. Neutrophils rolling on E-selectin induce integrin alpha(L)beta(2)-mediated slow rolling on ICAM-1 by activating a phospholipase C (PLC)gamma(2)-dependent and a separate PI3K gamma-dependent pathway. E-selectin-signaling cooperates with chemokine signaling to recruit neutrophils into inflamed tissues. However, the distal signaling pathway linking PLC gamma 2 (Plcg2) to alpha(L)beta(2)-activation is unknown. To identify this pathway, we used different Tat-fusion-mutants and gene-deficient mice in intravital microscopy, autoperfused flow chamber, peritonitis, and biochemical studies. We found that the small GTPase Rap1 is activated following E-selectin engagement and that blocking Rap1a in Pik3cg(-/-) mice by a dominant-negative Tat-fusion mutant completely abolished E-selectin-mediated slow rolling. We identified CalDAG-GEFI (Rasgrp2) and p38 MAPK as key signaling intermediates between PLC gamma 2 and Rap1a. G alpha(i)-independent leukocyte adhesion to and transmigration through endothelial cells in inflamed postcapillary venules of the cremaster muscle were completely abolished in Rasgrp2(-/-) mice. The physiological importance of CalDAG-GEFI in E-selectin-dependent integrin activation is shown by complete inhibition of neutrophil recruitment into the inflamed peritoneal cavity of Rasgrp2(-/-) leukocytes treated with pertussis toxin to block G alpha(i)-signaling. Our data demonstrate that Rap1a activation by p38 MAPK and CalDAG-GEFI is involved in E-selectin-dependent slow rolling and leukocyte recruitment. C1 [Stadtmann, Anika; Brinkhaus, Laura; Mueller, Helena; Rossaint, Jan; Zarbock, Alexander] Max Planck Inst Munster, Munster, Germany. [Bolomini-Vittori, Matteo; Laudanna, Carlo] Univ Verona, Dept Pathol & Diagnost, I-37100 Verona, Italy. [Bergmeier, Wolfgang] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Wagner, Denisa D.] Childrens Hosp, Immune Dis Inst, Program Cellular & Mol Med, Boston, MA 02115 USA. [Wagner, Denisa D.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Ley, Klaus] La Jolla Inst Allergy & Immunol, La Jolla, CA USA. [Stadtmann, Anika; Brinkhaus, Laura; Mueller, Helena; Rossaint, Jan; Van Aken, Hugo; Zarbock, Alexander] Univ Munster, Dept Anesthesiol & Intens Care Med, D-48149 Munster, Germany. RP Zarbock, A (reprint author), Univ Munster, Dept Anesthesiol & Crit Care Med, Albert Schweitzer Str 33, D-48149 Munster, Germany. EM zarbock@uni-muenster.de RI Bolomini-Vittori, Matteo/Q-5659-2016 OI Bolomini-Vittori, Matteo/0000-0002-5762-0791 FU German Research Foundation [AZ 428/3-1]; Interdisciplinary Clinical Research Center (IZKF Muenster, Germany) [Za2/001/10]; NIH [NHLBI POI HL056949]; American Heart Association; Fondazione Cariverona, Verona, Italy; Associazione Ricerca sul Cancro (AIRC), Italy FX The authors wish to thank Katrin Tkotz for technical support and Stefanie Kliche for providing the GST-RalGDS fusion protein for Rap1. This study was supported by grants from the German Research Foundation (AZ 428/3-1 to A.Z.), Interdisciplinary Clinical Research Center (IZKF Muenster, Germany, Za2/001/10 to A.Z.), and the NIH (NHLBI POI HL056949 to D. D. W). W. B. was supported by a Scientist Development grant from the American Heart Association. CL was supported by Fondazione Cariverona, Verona, Italy, and by Associazione Ricerca sul Cancro (AIRC), Italy. NR 44 TC 45 Z9 45 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JUL PY 2011 VL 41 IS 7 BP 2074 EP 2085 DI 10.1002/eji.201041196 PG 12 WC Immunology SC Immunology GA 797ME UT WOS:000293131200028 PM 21480213 ER PT J AU Dismuke, CE Egede, LE AF Dismuke, Clara E. Egede, Leonard E. TI Association of serious psychological distress with health services expenditures and utilization in a national sample of US adults SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Serious psychological distress; Health services expenditures; Utilization; US adults ID FACTOR SURVEILLANCE SYSTEM; MENTAL-HEALTH; SCREENING SCALES; UNITED-STATES; PREVALENCE; K6; PERFORMANCE; ARTHRITIS; OLDER; BRFSS AB Objective: The Kessler six-item scale has been shown to be a valid and reliable measure of serious psychological distress (SPD) in community samples. We examined the effect of SPD on health service expenditures and utilization for seven categories in a national probability sample of community dwelling adults in the United States. Methods: We used the two-step sample selection model to examine the association between SPD and total, office-based, outpatient, emergency department (ED), inpatient, dental, home health and prescription expenditures and utilization in 18,330 US adults who participated in the 2007 Medical Expenditure Panel Survey (MEPS). Results: SPD was significantly associated with $1735 (95% CI: $702-2769) higher total expenditures, $285 higher office expenditures ( 95% CI: $30-539), $183 higher ED expenditures (95% CI: $64-303), $282 (95% CI: $62-503) higher home health expenditures, $614 (95% CI: $403-825) higher prescription expenditures and $41 (95% CI: -$103 to $22) lower dental expenditures. SPD was associated with 3.09 (95% CI: 2.09-4.08) more office visits, 0.27 (95% CI: 0.17-0.36) more ED visits, 0.84 (95% CI: 0.36-1.32) more inpatient visits, 2.93 (95% CI: 0.13-5.70) more home health visits, 8.13 (95% CI: 6.08-10.18) more prescriptions and 0.18 (95% CI: -0.30 to -0.07) less dental visits. Conclusions: Among US adults, SPD is associated with significant increases in total expenditures and most other categories of expenditure and utilization. Targeted interventions to mitigate the adverse effects of SPD are needed. (C) 2011 Elsevier Inc. All rights reserved. C1 [Dismuke, Clara E.; Egede, Leonard E.] Med Univ S Carolina, Ctr Hlth Dispar Res, Dept Med, Charleston, SC 29425 USA. [Dismuke, Clara E.; Egede, Leonard E.] Ralph H Johnson VA Med Ctr, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Charleston, SC 29401 USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Dispar Res, Dept Med, Charleston, SC 29425 USA. EM egedel@musc.edu FU NIDDK NIH HHS [K24 DK093699] NR 34 TC 17 Z9 17 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD JUL-AUG PY 2011 VL 33 IS 4 BP 311 EP 317 DI 10.1016/j.genhosppsych.2011.03.014 PG 7 WC Psychiatry SC Psychiatry GA 796LP UT WOS:000293053100002 PM 21762826 ER PT J AU Patterson, AL Morasco, BJ Fuller, BE Indest, DW Loftis, JM Hauser, P AF Patterson, Alexander L. Morasco, Benjamin J. Fuller, Bret E. Indest, David W. Loftis, Jennifer M. Hauser, Peter TI Screening for depression in patients with hepatitis C using the Beck Depression Inventory-II: do somatic symptoms compromise validity? SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Hepatitis C virus; Depression; Factor analysis; Liver disease; Beck Depression Inventory ID ACUTE MYOCARDIAL-INFARCTION; QUALITY-OF-LIFE; INTERFERON-ALPHA; VIRUS-INFECTION; UNITED-STATES; PSYCHIATRIC OUTPATIENTS; ANTIVIRAL THERAPY; CHRONIC PAIN; PREVALENCE; VETERANS AB Objective: The objective of the study was to evaluate the validity of the Beck Depression Inventory-II (BDI-II) when used to measure depression in patients with hepatitis C virus (HCV). Method: Factor analysis was utilized to validate the BDI-II in a sample of 671 patients with HCV recruited from a large Veterans Affairs medical center. The data were split randomly: the first half was subjected to exploratory factor analysis, and confirmatory factor analysis was used with the second half to confirm the model. Diagnostic data were retrieved from the electronic medical records. Results: Subjects were 97.0% male, average age was 52.8 years, 16.1% had a cirrhosis diagnosis, 62.9% had a current major depressive disorder diagnosis, and 42.3% endorsed significant depressive symptoms on the BDI-II. A two-factor model was an excellent fit for the data; the factors were labeled Cognitive Affective and Somatic. Patients scored significantly higher on the Somatic factor than on the Cognitive Affective factor (P<.001), and this discrepancy increased when comparing patients based on whether they had a diagnosis of cirrhosis. Conclusions: When screening for depression in HCV patients, questions targeting cognitive and affective symptoms of depression may provide a more valid measurement of depression than questions targeting somatic symptoms of depression, particularly for patients with more advanced liver disease. Published by Elsevier Inc. C1 [Patterson, Alexander L.; Morasco, Benjamin J.; Fuller, Bret E.; Indest, David W.; Loftis, Jennifer M.] Portland VA Med Ctr, Mental Hlth & Clin Neurosci Div, Portland, OR USA. [Morasco, Benjamin J.; Fuller, Bret E.; Indest, David W.; Loftis, Jennifer M.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Hauser, Peter] Long Beach VA Med Ctr, Long Beach, CA USA. RP Patterson, AL (reprint author), Portland VA Med Ctr, Mental Hlth & Clin Neurosci Div, Portland, OR USA. EM alexander.patterson@va.gov NR 47 TC 19 Z9 19 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD JUL-AUG PY 2011 VL 33 IS 4 BP 354 EP 362 DI 10.1016/j.genhosppsych.2011.04.005 PG 9 WC Psychiatry SC Psychiatry GA 796LP UT WOS:000293053100008 PM 21762832 ER PT J AU Largent, EA Joffe, S Miller, FG AF Largent, Emily A. Joffe, Steven Miller, Franklin G. TI Can RESEARCH and CARE Be Ethically Integrated? SO HASTINGS CENTER REPORT LA English DT Article ID CLINICAL-TRIALS C1 [Largent, Emily A.] Harvard Univ, PhD Program Hlth Policy, Cambridge, MA 02138 USA. [Joffe, Steven] Childrens Hosp Boston, Dana Farber Canc Inst, Boston, MA USA. [Miller, Franklin G.] Natl Inst Hlth, Dept Bioeth, Bethesda, MD 20892 USA. [Joffe, Steven] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Largent, EA (reprint author), Harvard Univ, PhD Program Hlth Policy, Cambridge, MA 02138 USA. OI Joffe, Steven/0000-0002-0667-7384 FU Greenwall Foundation FX Steven Joffe's work was supported by a faculty scholar award from the Greenwall Foundation. NR 25 TC 37 Z9 37 U1 0 U2 3 PU HASTINGS CENTER PI BRIARCLIFF MANOR PA 255 ELM ROAD, BRIARCLIFF MANOR, NY 10510 USA SN 0093-0334 J9 HASTINGS CENT REP JI Hastings Cent. Rep. PD JUL-AUG PY 2011 VL 41 IS 4 BP 37 EP 46 PG 10 WC Ethics; Health Care Sciences & Services; Medical Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Health Care Sciences & Services; Medical Ethics; Biomedical Social Sciences GA 797WB UT WOS:000293159700019 PM 21845922 ER PT J AU Callahan, M AF Callahan, M. TI Vaccine security: building agile vaccine capabilities in the Pacific Rim SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES LA English DT Meeting Abstract C1 [Callahan, M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis,CIMIT, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1201-9712 J9 INT J INFECT DIS JI Int. J. Infect. Dis. PD JUL PY 2011 VL 15 SU 1 BP S31 EP S31 PG 1 WC Infectious Diseases SC Infectious Diseases GA 798OG UT WOS:000293218400087 ER PT J AU Przkora, R Euliano, TY Roussos-Ross, K Zumberg, M Robicsek, SA AF Przkora, R. Euliano, T. Y. Roussos-Ross, K. Zumberg, M. Robicsek, S. A. TI Labor and delivery in a patient with hemophilia B SO INTERNATIONAL JOURNAL OF OBSTETRIC ANESTHESIA LA English DT Article DE Hemophilia B; Labor and delivery; Coagulation; Cesarean section; General anesthesia; Thromboelastography ID INHERITED BLEEDING DISORDERS; FACTOR-IX DEFICIENCY; SOMATIC MOSAICISM; AFFECTED INFANT; X-CHROMOSOME; OPTIMAL-MODE; WOMEN; THROMBOELASTOGRAPHY; INACTIVATION; HEMOSTASIS AB Hemophilia B is a rare X-linked disorder that may cause dramatic bleeding. Women account for only 3.2% of those clinically affected. The X-linked inheritance frequently delays the diagnosis in women and may expose the patient to an increased risk of adverse events. There is limited experience with these patients during labor and delivery. A 28-year-old primiparous woman with hemophilia B (bleeding phenotype) delivered a male infant by an unplanned cesarean delivery under general anesthesia following treatment with factor IX and normalization of her coagulation parameters, guided by thromboelastography. Postpartum vaginal bleeding required transfusion of two units of packed red blood cells. Factor IX supplementation continued for one week. Once diagnosed with hemophilia B, a multidisciplinary approach and advanced antenatal planning can increase the likelihood of a safe delivery. Neuraxial approaches and cesarean delivery are recommended only after normalization of the coagulation profile. The male fetus of a hemophilia A or B patient requires special attention. Operative vaginal delivery and invasive fetal monitoring should be avoided. Thromboelastography is an excellent technique to assess parturients with bleeding disorders or peripartum hemorrhage and may be underused. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Euliano, T. Y.; Robicsek, S. A.] Univ Florida, Coll Med, Dept Anesthesiol, Gainesville, FL 32610 USA. [Przkora, R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. [Euliano, T. Y.] Univ Florida, Coll Med, Dept Physiol & Funct Genom, Gainesville, FL 32610 USA. [Euliano, T. Y.; Roussos-Ross, K.] Univ Florida, Coll Med, Dept Obstet & Gynecol, Gainesville, FL 32610 USA. [Zumberg, M.] Univ Florida, Coll Med, Dept Med, Gainesville, FL 32610 USA. RP Robicsek, SA (reprint author), Univ Florida, Coll Med, Dept Anesthesiol, POB 100254, Gainesville, FL 32610 USA. EM robicsek@ufl.edu NR 26 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-289X J9 INT J OBSTET ANESTH JI Int. J. Obstet. Anesth. PD JUL PY 2011 VL 20 IS 3 BP 250 EP 253 DI 10.1016/j.ijoa.2011.04.003 PG 4 WC Anesthesiology; Obstetrics & Gynecology SC Anesthesiology; Obstetrics & Gynecology GA 796HQ UT WOS:000293042800011 PM 21641201 ER PT J AU Gonzales, R Aagaard, EM Camargo, CA Ma, OJ Plautz, M Maselli, JH McCulloch, CE Levin, SK Metlay, JP AF Gonzales, Ralph Aagaard, Eva M. Camargo, Carlos A., Jr. Ma, O. John Plautz, Mark Maselli, Judith H. McCulloch, Charles E. Levin, Sara K. Metlay, Joshua P. TI C-REACTIVE PROTEIN TESTING DOES NOT DECREASE ANTIBIOTIC USE FOR ACUTE COUGH ILLNESS WHEN COMPARED TO A CLINICAL ALGORITHM SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE C-reactive protein; acute respiratory tract infections; quality improvement; antimicrobial agents ID RESPIRATORY-TRACT INFECTIONS; COMMUNITY-ACQUIRED PNEUMONIA; PRIMARY-CARE; GENERAL-PRACTICE; TRIAL; MANAGEMENT; DIAGNOSIS; ADULTS AB Background: Antibiotics are commonly overused in adults seeking emergency department (ED) care for acute cough illness. Objective: To evaluate the effect of a point-of-care C-reactive protein (CRP) blood test on antibiotic treatment of acute cough illness in adults. Methods: A randomized controlled trial was conducted in a single urban ED in the United States. The participants were adults (age >= 18 years) seeking care for acute cough illness (<= 21. days duration); 139 participants were enrolled, and 131 completed the ED visit. Between November 2005 and March 2006, study participants had attached to their medical charts a clinical algorithm with recommendations for chest X-ray study or antibiotic treatment. For CRP-tested patients, recommendations were based on the same algorithm plus the CRP level. Results: There was no difference in antibiotic use between CRP-tested and control participants (37% [95% confidence interval (CI) 29-45%] vs. 31% [95% CI 23-39%], respectively; p = 0.46) or chest X-ray use (52% [95% CI 43-61%] vs. 48% [95% CI 39-57%], respectively; p = 0.67). Among CRP-tested participants, those with normal CRP levels received antibiotics much less frequently than those with indeterminate CRP levels (20% [95% CI 7-33%] vs. 50% [95% CI 32-68%], respectively; p = 0.01). Conclusions: Point-of-care CRP testing does not seem to provide any additional value beyond a point-of-care clinical decision support for reducing antibiotic use in adults with acute cough illness. (C) 2011 Elsevier Inc. C1 [Gonzales, Ralph; Maselli, Judith H.; Levin, Sara K.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Aagaard, Eva M.] Univ Colorado, Hlth Sci Ctr, Denver, CO USA. [Aagaard, Eva M.] Univ Colorado, Dept Med, Denver, CO USA. [Camargo, Carlos A., Jr.] Massachussetts Gen Hosp, Dept Emergency Med, Boston, MA USA. [Ma, O. John] Oregon Hlth & Sci Univ, Dept Emergency Med, Portland, OR 97201 USA. [Plautz, Mark] Vet Affairs Med Ctr, Med Serv 111, Kansas City, MO USA. [McCulloch, Charles E.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Metlay, Joshua P.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Metlay, Joshua P.] VA Med Ctr, Philadelphia, PA USA. RP Gonzales, R (reprint author), Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. FU Translating Research into Practice initiative; Agency for Healthcare Research and Quality [1 R01 HS013915]; Health Services Research and Development Service of the Department of Veterans Affairs [AVA-03-239] FX This study was funded by the Translating Research into Practice initiative, jointly sponsored by the Agency for Healthcare Research and Quality (1 R01 HS013915) and the Health Services Research and Development Service of the Department of Veterans Affairs (AVA-03-239). NR 18 TC 13 Z9 13 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 JUL PY 2011 VL 41 IS 1 BP 1 EP 7 DI 10.1016/j.jemermed.2008.06.021 PG 7 WC Emergency Medicine SC Emergency Medicine GA 798KB UT WOS:000293203500001 PM 19095403 ER PT J AU Millen, JC Lindberg, D AF Millen, Jennifer Clare Lindberg, Daniel TI MAISONNEUVE FRACTURE SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article C1 [Millen, Jennifer Clare; Lindberg, Daniel] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Millen, Jennifer Clare] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Millen, JC (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. NR 6 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD JUL PY 2011 VL 41 IS 1 BP 77 EP 78 DI 10.1016/j.jemermed.2008.08.021 PG 2 WC Emergency Medicine SC Emergency Medicine GA 798KB UT WOS:000293203500015 PM 19157747 ER PT J AU Rosalem, W Rescala, B Teles, RP Fischer, RG Gustafsson, A Figueredo, CM AF Rosalem, W. Rescala, B. Teles, R. P. Fischer, R. G. Gustafsson, A. Figueredo, C. M. TI Effect of Non-Surgical Treatment on Chronic and Aggressive Periodontitis: Clinical, Immunologic, and Microbiologic Findings SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE Aggressive periodontitis; chronic periodontitis; cytokine; pathogenesis ID GINGIVAL CREVICULAR FLUID; ADULT PERIODONTITIS; GRANULOCYTE ELASTASE; NEUTROPHIL ELASTASE; SUBGINGIVAL PLAQUE; MOUTH DISINFECTION; LEUKOCYTE ACTIVITY; CIGARETTE-SMOKING; ATTACHMENT LOSS; THERAPY AB Background: Our goalwas to examine differences in clinical, microbiologic, and immunologic responses to non-surgical mechanical therapy in patients with generalized chronic periodontitis (GCP) and generalized aggressive periodontitis (GAgP). Methods: Twenty patients with GCP and 14 patients with GAgP were evaluated. Clinical data, gingival crevicular fluid (GCF), and subgingival plaque samples were collected at baseline and 3 months after non-surgical periodontal treatment. Levels of 40 subgingival species were measured using checker-board DNA-DNA hybridization. GCF interleukin (IL)-1 beta, -4, and -8 and interferon-gamma (IFN-gamma) were analyzed using a multiplexed bead immunoassay, and elastase activity was measured using an enzymatic assay. The significance of changes with time was examined using the Wilcoxon rank sum test. Changes in clinical, microbiologic, and immunologic parameters after therapy were compared between groups using the Mann-Whitney U test. Results: After periodontal therapy, we found significant improvements for all clinical parameters in both groups. We also observed significant reductions in elastase activity in shallow and deep sites from the GAgP group and in deep sites from the GCP group. Microbiologic data showed significant reductions in proportions of orange and red complexes and an increase in proportions of Actinomyces species in both clinical groups. When the clinical, microbiologic, and immunologic responses after therapy were compared between groups, only minor differences were found. Conclusion: This study fails to show any significant differences between severe forms of GCP and GAgP in response to non-surgical periodontal treatment. J Periodontol 2011; 82: 979989. C1 [Rosalem, W.] Univ Estado Rio De Janeiro, Sch Dent, Dept Periodontol, BR-20551030 Rio De Janeiro, Brazil. [Teles, R. P.] Forsyth Inst, Dept Periodontol, Cambridge, MA USA. [Gustafsson, A.; Figueredo, C. M.] Karolinska Inst, Inst Odontol, Div Periodontol, Stockholm, Sweden. RP Figueredo, CM (reprint author), Univ Estado Rio De Janeiro, Sch Dent, Dept Periodontol, Av 28 Setembro,157 Vila Isabel, BR-20551030 Rio De Janeiro, Brazil. EM cmfigueredo@hotmail.com RI Fischer, Ricardo/F-8788-2012; Figueredo, Carlos Marcelo/H-3356-2013 OI Figueredo, Carlos Marcelo/0000-0003-0222-9231 NR 60 TC 23 Z9 24 U1 0 U2 10 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA SN 0022-3492 J9 J PERIODONTOL JI J. Periodont. PD JUL PY 2011 VL 82 IS 7 BP 979 EP 989 DI 10.1902/jop.2011.100579 PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 795YG UT WOS:000293015100005 PM 21309718 ER PT J AU O'Seaghdha, CM Fox, CS AF O'Seaghdha, Conall M. Fox, Caroline S. TI The Fourth Dimension: Associations of Change in Albuminuria over Time SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material ID RECLASSIFICATION; MICROALBUMINURIA; MARKER C1 [O'Seaghdha, Conall M.; Fox, Caroline S.] NHLBI, Framingham Offspring Study, Framingham, MA 01702 USA. [O'Seaghdha, Conall M.; Fox, Caroline S.] Ctr Populat Studies, Framingham, MA USA. [O'Seaghdha, Conall M.; Fox, Caroline S.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA. [O'Seaghdha, Conall M.] Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA. [O'Seaghdha, Conall M.] Massachusetts Gen Hosp, Div Renal, Boston, MA 02114 USA. [O'Seaghdha, Conall M.] Harvard Univ, Sch Med, Div Renal, Boston, MA USA. [Fox, Caroline S.] Harvard Univ, Sch Med, Div Endocrinol, Boston, MA 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 11 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JUL PY 2011 VL 22 IS 7 BP 1186 EP 1188 DI 10.1681/ASN.2011050488 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 798KA UT WOS:000293203400005 PM 21680650 ER PT J AU Peralta, CA Katz, R DeBoer, I Ix, J Sarnak, M Kramer, H Siscovick, D Shea, S Szklo, M Shlipak, M AF Peralta, Carmen A. Katz, Ronit DeBoer, Ian Ix, Joachim Sarnak, Mark Kramer, Holly Siscovick, David Shea, Steven Szklo, Moyses Shlipak, Michael TI Racial and Ethnic Differences in Kidney Function Decline among Persons without Chronic Kidney Disease SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID STAGE RENAL-DISEASE; NUTRITION EXAMINATION SURVEY; GLOMERULAR-FILTRATION-RATE; 3RD NATIONAL-HEALTH; SERUM CYSTATIN-C; CARDIOVASCULAR EVENTS; ATHEROSCLEROSIS MESA; SERIAL MEASUREMENTS; AFRICAN-AMERICANS; ELDERLY PERSONS AB Whether the rate of kidney function decline before the onset of CKD differs among racial and ethnic groups remains unclear. Here, we evaluated kidney function decline and incident CKD among white, black, Hispanic, and Chinese participants in the Multi-Ethnic Study of Atherosclerosis (MESA) during 5 years of follow-up. We estimated GFR using both cystatin C (eGFRcys) and creatinine (eGFRcreat). The definition of incident CKD required eGFRcys <60 ml/min per 1.73 m(2) and a decline in eGFRcys >= 1 ml/min per year. Among participants with eGFRcreat >60 ml/min per 1.73 m(2) at baseline, blacks had a significantly higher rate of kidney function decline than whites (0.31 ml/min per 1.73 m(2)/yr faster on average, P = 0.001), even after adjusting for multiple potential confounders. Among Hispanics, Dominicans and Puerto Ricans had faster rates of decline than whites (0.55 and 0.47 ml/min per 1.73 m(2)/yr faster, respectively). Mexicans, South Americans, or other Hispanics had similar rates of decline compared to whites. We did not detect significant differences in the rates of kidney function decline among Chinese and white participants. Among those with normal or near-normal kidney function at baseline, blacks and Hispanics had the highest rates of incident CKD during follow-up. Adjustment for comorbidities attenuated some of these differences. In conclusion, the average rate of kidney function decline before the onset of CKD differs among racial and ethnic groups. Traditional risk factors do not explain these differences fully, highlighting the need to explore these disparities. C1 [Peralta, Carmen A.; Shlipak, Michael] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Katz, Ronit] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [DeBoer, Ian] Univ Washington, Div Nephrol, Seattle, WA 98195 USA. [Siscovick, David] Univ Washington, Dept Epidemiol & Biostat, Seattle, WA 98195 USA. [Ix, Joachim] Univ Calif San Diego, Div Nephrol, San Diego, CA 92103 USA. [Sarnak, Mark] Tufts Univ New England Med Ctr, Div Nephrol, Boston, MA USA. [Kramer, Holly] Loyola Univ, Med Ctr, Div Nephrol, Maywood, IL 60153 USA. [Shea, Steven] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. [Szklo, Moyses] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Shlipak, Michael] San Francisco VA Med Ctr, Div Gen Internal Med, San Francisco, CA USA. RP Peralta, CA (reprint author), 4150 Clement St,111A1, San Francisco, CA 94121 USA. EM Carmenalicia.peralta@ucsf.edu RI Inca, Inct/K-2204-2013 FU National Heart, Lung, and Blood Institute for MESA [N01-HC-95159, N01-HC-951651, N01-HC-95169]; NIDDK [IK23DK082793-01] FX This work was supported by contracts [N01-HC-95159 through N01-HC-951651 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-nhIbi.org. This work was also funded by the NIDDK (IK23DK082793-01 to C.P.) NR 31 TC 25 Z9 28 U1 0 U2 3 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 JUL PY 2011 VL 22 IS 7 BP 1327 EP 1334 DI 10.1681/ASN.2010090960 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 798KA UT WOS:000293203400020 PM 21700831 ER PT J AU Raissian, Y Nasr, SH Larsen, CP Colvin, RB Smyrk, TC Takahashi, N Bhalodia, A Sohani, AR Zhang, LZ Chari, S Sethi, S Fidler, ME Cornell, LD AF Raissian, Yassaman Nasr, Samih H. Larsen, Christopher P. Colvin, Robert B. Smyrk, Thomas C. Takahashi, Naoki Bhalodia, Ami Sohani, Aliyah R. Zhang, Lizhi Chari, Suresh Sethi, Sanjeev Fidler, Mary E. Cornell, Lynn D. TI Diagnosis of IgG4-Related Tubulointerstitial Nephritis SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID PLASMA-CELL INFILTRATION; AUTOIMMUNE PANCREATITIS; CLINICOPATHOLOGICAL-ENTITY; SCLEROSING PANCREATITIS; SYSTEMIC-DISEASE; TUMOR AB IgG4-related systemic disease is an autoimmune disease that was first recognized in the pancreas but also affects other organs. This disease may manifest as tubulointerstitial nephritis (IgG4-TIN), but its clinicopathologic features in the kidney are not well described. Of the 35 patients with IgG4-TIN whose renal tissue specimens we examined, 27 (77%) had acute or progressive chronic renal failure, 29 (83%) had involvement of other organ systems, and 18 of 23 (78%) had radiographic abnormalities. Elevated total IgG or IgG4 serum levels were present in 79%. All pathologic specimens featured plasma cell rich TIN, with most showing diffuse, expansile interstitial fibrosis. Immune complexes along the tubular basement membranes were present in 25 of 30 (83%). All specimens had a moderate to marked increase in IgG4+ plasma cells by immunohistochemistry. We used a control group of 175 pathologic specimens with plasma cell rich interstitial infiltrates that can mimic IgG4-TIN to examine the diagnostic utility of IgG4 immunostaining. Excluding pauci-immune necrotizing and crescentic glomerulonephritis, IgG4 immunohistochemistry had a sensitivity of 100% (95% CI 90-100%) and a specificity of 92% (95% CI 86-95%) for IgG4-TIN. Of the 19 patients with renal failure for whom treatment and follow-up data were available, 17 (89%) responded to prednisone. In summary, because no single test definitively diagnoses IgG4-related systemic disease, we rely on a combination of histologic, immunophenotypic, clinical, radiographic, and laboratory features. When the disease manifests in the kidney, our data support diagnostic criteria that can distinguish IgG4-TIN from other types of TIN. C1 [Raissian, Yassaman; Nasr, Samih H.; Smyrk, Thomas C.; Zhang, Lizhi; Sethi, Sanjeev; Fidler, Mary E.; Cornell, Lynn D.] Mayo Clin, Div Anat Pathol, Dept Lab Med & Pathol, Rochester, MN 55905 USA. [Takahashi, Naoki] Mayo Clin, Dept Radiol, Rochester, MN 55905 USA. [Chari, Suresh] Mayo Clin, Dept Internal Med, Div Gastroenterol & Hepatol, Rochester, MN 55905 USA. [Larsen, Christopher P.] Neohropathol Associates, Little Rock, AR USA. [Colvin, Robert B.; Sohani, Aliyah R.] Massachusetts Gen Hosp, Pathol Serv, Boston, MA 02114 USA. [Bhalodia, Ami] Louisiana State Univ, Dept Pathol, Heath Sci Ctr, Shreveport, LA 71105 USA. RP Cornell, LD (reprint author), Mayo Clin, Div Anat Pathol, Dept Lab Med & Pathol, 200 1st St SW, Rochester, MN 55905 USA. EM cornell.lynn@mayo.edu NR 25 TC 93 Z9 116 U1 0 U2 3 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 JUL PY 2011 VL 22 IS 7 BP 1343 EP 1352 DI 10.1681/ASN.2011010062 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 798KA UT WOS:000293203400022 PM 21719792 ER PT J AU Bauer, KA AF Bauer, K. A. TI Recent progress in anticoagulant therapy: oral direct inhibitors of thrombin and factor Xa SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Review DE anticoagulants; factor Xa; thrombin; venous thromboembolism ID NONVALVULAR ATRIAL-FIBRILLATION; TOTAL KNEE ARTHROPLASTY; RANDOMIZED CONTROLLED-TRIAL; RE-LY TRIAL; VENOUS THROMBOEMBOLISM; STROKE PREVENTION; DABIGATRAN ETEXILATE; DOUBLE-BLIND; TOTAL HIP; RIVAROXABAN AB While parenteral anticoagulants such as unfractionated and low molecular weight heparins and the oral vitamin K antagonists are effective for the prevention and treatment of thrombosis, they have a number of limitations. Up until recently, vitamin K antagonists (e. g. warfarin) have been the only available oral anticoagulants. These drugs have a delayed onset of action, food and drug interactions, and variable pharmacokinetics/pharmacodynamics such that regular laboratory monitoring and dose adjustments are required to maintain the International Normalized Ratio (INR) in the therapeutic range. New oral anticoagulants that selectively inhibit either thrombin (dabigatran etexilate) or factor Xa (rivaroxaban, apixaban) have now gained approval in many countries for some clinical indications. Unlike warfarin, these drugs have a rapid onset of action and a relatively wide therapeutic range such that coagulation monitoring is not required. These agents are more convenient for patients and health care providers, but also have potential for improving clinical outcomes and being more cost-effective than existing agents. This will result in major changes in the way that thrombosis is managed, both with respect to prevention and treatment. The new oral inhibitors of thrombin and factor Xa, however, have limitations and the absence of a need for regular laboratory monitoring makes medication compliance extremely important for maintaining efficacy given their relatively short half-lives. Furthermore there will be challenges in managing patients on these agents who develop recurrent thrombosis or major bleeding until methods to monitor and assess the levels of the new agents are readily available and specific antidotes are developed. C1 [Bauer, K. A.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Bauer, K. A.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02215 USA. RP Bauer, KA (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, 330 Brookline Ave, Boston, MA 02215 USA. EM kbauer@bidmc.harvard.edu NR 43 TC 57 Z9 60 U1 1 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1538-7933 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD JUL PY 2011 VL 9 SU 1 SI SI BP 12 EP 19 DI 10.1111/j.1538-7836.2011.04321.x PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 796BG UT WOS:000293024600003 PM 21781237 ER PT J AU Ho-Tin-Noe, B Demers, M Wagner, DD AF Ho-Tin-Noe, B. Demers, M. Wagner, D. D. TI How platelets safeguard vascular integrity SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Review DE bleeding; inflammation; platelets; thrombocytopenia; tumour; vascular permeability ID TUMOR-ASSOCIATED MACROPHAGES; HUMAN ENDOTHELIAL CELLS; PROGENITOR CELLS; P-SELECTIN; IN-VIVO; INFLAMED GLOMERULUS; ADENINE-NUCLEOTIDES; PROTEASE NEXIN-1; ANGIOGENESIS; PERMEABILITY AB The haemostatic role of platelets was established in the 1880s by Bizzozero who observed their ability to adhere and aggregate at sites of vascular injury. It was only some 80 years later that the function of platelets in maintaining the structural integrity of intact blood vessels was reported by Danielli. Danielli noted that platelets help preserve the barrier function of endothelium during organ perfusion. Subsequent studies have demonstrated further that platelets are continuously needed to support intact mature blood vessels. More recently, platelets were shown to safeguard developing vessels, lymphatics, as well as the microvasculature at sites of leukocyte infiltration, including inflamed organs and tumours. Interestingly, from a mechanistic point of view, the supporting role of platelets in these various vessels does not necessarily involve the well-understood process of platelet plug formation but, rather, may rely on secretion of the various platelet granules and their many active components. The present review focuses on these nonconventional aspects of platelet biology and function by presenting situations in which platelets intervene to maintain vascular integrity and discusses possible mechanisms of their actions. We propose that modulating these newly described platelet functions may help treat haemorrhage as well as treat cancer by increasing the efficacy of drug delivery to tumours. C1 [Ho-Tin-Noe, B.; Demers, M.; Wagner, D. D.] Immune Dis Inst, Boston, MA 02115 USA. [Ho-Tin-Noe, B.; Demers, M.; Wagner, D. D.] Childrens Hosp Boston, Program Cellular & Mol Med, Boston, MA USA. [Ho-Tin-Noe, B.; Demers, M.; Wagner, D. D.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Ho-Tin-Noe, B.] Bichat Claude Bernard Hosp, Unit 698, INSERM, Paris, France. [Ho-Tin-Noe, B.] Univ Paris 07, Paris, France. RP Wagner, DD (reprint author), Immune Dis Inst, 3 Blackfan Circle, Boston, MA 02115 USA. EM wagner@idi.harvard.edu FU National Heart, Lung, and Blood Institute of the National Institutes of Health [P01 HL056949, R01 HL041002]; La Fondation pour la Recherche Medicale, France; Terry Fox Foundation through the Canadian Cancer Society FX We thank the anonymous reviewers for careful reading and helpful suggestions for the manuscript. We thank Lesley Cowan and Daphne Schatzberg for help in editing this manuscript. This work was supported by National Heart, Lung, and Blood Institute of the National Institutes of Health grants P01 HL056949 and R01 HL041002 (to D. D. W.), La Fondation pour la Recherche Medicale, France (to B. H.) and the Terry Fox Foundation through the Canadian Cancer Society (to M. D.). NR 93 TC 63 Z9 65 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1538-7933 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD JUL PY 2011 VL 9 SU 1 SI SI BP 56 EP 65 DI 10.1111/j.1538-7836.2011.04317.x PG 10 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 796BG UT WOS:000293024600008 PM 21781242 ER PT J AU Springer, TA AF Springer, T. A. TI Biology and physics of von Willebrand factor concatamers SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Review DE biosynthesis; secretion; shear flow; thrombotic thrombocytopenic purpura; von Willebrand disease; weibel palade body ID IB-IX-V; HUMAN VONWILLEBRAND-FACTOR; WEIBEL-PALADE BODIES; LEUCINE-RICH REPEATS; FACTOR A2 DOMAIN; FACTOR A1 DOMAIN; ENDOTHELIAL-CELLS; DISEASE MUTATIONS; PLATELET-AGGREGATION; THROMBUS FORMATION AB Structural specialisations enable von Willebrand factor (VWF) to assemble during biosynthesis into helical tubules in Weibel-Palade bodies (WPB). Specialisations include a pH-regulated dimeric bouquet formed by the C-terminal half of VWF and helical assembly guided by the N-terminal half that templates inter-dimer disulphide bridges. Orderly assembly and storage of ultra-long concatamers in helical tubules, without crosslinking of neighboring tubules, enables unfurling during secretion without entanglement. Length regulation occurs post-secretion, by hydrodynamic force-regulated unfolding of the VWF A2 domain, and its cleavage by the plasma protease ADAMTS13 (a disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13). VWF is longest at its site of secretion, where its haemostatic function is most important. Moreover, elongational hydrodynamic forces on VWF are strongest just where needed, when bound to the vessel wall, or in elongational flow in the circulation at sites of vessel rupture or vasoconstriction in haemostasis. Elongational forces regulate haemostasis by activating binding of the A1 domain to platelet GPIb alpha, and over longer time periods, regulate VWF length by unfolding of the A2 domain for cleavage by ADAMTS13. Recent structures of A2 and single molecule measurements of A2 unfolding and cleavage by ADAMTS13 illuminate the mechanisms of VWF length regulation. Single molecule studies on the A1-GPIb receptor-ligand bond demonstrate a specialised flex-bond that enhances resistance to the strong hydrodynamic forces experienced at sites of haemorrhage. C1 [Springer, T. A.] Childrens Hosp Boston, Immune Dis Inst, Boston, MA 02115 USA. [Springer, T. A.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Springer, TA (reprint author), Childrens Hosp Boston, Immune Dis Inst, Boston, MA 02115 USA. EM springer@idi.harvard.edu FU NIH [HL-48675, HL-108248] FX I am grateful to collaborators in cited publications for discussion that contributed to the concepts presented here. Yan-Feng Zhou, Jongseong Kim, and Cheng-Zhong Zhang are thanked for preparation of special figures for this review. Author's work was supported by NIH grants HL-48675 and HL-108248. NR 68 TC 57 Z9 58 U1 1 U2 18 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1538-7933 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD JUL PY 2011 VL 9 SU 1 SI SI BP 130 EP 143 DI 10.1111/j.1538-7836.2011.04320.x PG 14 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 796BG UT WOS:000293024600014 PM 21781248 ER PT J AU Hegde, M Glass, GA Dalmau, J Christine, CW AF Hegde, Manu Glass, Graham A. Dalmau, Josep Christine, Chadwick W. TI A Case of Slow Orthostatic Tremor, Responsive to Intravenous Immunoglobulin SO MOVEMENT DISORDERS LA English DT Letter C1 [Hegde, Manu; Glass, Graham A.; Christine, Chadwick W.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Glass, Graham A.] San Francisco VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, San Francisco, CA USA. [Dalmau, Josep] Hosp Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. RP Hegde, M (reprint author), Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. EM manu.hegde@ucsf.edu OI Dalmau, Josep/0000-0001-5856-2813 FU NINDS NIH HHS [5U10NS044460, R01NS046487] NR 7 TC 4 Z9 4 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD JUL PY 2011 VL 26 IS 8 BP 1563 EP 1565 DI 10.1002/mds.23610 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 800CB UT WOS:000293334800038 PM 21469203 ER PT J AU Nagel, MA Traktinskiy, I Azarkh, Y Kleinschmidt-DeMasters, B Hedley-Whyte, T Russman, A VanEgmond, EM Stenmark, K Frid, M Mahalingam, R Wellish, M Choe, A Cordery-Cotter, R Cohrs, RJ Gilden, D AF Nagel, M. A. Traktinskiy, I. Azarkh, Y. Kleinschmidt-DeMasters, B. Hedley-Whyte, T. Russman, A. VanEgmond, E. M. Stenmark, K. Frid, M. Mahalingam, R. Wellish, M. Choe, A. Cordery-Cotter, R. Cohrs, R. J. Gilden, D. TI Varicella zoster virus vasculopathy Analysis of virus-infected arteries SO NEUROLOGY LA English DT Article ID RAT CAROTID ARTERIES; HERPES-ZOSTER; ADVENTITIAL FIBROBLASTS; PULMONARY-HYPERTENSION; NEOINTIMAL FORMATION; TRIGEMINAL GANGLIA; BALLOON INJURY; BLOOD-VESSELS; LESIONS; TRANSPLANTATION AB Objective: Varicella zoster virus (VZV) is an under-recognized yet treatable cause of stroke. No animal model exists for stroke caused by VZV infection of cerebral arteries. Thus, we analyzed cerebral and temporal arteries from 3 patients with VZV vasculopathy to identify features that will help in diagnosis and lead to a better understanding of VZV-induced vascular remodeling. Methods: Normal and VZV-infected cerebral and temporal arteries were examined histologically and by immunohistochemistry using antibodies directed against VZV, endothelium, and smooth muscle actin and myosin. Results: All VZV-infected arteries contained 1) a disrupted internal elastic lamina; 2) a hyperplastic intima composed of cells expressing alpha-smooth muscle actin (alpha-SMA) and smooth muscle myosin heavy chain (SM-myosin) but not endothelial cells expressing CD31; and 3) decreased medial smooth muscle cells. The location of VZV antigen, degree of neointimal thickening, and disruption of the media were related to the duration of disease. Conclusions: The presence of VZV primarily in the adventitia early in infection and in the media and intima later supports the notion that after reactivation from ganglia, VZV spreads transaxonally to the arterial adventitia followed by transmural spread of virus. Disruption of the internal elastic lamina, progressive intimal thickening with cells expressing alpha-SMA and SM-MHC, and decreased smooth muscle cells in the media are characteristic features of VZV vasculopathy. Stroke in VZV vasculopathy may result from changes in arterial caliber and contractility produced in part by abnormal accumulation of smooth muscle cells and myofibroblasts in thickened neointima and disruption of the media. Neurology (R) 2011; 77: 364-370 C1 [Nagel, M. A.; Traktinskiy, I.; Azarkh, Y.; Mahalingam, R.; Wellish, M.; Choe, A.; Cordery-Cotter, R.; Cohrs, R. J.; Gilden, D.] Univ Colorado, Sch Med, Dept Neurol, Aurora, CO 80045 USA. [Kleinschmidt-DeMasters, B.] Univ Colorado, Sch Med, Dept Pathol, Aurora, CO 80045 USA. [Stenmark, K.; Frid, M.] Univ Colorado, Sch Med, Dept Pediat, Aurora, CO 80045 USA. [Gilden, D.] Univ Colorado, Sch Med, Dept Microbiol, Aurora, CO 80045 USA. [Hedley-Whyte, T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol Neuropathol, Boston, MA USA. [Russman, A.] Henry Ford Hosp, Dept Neurol, Detroit, MI 48202 USA. [VanEgmond, E. M.] Henry Ford Hosp, Dept Pathol & Lab Med, Detroit, MI 48202 USA. RP Gilden, D (reprint author), Univ Colorado, Sch Med, Dept Neurol, 12700 E 19th Ave,Box B182, Aurora, CO 80045 USA. EM don.gilden@ucdenver.edu FU NIH [AG006127, AG032958, NS067070] FX Supported in part by the NIH (AG006127, D.G.; AG032958, R.M., R.J.C., D.G.; and NS067070, M.A.).; Dr. Nagel receives research support from the NIH. I. Traktinskiy reports no disclosures. Dr. Azarkh receives research support from the NIH. Dr. Kleinschmidt-DeMasters reports no disclosures. Dr. Hedley-Whyte serves on the editorial board of Human Pathology and holds stock/stock options in Becton Dickinson. Dr. Russman serves on speakers' bureaus for Boehringer Ingelheim and Pfizer Inc and receives research support from the NIH. Dr. VanEgmond reports no disclosures. Dr. Stenmark serves on the editorial boards of the American Journal of Respiratory and Critical Care Medicine, the American Journal of Respiratory Cell and Molecular Biology, the American Journal of Physiology-Lung Cellular and Molecular Physiology, and as an Associate Editor for Pulmonary Circulation; and receives research support from the NIH. Dr. Frid reports no disclosures. Dr. Mahalingam serves on the editorial board of the Journal of Neurovirology and receives research support from the NIH. M. Wellish and A. Choe report no disclosures. Dr. Cordery-Cotter reports no disclosures. Dr. Cohrs serves on the editorial board of Archives of Clinical Microbiology and receives research support from the NIH. Dr. Gilden has received a speaker honorarium from Merck & Co., Inc.; serves as Senior Associate Editor for the Journal of Neurovirology and on the editorial boards of In Vivo, the Journal of Virology, Scientific American Medicine, Virus Genes, and Neurology (R); has served as a consultant for Teva Pharmaceutical Industries Ltd. and Epiphany Laboratories; and receives research support from the NIH. NR 37 TC 62 Z9 64 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUL PY 2011 VL 77 IS 4 BP 364 EP 370 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 797KA UT WOS:000293123300015 PM 21753174 ER PT J AU Moy, B Chabner, BA AF Moy, Beverly Chabner, Bruce A. TI Patient Navigator Programs, Cancer Disparities, and the Patient Protection and Affordable Care Act SO ONCOLOGIST LA English DT Article DE Disparities in cancer care; Health care law; Patient navigator programs; Patient Protection and Affordable Care Act AB Patients in vulnerable population groups suffer disproportionately from cancer. The elimination of cancer disparities is critically important for lessening the burden of cancer. Patient navigator programs have been shown to improve clinical outcomes. Among its provisions relevant to disparities in cancer care, The Patient Protection and Affordability Care Act authorizes continued funding of patient navigator programs. However, given the current economic and political environment, this funding is in jeopardy. This article describes patient navigator programs and summarizes the elements of the health care law that are relevant to these programs. It is vital that the entire oncology community remain committed to leading efforts toward the improvement of cancer care among our most vulnerable patients. The Oncologist 2011;16:926-929 C1 [Moy, Beverly; Chabner, Bruce A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Moy, B (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St, Boston, MA 02114 USA. EM bmoy@partners.org RI Inov Farmaceutica, Inct/K-2313-2013 NR 11 TC 9 Z9 9 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 PD JUL PY 2011 VL 16 IS 7 BP 926 EP 929 DI 10.1634/theoncologist.2011-0140 PG 4 WC Oncology SC Oncology GA 799EK UT WOS:000293266400003 PM 21804070 ER PT J AU Marchese, AD Sulemanji, D Chipman, D Villar, J Kacmarek, RM AF Marchese, Andrew D. Sulemanji, Demet Chipman, Daniel Villar, Jesus Kacmarek, Robert M. TI Performance of Current Intensive Care Unit Ventilators During Pressure and Volume Ventilation SO RESPIRATORY CARE LA English DT Article DE ventilator; mechanical ventilation; intensive care; pressure support; pressure assist/control; volume assist/control ID ICU VENTILATORS; COMPARATIVE BENCH; LUNG MODEL; SUPPORT; ANESTHESIA AB BACKGROUND: Intensive-care mechanical ventilators regularly enter the market, but the gas-delivery capabilities of many have never been assessed. METHODS: We evaluated 6 intensive-care ventilators in the pressure support (PS), pressure assist/control (PA/C), and volume assist/control (VA/C) modes, with lung-model mechanics combinations of compliance and resistance of 60 mL/cm H(2)O and 10 cm H(2)O/L/s, 60 mL/cm H(2)O and 5 cm H(2)O/L/s, and 30 mL/cm H(2)O and 10 cm H(2)O/L/s, and inspiratory muscle effort of 5 and 10 cm H(2)O. PS and PA/C were set to 15 cm H(2)O, and PEEP to 5 and 15 cm H(2)O in all modes. During VA/C, tidal volume was set at 500 mL and inspiratory time was set at 0.8 second. Rise time and termination criteria were set at the manufacturers' defaults, and to an optimal level during PS and PA/C. RESULTS: There were marked differences in ventilator performance in all 3 modes. VA/C had the greatest difficulty meeting lung model demand and the greatest variability across all tested scenarios and ventilators. From high to low inspiratory muscle effort, pressure-to-trigger, time for pressure to return to baseline, and triggering pressure-time product decreased in all modes. With increasing resistance and decreasing compliance, tidal volume, pressure-to-trigger, time-to-trigger, time for pressure to return to baseline, time to 90% of peak pressure, and pressure-time product decreased. There were large differences between the default and optimal settings for all the variables in PS and PA/C. Performance was not affected by PEEP. CONCLUSIONS: Most of the tested ventilators performed at an acceptable level during the majority of evaluations, but some ventilators performed inadequately during specific settings. Bedside clinical evaluation is needed. C1 [Marchese, Andrew D.; Chipman, Daniel; Kacmarek, Robert M.] Massachusetts Gen Hosp, Resp Care Dept, Boston, MA 02114 USA. [Sulemanji, Demet] Harvard Univ, Sch Med, Dept Resp Care, Boston, MA USA. [Sulemanji, Demet] Harvard Univ, Sch Med, Dept Anesthesiol & Crit Care, Boston, MA USA. [Villar, Jesus] Inst Salud Carlos III, Ctr Invest Biomed Red CIBER Enfermedades Resp, Madrid, Spain. [Villar, Jesus] Hosp Univ Dr Negrin, Multidisciplinary Organ Dysfunct Evaluat Res Netw, Res Unit, Las Palmas Gran Canaria, Spain. RP Kacmarek, RM (reprint author), Massachusetts Gen Hosp, Resp Care Dept, 55 Fruit St,Ellison 401, Boston, MA 02114 USA. EM rkacmarek@partners.org FU Covidien; Drager Medical; General Electric; Hamilton Medical; Newport Medical FX This research was partly supported by Covidien, Drager Medical, General Electric, Hamilton Medical, and Newport Medical. Mr Chipman has disclosed a relationship with Maquet Medical. Dr Villar has disclosed a relationship with Maquet Medical. Dr Kacmarek has disclosed relationships with Covidien, Carefusion, Drager Medical, General Electric, Hamilton Medical, Newport Medical, and KCI. The other authors have disclosed no conflicts of interest. NR 15 TC 8 Z9 8 U1 0 U2 2 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESP CARE JI Respir. Care PD JUL PY 2011 VL 56 IS 7 BP 928 EP 940 DI 10.4187/respcare.00981 PG 13 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 796KC UT WOS:000293049200002 PM 21352662 ER PT J AU Firth, PG Gray, C Novis, CA AF Firth, P. G. Gray, C. Novis, C. A. TI High-altitude corneal oedema associated with acetazolamide SO SAMJ SOUTH AFRICAN MEDICAL JOURNAL LA English DT Editorial Material ID THICKNESS C1 [Firth, P. G.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Firth, P. G.] Harvard Univ, Sch Med, Boston, MA USA. RP Firth, PG (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM pfirth@partners.org NR 6 TC 3 Z9 3 U1 0 U2 0 PU SA MEDICAL ASSOC PI PRETORIA PA BLOCK F CASTLE WALK CORPORATE PARK, NOSSOB STREET, ERASMUSKLOOF EXT3, PRETORIA, 0002, SOUTH AFRICA SN 0256-9574 J9 SAMJ S AFR MED J JI SAMJ S. Afr. Med. J. PD JUL PY 2011 VL 101 IS 7 BP 462 EP 462 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 799UA UT WOS:000293310400013 PM 21920105 ER PT J AU Veves, A Tecilazich, F AF Veves, Aristidis Tecilazich, Francesco TI Biology and Treatment of Diabetic Foot Ulcers SO WOUNDS-A COMPENDIUM OF CLINICAL RESEARCH AND PRACTICE LA English DT Editorial Material C1 [Veves, Aristidis; Tecilazich, Francesco] Joslin Beth Israel Deaconess Foot Ctr, Boston, MA 02215 USA. [Veves, Aristidis; Tecilazich, Francesco] Harvard Univ, Sch Med, Microcirculat Lab, Boston, MA USA. RP Veves, A (reprint author), Joslin Beth Israel Deaconess Foot Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU H M P COMMUNICATIONS PI MALVERN PA 83 GENERAL WARREN BLVD, STE 100, MALVERN, PA 19355 USA SN 1044-7946 J9 WOUNDS JI Wounds-Compend. Clin. Res. Pract. PD JUL PY 2011 VL 23 IS 7 BP 183 EP 183 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 799TF UT WOS:000293308300002 ER PT J AU Tecilazich, F Kafanas, A Veves, A AF Tecilazich, Francesco Kafanas, Antonios Veves, Aristidis TI Cutaneous Alterations in Diabetes Mellitus SO WOUNDS-A COMPENDIUM OF CLINICAL RESEARCH AND PRACTICE LA English DT Review ID ACQUIRED PERFORATING DERMATOSIS; ULCERATED NECROBIOSIS LIPOIDICA; REFLEX-RELATED VASODILATION; DUPUYTRENS-DISEASE; GRANULOMA-ANNULARE; SKIN TAGS; ACANTHOSIS NIGRICANS; FOOT ULCERATION; MANIFESTATIONS; CONTRACTURE AB Dermatological problems occur with increased frequency in individuals with diabetes mellitus (DM). Cutaneous manifestations may be the first presenting sign of DM or even precede the diagnosis by many years. The main changes in the skin are due to alterations of microcirculation, the nervous system, and collagen. The most common skin problems in DM are acanthosis nigricans, necrobiosis lipoidica, diabetic dermopathy, scleredema, and granuloma anulare. The purpose of this review is to describe the molecular and anatomopathological alterations occurring at the skin during DM, and to illustrate the most important and common clinical skin manifestations in patients with DM. C1 [Tecilazich, Francesco; Veves, Aristidis] Harvard Univ, Sch Med, Microcirculat Lab, Boston, MA 02215 USA. [Tecilazich, Francesco; Veves, Aristidis] Joslin Beth Israel Deaconess Foot Ctr, Boston, MA 02215 USA. RP Veves, A (reprint author), Harvard Univ, Sch Med, Microcirculat Lab, 1 Deaconess Rd, Boston, MA 02215 USA. EM aveves@bidmc.harvard.edu NR 63 TC 0 Z9 0 U1 0 U2 2 PU H M P COMMUNICATIONS PI MALVERN PA 83 GENERAL WARREN BLVD, STE 100, MALVERN, PA 19355 USA SN 1044-7946 J9 WOUNDS JI Wounds-Compend. Clin. Res. Pract. PD JUL PY 2011 VL 23 IS 7 BP 192 EP 203 PG 12 WC Dermatology; Surgery SC Dermatology; Surgery GA 799TF UT WOS:000293308300005 PM 25879173 ER PT J AU Cotter, SE Dunn, GP Collins, KM Sahni, D Zukotynski, KA Hansen, JL O'Farrell, DA Ng, AK Devlin, PM Wang, LC AF Cotter, Shane E. Dunn, Gavin P. Collins, Kristina M. Sahni, Debjani Zukotynski, Katherine A. Hansen, Jorgen L. O'Farrell, Desmond A. Ng, Andrea K. Devlin, Phillip M. Wang, Linda C. TI Abscopal Effect in a Patient With Metastatic Merkel Cell Carcinoma Following Radiation Therapy: Potential Role of Induced Antitumor Immunity SO ARCHIVES OF DERMATOLOGY LA English DT Letter C1 [Sahni, Debjani; Wang, Linda C.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. [Cotter, Shane E.] Harvard Univ, Sch Med, Harvard Radiat Oncol Program, Boston, MA 02115 USA. [Collins, Kristina M.] Harvard Univ, Sch Med, Dermatol Program, Boston, MA 02115 USA. [Dunn, Gavin P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Zukotynski, Katherine A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Hansen, Jorgen L.; O'Farrell, Desmond A.; Ng, Andrea K.; Devlin, Phillip M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. RP Wang, LC (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Dermatol, 221 Longwood Ave, Boston, MA 02115 USA. EM lcwang@partners.org NR 5 TC 20 Z9 20 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD JUL PY 2011 VL 147 IS 7 BP 870 EP 872 PG 4 WC Dermatology SC Dermatology GA 793RL UT WOS:000292840700026 PM 21768497 ER PT J AU Donahue, TR Isacoff, WH Hines, OJ Tomlinson, JS Farrell, JJ Bhat, YM Garon, E Clerkin, B Reber, HA AF Donahue, Timothy R. Isacoff, William H. Hines, O. Joe Tomlinson, James S. Farrell, James J. Bhat, Yasser M. Garon, Edward Clerkin, Barbara Reber, Howard A. TI Downstaging Chemotherapy and Alteration in the Classic Computed Tomography/Magnetic Resonance Imaging Signs of Vascular Involvement in Patients With Pancreaticobiliary Malignant Tumors Influence on Patient Selection for Surgery SO ARCHIVES OF SURGERY LA English DT Article ID PHASE HELICAL CT; MULTIDETECTOR CT; CANCER; ADENOCARCINOMA; PANCREAS; SURVIVAL; PANCREATICODUODENECTOMY; CHOLANGIOCARCINOMA; UNRESECTABILITY; CHEMORADIATION AB Objectives: To determine whether computed tomography (CT)/magnetic resonance imaging (MRI) signs of vascular involvement are accurate after downstaging chemotherapy (DCTx) and to highlight factors associated with survival in patients who have undergone resection. Design: Retrospective cohort study; prospective database. Setting: University pancreatic disease center. Patients: Patients with unresectable pancreaticobiliary cancer who underwent curative intent surgery after completing DCTx. Interventions: Use of CT/MRI scan, pancreatic resection, and palliative bypass. Main Outcome Measures: Resectability after DCTx and disease-specific survival. Results: We operated on 41 patients (1992-2009) with locally advanced periampullary malignant tumors after a median of 8.5 months of DCTx. Before DCTx, most patients (38 [93%]) were unresectable because of evidence of vascular contact on CT/MRI scan or operative exploration. Criteria for exploration after DCTx were CT/MRI evidence of tumor shrinkage and/or change in signs of vascular involvement, cancer antigen 19-9 decrease, and good functional status. None had progressive disease. At operation, we resected tumors in 34 of 41 patients (83%), and 6 had persistent vascular involvement. Surprisingly, CT/MRI scan was only 71% sensitive and 58% specific to detect vascular involvement after DCTx. "Involvement" on imaging was often from tumor fibrosis rather than viable cancer. Radiographic decrease in tumor size also did not predict resectability (P=.10). Patients with tumors that were resected had a median 87% decrease in cancer antigen 19-9 (P=.04) during DCTx. The median follow-up (all survivors) was 31 months, and disease-specific survival was 52 months for patients with resected tumors. Conclusions: In patients with initially unresectable periampullary malignant tumors, original CT/MRI signs of vascular involvement may persist after successful DCTx. Patients should be chosen for surgery on the basis of lack of disease progression, good functional status, and decrease in cancer antigen 19-9. C1 [Donahue, Timothy R.; Hines, O. Joe; Clerkin, Barbara; Reber, Howard A.] Univ Calif Los Angeles, Dept Surg, David Geffen Sch Med, Div Gen Surg, Los Angeles, CA 90095 USA. [Isacoff, William H.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Tomlinson, James S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg Oncol, Los Angeles, CA 90095 USA. [Farrell, James J.; Bhat, Yasser M.] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Los Angeles, CA 90095 USA. [Garon, Edward] Univ Calif Los Angeles, David Geffen Sch Med, Div Hematol & Oncol, Dept Med, Los Angeles, CA 90095 USA. [Tomlinson, James S.; Farrell, James J.] Greater Los Angeles Vet Healthcare Syst, Los Angeles, CA USA. RP Donahue, TR (reprint author), Univ Calif Los Angeles, Dept Surg, David Geffen Sch Med, Div Gen Surg, 72-215 CHS,10833 LeConte Ave, Los Angeles, CA 90095 USA. EM tdonahue@mednet.ucla.edu NR 28 TC 27 Z9 27 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD JUL PY 2011 VL 146 IS 7 BP 836 EP 843 PG 8 WC Surgery SC Surgery GA 794EH UT WOS:000292877800015 PM 21768431 ER PT J AU Hsu, HC Yang, P Wu, Q Wang, JH Job, G Guentert, T Li, J Stockard, CR Le, TVL Chaplin, DD Grizzle, WE Mountz, JD AF Hsu, Hui-Chen Yang, PingAr Wu, Qi Wang, John H. Job, Godwin Guentert, Tanja Li, Jun Stockard, Cecil R. Le, Thuc-vy L. Chaplin, David D. Grizzle, William E. Mountz, John D. TI Inhibition of the Catalytic Function of Activation-Induced Cytidine Deaminase Promotes Apoptosis of Germinal Center B Cells in BXD2 Mice SO ARTHRITIS AND RHEUMATISM LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; CYCLIC CITRULLINATED PEPTIDE; CLASS SWITCH RECOMBINATION; RHEUMATOID-ARTHRITIS; SOMATIC HYPERMUTATION; PATHOGENIC AUTOANTIBODIES; AUTOIMMUNE-DISEASE; MEDIATED APOPTOSIS; EROSIVE ARTHRITIS; MRL/LPR MICE AB Objective. To determine whether functional suppression of the catalytic domain of activation-induced cytidine deaminase (AID) can suppress the hyperreactive germinal center (GC) responses in BXD2 mice. Methods. We generated transgenic BXD2 mice expressing a dominant-negative (DN) form of Aicda at the somatic hypermutation site (BXD2-Aicda-DN-transgenic mice). Real-time quantitative reverse transcriptase polymerase chain reaction was used to determine the expression of Aicda and DNA damage/repair genes. Enzyme-linked immunosorbent assay was used to measure serum levels of autoantibodies and immune complexes (ICs). Development of GCs and antibody-containing ICs as well as numbers of proliferative and apoptotic cells were determined using flow cytometry and/or immunohistochemical analyses. Development of arthritis and kidney disease was evaluated histologically in 6-8-month-old mice. Results. Suppression of the somatic hypermutation function of AID resulted in a significant decrease in autoantibody production without affecting the expression of DNA damage related genes in GC B cells of BXD2-Aicda-DN-transgenic mice. There was decreased proliferation, increased apoptosis, increased expression of caspase 9 messenger RNA in GC B cells, and lower numbers of GCs in the spleens of BXD2-Aicda-DN-transgenic mice. Decreased GC response was associated with lower levels of IgG-containing ICs. Anti-IgM- and anti-CD40 plus anti-Ig-induced B cell proliferative responses were decreased in BXD2-Aicda-DN-transgenic mice. Conclusion. Inhibition of the AID somatic hypermutation function in BXD2 mice suppressed development of spontaneous GCs, generation of autoantibody-producing B cells, and autoimmunity in BXD2 mice. Suppression of AID catalytic function to limit selection-based survival of GC B cells could become a novel therapy for the treatment of autoimmune disease. C1 [Mountz, John D.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Le, Thuc-vy L.] Emory Univ, Atlanta, GA 30322 USA. [Mountz, John D.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Mountz, JD (reprint author), Univ Alabama Birmingham, Dept Med, 1825 Univ Blvd,SHELB 307, Birmingham, AL 35294 USA. EM jdmountz@uab.edu OI Chaplin, David/0000-0002-1354-3069 FU Lupus Research Institute; Arthritis Foundation; American College of Rheumatology Research and Education Foundation; Alliance for Lupus Research; Department of Veterans Affairs [1I01BX000600-01]; Daiichi-Sankyo Co., Ltd; NIH [1-AI-071110-01A1, ARRA-3-R01-AI-71110-02S1] FX Supported by grants to Dr. Hsu from the Lupus Research Institute (Novel Research project grant) and the Arthritis Foundation (Arthritis Investigator Award) and by grants to Dr. Mountz from the American College of Rheumatology Research and Education Foundation (Within Our Reach research grant), the Alliance for Lupus Research (Target Identification in Lupus program grant), the Department of Veterans Affairs (Merit Review grant 1I01BX000600-01), Daiichi-Sankyo Co., Ltd, and the NIH (grants 1-AI-071110-01A1 and ARRA-3-R01-AI-71110-02S1). NR 50 TC 20 Z9 20 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD JUL PY 2011 VL 63 IS 7 BP 2038 EP 2048 DI 10.1002/art.30257 PG 11 WC Rheumatology SC Rheumatology GA 793GZ UT WOS:000292809700034 PM 21305519 ER PT J AU Au, K Singh, MK Bodukam, V Bae, S Maranian, P Ogawa, R Spiege, B McMahon, M Hahn, B Khanna, D AF Au, Karen Singh, Manjit K. Bodukam, Vijay Bae, Sangmee Maranian, Paul Ogawa, Rikke Spiege, Brennan McMahon, Maureen Hahn, Bevra Khanna, Dinesh TI Atherosclerosis in Systemic Sclerosis A Systematic Review and Meta-Analysis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID INTIMA-MEDIA THICKNESS; HIGH-DENSITY-LIPOPROTEIN; BRAIN MAGNETIC-RESONANCE; LUPUS-ERYTHEMATOSUS; RHEUMATOID-ARTHRITIS; MACROVASCULAR DISEASE; ENDOTHELIAL DYSFUNCTION; SUBCLINICAL ATHEROSCLEROSIS; CORONARY ATHEROSCLEROSIS; MYOCARDIAL-INFARCTION AB Objective. Systemic sclerosis (SSc) is characterized by calcification, vasculopathy, and endothelial wall damage, all of which can increase the risk of developing atherosclerosis and cardiovascular disease. The aim of this study was to perform a systematic review and meta-analysis to determine whether the risk of atherosclerosis is increased in SSc patients compared to healthy individuals. Methods. A systematic search was performed to identify studies published in PubMed and the Cochrane database up to May 2010, and recently published abstracts were also reviewed. Two reviewers independently screened articles to identify studies comparing the rate of atherosclerosis in SSc patients to that in healthy controls. The studies utilized one of the following methods: angiography, Doppler ultrasound to assess plaque and carotid intima-media thickness (IMT), computed tomography, magnetic resonance imaging, flow-mediated vasodilation (assessed as the FMD%), the ankle brachial index, or autopsy. For carotid IMT and FMD% values, we computed a pooled estimate of the summary mean difference and explored predictors of carotid IMT using random-effects meta-regression. Results. Of the 3,156 articles initially identified, 31 were selected for systematic review. The meta-analysis included 14 studies assessing carotid IMT and 7 assessing brachial artery FMD%. Compared to healthy controls, SSc patients had a higher prevalence of coronary atherosclerosis, peripheral vascular disease, and cerebrovascular calcification. Meta-analysis showed that SSc patients had increased carotid IMT (summary mean difference 0.11 mm, 95% confidence interval [95% CI] 0.05 mm, 0.17 mm; P = 0.0006) and lower FMD% (summary mean difference -3.07%, 95% CI -5.44%, -0.69%; P = 0.01) compared to controls. There was marked heterogeneity between the studies, which was mainly attributable to variations in disease duration and differences in the mean/median age between SSc patients and controls. Conclusion. Patients with SSc have an increased risk of atherosclerosis compared to healthy subjects. Further studies should elucidate the mechanism of this increased risk. C1 [Khanna, Dinesh] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Rheumatol, Los Angeles, CA 90095 USA. [Spiege, Brennan] VA Greater Los Angeles Healthcare Syst, CURE Digest Dis Res Ctr, Los Angeles, CA USA. RP Khanna, D (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Rheumatol, 1000 Vet Ave,Room 32-59 Rehabil Bldg, Los Angeles, CA 90095 USA. EM dkhanna@mednet.ucla.edu RI Ogawa, Rikke/I-2538-2013 OI Ogawa, Rikke/0000-0003-2681-8794 FU American College of Rheumatology Research and Education Foundation; Scleroderma Foundation; NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases) [K23-AR-053858-04] FX Dr. Au's work was supported by the American College of Rheumatology Research and Education Foundation (Physician Scientist Development Award) and the Scleroderma Foundation. Dr. Khanna's work was supported by the NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases grant K23-AR-053858-04). NR 67 TC 50 Z9 52 U1 0 U2 12 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD JUL PY 2011 VL 63 IS 7 BP 2078 EP 2090 DI 10.1002/art.30380 PG 13 WC Rheumatology SC Rheumatology GA 793GZ UT WOS:000292809700038 PM 21480189 ER PT J AU Agostinis, P Berg, K Cengel, KA Foster, TH Girotti, AW Gollnick, SO Hahn, SM Hamblin, MR Juzeniene, A Kessel, D Korbelik, M Moan, J Mroz, P Nowis, D Piette, J Wilson, BC Golab, J AF Agostinis, Patrizia Berg, Kristian Cengel, Keith A. Foster, Thomas H. Girotti, Albert W. Gollnick, Sandra O. Hahn, Stephen M. Hamblin, Michael R. Juzeniene, Asta Kessel, David Korbelik, Mladen Moan, Johan Mroz, Pawel Nowis, Dominika Piette, Jacques Wilson, Brian C. Golab, Jakub TI Photodynamic Therapy of Cancer: An Update SO CA-A CANCER JOURNAL FOR CLINICIANS LA English DT Article ID BASAL-CELL CARCINOMA; TOPICAL METHYL AMINOLEVULINATE; HIGH-GRADE DYSPLASIA; HEAT-SHOCK PROTEINS; MOUSE-TUMOR MODEL; PHASE-II TRIAL; FLUORESCENCE-GUIDED RESECTION; ENDOPLASMIC-RETICULUM STRESS; RANDOMIZED CONTROLLED-TRIAL; RECURRENT PROSTATE-CANCER AB Photodynamic therapy (PDT) is a clinically approved, minimally invasive therapeutic procedure that can exert a selective cytotoxic activity toward malignant cells. The procedure involves administration of a photosensitizing agent followed by irradiation at a wavelength corresponding to an absorbance band of the sensitizer. In the presence of oxygen, a series of events lead to direct tumor cell death, damage to the microvasculature, and induction of a local inflammatory reaction. Clinical studies revealed that PDT. can be curative, particularly in early stage tumors. It can prolong survival in patients with inoperable cancers and significantly improve quality of life. Minimal normal tissue toxicity, negligible systemic effects, greatly reduced long-term morbidity, lack of intrinsic or acquired resistance mechanisms, and excellent cosmetic as well as organ function-sparing effects of this treatment make it a valuable therapeutic option for combination treatments. With a number of recent technological improvements, PDT has the potential to become integrated into the mainstream of cancer treatment. CA Cancer Clin 2011;61:250-281. (C) 2011 American Cancer Society, Inc. C1 [Nowis, Dominika; Golab, Jakub] Med Univ Warsaw, Ctr Biostruct Res, Dept Immunol, PL-02097 Warsaw, Poland. [Golab, Jakub] Polish Acad Sci, Inst Phys Chem, Warsaw, Poland. [Agostinis, Patrizia] Catholic Univ Louvain, Dept Mol Cell Biol, Cell Death Res & Therapy Lab, B-3000 Louvain, Belgium. [Berg, Kristian; Juzeniene, Asta; Moan, Johan] Oslo Univ Hosp, Norwegian Radium Hosp, Inst Canc Res, Dept Radiat Biol, Oslo, Norway. [Cengel, Keith A.; Hahn, Stephen M.] Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA. [Foster, Thomas H.] Univ Rochester, Dept Imaging Sci, Rochester, NY USA. [Girotti, Albert W.] Med Coll Wisconsin, Dept Biochem, Milwaukee, WI 53226 USA. [Gollnick, Sandra O.] Roswell Pk Canc Inst, Dept Cell Stress Biol, Buffalo, NY 14263 USA. [Hamblin, Michael R.; Mroz, Pawel] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Hamblin, Michael R.; Mroz, Pawel] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Kessel, David] Wayne State Univ, Sch Med, Dept Pharmacol, Detroit, MI 48201 USA. [Korbelik, Mladen] British Columbia Canc Agcy, Integrat Oncol Dept, Vancouver, BC V5Z 4E6, Canada. [Moan, Johan] Univ Oslo, Inst Phys, Grp Plasma & Space Phys, Oslo, Norway. [Piette, Jacques] Univ Liege, Lab Virol & Immunol, Liege, Belgium. [Wilson, Brian C.] Univ Toronto, Ontario Canc Inst, Div Biophys & Imaging, Toronto, ON, Canada. RP Golab, J (reprint author), Med Univ Warsaw, Ctr Biostruct Res, Dept Immunol, 1A Banacha St,F Bldg, PL-02097 Warsaw, Poland. EM jakub.golab@wum.edu.pl RI Golab, Jakub/K-6974-2013; OI Golab, Jakub/0000-0002-2830-5100; , Asta/0000-0001-9426-0062; Nowis, Dominika/0000-0003-2748-9523; Hamblin, Michael/0000-0001-6431-4605 FU Fund for Scientific Research (FWO)-Flanders (Belgium) [G.0661.09, G.0728.10]; Belgian Federal Government [IAP6/18]; Catholic University of Leuven [OT/06/49, GOA/11/009]; National Institutes of Health (NIH) [CA-087971, CA72630, CA70823, HL85677, CA55791, CA98156, CA68409, CA122093, AI050875, CA083882, CA23378]; European Regional Development Fund [POIG.01.01.02-00-008/08]; Norwegian Cancer Society; Genzyme; Foundation for Polish Science; European Union FX Supported by the Fund for Scientific Research (FWO)-Flanders (Belgium) (grant numbers G.0661.09 and G.0728.10), the Interuniversity Attraction Pole IAP6/18 of the Belgian Federal Government, and the Catholic University of Leuven (OT/06/49 and GOA/11/009) (to P.A.); National Institutes of Health (NIH) grant CA-087971 (to K.A.C. and S.M.H.); NIH grants CA72630, CA70823, and HL85677 (to A.W.G.); NIH grants CA55791 and CA98156 (to S.O.G.); NIH grants CA68409 and CA122093 (to T.H.F.); NIH grants AI050875 and CA083882 (to M.R.H.); and the European Regional Development Fund through Innovative Economy grant POIG.01.01.02-00-008/08 (to J.G.). Dr. Kessel's research has been supported by NIH grants since 1980, predominantly by CA23378. Dr. Juzeniene' research has been supported by the Norwegian Cancer Society. Dr. Mroz was partly supported by a Genzyme-Partners Translational Research Grant. Dr. Golab is a recipient of the Mistrz Award from the Foundation for Polish Science and a member of the TEAM Programme cofinanced by the Foundation for Polish Science and the European Union European Regional Development Fund. NR 293 TC 919 Z9 953 U1 79 U2 425 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-9235 J9 CA-CANCER J CLIN JI CA-Cancer J. Clin. PD JUL-AUG PY 2011 VL 61 IS 4 BP 250 EP 281 DI 10.3322/caac.20114 PG 32 WC Oncology SC Oncology GA 792XK UT WOS:000292783500006 PM 21617154 ER PT J AU Hoft, DF Brusic, V Sakala, IG AF Hoft, Daniel F. Brusic, Vladimir Sakala, Isaac G. TI Optimizing vaccine development SO CELLULAR MICROBIOLOGY LA English DT Review ID T-CELL RESPONSES; MYCOBACTERIUM-TUBERCULOSIS; LEISHMANIA-MAJOR; INNATE IMMUNITY; CENTRAL MEMORY; EFFECTOR; MUCOSAL; DIFFERENTIATION; PROTECTION; CHALLENGE AB Optimizing the development of modern molecular vaccines requires a complex series of interdisciplinary efforts involving basic scientists, immunologists, molecular biologists, clinical vaccinologists, bioinformaticians and epidemiologists. This review summarizes some of the major issues that must be carefully considered. The intent of the authors is to briefly describe key components of the development process to give the reader an overview of the challenges faced from vaccine concept to vaccine delivery. Every vaccine requires unique features based on the biology of the pathogen, the nature of the disease and the target population for vaccination. This review presents general concepts relevant for the design and development of ideal vaccines protective against diverse pathogens. C1 [Hoft, Daniel F.; Sakala, Isaac G.] St Louis Univ, Sch Med, Div Infect Dis Allergy & Immunol, St Louis, MO 63103 USA. [Brusic, Vladimir] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. RP Hoft, DF (reprint author), St Louis Univ, Sch Med, Div Infect Dis Allergy & Immunol, St Louis, MO 63103 USA. EM hoftdf@slu.edu NR 53 TC 14 Z9 15 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1462-5814 J9 CELL MICROBIOL JI Cell Microbiol. PD JUL PY 2011 VL 13 IS 7 BP 934 EP 942 DI 10.1111/j.1462-5822.2011.01609.x PG 9 WC Cell Biology; Microbiology SC Cell Biology; Microbiology GA 793SX UT WOS:000292844500002 PM 21631691 ER PT J AU de Barsy, M Jamet, A Filopon, D Nicolas, C Laloux, G Rual, JF Muller, A Twizere, JC Nkengfac, B Vandenhaute, J Hill, DE Salcedo, SP Gorvel, JP Letesson, JJ De Bolle, X AF de Barsy, Marie Jamet, Alexandre Filopon, Didier Nicolas, Cecile Laloux, Geraldine Rual, Jean-Francois Muller, Alexandre Twizere, Jean-Claude Nkengfac, Bernard Vandenhaute, Jean Hill, David E. Salcedo, Suzana P. Gorvel, Jean-Pierre Letesson, Jean-Jacques De Bolle, Xavier TI Identification of a Brucella spp. secreted effector specifically interacting with human small GTPase Rab2 SO CELLULAR MICROBIOLOGY LA English DT Article ID PROTEIN INTERACTION NETWORK; GRAM-NEGATIVE BACTERIA; OPEN READING FRAMES; ORFEOME VERSION 1.1; ENDOPLASMIC-RETICULUM; LEGIONELLA-PNEUMOPHILA; RHO-GTPASES; MELITENSIS; SYSTEM; VIRB AB Bacteria of the Brucella genus are facultative intracellular class III pathogens. These bacteria are able to control the intracellular trafficking of their vacuole, presumably by the use of yet unknown translocated effectors. To identify such effectors, we used a high-throughput yeast two-hybrid screen to identify interactions between putative human phagosomal proteins and predicted Brucella spp. proteins. We identified a specific interaction between the human small GTPase Rab2 and a Brucella spp. protein named RicA. This interaction was confirmed by GST-pull-down with the GDP-bound form of Rab2. A TEM-beta-lactamase-RicA fusion was translocated from Brucella abortus to RAW264.7 macrophages during infection. This translocation was not detectable in a strain deleted for the virB operon, coding for the type IV secretion system. However, RicA secretion in a bacteriological culture was still observed in a DvirB mutant. In HeLa cells, a DricA mutant recruits less GTP-locked myc-Rab2 on its Brucella-containing vacuoles, compared with the wild-type strain. We observed altered kinetics of intracellular trafficking and faster proliferation of the B. abortus DricA mutant in HeLa cells, compared with the wild-type control. Altogether, the data reported here suggest RicA as the first reported effector with a proposed function for B. abortus. C1 [de Barsy, Marie; Jamet, Alexandre; Filopon, Didier; Nicolas, Cecile; Laloux, Geraldine; Nkengfac, Bernard; Vandenhaute, Jean; Letesson, Jean-Jacques; De Bolle, Xavier] Univ Namur FUNDP, URBM, Liege, Belgium. [Jamet, Alexandre] INRA, UMR Micalis, Micalis & AgroParisTech UMR1319, F-78350 Jouy En Josas, France. [Rual, Jean-Francois; Hill, David E.] Harvard Univ, Sch Med, Ctr Canc Syst Biol CCSB, Boston, MA 02115 USA. [Rual, Jean-Francois; Hill, David E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Rual, Jean-Francois; Hill, David E.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Muller, Alexandre; Salcedo, Suzana P.; Gorvel, Jean-Pierre] Aix Marseille Univ, Fac Sci Luminy, Ctr Immunol Marseille Luminy, F-13288 Marseille 9, France. [Muller, Alexandre; Salcedo, Suzana P.; Gorvel, Jean-Pierre] INSERM, U631, F-13288 Marseille, France. [Muller, Alexandre; Salcedo, Suzana P.; Gorvel, Jean-Pierre] CNRS, UMR6102, F-13288 Marseille, France. [Rual, Jean-Francois] Univ Liege, Gembloux ABT, Ctr Cellular & Mol Biol, B-4000 Liege, Belgium. [Twizere, Jean-Claude] Univ Liege, GIGA Res Ctr, B-4000 Liege, Belgium. RP De Bolle, X (reprint author), Univ Namur FUNDP, URBM, Liege, Belgium. RI Hill, David/B-6617-2011; salcedo, suzana/C-2853-2014; OI salcedo, suzana/0000-0001-5149-7756; Rual, Jean-Francois/0000-0003-4465-8819; LETESSON, Jean-Jacques/0000-0002-5838-0224; Gorvel, Jean-Pierre/0000-0002-2829-9804 FU Communaute Francaise de Belgique [04/09-325, 08/13-015]; Fonds pour la Recherche Scientifique-Fonds National pour la Recherche Scientifique (FRS-FNRS) [2.4521.04, 2.4541.08]; Ellison Foundation; Institute Sponsored Research from the DFCI Strategic Initiative; University of Namur; 'Fonds pour la formation a la Recherche dans l'Industrie et dans l'Agriculture' (FRIA); FRS-FNRS FX We thank Bruno Goud for his advices about GEF assays with GST-Rab2, Nicolas Lapaque for his advices, helpful discussion and help about immunofluorescence, Rose-Marie Genicot for her technical help, and Sophie Le Blastier for advices about culture supernatant concentration using pyrogallol red-molybdate-methanol. We also thank Stephane Meresse for providing the pCMV-HA-GW vector. The confocal microscope platforms MIMA2 (Microscopie et imagerie des Microorganismes, Animaux et and URBC (Unite de Recherche en Biologie Cellulaire, University of Namur) are acknowledged. Noelle Ninnane and Catherine Demazy are acknowledged for their technical help regarding confocal microscopy. Funding sources were Communaute Francaise de Belgique (Action de Recherches Concertees 04/09-325 and 08/13-015), the Fonds pour la Recherche Scientifique-Fonds National pour la Recherche Scientifique (FRS-FNRS, FRFC Grants 2.4521.04 and 2.4541.08), the Ellison Foundation (awarded to Marc Vidal), Institute Sponsored Research from the DFCI Strategic Initiative in support of CCSB, and the University of Namur (FUNDP). We also thank the 'Fonds pour la formation a la Recherche dans l'Industrie et dans l'Agriculture' (FRIA) and the FRS-FNRS for PhD thesis fellowships held by M. de Barsy and G. Laloux respectively. NR 61 TC 51 Z9 52 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1462-5814 EI 1462-5822 J9 CELL MICROBIOL JI Cell Microbiol. PD JUL PY 2011 VL 13 IS 7 BP 1044 EP 1058 DI 10.1111/j.1462-5822.2011.01601.x PG 15 WC Cell Biology; Microbiology SC Cell Biology; Microbiology GA 793SX UT WOS:000292844500010 PM 21501366 ER PT J AU Bostic, JQ Brunt, CC AF Bostic, Jeff Q. Brunt, Colby C. TI Cornered: An Approach to School Bullying and Cyberbullying, and Forensic Implications SO CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article DE Bullying; Cyberbullying; Prevention; Forensic implications ID PREVENTION PROGRAM; PARTICIPANT ROLES; NORTHERN FINLAND; STUDENTS; BEHAVIOR; PEER; AGGRESSION; TEACHERS; VIOLENCE; VICTIMS AB Bullying is an abuse of power and control that can cause significant harm to individuals. School systems have the difficult task of trying to police this behavior to maintain a safe learning environment for their students. Although there may be an identified bully, the ramifications of the behavior affect the system as a whole. Bullies, targeted victims, and bystanders play an integral role in ameliorating this problem. A change of culture within the school system is often the best, yet often the most difficult, intervention. In addition, cyberbullying has become a powerful avenue for bullying, resulting in significant morbidity within schools. C1 [Bostic, Jeff Q.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Brunt, Colby C.] Chandler & Miller, Stoneman, Boston, MA USA. RP Bostic, JQ (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM jbostic@partners.org NR 36 TC 5 Z9 5 U1 4 U2 24 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1056-4993 J9 CHILD ADOL PSYCH CL JI Child Adolesc. Psychiatr. N. Am. PD JUL PY 2011 VL 20 IS 3 BP 447 EP + DI 10.1016/j.chc.2011.03.004 PG 21 WC Psychiatry SC Psychiatry GA 793XX UT WOS:000292858300005 PM 21683912 ER PT J AU Nahrendorf, M AF Nahrendorf, Matthias TI Imaging of Infarct Healing Predicts Left Ventricular Remodeling and Evolution of Heart Failure Focus on Protease Activity SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Editorial Material DE Editorials; myocardial infarction; molecular imaging; healing; matrix metalloproteinase ID ACUTE MYOCARDIAL-INFARCTION; IN-VIVO; REPERFUSION INJURY; MATRIX; MICE; INFLAMMATION; EXPRESSION; ISCHEMIA; AGENT C1 [Nahrendorf, Matthias] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Nahrendorf, Matthias] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Nahrendorf, M (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM mnahrendorf@mgh.harvard.edu FU NHLBI NIH HHS [R01HL096576, R01HL095629, HHSN268201000044C, R01 HL095629-03, R01 HL095629, R01 HL096576, R01 HL096576-03]; PHS HHS [HHSN268201000044C] NR 18 TC 2 Z9 2 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-9651 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD JUL PY 2011 VL 4 IS 4 BP 351 EP 353 DI 10.1161/CIRCIMAGING.111.966671 PG 3 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 794BV UT WOS:000292871000003 PM 21772011 ER PT J AU Sahul, ZH Mukherjee, R Song, J McAteer, J Stroud, RE Dione, DP Staib, L Papademetris, X Dobrucki, LW Duncan, JS Spinale, FG Sinusas, AJ AF Sahul, Zakir H. Mukherjee, Rupak Song, James McAteer, Jarod Stroud, Robert E. Dione, Donald P. Staib, Lawrence Papademetris, Xenophon Dobrucki, Lawrence W. Duncan, James S. Spinale, Francis G. Sinusas, Albert J. TI Targeted Imaging of the Spatial and Temporal Variation of Matrix Metalloproteinase Activity in a Porcine Model of Postinfarct Remodeling Relationship to Myocardial Dysfunction SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Article DE matrix metalloproteinases; ventricular remodeling; imaging ID LEFT-VENTRICULAR ENLARGEMENT; CLINICAL-IMPLICATIONS; TISSUE INHIBITOR; HEART-FAILURE; INFARCT SIZE; MATRIX-METALLOPROTEINASE-9; ACTIVATION; RECEPTOR; MICE; RAT AB Background-Matrix metalloproteinases (MMPs) are known to modulate left ventricular (LV) remodeling after a myocardial infarction (MI). However, the temporal and spatial variation of MMP activation and their relationship to mechanical dysfunction after MI remain undefined. Methods and Results-MI was surgically induced in pigs (n=23) and cine magnetic resonance (MR) and dual-isotope hybrid single-photon emission CT (SPECT)/CT imaging obtained using thallium-201 and a technetium-99m-labeled MMP targeted tracer ((99m)Tc-RP805) at 1, 2, and 4 weeks post-MI along with controls (n=5). Regional myocardial strain was computed from MR images and related to MMP zymography and ex vivo myocardial (99m)Tc-RP805 retention. MMP activation as assessed by in vivo and ex vivo (99m)Tc-RP805 imaging and retention studies was increased nearly 4-fold within the infarct region at 1 week post-MI and remained elevated up to 1 month post-MI. The post-MI change in LV end-diastolic volumes was correlated with MMP activity (y=31.34e(0.48x), P=0.04). MMP activity was increased within the border and remote regions early post-MI, but declined over 1 month. There was a high concordance between regional (99m)Tc-RP805 uptake and ex vivo MMP-2 activity. Conclusions-A novel, multimodality, noninvasive hybrid SPECT/CT imaging approach was validated and applied for in vivo evaluation of MMP activation in combination with cine MR analysis of LV deformation. Increased (99m)Tc-RP805 retention was seen throughout the heart early post-MI and was not purely a reciprocal of thallium-201 perfusion. The (99m)Tc-RP805 SPECT/CT imaging may provide unique information regarding regional myocardial MMP activation and predict late post-MI LV remodeling. (Circ Cardiovasc Imaging. 2011;4:381-391.) C1 [Sahul, Zakir H.; Song, James; McAteer, Jarod; Dione, Donald P.; Dobrucki, Lawrence W.; Duncan, James S.; Sinusas, Albert J.] Yale Univ, Sch Med, Expt Nucl Cardiol Lab, New Haven, CT 06520 USA. [Staib, Lawrence; Papademetris, Xenophon; Sinusas, Albert J.] Yale Univ, Sch Med, Div Cardiovasc Med, Dept Internal Med, New Haven, CT 06520 USA. [Staib, Lawrence; Papademetris, Xenophon; Sinusas, Albert J.] Yale Univ, Sch Med, Dept Diagnost Radiol, New Haven, CT 06520 USA. [Mukherjee, Rupak; Stroud, Robert E.; Spinale, Francis G.] Med Univ S Carolina, Charleston, SC 29425 USA. [Mukherjee, Rupak; Stroud, Robert E.; Spinale, Francis G.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. RP Sinusas, AJ (reprint author), Yale Univ, Sch Med, Expt Nucl Cardiol Lab, 3FMP,POB 208017, New Haven, CT 06520 USA. EM albert.sinusas@yale.edu OI Staib, Lawrence/0000-0002-9516-5136 FU National Institutes of Health [HL078650, HL078825, HL057952, HL059165, HL095608]; Research Service of the Department of Veterans Affairs FX This work was supported by National Institutes of Health grants HL078650, HL078825, HL057952, HL059165, and HL095608 and the Research Service of the Department of Veterans Affairs. The 99mTc-RP805 used in this study was provided in kind by Lantheus Medical Imaging. NR 28 TC 38 Z9 38 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-9651 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD JUL PY 2011 VL 4 IS 4 BP 381 EP 391 DI 10.1161/CIRCIMAGING.110.961854 PG 11 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 794BV UT WOS:000292871000007 PM 21505092 ER PT J AU Freiberg, MS Chang, CCH Skanderson, M McGinnis, K Kuller, LH Kraemer, KL Rimland, D Goetz, MB Butt, AA Barradas, MCR Gibert, C Leaf, D Brown, ST Samet, J Kazis, L Bryant, K Justice, AC AF Freiberg, Matthew S. Chang, Chung-Chou H. Skanderson, Melissa McGinnis, Kathleen Kuller, Lewis H. Kraemer, Kevin L. Rimland, David Goetz, Matthew B. Butt, Adeel A. Barradas, Maria C. Rodriguez Gibert, Cynthia Leaf, David Brown, Sheldon T. Samet, Jeffrey Kazis, Lewis Bryant, Kendall Justice, Amy C. CA Vet Aging Cohort Study TI The Risk of Incident Coronary Heart Disease Among Veterans With and Without HIV and Hepatitis C SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE viruses; coronary disease; mortality; comorbidity ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACUTE MYOCARDIAL-INFARCTION; MICROBIAL TRANSLOCATION; CARDIOVASCULAR-DISEASE; INFECTED INDIVIDUALS; ARTERY-DISEASE; ASSOCIATION; SEROPOSITIVITY; ATHEROSCLEROSIS; PREVALENCE AB Background-Whether hepatitis C virus (HCV) confers additional coronary heart disease (CHD) risk among human immunodeficiency virus (HIV) infected individuals is unclear. Without appropriate adjustment for antiretroviral therapy, CD4 count, and HIV-1 RNA and substantially different mortality rates among those with and without HIV and HCV infection, the association between HIV, HCV, and CHD may be obscured. Methods and Results-We analyzed data on 8579 participants (28% HIV+, 9% HIV + HCV+) from the Veterans Aging Cohort Study Virtual Cohort who participated in the 1999 Large Health Study of Veteran Enrollees. We analyzed data collected on HIV and HCV status, risk factors for and the incidence of CHD, and mortality from January 2000 to July 2007. We compared models to assess CHD risk when death was treated as a censoring event and as a competing risk. During the median 7.3 years of follow-up, there were 194 CHD events and 1186 deaths. Compared with HIV - HCV - Veterans, HIV + HCV + Veterans had a significantly higher risk of CHD regardless of whether death was adjusted for as a censoring event (adjusted hazard ratio, 2.03; 95% confidence interval, 1.28 to 3.21) or a competing risk (adjusted HR, 2.45; 95% confidence interval, 1.83 to 3.27 respectively). Compared with HIV - HCV - Veterans, HIV + HCV + Veterans also had a significantly higher adjusted risk of CHD regardless of whether death was treated as a censored event (adjusted hazard ratio, 1.93; 95% confidence interval, 1.02 to 3.62) or a competing risk (adjusted hazard ratio, 1.46; 95% confidence interval, 1.03 to 2.07). Conclusions-HIV + HCV + Veterans have an increased risk of CHD compared with HIV + HCV - and HIV - HCV - Veterans. (Circ Cardiovasc Qual Outcomes. 2011;4:425-432.) C1 [Freiberg, Matthew S.; Chang, Chung-Chou H.; Butt, Adeel A.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15213 USA. [Freiberg, Matthew S.; Chang, Chung-Chou H.; Kuller, Lewis H.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. [Skanderson, Melissa; McGinnis, Kathleen; Justice, Amy C.] W Haven Vet Adm Med Ctr, VA Connecticut Hlth Care Syst, West Haven, CT USA. [Rimland, David] Emory Univ, Sch Med, Atlanta, GA USA. [Rimland, David] Atlanta Vet Adm Med Ctr, Atlanta, GA USA. [Goetz, Matthew B.; Leaf, David] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Goetz, Matthew B.; Leaf, David] VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90095 USA. [Butt, Adeel A.] VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. [Barradas, Maria C. Rodriguez] Baylor Coll Med, Houston, TX 77030 USA. [Barradas, Maria C. Rodriguez] Michael E DeBakey Vet Adm Med Ctr, Houston, TX USA. [Gibert, Cynthia] George Washington Univ, Sch Med, Washington, DC USA. [Gibert, Cynthia] Washington DC Vet Adm Med Ctr, Washington, DC USA. [Brown, Sheldon T.] James J Peters VA Bronx, New York, NY USA. [Brown, Sheldon T.] Mt Sinai Sch Med, New York, NY USA. [Samet, Jeffrey] Boston Univ, Sch Med, Boston, MA 02118 USA. [Kazis, Lewis] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Bryant, Kendall] NIAAA, Bethesda, MD USA. [Justice, Amy C.] Yale Univ, Sch Med, New Haven, CT USA. RP Freiberg, MS (reprint author), Univ Pittsburgh, Sch Med, 230 McKee Pl, Pittsburgh, PA 15213 USA. EM freibergms@upmc.edu OI Kazis, Lewis/0000-0003-1800-5849; Samet, Jeffrey/0000-0002-0897-3400; Goetz, Matthew/0000-0003-4542-992X FU National Institute on Alcohol Abuse and Alcoholism [2U10 AA 13566, K23 AA015914]; National Heart, Lung, and Blood Institute [1RO1HL095136-03] FX This study was supported by the National Institute on Alcohol Abuse and Alcoholism (2U10 AA 13566 and K23 AA015914) and the National Heart, Lung, and Blood Institute (1RO1HL095136-03). NR 33 TC 54 Z9 56 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD JUL PY 2011 VL 4 IS 4 BP 425 EP 432 DI 10.1161/CIRCOUTCOMES.110.957415 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 794CH UT WOS:000292872500009 PM 21712519 ER PT J AU Tricoci, P Newby, LK Hasselblad, V Kong, DF Giugliano, RP White, HD Theroux, P Stone, GW Moliterno, DJ Van de Werf, F Armstrong, PW Prabhakaran, D Rasoul, S Bolognese, L Durand, E Braunwald, E Califf, RM Harrington, RA AF Tricoci, Pierluigi Newby, L. Kristin Hasselblad, Vic Kong, David F. Giugliano, Robert P. White, Harvey D. Theroux, Pierre Stone, Gregg W. Moliterno, David J. Van de Werf, Frans Armstrong, Paul W. Prabhakaran, Dorairaj Rasoul, Saman Bolognese, Leonardo Durand, Eric Braunwald, Eugene Califf, Robert M. Harrington, Robert A. TI Upstream Use of Small-Molecule Glycoprotein IIb/IIIa Inhibitors in Patients With Non-ST-Segment Elevation Acute Coronary Syndromes A Systematic Overview of Randomized Clinical Trials SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE glycoprotein IIb/IIIa inhibitors; non-ST-segment elevation acute coronary syndromes; bleeding; meta-analysis ID TISSUE-LEVEL PERFUSION; MYOCARDIAL-INFARCTION; UNSTABLE ANGINA; ACC/AHA GUIDELINES; ROUTINE UPSTREAM; REDUCE MORTALITY; OUTCOMES; TIROFIBAN; RECEPTOR; RISK AB Background-The use of upstream small-molecule glycoprotein (GP) IIb/IIIa inhibitors in non-ST-segment elevation acute coronary syndromes (NSTE ACS) has been studied in multiple randomized clinical trials. We systematically reviewed the effect of upstream GP IIb/IIIa inhibitor use in NSTE ACS as reported in published clinical trials. Methods and Results-Randomized clinical trials of upstream small-molecule GP IIb/IIIa inhibitors in NSTE ACS were identified through a PubMed and EMBASE search and were included if they contained 30-day outcome data. Odds ratios were generated from the published data and pooled by means of random effects modeling. The primary outcome measures were 30-day death and 30-day death or myocardial infarction. Primary safety measures were major bleeding and transfusion during the index hospitalization. Twelve clinical trials were included, evaluating tirofiban, eptifibatide, and lamifiban. Of these, 7 evaluated upstream GP IIb/IIIa inhibitors versus placebo (n = 24 031) and 5 evaluated a strategy of upstream GP IIb/IIIa inhibitors versus upstream placebo with later provisional use at the time of percutaneous coronary intervention (n = 19 643). Overall, upstream GP IIb/IIIa inhibitor use was associated with an 11% reduction in 30-day death/myocardial infarction (odds ratio [OR], 0.89; 95% confidence interval [CI], 0.83 to 0.95) but no significant mortality effect (OR, 0.93; 95% CI, 0.83 to 1.05). The risk of major bleeding was 23% higher in patients treated with upstream GP IIb/IIIa inhibitors (OR, 1.23; 95% CI, 1.02 to 1.48). Results were similar when only trials comparing upstream GP IIb/IIIa inhibitors versus placebo were considered: 30-day death/myocardial infarction (OR, 0.88; 95% CI, 0.81 to 0.95); 30-day death (OR, 0.89; 95% CI, 0.76 to 1.03); and major bleeding (OR, 1.17; 95% CI, 0.88 to 1.54). Upstream versus selective use at percutaneous coronary intervention trended toward lower 30-day death/myocardial infarction (OR, 0.91; 95% CI, 0.82 to 1.01) but had no effect on mortality (OR, 1.00; 95% CI, 0.81 to 1.23) and increased major bleeding risk by 34% (OR, 1.34; 95% CI, 1.10 to 1.63). Conclusions-In NSTE ACS, treatment with upstream small-molecule GP IIb/IIIa inhibitors provides a significant but modest ischemic benefit when compared with initial placebo. Compared with delayed, selective use at percutaneous coronary intervention, early upstream use is associated with a trend toward fewer ischemic events. However, these modest benefits are associated with an increased risk of bleeding. (Circ Cardiovasc Qual Outcomes. 2011;4:448-458.) C1 [Tricoci, Pierluigi; Newby, L. Kristin; Hasselblad, Vic; Kong, David F.; Harrington, Robert A.] Duke Clin Res Inst, Durham, NC 27715 USA. [Giugliano, Robert P.; Braunwald, Eugene] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [White, Harvey D.] Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand. [Tricoci, Pierluigi] Univ Montreal, Inst Cardiol Montreal, Quebec City, PQ, Canada. [Stone, Gregg W.] Columbia Univ, Med Ctr, New York Presbyterian Hosp, New York, NY USA. [Moliterno, David J.] Univ Kentucky, Gill Heart Inst, Lexington, KY USA. [Van de Werf, Frans] Univ Hosp Gasthuisberg, B-3000 Leuven, Belgium. [Van de Werf, Frans] Leuven Coordinating Ctr, Leuven, Belgium. [Armstrong, Paul W.] Univ Alberta, Edmonton, AB, Canada. [Prabhakaran, Dorairaj] Safdarjung Dev Area, Ctr Chron Dis Control, New Delhi, India. [Rasoul, Saman] Isala Klin, Dept Cardiol, Zwolle, Netherlands. [Bolognese, Leonardo] San Donato Hosp, Div Cardiol, Arezzo, Italy. [Durand, Eric] Univ Paris 05, European Georges Pompidou Hosp, Dept Cardiol, AP HP, Paris, France. [Califf, Robert M.] Duke Translat Med Inst, Durham, NC USA. RP Tricoci, P (reprint author), Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA. EM pierluigi.tricoci@duke.edu OI Van de Werf, Frans/0000-0001-9479-7767; Prabhakaran, Dorairaj/0000-0002-3172-834X FU Schering-Plough; Merck & Co, Inc, Whitehouse Station, NJ; Merck & Co, Inc, Whitehouse Station, NJ, through the Duke Clinical Research Institute; Schering Plough; Merck & Co, Inc, through the Duke Clinical Research Institute; Schering-Plough, Inc; Merck Co, Inc.; Sanofi-Aventis; Eli Lilly; Medicines Company; NIH; Pfizer; Roche; Johnson Johnson; Merck, Sharpe Dohme; AstraZeneca; GlaxoSmithKline; Daiichi Sankyo Pharma Development; Bristol-Myers Squibb; Schering-Plough (now Merck); Boston Scientific; Abbott Vascular; Bristol-Myers Squibb Canada; Merck Frosst Canada Ltd; Abbott Laboratories; Bristol-Myers Squibb/Pfizer; Regado Biosciences; F. Hoffmann-La Roche Ltd; Boehringer Ingelheim (Canada) Ltd; Sanofi-Aventis Canada; Schering-Plough Research Institute; Scios Inc/Ortho-Biotech; Portola Pharmaceutical Inc; Uppsala Clinical Research Center; Merck Company Inc; Eli Lilly through the Duke Clinical Research Institute, Durham, NC; Merck; Unilever; Merck Co, Inc; Daiichi Sankyo FX The EARLY ACS trial was funded by Schering-Plough. The study was supported in part by a research grant from Merck & Co, Inc, Whitehouse Station, NJ, to the Duke Clinical Research Institute.; Dr Tricoci receives research grants from Merck & Co, Inc, Whitehouse Station, NJ, through the Duke Clinical Research Institute; he serves on an advisory board for Merck & Co. Dr Newby receives research grants from Schering Plough and Merck & Co, Inc, through the Duke Clinical Research Institute; she also receives consulting honoraria from Schering-Plough. A complete listing of Dr Newby's relationships with industry is available at www.dcri.duke.edu/research/coi.jsp. Dr Kong is a consultant for Allmed Healthcare Management; he is also a principal investigator for IBM. Dr Giugliano receives research grant support, advisory board, and honoraria for lectures from Schering-Plough, Inc, and Merck & Co, Inc. Dr White receives research grants from Sanofi-Aventis, Eli Lilly, The Medicines Company, NIH, Pfizer, Roche, Johnson & Johnson, Schering-Plough, Merck, Sharpe & Dohme, AstraZeneca, GlaxoSmithKline, Daiichi Sankyo Pharma Development, and Bristol-Myers Squibb; he is a consultant for Regado Biosciences. Dr Theroux receives research grants from Schering-Plough (now Merck); he is on the advisory board for Sanofi-Aventis, BMS, and AstraZeneca; he receives speakers fees from Schering-Plough, Sanofi-Aventis, and AstraZeneca. Dr Stone is on the advisory board for and receives research grants from Boston Scientific and Abbott Vascular; he receives a research grant from The Medicines Company and honoraria from BMS-Sanofi, Eli Lilly, AstraZeneca, GlaxoSmithKline, Merck, and Medtronic. Dr Moliterno receives research funding and consulting fees from Schering-Plough, now Merck (all consulting funds donated to not-for-profits). Dr Van de Werf receives research grants from Schering-Plough (now Merck) and Roche; he is on the advisory board and speakers bureaus for Schering-Plough, Merck, and Roche. Dr Armstrong performs consulting or other services that generate personal income for Sanofi-Aventis, Bristol-Myers Squibb Canada, Merck Frosst Canada Ltd, Abbott Laboratories, GlaxoSmithKline, Bristol-Myers Squibb/Pfizer, Regado Biosciences, and F. Hoffmann-La Roche Ltd; he receives a research grant or contract from Boehringer Ingelheim (Canada) Ltd, Sanofi-Aventis Canada, Eli Lilly, Schering-Plough Research Institute, Scios Inc/Ortho-Biotech, GlaxoSmithKline, Portola Pharmaceutical Inc, Uppsala Clinical Research Center and AstraZeneca, and Merck & Company Inc, that partially supports his university salary and/or research projects. Dr Prabhakaran receives research grants from Eli Lilly through the Duke Clinical Research Institute, Durham, NC, and from Merck and Unilever. Dr Durand receives honoraria from Schering-Plough and The Medicines Company. Dr Braunwald is chairman of the TIMI Study Group at the Brigham and Women's Hospital, which receives (or has received within the past 24 months) grant support for the TIMI Study Group from the following pharmaceutical companies (all >$10 000): Eli Lilly, Merck & Co, Inc, Schering-Plough Research Institute, and Daiichi Sankyo. He has also participated occasionally (maximum 2 to 3 per year) in symposia/advisory board meetings/consultancies for the following companies for which he receives an honorarium (always >$10 000) and reimbursement of travel-related expenses: Daiichi Sankyo, Eli Lilly, Merck & Co, Inc, and Schering-Plough. Dr Califf receives research funding and consulting fees from Schering-Plough, now Merck. A complete listing of Dr Califf's relationships with industry is available at http://www.dcri.duke.edu/research/coi.jsp.; Dr Harrington receives research funding and consulting fees from Schering-Plough, now Mrck. A complete listing of Dr Harrington's relationships with industry is available at http://www.dcri.duke.edu/research/coi.jsp. NR 41 TC 18 Z9 20 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD JUL PY 2011 VL 4 IS 4 BP 448 EP 458 DI 10.1161/CIRCOUTCOMES.110.960294 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 794CH UT WOS:000292872500012 PM 21712522 ER PT J AU Haug, U Knudsen, AB Brenner, H Kuntz, KM AF Haug, Ulrike Knudsen, Amy B. Brenner, Hermann Kuntz, Karen M. TI Is fecal occult blood testing more sensitive for left- versus right-sided colorectal neoplasia? A systematic literature review SO EXPERT REVIEW OF MOLECULAR DIAGNOSTICS LA English DT Review DE colorectal cancer; colorectal neoplasia; fecal occult blood testing; screening ID DIGITAL RECTAL EXAMINATION; SERVICES TASK-FORCE; AVERAGE RISK; LARGE BOWEL; MISS RATE; CANCER; COLONOSCOPY; POPULATION; ACCURACY; POLYPS AB Owing to its slow development from removable precursor lesions and early cancer stages with good prognosis, screening for colorectal cancer holds potential to reduce both the incidence and mortality of the disease. While sigmoidoscopy only detects left-sided neoplasia, there is accumulating evidence that colonoscopy is also more effective in protecting from neoplasia in the left versus the right colon and rectum. In this context, it is an important question whether the sensitivity of the most common noninvasive screening tool for colorectal cancer, fecal occult blood testing (FOBT), also differs for left-versus right-sided neoplasia. Therefore, we systematically searched the literature for prospective screening studies conducted in average-risk adults that performed FOBT (immunochemical and/or guaiac-based) and colonoscopy among all participants, and reported site-specific sensitivities of FOBT for advanced colorectal neoplasia. Most of the seven included studies showed a higher sensitivity of FOBT for advanced neoplasia in the left versus right colon, but this finding needs to be confirmed since the available literature is scarce and not entirely consistent. C1 [Haug, Ulrike] German Canc Res Ctr, Natl Ctr Tumor Dis, Div Prevent Oncol, D-69120 Heidelberg, Germany. [Knudsen, Amy B.] Massachusetts Gen Hosp, Inst Technol Assessment, Dept Radiol, Boston, MA 02114 USA. [Brenner, Hermann] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, D-69120 Heidelberg, Germany. [Kuntz, Karen M.] Univ Minnesota, Div Hlth Policy & Management, Minneapolis, MN 55455 USA. RP Haug, U (reprint author), German Canc Res Ctr, Natl Ctr Tumor Dis, Div Prevent Oncol, Neuenheimer Feld 460, D-69120 Heidelberg, Germany. EM u.haug@dkfz.de RI Brenner, Hermann/B-4627-2017; OI Brenner, Hermann/0000-0002-6129-1572; Haug, Ulrike/0000-0002-1886-2923 FU German Cancer Aid (Deutsche Krebshilfe) [109421] FX The study was, in part, supported by a grant from the German Cancer Aid (Deutsche Krebshilfe; project number: 109421). The grant giver had no influence on conducting the review, on the interpretation of the results or on the decision to submit the manuscript for publication. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 36 TC 18 Z9 18 U1 0 U2 3 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7159 J9 EXPERT REV MOL DIAGN JI Expert Rev. Mol. Diagn. PD JUL PY 2011 VL 11 IS 6 BP 605 EP 616 DI 10.1586/ERM.11.41 PG 12 WC Pathology SC Pathology GA 794PH UT WOS:000292912200011 PM 21745014 ER PT J AU Kim, JY Jo, MW Brauner, SC Ferrufino-Ponce, Z Ali, R Cremers, SL Henderson, BA AF Kim, J. Y. Jo, M-W Brauner, S. C. Ferrufino-Ponce, Z. Ali, R. Cremers, S. L. Henderson, B. An TI Increased intraocular pressure on the first postoperative day following resident-performed cataract surgery SO EYE LA English DT Article DE intraocular pressure; postoperative day 1; cataract surgery; resident-performed cataract surgery ID OPEN-ANGLE GLAUCOMA; CENTRAL CORNEAL THICKNESS; LENS IMPLANTATION; RISK-FACTORS; NONGLAUCOMATOUS EYES; UNCOMPLICATED PHACOEMULSIFICATION; ANTERIOR-CHAMBER; OUTCOMES; EXTRACTION; COMPLICATIONS AB Purpose The aim of this study was to investigate the incidence of intraocular pressure (IOP) elevation after resident-performed cataract surgery and to determine variables, which influence postoperative day 1 (POD1) IOP. Methods In all, 1111 consecutive cataract surgeries performed only by training residents between 1 July 2001 and 30 June 2006 were included. Elevated IOP was defined as >= 23 mm Hg. Surgeries were classified according to the presence of POD1-IOP elevation. Fisher's exact test and Student t-test were used to compare both groups. Multivariate analyses using generalized estimating equations were performed to investigate predictor variables associated with POD1-IOP elevation. Results The average preoperative IOP was 16.0 +/- 3.2mmHg and the average POD1-IOP was 19.3 +/- 7.1 mm Hg, reflecting a significant increase in IOP (P<0.001, paired t-test). The incidence of POD1-IOP elevation >= 23 mm Hg was 22.0% (244/1111). Presence of glaucoma and ocular hypertension, higher preoperative IOP, and longer axial length were frequently encountered variables in the POD1-IOP elevation group (all P<0.05). Using a multivariate analysis, presence of glaucoma (P = 0.004, OR = 2.38; 95% confidence interval (95% CI) = 1.31-4.30), presence of ocular hypertension (P = 0.003, OR = 6.09; 95% CI = 1.81-20.47), higher preoperative IOP (P<0.001, OR = 3.73; 95% CI = 1.92-7.25), and longer axial length (P = 0.01, OR = 1.15; 95% CI = 1.03-1.29) were significant predictive factors for POD1-IOP elevation. Conclusions IOP elevation on the first postoperative day following resident-performed cataract surgery occurred frequently (22.0%). Increased early postoperative IOP was associated with presence of glaucoma and ocular hypertension, higher preoperative IOP, and longer axial length. Eye (2011) 25, 929-936; doi: 10.1038/eye.2011.93; published online 29 April 2011 C1 [Kim, J. Y.] Univ Ulsan, Asan Med Ctr, Coll Med, Dept Ophthalmol, Seoul 138736, South Korea. [Kim, J. Y.] Univ Ulsan, Asan Med Ctr, Coll Med, Res Inst Biomacromol, Seoul 138736, South Korea. [Kim, J. Y.; Brauner, S. C.; Cremers, S. L.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. [Jo, M-W] Univ Ulsan, Coll Med, Dept Prevent Med, Seoul 138736, South Korea. [Ferrufino-Ponce, Z.] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. [Ali, R.] Univ Texas Med Branch, Dept Ophthalmol & Visual Sci, Galveston, TX USA. RP Kim, JY (reprint author), Univ Ulsan, Asan Med Ctr, Coll Med, Dept Ophthalmol, 388-1 Pungnab 2Dong, Seoul 138736, South Korea. EM jykim2311@amc.seoul.kr NR 49 TC 14 Z9 15 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-222X J9 EYE JI Eye PD JUL PY 2011 VL 25 IS 7 BP 928 EP 935 DI 10.1038/eye.2011.93 PG 8 WC Ophthalmology SC Ophthalmology GA 793ZH UT WOS:000292862500015 PM 21527959 ER PT J AU Patil, VK St Andre, JR Crisan, E Smith, BM Evans, CT Steiner, ML Pape, TL AF Patil, Vijaya K. St Andre, Justin R. Crisan, Elena Smith, Bridget M. Evans, Charlesnika T. Steiner, Monica L. Pape, Theresa L. TI Prevalence and Treatment of Headaches in Veterans With Mild Traumatic Brain Injury SO HEADACHE LA English DT Article DE headache; brain injury; veteran; blast injury ID PERSISTENT POSTCONCUSSIVE SYMPTOMS; POSTTRAUMATIC-STRESS-DISORDER; POLYTRAUMA CLINICAL TRIAD; US SOLDIERS; CHRONIC PAIN; HEAD-INJURY; IRAQ; EPIDEMIOLOGY; AFGHANISTAN; WAR AB Objectives.-To report the prevalence and characteristics of headaches in veterans with mild traumatic brain injury (TBI) and to describe most common treatment strategies after neurological evaluation. Methods.-We conducted a retrospective cohort study. The setting was a United States Veterans Healthcare Administration Polytrauma Network Site. The study participants consisted of 246 veterans with confirmed diagnosis of mild TBI. The main outcome measures were: Self-reported head pain occurring 30 days prior to initial mild TBI screening; headache severity measured by the Neurobehavioral Symptom Inventory; headache characteristics; and treatment prescribed by neurologists. Results.-The majority (74%) of veterans with a confirmed diagnosis of mild TBI (N = 246), due largely to blast exposure, reported headaches in the 30 days preceding the initial mild TBI evaluation. Thirty-three percent of these veterans (N = 81) were referred to neurology for persistent headaches. Of the 56 veterans attending the neurology evaluation, 45% were diagnosed with migraine headaches and 20% with chronic daily headaches. The most commonly used abortive agents were triptans (68%) and the most common preventive medications were anticonvulsants (55%) and tricyclics (40%). Conclusion.-There was an increased prevalence of headaches in veterans with mild TBI. Most of the TBI veterans in our study group were exposed to blast injury and findings indicate that the nature of head trauma may be contributing to headaches. Findings highlight the need for developing effective headache prevention and treatment strategies for all persons with mild TBI and in particular for veterans with blast-related mild TBI. C1 [St Andre, Justin R.; Smith, Bridget M.; Evans, Charlesnika T.; Pape, Theresa L.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Spinal Cord Injury Qual Enhancement Res Initiat, Ctr Management Complex Chron Care, Hines, IL 60141 USA. [Patil, Vijaya K.; Crisan, Elena] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Dept Neurol, Hines, IL 60141 USA. [Steiner, Monica L.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Dept Phys Med & Rehabil, Hines, IL 60141 USA. [Patil, Vijaya K.; Crisan, Elena; Smith, Bridget M.; Steiner, Monica L.] Loyola Univ, Med Ctr, Maywood, IL 60153 USA. [Evans, Charlesnika T.] Northwestern Univ, Inst Healthcare Studies, Feinberg Sch Med, Chicago, IL 60611 USA. [Pape, Theresa L.] Northwestern Univ, Dept Phys Med & Rehabil, Feinberg Sch Med, Chicago, IL 60611 USA. RP Patil, VK (reprint author), Edward Hines Jr VA Hosp, Dept Neurol, Bldg 228,5th Floor,5000A,M-C 127,POB 5000, Hines, IL 60141 USA. EM vijaya.patil2@va.gov OI Pape, Theresa/0000-0001-7738-5963 FU Department of Veterans Affairs; Office of Research and Development, Health Services Research and Development Service [IIR 07-188-3]; Locally-Initiated [42-533]; Edward Hines Jr. VA Hospital, Center for Management of Complex Chronic Care (CMC3) FX This study was supported by the Department of Veterans Affairs, Office of Research and Development, Health Services Research and Development Service as grant IIR 07-188-3, Locally-Initiated Project 42-533 and the Edward Hines Jr. VA Hospital, Center for Management of Complex Chronic Care (CMC3). The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government. NR 35 TC 15 Z9 15 U1 1 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0017-8748 J9 HEADACHE JI Headache PD JUL-AUG PY 2011 VL 51 IS 7 BP 1112 EP 1121 DI 10.1111/j.1526-4610.2011.01946.x PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 793ZD UT WOS:000292862100006 PM 21762135 ER PT J AU Linares, LA Thornton, DJ Strymish, J Baker, E Gupta, K AF Linares, Leslie A. Thornton, David J. Strymish, Judith Baker, Errol Gupta, Kalpana TI Electronic Memorandum Decreases Unnecessary Antimicrobial Use for Asymptomatic Bacteriuria and Culture-Negative Pyuria SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID URINARY-TRACT-INFECTION; CLINICAL-PRACTICE GUIDELINES; TERM-CARE FACILITY; DISEASES-SOCIETY; EDUCATIONAL INTERVENTION; INAPPROPRIATE TREATMENT; HOSPITALIZED-PATIENTS; ORDER ENTRY; AMERICA; ADULTS AB OBJECTIVES. Asymptomatic bacteriuria/candidiuria (ASB) and culture-negative pyuria (CNP) are common and often result in inappropriate antibiotic use. We aimed to evaluate whether a standardized educational memorandum could reduce antimicrobial utilization for ASB/CNP. DESIGN, SETTING, AND PATIENTS. Quasi-experimental study with a control group, from a convenience sample of inpatients with abnormal urinalysis or urine culture results in a Veterans Affairs hospital. intervention. An educational memorandum outlining guidelines for diagnosis and treatment of ASB was placed in the chart of patients with ASB/CNP who were receiving antimicrobials. METHODS. The records of patients meeting inclusion criteria were abstracted for demographics, comorbidities, antimicrobials, and symptoms suggestive of possible urinary tract infection (UTI). Patients were categorized as having ASB, CNP, or UTI. The number of antimicrobial-days attributed to ASB/CNP was compared between the control group and the intervention group. RESULTS. Charts of 301 patients with abnormal urine results were reviewed. Thirty of 117 (26%) patients in the control group received antimicrobials for ASB/CNP for an average of 6.3 days. In the intervention group, 24 of 92 (26%) patients received antimicrobials for ASB/CNP for an average of 2.2 days (t-test:). P < .001 Adverse events from antimicrobials for ASB/CNP occurred in 3 of the 30 (10%) patients in the control group. There were no adverse events from untreated ASB/CNP in the intervention group. CONCLUSIONS. ASB and CNP resulted in antimicrobial exposure in more than one-quarter of our study patients. Placing a standardized memorandum in the electronic record was associated with a 65% relative reduction in antimicrobial-days for ASB and CNP. Infect Control Hosp Epidemiol 2011;32(7):644-648 C1 [Linares, Leslie A.; Thornton, David J.; Baker, Errol; Gupta, Kalpana] Vet Affairs Boston Hlth Care Syst, Boston, MA USA. [Linares, Leslie A.; Thornton, David J.; Strymish, Judith; Gupta, Kalpana] Boston Univ, Sch Med, Boston, MA 02118 USA. [Strymish, Judith] Harvard Univ, Sch Med, Boston, MA USA. RP Gupta, K (reprint author), VA Boston HCS, 1400 VFW Pkwy,111 Med, W Roxbury, MA 02132 USA. EM kalpana.gupta@va.gov NR 22 TC 17 Z9 17 U1 1 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD JUL PY 2011 VL 32 IS 7 BP 644 EP 648 DI 10.1086/660764 PG 5 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 795LR UT WOS:000292976200002 PM 21666393 ER PT J AU Kim, JH Toy, D Muder, RR AF Kim, Jong Hun Toy, Diana Muder, Robert R. TI Clostridium difficile Infection in a Long-Term Care Facility: Hospital-Associated Illness Compared with Long-Term Care-Associated Illness SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID DIARRHEA; EPIDEMIOLOGY; DISEASE; SURVEILLANCE; DIAGNOSIS; COLITIS; TIME AB BACKGROUND. Controversy exists over whether Clostridium difficile infection (CDI) commonly occurs in long-term care facility residents who have not been recently transferred from an acute care hospital. objective. To assess the incidence and outcome of CDI in a long-term care facility. METHODS. Retrospective cohort study in a 262-bed long-term care Veterans Affairs facility in Pittsburgh, Pennsylvania, for the period January 2004 through June 2010. CDI was identified by positive stool C. difficile toxin assay and acute diarrhea. Patients were categorized as hospital-associated CDI (HACDI) or long-term care facility-associated CDI (LACDI) and followed for 6 months. RESULTS. The annual rate of CDI varied between 0.11 and 0.23 per 1,000 resident-days for HACDI patients and between 0.04 and 0.28 per 1,000 resident-days for LACDI patients. We identified 162 patients, 96 patients (59.3%) with HACDI and 66 patients (40.7%) with LACDI. Median age was 74 and 77 years, respectively, for HACDI and LACDI (P = .055) patients. There were more patients with at least 1 relapse of CDI during 6 months of follow up in LACDI patients (32/66, 48.5%) than in HACDI patients (28/96, 29.2%; P = .009). Logistic regression showed that ages of at least 75 years (odds ratio [OR], 2.33; 95% confidence interval [CI], 1.07-5.07; P = .033), more than 2 transfers to an acute care hospital (OR, 7.88; 95% CI, 1.88-32.95; P = .005), and LACDI (OR, 3.15; 95% CI, 1.41-7.05; P = .005) were associated with relapse of CDI. CONCLUSIONS. Forty percent of CDI cases were acquired within the long-term care facility, indicating a substantial degree of transmission. Optimal strategies to prevent CDI in the long-term care facility are needed. Infect Control Hosp Epidemiol 2011;32(7):656-660 C1 [Toy, Diana; Muder, Robert R.] VA Pittsburgh Healthcare Syst, Infect Dis Sect, VA Med Ctr, Pittsburgh, PA 15240 USA. [Kim, Jong Hun; Muder, Robert R.] Univ Pittsburgh, Med Ctr, Div Infect Dis, Pittsburgh, PA USA. RP Muder, RR (reprint author), VA Pittsburgh Healthcare Syst, Infect Dis Sect, VA Med Ctr, Univ Dr C, Pittsburgh, PA 15240 USA. EM robert.muder@va.gov FU Department of Veterans Affairs FX This work was supported by the Department of Veterans Affairs. NR 19 TC 23 Z9 23 U1 1 U2 9 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD JUL PY 2011 VL 32 IS 7 BP 656 EP 660 DI 10.1086/660767 PG 5 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 795LR UT WOS:000292976200004 PM 21666395 ER PT J AU Heist, EK Barrett, C Perna, F Danik, S Ruskin, JN Mansour, M AF Heist, E. Kevin Barrett, Conor Perna, Francesco Danik, Stephan Ruskin, Jeremy N. Mansour, Moussa TI Direct Visualization of Epicardial Structures and Ablation Utilizing a Visually Guided Laser Balloon Catheter: Preliminary Findings SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE catheter ablation; epicardium; laser ablation; pericardium; ventricular myocardium ID PULMONARY VEIN ISOLATION; VENTRICULAR-TACHYCARDIA AB Epicardial Laser Balloon Ablation. Background: Intrapericardial mapping and ablation can be utilized to target epicardial arrhythmic circuits. Current epicardial ablation strategies are associated with risk of damage to adjacent structures, including the coronary vasculature and phrenic nerves. Objectives: The purpose of this study was to evaluate the feasibility of an investigational, visually guided laser balloon catheter for manipulation within the pericardial space, visualization of epicardial structures, and delivery of laser ablation lesions to the ventricular myocardium. Methods: Pericardial access was obtained in 4 anesthetized swine by subxyphoid puncture. The laser balloon catheter was introduced into the pericardial space via a deflectable sheath, and was manipulated to predefined regions in all animals. Visually guided laser ablation was performed on the ventricular myocardium, with post mortem examination of lesion size and depth. Results: The laser ablation catheter could be manipulated to all targeted regions in all animals. Associated structures, including epicardial coronary arteries and veins as well as an endocardial catheter in the left atrial appendage, were easily visualized. A total of 9 laser energy applications at varying power/time settings were performed. Ablation utilizing moderate (7-8.5W) power produced relatively uniform lesions (diameter 5-12 mm, depth 6-9 mm), while high (14W) power produced a visible "steam pop" with a large, hemorrhagic lesion (22x11x11 mm). Conclusions: The investigational laser balloon catheter can be manipulated within the epicardial space, allowing for direct visualization of surrounding structures during ablation. Titration of laser power can be utilized to create moderate-sized ablation lesions while avoiding steam pops. (J Cardiovasc Electrophysiol, Vol. 22, pp. 808-812, July 2011) C1 [Heist, E. Kevin; Barrett, Conor; Perna, Francesco; Danik, Stephan; Ruskin, Jeremy N.; Mansour, Moussa] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, Boston, MA USA. RP Mansour, M (reprint author), Massachusetts Gen Hosp Gray 109, Cardiac Arrhythmia Serv, 55 Fruit St, Boston, MA 02114 USA. EM mmansour@partners.org OI Perna, Francesco/0000-0002-9019-9492 FU M.G.H. Deane Institute for Integrative Research in Atrial Fibrillation and Stroke; St. Jude Medical; Boston Scientific; Medtronic; Biosense-Webster FX This work was supported in part by the M.G.H. Deane Institute for Integrative Research in Atrial Fibrillation and Stroke.; Conflict of Interest/Financial Disclosures reported: E. K. Heist: St. Jude Medical (consultant, honoraria, research grants), Boston Scientific (consultant, honoraria, research grants); C. Barrett: St. Jude Medical (research grants); J.N. Ruskin: Biosense Webster (consultant, fellowship support), Boston Scientific (fellowship support), CardioFocus (clinical oversight committee-no compensation), CardioInsight (scientific advisory board), CryoCath (scientific steering committee-no compensation), Medtronic (consultant, fellowship support), St. Jude Medical (fellowship support); M. Mansour: Cardiofocus (research grants), St. Jude Medical (research grants), Biosense-Webster (research grants). Other authors: No disclosures. NR 14 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD JUL PY 2011 VL 22 IS 7 BP 808 EP 812 DI 10.1111/j.1540-8167.2010.02004.x PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 795LH UT WOS:000292975200014 PM 21288277 ER PT J AU Imel, ZE Baldwin, S Atkins, DC Owen, J Baardseth, T Wampold, BE AF Imel, Zac E. Baldwin, Scott Atkins, David C. Owen, Jesse Baardseth, Tim Wampold, Bruce E. TI Racial/Ethnic Disparities in Therapist Effectiveness: A Conceptualization and Initial Study of Cultural Competence SO JOURNAL OF COUNSELING PSYCHOLOGY LA English DT Article DE cultural competence; health disparities; multilevel modeling; therapist effects ID MULTICULTURAL COUNSELING COMPETENCES; YOUTH TREATMENT CYT; HEALTH-CARE; MODEL; INTERVENTIONS; PROVIDER; OUTCOMES; CLIENTS; DESIGN AB As a result of mental health disparities between White and racial/ethnic minority clients, researchers have argued that some therapists may be generally competent to provide effective services but lack cultural competence. This distinction assumes that client racial/ethnic background is a source of variability in therapist effectiveness. However, there have been no direct tests of the therapist as a source of health disparities. We provided an initial test of the distinction between general and cultural competence by examining client racial/ethnic background as a source of variability in therapist effectiveness. We analyzed cannabis use outcomes from a psychotherapy trial (N = 582) for adolescent cannabis abuse and dependence using Bayesian multilevel models for count outcomes. We first tested whether therapists differed in their effectiveness and then tested whether disparities in treatment outcomes varied across therapist caseloads. Results suggested that therapists differed in their effectiveness in general and that effectiveness varied according to client racial/ethnic background. Therapist effectiveness may depend partially on client racial/ethnic minority background, providing evidence that it is valid to distinguish between general and cultural competence. C1 [Imel, Zac E.; Baardseth, Tim; Wampold, Bruce E.] Univ Wisconsin, Dept Counseling Psychol, Madison, WI 53706 USA. [Baldwin, Scott] Brigham Young Univ, Dept Psychol, Provo, UT 84602 USA. [Atkins, David C.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Owen, Jesse] Univ Louisville, Dept Counseling Psychol, Louisville, KY 40292 USA. RP Imel, ZE (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, S-116 MHC,1660 S Columbian Way, Seattle, WA 98116 USA. EM zeimel@u.washington.edu OI imel, zachary/0000-0001-9645-7184; Atkins, David/0000-0002-5781-9880 NR 43 TC 21 Z9 21 U1 2 U2 13 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-0167 J9 J COUNS PSYCHOL JI J. Couns. Psychol. PD JUL PY 2011 VL 58 IS 3 BP 290 EP 298 DI 10.1037/a0023284 PG 9 WC Psychology, Educational; Psychology, Applied SC Psychology GA 792SC UT WOS:000292768500002 PM 21534654 ER PT J AU Zafar, SN Iqbal, A Farez, MF Kamatkar, S de Moya, MA AF Zafar, Syed Nabeel Iqbal, Aftab Farez, Mauricio F. Kamatkar, Suyog de Moya, Marc A. TI Intensive Insulin Therapy in Brain Injury: A Meta-Analysis SO JOURNAL OF NEUROTRAUMA LA English DT Review DE brain injury; critical care; insulin; nervous system trauma; stroke; traumatic brain injury ID CRITICALLY-ILL PATIENTS; BLOOD-GLUCOSE CONTROL; UNITED-STATES; ISCHEMIC-STROKE; CARE PATIENTS; HYPERGLYCEMIA; BENEFITS; MANAGEMENT; ADULTS; RISKS AB Many studies have addressed the question of whether intensive insulin therapy (IIT) provides better outcomes for brain-injured patients than does conventional insulin therapy (CIT), with conflicting results. We performed a systematic review and meta-analysis of the literature to estimate the effect of IIT on patients with brain injury. We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and citations of key articles and selected "all randomized controlled trials" (RCTs) comparing the effect of IIT to CIT among adult patients with acute brain injury (traumatic brain injury, stroke, subarachnoid hemorrhage, and encephalitis). Of the 2807 studies, we identified 9 RCTs with a total of 1160 patients for analysis. IIT did not appear to decrease the risk of in-hospital or late mortality (RR = 1.04, 95% CI = 0.75, 1.43 and RR = 1.07, 95% CI = 0.91, 1.27 respectively). No significant heterogeneity was found (I-2 = 0.0%). IIT also did not have a protective effect on long-term neurological outcomes (LTNO) (RR = 1.10, 95% CI = 0.96, 1.27). IIT, however, did decrease the rate of infections (RR = 0.76, 95% CI = 0.58, 0.98). Heterogeneity was present (I-2 = 64%), which was eliminated upon sensitivity analysis bringing the RR to 0.66 (95% CI = 0.55, 0.80, I-2 = 0%). IIT increased the rate of hypoglycemic episodes (RR = 1.72, 95% CI = 1.20, 2.46) however there was intractable heterogeneity present (I-2 = 89%), which did not resolve upon sensitivity analysis. We found no evidence of publication bias by Egger's test (p = 0.50). To conclude, IIT has no mortality or LTNO benefit to patients with brain injury, but is beneficial at decreasing infection rates. C1 [de Moya, Marc A.] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. [Zafar, Syed Nabeel] Aga Khan Univ, Dept Surg, Karachi, Pakistan. [Iqbal, Aftab] Naya Jeevan, Karachi, Pakistan. [Farez, Mauricio F.] Inst Neurol Res Dr Raul Carrea, Buenos Aires, DF, Argentina. [Kamatkar, Suyog] Massachusetts Board Registrat Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. RP de Moya, MA (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM mdemoya@partners.org OI KAMATKAR, SUYOG/0000-0002-2944-3142 NR 39 TC 7 Z9 9 U1 1 U2 5 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD JUL PY 2011 VL 28 IS 7 BP 1307 EP 1317 DI 10.1089/neu.2010.1724 PG 11 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 794BL UT WOS:000292869600019 PM 21534731 ER PT J AU Tanaka, K Morii, T Weissbach, L Horiuchi, K Takeuchi, K Toyama, Y Morioka, H AF Tanaka, Koichiro Morii, Takeshi Weissbach, Lawrence Horiuchi, Keisuke Takeuchi, Katsuhito Toyama, Yoshiaki Morioka, Hideo TI Treatment of collagen-induced arthritis with recombinant plasminogen-related protein B: a novel inhibitor of angiogenesis SO JOURNAL OF ORTHOPAEDIC SCIENCE LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; RHEUMATOID-ARTHRITIS; TUMOR-GROWTH; ENDOSTATIN; CELLS; GENE; ALPHA-V-BETA-3; RESISTANCE; DISEASE AB We have previously reported that recombinant human plasminogen-related protein B (rPRP-B), a putative 9-kDa protein that closely resembles the activation peptide of plasminogen, has shown significant inhibition of tumor growth through inhibition of angiogenesis. Based on recent reports suggesting a close relationship between rheumatoid arthritis (RA) and angiogenesis, we hypothesized that this compound would regulate inflammatory conditions in RA. The present study therefore tested the effects of rPRP-B in the treatment of collagen-induced arthritis (CIA) to elucidate the mechanisms underlying these effects. DBA/1J mice immunized with type II collagen to induce CIA were monitored to assess the effects of rPRP-B on clinical severity of the disease. Pathological changes in joints, including vessel formation and vascular endothelial growth factor (VEGF) production, were examined histologically. Bone destruction was radiologically evaluated. In vitro studies on the effects of rPRP-B on cell proliferation and production of VEGF in interleukin (IL)-1 beta or basic fibroblast growth factor (bFGF)-stimulated human synoviocytes were also performed. Development of CIA was effectively inhibited by rPRP-B. Radiological examinations revealed that the protein reduced bone destruction in CIA. CIA-induced vessel formation and VEGF expression in vivo were also reduced. In vitro mechanistic studies demonstrated that rPRP-B affected human synoviocyte proliferation and VEGF production stimulated by IL-1 beta and bFGF. Given the ability to effectively promote multistep anti-angiogenic activities, including cell growth inhibition and cytokine regulation, rPRP-B represents a promising candidate for a novel therapeutic agent against RA. C1 [Tanaka, Koichiro; Horiuchi, Keisuke; Takeuchi, Katsuhito; Toyama, Yoshiaki; Morioka, Hideo] Keio Univ, Sch Med, Dept Orthopaed Surg, Shinjuku Ku, Tokyo 1608582, Japan. [Morii, Takeshi] Kyorin Univ, Dept Orthopaed Surg, Tokyo 1818611, Japan. [Weissbach, Lawrence] Massachusetts Gen Hosp, Sarcoma Mol Biol Lab, Boston, MA 02114 USA. RP Tanaka, K (reprint author), Keio Univ, Sch Med, Dept Orthopaed Surg, Shinjuku Ku, 35 Shinanomachi, Tokyo 1608582, Japan. EM koichiro@bd.mbn.or.jp; t-morii@gb3.so-net.ne.jp; lawrence.weissbach@gmail.com; horiuchi@z3.keio.jp; ktakeuch@tcc.pref.tochigi.lg.jp; toyama@sc.itc.keio.ac.jp; morioka@sc.itc.keio.ac.jp RI Toyama, Yoshiaki/K-5743-2013; Horiuchi, Keisuke/L-2277-2013 OI Horiuchi, Keisuke/0000-0001-7063-9609 NR 23 TC 2 Z9 3 U1 0 U2 2 PU SPRINGER TOKYO PI TOKYO PA 1-11-11 KUDAN-KITA, CHIYODA-KU, TOKYO, 102-0073, JAPAN SN 0949-2658 J9 J ORTHOP SCI JI J. Orthop. Sci. PD JUL PY 2011 VL 16 IS 4 BP 443 EP 450 DI 10.1007/s00776-011-0091-x PG 8 WC Orthopedics SC Orthopedics GA 795UO UT WOS:000293001600017 PM 21584744 ER PT J AU Abbott, MM Kokorowski, PJ Meara, JG AF Abbott, Megan M. Kokorowski, Paul J. Meara, John G. TI Timeliness of surgical care in children with special health care needs: delayed palate repair for publicly insured and minority children with cleft palate SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article DE Cleft palate; Timeliness; Access; Disparities; Public insurance; Minority ID US CHILDREN; ACCESS; INSURANCE; EXPENDITURES; DISPARITIES; SERVICES AB Background/Purpose: Disparities in access to health care are known to exist for the most vulnerable pediatric population, children with special health care needs. Timely access to surgical care in this population is critical, yet poorly studied. Methods: A national database of pediatric hospitals in the United States was searched for nonsyndromic, healthy patients younger than 24 months who underwent cleft palate repair from 2003 to 2008. A multivariate, linear regression model was constructed to determine the relationship of public payer status and race with age at palatal repair. Results: Age at palate repair was significantly delayed for patients who were publicly insured (1.2 weeks, P = .01), were of nonwhite race/ethnicity (1.5-3.5 weeks, P = .009), and had a diagnosis of cleft lip in addition to cleft palate (3.4 weeks, P = .006) compared to their counterparts in a sample of 2995 patients with cleft palate. Conclusion: There is a small but significant delay in age at repair for patients who are publicly insured or of nonwhite race/ethnicity. These results may herald broader access disparities that could adversely affect clinical outcomes and should be investigated further. (C) 2011 Elsevier Inc. All rights reserved. C1 [Abbott, Megan M.; Meara, John G.] Childrens Hosp Boston, Dept Plast & Oral Surg, Boston, MA 02115 USA. [Abbott, Megan M.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Kokorowski, Paul J.] Childrens Hosp Boston, Dept Urol, Boston, MA 02115 USA. [Abbott, Megan M.; Kokorowski, Paul J.; Meara, John G.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Meara, JG (reprint author), Childrens Hosp Boston, Dept Plast & Oral Surg, Boston, MA 02115 USA. EM john.meara@childrens.harvard.edu NR 24 TC 13 Z9 13 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD JUL PY 2011 VL 46 IS 7 BP 1319 EP 1324 DI 10.1016/j.jpedsurg.2010.10.002 PG 6 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 794FX UT WOS:000292882000011 PM 21763828 ER PT J AU French-Rosas, LN Moye, J Naik, AD AF French-Rosas, Lindsay N. Moye, Jennifer Naik, Aanand D. TI Improving the Recognition and Treatment of Cancer-Related Posttraumatic Stress Disorder SO JOURNAL OF PSYCHIATRIC PRACTICE LA English DT Article DE cancer; posttraumatic stress disorder; cancer survivorship; treatment development ID QUALITY-OF-LIFE; PSYCHOSOCIAL INTERVENTIONS; GROWTH; SURVIVORSHIP; SYMPTOMS AB Life-threatening illness has been identified as a stressor that can precipitate posttraumatic stress disorder (PTSD). Major advances in cancer treatment have led to increased survival periods. At the same time, there is a growing awareness of the psychological impact of cancer diagnosis and treatment on the patient. Cancer survivors report that cancer can elicit symptoms of traumatic stress. When cancer-related PTSD is untreated, medical and psychiatric morbidity increase. Despite the prevalence, impact, and morbidity of cancer-related PTSD, access to mental health care in cancer patients remains limited. It is important to increase mental health providers' awareness of cancer-related PTSD, given rising cancer rates and the potential for enhancing quality of life. This article presents an overview of the recognition, diagnosis, management, and follow-up of cancer-related PTSD for the mental health clinician. (Journal of Psychiatric Practice 2011;17:270-276) C1 [French-Rosas, Lindsay N.] Baylor Coll Med, Menninger Dept Psychiat, Houston, TX 77030 USA. [French-Rosas, Lindsay N.; Naik, Aanand D.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Moye, Jennifer] VA Boston Healthcare Syst, Boston, MA USA. [Moye, Jennifer] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP French-Rosas, LN (reprint author), Baylor Coll Med, Menninger Dept Psychiat, 1977 Butler Blvd,Suite E4-400, Houston, TX 77030 USA. EM frenchro@bcm.edu RI Moye, Jennifer/F-2240-2017 OI Moye, Jennifer/0000-0002-3434-347X FU Houston VA HSR&D Center of Excellence at the Michael E. DeBakey Veterans Affairs Medical Center [HFP90-020]; National Institute of Aging [5K23AG027144]; Doris Duke Charitable Foundation; Boston VA Healthcare System; Boston VA Research Institute (BVARI) FX This work was supported by the Houston VA HSR&D Center of Excellence (HFP90-020) at the Michael E. DeBakey Veterans Affairs Medical Center for Drs. Naik and French-Rosas. Additional support came from a National Institute of Aging Career Development Award (5K23AG027144) and a Doris Duke Charitable Foundation Clinical Scientist Development Award to Dr. Naik. This work was also supported by the Boston VA Healthcare System and the Boston VA Research Institute (BVARI). We thank Kelly Doherty for her assistance, as well as the many veterans who have allowed us to contribute to their care and who have participated in our research projects. NR 22 TC 15 Z9 15 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1527-4160 J9 J PSYCHIATR PRACT JI J. Psychiatr. Pract. PD JUL PY 2011 VL 17 IS 4 BP 270 EP 276 DI 10.1097/01.pra.0000400264.30043.ae PG 7 WC Psychiatry SC Psychiatry GA 795EQ UT WOS:000292955400005 PM 21775828 ER PT J AU Robinson, TN Wallace, JI Wu, DS Wiktor, A Pointer, LF Pfister, SM Sharp, TJ Buckley, MJ Moss, M AF Robinson, Thomas N. Wallace, Jeffrey I. Wu, Daniel S. Wiktor, Arek Pointer, Lauren F. Pfister, Shirley M. Sharp, Terra J. Buckley, Mary J. Moss, Marc TI Accumulated Frailty Characteristics Predict Postoperative Discharge Institutionalization in the Geriatric Patient SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article; Proceedings Paper CT 118th Scientific Session of the Western-Surgical-Association CY NOV, 2010 CL Chicago, IL SP Western Surg Assoc ID ELDERLY-PEOPLE; OLDER-ADULTS; CO-MORBIDITY; OUTCOMES; VALIDATION; SURGERY; AGE AB BACKGROUND: Frailty is a state of increased vulnerability to health-related stressors and can be measured by summing the number of frailty characteristics present in an individual. Discharge institutionalization (rather than discharge to home) represents disease burden and functional dependence after hospitalization. Our aim was to determine the relationship between frailty and need for postoperative discharge institutionalization. STUDY DESIGN: Subjects >= 65 years undergoing major elective operations requiring postoperative ICU admission were enrolled. Discharge institutionalization was defined as need for institutionalized care at hospital discharge. Fourteen preoperative frailty characteristics were measured in 6 domains: comorbidity burden, function, nutrition, cognition, geriatric syndromes, and extrinsic frailty. RESULTS: A total of 223 subjects (mean age 73 +/- 6 years) were studied. Discharge institutionalization occurred in 30% (n = 66). Frailty characteristics related to need for postoperative discharge institutionalization included: older age, Charlson index >= 3, hematocrit <35%, any functional dependence, up-and-go >= 15 seconds, albumin <3.4 mg/dL, Mini-Cog score <= 3, and having fallen within 6 months (p < 0.0001 for all comparisons). Multivariate logistic regression retained prolonged timed up-and-go (p < 0.0001) and any functional dependence (p < 0.0001) as the variables most closely related to need for discharge institutionalization. An increased number of frailty characteristics present in any one subject resulted in increased rate of discharge institutionalization. CONCLUSIONS: Nearly 1 in 3 geriatric patients required discharge to an institutional care facility after major surgery. The frailty characteristics of prolonged up-and-go and any functional dependence were most closely related to the need for discharge institutionalization. Accumulation of a higher number of frailty characteristics in any one geriatric patient increased their risk of discharge institutionalization. (J Am Coll Surg 2011; 213: 37-44. (C) 2011 by the American College of Surgeons) C1 [Robinson, Thomas N.; Wu, Daniel S.; Wiktor, Arek] Univ Colorado, Denver Sch Med, Dept Surg, Aurora, CO USA. [Wallace, Jeffrey I.; Moss, Marc] Univ Colorado, Denver Sch Med, Dept Med, Aurora, CO USA. [Robinson, Thomas N.; Wu, Daniel S.; Wiktor, Arek] Denver Vet Affairs Med Ctr, Dept Surg, Denver, CO USA. [Pointer, Lauren F.] Denver Vet Affairs Med Ctr, Dept Biostat, Denver, CO USA. [Pfister, Shirley M.; Sharp, Terra J.; Buckley, Mary J.] Denver Vet Affairs Med Ctr, Dept Anesthesia, Denver, CO USA. RP Robinson, TN (reprint author), 12631 E 17th Ave,MS C313, Aurora, CO 80045 USA. EM thomas.robinson@ucdenver.edu FU NHLBI NIH HHS [K24 HL089223-04, K24 HL089223, K24 HL089223-05, K24-HL-089223]; NIA NIH HHS [K23 AG034632, K23 AG034632-01A1, K23AG034632] NR 30 TC 102 Z9 103 U1 0 U2 6 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 JUL PY 2011 VL 213 IS 1 BP 37 EP 42 DI 10.1016/j.jamcollsurg.2011.01.056 PG 6 WC Surgery SC Surgery GA 794SU UT WOS:000292922400009 PM 21435921 ER PT J AU Stengel, A Goebel-Stengel, M Wang, L Luckey, A Hu, E Rivier, J Tache, Y AF Stengel, A. Goebel-Stengel, M. Wang, L. Luckey, A. Hu, E. Rivier, J. Tache, Y. TI Central administration of pan-somatostatin agonist ODT8-SST prevents abdominal surgery-induced inhibition of circulating ghrelin, food intake and gastric emptying in rats SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Article DE acyl ghrelin; food intake; gastric emptying; postoperative gastric ileus; somatostatin agonist; somatostatin-28 ID CORTICOTROPIN-RELEASING-FACTOR; CENTRAL-NERVOUS-SYSTEM; C-FOS EXPRESSION; POSTOPERATIVE ILEUS; RECEPTOR SUBTYPES; CENTRAL INJECTION; GROWTH-HORMONE; MESSENGER-RNA; BRAIN; ACTIVATION AB Background Activation of brain somatostatin receptors (sst(1-5)) with the stable pan-sst(1-5) somatostatin agonist, ODT8-SST blocks acute stress and central corticotropin-releasing factor (CRF)-mediated activation of endocrine and adrenal sympathetic responses. Brain CRF signaling is involved in delaying gastric emptying (GE) immediately post surgery. We investigated whether activation of brain sst signaling pathways modulates surgical stress-induced inhibition of gastric emptying and food intake. Methods Fasted rats were injected intracisternally (i.c.) with somatostatin agonists and underwent laparotomy and 1-min cecal palpation. Gastric emptying of a non-nutrient solution and circulating acyl and desacyl ghrelin levels were assessed 50 min post surgery. Food intake was monitored for 24 h. Key Results The abdominal surgeryinduced inhibition of GE (65%), food intake (73% at 2 h) and plasma acyl ghrelin levels (67%) was completely prevented by ODT8-SST (1 mu g per rat, i.c.). The selective sst(5) agonist, BIM-23052 prevented surgeryinduced delayed GE, whereas selective sst(1), sst(2), or sst(4) agonists had no effect. However, the selective sst(2) agonist, S-346-011 (1 mu g per rat, i.c.) counteracted the abdominal surgery-induced inhibition of acyl ghrelin and food intake but not the delayed GE. The ghrelin receptor antagonist, [D-Lys(3)]-GHRP-6 (0.93 mg kg(-1), intraperitoneal, i.p.) blocked i.p. ghrelin-induced increased GE, while not influencing i.c. ODT8-SST-induced prevention of delayed GE and reduced food intake after surgery. Conclusions & Inferences ODT8-SST acts in the brain to prevent surgery-induced delayed GE likely via activating sst(5). ODT8-SST and the sst(2) agonist prevent the abdominal surgeryinduced decrease in food intake and plasma acyl ghrelin indicating dissociation between brain somatostatin signaling involved in preventing surgeryinduced suppression of GE and feeding response. C1 [Stengel, A.; Goebel-Stengel, M.; Wang, L.; Luckey, A.; Hu, E.; Tache, Y.] Univ Calif Los Angeles, CURE Digest Dis Res Ctr, Ctr Neurobiol Stress, Dept Med,Digest Dis Div, Los Angeles, CA 90024 USA. [Stengel, A.; Goebel-Stengel, M.; Wang, L.; Luckey, A.; Hu, E.; Tache, Y.] VA Greater Angeles Hlth Care Syst, Los Angeles, CA USA. [Rivier, J.] Salk Inst Biol Studies, Peptide Biol Labs, La Jolla, CA 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 Research Career Scientist Award, VA Merit Award, Center [NIH DK-41301, R01 NIH DK 33061] FX This work was supported by the Veterans Administration Research Career Scientist Award, VA Merit Award, Center Grant NIH DK-41301 (Animal Core) and R01 NIH DK 33061 (YT). JR is the Dr. Frederik Paulsen Chair in Neurosciences Professor. We are grateful to Mrs. Honghui Liang for the excellent technical support. DISCLOSURE NR 75 TC 18 Z9 18 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1350-1925 J9 NEUROGASTROENT MOTIL JI Neurogastroenterol. Motil. PD JUL PY 2011 VL 23 IS 7 BP E294 EP E308 DI 10.1111/j.1365-2982.2011.01721.x PG 15 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA 793OU UT WOS:000292833800004 PM 21569179 ER PT J AU Shefner, JM Watson, ML Simionescu, L Caress, JB Burns, TM Maragakis, NJ Benatar, M David, WS Sharma, KR Rutkove, SB AF Shefner, J. M. Watson, M. L. Simionescu, L. Caress, J. B. Burns, T. M. Maragakis, N. J. Benatar, M. David, W. S. Sharma, K. R. Rutkove, S. B. TI Multipoint incremental motor unit number estimation as an outcome measure in ALS SO NEUROLOGY LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; POINT STIMULATION METHOD; RELATIVE SIZE; TRIAL; SURVIVAL AB Background: Improved outcome measures are necessary to reduce sample size and increase power in amyotrophic lateral sclerosis (ALS) clinical trials. Motor unit number estimation (MUNE) is a potentially attractive tool. MUNE methods previously employed in multicenter trials exhibited excessive variability and were prone to artifact. Objective: To evaluate a modification of standard incremental MUNE in a multicenter natural history study of subjects with ALS. Methods: Fifty healthy subjects were evaluated twice and 71 subjects with ALS were studied repeatedly for up to 500 days. Side and nerve studied was based on clinical examination findings. Nerves were stimulated at 3 specified locations and 3 increments were obtained at each location. Average single motor unit action potential (SMUP) amplitude was calculated by adding the amplitude of the third increment at each location and dividing by 9; SMUP was divided into maximum CMAP amplitude to determine the MUNE. Results: Test-retest variability was 9% in normal subjects. Average MUNE for normal subjects was 225 (+/- 87), and was 41.9 (+/- 39) among subjects with ALS at baseline. Subjects with ALS showed clear decrements over time, with an overage rate of decline of approximately 9% per month. SMUP amplitude increased with time in a fashion consistent with the known pathophysiology of ALS. Conclusion: Multipoint incremental MUNE has a number of attributes that make it attractive as an outcome measure in ALS and other diseases characterized by motor unit loss. It can be rapidly performed on any EMG machine and has repeatability and rates of decline that favorably compare to other previously described methods. Neurology (R) 2011;77:235-241 C1 [Shefner, J. M.; Watson, M. L.; Simionescu, L.] Upstate Med Univ, Syracuse, NY USA. [Caress, J. B.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Burns, T. M.] Univ Virginia, Charlottesville, VA USA. [Maragakis, N. J.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Benatar, M.] Emory Univ, Atlanta, GA 30322 USA. [David, W. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sharma, K. R.] Univ Miami, Miami, FL USA. [Rutkove, S. B.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Shefner, JM (reprint author), SUNY Upstate Med Univ, Dept Neurol, 750 E Adams St, Syracuse, NY 13210 USA. EM shefnerj@upstate.edu OI Caress, James/0000-0002-5814-6083 FU ALS Association; Isis Pharmaceuticals, Inc.; Neuralstem, Inc.; GlaxoSmithKline; sanofi-aventis; Teva Pharmaceutical Industries Ltd.; Knopp Neurosciences Inc.; Cytokinetics Inc.; NIH; NIH/NINDS; Talecris Biotherapeutics; Myasthenia Gravis Foundation of America; Michael S. Ansari Gift Fund; Sangamo BioSciences, Inc.; TEDCO-Maryland Stem Cell Research Fund; U.S. Department of Defense; ALS Association Packard Center for ALS Research at Johns Hopkins; CytRx Corporation; Muscular Dystrophy Association; Food & Drug Administration; Centers for Disease Control and Prevention; Woodruff Health Sciences Center (Emory University); UpToDate, Inc.; SMA Foundation FX Supported by the ALS Association.; Dr. Shefner serves on a DSMB for the NIH; serves as Neuromuscular Section Editor for and receives publishing royalties from UpToDate; has served as a consultant for Teva Pharmaceutical Industries Ltd., Gilead Sciences, Inc., GlaxoSmithKline, Trophos, and BrainGate; and receives research support from Isis Pharmaceuticals, Inc., Neuralstem, Inc., GlaxoSmithKline, sanofi-aventis, Teva Pharmaceutical Industries Ltd., Knopp Neurosciences Inc., Cytokinetics Inc., the NIH, and the ALS Association. M. L. Watson reports no disclosures. Dr. Simionescu receives research support from the NIH/NINDS. Dr. Caress has served as a consultant for ALS Biopharma, LLC and has received research support from GlaxoSmithKline, Talecris Biotherapeutics, the NIH/NINDS, and the ALS Association. Dr. Burns serves as Podcast Section Editor for Neurology (R); has served as a consultant for Bayhill Therapeutics; and has received research support from Knopp Neurosciences Inc. and the Myasthenia Gravis Foundation of America. Dr. Maragakis serves on a scientific advisory board for Q Therapeutics, Inc.; received support from the Michael S. Ansari Gift Fund for basic science research; serves as a contributor to UpToDate; has served as a consultant for California Institute for Regenerative Medicine (CIRM); and receives/has received research support from Cytokinetics Inc., Sangamo BioSciences, Inc., TEDCO-Maryland Stem Cell Research Fund, NIH/NINDS, U.S. Department of Defense, and the ALS Association Packard Center for ALS Research at Johns Hopkins. Dr. Benatar has served as a consultant for Bayhill Therapeutics and Cytokinetics Inc.; receives publishing royalties for Neuromuscular Disease: Evidence and Analysis in Clinical Neurology (Humana Press, 2006), BluePrints in Neurology, (Lippincott Williams & Wilkins, 2002), and Field of Vision: A Manual and Atlas of Perimetry (Humana Press, 2010); receives/has received research support from CytRx Corporation, the Muscular Dystrophy Association, the ALS Association, the Food & Drug Administration, and the Centers for Disease Control and Prevention, the Woodruff Health Sciences Center (Emory University), and the NIH; and has participated in medico-legal cases. Dr. David has served as a consultant for Apnex Medical (TM), Inc. and Allergan, Inc. Dr. Sharma reports no disclosures. Dr. Rutkove has 2 patents pending re: Electrical impedance myography; receives royalties from UpToDate, Inc. and for the publication of The Clinical Neurophysiology Primer (Humana Press, 2007); serves as a consultant for and holds stock in Convergence Medical Devices, Inc.; serves as a consultant to Neuralstem, Inc.; and receives research support from the NIH/NINDS, the SMA Foundation, and the ALS Association. NR 21 TC 57 Z9 58 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUL PY 2011 VL 77 IS 3 BP 235 EP 241 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 793ZS UT WOS:000292863600010 PM 21676915 ER PT J AU Snapinn, KW Larson, EB Kawakami, H Ujike, H Borenstein, AR Izumi, Y Kaji, R Maruyama, H Mata, IF Morino, H Oda, M Tsuang, DW Yearout, D Edwards, KL Zabetian, CP AF Snapinn, Katherine W. Larson, Eric B. Kawakami, Hideshi Ujike, Hiroshi Borenstein, Amy R. Izumi, Yuishin Kaji, Ryuji Maruyama, Hirofumi Mata, Ignacio F. Morino, Hiroyuki Oda, Masaya Tsuang, Debby W. Yearout, Dora Edwards, Karen L. Zabetian, Cyrus P. TI The UCHL1 S18Y polymorphism and Parkinson's disease in a Japanese population SO PARKINSONISM & RELATED DISORDERS LA English DT Article DE Parkinson's disease; UCHL1; Association study ID UCH-L1 GENE; SUSCEPTIBILITY GENE; ASSOCIATION; VARIANT AB UCHL1 plays an important role in the ubiquitin-proteasome system and is a biologically plausible candidate gene for Parkinson's disease (PD). However, results from genetic association studies of the UCHL1 S18Y polymorphism have been equivocal. Meta-analyses indicate that the polymorphism's risk effect might be restricted to Asian populations and early-onset disease. To further explore the role of UCHL1 in PD, we genotyped S18Y in 605 PD patients and 1620 controls of Japanese ancestry. We did not find evidence of an association in the overall sample (SY vs. SS: adjusted OR=1.11, P=0.37; YY vs. SS: adjusted OR=1.01, P=0.94). In the early-onset stratum, however, we observed a trend toward a reduction in risk for those with the Y allele (SY vs. SS, adjusted OR, 0.75; 95% CI, 0.47-1.20; YY vs. SS, OR, 0.64; 95% CI, 0.36-1.14; trend test, P=0.12). These results indicate that, if involved in PD, the S18Y variant is not a major determinant of risk and its effect might be restricted to early-onset disease. Published by Elsevier Ltd. C1 [Mata, Ignacio F.; Yearout, Dora; Zabetian, Cyrus P.] VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. [Snapinn, Katherine W.; Edwards, Karen L.] Univ Washington, Dept Epidemiol, Sch Publ Hlth, Seattle, WA 98195 USA. [Larson, Eric B.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Larson, Eric B.] Univ Washington, Dept Hlth Serv, Sch Publ Hlth, Seattle, WA 98195 USA. [Kawakami, Hideshi; Maruyama, Hirofumi; Morino, Hiroyuki] Hiroshima Univ, Dept Epidemiol, Res Inst Radiat Biol & Med, Hiroshima, Japan. [Ujike, Hiroshi] Okayama Univ, Dept Neuropsychiat, Grad Sch Med Dent & Pharmaceut Sci, Okayama 7008530, Japan. [Borenstein, Amy R.] Univ S Florida, Coll Publ Hlth, Dept Epidemiol & Biostat, Tampa, FL USA. [Izumi, Yuishin; Kaji, Ryuji] Univ Tokushima, Inst Hlth Biosci, Dept Clin Neurosci, Grad Sch, Tokushima 770, Japan. [Mata, Ignacio F.; Yearout, Dora; Zabetian, Cyrus P.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. [Oda, Masaya] Vihara Hananosato Hosp, Dept Neurol, Miyoshi City, Hiroshima, Japan. [Tsuang, Debby W.] VA Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Tsuang, Debby W.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Zabetian, Cyrus P.] VA Puget Sound Hlth Care Syst, NW Parkinsons Dis Res Educ & Clin Ctr, Seattle, WA 98108 USA. RP Zabetian, CP (reprint author), VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr S 182, 1660 S Columbian Way, Seattle, WA 98108 USA. EM zabetian@u.washington.edu RI Maruyama, Hirofumi/B-9333-2011; Kawakami, Hideshi/A-2086-2009; Morino, Hiroyuki/H-9583-2013; Tsuang, Debby/L-7234-2016; OI Kawakami, Hideshi/0000-0002-1405-0901; Morino, Hiroyuki/0000-0002-5190-3547; Tsuang, Debby/0000-0002-4716-1894; Fernandez Mata, Ignacio/0000-0003-1198-0633; Zabetian, Cyrus/0000-0002-7739-4306 FU National Institutes of Health [R01 NS065070, R01 AG009769, P50 NS062684]; Department of Veterans Affairs [1I01BX000531]; Smoking Research Foundation of Japan FX This work was supported by grants from the National Institutes of Health (R01 NS065070, R01 AG009769, and P50 NS062684), Department of Veterans Affairs (1I01BX000531), and the Smoking Research Foundation of Japan. NR 12 TC 9 Z9 10 U1 0 U2 2 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 JUL PY 2011 VL 17 IS 6 BP 473 EP 475 DI 10.1016/j.parkreldis.2011.01.019 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 795CG UT WOS:000292948500016 PM 21345711 ER PT J AU Wainwright, M Dai, TH Hamblin, MR AF Wainwright, Mark Dai, Tianhong Hamblin, Michael R. TI Antimicrobial Photodynamic Therapy in the Colon: Delivering a Light Punch to the Guts? SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID CLOSTRIDIUM-DIFFICILE AB A paper in this issue of Photochemistry and Photobiology by Cassidy et al. describes the use of a sophisticated drug delivery vehicle prepared by the hot melt extrusion process to deliver photosensitizers to the colon. The smart vehicle protects its cargo through the acidic environment of the stomach but releases the active photosensitizers in the higher pH and anaerobic environment of the colon. The goal is to use photodynamic therapy (PDT) to destroy pathogenic microorganisms that can cause disease when they grow out of control in the colon. Since the colon is an environment with a low oxygen concentration the investigators also used tetrachlorodecaoxide, an oxygen donor to boost the available oxygen concentration. The paper reports results with Enterococcus faecalis and Bacteroides fragilis but the real medical problem demanding to be solved is Clostridium difficile that can cause intractable drug-resistant infections after antibiotic use. There still remain barriers to implementing this strategy in vivo, including light delivery to the upper colon, oxygen availability and optimizing the selectivity of photosensitizers for bacteria over colon epithelial cells. Nevertheless, this highly innovative paper lays the ground for the study of an entirely new and significant application for antimicrobial PDT. C1 [Dai, Tianhong; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Wainwright, Mark] Liverpool John Moores Univ, Sch Pharm & Biomol Sci, Liverpool L3 5UX, Merseyside, England. [Dai, Tianhong; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 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 OI Hamblin, Michael/0000-0001-6431-4605 FU Airlift Research Foundation [109421]; US-NIH [R01AI050875] FX TD was supported by Airlift Research Foundation grant 109421. MRH was supported by US-NIH grant R01AI050875. NR 10 TC 3 Z9 3 U1 0 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD JUL-AUG PY 2011 VL 87 IS 4 BP 754 EP 756 DI 10.1111/j.1751-1097.2011.00925.x PG 3 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 793ZX UT WOS:000292864200002 PM 21418077 ER PT J AU Thornburg, K Jonker, S O'Tierney, P Chattergoon, N Louey, S Faber, J Giraud, G AF Thornburg, Kent Jonker, Sonnet O'Tierney, Perrie Chattergoon, Natasha Louey, Samantha Faber, Job Giraud, George TI Regulation of the cardiomyocyte population in the developing heart SO PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY LA English DT Review DE Cardiomyocyte; Fetus; Programming; Terminal differentiation; Atrial natriuretic peptide; Tri-iodo-L-thyronine ID INTRAUTERINE GROWTH RESTRICTION; ATRIAL-NATRIURETIC-FACTOR; CELL-CYCLE ACTIVITY; PLACENTAL EXTRAVILLOUS TROPHOBLASTS; FETAL SHEEP CARDIOMYOCYTES; CARDIAC MYOCYTES; ADULT LIFE; IN-VITRO; VENOUS HYPERTENSION; PRENATAL HYPOXIA AB During fetal life the myocardium expands through replication of cardiomyocytes. In sheep, cardiomyocytes begin the process of becoming terminally differentiated at about 100 gestation days out of 145 days term. In this final step of development, cardiomyocytes become binucleated and stop dividing. The number of cells at birth is important in determining the number of cardiomyocytes for life. Therefore, the regulation of cardiomyocyte growth in the womb is critical to long term disease outcome. Growth factors that stimulate proliferation of fetal cardiomyocytes include angiotensin II, cortisol and insulin-like growth factor-1. Increased ventricular wall stress leads to short term increases in proliferation but longer-term loss of cardiomyocyte generative capacity. Two normally circulating hormones have been identified that suppress proliferation: atrial natriuretic peptide (ANP) and tri-iodo-L-thyronine (T-3). Atrial natriuretic peptide signals through the NPRA receptor that serves as a guanylate cyclase and signals through cGMP. ANP powerfully suppresses mitotic activity in cardiomyocytes in the presence of angiotensin II in culture. Addition of a cGMP analog has the same effect as ANP. ANP suppresses both the extracellular receptor kinases and the phosphoinositol-3 kinase pathways. T-3 also suppresses increased mitotic activity of stimulated cardiomyocytes but does so by increasing the cell cycle suppressant, p21, and decreasing the cell cycle activator, cyclin D1. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Thornburg, Kent; Jonker, Sonnet; O'Tierney, Perrie; Chattergoon, Natasha; Louey, Samantha; Faber, Job; Giraud, George] Oregon Hlth & Sci Univ, Heart Res Ctr, Portland, OR 97239 USA. [Thornburg, Kent; Jonker, Sonnet; Louey, Samantha; Giraud, George] Oregon Hlth & Sci Univ, Sch Med Cardiovasc Med, Portland, OR 97239 USA. [Giraud, George] Portland VA Med Ctr, Portland, OR 97201 USA. RP Thornburg, K (reprint author), Oregon Hlth & Sci Univ, Heart Res Ctr, 3303 SW Bond,CH15H, Portland, OR 97239 USA. EM thornbur@ohsu.edu OI Thornburg, Kent/0000-0002-5561-4785; Jonker, Sonnet/0000-0002-1097-2562 FU NICHD [P01 HD 34430]; NHLBI [R21 HL093617, R01 HL102763, T32HL094294]; Office of Research on Women's Health; National Institute of Child Health and Human Development; Oregon BIRCWH [HD043488]; M. Lowell Edwards Endowment FX This study was supported by funds from NICHD P01 HD 34430, NHLBI R21 HL093617, and R01 HL102763. Dr. Natasha Chattergoon was supported by NHLBI training grant T32HL094294. Dr. Sonnet Jonker was supported by Office of Research on Women's Health and the National Institute of Child Health and Human Development, Oregon BIRCWH HD043488. Dr. Thornburg was supported by the M. Lowell Edwards Endowment. NR 68 TC 24 Z9 24 U1 0 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0079-6107 J9 PROG BIOPHYS MOL BIO JI Prog. Biophys. Mol. Biol. PD JUL PY 2011 VL 106 IS 1 SI SI BP 289 EP 299 DI 10.1016/j.pbiomolbio.2010.11.010 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 793XI UT WOS:000292856800004 PM 21147149 ER PT J AU Bean-Mayberry, B Yano, EM Washington, DL Goldzweig, C Batuman, F Huang, C Miake-Lye, I Shekelle, PG AF Bean-Mayberry, Bevanne Yano, Elizabeth M. Washington, Donna L. Goldzweig, Caroline Batuman, Fatma Huang, Christine Miake-Lye, Isomi Shekelle, Paul G. TI Systematic Review of Women Veterans' Health: Update on Successes and Gaps SO WOMENS HEALTH ISSUES LA English DT Review ID POSTTRAUMATIC-STRESS-DISORDER; QUALITY-OF-LIFE; PRIMARY-CARE CLINICS; UNIVERSITY MEDICAL-CENTERS; OPERATION-IRAQI-FREEDOM; MILITARY SEXUAL TRAUMA; 30-DAY POSTOPERATIVE MORTALITY; RANDOMIZED CONTROLLED-TRIAL; SMOKING-CESSATION PROGRAM; INTIMATE PARTNER VIOLENCE AB Objective: We assessed the state of women veterans' health research by conducting a systematic review of scientific literature published from 2004 to 2008, updating a prior review spanning the history of this literature to 2004. Methods: We identified articles by searching scientific databases and contacting experts. Relevant articles were independently evaluated by two physician reviewers. We categorized 195 articles by study design, funding source, period of military service, research topic, and health condition. Results: More research was published during this 5-year review (n = 195) than in the 25 years beforehand (n = 182). The 195 studies included five trials, but only one randomized trial, a study that examined treatment outcomes for women with posttraumatic stress disorder (PTSD). The large number of articles focused on Operation Enduring Freedom and Operation Iraqi Freedom (OEF/OIF) soldiers' health issues (n = 23) reflects the growing participation of women in these conflicts. High rates of positive PTSD symptoms (range, 10%-19%) and other mental health disorders were found among OEF/OIF returning military women. The recent post-deployment literature underscores the need for repeated PTSD/mental health screening in returning veterans, and points to continuity of care needs for psychiatric and gynecological problems which occur in the field. The psychiatric and access/utilization literature confirmed the positive relationship between military sexual trauma and PTSD and the associated negative health effects. Conclusion: Although most VA women's health research remains observational, methods are evolving toward an analytical focus. Even though successes are evident in the breadth and depth of publications, remaining gaps in the literature include post-deployment readjustment for veterans/families, and quality-of-care interventions/outcomes for physical and mental conditions. Published by Elsevier Inc. C1 [Bean-Mayberry, Bevanne; Yano, Elizabeth M.; Washington, Donna L.; Miake-Lye, Isomi; Shekelle, Paul G.] VA Greater Los Angeles Hlth Serv Res & Dev Ctr Ex, Sepulveda, CA USA. [Bean-Mayberry, Bevanne; Yano, Elizabeth M.; Washington, Donna L.; Goldzweig, Caroline; Batuman, Fatma; Huang, Christine; Miake-Lye, Isomi; Shekelle, Paul G.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Bean-Mayberry, Bevanne; Washington, Donna L.; Goldzweig, Caroline; Batuman, Fatma; Huang, Christine; Shekelle, Paul G.] UCLA David Geffen Sch Med, Dept Med, Los Angeles, CA USA. [Yano, Elizabeth M.] UCLA Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA USA. [Shekelle, Paul G.] W Los Angeles VA Med Ctr, Evidence Synth Program, Los Angeles, CA USA. RP Bean-Mayberry, B (reprint author), VA Sepulveda, VA GLA HSR&D Ctr Study Healthcare Provider Behav, 16111 Plummer St,152, Sepulveda, CA 91343 USA. EM bevanne.bean-mayberry@va.gov RI Schueter, nicos/A-3625-2014 NR 201 TC 58 Z9 58 U1 5 U2 17 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD JUL-AUG PY 2011 VL 21 IS 4 SU S SI SI BP S84 EP S97 DI 10.1016/j.whi.2011.04.022 PG 14 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 792YA UT WOS:000292785100006 PM 21724149 ER PT J AU Dichter, ME Cerulli, C Bossarte, RM AF Dichter, Melissa E. Cerulli, Catherine Bossarte, Robert M. TI Intimate Partner Violence Victimization Among Women Veterans and Associated Heart Health Risks SO WOMENS HEALTH ISSUES LA English DT Article ID SEXUAL-ABUSE; CARDIOVASCULAR-DISEASE; PHYSICAL-ACTIVITY; SOCIAL SUPPORT; CARE; DEPRESSION; TRAUMA; EXPERIENCES; MECHANISMS; MILITARY AB Purpose: Cardiovascular disease (CVD) is the leading cause of death for women in the United States. CVD risk factors, including depression, smoking, heavy drinking, being overweight, and physical inactivity, are associated with stress and may be linked to women's experiences of intimate partner violence (IPV) victimization. We know little about IPV and CVD risk factors among veteran women. The purpose of this study was to identify the association between lifetime IPV victimization and CVD risk factors among women, accounting for veteran status. Methods: We used data from the Centers for Disease Control and Prevention's Behavioral Risk Factor Surveillance System for 2006 for the eight states that included the IPV module. We explored the associations between veteran status and lifetime IPV victimization and between IPV exposure and CVD risk factors, for veteran and non-veteran women. Findings: Veteran women were more likely than non-veteran women to report lifetime IPV victimization (33.0% vs. 23.8%). IPV exposure was associated with depression, smoking, and heavy drinking. We did not find evidence for an association between IPV exposure and lack of exercise or being overweight or obese, when controlling for demographic characteristics and veteran status. Conclusion: Women veterans have particularly high rates of lifetime IPV victimization. In addition, IPV victimization is associated with an increased risk of heart health risk factors. The findings suggest that we should attend to IPV exposure among veteran women and further investigate the link between IPV and military service, and the associated health impacts. Published by Elsevier Inc. C1 [Dichter, Melissa E.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. [Cerulli, Catherine] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Bossarte, Robert M.] Canandaigua VA Med Ctr, VISN Ctr Excellence 2, Canandaigua, NY USA. RP Dichter, ME (reprint author), Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, 3900 Woodland Ave,Bldg 4100, Philadelphia, PA 19104 USA. EM mdichter@sp2.upenn.edu NR 40 TC 30 Z9 30 U1 3 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 EI 1878-4321 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD JUL-AUG PY 2011 VL 21 IS 4 SU S SI SI BP S190 EP S194 DI 10.1016/j.whi.2011.04.008 PG 5 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 792YA UT WOS:000292785100019 PM 21724140 ER PT J AU Farmer, MM Rose, DE Riopelle, D Lanto, AB Yano, EM AF Farmer, Melissa M. Rose, Danielle E. Riopelle, Deborah Lanto, Andy B. Yano, Elizabeth M. TI Gender Differences in Smoking and Smoking Cessation Treatment: An Examination of the Organizational Features Related to Care SO WOMENS HEALTH ISSUES LA English DT Article ID QUALITY-OF-CARE; WOMEN VETERANS; UNITED-STATES; MANAGED CARE; DISPARITIES; DEPRESSION; ABSTINENCE; SERVICES; PROGRAM; RECALL AB Objectives: Veterans experience a particularly heavy burden with smoking rates higher than the general population, and the smoking prevalence for women Veterans has increased in recent years. We examined differences in smoking prevalence and treatment by gender for Veterans receiving at least some of their care at a VA facility, and examined the degree to which organizational factors may be associated with reductions in gender disparities in smoking cessation treatment. Methods: We merged national organizational-level data focused on primary care (sites = 225) and women's health (sites = 195) with patient-level survey data (n = 15,033 smokers). Organizational measures focused on smoking cessation-specific structure and processes in primary care and women's health. Primary outcomes were patient-reported receipt of smoking cessation treatments advised to quit, medication recommendation, and other treatment recommendation. We used multi-level, random-intercept logistic regression. Results: In 2007, 29% of women and 23% of men were smokers. Overall, 83% of smokers reported they had been advised to quit, 62% recommended medications, and 60% recommended other treatments. Women were more likely to report being advised to quit (odds ratio, 1.33; 95% confidence interval, 1.07-1.64) but equally likely as men to have medications or other treatment recommended. Organizational factors did not eliminate the gender differences in being advised to quit. Conclusion: Despite having equivalent or higher smoking cessation treatment rates, women Veterans were more likely to smoke than men. With the rapid growth of women entering VA care, the need for effective gender-focused and gender-sensitive smoking cessation care arrangements is critical for the future health of women who have served. Published by Elsevier Inc. C1 [Farmer, Melissa M.; Rose, Danielle E.; Riopelle, Deborah; Lanto, Andy B.; Yano, Elizabeth M.] VA Greater Los Angeles Healthcare Syst, Ctr Study Healthcare Provider Behav, HSR&D, VA Hlth Serv Res & Dev Ctr Excellence, Sepulveda, CA 91343 USA. [Farmer, Melissa M.; Yano, Elizabeth M.] UCLA Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA USA. RP Farmer, MM (reprint author), VA Greater Los Angeles Healthcare Syst, Ctr Study Healthcare Provider Behav, HSR&D, VA Hlth Serv Res & Dev Ctr Excellence, 16111 Plummer St,152, Sepulveda, CA 91343 USA. EM Melissa.Farmer@va.gov NR 41 TC 18 Z9 18 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD JUL-AUG PY 2011 VL 21 IS 4 SU S SI SI BP S182 EP S189 DI 10.1016/j.whi.2011.04.018 PG 8 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 792YA UT WOS:000292785100018 PM 21724139 ER PT J AU Iverson, KM Hendricks, AM Kimerling, R Krengel, M Meterko, M Stolzmann, KL Baker, E Pogoda, TK Vasterling, JJ Lew, HL AF Iverson, Katherine M. Hendricks, Ann M. Kimerling, Rachel Krengel, Maxine Meterko, Mark Stolzmann, Kelly L. Baker, Errol Pogoda, Terri K. Vasterling, Jennifer J. Lew, Henry L. TI Psychiatric Diagnoses and Neurobehavioral Symptom Severity among OEF/OIF VA Patients with Deployment-Related Traumatic Brain Injury: A Gender Comparison SO WOMENS HEALTH ISSUES LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; HEALTH-CARE; VETERANS; IRAQ; AFGHANISTAN; WAR; WOMEN; ORGANIZATION; DEPRESSION; OUTCOMES AB Background: Traumatic brain injury (TBI) has substantial negative implications for the post-deployment adjustment of veterans who served in Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF); however, most research on veterans has focused on males. This study investigated gender differences in psychiatric diagnoses and neurobehavioral symptom severity among OEF/OIF veterans with deployment-related TBI. Methods: This population-based study examined psychiatric diagnoses and self-reported neurobehavioral symptom severity from administrative records for 12,605 United States OEF/OIF veterans evaluated as having deployment-related TBI. Men (n = 11,951) and women (n = 654) who were evaluated to have deployment-related TBI during a standardized comprehensive TBI evaluation in Department of Veterans Affairs facilities were compared on the presence of psychiatric diagnoses and severity of neurobehavioral symptoms. Findings: Posttraumatic stress disorder (PTSD) was the most common psychiatric condition for both genders, although women were less likely than men to have a PTSD diagnosis. In contrast, relative to men, women were 2 times more likely to have a depression diagnosis, 1.3 times more likely to have a non-PTSD anxiety disorder, and 1.5 times more likely to have PTSD with comorbid depression. Multivariate analyses indicated that blast exposure during deployment may account for some of these differences. Additionally, women reported significantly more severe symptoms across a range of neurobehavioral domains. Conclusion: Although PTSD was the most common condition for both men and women, it is also critical for providers to identify and treat other conditions, especially depression and neurobehavioral symptoms, among women veterans with deployment-related TBI. Published by Elsevier Inc. C1 [Iverson, Katherine M.; Vasterling, Jennifer J.] VA Boston Healthcare Syst, Psychol Serv, WHSD NCPTSD 116B 3, Boston, MA 02130 USA. [Iverson, Katherine M.] Natl Ctr Posttraumat Stress Disorder, Womens Hlth Sci Div, Boston, MA USA. [Iverson, Katherine M.; Meterko, Mark; Stolzmann, Kelly L.; Baker, Errol; Pogoda, Terri K.] Ctr Org Leadership & Management Res, Boston, MA USA. [Iverson, Katherine M.; Krengel, Maxine; Vasterling, Jennifer J.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Hendricks, Ann M.; Meterko, Mark; Pogoda, Terri K.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Kimerling, Rachel] VA Palo Alto Hlth Care Syst, Menlo Pk, CA USA. [Vasterling, Jennifer J.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. [Lew, Henry L.] DVBIC, Richmond, VA USA. [Lew, Henry L.] Univ Richmond, Sch Med, Dept PM&R, Richmond, VA 23173 USA. RP Iverson, KM (reprint author), VA Boston Healthcare Syst, Psychol Serv, WHSD NCPTSD 116B 3, 150 S Huntington Ave, Boston, MA 02130 USA. EM Katherine.lverson@va.gov RI Schueter, nicos/A-3625-2014; OI Krengel, Maxine/0000-0001-7632-590X; Kimerling, Rachel/0000-0003-0996-4212 FU NIMH NIH HHS [T32 MH019836, T32 MH019836-14, T32MH019836] NR 35 TC 35 Z9 35 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD JUL-AUG PY 2011 VL 21 IS 4 SU S SI SI BP S210 EP S217 DI 10.1016/j.whi.2011.04.019 PG 8 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 792YA UT WOS:000292785100022 PM 21724143 ER PT J AU Lipson, L Eisen, S AF Lipson, Linda Eisen, Seth TI VA Research: Committed to Women Who Have "Borne the Battle" and Beyond SO WOMENS HEALTH ISSUES LA English DT Editorial Material ID HEALTH-CARE; VETERANS; QUALITY C1 [Lipson, Linda; Eisen, Seth] Hlth Serv Res & Dev Serv, US Dept Vet Affairs, Washington, DC USA. RP Lipson, L (reprint author), Hlth Serv Res & Dev Serv, Dept Vet Affairs, Mail Code 124,810 Vermont Ave NW, Washington, DC 20420 USA. EM Linda.Lipson@va.gov NR 12 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD JUL-AUG PY 2011 VL 21 IS 4 SU S SI SI BP S67 EP S69 DI 10.1016/j.whi.2011.04.026 PG 3 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 792YA UT WOS:000292785100003 PM 21724146 ER PT J AU MacGregor, C Hamilton, AB Oishi, SM Yano, EM AF MacGregor, Casey Hamilton, Alison B. Oishi, Sabine M. Yano, Elizabeth M. TI Description, Development, and Philosophies of Mental Health Service Delivery for Female Veterans in the VA: A Qualitative Study SO WOMENS HEALTH ISSUES LA English DT Article ID WOMEN VETERANS; PRIMARY-CARE; GENDER-DIFFERENCES; AFGHANISTAN; CLINICS; IRAQ; INNOVATION; TRAUMA AB Purpose: National Veterans Health Administration (VA) organizational data suggested the presence of separate and formal mental health services for female veterans, prompting qualitative exploration of their structure and development. Methods: Semistructured telephone interviews were conducted with a purposeful sample of 36 VA mental health administrators and providers from 26 VA Medical Centers and large community-based outpatient clinics that reported having separate women's mental health clinics and/or designated women's mental health providers in their outpatient mental health clinics. Main Findings: VA facilities have implemented a spectrum of women's mental health service delivery arrangements, including specialized mental health providers, co-located mental health providers in women's health clinics, women-only mental health groups, and women's mental health clinics. Most facilities had one or more "champions" developing such services, but some faced challenges in maintaining viability. Some respondents expressed concern about possible stigmatization associated with creating separate mental health services for female veterans. Conclusion: Arrangements of VA mental health services for female veterans vary across facilities. This study identified a lack of consensus in the field regarding the need for and consequences of adapting existing programs specifically for the mental health needs of female veterans. Implementation of VA policy may require greater attention to frontline providers' perspectives. Comparative impact studies of female veterans' mental health service delivery arrangements are also needed. Published by Elsevier Inc. C1 [MacGregor, Casey] VA Greater Los Angeles Healthcare Syst, QUERI Ctr Implementat Practice & Res Support CIPR, VA HSR&D Ctr Excellence Study Healthcare Provider, Sepulveda, CA 91343 USA. [Hamilton, Alison B.] VA Greater Los Angeles Healthcare Syst, Desert Pacific Mental Illness Res Educ & Clin Ctr, Los Angeles, CA USA. [Hamilton, Alison B.] Univ Calif Los Angeles, Sch Med, Dept Psychiat, Integrated Substance Abuse Programs, Los Angeles, CA 90024 USA. [Yano, Elizabeth M.] UCLA Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA USA. RP MacGregor, C (reprint author), VA Greater Los Angeles Healthcare Syst, QUERI Ctr Implementat Practice & Res Support CIPR, VA HSR&D Ctr Excellence Study Healthcare Provider, 16111 Plummer St,152, Sepulveda, CA 91343 USA. EM Casey.Macgregor@va.gov NR 22 TC 10 Z9 10 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD JUL-AUG PY 2011 VL 21 IS 4 SU S SI SI BP S138 EP S144 DI 10.1016/j.whi.2011.04.006 PG 7 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 792YA UT WOS:000292785100012 PM 21724133 ER PT J AU Oishi, SM Rose, DE Washington, DL MacGregor, C Bean-Mayberry, B Yano, EM AF Oishi, Sabine M. Rose, Danielle E. Washington, Donna L. MacGregor, Casey Bean-Mayberry, Bevanne Yano, Elizabeth M. TI National Variations in VA Mental Health Care for Women Veterans SO WOMENS HEALTH ISSUES LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; FEMALE VETERANS; SEXUAL TRAUMA; GENDER; ENVIRONMENT; IMPROVEMENT; DEPRESSION; PREVALENCE; ANXIETY; ABUSE AB Objectives: Although the Veterans Health Administration (VA) has recently adopted new policies encouraging gender-specific mental health (MH) care delivery to women veterans, little is known about the potential difficulties local facilities may face in achieving compliance. We assessed variations in women's mental health care delivery arrangements in VA facilities nationwide. Methods: We used results from the VA Survey of Women Veterans Health Programs, a key informant survey of senior women's health clinicians representing all VA facilities serving more than 300 women veterans, to assess the array of gender-sensitive mental health care arrangements (response rate, 86%; n = 195). We also examined organizational and area factors related to availability of women's specialty mental health arrangements using multivariable logistic regression. Results: Nationally, over half (53%) of VA facilities had some form of gender-sensitive mental health care arrangements. Overall, 34% of sites reported having designated women's mental health providers in general outpatient mental health clinics (MHCs). Almost half (48%) had therapy groups for women in their MHCs. VAs with women's primary care clinics also delivered mental health services (24%), and 12% of VAs reported having a separate women's MHC, most of which (88%) offered sexual trauma group counseling. Assignment to same-gender mental health providers is not routine. VAs with comprehensive women's primary care clinics were more likely to integrate mental health care for women as well. Conclusion: Local implementation of gender-sensitive mental health care in VA settings is highly variable. Although this variation may reflect diverse local needs and resources, women veterans may also sometimes face challenges in accessing needed services. Published by Elsevier Inc. C1 [Oishi, Sabine M.; Rose, Danielle E.; Washington, Donna L.; MacGregor, Casey; Bean-Mayberry, Bevanne; Yano, Elizabeth M.] VA Greater Los Angeles Healthcare Syst, VA HSR&D Ctr Excellence Study Healthcare Provider, Sepulveda, CA 91343 USA. [Washington, Donna L.; Bean-Mayberry, Bevanne] VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA. [Washington, Donna L.; Bean-Mayberry, Bevanne] UCLA Sch Med, Los Angeles, CA USA. [MacGregor, Casey] QUERI Ctr Implementat Practice & Res Support CIPR, Los Angeles, CA USA. [Yano, Elizabeth M.] UCLA Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA USA. RP Oishi, SM (reprint author), VA Greater Los Angeles Healthcare Syst, VA HSR&D Ctr Excellence Study Healthcare Provider, 16111 Plummer St,152, Sepulveda, CA 91343 USA. EM sabine.oishi@va.gov NR 30 TC 17 Z9 17 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD JUL-AUG PY 2011 VL 21 IS 4 SU S SI SI BP S130 EP S137 DI 10.1016/j.whi.2011.04.029 PG 8 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 792YA UT WOS:000292785100011 PM 21724132 ER PT J AU Sternke, LM AF Sternke, Lisa Marie TI Measurement of Military Combat Exposure Among Women: Analysis and Implications SO WOMENS HEALTH ISSUES LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; MENTAL-HEALTH PROBLEMS; FEMALE VIETNAM VETERANS; GENDER-DIFFERENCES; TRAUMA EXPOSURE; WAR VETERANS; LONGITUDINAL ASSESSMENT; FUNCTIONAL HEALTH; ABUSIVE VIOLENCE; PHYSICAL HEALTH AB Purpose: To examine combat exposure measurement instruments utilized since the Vietnam War, determine how these instruments were developed and psychometrically tested, and if they are appropriate for use with women veterans exposed to combat. Methods: A literature search for articles concerning combat exposure instruments, their development, and their psychometric properties in relation to women was conducted in several electronic databases. Limited MeSH subject headings required keyword searches with terms such as combat stress, war trauma, and deployment stressors. Instruments were selected for analysis based on their inclusion of combat and combat-related traumatic event measures. Results: Eight instruments were retained for critical appraisal. The majority of instruments were developed and validated based on male veterans' combat experiences from the Vietnam War through the Gulf War. Located instruments explained their methodological development and indicated the type of exposure being measured. Reliability measures for the majority were acceptable, and validity was established to varying degrees and with different methods. Limitations of all instruments included retrospective self-reporting, potential recall error, and the inability to validate individual exposure objectively. Conclusion: Women veterans are substantially under-represented in the development and psychometric testing of combat exposure instruments, indicating a male gender bias in most combat measures. Only two instruments utilized women veterans in their validation samples, and six instruments used gender-neutral terminology. Instruments developed and validated with male veterans for specific military conflicts may not reflect the combat experiences of women. Published by Elsevier Inc. C1 [Sternke, Lisa Marie] Ralph H Johnson VA Med Ctr, VA Nursing Acad, Dept Vet Affairs, Charleston, SC USA. [Sternke, Lisa Marie] Med Univ S Carolina, Coll Nursing, Charleston, SC USA. RP Sternke, LM (reprint author), 109 Bee St, Charleston, SC 29401 USA. EM Lisa.Sternke@va.gov NR 84 TC 6 Z9 6 U1 3 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD JUL-AUG PY 2011 VL 21 IS 4 SU S SI SI BP S160 EP S168 DI 10.1016/j.whi.2011.04.020 PG 9 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 792YA UT WOS:000292785100015 PM 21724136 ER PT J AU Washington, DL Bean-Mayberry, B Mitchell, MN Riopelle, D Yano, EM AF Washington, Donna L. Bean-Mayberry, Bevanne Mitchell, Michael N. Riopelle, Deborah Yano, Elizabeth M. TI Tailoring VA Primary Care to Women Veterans: Association with Patient-Rated Quality and Satisfaction SO WOMENS HEALTH ISSUES LA English DT Article ID AFFAIRS MEDICAL-CENTER; HEALTH-CARE; NATIONAL-CENTERS; AVAILABILITY; CLINICS; DELIVERY; EXCELLENCE; INNOVATION; SERVICES AB Background: Primary care delivery models tailored to women's needs and preferences are associated with higher quality and satisfaction. Therefore, the U.S. Department of Veterans Affairs (VA) recommends adoption of designated providers for women in primary care clinics or women's health centers as the optimal models for women's primary care. We assessed women veterans' ratings of their VA health care quality, gender-related satisfaction, gender appropriateness, and VA provider skills in treating women, in relation to primary care model at VA sites nationwide. Methods: Health care ratings were obtained from VA users in the 2008-2009 National Survey of Women Veterans. VA administrative data identified the site for each respondent's primary care. Facility data identified the site's primary care model for women. We conducted multilevel modeling to compare health care ratings for sites serving 300 or more women veterans who had adopted VA recommendations for women's primary care models (adopter sites), with non-adopter sites, and with small sites serving fewer women veterans, adjusting for patient characteristics. Results: Adopter sites received higher adjusted ratings of gender-related satisfaction and perceptions of VA provider skills than non-adopter and small sites. Adopter sites also received higher adjusted ratings of gender appropriateness than small sites. Adjusted ratings of quality of care did not differ by type of site. Conclusion: VA sites with primary care models tailored to women were rated higher on most dimensions of care. Facilitating establishment of these optimal care models at other sites is one strategy for improving women veterans' experiences with VA care. Research to identify other features of care associated with quality could inform ongoing VA quality transformation efforts. Published by Elsevier Inc. C1 [Washington, Donna L.; Bean-Mayberry, Bevanne; Mitchell, Michael N.; Riopelle, Deborah; Yano, Elizabeth M.] VA Greater Los Angeles Hlth Serv Res & Dev HSR&D, Ctr Excellence, Sepulveda, CA USA. [Washington, Donna L.; Bean-Mayberry, Bevanne] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. [Yano, Elizabeth M.] UCLA Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA USA. RP Washington, DL (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,111G, Los Angeles, CA 90073 USA. EM donna.washington@va.gov NR 32 TC 20 Z9 20 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD JUL-AUG PY 2011 VL 21 IS 4 SU S SI SI BP S112 EP S119 DI 10.1016/j.whi.2011.04.004 PG 8 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 792YA UT WOS:000292785100009 PM 21724130 ER PT J AU Yano, EM Bastian, LA Bean-Mayberry, B Eisen, S Frayne, S Hayes, P Klap, R Lipson, L Mattocks, K McGlynn, G Sadler, A Schnurr, P Washington, DL AF Yano, Elizabeth M. Bastian, Lori A. Bean-Mayberry, Bevanne Eisen, Seth Frayne, Susan Hayes, Patricia Klap, Ruth Lipson, Linda Mattocks, Kristin McGlynn, Geraldine Sadler, Anne Schnurr, Paula Washington, Donna L. TI Using Research to Transform Care for Women Veterans: Advancing the Research Agenda and Enhancing Research-Clinical Partnerships SO WOMENS HEALTH ISSUES LA English DT Article ID AFFAIRS HEALTH-CARE; INSTITUTES-OF-HEALTH; PATIENT SATISFACTION; QUALITY; SYSTEM; GENDER; FEMALE AB The purpose of this paper is to report on the outcomes of the 2010 VA Women's Health Services Research Conference, which brought together investigators interested in pursuing research on women veterans and women in the military with leaders in women's health care delivery and policy within and outside the VA, to significantly advance the state and future direction of VA women's health research and its potential impacts on practice and policy. Building on priorities assembled in the previous VA research agenda (2004) and the research conducted in the intervening six years, we used an array of approaches to foster research-clinical partnerships that integrated the state-of-the-science with the informational and strategic needs of senior policy and practice leaders. With demonstrated leadership commitment and support, broad field-based participation, strong interagency collaboration and a push to accelerate the move from observational to interventional and implementation research, the Conference provided a vital venue for establishing the foundation for a new research agenda. In this paper, we provide the historical evolution of the emergence of women veterans' health services research and an overview of the research in the intervening years since the first VA women's health research agenda. We then present the resulting VA Women's Health Research Agenda priorities and supporting activities designed to transform care for women veterans in six broad areas of study, including access to care and rural health; primary care and prevention; mental health; post deployment health; complex chronic conditions, aging and long-term care; and reproductive health. Published by Elsevier Inc. C1 [Yano, Elizabeth M.; Bean-Mayberry, Bevanne; Klap, Ruth; Washington, Donna L.] VA Greater Los Angeles HSR&D Ctr Excellence, Study Healthcare Provider Behav, Los Angeles, CA USA. [Yano, Elizabeth M.; Klap, Ruth] VA Greater Los Angeles Healthcare Syst, VA Womens Hlth Res Consortium, Sepulveda, CA USA. [Yano, Elizabeth M.] UCLA Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA USA. [Yano, Elizabeth M.; Bastian, Lori A.; Bean-Mayberry, Bevanne; Frayne, Susan] Women Vet Practice Based Res Network, Iowa City, IA USA. [Bastian, Lori A.] Durham VA Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC USA. [Bastian, Lori A.] Duke Univ, Med Ctr, Div Gen Internal Med, Durham, NC 27710 USA. [Bean-Mayberry, Bevanne] VA Greater Los Angeles Healthcare Syst, Comprehens Womens Hlth Ctr, Sepulveda, CA USA. [Bean-Mayberry, Bevanne; Washington, Donna L.] VA Greater Angeles Healthcare Syst, Div Gen Internal Med, Los Angeles, CA USA. [Bean-Mayberry, Bevanne; Washington, Donna L.] UCLA Sch Med, Los Angeles, CA USA. [Eisen, Seth; Lipson, Linda] Vet Hlth Adm, VA HSR&D Serv, VA Cent Off, Washington, DC USA. [Frayne, Susan] VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, Palo Alto, CA USA. [Frayne, Susan] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA. [Hayes, Patricia] Vet Hlth Adm, Women Vet Hlth Strateg Hlth Care Grp, Off Patient Care Serv, Washington, DC USA. [Mattocks, Kristin] W Haven VA Med Ctr, West Haven, CT USA. [Mattocks, Kristin] Yale Univ, Sch Publ Hlth, New Haven, CT USA. [McGlynn, Geraldine] Ctr Informat Disseminat & Educ Resources, Boston, MA USA. [Sadler, Anne] Iowa City VA, CRIISP, Iowa City, IA USA. [Sadler, Anne] Univ Iowa, Coll Nursing, Iowa City, IA 52242 USA. [Schnurr, Paula] White River Junct VA Med Ctr, Natl Ctr Posttraumat Stress Disorder PTSD, White River Jct, VT USA. [Schnurr, Paula] Dartmouth Coll, Dept Psychiat, Hanover, NH USA. [Washington, Donna L.] VA Greater Los Angeles Healthcare Syst, Comprehens Womens Hlth Ctr, Los Angeles, CA USA. RP Yano, EM (reprint author), VA Greater Los Angeles HSR&D Ctr Excellence, 16111 Plummer St,Mailcode 152, Sepulveda, CA 91343 USA. EM elizabeth.yano@va.gov NR 41 TC 29 Z9 29 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD JUL-AUG PY 2011 VL 21 IS 4 SU S SI SI BP S73 EP S83 DI 10.1016/j.whi.2011.04.002 PG 11 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 792YA UT WOS:000292785100005 PM 21724148 ER PT J AU Yano, EM Frayne, SM AF Yano, Elizabeth M. Frayne, Susan M. TI Health and Health Care of Women Veterans and Women in the Military: Research Informing Evidence-Based Practice and Policy SO WOMENS HEALTH ISSUES LA English DT Editorial Material C1 [Yano, Elizabeth M.; Frayne, Susan M.] VA Womens Hlth Res Network, Los Angeles, CA USA. [Yano, Elizabeth M.; Frayne, Susan M.] VA Womens Hlth Res Network, Palo Alto, CA USA. [Yano, Elizabeth M.] UCLA Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA USA. [Frayne, Susan M.] VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, Palo Alto, CA USA. [Frayne, Susan M.] Stanford Univ, Div Gen Med Disciplines, Stanford, CA 94305 USA. [Yano, Elizabeth M.] VA Greater Los Angeles HSR&D Ctr Excellence, Study Healthcare Provider Behav, Sepulveda, CA 91343 USA. RP Yano, EM (reprint author), VA Greater Los Angeles HSR&D Ctr Excellence, Study Healthcare Provider Behav, 16111 Plummer St,Mailcode 152, Sepulveda, CA 91343 USA. EM elizabeth.yano@va.gov NR 8 TC 1 Z9 1 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD JUL-AUG PY 2011 VL 21 IS 4 SU S SI SI BP S64 EP S66 DI 10.1016/j.whi.2011.04.030 PG 3 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 792YA UT WOS:000292785100002 PM 21724145 ER PT J AU Yee, EFT White, R Lee, SJ Washington, DL Yano, EM Murata, G Handanos, C Hoffman, RM AF Yee, Ellen F. T. White, Robert Lee, Sang-Joon Washington, Donna L. Yano, Elizabeth M. Murata, Glen Handanos, Christine Hoffman, Richard M. TI Mental Illness: Is there an Association With Cancer Screening Among Women Veterans? SO WOMENS HEALTH ISSUES LA English DT Article ID INTEGRATED MEDICAL-CARE; COLORECTAL-CANCER; HEALTH-CARE; CERVICAL-CANCER; UNITED-STATES; PREVENTIVE SERVICES; BREAST; QUALITY; ACCESS; MAMMOGRAPHY AB Purpose: Mental illness may be a barrier to achieving timely and appropriate cancer screening. We evaluated the association of mental illness with receipt of and adherence to breast, cervical, and colorectal cancer screening among women Veterans. Methods: The study population included all female Veterans ages 50 to 65 who obtained care at the New Mexico VA Health Care System continuously from fiscal years 2004 to 2006 (n = 606). Measures were odds ratios (OR) for receipt of any cancer screening, and adherence to recommended cancer screening frequency, adjusted for age, insurance, service connection, and primary care and women's clinic visits. Results: Overall, 53% of the women had a mental health diagnosis (MHD). Women with an MHD were less likely to adhere to recommended breast cancer screening than women without MHD: unadjusted OR (95% CI): 0.73 (0.54-0.98; p < .05), adjusted OR (aOR) (95% CI) 0.60 (0.44-0.82; p < .01). Women with an MHD were as likely as women without MHD to receive any breast, cervical, and colon cancer screening; Respective aORs (95% CI): 0.79 (0.50-1.25); 1.71 (0.91-3.21); and 0.85 (0.56-1.28). Conclusion: Women with a mental illness are at risk for not adhering to recommended routine breast cancer screening, and may require more intensive efforts to achieve optimal rates of recommended breast cancer screening. Published by Elsevier Inc. C1 [Yee, Ellen F. T.; Murata, Glen; Hoffman, Richard M.] Univ New Mexico, Sch Med, Dept Med, New Mexico VA Hlth Care Syst, Albuquerque, NM 87131 USA. [White, Robert] ABQ Hlth Partners, Albuquerque, NM USA. [Lee, Sang-Joon] Univ New Mexico, Sch Med, Dept Internal Med, Albuquerque, NM 87131 USA. [Washington, Donna L.; Yano, Elizabeth M.] VA Greater Angeles Hlth Serv Res & Dev, Ctr Excellence, Sepulveda, CA USA. [Washington, Donna L.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Yano, Elizabeth M.] UCLA Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA USA. [Handanos, Christine] So Maine Med Ctr, Biddeford, ME USA. RP Yee, EFT (reprint author), New Mexico VA Hlth Care, 1501 San Pedro Dr SE,MC 111, Albuquerque, NM 87108 USA. EM Ellen.yee2@va.gov NR 57 TC 14 Z9 14 U1 2 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD JUL-AUG PY 2011 VL 21 IS 4 SU S SI SI BP S195 EP S202 DI 10.1016/j.whi.2011.04.027 PG 8 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 792YA UT WOS:000292785100020 PM 21724141 ER PT J AU Berger, JS Bhatt, DL Steg, PG Steinhubl, SR Montalescot, G Shao, MY Hacke, W Fox, KA Berger, PB Topol, EJ Lincoff, AM AF Berger, Jeffrey S. Bhatt, Deepak L. Steg, P. Gabriel Steinhubl, Steven R. Montalescot, Gilles Shao, Mingyuan Hacke, Werner Fox, Keith A. Berger, Peter B. Topol, Eric J. Lincoff, A. Michael CA CHARISMA Investigators TI Bleeding, mortality, and antiplatelet therapy: Results from the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE CORONARY SYNDROMES; ACUTE MYOCARDIAL-INFARCTION; COLLABORATIVE METAANALYSIS; PLATELET INHIBITION; RANDOMIZED-TRIALS; CLINICAL-OUTCOMES; BLOOD-TRANSFUSION; VASCULAR-DISEASE; PREVENTION; ASPIRIN AB Background The association between bleeding severity and cause of mortality in the non-acute setting is unclear. We sought to investigate the association between bleeding and mortality subtype, and assess whether this association differs in patients on dual antiplatelet therapy (DAPT) versus aspirin alone. Methods Using multivariable Cox proportional hazards survival regression, we examined the association between moderate or severe bleeding and all-cause, cardiovascular, and cancer mortality in 15,603 patients with cardiovascular disease or multiple risk factors enrolled in the CHARISMA trial. Results Patients with moderate or severe bleeding had a higher incidence of all-cause, cardiovascular, and cancer mortality (P < .001 for each). After multivariable adjustment, moderate/severe bleeding remained independently associated with not only all-cause mortality (adjusted hazard ratio [HR] 1.66; 95% confidence interval [CI] 1.24-2.21) and cardiovascular mortality (HR 2.05, 95% CI 1.38-3.04) but also cancer mortality (HR 4.76, 95% CI 2.60-8.69). However, there was a significant interaction between bleeding and potency of antiplatelet therapy for all-cause (P = .002), cardiovascular (P = .02), and cancer mortality (P = .03); in subjects on aspirin alone, moderate/severe bleeding was associated with all-cause (HR 5.27, 95% CI 3.56-7.80), cardiovascular (HR 4.33, 95% CI 2.55-7.37), and cancer mortality (HR 9.01, 95% CI 4.41-18.43), but not in subjects on DAPT (all-cause: HR 1.48, 95% CI 0.93-2.34; cardiovascular: HR 1.04, 95% CI 0.58-1.86; and cancer mortality: HR 1.79, 95% CI 0.56-5.74). Conclusions In stable patients, moderate or severe bleeding is associated with a significantly increased risk of all-cause, cardiovascular, and cancer mortality. However, this risk appeared different in subjects on single antiplatelet therapy versus DAPT. (Am Heart J 2011;162:98-105.e1.) C1 [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02132 USA. [Berger, Jeffrey S.] NYU, Sch Med, New York, NY USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA 02132 USA. [Steg, P. Gabriel] Univ Paris 07, INSERM, U698, Paris, France. [Steg, P. Gabriel] AP HP, Paris, France. [Steinhubl, Steven R.; Berger, Peter B.] Geisinger Med Ctr, Danville, PA 17822 USA. [Montalescot, Gilles] Hop La Pitie Salpetriere, AP HP, Inst Cardiol, INSERM 937, Paris, France. [Montalescot, Gilles] Univ Paris 06, Pitie Salpetriere Hosp, Paris, France. [Shao, Mingyuan; Lincoff, A. Michael] Cleveland Clin, Cleveland, OH 44106 USA. [Hacke, Werner] Univ Heidelberg, Heidelberg, Germany. [Fox, Keith A.] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Fox, Keith A.] Royal Infirm Edinburgh NHS Trust, Edinburgh, Midlothian, Scotland. [Topol, Eric J.] Scripps Clin, La Jolla, CA USA. RP Bhatt, DL (reprint author), Brigham & Womens Hosp, VA Boston Healthcare Syst, 1400 VFW Pkwy, Boston, MA 02132 USA. EM dlbhattmd@post.harvard.edu OI Topol, Eric/0000-0002-1478-4729 FU American Heart Association [0775074N]; Astra Zeneca (modest); Bristol-Myers Squibb; Eisai; Sanofi-Aventis; Medicines Company; AstraZeneca; Atherogenics; BristolMyers Squibb; Edwards Lifesciences; Esperion; Johnson Johnson; Kai Pharmaceuticals; Lilly; Medtronic; Novartis; Novo Nordisk; Pfizer; Roche; Sankyo; Schering-Plough; Scios; Takeda; VasoGenix; Geisinger Clinic; Bristol Myers Squibb; Boston Scientific; Centocor; Cordis; Eli-Lilly; Fedration Fran aise de Cardiologie; Fondation de France; Guerbet Medical; INSERM; Sanofi-Aventis Group; Societe Fran aise de Cardiologie; Bayer; Boehringer-Ingelheim; DaichiSankyo; Menarini; MSD; Portola Sanofi-Aventis Group FX Dr Jeffrey Berger was partially funded by an American Heart Association Fellow to Faculty Award (0775074N). The authors are solely responsible for the design and conduct of this study, all study analyses, and the drafting and editing of the paper and its final contents.; Dr Jeffrey Berger has received research support and honoraria for advisory board participation from Astra Zeneca (modest).; Dr Bhatt has received research grants (to the institution) from Astra Zeneca, Bristol-Myers Squibb, Eisai, Sanofi-Aventis, and The Medicines Company.; Dr Lincoff has received research grants (to the institution) from AstraZeneca, Atherogenics, BristolMyers Squibb, Edwards Lifesciences, Esperion, Johnson & Johnson, Kai Pharmaceuticals, Lilly, Medicines Company, Medtronic, Novartis, Novo Nordisk, Pfizer, Roche, Sankyo, Sanofi-Aventis, Schering-Plough, Scios, Takeda, and VasoGenix.; Dr Peter Berger has served as a consultant for AstraZeneca, Boehringer Ingelheim, Eli Lilly/DaiichiSankyo, and Ortho McNeil (each for "modest" honoraria) and has received research funding for Geisinger Clinic for studies on which he is the PI from Thrombovision, Helena, Accumetrics, AstraZeneca, Haemoscope, The Medicines Company, Corgenix/Aspirinworks, and Lilly/Daiichi-Sankyo (all for more than $ 10,000).; Dr Montalescot discloses the following relationships: research grants (to the institution) from Bristol Myers Squibb, Boston Scientific, Centocor, Cordis, Eli-Lilly, Fedration Fran aise de Cardiologie, Fondation de France, Guerbet Medical, INSERM, Medtronic, Pfizer, Sanofi-Aventis Group, Societe Fran aise de Cardiologie; Consulting or Lecture fees from Astra-Zeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, DaichiSankyo, Eisai, Eli-Lilly, Menarini, MSD, Novartis, Portola Sanofi-Aventis Group, Schering-Plough, and The Medicines Company. NR 30 TC 10 Z9 11 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JUL PY 2011 VL 162 IS 1 BP 98 EP U136 DI 10.1016/j.ahj.2011.04.015 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 789UR UT WOS:000292542400023 PM 21742095 ER PT J AU Granholm, E Tate, SR Link, PC Lydecker, KP Cummins, KM McQuaid, J Shriver, C Brown, SA AF Granholm, Eric Tate, Susan R. Link, Peter C. Lydecker, Katherine P. Cummins, Kevin M. McQuaid, John Shriver, Chris Brown, Sandra A. TI Neuropsychological Functioning and Outcomes of Treatment for Co-occurring Depression and Substance Use Disorders SO AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE LA English DT Article DE depression; substance use disorders; cognitive behavioral therapy; neuropsychological impairment ID COGNITIVE IMPAIRMENT; ALCOHOL-USE; 12-STEP FACILITATION; DEPENDENT ADULTS; MAJOR DEPRESSION; DRUG-USE; COMORBIDITY; DRINKING; REPLICATION; MECHANISMS AB Background: We previously published findings from our clinical trial comparing treatment outcomes for substance-dependent veterans with co-occurring depression who received Integrated Cognitive Behavioral Therapy (ICBT) or Twelve-Step Facilitation (TSF) Therapy. Objectives: This study is a secondary analysis that examined whether neuropsychological functioning at baseline moderated substance use and depression outcomes in ICBT relative to TSF. Methods: This study was a randomized clinical trial in which 164 veterans with major depressive disorder and comorbid alcohol, cannabinol, and/or stimulant dependence were randomly assigned to either ICBT or TSF group therapy. A comprehensive neuropsychological test battery was administered at baseline. Results: Contrary to our hypothesis, participants with poor neuropsychological functioning had better substance use outcome in ICBT than in TSF, whereas participants with good neuropsychological functioning had comparable substance use outcomes in TSF and ICBT by 18-month follow-up. Depression outcomes, in contrast, were not moderated by neuropsychological functioning by 18-month follow-up. Conclusions and Scientific Significance: The substance use outcomes may suggest that substance-dependent depressed adults with poorer neuropsychological functioning should be offered ICBT over TSF. These individuals may be less able to develop and use novel coping skills for managing substance use and depressive symptoms on their own without formal structured training in cognitive and behavioral skills provided in ICBT. C1 [Granholm, Eric; Tate, Susan R.; Link, Peter C.] VA San Diego Healthcare Syst, San Diego, CA 92161 USA. [Granholm, Eric; Tate, Susan R.; Cummins, Kevin M.; Brown, Sandra A.] Univ Calif San Diego, Dept Psychol, San Diego, CA 92161 USA. [Lydecker, Katherine P.] San Diego State Univ, San Diego Joint Doctoral Program Clin Psychol, San Diego, CA 92182 USA. [McQuaid, John] San Francisco VA Med Ctr, San Francisco, CA USA. [McQuaid, John] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Shriver, Chris] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92161 USA. RP Tate, SR (reprint author), VA San Diego Healthcare Syst, 3350 La Jolla Village Dr 116B, San Diego, CA 92161 USA. EM srtate@ucsd.edu RI Granholm, Eric/P-7680-2014 NR 45 TC 4 Z9 4 U1 1 U2 7 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0095-2990 J9 AM J DRUG ALCOHOL AB JI Am. J. Drug Alcohol Abuse PD JUL PY 2011 VL 37 IS 4 BP 240 EP 249 DI 10.3109/00952990.2011.570829 PG 10 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 791VO UT WOS:000292695600006 PM 21517712 ER PT J AU Day, LW Walter, LC Velayos, F AF Day, Lukejohn W. Walter, Louise C. Velayos, Fernando TI Colorectal Cancer Screening and Surveillance in the Elderly Patient SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Review ID ORAL SODIUM-PHOSPHATE; ELECTROLYTE LAVAGE SOLUTION; SERVICES TASK-FORCE; SINGLE-BLIND TRIAL; AGED 80 YEARS; POLYETHYLENE-GLYCOL; BOWEL PREPARATION; COLONOSCOPIC PERFORATIONS; CURATIVE RESECTION; RADICAL SURGERY AB Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in the United States. Older age is associated with a rise in colorectal cancer and adenomas, necessitating the need for CRC screening in older patients. However, decisions about CRC screening and surveillance in older adults are often difficult and challenging. The decision requires an individualized assessment that incorporates factors unique to performing colonoscopy in older adults in order to weigh the risks and benefits for each patient according to their overall health and preferences. This review addresses the factors unique to colorectal cancer and performing colonoscopy in older adults that are relevant in weighing the risks and benefits of screening and surveillance in this population. C1 [Day, Lukejohn W.] San Francisco Gen Hosp, Div Gastroenterol, San Francisco, CA 94110 USA. [Day, Lukejohn W.] Univ Calif San Francisco, Dept Med, GI Hlth Outcomes Policy & Econ HOPE Res Program, San Francisco, CA USA. [Walter, Louise C.] San Francisco VA Med Ctr, Div Geriatr, San Francisco, CA USA. [Velayos, Fernando] Univ Calif San Francisco, Dept Med, Div Gastroenterol, San Francisco, CA USA. RP Day, LW (reprint author), San Francisco Gen Hosp, Div Gastroenterol, 1001 Potrero Ave,3D-5, San Francisco, CA 94110 USA. EM lukejohn.day@ucsf.edu FU NIH UCSF-CTSI [KL2 RR024130]; VA Health Services Research and Development [IIR-04-427]; National Cancer Institute [1R01CA134425] FX F.V. was supported in part by NIH UCSF-CTSI Grant number KL2 RR024130. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. L. C. W. was supported by a VA Health Services Research and Development Grant IIR-04-427 and by Grant 1R01CA134425 from the National Cancer Institute. NR 117 TC 19 Z9 21 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD JUL PY 2011 VL 106 IS 7 BP 1197 EP 1206 DI 10.1038/ajg.2011.128 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 789JG UT WOS:000292511100004 PM 21519362 ER PT J AU Sproul, A Steele, SL Thai, TL Yu, SP Klein, JD Sands, JM Bell, PD AF Sproul, Adrian Steele, Stacy L. Thai, Tiffany L. Yu, ShanPing Klein, Janet D. Sands, Jeff M. Bell, P. Darwin TI N-methyl-D-aspartate receptor subunit NR3a expression and function in principal cells of the collecting duct SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE cytosolic calcium; aquaporin 2; medullary tonicity ID NR3A-CONTAINING NMDA RECEPTORS; PROTEIN PHOSPHATASE 2A; NONMUSCLE MYOSIN-II; RAT-KIDNEY; DEVELOPMENTAL REGULATION; DIABETES-INSIPIDUS; UP-REGULATION; MICE LACKING; VASOPRESSIN; IDENTIFICATION AB Sproul A, Steele SL, Thai TL, Yu S, Klein JD, Sands JM, Bell PD. N-methyl-D-aspartate receptor subunit NR3a expression and function in principal cells of the collecting duct. Am J Physiol Renal Physiol 301: F44-F54, 2011. First published March 23, 2011; doi: 10.1152/ajprenal.00666.2010.-N-methyl-D-aspartate receptors (NMDARs) are Ca(2+) -permeable, ligand-gated, nonselective cation channels that function as neuronal synaptic receptors but which are also expressed in multiple peripheral tissues. Here, we show for the first time that NMDAR subunits NR3a and NR3b are highly expressed in the neonatal kidney and that there is continued expression of NR3a in the renal medulla and papilla of the adult mouse. NR3a was also expressed in mIMCD-3 cells, where it was found that hypoxia and hypertonicity upregulated NR3a expression. Using short-hairpin (sh) RNA-based knockdown, a stable inner medullary collecting duct (IMCD) cell line was established that had similar to 80% decrease in NR3a. Knockdown cells exhibited an increased basal intracellular calcium concentration, reduced cell proliferation, and increased cell death. In addition, NR3a knockdown cells exhibited reduced water transport in response to the addition of vasopressin, suggesting an alteration in aquaporin-2 (AQP2) expression/function. Consistent with this notion, we demonstrate decreased surface expression of glycosylated AQP2 in IMCD cells transfected with NR3a shRNA. To determine whether this also occurred in vivo, we compared AQP2 levels in wild-type vs. in NR3a(-/-) mice. Total AQP2 protein levels in the outer and inner medulla were significantly reduced in knockout mice compared with control mice. Finally, NR3a(-/-) mice showed a significant delay in their ability to increase urine osmolality during water restriction. Thus NR3a may play a renoprotective role in collecting duct cells. Therefore, under conditions that are associated with high vasopressin levels, NR3a, by maintaining low intracellular calcium levels, protects the function of the principal cells to reabsorb water and thereby increase medullary osmolality. C1 [Sproul, Adrian; Steele, Stacy L.; Bell, P. Darwin] Med Univ S Carolina, Dept Med, Charleston, SC 29403 USA. [Steele, Stacy L.; Bell, P. Darwin] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Thai, Tiffany L.; Klein, Janet D.; Sands, Jeff M.] Emory Univ, Dept Med, Atlanta, GA 30322 USA. [Yu, ShanPing] Emory Univ, Dept Anesthesiol, Atlanta, GA 30322 USA. RP Bell, PD (reprint author), Med Univ S Carolina, Dept Med, 173 Ashley Ave,210 CRI, Charleston, SC 29403 USA. EM Bellpd@musc.edu FU Veterans Affairs Merit Award; National Institutes of Health (NIH) [DK32032, P30 DK074038]; National Center for Research Resources FX This work was supported by a Veterans Affairs Merit Award (P. D. Bell) and National Institutes of Health (NIH) Grants DK32032 (P. D. Bell) and P30 DK074038 (P. D. Bell; UAB Core Center, Lisa Guay-Woodford, PI). This work was conducted in a facility constructed with NIH support (Grant C06 RR015455 from the Extramural Research Facilities Program of the National Center for Research Resources). NR 49 TC 14 Z9 14 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JUL PY 2011 VL 301 IS 1 BP F44 EP F54 DI 10.1152/ajprenal.00666.2010 PG 11 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 791CY UT WOS:000292641000009 PM 21429969 ER PT J AU Allison, GM Rogers, KA Borad, A Ahmed, S Karim, MM Kane, AV Hibberd, PL Naumova, EN Calderwood, SB Ryan, ET Khan, WA Ward, HD AF Allison, Geneve M. Rogers, Kathleen A. Borad, Anoli Ahmed, Sabeena Karim, Mohammad Mahbubul Kane, Anne V. Hibberd, Patricia L. Naumova, Elena N. Calderwood, Stephen B. Ryan, Edward T. Khan, Wasif A. Ward, Honorine D. TI Antibody Responses to the Immunodominant Cryptosporidium gp15 Antigen and gp15 Polymorphisms in a Case-Control Study of Cryptosporidiosis in Children in Bangladesh SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID CHILDHOOD DIARRHEA; PERUVIAN CHILDREN; 17-KDA ANTIGEN; PARVUM; INFECTION; OUTBREAK; CLONING; GENE; EPIDEMIOLOGY; ASSOCIATION AB Although Cryptospridium hominis is the dominant Cryptosporidium species infecting humans, immune responses to cognate antigens in C. hominis-infected persons have not been reported. We investigated antibody responses to the immunodominant gp15 antigen from C. hominis and C. parvum, in C. hominis-infected Bangladeshi children less than five years of age with diarrhea (cases) and uninfected children with diarrhea (controls). We also investigated polymorphisms in the C. hominis gp15 sequence from cases. Serum IgG responses to gp15 from both species were significantly greater in cases than controls. In spite of polymorphisms in the gp15 sequence, there was a significant correlation between antibody levels to gp15 from both species, indicating cross-reactivity to conserved epitopes. Cases with acute diarrhea had a significantly greater serum IgA response to gp15 compared with those with persistent diarrhea, suggesting that this response may be associated with protection from prolonged disease. These findings support further investigation of gp15 as a vaccine candidate. C1 Tufts Univ, Sch Med, Dept Publ Hlth & Community Med, Boston, MA 02111 USA. Int Ctr Diarrheal Dis Res, Ctr Hlth & Populat Res, Div Clin Sci, Dhaka, Bangladesh. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Ward, HD (reprint author), Tufts Med Ctr, Div Geog Med & Infect Dis, Box 041,800 Washington St, Boston, MA 02111 USA. EM hward@tuftsmedicalcenter.org OI Naumova, Elena/0000-0002-9562-4734 FU National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH) [UO1 AI45508, U01 AI058935, RO1 AI52786, T32 AI07389, T32 AI007438]; National Center for Complementary and Alternative Medicine, NIH [K24 AT003683] FX This study was supported by an opportunity pool grant and in part by grants UO1 AI45508, U01 AI058935, and RO1 AI52786, all from the National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH) and K24 AT003683 from the National Center for Complementary and Alternative Medicine, NIH. Geneve M. Allison and Kathleen Rogers were supported by T32 AI07389, and Anoli Borad was supported by T32 AI007438 from the National Institute of Allergy and Infectious Diseases, NIH. NR 38 TC 10 Z9 11 U1 0 U2 4 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD JUL PY 2011 VL 85 IS 1 BP 97 EP 104 DI 10.4269/ajtmh.2011.11-0043 PG 8 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 788GK UT WOS:000292433200018 PM 21734132 ER PT J AU Wachman, EM Lahav, A AF Wachman, Elisha M. Lahav, Amir TI The effects of noise on preterm infants in the NICU SO ARCHIVES OF DISEASE IN CHILDHOOD-FETAL AND NEONATAL EDITION LA English DT Article ID LOW-BIRTH-WEIGHT; INTENSIVE-CARE; AUDITORY-STIMULATION; PREMATURE-INFANTS; NEWBORN; RESPONSES; OTOTOXICITY; CHILDREN; HEARING; SOUND AB Preterm infants in the neonatal intensive care unit (NICU) are constantly exposed to ambient noise that often exceeds recommended levels. There is a growing concern that such noise puts preterm infants at high risk for adverse health effects. This review looks at the effects of NICU noise on the cardiovascular, respiratory, auditory and nervous systems. Loud transient noise has negative short-term effects on the cardiovascular and respiratory systems of preterm infants, although direct evidence linking noise to neonatal pathology is still unclear. Further controlled trials with larger sample sizes are needed to determine the effects of more extensive exposure to NICU noise on early brain maturation and long-term developmental outcomes. C1 [Wachman, Elisha M.; Lahav, Amir] Brigham & Womens Hosp, Dept Newborn Med, CWN, Boston, MA 02115 USA. [Lahav, Amir] Harvard Univ, Sch Med, Dept Pediat, MassGen Hosp Children, Boston, MA 02115 USA. RP Lahav, A (reprint author), Brigham & Womens Hosp, Dept Newborn Med, CWN, 418,75 Francis St, Boston, MA 02115 USA. EM amir_lahav@hms.harvard.edu FU Department of Newborn Medicine at Brigham; Women's Hospital, Boston, Massachusetts, USA FX The authors gratefully acknowledge the support of the Department of Newborn Medicine at Brigham and Women's Hospital, Boston, Massachusetts, USA. NR 40 TC 30 Z9 31 U1 0 U2 14 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1359-2998 J9 ARCH DIS CHILD-FETAL JI Arch. Dis. Child.-Fetal Neonatal Ed. PD JUL PY 2011 VL 96 IS 4 BP F305 EP F309 DI 10.1136/adc.2009.182014 PG 5 WC Pediatrics SC Pediatrics GA 792KN UT WOS:000292743500020 PM 20547580 ER PT J AU Weintraub, D Chen, PJ Ignacio, RV Mamikonyan, E Kales, HC AF Weintraub, Daniel Chen, Peijun Ignacio, Rosalinda V. Mamikonyan, Eugenia Kales, Helen C. TI Patterns and Trends in Antipsychotic Prescribing for Parkinson Disease Psychosis SO ARCHIVES OF NEUROLOGY LA English DT Article ID DRUG-INDUCED PSYCHOSIS; NURSING-HOME PLACEMENT; ATYPICAL ANTIPSYCHOTICS; ELDERLY USERS; OLDER-ADULTS; DOUBLE-BLIND; LEWY BODIES; DEMENTIA; RISK; POPULATION AB Background: Antipsychotic (AP) use is common in Parkinson disease (PD), but APs can worsen parkinsonism, evidence for efficacy is limited, and use in patients with dementia increases mortality. Objective: To examine the frequency and characteristics, including changes over time, of AP use in a large cohort of patients with PD. Design: Using Veterans Affairs data from fiscal year (FY) 2008, rates and predictors of AP prescribing were determined for patients with PD and psychosis stratified by dementia status (N = 2597) and a comparison group of patients with dementia and psychosis without PD (N = 6907). Fiscal year 2008 and FY2002 data were compared to examine changes in AP prescribing over time. Setting: Department of Veterans Affairs outpatient facilities. Participants: Outpatients with PD and psychosis and outpatients without PD with dementia and psychosis, all receiving care at Veterans Affairs facilities in FY2002 and FY2008. Main Outcome Measure: Antipsychotic prescribing, including overall, class, and specific medications. Results: In FY2008, 50% of patients with PD having a diagnosis of psychosis were prescribed an AP. Among treated patients, the atypical AP quetiapine was most frequently prescribed (66%), but approximately 30% received high-potency APs. Clozapine was rarely prescribed (<2%). In multivariate models, diagnoses of PD and dementia were associated with AP use. Comparing FY2008 with FY2002, AP use in PD was unchanged, with decreases in risperidone and olanzapine use offset by an increase in quetiapine prescribing and the introduction of aripiprazole. Conclusions: Half of the patients with PD and psychosis receive APs, not uncommonly high-potency agents associated with worsening parkinsonism, and frequency of use has been unchanged since the "black box" warning for AP use in patients with dementia was issued. Recent trends are a shift to quetiapine use and the common use of aripiprazole. As psychosis and dementia are frequently comorbid in PD, safety risks associated with AP use in this population need to be assessed. C1 [Weintraub, Daniel; Mamikonyan, Eugenia] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Mental Illness Ctr, Philadelphia, PA USA. [Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA USA. [Chen, Peijun] Cleveland Vet Affairs Med Ctr, Psychiat Serv, Cleveland, OH USA. [Chen, Peijun] Case Western Reserve Univ, Dept Psychiat, Cleveland, OH 44106 USA. [Ignacio, Rosalinda V.; Kales, Helen C.] Univ Michigan, Natl Vet Affairs Serious Mental Illness Treatment, VA Ann Arbor Healthcare Syst, Ann Arbor, MI 48109 USA. [Ignacio, Rosalinda V.; Kales, Helen C.] Univ Michigan, Mental Hlth Serv Outcomes & Translat Sect, Ann Arbor, MI 48109 USA. [Kales, Helen C.] Univ Michigan, Dept Psychiat, Geriatr Psychiat Sect, Ann Arbor, MI 48109 USA. RP Weintraub, D (reprint author), Univ Penn, Dept Psychiat, 3615 Chestnut St,Room 330, Philadelphia, PA 19104 USA. EM daniel.weintraub@uphs.upenn.edu FU National Institute of Mental Health [K23 MH067894, R01 MH081070] FX This research was supported by grants K23 MH067894 (Dr Weintraub) and R01 MH081070 (Dr Kales) from the National Institute of Mental Health. Online-Only Material: The eTable is available at http://www.archneurol.com. NR 41 TC 41 Z9 41 U1 1 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JUL PY 2011 VL 68 IS 7 BP 899 EP 904 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 790QG UT WOS:000292603700008 PM 21747029 ER PT J AU Schlosser, RJ Harvey, RJ AF Schlosser, Rodney J. Harvey, Richard J. TI Untitled SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Editorial Material ID ENDOSCOPIC SINUS SURGERY; EDUCATIONAL INTERVENTION; CHRONIC RHINOSINUSITIS; PARANASAL SINUSES; FACIAL GROWTH; CHILDREN; ADENOIDECTOMY; MANAGEMENT; EFFICACY; BIOFILMS C1 [Schlosser, Rodney J.] Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA. [Schlosser, Rodney J.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Harvey, Richard J.] St Vincents Hosp, Dept Otolaryngol & Skull Base Surg, Sydney, NSW 2010, Australia. RP Schlosser, RJ (reprint author), Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, 135 Rutledge Ave,Ste 1130,POB 250550, Charleston, SC 29425 USA. EM schlossr@musc.edu NR 28 TC 0 Z9 0 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0886-4470 EI 1538-361X J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD JUL PY 2011 VL 137 IS 7 BP 702 EP 704 PG 3 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 793GL UT WOS:000292808300010 PM 21768417 ER PT J AU Braunstein, LZ Lin, HW Faquin, WC Fay, A Gray, ST AF Braunstein, Lior Z. Lin, Harrison W. Faquin, William C. Fay, Aaron Gray, Stacey T. TI Pathology Quiz Case 2 Wegener granulomatosis (WG) of the orbit SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Editorial Material ID RITUXIMAB; CYCLOPHOSPHAMIDE; VASCULITIS C1 [Braunstein, Lior Z.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Lin, Harrison W.; Faquin, William C.; Fay, Aaron; Gray, Stacey T.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Faquin, William C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Braunstein, LZ (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD JUL PY 2011 VL 137 IS 7 BP 724 EP + PG 3 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 793GL UT WOS:000292808300019 PM 21768424 ER PT J AU Guo, DP Bergmark, RWJ Lin, HW Faquin, WC Frankenthaler, RA AF Guo, David P. Bergmark, Regan W. J. Lin, Harrison W. Faquin, William C. Frankenthaler, Robert A. TI Pathology Quiz Case 3 Atypical fibroxanthoma (AFX) SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Editorial Material ID MOHS MICROGRAPHIC SURGERY; HEAD; NECK C1 [Guo, David P.; Bergmark, Regan W. J.; Lin, Harrison W.; Frankenthaler, Robert A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Lin, Harrison W.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Faquin, William C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Frankenthaler, Robert A.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Guo, DP (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 10 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD JUL PY 2011 VL 137 IS 7 BP 725 EP + PG 2 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 793GL UT WOS:000292808300020 PM 21768425 ER PT J AU Folmer, RL AF Folmer, Robert L. TI Repetitive Transcranial Magnetic Stimulation for Tinnitus SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Letter ID RTMS C1 [Folmer, Robert L.] Portland VA Med Ctr, Natl Ctr Rehabil Auditory Res, Portland, OR 97239 USA. [Folmer, Robert L.] Oregon Hlth & Sci Univ, Dept Otolaryngol, Portland, OR 97201 USA. RP Folmer, RL (reprint author), Portland VA Med Ctr, Natl Ctr Rehabil Auditory Res, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM Robert.Folmer@va.gov NR 5 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD JUL PY 2011 VL 137 IS 7 BP 730 EP 730 PG 1 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 793GL UT WOS:000292808300021 PM 21768426 ER PT J AU Gross, KD Felson, DT Niu, JB Hunter, DJ Guermazi, A Roemer, FW Dufour, AB Gensure, RH Hannan, MT AF Gross, K. Douglas Felson, David T. Niu, Jingbo Hunter, David J. Guermazi, Ali Roemer, Frank W. Dufour, Alyssa B. Gensure, Rebekah H. Hannan, Marian T. TI Association of Flat Feet With Knee Pain and Cartilage Damage in Older Adults SO ARTHRITIS CARE & RESEARCH LA English DT Article ID ARCH HEIGHT; OSTEOARTHRITIS; FOOT; ALIGNMENT; PROGRESSION; KINEMATICS; REARFOOT; WALKING; JOINT; RUNNERS AB Objective. To assess the cross-sectional relation of planus foot morphology to ipsilateral knee pain and compartment-specific knee cartilage damage in older adults. Methods. In the Framingham Studies, we adapted the Staheli Arch Index (SAI) to quantify standing foot morphology from pedobarographic recordings. We inquired about knee pain and read 1.5 T magnetic resonance image (MRI) scans using the Whole-Organ MRI Score. Logistic regression compared the odds of knee pain among the most planus feet to the odds among all other feet, and estimated odds within categories of increasing SAL Similar methods estimated the odds of cartilage damage in each knee compartment. Generalized estimating equations adjusted for age, sex, body mass index, and nonindependent observations. Results. Among 1,903 participants (56% women, mean +/- SD age 65 +/- 9 years), 22% of knees were painful most days. Cartilage damage was identified in 45% of medial tibiofemoral (TF), 27% of lateral TF, 58% of medial patellofemoral (1311, and 42% of lateral PF compartments. Compared with other feet, the most planus feet had 1.3 times (95% confidence interval [95% CI] 1.1-1.6) the odds of knee pain (P = 0.009), and 1.4 times (95% CI 1.1-1.8) the odds of medial TF cartilage damage (P = 0.002). Odds of pain (P for linear trend = 0.05) and medial TF cartilage damage (P for linear trend = 0.001) increased linearly across categories Of increasing SAI. There was no association between foot morphology and cartilage damage in other knee compartments. Conclusion. Planus foot morphology is associated with frequent knee pain and medial TF cartilage damage in older adults. C1 [Gross, K. Douglas; Felson, David T.; Niu, Jingbo; Guermazi, Ali; Roemer, Frank W.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Gross, K. Douglas] Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. [Hunter, David J.] Univ Sydney, Royal N Shore Hosp, Sydney, NSW 2006, Australia. [Hunter, David J.] Univ Sydney, No Clin Sch, Sydney, NSW 2006, Australia. [Dufour, Alyssa B.; Gensure, Rebekah H.; Hannan, Marian T.] Hebrew SeniorLife, Boston, MA USA. [Dufour, Alyssa B.; Gensure, Rebekah H.; Hannan, Marian T.] Harvard Univ, Sch Med, Roslindale, MA USA. RP Gross, KD (reprint author), Boston Univ, Sch Med, 650 Albany St,Suite X200, Boston, MA 02118 USA. EM grossd@hu.edu RI Hunter, David/A-4622-2010; OI Hunter, David/0000-0003-3197-752X; Niu, Jingbo/0000-0002-6170-1965; Hannan, Marian/0000-0002-9586-6928; Felson, David/0000-0002-2668-2447; Dufour, Alyssa/0000-0001-8061-9599 FU NIH [AR47785, AG18393, AR47853]; National Heart Lung and Blood Institute of the NIH [N01-HC-25195]; Arthritis Foundation; Stryker; Novartis; Merck Serono; Facet Solutions FX The Framingham Osteoarthritis Study was supported by NIH grants AR47785 and AG18393. and the Framingham Foot Study was supported by NIH grant AR47853. This study was derived from the Framingham Heart Study of the National Heart Lung and Blood Institute of the NIH (contract N01-HC-25195) and Boston University School of Medicine. Dr. Gross's work was supported by a New Investigator Award from the Arthritis Foundation.; Dr. Guermazi received consultancy fees (more than $10.000 each) from Stryker and Novartis, and (less than $10,000 each) from Merck Serono. Facet Solutions. and Genzyme, owns stock and/or holds stock options in Synarc. and is president of Boston Imaging Core Lab, LLC. Dr. Roemer owns stock and/or holds stock options in Boston Imaging Core Lab. LLC. NR 36 TC 25 Z9 27 U1 4 U2 15 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 2151-464X J9 ARTHRIT CARE RES JI Arthritis Care Res. PD JUL PY 2011 VL 63 IS 7 BP 937 EP 944 DI 10.1002/acr.20431 PG 8 WC Rheumatology SC Rheumatology GA 793GU UT WOS:000292809200004 PM 21717597 ER PT J AU Johnson, MR Singh, JA Stewart, T Gioe, TJ AF Johnson, Michael R. Singh, Jasvinder A. Stewart, Thomas Gioe, Terence J. TI Patient Understanding and Satisfaction in Informed Consent for Total Knee Arthroplasty: A Randomized Study SO ARTHRITIS CARE & RESEARCH LA English DT Article ID SURGERY; RECALL AB Objective. Informed consent is a critical component of all surgical procedures, but patients' understanding and recall of the potential risks/benefits is poor. We hypothesized that utilization of multiple standardized education modalities in the informed consent process would allow for better retention and a more informed patient. Methods. A total of 151 patients undergoing primary total knee arthroplasty (TKA) were randomized to 3 groups: group 1 received standardized informed consent and a paper handout detailing the risks/benefits of TKA; group 2 received standardized informed consent, a paper handout, and a video discussing the risks/benefits of TKA; and group 3 followed the same process as group 2 plus formal nurse education. All patients completed a 15-item questionnaire (risks, indications, and expectations) immediately following this consent process on the morning of surgery and 6 weeks postoperatively. We used t-test and analysis of variance for data analyses. Results. There was no difference (P = 0.79) in satisfaction with the consent process between the 3 groups; 92-97% of the patients rated the consent process as good to excellent at all time points. The number of correct answers did not differ significantly between the groups at any time period (P = 0.31-0.81). Scores dropped significantly (P = 0.004) from preoperatively to the 6-week postoperative visit in all groups combined. A higher level of satisfaction with the process was reflected in higher scores preoperatively in all groups (P = 0.028). Conclusion. Preoperatively, patients satisfied with the consent process may have better recall of risks/benefits and expectations of surgery. Neither retention nor satisfaction was influenced by reinforcement methods, such as video or nurse education; they may therefore be unnecessary. C1 [Johnson, Michael R.; Stewart, Thomas; Gioe, Terence J.] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama, Birmingham, AL USA. [Gioe, Terence J.] Minneapolis Vet Affairs Med Ctr, Minneapolis, MN 55417 USA. RP Gioe, TJ (reprint author), Minneapolis Vet Affairs Med Ctr, Sect 112E,1 Vet Dr, Minneapolis, MN 55417 USA. EM tjgioe@gmail.com OI singh, jasvinder/0000-0003-3485-0006 FU Minneapolis VA Medical Center; Birmingham VA Medical Center; URL Pharmaceuticals; Savient; Takeda; Novartis; Abbott; Wyeth; Amgen; Arthritis Foundation; University of Minnesota; Cochrane Library; Department of Veterans Affairs; Allergan; Depuy, Inc. FX Supported by the Minneapolis VA Medical Center and the Birmingham VA Medical Center.; Dr. Singh has received consultant fees, speaking fees. and/or. honoraria (less than $10,000 each) from URL Pharmaceuticals, Savient, Takeda, Novartis, and Abbott; research and travel grants from Takeda, Savient, Wyeth, Amgen, the Arthritis Foundation, University of Minnesota, Cochrane Library, and Department of Veterans Affairs; and investigator-initiator grants from Allergan, Savient, and Takeda. Dr. Gioe has received research support (more than $10,000) from Depuy, Inc. NR 20 TC 11 Z9 11 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 2151-464X J9 ARTHRIT CARE RES JI Arthritis Care Res. PD JUL PY 2011 VL 63 IS 7 BP 1048 EP 1054 DI 10.1002/acr.20475 PG 7 WC Rheumatology SC Rheumatology GA 793GU UT WOS:000292809200017 PM 21485018 ER PT J AU Duailibi, MT Duailibi, SE Neto, EFD Negreiros, RM Jorge, WA Ferreira, LM Vacanti, JP Yelick, PC AF Duailibi, Monica Talarico Duailibi, Silvio Eduardo Duailibi Neto, Eduardo Felippe Negreiros, Renata Matalon Jorge, Waldyr Antonio Ferreira, Lydia Masako Vacanti, Joseph Phillip Yelick, Pamela Crotty TI Tooth Tissue Engineering: Optimal Dental Stem Cell Harvest Based on Tooth Development SO ARTIFICIAL ORGANS LA English DT Article DE Tooth development; Tooth tissue engineering; Human dental stem cells; Human tooth development; Tooth rapid prototyping ID BIOENGINEERED TEETH; CHRONOLOGICAL AGE; INDICATOR; ACCURACY AB Our long-term objective is to devise reliable methods to generate biological replacement teeth exhibiting the physical properties and functions of naturally formed human teeth. Previously, we demonstrated the successful use of tissue engineering approaches to generate small, bioengineered tooth crowns from harvested pig and rat postnatal dental stem cells (DSCs). To facilitate characterizations of human DSCs, we have developed a novel radiographic staging system to accurately correlate human third molar tooth developmental stage with anticipated harvested DSC yield. Our results demonstrated that DSC yields were higher in less developed teeth (Stages 1 and 2), and lower in more developed teeth (Stages 3, 4, and 5). The greatest cell yields and colony-forming units (CFUs) capability was obtained from Stages 1 and 2 tooth dental pulp. We conclude that radiographic developmental staging can be used to accurately assess the utility of harvested human teeth for future dental tissue engineering applications. C1 [Yelick, Pamela Crotty] Tufts Univ, Div Craniofacial & Mol Genet, Dept Oral & Maxillofacial Pathol, Boston, MA 02111 USA. [Duailibi, Monica Talarico; Duailibi, Silvio Eduardo; Ferreira, Lydia Masako] Univ Fed Sao Paulo, Dept Plast Surg, UNIFESP CINTERGEN, Interdisciplinary Ctr Gene Therapy, Sao Paulo, Brazil. [Duailibi, Monica Talarico; Duailibi, Silvio Eduardo] Natl Inst Sci & Technol, INCT Biofabris, Biofabricat Inst, Sao Paulo, Brazil. [Duailibi Neto, Eduardo Felippe; Jorge, Waldyr Antonio] Univ Sao Paulo, Sch Dent, FFO FOUSP, Sao Paulo, Brazil. [Negreiros, Renata Matalon; Jorge, Waldyr Antonio] Univ Sao Paulo, Oral Maxillofacial Surg Course Dent Sch, FFO FOUSP, Sao Paulo, Brazil. [Vacanti, Joseph Phillip] Massachusetts Gen Hosp, Lab Tissue Engn & Organ Fabricat, Boston, MA 02114 USA. [Vacanti, Joseph Phillip] Dept Surg, Boston, MA USA. [Vacanti, Joseph Phillip] Harvard Univ, Sch Med, Boston, MA USA. RP Yelick, PC (reprint author), Tufts Univ, Div Craniofacial & Mol Genet, Dept Oral & Maxillofacial Pathol, 136 Harrison Ave,Room M824, Boston, MA 02111 USA. EM pamela.yelick@tufts.edu RI Ferreira, Lydia/B-7511-2012 FU FAPESP [07-58856-7, 07-51227-4, 07-59488-1]; NIH/NIDCR [R01DE016132, R03TW007665] FX We wish to thank the INCT-Biofabrication Institute, CNPq 573661/2008-1, FAPESP 08/57860-3, and the Rede Biofab, Ibero-American Network of Biofabrication-BIOFABCYTED (208RT0340). We are also grateful to Dr. Israel Chilvarquer, PhD, Associate Professor of Stomatology, University Sao Paulo Dental School, for the tomography images, CTI (Information Technology Center) engineers Drs. Jorge Vicente Lopes da Silva and Gustavo Paschoal for generating CAD/CAM images and tooth scaffolds models and Eliseu Soares for professional photography. This work was supported by FAPESP grants 07-58856-7, 07-51227-4, 07-59488-1, and NIH/NIDCR R01DE016132 (PCY), and R03TW007665 (PCY, MTD, SED) awards. NR 25 TC 5 Z9 5 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0160-564X J9 ARTIF ORGANS JI Artif. Organs PD JUL PY 2011 VL 35 IS 7 BP E129 EP E135 DI 10.1111/j.1525-1594.2010.01200.x PG 7 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA 791FU UT WOS:000292651100002 PM 21702761 ER PT J AU Lombardi, R Nin, N Lorente, JA Frutos-Vivar, F Ferguson, ND Hurtado, J Apezteguia, C Desmery, P Raymondos, K Tomicic, V Cakar, N Gonzalez, M Elizalde, J Nightingale, P Abroug, F Jibaja, M Arabi, Y Moreno, R Matamis, D Anzueto, A Esteban, A AF Lombardi, Raul Nin, Nicolas Lorente, Jose A. Frutos-Vivar, Fernando Ferguson, Niall D. Hurtado, Javier Apezteguia, Carlos Desmery, Pablo Raymondos, Konstantinos Tomicic, Vinko Cakar, Nahit Gonzalez, Marco Elizalde, Jose Nightingale, Peter Abroug, Fekri Jibaja, Manuel Arabi, Yaseen Moreno, Rui Matamis, Dimitros Anzueto, Antonio Esteban, Andres CA VENTILA Grp TI An Assessment of the Acute Kidney Injury Network Creatinine-Based Criteria in Patients Submitted to Mechanical Ventilation SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID ACUTE-RENAL-FAILURE; INTENSIVE-CARE-UNIT; CRITICALLY-ILL PATIENTS; SERUM CREATININE; CARDIOTHORACIC SURGERY; HOSPITALIZED-PATIENTS; RIFLE CRITERIA; MORTALITY; OUTCOMES; CLASSIFICATION AB Background and objectives The aim of our study was to assess the new diagnostic criteria of acute kidney injury (AKI) proposed by the Acute Kidney Injury Network (AKIN) in a large cohort of mechanically ventilated patients. Design, setting, participants, & measurements This is a prospective observational cohort study enrolling 2783 adult intensive care unit patients under mechanical ventilation (MV) with data on serum creatinine concentration (SCr) in the first 48 hours. The absolute and the relative AKIN diagnostic criteria (changes in SCr >= 0.3 mg/dl or >= 50% over the first 48 hours of MV, respectively) were analyzed separately. In addition, patients were classified into three groups according to their change in SCr (Delta SCr) over the first day on MV (Delta SCr): group 1, Delta SCr <= -0.3 mg/dl; group 2, Delta SCr between -0.3 and +0.29 mg/dl; and group 3, Delta SCr >= +0.3 mg/dl). The primary end point was in-hospital mortality, and secondary end points were intensive care unit and hospital length of stay, and duration of MV. Results Of 2783 patients, 803 (28.8%) had AKI according to both criteria: 431 only absolute (AKI(A)), 362 both relative and absolute (AKI(R+A)), and 10 only relative. The relative criterion identified more patients when baseline SCr (SCr(0)) was <0.9 mg/dl and the absolute when SCr(0) was >1.5 mg/dl. The diagnosis of AKI was associated with mortality. Conclusions Our study confirms the validity of the AKIN criteria in a population of mechanically patients and the criteria's relationship with the baseline SCr. Clin J Am Soc Nephrol 6: 1547-1555, 2011. doi: 10.2215/CJN.09531010 C1 [Esteban, Andres] Hosp Univ Getafe, Intens Care Unit, Madrid 28905, Spain. [Lombardi, Raul] Inst Med Previs & Asistencia IMPASA, Montevideo, Uruguay. [Nin, Nicolas; Lorente, Jose A.; Frutos-Vivar, Fernando; Esteban, Andres] Ctr Invest Biomed Red Enfermedades Resp CIBERES, Madrid, Spain. [Ferguson, Niall D.] Univ Toronto, Interdept Div Crit Care Med, Toronto, ON, Canada. [Ferguson, Niall D.] Univ Toronto, Dept Med, Div Respirol, Univ Hlth Network, Toronto, ON, Canada. [Hurtado, Javier] Hosp Espanol, Hosp Clin, Depto Fisiopatol, Montevideo, Uruguay. [Apezteguia, Carlos] Hosp Profesor A Posadas, Buenos Aires, DF, Argentina. [Desmery, Pablo] Sanatorio Mitre, Buenos Aires, DF, Argentina. [Raymondos, Konstantinos] Hannover Med Sch, D-30623 Hannover, Germany. [Tomicic, Vinko] Clin Alemana Santiago, Santiago, Chile. [Cakar, Nahit] Dokuz Eylun Univ, Istanbul, Turkey. [Gonzalez, Marco] Univ Pontificia Bolivariana, Medellin, Colombia. [Gonzalez, Marco] Clin Medellin, Medellin, Colombia. [Elizalde, Jose] Hosp ABC, Mexico City, DF, Mexico. [Nightingale, Peter] Wythenshawe Hosp, Manchester M23 9LT, Lancs, England. [Abroug, Fekri] Fattouma Bourguiba Monastir, Monastir, Tunisia. [Arabi, Yaseen] King Fahad Natl Guard Hosp, Riyadh, Saudi Arabia. [Moreno, Rui] Ctr Hosp Lisboa Cent, EPE, Hosp Santo Antonio Capuchos, Lisbon, Portugal. [Matamis, Dimitros] Papageorgiou Gen Hosp, Thessaloniki, Greece. [Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Anzueto, Antonio] Audie L Murphy Hosp, S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Esteban, A (reprint author), Hosp Univ Getafe, Intens Care Unit, Carretera Toledo Km 12,500, Madrid 28905, Spain. EM aesteban@ucigetafe.com RI Pesenti, Antonio/H-7483-2012; koca, ugur/F-1265-2016; Malbrain, Manu/B-3680-2017; OI CHIUMELLO, DAVIDE ALBERTO/0000-0001-9260-3930; koca, ugur/0000-0002-2949-4265; Malbrain, Manu/0000-0002-1816-5255; Severgnini, Paolo/0000-0001-8027-0059; Frutos-Vivar, Fernando/0000-0002-4648-9636; Ferguson, Niall/0000-0002-6213-5264 FU Instituto de Salud Carlos III, Spain FX This study was supported by CIBERES from Instituto de Salud Carlos III, Spain. The study sponsor had no role in study design, in the collection, analysis, and interpretation of data;, in the writing of the report, nor in the decision to submit the paper for publication. NR 26 TC 13 Z9 14 U1 0 U2 9 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD JUL PY 2011 VL 6 IS 7 BP 1547 EP 1555 DI 10.2215/CJN.09531010 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 790VL UT WOS:000292618300008 PM 21700822 ER PT J AU Dalrymple, LS Mohammed, SM Mu, Y Johansen, KL Chertow, GM Grimes, B Kaysen, GA Nguyen, DV AF Dalrymple, Lorien S. Mohammed, Sandra M. Mu, Yi Johansen, Kirsten L. Chertow, Glenn M. Grimes, Barbara Kaysen, George A. Nguyen, Danh V. TI Risk of Cardiovascular Events after Infection-Related Hospitalizations in Older Patients on Dialysis SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CORONARY-ARTERY-DISEASE; CASE SERIES; INFLAMMATION; SEPTICEMIA; STROKE; SYSTEM AB Background and objectives Infection and cardiovascular disease are leading causes of hospitalization and death in patients on dialysis. The objective of this study was to determine whether an infection-related hospitalization increased the short-term risk of a cardiovascular event in older patients on dialysis. Design, setting, participants, & measurements With use of the United States Renal Data System, patients aged 65 to 100 years who started dialysis between January 1, 2000, and December 31, 2002, were examined. All hospitalizations were examined from study entry until time of transplant, death, or December 31, 2004. All discharge diagnoses were examined to determine if an infection occurred during hospitalization. Only principal discharge diagnoses were examined to ascertain cardiovascular events of interest. We used the self-controlled case-series method to estimate the relative incidence of a cardiovascular event within 90 days after an infection-related hospitalization as compared with other times not within 90 days of such a hospitalization. Results A total of 16,874 patients had at least one cardiovascular event and were included in the self-controlled case-series analysis. The risk of a cardiovascular event was increased by 25% in the first 30 days after an infection and was overall increased 18% in the 90 days after an infection-related hospitalization relative to control periods. Conclusions The first 90 days, and in particular the first 30 days, after an infection-related hospitalization is a high-risk period for cardiovascular events and may be an important timeframe for cardiovascular risk reduction, monitoring, and intervention in older patients on dialysis. Clin J Am Soc Nephrol 6: 1708-1713, 2011. doi: 10.2215/CJN.10151110 C1 [Dalrymple, Lorien S.] Univ Calif Davis, Div Nephrol, Dept Med, Sacramento, CA 95817 USA. [Mohammed, Sandra M.; Mu, Yi; Nguyen, Danh V.] Univ Calif Davis, Dept Publ Hlth Sci, Sacramento, CA 95817 USA. [Kaysen, George A.] Univ Calif Davis, Dept Biochem & Mol Med, Sacramento, CA 95817 USA. [Johansen, Kirsten L.] San Francisco VA Med Ctr, San Francisco, CA USA. [Johansen, Kirsten L.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Johansen, Kirsten L.; Grimes, Barbara] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Johansen, Kirsten L.; Chertow, Glenn M.; Grimes, Barbara] US Renal Data Syst Nutr Special Studies Ctr, San Francisco, CA USA. [Chertow, Glenn M.] Stanford Univ, Sch Med, Dept Med, Palo Alto, CA 94304 USA. [Kaysen, George A.] Dept Vet Affairs Mather, Sacramento, CA USA. RP Dalrymple, LS (reprint author), Univ Calif Davis, Div Nephrol, Dept Med, 4150 5 St,Suite 3500, Sacramento, CA 95817 USA. EM Lorien.Dalrymple@ucdmc.ucdavis.edu FU National Center for Research Resources (NCRR) [UL1 RR024146]; National Institutes of Diabetes and Digestive and Kidney Diseases [N01-DK-7-0005] FX This publication was made possible by Grant UL1 RR024146 from the National Center for Research Resources (NCRR) and Contract N01-DK-7-0005 from the National Institutes of Diabetes and Digestive and Kidney Diseases. NR 13 TC 17 Z9 17 U1 0 U2 2 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD JUL PY 2011 VL 6 IS 7 BP 1708 EP 1713 DI 10.2215/CJN.10151110 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 790VL UT WOS:000292618300027 PM 21566109 ER PT J AU Roberts, LW Warner, TD Smithpeter, M Rogers, M Horwitz, R AF Roberts, Laura Weiss Warner, Teddy D. Smithpeter, Megan Rogers, Melinda Horwitz, Russell TI Medical students as patients: implications of their dual role as explored in a vignette-based survey study of 1027 medical students at nine medical schools SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID PERSONAL HEALTH-CARE; ACADEMIC PSYCHIATRY; PROMOTION PROGRAMS; RESIDENTS; SERVICES; SEEKING; DOCTORS AB Objective: Medical students experience a range of mental and physical illnesses during training and may encounter significant barriers in seeking health care. Little is known about the issues surrounding the dual role as both learner and patient when a medical student seeks care at his or her training institution. Method: A confidential survey examining medical students' health care needs, practices, and concerns was administered at 9 US medical schools. One part of the survey focused on responses to 4 medical student-patient vignettes. The vignettes systematically varied preexisting student vs preexisting patient status before assuming a medical student-patient role, and the vignettes also varied illness situations that were more vs less stigmatizing. Responses were analyzed using chi(2) and multivariate analysis of variance tests. Results: A total of 1027 students participated. We found that students were more likely to accept the dual role as medical student-patient in vignettes depicting a preexisting patient role than a preexisting student role. Students sought to avoid the dual role as student-patient in the context of stigmatizing health concerns. Women students were more likely than men to reject the dual role in all cases. Conclusion: Medical students appear to be sensitive to the conflicts that may be associated with the dual role as both medical student and patient when seeking care at their training institution. Our data suggest the importance of substantive efforts to promote the health, interests, and well-being of medical student-patients. (C) 2011 Elsevier Inc. All rights reserved. C1 [Roberts, Laura Weiss] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Warner, Teddy D.] Univ New Mexico, Sch Med, Dept Family & Community Med, Albuquerque, NM 87131 USA. [Smithpeter, Megan] Oregon Hlth & Sci Univ, Portland, OR USA. [Horwitz, Russell] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Roberts, LW (reprint author), Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. EM robertsl@stanford.edu OI Roberts, Laura Weiss/0000-0003-4270-253X NR 31 TC 2 Z9 2 U1 0 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD JUL-AUG PY 2011 VL 52 IS 4 BP 405 EP 412 DI 10.1016/j.comppsych.2010.09.004 PG 8 WC Psychiatry SC Psychiatry GA 785HY UT WOS:000292220600008 PM 21683176 ER PT J AU Beverly, EA Wray, LA Chiu, CJ Weinger, K AF Beverly, E. A. Wray, L. A. Chiu, C. J. Weinger, K. TI Perceived challenges and priorities in co-morbidity management of older patients with Type 2 diabetes SO DIABETIC MEDICINE LA English DT Article DE co-morbidity; diabetes self-management; qualitative research; Type 2 diabetes ID COMPETING DEMANDS; SELF-MANAGEMENT; PRIMARY-CARE; ADULTS; IMPACT AB Aims To explore older patients' perceived impact of chronic co-morbid conditions on Type 2 diabetes self-management. Methods We used purposive sampling to select 32 mentally alert community-dwelling adults, aged 60 years or older, diagnosed with Type 2 diabetes and at least one other chronic health condition to participate in focus groups. We summarized the discussions following each focus group and identified codes to describe the overarching themes. Results We conducted eight 90-min focus groups, each consisting of two to six patients. Three themes emerged. (i) Diabetes complications as a motivator: managing co-morbid conditions made health an important focal point in the lives of older patients. Most patients acknowledged the positive effect complications had on their diabetes self-management by motivating them to pay greater attention to their diabetes to diminish the progression of these complications. (ii) Prioritizing health conditions: patients reported prioritizing health conditions and selectively attending to the management of those conditions based on perceived severity or importance. Further, many patients perceived some conditions as more serious than others and admitted to prioritizing another health condition over their diabetes. (iii) Emotional impact of co-morbidity management: patients described feeling frustrated, confused, and overwhelmed in response to conflicting treatment recommendations, particularly for diet, physical activity and medication regimens. Conclusions Complications and co-morbidities may have differential impacts on the diabetes self-management of older patients. Addressing the perceived impact of co-morbidity on diabetes self-management may improve patients' outcomes; however, the most effective method of utilizing this information in clinical practice needs to be examined. C1 [Beverly, E. A.; Weinger, K.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Beverly, E. A.; Wray, L. A.; Chiu, C. J.] Penn State Univ, University Pk, PA 16802 USA. [Beverly, E. A.; Weinger, K.] Harvard Univ, Sch Med, Boston, MA USA. RP Beverly, EA (reprint author), Joslin Diabet Ctr, 1 Joslin Pl,Room 350C, Boston, MA 02215 USA. EM elizabeth.beverly@joslin.harvard.edu FU NIA [T32 AG00048]; Pennsylvania State Graduate Alumni Association Dissertation Award; Ed and Helen Hintz Award for Outstanding Graduate Work in the Department of Biobehavioural Health FX We thank the older patients who participated in this study and shared their experiences managing multiple chronic health conditions. We thank Dr Janice Penrod for her guidance in qualitative methodology. We also thank Drs Michael D. Grant and Marilyn D. Ritholz for their useful comments on the manuscript. This research was supported by NIA Grant T32 AG00048 awarded to The Pennsylvania State University, The Pennsylvania State Graduate Alumni Association Dissertation Award, and the Ed and Helen Hintz Award for Outstanding Graduate Work in the Department of Biobehavioural Health. NR 27 TC 17 Z9 17 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0742-3071 J9 DIABETIC MED JI Diabetic Med. PD JUL PY 2011 VL 28 IS 7 BP 781 EP 784 DI 10.1111/j.1464-5491.2011.03282.x PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 791XY UT WOS:000292704300006 PM 21395674 ER PT J AU Schwarz, AJ Becerra, L Upadhyay, J Anderson, J Baumgartner, R Coimbra, A Evelhoch, J Hargreaves, R Robertson, B Iyengar, S Tauscher, J Bleakman, D Borsook, D AF Schwarz, Adam J. Becerra, Lino Upadhyay, Jaymin Anderson, Julie Baumgartner, Richard Coimbra, Alexandre Evelhoch, Jeff Hargreaves, Richard Robertson, Brigitte Iyengar, Smriti Tauscher, Johannes Bleakman, David Borsook, David TI A procedural framework for good imaging practice in pharmacological fMRI studies applied to drug development #1: processes and requirements SO DRUG DISCOVERY TODAY LA English DT Review ID GENERALIZED ANXIETY DISORDER; ANTIDEPRESSANT TREATMENT; QUANTITATIVE ASSESSMENT; HEALTHY-VOLUNTEERS; DEPRESSED-PATIENTS; TREATMENT RESPONSE; MAJOR DEPRESSION; FUNCTIONAL MRI; CRITICAL PATH; RESONANCE AB There is increasing interest in the application of quantitative magnetic resonance imaging (MRI) methods to drug development, but as yet little standardization or best practice guidelines for its use in this context. Pharmaceutical trials are subject to regulatory constraints and sponsor company processes, including site qualification and expectations around study oversight, blinding, quality assurance and quality control (QA/QC), analysis and reporting of results. In this article, we review the processes on the sponsor side and also the procedures involved in data acquisition at the imaging site. We then propose summary recommendations to help guide appropriate imaging site qualification, as part of a framework of 'good imaging practice' for functional (f)MRI studies applied to drug development. C1 [Becerra, Lino; Upadhyay, Jaymin; Anderson, Julie; Borsook, David] McLean Hosp, Brain Imaging Ctr, PAIN Grp, Belmont, MA 02478 USA. [Schwarz, Adam J.; Iyengar, Smriti; Tauscher, Johannes; Bleakman, David] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. [Baumgartner, Richard; Coimbra, Alexandre; Evelhoch, Jeff; Hargreaves, Richard] Merck Res Labs, West Point, PA 19486 USA. [Robertson, Brigitte] Sepracor Inc, Marlborough, MA 01752 USA. [Becerra, Lino; Borsook, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Becerra, L (reprint author), McLean Hosp, Brain Imaging Ctr, PAIN Grp, 115 Mill St, Belmont, MA 02478 USA. EM lbecerra@partners.org RI Tauscher, Johannes/M-5976-2016 NR 52 TC 14 Z9 14 U1 1 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1359-6446 J9 DRUG DISCOV TODAY JI Drug Discov. Today PD JUL PY 2011 VL 16 IS 13-14 BP 583 EP 593 DI 10.1016/j.drudis.2011.05.006 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 792CX UT WOS:000292719200006 PM 21635967 ER PT J AU Indic, P Bloch-Salisbury, E Bednarek, F Brown, EN Paydarfar, D Barbieri, R AF Indic, Premananda Bloch-Salisbury, Elisabeth Bednarek, Frank Brown, Emery N. Paydarfar, David Barbieri, Riccardo TI Assessment of cardio-respiratory interactions in preterm infants by bivariate autoregressive modeling and surrogate data analysis SO EARLY HUMAN DEVELOPMENT LA English DT Article DE Heart rate variability; Preterm infants; Bivariate analysis; Surrogate data analysis; Coherence ID HEART-RATE-VARIABILITY; CYCLICAL FLUCTUATIONS; MYOCARDIAL-INFARCTION; BREATHING PATTERNS; HUMAN RESPIRATION; BLOOD-PRESSURE; TERM INFANTS; ORIGINS; VOLUME; SLEEP AB Background: Cardio-respiratory interactions are weak at the earliest stages of human development, suggesting that assessment of their presence and integrity may be an important indicator of development in infants. Despite the valuable research devoted to infant development, there is still a need for specifically targeted standards and methods to assess cardiopulmonary functions in the early stages of life. We present a new methodological framework for the analysis of cardiovascular variables in preterm infants. Our approach is based on a set of mathematical tools that have been successful in quantifying important cardiovascular control mechanisms in adult humans, here specifically adapted to reflect the physiology of the developing cardiovascular system. Methods: We applied our methodology in a study of cardio-respiratory responses for 11 preterm infants. We quantified cardio-respiratory interactions using specifically tailored multivariate autoregressive analysis and calculated the coherence as well as gain using causal approaches. The significance of the interactions in each subject was determined by surrogate data analysis. The method was tested in control conditions as well as in two different experimental conditions: with and without use of mild mechanosensory intervention. Results: Our multivariate analysis revealed a significantly higher coherence, as confirmed by surrogate data analysis, in the frequency range associated with eupneic breathing compared to the other ranges. Conclusions: Our analysis validates the models behind our new approaches, and our results confirm the presence of cardio-respiratory coupling in early stages of development, particularly during periods of mild mechanosensory intervention, thus encouraging further application of our approach. (c) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Indic, Premananda; Bloch-Salisbury, Elisabeth; Paydarfar, David] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA 01656 USA. [Indic, Premananda; Brown, Emery N.; Barbieri, Riccardo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA USA. [Bloch-Salisbury, Elisabeth; Bednarek, Frank] Univ Massachusetts, Sch Med, Dept Pediat, Worcester, MA 01656 USA. [Paydarfar, David] Univ Massachusetts, Sch Med, Dept Physiol, Worcester, MA 01656 USA. [Brown, Emery N.; Barbieri, Riccardo] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Paydarfar, David] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA. RP Indic, P (reprint author), Univ Massachusetts, Sch Med, Dept Neurol, 55 Lake Ave N, Worcester, MA 01656 USA. EM Premananda.Indic@umassmed.edu OI Barbieri, Riccardo/0000-0001-9381-3833; Salisbury, Elisabeth/0000-0002-7708-3428 FU CIMIT under U.S. Army [W81XWH-07-2-0011]; National Institutes of Health (NIH) [R01-HL084502, R01-DA015644, DP1-OD003646, R01-HL49848, R01-HL071884]; American Heart Association; University of Massachusetts Medical School and Mental Retardation Developmental Disabilities Research Center; Hansjorg Wyss Institute for Biologically Inspired Engineering at Harvard University FX This work was supported by the CIMIT under U.S. Army Medical Research Acquisition Activity Cooperative Agreement W81XWH-07-2-0011 (R.B.), by the National Institutes of Health (NIH) Grants R01-HL084502 (R.B), R01-DA015644 (E.N.B), DP1-OD003646 (E.N.B), R01-HL49848 (D.P.), R01-HL071884 (D.P.), by an American Heart Association Scientist Development Grant (E.B.S.), intramural Pilot Project Programs of the University of Massachusetts Medical School and Mental Retardation Developmental Disabilities Research Center (D.P.) and the Hansjorg Wyss Institute for Biologically Inspired Engineering at Harvard University (D.P.). The information contained herein does not necessarily reflect the position or policy of the Government, and no official endorsement should be inferred. NR 43 TC 3 Z9 3 U1 0 U2 7 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-3782 J9 EARLY HUM DEV JI Early Hum. Dev. PD JUL PY 2011 VL 87 IS 7 BP 477 EP 487 DI 10.1016/j.earlhumdev.2011.04.001 PG 11 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 791MQ UT WOS:000292669700005 PM 21511413 ER PT J AU San-Juan, D Mayorga, APM Anschel, DJ Avellan, AM Gonzalez-Aragon, MF Cole, AJ AF San-Juan, Daniel Mayorga, Adriana Patricia M. Anschel, David J. Moreno Avellan, Alvaro Gonzalez-Aragon, Maricarmen F. Cole, Andrew J. TI The double generalization phenomenon in juvenile absence epilepsy SO EPILEPSY & BEHAVIOR LA English DT Article DE Juvenile absence epilepsy; Generalized epilepsy; Focal findings; Electroencephalogram; Diagnosis; Absence epilepsy; Classification ID VIDEO-EEG; SEIZURES; ILAE AB The characterization of a seizure as generalized or focal onset depends on a basic knowledge of the underlying pathophysiology. Recently, an uncommon phenomenon in generalized epilepsy evolution of seizures from generalized to focal followed by secondary generalization was reported for the first time. We describe a 15-year-old boy, initially classified as having partial epilepsy, who had a typical absence seizure that became focal with second secondary generalization (double generalization). On the basis of these findings his epilepsy was classified as juvenile absence epilepsy and his treatment was changed, resulting in seizure freedom. This is the first report of this unusual electroclinical evolution in a patient with juvenile absence epilepsy. The recognition of this particular pattern allows correct classification and impacts both treatment and prognosis. (C) 2011 Elsevier Inc. All rights reserved. C1 [San-Juan, Daniel; Mayorga, Adriana Patricia M.; Moreno Avellan, Alvaro; Gonzalez-Aragon, Maricarmen F.] Natl Inst Neurol, Dept Clin Neurophysiol, Mexico City, DF, Mexico. [San-Juan, Daniel] Hosp ABC Santa Fe, Ctr Neurol, Mexico City, DF, Mexico. [Anschel, David J.] St Charles Hosp, Dept Clin Neurophysiol, Port Jefferson, NY USA. [Cole, Andrew J.] Massachusetts Gen Hosp, Epilepsy Serv, Boston, MA 02114 USA. RP San-Juan, D (reprint author), Av Insurgentes 3877, Mexico City 14269, DF, Mexico. EM pegaso31@yahoo.com NR 8 TC 1 Z9 1 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD JUL PY 2011 VL 21 IS 3 BP 318 EP 320 DI 10.1016/j.yebeh.2011.04.010 PG 3 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA 790IG UT WOS:000292581100021 PM 21571594 ER PT J AU Biederman, J Mick, E Fried, R Wilner, N Spencer, TJ Faraone, SV AF Biederman, Joseph Mick, Eric Fried, Ronna Wilner, Nicole Spencer, Thomas J. Faraone, Stephen V. TI Are stimulants effective in the treatment of executive function deficits? Results from a randomized double blind study of OROS-methylphenidate in adults with ADHD SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Article DE ADHD; Adults; OROS-methylphenidate; Cognitive performance ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; COMORBIDITY SURVEY REPLICATION; PLACEBO-CONTROLLED TRIAL; HYPERACTIVITY DISORDER; SUBTHRESHOLD DIAGNOSES; RATING-SCALE; LATE-ONSET; EFFICACY; METAANALYSIS; GENETICS AB The objective of this study was to evaluate the association between executive function deficits (EFDs) and response to methylphenidate treatment in ADHD in adults. We conducted a 6-week, parallel design, randomized, placebo controlled study in adults with DSM-IV ADHD. Our psychometric index of executive function used standardized neuropsychological testing. We assessed behaviors reflective of EFDs using the Behavior Rating Inventory of Executive Function - Adult Version (BRIEF-A). Subjects with available measures of executive functioning (OROS-MPH N=40; Placebo N=47) were included for analysis. There was no difference in the percent of subjects completing the 6-week acute efficacy Phase I of the trial (100% (N=40) vs. 98% (N=46), p=0.4). The mean daily dose at Phase I endpoint was 84.6 +/- 31.6 mg (1.04 +/- 0.29 mg/kg) OROS-MPH and 100.5 +/- 21.9 mg (1.20 +/- 0.11 mg/kg) placebo (p=0.0007). Based on the neuropsychological testing at the baseline assessment, 40% of the ADHD subjects (N=35/87) were considered to have EFDs but 93% (N=81) of subjects had >= 2 BRIEF-A clinical scale T-scores >65. Regardless of the definition used, however, EFDs did not impact the clinical response to OROS-MPH. This randomized clinical trial showed that executive function deficits do not moderate the response to methylphenidate and measures of executive function deficits are not associated with response to OROS-MPH. (C) 2010 Elsevier B.V. and ECNP. All rights reserved. C1 [Biederman, Joseph; Mick, Eric; Fried, Ronna; Wilner, Nicole; Spencer, Thomas J.] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol & Adult, Boston, MA 02114 USA. [Biederman, Joseph; Spencer, Thomas J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 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, Clin & Res Program Pediat Psychopharmacol & Adult, 55 Fruit St,YAW 6A Boston, Boston, MA 02114 USA. EM jbiederman@partners.org OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 FU Ortho-McNeil Janssen Scientific Affairs, LLC; Pediatric Psychopharmacology Council; Elminda; Janssen; McNeil; Shire; Fundacion Areces; Medice Pharmaceuticals; Spanish Child Psychiatry Association; Abbott; Alza; AstraZeneca; Bristol Myers Squibb; Celltech; Cephalon; Eli Lilly and Co.; Esai; Forest; Glaxo; Gliatech; Merck; NARSAD; NIDA; New River; NICHD; NIMH; Novartis; Noven; Neurosearch; Organon; Otsuka; Pfizer; Pharmacia; Prechter Foundation; Stanley Foundation; UCB Pharma, Inc.; Wyeth; Shire Pharmaceuticals; Eli Lilly; National Institutes of Health; Ortho-McNeil; Shire Development; Shire Laboratories, Inc; Glaxo-Smith Kline; Janssen Pharmaceutical; McNeil Pharmaceutical; Novartis Pharmaceuticals; National Institute of Mental Health FX The study was funded by Ortho-McNeil Janssen Scientific Affairs, LLC. Secondary analyses were conducted with the support of the Pediatric Psychopharmacology Council Fund. Neither funding source had any involvement in the study design, in the collection, analysis and interpretation of the data.; Dr. Joseph Biederman is currently receiving research support from the following sources: Elminda, Janssen, McNeil, and Shire. In 2010, Dr. Joseph Biederman did not receive any outside income. In 2009, Dr. Joseph Biederman received a speakers fee from the following sources: Fundacion Areces, Medice Pharmaceuticals, and the Spanish Child Psychiatry Association. In previous years, Dr. Joseph Biederman received research support, consultation fees, or speaker's fees for/from the following additional sources: Abbott, Alza, AstraZeneca, Bristol Myers Squibb, Celltech, Cephalon, Eli Lilly and Co., Esai, Forest, Glaxo, Gliatech, Janssen, McNeil, Merck, NARSAD, NIDA, New River, NICHD, NIMH, Novartis, Noven, Neurosearch, Organon, Otsuka, Pfizer, Pharmacia, The Prechter Foundation, Shire, The Stanley Foundation, UCB Pharma, Inc. and Wyeth.; Dr, Eric Mick receives research support from the following sources: Ortho-McNeilJanssen Scientific Affairs, Pfizer, Shire Pharmaceuticals, and has been an advisoryboard member for Shire Pharmaceuticals.; In the past year, Dr. Stephen Faraone has received consulting fees and has been on Advisory Boards for Eli Lilly, Ortho-McNeil and Shire Development and has received research support from Eli Lilly, Pfizer, Shire and the National Institutes of Health. In previous years, Dr. Faraone has received consulting fees or has been on Advisory Boards or has been a speaker for the following sources: Shire, McNeil, Janssen, Novartis, Pfizer and Eli Lilly. In previous years he has received research support from Eli Lilly, Shire, Pfizer and the National Institutes of Health.; Dr, Thomas Spencer has received research support from, has been a speaker for or on a speaker bureau or has been an Advisor or on an Advisory Board of the following sources: Shire Laboratories, Inc, Eli Lilly & Company, Glaxo-Smith Kline, Janssen Pharmaceutical, McNeil Pharmaceutical, Novartis Pharmaceuticals, Cephalon, Pfizer and the National Institute of Mental Health. NR 40 TC 20 Z9 22 U1 2 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD JUL PY 2011 VL 21 IS 7 BP 508 EP 515 DI 10.1016/j.euroneuro.2010.11.005 PG 8 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 791MO UT WOS:000292669500001 PM 21303732 ER PT J AU Martin, JN Wolken, N Brown, T Dauer, WT Ehrlich, ME Gonzalez-Alegre, P AF Martin, J. N. Wolken, N. Brown, T. Dauer, W. T. Ehrlich, M. E. Gonzalez-Alegre, P. TI Lethal toxicity caused by expression of shRNA in the mouse striatum: implications for therapeutic design SO GENE THERAPY LA English DT Article DE RNAi; AAV; DYT1 dystonia; torsinA; TOR1A ID MEDIATED RNA INTERFERENCE; MUTANT TORSINA; DYT1 DYSTONIA; PROTEIN; NEURONS; BRAIN; LIVER; MICE AB Therapeutic RNA interference (RNAi) has emerged as a promising approach for the treatment of many incurable diseases, including cancer, infectious disease or neurodegenerative disorders. Demonstration of efficacy and safety in animal models is necessary before planning human application. Our group and others have previously shown the potential of this approach for the dominantly inherited neurological disease DYT1 dystonia by achieving potent short-hairpin RNA (shRNA)-mediated silencing of the disease protein, torsinA, in cultured cells. To establish the feasibility of this approach in vivo, we pursued viral delivery of shRNA in two different mouse models. Surprisingly, intrastriatal injections of adeno-associated virus serotype 2/1 (AAV2/1) vectors expressing different shRNAs, whether targeting torsinA expression or mismatched controls, resulted in significant toxicity with progressive weight loss, motor dysfunction and animal demise. Histological analysis showed shRNA-induced neurodegeneration. Toxicity was not observed in animals that received control AAV2/1 encoding no shRNA, and was independent of genotype, occurring in both DYT1 and wild-type animals. Interestingly, the different genetic background of both mouse models influenced toxicity, being earlier and more severe in 129/SvEv than in C57BL/6 mice. In conclusion, our studies demonstrate that expression of shRNA in the mammalian brain can lead to lethal toxicity. Furthermore, the genetic background of rodents modifies their sensitivity to this form of toxicity, a factor that should be taken into consideration in the design of preclinical therapeutic RNAi trials. Gene Therapy (2011) 18, 666-673; doi:10.1038/gt.2011.10; published online 3 March 2011 C1 [Gonzalez-Alegre, P.] Univ Iowa, Dept Neurol, Carver Coll Med, Iowa City, IA 52242 USA. [Martin, J. N.; Gonzalez-Alegre, P.] Univ Iowa, Grad Program Genet, Iowa City, IA 52242 USA. [Brown, T.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Dauer, W. T.] Univ Michigan, Dept Neurol, Ann Arbor, MI USA. [Dauer, W. T.] Univ Michigan, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA. [Ehrlich, M. E.] Mt Sinai Sch Med, Dept Neurol, New York, NY USA. RP Gonzalez-Alegre, P (reprint author), Univ Iowa, Dept Neurol, Carver Coll Med, 3111 MERF,375 Newton Rd, Iowa City, IA 52242 USA. EM pedro-gonzalez-alegre@uiowa.edu FU NIH; Dystonia Medical Research Foundation; Tyler's Hope for a Dystonia Cure; NIH/NINDS [P01NS050210, R21NS047432] FX Janine N Martin, Nicolle Wolken and Timothy Brown declare no conflict of interest. Dr Pedro Gonzalez-Alegre's work has been funded by the NIH, Dystonia Medical Research Foundation and Tyler's Hope for a Dystonia Cure. He co-owns a patent on the technology described in this report. Dr William T Dauer's work has been funded by the NIH and Dystonia Medical Research Foundation. Dr Michelle E Ehrlich's work has been funded by the NIH.; We thank Drs Beverly Davidson, Kevin Glenn, Anton McCaffrey and Henry Paulson, and members of their laboratories for their help and suggestions, Nicole Bode for her assistance with cresyl violet staining and Dr Bridgett Zimmerman for aid with statistical analyses. This work was supported by NIH/NINDS (P01NS050210 and R21NS047432), Dystonia Medical Research Foundation and Tyler's Hope For A Dystonia Cure. NR 23 TC 46 Z9 47 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD JUL PY 2011 VL 18 IS 7 BP 666 EP 673 DI 10.1038/gt.2011.10 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 789IU UT WOS:000292509900004 PM 21368900 ER PT J AU Tsiachristas, A Hipple-Walters, B Lemmens, KMM Nieboer, AP Rutten-van Molken, MPMH AF Tsiachristas, Apostolos Hipple-Walters, Bethany Lemmens, Karin M. M. Nieboer, Anna P. Rutten-van Molken, Maureen P. M. H. TI Towards integrated care for chronic conditions: Dutch policy developments to overcome the (financial) barriers SO HEALTH POLICY LA English DT Article DE Chronic diseases; Integrated care; Disease management programs; Integrated payment; The Netherlands ID CHRONIC ILLNESS CARE; DISEASE MANAGEMENT; HEALTH-CARE; MODEL; NETHERLANDS; COMPETITION AB Chronic non-communicable diseases are a major threat to population health and have a major economic impact on health care systems. Worldwide, integrated chronic care delivery systems have been developed to tackle this challenge. In the Netherlands, the recently introduced integrated payment system - the chain-DTC - is seen as the cornerstone of a policy stimulating the development of a well-functioning integrated chronic care system. The purpose of this paper is to describe the recent attempts in the Netherlands to stimulate the delivery of integrated chronic care, focusing specifically on the new integrated payment scheme and the barriers to introducing this scheme. We also highlight possible threats and identify necessary conditions to the success of the system. This paper is based on a combination of methods and sources including literature, government documents, personal communications and site visits to disease management programs (DMPs). The most important conditions for the success of the new payment system are: complete care protocols describing both general (e.g. smoking cessation, physical activity) and disease-specific chronic care modules, coverage of all components of a DMP by basic health care insurance, adequate information systems that facilitate communication between care-givers, explicit links between the quality and the price of a DMP, expansion of the amount of specialized care included in the chain-DTC, inclusion of a multi-morbidity factor in the risk equalization formula of insurers, and thorough economic evaluation of DMPs. (C) 2010 Elsevier Ireland Ltd. All rights reserved. C1 [Tsiachristas, Apostolos; Rutten-van Molken, Maureen P. M. H.] Erasmus Univ, Inst Med Technol Assessment, NL-3000 DR Rotterdam, Netherlands. [Tsiachristas, Apostolos; Hipple-Walters, Bethany; Lemmens, Karin M. M.; Nieboer, Anna P.; Rutten-van Molken, Maureen P. M. H.] Erasmus Univ, Dept Hlth Policy & Management, NL-3000 DR Rotterdam, Netherlands. [Hipple-Walters, Bethany] Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. RP Tsiachristas, A (reprint author), POB 1738, NL-3000 DR Rotterdam, Netherlands. EM tsiachristas@bmg.eur.nl RI Nieboer, Anna/H-9014-2013; Rutten-van Molken, Maureen/G-8481-2014 OI Rutten-van Molken, Maureen/0000-0001-8706-3159 FU The Netherlands Organization for Health Research and Development [300030201] FX The study is funded by ZonMw, The Netherlands Organization for Health Research and Development (ZonMw project number 300030201). NR 51 TC 28 Z9 28 U1 1 U2 10 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-8510 J9 HEALTH POLICY JI Health Policy PD JUL PY 2011 VL 101 IS 2 BP 122 EP 132 DI 10.1016/j.healthpol.2010.10.013 PG 11 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 791NG UT WOS:000292671300002 PM 21067841 ER PT J AU Corradini, E Meynard, D Wu, QF Chen, S Ventura, P Pietrangelo, A Babitt, JL AF Corradini, Elena Meynard, Delphine Wu, Qifang Chen, Shan Ventura, Paolo Pietrangelo, Antonello Babitt, Jodie L. TI Serum and Liver Iron Differently Regulate the Bone Morphogenetic Protein 6 (BMP6)-SMAD Signaling Pathway in Mice SO HEPATOLOGY LA English DT Article ID HEPCIDIN EXPRESSION; PEPTIDE HEPCIDIN; MOUSE-LIVER; CROSS-TALK; IN-VIVO; HEMOCHROMATOSIS; OVERLOAD; BMP6; HFE; METABOLISM AB The bone morphogenetic protein 6 (BMP6)-SMAD signaling pathway is a central regulator of hepcidin expression and systemic iron balance. However, the molecular mechanisms by which iron is sensed to regulate BMP6-SMAD signaling and hepcidin expression are unknown. Here we examined the effects of circulating and tissue iron on Bmp6-Smad pathway activation and hepcidin expression in vivo after acute and chronic enteral iron administration in mice. We demonstrated that both transferrin saturation and liver iron content independently influence hepcidin expression. Although liver iron content is independently positively correlated with hepatic Bmp6 messenger RNA (mRNA) expression and overall activation of the Smad1/5/8 signaling pathway, transferrin saturation activates the downstream Smad1/5/8 signaling cascade, but does not induce Bmp6 mRNA expression in the liver. Hepatic inhibitory Smad7 mRNA expression is increased by both acute and chronic iron administration and mirrors overall activation of the Smad1/5/8 signaling cascade. In contrast to the Smad pathway, the extracellular signal-regulated kinase 1 and 2 (Erk1/2) mitogen-activated protein kinase (Mapk) signaling pathway in the liver is not activated by acute or chronic iron administration in mice. Conclusion: Our data demonstrate that the hepatic Bmp6-Smad signaling pathway is differentially activated by circulating and tissue iron to induce hepcidin expression, whereas the hepatic Erk1/2 signaling pathway is not activated by iron in vivo. (HEPATOLOGY 2011;54:273-284) C1 [Corradini, Elena; Meynard, Delphine; Wu, Qifang; Chen, Shan; Babitt, Jodie L.] Harvard Univ, Program Membrane Biol,Massachusetts Gen Hosp, Div Nephrol,Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. [Corradini, Elena; Ventura, Paolo; Pietrangelo, Antonello] Univ Hosp Modena & Reggio Emilia, Lab Hereditary & Metab Dis Liver, Mario Coppo Liver Res Ctr, Modena, Italy. RP Babitt, JL (reprint author), Harvard Univ, Program Membrane Biol,Massachusetts Gen Hosp, Div Nephrol,Sch Med, Ctr Syst Biol, 185 Cambridge St,CPZN 8216, Boston, MA 02114 USA. EM babitt.jodie@mgh.harvard.edu RI meynard, delphine/B-4236-2014; Corradini, Elena/O-4167-2016; Pietrangelo, Antonello/K-1517-2016 OI Corradini, Elena/0000-0001-9477-2164; Pietrangelo, Antonello/0000-0002-7411-935X FU Massachusetts Biomedical Research Corporation (MBRC) at Massachusetts General Hospital; PRIN; Telethon [GGP10233]; NIH [K08 DK075846, RO1 DK087727]; Massachusetts General Hospital FX E.C. was supported in part by a Tosteson Postdoctoral Fellowship Awards from the Massachusetts Biomedical Research Corporation (MBRC) at Massachusetts General Hospital. P.V. and A.P. were supported in part by PRIN '08 grant and Telethon GGP10233 grant. J.L.B. was supported in part by NIH grants K08 DK075846 and RO1 DK087727, and by a Claflin Distinguished Scholar Award from the Massachusetts General Hospital. NR 36 TC 78 Z9 80 U1 1 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JUL PY 2011 VL 54 IS 1 BP 273 EP 284 DI 10.1002/hep.24359 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 788JH UT WOS:000292440700031 PM 21488083 ER PT J AU Bauman, WA Cirnigliaro, CM La Fountaine, MF Jensen, AM Wecht, JM Kirshblum, SC Spungen, AM AF Bauman, W. A. Cirnigliaro, C. M. La Fountaine, M. F. Jensen, A. M. Wecht, J. M. Kirshblum, S. C. Spungen, A. M. TI A Small-Scale Clinical Trial to Determine the Safety and Efficacy of Testosterone Replacement Therapy in Hypogonadal Men with Spinal Cord Injury SO HORMONE AND METABOLIC RESEARCH LA English DT Article DE lean tissue mass; tetraplegia; paraplegia; hypogonadism; androgen replacement therapy ID RANDOMIZED CONTROLLED-TRIAL; RESTING ENERGY-EXPENDITURE; BODY-COMPOSITION; MUSCLE STRENGTH; ELDERLY-MEN; OLDER MEN; INDIVIDUALS; TETRAPLEGIA; PARAPLEGIA; ADULTS AB Men with spinal cord injury are at an increased risk for secondary medical conditions, including metabolic disorders, accelerated musculoskeletal atrophy, and, for some, hypogonadism, a deficiency, which may further adversely affect metabolism and body composition. A prospective, open label, controlled drug intervention trial was performed to determine whether 12 months of testosterone replacement therapy increases lean tissue mass and resting energy expenditure in hypogonadal males with spinal cord injury. Healthy eugonadal (n = 11) and hypogonadal (n = 11) outpatients with chronic spinal cord injury were enrolled. Hypogonadal subjects received transdermal testosterone (5 or 10 mg) daily for 12 months. Measurements of body composition and resting energy expenditure were obtained at baseline and 12 months. The testosterone replacement therapy group increased lean tissue mass for total body (49.6 +/- 7.6 vs. 53.1 +/- 6.9 kg; p <0.0005), trunk (24.1 +/- 4.1 vs. 25.8 +/- 3.8 kg; p <0.005), leg (14.5 +/- 2.7 vs. 15.8 +/- 2.6 kg; p = 0.005), and arm (7.6 +/- 2.3 vs. 8.0 +/- 2.2 kg; p <0.005) from baseline to month 12. After testosterone replacement therapy, resting energy expenditure (1328 +/- 262 vs. 1440 +/- 262 kcal/d; p <0.01) and percent predicted basal energy expenditure (73 +/- 9 vs. 79 +/- 10%; p <0.05) were significantly increased. In conclusion, testosterone replacement therapy significantly improved lean tissue mass and energy expenditure in hypogonadal men with spinal cord injury, findings that would be expected to influence the practice of clinical care, if confirmed. Larger, randomized, controlled clinical trials should be performed to confirm and extend our preliminary findings. C1 [Bauman, W. A.; Cirnigliaro, C. M.; La Fountaine, M. F.; Jensen, A. M.; Wecht, J. M.; Spungen, A. M.] James J Peters VA Med Ctr, VA RR&D Natl Ctr Excellence Med Consequences Spin, Bronx, NY 10468 USA. [Bauman, W. A.; La Fountaine, M. F.; Wecht, J. M.; Spungen, A. M.] James J Peters VA Med Ctr, Med Serv, Bronx, NY 10468 USA. [Bauman, W. A.; La Fountaine, M. F.; Spungen, A. M.] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Bauman, W. A.; Wecht, J. M.; Spungen, A. M.] Mt Sinai Sch Med, Dept Rehabil Med, New York, NY USA. [Kirshblum, S. C.] Kessler Inst Rehabil, W Orange, NJ USA. [Kirshblum, S. C.] Univ Med & Dent New Jersey, Dept Phys Med & Rehabil, Newark, NJ 07103 USA. RP Bauman, WA (reprint author), James J Peters VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM william.bauman@va.gov FU James J Peters VA Medical Center, Bronx, NY; Department of Veterans Affairs Rehabilitation Research & Development Service; Kessler Institute for Rehabilitation, West Orange, NJ; Rehabilitation Research & Development (RR & D) National Center of Excellence for the Medical Consequences of Spinal Cord Injury [B2648C, B4162C] FX The authors wish to thank the James J Peters VA Medical Center, Bronx, NY, the Department of Veterans Affairs Rehabilitation Research & Development Service, and the Kessler Institute for Rehabilitation, West Orange, NJ for their support. This work was funded by a Rehabilitation Research & Development (RR & D) National Center of Excellence for the Medical Consequences of Spinal Cord Injury (# B2648C & B4162C). This work has the Clinical Trial Registration Number: NCT00266864. NR 31 TC 17 Z9 18 U1 0 U2 3 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD JUL PY 2011 VL 43 IS 8 BP 574 EP 579 DI 10.1055/s-0031-1280797 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 794DQ UT WOS:000292876100010 PM 21717386 ER PT J AU Muntner, P Halanych, JH Reynolds, K Durant, R Vupputuri, S Sung, VW Meschia, JF Howard, VJ Safford, MM Krousel-Wood, M AF Muntner, Paul Halanych, Jewell H. Reynolds, Kristi Durant, Raegan Vupputuri, Suma Sung, Victor W. Meschia, James F. Howard, Virginia J. Safford, Monika M. Krousel-Wood, Marie TI Low Medication Adherence and the Incidence of Stroke Symptoms Among Individuals With Hypertension: The REGARDS Study SO JOURNAL OF CLINICAL HYPERTENSION LA English DT Article ID TRANSIENT ISCHEMIC ATTACK; BLOOD-PRESSURE CONTROL; RISK-FACTORS; PREDICTIVE-VALIDITY; GENERAL-POPULATION; RACIAL-DIFFERENCES; QUESTIONNAIRE; ASSOCIATION; PREVALENCE; METAANALYSIS AB The authors analyzed data on 9950 participants taking antihypertensive medications in the nationwide Reasons for Geographic and Racial Differences in Stroke (REGARDS) study to determine the association between medication adherence and incident stroke symptoms. Medication adherence was assessed using a validated 4-item self-report scale and participants were categorized into 4 groups (scores of 0, 1, 2, and 3 or 4, with higher scores indicating worse adherence). The incidence of 6 stroke symptoms (sudden weakness on one side of the body, numbness, painless loss of vision in one or both eyes, loss of half vision, losing the ability to understand people, and losing the ability to express oneself verbally or in writing) was assessed via telephone interviews every 6 months. During a median of 4 years, the incidence of any stroke symptom was 14.6%, 17.9%, 20.2%, and 24.9% among participants with adherence scores of 0, 1, 2, and 3 or 4, respectively (P <.001). The multivariable adjusted hazard ratio (95% confidence interval) for any stroke symptom associated with adherence scores of 1, 2, and 3 or 4, vs 0, was 1.20 (1.04-1.39), 1.23 (0.94-1.60), and 1.59 (1.08-2.33), respectively (P <.001). Worse adherence was also associated with higher multivariable adjusted hazard ratios for each of the 6 stroke symptoms. J Clin Hypertens (Greenwich). 2011; 13: 479-486. (c) 2011 Wiley Periodicals, Inc. C1 [Muntner, Paul] Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA. [Muntner, Paul; Halanych, Jewell H.; Durant, Raegan; Safford, Monika M.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Reynolds, Kristi] Kaiser Permanente So Calif, Dept Res & Evaluat, Pasadena, CA USA. [Durant, Raegan] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Vupputuri, Suma] Kaiser Permanente Georgia, Ctr Hlth Res, Atlanta, GA USA. [Sung, Victor W.] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL 35294 USA. [Meschia, James F.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Krousel-Wood, Marie] Ochsner Clin Fdn, Ctr Hlth Res, New Orleans, LA USA. [Krousel-Wood, Marie] Tulane Univ, Dept Epidemiol, New Orleans, LA 70118 USA. [Krousel-Wood, Marie] Tulane Univ, Dept Family & Community Med, New Orleans, LA 70118 USA. RP Muntner, P (reprint author), Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, RPHB 230J 1530,3rd Ave S, Birmingham, AL 35294 USA. EM pmuntner@uab.edu RI Krousel-Wood, Marie Antoinette/D-4718-2011; OI Sung, Victor/0000-0003-1024-3404 FU National Institute of Neurological Disorders and Stroke, National Institutes of Health, Department of Health and Human Services [U01 NS041588]; National Institute on Aging [R01 AG022536]; [R01 HL80477] FX This research project is supported by a cooperative agreement U01 NS041588 from the National Institute of Neurological Disorders and Stroke, National Institutes of Health, Department of Health and Human Services. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Neurological Disorders and Stroke or the National Institutes of Health. Representatives of the funding agency have been involved in the review of the manuscript but not directly involved in the collection, management, analysis, or interpretation of the data. The authors thank the investigators, staff, and participants of the REGARDS study for their valuable contributions. A full list of participating REGARDS investigators and institutions can be found at http://www.regardsstudy.org. Drs Muntner and Krousel-Wood received support from the National Institute on Aging grant number R01 AG022536. Drs Safford, Halanych, and Durant received support from grant number R01 HL80477. NR 41 TC 17 Z9 17 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1524-6175 J9 J CLIN HYPERTENS JI J. Clin. Hypertens. PD JUL PY 2011 VL 13 IS 7 BP 479 EP 486 DI 10.1111/j.1751-7176.2011.00464.x PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 793SQ UT WOS:000292843800004 PM 21762360 ER PT J AU Dighe, MK Bhargava, P Wright, J AF Dighe, Manjiri K. Bhargava, Puneet Wright, Jonathan TI Urinary Bladder Masses: Techniques, Imaging Spectrum, and Staging SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Review DE bladder carcinoma; imaging; cystoscopy; urinary bladder; transitional cell carcinoma ID TRANSITIONAL-CELL-CARCINOMA; RADIOLOGIC-PATHOLOGICAL CORRELATION; VIRTUAL CYSTOSCOPY; FLUORESCENCE CYSTOSCOPY; UROTHELIAL CARCINOMA; SECONDARY NEOPLASMS; MALIGNANT-LYMPHOMA; GROSS HEMATURIA; RENAL PELVIS; CT UROGRAPHY AB Bladder carcinoma is the fourth most common cancer in men and women. Knowledge of imaging options and appearance is necessary for both radiologists and urologists. Transitional cell carcinoma is the most common bladder neoplasm with squamous cell and adenocarcinoma found in less than 10% of cases. Benign lesions are uncommon, but some can be suggested by their imaging appearance. Similarly, malignant lesions often have suggestive appearance and/or location. Cystoscopy allows tissue diagnosis and treatment of superficial lesions. Although magnetic resonance imaging (MRI) and computed tomography (CT) both have limitations in detailing depth of muscle invasion, both have a prominent role helping to define the lesion and in staging. This article illustrates the role of MRI and CT in evaluating bladder masses with a discussion of the newer techniques of MR diffusion-weighted imaging and virtual cystoscopy by CT or MRI. This article reviews the multiple benign and malignant lesions of the bladder so that the reader can appreciate the role of cystoscopy, CT, MRI, diffusion-weighted imaging, and virtual cystoscopy in dealing with these relatively common tumors. C1 [Dighe, Manjiri K.] Univ Washington, Med Ctr, Dept Radiol, Seattle, WA 98195 USA. [Bhargava, Puneet] VA Puget Sound HCS, Dept Radiol, Seattle, WA USA. [Wright, Jonathan] Univ Washington, Med Ctr, Dept Urol, Seattle, WA 98195 USA. RP Dighe, MK (reprint author), Univ Washington, Med Ctr, Dept Radiol, 1959 NE Pacific St,Box 357115, Seattle, WA 98195 USA. EM dighe@u.washington.edu RI Bhargava, Puneet /F-1330-2011; OI Bhargava, Puneet/0000-0002-3849-9666 NR 79 TC 8 Z9 9 U1 0 U2 4 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 JUL-AUG PY 2011 VL 35 IS 4 BP 411 EP 424 DI 10.1097/RCT.0b013e31821c2e9d PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 792TR UT WOS:000292773800001 PM 21765295 ER PT J AU Howell, SC Haffajee, AD Pagonis, TC Guze, KA AF Howell, Scott C. Haffajee, Anne D. Pagonis, Tom C. Guze, Kevin A. TI Laser Raman Spectroscopy as a Potential Chair-side Microbiological Diagnostic Device SO JOURNAL OF ENDODONTICS LA English DT Article DE Chair-side bacterial identification; Raman spectroscopy; rapid bacterial identification; reagentless bacterial identification ID DNA-DNA HYBRIDIZATION; CANCER; PRINCIPLE; PROOF; SKIN AB Introduction: Culture-dependent and -independent techniques are time-consuming processes requiring highly trained personnel to identify microorganisms contained within a sample. Rapid chair-side identification of microorganisms, could reduce the lag time between patient presentation and ideal treatment. As a first step toward this goal, this study aims to determine if laser Raman spectroscopy (LRS) can discern uniqueness among 10 different species of bacteria contained within a medium in unprocessed and processed samples. Methods: Ten bacterial species were individually grown on blood agar plates for 3 days. Checkerboard DNA-DNA hybridization was used for species verification. For the unprocessed samples, a 1.0-cm diameter agar sample, with undisturbed bacterial growth, was transferred for each species. to a barium fluoride crystal (BaF(2)) slide and laser scanned for a total of 15 seconds per sample. For the processed samples, bacterial cells were harvested, washed, and resuspended in phosphate-buffered saline buffer at 10(9) cells/mL concentration. Each suspension was laser scanned for 15 seconds on a BaF2 slide. Select regions of Raman spectra for each species/agar and species/suspension combination were processed using a two-sided t test. Results: For the 10 bacterial species, 45 bacteria pair combinations were tested for each group. In both groups, LRS was capable of statistically distinguishing among a majority of bacterial pairings based on RS signature differences of means. Conclusions: Results show each bacterial species generated restricted ranges of unique spectral signatures that were not masked by their containing medium. Chair-side LRS is a promising technique that differentiates among oral bacterial species with a high degree of specificity. (J Endod 2011;37:968-972) C1 [Howell, Scott C.; Pagonis, Tom C.; Guze, Kevin A.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Haffajee, Anne D.] Forsyth Inst, Boston, MA USA. RP Howell, SC (reprint author), 30131 Town Ctr Dr,Suite 105, Laguna Niguel, CA 92660 USA. EM sch2010a@gmail.com NR 28 TC 1 Z9 2 U1 1 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0099-2399 J9 J ENDODONT JI J. Endod. PD JUL PY 2011 VL 37 IS 7 BP 968 EP 972 DI 10.1016/j.joen.2011.03.027 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 793AW UT WOS:000292793800013 PM 21689553 ER PT J AU Anderson, E Siegel, EH Barrett, LF AF Anderson, Eric Siegel, Erika H. Barrett, Lisa Feldman TI What you feel influences what you see: The role of affective feelings in resolving binocular rivalry SO JOURNAL OF EXPERIMENTAL SOCIAL PSYCHOLOGY LA English DT Article DE Affect; Perception; Binocular rivalry ID MEDIAL PREFRONTAL CORTEX; FACIAL EXPRESSIONS; MACAQUE MONKEYS; AREAS TE; PERCEPTION; ATTENTION; CONNECTIONS; ORGANIZATION; RECIPIENT; EMOTION AB It seems obvious that what you see influences what you feel, but what if the opposite were also true? What if how you feel can shape your visual experience? In this experiment, we demonstrate that the affective state of a perceiver influences the contents of visual awareness. Participants received positive, negative, and neutral affect inductions and then completed a series of binocular rivalry trials in which a face (smiling, scowling, or neutral) was presented to one eye and a house to the other. The percepts "competed" for dominance in visual consciousness. We found, as predicted, that all faces (smiling, scowling, and neutral) were dominant for longer when perceivers experienced unpleasant affect compared to when they were in a neutral state (a social vigilance effect), although scowling faces increased their dominance when perceivers felt unpleasant (a relative negative congruence effect). Relatively speaking, smiling faces increased their dominance more when perceivers were experiencing pleasant affect (a positive congruence effect). These findings illustrate that the affective state of a perceiver serves as a context that influences the contents of consciousness. (C) 2011 Elsevier Inc. All rights reserved. C1 [Barrett, Lisa Feldman] Northeastern Univ, Dept Psychol, Boston, MA 02115 USA. [Barrett, Lisa Feldman] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. RP Barrett, LF (reprint author), Northeastern Univ, Dept Psychol, Boston, MA 02115 USA. EM l.barrett@neu.edu OI Anderson, Eric/0000-0002-4215-6308 FU NIH HHS [DP1 OD003312, DP1 OD003312-03, DP1 OD003312-04] NR 45 TC 21 Z9 22 U1 2 U2 20 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-1031 J9 J EXP SOC PSYCHOL JI J. Exp. Soc. Psychol. PD JUL PY 2011 VL 47 IS 4 BP 856 EP 860 DI 10.1016/j.jesp.2011.02.009 PG 5 WC Psychology, Social SC Psychology GA 791KD UT WOS:000292663200021 PM 21789027 ER PT J AU Burdo, TH Lentz, MR Autissier, P Krishnan, A Halpern, E Letendre, S Rosenberg, ES Ellis, RJ Williams, KC AF Burdo, Tricia H. Lentz, Margaret R. Autissier, Patrick Krishnan, Anitha Halpern, Elkan Letendre, Scott Rosenberg, Eric S. Ellis, Ronald J. Williams, Kenneth C. TI Soluble CD163 Made by Monocyte/Macrophages Is a Novel Marker of HIV Activity in Early and Chronic Infection Prior to and After Antiretroviral Therapy SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID SCAVENGER RECEPTOR CD163; NECROSIS-FACTOR-ALPHA; HUMAN MONOCYTE CD163; TOLL-LIKE RECEPTORS; MICROBIAL TRANSLOCATION; REPLICATION-COMPETENT; IMMUNE ACTIVATION; UP-REGULATION; INNATE; MACROPHAGES AB CD163, a monocyte- and macrophage-specific scavenger receptor, is shed during activation as soluble CD163 (sCD163). We have previously demonstrated that monocyte expansion from bone marrow with simian immunodeficiency virus (SIV) infection correlated with plasma sCD163, the rate of AIDS progression, and the severity of macrophage-mediated pathogenesis. Here, we examined sCD163 in human immunodeficiency virus (HIV) infection. sCD163 was elevated in the plasma of individuals with chronic HIV infection (>1 year in duration), compared with HIV-seronegative individuals. With effective antiretroviral therapy (ART), sCD163 levels decreased in parallel with HIV RNA levels but did not return to HIV-seronegative levels, suggesting the presence of residual monocyte/macrophage activation even with plasma viral loads below the limit of detection. In individuals with early HIV infection (<= 1 year in duration), effective ART resulted in decreased sCD163 levels that were comparable to levels in HIV-seronegative individuals. sCD163 levels in plasma were positively correlated with the percentage of CD14+CD16+ monocytes and activated CD8+HLA-DR+CD38+ T lymphocytes and were inversely correlated with CD163 expression on CD14+CD16+ monocytes. With ART interruption in subjects with early HIV infection, sCD163 and plasma virus levels spiked but rapidly returned to baseline with reinitiation of ART. This study points to the utility of monocyte-and macrophage-derived sCD163 as a marker of HIV activity that links viral replication with monocyte and macrophage activation. These observations underscore the significance of monocyte and macrophage immune responses with HIV pathogenesis. C1 [Burdo, Tricia H.; Autissier, Patrick; Krishnan, Anitha; Williams, Kenneth C.] Boston Coll, Dept Biol, Chestnut Hill, MA 02467 USA. [Lentz, Margaret R.; Halpern, Elkan] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Rosenberg, Eric S.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Letendre, Scott; Ellis, Ronald J.] Univ Calif San Diego, HIV Neurobehav Res Ctr, San Diego, CA 92103 USA. RP Williams, KC (reprint author), Boston Coll, Dept Biol, 140 Commonwealth Ave, Chestnut Hill, MA 02467 USA. EM kenneth.williams.3@bc.edu RI Ellis, Ronald/K-3543-2015 OI Ellis, Ronald/0000-0003-4931-752X FU National Institutes of Health [NIH-NS37654, NIH-NS40237, NIH-AI071915, NIH-NS051129, NIH-MH58076, NIH-MH62512] FX National Institutes of Health (NIH-NS37654 to K. W., NIH-NS40237 to K. W., NIH-AI071915 to E. R., NIH-NS051129 to M. L., NIH-MH58076 to R. J. E. and S. L., and NIH-MH62512 to Igor Grant, R. J. E. and S. L. are coinvestigators). NR 48 TC 124 Z9 125 U1 0 U2 3 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 JUL 1 PY 2011 VL 204 IS 1 BP 154 EP 163 DI 10.1093/infdis/jir214 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 790AV UT WOS:000292561800021 PM 21628670 ER PT J AU Levy, MS Laham, RJ AF Levy, Michael S. Laham, Roger J. TI Virtual Histologic Guidance of Percutaneous Peripheral Atherectomy: The Evolution of a New Paradigm? SO JOURNAL OF INVASIVE CARDIOLOGY LA English DT Editorial Material ID LESIONS C1 [Levy, Michael S.; Laham, Roger J.] Harvard Univ, Sch Med, BIDMC, Intervent Cardiol Sect,Div Cardiol, Boston, MA 02215 USA. RP Laham, RJ (reprint author), Harvard Univ, Sch Med, BIDMC, Intervent Cardiol Sect,Div Cardiol, 330 Brookline Ave, Boston, MA 02215 USA. EM rlaham@bidmc.harvard.edu NR 9 TC 0 Z9 0 U1 0 U2 0 PU H M P COMMUNICATIONS PI MALVERN PA 83 GENERAL WARREN BLVD, STE 100, MALVERN, PA 19355 USA SN 1042-3931 J9 J INVASIVE CARDIOL JI J. Invasive Cardiol. PD JUL PY 2011 VL 23 IS 7 BP 274 EP 275 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 794MV UT WOS:000292902600005 PM 21725121 ER PT J AU Pervaiz, MH Laham, RJ AF Pervaiz, Mohammad H. Laham, Roger J. TI Distal Anchoring Technique: Yet Another Weapon for Successful Intervention SO JOURNAL OF INVASIVE CARDIOLOGY LA English DT Editorial Material ID GUIDING CATHETER SUPPORT; CORONARY ANGIOPLASTY C1 [Pervaiz, Mohammad H.; Laham, Roger J.] Harvard Univ, Sch Med, BIDMC, Intervent Cardiol Sect,Div Cardiol, Boston, MA 02215 USA. RP Laham, RJ (reprint author), Harvard Univ, Sch Med, BIDMC, Intervent Cardiol Sect,Div Cardiol, 330 Brookline Avenue, Boston, MA 02215 USA. EM rlaham@bidmc.harvard.edu NR 8 TC 0 Z9 0 U1 0 U2 0 PU H M P COMMUNICATIONS PI MALVERN PA 83 GENERAL WARREN BLVD, STE 100, MALVERN, PA 19355 USA SN 1042-3931 J9 J INVASIVE CARDIOL JI J. Invasive Cardiol. PD JUL PY 2011 VL 23 IS 7 BP 295 EP 296 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 794MV UT WOS:000292902600010 PM 21725126 ER PT J AU Lok, J Leung, WD Zhao, S Pallast, S van Leyen, K Guo, SZ Wang, XY Yalcin, A Lo, EH AF Lok, Josephine Leung, Wendy Zhao, Song Pallast, Stefanie van Leyen, Klaus Guo, Shuzhen Wang, Xiaoying Yalcin, Ayfer Lo, Eng H. TI Gamma-glutamylcysteine ethyl ester protects cerebral endothelial cells during injury and decreases blood-brain barrier permeability after experimental brain trauma SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE blood-brain barrier; endothelial; GCEE; glutathione; neuroprotection; oxidative stress ID INDUCED OXIDATIVE STRESS; PARKINSONS-DISEASE; THERAPEUTIC STRATEGY; GLUTATHIONE; NEURODEGENERATION; ELEVATION; MICE; MONOCHLOROBIMANE; EXCITOTOXICITY; METABOLISM AB Oxidative stress is a pathway of injury that is common to almost all neurological conditions. Hence, methods to scavenge radicals have been extensively tested for neuroprotection. However, saving neurons alone may not be sufficient in treating CNS disease. In this study, we tested the cytoprotective actions of the glutathione precursor gamma-glutamylcysteine ethyl ester (GCEE) in brain endothelium. First, oxidative stress was induced in a human brain microvascular endothelial cell line by exposure to H(2)O(2). Addition of GCEE significantly reduced formation of reactive oxygen species, restored glutathione levels which were reduced in the presence of H(2)O(2), and decreased cell death during H(2)O(2)-mediated injury. Next, we asked whether GCEE can also protect brain endothelial cells against oxygen-glucose deprivation OGD). As expected, OGD disrupted mitochondrial membrane potentials. GCEE was able to ameliorate these mitochondrial effects. Concomitantly, GCEE significantly decreased endothelial cell death after OGD. Lastly, our in vivo experiments using a mouse model of brain trauma show that post-trauma (10 min after controlled cortical impact) administration of GCEE by intraperitoneal injection results in a decrease in acute blood-brain barrier permeability. These data suggest that the beneficial effects of GCEE on brain endothelial cells and microvessels may contribute to its potential efficacy as a neuroprotective agent in traumatic brain injury. C1 [Lok, Josephine; Leung, Wendy; Zhao, Song; Pallast, Stefanie; van Leyen, Klaus; Guo, Shuzhen; Wang, Xiaoying; Lo, Eng H.] Massachusetts Gen Hosp, Neuroprotect Res Lab, Boston, MA 02114 USA. [Lok, Josephine; Leung, Wendy] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Zhao, Song] Jilin Univ, Hosp 1, Spine Div, Dept Orthoped, Changchun 130023, Jilin, Peoples R China. [Yalcin, Ayfer] Ege Univ, Fac Pharm, Dept Biochem, Izmir, Turkey. [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, 175 Cambridge St,5th Floor, Boston, MA 02114 USA. EM jlok1@partners.org RI van Leyen, Klaus/C-9126-2013 FU NIH [K08NS057339, R01NS049430, R01NS53560, P01NS555104]; American Heart Association; Fulbright Program; Technological and Scientific Council of Turkey [SBAG-K69-104S280] FX This study was supported by NIH grants (K08NS057339 to J.L., R01NS049430 to K.v.L., R01NS53560 and P01NS555104 to E.H.L.), a Scientist Development Grant from the American Heart Association (to K.v.L.), a fellowship from the Fulbright Program (to A.Y.), and by the Technological and Scientific Council of Turkey (SBAG-K69-104S280 to A.Y). The authors thank Dr Michael J. Whalen for helpful discussions regarding the CCI model. The authors declare no conflicts of interest. NR 40 TC 12 Z9 12 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUL PY 2011 VL 118 IS 2 BP 248 EP 255 DI 10.1111/j.1471-4159.2011.07294.x PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 791HH UT WOS:000292655300009 PM 21534958 ER PT J AU Rapaport, MH Nierenberg, AA Howland, R Dording, C Schettler, PJ Mischoulon, D AF Rapaport, Mark Hyman Nierenberg, Andrew A. Howland, Robert Dording, Christina Schettler, Pamela J. Mischoulon, David TI The treatment of minor depression with St. John's Wort or citalopram: Failure to show benefit over placebo SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Minor depression; St. John's Wort; Pharmacotherapy treatment ID RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-LIFE; MAJOR DEPRESSION; ANTIDEPRESSANT TRIALS; SEVERITY; EFFICACY; METAANALYSIS; DISORDERS; THERAPY; SYMPTOMATOLOGY AB This paper presents new data addressing two important controversies in psychiatry: the construct of Minor Depression (MinD) and the efficacy of St. John's Wort for milder forms of depressive disorders. Data are from a three-arm, 12 week, randomized clinical trial of investigating the efficacy of St. John's Wort (810 mg/day), citalopram (20 mg/day), or placebo for acute treatment of MinD. Due to a high placebo response on all outcome measures, neither St. John's Wort nor citalopram separated from placebo on change in depressive symptom severity, quality of life, or well-being. However, systematic assessment of potential adverse effects (AEs) led to three important observations: (1) prior to the administration of study compound, 60% of subjects endorsed items that would be characterized as AEs once study compound was administered, (2) St. John's Wort and citalopram were each associated with a significant number of new or worsening AEs during treatment, and (3) using a structured interview for identifying AEs at baseline and during treatment is informative. MinD was not responsive to either a conventional antidepressant or a nutraceutical, and both compounds were associated with a notable side effects burden. Other treatment approaches for MinD should be investigated. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Rapaport, Mark Hyman; Schettler, Pamela J.] Cedars Sinai Med Ctr, Dept Psychiat & Behav Neurosci, Los Angeles, CA 90048 USA. [Rapaport, Mark Hyman] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90095 USA. [Nierenberg, Andrew A.; Dording, Christina; Mischoulon, David] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Howland, Robert] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA. RP Rapaport, MH (reprint author), Cedars Sinai Med Ctr, Dept Psychiat & Behav Neurosci, 8730 Alden Dr,Thalians C301, Los Angeles, CA 90048 USA. EM mark.rapaport@cshs.org RI Howland, Robert/K-6937-2015 OI Howland, Robert/0000-0002-6533-6010 FU NIMH-NCCAM [5R0-1MH61757]; MGH from NIMH; PamLabs; Pfizer Pharmaceuticals; Shire; Astra Zeneca; Eli Lilly; Jarssen Pharmaceuticals; Bristol Meyers Squibb; Abbott Laboratories; Alkermes; Aspect Medical Systems; Astra-Zeneca; Bristol-Myers Squibb Company; Cephalon; Eli Lilly Company; Forest Pharmaceuticals Inc.; GlaxoSmithkline; J & J Pharmaceuticals; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; Novartis; Organon Inc.; LLC; Pfizer Inc; Pharmavite; Roche; Sanofi-Aventis; Solvay Pharmaceuticals, Inc.; Synthelabo; Wyeth-Ayerst Laboratories FX Funding for this study was provided by NIMH-NCCAM grant 5R0-1MH61757: "Pharmacotherapy for Minor Depression." NIMH and NCCAM had no further role in study design; in the collection, analysis, and interpretation of data; in the writing of this report; or in the decision to submit this paper for publication.; Andrew A. Nierenberg, MD: Dr. Nierenberg has served as a consultant to the American Pychiatric Association (only travel expenses were paid) and to Appliance Computing, Inc. Through the MGH Clinical Trials Network and Institute, he has consulted for Brain Cells, Inc.; Dianippon Sumitomo/Sepracor, Novartis, PGx Health, Shire, Schering-Plough, Targacept, and Takeda/Lundbeck Pharmaceuticals. He has received grant/research support through MGH from NIMH, PamLabs, Pfizer Pharmaceuticals, and Shire. He has received honoraria from Belvior Publishing, University of Texas Southwestern Dallas, Hillside Hospital, American Drug Utilization Review, American Society for Clinical Psychopharmacology, Baystate Medical Center, Columbia University, IMEDEX, MJ Consulting, New York State, MBL Publishing, Physicians Postgraduate Press, SUNY Buffalo, University of Wisconsin, and the University of Pisa. Dr. Nierenberg is a presenter for the Massachusetts General Hospital Psychiatry Academy (MGHPA). The education programs conducted by the MGHPA were supported through Independent Medical Education (IME) grants from the following pharmaceutical companies in 2008: Astra Zeneca, Eli Lilly, and Jarssen Pharmaceuticals; in 2009 by Astra Zeneca, Eli Lilly, and Bristol Meyers Squibb. He is on the advisory boards of Appliance Computing, Inc.; Brain Cells, Inc.; Eli Lilly and Company, Takeda/Lundbeck, and Targacept. Dr. Nierenberg owns stock options in Appliance Computing, Inc., and Brain Cells, Inc. Through MGH, he has a patent extension application for the combination of buspirone, bupropion, and melatonin for the treatment of depression.; Christina Dording, MD: Dr. Dording has received Research Support from Abbott Laboratories, Alkermes, Aspect Medical Systems, Astra-Zeneca, Bristol-Myers Squibb Company, Cephalon, Eli Lilly & Company, Forest Pharmaceuticals Inc., GlaxoSmithkline, J & J Pharmaceuticals, Lichtwer Pharma GmbH, Lorex Pharmaceuticals, Novartis, Organon Inc., PamLab, LLC, Pfizer Inc, Pharmavite, Roche, Sanofi-Aventis, Solvay Pharmaceuticals, Inc., Synthelabo, Wyeth-Ayerst Laboratories. Dr Dording has served as an advisor/consultant for Takeda. Dr. Dording has been a speaker for Wyeth-Ayerst Laboratories. NR 50 TC 23 Z9 24 U1 4 U2 24 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 JUL PY 2011 VL 45 IS 7 BP 931 EP 941 DI 10.1016/j.jpsychires.2011.05.001 PG 11 WC Psychiatry SC Psychiatry GA 791LY UT WOS:000292667900011 PM 21632064 ER PT J AU Keuroghlian, AS Kamen, CS Neri, E Lee, S Liu, RO Gore-Felton, C AF Keuroghlian, Alex S. Kamen, Charles S. Neri, Eric Lee, Susanne Liu, Rhianon Gore-Felton, Cheryl TI Trauma, dissociation, and antiretroviral adherence among persons living with HIV/AIDS SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Dissociation; Post-traumatic stress disorder; Depression; HIV/AIDS; Adherence; Medication ID POSTTRAUMATIC-STRESS-DISORDER; HIV-INFECTED PATIENTS; NATIONAL COMORBIDITY SURVEY; MEDICATION ADHERENCE; HEPATITIS-C; METHODOLOGICAL ISSUES; DEPRESSIVE SYMPTOMS; DISEASE PROGRESSION; DRUG-RESISTANCE; SUBSTANCE USE AB Background: There are approximately 1,000,000 persons living with HIV/AIDS (PLH) in the United States: to reduce rates of new infection and curb disease progression, adherence to HIV medication among PLH is critical. Despite elevated trauma rates in PLH, no studies to date have investigated the relationship between dissociation, a specific symptom of trauma, and HIV medication adherence. We hypothesized that Post-Traumatic Stress Disorder (PTSD) symptoms would be associated with lower adherence, and that dissociation would moderate this relationship. Methods: Forty-three individuals with HIV were recruited from community-based clinics to participate in a cross-sectional study. The relationship of trauma, dissociation, and their interaction to the probability of antiretroviral adherence was assessed using a hierarchical binary logistic regression analysis. Results: Among 38 eligible participants, greater PTSD was associated with lower odds of adherence (OR = .92, p < .05). Dissociation moderated the effect of PTSD on adherence, resulting in lower odds of adherence (OR = .95, p < .05). PTSD symptoms were significantly associated with lower odds of adherence in individuals reporting high levels of dissociation (OR = .86, p < .05) but not in those reporting low levels of dissociation (OR = 1.02, p > .05). Conclusions: This is the first study to demonstrate a relationship between dissociation and medication adherence. Findings are discussed in the context of clinical management of PLH with trauma histories and the need for interventions targeting dissociative symptomatology to optimize adherence. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Keuroghlian, Alex S.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Keuroghlian, Alex S.] McLean Hosp, Belmont, MA 02478 USA. [Kamen, Charles S.; Neri, Eric; Lee, Susanne; Liu, Rhianon; Gore-Felton, Cheryl] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. RP Keuroghlian, AS (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St,WACC 812, Boston, MA 02114 USA. EM akeuroghlian@partners.org FU Stanford University School of Medicine; National Institute of Mental Health (NIMH) [R01MH072386] FX This research was supported in part by the Stanford University School of Medicine Medical Scholars Research Program (PI: Alex Keuroghlian, MD; Faculty Research Advisor: Cheryl Gore-Felton, PhD) and the National Institute of Mental Health (NIMH) grant #R01MH072386 (PI: Cheryl Gore-Felton, PhD). Both sources of funding had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. NR 77 TC 15 Z9 15 U1 4 U2 8 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 JUL PY 2011 VL 45 IS 7 BP 942 EP 948 DI 10.1016/j.jpsychires.2011.05.003 PG 7 WC Psychiatry SC Psychiatry GA 791LY UT WOS:000292667900012 PM 21636097 ER PT J AU Kwon, YM AF Kwon, Young-Min TI An Evidence-based Approach in Understanding "Pseudotumors" in Metal-on-metal Hip Replacements SO JOURNAL OF THE AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS LA English DT Editorial Material ID DISC DEGENERATION; RESURFACING ARTHROPLASTY; INTERVERTEBRAL DISC; MODEL; PUNCTURE C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Kwon, YM (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD ORTHOPAEDIC SURGEONS PI ROSEMENT PA 6300 N RIVER ROAD, ROSEMENT, IL 60018-4262 USA SN 1067-151X J9 J AM ACAD ORTHOP SUR JI J. Am. Acad. Orthop. Surg. PD JUL PY 2011 VL 19 IS 7 BP 451 EP 452 PG 2 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 792NB UT WOS:000292752700009 ER PT J AU Denisco, RC Kenna, GA O'Neil, MG Kulich, RJ Moore, PA Kane, WT Mehta, NR Hersh, EV Katz, NP AF Denisco, Richard C. Kenna, George A. O'Neil, Michael G. Kulich, Ronald J. Moore, Paul A. Kane, William T. Mehta, Noshir R. Hersh, Elliot V. Katz, Nathaniel P. TI Prevention of prescription opioid abuse The role of the dentist SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article DE Opioids; abuse; diversion; addiction; misuse; substance abuse; pain; dentists ID PAIN MEDICATION; SCHOOL-DISTRICT; NONMEDICAL USE; DENTAL PAIN; DRUG-ABUSE; MANAGEMENT; IBUPROFEN; SURGERY; PATIENT AB Background. Opioids are analgesics that have potential for misuse, abuse or addiction. Up to an estimated 23 percent of prescribed doses are used nonmedically. As prescribers of 12 percent of immediate-release (IR) opioids in the United States, dentists can minimize the potential for misuse or abuse. Methods. The authors participated in a two-day meeting in March 2010 cohosted by Tufts Health Care Institute Program on Opioid Risk Management, Boston, and Tufts University School of Dental Medicine, Boston. The purpose of the meeting was to synthesize available opioid abuse literature and data from a 2010 survey regarding West Virginia dentists' analgesic prescribing practices, identify dentists' roles in prescribing opioids that are used nonmedically, highlight practices that dentists can implement and identify research gaps. Results. Dentists can play a role in minimizing opioid abuse through patient education, careful patient assessment and referral for substance abuse treatment when indicated, and using tools such as prescription monitoring programs. Research is needed to determine the optimal number of doses needed to treat dental-related pain. Conclusions. Dentists cannot assume that their prescribing of opioids does not affect the opioid abuse problem in the United States. The authors suggest that dentists, along with other prescribers, take steps to identify problems and minimize prescription opioid abuse through greater prescriber and patient education; use of peer-reviewed recommendations for analgesia; and, when indicated, the tailoring of the appropriate and legitimate prescribing of opioids to adequately treat pain. Practice Implications. The authors encourage dentists to incorporate practical safeguards when prescribing opioids, consistently educate patients about how to secure unused opioids properly, screen patients for substance use disorders and develop a referral network for the treatment of substance use disorders. C1 [Kenna, George A.] Brown Univ, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA. [Denisco, Richard C.] Natl Inst Drug Abuse, Div Epidemiol Serv & Prevent Res, Rockville, MD USA. [Kenna, George A.; Katz, Nathaniel P.] Tufts Hlth Care Inst Program Opioid Risk Manageme, Boston, MA USA. [O'Neil, Michael G.] Univ Charleston, Sch Pharm, Ctr Excellence Educ & Prevent Drug Divers & Subst, Charleston, WV USA. [Kulich, Ronald J.] Massachusetts Gen Hosp, Ctr Pain Med, Boston, MA 02114 USA. [Kulich, Ronald J.] Harvard Univ, Sch Med, Boston, MA USA. [Moore, Paul A.] Univ Pittsburgh, Sch Dent Med, Dept Dent Anesthesiol, Pittsburgh, PA 15260 USA. [Kane, William T.] Missouri Dent Assoc Well Being Program, Jefferson City, MO USA. [Mehta, Noshir R.] Tufts Univ, Sch Dent Med, Dept Gen Dent, Boston, MA 02111 USA. [Mehta, Noshir R.] Tufts Univ, Sch Dent Med, Craniofacial Pain Ctr, Boston, MA 02111 USA. [Hersh, Elliot V.] Univ Penn, Sch Dent Med, Div Pharmacol & Therapeut, Philadelphia, PA 19104 USA. [Katz, Nathaniel P.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Katz, Nathaniel P.] Analges Solut, Natick, MA USA. RP Kenna, GA (reprint author), Brown Univ, Ctr Alcohol & Addict Studies, Box G-S121-5, Providence, RI 02912 USA. EM George_Kenna@Brown.edu FU Endo Pharmaceuticals, Newark, Del.; Grunenthal, Aachen, Germany; King Pharmaceuticals [now part of Pfizer, New York City]; Dominion Diagnostics, North Kingstown, R.I.; Covdien, Dublin; Purdue Pharma, Stamford, Conn. FX The authors thank Amy Rosenstein, Rosemarie Curran, Rosalie Phillips and Sarah Haile from the Tufts Health Care Institute for their administrative support. In addition, the authors thank the supporters of the Tufts Health Care Institute Program on Opioid Risk Management (Endo Pharmaceuticals, Newark, Del.; Grunenthal, Aachen, Germany; King Pharmaceuticals [now part of Pfizer, New York City]; Dominion Diagnostics, North Kingstown, R.I.; Covdien, Dublin; and Purdue Pharma, Stamford, Conn.) for their financial support of The Role of Dentists in Preventing Opioid Abuse Meeting in March 2010, as well as Angela Casey for her assistance in writing this article. NR 80 TC 25 Z9 28 U1 0 U2 7 PU AMER DENTAL ASSOC PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD JUL PY 2011 VL 142 IS 7 BP 800 EP 810 PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 790HM UT WOS:000292579100011 PM 21719802 ER PT J AU Mehta, KM Pierluissi, E Boscardin, WJ Kirby, KA Walter, LC Chren, MM Palmer, RM Counsell, SR Landefeld, CS AF Mehta, Kala M. Pierluissi, Edgar Boscardin, W. John Kirby, Katharine A. Walter, Louise C. Chren, Mary-Margaret Palmer, Robert M. Counsell, Steven R. Landefeld, C. Seth TI A Clinical Index to Stratify Hospitalized Older Adults According to Risk for New-Onset Disability SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE hospitalization; prognosis; disability; activities of daily living ID ACUTE MEDICAL ILLNESS; RANDOMIZED CONTROLLED-TRIAL; FUNCTIONAL DECLINE; ELDERLY-PATIENTS; OUTCOMES; PREDICTORS; HEALTH; CARE; INTERVENTION; TRANSITIONS AB BACKGROUND: Many older adults who are independent prior to hospitalization develop a new disability by hospital discharge. Early risk stratification for new-onset disability may improve care. Thus, this study's objective was to develop and validate a clinical index to determine, at admission, risk for new-onset disability among older, hospitalized adults at discharge. DESIGN: Data analyses derived from two prospective studies. SETTING: Two teaching hospitals in Ohio. PARTICIPANTS: Eight hundred eighty-five patients aged 70 years and older were discharged from a general medical service at a tertiary care hospital (mean age 78, 59% female) and 753 patients discharged from a separate community teaching hospital (mean age 79, 63% female). All participants reported being independent in five activities of daily living (ADLs: bathing, dressing, transferring, toileting, and eating) 2 weeks before admission. MEASUREMENTS: New-onset disability, defined as a new need for personal assistance in one or more ADLs at discharge in participants who were independent 2 weeks before hospital admission. RESULTS: Seven independent risk factors known on admission were identified and weighted using logistic regression: age (80-89, 1 point; >= 90, 2 points); dependence in three or more instrumental ADLs at baseline (2 points); impaired mobility at baseline (unable to run, 1 point; unable to climb stairs, 2 points); dependence in ADLs at admission (2-3 ADLs, 1 point; 4-5 ADLs, 3 points); acute stroke or metastatic cancer (2 points); severe cognitive impairment (1 point); and albumin less than 3.0 g/dL (2 points). New-onset disability occurred in 6%, 13%, 18%, 34%, 35%, 45%, 50%, and 87% of participants with 0, 1, 2, 3, 4, 5, 6, and 7 or more points, respectively, in the derivation cohort (area under the receiver operating characteristic curve (AUC) = 0.784), and in 8%, 10%, 27%, 38%, 44%, 45%, 58%, and 83%, respectively, in the validation cohort (AUC = 0.784). The risk score also predicted (P<.001) disability severity, nursing home placement, and long-term survival. CONCLUSION: This clinical index determines risk for new-onset disability in hospitalized older adults and may inform clinical care. J AmGeriatr Soc 59:1206-1216, 2011. C1 [Mehta, Kala M.; Pierluissi, Edgar; Boscardin, W. John; Kirby, Katharine A.; Walter, Louise C.; Landefeld, C. Seth] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94121 USA. [Boscardin, W. John; Landefeld, C. Seth] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94121 USA. [Chren, Mary-Margaret] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94121 USA. [Mehta, Kala M.; Boscardin, W. John; Walter, Louise C.; Chren, Mary-Margaret; Landefeld, C. Seth] San Francisco VA Med Ctr, Hlth Serv Res Enhancement Award Program, San Francisco, CA USA. [Palmer, Robert M.] Univ Pittsburgh, Div Geriatr Med & Gerontol, Pittsburgh, PA USA. [Counsell, Steven R.] Indiana Univ, Sch Med, Dept Med, Indianapolis, IN USA. [Counsell, Steven R.] Indiana Univ, Sch Med, Indiana Univ Ctr Aging Res, Indianapolis, IN USA. RP Mehta, KM (reprint author), Univ Calif San Francisco, Div Geriatr, 4150 Clement St,Box 181G, San Francisco, CA 94121 USA. EM Kala.mehta@ucsf.edu FU National Institute on Aging (NIA) [RO1 AG029233, K-01AG025444, AG-10418-03]; S.D. Bechtel, Jr. Foundation; National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health [K24 AR052667]; National Cancer Institute [R01CA134425-01A2]; Veterans Affairs Merit Review [IIR 04-427]; John A. Hartford Foundation [88277-3G, 2006-0108]; Summa Health System Foundation FX This work was supported by National Institute on Aging (NIA) Grant RO1 AG029233 and a grant from the S.D. Bechtel, Jr. Foundation (PI: Dr. Landefeld). Dr. Mehta was supported by a Research Career Scientist Award from the NIA (K-01AG025444). She was an affiliate of the Center for Aging in Diverse Communities at the University of California at San Francisco, a part of the P30 AG 15272 350 Resource Centers for Minority Aging Research Program (NIA, National Institute of Nursing Research, and the National Center for Minority Health and Health Disparities). Dr. Pierluissi was supported by an administrative supplement to NIA Grant RO1 AG029233. Dr. Chren was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health (K24 AR052667). Dr. Walter was supported by a grant from the National Cancer Institute (R01CA134425-01A2) and a Veterans Affairs Merit Review Grant (IIR 04-427). The Acute Care for Elders studies were supported by grants from the John A. Hartford Foundation (88277-3G and 2006-0108), the NIA (AG-10418-03), and the Summa Health System Foundation. NR 49 TC 26 Z9 26 U1 5 U2 10 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 JUL PY 2011 VL 59 IS 7 BP 1206 EP 1216 DI 10.1111/j.1532-5415.2011.03409.x PG 11 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 791VT UT WOS:000292696100006 PM 21649616 ER PT J AU Patel, VI Conrad, MF Kwolek, CJ Ouriel, K Fairman, RM Cambria, RP AF Patel, Virendra I. Conrad, Mark F. Kwolek, Christopher J. Ouriel, Kenneth Fairman, Ronald M. Cambria, Richard P. TI Propensity-matched cohort validates findings of the VALOR trial SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID THORACIC AORTIC-ANEURYSMS; STENT-GRAFT; ENDOVASCULAR TREATMENT; OPEN REPAIR; EXPERIENCE; POPULATION; SCORE; ENDOGRAFT; DISEASE; BIAS AB Introduction: The Evaluation of the Medtronic Vascular Talent Thoracic Stent Graft System for the Treatment of Thoracic Aortic Aneurysms (VALOR) trial findings noted superior 30-day and 1-year outcomes of the Talent thoracic endograft (Medtronic Vascular, Santa Rosa, Calif) compared with surgical repair of descending thoracic aneurysms (DTAs). Data from 195 prospective thoracic endovascular aneurysm repair (TEVAR) patients treated with the Talent device and 189 retrospective controls undergoing open surgical repair (OSR) from three centers of excellence were included in the trial after completion of TEVAR enrollment and compared. Such comparisons are biased by baseline differences among TEVAR vs OSR, however, propensity score (PS) analysis can reduce bias and validate such comparisons. Methods: Logistic regression was used to generate a PS (range, 0-1) to identify baseline characteristics more likely in TEVAR. The PS estimated the probability that any patient would undergo TEVAR (eg, a PS of 0.99 represents a 99% chance a patient belongs to TEVAR). PSs were then generated for all patients, and TEVAR and OSR patients were divided into tertiles based on the PS to reduce up to 80% of inherent bias. Outcomes from the middle tertile (T2), patients equally likely (midrange PS) to be in TEVAR or OSR and therefore best matched, were compared using regression analysis and were also compared with the outcomes in the overall trial group. Results: Correlates of membership in TEVAR were smaller aneurysm (P < .001), anticoagulants (P < .01), no previous abdominal aortic aneurysm (AAA) repair (P < .01), no peripheral vascular disease (P = .001), statin use (P = .002), aspirin use (P = .002), older age (P = .028), race (P = .007), male gender (P = .02), and heart failure (P = .035). T2 included 68 TEVAR (PS, 0.58 +/- 0.2) and 67 OSR patients (PS, 0.46 +/- 0.2). VALOR overall reported differences in aneurysm size (56 mm TEVAR vs 69 mm open) and prior AAA repair (19% TEVAR vs 37% open), and this adjusted to no differences in T2 patients. In the well-matched T2 cohort, TEVAR patients had similar 30-day mortality (0% vs 3% OSR; P = .2) and improved 1-year aneurysm-related mortality rates (0% TEVAR vs 8% OSR; P = .05) compared with the OSR patients. This finding was in concurrence with the VALOR trial reporting similar benefit in TEVAR patients. The all-cause 1-year mortality showed a favorable trend for TEVAR in the VALOR trial; however, in T2 patients, 1-year all-cause mortality was similar in both groups of patients (17% TEVAR vs 15% OSR; P = .8). Age (P = .01), history of cerebrovascular accident (P < .05), antiarrhythmia medication (P = .04), and renal disease (P < .03) independently predicted all-cause and aneurysm-related mortality by regression analysis. Conclusions: PS analysis is an important tool for elimination of bias inherent when retrospective controls are used. Its application to VALOR validates the long-term benefit in aneurysm-related mortality conferred by TEVAR in patients undergoing endovascular DTA repair. (J Vasc Surg 2011;54:22-9.) C1 [Patel, Virendra I.; Conrad, Mark F.; Kwolek, Christopher J.; Cambria, Richard P.] Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. [Ouriel, Kenneth] NewYork Presbyterian Hosp, Dept Surg, New York, NY USA. [Fairman, Ronald M.] Hosp Univ Penn, Div Vasc & Endovasc Therapy, Philadelphia, PA 19104 USA. RP Patel, VI (reprint author), Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. NR 26 TC 7 Z9 7 U1 1 U2 2 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 JUL PY 2011 VL 54 IS 1 BP 22 EP 29 DI 10.1016/j.jvs.2010.12.052 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 788GJ UT WOS:000292433100003 PM 21367561 ER PT J AU Staal, FJT Baum, C Cowan, C Dzierzak, E Hacein-Bey-Abina, S Karlsson, S Lapidot, T Lemischka, I Mendez-Ferrer, S Mikkers, H Moore, K Moreno, E Mummery, CL Robin, C Suda, T Van Pel, M Brink, GV Zwaginga, JJ Fibbe, WE AF Staal, F. J. T. Baum, C. Cowan, C. Dzierzak, E. Hacein-Bey-Abina, S. Karlsson, S. Lapidot, T. Lemischka, I. Mendez-Ferrer, S. Mikkers, H. Moore, K. Moreno, E. Mummery, C. L. Robin, C. Suda, T. Van Pel, M. Brink, G. Vanden Zwaginga, J. J. Fibbe, W. E. TI Stem cell self-renewal: lessons from bone marrow, gut and iPS toward clinical applications SO LEUKEMIA LA English DT Review DE stem cell; iPS; gene therapy; embryonic stem cell; transplantation ID SEVERE COMBINED IMMUNODEFICIENCY; GENE-THERAPY; AORTIC ENDOTHELIUM; IN-VIVO; INSERTIONAL MUTAGENESIS; HEMATOPOIETIC-CELLS; VECTOR INTEGRATION; SIGNALING PATHWAYS; (SCID)-X1 DISEASE; SYSTEMS BIOLOGY AB The hematopoietic stem cell (HSC) is the prototype organ-regenerating stem cell (SC), and by far the most studied type of SC in the body. Currently, HSC-based therapy is the only routinely used SC therapy; however, advances in the field of embryonic SCs and induced pluripotent SCs may change this situation. Interest into in vitro generation of HSCs, including signals for HSC expansion and differentiation from these more primitive SCs, as well as advances in other organ-specific SCs, in particular the intestine, provide promising new applications for SC therapies. Here, we review the basic principles of different SC systems, and on the basis of the experience with HSC-based SC therapy, provide recommendations for clinical application of emerging SC technologies. Leukemia (2011) 25, 1095-1102; doi:10.1038/leu.2011.52; published online 29 April 2011 C1 [Staal, F. J. T.; Van Pel, M.; Zwaginga, J. J.; Fibbe, W. E.] Leiden Univ, Med Ctr, Dept Immunohematol & Blood Transfus, NL-2300 RC Leiden, Netherlands. [Baum, C.] Hannover Med Sch, Dept Expt Hematol, D-3000 Hannover, Germany. [Cowan, C.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Dzierzak, E.; Robin, C.] Erasmus MC Stem Cell Inst, Dept Cell Biol, Rotterdam, Netherlands. [Hacein-Bey-Abina, S.] Hop Necker Enfants Malad, Dept Biotherapy, Paris, France. [Karlsson, S.] Lund Univ, Dept Mol Med, Lund, Sweden. [Lapidot, T.] Weizmann Inst Sci, Dept Immunol, Rehovot, Israel. [Lemischka, I.; Mendez-Ferrer, S.; Moore, K.] Mt Sinai Sch Med, Dept Dev & Regenerat Biol, New York, NY USA. [Mikkers, H.] Leiden Univ, Med Ctr, Dept Mol Cell Biol, NL-2300 RC Leiden, Netherlands. [Moreno, E.] Ctr Nacl Invest Oncol, Dept Mol Oncol, Madrid, Spain. [Mummery, C. L.] Leiden Univ, Med Ctr, Dept Anat & Embryol, NL-2300 RC Leiden, Netherlands. [Suda, T.] Keio Univ, Sch Med, Dept Cell Differentiat, Tokyo, Japan. [Brink, G. Vanden] Leiden Univ, Med Ctr, Dept Gastroenterol & Hepatol, NL-2300 RC Leiden, Netherlands. RP Staal, FJT (reprint author), Leiden Univ, Med Ctr, Dept Immunohematol & Blood Transfus, Albinusdreef 2,POB 9600, NL-2300 RC Leiden, Netherlands. EM F.J.T.StaaL@LUMC.nl RI Lapidot, Tsvee/A-1812-2010; OI Mendez-Ferrer, Simon/0000-0002-9805-9988 NR 75 TC 11 Z9 11 U1 0 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD JUL PY 2011 VL 25 IS 7 BP 1095 EP 1102 DI 10.1038/leu.2011.52 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA 791RP UT WOS:000292682600004 PM 21527933 ER PT J AU Vallet, S Pozzi, S Patel, K Vaghela, N Fulciniti, MT Veiby, P Hideshima, T Santo, L Cirstea, D Scadden, DT Anderson, KC Raje, N AF Vallet, S. Pozzi, S. Patel, K. Vaghela, N. Fulciniti, M. T. Veiby, P. Hideshima, T. Santo, L. Cirstea, D. Scadden, D. T. Anderson, K. C. Raje, N. TI A novel role for CCL3 (MIP-1 alpha) in myeloma-induced bone disease via osteocalcin downregulation and inhibition of osteoblast function SO LEUKEMIA LA English DT Article DE myeloma; CCL3; osteoblast; osteocalcin; ERK; osterix ID MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA; HUMAN MULTIPLE-MYELOMA; ACTIVATED PROTEIN-KINASE; CHEMOKINE RECEPTORS; CELL-LINES; GENE-EXPRESSION; MM CELLS; DIFFERENTIATION; ALPHA; PATHWAYS AB Upregulation of cytokines and chemokines is a frequent finding in multiple myeloma (MM). CCL3 (also known as MIP-1 alpha) is a pro-inflammatory chemokine, levels of which in the MM microenvironment correlate with osteolytic lesions and tumor burden. CCL3 and its receptors, CCR1 and CCR5, contribute to the development of bone disease in MM by supporting tumor growth and regulating osteoclast (OC) differentiation. In this study, we identify inhibition of osteoblast (OB) function as an additional pathogenic mechanism in CCL3-induced bone disease. MM-derived and exogenous CCL3 represses mineralization and osteocalcin production by primary human bone marrow stromal cells and HS27A cells. Our results suggest that CCL3 effects on OBs are mediated by ERK activation and subsequent downregulation of the osteogenic transcription factor osterix. CCR1 inhibition reduced ERK phosphorylation and restored both osterix and osteocalcin expression in the presence of CCL3. Finally, treating SCID-hu mice with a small molecule CCR1 inhibitor suggests an upregulation of osteocalcin expression along with OC downregulation. Our results show that CCL3, in addition to its known catabolic activity, reduces bone formation by inhibiting OB function, and therefore contributes to OB/OC uncoupling in MM. Leukemia (2011) 25, 1174-1181; doi:10.1038/leu.2011.43; published online 15 March 2011 C1 [Raje, N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med Oncol,MGH Canc Ctr,Div Hematol & Oncol, Boston, MA 02114 USA. [Vallet, S.; Pozzi, S.; Fulciniti, M. T.; Hideshima, T.; Santo, L.; Cirstea, D.; Anderson, K. C.; Raje, N.] Harvard Univ, Dana Farber Canc Inst, Sch Med, Jerome Lipper Multiple Myeloma Dis Ctr, Boston, MA 02114 USA. [Vallet, S.] Univ Heidelberg, Natl Ctr Tumor Dis NCT, Heidelberg, Germany. [Veiby, P.] Millennium Pharmaceut Inc, Cambridge, MA USA. RP Raje, N (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med Oncol,MGH Canc Ctr,Div Hematol & Oncol, 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 Astra Zeneca; Acetylon; IMF junior award; ASCO CDA; MMRF; LLS CDA; NIH [P50 CA 100707-06] FX The author NR is consultant for Celgene and Novartis, member of the advisory committee for Celgene and Amgen, and she had received research funding from Astra Zeneca and Acetylon. PV is an employee of Millennium Pharmaceuticals.; This study was supported by IMF junior award (SV, SP, LS), ASCO CDA, MMRF, LLS CDA, NIH P50 CA 100707-06 (NR). MLN3897 was kindly provided by Millennium Pharmaceuticals, Cambridge, MA, USA. NR 30 TC 46 Z9 54 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD JUL PY 2011 VL 25 IS 7 BP 1174 EP 1181 DI 10.1038/leu.2011.43 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA 791RP UT WOS:000292682600014 PM 21403648 ER PT J AU Abdel-Wahab, O Pardanani, A Patel, J Wadleigh, M Lasho, T Heguy, A Beran, M Gilliland, DG Levine, RL Tefferi, A AF Abdel-Wahab, O. Pardanani, A. Patel, J. Wadleigh, M. Lasho, T. Heguy, A. Beran, M. Gilliland, D. G. Levine, R. L. Tefferi, A. TI Concomitant analysis of EZH2 and ASXL1 mutations in myelofibrosis, chronic myelomonocytic leukemia and blast-phase myeloproliferative neoplasms SO LEUKEMIA LA English DT Letter ID MYELOID-LEUKEMIA; GENE; PROGRESSION; TET2 C1 [Abdel-Wahab, O.; Patel, J.; Heguy, A.; Levine, R. L.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10021 USA. [Abdel-Wahab, O.; Levine, R. L.] Mem Sloan Kettering Canc Ctr, Leukemia Serv, Dept Med, New York, NY 10021 USA. [Pardanani, A.; Lasho, T.; Tefferi, A.] Mayo Clin, Div Hematol, Rochester, MN USA. [Wadleigh, M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Beran, M.] MD Anderson Canc, Div Leukemia, Houston, TX 77030 USA. [Gilliland, D. G.] Merck & Co Inc, N Wales, PA USA. RP Abdel-Wahab, O (reprint author), Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, 1275 York Ave, New York, NY 10021 USA. EM abdelwao@mskcc.org OI Abdel-Wahab, Omar/0000-0002-3907-6171 FU NCI NIH HHS [R01 CA151949] NR 8 TC 108 Z9 115 U1 1 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 JUL PY 2011 VL 25 IS 7 BP 1200 EP 1202 DI 10.1038/leu.2011.58 PG 3 WC Oncology; Hematology SC Oncology; Hematology GA 791RP UT WOS:000292682600020 PM 21455215 ER PT J AU Lu, J Ma, Y Kong, N Alipio, Z Gao, C Krause, DS Silberstein, LE Chai, L AF Lu, J. Ma, Y. Kong, N. Alipio, Z. Gao, C. Krause, D. S. Silberstein, L. E. Chai, L. TI Dissecting the role of SALL4, a newly identified stem cell factor, in chronic myelogenous leukemia SO LEUKEMIA LA English DT Letter ID CHRONIC MYELOID-LEUKEMIA; BMI-1; GENE; ONCOGENE; MICE C1 [Lu, J.; Kong, N.; Gao, C.; Silberstein, L. E.; Chai, L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Ma, Y.] SUNY Stony Brook, Dept Pathol, Med Ctr, Stony Brook, NY 11794 USA. [Ma, Y.; Alipio, Z.] Nevada Canc Inst, Div Lab Med, Las Vegas, NV USA. [Krause, D. S.] Massachusetts Gen Hosp, Dept Pathol, Blood Transfus Serv, Boston, MA 02114 USA. RP Lu, J (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. EM lchai@partners.org FU NCI NIH HHS [K08 CA138916]; NHLBI NIH HHS [P01 HL095489, P01HL095489, R01 HL087948, R01 HL092437, R01HL087948, R01HL092437, R01HL092437-A1S1]; NIDDK NIH HHS [P01 DK080665] NR 8 TC 15 Z9 19 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD JUL PY 2011 VL 25 IS 7 BP 1211 EP 1213 DI 10.1038/leu.2011.65 PG 3 WC Oncology; Hematology SC Oncology; Hematology GA 791RP UT WOS:000292682600024 PM 21468036 ER PT J AU Kuntz, KM Lansdorp-Vogelaar, I Rutter, CM Knudsen, AB van Ballegooijen, M Savarino, JE Feuer, EJ Zauber, AG AF Kuntz, Karen M. Lansdorp-Vogelaar, Iris Rutter, Carolyn M. Knudsen, Amy B. van Ballegooijen, Marjolein Savarino, James E. Feuer, Eric J. Zauber, Ann G. TI A Systematic Comparison of Microsimulation Models of Colorectal Cancer: The Role of Assumptions about Adenoma Progression SO MEDICAL DECISION MAKING LA English DT Article DE microsimulation; colorectal cancer; screening ID FECAL-OCCULT-BLOOD; RANDOMIZED CONTROLLED-TRIAL; COST-EFFECTIVENESS ANALYSIS; SERVICES TASK-FORCE; LARGE-INTESTINE; LARGE-BOWEL; CLINICAL GUIDELINES; MEDICARE POPULATION; POLYPS; AUTOPSY AB Background. As the complexity of microsimulation models increases, concerns about model transparency are heightened. Methods. The authors conducted model "experiments" to explore the impact of variations in "deep" model parameters using 3 colorectal cancer (CRC) models. All natural history models were calibrated to match observed data on adenoma prevalence and cancer incidence but varied in their underlying specification of the adenocarcinoma process. The authors projected CRC incidence among individuals with an underlying adenoma or preclinical cancer v. those without any underlying condition and examined the impact of removing adenomas. They calculated the percentage of simulated CRC cases arising from adenomas that developed within 10 or 20 years prior to cancer diagnosis and estimated dwell time-defined as the time from the development of an adenoma to symptom-detected cancer in the absence of screening among individuals with a CRC diagnosis. Results. The 20-year CRC incidence among 55-year-old individuals with an adenoma or preclinical cancer was 7 to 75 times greater than in the condition-free group. The removal of all adenomas among the subgroup with an underlying adenoma or cancer resulted in a reduction of 30% to 89% in cumulative incidence. Among CRCs diagnosed at age 65 years, the proportion arising from adenomas formed within 10 years ranged between 4% and 67%. The mean dwell time varied from 10.6 to 25.8 years. Conclusions. Models that all match observed data on adenoma prevalence and cancer incidence can produce quite different dwell times and very different answers with respect to the effectiveness of interventions. When conducting applied analyses to inform policy, using multiple models provides a sensitivity analysis on key (unobserved) "deep" model parameters and can provide guidance about specific areas in need of additional research and validation. C1 [Kuntz, Karen M.] Univ Minnesota, Sch Publ Hlth, Div Hlth Policy & Management, Minneapolis, MN 55455 USA. [Lansdorp-Vogelaar, Iris; van Ballegooijen, Marjolein] Erasmus MC, Dept Publ Hlth, Rotterdam, Netherlands. [Rutter, Carolyn M.; Savarino, James E.] Grp Hlth Res Inst, Ctr Hlth Studies, Seattle, WA USA. [Knudsen, Amy B.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Feuer, Eric J.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Zauber, Ann G.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. RP Kuntz, KM (reprint author), Univ Minnesota, Sch Publ Hlth, Div Hlth Policy & Management, MMC 729,420 Delaware St SE, Minneapolis, MN 55455 USA. EM kmkuntz@umn.edu FU National Cancer Institute [U01-CA-088204, U01-CA-097426, U01-CA-097427, U01-CA-115953] FX Received 15 January 2009 from the Division of Health Policy and Management, School of Public Health, University of Minnesota, Minneapolis (KMK); Department of Public Health, Erasmus MC, Rotterdam, the Netherlands (IL-V, MvB); Center for Health Studies, Group Health Research Institute, Seattle, Washington (CMR, JES); Institute for Technology Assessment, Massachusetts General Hospital, Boston (ABK); Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, Maryland (EJF); and Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY (AGZ). This research was supported by the National Cancer Institute (U01-CA-088204, U01-CA-097426, U01-CA-097427, and U01-CA-115953). Revision accepted for publication 5 April 2011. NR 48 TC 28 Z9 29 U1 0 U2 2 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 JUL-AUG PY 2011 VL 31 IS 4 BP 530 EP 539 DI 10.1177/0272989X11408730 PG 10 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 792HL UT WOS:000292732800004 PM 21673186 ER PT J AU van Ballegooijen, M Rutter, CM Knudsen, AB Zauber, AG Savarino, JE Lansdorp-Vogelaar, I Boer, R Feuer, EJ Habbema, JDF Kuntz, KM AF van Ballegooijen, Marjolein Rutter, Carolyn M. Knudsen, Amy B. Zauber, Ann G. Savarino, James E. Lansdorp-Vogelaar, Iris Boer, Rob Feuer, Eric J. Habbema, J. Dik F. Kuntz, Karen M. TI Clarifying Differences in Natural History between Models of Screening: The Case of Colorectal Cancer SO MEDICAL DECISION MAKING LA English DT Article DE microsimulation; natural history; colorectal cancer; screening models; standard model output ID SOCIETY-TASK-FORCE; COST-EFFECTIVENESS; DECISION-ANALYSIS; COLONOGRAPHY; SURVEILLANCE; STRATEGIES AB Background. Microsimulation models are important decision support tools for screening. However, their complexity makes them difficult to understand and limits realization of their full potential. Therefore, it is important to develop documentation that clarifies their structure and assumptions. The authors demonstrate this problem and explore a solution for natural history using 3 independently developed colorectal cancer screening models. Methods. The authors first project effectiveness and cost-effectiveness of colonoscopy screening for the 3 models (CRC-SPIN, SimCRC, and MISCAN). Next, they provide a conventional presentation of each model, including information on structure and parameter values. Finally, they report the simulated reduction in clinical cancer incidence following a one-time complete removal of adenomas and preclinical cancers for each model. They call this new measure the maximum clinical incidence reduction (MCLIR). Results. Projected effectiveness varies widely across models. For example, estimated mortality reduction for colonoscopy screening every 10 years from age 50 to 80 years, with surveillance in adenoma patients, ranges from 65% to 92%. Given only conventional information, it is difficult to explain these differences, largely because differences in structure make parameter values incomparable. In contrast, the MCLIR clearly shows the impact of model differences on the key feature of natural history, the dwell time of preclinical disease. Dwell times vary from 8 to 25 years across models and help explain differences in projected screening effectiveness. Conclusions. The authors propose a new measure, the MCLIR, which summarizes the implications for predicted screening effectiveness of differences in natural history assumptions. Including the MCLIR in the standard description of a screening model would improve the transparency of these models. C1 [van Ballegooijen, Marjolein; Lansdorp-Vogelaar, Iris; Boer, Rob; Habbema, J. Dik F.] Erasmus MC, Dept Publ Hlth, NL-3000 CA Rotterdam, Netherlands. [Rutter, Carolyn M.; Savarino, James E.] Grp Hlth Res Inst, Seattle, WA USA. [Knudsen, Amy B.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Zauber, Ann G.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Feuer, Eric J.] NCI, Div Canc Control & Populat Sci, Washington, DC USA. [Kuntz, Karen M.] Univ Minnesota, Sch Publ Hlth, Div Hlth Policy & Management, Minneapolis, MN USA. RP van Ballegooijen, M (reprint author), Erasmus MC, Dept Publ Hlth, POB 2040, NL-3000 CA Rotterdam, Netherlands. EM m.vanballegooijen@erasmusmc.nl RI Boer, Rob/E-6473-2015 OI Boer, Rob/0000-0003-0680-001X FU National Institutes of Health/National Cancer Institute [U01-CA-088204, U01-CA-097427, U01-CA-097426, U01-CA-115953] FX Received 18 July 2010 from the Department of Public Health, Erasmus MC, Rotterdam, the Netherlands (MvB, IL-V, RB, JDFH); Group Health Research Institute, Seattle, Washington (CMR, JES); Institute for Technology Assessment, Massachusetts General Hospital, Boston (ABK); Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (AGZ); Division of Cancer Control and Population Sciences, National Cancer Institute, Washington, DC (EJF); and Division of Health Policy and Management, School of Public Health, University of Minnesota, Minneapolis (KMK). This work was supported by the National Institutes of Health/National Cancer Institute (U01-CA-088204, U01-CA-097427, U01-CA-097426, and U01-CA-115953). Revision accepted for publication 4 April 2011. NR 24 TC 15 Z9 15 U1 0 U2 2 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 JUL-AUG PY 2011 VL 31 IS 4 BP 540 EP 549 DI 10.1177/0272989X11408915 PG 10 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 792HL UT WOS:000292732800005 PM 21673187 ER PT J AU Brown, MA AF Brown, Mark A. TI Science Versus Policy in Establishing Equitable Agent Orange Disability Compensation Policy SO MILITARY MEDICINE LA English DT Article ID VIETNAM; HERBICIDES; VETERANS AB This article makes the case that current Agent Orange compensation policy for Vietnam War veterans is based neither wholly upon scientific findings about Agent Orange health effects nor on pure public health policy considerations. Rather, it is the logical culmination of decades of experience among policy makers and public health scientists trying to establish clear-cut, equitable, and scientifically defensible compensation policy in the face of limited relevant science and poor or nonexistent exposure data-all within the broader context of Veterans Affairs disability compensation policies, and a deep-seated commitment to support the men and women who served their country during the Vietnam War. Finally, attempts to update current policy will benefit from an understanding of this background. C1 [Brown, Mark A.] US Dept Vet Affairs, Off Publ Hlth & Environm Agents Serv, Richmond, VA USA. RP Brown, MA (reprint author), 803 Aspen St NW, Washington, DC 20012 USA. NR 21 TC 3 Z9 3 U1 0 U2 3 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 J9 MIL MED JI Milit. Med. PD JUL PY 2011 VL 176 IS 7 SU S BP 35 EP 40 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 792XQ UT WOS:000292784100011 PM 21916328 ER PT J AU McNally, RJ Hatch, JP Cedillos, EM Luethcke, CA Baker, MT Peterson, AL Litz, BT AF McNally, Richard J. Hatch, John P. Cedillos, Elizabeth M. Luethcke, Cynthia A. Baker, Monty T. Peterson, Alan L. Litz, Brett T. TI Does the Repressor Coping Style Predict Lower Posttraumatic Stress Symptoms? SO MILITARY MEDICINE LA English DT Article ID SOCIAL DESIRABILITY SCALE; MANIFEST ANXIETY SCALE; FOLLOW-UP; PSYCHOLOGICAL-RESILIENCE; YOUNG-ADULTS; SHORT FORM; DISORDER; TRAUMA; IRAQ; PSYCHOPATHOLOGY AB We tested whether a continuous measure of repressor coping style predicted lower posttraumatic stress disorder (PTSD) symptoms in 122 health care professionals serving in Operation Iraqi Freedom. Zero-order correlational analyses indicated that predeployment repressor coping scores negatively predicted postdeployment PTSD symptoms, r(s) = 0.29, p = 0.001, whereas predeployment Connor Davidson Resilience Scale (CD-RISC) scores did not predict postdeployment PTSD symptoms, r(s) = 0.13, p = 0.14. However, predeployment trait anxiety was chiefly responsible for the association between repressor coping and PTSD symptom severity, r(s) = 0.38, p = 0.001. Four percent of the subjects qualified for a probable PTSD diagnosis. Although service members with relatively higher PTSD scores had lower repressor coping scores than did the other subjects, their level of predeployment anxiety was chiefly responsible for this relationship. Knowing someone's predeployment level of trait anxiety permits better prediction of PTSD symptoms among trauma-exposed service members than does knowing his or her level of repressive coping. C1 [McNally, Richard J.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Hatch, John P.; Cedillos, Elizabeth M.; Luethcke, Cynthia A.; Baker, Monty T.; Peterson, Alan L.] Univ Texas Hlth Sci Ctr San Antonio, Div Behav Med, San Antonio, TX 78229 USA. [Baker, Monty T.; Peterson, Alan L.] Wilford Hall USAF Med Ctr, Dept Behav Med, Lackland AFB, TX 78236 USA. [Litz, Brett T.] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA 02130 USA. [Litz, Brett T.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. RP McNally, RJ (reprint author), Harvard Univ, Dept Psychol, 1230 William James Hall,33 Kirkland St, Cambridge, MA 02138 USA. FU United States Air Force [FA7014-07-C-0036] FX This work was supported by a grant to Alan L. Peterson from the United States Air Force Surgeon General's Operational Medicine Research Program (FA7014-07-C-0036). NR 36 TC 7 Z9 7 U1 2 U2 3 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 J9 MIL MED JI Milit. Med. PD JUL PY 2011 VL 176 IS 7 BP 752 EP 756 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 792XO UT WOS:000292783900004 PM 22128715 ER PT J AU Bigatello, LM Kistler, EB Noto, A AF Bigatello, L. M. Kistler, E. B. Noto, A. TI Volumetric indices obtained by transthoracic thermodilution SO MINERVA ANESTESIOLOGICA LA English DT Letter C1 [Bigatello, L. M.] Harvard Univ, Sch Med, Anesthesiol Serv, VA Boston Healthcare Syst, Boston, MA USA. [Kistler, E. B.] Univ Calif San Diego, Dept Anesthesia, San Diego, CA 92103 USA. [Noto, A.] Univ Messina, Dept Cardiothorac & Vasc Anesthesia, Policlin G Martino, Messina, Italy. RP Bigatello, LM (reprint author), VA Boston Healthcare Syst, Anesthesia & Crit Care Serv, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM lbigatello@partners.org RI Noto, Alberto/G-6468-2012 NR 5 TC 0 Z9 0 U1 0 U2 0 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 JUL PY 2011 VL 77 IS 7 BP 756 EP 757 PG 2 WC Anesthesiology; Critical Care Medicine SC Anesthesiology; General & Internal Medicine GA 792XV UT WOS:000292784600015 ER PT J AU Addona, TA Shi, X Keshishian, H Mani, DR Burgess, M Gillette, MA Clauser, KR Shen, DX Lewis, GD Farrell, LA Fifer, MA Sabatine, MS Gerszten, RE Carr, SA AF Addona, Terri A. Shi, Xu Keshishian, Hasmik Mani, D. R. Burgess, Michael Gillette, Michael A. Clauser, Karl R. Shen, Dongxiao Lewis, Gregory D. Farrell, Laurie A. Fifer, Michael A. Sabatine, Marc S. Gerszten, Robert E. Carr, Steven A. TI A pipeline that integrates the discovery and verification of plasma protein biomarkers reveals candidate markers for cardiovascular disease SO NATURE BIOTECHNOLOGY LA English DT Article ID HYPERTROPHIC OBSTRUCTIVE CARDIOMYOPATHY; ACUTE CORONARY SYNDROMES; MASS-SPECTROMETRY; CLINICAL UTILITY; HIGH-CONFIDENCE; REDUCTION; ASSAYS; VALIDATION; PROTEOMICS; SERUM AB We developed a pipeline to integrate the proteomic technologies used from the discovery to the verification stages of plasma biomarker identification and applied it to identify early biomarkers of cardiac injury from the blood of patients undergoing a therapeutic, planned myocardial infarction (PMI) for treatment of hypertrophic cardiomyopathy. Sampling of blood directly from patient hearts before, during and after controlled myocardial injury ensured enrichment for candidate biomarkers and allowed patients to serve as their own biological controls. LC-MS/MS analyses detected 121 highly differentially expressed proteins, including previously credentialed markers of cardiovascular disease and > 100 novel candidate biomarkers for myocardial infarction (MI). Accurate inclusion mass screening (AIMS) qualified a subset of the candidates based on highly specific, targeted detection in peripheral plasma, including some markers unlikely to have been identified without this step. Analyses of peripheral plasma from controls and patients with PMI or spontaneous MI by quantitative multiple reaction monitoring mass spectrometry or immunoassays suggest that the candidate biomarkers may be specific to MI. This study demonstrates that modern proteomic technologies, when coherently integrated, can yield novel cardiovascular biomarkers meriting further evaluation in large, heterogeneous cohorts. C1 [Addona, Terri A.; Keshishian, Hasmik; Mani, D. R.; Burgess, Michael; Gillette, Michael A.; Clauser, Karl R.; Gerszten, Robert E.; Carr, Steven A.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Shi, Xu; Shen, Dongxiao; Lewis, Gregory D.; Farrell, Laurie A.; Fifer, Michael A.; Sabatine, Marc S.; Gerszten, Robert E.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Gillette, Michael A.] Massachusetts Gen Hosp, Div Pulm, Boston, MA 02114 USA. [Lewis, Gregory D.; Gerszten, Robert E.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [Lewis, Gregory D.; Sabatine, Marc S.; Gerszten, Robert E.] Harvard Univ, Sch Med, Donald W Reynolds Cardiovasc Clin Res Ctr Atheros, Boston, MA USA. [Sabatine, Marc S.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. RP Carr, SA (reprint author), Broad Inst MIT & Harvard, Cambridge, MA USA. EM gerszten.robert@mgh.harvard.edu; scarr@broad.mit.edu FU US National Institutes of Health (NIH) National Heart, Lung, and Blood Institute [U01HL083141, R01HL096738-02]; Donald W. Reynolds Foundation; Foundation Leducq; NIH [1U24 CA126476]; Entertainment Industry Foundation; NCI Clinical Proteomic Technologies Initiative [R01 CA126219] FX The authors gratefully acknowledge support from the US National Institutes of Health (NIH) National Heart, Lung, and Blood Institute U01HL083141 and R01HL096738-02 to R.E.G., S.A.C. and M.S.S., the Donald W. Reynolds Foundation (to R.E.G. and M.S.S.) and Foundation Leducq (to R.E.G.). S.A.C. also acknowledges support from the NIH 1U24 CA126476 as part of the National Cancer Institute (NCI)'s Clinical Proteomic Technologies Assessment in Cancer Program, from the Women's Cancer Research Fund of the Entertainment Industry Foundation and to D.R.M. from the NCI Clinical Proteomic Technologies Initiative (R01 CA126219). We also appreciate the excellent technical assistance of C. Bodycombe. NR 36 TC 132 Z9 135 U1 2 U2 42 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 JUL PY 2011 VL 29 IS 7 BP 635 EP U119 DI 10.1038/nbt.1899 PG 11 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 790NM UT WOS:000292595200022 PM 21685905 ER PT J AU Boehm, JS Hahn, WC AF Boehm, Jesse S. Hahn, William C. TI Towards systematic functional characterization of cancer genomes SO NATURE REVIEWS GENETICS LA English DT Review ID RNA INTERFERENCE SCREEN; LOSS-OF-FUNCTION; SYNTHETIC LETHAL INTERACTIONS; CELL LUNG-CANCER; NF-KAPPA-B; GENETIC SCREEN; BREAST-CANCER; KINASE REQUIREMENTS; SMALL-MOLECULE; LIVER-CANCER AB Whole-genome approaches to identify genetic and epigenetic alterations in cancer genomes have begun to provide new insights into the range of molecular events that occurs in human tumours. Although in some cases this knowledge immediately illuminates a path towards diagnostic or therapeutic implementation, the bewildering lists of mutations in each tumour make it clear that systematic functional approaches are also necessary to obtain a comprehensive molecular understanding of cancer. Here we review the current range of methods, assays and approaches for genome-scale interrogation of gene function in cancer. We also discuss the integration of functional-genomics approaches with the outputs from cancer genome sequencing efforts. C1 [Boehm, Jesse S.; Hahn, William C.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Hahn, William C.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Dept Med Oncol, Boston, MA 02115 USA. [Hahn, William C.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Hahn, William C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Hahn, WC (reprint author), Broad Inst MIT & Harvard, 7 Cambridge Ctr, Cambridge, MA 02142 USA. EM william_hahn@dfci.harvard.edu OI Boehm, Jesse/0000-0002-6795-6336 FU US National Institutes of Health; Starr Cancer Consortium; Ivy Foundation; H.L. Snyder Foundation; Prostate Cancer Foundation FX We thank the members of the Hahn laboratory and the Broad Institute Cancer Program for discussions. W.C.H. is supported in part by grants from the US National Institutes of Health, the Starr Cancer Consortium, the Ivy Foundation, the H.L. Snyder Foundation and the Prostate Cancer Foundation. We apologize to those authors whose relevant work could not be cited owing to space considerations. NR 113 TC 47 Z9 48 U1 0 U2 13 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 JUL PY 2011 VL 12 IS 7 BP 487 EP 498 DI 10.1038/nrg3013 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 793IT UT WOS:000292814500011 PM 21681210 ER PT J AU Iwase, S Xiang, B Ghosh, S Ren, T Lewis, PW Cochrane, JC Allis, CD Picketts, DJ Patel, DJ Li, HT Shi, Y AF Iwase, Shigeki Xiang, Bin Ghosh, Sharmistha Ren, Ting Lewis, Peter W. Cochrane, Jesse C. Allis, C. David Picketts, David J. Patel, Dinshaw J. Li, Haitao Shi, Yang TI ATRX ADD domain links an atypical histone methylation recognition mechanism to human mental-retardation syndrome SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID HP1 CHROMO DOMAIN; PROTEIN ATRX; PHD FINGER; BINDING MODULES; MOLECULAR-BASIS; X SYNDROME; LYSINE 9; H3; HETEROCHROMATIN; MUTATIONS AB ATR-X (alpha-thalassemia/mental retardation, X-linked) syndrome is a human congenital disorder that causes severe intellectual disabilities. Mutations in the ATRX gene, which encodes an ATP-dependent chromatin-remodeler, are responsible for the syndrome. Approximately 50% of the missense mutations in affected persons are clustered in a cysteine-rich domain termed ADD (ATRX-DNMT3-DNMT3L, ADD(ATRX)), whose function has remained elusive. Here we identify ADD(ATRX) as a previously unknown histone H3-binding module, whose binding is promoted by lysine 9 trimethylation (H3K9me3) but inhibited by lysine 4 trimethylation (H3K4me3). The cocrystal structure of ADD(ATRX) bound to H3(1-15)K9me3 peptide reveals an atypical composite H3K9me3-binding pocket, which is distinct from the conventional trimethyllysine-binding aromatic cage. Notably, H3K9me3-pocket mutants and ATR-X syndrome mutants are defective in both H3K9me3 binding and localization at pericentromeric heterochromatin; thus, we have discovered a unique histone-recognition mechanism underlying the ATR-X etiology. C1 [Xiang, Bin; Li, Haitao] Tsinghua Univ, Sch Life Sci, Ctr Struct Biol, Beijing 100084, Peoples R China. [Iwase, Shigeki; Ren, Ting; Shi, Yang] Harvard Univ, Sch Med, Dept Med, Div Newborn Med,Childrens Hosp Boston, Boston, MA USA. [Iwase, Shigeki; Ren, Ting; Shi, Yang] Harvard Univ, Sch Med, Dept Med, Epigenet Program,Childrens Hosp Boston, Boston, MA USA. [Xiang, Bin; Li, Haitao] Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China. [Ghosh, Sharmistha] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Lewis, Peter W.; Allis, C. David] Rockefeller Univ, Lab Chromatin Biol & Epigenet, New York, NY 10021 USA. [Cochrane, Jesse C.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Picketts, David J.] Ottawa Hosp, Res Inst, Regenerat Med Program, Ottawa, ON, Canada. [Patel, Dinshaw J.] Mem Sloan Kettering Canc Ctr, Struct Biol Program, New York, NY 10021 USA. RP Li, HT (reprint author), Tsinghua Univ, Sch Life Sci, Ctr Struct Biol, Beijing 100084, Peoples R China. EM pateld@mskcc.org; lht@tsinghua.edu.cn; yshi@hms.harvard.edu RI Lewis, Peter/C-4348-2008; Li, Haitao/B-2668-2012; OI Li, Haitao/0000-0001-6741-293X; Lewis, Peter/0000-0002-9816-7823 FU Jane Coffin Childs Memorial Fund; Japan Society for the Promotion of Science; US National Institutes of Health [GM071004, GM058012]; Starr Foundation; Leukemia and Lymphoma Society; Abby Rockefeller Mauze Trust; Maloris Foundation; Canadian Institutes of Health Research; Major State Basic Research Development Program in China [2011CB965300]; Tsinghua University FX The authors are grateful to the staffs of beamlines X-29 at the Brookhaven National Laboratory, 24IDC at the Advanced Photon Source and 3W1A at the Beijing Synchrotron Radiation Facility (BSRF) for their assistance in the synchrotron data collection, with special thanks to Y. Dong of BSRF. We thank A. Vaquero (Bellvitge Institute for Biomedical Research) and S. Minucci (European Institute of Oncology) for providing the Suv39h1 and Suv39h2 double knockout cells and SUV39H1 expression vectors. Anti-MeCP2 antiserum was a generous gift from M. Greenberg (Harvard Medical School, HMS). We are grateful to A. Ruthenburg (Rockefeller University) for providing histone H3 peptides and to L. Liang (Memorial Sloan-Kettering Cancer Center), Y. Y. Chen (Institute of Biophysics, Chinese Academy of Sciences) and M. Geigges (Children's Hospital Boston) for experimental help. We express great appreciation to C. Richardson, M. Takahashi at HMS and individual members of the Shi, Li and Patel laboratories for helpful discussions. S. I. was a Jane Coffin Childs Memorial Fund Postdoctoral Fellowship Award recipient and is currently supported by the Japan Society for the Promotion of Science Postdoctoral Fellowship for Research Abroad. This work was supported by grants GM071004 and GM058012 from the US National Institutes of Health (Y. S.) and by the Starr Foundation, the Leukemia and Lymphoma Society, the Abby Rockefeller Mauze Trust and the Maloris Foundation (D.J. Patel); the Canadian Institutes of Health Research (D.J. Picketts); the Major State Basic Research Development Program in China (grant # 2011CB965300, H. L.) and by Tsinghua University 985 Phase II funds (H.L.). NR 55 TC 98 Z9 101 U1 2 U2 19 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1545-9993 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD JUL PY 2011 VL 18 IS 7 BP 769 EP U41 DI 10.1038/nsmb.2062 PG 9 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 789HY UT WOS:000292507500004 PM 21666679 ER PT J AU Li, A Liu, ZZ Lezon-Geyda, K Sarkar, S Lannin, D Schulz, V Krop, I Winer, E Harris, L Tuck, D AF Li, Ao Liu, Zongzhi Lezon-Geyda, Kimberly Sarkar, Sudipa Lannin, Donald Schulz, Vincent Krop, Ian Winer, Eric Harris, Lyndsay Tuck, David TI GPHMM: an integrated hidden Markov model for identification of copy number alteration and loss of heterozygosity in complex tumor samples using whole genome SNP arrays SO NUCLEIC ACIDS RESEARCH LA English DT Article ID TOPOISOMERASE-II-ALPHA; BREAST-CANCER; GENOTYPING DATA; CELLS; COAMPLIFICATION; HYBRIDIZATION; ABERRATIONS; MICROARRAYS; GENES; ERBB2 AB There is an increasing interest in using single nucleotide polymorphism (SNP) genotyping arrays for profiling chromosomal rearrangements in tumors, as they allow simultaneous detection of copy number and loss of heterozygosity with high resolution. Critical issues such as signal baseline shift due to aneuploidy, normal cell contamination, and the presence of GC content bias have been reported to dramatically alter SNP array signals and complicate accurate identification of aberrations in cancer genomes. To address these issues, we propose a novel Global Parameter Hidden Markov Model (GPHMM) to unravel tangled genotyping data generated from tumor samples. In contrast to other HMM methods, a distinct feature of GPHMM is that the issues mentioned above are quantitatively modeled by global parameters and integrated within the statistical framework. We developed an efficient EM algorithm for parameter estimation. We evaluated performance on three data sets and show that GPHMM can correctly identify chromosomal aberrations in tumor samples containing as few as 10% cancer cells. Furthermore, we demonstrated that the estimation of global parameters in GPHMM provides information about the biological characteristics of tumor samples and the quality of genotyping signal from SNP array experiments, which is helpful for data quality control and outlier detection in cohort studies. C1 [Li, Ao; Liu, Zongzhi; Tuck, David] Yale Univ, Dept Pathol, New Haven, CT 06520 USA. [Li, Ao] Univ Sci & Technol China, Dept Elect Sci & Technol, Hefei, Peoples R China. [Lezon-Geyda, Kimberly; Harris, Lyndsay] Yale Univ, Ctr Canc, New Haven, CT 06520 USA. [Sarkar, Sudipa] Yale Univ, Sch Med, New Haven, CT 06520 USA. [Lannin, Donald] Yale Univ, Dept Surg, New Haven, CT 06520 USA. [Schulz, Vincent] Yale Univ, Dept Pediat, New Haven, CT 06520 USA. [Krop, Ian; Winer, Eric] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. RP Tuck, D (reprint author), Yale Univ, Dept Pathol, New Haven, CT 06520 USA. EM David.Tuck@yale.edu OI Schulz, Vincent/0000-0001-6333-4284 FU Department of Defense [W81XWH-04-1-0549]; Yale Center of Excellence in Molecular Hematology [P30 DK072442-03 NIDDK]; Susan G. Komen Foundation [FAS0703853] FX Funding for open access charge: Department of Defense (grant W81XWH-04-1-0549 to L.H.); Yale Center of Excellence in Molecular Hematology P30 DK072442-03 NIDDK (to D.T. and V.S.); Susan G. Komen Foundation (grant number FAS0703853 to D.L.). NR 33 TC 48 Z9 49 U1 0 U2 6 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 JUL PY 2011 VL 39 IS 12 BP 4928 EP 4941 DI 10.1093/nar/gkr014 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 790CA UT WOS:000292564900010 PM 21398628 ER PT J AU Wang, YF Chen, JJ Wei, GF He, HS Zhu, XP Xiao, TF Yuan, J Dong, B He, SM Skogerbo, G Chen, RS AF Wang, Yunfei Chen, Jingjing Wei, Guifeng He, Housheng Zhu, Xiaopeng Xiao, Tengfei Yuan, Jiao Dong, Bo He, Shunmin Skogerbo, Geir Chen, Runsheng TI The Caenorhabditis elegans intermediate-size transcriptome shows high degree of stage-specific expression SO NUCLEIC ACIDS RESEARCH LA English DT Article ID INTRON-MEDIATED ENHANCEMENT; NONCODING RNAS; PERVASIVE TRANSCRIPTION; BIDIRECTIONAL PROMOTERS; GENE-EXPRESSION; TILING ARRAYS; GUIDE SNORNAS; DNA ELEMENTS; GENOME; IDENTIFICATION AB Earlier studies have revealed a substantial amount of transcriptional activity occurring outside annotated protein-coding genes of the Caenorhabditis elegans genome. One important fraction of this transcriptional activity relates to intermediate-size (70-500 nt) transcripts (is-ncRNAs) of mostly unknown function. Profiling the expression of this segment of the transcriptome on a tiling array through the C. elegans life cycle identified 5866 hitherto unannotated transcripts. The novel loci were distributed across intronic and intergenic space, with some enrichment toward protein-coding gene termini. The majority of the putative is-ncRNAs showed either stage-specific expression, or distinct developmental variation in their expression levels. More than 200 loci showed male-specific expression, and conserved loci were significantly enriched on the X chromosome, both observations strongly suggesting involvement of is-ncRNAs in sex-specific functions. Half of the novel loci were conserved in other nematodes, and numerous loci showed significant conservational correlations to nearby coding genes. Assuming functional roles for most of the novel loci, the data imply a nematode is-ncRNA tool kit of considerable size and variety. C1 [Wang, Yunfei; Chen, Jingjing; Wei, Guifeng; He, Housheng; Zhu, Xiaopeng; Xiao, Tengfei; Yuan, Jiao; Dong, Bo; He, Shunmin; Skogerbo, Geir; Chen, Runsheng] Chinese Acad Sci, Bioinformat Lab, Beijing 100101, Peoples R China. [Wang, Yunfei; Chen, Jingjing; Wei, Guifeng; He, Housheng; Zhu, Xiaopeng; Xiao, Tengfei; Yuan, Jiao; Dong, Bo; He, Shunmin; Skogerbo, Geir; Chen, Runsheng] Chinese Acad Sci, Natl Lab Biomacromol, Inst Biophys, Beijing 100101, Peoples R China. [Wang, Yunfei; Chen, Jingjing; Wei, Guifeng; Xiao, Tengfei; Yuan, Jiao; Dong, Bo] Chinese Acad Sci, Grad Sch, Beijing 100080, Peoples R China. [He, Housheng] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [He, Shunmin] Chinese Acad Sci, Inst Zool, Key Lab Zool Syst & Evolut, Beijing 100101, Peoples R China. [Chen, Runsheng] Chinese Acad Sci, Inst Comp Technol, Bioinformat Res Grp, Key Lab Intelligent Informat Proc, Beijing 100080, Peoples R China. [Chen, Runsheng] Chinese Natl Human Genome Ctr, Beijing 100176, Peoples R China. RP Skogerbo, G (reprint author), Chinese Acad Sci, Bioinformat Lab, Beijing 100101, Peoples R China. EM crs@sun5.ibp.ac.cn; zgb@moon.ibp.ac.cn RI He, Housheng/G-9614-2011; Wei, Guifeng/A-2184-2013; he, shunmin/B-8037-2011; Zhu, Xiaopeng/A-6755-2011 OI he, shunmin/0000-0002-7294-0865; Zhu, Xiaopeng/0000-0003-2007-9820 FU National Institutes of Health-National Center for Research Resources; National Sciences Foundation of China [30630040]; National Key Basic Research and Development Program 973 [2009CB825400, 2007CB946901, 2007CB935703] FX We thank Dandan He for early discussion on experimental design and Jie Wang and Tao Liu for instructions in tiling array data analysis. The C. elegans strains used in this work was provided by the Caenorhabditis Genetics Center, which is funded by the National Institutes of Health-National Center for Research Resources.; Funding for open access charge: National Sciences Foundation of China (30630040); National Key Basic Research and Development Program 973 (2009CB825400, 2007CB946901, 2007CB935703). NR 66 TC 9 Z9 10 U1 2 U2 11 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 JUL PY 2011 VL 39 IS 12 BP 5203 EP 5214 DI 10.1093/nar/gkr102 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 790CA UT WOS:000292564900033 PM 21378118 ER PT J AU Takahashi, F Chiba, N Tajima, K Hayashida, T Shimada, T Takahashi, M Moriyama, H Brachtel, E Edelman, EJ Ramaswamy, S Maheswaran, S AF Takahashi, F. Chiba, N. Tajima, K. Hayashida, T. Shimada, T. Takahashi, M. Moriyama, H. Brachtel, E. Edelman, E. J. Ramaswamy, S. Maheswaran, S. TI Breast tumor progression induced by loss of BTG2 expression is inhibited by targeted therapy with the ErbB/HER inhibitor lapatinib SO ONCOGENE LA English DT Article DE breast cancer; BTG2; invasion; metastasis; ErbB/HER pathway ID TRANSLOCATION GENE-2 PROTEIN; ESTROGEN-RECEPTOR; CANCER PATIENTS; MOLECULAR SIGNATURE; PHASE-II; GROWTH; CELLS; METASTASIS; CARCINOMA; PROGNOSIS AB The B-cell translocation gene-2 (BTG2), a p53-inducible gene, is suppressed in mammary epithelial cells during gestation and lactation. In human breast cancer, decreased BTG2 expression correlates with high tumor grade and size, p53 status, blood and lymph vessel invasion, local and metastatic recurrence and decrease in overall survival, suggesting that suppression of BTG2 has a critical role in disease progression. To analyze the role of BTG2 in breast cancer progression, BTG2 expression was knocked down in mammary epithelial cells. Suppression of BTG2 enhances the motility of cells in vitro and tumor growth and metastasis in vivo. The effects of BTG2 knockdown are mediated through stabilization of the human epidermal growth factor receptor (HER) ligands neuregulin and epiregulin and activation of the HER2 and HER3 receptors, leading to elevated AKT phosphorylation. Suppression of HER activation using the tyrosine kinase inhibitor lapatinib abrogates the effects of BTG2 knockdown, including the increased cell migration observed in vitro and the enhancement of tumorigenesis and metastasis in vivo. These results link BTG2-dependent effects on tumor progression to ErbB receptor signaling, and raise the possibility that targeted inhibition of this pathway may be relevant in the treatment of breast cancers that have reduced BTG2 expression. Oncogene (2011) 30, 3084-3095; doi: 10.1038/onc.2011.24; published online 21 February 2011 C1 [Maheswaran, S.] Massachusetts Gen Hosp, Ctr Canc, Dept Surg, Charlestown, MA 02129 USA. [Takahashi, F.; Chiba, N.; Tajima, K.; Hayashida, T.; Shimada, T.; Takahashi, M.; Moriyama, H.; Brachtel, E.; Edelman, E. J.; Ramaswamy, S.; Maheswaran, S.] Harvard Univ, Sch Med, Charlestown, MA USA. [Takahashi, F.; Chiba, N.; Tajima, K.; Hayashida, T.; Shimada, T.; Takahashi, M.; Edelman, E. J.; Ramaswamy, S.; Maheswaran, S.] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA. [Moriyama, H.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. [Brachtel, E.] Massachusetts Gen Hosp, Dept Pathol, Charlestown, MA 02129 USA. RP Maheswaran, S (reprint author), Massachusetts Gen Hosp, Ctr Canc, Dept Surg, Bldg 149,13th St, Charlestown, MA 02129 USA. EM maheswaran@helix.mgh.harvard.edu FU NIH/NCI [CA89138]; Susan G Komen for the Cure Grants [PDF0600282, KG090412]; ESSCO breast cancer research grant FX We thank Drs Isselbacher, Haber, Engelman and Zou for critically reading the paper. This work was supported by the NIH/NCI Grant CA89138 (to SM), the Susan G Komen for the Cure Grants PDF0600282 and KG090412 (to SM) and ESSCO breast cancer research grant (to SM). NR 62 TC 25 Z9 26 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL PY 2011 VL 30 IS 27 BP 3084 EP 3095 DI 10.1038/onc.2011.24 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 789IW UT WOS:000292510100008 PM 21339742 ER PT J AU Borodic, G Hinkle, DM Cia, YH AF Borodic, Gary Hinkle, David M. Cia, Yihong TI Drug-Induced Graves Disease From CTLA-4 Receptor Suppression SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article AB Monoclonal antibody, ipilimumab, useful for treatment of metastatic melanoma, blocks CTLA-4 mediated T-cell suppression and can also cause a Graves ophthalmopathy like syndrome. Epidemiologic study has linked variant polymorphisms of CTLA-4 receptor gene to the presence of thyroid eye disease. The combination of these observations suggests CTLA-4 mediated T-cell functions are important to the pathogenesis of thyroid-associated eye disease. C1 [Borodic, Gary] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Hinkle, David M.] Ocular Immunol & Uveitis Fdn, Cambridge, England. [Borodic, Gary; Hinkle, David M.] Harvard Univ, Sch Med, Boston, MA USA. RP Borodic, G (reprint author), Harvard Univ, Sch Med, 5 Cambridge Ctr, Cambridge, MA 02142 USA. EM borodic@aol.com NR 5 TC 30 Z9 31 U1 0 U2 0 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 JUL-AUG PY 2011 VL 27 IS 4 BP E87 EP E88 DI 10.1097/IOP.0b013e3181ef72a1 PG 2 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 791BB UT WOS:000292633700003 PM 21242854 ER PT J AU Yacoub, R Ferrucci, S AF Yacoub, Robert Ferrucci, Steven TI Charles Bonnet syndrome SO OPTOMETRY-JOURNAL OF THE AMERICAN OPTOMETRIC ASSOCIATION LA English DT Article DE Charles Bonnet syndrome; Visual hallucinations; Visual impairment ID COMPLEX VISUAL HALLUCINATIONS; MACULAR DEGENERATION; VISION; IMPAIRMENT AB BACKGROUND: Charles Bonnet syndrome (CBS) involves nonthreatening hallucinations in patients who have no neurological and no psychological abnormalities but with significant visual impairment secondary to ocular disease, such as macular degeneration and diabetic retinopathy. Because of the fear of a mental illness being diagnosed, patients are often reluctant to discuss these hallucinations. CASE REPORTS: Three cases are presented of patients who experienced CBS caused by decreased vision. Each patient had decreased vision and related visual hallucinations that were consistent with CBS. The first patient underwent magnetic resonance imaging and psychological evaluation, which confirmed our suspicion. The other 2 patents were not willing to undergo further testing, so our diagnosis is presumptive. CONCLUSION: Management for these hallucinations includes treatment of the actual ocular disease as well as optimizing vision for the patient using appropriate low vision devices. As the population continues to age, more patients will be seen with reduced vision caused by a myriad of ocular diseases, increasing the likelihood that more patients may present with CBS in the future. It is therefore prudent to become familiar with the syndrome so primary care optometrists can properly identify CBS and help their patients deal with it. Optometry 2011;82:421-427 C1 [Yacoub, Robert; Ferrucci, Steven] So Calif Coll Optometry, Fullerton, CA USA. [Ferrucci, Steven] Vet Affairs Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr & Nursing Home, Sepulveda, CA USA. RP Ferrucci, S (reprint author), Sepulveda Vet Affairs Ambulatory Care Ctr, Dept Optometry, Sepulveda, CA 91343 USA. EM Steven.ferrucci@va.gov NR 32 TC 7 Z9 7 U1 0 U2 12 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 JUL PY 2011 VL 82 IS 7 BP 421 EP 427 DI 10.1016/j.optm.2010.11.014 PG 7 WC Ophthalmology SC Ophthalmology GA 791MU UT WOS:000292670100005 PM 21511535 ER PT J AU Goel, S Duda, DG Xu, L Munn, LL Boucher, Y Fukumura, D Jain, RK AF Goel, Shom Duda, Dan G. Xu, Lei Munn, Lance L. Boucher, Yves Fukumura, Dai Jain, Rakesh K. TI NORMALIZATION OF THE VASCULATURE FOR TREATMENT OF CANCER AND OTHER DISEASES SO PHYSIOLOGICAL REVIEWS LA English DT Review ID ENDOTHELIAL GROWTH-FACTOR; METASTATIC COLORECTAL-CANCER; ANTI-VEGF TREATMENT; CELL LUNG-CANCER; INTERSTITIAL FLUID PRESSURE; TYROSINE KINASE INHIBITOR; EMBRYONIC STEM-CELLS; BEVACIZUMAB PLUS IRINOTECAN; FACTOR-INDUCED ANGIOGENESIS; FACTOR RECEPTOR-2 BLOCKADE AB Goel S, Duda DG, Xu L, Munn LL, Boucher Y, Fukumura D, Jain RK. Normalization of the Vasculature for Treatment of Cancer and Other Diseases. Physiol Rev 91: 1071-1121, 2011; doi: 10.1152/physrev.00038.2010.-New vessel formation (angiogenesis) is an essential physiological process for embryologic development, normal growth, and tissue repair. Angiogenesis is tightly regulated at the molecular level. Dysregulation of angiogenesis occurs in various pathologies and is one of the hallmarks of cancer. The imbalance of pro-and anti-angiogenic signaling within tumors creates an abnormal vascular network that is characterized by dilated, tortuous, and hyperpermeable vessels. The physiological consequences of these vascular abnormalities include temporal and spatial heterogeneity in tumor blood flow and oxygenation and increased tumor interstitial fluid pressure. These abnormalities and the resultant microenvironment fuel tumor progression, and also lead to a reduction in the efficacy of chemotherapy, radiotherapy, and immunotherapy. With the discovery of vascular endothelial growth factor (VEGF) as a major driver of tumor angiogenesis, efforts have focused on novel therapeutics aimed at inhibiting VEGF activity, with the goal of regressing tumors by starvation. Unfortunately, clinical trials of anti-VEGF monotherapy in patients with solid tumors have been largely negative. Intriguingly, the combination of anti-VEGF therapy with conventional chemotherapy has improved survival in cancer patients compared with chemotherapy alone. These seemingly paradoxical results could be explained by a "normalization" of the tumor vasculature by anti-VEGF therapy. Preclinical studies have shown that anti-VEGF therapy changes tumor vasculature towards a more "mature" or "normal" phenotype. This "vascular normalization" is characterized by attenuation of hyperpermeability, increased vascular pericyte coverage, a more normal basement membrane, and a resultant reduction in tumor hypoxia and interstitial fluid pressure. These in turn can lead to an improvement in the metabolic profile of the tumor microenvironment, the delivery and efficacy of exogenously administered therapeutics, the efficacy of radiotherapy and of effector immune cells, and a reduction in number of metastatic cells shed by tumors into circulation in mice. These findings are consistent with data from clinical trials of anti-VEGF agents in patients with various solid tumors. More recently, genetic and pharmacological approaches have begun to unravel some other key regulators of vascular normalization such as proteins that regulate tissue oxygen sensing (PHD2) and vessel maturation (PDGFR beta, RGS5, Ang1/2, TGF-beta). Here, we review the pathophysiology of tumor angiogenesis, the molecular underpinnings and functional consequences of vascular normalization, and the implications for treatment of cancer and nonmalignant diseases. C1 [Jain, Rakesh K.] Massachusetts Gen Hosp, Edwin L Steele Lab Tumor Biol, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Edwin L Steele Lab Tumor Biol, Dept Radiat Oncol, Cox 7,100 Blossom St, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 FU Australian-American Fulbright Commission; American Society of Clinical Oncology; National Institutes of Health [R01-CA115767, P01-CA080124, R01-CA085140, R01-CA126642]; Federal Share/National Cancer Institute; Department of Defense [W81XWH-10-1-0016]; National Foundation for Cancer Research (NFCR); American Cancer Society [RSG-11-073-01-346TBG]; [R01-CA096915]; [R21-CA139168] FX S. Goel is supported by the Australian-American Fulbright Commission and an American Society of Clinical Oncology Young Investigator Award. This work is also supported by National Institutes of Health Grants R01-CA115767, P01-CA080124, R01-CA085140, and R01-CA126642 (all to R. K. Jain); Federal Share/National Cancer Institute Proton Beam Program Income Grants (to R. K. Jain, D. G. Duda, L. L. Munn, and D. Fukumura); and Grants R01-CA096915 (to D. Fukumura) and R21-CA139168 (to D. G. Duda). R. K. Jain is also a recipient of the Department of Defense Breast Cancer Research Innovator Award W81XWH-10-1-0016 and is funded by the National Foundation for Cancer Research (NFCR) as a NFCR Project Director. D. G. Duda is the recipient of the American Cancer Society Grant RSG-11-073-01-346TBG. NR 320 TC 475 Z9 493 U1 13 U2 126 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0031-9333 J9 PHYSIOL REV JI Physiol. Rev. PD JUL PY 2011 VL 91 IS 3 BP 1071 EP 1121 DI 10.1152/physrev.00038.2010 PG 51 WC Physiology SC Physiology GA 792FA UT WOS:000292724700009 PM 21742796 ER PT J AU Gordon, CR AF Gordon, Chad R. TI A Four-Type Classification System for Microvascular Reconstruction of Oncologic Midface Defects: But What about Maxillofacial Allotransplantation? SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Letter ID FACE; TRANSPLANT C1 Harvard Univ, Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, Sch Med, Boston, MA 02114 USA. RP Gordon, CR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, Sch Med, 15 Parkman St,WACC 435, Boston, MA 02114 USA. EM cgordon5@partners.org NR 5 TC 4 Z9 4 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 JUL PY 2011 VL 128 IS 1 BP 323 EP 325 DI 10.1097/PRS.0b013e3182174373 PG 3 WC Surgery SC Surgery GA 789FJ UT WOS:000292499600074 PM 21701356 ER PT J AU White, CJ Jaff, MR AF White, Christopher J. Jaff, Michael R. TI UPDATES IN VASCULAR MEDICINE AND ENDOVASCULAR INTERVENTION Introduction SO PROGRESS IN CARDIOVASCULAR DISEASES LA English DT Editorial Material C1 [White, Christopher J.] Ochsner Clin Fdn, John Ochsner Heart & Vasc Inst, Dept Cardiovasc Dis, New Orleans, LA 70121 USA. [Jaff, Michael R.] Massachusetts Gen Hosp, Vasc Ctr, Boston, MA 02114 USA. RP White, CJ (reprint author), Ochsner Clin Fdn, John Ochsner Heart & Vasc Inst, Dept Cardiovasc Dis, New Orleans, LA 70121 USA. EM cwhite@ochsner.org RI White, Christopher/J-6686-2012 OI White, Christopher/0000-0001-8618-7539 NR 0 TC 0 Z9 0 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 0033-0620 J9 PROG CARDIOVASC DIS JI Prog. Cardiovasc. Dis. PD JUL-AUG PY 2011 VL 54 IS 1 BP 1 EP 1 DI 10.1016/j.pcad.2011.04.004 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 792DD UT WOS:000292719800001 PM 21722780 ER PT J AU Gandhi, S Weinberg, I Margey, R Jaff, MR AF Gandhi, Sanjay Weinberg, Ido Margey, Ronan Jaff, Michael R. TI Comprehensive Medical Management of Peripheral Arterial Disease SO PROGRESS IN CARDIOVASCULAR DISEASES LA English DT Review DE Peripheral arterial disease; Medical therapy ID RANDOMIZED CONTROLLED-TRIAL; CRITICAL LIMB ISCHEMIA; PLACEBO-CONTROLLED TRIAL; ANKLE BRACHIAL INDEX; BLOOD-GLUCOSE CONTROL; HIGH-RISK PATIENTS; INTERMITTENT CLAUDICATION; CARDIOVASCULAR EVENTS; DOUBLE-BLIND; MYOCARDIAL-INFARCTION AB Peripheral arterial disease (PAD) is highly prevalent and is associated with high morbidity and mortality. The medical management of PAD involves a comprehensive approach to the patient with emphasis on cardiovascular risk factor modification in addition to therapies directed at treatment of limb symptoms. This manuscript will review the current status of medical therapy in management of patients with PAD. (Prog Cardiovasc Dis 2011;54:2-13) (C) 2011 Elsevier Inc. All rights reserved. C1 [Gandhi, Sanjay; Weinberg, Ido; Margey, Ronan; Jaff, Michael R.] Massachusetts Gen Hosp, Dept Cardiovasc Med, Sect Vasc Med, Boston, MA 02114 USA. RP Jaff, MR (reprint author), Vasc Ctr, 55 Fruit St,GRB-800, Boston, MA 02114 USA. EM mjaff@partners.org NR 113 TC 11 Z9 12 U1 0 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0033-0620 J9 PROG CARDIOVASC DIS JI Prog. Cardiovasc. Dis. PD JUL-AUG PY 2011 VL 54 IS 1 BP 2 EP 13 DI 10.1016/j.pcad.2011.02.004 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 792DD UT WOS:000292719800002 PM 21722781 ER PT J AU Stoughton, J AF Stoughton, Julianne TI Venous Ablation Therapy: Indications and Outcomes SO PROGRESS IN CARDIOVASCULAR DISEASES LA English DT Review DE Endovenous radiofrequency ablation; Endovenous laser ablation; Venous insufficiency ID ENDOVENOUS LASER-ABLATION; GREAT SAPHENOUS-VEIN; PRIMARY VARICOSE-VEINS; 2-YEAR FOLLOW-UP; RADIOFREQUENCY OBLITERATION; SURGERY; REFLUX; TRIAL; INSUFFICIENCY; METAANALYSIS AB Venous disease has long been recognized as a progressive, debilitating, and recurrent problem. Until recently, venous insufficiency was often undertreated due to a lack of therapeutic modalities. During the past decade, an explosion in the treatment options has occurred. Endovenous ablation therapy has nearly replaced the conventional surgical treatments for patients with superficial venous insufficiency. Dramatic changes in therapy are also available for deep venous thrombosis but are not the subject of this review. These newer techniques are much less invasive and consequently have reduced risks of wound complications or bleeding. In addition, they can be performed easily in the office setting with local anesthesia. Higher-risk patients can now be considered for these less invasive treatments to reduce their ambulatory venous hypertension. With the lower procedural risks and the dramatically shortened recovery times, earlier intervention can be entertained. This helps prevent the development of venous stasis ulceration and other sequelae of progressive venous insufficiency. (Prog Cardiovasc Dis 2011;54:61-69) (C) 2011 Elsevier Inc. All rights reserved. C1 [Stoughton, Julianne] Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. [Stoughton, Julianne] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Stoughton, J (reprint author), Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Wang Bldg,ACC 440, Boston, MA 02114 USA. EM jstoughton@partners.org NR 24 TC 3 Z9 3 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 0033-0620 J9 PROG CARDIOVASC DIS JI Prog. Cardiovasc. Dis. PD JUL-AUG PY 2011 VL 54 IS 1 BP 61 EP 69 DI 10.1016/j.pcad.2011.04.006 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 792DD UT WOS:000292719800009 PM 21722788 ER PT J AU Brynolf, M Sommer, M Desjardins, AE van der Voort, M Roggeveen, S Bierhoff, W Hendriks, BHW Rathmell, JP Kessels, AGH Soderman, M Holmstrom, B AF Brynolf, Marcus Sommer, Micha Desjardins, Adrien E. van der Voort, Marjolein Roggeveen, Stefan Bierhoff, Walter Hendriks, Benno H. W. Rathmell, James P. Kessels, Alfons G. H. Soderman, Michael Holmstrom, Bjorn TI Optical Detection of the Brachial Plexus for Peripheral Nerve Blocks An In Vivo Swine Study SO REGIONAL ANESTHESIA AND PAIN MEDICINE LA English DT Article ID GUIDED REGIONAL ANESTHESIA; INTRAVASCULAR INJECTION; EPIDURAL SPACE; ADIPOSE-TISSUE; AXILLARY BLOCK; ROPIVACAINE; SPECTROSCOPY AB Background and Objectives: Accurate identification of nerves is critical to ensure safe and effective delivery of regional anesthesia during peripheral nerve blocks. Nerve stimulation is commonly used, but it is not perfect. Even when nerve stimulation is performed in conjunction with ultrasound guidance, determining when the needle tip is at the nerve target region can be challenging. In this in vivo pilot study, we investigated whether close proximity to the brachial plexus and penetration of the axillary artery can be identified with optical reflectance spectroscopy, using a custom needle stylet with integrated optical fibers. Methods: Ultrasound-guided insertions to place the needle tip near the brachial plexus at the axillary level were performed at multiple locations in 2 swine, with the stylet positioned in the cannula of a 20-gauge stimulation needle. During each insertion, optical reflectance spectra were acquired with the needle tip in skeletal muscle, at the surface of muscle fascia, and at the nerve target region; confirmation of the final needle position was provided by nerve stimulation. In addition, an insertion to the lumen of the axillary artery was performed in a third swine. Differences in the spectra were quantified with lipid and hemoglobin parameters that provide contrast for optical absorption by the respective chromophores. Results: The transition of the needle tip from skeletal muscle to the nerve target region was associated with higher lipid parameter values (P < 0.001) and lower hemoglobin parameter values (P < 0.001). The transition of the needle tip from muscle fascia to the nerve target region was associated with higher lipid parameter values (P = 0.001). Intraluminal access of the axillary artery was associated with an elevated hemoglobin parameter. Conclusions: Spectroscopic information obtained with the optical needle is distinct from nerve stimulation and complementary to ultrasound imaging, and it could potentially allow for reliable identification of the injection site during peripheral nerve blocks. C1 [Brynolf, Marcus] Karolinska Univ Hosp, Dept Anesthesiol & Intens Care, SE-14186 Stockholm, Sweden. [Sommer, Micha] Univ Limburg, Acad Hosp Maastricht, Dept Anesthesiol, Maastricht, Netherlands. [Desjardins, Adrien E.; van der Voort, Marjolein; Roggeveen, Stefan; Bierhoff, Walter; Hendriks, Benno H. W.] Philips Res Labs, Eindhoven, Netherlands. [Rathmell, James P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. [Kessels, Alfons G. H.] Univ Limburg, Acad Hosp Maastricht, Dept Clin Epidemiol & Med Technol Assessment, Maastricht, Netherlands. [Soderman, Michael] Karolinska Univ Hosp, Dept Clin Neurosci, Karolinska Inst, SE-14186 Stockholm, Sweden. [Soderman, Michael] Karolinska Univ Hosp, Dept Neuroradiol, SE-14186 Stockholm, Sweden. [Holmstrom, Bjorn] Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden. [Holmstrom, Bjorn] Karolinska Univ Hosp, Dept Anesthesiol & Intens Care, Huddinge, Sweden. RP Holmstrom, B (reprint author), Karolinska Univ Hosp, Dept Anesthesiol & Intens Care, B31, SE-14186 Stockholm, Sweden. EM bjorn.holmstrom@karolinska.se FU Philips Research, Eindhoven, The Netherlands FX This study was supported by Philips Research, Eindhoven, The Netherlands. None of the authors who are affiliated with clinical institutions (M. B., M. S., J.R., A. K., M. S., and B. H.) have financial interests in the subject matter, materials, or equipment or with any competing materials. These authors received no payment of any kind for their participation in this research project, nor did their institutions receive payment for anything beyond the direct costs of performing this research project at Karolinska University Hospital. Their interests are purely at a scientific level. NR 31 TC 14 Z9 14 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-7339 J9 REGION ANESTH PAIN M JI Region. Anesth. Pain Med. PD JUL-AUG PY 2011 VL 36 IS 4 BP 350 EP 357 DI 10.1097/AAP.0b013e318220f15a PG 8 WC Anesthesiology SC Anesthesiology GA 792UB UT WOS:000292774800009 PM 21654551 ER PT J AU Milanovic, SM Thermenos, HW Goldstein, JM Brown, A Gabrieli, SW Makris, N Tsuang, MT Buka, SL Seidman, LJ AF Milanovic, Snezana M. Thermenos, Heidi W. Goldstein, Jill M. Brown, Ariel Gabrieli, Susan Whitfield Makris, Nikos Tsuang, Ming T. Buka, Stephen L. Seidman, Larry J. TI Medial prefrontal cortical activation during working memory differentiates schizophrenia and bipolar psychotic patients: A pilot FMRI study SO SCHIZOPHRENIA RESEARCH LA English DT Letter ID DISORDER C1 [Milanovic, Snezana M.; Thermenos, Heidi W.; Goldstein, Jill M.; Brown, Ariel; Makris, Nikos; Tsuang, Ming T.; Seidman, Larry J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. [Thermenos, Heidi W.; Goldstein, Jill M.; Tsuang, Ming T.; Seidman, Larry J.] Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr,Div Publ Psychiat, Dept Psychiat,Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Goldstein, Jill M.] Harvard Univ, Sch Med, Dept Med,Div Womens Hlth, Connors Ctr Womens Hlth & Gender Biol, Boston, MA 02115 USA. [Goldstein, Jill M.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Brown, Ariel; Seidman, Larry J.] Massachusetts Gen Hosp, Dept Psychiat, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. [Gabrieli, Susan Whitfield] MIT, Harvard MIT Div Hlth Sci & Technol, Poitras Ctr, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Makris, Nikos] Harvard Univ, Sch Med, Dept Neurol, Athinoula A Martinos Ctr, Boston, MA 02129 USA. [Makris, Nikos] Massachusetts Gen Hosp, Ctr Morphometr Anal, Dept Radiol Serv, Boston, MA 02129 USA. [Tsuang, Ming T.] Univ Calif San Diego, Dept Psychiat, Ctr Behav Gen, La Jolla, CA 92093 USA. [Buka, Stephen L.] Brown Univ, Dept Community Hlth, Providence, RI 02810 USA. RP Milanovic, SM (reprint author), Athinoula A Martinos Ctr Biomed Imaging, Bldg 149,2nd Floor,Room 2603,13th St, Charlestown, MA 02129 USA. EM smilanovic@partners.org RI Buka, Stephen/H-7335-2014 OI Buka, Stephen/0000-0002-8578-9308 FU NIMH NIH HHS [R01 MH050647, R01 MH056956, R01 MH063951] NR 10 TC 9 Z9 10 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JUL PY 2011 VL 129 IS 2-3 BP 208 EP 210 DI 10.1016/j.schres.2011.02.025 PG 3 WC Psychiatry SC Psychiatry GA 791OX UT WOS:000292675600020 PM 21440419 ER PT J AU Salti, H Cavallerano, JD Salti, N Jawhari, DJ Haddad, S Sun, JK Salti, I Aiello, LP AF Salti, Haytham Cavallerano, Jerry D. Salti, Nisreen Jawhari, Dalida Jaafar Haddad, Sandra Sun, Jennifer K. Salti, Ibrahim Aiello, Lloyd Paul TI Nonmydriatic Retinal Image Review at Time of Endocrinology Visit Results in Short-Term HbA1c Reduction in Poorly Controlled Patients with Diabetic Retinopathy SO TELEMEDICINE AND E-HEALTH LA English DT Review DE diabetic retinopathy; nonmydriatic retinal imaging; glycemic control ID COMPLICATIONS; MELLITUS; EXERCISE AB Objectives: The objective of this study was to evaluate the effect of discussing retinal findings following nonmydriatic retinal imaging during an endocrinology visit on subsequent HbA1c in poorly controlled diabetic patients with diabetic retinopathy (DR). Materials and Methods: During a visit to an endocrinologist, patients with DR and documented HbA1c >= 8.0% within the preceding month were assigned to either addition of nonmydriatic imaging and discussion of retinal findings or standard endocrinology evaluation alone. Ophthalmology care was otherwise the same in both groups. Changes in HbA1c were evaluated 3 months later. Results: One hundred thirteen (94%) of the original 120 subjects completed the study. The mean HbA1c change in the retinal imaging group was a decline of 1.35%, whereas the control group had a 0.26% increase. Controlling for gender, age, duration of diabetes, presence of hypertension, and use of insulin, the difference between groups was significant (p < 0.0003). Conclusions: Nonmydriatic imaging and discussion of retinal findings during an endocrinologist visit may contribute, at least in the short term, to improved glycemic control in patients with DR and elevated HbA1c. C1 [Salti, Haytham; Jawhari, Dalida Jaafar; Haddad, Sandra] Amer Univ Beirut, Med Ctr, Dept Ophthalmol, Beirut 11072020, Lebanon. [Cavallerano, Jerry D.; Sun, Jennifer K.; Aiello, Lloyd Paul] Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. [Cavallerano, Jerry D.; Sun, Jennifer K.; Aiello, Lloyd Paul] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Salti, Nisreen] Amer Univ Beirut, Fac Arts & Sci, Dept Econ, Beirut 11072020, Lebanon. [Salti, Ibrahim] Amer Univ Beirut, Med Ctr, Dept Internal Med, Div Endocrinol & Metab, Beirut 11072020, Lebanon. RP Salti, H (reprint author), Amer Univ Beirut, Med Ctr, Dept Ophthalmol, Bliss St,POB 110236, Beirut 11072020, Lebanon. EM hs06@aub.edu.lb OI Salti, Nisreen/0000-0002-4585-6430 FU Merk Company FX This project was supported in part by the Merk Company through a grant for research in diabetes. NR 19 TC 5 Z9 5 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1530-5627 J9 TELEMED E-HEALTH JI Telemed. e-Health PD JUL-AUG PY 2011 VL 17 IS 6 BP 415 EP 419 DI 10.1089/tmj.2010.0180 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 794CD UT WOS:000292872100004 PM 21675867 ER PT J AU Borba, CPC DePadilla, L Druss, BG McCarty, FA von Esenwein, SA Sterk, CE AF Borba, Christina P. C. DePadilla, Lara Druss, Benjamin G. McCarty, Frances A. von Esenwein, Silke A. Sterk, Claire E. TI A Day in the Life of Women with a Serious Mental Illness: A Qualitative Investigation SO WOMENS HEALTH ISSUES LA English DT Article ID SUBSTANCE USE DISORDERS; CHILDHOOD SEXUAL-ABUSE; HOMELESS WOMEN; VIOLENT VICTIMIZATION; SCHIZOPHRENIA; HEALTH; CARE; PSYCHOPATHOLOGY; SYMPTOMS; MOTHERS AB Purpose: Few studies have taken a holistic perspective to the lives of women with a serious mental illness (SMI). This qualitative study of women with an SMI describes and interprets women's experiences and provides a new understanding about the nature and needs of these women. Methods: A convenience sample of 30 poor, urban, predominantly African-American women with a diagnosis of an SMI was recruited from an ongoing National Institutes of Mental Health study. Data collection involved face-to-face, in-depth interviews. The interviews were audio-recorded and transcribed verbatim. Data analysis occurred concurrently with data collection using a modified constant comparative method. Results: The majority of the women self-identified as African American, single, having completed high school, and at the time of the interview were either unemployed or on disability. The most common SMI was major depression. A common topic in the women's reflections on their lives was that of social disadvantage both before being diagnosed as well as after to their diagnosis with an SMI. Salient themes of their stories included social isolation, experiencing loss, and having a lack of control over one's own life decisions. Conclusion: The findings from this study revealed varied experiences among these women as well as the complexity of their situation. The enhanced understanding of women's situation will allow mental health professionals to improve the quality of life for women with an SMI by taking a contextual approach to the treatment of their mental illness. Copyright (C) 2011 by the Jacobs Institute of Women's Health. Published by Elsevier Inc. C1 [Borba, Christina P. C.; DePadilla, Lara; Druss, Benjamin G.; Sterk, Claire E.] Emory Univ, Rollins Sch Publ Hlth, Dept Behav Sci & Hlth Educ, Atlanta, GA 30322 USA. [Druss, Benjamin G.; von Esenwein, Silke A.] Emory Univ, Rollins Sch Publ Hlth, Dept Hlth Policy & Management, Atlanta, GA 30322 USA. [Borba, Christina P. C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Borba, Christina P. C.] Massachusetts Gen Hosp, Div Global Psychiat, Boston, MA 02114 USA. [McCarty, Frances A.] Georgia State Univ, Inst Publ Hlth, Coll Hlth & Human Sci, Atlanta, GA 30303 USA. RP Borba, CPC (reprint author), 25 Staniford St, Boston, MA 02114 USA. EM cborba@partners.org NR 46 TC 9 Z9 9 U1 2 U2 19 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD JUL-AUG PY 2011 VL 21 IS 4 BP 286 EP 292 DI 10.1016/j.whi.2010.11.003 PG 7 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 792XZ UT WOS:000292785000006 PM 21330152 ER PT J AU Hsia, RY Asch, SM Weiss, RE Zingmond, D Liang, LJ Han, WJ McCreath, H Sun, BC AF Hsia, Renee Y. Asch, Steven M. Weiss, Robert E. Zingmond, David Liang, Li-Jung Han, Weijuan McCreath, Heather Sun, Benjamin C. TI Hospital Determinants of Emergency Department Left Without Being Seen Rates SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID MEDICAL-CARE; LEAVE; ACCESS; PHYSICIAN; SERVICES; TRENDS; CONSEQUENCES; EXPERIENCE; CAPACITY; PATIENT AB Study objective: The proportion of patients who leave without being seen in the emergency department (ED) is an outcome-oriented measure of impaired access to emergency care and represents the failure of an emergency care delivery system to meet its goals of providing care to those most in need. Little is known about variation in the amount of left without being seen or about hospital-level determinants. Such knowledge is necessary to target hospital-level interventions to improve access to emergency care. We seek to determine whether hospital-level socioeconomic status case mix or hospital structural characteristics are predictive of ED left without being seen rates. Methods: We performed a cross-sectional study of all acute-care, nonfederal hospitals in California that operated an ED in 2007, using data from the California Office of Statewide Health Planning and Development database and the US census. Our outcome of interest was whether a visit to a given hospital ED resulted in left without being seen. The proportion of left without being seen was measured by the number of left without being seen cases out of the total number of visits. Results: We studied 9.2 million ED visits to 262 hospitals in California. The percentage of left without being seen varied greatly over hospitals, ranging from 0% to 20.3%, with a median percentage of 2.6%. In multivariable analyses adjusting for hospital-level socioeconomic status case mix, visitors to EDs with a higher proportion of low-income and poorly insured patients experienced a higher risk of left without being seen. We found that the odds of an ED visit resulting in left without being seen increased by a factor of 1.15 for each 10-percentage-point increase in poorly insured patients, and odds of left without being seen decreased by a factor of 0.86 for each $10,000 increase in household income. When hospital structural characteristics were added to the model, county ownership, trauma center designation, and teaching program affiliation were positively associated with increased probability of left without being seen (odds ratio 2.09; 1.62, and 2.14, respectively), and these factors attenuated the association with insurance status. Conclusion: Visitors to different EDs experience a large variation in their probability of left without being seen, and visitors to hospitals serving a high proportion of low-income and poorly insured patients are at disproportionately higher risk of leaving without being seen. Our findings suggest that there is room for substantial improvement in this outcome, and regional interventions can be targeted toward certain at-risk hospitals to improve access to emergency care. [Ann Emerg Med. 2011;58:24-32.] C1 [Hsia, Renee Y.] Univ Calif San Francisco, Dept Emergency Med, San Francisco, CA 94110 USA. [Asch, Steven M.; Zingmond, David; Liang, Li-Jung; Sun, Benjamin C.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Weiss, Robert E.; Han, Weijuan; McCreath, Heather] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90024 USA. [Asch, Steven M.; Sun, Benjamin C.] VA Greater Angeles Hlth Syst, Los Angeles, CA USA. RP Hsia, RY (reprint author), Univ Calif San Francisco, Dept Emergency Med, San Francisco Gen Hosp, 1001 Potrero Ave,1E21, San Francisco, CA 94110 USA. EM rhsia@sfghed.ucsf.edu FU Emergency Medicine Foundation; Agency for Healthcare Research and Quality [R03 HS18098]; UCLA Older Americans Independence Center NIH/NIA [P30-AG028748]; NIH/NCRR/OD [KL2 RR024130]; Robert Wood Johnson Foundation FX By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article as per ICMJE conflict of interest guidelines (see www.icmje.org). This publication was supported by the Emergency Medicine Foundation (Dr. Sun), Agency for Healthcare Research and Quality (R03 HS18098) (Dr. Sun), UCLA Older Americans Independence Center NIH/NIA grant P30-AG028748 (Ms. Han and Drs. McCreath and Sun), NIH/NCRR/OD UCSF-CTSI grant number KL2 RR024130 (Dr. Hsia), and the Robert Wood Johnson Foundation Physician Faculty Scholars (Dr. Hsia). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of any of the funding agencies. NR 56 TC 26 Z9 26 U1 1 U2 9 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD JUL PY 2011 VL 58 IS 1 BP 24 EP 32 DI 10.1016/j.annemergmed.2011.01.009 PG 9 WC Emergency Medicine SC Emergency Medicine GA 786XL UT WOS:000292341100008 PM 21334761 ER PT J AU Kuhlthau, K Jellinek, M White, G VanCleave, J Simons, J Murphy, M AF Kuhlthau, Karen Jellinek, Michael White, Gwyne VanCleave, Jeanne Simons, Jack Murphy, Michael TI Increases in Behavioral Health Screening in Pediatric Care for Massachusetts Medicaid Patients SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID CHILDREN AB Objective: To explore rates of screening and identification and treatment for behavioral problems using billing data from Massachusetts Medicaid immediately following the start of the state's new court-ordered screening and intervention program. Design: Retrospective review of the number of pediatric well-child visits, number of screens, and number of screens that identify risk for psychosocial problems from January 2008 (the month pediatric screening started) to March 2009. During the surrounding 1-year period, we also examined the number of claims with a behavioral health evaluation code. Setting: Massachusetts. Participants: Massachusetts Medicaid-enrolled children. Intervention: Funded court-ordered mandate to screen for mental health during Medicaid well-child visits. Outcome Measures: Percentage of visits with a screen, percentage of screens identified at risk, and number of children seen for behavioral health evaluations. Results: Major increase from 16.6% of all Medicaid well-child visits coded for behavioral screens in the first quarter of 2008 to 53.6% in the first quarter of 2009. Additionally, the children identified as at risk increased substantially from about 1600 in the first quarter of 2008 to nearly 5000 in quarter 1 of 2009. The children with mental health evaluations increased from an average of 4543 to 5715 per month over a 1-year period. Conclusions: The data suggest payment and a supported mandate for use of a formal screening tool can substantially increase the identification of children at behavioral health risk. Findings suggest that increased screening may have the desired effect of increasing referrals for mental health services. C1 [Kuhlthau, Karen; VanCleave, Jeanne] Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. [Jellinek, Michael; White, Gwyne; Murphy, Michael] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Kuhlthau, Karen; Jellinek, Michael; VanCleave, Jeanne; Murphy, Michael] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Simons, Jack] Execut Off Hlth & Human Serv, Boston, MA USA. [Jellinek, Michael] Newton Wellesley Hosp, Newton, MA USA. [White, Gwyne] Rutgers State Univ, Dept Psychol, New Brunswick, NJ 08903 USA. RP Kuhlthau, K (reprint author), Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. EM kkuhlthau@partners.org FU Fuss Family Fund FX A Fuss Family Fund grant to Newton Wellesley Hospital made the current data analysis and paper writing possible. NR 25 TC 23 Z9 23 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 1072-4710 EI 1538-3628 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD JUL PY 2011 VL 165 IS 7 BP 660 EP 664 DI 10.1001/archpediatrics.2011.18 PG 5 WC Pediatrics SC Pediatrics GA 787JT UT WOS:000292373100013 PM 21383254 ER PT J AU Richardson, S Browne, ML Rasmussen, SA Druschel, CM Sun, LX Jabs, EW Romitti, PA AF Richardson, Sandra Browne, Marilyn L. Rasmussen, Sonja A. Druschel, Charlotte M. Sun, Lixian Jabs, Ethylin Wang Romitti, Paul A. CA Natl Birth Defects Prevention Stud TI Associations Between Periconceptional Alcohol Consumption and Craniosynostosis, Omphalocele, and Gastroschisis SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Article DE alcohol drinking; case-control studies; congenital abnormalities; craniosynostosis; gastroschisis; omphalocele ID BIRTH-DEFECTS PREVENTION; RETINOIC ACID; RISK-FACTORS; PREGNANCY; EXPOSURE; SMOKING; BIOLOGY; GROWTH; WOMEN; MICE AB BACKGROUND: Alcohol consumption during pregnancy is known to be associated with certain birth defects, but the risk of other birth defects is less certain. The authors examined associations between maternal alcohol consumption during pregnancy and craniosynostosis, omphalocele, and gastroschisis among participants in the National Birth Defects Prevention Study, a large, multicenter case-control study. METHODS: A total of 6622 control infants and 1768 infants with birth defects delivered from 1997-2005 were included in the present analysis. Maternal alcohol consumption was assessed as any periconceptional consumption (1 month prepregnancy through the third pregnancy month), and by quantity-frequency, duration, and beverage type. Alcohol consumption throughout pregnancy was explored for craniosynostosis since the period of development may extend beyond the first trimester. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression analysis. OR were adjusted for age, race/ethnicity, and state of residence at time of infant's birth. Gastroschisis OR were also adjusted for periconceptional smoking. RESULTS: Periconceptional alcohol consumption and craniosynostosis showed little evidence of an association (OR = 0.92; CI: 0.78-1.08), but alcohol consumption in the second (OR = 0.65; CI: 0.47-0.92) and third trimesters (OR = 0.68; CI: 0.49-0.95) was inversely associated with craniosynostosis. Periconceptional alcohol consumption was associated with omphalocele (OR = 1.50; CI: 1.15-1.96) and gastroschisis (OR = 1.40; CI: 1.17-1.67). CONCLUSIONS: Results suggest that maternal periconceptional alcohol consumption is associated with omphalocele and gastroschisis, and second and third trimester alcohol consumption are inversely associated with craniosynostosis. Birth Defects Research (Part A) 91:623-630, 2011. (C) 2011 Wiley-Liss, Inc. C1 [Richardson, Sandra; Browne, Marilyn L.; Druschel, Charlotte M.] Bur Environm & Occupat Epidemiol, Congenital Malformat Registry, New York State Dept Hlth, Troy, NY 12180 USA. [Browne, Marilyn L.; Druschel, Charlotte M.] SUNY Albany, Sch Publ Hlth, Dept Epidemiol & Biostat, Rensselaer, NY USA. [Rasmussen, Sonja A.] Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA USA. [Sun, Lixian; Romitti, Paul A.] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA. [Sun, Lixian] Dana Farber Canc Inst, Boston, MA 02115 USA. [Jabs, Ethylin Wang] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA. [Jabs, Ethylin Wang] Mt Sinai Sch Med, Dept Pediat, New York, NY USA. [Jabs, Ethylin Wang] Mt Sinai Sch Med, Dept Dev & Regenerat Biol, New York, NY USA. RP Richardson, S (reprint author), Bur Environm & Occupat Epidemiol, Congenital Malformat Registry, New York State Dept Hlth, 547 River St,Room 200, Troy, NY 12180 USA. EM sdr06@health.state.ny.us RI Publications, NBDPS/B-7692-2013; OI Jabs, Ethylin/0000-0001-8983-5466 FU Centers for Disease Control and Prevention [5U01DD000487-02, 5R01DD000350] FX This work was supported by the Centers for Disease Control and Prevention, grant number 5U01DD000487-02; and in part by Centers for Disease Control and Prevention, grant number 5R01DD000350. NR 31 TC 17 Z9 18 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD JUL PY 2011 VL 91 IS 7 BP 623 EP 630 DI 10.1002/bdra.20823 PG 8 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 790PY UT WOS:000292602900005 PM 21630421 ER PT J AU Holloway, CL Macklin, EA Cormack, RA Viswanathan, AN AF Holloway, Caroline L. Macklin, Eric A. Cormack, Robert A. Viswanathan, Akila N. TI Should the organs at risk be contoured in vaginal cuff brachytherapy? SO BRACHYTHERAPY LA English DT Article DE Vaginal vault; HDR brachytherapy ID HIGH-DOSE-RATE; ENDOMETRIAL CANCER; INTRACAVITARY BRACHYTHERAPY; VOLUME HISTOGRAMS; PRACTICE PATTERNS; CERVICAL-CANCER; REFERENCE-POINT; BLADDER; RECTUM; RADIOTHERAPY AB PURPOSE: To assess the dose to the organs at risk (OARs) and utility of repeated OAR dose-volume histogram calculations in multifraction high-dose-rate vaginal cylinder brachytherapy using 3-dimensional imaging. METHODS AND MATERIALS: Thirty-eight patients (125 fractions) received high-dose-rate brachytherapy to the vaginal vault between January 2005 and October 2005. All patients emptied their bladders before insertion. After each insertion, a CT scan with 2.5-mm slices and contours of the bladder, rectum, and sigmoid was performed. Dose-volume histograms were generated for the D(0.1cc), and D(2cc) for the OAR using a software program created at our institution. Variance component models estimated the within-patient variance of the dose to the OAR between fractions. Predictors of dose to the OAR were identified using linear mixed models. RESULTS: The within-patient coefficients of variation of total D(0.1cc) dose were bladder 14.0%, rectum 7.9%, and sigmoid 27.6%; for D(2cc), these were 8.1%, 5.9%, and 20.3%, respectively. Intraclass correlations ranged from 0.27 to 0.79. Larger OAR predicted greater total D(0.1cc) and D(2cc). Other predictors of total D(0.1cc) and D(2cc) dose included the size of the cylinder and the length of the treatment field for rectum. CONCLUSIONS: CT simulation provides a noninvasive assessment of the dose to the bladder, rectum, and sigmoid. The small within-patient variation in doses to the bladder and rectum do not support reporting doses to the OARs beyond the initial fraction. (C) 2011 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved. C1 [Holloway, Caroline L.; Cormack, Robert A.; Viswanathan, Akila N.] Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Macklin, Eric A.] Massachusetts Gen Hosp, MGH Biostat Ctr, Boston, MA 02114 USA. RP Viswanathan, AN (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, 75 Francis St,L2, Boston, MA 02115 USA. EM aviswanathan@lroc.harvard.edu RI Macklin, Eric/E-2955-2013; OI Macklin, Eric/0000-0003-1618-3502; Cormack, Robert/0000-0001-5553-9984 NR 19 TC 22 Z9 22 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1538-4721 J9 BRACHYTHERAPY JI Brachytherapy PD JUL-AUG PY 2011 VL 10 IS 4 BP 313 EP 317 DI 10.1016/j.brachy.2010.10.005 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 788AA UT WOS:000292416600008 PM 21193355 ER PT J AU Caretti, V Zondervan, I Meijer, DH Idema, S Vos, W Hamans, B Bugiani, M Hulleman, E Wesseling, P Vandertop, WP Noske, DP Kaspers, G Molthoff, CFM Wurdinger, T AF Caretti, Viola Zondervan, Ilse Meijer, Dimphna H. Idema, Sander Vos, Wim Hamans, Bob Bugiani, Marianna Hulleman, Esther Wesseling, Pieter Vandertop, W. Peter Noske, David P. Kaspers, Gertjan Molthoff, Carla F. M. Wurdinger, Thomas TI Monitoring of Tumor Growth and Post-Irradiation Recurrence in a Diffuse Intrinsic Pontine Glioma Mouse Model SO BRAIN PATHOLOGY LA English DT Article DE brainstem glioma; DIPG; imaging; luciferase; pons ID BRAIN-STEM GLIOMAS; MALIGNANT GLIOMAS; IN-VIVO; CANCER; CHILDREN; AUTOPSY AB Diffuse intrinsic pontine glioma (DIPG) is a fatal malignancy because of its diffuse infiltrative growth pattern. Translational research suffers from the lack of a representative DIPG animal model. Hence, human E98 glioma cells were stereotactically injected into the pons of nude mice. The E98 DIPG tumors presented a strikingly similar histhopathology to autopsy material of a DIPG patient, including diffuse and perivascular growth, brainstem- and supratentorial invasiveness and leptomeningeal growth. Magnetic resonance imaging (MRI) was effectively employed to image the E98 DIPG tumor. [F-18] 3'-deoxy-3'-[F-18] fluorothymidine (FLT) positron emission tomography (PET) imaging was applied to assess the subcutaneous (s.c.) E98 tumor proliferation status but no orthotopic DIPG activity could be visualized. Next, E98 cells were cultured in vitro and engineered to express firefly luciferase and mCherry (E98-Fluc-mCherry). These cultured E98-Fluc-mCherry cells developed focal pontine glioma when injected into the pons directly. However, the diffuse E98 DIPG infiltrative phenotype was restored when cells were injected into the pons immediately after an intermediate s.c. passage. The diffuse E98-Fluc-mCherry model was subsequently used to test escalating doses of irradiation, applying the bioluminescent Fluc signal to monitor tumor recurrence over time. Altogether, we here describe an accurate DIPG mouse model that can be of clinical relevance for testing experimental therapeutics in vivo. C1 [Wurdinger, Thomas] Vrije Univ Amsterdam Med Ctr, Canc Ctr Amsterdam, Neurooncol Res Grp, NL-1081 HV Amsterdam, Netherlands. [Caretti, Viola; Hulleman, Esther; Kaspers, Gertjan] Vrije Univ Amsterdam Med Ctr, Dept Pediat Oncol, NL-1081 HV Amsterdam, Netherlands. [Caretti, Viola; Zondervan, Ilse; Idema, Sander; Hulleman, Esther; Vandertop, W. Peter; Noske, David P.; Wurdinger, Thomas] Vrije Univ Amsterdam Med Ctr, Dept Neurosurg, NL-1081 HV Amsterdam, Netherlands. [Vos, Wim; Bugiani, Marianna] Vrije Univ Amsterdam Med Ctr, Dept Pathol, NL-1081 HV Amsterdam, Netherlands. [Hamans, Bob] Radboud Univ Nijmegen, Med Ctr, Dept Radiol, NL-6525 ED Nijmegen, Netherlands. [Wesseling, Pieter] Radboud Univ Nijmegen, Med Ctr, Dept Pathol, NL-6525 ED Nijmegen, Netherlands. [Meijer, Dimphna H.] Harvard Univ, Sch Med, Dept Canc Biol, Boston, MA USA. [Meijer, Dimphna H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wurdinger, Thomas] Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Boston, MA 02114 USA. RP Wurdinger, T (reprint author), Vrije Univ Amsterdam Med Ctr, Canc Ctr Amsterdam, Neurooncol Res Grp, Boelelaan 1117, NL-1081 HV Amsterdam, Netherlands. EM t.wurdinger@vumc.nl RI Wesseling, P./H-8114-2014 OI Wesseling, P./0000-0001-5453-5201 FU Semmy foundation; Egbers foundation FX This work was supported by the Semmy foundation and the Egbers foundation. NR 33 TC 24 Z9 24 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1015-6305 EI 1750-3639 J9 BRAIN PATHOL JI Brain Pathol. PD JUL PY 2011 VL 21 IS 4 BP 441 EP 451 DI 10.1111/j.1750-3639.2010.00468.x PG 11 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 788TR UT WOS:000292467800008 PM 21159008 ER PT J AU Hamer, PCD Mir, SE Noske, D Van Noorden, CJF Wurdinger, T AF Hamer, Philip C. De Witt Mir, Shahryar E. Noske, David Van Noorden, Cornelis J. F. Wuerdinger, Tom TI WEE1 Kinase Targeting Combined with DNA-Damaging Cancer Therapy Catalyzes Mitotic Catastrophe SO CLINICAL CANCER RESEARCH LA English DT Article ID CELL-CYCLE PROGRESSION; PHASE-II TRIAL; CHK1 CHECKPOINT KINASES; TYROSINE KINASE; GENE-EXPRESSION; DEPENDENT DEGRADATION; DOSE-ESCALATION; G(2) CHECKPOINT; CARCINOMA CELLS; SOMATIC WEE1 AB WEE1 kinase is a key molecule in maintaining G(2)-cell-cycle checkpoint arrest for premitotic DNA repair. Whereas normal cells repair damaged DNA during G(1)-arrest, cancer cells often have a deficient G(1)-arrest and largely depend on G(2)-arrest. The molecular switch for the G(2)-M transition is held by WEE1 and is pushed forward by CDC25. WEE1 is overexpressed in various cancer types, including glioblastoma and breast cancer. Preclinical studies with cancer cell lines and animal models showed decreased cancer cell viability, reduced tumor burden, and improved survival after WEE1 inhibition by siRNA or small molecule inhibitors, which is enhanced by combination with conventional DNA-damaging therapy, such as radiotherapy and/or cytostatics. Mitotic catastrophe results from premature entry into mitosis with unrepaired lethal DNA damage. As such, cancer cells become sensitized to conventional therapy by WEE1 inhibition, in particular those with insufficient G(1)-arrest due to deficient p53 signaling, like glioblastoma cells. One WEE1 inhibitor has now reached clinical phase I studies. Dose-limiting toxicity consisted of hematologic events, nausea and/or vomiting, and fatigue. The combination of DNA-damaging cancer therapy with WEE1 inhibition seems to be a rational approach to push cancer cells in mitotic catastrophe. Its safety and efficacy are being evaluated in clinical studies. Clin Cancer Res; 17(13);4200-7. (C) 2011 AACR. C1 [Hamer, Philip C. De Witt] Vrije Univ Amsterdam Med Ctr, Neurosurg Ctr Amsterdam, Dept Neurosurg, NL-1007 MB Amsterdam, Netherlands. [Mir, Shahryar E.] Vrije Univ Amsterdam Med Ctr, Dept Pediat Oncol, NL-1007 MB Amsterdam, Netherlands. [Hamer, Philip C. De Witt; Mir, Shahryar E.; Noske, David; Wuerdinger, Tom] Vrije Univ Amsterdam Med Ctr, Neurooncol Res Grp, NL-1007 MB Amsterdam, Netherlands. [Van Noorden, Cornelis J. F.] Univ Amsterdam, Acad Med Ctr, Dept Cell Biol & Histol, NL-1105 AZ Amsterdam, Netherlands. [Wuerdinger, Tom] Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Charlestown, MA USA. [Wuerdinger, Tom] Harvard Univ, Sch Med, Charlestown, MA USA. RP Hamer, PCD (reprint author), Vrije Univ Amsterdam Med Ctr, Neurosurg Ctr Amsterdam, Dept Neurosurg, POB 7057, NL-1007 MB Amsterdam, Netherlands. EM p.dewitthamer@vumc.nl RI De Witt Hamer, Philip/E-7630-2013 OI De Witt Hamer, Philip/0000-0003-2988-8544 NR 82 TC 63 Z9 63 U1 1 U2 12 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUL 1 PY 2011 VL 17 IS 13 BP 4200 EP 4207 DI 10.1158/1078-0432.CCR-10-2537 PG 8 WC Oncology SC Oncology GA 788LO UT WOS:000292446600003 PM 21562035 ER PT J AU Yu, WD Feng, S Dakhova, O Creighton, CJ Cai, Y Wang, JH Li, RL Frolov, A Ayala, G Ittmann, M AF Yu, Wendong Feng, Shu Dakhova, Olga Creighton, Chad J. Cai, Yi Wang, Jianghua Li, Rile Frolov, Anna Ayala, Gustavo Ittmann, Michael TI FGFR-4 Arg(388) Enhances Prostate Cancer Progression via Extracellular Signal-Related Kinase and Serum Response Factor Signaling SO CLINICAL CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR RECEPTOR-4; SQUAMOUS-CELL CARCINOMA; ANDROGEN RECEPTOR; BREAST-CANCER; ARG388 ALLELE; INTRAEPITHELIAL NEOPLASIA; RADICAL PROSTATECTOMY; REACTIVE STROMA; UP-REGULATION; EXPRESSION AB Purpose: Increased expression of FGFR-4 and its ligands have been linked to lethal prostate cancer (PCa). Furthermore, a germ line polymorphism in the FGFR-4 gene, resulting in arginine at codon 388 (Arg(388)) instead of glycine (Gly(388)), is associated with aggressive disease. The FGFR-4 Arg(388) variant results in increased receptor stability, sustained receptor activation, and increased motility and invasion compared with Gly(388). However, the impact of sustained signaling on cellular signal transduction pathways is unknown. Experimental Design: Expression microarray analysis of immortalized prostatic epithelial cells lines expressing FGFR-4 Arg(388) or Gly(388) was used to establish a gene signature associated with FGFR-4 Arg(388) expression. Transient transfection of reporters and inhibitors was used to establish the pathways activated by FGFR-4 Arg(388) expression. The impact of pathway knockdown in vitro and in an orthotopic model was assessed using inhibitors and/or short hairpin RNA (shRNA). Results: Expression of the FGFR-4 Arg(388) protein leads to increased activity of the extracellular signal-related kinase (ERK) pathway, increased activity of serum response factor (SRF) and AP1, and transcription of multiple genes that are correlated with aggressive clinical behavior in PCa. Increased expression of SRF is associated with biochemical recurrence in men undergoing radical prostatectomy. Consistent with these observations, knockdown of FGFR-4 Arg(388) in PCa cells decreases proliferation and invasion in vitro and primary tumor growth and metastasis in vivo. Conclusions: These studies define a signal transduction pathway downstream of FGFR-4 Arg(388) that acts via ERK and SRF to promote PCa progression. Clin Cancer Res; 17(13); 4355-66. (C) 2011 AACR. C1 [Yu, Wendong; Feng, Shu; Dakhova, Olga; Cai, Yi; Wang, Jianghua; Li, Rile; Frolov, Anna; Ayala, Gustavo; Ittmann, Michael] Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA. [Creighton, Chad J.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Yu, Wendong; Feng, Shu; Dakhova, Olga; Cai, Yi; Wang, Jianghua; Ittmann, Michael] Michael E DeBakey Dept Vet Affairs Med Ctr, Houston, TX USA. RP Ittmann, M (reprint author), Baylor Coll Med, Dept Pathol, 1 Baylor Plaza, Houston, TX 77030 USA. EM mittmann@bcm.tmc.edu FU Department of Veterans Affairs; DOD [W81XWH-09-1-0172]; National Cancer Institute [1U54CA126568]; Baylor Prostate Cancer SPORE [P50CA058204]; Dan L. Duncan Cancer Center [P30CA125123] FX This work was supported by grants from the Department of Veterans Affairs Merit Review (M. Ittmann), the DOD Prostate Cancer Research program (W81XWH-09-1-0172; W. Yu), the National Cancer Institute to the Tumor Microenvironment Network (1U54CA126568), the Baylor Prostate Cancer SPORE (P50CA058204), and the Dan L. Duncan Cancer Center (P30CA125123) and by the use of the facilities of the Michael E. DeBakey VAMC. NR 50 TC 24 Z9 24 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUL 1 PY 2011 VL 17 IS 13 BP 4355 EP 4366 DI 10.1158/1078-0432.CCR-10-2858 PG 12 WC Oncology SC Oncology GA 788LO UT WOS:000292446600018 PM 21622724 ER PT J AU Azab, AK Azab, F Quang, P Maiso, P Sacco, A Ngo, HT Liu, Y Zhang, Y Morgan, BL Roccaro, AM Ghobrial, IM AF Azab, Abdel Kareem Azab, Feda Quang, Phong Maiso, Patricia Sacco, Antonio Ngo, Hai T. Liu, Yang Zhang, Yong Morgan, Brittany L. Roccaro, Aldo M. Ghobrial, Irene M. TI FGFR3 Is Overexpressed Waldenstrom Macroglobulinemia and Its Inhibition by Dovitinib Induces Apoptosis and Overcomes Stroma-Induced Proliferation SO CLINICAL CANCER RESEARCH LA English DT Article ID TYROSINE KINASE INHIBITOR; GROWTH-FACTOR RECEPTOR-3; MULTIPLE-MYELOMA; CHIR-258; CANCER; LEUKEMIA; MUTATION; MODELS AB Purpose: There is no standard of therapy for the treatment of Waldenstrom macroglobulinemia (WM), therefore there is a need for the development of new agents. Fibroblast growth factor receptor 3 (FGFR3) was shown to play a major role in several types in cancer. Dovitinib, an inhibitor of FGFR3, was effective in hematologic malignancies. In this study, we tested FGFR3 as a therapeutic target in WM and tested the effect of dovitinib on cell proliferation and apoptosis of WM cells in the context of BM microenvironment. Methods: The expression of FGFR3 in WM cells was tested using immunofluorescence and flow cytometry. Cell signaling in response to stimulation with FGF3 and stromal cells, and its inhibition by dovitinib was performed using immunoblotting. Cell survival and cell proliferation were assessed by MTT and BrdU assays. Apoptosis was measured by detection of APO-2.7 and cleavage of caspase-3 using flow cytometry. Cell cycle was performed by PI staining of cells and flow cytometry. The combinatory effect of dovitinib with other drugs was analyzed using Calcusyn software. The effect of dovitinib was tested in vivo. Results: FGFR3 was overexpressed in WM cells and its activation induced cell proliferation. Inhibition of FGFR3 with dovitinib decreased cell survival, increased apoptosis, and induced cell cycle arrest. Inhibition of FGFR3 by dovitinib reduced the interaction of WM to bone marrow components, and reversed its proliferative effect. Dovitinib had an additive effect with other drugs. Moreover, dovitinib reduced WM tumor progression in vivo. Conclusion: We report that FGFR3 is a novel therapeutic target in WM, and suggest dovitinib for future clinical trial the treatment of patients with WM. Clin Cancer Res; 17(13); 4389-99. (C) 2011 AACR. C1 [Ghobrial, Irene M.] Dana Farber Canc Inst, Kirsch Lab Waldenstrom, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Ghobrial, IM (reprint author), Dana Farber Canc Inst, Kirsch Lab Waldenstrom, Dept Med Oncol, 44 Binney St,Mayer 548A, Boston, MA 02115 USA. EM irene_ghobrial@dfci.harvard.edu RI Sacco, Antonio/K-4681-2016; OI Sacco, Antonio/0000-0003-2945-9416; Maiso, Patricia/0000-0003-3745-1924; Roccaro, Aldo/0000-0002-1872-5128 FU Novartis; BMS; Noxxon; Millennium; Michelle and Steven Kirsch Lab for Waldenstrom FX I.M. Ghobrial is on the advisory boards of Millennium, Celgene, Novartis, and Onyx and receives research funding from Novartis, BMS, Noxxon, and Millennium. The other authors disclosed no conflicts of interest.; This work is supported in part by the Michelle and Steven Kirsch Lab for Waldenstrom. NR 22 TC 13 Z9 13 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUL 1 PY 2011 VL 17 IS 13 BP 4389 EP 4399 DI 10.1158/1078-0432.CCR-10-2772 PG 11 WC Oncology SC Oncology GA 788LO UT WOS:000292446600021 PM 21521775 ER PT J AU Kleijn, A Chen, JW Buhrman, JS Wojtkiewicz, GR Iwamoto, Y Lamfers, ML Stemmer-Rachamimov, AO Rabkin, SD Weissleder, R Martuza, RL Fulci, G AF Kleijn, Anne Chen, John W. Buhrman, Jason S. Wojtkiewicz, Gregory R. Iwamoto, Yoshiko Lamfers, Martine L. Stemmer-Rachamimov, Anat O. Rabkin, Samuel D. Weissleder, Ralph Martuza, Robert L. Fulci, Giulia TI Distinguishing Inflammation from Tumor and Peritumoral Edema by Myeloperoxidase Magnetic Resonance Imaging SO CLINICAL CANCER RESEARCH LA English DT Article ID ONCOLYTIC VIRUS THERAPY; HERPES-SIMPLEX-VIRUS; GLIOMA-CELLS; GLIOBLASTOMA CELLS; INNATE IMMUNITY; MICROGLIA; MACROPHAGES; EXPRESSION; MONOCYTE; STAGE AB Purpose: Inflammation occurs routinely when managing gliomas and is not easily distinguishable from tumor regrowth by current MRI methods. The lack of noninvasive technologies that monitor inflammation prevents us to understand whether it is beneficial or detrimental for the patient, and current therapies do not take this host response in consideration. We aim to establish whether a gadolinium (Gd)-based agent targeting the inflammatory enzyme myeloperoxidase (MPO) can selectively detect intra-and peritumoral inflammation as well as glioma response to treatment by MRI. Methods: We carried out serial Gd-bis-5-HT-DTPA (MPO-Gd) MRI before and after treating rodent gliomas with different doses of oncolytic virus (OV) and analyzed animal survival. The imaging results were compared with histopathologic and molecular analyses of the tumors for macrophage/microglia infiltration, virus persistence, and MPO levels. Results: Elevated MPO activity was observed by MRI inside the tumor and in the peritumoral cerebrum at day 1 post-OV injection, which corresponded with activation/infiltration of myeloid cells inhibiting OV intratumoral persistence. MPO activity decreased, whereas tumor size increased, as the virus and the immune cells were cleared (days 1-7 post-OV injection). A 10-fold increase in viral dose temporally decreased tumor size, but augmented MPO activity, thus preventing extension of viral intratumoral persistence. Conclusions: MPO-Gd MRI can distinguish enhancement patterns that reflect treatment-induced spatiotemporal changes of intratumoral and intracerebral inflammation from those indicating tumor and peritumoral edema. This technology improves the posttreatment diagnosis of gliomas and will increase our understanding of the role of inflammation in cancer therapy. Clin Cancer Res; 17(13); 4484-93. (C) 2011 AACR. C1 [Kleijn, Anne; Buhrman, Jason S.; Rabkin, Samuel D.; Martuza, Robert L.; Fulci, Giulia] Massachusetts Gen Hosp, Brain Tumor Res Ctr, Boston, MA 02114 USA. [Chen, John W.; Wojtkiewicz, Gregory R.; Iwamoto, Yoshiko; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Chen, John W.; Wojtkiewicz, Gregory R.; Iwamoto, Yoshiko; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. [Stemmer-Rachamimov, Anat O.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Kleijn, Anne; Lamfers, Martine L.] Erasmus MC, Dept Neurosurg, Rotterdam, Netherlands. RP Fulci, G (reprint author), Massachusetts Gen Hosp, Brain Tumor Res Ctr, Simches Res Bldg,CRPZN 3800,185 Cambridge St, Boston, MA 02114 USA. EM gfulci@partners.org RI rabkin, samuel/C-2443-2012; Lamfers, Martine/C-6246-2016; OI rabkin, samuel/0000-0003-2344-2795; Lamfers, Martine/0000-0001-7745-9029 FU National Cancer Institute [R21-CA135526]; National Institute for Neurological Disorders [R01-NS070835, R01-NS072167, R01-NS032677, P30-NS045776]; National Heart, Lung and Blood Institute at the NIH [K08-HL081170] FX This work was supported by the National Cancer Institute (R21-CA135526 to G. Fulci), the National Institute for Neurological Disorders (R01-NS070835 and R01-NS072167 to J.W. Chen, R01-NS032677 to R. L. Martuza, and P30-NS045776 to S. Rabkin), and the National Heart, Lung and Blood Institute (K08-HL081170 to J.W. Chen) at the NIH. NR 48 TC 12 Z9 13 U1 1 U2 12 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUL 1 PY 2011 VL 17 IS 13 BP 4484 EP 4493 DI 10.1158/1078-0432.CCR-11-0575 PG 10 WC Oncology SC Oncology GA 788LO UT WOS:000292446600029 PM 21558403 ER PT J AU Kakkar, R Lee, RT AF Kakkar, Rahul Lee, Richard T. TI Directions from Hecate: towards a multi-marker approach for heart failure assessment SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Editorial Material ID NATRIURETIC PEPTIDE; TROPONIN-I; DYSPNEA; BNP; ST2 AB This editorial refers to 'Soluble ST2, high-sensitivity troponin T- and N-terminal pro-B-type natriuretic peptide: complementary role for risk stratification in acutely decompensated heart failure' by D. A. Pascual-Figal et al., published in this issue on pages 718-725. C1 [Kakkar, Rahul] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lee, Richard T.] Partners Res Facil, Cambridge, MA 02139 USA. RP Kakkar, R (reprint author), Massachusetts Gen Hosp, Yaw 5700,55 Fruit St, Boston, MA 02114 USA. EM rkakkar@partners.org NR 14 TC 1 Z9 1 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1388-9842 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD JUL PY 2011 VL 13 IS 7 BP 691 EP 693 DI 10.1093/eurjhf/hfr059 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 787JW UT WOS:000292373400001 PM 21712290 ER PT J AU Pascual-Figal, DA Manzano-Fernandez, S Boronat, M Casas, T Garrido, IP Bonaque, JC Pastor-Perez, F Valdes, M Januzzi, JL AF Pascual-Figal, Domingo A. Manzano-Fernandez, Sergio Boronat, Miguel Casas, Teresa Garrido, Iris P. Bonaque, Juan C. Pastor-Perez, Francisco Valdes, Mariano Januzzi, James L. TI Soluble ST2, high-sensitivity troponin T- and N-terminal pro-B-type natriuretic peptide: complementary role for risk stratification in acutely decompensated heart failure SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Article DE Heart failure; Soluble ST2; Troponin; NT-proBNP; Prognosis ID RECEPTOR FAMILY-MEMBER; PRESERVED EJECTION FRACTION; ACUTE MYOCARDIAL-INFARCTION; CARDIAC TROPONIN; PLASMA-CONCENTRATIONS; ACUTE DYSPNEA; SERUM-LEVELS; MORTALITY; DIAGNOSIS; PROGNOSIS AB Aim To investigate the use of biomarkers providing independent information regarding physiology in acutely decompensated heart failure (ADHF) for assessment of risk. Methods and results This was a prospective study of 107 patients hospitalized with ADHF (mean age 72 +/- 13 years, 44% male, left ventricular ejection fraction 47 +/- 15%). Blood samples were collected on presentation to measure soluble (s)ST2, high-sensitivity troponin T (hsTnT), and amino-terminal pro-B type natriuretic peptide (NT-proBNP) levels. Clinical follow-up was obtained for all patients over a median period of 739 days, and all-cause mortality was registered. Concentrations of sST2 [per 10 ng/mL, hazard ratio (HR) 1.09, 95% confidence interval (CI) 1.04-1.13; P < 0.001], hsTnT (per 0.1 ng/mL, HR 1.16, 95% CI 1.09-1.24; P < 0.001), and NT-proBNP (per 100 pg/mL, HR 1.01, 95% CI 1.003-1.01; P < 0.001) were each predictive of a higher risk of death. In bootstrapped models, each biomarker retained independent predictive value for mortality. Patients with all three biomarkers below their optimal cut-off at presentation were free of death (0%) during follow-up, whereas 53% of those with elevations of all three biomarkers had died. For each elevated marker (from 0 to 3) adjusted analysis suggested a tripling of the risk of death (for each elevated marker, HR 2.64, 95% CI 1.63-4.28, P < 0.001). Integrated discrimination analyses indicated that the use of these three markers in a multimarker approach uniquely improved prediction of death. Conclusions Biomarkers reflecting remodelling (sST2), myonecrosis (hsTnT), and myocardial stretch (NT-proBNP) provide complementary prognostic information in patients with ADHF. When used together, these novel markers provide superior risk stratification. C1 [Pascual-Figal, Domingo A.; Manzano-Fernandez, Sergio; Garrido, Iris P.; Bonaque, Juan C.; Pastor-Perez, Francisco; Valdes, Mariano] Univ Murcia, Dept Cardiol, Virgen Arrixaca Hosp, Murcia, Spain. [Pascual-Figal, Domingo A.; Manzano-Fernandez, Sergio; Garrido, Iris P.; Bonaque, Juan C.; Pastor-Perez, Francisco; Valdes, Mariano] Univ Murcia, Sch Med, Murcia, Spain. [Boronat, Miguel; Casas, Teresa] Virgen Arrixaca Hosp, Serv Biochem, Murcia, Spain. [Januzzi, James L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Pascual-Figal, DA (reprint author), Univ Murcia, Dept Cardiol, Virgen Arrixaca Hosp, Murcia, Spain. EM dapascual@servicam.com RI Pascual Figal, Domingo /B-3794-2008 OI Pascual Figal, Domingo /0000-0002-4993-9540 FU national network of investigation on heart failure 'REDINSCOR' [RD06/0003]; Instituto de Salud Carlos III, Ministry of Health, Madrid, Spain; Balson Cardiac Scholar fund; Roche Diagnostics; Siemens Diagnostics; Critical Diagnostics FX This study was supported by the national network of investigation on heart failure 'REDINSCOR': Grant RD06/0003, Instituto de Salud Carlos III, Ministry of Health, Madrid, Spain. Dr Januzzi is supported in part by the Balson Cardiac Scholar fund.; Conflict of interest: Dr Januzzi reports grant support from Roche Diagnostics, Siemens Diagnostics, and Critical Diagnostics. Dr Pascual-Figal reports grant support from Roche Diagnostics. NR 32 TC 95 Z9 102 U1 3 U2 15 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1388-9842 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD JUL PY 2011 VL 13 IS 7 BP 718 EP 725 DI 10.1093/eurjhf/hfr047 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 787JW UT WOS:000292373400006 PM 21551163 ER PT J AU Lee, JE Chan, AT AF Lee, Jung Eun Chan, Andrew T. TI Fruit, Vegetables, and Folate: Cultivating the Evidence for Cancer Prevention SO GASTROENTEROLOGY LA English DT Editorial Material ID RANDOMIZED CLINICAL-TRIAL; FOLIC-ACID FORTIFICATION; COLORECTAL-CANCER; DIETARY FIBER; COLON-CANCER; DNA METHYLATION; UNITED-STATES; RISK; ADENOMAS; EXPRESSION C1 [Chan, Andrew T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA USA. [Lee, Jung Eun] Sookmyung Womens Univ, Dept Food & Nutr, Seoul, South Korea. RP Chan, AT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St,GRJ-722, Boston, MA 02114 USA. EM achan@partners.org OI Lee, Jung Eun/0000-0003-1141-878X FU NCI NIH HHS [R01 CA137178] NR 33 TC 21 Z9 21 U1 0 U2 13 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUL PY 2011 VL 141 IS 1 BP 16 EP 20 DI 10.1053/j.gastro.2011.05.020 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 786IX UT WOS:000292299700015 PM 21620843 ER PT J AU Dranoff, G AF Dranoff, Glenn TI Granulocyte-Macrophage Colony Stimulating Factor and Inflammatory Bowel Disease: Establishing a Connection SO GASTROENTEROLOGY LA English DT Editorial Material ID ACTIVE CROHNS-DISEASE; GM-CSF; CELLS; AUTOANTIBODIES; DEFICIENCIES; PATHOGENESIS; HOMEOSTASIS; COLITIS; CANCER; GAMMA C1 [Dranoff, Glenn] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Dranoff, Glenn] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. [Dranoff, Glenn] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Dranoff, Glenn] Harvard Univ, Sch Med, Boston, MA USA. RP Dranoff, G (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Dana 520C,450 Brookline Ave, Boston, MA 02115 USA. EM glenn_dranoff@dfci.harvard.edu FU NCI NIH HHS [CA143083, R01 CA143083] NR 29 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUL PY 2011 VL 141 IS 1 BP 28 EP 31 DI 10.1053/j.gastro.2011.05.023 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 786IX UT WOS:000292299700018 PM 21620840 ER PT J AU Zhang, J Roberts, TM Shivdasani, RA AF Zhang, Jing Roberts, Thomas M. Shivdasani, Ramesh A. TI Targeting PI3K Signaling as a Therapeutic Approach for Colorectal Cancer SO GASTROENTEROLOGY LA English DT Review DE Colon Cancer; Neoplasm; Signal Transduction; Genetics; Tumor ID ISLAND METHYLATOR PHENOTYPE; TYROSINE KINASE INHIBITORS; 3-KINASE CATALYTIC SUBUNIT; PIK3CA GENE-MUTATIONS; GROWTH IN-VITRO; PHOSPHOINOSITIDE 3-KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; COLON-CANCER; MICROSATELLITE INSTABILITY; P110-ALPHA ISOFORM AB Survival times of patients with colorectal cancer (CRC) have increased over the past decade, primarily as a result of treatment with combinations of conventional cytotoxic agents. Because CRC is commonly associated with mutations in genes that control growth factor signaling, therapies are being developed to target the products of these genes; individualized treatment might also be guided by specific mutations in tumors and by new biomarkers. Currently, targeted therapies confer limited clinical benefit; better drugs are therefore needed. Genomic studies indicate that phosphoinositide 3-kinase (PI3K) signaling is one of the most frequently deregulated pathways in several human cancers, including CRC. PI3K signaling has an important role in cancer cell proliferation, survival, motility, and metabolism and therefore could be an attractive therapeutic target. We review PI3K signaling in CRC and discuss current therapeutic approaches. C1 [Zhang, Jing; Roberts, Thomas M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Shivdasani, Ramesh A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Zhang, Jing; Roberts, Thomas M.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02215 USA. [Shivdasani, Ramesh A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Roberts, TM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, 450 Brookline Ave, Boston, MA 02215 USA. EM thomas_roberts@dfci.harvard.edu; ramesh_shivdasani@dfci.harvard.edu NR 120 TC 43 Z9 44 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 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD JUL PY 2011 VL 141 IS 1 BP 50 EP 61 DI 10.1053/j.gastro.2011.05.010 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 786IX UT WOS:000292299700026 PM 21723986 ER PT J AU Abu Dayyeh, BK Yang, M Fuchs, BC Karl, DL Yamada, S Sninsky, JJ O'Brien, TR Dienstag, JL Tanabe, KK Chung, RT AF Abu Dayyeh, Barham K. Yang, May Fuchs, Bryan C. Karl, Daniel L. Yamada, Suguru Sninsky, John J. O'Brien, Thomas R. Dienstag, Jules L. Tanabe, Kenneth K. Chung, Raymond T. CA HALT-C Trial Grp TI A Functional Polymorphism in the Epidermal Growth Factor Gene Is Associated With Risk for Hepatocellular Carcinoma SO GASTROENTEROLOGY LA English DT Article DE Liver Disease; Cancer; Tumor; Prognosis; HCV ID SERUM ALPHA-FETOPROTEIN; CHRONIC LIVER-DISEASE; CHRONIC HEPATITIS-C; EGF POLYMORPHISM; CIRRHOTIC LIVER; EXPRESSION; RECEPTOR; REGENERATION; DIAGNOSIS; MICE AB BACKGROUND & AIMS: A single nucleotide polymorphism 61*G (rs4444903) in the epidermal growth factor (EGF) gene has been associated, in 2 case-control studies, with hepatocellular carcinoma (HCC). We tested associations between demographic, clinical, and genetic data and development of HCC, and developed a simple predictive model in a cohort of patients with chronic hepatitis C and advanced fibrosis. METHODS: Black and white subjects from the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) trial (n = 816) were followed up prospectively for development of a definite or presumed case of HCC for a median time period of 6.1 years. We used the Cox proportional hazards regression model to determine the hazard ratio for risk of HCC and to develop prediction models. RESULTS: Subjects with EGF genotype G/G had a higher adjusted risk for HCC than those with genotype A/A (hazard ratio, 2.10; 95% confidence interval, 1.05-4.23; P = .03). After adjusting for EGF genotype, blacks had no increased risk of HCC risk compared with whites. Higher serum levels of EGF were observed among subjects with at least one G allele (P = .08); the subset of subjects with EGF G/G genotype and above-median serum levels of EGF had the highest risk of HCC. We developed a simple prediction model that included the EGF genotype to identify patients at low, intermediate, and high risk for HCC; 6-year cumulative HCC incidences were 2.3%, 10.4%, and 26%, respectively. CONCLUSIONS: We associated the EGF genotype G/G with increased risk for HCC; differences in its frequency among black and white subjects might account for differences in HCC incidence between these groups. We developed a model that incorporates EGF genotype and demographic and clinical variables to identify patients at low, intermediate, and high risk for HCC. C1 [Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. [Fuchs, Bryan C.; Karl, Daniel L.; Yamada, Suguru; Tanabe, Kenneth K.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Abu Dayyeh, Barham K.; Dienstag, Jules L.] Harvard Univ, Dept Med, Sch Med, Boston, MA 02114 USA. [Fuchs, Bryan C.; Karl, Daniel L.; Yamada, Suguru; Tanabe, Kenneth K.] Harvard Univ, Dept Surg, Sch Med, Boston, MA 02114 USA. [Yang, May] New England Res Inst, Watertown, MA 02172 USA. [Sninsky, John J.] Celera Corp, Alameda, CA USA. [O'Brien, Thomas R.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Chung, RT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Warren 1007C,55 Fruit St, Boston, MA 02114 USA. EM rtchung@partners.org FU Hoffmann-La Roche, Inc (now Genentech); Schering-Plough (now Merck); Novartis; Romark; National Institutes of Health [DK078772]; Vertex Pharmaceuticals; National Cancer Institute [5 K01 CA140861-02]; National Institute of Diabetes & Digestive & Kidney Diseases; National Institute of Allergy and Infectious Diseases; National Cancer Institute; National Center for Minority Health and Health Disparities; General Clinical Research Center; National Center for Research Resources, National Institutes of Health; Celera Corporation; National Institutes of Health FX These authors disclose the following: Raymond Chung receives research support from Hoffmann-La Roche, Inc (now Genentech), Schering-Plough (now Merck), Novartis, and Romark; is a consultant for Merck, Pfizer, and Gilead; and is supported by National Institutes of Health grant number DK078772. John Sninsky is an employee and has equity interest in Celera Corporation. Jules Dienstag receives research support from Vertex Pharmaceuticals; serves on the data monitoring committee for Schering-Plough Research Institute, Human Genome Sciences, and Medtronic; is on the Ad hoc Hepatitis Advisory Board for Boehringer-Ingelheim; Antiviral Advisory Board for Gilead Sciences; is an ad hoc consultant (with stock options) for Achillion; is on the Clinical Advisory Board (with stock options) for Nucleonics; and is on the Scientific Advisory Board (with stock options) for Metabasis. Kenneth Tanabe received honoraria for a scientific lecture on January 1, 2008, from Vertex. Bryan Fuchs is supported by a K award from the National Cancer Institute (5 K01 CA140861-02). The remaining authors disclose no conflicts.; This study was supported by the National Institute of Diabetes & Digestive & Kidney Diseases. Additional support was provided by the National Institute of Allergy and Infectious Diseases, the National Cancer Institute, the National Center for Minority Health and Health Disparities, and by General Clinical Research Center and Clinical and Translational Science Center grants from the National Center for Research Resources, National Institutes of Health. Additional funding to conduct this study was supplied by Hoffmann-La Roche, Inc (now Genentech), and Celera Corporation through Cooperative Research and Development Agreements with the National Institutes of Health. NR 40 TC 61 Z9 62 U1 0 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUL PY 2011 VL 141 IS 1 BP 141 EP 149 DI 10.1053/j.gastro.2011.03.045 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 786IX UT WOS:000292299700035 PM 21440548 ER PT J AU Villablanca, EJ Wang, S de Calisto, J Gomes, DCO Kane, MA Napoli, JL Blaner, WS Kagechika, H Blomhoff, R Rosemblatt, M Bono, MR von Andrian, UH Mora, JR AF Villablanca, Eduardo J. Wang, Sen de Calisto, Jaime Gomes, Daniel C. O. Kane, Maureen A. Napoli, Joseph L. Blaner, William S. Kagechika, Hiroyuki Blomhoff, Rune Rosemblatt, Mario Bono, Maria Rosa von Andrian, Ulrich H. Mora, J. Rodrigo TI MyD88 and Retinoic Acid Signaling Pathways Interact to Modulate Gastrointestinal Activities of Dendritic Cells SO GASTROENTEROLOGY LA English DT Article DE Inflammation; IBD; Immune Response; Mouse Model ID VITAMIN-A; T-CELLS; SMALL-INTESTINE; GUT; EXPRESSION; RECEPTOR; DIFFERENTIATION; METABOLISM; ACTIVATION; GENERATION AB BACKGROUND & AIMS: Gut-associated dendritic cells (DC) metabolize vitamin A into all-trans retinoic acid (RA), which is required to induce lymphocytes to localize to the gastrointestinal tract and promotes the differentiation of Foxp3(+) regulatory T cells and IgA antibody-secreting cells. We investigated whether RA functions in a positive-feedback loop in DC to induce its own synthesis. METHODS: We measured levels of retinoids in intestinal tissues from mice and assessed the role of RA in the functional specialization of gut-associated DC in cell cultures and mice. We used pharmacologic antagonists to determine the signaling pathways involved in regulation of DC and used MyD88(-/-) mice to determine the contribution of Toll-like receptor signaling in RA-mediated effects on DC. RESULTS: The concentration of retinoids decreased in a proximal-to-distal gradient along the intestine, which correlated with the activity of gut-specific DC. Importantly, RA regulated the ability of gut-associated DC to produce RA, induce T cells to localize to the gastrointestinal tract, and generate regulatory T cells and IgA-secreting cells. RA was sufficient to induce its own production by extra-intestinal DC in vitro and in vivo. RA-mediated regulation of DC required signaling through the mitogen-activated protein kinase signaling pathway and unexpectedly required MyD88, which is conventionally associated with Toll-like receptor, interleukin-1, and interleukin-18 signaling. CONCLUSIONS: RA is necessary and sufficient to induce DC to regulate T-cell localization to the gastrointestinal tract and IgA secretion. Our findings also indicate crosstalk between the RA receptor and MyD88-dependent Toll-like receptor signaling pathways. C1 [Villablanca, Eduardo J.; Wang, Sen; de Calisto, Jaime; Mora, J. Rodrigo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. [de Calisto, Jaime; Rosemblatt, Mario] Univ Chile, Fac Ciencias, Santiago, Chile. [Gomes, Daniel C. O.] Univ Fed Espirito Santo, Vitoria, ES, Brazil. [Gomes, Daniel C. O.] Univ Fed Rio de Janeiro, BR-21941 Rio De Janeiro, Brazil. [Kane, Maureen A.; Napoli, Joseph L.] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Blaner, William S.] Columbia Univ, New York, NY USA. [Kagechika, Hiroyuki] Tokyo Med & Dent Univ, Tokyo, Japan. [Blomhoff, Rune] Univ Oslo, Inst Basic Med Sci, Oslo, Norway. [Rosemblatt, Mario] Fdn Ciencia Vida, Santiago, Chile. [Rosemblatt, Mario] Univ Andres Bello, Santiago, Chile. [von Andrian, Ulrich H.] Harvard Univ, Immune Dis Inst, Sch Med, Boston, MA 02114 USA. RP Mora, JR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, 55 Fruit St, Boston, MA 02114 USA. EM j_rodrigo_mora@hms.harvard.edu RI von Andrian, Ulrich/A-5775-2008; Bono, Maria/G-7461-2014; Villablanca, Eduardo/E-1380-2016 OI Villablanca, Eduardo/0000-0001-9522-9729 FU Crohn's & Colitis Foundation of America; Fondecyt [1100557, 1100448]; Conicyt [PFB16]; National Institutes of Health [DP2 2009A054301]; Cancer Research Institute; Massachusetts Life Science Center FX EJV was supported by a grant from Crohn's & Colitis Foundation of America. MRB and MR were supported by Fondecyt Grants 1100557 and 1100448 and PFB16 from Conicyt. UHvA was supported by grants from National Institutes of Health. JRM was supported by grants from Crohn's & Colitis Foundation of America, Cancer Research Institute, Howard H. Goodman (Massachusetts General Hospital), Massachusetts Life Science Center, and National Institutes of Health DP2 2009A054301. NR 34 TC 41 Z9 43 U1 0 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUL PY 2011 VL 141 IS 1 BP 176 EP 185 DI 10.1053/j.gastro.2011.04.010 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 786IX UT WOS:000292299700039 PM 21596042 ER PT J AU Masciari, S Dewanwala, A Stoffel, EM Lauwers, GY Zheng, H Achatz, MI Riegert-Johnson, D Foretova, L Silva, EM Digianni, L Verselis, SJ Schneider, K Li, FP Fraumeni, J Garber, JE Syngal, S AF Masciari, Serena Dewanwala, Akriti Stoffel, Elena M. Lauwers, Gregory Y. Zheng, Hui Achatz, Maria Isabel Riegert-Johnson, Douglas Foretova, Lenka Silva, Edaise M. Digianni, Lisa Verselis, Sigitas J. Schneider, Katherine Li, Frederick P. Fraumeni, Joseph Garber, Judy E. Syngal, Sapna TI Gastric cancer in individuals with Li-Fraumeni syndrome SO GENETICS IN MEDICINE LA English DT Article DE Li Fraumeni syndrome; gastric cancer; hereditary gastric cancer syndromes; germline mutations; TP53 ID FAMILIAL ADENOMATOUS POLYPOSIS; BRCA1 MUTATION CARRIERS; P53 GERMLINE MUTATIONS; E-CADHERIN GENE; BREAST-CANCER; COLORECTAL-CANCER; CHILDHOOD-CANCER; DIFFUSE; TP53; RISK AB Purpose: Li-Fraumeni syndrome is a rare hereditary cancer syndrome associated with germline mutations in the TP53 gene. Although sarcomas, brain tumors, leukemias, breast and adrenal cortical carcinomas are typically recognized as Li-Fraumeni syndrome-associated tumors, the occurrence of gastrointestinal neoplasms has not been fully evaluated. In this analysis, we investigated the frequency and characteristics of gastric cancer in Li-Fraumeni syndrome. Methods: Pedigrees and medical records of 62 TP53 mutation-positive families were retrospectively reviewed from the Dana-Farber/National Cancer Institute Li-Fraumeni syndrome registry. We identified subjects with gastric cancer documented either by pathology report or death certificate and performed pathology review of the available specimens. Results: Among 62 TP53 mutation-positive families, there were 429 cancer-affected individuals. Gastric cancer was the diagnosis in the lineages of 21 (4.9%) subjects from 14 families (22.6%). The mean and median ages at gastric cancer diagnosis were 43 and 36 years, respectively (range: 24-74 years), significantly younger compared with the median age at diagnosis in the general population based on Surveillance Epidemiology and End Results data (71 years). Five (8.1%) families reported two or more cases of gastric cancer, and six (9.7%) families had cases of both colorectal and gastric cancers. No association was seen between phenotype and type/location of the TP53 mutations. Pathology review of the available tumors revealed both intestinal and diffuse histologies. Conclusions: Early-onset gastric cancer seems to be a component of Li-Fraumeni syndrome, suggesting the need for early and regular endoscopic screening in individuals with germline TP53 mutations, particularly among those with a family history of gastric cancer. Genet Med 2011:13(7):651-657. C1 [Masciari, Serena; Dewanwala, Akriti; Stoffel, Elena M.; Digianni, Lisa; Schneider, Katherine; Li, Frederick P.; Garber, Judy E.; Syngal, Sapna] Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. [Stoffel, Elena M.; Syngal, Sapna] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. [Lauwers, Gregory Y.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Zheng, Hui] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Biostat, Boston, MA USA. [Lauwers, Gregory Y.] Harvard Univ, Sch Med, Boston, MA USA. [Achatz, Maria Isabel] Hosp AC Camargo Fund Antonio Prudente, Dept Oncogenet, Sao Paulo, Brazil. [Achatz, Maria Isabel] Natl Inst Sci & Technol Oncogen, Sao Paulo, Brazil. [Riegert-Johnson, Douglas] Mayo Clin, Coll Med, Div Gastroenterol & Hepatol, Jacksonville, FL 32224 USA. [Foretova, Lenka] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic. [Silva, Edaise M.] Hosp AC Camargo Fund Antonio Prudente, Dept Anat Pathol, Sao Paulo, Brazil. [Verselis, Sigitas J.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Fraumeni, Joseph] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Syngal, S (reprint author), Dana Farber Canc Inst, Div Populat Sci, 44 Binney St,SM 209, Boston, MA 02115 USA. EM ssyngal@partners.org RI Achatz, Maria Isabel /C-5751-2013; Oncogenomica, Inct/H-9999-2013 OI Achatz, Maria Isabel /0000-0001-6894-1219; FU Charles A. King Trust; Bank of America (Boston, MA); Humane Society of the Commonwealth of Massachusetts; US National Cancer Institute [K24 CA 113433]; Harvard Catalyst/The Harvard Clinical and Translational Science Center [UL1 RR 025758]; STARR Foundation; [MZ0 MOU 2005] FX This work 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 (S.M.), the US National Cancer Institute Grant K24 CA 113433 (S.S.), Scholars in Clinical Science Program of Harvard Catalyst/The Harvard Clinical and Translational Science Center (Award no. UL1 RR 025758 and financial contributions from Harvard University and its affiliated academic health care centers), and supported, in part, by the STARR Foundation. Genetic testing in CR (L.F.) was supported by Grant MZ0 MOU 2005. The authors are grateful to the Li-Fraumeni patients and families who kindly consented over the years to be part of the DFCI/NCI LFS registry. NR 51 TC 39 Z9 40 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD JUL PY 2011 VL 13 IS 7 BP 651 EP 657 DI 10.1097/GIM.0b013e31821628b6 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 789TC UT WOS:000292538200008 PM 21552135 ER PT J AU Grande, D Gollust, SE Asch, DA AF Grande, David Gollust, Sarah E. Asch, David A. TI Polling Analysis: Public Support For Health Reform Was Broader Than Reported And Depended On How Proposals Were Framed SO HEALTH AFFAIRS LA English DT Article ID OPINION; CARE AB The excessive focus of news organizations on "horse race" public opinion polls during the debate about health reform in 2010 left the impression that the public was fickle, as well as sharply divided on whether the government's role in health care should expand. We examined polling data and found that public support for health reform depended very much on how individual policies were described. For example, support for the public insurance option, which was not included in the final version of the Affordable Care Act, ranged from 46.5 percent to 64.6 percent depending on how pollsters worded their questions. Our findings indicate that public support for health reform was broader and more consistent than portrayed at the time. Going forward, policy makers should strive to communicate how health care policy choices are consistent with existing public preferences or should make changes to policy that reflect those preferences. C1 [Grande, David; Asch, David A.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Grande, David] Univ Penn, Robert Wood Johnson Clin Scholars Program, Philadelphia, PA 19104 USA. [Gollust, Sarah E.] Univ Minnesota, Sch Publ Hlth, Div Hlth Policy & Management, Minneapolis, MN USA. [Asch, David A.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Grande, D (reprint author), Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. EM dgrande@wharton.upenn.edu OI Asch, David/0000-0002-7970-286X FU Robert Wood Johnson Foundation; HealthWell Foundation FX Funding for this research was provided by the Robert Wood Johnson Foundation Health and Society Scholars Program. The funder had no role in the design or conduct of the study; the collection, management, analysis, or interpretation of the data; or the preparation, review, or approval of the manuscript. David Grande reports receiving research support from the HealthWell Foundation, serving as a consultant to the National Nursing Centers Consortium, providing expert testimony of behalf of the State of Vermont, receiving honoraria for lectures from Temple University and the Johns Hopkins University continuing medical education program, and previously serving as a voluntary member of the board of directors of the National Physicians Alliance. The authors thank Jeffrey Then for his research assistance. NR 16 TC 5 Z9 5 U1 0 U2 5 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD JUL PY 2011 VL 30 IS 7 BP 1242 EP 1249 DI 10.1377/hlthaff.2011.0180 PG 8 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 789ET UT WOS:000292497600004 PM 21734196 ER PT J AU Messou, E Kouakou, M Gabillard, D Gouesse, P Kone, M Tchehy, A Losina, E Freedberg, KA Dri-Yoman, TN Anzian, A Toure, S Anglaret, X AF Messou, Eugene Kouakou, Martial Gabillard, Delphine Gouesse, Patrice Kone, Mamadou Tchehy, Amah Losina, Elena Freedberg, Kenneth A. Dri-Yoman, Therese N. Anzian, Amani Toure, Siaka Anglaret, Xavier TI Medication Possession Ratio: Predicting and Decreasing Loss to Follow-Up in Antiretroviral Treatment Programs in Cote d'Ivoire SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE adults; cART; lost to follow-up; medication possession ratio; sub-Saharan Africa ID HIV-INFECTED PATIENTS; SUB-SAHARAN AFRICA; THERAPY PROGRAMS; SOUTH-AFRICA; PATIENT RETENTION; RISK-FACTORS; SCALE-UP; OUTCOMES; SURVIVAL; ADULTS AB Background: In antiretroviral therapy (ART) programs, decreasing loss to follow up (LTFU) is a major priority. Methods: We conducted a prospective study in Abidjan. Adults who started ART between June 2005 and May 2008 and were still in care 6 months later had monthly visits, biannual CD4 counts, computerized data collection and home visits (routine follow-up). A subset of patients also had biannual plasma HIV-1 RNA measurements, with a physician and a research assistant hired to pay particular attention to their visits (enhanced follow-up). We analyzed the association between 18-month outcomes and pre-ART characteristics, medication possession ratio (MPR) and type of follow-up. Patients were LTFU if their last visit was before month-18 and they had not returned to care by month-24. Results: 2,074 patients started ART, of whom 1,636 (79%) were still in care at month-6. The routine (n = 999) and enhanced (n = 637) groups had similar baseline characteristics. From month-6 to month-18, they had similar death rates (routine 3.6%, enhanced 3.9%, P = 0.74), but the enhanced group had significantly less LTFU (routine 11.3%, enhanced 5.8%, P < 0.001). In multivariate analysis, the risk of LTFU from month-6 to month-18 was 46% lower with enhanced follow-up, 56% higher in patients living outside the centre area, and 4.0 fold higher in patients with a low MPR (< 80%) between ART initiation and month-6. Conclusions: In patients still in care at 6 months, a low MPR in the first 6 months was strongly associated with further LTFU. Simple follow-up enhancement halved the LTFU rate in the following year. C1 [Gabillard, Delphine; Anglaret, Xavier] Univ Bordeaux 2, INSERM, U897, F-33076 Bordeaux, France. [Messou, Eugene; Gabillard, Delphine; Dri-Yoman, Therese N.; Anzian, Amani; Toure, Siaka; Anglaret, Xavier] PACCI CI Program, Abidjan, Cote Ivoire. [Messou, Eugene; Kouakou, Martial; Gouesse, Patrice; Kone, Mamadou; Tchehy, Amah; Dri-Yoman, Therese N.; Anzian, Amani; Toure, Siaka] Aconda Program, CePReF Clin, Abidjan, Cote Ivoire. [Messou, Eugene; Losina, Elena; Freedberg, Kenneth A.] Brigham & Womens Hosp, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Messou, Eugene; Losina, Elena; Freedberg, Kenneth A.] Harvard Univ, Sch Med, Boston, MA USA. RP Anglaret, X (reprint author), Univ Bordeaux 2, INSERM, U897, 146 Rue Leo Saignat, F-33076 Bordeaux, France. EM xavier.anglaret@isped.u-bordeaux2.fr RI Anglaret, Xavier/F-7333-2013 FU Agence Nationale de Recherches sur le SIDA et les hepatites virales [ANRS 12136, ANRS 12212]; National Institute of Allergy and Infectious Diseases [R01 AI058736, K24 AI062476] FX Supported by Agence Nationale de Recherches sur le SIDA et les hepatites virales (ANRS 12136, ANRS 12212) and National Institute of Allergy and Infectious Diseases (R01 AI058736, K24 AI062476). NR 25 TC 8 Z9 8 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 JUL 1 PY 2011 VL 57 SU 1 BP S34 EP S39 DI 10.1097/QAI.0b013e3182208003 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 788RO UT WOS:000292462300007 PM 21857284 ER PT J AU Escamilla, I Wozniak, J Soutullo, CA Gamazo-Garran, P Figueroa-Quintana, A Biederman, J AF Escamilla, Inmaculada Wozniak, Janet Soutullo, Cesar A. Gamazo-Garran, Pilar Figueroa-Quintana, Ana Biederman, Joseph TI Pediatric bipolar disorder in a Spanish sample: Results after 2.6 years of follow-up SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Mania; Bipolar; Children; Adolescents; Phenomenology; Europe ID SPECTRUM DISORDERS; I DISORDER; CHILDREN; ADOLESCENTS; PHENOMENOLOGY; PHENOTYPE; SYMPTOMS; MANIA; RECOVERY; ILLNESS AB Introduction: Bipolar disorder (BD) often starts in childhood or adolescence. There is considerable scepticism outside the United States over the validity, stability and prevalence of BD in children and adolescents. Persistence of course lends support to the validity of a diagnosis. Objectives: To describe the longitudinal course of pediatric BD in a Spanish sample over a median follow-up period of 2.6 years and to examine risk factors associated with outcome. Methods: We retrospectively reviewed the medical records of all children and adolescents (N = 38) with DSM-IV-TR BD-I, II and NOS evaluated in the Child and Adolescent Psychiatry Unit, University of Navarra (Pamplona, Spain) from 1999 to 2005. We used the NIMH Lifetime Mood Chart and the Clinical Global Impression-Severity Scale to assess clinical course. Results: 79% (N = 30) were boys and 21% (N = 8) were girls; 44.7% (N = 17) had BD-I, 5.3% (N = 2) BD-II, and 50% (N = 19) BD-NOS. Median (inter-quartile range: IQR: Q25; Q75) age at diagnosis was 13.9 (10.64; 15.84). Median follow-up period was 2.6 years (0.91; 3.66). Mean percentage of time in an episode was 46.17% (23.36; 75.26), and it was longer in younger children (p < 0.05). 2.6% had rapid cycling. At the end of follow-up, only 47% achieved remission or recovery. Younger children showed a worse treatment response (p < 0.05). We found higher rates of hospitalization in children with ADHD (21%) (p < 0.05). Conclusion: Children with BD had a chronic course with little interepisodic recovery. BD can be diagnosed in children using DSM-IV-TR criteria. An early age of onset and ADHD comorbidity are risk factors for worse prognosis. (C) 2011 Elsevier B.V. All rights reserved. C1 [Escamilla, Inmaculada; Gamazo-Garran, Pilar] Univ Navarra Clin, Dept Psychiat & Med Psychol, Child & Adolescent Psychiat Unit, Madrid 28036, Spain. [Wozniak, Janet; Biederman, Joseph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Psychopharmacol Res Unit, Boston, MA USA. [Soutullo, Cesar A.] Univ Navarra Clin, Dept Psychiat & Med Psychol, Child & Adolescent Psychiat Unit, Pamplona, Spain. [Figueroa-Quintana, Ana] Hosp Perpetuo Socorro, Child & Adolescent Psychiat Unit, Alicante, Spain. [Figueroa-Quintana, Ana] Hosp Gen La Palma, Serv Canario Salud, Palma De Mallorca, Spain. RP Escamilla, I (reprint author), Univ Navarra Clin, Dept Psychiat & Med Psychol, Child & Adolescent Psychiat Unit, Gen Lopez Pozas 10,Madrid Campus, Madrid 28036, Spain. EM iescamilla@unav.es FU Alicia Koplowitz Foundation; Eli Lilly; Lilly; Janssen; Shire; NIMH; Mcneil; Boehringer-Ingelheim; GlaxoSmithKline; UCB (Schwqarz) Pharma, Separcor; Abbott; Bristol-Myers Squibb; Gobierno de Navarra; Carlos III Institute(FIS); Redes Tematicas de Investigacion Cooperativa; PIUNA; Stanley Medical Research Institute-NAMI; Solvay; Alza; AstraZeneca; Eli Lilly and Co.; Janssen Pharmaceuticals Inc.; Merck; Organon; Otsuka; NICHD; Celltech; Cephalon; Esai; Forest; Glaxo; Gliatech; NARSAD; NIDA; New River; Novartis; Noven; Neurosearch; Pfizer; Pharmacia; Prechter Foundation; Stanley Foundation; UCB Pharma, Inc.; Wyeth FX Dr. Escamilla has received research funding from the Alicia Koplowitz Foundation and Eli Lilly. She has served on the speaker's bureau of Janssen. She received a teaching grant from the Alicia Koplowitz Foundation. Also, she has received funding for continued medical education from Lilly. Janssen and Shire.; Dr. Wozniak is the author of the book, "Is Your Child Bipolar" published May 2008, Bantam Books. During 2005-2009, she has been a speaker for MCNeil, Primedia/MGH Psychiatry Academy, on the Advisory Board for Pfizer and Shire and received research suppor from NIMH, Mcneil, Shire and Lilly. Her spouse John Winkelman M.D., Ph.D. has been on the Speakers Bureau for Beohringer-Oingelheim, Cephalon, GlaxoSmithKline, King, Sanofi-Aventis, Sepracor, Takeda, on the Adviosry Board for Axon Labs, Boehringer-Ingelheim, GlaxoSmithKline, Jazz Pharmaceuticals, Novartis, Neurogen,m Novadel Pharma, Pfizer. UCB (Schwarz) Pharma, Separacor, Takeda, Covance, Impax Laboratoires, Luitpold, Zeo Inc and recived research support from Boehringer-Ingelheim, GlaxoSmithKline, UCB (Schwqarz) Pharma, Separcor.; Dr. Cesar Soutullo has received research funding from: Abbott, Alicia Koplowitz Foundation, Bristol-Myers Squibb, Eli Lilly, Gobierno de Navarra, Carlos III Institute(FIS): Redes Tematicas de Investigacion Cooperativa, Pfizer, PIUNA, Stanley Medical Research Institute-NAMI, and Solvay.; Dr. Joseph Biederman is currently receiving research support from the following sources: Alza, AstraZeneca, Bristol-Myers Squibb, Eli Lilly and Co., Janssen Pharmaceuticals Inc., McNeil, Merck. Organon, Otsuka, Shire, NIMH, and NICHD; In previous years, Dr. Joseph Biederman received research support, consultation fees, or speaker's fees for/from the following additional sources: Abbott, AstraZeneca, Celltech, Cephalon, Eli Lilly and Co., Esai, Forest, Glaxo, Gliatech, Janssen, McNeil, NARSAD, NIDA, New River, Novartis, Noven, Neurosearch, Pfizer, Pharmacia, The Prechter Foundation, Shire, The Stanley Foundation, UCB Pharma, Inc. and Wyeth. NR 24 TC 5 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD JUL PY 2011 VL 132 IS 1-2 BP 270 EP 274 DI 10.1016/j.jad.2011.01.013 PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 788IK UT WOS:000292438400036 PM 21334070 ER PT J AU Baron, JM Griggs, DA Nixon, AL Long, WH Flood, JG AF Baron, Jason M. Griggs, David A. Nixon, Andrea L. Long, William H. Flood, James G. TI The Trazodone Metabolite meta-Chlorophenylpiperazine Can Cause False-Positive Urine Amphetamine Immunoassay Results SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID PHOTODIODE-ARRAY DETECTION; LIQUID-CHROMATOGRAPHY; DRUGS; CONFIRMATION; QUANTIFICATION; TOXICOLOGY; OVERDOSE; ECSTASY; SERUM C1 [Baron, Jason M.; Griggs, David A.; Nixon, Andrea L.; Long, William H.; Flood, James G.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Baron, JM (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,GRJ 235, Boston, MA 02114 USA. EM jmbaron@partners.org NR 14 TC 16 Z9 16 U1 1 U2 3 PU PRESTON PUBL INC PI NILES PA 6600 W TOUHY AVE, NILES, IL 60714-4588 USA SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD JUL-AUG PY 2011 VL 35 IS 6 BP 364 EP 368 PG 5 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA 787HV UT WOS:000292368100007 PM 21740694 ER PT J AU Loeffler, JS Shih, HA AF Loeffler, Jay S. Shih, Helen A. TI Radiation Therapy in the Management of Pituitary Adenomas SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Review ID GAMMA-KNIFE RADIOSURGERY; TERM-FOLLOW-UP; LINEAR-ACCELERATOR RADIOSURGERY; GROWTH-FACTOR-I; STEREOTACTIC RADIOSURGERY; CUSHINGS-DISEASE; POSTOPERATIVE RADIOTHERAPY; TRANSSPHENOIDAL SURGERY; CLINICAL ARTICLE; EFFICACY AB Context: Optimal management of pituitary adenomas involves consideration of the roles of medical therapy, surgery, and radiation therapy. The different forms of radiation therapy and their results are reviewed here. Evidence Acquisition: A literature search through the U. S. National Library of Medicine was used to identify and review clinical experiences of radiation therapy in the management of pituitary adenomas. Emphasis was placed on studies within the last 5-10 yr, with 5 or more years of follow-up data, and of reasonable quality of data. Older studies with larger numbers or particular significance are also highlighted. Evidence Synthesis: Success of radiation therapy in controlling tumor growth is high, 90-100% in most series, regardless of radiation technique and adenoma subtype. Success in achieving hormonal normalization in secretory tumors is more variable because of differences in patient population, radiation technique, and doses employed and variation of the definition of success. Complete biochemical remission is generally achieved in 50% of patients at 10 yr after treatment for most adenomas. Higher rates of normalization can be achieved with additional medical therapy. Hypopituitarism is an expectant result of radiation therapy. Overall rate of other treatment-related adverse effects is low. Conclusions: Radiation therapy should be considered in the management of patients with pituitary adenomas, particularly when medical and surgical options have been exhausted. Because response evolves slowly over many years and because hypopituitarism is likely to occur, patients should be counseled on the importance of continued endocrinological surveillance and medical management. (J Clin Endocrinol Metab 96: 1992-2003, 2011) C1 [Loeffler, Jay S.; Shih, Helen A.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Loeffler, Jay S.; Shih, Helen A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Shih, HA (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA. NR 65 TC 58 Z9 61 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 2011 VL 96 IS 7 BP 1992 EP 2003 DI 10.1210/jc.2011-0251 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 788OO UT WOS:000292454500033 PM 21525155 ER PT J AU Miller, KK Meenaghan, E Lawson, EA Misra, M Gleysteen, S Schoenfeld, D Herzog, D Klibanski, A AF Miller, Karen K. Meenaghan, Erinne Lawson, Elizabeth A. Misra, Madhusmita Gleysteen, Suzanne Schoenfeld, David Herzog, David Klibanski, Anne TI Effects of Risedronate and Low-Dose Transdermal Testosterone on Bone Mineral Density in Women with Anorexia Nervosa: A Randomized, Placebo-Controlled Study SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GROWTH-HORMONE DEFICIENCY; FRACTURE INTERVENTION TRIAL; DOUBLE-BLIND; POSTMENOPAUSAL OSTEOPOROSIS; HYPOTHALAMIC AMENORRHEA; VERTEBRAL FRACTURES; PARATHYROID-HORMONE; ELDERLY WOMEN; HIP FRACTURE; ALENDRONATE AB Context: Anorexia nervosa is complicated by severe bone loss and clinical fractures. Mechanisms underlying bone loss in adults with anorexia nervosa include increased bone resorption and decreased formation. Estrogen administration has not been shown to prevent bone loss in this population, and to date, there are no approved, effective therapies for this comorbidity. Objective: To determine whether antiresorptive therapy with a bisphosphonate alone or in combination with low-dose transdermal testosterone replacement would increase bone mineral density (BMD) in women with anorexia nervosa. Design and Setting: We conducted a 12-month, randomized, placebo-controlled study at a clinical research center. Study Participants: Participants included 77 ambulatory women with anorexia nervosa. Intervention: Subjects were randomized to risedronate 35 mg weekly, low-dose transdermal testosterone replacement therapy, combination therapy or double placebo. Main Outcome Measures: BMD at the spine (primary endpoint), hip, and radius and body composition were measured by dual-energy x-ray absorptiometry. Results: Risedronate increased posteroanterior spine BMD 3%, lateral spine BMD 4%, and hip BMD 2% in women with anorexia nervosa compared with placebo in a 12-month clinical trial. Testosterone administration did not improve BMD but increased lean body mass. There were few side effects associated with either therapy. Conclusions: Risedronate administration for 1 yr increased spinal BMD, the primary site of bone loss in women with anorexia nervosa. Low-dose testosterone did not change BMD but increased lean body mass. (J Clin Endocrinol Metab 96: 2081-2088, 2011) C1 [Miller, Karen K.; Meenaghan, Erinne; Lawson, Elizabeth A.; Misra, Madhusmita; Klibanski, Anne] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Schoenfeld, David] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. [Herzog, David] Massachusetts Gen Hosp, Harris Ctr Eating Disorders, Boston, MA 02114 USA. [Herzog, David] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Gleysteen, Suzanne] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Miller, KK (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B, Boston, MA 02114 USA. EM KKMiller@Partners.org FU National Institutes of Health [R01 DK052625, MO1 RR01066, ULI RR0257801] FX This work was supported in part by National Institutes of Health Grants R01 DK052625, MO1 RR01066, and ULI RR0257801. Study drugs were provided for the study at no cost by Procter and Gamble Pharmaceuticals. NR 42 TC 40 Z9 40 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 JUL PY 2011 VL 96 IS 7 BP 2081 EP 2088 DI 10.1210/jc.2011-0380 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 788OO UT WOS:000292454500045 PM 21525157 ER PT J AU Ahima, RS Stanley, TL Khor, VK Zanni, MV Grinspoon, SK AF Ahima, Rexford S. Stanley, Takara L. Khor, Victor K. Zanni, Markella V. Grinspoon, Steven K. TI Estrogen Sulfotransferase Is Expressed in Subcutaneous Adipose Tissue of Obese Humans in Association with TNF-alpha and SOCS3 SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID STEROID SULFATASE; RECEPTOR-ALPHA; CARCINOMA; GLUCOSE; MICE; HOMEOSTASIS; ADIPOCYTES; MOUSE; BETA; FAT AB Context and Objective: Estrogen sulfotransferase (EST) catalyzes the inactivation of estrone and estradiol in numerous tissues. Animal studies suggest that EST modulates glucose and lipid metabolism in adipose tissue, but it is unknown whether EST is expressed in human adipose tissue and, if so, how its expression relates to features of the metabolic syndrome. Design and Participants: Cross-sectional data from 16 obese men and women with metabolic dysregulation were collected as part of a larger randomized trial at an academic medical center. Outcome Measures: Participants underwent assessment of body composition, oral glucose tolerance testing, measurement of serum hormones and inflammatory markers, and sc fat biopsy to assess adipose expression of TNF-alpha, suppressor of cytokine signaling 3 (SOCS3), leptin, adiponectin, and EST. Results: EST expression was detectable in sc adipose tissue from both men and women. Log(10) EST mRNA was not significantly associated with age, race, sex or menopausal status, or circulating levels of estrogen or testosterone. In univariate analysis, log(10) EST mRNA was significantly associated with visceral adipose tissue area (r = 0.57, P = 0.02) as well as adipose tissue expression of TNF-alpha (r = 0.94, P < 0.0001) and SOCS3 mRNA (r = 0.93, P < 0.0001). The associations between EST expression and TNF-alpha and SOCS3 held in multivariate modeling controlling for age, race, sex and menopausal status, and visceral adiposity. EST expression was not significantly associated with the adipose tissue levels of leptin or adiponectin expression. Conclusions: EST is expressed in abdominal sc adipose tissue of both obese males and females in association with expression of TNF-alpha and SOCS3, suggesting potential roles in inflammation. Further studies are needed to determine the specific metabolic roles of EST expression in human adipose tissue. (J Clin Endocrinol Metab 96: E1153-E1158, 2011) C1 [Ahima, Rexford S.; Khor, Victor K.] Univ Penn, Sch Med, Div Endocrinol Diabet & Metab, Dept Med, Philadelphia, PA 19104 USA. [Stanley, Takara L.; Zanni, Markella V.; Grinspoon, Steven K.] Massachusetts Gen Hosp, Program Nutrit Metab, Boston, MA 02114 USA. [Stanley, Takara L.; Zanni, Markella V.; Grinspoon, Steven K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Ahima, RS (reprint author), Univ Penn, Sch Med, Div Endocrinol Diabet & Metab, Dept Med, 764 Clin Res Bldg, Philadelphia, PA 19104 USA. EM ahima@mail.med.upenn.edu FU National Institutes of Health [M01-RR-01066, 1 UL1 RR025758-01, F32 DK080642-02, K23 DK089910-01, K24 DK064545-06, PO1-DK049210, F32 DK085969-01]; Harvard Clinical and Translational Science Center; National Center for Research Resources; Amgen FX This work was supported by National Institutes of Health Grants M01-RR-01066 and 1 UL1 RR025758-01, Harvard Clinical and Translational Science Center, and the National Center for Research Resources. National Institutes of Health funding was also provided through Grants F32 DK080642-02 and K23 DK089910-01 (to T. L. S.); Grant K24 DK064545-06 (to S. K. G.); Grant PO1-DK049210 (to R. S. A.); and Grant F32 DK085969-01 (to M.V.Z.).; R.S.A., T. L. S., V. K. K., and M.V.Z., have nothing to disclose. S. K. G. received funding for this project from Amgen in the form of an investigator-initiated research grant. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health. NR 18 TC 7 Z9 8 U1 1 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 2011 VL 96 IS 7 BP E1153 EP E1158 DI 10.1210/jc.2010-2903 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 788OO UT WOS:000292454500016 PM 21543429 ER PT J AU Joffe, H Petrillo, LF Koukopoulos, A Viguera, AC Hirschberg, A Nonacs, R Somley, B Pasciullo, E White, DP Hall, JE Cohen, LS AF Joffe, Hadine Petrillo, Laura Fagioli Koukopoulos, Alexia Viguera, Adele C. Hirschberg, April Nonacs, Ruta Somley, Brittny Pasciullo, Erica White, David P. Hall, Janet E. Cohen, Lee S. TI Increased Estradiol and Improved Sleep, But Not Hot Flashes, Predict Enhanced Mood during the Menopausal Transition SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PLACEBO-CONTROLLED TRIAL; VASOMOTOR SYMPTOMS; PERIMENOPAUSAL WOMEN; ESTROGEN REPLACEMENT; DOUBLE-BLIND; DEPRESSION; DISORDERS; INSOMNIA; THERAPY; QUALITY AB Background: The antidepressant effect of estrogen in women undergoing the menopause transition is hypothesized to be mediated by central nervous system effects of increasing estradiol on mood or through a pathway involving suppression of hot flashes and associated sleep disturbance. Estrogen therapy (ET) and the hypnotic agent zolpidem were selected as interventions in a three-arm, double-blind, placebo-controlled trial to distinguish the effects of estradiol, sleep, and hot flashes on depression. Methods: Women with depressive disorders, hot flashes, and sleep disturbance were randomly assigned to transdermal 17 beta-estradiol 0.05 mg/d, zolpidem 10 mg/d, or placebo for 8 wk. Changes in serum estradiol, perceived sleep quality, objectively measured sleep, and hot flashes were examined as predictors of depression improvement [Montgomery-Asberg Depression Rating Scale (MADRS)] using multivariate linear regression. Results: Seventy-two peri/postmenopausal women with depression disorders were randomized to 17 beta-estradiol (n = 27), zolpidem (n = 31), or placebo (n = 14). There was no significant difference between groups in depression improvement (overall MADRS decrease 11.8 +/- 8.6). Increasing estradiol (P = 0.009) and improved sleep quality (P < 0.001) predicted improved mood in adjusted models but reduced hot flashes (P = 0.99) did not. Post hoc subgroup analyses revealed that the therapeutic effect of increasing estradiol levels on mood was seen in perimenopausal (P = 0.009), but not postmenopausal, women. Conclusions: For women with menopause-associated depression, improvement in depression is predicted by improved sleep, and among perimenopausal women, by increasing estradiol levels. These results suggest that changes in estradiol and sleep quality, rather than hot flashes, mediate depression during the menopause transition. Therapies targeting insomnia may be valuable in treating menopause-associated depression. (J Clin Endocrinol Metab 96: E1044-E1054, 2011) C1 [Joffe, Hadine; Petrillo, Laura Fagioli; Koukopoulos, Alexia; Viguera, Adele C.; Hirschberg, April; Nonacs, Ruta; Somley, Brittny; Pasciullo, Erica; Cohen, Lee S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Womens Mental Hlth, Boston, MA 02114 USA. [Hall, Janet E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. [Hall, Janet E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Reprod Endocrine Unit, Boston, MA 02114 USA. [White, David P.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Sleep Med, Boston, MA 02115 USA. RP Joffe, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Womens Mental Hlth, Simches Res Bldg,185 Cambridge St,Suite 2000, Boston, MA 02114 USA. EM hjoffe@partners.org FU National Institutes of Health [K23 MH066978]; National Institute on Aging; National Institute of Mental Health; Bayer HealthCare Pharmaceuticals; Eli Lilly and Co.; Forest Laboratories, Inc.; GlaxoSmithKline; Sanofi-Aventis; Pfizer Pharmaceuticals; Epilepsy Foundation; AstraZeneca Pharmaceuticals; Bristol-Myers Squibb; Janssen Pharmaceuticals; Ortho-McNeil Janssen; Pfizer; Sepracor; Wyeth-Ayerst Pharmaceuticals; Medco Health; Noven Pharmaceuticals FX This work was supported by Grant K23 MH066978 from the National Institutes of Health (to H.J.). The study medications were provided by Berlex/Bayer and Sanofi-Aventis.; H.J. reports research support from the National Institute on Aging, the National Institute of Mental Health, Bayer HealthCare Pharmaceuticals, Eli Lilly and Co., Forest Laboratories, Inc., and GlaxoSmithKline. H.J. also reports consulting/advisory fees from Sanofi-Aventis and Pfizer Pharmaceuticals. L. F. P. reports research support from the National Institute on Aging, the National Institute of Mental Health, Bayer HealthCare Pharmaceuticals, Eli Lilly and Co., Forest Laboratories, Inc., and GlaxoSmithKline. A. K. reports no conflicts of interest of financial disclosures. A. C. V. reports research support from the National Institute of Mental Health, the Epilepsy Foundation, AstraZeneca Pharmaceuticals, Bristol-Myers Squibb, Janssen Pharmaceuticals, and Pfizer Pharmaceuticals in addition to advisory fees from Medco Health. A. H. reports research support from the National Institute on Aging, the National Institute of Mental Health, Bayer HealthCare Pharmaceuticals, Eli Lilly and Co., Forest Laboratories, Inc., and GlaxoSmithKline. R.N. reports no conflicts of interest or financial disclosures. B. S. reports no conflicts of interest or financial disclosures. E. P. reports no conflicts of interest or financial disclosures. D. P. W. reports employment as Chief Medical Officer of Philips Respironics. J.E.H. reports research support from the National Institutes of Health and consultant relations with GlaxoSmithKline and Vyteris. L. S. C. reports research support from AstraZeneca Pharmaceuticals, Bayer HealthCare Pharmaceuticals, Bristol-Myers Squibb, Forest Laboratories, Inc., GlaxoSmithKline, the National Institute on Aging, the National Institute of Mental Health, Ortho-McNeil Janssen, Pfizer, Sepracor, and Wyeth-Ayerst Pharmaceuticals. L. S. C. also reports advisory/consulting fees from Eli Lilly and Co., GlaxoSmithKline, and Noven Pharmaceuticals and honoraria from Eli Lilly and Co. and GlaxoSmithKline. NR 42 TC 26 Z9 27 U1 1 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 2011 VL 96 IS 7 BP E1044 EP E1054 DI 10.1210/jc.2010-2503 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 788OO UT WOS:000292454500001 PM 21525161 ER PT J AU Pollin, TI Jablonski, KA McAteer, JB Saxena, R Kathiresan, S Kahn, SE Goldberg, RB Altshuler, D Florez, JC AF Pollin, Toni I. Jablonski, Kathleen A. McAteer, Jarred B. Saxena, Richa Kathiresan, Sekar Kahn, Steven E. Goldberg, Ronald B. Altshuler, David Florez, Jose C. CA Diabet Prevention Program Res Grp TI Triglyceride Response to an Intensive Lifestyle Intervention Is Enhanced in Carriers of the GCKR Pro446Leu Polymorphism SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID DIABETES-PREVENTION-PROGRAM; FASTING PLASMA-GLUCOSE; C-REACTIVE-PROTEIN; RS780094 POLYMORPHISM; RISK; LOCI; POPULATION; METFORMIN; LIPOPROTEINS; HOMEOSTASIS AB Context: Glucokinase regulatory protein (GCKR) regulates the trafficking and enzymatic activity of hepatic glucokinase, the rate-limiting enzyme in glycogen synthesis and glycolysis. The intronic single-nucleotide polymorphism (SNP) rs780094 (intron 16) and the missense SNP rs1260326 (P446L) in the GCKR gene are strongly associated with increased circulating triglyceride and C-reactive protein levels and, paradoxically, reductions in diabetes incidence, fasting glucose levels, and insulin resistance. Objective, Setting, and Patients: We sought to replicate these associations and evaluate interactions with lifestyle and metformin interventions in the multiethnic Diabetes Prevention Program (DPP). Interventions and Main Outcome Measures: We genotyped the two GCKR SNP in 3346 DPP participants and evaluated association with progression to diabetes and both baseline levels and changes in triglycerides, homeostasis model assessment of insulin resistance (HOMA-IR), oral disposition index, and inflammatory markers along with their interactions with DPP interventions. Results: GCKR variation did not predict development of type 2 diabetes. At baseline, the 446L allele was associated with higher triglyceride and C-reactive protein levels (both P < 0.0001) and lower fasting glucose (P = 0.001) and HOMA-IR (P = 0.06). The lifestyle intervention was associated with a decrease in magnitude of the effect of the 446L allele on triglyceride levels (interaction P = 0.04). Metformin was more effective in reducing HOMA-IR in carriers of the P446 allele (interaction P = 0.05). Conclusions: Intensive lifestyle intervention appears to partially mitigate the effect of the 446L allele on higher triglycerides, whereas the P446 allele appears to enhance responsiveness to the HOMA-IR-lowering effect of metformin. (J Clin Endocrinol Metab 96: E1142-E1147, 2011) C1 [Pollin, Toni I.] George Washington Univ, Ctr Biostat, Diabet Prevent Program Coordinating Ctr, Rockville, MD 20852 USA. Univ Maryland, Sch Med, Program Genet & Genom Med, Baltimore, MD 21201 USA. [Pollin, Toni I.] Univ Maryland, Sch Med, Dept Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA. [McAteer, Jarred B.; Saxena, Richa; Altshuler, David; Florez, Jose C.] Massachusetts Gen Hosp, Diabet Res Ctr, Dept Med, Diabet Unit, Boston, MA 02114 USA. [Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Div Cardiol, Diabet Unit,Diabet Res Ctr, Boston, MA 02114 USA. [Kathiresan, Sekar; Altshuler, David; Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. [Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. [McAteer, Jarred B.; Saxena, Richa; Kathiresan, Sekar; Altshuler, David; Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. Univ Washington, Seattle, WA 98108 USA. [Kahn, Steven E.] Vet Affairs Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. Univ Miami, Leonard M Miller Sch Med, Diabet Res Inst, Miami, FL 33136 USA. [Goldberg, Ronald B.] Univ Miami, Div Endocrinol Diabet & Metab, Lipid Disorders Clin, Miami, FL 33136 USA. RP Pollin, TI (reprint author), George Washington Univ, Ctr Biostat, Diabet Prevent Program Coordinating Ctr, 6110 Execut Blvd,Suite 750, Rockville, MD 20852 USA. EM dppmail@bsc.gwu.edu RI Altshuler, David/A-4476-2009; OI Altshuler, David/0000-0002-7250-4107; Kahn, Steven/0000-0001-7307-9002 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health; NIDDK; Indian Health Service; Office of Research on Minority Health; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute on Aging; Office of Research on Women's Health; Centers for Disease Control and Prevention; American Diabetes Association; LifeScan Inc.; Health O Meter; Hoechst Marion Roussel, Inc.; Merck-Medco Managed Care, Inc.; Merck and Co.; Nike Sports Marketing; Slim Fast Foods Co.; Quaker Oats Co.; Doris Duke Charitable Foundation; Department of Veterans Affairs; [R01 DK072041] FX We gratefully acknowledge the commitment and dedication of the participants of the DPP. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health provided funding to the clinical centers and the Coordinating Center for the design and conduct of the study; and collection, management, analysis, and interpretation of the data. The Southwestern American Indian Centers were supported directly by the NIDDK and the Indian Health Service. The General Clinical Research Center Program, National Center for Research Resources, and the Department of Veterans Affairs supported data collection at many of the clinical centers. Funding for data collection and participant support was also provided by the Office of Research on Minority Health, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute on Aging, the Office of Research on Women's Health, the Centers for Disease Control and Prevention, and the American Diabetes Association. Bristol-Myers Squibb and Parke-Davis provided medication. This research was also supported, in part, by the intramural research program of the NIDDK. LifeScan Inc., Health O Meter, Hoechst Marion Roussel, Inc., Merck-Medco Managed Care, Inc., Merck and Co., Nike Sports Marketing, Slim Fast Foods Co., and Quaker Oats Co. donated materials, equipment, or medicines for concomitant conditions. McKesson BioServices Corp., Matthews Media Group, Inc., and the Henry M. Jackson Foundation provided support services under subcontract with the Coordinating Center. The opinions expressed are those of the investigators and do not necessarily reflect the views of the Indian Health Service or other funding agencies. A complete list of centers, investigators, and staff can be found in the Supplemental Appendix.; This work was supported in part by Grant R01 DK072041 (to D. A., J.C.F., K.A.J., and T. I. P.), and a Doris Duke Charitable Foundation Distinguished Scientist Clinical Award (to D. A.). S. E. K. is supported in part by the Department of Veterans Affairs. J.C.F. is supported by a Physician Scientist Development Award by the Massachusetts General Hospital and a Clinical Scientist Development Award from the Doris Duke Charitable Foundation. NR 25 TC 18 Z9 20 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 2011 VL 96 IS 7 BP E1142 EP E1147 DI 10.1210/jc.2010-2324 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 788OO UT WOS:000292454500014 PM 21525158 ER PT J AU Chew, BH Paterson, RF Ferlic, EA Humphreys, MR Gershman, B Eisner, BH AF Chew, Ben H. Paterson, Ryan F. Ferlic, Elisabeth A. Humphreys, Mitchell R. Gershman, Boris Eisner, Brian H. TI Controversial Case in Endourology SO JOURNAL OF ENDOUROLOGY LA English DT Article ID URINARY-TRACT-INFECTION; CALICEAL DIVERTICULA; CALYCEAL DIVERTICULUM; MANAGEMENT; CALCULI C1 [Chew, Ben H.; Paterson, Ryan F.] Univ British Columbia, Dept Urol Sci, Vancouver, BC V5Z 1M9, Canada. [Ferlic, Elisabeth A.; Humphreys, Mitchell R.] Mayo Clin, Grad Sch Med, Phoenix, AZ USA. [Gershman, Boris; Eisner, Brian H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA USA. RP Chew, BH (reprint author), Univ British Columbia, Dept Urol Sci, Vancouver, BC V5Z 1M9, Canada. NR 22 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0892-7790 J9 J ENDOUROL JI J. Endourol. PD JUL PY 2011 VL 25 IS 7 BP 1105 EP 1109 DI 10.1089/end.2011.1522 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 789UV UT WOS:000292542900004 PM 21711133 ER PT J AU Tamers, SL Beresford, SAA Thompson, B Zheng, YY Cheadle, AD AF Tamers, Sara L. Beresford, Shirley A. A. Thompson, Beti Zheng, Yingye Cheadle, Allen D. TI Exploring the Role of Co-worker Social Support on Health Care Utilization and Sickness Absence SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID PSYCHOSOCIAL WORK FACTORS; GAZEL COHORT; WHITEHALL-II; QUALITY; DIETARY; DETERMINANTS; ILLNESSES; BEHAVIOR; COSTS; MODEL AB Objectives: To explore the association of baseline co-worker social support with follow-up measures of health care use and sickness absence. Methods: Data were obtained on 1240 employees from 33 worksites, through Promoting Activity and Changes in Eating, a group randomized weight maintenance trial. Co-worker social support, health care utilization, and absenteeism were assessed via a self-reported questionnaire. Generalized Estimating Equations were employed using STATA version 10. Results: Higher baseline co-worker social support was significantly associated with a greater number of doctors' visits (P = 0.015). Co-worker social support was unrelated to number of hospitalizations, emergency department visits, or absenteeism. Conclusions: The relationship between co-worker social support and health care utilization and absenteeism is complex and uncertain. Future studies should measure more specific outcomes, incorporate important mediating variables, and distill how social networks influence these outcomes. C1 [Tamers, Sara L.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Tamers, Sara L.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Tamers, Sara L.; Thompson, Beti; Cheadle, Allen D.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Tamers, Sara L.; Beresford, Shirley A. A.; Thompson, Beti; Zheng, Yingye] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA. [Beresford, Shirley A. A.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Zheng, Yingye] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Cheadle, Allen D.] Univ Washington, Hlth Promot Res Ctr, Seattle, WA 98195 USA. RP Tamers, SL (reprint author), Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, 677 Huntington Ave, Boston, MA 02115 USA. EM sara_tamers@dfci.harvard.edu FU University of Washington's Department of Health Services; NCI [R25 CA092408]; National Heart, Lung, and Blood Institute [R01 HL079491]; NIH/NCI [R25 CA057713] FX The author wishes to acknowledge the training and support of the University of Washington's Department of Health Services, the NCI's Biobehavioral Cancer Prevention and Control Fellowship Grant (R25 CA092408; PI: Donald Patrick, PhD), the National Heart, Lung, and Blood Institute Grant (R01 HL079491; PI: Shirley Beresford, PhD), and the NIH/NCI Harvard Education Program in Cancer Prevention and Control (R25 CA057713; PI: Glorian Sorensen, PhD). NR 46 TC 5 Z9 5 U1 0 U2 5 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 JUL PY 2011 VL 53 IS 7 BP 751 EP 757 DI 10.1097/JOM.0b013e318223d42f PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 789TQ UT WOS:000292539600010 PM 21685798 ER PT J AU Guralnick, WC Kaban, LB AF Guralnick, Walter C. Kaban, Leonard B. TI Keeping Ether "En-Vogue": The Role of Nathan Cooley Keep in the History of Ether Anesthesia SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article AB In this report, we explore the little known role of Dr Nathan Cooley Keep in the dissemination of ether anesthesia in Boston. Keep was a prominent Boston dentist who, for a short time, taught and employed both William Morton and Horace Wells. He used ether anesthesia for a variety of dental and other surgical procedures requiring pain control. Keep administered ether to anesthetize Henry Wadsworth Longfellow's wife during the delivery of their daughter. This was the first use of ether for obstetric anesthesia. Dr Keep was also the first Dean of the Harvard Dental School and convinced the Massachusetts General Hospital to appoint a dentist to the staff of the hospital for the first time. (C) 2011 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 69:1892-1897, 2011 C1 [Guralnick, Walter C.; Kaban, Leonard B.] Harvard Univ, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Sch Dent Med, Boston, MA 02114 USA. RP Kaban, LB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Sch Dent Med, Warren Bldg 1201,55 Fruit St, Boston, MA 02114 USA. EM LKaban@Partners.org NR 23 TC 2 Z9 2 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 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD JUL PY 2011 VL 69 IS 7 BP 1892 EP 1897 DI 10.1016/j.joms.2011.02.121 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 789EB UT WOS:000292495600021 PM 21549472 ER PT J AU Giro, G Coelho, PG Sales-Pessoa, R Pereira, RMR Kawai, T Orrico, SRP AF Giro, Gabriela Coelho, Paulo G. Sales-Pessoa, Roberto Rodrigues Pereira, Rosa Maria Kawai, Toshihisa Perez Orrico, Silvana Regina TI Influence of Estrogen Deficiency on Bone Around Osseointegrated Dental Implants: An Experimental Study in the Rat Jaw Model SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID HYDROXYAPATITE-COATED IMPLANTS; OVARIECTOMIZED RATS; TITANIUM IMPLANTS; MINERAL DENSITY; FEMALE RATS; OSTEOPOROSIS; ALENDRONATE; 17-BETA-ESTRADIOL AB Purpose: The aim of this study was to evaluate the influence of estrogen deficiency on bone around osseointegrated dental implants in a rat jaw model. Materials and Methods: This study used 16 female rats that had the first molars bilaterally extracted and were allowed to heal for 30 days before implant placement. Sixty days after implant placement, the animals were randomly subjected to sham surgery or ovariectomy (OVX). The animals were euthanized 90 days after OVX. Bone-to-implant contact, bone area fraction occupancy between implant threads, mineral density, turnover markers, and cells positive for tartrate-resistant acid phosphatase were assessed for the 2 groups. Results: The results showed that OVX group presented a decrease of systemic bone density, alterations in bone turnover markers, and an increase of cells positive for tartrate-resistant acid phosphatase compared with the sham-surgery group. However, no difference relative to bone-to-implant contact and bone area fraction occupancy was observed between groups. Conclusions: The findings of this study demonstrate that estrogen deficiency may not be considered a risk factor for osseointegrated implant failure in jaw bone. (C) 2011 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 69:1911-1918, 2011 C1 [Giro, Gabriela; Perez Orrico, Silvana Regina] UNESP Univ Estadual Paulista, Dept Oral Diag & Surg, Araraquara Dent Sch, Sao Paulo, Brazil. [Coelho, Paulo G.] NYU, Coll Dent, Dept Periodontol & Implant Dent, New York, NY USA. [Sales-Pessoa, Roberto] Inst Pesquisa & Ensino Saude, Uberlandia, MG, Brazil. [Rodrigues Pereira, Rosa Maria] Univ Sao Paulo, Fac Med, Bone Metab Lab, Div Rheumatol, Sao Paulo, Brazil. [Kawai, Toshihisa] Forsyth Inst, Dept Immunol, Boston, MA USA. RP Giro, G (reprint author), Rua Humaita 1680, BR-14801903 Sao Paulo, Brazil. EM gabi.giro@gmail.com RI Giro, Gabriela/D-2746-2009; Pereira, Rosa /C-5192-2012 OI Giro, Gabriela/0000-0002-7590-8158; FU Sao Paulo State Research Support Foundation (FAPESP) [2005/03737-8]; Coordination for Improvement of Higher Education Students (CAPES); National Institute of Dental and Craniofacial Research [DE-018499, DE-019917] FX Dr Giro was supported by the Sao Paulo State Research Support Foundation (FAPESP, grant 2005/03737-8) and the Coordination for Improvement of Higher Education Students (CAPES, PDEEE program). This study was also supported by National Institutes of Health grants DE-018499 and DE-019917 from the National Institute of Dental and Craniofacial Research. The authors gratefully acknowledge SIN-Sistema de Implante for supplying the implants used in this study. NR 37 TC 7 Z9 7 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 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD JUL PY 2011 VL 69 IS 7 BP 1911 EP 1918 DI 10.1016/j.joms.2011.01.028 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 789EB UT WOS:000292495600024 PM 21530046 ER PT J AU Linas, BP Wang, B Smurzynski, M Losina, E Bosch, RJ Schackman, BR Rong, J Sax, PE Walensky, RP Schouten, J Freedberg, KA AF Linas, B. P. Wang, B. Smurzynski, M. Losina, E. Bosch, R. J. Schackman, B. R. Rong, J. Sax, P. E. Walensky, R. P. Schouten, J. Freedberg, K. A. TI The impact of HIV/HCV co-infection on health care utilization and disability: results of the ACTG Longitudinal Linked Randomized Trials (ALLRT) Cohort SO JOURNAL OF VIRAL HEPATITIS LA English DT Article DE health services research; hepatitis C/economics; HIV infections/economics; outcomes research; resource allocation ID HEPATITIS-C VIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; HIV-INFECTED PATIENTS; ALPHA-2A PLUS RIBAVIRIN; UNITED-STATES; MORTALITY; DISEASE; PREVALENCE; METAANALYSIS AB HIV/hepatitis C virus (HCV) co-infection places a growing burden on the HIV/AIDS care delivery system. Evidence-based estimates of health services utilization among HIV/HCV co-infected patients can inform efficient planning. We analyzed data from the ACTG Longitudinal Linked Randomized Trials (ALLRT) cohort to estimate resource utilization and disability among HIV/HCV co-infected patients and compare them to rates seen in HIV mono-infected patients. The analysis included HIV-infected subjects enrolled in the ALLRT cohort between 2000 and 2007 who had at least one CD4 count measured and completed at least one resource utilization data collection form (N = 3143). Primary outcomes included the relative risk of hospital nights, emergency department (ED) visits, and disability days for HIV/HCV co-infected vs HIV mono-infected subjects. When controlling for age, sex, race, history of AIDS-defining events, current CD4 count and current HIV RNA, the relative risk of hospitalization, ED visits, and disability days for subjects with HIV/HCV co-infection compared to those with HIV mono-infection were 1.8 (95% CI: 1.3-2.5), 1.7 (95% CI: 1.4-2.1), and 1.6 (95% CI: 1.3-1.9) respectively. Programs serving HIV/HCV co-infected patients can expect approximately 70% higher rates of utilization than expected from a similar cohort of HIV mono-infected patients. C1 [Linas, B. P.; Walensky, R. P.; Freedberg, K. A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Wang, B.; Losina, E.; Sax, P. E.; Walensky, R. P.; Freedberg, K. A.] Harvard Univ, AIDS Res CFAR, Boston, MA 02115 USA. [Smurzynski, M.; Bosch, R. J.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Losina, E.] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Losina, E.; Rong, J.; Freedberg, K. A.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Losina, E.; Rong, J.; Freedberg, K. A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Schackman, B. R.] Weill Cornell Med Coll, Dept Publ Hlth, New York, NY USA. [Sax, P. E.; Walensky, R. P.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Schouten, J.] Univ Washington, Dept Surg, Seattle, WA 98195 USA. RP Linas, BP (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM blinas@partners.org OI Linas, Benjamin/0000-0001-9574-7075; Walensky, Rochelle P./0000-0002-8795-379X FU National Institute of Allergy and Infectious Diseases [K01AI073193, K24AI062476, R37AI42006, P30AI060354, U01AI68636, U01AI038858, U01AI068634, U01AI038855]; National Institute on Drug Abuse [K01DA017179] FX This work was presented in part at the 16th Conference on Retroviruses and Opportunistic Infections - Montreal, January 10, 2009. Supported by the National Institute of Allergy and Infectious Diseases (K01AI073193, K24AI062476, R37AI42006, P30AI060354, U01AI68636, U01AI038858, U01AI068634, U01AI038855), and the National Institute on Drug Abuse K01DA017179). NR 31 TC 18 Z9 19 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1352-0504 J9 J VIRAL HEPATITIS JI J. Viral Hepatitis PD JUL PY 2011 VL 18 IS 7 BP 506 EP 512 DI 10.1111/j.1365-2893.2010.01325.x PG 7 WC Gastroenterology & Hepatology; Infectious Diseases; Virology SC Gastroenterology & Hepatology; Infectious Diseases; Virology GA 785XE UT WOS:000292265400039 PM 20546501 ER PT J AU Corey, KE Mendez-Navarro, J Barlow, LL Patwardhan, V Zheng, H Kim, AY Lauer, GM Chung, RT AF Corey, K. E. Mendez-Navarro, J. Barlow, L. L. Patwardhan, V. Zheng, H. Kim, A. Y. Lauer, G. M. Chung, R. T. TI Acute hepatitis C infection lowers serum lipid levels SO JOURNAL OF VIRAL HEPATITIS LA English DT Article DE cholesterol; hepatitis C; low-density lipoprotein; non-HDL cholesterol ID CORONARY-HEART-DISEASE; LOW-DENSITY; CHOLESTEROL LEVELS; VIRUS-INFECTION; PROTEIN; LIPOPROTEINS; TRIGLYCERIDE; RISK AB Chronic hepatitis C infection is associated with hypolipidaemia that resolves with viral clearance. Lipid levels in a subgroup of patients rebound to levels that may increase the risk of coronary heart disease. The impact of acute hepatitis C infection and its clearance on lipid levels is unknown. We undertook a retrospective evaluation of subjects with acute hepatitis C infection evaluating lipid levels before, during and following acute infection. Thirty-eight subjects with acute hepatitis C infection had lipid levels available. Twelve patients had pre-infection and intra-infection lipid levels available. Cholesterol (197.8-152.4 mg/dL, P = 0.025), low-density lipoprotein (LDL) (116.1-76.3 mg/dL, P = 0.001) and non-high-density lipoprotein (non-HDL) cholesterol (164.0-122.7 mg/dL, P = 0.007) decreased dramatically during acute hepatitis C virus infection. Nineteen patients who achieved viral clearance had lipid levels available during infection and following resolution of infection. In these patients, cholesterol (145.0-176.0 mg/dL, P = 0.01), LDL (87.0-110.1 P = 0.0046) and non-HDL cholesterol (108.6-133.6 mg/dL, P = 0.008) increased significantly. No change was seen in patients who developed chronic infection. Four patients had lipid levels before, during and following resolution of infections and had increased postinfection LDL, cholesterol and non-HDL cholesterol from pre-infection levels, indicating acute infection may be associated with an increase in postinfection lipid levels and may confer an increased risk of coronary heart disease. Acute hepatitis C infection results in hypolipidaemia with decreased LDL, cholesterol and non-HDL cholesterol levels that increase following infection resolution. Levels may increase above pre-infection baseline lipid levels and should be monitored. C1 [Corey, K. E.; Mendez-Navarro, J.; Barlow, L. L.; Lauer, G. M.; Chung, R. T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Mendez-Navarro, J.] Hosp Especialidades CMN Siglo XXI, Natl Med Ctr, IMSS, Mexico City, DF, Mexico. [Patwardhan, V.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Zheng, H.] Massachusetts Gen Hosp, MGH Biostat Ctr, Boston, MA 02114 USA. [Kim, A. Y.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Warren 1007,55 Fruit St, Boston, MA 02114 USA. EM rtchung@partners.org FU NIDDK [1F32DK083252-01] FX The authors have no personal interests to disclose. This study was funded in part by a grant from the NIDDK 1F32DK083252-01 (Corey). NR 19 TC 9 Z9 9 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1352-0504 J9 J VIRAL HEPATITIS JI J. Viral Hepatitis PD JUL PY 2011 VL 18 IS 7 BP E366 EP E371 DI 10.1111/j.1365-2893.2011.01434.x PG 6 WC Gastroenterology & Hepatology; Infectious Diseases; Virology SC Gastroenterology & Hepatology; Infectious Diseases; Virology GA 785XE UT WOS:000292265400028 PM 21692949 ER PT J AU Bleier, BS Curry, WT Wang, EW Schlosser, RJ AF Bleier, Benjamin S. Curry, William T. Wang, Eric W. Schlosser, Rodney J. TI The Bipedicled Anterior Septal Flap: A radioanatomic and cadaveric study SO LARYNGOSCOPE LA English DT Article DE Skull base reconstruction; vascularized mucosal flap; cerebrospinal fluid leak; bipedicled anterior septal flap ID SKULL BASE RECONSTRUCTION; NASOSEPTAL FLAP; TURBINATE FLAP AB Objectives/Hypothesis: Pedicled mucosal flaps are the preferred method of endoscopic skull base reconstruction. Vascularized coverage of the anterior and posterior frontal tables remains a challenge given the lack of large caliber vessels supplying the anterior septum. The objective of this study was to define a novel bipedicled anterior septal (BAS) flap that is hypothesized to be capable of providing reproducible coverage of these difficult areas. Study Design: Radioanatomic and cadaveric study. Methods: The flap outline was superimposed over nine midline sagittal computed tomography images. The pedicles are comprised of the septal branch of the superior labial artery and the nasopalatine artery. The flap length subtended the distance from the incisive canal to the sphenoid face at the level of the choanal arch. Radiometric analysis of the flap length to base ratio and anterior/posterior frontal table coverage were calculated. These projected values were confirmed in four cadaveric dissection specimens. Results: The mean flap length was 39.64 +/- 4.26 mm with a mean length:base ratio of 3.29 +/- 0.70 and a total surface area of 916.46 +/- 262.66 mm(2). The flap was estimated to provide coverage of 100.31 +/- 21.34% of the frontal beak and 50.74 +/- 32.54% of the posterior frontal table. In all cadaveric specimens the flap extended beyond the superior aspect of the frontal beak and at least 50% of the posterior table. Conclusions: The BAS flap represents a novel septal mucosal flap based on two well-defined arterial inputs. This flap is capable of providing reliable vascularized coverage of the posterior frontal table and the frontal beak following frontal drillout. C1 [Bleier, Benjamin S.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. [Curry, William T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. [Wang, Eric W.; Schlosser, Rodney J.] Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA. RP Bleier, BS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA. EM benjamin_bleier@meei.harvard.edu OI Wang, Eric/0000-0002-1180-5854 NR 11 TC 10 Z9 10 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 JUL PY 2011 VL 121 IS 7 BP 1367 EP 1371 DI 10.1002/lary.21824 PG 5 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 788DJ UT WOS:000292425300003 PM 21671235 ER PT J AU Lin, HW Bhattacharyya, N AF Lin, Harrison W. Bhattacharyya, Neil TI Otologic Diagnoses in the Elderly: Current Utilization and Predicted Workload Increase SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT 114th Annual Meeting of the Triological-Society CY APR 29, 2011 CL COSM, Chicago, IL SP Triol Soc HO COSM DE Otology; elderly; workload; epidemiology ID NUTRITION-EXAMINATION-SURVEY; COCHLEAR IMPLANTATION; HEARING-LOSS; NATIONAL-HEALTH; US ADULTS; PERFORMANCE; PREVALENCE; SURGERY AB Objectives/Hypothesis: To establish the current outpatient workload for otologic conditions in the elderly and to estimate its potential increase based on an anticipated aging population. Study Design: Cross-sectional analysis of a national database. Methods: All outpatient clinic visits for patients aged >= 65 years receiving one of six common otologic diagnoses from 2005 to 2007 in the United States were determined from the National Ambulatory Medical Care Survey. The distribution of the visits for these diagnoses across 15 specialties was assessed. The number of visits was projected to the 2020 population based on changes in population demographics predicted by the US Census Bureau. Results: An estimated 4.48 +/- 0.49 million clinic visits with an otologic issue as a coded diagnosis were conducted in 2005 to 2007 in patients aged >= 65 years. These consisted of 230,000 visits for benign positional paroxysmal vertigo, 263,000 visits for vestibular neuritis, 292,000 visits for Meniere's disease, 1.09 million visits for tinnitus, and 2.85 million visits for sensorineural hearing loss. Otolaryngology, internal medicine, family practice, and neurology managed the most visits, seeing 57.0%, 21.0%, 14.3%, and 2.2% of the cases, respectively. With expected changes in population demographics by 2020, annual clinic visits for an otologic diagnosis will increase from 1.49 +/- 0.78 million to 2.14 million visits in the elderly, annualized, including 1.218 million visits to otolaryngology. Conclusions: These data quantify the current outpatient otology workload and predict a substantial increase for many specialties, including otolaryngology. Efforts to prepare for this increase including manpower planning and education appear imperative. C1 [Lin, Harrison W.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Lin, Harrison W.; Bhattacharyya, Neil] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Bhattacharyya, Neil] Brigham & Womens Hosp, Div Otolaryngol Head & Neck Surg, Boston, MA 02115 USA. RP Bhattacharyya, N (reprint author), 45 Francis St, Boston, MA 02115 USA. EM neiloy@massmed.org NR 20 TC 16 Z9 16 U1 1 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD JUL PY 2011 VL 121 IS 7 BP 1504 EP 1507 DI 10.1002/lary.21827 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 788DJ UT WOS:000292425300029 PM 21557249 ER PT J AU Nam, SI Linthicum, FH Merchant, SN AF Nam, Sung-Il Linthicum, Fred H., Jr. Merchant, Saumil N. TI Temporal Bone Histopathology in Neurofibromatosis Type 2 SO LARYNGOSCOPE LA English DT Article DE Neurofibromatosis type 2; bilateral acoustic neuroma; temporal bone histopathology; otopathology ID VESTIBULAR SCHWANNOMA; ACOUSTIC SCHWANNOMAS; INNER-EAR; ERLOTINIB; NEUROMA AB Objectives/Hypothesis: To describe the histopathologic findings in the temporal bone in patients with neurofibromatosis type 2 (NF2). The literature contains limited data on otopathology of NF2. Study Design: Basic science study. Methods: Twenty-six temporal bones from 16 patients with NF2 were examined by light microscopy. The diagnosis of NF2 was made on the basis of bilateral cochleovestibular schwannomas. Clinical information was obtained from review of the medical records. Results: The tumors were multicentric in origin in 19 of 26 (73%) ears. Typically, tumors were seen arising within the internal auditory canal and from various locations within the labyrinth. The majority of schwannomas showed high cellularity with involvement of the labyrinth. Most cases showed significant degrees of degeneration of sensory and neural elements within the cochlea. Fusion tumors were sometimes seen as a result of a schwannoma merging with an adjacent meningioma. Fifteen of 26 (58%) ears showed facial nerve involvement by schwannoma. Conclusions: Cochleovestibular schwannomas in NF2 are aggressive neoplasms; they are often multicentric and demonstrate a propensity to involve the labyrinth. There is often associated secondary degeneration within the cochlea. These features make total removal of these tumors and their removal with preservation of hearing more difficult than with sporadic unilateral cochleovestibular schwannoma. C1 [Nam, Sung-Il; Merchant, Saumil N.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Nam, Sung-Il; Merchant, Saumil N.] Harvard Univ, Sch Med, Boston, MA USA. [Linthicum, Fred H., Jr.] House Ear Res Inst, Los Angeles, CA USA. RP Merchant, SN (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM Saumil_merchant@meei.harvard.edu FU NIH [U24 DC008559, U24DC008625] FX This work was supported by NIH grants U24 DC008559 and U24DC008625. The authors have no other funding, financial relationships, or conflicts of interest to disclose. NR 16 TC 10 Z9 10 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD JUL PY 2011 VL 121 IS 7 BP 1548 EP 1554 DI 10.1002/lary.21822 PG 7 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 788DJ UT WOS:000292425300036 PM 21671232 ER PT J AU Chan, NPY Shek, SYN Yu, CS Ho, SGY Yeung, CK Chan, HHL AF Chan, Nicola P. Y. Shek, Samantha Y. N. Yu, Carol S. Ho, Stephanie G. Y. Yeung, Chi K. Chan, Henry H. L. TI Safety Study of Transcutaneous Focused Ultrasound for Non-Invasive Skin Tightening in Asians SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE Asian; non-ablative; safety; tightening; ultrasound ID FACIAL SKIN; RADIOFREQUENCY TREATMENT; BIPOLAR RADIOFREQUENCY; INFRARED DEVICE; MULTIPLE-PASS; FACE LIFT; REJUVENATION; TECHNOLOGY; LAXITY; ALGORITHM AB Background and Objectives: Transcutaneous intense focused ultrasound has emerged as a novel technology for non-invasive skin tightening. The objective of this study was to evaluate the safety profile of a transcutaneous focused ultrasound device for the treatment of facial skin laxity in Asians. Materials and Methods: The patients received one to three full-face treatments with the transcutaneous focused ultrasound device. Three transducers (7.0 MHz, 3.0 mm focal depth; 7.0 MHz, 4.5 mm focal depth; 4.0 MHz, 4.5 mm focal depth) were used to deliver a single pass of microthermal coagulation zones without any topical anesthetics. Standardized photos were taken at baseline and at each follow-up with the Canfield Visia CR system (R) and were assessed by two independent physicians. Adverse effects were assessed up to 6 months post treatment. Subjective assessments in terms of pain and tolerability were also evaluated with patient questionnaires. Results: Forty nine Chinese patients (skin types III-IV, mean age 53.3) completed a total of 68 treatment sessions. Transient erythema and edema were seen in the majority of patients. Focal bruising was present in up to 25% of treatment sessions. Two cases of post-inflammatory hyperpigmentation were seen on the forehead at 1-month post-treatment. One patient experienced focal twitching over the lower eyelid at 1-month follow-up, which was clinically consistent with hemifacial spasm and was unrelated to the ultrasound device. The degree of pain during treatment was recorded as severe in 54.4% of treatment sessions. Conclusions: Transcutaneous intense focused ultrasound appeared to be safe for non-invasive facial skin tightening in Asians. Adverse events were mild and transient. Pain control during treatment should be optimized. No serious permanent or delayed side effects were noted up to 6 months post treatment. Lasers Surg. Med. 43:366-375, 2011. (C) 2011 Wiley-Liss, Inc. C1 [Chan, Nicola P. Y.; Shek, Samantha Y. N.; Ho, Stephanie G. Y.; Yeung, Chi K.; Chan, Henry H. L.] Univ Hong Kong, Div Dermatol, Dept Med, Hong Kong, Hong Kong, Peoples R China. [Yu, Carol S.] Univ Hong Kong, Inst Eye, Hong Kong, Hong Kong, Peoples R China. [Chan, Henry H. L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. RP Chan, HHL (reprint author), Dermatol & Laser Ctr, 13th Floor,Club Lusitano,16 Ice House St, Hong Kong, Peoples R China. EM hhlchan@hku.hk RI Yeung, Chi Keung/L-4795-2013; Chan, Henry Hin Lee/L-2267-2013 NR 34 TC 36 Z9 36 U1 1 U2 9 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 JUL PY 2011 VL 43 IS 5 BP 366 EP 375 DI 10.1002/lsm.21070 PG 10 WC Dermatology; Surgery SC Dermatology; Surgery GA 788UN UT WOS:000292470000002 PM 21674541 ER PT J AU Kosaka, S Miyoshi, N Akilov, OE Hasan, T Kawana, S AF Kosaka, Sachiko Miyoshi, Norio Akilov, Oleg E. Hasan, Tayyaba Kawana, Seiji TI Targeting of Sebaceous Glands by delta-Aminolevulinic Acid-Based Photodynamic Therapy: An In Vivo Study SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE acne; ALA-PDT; rhino mouse ID TOPICAL 5-AMINOLEVULINIC ACID; INTENSE PULSED-LIGHT; RHINO MOUSE MODEL; ACNE-VULGARIS; BLUE-LIGHT; EFFICACY; PDT AB Background and Objectives: Wide application of ALA-PDT for acne is limited due to relative strong side effects, such as pain and erythema. The objective of this study was to establish a protocol for ALA-PDT that would provide specific destruction of sebaceous glands at the lowest concentrations and shortest contact times of ALA. Materials and Methods: The rhino (hr(rh)hr(rh)) murine model, an experimental acne model, was used in this study. A freshly prepared hydrophilic ALA hydrochloride ointment (2.5%, 5%, and 20%) was applied to the backs of 16-week-old male rhino mice. The fluorescence intensity (FI) of ALA-induced protoporphyrin IX (ALA-PpIX) on the skin was measured by spectrofluorometry. Skin samples were taken at 1, 2, and 4 hours after ALA application to determine the tissue distribution of ALA-PpIX by fluorescence microscopy. Light irradiation was also performed with a broadband light source (600-1100 nm, 15 J/cm(2), 60 mW/cm(2)) with subsequent histological examination 1 day after treatment. Results: Prominent increases of ALA-PpIX were observed 1 hour after application of 5% and 20% ALA, while no increase was observed with 2.5% ALA until 2 hours. A direct correlation was found between ALA concentration and ALA-PpIX FI. While no fluorescence was detected 1 hour after application of 2.5% or 5% ALA, 20% ALA produced a strong fluorescence in the epidermis, utricle walls, and sebaceous glands. Histological evaluation showed no damage to skin treated with 2.5% ALA-PDT incubated for 1 hour. Damage was still focused within the sebaceous glands with longer incubation times. Increased ALA concentrations resulted in more prominent damage to the epidermis and sebaceous glands, with deeper damage to the dermis when longer incubation times were used. Conclusion: Focused damage of sebaceous glands can be achieved with ALA-PDT when low concentrations of ALA (2.5-5.0%) and short incubation times (to 2 hours) were used. Lasers Surg. Med. 43:376-381, 2011. (C) 2011 Wiley-Liss, Inc. C1 [Kosaka, Sachiko] Nippon Med Sch, Dept Dermatol, Bunkyo Ku, Tokyo 1138603, Japan. [Miyoshi, Norio] Univ Fukui, Div Tumor Pathol, Dept Pathol, Fac Med, Fukui 9101193, Japan. [Akilov, Oleg E.; Hasan, Tayyaba] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed,Dept Dermatol, Boston, MA 02114 USA. RP Kosaka, S (reprint author), Nippon Med Sch, Dept Dermatol, Bunkyo Ku, 1-1-5 Sendagi, Tokyo 1138603, Japan. EM p-chan@nms.ac.jp NR 21 TC 14 Z9 18 U1 2 U2 7 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 JUL PY 2011 VL 43 IS 5 BP 376 EP 381 DI 10.1002/lsm.21062 PG 6 WC Dermatology; Surgery SC Dermatology; Surgery GA 788UN UT WOS:000292470000003 PM 21674542 ER PT J AU Gu, C Ni, T Verter, EE Redmond, RW Kochevar, IE Yao, M AF Gu, Chuan Ni, Tao Verter, Erol E. Redmond, Robert W. Kochevar, Irene E. Yao, Min TI Photochemical Tissue Bonding: A Potential Strategy for Treating Limbal Stem Cell Deficiency SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE cornea; corneal epithelium; collagen; inflammation; laser; neovascularization; suture; wound repair ID AMNIOTIC MEMBRANE; EPITHELIAL-CELLS; TRANSPLANTATION; SUSPENSION; CULTURE; CORNEA; BURN AB Background and Objective: To determine the feasibility of attaching human amniotic membrane (HAM), pre-cultured with limbal stem cells (LSCs), to cornea using a novel, light-activated tissue bonding method. Materials and Methods: LSCs were isolated from rabbit eyes, and then cultured on de-epithelialized HAM to create grafts (HAM/LSC). These were then transplanted onto rabbit eyes with surgically created limbal stem cell deficiency (LSCD). The grafts were secured either by sutures or by a light-activated method called photochemical tissue bonding (PTB). Outcomes included corneal opacity, inflammation, neovascularization, and collagen alignment. Results: The isolated and cultured cells were verified to be LSCs based on their K19+/intergrin beta 1+/P63+/K3 profile. Securing the HAM/LSC graft with PTB provided better outcomes. At 28 days post-surgery, the corneal opacity scores were significantly lower after securing the graft with PTB compared with suture attachment (0.8 +/- 0.5 vs. 1.8 +/- 0.5, P < 0.01). Similarly, neovascularization scores were lower after PTB (0.8 +/- 0.5 vs. 1.5 +/- 0.6, P < 0.01). Quantification of MPO and CD31 levels from immunofluorecent staining indicated that PTB stimulated less neutrophil infiltration (5.3 +/- 2.2 vs. 13.3 +/- 3.1, P < 0.01) and less new blood vessels formation (2.0 +/- 0.8 vs. 6.3 +/- 1.3, P < 0.01) at the wound site. The collagen alignment in PTB-treated corneas, as shown by immunofluorescence and second harmonic generation image, was better organized in the PTB-treated group than in the suture group. Conclusion: Bonding LSC grafts with PTB produced improved outcomes compared to suture attachment. This light-activated method is a promising modality for treating patients with LSCD. Lasers Surg. Med. 43: 433-442, 2011. (C) 2011 Wiley-Liss, Inc. C1 [Gu, Chuan; Ni, Tao; Verter, Erol E.; Redmond, Robert W.; Kochevar, Irene E.; Yao, Min] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Gu, Chuan; Ni, Tao; Yao, Min] Shanghai Jiao Tong Univ, Sch Med, Dept Burns & Plast Surg, Peoples Hosp 3, Shanghai 201900, Peoples R China. [Gu, Chuan; Ni, Tao; Yao, Min] Shanghai Jiao Tong Univ, Sch Med, Inst Traumat Med, Shanghai 201900, Peoples R China. RP Yao, M (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Thier 224,50 Fruit St, Boston, MA 02114 USA. EM myao2@partners.org FU American Society for Laser Medicine and Surgery; Shanghai PuJiang Project [10PJ1407000] FX We sincerely appreciate Dr. Jenny Zhao and Chun-Qiang Li for technical support. This study was partially supported by a grant from the American Society for Laser Medicine and Surgery to Min Yao (2009) and Shanghai PuJiang Project (10PJ1407000). NR 19 TC 6 Z9 8 U1 2 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 JUL PY 2011 VL 43 IS 5 BP 433 EP 442 DI 10.1002/lsm.21066 PG 10 WC Dermatology; Surgery SC Dermatology; Surgery GA 788UN UT WOS:000292470000009 PM 21674548 ER PT J AU Barnes, SRS Haacke, EM Ayaz, M Boikov, AS Kirsch, W Kido, D AF Barnes, Samuel R. S. Haacke, E. Mark Ayaz, Muhammad Boikov, Alexander S. Kirsch, Wolff Kido, Dan TI Semiautomated detection of cerebral microbleeds in magnetic resonance images SO MAGNETIC RESONANCE IMAGING LA English DT Article DE Susceptibility weighted imaging; Segmentation; Support vector machine; Cerebral microbleed ID INTRACEREBRAL HEMORRHAGE; MR-IMAGES; SUSCEPTIBILITY; SEGMENTATION; LESIONS; STROKE AB Cerebral microbleeds (CMBs) are increasingly being recognized as an important biomarker for neurovascular diseases. So far, all attempts to count and quantify them have relied on manual methods that are time-consuming and can be inconsistent. A technique is presented that semiautomatically identifies CMBs in susceptibility weighted images (SWI). This will both reduce the processing time and increase the consistency over manual methods. This technique relies on a statistical thresholding algorithm to identify hypointensities within the image. A support vector machine (SVM) supervised learning classifier is then used to separate true CMB from other marked hypointensities. The classifier relies on identifying features such as shape and signal intensity to identify true CMBs. The results from the automated section are then subject to manual review to remove false-positives. This technique is able to achieve a sensitivity of 81.7% compared with the gold standard of manual review and consensus by multiple reviewers. In subjects with many CMBs, this presents a faster alternative to current manual techniques at the cost of some lost sensitivity. (C) 2011 Elsevier Inc. All rights reserved. C1 [Barnes, Samuel R. S.; Haacke, E. Mark; Kido, Dan] Loma Linda Univ, Med Ctr, Dept Radiol, Loma Linda, CA 92350 USA. [Barnes, Samuel R. S.; Haacke, E. Mark] Wayne State Univ, Dept Biomed Engn, Detroit, MI 48201 USA. [Barnes, Samuel R. S.; Haacke, E. Mark; Boikov, Alexander S.] Magnet Resonance Imaging Inst Biomed Res, Detroit, MI 48202 USA. [Haacke, E. Mark] Wayne State Univ, Dept Radiol, Detroit, MI 48201 USA. [Ayaz, Muhammad] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hemorrhag Stroke Res Ctr,Dept Neurol, Boston, MA 02114 USA. [Boikov, Alexander S.] Wayne State Univ, Sch Med, Detroit, MI 48201 USA. [Kirsch, Wolff] Loma Linda Univ, Neurosurg Ctr Res Training & Educ, Loma Linda, CA 92350 USA. RP Barnes, SRS (reprint author), Loma Linda Univ, Med Ctr, Dept Radiol, Room B623,11234 Anderson St, Loma Linda, CA 92350 USA. EM sbarnes@llu.edu RI Barnes, Samuel/B-7673-2013 OI Barnes, Samuel/0000-0002-1065-8442 FU National Institutes of Health (NIH) [2R01 HL062983-04A2] FX This work was supported by the National Institutes of Health (NIH) (contract grant number 2R01 HL062983-04A2). They had no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. NR 24 TC 25 Z9 28 U1 1 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0730-725X J9 MAGN RESON IMAGING JI Magn. Reson. Imaging PD JUL PY 2011 VL 29 IS 6 BP 844 EP 852 DI 10.1016/j.mri.2011.02.028 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 787EG UT WOS:000292358800011 PM 21571479 ER PT J AU Loftis, JM AF Loftis, J. M. TI Sertoli cell therapy: A novel possible treatment strategy for treatment-resistant major depressive disorder SO MEDICAL HYPOTHESES LA English DT Article ID TUMOR-NECROSIS-FACTOR; NITRIC-OXIDE PRODUCTION; PITUITARY-ADRENAL AXIS; LONG-TERM POTENTIATION; INDUCED RAT MODEL; HIPPOCAMPAL VOLUME; ANTIDEPRESSANT TREATMENT; WHITE-MATTER; PSYCHIATRIC-DISORDERS; MOOD DISORDERS AB By the year 2020, depression will be the 2nd most common health problem in the world. Current medications to treat depression are effective in less than 50% of patients. There is the need for novel treatments for depression to address the high rates of resistance to current treatment and the chronic residual symptoms in many patients treated for depression. The heterogeneity of major depressive disorder suggests that multiple neurocircuits and neurochemicals are involved in its pathogenesis thus, finding an alternative to neurotransmitter agonist- or antagonist-based treatments offers an important new approach. Cellular therapy is an emerging treatment strategy for multiple diseases, including depression. Based upon their in vivo function as "nurse cells" within the testis and the documented viability, efficacy, and safety of Sertoli cells transplanted into multiple tissues, including brain, the potential for these cells to provide a neuroprotective, anti-inflammatory, and trophic environment for neurons should be considered. It is proposed that the combination of self-protective, immunoregulatory and trophic properties of Sertoli cells may confer a unique potential for depression treatment and avoid many of the risks and challenges associated with stem cell therapies. At the very least, studies of the effects of Sertoli cell transplantation will add substantially to our understanding of the cellular and molecular processes that underlie depression. Published by Elsevier Ltd. C1 [Loftis, J. M.] Portland VA Med Ctr, Res & Dev Serv, Portland, OR 97239 USA. [Loftis, J. M.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97239 USA. RP Loftis, JM (reprint author), 3710 SW US Vet Hosp Rd,Mail Code R&D 16, Portland, OR 97239 USA. EM jennifer.loftis2@va.gov FU Department of Veterans Affairs, Veterans Health Administration. Office of Research and Development, Clinical Sciences Research and Development; Oregon Health and Science University; VA Career Development Award FX 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 manuscript was funded through a VA Career Development Award (J.M.L). NR 151 TC 3 Z9 4 U1 3 U2 8 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0306-9877 J9 MED HYPOTHESES JI Med. Hypotheses PD JUL PY 2011 VL 77 IS 1 BP 35 EP 42 DI 10.1016/j.mehy.2011.03.017 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 788FM UT WOS:000292430800010 PM 21454019 ER PT J AU Prahl, S Jepson, PD Sanchez-Hanke, M Deaville, R Siebert, U AF Prahl, Susanne Jepson, Paul D. Sanchez-Hanke, Marcos Deaville, Rob Siebert, Ursula TI Aspergillosis in the middle ear of a harbour porpoise (Phocoena phocoena): a case report SO MYCOSES LA English DT Article AB Hearing is one of the major senses in whales and dolphins (cetaceans). This is the first report of severe mycotic otitis media in a cetacean, a juvenile female harbour porpoise (Phocoena phocoena) from British waters that stranded alive. Gross examinations were followed by histological and microbiological investigations of the auditory apparatus. Both tympanic cavities and periotic sinuses displayed copious greenish-yellow purulent and caseous material. Severe fungal infestation by Aspergillus terreus was documented in the otic region but not in any other site of the body. Adjacent to the promontorium, massive accumulation of fibrinous secretion and infiltration of clusters of inflammatory cells were present. Newly formed cysts and vessels replaced the round window membrane location, reminiscent of granulation tissue. Inflammatory cells and a severe fibrin net were noted within the perilymphatic spaces of scala tympani and scala vestibuli, indicative of an acute fibrinous otitis. Inflammatory reactions have probably been caused by this fungal organism. The basilar membrane was solely covered by a simple cuboidal epithelium. Complete absence of sensory cells of the Organ of Corti characterised a further severe phenomenon, which possibly led to the animal's poor nutritional status and stranding. Potential portals of entry are being discussed. C1 [Prahl, Susanne; Siebert, Ursula] Univ Kiel, Forsch & Technol Zentrum W Kuste, Buesum, Germany. [Jepson, Paul D.; Deaville, Rob] Zool Soc London, Inst Zool, London NW1 4RY, England. [Sanchez-Hanke, Marcos] ENT Clin Speersort, Hamburg, Germany. RP Prahl, S (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM susanneprahl@web.de FU UK Department for Environment, Food and Rural Affairs (Defra); Devolved Administrations in the UK; Defra [CRO238] FX The retrieval and necropsy of the porpoise described in this study was carried out under the collaborative UK Cetacean Strandings Investigation Programme, which is jointly funded by the UK Department for Environment, Food and Rural Affairs (Defra) and the Devolved Administrations in the UK. The authors wish to thank the persons involved in collecting marine mammals from beaches in the UK. They cordially thank Bettina Buck for excellent technical skills in processing Grocott staining in celloidin sections and Evan Kuhn for technical assistance. Special thanks go to Carola Buchner and Peter Vander of OLYMPUS Hamburg for excellent support with optical equipment. Two anonymous reviewers are thanked for their productive comments on a previous version of this manuscript. A special thanks goes to Jennifer T. O'Malley for histological processing advice. This study was funded by Defra, contract no. CRO238. NR 0 TC 4 Z9 4 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0933-7407 J9 MYCOSES JI Mycoses PD JUL PY 2011 VL 54 IS 4 BP E260 EP E264 DI 10.1111/j.1439-0507.2010.01863.x PG 5 WC Dermatology; Mycology SC Dermatology; Mycology GA 789FY UT WOS:000292501600046 PM 20236242 ER PT J AU Haggarty, SJ Tsai, LH AF Haggarty, Stephen J. Tsai, Li-Huei TI Probing the role of HDACs and mechanisms of chromatin-mediated neuroplasticity SO NEUROBIOLOGY OF LEARNING AND MEMORY LA English DT Article DE Epigenetics; Chromatin; Neuroplasticity; Memory; HDAC; Therapeutics ID HISTONE DEACETYLASE INHIBITORS; LONG-TERM-MEMORY; EARLY GENE ZIF268; SYNAPTIC PLASTICITY; MOUSE MODEL; ALZHEIMERS-DISEASE; EPIGENETIC MECHANISMS; NEURONAL PLASTICITY; COGNITIVE DEFICIT; CONDITIONED FEAR AB Advancing our understanding of neuroplasticity and the development of novel therapeutics based upon this knowledge is critical in order to improve the treatment and prevention of a myriad of nervous system disorders. Epigenetic mechanisms of neuroplasticity involve the post-translational modification of chromatin and the recruitment or loss of macromolecular complexes that control neuronal activity-dependent gene expression. While over a century after Ramon y Cajal first described nuclear subcompartments and foci that we now know correspond to sites of active transcription with acetylated histones that are under epigenetic control, the rate and extent to which epigenetic processes act in a dynamic and combinatorial fashion to shape experience-dependent phenotypic and behavioral plasticity in response to various types of neuronal stimuli over a range of time scales is only now coming into focus. With growing recognition that a subset of human diseases involving cognitive dysfunction can be classified as 'chromat-inopathies', in which aberrant chromatin-mediated neuroplasticity plays a causal role in the underlying disease pathophysiology, understanding the molecular nature of epigenetic mechanisms in the nervous system may provide important new avenues for the development of novel therapeutics. In this review, we discuss the chemistry and neurobiology of the histone deacetylase (HDAC) family of chromatin-modifying enzymes, outline the role of HDACs in the epigenetic control of neuronal function, and discuss the potential relevance of these epigenetic mechanisms to the development of therapeutics aiming to enhance memory and neuroplasticity. Finally, open questions, challenges, and critical needs for the field of 'neuroepigenetics' in the years to come will be summarized. (c) 2011 Elsevier Inc. All rights reserved. C1 [Haggarty, Stephen J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Haggarty, Stephen J.; Tsai, Li-Huei] Harvard Univ, Broad Inst, Stanley Ctr Psychiat Res, Cambridge, MA 02139 USA. [Tsai, Li-Huei] MIT, Howard Hughes Med Inst, Picower Inst Learning & Memory, Cambridge, MA 02139 USA. RP Haggarty, SJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. EM haggarty@chgr.mgh.harvard.edu OI Haggarty, Stephen J./0000-0002-7872-168X FU NIH [R01DA028301, R01DA030321, RC1AG035711, RO1NS051874, PO1AG027916]; Stanley Medical Research Institute; Howard Hughes Medical Institute FX We would like to thank members of the Haggarty and Tsai laboratories, as well as the Stanley Center for Psychiatric Research for their contributions to the critical questions and work ongoing. S.J.H. is supported through funding from the NIH (R01DA028301, R01DA030321, RC1AG035711) and the Stanley Medical Research Institute. L.H.T. is supported through funding from the NIH (R01DA028301, RC1AG035711, RO1NS051874, PO1AG027916), the Stanley Medical Research Institute, and the Howard Hughes Medical Institute. NR 91 TC 48 Z9 49 U1 0 U2 16 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1074-7427 EI 1095-9564 J9 NEUROBIOL LEARN MEM JI Neurobiol. Learn. Mem. PD JUL PY 2011 VL 96 IS 1 SI SI BP 41 EP 52 DI 10.1016/j.nlm.2011.04.009 PG 12 WC Behavioral Sciences; Neurosciences; Psychology; Psychology, Multidisciplinary SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 787XL UT WOS:000292409900007 PM 21545841 ER PT J AU Ikonomovic, MD Klunk, WE Abrahamson, EE Wuu, J Mathis, CA Scheff, SW Mufson, EJ DeKosky, ST AF Ikonomovic, M. D. Klunk, W. E. Abrahamson, E. E. Wuu, J. Mathis, C. A. Scheff, S. W. Mufson, E. J. DeKosky, S. T. TI Precuneus amyloid burden is associated with reduced cholinergic activity in Alzheimer disease SO NEUROLOGY LA English DT Article ID MILD COGNITIVE IMPAIRMENT; PITTSBURGH COMPOUND-B; A-BETA; FRONTAL-CORTEX; OLDER PERSONS; DEPOSITION; BRAIN; MEMORY; INDIVIDUALS; DIAGNOSIS AB Objective: This study examined the relationship between postmortem precuneus cholinergic enzyme activity, Pittsburgh compound B (PiB) binding, and soluble amyloid-beta concentration in mild cognitive impairment (MCI) and Alzheimer disease (AD). Methods: Choline acetyltransferase (ChAT) activity, [(3)H]PiB binding, and soluble amyloid-beta(1-42) (A beta 42) concentration were quantified in precuneus tissue samples harvested postmortem from subjects with no cognitive impairment (NCI), MCI, and mild AD and correlated with their last antemortem Mini-Mental State Examination (MMSE) score and postmortem pathologic evaluation according to the National Institute on Aging-Reagan criteria, recommendations of the Consortium to Establish a Registry for Alzheimer's Disease, and Braak stage. Results: Precuneus ChAT activity was lower in AD than in NCI and was comparable between MCI and NCI. Precuneus [(3)H]PiB binding and soluble A beta 42 levels were elevated in MCI and significantly higher in AD than in NCI. Across all case subjects, reduced ChAT activity was associated with increased [(3)H]PiB binding, increased soluble A beta 42, lower MMSE score, presence of the APOE*4 allele, and more advanced AD pathology. Conclusions: Despite accumulating amyloid burden, cholinergic enzyme activity is stable in the precuneus during prodromal AD. A decline in precuneus ChAT activity occurs only in clinical AD, when PiB binding and soluble A beta 42 levels are substantially elevated compared with those in MCI. Anti-amyloid interventions in MCI case subjects with a positive PiB PET scan may aid in reducing cholinergic deficits and cognitive decline later in the disease process. Neurology (R) 2011;77:39-47 C1 [Ikonomovic, M. D.; Klunk, W. E.; Abrahamson, E. E.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA. [Ikonomovic, M. D.; Klunk, W. E.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15213 USA. [Mathis, C. A.] Univ Pittsburgh, Dept Radiol, Pittsburgh, PA 15213 USA. [Ikonomovic, M. D.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Wuu, J.] Univ Miami, Dept Neurol, Miami, FL USA. [Scheff, S. W.] Univ Kentucky, Dept Anat & Neurobiol, Lexington, KY 40506 USA. [Mufson, E. J.] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA. [DeKosky, S. T.] Univ Virginia, Sch Med, Off Dean, Charlottesville, VA 22908 USA. [DeKosky, S. T.] Univ Virginia, Sch Med, Dept Neurol, Charlottesville, VA 22908 USA. RP Ikonomovic, MD (reprint author), Univ Pittsburgh, Dept Neurol, 200 Lothrop St,BST S521, Pittsburgh, PA 15213 USA. EM ikonomovicmd@upmc.edu OI Klunk, William/0000-0001-5512-0251 FU NIH [AG14449, AG025204, AG10161, AG05133, AG12138]; GE Healthcare; Forest Research Institute, Inc.; Elan/Janssen AI; Roche; AstraZeneca; Neuroptix Corporation; Anonymous Foundation; Cure Alzheimer's Fund; NIH/NIA; FDA; CDC; ALS Association; Muscular Dystrophy Association; Consolidated Anti-Aging Foundation; Bayer Schering Pharma; Biogen Idec; IBA; Takeda Pharmaceutical Company Limited; US Department of Energy; Dana Foundation FX Supported by NIH grants AG14449, AG025204, AG10161, AG05133, and AG12138.; Dr. Ikonomovic has served as a consultant for and received funding for travel from GE Healthcare; serves as an Associate Editor for Cardiovascular Psychiatry and Neurology; and receives research support from GE Healthcare, Forest Research Institute, Inc., and the NIH. Dr. Klunk serves on scientific advisory boards and as a consultant for GE Healthcare, Neuroptix Corporation, Elan/Janssen AI, Roche, Wyeth/Pfizer, and AstraZeneca; has received funding for travel from Elan/Janssen AI, Roche, and AstraZeneca; is author on patents re: PiB PET imaging and chrysamine-G derivatives for imaging and therapy; receives research support from GE Healthcare, Neuroptix Corporation, the NIH (NIA, NIBIB), Anonymous Foundation, and Cure Alzheimer's Fund; holds stock in Neuroptix Corporation; and receives license fee and royalty payment from GE Healthcare. Dr. Abrahamson reports no disclosures. J. Wuu has received research support from the NIH/NIA, the FDA, the CDC, the ALS Association, the Muscular Dystrophy Association, and the Consolidated Anti-Aging Foundation. Dr. Mathis serves on a scientific advisory board for Neuroptix Corporation; has received funding for travel and speaker honoraria from Elan/Janssen AI, GE Healthcare, Bayer Schering Pharma, Biogen Idec, IBA, and Takeda Pharmaceutical Company Limited; serves on the editorial board of Nuclear Medicine and Biology; serves/has served as a consultant for GE Healthcare, Elan/Janssen AI, Wyeth/Pfizer, and Novartis; is author on numerous US and international patents re: Amyloid imaging agents; receives/has received research support from GE Healthcare, Neuroptix Corporation, the NIH, the US Department of Energy, the Dana Foundation, and Anonymous Foundation; holds stock options in Neuroptix Corporation; and has received license fees and royalty payments from GE Healthcare and Neuroptix Corporation for patents re: Amyloid imaging agents. Dr. Scheff serves on a scientific advisory board for TIRR; serves on the editorial board of the Journal of Neurotrauma; and receives research support from the NIH. Dr. Mufson has served as a consultant for Ceregene and NeuroPhage and receives research support from the NIH. Dr. DeKosky has served on a scientific advisory board for Pfizer Inc and as a consultant for Eisai, PsychoGenics Inc., Merck, Elan/Wyeth, Novartis, Eli Lilly, and Janssen; is the site principal investigator at the University of Virginia Memory Disorders Clinics for experimental therapeutic trials of Alzheimer's disease medications for Elan, Novartis, Forest, and Janssen Pharmaceuticals; serves on the editorial boards of Annals of Neurology, Archives of Neurology, Neurodegenerative Diseases, Journal of Alzheimer's Disease, and Alzheimer Disease and Associated Disorders: An International Journal, and as Editor of Up to Date; receives research support from the NIH; and serves as a board member for the National Center for Complementary and Alternative Medicine, the American Board of Psychiatry and Neurology, and the Alzheimer's Association. NR 39 TC 37 Z9 41 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUL PY 2011 VL 77 IS 1 BP 39 EP 47 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 789TB UT WOS:000292538100010 PM 21700583 ER PT J AU Arsava, EM Bayrlee, A Vangel, M Rost, NS Rosand, J Furie, KL Sorensen, AG Ay, H AF Arsava, E. M. Bayrlee, A. Vangel, M. Rost, N. S. Rosand, J. Furie, K. L. Sorensen, A. G. Ay, H. TI Severity of leukoaraiosis determines clinical phenotype after brain infarction SO NEUROLOGY LA English DT Article ID CEREBRAL WHITE-MATTER; TRANSIENT ISCHEMIC ATTACK; STROKE SEVERITY; FUNCTIONAL MRI; LESIONS; HYPERINTENSITIES; ACTIVATION; SYSTEM; VOLUME; SCORE AB Objective: To determine whether the extent of leukoaraiosis, a composite marker of baseline brain integrity, differed between patients with TIA with diffusion-weighted imaging (DWI) evidence of infarction (transient symptoms with infarction [TSI]) and patients with ischemic stroke. Methods: Leukoaraiosis volume on MRI was quantified in a consecutive series of 153 TSI and 354 ischemic stroke patients with comparable infarct volumes on DWI. We explored the relationship between leukoaraiosis volume and clinical phenotype (TIA or ischemic stroke) using a logistic regression model. Results: Patients with TSI tended to be younger (median age 66 vs 69 years, p = 0.062) and had smaller median normalized leukoaraiosis volume (1.2 mL, interquartile range [IQR] 0.2-4.7 mL vs 3.5 mL, IQR 1.2-8.6 mL, p < 0.001). In multivariable analysis controlling for age, stroke risk factors, etiologic stroke mechanism, infarct volume, and infarct location, increasing leukoaraiosis volume remained associated with ischemic stroke (odds ratio 1.05 per mL, 95% confidence interval 1.02-1.09, p = 0.004), along with infarct volume and infarct location. Conclusion: The probability of ischemic stroke rather than TSI increases with increasing leukoaraiosis volume, independent of infarct size and location. Our findings support the concept that the integrity of white matter tracts connecting different parts of the brain could contribute to whether or not patients develop TSI or ischemic stroke in an event of brain infarction. Neurology (R) 2011;77:55-61 C1 [Arsava, E. M.; Vangel, M.; Sorensen, A. G.; Ay, H.] Harvard Univ, Sch Med, Dept Radiol, AA Martinos Ctr Biomed Imaging,Massachusetts Gen, Boston, MA 02115 USA. [Bayrlee, A.; Rost, N. S.; Rosand, J.; Furie, K. L.; Ay, H.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp,Stroke Serv, Boston, MA 02115 USA. [Rosand, J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA. [Rosand, J.] MIT & Harvard, Program Med & Populat Genet, Broad Inst, Cambridge, MA USA. RP Ay, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, AA Martinos Ctr Biomed Imaging, 149 13th St,Room 2301, Charlestown, MA 02129 USA. EM hay@partners.org FU NIH [R01-NS059727, U01 NS069208-01, P50-NS051343, R01-NS038477, R01-NS063925, R01-NS059710]; NIH/NINDS; National Stroke Association; American Heart Association-Bugher Foundation; American Heart Association; Deane Institute; International Society of Magnetic Resonance in Medicine; Genentech, Inc.; Siemens Healthcare; American College of Radiology Imaging Network; Millennium Pharmaceuticals, Inc.; AstraZeneca; Society of Nuclear Medicine; ASCO Foundation; Olea Medical; Novartis; Schering-Plough Corp.; Surface Logix Inc.; sanofi-aventis FX Supported by the NIH R01-NS059727 and U01 NS069208-01 to J.R.; P50-NS051343 to K. L. F.; R01-NS038477, R01-NS063925, and U01 NS069208-01 to A. G. S.; and R01-NS059710 to H.A.).; (Dr. Arsava, Dr. Bayrlee, and Dr. Vangel report no disclosures. Dr. Rost serves as Associate Editor for Frontiers in Hospitalist Neurology and Assistant Editor for Stroke and receives research support from the NIH/NINDS, the National Stroke Association, and the American Heart Association-Bugher Foundation. Dr. Rosand receives research support from the NIH/NINDS and the American Heart Association-Bugher Foundation. Dr. Furie serves on a data safety monitoring board for the NIH/NINDS; serves as Vice Editor of Stroke; receives publishing royalties from UpToDate, Inc.; and receives research support from the NIH/NINDS, the American Heart Association, and the Deane Institute. Dr. Sorensen serves on a scientific advisory board for Olea Medical and Breakaway Imaging, LLC; has received funding for travel from the NIH, the International Society of Magnetic Resonance in Medicine, Genentech, Inc., Siemens Healthcare, American College of Radiology Imaging Network, Millennium Pharmaceuticals, Inc., AstraZeneca, Society of Nuclear Medicine, ASCO Foundation, Olea Medical, and GE Healthcare; serves as a Section Editor for Stroke and on the editorial boards of The Oncologist and the Journal of Clinical Oncology; is listed as an author on patents re: Method for evaluating novel, stroke treatments using a tissue risk map, Imaging system for obtaining quantitative perfusion indices, Delay-compensated calculation of tissue blood flow, High-flow oxygen delivery system and methods of use thereof, and Magnetic resonance spatial risk map for tissue outcome prediction; receives publishing royalties for Cerebral MR Perfusion Imaging (Thieme, 2000); has received speaker honoraria from Society of Nuclear Medicine, American Society for Radiation Oncology, Siemens Healthcare, Novartis Institute for Biomedical Research, King Faisal Specialist Hospital, and GE Healthcare; has served as a consultant for Mitsubishi Tanabe Pharma Corporation, AstraZeneca, Genentech, Inc., Novartis, Lantheus Medical Imaging, Bayer Schering Pharma, Regeneron Pharmaceuticals Inc., Merrimack Pharmaceuticals, Inc., Bristol-Myers Squibb, GE Healthcare, Siemens Healthcare, and Biogen Idec; serves as Director, American College of Radiology Image Metrix; receives research support from Millennium Pharmaceuticals, Inc., Siemens Healthcare, AstraZeneca, Genentech, Inc., Novartis, Schering-Plough Corp., Surface Logix Inc., sanofi-aventis, the NIH (NINDS, NCI); has received license fee payments from Bayer Schering Pharma, GE Healthcare, and Olea Medical; has received royalty payments from Massachusetts General Hospital for a patent re: Delay-compensated calculation of tissue blood flow; and has participated in medico-legal cases. Dr. Ay serves on the editorial boards of Stroke and Cerebrovascular Diseases and receives research support from the NIH. NR 37 TC 13 Z9 14 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUL PY 2011 VL 77 IS 1 BP 55 EP 61 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 789TB UT WOS:000292538100012 PM 21700580 ER PT J AU Zhu, JM Spencer, TJ Liu-Chen, LY Biederman, J Bhide, PG AF Zhu, Jinmin Spencer, Thomas J. Liu-Chen, Lee-Yuan Biederman, Joseph Bhide, Pradeep G. TI Methylphenidate and mu opioid receptor interactions: A pharmacological target for prevention of stimulant abuse SO NEUROPHARMACOLOGY LA English DT Article DE Methylphenidate; Stimulants; Dopamine receptor; Opioid receptor; Reward; Reinforcement; Addiction ID CONDITIONED PLACE PREFERENCE; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; INCENTIVE-SENSITIZATION THEORY; COCAINE-INDUCED LOCOMOTION; QUALITY-OF-LIFE; ORAL METHYLPHENIDATE; SUBSTANCE-ABUSE; RAT STRIATUM; ADULT RATS AB Methylphenidate (MPH) is one of the most commonly used and highly effective treatments for attention deficit hyperactivity disorder (ADHD) in children and adults. As the therapeutic use of MPH has increased, so has its abuse and illicit street-use. Yet, the mechanisms associated with development of MPH-associated abuse and dependence are not well understood making it difficult to develop methods to help its mitigation. As a result, many ADHD patients especially children and youth, that could benefit from MPH treatment do not receive it and risk lifelong disabilities associated with untreated ADHD. Therefore, understanding the mechanisms associated with development of MPH addiction and designing methods to prevent it assume high public health significance. Using a mouse model we show that supra-therapeutic doses of MPH produce rewarding effects (surrogate measure for addiction in humans) in a conditioned place preference paradigm and upregulate mu opioid receptor (MOPR) activity in the striatum and nucleus accumbens, brain regions associated with reward circuitry. Co-administration of naltrexone, a non-selective opioid receptor antagonist, prevents MPH-induced MOPR activation and the rewarding effects. The MPH-induced MOPR activation and rewarding effect require activation of the dopamine D1 but not the D2-receptor. These findings identify the MOPR as a potential target for attenuating rewarding effects of MPH and suggest that a formulation that combines naltrexone with MPH could be a useful pharmaceutical approach to alleviate abuse potential of MPH and other stimulants. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Zhu, Jinmin; Bhide, Pradeep G.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02129 USA. [Liu-Chen, Lee-Yuan] Temple Univ, Sch Med, Ctr Subst Abuse Res, Dept Pharmacol, Philadelphia, PA 19140 USA. RP Bhide, PG (reprint author), Massachusetts Gen Hosp, 149,13th St, Charlestown, MA 02129 USA. EM bhide@helix.mgh.harvard.edu FU PHS [RO1DA020796, R21DA027358]; Massachusetts General Hospital FX This study was supported by PHS grant RO1DA020796 (PGB), R21DA027358 (JZ), and additional partial support was received from The Massachusetts General Hospital Pediatric Psychopharmacology Philanthropic Fund. We thank Dr. Michael Schwarzschild, Massachusetts General Hospital, Boston, MA for giving us access to the rodent behavioral testing facility in his laboratory. NR 67 TC 11 Z9 11 U1 1 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 EI 1873-7064 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD JUL-AUG PY 2011 VL 61 IS 1-2 BP 283 EP 292 DI 10.1016/j.neuropharm.2011.04.015 PG 10 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 787WU UT WOS:000292408200033 PM 21545805 ER PT J AU Naeser, MA Hamblin, MR AF Naeser, Margaret A. Hamblin, Michael R. TI Potential for Transcranial Laser or LED Therapy to Treat Stroke, Traumatic Brain Injury, and Neurodegenerative Disease SO PHOTOMEDICINE AND LASER SURGERY LA English DT Editorial Material ID TERM NEUROLOGICAL DEFICITS; ACUTE ISCHEMIC-STROKE; LIGHT THERAPY; HUMAN BLOOD; IN-VITRO; NEUROGENESIS; IRRADIATION; PHOTOBIOMODULATION; ACUPUNCTURE; DEPRESSION C1 [Naeser, Margaret A.] VA Boston Healthcare Syst, W Roxbury, MA USA. [Naeser, Margaret A.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Hamblin, Michael R.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA USA. RP Naeser, MA (reprint author), VA Boston Healthcare Syst, 12-A,150 So Huntington Ave, Boston, MA 02130 USA. EM mnaeser@bu.edu OI Hamblin, Michael/0000-0001-6431-4605 FU NCI NIH HHS [R01CA137108]; NIAID NIH HHS [R01AI50875, R01CA/AI838801] NR 43 TC 33 Z9 34 U1 1 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1549-5418 J9 PHOTOMED LASER SURG JI Photomed. Laser Surg. PD JUL PY 2011 VL 29 IS 7 BP 443 EP 446 DI 10.1089/pho.2011.9908 PG 4 WC Surgery SC Surgery GA 788MB UT WOS:000292447900001 PM 21728786 ER PT J AU Green, MF Lee, J Wynn, JK Mathis, KI AF Green, Michael F. Lee, Junghee Wynn, Jonathan K. Mathis, Kristopher I. TI Visual Masking in Schizophrenia: Overview and Theoretical Implications SO SCHIZOPHRENIA BULLETIN LA English DT Article DE visual masking; visual processing; neural tuning; schizophrenia ID BACKWARD-MASKING; BIPOLAR DISORDER; OBJECT-SUBSTITUTION; UNAFFECTED SIBLINGS; SOCIAL-PERCEPTION; DEFICITS; PERFORMANCE; PATTERNS; CORTEX; GABA AB Visual masking provides several key advantages for exploring the earliest stages of visual processing in schizophrenia: it allows for control over timing at the millisecond level, there are several well-supported theories of the underlying neurobiology of visual masking, and it is amenable to examination by electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI). In this paper, we provide an overview of the visual masking impairment schizophrenia, including the relevant theoretical mechanisms for masking impairment. We will discuss its relationship to clinical symptoms, antipsychotic medications, diagnostic specificity, and presence in at-risk populations. As part of this overview, we will cover the neural correlates of visual masking based on recent findings from EEG and fMRI. Finally, we will suggest a possible mechanism that could explain the patterns of masking findings and other visual processing findings in schizophrenia. C1 [Green, Michael F.; Lee, Junghee; Wynn, Jonathan K.; Mathis, Kristopher I.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Green, Michael F.; Lee, Junghee; Wynn, Jonathan K.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. RP Green, MF (reprint author), VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. EM mgreen@ucla.edu RI Lee, Junghee/C-5226-2014; Wynn, Jonathan/H-3749-2014 OI Lee, Junghee/0000-0001-9567-8700; Wynn, Jonathan/0000-0002-1763-8540 FU National Institute of Mental Health [043292, 065707]; VA FX National Institute of Mental Health Grants (043292 and 065707 to M.F.G.); VA Career Development Award (to J.K.W.). NR 49 TC 32 Z9 33 U1 1 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD JUL PY 2011 VL 37 IS 4 BP 700 EP 708 DI 10.1093/schbul/sbr051 PG 9 WC Psychiatry SC Psychiatry GA 789PI UT WOS:000292527400009 PM 21606322 ER PT J AU Valenstein, M Kavanagh, J Lee, T Reilly, P Dalack, GW Grabowski, J Smelson, D Ronis, DL Ganoczy, D Woltmann, E Metreger, T Wolschon, P Jensen, A Poddig, B Blow, FC AF Valenstein, Marcia Kavanagh, Janet Lee, Todd Reilly, Peter Dalack, Gregory W. Grabowski, John Smelson, David Ronis, David L. Ganoczy, Dara Woltmann, Emily Metreger, Tabitha Wolschon, Patricia Jensen, Agnes Poddig, Barbara Blow, Frederic C. TI Using A Pharmacy-Based Intervention To Improve Antipsychotic Adherence Among Patients With Serious Mental Illness SO SCHIZOPHRENIA BULLETIN LA English DT Article DE adherence; antipsychotic medications; health services ID PRESCRIPTION REFILL COMPLIANCE; HEALTH-CARE EXPENDITURES; GROUP RANDOMIZED TRIALS; VALUE-ADDED UTILITIES; MEDICATION ADHERENCE; CONSORT STATEMENT; BIPOLAR DISORDER; REVISED RECOMMENDATIONS; NEUROLEPTIC TREATMENT; SCHIZOPHRENIA AB Background: Similar to patients with other chronic disorders, patients with serious mental illness (SMI) are often poorly adherent with prescribed medications. Objective: We conducted a randomized controlled trial examining the effectiveness of a pharmacy-based intervention (Meds-Help) in increasing antipsychotic medication adherence among Department of Veterans Affairs (VA) patients with SMI. We also examined the impact of Meds-Help on psychiatric symptoms, quality of life, and satisfaction with care. Methods: We enrolled 118 patients from 4 VA facilities with schizophrenia, schizoaffective, or bipolar disorder who were on long-term antipsychotics but had antipsychotic medication possession ratios (MPRs) <0.8 in the prior year. Patients were randomized to usual care (UC; n = 60) or the pharmacy-based intervention (Meds-Help; n = 58). We reassessed adherence at 6 and 12 months, at which time patients completed Positive and Negative Symptom Scales (PANSS), Quality of Well-being Scales (QWB), and Client Satisfaction Questionnaires (CSQ-8). Results: Prior to enrollment, Meds-Help and UC patients had mean antipsychotic MPRs of 0.54 and 0.55, respectively. At 6 months, mean MPRs were 0.91 for Meds-Help and 0.64 for UC patients; at 12 months, they were 0.86 for Meds-Help and 0.62 for UC patients. In multivariate analyses adjusting for patient factors, Meds-Help patients had significantly higher MPRs at 6 and 12 months (P < .0001). There were no significant differences between groups in PANSS, QWB, or CSQ-8 scores, but power to detect small effects was limited. Conclusions: Congruent with prior studies of patients with other disorders, a practical pharmacy-based intervention increased antipsychotic adherence among patients with SMI. However, SMI patients may require additional care management components to improve outcomes. C1 [Valenstein, Marcia; Ronis, David L.; Woltmann, Emily; Jensen, Agnes; Blow, Frederic C.] Dept Vet Affairs, Serious Mental Illness Treatment Res & Evaluat Ct, Ann Arbor, MI 48104 USA. [Valenstein, Marcia; Kavanagh, Janet; Dalack, Gregory W.; Ganoczy, Dara; Woltmann, Emily; Metreger, Tabitha; Blow, Frederic C.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Lee, Todd; Poddig, Barbara] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Ctr Management Complex Chron Care, Hines, IL 60141 USA. [Lee, Todd] Northwestern Univ, Feinberg Sch Med, Inst Healthcare Studies, Chicago, IL 60611 USA. [Lee, Todd] Northwestern Univ, Feinberg Sch Med, Div Gen Internal Med, Chicago, IL 60611 USA. [Reilly, Peter; Grabowski, John; Wolschon, Patricia] Dept Vet Affairs, John D Dingell Med Ctr, Detroit, MI USA. [Smelson, David] Edith Nourse Rogers Mem Vet Hosp, Bedford, MA USA. [Smelson, David] Univ Massachusetts, Sch Med, Dept Psychiat, Worcester, MA 01655 USA. [Ronis, David L.] Univ Michigan, Sch Nursing, Ann Arbor, MI 48109 USA. RP Valenstein, M (reprint author), Dept Vet Affairs, Serious Mental Illness Treatment Res & Evaluat Ct, Ann Arbor, MI 48104 USA. EM marciav@umich.edu FU Department of Veterans Affairs Health Services Research and Development [IIR 01-174-01] FX Department of Veterans Affairs Health Services Research and Development (IIR 01-174-01). NR 33 TC 28 Z9 29 U1 1 U2 13 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD JUL PY 2011 VL 37 IS 4 BP 727 EP 736 DI 10.1093/schbul/sbp121 PG 10 WC Psychiatry SC Psychiatry GA 789PI UT WOS:000292527400012 PM 19933540 ER PT J AU Becker, KD Stirman, SW AF Becker, Kimberly D. Stirman, Shannon Wiltsey TI The Science of Training in Evidence-Based Treatments in the Context of Implementation Programs: Current Status and Prospects for the Future SO ADMINISTRATION AND POLICY IN MENTAL HEALTH AND MENTAL HEALTH SERVICES RESEARCH LA English DT Editorial Material ID LARGE-SCALE IMPLEMENTATION; MENTAL-HEALTH; PSYCHOLOGICAL TREATMENTS; DISSEMINATION; CLINICIAN; SERVICES; OUTCOMES; PSYCHOTHERAPIES; ATTITUDES; SETTINGS C1 [Becker, Kimberly D.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD 21205 USA. [Stirman, Shannon Wiltsey] Natl Ctr PTSD, Womens Hlth Sci Div, VA Boston Healthcare Syst 116B 3, Boston, MA 02130 USA. [Stirman, Shannon Wiltsey] Boston Univ, Dept Psychiat, Boston, MA 02215 USA. RP Becker, KD (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, 624 N Broadway,8th Floor, Baltimore, MD 21205 USA. EM kbecker@jhsph.edu; Shannon.Wiltsey-Stirman@va.gov FU NIMH NIH HHS [R00 MH080100, R25 MH080916, T32 MH018834, T32 MH18834] NR 47 TC 11 Z9 11 U1 1 U2 5 PU MAIK NAUKA/INTERPERIODICA/SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 0894-587X J9 ADM POLICY MENT HLTH JI Adm. Policy. Ment. Health PD JUL PY 2011 VL 38 IS 4 SI SI BP 217 EP 222 DI 10.1007/s10488-011-0361-0 PG 6 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 779TF UT WOS:000291804400001 PM 21644028 ER PT J AU Lyon, AR Stirman, SW Kerns, SEU Bruns, EJ AF Lyon, Aaron R. Stirman, Shannon Wiltsey Kerns, Suzanne E. U. Bruns, Eric J. TI Developing the Mental Health Workforce: Review and Application of Training Approaches from Multiple Disciplines SO ADMINISTRATION AND POLICY IN MENTAL HEALTH AND MENTAL HEALTH SERVICES RESEARCH LA English DT Review DE Training; Uptake; Workforce development; Implementation; Dissemination ID CLINICAL-PRACTICE GUIDELINES; EVIDENCE-BASED MEDICINE; CONTINUING PROFESSIONAL-DEVELOPMENT; RANDOMIZED CONTROLLED-TRIALS; INTERPROFESSIONAL EDUCATION; PREVENTIVE CARE; PHYSICIAN PERFORMANCE; QUALITY IMPROVEMENT; WRAPAROUND PROCESS; BEHAVIORAL HEALTH AB Strategies specifically designed to facilitate the training of mental health practitioners in evidence-based practices (EBPs) have lagged behind the development of the interventions themselves. The current paper draws from an interdisciplinary literature (including medical training, adult education, and teacher training) to identify useful training and support approaches as well as important conceptual frameworks that may be applied to training in mental health. Theory and research findings are reviewed, which highlight the importance of continued consultation/support following training workshops, congruence between the training content and practitioner experience, and focus on motivational issues. In addition, six individual approaches are presented with careful attention to their empirical foundations and potential applications. Common techniques are highlighted and applications and future directions for mental health workforce training and research are discussed. C1 [Lyon, Aaron R.] Univ Washington, Inst Child Hlth, Seattle, WA 98115 USA. [Stirman, Shannon Wiltsey] Natl Ctr PTSD, Boston, MA USA. [Stirman, Shannon Wiltsey] VA Boston Healthcare Syst, Boston, MA USA. [Stirman, Shannon Wiltsey] Boston Univ, Washington, DC USA. [Kerns, Suzanne E. U.; Bruns, Eric J.] Univ Washington, Seattle, WA 98195 USA. RP Lyon, AR (reprint author), Univ Washington, Inst Child Hlth, 6200 NE 74th St,Suite 100, Seattle, WA 98115 USA. EM lyona@uw.edu FU NIMH NIH HHS [F32 MH086978-02, K99 MH080100, R00 MH080100, R25 MH080916, F32 MH086978] NR 126 TC 43 Z9 44 U1 1 U2 13 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0894-587X EI 1573-3289 J9 ADM POLICY MENT HLTH JI Adm. Policy. Ment. Health PD JUL PY 2011 VL 38 IS 4 SI SI BP 238 EP 253 DI 10.1007/s10488-010-0331-y PG 16 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 779TF UT WOS:000291804400003 PM 21190075 ER PT J AU Sharma, AK Heist, K Russell, G Krahn, T Ferrell, M AF Sharma, Ajay K. Heist, Kevin Russell, Gregory Krahn, Thomas Ferrell, Margaret TI A True MI? SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material ID ACUTE MYOCARDIAL-INFARCTION; PSEUDOINFARCTION PATTERN; HYPERKALEMIA C1 [Sharma, Ajay K.] Charlton Mem Hosp, Dept Internal Med, Fall River, MA 02720 USA. [Russell, Gregory; Ferrell, Margaret] Charlton Mem Hosp, Dept Cardiol, Fall River, MA 02720 USA. [Krahn, Thomas] Charlton Mem Hosp, Dept Nephrol, Fall River, MA 02720 USA. [Heist, Kevin] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP Sharma, AK (reprint author), Charlton Mem Hosp, Dept Internal Med, 363 Highland Ave, Fall River, MA 02720 USA. EM ajayrattan12@gmail.com NR 10 TC 1 Z9 1 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD JUL PY 2011 VL 124 IS 7 BP 608 EP 610 DI 10.1016/j.amjmed.2011.02.003 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 778RG UT WOS:000291721900016 PM 21531370 ER PT J AU Shahian, DM Nordberg, P Meyer, GS Mort, E Atamian, S Liu, X Karson, AS Zheng, H AF Shahian, David M. Nordberg, Paul Meyer, Gregg S. Mort, Elizabeth Atamian, Susan Liu, Xiu Karson, Andrew S. Zheng, Hui TI Predictors of Nonadherence to National Hospital Quality Measures for Heart Failure and Pneumonia SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Performance; Predictors; Process measure; Quality ID ACUTE MYOCARDIAL-INFARCTION; ACUTE CORONARY SYNDROMES; CARE PERFORMANCE-MEASURES; ETHNIC DISPARITIES; WEEKDAY ADMISSION; PATIENT-OUTCOMES; ARTERY-DISEASE; OF-CARE; MORTALITY; IMPACT AB BACKGROUND: Understanding factors associated with process measure nonadherence may improve both patient care and future measure design. METHODS: We analyzed 3401 patients with heart failure and 2186 patients with pneumonia who were eligible for at least 1 National Hospital Quality Measure at an urban tertiary medical center from July 1, 2004, to June 30, 2008. We investigated the association of socioeconomic, demographic, clinical, and care delivery factors with process measure nonadherence, using multivariable analysis. RESULTS: Demographic and socioeconomic variables were unrelated to heart failure measure adherence. Nonadherence with angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker use was more common in patients with renal failure (odds ratio [OR] 2.56; 95% confidence interval [CI], 1.46-4.49), and patients admitted to noncardiac units more often failed the heart failure all-or-none measure (OR 2.22; 95% CI, 1.79-2.75). Patients with pneumonia who were admitted via the emergency department were less likely to fail antibiotic timing (OR 0.41; 95% CI, 0.27-0.63), whereas those with a history of methicillin-resistant Staphylococcus aureus (OR 2.63; 95% CI, 1.31-5.28) or requiring intensive care unit admission (OR 11.4; 95% CI, 6.3-20.8) were more likely to fail the antibiotic selection measure. CONCLUSION: Demographic and socioeconomic factors were generally unrelated to process measure nonadherence, demonstrating that excellent inpatient care can be delivered even to vulnerable populations. Clinical predictors suggest opportunities for improving both medical record documentation of appropriate exclusions and future measure specifications, especially for complex patients. Care delivery factors substantially affect process adherence. (C) 2011 Elsevier Inc. All rights reserved. The American Journal of Medicine (2011) 124, 636-646 C1 [Shahian, David M.] Harvard Univ, Ctr Qual & Safety, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Shahian, David M.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02114 USA. [Zheng, Hui] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Shahian, DM (reprint author), Harvard Univ, Ctr Qual & Safety, Massachusetts Gen Hosp, Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM dshahian@partners.org NR 41 TC 3 Z9 3 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD JUL PY 2011 VL 124 IS 7 BP 636 EP 646 DI 10.1016/j.amjmed.2011.03.021 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 778RG UT WOS:000291721900021 PM 21683830 ER PT J AU Chester, JG Grande, LJ Milberg, WP McGlinchey, RE Lipsitz, LA Rudolph, JL AF Chester, Jennifer G. Grande, Laura J. Milberg, William P. McGlinchey, Regina E. Lipsitz, Lewis A. Rudolph, James L. TI Cognitive Screening in Community-Dwelling Elders: Performance on the Clock-in-the-Box SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Aged; Cognition; Dementia; Function; Neuropsychologic testing; Screening ID MINI-MENTAL-STATE; ALZHEIMERS-DISEASE; DEMENTIA; BATTERY; ASSOCIATION; DYSFUNCTION; NORMS; AGE AB BACKGROUND: The Clock-in-the-Box is a rapid (2-minute) cognitive screening tool. The purpose of this study was to compare the Clock-in-the-Box with the Mini-Mental State Exam and neuropsychologic tests; to determine Clock-in-the-Box score normative values by age and education group; and to determine if the Clock-in-the-Box score is associated with measures of physical function. METHODS: Community-dwelling older participants in the Boston area were recruited for a prospective, longitudinal study in which they completed a variety of cognitive and functional assessments. RESULTS: At baseline, participants (n = 798; mean age [+/- standard deviation] = 78.2 [+/- 5.5] years; 14 [+/- 3] mean years of education) completed in-home assessments of cognition (Clock-in-the-Box and Mini-Mental State Exam), measures of independent function (Activities of Daily Living and Instrumental Activities of Daily Living), and measures of physical function (Short Physical Performance Battery). The mean Mini-Mental State Exam score was 27.1 (+/- 1.6; range 0-30 [0 worst]), and the mean Clock-in-the-Box score was 6.2 (+/- 1.6; range 0-8 [0 worst]). Performance on the Clock-in-the-Box was correlated (Spearman) with the Mini-Mental State Exam (r = 0.49, P < .001) and neuropsychologic measures (r = 0.37-0.50; P < .001). Higher Clock-in-the-Box score was significantly associated with no difficulty in Activities of Daily Living (chi(2) = 39.6, P < .001) and Instrumental Activities of Daily Living (chi(2) = 35.5, P < .001). In addition, higher Clock-in-the-Box scores were associated with higher scores on the Short Physical Performance Battery (F = 5.4, P < .001). CONCLUSION: The Clock-in-the-Box is a brief cognitive screening test that is correlated with the Mini-Mental State Exam, neuropsychologic tests, and measures of independent and physical function in community-dwelling older adults. Published by Elsevier Inc. The American Journal of Medicine (2011) 124, 662-669 C1 [Milberg, William P.; McGlinchey, Regina E.; Rudolph, James L.] VABHS, GRECC, Boston, MA 02130 USA. [Chester, Jennifer G.] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Lipsitz, Lewis A.] Hebrew SeniorLife, Inst Aging Res, Boston, MA USA. [Lipsitz, Lewis A.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Rudolph, James L.] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. [Grande, Laura J.; Milberg, William P.; McGlinchey, Regina E.; Lipsitz, Lewis A.; Rudolph, James L.] Harvard Univ, Sch Med, Boston, MA USA. RP Rudolph, JL (reprint author), VABHS, GRECC, 150 S Huntington Ave, Boston, MA 02130 USA. EM James.Rudolph@va.gov RI McGlinchey, Regina/R-1971-2016 FU Einstein Research Fellowship; Veterans Affairs Rehabilitation Career Development Award; American Federation for Aging Research; Boston MSTAR; National Institutes of Health [AG-038027-01 AG-023480, AG-08812, AG-029861]; National Institutes of Health/National Institute on Aging [P01AG 004390] FX JGC was funded by an Einstein Research Fellowship. JLR is funded by a Veterans Affairs Rehabilitation Career Development Award. Additional support provided by the American Federation for Aging Research, the Boston MSTAR, and National Institutes of Health Grants AG-038027-01 AG-023480, AG-08812, and AG-029861. The data for this project were collected by the Hebrew SeniorLife/Harvard Research Nursing Home-Maintenance Of Balance, Independent Living, Intellect, and Zest in the Elderly (MOBILIZE) Boston Project (AG004390). The MOBILIZE Boston Study is funded by National Institutes of Health/National Institute on Aging under Grant P01AG 004390. NR 29 TC 10 Z9 10 U1 4 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD JUL PY 2011 VL 124 IS 7 BP 662 EP 669 DI 10.1016/j.amjmed.2011.02.023 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 778RG UT WOS:000291721900024 PM 21592451 ER PT J AU Shin, N Jo, HJ Kim, WK Park, WY Lee, JH Shin, DH Choi, KU Kim, JY Lee, CH Sol, MY Jeon, TY Kim, DW Huh, GY Kim, GH Lauwers, GY Park, DY AF Shin, Nari Jo, Hong-Jae Kim, Woo-Kyung Park, Won-Young Lee, Jeong-Hee Shin, Dong Hun Choi, Kyung Un Kim, Jee-Yeon Lee, Chang-Hun Sol, Mee Young Jeon, Tae Yong Kim, Dae Whan Huh, Gi-Young Kim, Gwang Ha Lauwers, Gregory Y. Park, Do Youn TI Gastric Pit Dysplasia in Adjacent Gastric Mucosa in 414 Gastric Cancers: Prevalence and Characteristics SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE stomach; adenocarcinoma; pit dysplasia ID INTESTINAL METAPLASIA; BARRETTS-ESOPHAGUS; CRYPT DYSPLASIA; P53 EXPRESSION; HUMAN STOMACH; CLASSIFICATION; LESIONS; ADENOCARCINOMA; PROLIFERATION; EPIDEMIOLOGY AB Despite wide acceptance of the chronic gastritis-intestinal metaplasia-dysplasia-carcinoma sequence, especially for intestinal-type gastric adenocarcinoma, the precise nature of the subtle precursor lesions of gastric cancer remains to be delineated. For example, pit dysplasia with surface foveolar maturation is not well defined, nor is its prevalence and biological characteristics well characterized. We have evaluated the surrounding gastric mucosa of 414 gastric cancers for the presence of gastric pit dysplasia. We investigated its relationship with various clinicopathological and immunophenotypic features of gastric adenocarcinoma, as well as the severity and extent of any surrounding gastritis and intestinal metaplasia. p53 expression and Ki-67 proliferation index were also evaluated. We have found that 21.0% (n = 87) of gastric cancer cases showed pit dysplasia in adjacent gastric mucosa. Gastric cancers with pit dysplasia were significantly associated with older age, male sex, body/fundic location, and intestinal histologic type (P < 0.05). Interestingly, gastric mucin-containing intestinal metaplasia (incomplete intestinal metaplasia) was highly associated with adenocarcinoma with pit dysplasia (P = 0.000). In addition, MUC6 expression in gastric adenocarcinoma was associated with pit dysplasia (P = 0.036). p53 overexpression and increased Ki-67 proliferation index were more evident in gastric pit dysplasia compared with adjacent gastric mucosa. We suggest that gastric pit dysplasia is an important candidate precursor of gastric adenocarcinoma and may represent another morphologic step in the pathogenesis of gastric adenocarcinoma, especially of intestinal type. More detailed prospective studies are needed to determine the precise significance of these findings. C1 [Shin, Nari; Kim, Woo-Kyung; Park, Won-Young; Lee, Jeong-Hee; Shin, Dong Hun; Choi, Kyung Un; Kim, Jee-Yeon; Lee, Chang-Hun; Sol, Mee Young; Park, Do Youn] Pusan Natl Univ, Pusan Natl Univ Hosp, Sch Med, Med Res Inst,Dept Pathol, Pusan 602739, South Korea. [Jo, Hong-Jae; Jeon, Tae Yong; Kim, Dae Whan] Pusan Natl Univ, Pusan Natl Univ Hosp, Sch Med, Med Res Inst,Dept Surg, Pusan 602739, South Korea. [Huh, Gi-Young] Pusan Natl Univ, Pusan Natl Univ Hosp, Sch Med, Med Res Inst,Dept Forens Med, Pusan 602739, South Korea. [Kim, Gwang Ha] Pusan Natl Univ, Pusan Natl Univ Hosp, Sch Med, Med Res Inst,Dept Internal Med, Pusan 602739, South Korea. [Lauwers, Gregory Y.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Park, DY (reprint author), Pusan Natl Univ, Pusan Natl Univ Hosp, Sch Med, Med Res Inst,Dept Pathol, 1-10 Ami Dong, Pusan 602739, South Korea. EM pdy220@pusan.ac.kr FU Ministry for Health, Welfare and Family affairs, Republic of Korea [0920050] FX Supported by a grant (0920050) from the National R&D Program for Cancer Control, Ministry for Health, Welfare and Family affairs, Republic of Korea. NR 24 TC 8 Z9 8 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JUL PY 2011 VL 35 IS 7 BP 1021 EP 1029 DI 10.1097/PAS.0b013e31821ec495 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA 778CG UT WOS:000291676200010 PM 21677540 ER PT J AU Truong-Bolduc, QC Bolduc, GR Okumura, R Celino, B Bevis, J Liao, CH Hooper, DC AF Truong-Bolduc, Que Chi Bolduc, Gilles R. Okumura, Ryo Celino, Brian Bevis, Jennifer Liao, Chun-Hsing Hooper, David C. TI Implication of the NorB Efflux Pump in the Adaptation of Staphylococcus aureus to Growth at Acid pH and in Resistance to Moxifloxacin SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID MESSENGER-RNA TURNOVER; GENE-EXPRESSION; SIGNAL-TRANSDUCTION; REGULATORY SYSTEM; MGRA; VIRULENCE; SHOCK; TRANSCRIPTOME; CONTRIBUTES; RESPONSES AB Staphylococcus aureus is an important pathogen that adapts and survives in low-pH environments. One component of this adaptation involves the regulation of genes encoding bacterial transporters that could affect response to antibiotics under these conditions. We previously demonstrated that the transcriptional regulator MgrA in its phosphorylated form (MgrA-P) represses the expression of norB, encoding the NorB multidrug resistance efflux pump. In this study, we focused on changes in the expression of mgrA at the transcriptional and posttranslational levels, following a shift from pH 7.0 to pH 4.5. We then correlated those changes with modifications in transcript levels of norB and to resistance to moxifloxacin, a substrate of NorB. At pH 4.5, S. aureus MgrA increased 2-fold and MgrA-P decreased 4-fold, associated with an 8-fold increase in norB transcripts and a 6-fold reduction in bacterial killing by moxifloxacin, and the phenomenon was dependent on intact mgrA. Taken together, these new data showed that phosphoregulation of MgrA at low pH reverses its repression of norB expression, conferring resistance to moxifloxacin. C1 [Truong-Bolduc, Que Chi; Okumura, Ryo; Liao, Chun-Hsing; Hooper, David C.] Harvard Univ, Massachusetts Gen Hosp, Div Infect Dis, Sch Med, Boston, MA 02114 USA. [Bolduc, Gilles R.; Celino, Brian; Bevis, Jennifer] Massasoit Community Coll, Brockton, MA 02302 USA. RP Hooper, DC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Div Infect Dis, Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM dhooper@partners.org FU National Institutes of Health [R37-AI23988]; National Science Foundation [NSF 06-502] FX This work was supported in part by a Public Health Service grant (R37-AI23988) from the National Institutes of Health to D. C. H. and in part by the NSF-STEP Summer Research Program (NSF 06-502) from the National Science Foundation to G. R. B., B. C., and J.B., who were with the Stonehill Undergraduate Research Experience ( SURE), Easton, MA, for the period of June to August 2010. NR 28 TC 12 Z9 12 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUL PY 2011 VL 55 IS 7 BP 3214 EP 3219 DI 10.1128/AAC.00289-11 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 778FK UT WOS:000291687900020 PM 21555767 ER PT J AU Wiederhold, NP Najvar, LK Bocanegra, RA Kirkpatrick, WR Patterson, TF AF Wiederhold, Nathan P. Najvar, Laura K. Bocanegra, Rosie A. Kirkpatrick, William R. Patterson, Thomas F. TI Caspofungin Dose Escalation for Invasive Candidiasis Due to Resistant Candida albicans SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID REDUCED ECHINOCANDIN SUSCEPTIBILITY; DOUBLE-BLIND TRIAL; AMPHOTERICIN-B; IN-VITRO; ASPERGILLUS-FUMIGATUS; MICAFUNGIN FK463; ADULT PATIENTS; IMMUNE-SYSTEM; MURINE MODEL; GLABRATA AB Previous in vivo studies have reported caspofungin dose escalation to be effective against Candida glabrata with reduced susceptibility. We hypothesized that higher doses of caspofungin would be effective against invasive candidiasis caused by the more virulent species Candida albicans, including isolates resistant to this echinocandin. Immunocompetent mice were inoculated with one of three C. albicans isolates, including one susceptible and two resistant isolates with different FKS1 hot spot 1 point mutations. Mice received daily caspofungin treatment for 7 days and were then followed off therapy for 2 weeks to assess survival. Kidney tissue and blood were collected, and fungal burden and serum (1 -> 3)-beta-D-glucan were measured. Significant differences in virulence were observed among the three C. albicans isolates, which translated into differences in responses to caspofungin. The most virulent of the resistant isolates studied (isolate 43001; Fks1p F641S) did not respond to caspofungin doses of up to 10 mg/kg of body weight, as there were no differences in survival (survival range, 0 to 12% with treatment), tissue burden, or (1 -> 3)-beta-D-glucan concentration compared to those for untreated controls. Higher doses of caspofungin did improve survival against the second resistant isolate (53264; Fks1p S645P) that demonstrated reduced virulence (5 and 10 mg/kg; 80% survival). In contrast, caspofungin doses as low as 1 mg/kg improved survival (85 to 95%) and reduced tissue burden and (1 -> 3)-beta-D-glucan concentration against the susceptible isolate (ATCC 90028). These data suggest that caspofungin dose escalation for invasive candidiasis may not be consistently effective against resistant C. albicans isolates, and this may be associated with the virulence of the strain. C1 [Wiederhold, Nathan P.; Najvar, Laura K.; Bocanegra, Rosie A.; Kirkpatrick, William R.; Patterson, Thomas F.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Wiederhold, Nathan P.] Univ Texas Austin, Coll Pharm, Austin, TX 78712 USA. [Wiederhold, Nathan P.; Najvar, Laura K.; Bocanegra, Rosie A.; Kirkpatrick, William R.; Patterson, Thomas F.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Wiederhold, NP (reprint author), Univ Texas Hlth Sci Ctr San Antonio, PERC MSC 6220,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM wiederholdn@uthscsa.edu OI Wiederhold, Nathan/0000-0002-2225-5122 FU Merck Co., Inc.; Pfizer; Schering-Plough; Merck; Basilea; Astellas; Nektar Therapeutics FX This work was supported in part by a research grant from the Investigator-Initiated Studies Program of Merck & Co., Inc.; N.P.W. has received research support from Pfizer, Schering-Plough, Merck, Basilea, and Astellas. T. F. P. has received research support from Basilea, Astellas, Merck, Pfizer, Schering-Plough, and Nektar Therapeutics and has served as a consultant for Basilea, Merck, Pfizer, and Toyama. NR 39 TC 29 Z9 32 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUL PY 2011 VL 55 IS 7 BP 3254 EP 3260 DI 10.1128/AAC.01750-10 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 778FK UT WOS:000291687900026 PM 21502632 ER PT J AU Huang, LY Dai, TH Xuan, Y Tegos, GP Hamblin, MR AF Huang, Liyi Dai, Tianhong Xuan, Yi Tegos, George P. Hamblin, Michael R. TI Synergistic Combination of Chitosan Acetate with Nanoparticle Silver as a Topical Antimicrobial: Efficacy against Bacterial Burn Infections SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID PSEUDOMONAS-AERUGINOSA; ESCHERICHIA-COLI; ANTIBACTERIAL PROPERTIES; STAPHYLOCOCCUS-AUREUS; WOUND INFECTIONS; MEDICAL DEVICES; BIOFILMS; COMPLEX; BANDAGE; FILMS AB Chitosan and nanoparticle silver are both materials with demonstrated antimicrobial properties and have been proposed singly or in combination as constituents of antimicrobial burn dressings. Here, we show that they combine synergistically to inhibit the in vitro growth of Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative bacteria (Pseudomonas aeruginosa, Proteus mirabilis, and Acinetobacter baumannii), as judged by bioluminescence monitoring and isobolographic analysis, and also produce synergistic killing after 30 min of incubation, as measured by a CFU assay. The hypothesized explanation involves chitosan-mediated permeabilization of bacterial cells, allowing better penetration of silver ions into the cell. A dressing composed of freeze-dried chitosan acetate incorporating nanoparticle silver was compared with a dressing of chitosan acetate alone in an in vivo burn model infected with bioluminescent P. aeruginosa. The survival rates of mice treated with silver-chitosan or regular chitosan or left untreated were 64.3% (P = 0.0082 versus regular chitosan and P = 0.0003 versus the control), 21.4%, and 0%, respectively. Most of the fatalities occurred between 2 and 5 days postinfection. Silver-chitosan dressings effectively controlled the development of systemic sepsis, as shown by blood culture. These data suggest that a dressing combining chitosan acetate with silver leads to improved antimicrobial efficacy against fatal burn infections. C1 [Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, BAR414, Boston, MA 02114 USA. [Huang, Liyi; Dai, Tianhong; Tegos, George P.; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Huang, Liyi] Guangxi Med Univ, Dept Infect Dis, Affiliated Coll & Hosp 1, Nanning, Peoples R China. [Xuan, Yi] Tufts Univ, Sch Engn, Medford, MA 02155 USA. [Tegos, George P.] Univ New Mexico, Sch Med, Dept Pathol, Albuquerque, NM 87131 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, BAR414, 40 Blossom St, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 FU U.S. Army [W81XWH-08-2-0120]; HemCon Inc.; U.S. NIH [R01A1050875, R01CA137108]; U.S. Air Force MFEL [FA9550-04-1-0079]; Airlift Research Foundation [109421] FX This work was funded by a contract from the U.S. Army (W81XWH-08-2-0120) with HemCon Inc., by the U.S. NIH (grants R01A1050875 to M. R. H. and R01CA137108 to Long Y. Chiang), and by the U.S. Air Force MFEL Program (FA9550-04-1-0079). T. D. was supported by Airlift Research Foundation grant 109421. NR 52 TC 38 Z9 41 U1 4 U2 26 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUL PY 2011 VL 55 IS 7 BP 3432 EP 3438 DI 10.1128/AAC.01803-10 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 778FK UT WOS:000291687900046 PM 21502618 ER PT J AU Palacio, F Lewis, JS Sadkowski, L Echevarria, K Jorgensen, JH AF Palacio, Federico Lewis, James S., II Sadkowski, Lee Echevarria, Kelly Jorgensen, James H. TI Breakthrough Bacteremia and Septic Shock Due to Streptococcus anginosus Resistant to Daptomycin in a Patient Receiving Daptomycin Therapy SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Letter ID MILLERI; INFECTIONS; INTERMEDIUS C1 [Palacio, Federico] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Infect Dis, San Antonio, TX 78229 USA. [Lewis, James S., II] Univ Hlth Syst, Dept Pharm, San Antonio, TX USA. [Sadkowski, Lee; Echevarria, Kelly] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Jorgensen, James H.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. RP Palacio, F (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Infect Dis, San Antonio, TX 78229 USA. EM jorgensen@uthscsa.edu NR 14 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 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUL PY 2011 VL 55 IS 7 BP 3639 EP 3640 DI 10.1128/AAC.00231-11 PG 2 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 778FK UT WOS:000291687900086 PM 21502623 ER PT J AU Swirski, FK AF Swirski, Filip K. TI The Spatial and Developmental Relationships in the Macrophage Family SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE blood cells; immune system; leukocytes; macrophages; hematopoiesis ID HEMATOPOIETIC STEM-CELL; COLONY-STIMULATING FACTOR; BONE-MARROW; DENDRITIC CELLS; PROGENITOR CELLS; MYOCARDIAL-INFARCTION; BACTERIAL-INFECTION; INFLAMMATORY SITES; SPLENIC RESERVOIR; MONOCYTE SUBSETS AB A classic study in 1968 proposed that bone marrow-dwelling promonocytes differentiate to monocytes, which then intravasate, circulate, and, on tissue entry, differentiate to sessile macrophages. Since then, understanding of the macrophage family relationship has undergone substantial enhancement and occasional revision. It is currently recognized that in addition to their role in the bone marrow, hematopoietic progenitors circulate and give rise to their descendants in extramedullary niches. Monocytes, of which there are several subsets, are not merely circulating macrophage precursors but participate in the immune response in their own right. Macrophages are highly heterogeneous and, as recent studies indicate, can arise in the absence of a monocyte intermediate. These spatial and developmental relationships reveal a complex interactive network and underscore the importance of context in evaluating biological systems. The observations have significant implications for how we image, target, and treat disease. (Arterioscler Thromb Vasc Biol. 2011; 31:1517-1522.) C1 [Swirski, Filip K.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Swirski, Filip K.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Swirski, FK (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM fswirski@mgh.harvard.edu FU National Institutes of Health [R01-HL095612] FX This work was supported by National Institutes of Health Grant R01-HL095612 (to F.K.S.). NR 86 TC 17 Z9 20 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUL PY 2011 VL 31 IS 7 BP 1517 EP 1522 DI 10.1161/ATVBAHA.110.221150 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 777WR UT WOS:000291656300011 PM 21677294 ER PT J AU Meyer, CA He, HSH Brown, M Liu, XS AF Meyer, Clifford A. He, Housheng H. Brown, Myles Liu, X. Sirley TI BINOCh: binding inference from nucleosome occupancy changes SO BIOINFORMATICS LA English DT Article ID ENHANCERS; GENOME AB Transcription factor binding events are frequently associated with a pattern of nucleosome occupancy changes in which nucleosomes flanking the binding site increase in occupancy, while those in the vicinity of the binding site itself are displaced. Genome-wide information on enhancer proximal nucleosome occupancy can be readily acquired using ChIP-seq targeting enhancer-related histone modifications such as H3K4me2. Here, we present a software package, BINOCh that allows biologists to use such data to infer the identity of key transcription factors that regulate the response of a cell to a stimulus or determine a program of differentiation. C1 [Meyer, Clifford A.; He, Housheng H.; Liu, X. Sirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Meyer, Clifford A.; He, Housheng H.; Liu, X. Sirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [He, Housheng H.; Brown, Myles] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [He, Housheng H.; Brown, Myles] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Meyer, CA (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. EM cliff@jimmy.harvard.edu; xsliu@jimmy.harvard.edu RI He, Housheng/G-9614-2011; OI Brown, Myles/0000-0002-8213-1658 FU National Institutes of Health [R01 HG4069] FX National Institutes of Health (R01 HG4069). NR 7 TC 12 Z9 12 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD JUL 1 PY 2011 VL 27 IS 13 BP 1867 EP 1868 DI 10.1093/bioinformatics/btr279 PG 2 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 779BH UT WOS:000291752600067 PM 21551136 ER PT J AU Ovretveit, JC Shekelle, PG Dy, SM McDonald, KM Hempel, S Pronovost, P Rubenstein, L Taylor, SL Foy, R Wachter, RM AF Ovretveit, John C. Shekelle, Paul G. Dy, Sydney M. McDonald, Kathryn M. Hempel, Susanne Pronovost, Peter Rubenstein, Lisa Taylor, Stephanie L. Foy, Robbie Wachter, Robert M. TI How does context affect interventions to improve patient safety? An assessment of evidence from studies of five patient safety practices and proposals for research SO BMJ QUALITY & SAFETY LA English DT Article ID INTENSIVE-CARE UNITS AB Background: Logic and experience suggest that it is easier in some situations than in others to change behaviour and organisation to improve patient safety. Knowing which 'context factors' help and hinder implementation of different changes would help implementers, as well as managers, policy makers, regulators and purchasers of healthcare. It could help to judge the likely success of possible improvements, given the conditions that they have, and to decide which of these conditions could be modified to make implementation more effective. Methods: The study presented in this paper examined research to discover any evidence reported about whether or how context factors influence the effectiveness of five patient safety interventions. Results: The review found that, for these five diverse interventions, there was little strong evidence of the influence of different context factors. However, the research was not designed to investigate context influence. Conclusions: The paper suggests that significant gaps in research exist and makes proposals for future research better to inform decision-making. C1 [Ovretveit, John C.] Karolinska Inst, MMC, Med Management Ctr, S-17177 Stockholm, Sweden. [Shekelle, Paul G.] Univ Calif Los Angeles, RAND Corp, Los Angeles, CA USA. [Shekelle, Paul G.] VA Greater Los Angeles, Los Angeles, CA USA. [Pronovost, Peter] Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care, Baltimore, MD USA. [McDonald, Kathryn M.] Stanford Univ, Stanford, CA 94305 USA. [Hempel, Susanne; Taylor, Stephanie L.] RAND Corp, Santa Monica, CA USA. [Pronovost, Peter] Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 USA. [Pronovost, Peter] Johns Hopkins Univ, Sch Med, Dept Hlth Policy & Management, Baltimore, MD 21205 USA. [Pronovost, Peter] Johns Hopkins Univ, Sch Med, Ctr Innovat Qual Patient Care, Baltimore, MD 21205 USA. [Rubenstein, Lisa] VA HSRD Ctr Excellence Study Healthcare Provider, North Hills, CA USA. [Foy, Robbie] Univ Leeds, Leeds Inst Hlth Sci, Leeds, W Yorkshire, England. [Wachter, Robert M.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. RP Ovretveit, JC (reprint author), Karolinska Inst, MMC, Med Management Ctr, Berzelius Vag 3, S-17177 Stockholm, Sweden. EM jovret@aol.com FU US Agency for Healthcare Research and Quality [HHSA-290-2009-10001C] FX This study was financed by the US Agency for Healthcare Research and Quality Contract No HHSA-290-2009-10001C. NR 29 TC 31 Z9 31 U1 1 U2 9 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-5415 J9 BMJ QUAL SAF JI BMJ Qual. Saf. PD JUL PY 2011 VL 20 IS 7 BP 604 EP 610 DI 10.1136/bmjqs.2010.047035 PG 7 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 778SX UT WOS:000291727100009 PM 21493589 ER PT J AU Taylor, SL Dy, S Foy, R Hempel, S McDonald, KM Ovretveit, J Pronovost, PJ Rubenstein, LV Wachter, RM Shekelle, PG AF Taylor, Stephanie L. Dy, Sydney Foy, Robbie Hempel, Susanne McDonald, Kathryn M. Ovretveit, John Pronovost, Peter J. Rubenstein, Lisa V. Wachter, Robert M. Shekelle, Paul G. TI What context features might be important determinants of the effectiveness of patient safety practice interventions? SO BMJ QUALITY & SAFETY LA English DT Article ID HEALTH-CARE RESEARCH; QUALITY IMPROVEMENT; GUIDELINES; RECOMMENDATIONS; IMPLEMENTATION; AGENCY AB Background: Differences in contexts (eg, policies, healthcare organisation characteristics) may explain variations in the effects of patient safety practice (PSP) implementations. However, knowledge of which contextual features are important determinants of PSP effectiveness is limited and consensus is lacking on a taxonomy of which contexts matter. Methods: Iterative, formal discussions were held with a 22-member technical expert panel composed of experts or leaders in patient safety, healthcare systems, and methods. First, potentially important contextual features were identified, focusing on five PSPs. Then, two surveys were conducted to determine the context likely to influence PSP implementations. Results: The panel reached a consensus on a taxonomy of four broad domains of contextual features important for PSP implementations: safety culture, teamwork and leadership involvement; structural organisational characteristics (eg, size, organisational complexity or financial status); external factors (eg, financial or performance incentives or PSP regulations); and availability of implementation and management tools (eg, training organisational incentives). Panelists also tended to rate specific patient safety culture, teamwork and leadership contexts as high priority for assessing their effects on PSP implementations, but tended to rate specific organisational characteristic contexts as high priority only for use in PSP evaluations. Panelists appeared split on whether specific external factors and implementation/management tools were important for assessment or only description. Conclusion: This work can guide research commissioners and evaluators on the contextual features of PSP implementations that are important to report or evaluate. It represents a first step towards developing guidelines on contexts in PSP implementation evaluations. However, the science of context measurement needs maturing. C1 [Taylor, Stephanie L.; Hempel, Susanne; Rubenstein, Lisa V.; Shekelle, Paul G.] RAND Corp, Santa Monica, CA USA. [Taylor, Stephanie L.; Rubenstein, Lisa V.; Shekelle, Paul G.] Vet Adm, Los Angeles, CA USA. [Dy, Sydney; Pronovost, Peter J.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Foy, Robbie] Univ Leeds, Leeds Inst Hlth Sci, Leeds, W Yorkshire, England. [McDonald, Kathryn M.] Stanford Univ, Stanford, CA 94305 USA. [Ovretveit, John] Karolinska Inst, Med Management Ctr, Stockholm, Sweden. [Wachter, Robert M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Taylor, SL (reprint author), VA Greater Los Angeles, 16111 Plummer St,Bldg 25 152, North Hills, CA 91343 USA. EM stephanie.taylor8@va.gov FU Agency for Healthcare Research and Quality; Agency for Healthcare Research and Quality, US Department of Health and Human Services [HHSA-290-2009-10001C] FX Funding Agency for Healthcare Research and Quality.; The technical expert panel included Alyce S. Adams, PhD, Peter Angood, MD, David W. Bates, MD, MSc, Len Bickman, PhD, Celia Brown, PhD, Pascale Carayon, PhD, Sir Liam Donaldson, MD, Naihua Duan, PhD, Donna O. Farley, PhD, MPH, Trisha Greenhalgh, MD, John Haughom, MD, Eileen T. Lake, PhD, RN, Richard Lilford, MB BCh, PhD, Kathleen N. Lohr, PhD, Gregg S. Meyer, MD, MSc, Marlene Miller, MD, MSc, Duncan Neuhauser, PhD, Gery Ryan, PhD, Sanjay Saint, MD, MPH, Kaveh Shojania, MD, Stephen M. Shortell, PhD, MPH, David P. Stevens, MD, and Kieran Walshe, PhD. The research reported here was supported under Contract No. HHSA-290-2009-10001C from the Agency for Healthcare Research and Quality, US Department of Health and Human Services. The authors of this paper are responsible for its content. Statements in this paper should not be construed as endorsement by the Agency for Healthcare Research and Quality or the US Department of Health and Human Services. NR 31 TC 60 Z9 60 U1 1 U2 20 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-5415 J9 BMJ QUAL SAF JI BMJ Qual. Saf. PD JUL PY 2011 VL 20 IS 7 BP 611 EP 617 DI 10.1136/bmjqs.2010.049379 PG 7 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 778SX UT WOS:000291727100010 PM 21617166 ER PT J AU Yu, YM AF Yu, Yong-Ming TI Data"-omics" and intensive care unit patient care SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE cognitive errors; electronic database; intensive care unit; task load; user interface C1 [Yu, Yong-Ming] Shriners Burns Hosp, Boston, MA USA. [Yu, Yong-Ming] Massachusetts Gen Hosp, Dept Surg, Burn Unit, Boston, MA 02114 USA. RP Yu, YM (reprint author), Shriners Burns Hosp, Boston, MA USA. FU NIDDK NIH HHS [P30 DK040561]; NIGMS NIH HHS [P50 GM 021700] NR 7 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JUL PY 2011 VL 39 IS 7 BP 1823 EP 1824 DI 10.1097/CCM.0b013e31821caf44 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 778RF UT WOS:000291721800029 PM 21685745 ER PT J AU Yang, J Weedon, MN Purcell, S Lettre, G Estrada, K Willer, CJ Smith, AV Ingelsson, E O'Connell, JR Mangino, M Magi, R Madden, PA Heath, AC Nyholt, DR Martin, NG Montgomery, GW Frayling, TM Hirschhorn, JN McCarthy, MI Goddard, ME Visscher, PM AF Yang, Jian Weedon, Michael N. Purcell, Shaun Lettre, Guillaume Estrada, Karol Willer, Cristen J. Smith, Albert V. Ingelsson, Erik O'Connell, Jeffrey R. Mangino, Massimo Maegi, Reedik Madden, Pamela A. Heath, Andrew C. Nyholt, Dale R. Martin, Nicholas G. Montgomery, Grant W. Frayling, Timothy M. Hirschhorn, Joel N. McCarthy, Mark I. Goddard, Michael E. Visscher, Peter M. CA GIANT Consortium TI Genomic inflation factors under polygenic inheritance SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE genome-wide association study; genomic inflation factor; polygenic inheritance ID POPULATION STRATIFICATION; MISSING HERITABILITY; HUMAN HEIGHT; ASSOCIATION; LOCI; DISEASES; POWER AB Population structure, including population stratification and cryptic relatedness, can cause spurious associations in genome-wide association studies (GWAS). Usually, the scaled median or mean test statistic for association calculated from multiple single-nucleotide-polymorphisms across the genome is used to assess such effects, and 'genomic control' can be applied subsequently to adjust test statistics at individual loci by a genomic inflation factor. Published GWAS have clearly shown that there are many loci underlying genetic variation for a wide range of complex diseases and traits, implying that a substantial proportion of the genome should show inflation of the test statistic. Here, we show by theory, simulation and analysis of data that in the absence of population structure and other technical artefacts, but in the presence of polygenic inheritance, substantial genomic inflation is expected. Its magnitude depends on sample size, heritability, linkage disequilibrium structure and the number of causal variants. Our predictions are consistent with empirical observations on height in independent samples of similar to 4000 and similar to 133 000 individuals. European Journal of Human Genetics (2011) 19, 807-812; doi:10.1038/ejhg.2011.39; published online 16 March 2011 C1 [Yang, Jian] Queensland Inst Med Res, Queensland Stat Genet Lab, Brisbane, Qld 4006, Australia. [Weedon, Michael N.; Frayling, Timothy M.] Univ Exeter, Peninsula Coll Med & Dent, Exeter, Devon, England. [Purcell, Shaun; Hirschhorn, Joel N.] Broad Inst, Cambridge, MA USA. [Purcell, Shaun] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Lettre, Guillaume] Univ Montreal, Montreal Heart Inst, Res Ctr, Montreal, PQ, Canada. [Estrada, Karol] Dept Internal Med, Rotterdam, Netherlands. [Willer, Cristen J.] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Smith, Albert V.] Heart Prevent Clin & Res Inst, Iceland Heart Assoc, Kopavogur, Iceland. [Ingelsson, Erik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [O'Connell, Jeffrey R.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. [Mangino, Massimo] Kings Coll London, St Thomas Hosp, Twin Res & Genet Epidemiol Dept, London WC2R 2LS, England. [Maegi, Reedik; McCarthy, Mark I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Madden, Pamela A.; Heath, Andrew C.] Washington Univ, Dept Psychiat, St Louis, MO USA. [Hirschhorn, Joel N.] Childrens Hosp, Program Genom, Boston, MA 02115 USA. [Hirschhorn, Joel N.] Childrens Hosp, Div Genet, Boston, MA 02115 USA. [Hirschhorn, Joel N.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [McCarthy, Mark I.] Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. [Goddard, Michael E.] Univ Melbourne, Dept Food & Agr Syst, Parkville, Vic 3052, Australia. RP Yang, J (reprint author), Queensland Inst Med Res, Queensland Stat Genet Lab, 300 Herston Rd, Brisbane, Qld 4006, Australia. EM jian.yang@qimr.edu.au RI Nyholt, Dale/C-8384-2013; Montgomery, Grant/B-7148-2008; Smith, Albert/K-5150-2015; mangino, massimo/F-5134-2011; Yang, Jian/A-5852-2010; OI Montgomery, Grant/0000-0002-4140-8139; Smith, Albert/0000-0003-1942-5845; mangino, massimo/0000-0002-2167-7470; Goddard, Michael/0000-0001-9917-7946; Magi, Reedik/0000-0002-2964-6011; Willer, Cristen/0000-0001-5645-4966; Visscher, Peter/0000-0002-2143-8760; Yang, Jian/0000-0003-2001-2474; Martin, Nicholas/0000-0003-4069-8020 FU Australian National Health and Medical Research Council (NHMRC) [389891, 389892, 613672, 613601]; Australian Research Council (ARC) [DP0770096, DP1093900]; US National Institute of Health (NIH) [AA13320, AA13321, DA12854] FX We thank all three reviewers for helpful comments. We acknowledge funding from the Australian National Health and Medical Research Council (NHMRC Grants 389891, 389892, 613672 and 613601), the Australian Research Council (ARC Grants DP0770096 and DP1093900) and the US National Institute of Health (NIH Grants AA13320, AA13321 and DA12854). NR 23 TC 121 Z9 122 U1 0 U2 22 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD JUL PY 2011 VL 19 IS 7 BP 807 EP 812 DI 10.1038/ejhg.2011.39 PG 6 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 778DA UT WOS:000291678400017 PM 21407268 ER PT J AU Roche-Labarbe, N Carp, SA Surova, A Patel, M Boas, DA Grant, PE Franceschini, MA AF Roche-Labarbe, Nadege Carp, Stefan A. Surova, Andrea Patel, Megha Boas, David A. Grant, P. Ellen Franceschini, Maria Angela TI Noninvasive Optical Measures of CBV, StO(2,) CBF Index, and rCMRO(2) in Human Premature Neonates' Brains in the First Six Weeks of Life (vol 31, pg 341, 2010) SO HUMAN BRAIN MAPPING LA English DT Correction C1 [Roche-Labarbe, Nadege; Carp, Stefan A.; Surova, Andrea; Patel, Megha; Boas, David A.; Franceschini, Maria Angela] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Grant, P. Ellen] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Roche-Labarbe, N (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA. RI Roche-Labarbe, Nadege/N-9101-2015 OI Roche-Labarbe, Nadege/0000-0002-5010-0400 NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD JUL PY 2011 VL 32 IS 7 BP 1179 EP 1179 DI 10.1002/hbm.21190 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 776UE UT WOS:000291562900014 ER PT J AU Mayer, EL Dallabrida, SM Rupnick, MA Redline, WM Hannagan, K Ismail, NS Burstein, HJ Beckman, JA AF Mayer, Erica L. Dallabrida, Susan M. Rupnick, Maria A. Redline, Whitney M. Hannagan, Keri Ismail, Nesreen S. Burstein, Harold J. Beckman, Joshua A. TI Contrary Effects of the Receptor Tyrosine Kinase Inhibitor Vandetanib on Constitutive and Flow-Stimulated Nitric Oxide Elaboration in Humans SO HYPERTENSION LA English DT Article DE vascular endothelial growth factor; VEGF receptor 2; secondary hypertension; endothelium; NO ID ENDOTHELIAL GROWTH-FACTOR; METASTATIC BREAST-CANCER; VASCULAR SMOOTH-MUSCLE; PACLITAXEL PLUS BEVACIZUMAB; COLORECTAL-CANCER; PHASE-II; BRACHIAL-ARTERY; BLOOD-PRESSURE; HYPERTENSION; VEGF AB Vascular endothelial growth factor regulates neoplastic angiogenesis through production of endothelium-derived NO. We performed a prospective evaluation of vascular function during treatment with vandetanib, a vascular endothelial growth receptor 2 and 3 receptor tyrosine kinase inhibitor, to determine the effects of vascular endothelial growth receptor signal interruption on endothelial function in humans. Seventeen patients with stage IV breast cancer received dose-escalated vandetanib in combination with low-dose oral chemotherapy. We measured blood pressure, systemic nitrate/nitrite levels, and brachial artery vascular function. In vitro analyses of cultured endothelial cells were performed to determine the effect of vandetanib on NO production, akt(473) phosphorylation, and endothelial NO synthase protein content and membrane localization. Vandetanib treatment for 6 weeks significantly increased blood pressure, decreased resting brachial artery diameter, and decreased plasma systemic nitrate/nitrite levels compared with baseline. Flow-mediated vasodilation was preserved, and no change was noted in nitroglycerin-mediated vasodilation. In vitro, endothelial cell nitrite levels and akt473 phosphorylation were reduced and vascular endothelial growth receptor 2 levels did not change, but endothelial NO synthase membrane concentration doubled. Vandetanib reduces constitutive NO production and increases blood pressure, yet flow-stimulated NO bioavailability was preserved. Changes in vascular function with tyrosine kinase inhibition are complex and require further study in humans. (Hypertension. 2011;58:85-92.) C1 [Mayer, Erica L.; Hannagan, Keri; Burstein, Harold J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Rupnick, Maria A.; Redline, Whitney M.; Beckman, Joshua A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Dallabrida, Susan M.; Rupnick, Maria A.; Ismail, Nesreen S.] Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. RP Beckman, JA (reprint author), 75 Francis St, Boston, MA 02115 USA. EM jbeckman@partners.org OI Beckman, Joshua/0000-0001-8332-8439 FU AstraZeneca; American Diabetes Association (ADA) [ADA 1-06-CD-01] FX This research was supported by a grant from the investigator-sponsored study program of AstraZeneca and the American Diabetes Association (ADA 1-06-CD-01). NR 52 TC 19 Z9 20 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD JUL PY 2011 VL 58 IS 1 BP 85 EP 92 DI 10.1161/HYPERTENSIONAHA.110.168120 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 777WE UT WOS:000291655000015 PM 21482957 ER PT J AU Plourde, E Champagne, B AF Plourde, Eric Champagne, Benoit TI Multidimensional STSA Estimators for Speech Enhancement With Correlated Spectral Components SO IEEE TRANSACTIONS ON SIGNAL PROCESSING LA English DT Article DE Bayesian estimators; correlated spectral components; noise reduction; short-time spectral amplitude; speech enhancement ID SQUARE ERROR ESTIMATION; AMPLITUDE ESTIMATORS; BAYESIAN-ESTIMATORS; LIKELIHOOD RATIO; PRIORS; ALGORITHMS; MODEL; GAMMA AB Speech enhancement algorithms are used to remove background noise in a speech signal. In Bayesian short-time spectral amplitude (STSA) estimation for single-channel speech enhancement, the spectral components are traditionally assumed uncorrelated. However, this assumption is inexact since some correlation is present in practice. In this paper, we investigate a multidimensional Bayesian STSA estimator that assumes correlated spectral components. Since the closed-form solution of this optimum estimator is not readily available, we alternatively derive closed-form expressions for an upper and a lower bound on the desired estimator. Using these bounds, we propose a new family of speech enhancement estimators that are characterized by a scalar parameter 0 <= gamma <= 1, with gamma = 0 corresponding to the lower bound and gamma = 1 to the upper bound. An appropriate estimator for the correlation matrix of the clean speech is further derived. Evaluation results from both objective and subjective speech quality measures show that at moderate to high SNR values, where spectral correlation of speech is most noticeable, the proposed estimators can achieve significant improvements over the traditional STSA and Wiener filter estimators. C1 [Plourde, Eric; Champagne, Benoit] McGill Univ, Dept Elect & Comp Engn, Montreal, PQ H3A 2A7, Canada. [Plourde, Eric] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. RP Plourde, E (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Stat Res Lab, Boston, MA 02114 USA. EM eric.plourde@mail.mcgill.ca; benoit.champagne@mcgill.ca FU Natural Sciences and Engineering Research Council of Canada (NSERC) FX Manuscript received June 22, 2010; revised October 22, 2010 and January 31, 2011; accepted March 21, 2011. Date of publication April 05, 2011; date of current version June 15, 2011. The associate editor coordinating the review of this manuscript and approving it for publication was Prof. Maciej Niedzwiecki. This work was supported by a grant from the Natural Sciences and Engineering Research Council of Canada (NSERC). NR 57 TC 14 Z9 16 U1 1 U2 4 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1053-587X EI 1941-0476 J9 IEEE T SIGNAL PROCES JI IEEE Trans. Signal Process. PD JUL PY 2011 VL 59 IS 7 BP 3013 EP 3024 DI 10.1109/TSP.2011.2138697 PG 12 WC Engineering, Electrical & Electronic SC Engineering GA 778DM UT WOS:000291680200002 ER PT J AU Nallapareddy, SR Sillanpaa, J Mitchell, J Singh, KV Chowdhury, SA Weinstock, GM Sullam, PM Murray, BE AF Nallapareddy, Sreedhar R. Sillanpaeae, Jouko Mitchell, Jennifer Singh, Kavindra V. Chowdhury, Shahreen A. Weinstock, George M. Sullam, Paul M. Murray, Barbara E. TI Conservation of Ebp-Type Pilus Genes among Enterococci and Demonstration of Their Role in Adherence of Enterococcus faecalis to Human Platelets SO INFECTION AND IMMUNITY LA English DT Article ID EXTRACELLULAR-MATRIX PROTEINS; URINARY-TRACT-INFECTION; CLUMPING FACTOR-A; STREPTOCOCCUS-PYOGENES; STAPHYLOCOCCUS-AUREUS; BIOFILM FORMATION; COLLAGEN ADHESIN; FAECIUM ISOLATE; ENDOCARDITIS; BACTERIA AB Ebp are endocarditis- and biofilm-associated pili of Enterococcus faecalis that are also important in experimental urinary tract infections (UTIs). Our analyses, using available genomes, found that the ebp locus is unique to enterococci. In E. faecalis, the ebp locus is very highly conserved and only 1/473 E. faecalis isolates tested lacked ebpABC, while only 1.2% had the bee pilus locus. No other pilus-encoding operon was identified in 55 available genomes, indicating that the vast majority of E. faecalis strains (unlike Enterococcus faecium and streptococci) have a single pilus locus. Surface expression studies showed that Ebp pili were produced in vitro by 91/91 brain heart infusion (BHI) plus serum-grown E. faecalis isolates and that strain OG1RF expressed pili at even higher levels in rat endocarditis vegetations. However, Ebp expression was restricted to 30 to 72% of E. faecalis cells, consistent with a bistability mode of expression. We also evaluated E. faecalis interactions with human platelets and found that growth of E. faecalis in BHI plus serum significantly enhanced adherence to human platelets and that sortase deletion mutants (the Delta srtA, Delta bps, and Delta bps Delta srtA mutants) were markedly defective. Further studies identified that Ebp pili, but not the microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) Ace and Fss2, mediate adherence of E. faecalis to platelets. Taken together, our data show that the immunogenic (in human endocarditis patients) and commonly expressed Ebp pili, which are known to be important for experimental endocarditis, are highly conserved and mediate adherence to platelets, suggesting that Ebp pili may be a reasonable immunotherapeutic target for prevention or possibly treatment of endocarditis caused by this species. C1 [Nallapareddy, Sreedhar R.; Sillanpaeae, Jouko; Singh, Kavindra V.; Chowdhury, Shahreen A.; Murray, Barbara E.] Univ Texas Med Sch, Div Infect Dis, Dept Internal Med, Houston, TX 77030 USA. [Nallapareddy, Sreedhar R.; Sillanpaeae, Jouko; Singh, Kavindra V.; Chowdhury, Shahreen A.; Murray, Barbara E.] Univ Texas Med Sch, Ctr Study Emerging & Reemerging Pathogens, Houston, TX 77030 USA. [Murray, Barbara E.] Univ Texas Med Sch, Dept Microbiol & Mol Genet, Houston, TX 77030 USA. [Mitchell, Jennifer] Univ Coll Dublin, Dublin 2, Ireland. [Weinstock, George M.] Washington Univ, Dept Genet, St Louis, MO 63108 USA. [Sullam, Paul M.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Sullam, Paul M.] Univ Calif San Francisco, San Francisco, CA 94121 USA. RP Murray, BE (reprint author), Univ Texas Med Sch Houston, Div Infect Dis, Dept Internal Med, 6431 Fannin St,MSB 2-112, Houston, TX 77030 USA. EM bem.asst@uth.tmc.edu RI Weinstock, George/C-6314-2013 OI Weinstock, George/0000-0002-2997-4592 FU Division of Microbiology and Infectious Diseases, NIAID, National Institutes of Health (NIH) [R37 AI47923, R01 AI47923]; Department of Veteran Affairs; NIH [R01 AI041513, R01 AI057433] FX This work was supported by National Institutes of Health (NIH) grants R37 AI47923 and R01 AI47923 from the Division of Microbiology and Infectious Diseases, NIAID, to B.E.M. and the Department of Veteran Affairs and NIH grants R01 AI041513 and R01 AI057433 to P.M.S. NR 75 TC 21 Z9 23 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 2011 VL 79 IS 7 BP 2911 EP 2920 DI 10.1128/IAI.00039-11 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 779OO UT WOS:000291788700044 PM 21502588 ER PT J AU Marques, L Alegria, M Becker, AE Chen, CN Fang, A Chosak, A Diniz, JB AF Marques, Luana Alegria, Margarita Becker, Anne E. Chen, Chih-nan Fang, Angela Chosak, Anne Diniz, Juliana Belo TI Comparative Prevalence, Correlates of Impairment, and Service Utilization for Eating Disorders Across US Ethnic Groups: Implications for Reducing Ethnic Disparities in Health Care Access for Eating Disorders SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article DE anorexia nervosa; bulimia nervosa; Binge-eating disorder; ethnicity ID COMORBIDITY SURVEY REPLICATION; ASIAN-AMERICAN; MENTAL-DISORDERS; NATIONAL LATINO; ORGANIZATION; SYMPTOMS; LIFE AB Objective: The study compared the prevalence, correlates of functional impairment, and service utilization for eating disorders across Latinos, Asians, and African Americans living in the United States to non-Latino Whites. Method: Pooled data from the NIMH Collaborative Psychiatric Epidemiological Studies (CPES; NIMH, 2007) were used. Results: The prevalence of anorexia nervosa (AN) and binge-eating disorder (BED) were similar across all groups examined, but bulimia nervosa (BN) was more prevalent among Latinos and African Americans than non-Latino Whites. Despite similar prevalence of BED among ethnic groups examined, lifetime prevalence of any binge eating (ABE) was greater among each of the ethnic minority groups in comparison to non-Latino Whites. Lifetime prevalence of mental health service utilization was lower among ethnic minority groups studied than for non-Latino Whites for respondents with a lifetime history of any eating disorder. Discussion: These findings suggest the need for clinician training and health policy interventions to achieve optimal and equitable care for eating disorders across all ethnic groups in the United States. (C) 2010 by Wiley Periodicals, Inc. C1 [Marques, Luana; Becker, Anne E.; Fang, Angela; Chosak, Anne] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Alegria, Margarita; Becker, Anne E.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Alegria, Margarita; Chen, Chih-nan] Cambridge Hlth Alliance, Cambridge, MA USA. [Alegria, Margarita; Chen, Chih-nan] Ctr Multicultural Mental Hlth Res, Cambridge, MA USA. [Becker, Anne E.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA. [Diniz, Juliana Belo] Univ Sao Paulo, Sch Med, Dept & Inst Psychiat, Hosp Clin, Sao Paulo, Brazil. RP Marques, L (reprint author), Simches Res Bldg,Off 2206,185 Cambridge St,2nd Fl, Boston, MA 02114 USA. EM lmarques@partners.org RI Diniz, Juliana/D-2503-2011 OI Diniz, Juliana/0000-0001-9486-3779 FU NIH (National Institute of Mental Health) [U01 MH 062209] FX Supported by U01 MH 062209 from NIH (National Institute of Mental Health) NR 29 TC 98 Z9 99 U1 3 U2 22 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD JUL PY 2011 VL 44 IS 5 BP 412 EP 420 DI 10.1002/eat.20787 PG 9 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 777KK UT WOS:000291614200005 PM 20665700 ER PT J AU Devisetty, K Kobayashi, W Suit, HD Goldberg, SI Niemierko, A Chen, YLE Raskin, KA Schwab, JH Springfield, DS Yoon, SS Hornicek, FJ DeLaney, TF AF Devisetty, Kiran Kobayashi, Wendy Suit, Herman D. Goldberg, Saveli I. Niemierko, Andrzej Chen, Yen-Lin E. Raskin, Kevin A. Schwab, Joseph H. Springfield, Dempsey S. Yoon, Sam S. Hornicek, Francis J. DeLaney, Thomas F. TI LOW-DOSE NEOADJUVANT EXTERNAL BEAM RADIATION THERAPY FOR SOFT TISSUE SARCOMA SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Soft tissue sarcoma; Neoadjuvant; Radiation; Toxicity; Brachytherapy ID PROGNOSTIC-FACTORS; POSTOPERATIVE RADIOTHERAPY; WOUND COMPLICATIONS; RETROPERITONEAL SARCOMA; RANDOMIZED-TRIAL; EXTREMITY; RESECTION; MANAGEMENT; SURVIVAL; SURGERY AB Purpose: For soft tissue sarcoma, neoadjuvant external beam radiation therapy (EBRT) to 50 Gy has the same local control (LC) and overall survival as postoperative radiation therapy (PORT) to 60 Gy, but with increased wound complications. We examined whether low-dose neoadjuvant EBRT would decrease acute toxicity while maintaining LC. Methods and Materials: From 1971 to 2008, 1,765 patients with nonmetastatic soft tissue sarcoma were treated with radiation therapy at Massachusetts General Hospital. We identified 42 patients treated with low-dose neoadjuvant EBRT (median, 20 Gy; range, 16-26) followed by surgical resection and PORT. PORT included EBRT (25 patients; median, 40 Gy; range, 20-56.2), brachytherapy (13 patients; median, 42 Gy; range, 26-50), and intraoperative radiation therapy (IORT) (4 patients; median, 12.5 Gy; range, 8-20). The median total dose was 63.3 Gy (range, 28-78.4). Results: Median follow-up was 36 months (range, 4-318). Severe acute wound complications were reported in 15 patients (36%) and correlated to PORT technique (16% EBRT, 69% brachytherapy, 50% IORT, p = 0.004). The 5-year LC was 73% and correlated to PORT technique (68% EBRT, 100% brachytherapy, 50% IORT, p = 0.03) and histology (p = 0.05), with a trend to improvement if > 60 Gy (p = 0.10). The 5-year overall survival was 65% and correlated to extent of resection (p < 0.001) and margin status (p < 0.001). Conclusions: Despite using low-dose neoadjuvant EBRT, we report a high rate of severe acute wound complications that was strongly associated with brachytherapy. Modification of the brachytherapy technique may decrease acute toxicity while maintaining excellent local control. Further study must be conducted before recommending broader application. (C) 2011 Elsevier Inc. C1 [Kobayashi, Wendy; Suit, Herman D.; Goldberg, Saveli I.; Niemierko, Andrzej; Chen, Yen-Lin E.; DeLaney, Thomas F.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Raskin, Kevin A.; Schwab, Joseph H.; Springfield, Dempsey S.; Hornicek, Francis J.] Massachusetts Gen Hosp, Dept Orthoped, Boston, MA 02114 USA. [Yoon, Sam S.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Devisetty, Kiran] Med Coll Wisconsin, Dept Radiat Oncol, Milwaukee, WI 53226 USA. RP DeLaney, TF (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St, Boston, MA 02114 USA. EM tdelaney@partners.org NR 24 TC 3 Z9 4 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUL 1 PY 2011 VL 80 IS 3 BP 779 EP 786 DI 10.1016/j.ijrobp.2010.02.067 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 778NP UT WOS:000291711700020 PM 20864266 ER PT J AU Mak, KS Lee, LK Mak, RH Wang, S Pile-Spellman, J Abrahm, JL Prigerson, HG Balboni, TA AF Mak, Kimberley S. Lee, Leslie K. Mak, Raymond H. Wang, Shuang Pile-Spellman, John Abrahm, Janet L. Prigerson, Holly G. Balboni, Tracy A. TI INCIDENCE AND TREATMENT PATTERNS IN HOSPITALIZATIONS FOR MALIGNANT SPINAL CORD COMPRESSION IN THE UNITED STATES, 1998-2006 SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Spinal cord compression; Spine metastasis; Health care costs; Radiotherapy; Surgery ID QUALITY-OF-LIFE; METASTATIC CANCER; POPULATION; DIAGNOSIS; SURVIVAL; DISEASE; CARE; RADIOTHERAPY; PROGNOSIS; SYMPTOMS AB Purpose: To characterize patterns in incidence, management, and costs of malignant spinal cord compression (MSCC) hospitalizations in the United States, using population-based data. Methods and Materials: Using the Nationwide Inpatient Sample, an all-payer healthcare database representative of all U.S. hospitalizations, MSCC-related hospitalizations were identified for the period 1998-2006. Cases were combined with age-adjusted Surveillance, Epidemiology and End Results cancer death data to estimate annual incidence. Linear regression characterized trends in patient, treatment, and hospital characteristics, costs, and outcomes. Logistic regression was used to examine inpatient treatment (radiotherapy [RT], surgery, or neither) by hospital characteristics and year, adjusting for confounding. Results: We identified 15,367 MSCC-related cases, representing 75,876 hospitalizations. Lung cancer (24.9%), prostate cancer (16.2%), and multiple myeloma (11.1%) were the most prevalent underlying cancer diagnoses. The annual incidence of MSCC hospitalization among patients dying of cancer was 3.4%; multiple myeloma (15.0%), Hodgkin and non-Hodgkin lymphomas (13.9%), and prostate cancer (5.5%) exhibited the highest cancer-specific incidence. Over the study period, inpatient RT for NISCC decreased (odds ratio [OR] 0.68, 95% confidence interval [CI] 0.61-0.81), whereas surgery increased (OR 1.48,95% CI 1.17-1.84). Hospitalization costs for MSCC increased (5.3% per year, p < 0.001). Odds of inpatient RT were greater at teaching hospitals (OR 1.41, 95% CI 1.19-1.67), whereas odds of surgery were greater at urban institutions (OR 1.82, 95% CI 1.29-2.58). Conclusions: In the United States, patients dying of cancer have an estimated 3.4% annual incidence of MSCC requiring hospitalization. Inpatient management of MSCC varied over time and by hospital characteristics, with hospitalization costs increasing. Future studies are required to determine the impact of treatment patterns on MSCC outcomes and strategies for reducing MSCC-related costs. (c) 2011 Elsevier Inc. C1 [Prigerson, Holly G.; Balboni, Tracy A.] Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, Boston, MA 01225 USA. [Abrahm, Janet L.; Prigerson, Holly G.; Balboni, Tracy A.] Harvard Univ, Sch Med, Ctr Palliat Care, Boston, MA USA. [Lee, Leslie K.; Pile-Spellman, John] Columbia Univ, Med Ctr, Div Intervent Neuroradiol, New York, NY USA. [Mak, Raymond H.] Harvard Radiat Oncol Program, Boston, MA USA. [Wang, Shuang] Columbia Univ, Mailman Sch Publ Hlth, Dept Biostat, New York, NY USA. [Abrahm, Janet L.; Prigerson, Holly G.; Balboni, Tracy A.] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 01225 USA. [Balboni, Tracy A.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 01225 USA. RP Balboni, TA (reprint author), Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, Smith 275,44 Binney St, Boston, MA 01225 USA. EM tbalboni@lroc.harvard.edu FU Doris Duke Clinical Research Fellowship FX L.K.L. was supported by the Doris Duke Clinical Research Fellowship. NR 34 TC 24 Z9 24 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUL 1 PY 2011 VL 80 IS 3 BP 824 EP 831 DI 10.1016/j.ijrobp.2010.03.022 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 778NP UT WOS:000291711700026 PM 20630663 ER PT J AU Aristophanous, M Yap, JT Killoran, JH Chen, AB Berbeco, RI AF Aristophanous, Michalis Yap, Jeffrey T. Killoran, Joseph H. Chen, Aileen B. Berbeco, Ross I. TI FOUR-DIMENSIONAL POSITRON EMISSION TOMOGRAPHY: IMPLICATIONS FOR DOSE PAINTING OF HIGH-UPTAKE REGIONS SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE 4D PET/CT; Dose painting; Biological target volume; Lung cancer ID CELL LUNG-CANCER; RADIATION-THERAPY; FDG-PET; RADIOTHERAPY; DEFINITION; IMPACT AB Purpose: To investigate the behavior of tumor subvolumes of high [18F]-fluorodeoxyglucose (FDG) uptake as seen on clinical four-dimensional (4D) FDG-positron emission tomography (PET) scans. Methods and Materials: Four-dimensional FDG-PET/computed tomography scans from 13 patients taken before radiotherapy were available. The analysis was focused on regions of high uptake that are potential dose-painting targets. A total of 17 lesions (primary tumors and lymph nodes) were analyzed. On each one of the five phases of the 4D scan a classification algorithm was applied to obtain the region of highest uptake and segment the tumor volume. We looked at the behavior of both the high-uptake subvolume, called "Boost," and the segmented tumor volume, called "Target." We measured several quantities that characterize the Target and Boost volumes and quantified correlations between them. Results: The behavior of the Target could not always predict the behavior of the Boost. The shape deformation of the Boost regions was on average 133% higher than that of the Target. The gross to internal target volume expansion was on average 27.4% for the Target and 64% for the Boost, a statistically significant difference (p < 0.05). Finally, the inhale-to-exhale phase (20%) had the highest shape deformation for the Boost regions. Conclusions: A complex relationship between the measured quantities for the Boost and Target volumes is revealed. The results suggest that in cases in which advanced therapy techniques such as dose painting are being used, a close examination of the 4D PET scan should be performed. (c) 2011 Elsevier Inc. C1 [Aristophanous, Michalis; Killoran, Joseph H.; Chen, Aileen B.; Berbeco, Ross I.] Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02115 USA. [Aristophanous, Michalis; Yap, Jeffrey T.; Killoran, Joseph H.; Chen, Aileen B.; Berbeco, Ross I.] Harvard Univ, Sch Med, Boston, MA USA. [Yap, Jeffrey T.] Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. RP Aristophanous, M (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Brigham & Womens Canc Ctr, 75 Francis St,ASBI L2, Boston, MA 02115 USA. EM maristophanous@lroc.harvard.edu OI Chen, Aileen/0000-0002-5385-3360 NR 22 TC 13 Z9 13 U1 1 U2 5 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 JUL 1 PY 2011 VL 80 IS 3 BP 900 EP 908 DI 10.1016/j.ijrobp.2010.08.028 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 778NP UT WOS:000291711700036 PM 20950956 ER PT J AU Trofimov, A Nguyen, PL Efstathiou, JA Wang, Y Lu, HM Engelsman, M Merrick, S Cheng, CW Wong, JR Zietman, AL AF Trofimov, Alexei Nguyen, Paul L. Efstathiou, Jason A. Wang, Yi Lu, Hsiao-Ming Engelsman, Martijn Merrick, Scott Cheng, Chee-Wai Wong, James R. Zietman, Anthony L. TI INTERFRACTIONAL VARIATIONS IN THE SETUP OF PELVIC BONY ANATOMY AND SOFT TISSUE, AND THEIR IMPLICATIONS ON THE DELIVERY OF PROTON THERAPY FOR LOCALIZED PROSTATE CANCER SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Prostate cancer; 3D-conformal proton therapy; Treatment setup; Interfractional motion; Serial CT scans ID RADIOTHERAPY TREATMENT; RANGE; BEAM; CT; VERIFICATION; TOMOGRAPHY; EMISSION; PATIENT; MOTION; ERRORS AB Purpose: To quantify daily variations in the anatomy of patients undergoing radiation therapy for prostate carcinoma, to estimate their effect on dose distribution, and to evaluate the effectiveness of current standard planning and setup approaches employed in proton therapy. Methods: We used series of computed tomography data, which included the pretreatment scan, and between 21 and 43 in-room scans acquired on different treatment days, from 10 patients treated with intensity-modulated radiation therapy at Morristown Memorial Hospital. Variations in femur rotation angles, thickness of subcutaneous adipose tissue, and physical depth to the distal surface of the prostate for lateral beam arrangement were recorded. Proton dose distributions were planned with the standard approach. Daily variations in the location of the prescription isodose were evaluated. Results: In all 10 datasets, substantial variation was observed in the lateral tissue thickness (standard deviation of 1.7-3.6 mm for individual patients, variations of > 5 mm from the planning computed tomography observed in all series), and femur rotation angle (standard deviation between 1.3 degrees and 4.8 degrees, with the maximum excursion exceeding 10 degrees in 6 of 10 datasets). Shifts in the position of treated volume (98% isodose) were correlated with the variations in the lateral tissue thickness. Conclusions: Analysis suggests that, combined with image-guided setup verification, the range compensator expansion technique prevents loss of dose to target from femur rotation and soft-tissue deformation, in the majority of cases. Anatomic changes coupled with the uncertainties of particle penetration in tissue restrict possibilities for margin reduction in proton therapy of prostate cancer. (c) 2011 Elsevier Inc. C1 [Trofimov, Alexei; Efstathiou, Jason A.; Wang, Yi; Lu, Hsiao-Ming; Engelsman, Martijn; Zietman, Anthony L.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Nguyen, Paul L.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Merrick, Scott; Wong, James R.] Morristown Mem Hosp, Dept Radiat Oncol, Morristown, NJ USA. [Cheng, Chee-Wai] Indiana Univ, Dept Radiat Oncol, Midwest Proton Radiotherapy Inst, Bloomington, IN USA. RP Trofimov, A (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 30 Fruit St, Boston, MA 02114 USA. EM atrofimov@partners.org FU Massachusetts General Hospital, Proton Therapy Research and Treatment Center [C06-CA059267] FX The 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 19 TC 31 Z9 31 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. PD JUL 1 PY 2011 VL 80 IS 3 BP 928 EP 937 DI 10.1016/j.ijrobp.2010.08.006 PG 10 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 778NP UT WOS:000291711700039 PM 20947266 ER PT J AU DeLaney, TF Chen, YLE AF DeLaney, Thomas F. Chen, Yen-Lin E. TI POSITIVE SURGICAL MARGINS IN SOFT TISSUE SARCOMA TREATED WITH PREOPERATIVE RADIATION: IS A POSTOPERATIVE BOOST NECESSARY: IN REGARD TO AL YAMI ET AL. (INT J RADIAT ONCOL BIOL PHYS 2010;77:1191-1197) SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Letter ID RADIOTHERAPY; EXTREMITY; RISK C1 [DeLaney, Thomas F.; Chen, Yen-Lin E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP DeLaney, TF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUL 1 PY 2011 VL 80 IS 3 BP 959 EP 959 DI 10.1016/j.ijrobp.2011.02.030 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 778NP UT WOS:000291711700042 PM 21621120 ER PT J AU Venditti, E Bruge, F Astolfi, P Kochevar, I Damiani, E AF Venditti, Elisabetta Bruge, Francesca Astolfi, Paola Kochevar, Irene Damiani, Elisabetta TI Nitroxides and a nitroxide-based UV filter have the potential to photoprotect UVA-irradiated human skin fibroblasts against oxidative damage SO JOURNAL OF DERMATOLOGICAL SCIENCE LA English DT Article DE Nitroxide; Dermal fibroblasts; UV-filters; MMP-1; UVA; Skin photodamage; ROS ID HUMAN DERMAL FIBROBLASTS; RADIATION EXPOSED FIBROBLASTS; SUN PROTECTION FACTOR; IN-VITRO; SINGLET OXYGEN; ULTRAVIOLET-RADIATION; EXTRACELLULAR-MATRIX; INTERSTITIAL COLLAGENASE; PERCUTANEOUS-ABSORPTION; SUPEROXIDE-DISMUTASE AB Background: Antioxidants are now being incorporated into sunscreens as additional topical measure for delaying the aging process and reducing photo-damage to skin induced by excessive UVA exposure. UVA radiation reaching the skin leads to the generation of ROS (reactive oxygen species) implicated in DNA damage and activation of matrix metalloproteinase-1 (MMP-1) responsible for collagen damage and photo-aging. Nitroxides are a class of compounds endowed with versatile antioxidant activity and recently, nitroxide-based UV filters in which a nitroxide moiety has been attached to the most popular UV filter present in sunscreens have been developed. Objective: This study explores the potential photo-protective effects of these compounds on ROS production and induction of MMP-1 in cultured human dermal fibroblasts exposed to UVA. For comparison, vitamin E was also tested. Methods: The effects were assessed by measuring intracellular ROS production using a ROS-index probe and MMP-1 mRNA expression levels using quantitative real-time PCR (qPCR). Results: Exposure of fibroblasts to 18 J/cm(2) UVA lead to a two-fold increase in ROS production which was reduced to non-irradiated control levels in the presence of 50 mu M nitroxide compounds and vitamin E. Under the same conditions, a ten-fold increase in MMP-1 mRNA expression levels was observed 24 h post-UVA treatment which was significantly reduced by all nitroxide compounds but not vitamin E. Conclusion: The results of this study support the potential use of nitroxide compounds, including novel nitroxide-based UV filters, as a useful and alternative strategy for improving the efficacy of topical formulations against photo-aging and possibly photo-carcinogenesis. (C) 2011 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved. C1 [Venditti, Elisabetta; Bruge, Francesca; Damiani, Elisabetta] Univ Politecn Marche, Dipartimento Biochim Biol & Genet, I-60131 Ancona, Italy. [Astolfi, Paola] Univ Politecn Marche, Dipartimento ISAC, Sez Chim, I-60131 Ancona, Italy. [Kochevar, Irene] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA 02114 USA. RP Damiani, E (reprint author), Univ Politecn Marche, Dipartimento Biochim Biol & Genet, I-60131 Ancona, Italy. EM e.damiani@univpm.it OI Damiani, Elisabetta/0000-0002-7885-1783; Astolfi, Paola/0000-0003-3226-082X FU Polytechnic University of the Marche; MIUR FX The authors thank the Polytechnic University of the Marche and MIUR for financial support. NR 73 TC 15 Z9 16 U1 1 U2 9 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0923-1811 J9 J DERMATOL SCI JI J. Dermatol. Sci. PD JUL PY 2011 VL 63 IS 1 BP 55 EP 61 DI 10.1016/j.jdermsci.2011.03.008 PG 7 WC Dermatology SC Dermatology GA 780IA UT WOS:000291846500008 PM 21530182 ER PT J AU Schuyler, CA Ta, NN Li, YC Lopes-Virella, MF Huang, Y AF Schuyler, Corinne A. Ta, Nga N. Li, Yanchun Lopes-Virella, Maria F. Huang, Yan TI Insulin treatment attenuates diabetes-increased atherosclerotic intimal lesions and matrix metalloproteinase 9 expression in apolipoprotein E-deficient mice SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID CORONARY-ARTERY-DISEASE; HIGH GLUCOSE; MATRIX METALLOPROTEINASES; CARDIOVASCULAR-DISEASE; MMP-1 EXPRESSION; GLYCEMIC CONTROL; RECEPTOR; PLAQUES; MACROPHAGES; MIGRATION AB Patients with diabetes mellitus have increased mortality and morbidity of cardiovascular diseases compared with nondiabetic patients. Although clinical studies have shown that effective glycemic control with insulin treatment in patients with type 1 diabetes is associated with reduced cardiovascular events, the underlying mechanisms have not been well understood. In this study, we treated diabetic apolipoprotein E-deficient (apoE(-/-)) mice with insulin for 20 weeks and studied the effect of insulin treatment on intimal lesion size and matrix metalloproteinase (MMP) 9 expression known to be involved in plaque destabilization. Results showed that insulin treatment, which effectively reduced plasma glucose level in diabetic mice, attenuated diabetes-increased intimal lesion size and significantly inhibited diabetes-increased MMP9 expression, but had no effect on tissue inhibitor of metalloproteinase 1 in atherosclerotic plaques. Furthermore, we observed that insulin treatment did not reduce diabetes-increased macrophage content but inhibited interleukin 6 expression, a stimulator for MMP expression. Taken together, this study has shown for the first time that insulin treatment in diabetic apoE(-/-) mice changes atherosclerotic lesions and gene expression to a state that favors plaque stability. Journal of Endocrinology (2011) 210, 37-46 C1 [Schuyler, Corinne A.; Lopes-Virella, Maria F.; Huang, Yan] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. [Ta, Nga N.; Li, Yanchun; Lopes-Virella, Maria F.; Huang, Yan] Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, Dept Med, Charleston, SC 29425 USA. RP Huang, Y (reprint author), Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, Dept Med, 114 Doughty St, Charleston, SC 29403 USA. EM huangyan@musc.edu FU Department of Veterans Affairs; NIH [DE016353] FX This study was supported by a Merit Review Grant from the Department of Veterans Affairs and NIH grant DE016353 (to Y H). NR 38 TC 12 Z9 12 U1 1 U2 4 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD JUL PY 2011 VL 210 IS 1 BP 37 EP 46 DI 10.1530/JOE-10-0420 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 777OY UT WOS:000291633800006 PM 21478228 ER PT J AU Rattner, DW Mahvi, DM Hunter, JG AF Rattner, David W. Mahvi, David M. Hunter, John G. CA Soc Surg Alimentary Tract TI Looking Ahead: The SSAT Strategic Plan for the Next Decade SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article DE Society for Alimentary Tract; SSAT; Strategic Plan AB The Society for Surgery of the Alimentary Tract's (SSAT) mission is to advance the science and practice of surgery in the treatment of digestive disease. An essential core value of the SSAT is multidisciplinary collaboration with both its sister societies in the Digestive Disease Week (DDW) Council and other surgical societies in Gastrointestinal Surgery. In order to achieve the society's goals, the strategic plan rests on the society's values of interdisciplinary collaboration, scholarship, education, and discovery. The strategic plan also creates a meritocracy system to foster the development of future leaders for both the SSAT and the broader house of surgery. In the short term, this plan will: Re-organize committee structure and reporting responsibilities; Clarify committee goals and deliverables; Facilitate member participation in the committees and governance of the society; Enhance member services by utilizing enhanced communication strategies; Accelerate efforts to meet the Maintenance of Certification needs of the membership; Re-focus the SSAT's energy on Quality and Outcome Assessment of GI surgery; Clarify and standardize the methodology for allocating funds for new projects. Over the course of the next few years, the SSAT will: Develop a financial model that increases revenue to support the expanded tasks the society intends to undertake; Play an active role in developing the evolving training paradigms for gastrointestinal surgeons through the continuum from residency, fellowship, and early mentored practice; Continue to support development of surgeon scientists through Career Development Award; Enhance relationship with the SSAT Foundation; Continue to improve the experience of members attending DDW; Develop surgeons interested in public policy to be leaders at a national level. The strategic plan is ambitious, and the current leadership realizes that all the tasks and objectives cannot be accomplished in 1 year. There is much to do in order to keep the SSAT the premier professional society for gastrointestinal surgery. Changes in the external environment may require modifications of the priorities or the plan itself in the coming years. Implicit in this plan is the need for annual review by the Board of Trustees at the May Board Meeting so that modifications can be made as the world around us changes. C1 [Rattner, David W.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Mahvi, David M.] Northwertern Mem Hosp, Dept Surg, Chicago, IL 60611 USA. [Hunter, John G.] Oregon Hlth & Sci Univ, Dept Surg, Portland, OR 97239 USA. RP Rattner, DW (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Parkman St, Boston, MA 02114 USA. EM drattner@partners.org; dmahvi@nmh.org; hunterj@ohsu.edu NR 0 TC 1 Z9 1 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD JUL PY 2011 VL 15 IS 7 BP 1077 EP 1085 DI 10.1007/s11605-011-1524-8 PG 9 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 778JU UT WOS:000291700800002 PM 21538193 ER PT J AU Fernandez-del Castillo, C AF Fernandez-del Castillo, Carlos TI Open Pancreatic Necrosectomy: Indications in the Minimally Invasive Era SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Editorial Material DE Pancreatitis; Debridement; Necrosectomy ID NECROTIZING PANCREATITIS; MANAGEMENT; MORTALITY C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pancreas & Biliary Surg Program, Boston, MA 02114 USA. RP Fernandez-del Castillo, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pancreas & Biliary Surg Program, 15 Parkman St,ACC 460, Boston, MA 02114 USA. EM cfernandez@partners.org NR 12 TC 4 Z9 4 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD JUL PY 2011 VL 15 IS 7 BP 1089 EP 1091 DI 10.1007/s11605-011-1508-8 PG 3 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 778JU UT WOS:000291700800004 PM 21484489 ER PT J AU Eid, GM Entabi, F Watson, AR Zuckerbraun, BS Wilson, MA AF Eid, George Michel Entabi, Fateh Watson, Andrew R. Zuckerbraun, Brian S. Wilson, Mark A. TI Robotic-Assisted Laparoscopic Side-to-Side Lateral Pancreaticojejunostomy SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article DE Puestow; Pancreaticojejunostomy; Robotic C1 [Eid, George Michel] Minimally Invas Surg Ctr, Pittsburgh, PA 15213 USA. [Eid, George Michel; Entabi, Fateh; Watson, Andrew R.; Zuckerbraun, Brian S.; Wilson, Mark A.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA. [Eid, George Michel; Wilson, Mark A.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Eid, GM (reprint author), Minimally Invas Surg Ctr, Suite 390,3380 Blvd Allies, Pittsburgh, PA 15213 USA. EM eidgm@upmc.edu NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD JUL PY 2011 VL 15 IS 7 BP 1243 EP 1243 DI 10.1007/s11605-011-1495-9 PG 1 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 778JU UT WOS:000291700800027 PM 21584825 ER PT J AU Humphrey, LL Shannon, J Partin, MR O'Malley, J Chen, ZQ Helfand, M AF Humphrey, Linda L. Shannon, Jackilen Partin, Melissa R. O'Malley, Jean Chen, Zunqiu Helfand, Mark TI Improving the Follow-Up of Positive Hemoccult Screening Tests: An Electronic Intervention SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE colorectal cancer; cancer screening; cancer prevention ID FECAL-OCCULT-BLOOD; COLORECTAL-CANCER; NOTIFICATION; MORTALITY; QUALITY; CARE; US AB BACKGROUND: Four population-based studies of screening for CRC with fecal occult blood testing (FOBT) have shown that mortality can be significantly reduced. However, nearly half of all positive screening tests are not appropriately evaluated. OBJECTIVES: We evaluated whether an electronic record intervention improved the follow-up of patients with a positive FOBT (FOBT+) result. DESIGN: We conducted a cluster randomized trial involving four Veteran's Affairs (VA) medical centers pair-matched by colonoscopy volume and randomized within the pair to receive the electronic intervention or usual care. PARTICIPANTS: All patients with FOBT+ results at participating facilities during a matched pre- and post-intervention time period. INTERVENTIONS: In the two intervention sites, an electronic consult that imported relevant clinical information was automatically submitted to the gastroenterology (GI) clinic for all FOBT+ patients at the time the result was recorded in the laboratory. In both intervention and control sites (usual care), PCPs continued to be notified of FOBT+ results in the usual manner MEASURES: Pre- and post-intervention changes in the proportion of FOBT+ patients having: (1) a GI consult or (2) a GI consult plus complete diagnostic evaluation (CDE) of the colon within 30, 90 and 180 days were compared across intervention and control sites. Log rank tests were used to determine statistical significance. RESULTS: The 30-, 90- and 180-day GI consult rates improved 21-33 % (p < 0.001) among intervention sites, but did not change in the usual care sites. Thirty-, 90- and 180-day CDE rates improved 9-31% (p < 0.03) in intervention sites, but did not significantly change in the usual care sites. Time to GI consult and CDE decreased significantly over time in the intervention sites (p < 0.001), but remained unchanged in the usual care sites. CONCLUSIONS: The relatively simple electronic intervention evaluated can significantly improve the follow-up of FOBT+ results. Interventions such as this could improve patient care and may be applicable to other practice settings, as well as other types of tests. C1 [Humphrey, Linda L.; Shannon, Jackilen; Helfand, Mark] Portland VA Med Ctr, Portland, OR 97239 USA. [Humphrey, Linda L.; Helfand, Mark] Oregon Hlth & Sci Univ, Dept Informat & Clin Epidemiol, Portland, OR 97201 USA. [Humphrey, Linda L.; Helfand, Mark] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Humphrey, Linda L.] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. [Partin, Melissa R.] Minneapolis Vet Affairs Med Ctr, Minneapolis, MN USA. [O'Malley, Jean; Chen, Zunqiu] Oregon Hlth & Sci Univ, Oregon Clin & Translat Res Ctr, Portland, OR 97201 USA. RP Humphrey, LL (reprint author), Portland VA Med Ctr, Mail Code P-3 Med,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM Linda.Humphrey@va.gov FU VA HSRD [CRT-02-059]; Oregon Clinical and Translational Research Institute (OCTRI); National Center for Research Resources (NCRR), National Institutes of Health (NIH) [UL1 RR024140 01]; NIH Roadmap for Medical Research FX This research was funded by VA HSR&D grant number CRT-02-059. This publication was made possible with support from the Oregon Clinical and Translational Research Institute (OCTRI); grant number UL1 RR024140 01 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH); and NIH Roadmap for Medical Research. The funding organizations had no direct involvement in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. We are grateful for the help of Barbara Genovese, MS; Courtney Maxcy, BS; Paige Farris, MSW; David Pauly, MBA, MSW; David Lieberman, MD; Joan Ash, PhD; Robert Socherman PhD; David Douglas, MD; and Michele Freeman, MPH, in the completion of this study and manuscript. We also acknowledge the help of the many co-investigators and programming staff involved with this study at each of the participating sites. NR 22 TC 12 Z9 12 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 JUL PY 2011 VL 26 IS 7 BP 691 EP 697 DI 10.1007/s11606-011-1639-3 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 778JY UT WOS:000291701200006 PM 21327529 ER PT J AU Lembke, A Bradley, KA Henderson, P Moos, R Harris, AHS AF Lembke, Anna Bradley, Katharine A. Henderson, Patricia Moos, Rudolf Harris, Alex H. S. TI Alcohol Screening Scores and the Risk of New-Onset Gastrointestinal Illness or Related Hospitalization SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE alcohol; AUDIT; gastrointestinal; hospitalization; new-onset; women ID IDENTIFICATION TEST AUDIT; USE DISORDERS; GENERAL-POPULATION; VETERANS-AFFAIRS; PRIMARY-CARE; DRINKING; QUESTIONNAIRES; CONSUMPTION; MORTALITY; SERVICES AB BACKGROUND: Excessive alcohol use is associated with a variety of negative health outcomes, including liver disease, upper gastrointestinal bleeding, and pancreatitis. OBJECTIVE: To determine the 2-year risk of gastrointestinal-related hospitalization and new-onset gastrointestinal illness based on alcohol screening scores. DESIGN: Retrospective cohort study. PARTICIPANTS: Male (N = 215, 924) and female (N = 9,168) outpatients who returned mailed questionnaires and were followed for 24 months. MEASUREMENTS: Alcohol Use Disorder Identification Test-Consumption Questionnaire (AUDIT-C), a validated three-item alcohol screening questionnaire (0-12 points). RESULTS: Two-year risk of hospitalization with a gastrointestinal disorder was increased in men with AUDIT-C scores of 5-8 and 9-12 (OR 1.54, 95% CI = 1.27-1.86; and OR 3.27; 95% CI = 2.62-4.09 respectively), and women with AUDIT-C scores of 9-12 (OR 6.84, 95% CI = 1.85 - 25.37). Men with AUDIT-C scores of 5-8 and 9-12 had increased risk of new-onset liver disease (OR 1.49, 95% CI = 1.30-1.71; and OR 2.82, 95% CI = 2.38-3.34 respectively), and new-onset of upper gastrointestinal bleeding (OR 1.28, 95% CI = 1.05-1.57; and OR 2.14, 95% CI = 1.54-2.97 respectively). Two-year risk of new-onset pancreatitis in men with AUDIT -C scores 9-12 was also increased (OR 2.14; 95% CI = 1.54-2.97). CONCLUSIONS: Excessive alcohol use as determined by AUDIT-C is associated with 2-year increased risk of gastrointestinal-related hospitalization in men and women and new-onset liver disease, upper gastrointestinal bleeding, and pancreatitis in men. These results provide risk information that clinicians can use in evidence-based conversations with patients about their alcohol consumption. C1 [Lembke, Anna] Stanford Univ, Sch Med, Dept Psychiat, Palo Alto, CA 94305 USA. [Bradley, Katharine A.] Vet Affairs VA Puget Sound Hlth Care Syst, Grp Hlth Res Inst, Hlth Serv Res & Dev HSR&D NW Ctr Excellence, Seattle, WA USA. [Bradley, Katharine A.] Grp Hlth Cooperat Puget Sound, Dept Med, Hlth Serv, Seattle, WA 98121 USA. [Bradley, Katharine A.] VA Puget Sound, Seattle, WA USA. [Bradley, Katharine A.] Univ WA, Seattle, WA USA. [Henderson, Patricia; Moos, Rudolf; Harris, Alex H. S.] VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, Palo Alto, CA USA. RP Lembke, A (reprint author), Stanford Univ, Sch Med, Dept Psychiat, 401 Quarry Rd, Palo Alto, CA 94305 USA. EM alembke@stanford.edu FU NIAAA [R03 AA016793-01]; VA Office of Quality and Performance FX This paper does not necessarily represent the views of the Department of Veterans Affairs, Stanford University, or University of Washington. This work was made possible through a grant from NIAAA (R03 AA016793-01) and support from the VA Office of Quality and Performance. NR 25 TC 13 Z9 13 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2011 VL 26 IS 7 BP 777 EP 782 DI 10.1007/s11606-011-1688-7 PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 778JY UT WOS:000291701200019 PM 21455813 ER PT J AU Brown, DR Calpe, S Keszei, M Wang, NH McArdel, S Terhorst, C Sharpe, AH AF Brown, Daniel R. Calpe, Silvia Keszei, Marton Wang, Ninghai McArdel, Shannon Terhorst, Cox Sharpe, Arlene H. TI Cutting Edge: An NK Cell-Independent Role for Slamf4 in Controlling Humoral Autoimmunity SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; MURINE LUPUS; GENETIC DISSECTION; C57BL/6 MICE; 2B4 GENE; ERYTHEMATOSUS; ASSOCIATION; RECEPTORS; TOLERANCE; CLUSTER AB Several genes within a syntenic region of human and mouse chromosome 1 are associated with predisposition to systemic lupus erythematosus. Analyses of lupusprone congenic mice have pointed to an important role for the signaling lymphocyte activation molecule family (slamf) 6 surface receptor in lupus pathogenesis. In this article, we demonstrate that a second member of the Slamf gene family, Slamf4 (Cd244), contributes to lupus-related autoimmunity. B6.Slamf4(-/-) mice spontaneously develop activated CD4 T cells and B cells and increased numbers of T follicular helper cells and a proportion develop autoantibodies to nuclear Ags. B6.Slamf4(-/-) mice also exhibit markedly increased autoantibody production in the B6.C-H-2bm12/KhEg -> B6 transfer model of lupus. Although slamf4 function is best characterized in NK cells, the enhanced humoral autoimmunity of B6.Slamf4(-/-) mice is NK cell independent, as judged by depletion studies. Taken together, our findings reveal that slamf4 has an NK cell-independent negative regulatory role in the pathogenesis of lupus a normally non-autoimmune prone genetic background. The Journal of Immunology, 2011, 187: 21-25. C1 [Brown, Daniel R.; McArdel, Shannon; Sharpe, Arlene H.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Brown, Daniel R.; McArdel, Shannon; Sharpe, Arlene H.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Brown, Daniel R.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Calpe, Silvia; Keszei, Marton; Wang, Ninghai; Terhorst, Cox] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Immunol, Boston, MA 02115 USA. RP Sharpe, AH (reprint author), Harvard Univ, Sch Med, Dept Pathol, 77 Ave Louis Pasteur,NRB-837, Boston, MA 02115 USA. EM arlene_sharpe@hms.harvard.edu RI Keszei, Marton/F-3295-2014 OI Keszei, Marton/0000-0002-1158-2179 FU National Institutes of Health [PO1-AI065687, K08AR0578b1] FX This work was supported by National Institutes of Health Grants PO1-AI065687 (to C.T. and A.H.S.) and K08AR0578b1 (to D.R.B.). NR 20 TC 17 Z9 17 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 2011 VL 187 IS 1 BP 21 EP 25 DI 10.4049/jimmunol.1100510 PG 5 WC Immunology SC Immunology GA 779RQ UT WOS:000291799300006 PM 21622868 ER PT J AU Wang, S Villablanca, EJ De Calisto, J Gomes, DCO Nguyen, DD Mizoguchi, E Kagan, JC Reinecker, HC Hacohen, N Nagler, C Xavier, RJ Rossi-Bergmann, B Chen, YB Blomhoff, R Snapper, SB Mora, JR AF Wang, Sen Villablanca, Eduardo J. De Calisto, Jaime Gomes, Daniel C. O. Nguyen, Deanna D. Mizoguchi, Emiko Kagan, Jonathan C. Reinecker, Hans-Christian Hacohen, Nir Nagler, Cathryn Xavier, Ramnik J. Rossi-Bergmann, Bartira Chen, Yi-Bin Blomhoff, Rune Snapper, Scott B. Mora, J. Rodrigo TI MyD88-Dependent TLR1/2 Signals Educate Dendritic Cells with Gut-Specific Imprinting Properties SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TOLL-LIKE RECEPTOR; ADAPTIVE IMMUNE-RESPONSES; ACTIVATED PROTEIN-KINASE; CD8 T-CELLS; RETINOIC-ACID; LAMINA-PROPRIA; SYNERGISTICALLY TRIGGER; TERMINAL KINASE; PEYERS PATCH; IN-VIVO AB Gut-associated dendritic cells (DC) synthesize all-trans retinoic acid, which is required for inducing gut-tropic lymphocytes. Gut-associated DC from MyD88(-/-) mice, which lack most TLR signals, expressed low levels of retinal dehydrogenases (critical enzymes for all-trans retinoic acid biosynthesis) and were significantly impaired in their ability to induce gut-homing T cells. Pretreatment of extraintestinal DC with a TLR1/2 agonist was sufficient to induce retinal dehydrogenases and to confer these DC with the capacity to induce gut-homing lymphocytes via a mechanism dependent on MyD88 and JNK/MAPK. Moreover, gut-associated DC from TLR2(-/-) mice, or from mice in which JNK was pharmacologically blocked, were impaired in their education to imprint gut-homing T cells, which correlated with a decreased induction of gut-tropic T cells in TLR2(-/-) mice upon immunization. Thus, MyD88-dependent TLR2 signals are necessary and sufficient to educate DC with gut-specific imprinting properties and contribute in vivo to the generation of gut-tropic T cells. The Journal of Immunology, 2011, 187: 141-150. C1 [Wang, Sen; Villablanca, Eduardo J.; De Calisto, Jaime; Gomes, Daniel C. O.; Nguyen, Deanna D.; Mizoguchi, Emiko; Reinecker, Hans-Christian; Xavier, Ramnik J.; Snapper, Scott B.; Mora, J. Rodrigo] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Gomes, Daniel C. O.; Rossi-Bergmann, Bartira] Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, BR-21941590 Rio De Janeiro, Brazil. [Kagan, Jonathan C.] Harvard Univ, Sch Med, Gastrointestinal Unit, Childrens Hosp, Boston, MA 02115 USA. [Hacohen, Nir] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [Nagler, Cathryn] Univ Chicago, Dept Pathol, Div Biol Sci, Comm Immunol, Chicago, IL 60637 USA. [Blomhoff, Rune] Univ Oslo, Inst Basic Med Sci, N-0316 Oslo, Norway. RP Mora, JR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St,GRJ-815, Boston, MA 02114 USA. EM j_rodrigo_mora@hms.harvard.edu RI Impetam, INCT/K-2199-2013; Villablanca, Eduardo/E-1380-2016 OI Villablanca, Eduardo/0000-0001-9522-9729 FU Crohn's and Colitis Foundation of America; National Institutes of Health [1DP2OD006512-01]; Cancer Research Institute; Massachusetts General Hospital; Massachusetts Life Science Center FX D.D.N. was supported by grants from the Crohn's and Colitis Foundation of America and the National Institutes of Health. J.C.K. was supported by a grant from the National Institutes of Health. Y.-B.C. is a Special Fellow in Clinical Research of the Leukemia and Lymphoma Society. S. B. S. was supported by grants from the National Institutes of Health. J.R.M. was supported by grants from the Crohn's and Colitis Foundation of America and the Cancer Research Institute, a Massachusetts General Hospital Howard Goodman fellowship, a Massachusetts Life Science Center award, and a National Institutes of Health Director's New Innovator award (1DP2OD006512-01). NR 63 TC 41 Z9 43 U1 0 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 2011 VL 187 IS 1 BP 141 EP 150 DI 10.4049/jimmunol.1003740 PG 10 WC Immunology SC Immunology GA 779RQ UT WOS:000291799300020 PM 21646294 ER PT J AU Curiel-Lewandrowski, C Nijsten, T Gomez, ML Hollestein, LM Atkins, MB Stern, RS AF Curiel-Lewandrowski, Clara Nijsten, Tamar Gomez, Maria L. Hollestein, Loes M. Atkins, Michael B. Stern, Robert S. TI Long-Term Use of Nonsteroidal Anti-inflammatory Drugs Decreases the Risk of Cutaneous Melanoma: Results of a United States Case-Control Study SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID SQUAMOUS-CELL CARCINOMAS; SUN EXPOSURE; PRIMARY PREVENTION; COLORECTAL-CANCER; BASAL-CELL; METAANALYSIS; STATINS; SKIN; EPIDEMIOLOGY; HELIOS AB Experimental and observational studies continue to demonstrate conflicting results regarding the role of several commonly used drugs as melanoma chemopreventive agents. This case-control study was designed to assess the associations between cutaneous melanoma (CM) and exposure to nonsteroidal anti-inflammatory drugs (NSAIDs) and statins in current users. A total of 400 CM and 600 eligible age-and gender-matched community-based controls were prospectively recruited and interviewed. We assessed participants' demographic characteristics, CM risk factors, and current and previous use of medications. Multivariable conditional logistic regression models were used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for associations between NSAIDs and/or aspirin (ASA), statin exposure, and CM risk. Half of the subjects were men (mean age 60 years). After adjusting for confounders, use of any type of NSAIDs for more than 5 years significantly reduced the risk of melanoma development compared with the low-exposure group (adjusted OR=0.57; 95% CI=0.43-0.77). Subgroup analyses showed that the observed risk reduction was primarily driven by continuous ASA use (45 years adjusted OR=0.51, 95% CI=0.35-0.75). No significant protective effect was observed with statin exposure (OR=0.97, 95% CI=0.73-1.29). Long-term use of NSAIDs, especially ASA, is associated with a significantly decreased risk of CM development. Clinical intervention studies are warranted to further investigate the potential role of ASA and other NSAIDs as chemopreventive agents for CM. C1 [Curiel-Lewandrowski, Clara] Univ Arizona, Arizona Canc Ctr, Dept Dermatol, Tucson, AZ 85724 USA. [Curiel-Lewandrowski, Clara; Gomez, Maria L.; Stern, Robert S.] Harvard Univ, Sch Med, Dept Dermatol, BIDMC, Boston, MA 02115 USA. [Nijsten, Tamar] Erasmus MC, Dept Dermatol, Rotterdam, Netherlands. [Hollestein, Loes M.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Atkins, Michael B.] Harvard Univ, Sch Med, Dept Hematol Oncol, BIDMC, Boston, MA USA. RP Curiel-Lewandrowski, C (reprint author), Univ Arizona, Arizona Canc Ctr, Dept Dermatol, 1515 N Campbell Ave,POB 245024, Tucson, AZ 85724 USA. EM ccuriel@azcc.arizona.edu RI Nijsten, Tamar/A-5876-2009; OI Nijsten, Tamar/0000-0001-9940-2875; Hollestein, Loes/0000-0001-8922-6791 FU Harry Lloyd Charitable Trust; Melanoma Foundation of New England; Kokos Research Fund; Harvard SPORE in Skin Cancer; Alan and Janice Levin Endowed Chair in Cancer Research, University of Arizona FX We thank the Dermatology and Medical Oncology Departments and the BIDMC, MGH, BWH/DFCI, and Dermatology Associates of Concord for their participation and referral of melanoma cases. We also thank Dr David Kaufman (Boston University) for his guidance in the design of drug exposure-related questions and access to the town book registry library, and Dr Martin Weinstock (Brown University) and Dr Jan Nico Bouwes (Leiden University Medical Center) for their guidance in the design of melanoma risk factor-related questions; the Survey Center at Harvard Medical School for their quality assessment on the study questionnaire; the Melanoma Prevention Working Group members for their valuable critiques at the time of the study design; Kathy Saboda, MS (University of Arizona), for her support on the preparation of the study-related scientific presentations; and Drs Robin Harris and Lois Loescher for their valuable critiques on the preparation of the manuscript. This work was supported by funding from the Harry Lloyd Charitable Trust; the Melanoma Foundation of New England; Kokos Research Fund; Harvard SPORE in Skin Cancer; and the Alan and Janice Levin Endowed Chair in Cancer Research, University of Arizona. NR 32 TC 41 Z9 42 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2011 VL 131 IS 7 BP 1460 EP 1468 DI 10.1038/jid.2011.58 PG 9 WC Dermatology SC Dermatology GA 777SI UT WOS:000291644900013 PM 21390049 ER PT J AU Fox, LM William, CM Adamowicz, DH Pitstick, R Carlson, GA Spires-Jones, TL Hyman, BT AF Fox, Leora M. William, Christopher M. Adamowicz, David H. Pitstick, Rose Carlson, George A. Spires-Jones, Tara L. Hyman, Bradley T. TI Soluble tau Species, Not Neurofibrillary Aggregates, Disrupt Neural System Integration in a tau Transgenic Model SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE Alzheimer; Arc; Environmental enrichment; Neurofibrillary tangle; rTg4510; Tauopathy ID MOUSE MODEL; ALZHEIMERS-DISEASE; SYNAPTOPHYSIN MESSAGE; GENE-TRANSCRIPTION; BETA OLIGOMERS; AMYLOID-BETA; ARC PROTEIN; EXPRESSION; NEURONS; HIPPOCAMPAL AB Neurofibrillary tangles are a feature of Alzheimer disease and other tauopathies, and although they are generally believed to be markers of neuronal pathology, there is little evidence evaluating whether tangles directly impact neuronal function. To investigate the response of cells in hippocampal circuits to complex behavioral stimuli, we used an environmental enrichment paradigm to induce expression of an immediate-early gene, Arc, in the rTg4510 mouse model of tauopathy. These mice reversibly overexpress P301L tau and exhibit substantial neurofibrillary tangle deposition, neuronal loss, and memory deficits. Using fluorescent in situ hybridization to detect Arc messenger RNA, we found that rTg4510 mice have impaired hippocampal Arc expression both without stimulation and in response to environmental enrichment; this likely reflects the combination of functional impairments of existing neurons and loss of neurons. However, tangle-bearing cells were at least as likely as non-tangle-bearing neurons to exhibit Arc expression in response to enrichment. Transgene suppression with doxycycline for 6 weeks resulted in increased percentages of Arc-positive cells in rTg4510 brains compared with untreated transgenics, restoring enrichment-induced Arc messenger RNA levels to that of wild-type controls despite the continued presence of neurofibrillary pathology. We interpret these data to indicate that soluble tau contributes to impairment of hippocampal function, although tangles do not preclude neurons from responding in a functional circuit. C1 [Fox, Leora M.; William, Christopher M.; Adamowicz, David H.; Spires-Jones, Tara L.; Hyman, Bradley T.] Harvard Univ, MassGen Inst Neurodegenerat Dis, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA. [Pitstick, Rose; Carlson, George A.] McLaughlin Res Inst, Great Falls, MT USA. RP Hyman, BT (reprint author), Harvard Univ, MassGen Inst Neurodegenerat Dis, Massachusetts Gen Hosp, Sch Med, 114 16th St, Charlestown, MA 02129 USA. EM bhyman@partners.org OI William, Christopher/0000-0001-8933-1639; Spires-Jones, Tara/0000-0003-2530-0598 FU Alzheimer's Association; National Institutes of Health [AG08487, K99AG33670, K08 NS069811, AG026249] FX This work was supported by an Alzheimer's Association Zenith Award and by National Institutes of Health grants AG08487, K99AG33670, K08 NS069811, and AG026249. NR 30 TC 36 Z9 37 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUL PY 2011 VL 70 IS 7 BP 588 EP 595 DI 10.1097/NEN.0b013e318220a658 PG 8 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 779NN UT WOS:000291785100004 PM 21666499 ER PT J AU Xu, YF Liu, M Peng, B Che, JP Zhang, HM Yan, Y Wang, GC Wu, YC Zheng, JH AF Xu, Yun-fei Liu, Min Peng, Bo Che, Jian-ping Zhang, Hai-min Yan, Yang Wang, Guang-chun Wu, Yi-chao Zheng, Jun-hua TI Protective Effects of SP600125 on Renal Ischemia-Reperfusion Injury in Rats SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE ischemia; reperfusion; JNK; kidney ID N-TERMINAL KINASE; JNK INHIBITOR; JUN; APOPTOSIS AB Background. Ischemia/reperfusion injury (IRI) has a negative effect on renal allograft survival. Using a rat model of kidney IRI in this study, we investigated the overall effect of selective c-Jun N-terminal kinase (JNK) inhibitor SP600125 on renal IRI events. Methods. All 45 Fisher rats were anesthetized and renal IRI model was established by 45 min clamp of bilateral renal pedicles and 24 h reperfusion. Vehicle solution or SP600125 solution was intraperitoneally injected 45 min before ischemia, respectively. Analysis of renal histology, function, reactive oxygen species (ROS) expression, JNK phosphorylation status, as well as intra-renal pro-inflammatory cytokines expression was evaluated in this study. Results. After IRI, the levels of blood urea nitrogen, creatinine, tissue malondialdehyde, TNF-alpha, IL-1 beta, IL-6 were all elevated significantly, while superoxide dismutase, catalase activity were decreased. Histologic findings showed severe devastating lesions and increased rodent cell apoptosis; SP600125 effectively improved morphologic features, reversed above-mentioned parameters, and significantly attenuated c-Jun phosphorylation, as well as intra-renal pro-inflammatory cytokines expression compared with vehicle-treated group. Conclusion. These data demonstrate that inhibition of c-Jun with SP600125 is capable of attenuating renal IRI, which might be a novel therapy target. (C) 2011 Elsevier Inc. All rights reserved. C1 [Xu, Yun-fei; Liu, Min; Peng, Bo; Che, Jian-ping; Zhang, Hai-min; Yan, Yang; Wang, Guang-chun; Zheng, Jun-hua] Tongji Univ, Shanghai Peoples Hosp 10, Dept Urol, Shanghai 200072, Peoples R China. [Wu, Yi-chao] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Zheng, JH (reprint author), Tongji Univ, Shanghai Peoples Hosp 10, Dept Urol, Shanghai 200072, Peoples R China. EM lucky_lm@263.net OI Liu, Min/0000-0002-8117-4808 FU National Natural Science Foundation of China [81000311] FX This work was supported by a research grant from the National Natural Science Foundation of China (no. 81000311). NR 21 TC 10 Z9 10 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD JUL PY 2011 VL 169 IS 1 BP E77 EP E84 DI 10.1016/j.jss.2011.02.021 PG 8 WC Surgery SC Surgery GA 778ED UT WOS:000291682500010 PM 21492872 ER PT J AU Wright, CD AF Wright, Cameron D. TI Historical perspectives of The American Association for Thoracic Surgery: Richard H. Sweet (1901-1962) SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Editorial Material ID TRANSTHORACIC RESECTION; ESOPHAGUS; STOMACH; TUMORS C1 Massachusetts Gen Hosp, Dept Thorac Surg, Boston, MA 02114 USA. RP Wright, CD (reprint author), Massachusetts Gen Hosp, Dept Thorac Surg, Blake 1570,55 Fruit St, Boston, MA 02114 USA. EM wright.cameron@mgh.harvard.edu NR 5 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD JUL PY 2011 VL 142 IS 1 BP 18 EP 19 DI 10.1016/j.jtcvs.2011.01.005 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 778QC UT WOS:000291718300005 PM 21683835 ER PT J AU Pezzolesi, MG Poznik, GD Skupien, J Smiles, AM Mychaleckyj, JC Rich, SS Warram, JH Krolewski, AS AF Pezzolesi, Marcus G. Poznik, G. David Skupien, Jan Smiles, Adam M. Mychaleckyj, Josyf C. Rich, Stephen S. Warram, James H. Krolewski, Andrzej S. TI An intergenic region on chromosome 13q33.3 is associated with the susceptibility to kidney disease in type 1 and 2 diabetes SO KIDNEY INTERNATIONAL LA English DT Article DE diabetic nephropathy; genetic association; type 1 diabetes; type 2 diabetes ID GENOME-WIDE ASSOCIATION; STAGE RENAL-DISEASE; AFRICAN-AMERICANS; NEPHROPATHY; SCAN; POPULATION; MELLITUS; GENES; LOCI; ESRD AB A genome-wide association scan of the Genetics of Kidneys in Diabetes (GoKinD) collections identified four novel susceptibility loci, located on chromosomes 7p14.3, 9q21.32, 11p15.4, and 13q33.3 associated with type 1 diabetic nephropathy. A recent evaluation of these loci in Japanese patients with type 2 diabetes supported an association at the 13q33.3 locus. To follow up these findings, we determined whether single-nucleotide polymorphisms (SNPs) at these same four loci were associated with diabetic nephropathy in the Joslin Study of Genetics of Nephropathy in Type 2 Diabetes collection. A total of 6 SNPs across these loci were genotyped in 646 normoalbuminuric controls and in 743 nephropathy patients of European ancestry. A significant association was identified at the 13q33.3 locus (rs9521445: P = 4.4 x 10(-3)). At this same locus, rs1411766 was also significantly associated with type 2 diabetic nephropathy (P = 0.03). Meta-analysis of these data with those of the Japanese and GoKinD collections significantly improved the strength of the association (P = 9.7 x 10(-9)). In addition, there was a significant association at the 11p15.4 locus (rs451041: P = 0.02). Thus, associations identified in the GoKinD collections on chromosomes 11p15.4 (near the CARS gene) and 13q33.3 (within an intergenic region between MYO16 and IRS2) are susceptibility loci of kidney disease common to both type 1 and 2 diabetes. C1 [Pezzolesi, Marcus G.; Poznik, G. David; Skupien, Jan; Smiles, Adam M.; Warram, James H.; Krolewski, Andrzej S.] Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Res, Boston, MA 02215 USA. [Pezzolesi, Marcus G.; Skupien, Jan; Krolewski, Andrzej S.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Mychaleckyj, Josyf C.; Rich, Stephen S.] Univ Virginia, Sch Med, Ctr Publ Hlth Genom, Charlottesville, VA 22908 USA. RP Krolewski, AS (reprint author), Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM Andrzej.Krolewski@joslin.harvard.edu FU National Institutes of Health (NIH) [DK58549, DK77532, DK36836]; Joslin Diabetes Center's NIH [DK007260-31]; Juvenile Diabetes Research Foundation (JDRF) [3-2009-397] FX We acknowledge the grant support from the National Institutes of Health (NIH) (DK58549 and DK77532 to ASK and DK36836 to the Genetics Core of the Diabetes and Endocrinology Research Center at the Joslin Diabetes Center). We also acknowledge the Joslin Diabetes Center's NIH T32 Training Grant (DK007260-31 to MGP) and support from the Juvenile Diabetes Research Foundation (JDRF) (3-2009-397 to JS). NR 22 TC 13 Z9 13 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 JUL PY 2011 VL 80 IS 1 BP 105 EP 111 DI 10.1038/ki.2011.64 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 778DH UT WOS:000291679400015 PM 21412220 ER PT J AU Hausmann, LRM Hannon, MJ Kresevic, DM Hanusa, BH Kwoh, CK Ibrahim, SA AF Hausmann, Leslie R. M. Hannon, Michael J. Kresevic, Denise M. Hanusa, Barbara H. Kwoh, C. Kent Ibrahim, Said A. TI Impact of Perceived Discrimination in Healthcare on Patient-Provider Communication SO MEDICAL CARE LA English DT Article DE social discrimination; communication; physician patient relations; minority health; Veterans health ID INTERACTION ANALYSIS SYSTEM; QUALITY-OF-CARE; AFRICAN-AMERICAN; PHYSICIANS COMMUNICATION; COMMUNITY SAMPLE; RACIAL BIAS; RACE; ASSOCIATION; PERCEPTIONS; DISPARITIES AB Background: The impact of patients' perceptions of discrimination in healthcare on patient-provider interactions is unknown. Objective: To examine association of past perceived discrimination with subsequent patient-provider communication. Research Design: Observational cross-sectional study. Subjects: African-American (N = 100) and white (N = 253) patients treated for osteoarthritis by orthopedic surgeons (N = 63) in 2 Veterans Affairs facilities. Measures: Patients were surveyed about past experiences with racism and classism in healthcare settings before a clinic visit. Visits were audio-recorded and coded for instrumental and affective communication content (biomedical exchange, psychosocial exchange, rapport-building, and patient engagement/activation) and nonverbal affective tone. After the encounter, patients rated visit informativeness, provider warmth/respectfulness, and ease of communicating with the provider. Regression models stratified by patient race assessed the associations of racism and classism with communication outcomes. Results: Perceived racism and classism were reported by more African-American patients than by white patients (racism: 70% vs. 26% and classism: 73% vs. 53%). High levels of perceived racism among African-American patients was associated with less positive nonverbal affect among patients [beta = -0.41, 95% confidence interval (CI) = -0.73 to -0.09] and providers (beta = -0.34, 95% CI = -0.66 to -0.01) and with low patient ratings of provider warmth/respectfulness [odds ratio (OR) = 0.19, 95% CI = 0.05-0.72] and ease of communication (OR = 0.22, 95% CI = 0.07-0.67). Any perceived racism among white patients was associated with less psychosocial communication (beta = -4.18, 95% CI = -7.68 to -0.68), and with low patient ratings of visit informativeness (OR = 0.40, 95% CI = 0.23-0.71) and ease of communication (OR = 0.43, 95% CI = 0.20-0.89). Perceived classism yielded similar results. Conclusions: Perceptions of past racism and classism in healthcare settings may negatively impact the affective tone of subsequent patient-provider communication. C1 [Hausmann, Leslie R. M.; Hannon, Michael J.; Hanusa, Barbara H.; Kwoh, C. Kent] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Hausmann, Leslie R. M.; Hannon, Michael J.; Hanusa, Barbara H.; Kwoh, C. Kent] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Kresevic, Denise M.] Univ Hosp Case Med Ctr, Louis Stokes DVA Med Ctr, Cleveland, OH USA. [Ibrahim, Said A.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Ibrahim, Said A.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Hausmann, LRM (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. EM leslie.hausmann@gmail.com FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development Service [IIR 04-137]; Veterans Affairs Health Services [RCD 06-287, ER 0280-1]; National Institutes of Musculoskeletal and Skin Disorders [1K24AR055259-01] FX This study was supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development Service (IIR 04-137, PI: Said A. Ibrahim). Dr. Hausmann's effort was supported by the Veterans Affairs Health Services Research and Development Career Development Program (RCD 06-287 and ER 0280-1). Dr. Ibrahim was also supported by a K24 Award (1K24AR055259-01) from the National Institutes of Musculoskeletal and Skin Disorders. The views expressed here are those of the authors and do not represent those of the Department of Veterans Affairs or the United States Government. NR 46 TC 32 Z9 34 U1 2 U2 14 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 JUL PY 2011 VL 49 IS 7 BP 626 EP 633 DI 10.1097/MLR.0b013e318215d93c PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 778VC UT WOS:000291735100003 PM 21478769 ER PT J AU Kpodzo, DS Calderwood, MS Ruchelsman, DE Abramson, JS Piris, A Winograd, JM Kotton, CN AF Kpodzo, Dzifa S. Calderwood, Michael S. Ruchelsman, David E. Abramson, Jeremy S. Piris, Adriano Winograd, Jonathan M. Kotton, Camille N. TI Primary subcutaneous Alternaria alternata infection of the hand in an immunocompromised host SO MEDICAL MYCOLOGY LA English DT Article DE Alternaria spp.; fungal hand infections; immunocompromised; surgical management; antifungal therapy ID IN-VITRO ACTIVITIES; CUTANEOUS-ALTERNARIOSIS; TRANSPLANT RECIPIENTS; CLINICAL-FEATURES; PATIENT; PHEOHYPHOMYCOSIS; VORICONAZOLE; MANAGEMENT; LEUKEMIA; POLLEN AB We describe a case of a progressive subcutaneous Alternaria alternata infection in the hand of a patient with chronic lymphocytic leukemia (CLL). The diagnosis was based upon the examination of tissue biopsy and isolation of the etiologic agent in culture. The identity of the isolate was determined by phenotypic characteristics and by sequencing the ITS and D1/D2 regions of the rDNA. Despite combination therapy with voriconazole and micafungin, the lesion continued to progress. Posaconazole therapy, along with surgical excision of the infected tissue, resulted in the eradication of infection. The limitations of the clinical management of invasive Alternaria infections are discussed.5 ng/mL), circumferential margin involvement, and a low-lying position may identify T3N0 patients at high risk for local recurrence who may benefit from the addition of radiation therapy. However, recent randomized data suggest an improvement in local control and disease-free survival with preoperative radiation therapy compared with selective postoperative radiation therapy in all patient subgroups, arguing in favor of routine preoperative therapy. Additionally, rates of clinical understaging may exceed 20%, representing the percentage of patients who would require the delivery of postoperative radiotherapy with its associated sequelae. Future prospective randomized studies of T3N0 patients with upfront stratification by known prognostic factors and studies evaluating the molecular profile of rectal cancers hold the promise of better classifying patients at high risk of local and systemic recurrence, and thus, in need of adjuvant radiation and chemotherapy. Semin Radiat Oncol 21:212-219 Published by Elsevier Inc. C1 [Wo, Jennifer Y.; Hong, Theodore S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. [Mamon, Harvey J.] Harvard Univ, Brigham & Womens Hosp, Boston, MA 02115 USA. [Ryan, David P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. RP Wo, JY (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM jwo@partners.org NR 44 TC 10 Z9 11 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 1053-4296 EI 1532-9461 J9 SEMIN RADIAT ONCOL JI Semin. Radiat. Oncol. PD JUL PY 2011 VL 21 IS 3 BP 212 EP 219 DI 10.1016/j.semradonc.2011.02.007 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 778OR UT WOS:000291714500007 PM 21645866 ER PT J AU Jackson, TD Wannares, JJ Lancaster, RT Rattner, DW Hutter, MM AF Jackson, Timothy D. Wannares, Jeffrey J. Lancaster, R. Todd Rattner, David W. Hutter, Matthew M. TI Does speed matter? The impact of operative time on outcome in laparoscopic surgery SO SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES LA English DT Article; Proceedings Paper CT 12th World Congress of Endoscopic Surgery (WCES) CY APR 14-17, 2010 CL Natl Harbor, MD DE Operative time; Laparoscopic surgery; Outcome ID QUALITY IMPROVEMENT PROGRAM; AFFAIRS SURGICAL RISK; PATIENT SAFETY; ADJUSTMENT; CARE AB Introduction Controversy exists concerning the importance of operative time on patient outcomes. It is unclear whether faster is better or haste makes waste or similarly whether slower procedures represent a safe, meticulous approach or inexperienced dawdling. The objective of the present study was to determine the effect of operative time on 30-day outcomes in laparoscopic surgery. Methods Patients who underwent laparoscopic general surgery procedures (colectomy, cholecystectomy, Nissen fundoplication, inguinal hernia, and gastric bypass) from the ACS-NSQIP 2005-2008 participant use file were identified. Exclusion criteria were defined a priori to identify same-day admission, elective procedures. Operative time was divided into deciles and summary statistics were analyzed. Univariate analyses using a Cochran-Armitage test for trend were completed. The effect of operative time on 30-day morbidity was further analyzed for each procedure type using multivariate regression controlling for case complexity and additional patient factors. Patients within the highest deciles were excluded to reduce outlier effect. Results A total of 76,748 elective general surgical patients who underwent laparoscopic procedures were analyzed. Univariate analyses of deciles of operative time demonstrated a statistically significant trend (p < 0.0001) toward increasing odds of complications with increasing operative time for laparoscopic colectomy (n = 10,135), cholecystectomy (n = 37,407), Nissen fundoplication (n = 4,934), and gastric bypass (n = 17,842). The trend was not found to be significant for laparoscopic inguinal hernia repair (n = 6,430; p = 0.14). Multivariate modeling revealed the effect of operative time to remain significant after controlling for additional patient factors. Conclusion Increasing operative time was associated with increased odds of complications and, therefore, it appears that speed may matter in laparoscopic surgery. These analyses are limited in their inability to adjust for all patient factors, potential confounders, and case complexities. Additional hierarchical multivariate analyses at the surgeon level would be important to examine this relationship further. C1 [Jackson, Timothy D.; Lancaster, R. Todd; Rattner, David W.; Hutter, Matthew M.] Massachusetts Gen Hosp, Dept Surg, Div Gen & Gastrointestinal Surg, Boston, MA 02114 USA. [Jackson, Timothy D.; Wannares, Jeffrey J.; Lancaster, R. Todd; Hutter, Matthew M.] Massachusetts Gen Hosp, Codman Ctr Clin Effectiveness Surg, Boston, MA 02114 USA. [Jackson, Timothy D.] Univ Toronto, Dept Surg, Toronto, ON, Canada. RP Hutter, MM (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Gen & Gastrointestinal Surg, 15 Parkman St,WACC 460, Boston, MA 02114 USA. EM mhutter@partners.org FU NIBIB NIH HHS [R01 EB005807, R01 EB009362, R01 EB009362-01A2, R01 EB009362-02, R01 EB010037] NR 10 TC 29 Z9 29 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0930-2794 J9 SURG ENDOSC JI Surg. Endosc. PD JUL PY 2011 VL 25 IS 7 BP 2288 EP 2295 DI 10.1007/s00464-010-1550-8 PG 8 WC Surgery SC Surgery GA 778GB UT WOS:000291690100032 PM 21298533 ER PT J AU Archer, N Moschovis, PP Le, PV Farmer, P AF Archer, Natasha Moschovis, Peter P. Le, Phuoc V. Farmer, Paul TI Perspective: Postearthquake Haiti Renews the Call for Global Health Training in Medical Education SO ACADEMIC MEDICINE LA English DT Editorial Material ID OPPORTUNITIES; EXPERIENCES AB On January 12, 2010, Haiti experienced one of the worst disasters in human history, a magnitude 7.0 earthquake, resulting in the deaths of approximately 222,000 Haitians and grievous injury to hundreds of thousands more. International agencies, academic institutions, nongovernmental organizations, and associations responded by sending thousands of medical professionals, including nurses, doctors, medics, and physical therapists, to support the underresourced Haitian health system. The volunteers who came to provide medical care to disaster victims worked tirelessly under extremely challenging conditions, but in many cases they had no previous work experience in resource-limited settings, minimal training in tropical disease, and no knowledge of the historical background that contributed to the catastrophe. Often, this lack of preparedness hindered their ability to care adequately for their patients. The authors of this perspective argue that the academic medicine community must prepare medical trainees not only to treat the illnesses of patients in resource-limited settings but also to fight the injustice that fosters disease and allows such catastrophes to unfold. The authors advocate purposeful attention to building global health curricula; providing adequate time, funding, and opportunity to work in resource-limited international settings; and ensuring sufficient supervision for trainees to work safely. They also call for an interdisciplinary approach to global health that both affirms health care as a fundamental human right and explores the historical, economic, and political causes of inequitable health care. C1 [Archer, Natasha; Farmer, Paul] Brigham & Womens Hosp, Div Global Hlth Equ, Boston, MA 02115 USA. [Farmer, Paul] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA. [Moschovis, Peter P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Archer, N (reprint author), Brigham & Womens Hosp, Div Global Hlth Equ, 75 Francis St, Boston, MA 02115 USA. EM narcher@partners.org RI liu, jing/D-9482-2012; yan, liu/A-1822-2015 OI yan, liu/0000-0001-8517-1084 NR 17 TC 13 Z9 13 U1 2 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD JUL PY 2011 VL 86 IS 7 BP 889 EP 891 DI 10.1097/ACM.0b013e31821b3e14 PG 3 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 786DJ UT WOS:000292283200025 PM 21494116 ER PT J AU Safren, SA O'Cleirigh, C Skeer, MR Driskell, J Goshe, BM Covahey, C Mayer, KH AF Safren, Steven A. O'Cleirigh, Conall Skeer, Margie R. Driskell, Jeffrey Goshe, Brett M. Covahey, Charles Mayer, Kenneth H. TI Demonstration and Evaluation of a Peer-Delivered, Individually-Tailored, HIV Prevention Intervention for HIV-Infected MSM in their Primary Care Setting SO AIDS AND BEHAVIOR LA English DT Article DE Secondary prevention; Peer-based; Prevention in treatment settings; HIV transmission risk behavior ID RISK BEHAVIORS; MEN; SEX; TRANSMISSION; INTERCOURSE; DISCLOSURE; CONDOM; MODEL; USA AB Employing HIV-infected peer counselors in secondary prevention interventions for MSM is appealing for scalable interventions. One-hundred-seventy-six HIV-infected MSM at their primary care facility participated in a secondary HIV-prevention study delivered by HIV-infected MSM peers. Of those who entered the intervention and completed the initial intake, 62% completed all four of the intervention sessions, and 93% completed at least one. While there was no overall change in transmission risk behavior (TRB) for the whole sample, among those who reported HIV TRB at baseline (n = 29), there were significant reductions in TRB over the next year. Themes that emerged in qualitative exit interviews conducted with a subset of participants centered on peer counselor quality, intervention implications, and intervention experience. This demonstration project provides initial evidence for the ability to recruit HIV-infected MSM in care into a peer-based intervention study, and shows how a peer-based intervention can be delivered in the context of HIV care. C1 [Safren, Steven A.; O'Cleirigh, Conall] Massachusetts Gen Hosp, MGH Behav Med, Boston, MA 02114 USA. [Safren, Steven A.; O'Cleirigh, Conall] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Safren, Steven A.; O'Cleirigh, Conall; Skeer, Margie R.; Driskell, Jeffrey; Goshe, Brett M.; Covahey, Charles; Mayer, Kenneth H.] Fenway Hlth, Fenway Inst, Boston, MA 02215 USA. [Skeer, Margie R.] Brown Univ, Dept Community Hlth, Providence, RI 02912 USA. [Driskell, Jeffrey] Salem State Coll, Dept Social Work, Salem, OR USA. [Mayer, Kenneth H.] Brown Univ, Sch Med, Providence, RI 02912 USA. RP Safren, SA (reprint author), Massachusetts Gen Hosp, MGH Behav Med, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM ssafren@partners.org OI Goshe, Jeffrey/0000-0001-8916-1094 FU PHS HHS [H97HA01293] NR 35 TC 18 Z9 19 U1 3 U2 10 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 EI 1573-3254 J9 AIDS BEHAV JI AIDS Behav. PD JUL PY 2011 VL 15 IS 5 BP 949 EP 958 DI 10.1007/s10461-010-9807-8 PG 10 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 785YE UT WOS:000292268300008 PM 20853023 ER PT J AU Ghebremichael, M Paintsil, E AF Ghebremichael, Musie Paintsil, Elijah TI High Risk Behaviors and Sexually Transmitted Infections Among Men in Tanzania SO AIDS AND BEHAVIOR LA English DT Article DE High-risk behaviors; Sexually transmitted infections; HIV; HSV-2; Sub-Saharan Africa ID NORTHERN TANZANIA; DIFFERENTIALS; AFRICA; WOMEN AB We assessed the association between risk behaviors and sexually transmitted infections (STIs) among men. We interviewed 794 men randomly selected from Moshi district of Tanzania. Blood and urine samples were tested for STIs. About 46% of the men tested positive for at least one STI including human immunodeficiency virus (HIV-1), herpes simplex virus (HSV-2), syphilis, chlamydia, trichomonas, and mycoplasma infection. Multiple sexual partners, casual sex, alcohol abuse, and older age were associated with higher odds of having an STI. Effective STI prevention programs in sub-Saharan Africa should have components aimed at addressing modifiable risk behaviors in men. C1 [Ghebremichael, Musie] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Ghebremichael, Musie] Dana Farber Canc Ctr, Boston, MA 02115 USA. [Paintsil, Elijah] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA. [Paintsil, Elijah] Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06510 USA. RP Ghebremichael, M (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 3 Blackfan Circle, Boston, MA 02115 USA. EM musie@jimmy.harvard.edu FU NIAID NIH HHS [P30 AI060354, K08 AI074404] NR 10 TC 4 Z9 4 U1 0 U2 3 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 J9 AIDS BEHAV JI AIDS behav. PD JUL PY 2011 VL 15 IS 5 BP 1026 EP 1032 DI 10.1007/s10461-009-9594-2 PG 7 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 785YE UT WOS:000292268300016 PM 19636698 ER PT J AU Samal, L Saha, S Chander, G Korthuis, PT Sharma, RK Sharp, V Cohn, J Moore, RD Beach, MC AF Samal, Lipika Saha, Somnath Chander, Geetanjali Korthuis, P. Todd Sharma, Rashmi K. Sharp, Victoria Cohn, Jonathan Moore, Richard D. Beach, Mary Catherine TI Internet Health Information Seeking Behavior and Antiretroviral Adherence in Persons Living with HIV/AIDS SO AIDS PATIENT CARE AND STDS LA English DT Article ID UNITED-STATES; HIV; CARE; INTERVENTION; PATIENTSLIKEME; COMMUNICATION; INFECTION; COMMUNITY; IMPACT; ADULTS AB While the Internet has the potential to educate persons living with HIV/AIDS (PLWHA), websites may contain inaccurate information and increase the risk of nonadherence with antiretroviral therapy (ART). The objectives of our study were to determine the extent to which PLWHA engage in Internet health information seeking behavior (IHISB) and to determine whether IHISB is associated with ART adherence. We conducted a survey of adult, English-speaking HIV-infected patients at four HIV outpatient clinic sites in the United States (Baltimore, Maryland; Detroit, Michigan; New York, and Portland, Oregon) between December 2004 and January 2006. We assessed IHISB by asking participants how much information they had received from the Internet since acquiring HIV. The main outcome was patient-reported ART adherence over the past three days. Data were available on IHISB for 433 patients, 334 of whom were on ART therapy. Patients had a mean age of 45 (standard error [SE] 0.45) years and were mostly male (66%), African American (58%), and had attained a high school degree (73%). Most (55%) reported no IHISB, 18% reported some, and 27% reported "a fair amount" or "a great deal." Patients who reported higher versus lower levels of IHISB were significantly younger, had achieved a higher level of education, and had higher medication self-efficacy. In unadjusted analyses, higher IHISB was associated with ART adherence (odds ratio [OR], 2.96, 95% confidence interval [CI] 1.27-6.94). This association persisted after adjustment for age, gender, race, education, clinic site, and medication self-efficacy (adjusted odds ratio [AOR] 2.76, 95% CI 1.11-6.87). Our findings indicate that IHISB is positively associated with ART adherence even after controlling for potentially confounding variables. Future studies should investigate the ways in which Internet health information may promote medication adherence among PLWHA. C1 [Samal, Lipika] Brigham & Womens Hosp, Div Gen Internal Med & Primary Care, Boston, MA 02115 USA. [Saha, Somnath] Portland VA Med Ctr, Gen Internal Med Sect, Portland, OR USA. [Saha, Somnath] Oregon Hlth & Sci Univ, Div Gen Internal Med & Geriatr, Portland, OR 97201 USA. [Korthuis, P. Todd] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Korthuis, P. Todd] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. [Chander, Geetanjali; Moore, Richard D.; Beach, Mary Catherine] Johns Hopkins Univ, Sch Med, Div Gen Internal Med, Baltimore, MD USA. [Sharma, Rashmi K.] Northwestern Univ, Div Hosp Med, Chicago, IL 60611 USA. [Sharp, Victoria] St Lukes Roosevelt Hosp, HIV Ctr Comprehens Care, New York, NY 10025 USA. [Cohn, Jonathan] Wayne State Univ, Div Infect Dis, Detroit, MI USA. RP Samal, L (reprint author), 1620 Tremont St,Suite BC 003-002V, Boston, MA 02120 USA. EM LSAMAL@PARTNERS.ORG FU Health Resources and Service Administration; Agency for Healthcare Research and Quality [AHRQ 290-01-0012, K08 HS013903-05]; National Institute of Drug Abuse [K23 DA019809]; National Institute on Alcoholism and Alcohol Abuse [K23 AA015313]; Department of Veterans Affairs; Robert Wood Johnson Generalist Physician Faculty Scholars Awards FX This research was supported by a contract from the Health Resources and Service Administration and the Agency for Healthcare Research and Quality (AHRQ 290-01-0012). Dr. Korthuis was supported by the National Institute of Drug Abuse (K23 DA019809), Dr. Chander was supported by the National Institute on Alcoholism and Alcohol Abuse (K23 AA015313), Dr. Saha was supported by the Department of Veterans Affairs, Dr. Beach was supported by the Agency for Healthcare Research and Quality (K08 HS013903-05) and both Drs. Beach and Saha were supported by Robert Wood Johnson Generalist Physician Faculty Scholars Awards. NR 33 TC 18 Z9 18 U1 2 U2 14 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD JUL PY 2011 VL 25 IS 7 BP 445 EP 449 DI 10.1089/apc.2011.0027 PG 5 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 784DW UT WOS:000292135900008 PM 21682586 ER PT J AU Thompson, V Medard, B Taseera, K Chakera, AJ Andia, I Emenyonu, N Hunt, PW Martin, J Scherzer, R Weiser, SD Bangsberg, DR Tien, PC AF Thompson, Vanessa Medard, Bitekyerezo Taseera, Kabanda Chakera, Ali J. Andia, Irene Emenyonu, Nneka Hunt, Peter W. Martin, Jeffrey Scherzer, Rebecca Weiser, Sheri D. Bangsberg, David R. Tien, Phyllis C. TI Regional Anthropometry Changes in Antiretroviral-Naive Persons Initiating a Zidovudine-Containing Regimen in Mbarara, Uganda SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID RANDOMIZED CLINICAL-TRIAL; ANOREXIA-NERVOSA; FAT REDISTRIBUTION; BODY-COMPOSITION; HIV-INFECTION; WEIGHT-GAIN; THERAPY; LIPODYSTROPHY; STAVUDINE; POPULATION AB Lipodystrophy is commonly reported in Africa after antiretroviral therapy (ART) is initiated, but few studies have objectively measured changes in body composition. Body composition was determined in 76 HIV-infected participants from Mbarara, Uganda after starting a thymidine-analog regimen, and annual change was determined using repeated measures analysis. We measured skinfolds (tricep, thigh, subscapular, and abdomen), circumferences (arm, hip, thigh, waist), and total lean and fat mass (using bioelectric impedance analysis). A cross-sectional sample of 49 HIV-uninfected participants was studied for comparison. At baseline, most body composition measures were lower in HIV-infected than uninfected participants, but waist circumference was similar. After 12 months on ART, there was little difference in body composition measures between HIV-infected and uninfected participants; median waist circumference appeared higher in HIV-infected participants (79 vs. 75 cm; p = 0.090). Among HIV-infected participants, increases were observed in total lean and fat mass, circumference, and skinfold measures; only the increase in tricep skinfold did not reach statistical significance (+1.05mm; 95% confidence interval: -0.24, 2.34; p = 0.11). Regional anthropometry in peripheral and central body sites increased over 12 months after ART initiation in HIV-infected persons from southwestern Uganda, suggesting a restoration to health. Gains in the tricep skinfold, a reliable marker of subcutaneous fat, appeared blunted, which could indicate an inhibitory effect of zidovudine on peripheral subcutaneous fat recovery. C1 [Tien, Phyllis C.] Univ Calif San Francisco, VAMC, Infect Dis Sect, Dept Med, San Francisco, CA 94121 USA. [Medard, Bitekyerezo; Taseera, Kabanda; Andia, Irene] Mbarara Univ Sci & Technol, Dept Med, Mbarara, Uganda. [Chakera, Ali J.] Royal Devon & Exeter Hosp, Dept Endocrinol, Exeter EX2 5DW, Devon, England. [Emenyonu, Nneka; Bangsberg, David R.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Martin, Jeffrey] Univ Calif San Francisco, Dept Biostat & Epidemiol, San Francisco, CA 94143 USA. [Scherzer, Rebecca] Dept Vet Affairs Med Ctr, Med Serv, San Francisco, CA USA. [Bangsberg, David R.] Ragon Inst MGH MIT & Harvard Univ, Boston, MA USA. [Bangsberg, David R.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Bangsberg, David R.] Harvard Initiat Global Hlth, Boston, MA USA. RP Tien, PC (reprint author), Univ Calif San Francisco, VAMC, Infect Dis Sect, Dept Med, 111W,4150 Clement St, San Francisco, CA 94121 USA. EM ptien@ucsf.edu FU Center for AIDS Research [P30AI027763-15, K23 AI-66943, ROI MH-54907] FX The authors would like to acknowledge the contributions of Annet Kawuma and Heather Southwell to this research. This work was supported in part by a Center for AIDS Research pilot grant: P30AI027763-15, K23 AI-66943, and ROI MH-54907. NR 27 TC 9 Z9 9 U1 0 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JUL PY 2011 VL 27 IS 7 BP 785 EP 791 DI 10.1089/aid.2010.0272 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 783MO UT WOS:000292087600012 PM 21128866 ER PT J AU Koskinen, SM Ahveninen, J Kujala, T Kaprio, J O'Donnell, BF Osipova, D Viken, RJ Naatanen, R Rose, RJ AF Koskinen, Sini M. Ahveninen, Jyrki Kujala, Teija Kaprio, Jaakko O'Donnell, Brian F. Osipova, Daria Viken, Richard J. Naatanen, Risto Rose, Richard J. TI A Longitudinal Twin Study of Effects of Adolescent Alcohol Abuse on the Neurophysiology of Attention and Orienting SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Adolescents; Alcohol Abuse; Event-Related Potentials; P3; Twin Study ID EVENT-RELATED POTENTIALS; HIGH-RISK; BRAIN POTENTIALS; P300 AMPLITUDE; ENVIRONMENTAL-INFLUENCES; YOUNG ADULTHOOD; DIZYGOTIC TWINS; FAMILY HISTORY; USE DISORDERS; VISUAL P3A AB Background: Long-term functional brain effects of adolescent alcohol abuse remain uncertain, partially because of difficulties in distinguishing inherited deficits from neuronal effects of ethanol and by confounds associated with alcohol abuse, especially nicotine exposure. We conducted a longitudinal twin study to determine neurocognitive effects of adolescent alcohol abuse, as measured with the auditory event-related potential (ERP) component P3, a putative marker of genetic vulnerability to alcoholism. Methods: Twin pairs (N = 177; 150 selected for intrapair concordance/discordance for alcohol-related problems at age 18 1/2) were recruited from ongoing studies of twins born 1975-1979 in Finland. Alcohol and tobacco use were assessed with questionnaires at ages 16, 17, 18 1/2, and similar to 25, and by a structured psychiatric interview concurrent with the ERP testing at mean age 25.8. During ERP recordings, subjects were instructed to detect target tones within a train of frequent "standards" and to ignore occasional "novel" sounds. To distinguish familial factors from ethanol effects, ERP and self-reported alcohol use measures were incorporated into hierarchical multiple regression (HMR) analysis, and intrapair differences in ERP were associated with intrapair differences in alcohol variables. Results: Novel-sound P3 amplitude correlated negatively with self-reported alcohol use in both between- and within-family analyses. No similar effect was observed for target-tone P3. HMR results suggest that twins' similarity for novel-sound P3 amplitude is modulated by their alcohol use, and this effect of alcohol use is influenced by genetic factors. Conclusions: Our results, from a large sample of twins selected from a population-based registry for pairwise concordance/discordance for alcohol problems at 18 1/2, demonstrate that adolescent alcohol abuse is associated with subtle neurophysiological changes in attention and orienting. The changes are reflected in decreased novel-sound P3 amplitude and may be modified by genetic factors. C1 [Koskinen, Sini M.; Kujala, Teija; Osipova, Daria; Naatanen, Risto] Univ Helsinki, Inst Behav Sci, Cognit Brain Res Unit, FIN-00014 Helsinki, Finland. [Koskinen, Sini M.] Univ Helsinki, Cent Hosp, Dept Neurol, FIN-00014 Helsinki, Finland. [Ahveninen, Jyrki] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Kaprio, Jaakko] Univ Helsinki, Dept Publ Hlth, FIN-00014 Helsinki, Finland. [Kaprio, Jaakko] Univ Helsinki, Inst Mol Med, FIN-00014 Helsinki, Finland. Natl Inst Hlth & Welf, Dept Mental Hlth & Subst Abuse Serv, Helsinki, Finland. [O'Donnell, Brian F.; Viken, Richard J.; Rose, Richard J.] Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN USA. [Naatanen, Risto] Univ Tartu, Dept Psychol, EE-50090 Tartu, Estonia. [Naatanen, Risto] Univ Aarhus, Ctr Functionally Integrated Neurosci, Aarhus, Denmark. RP Koskinen, SM (reprint author), Univ Helsinki, Inst Behav Sci, Cognit Brain Res Unit, POB 9, FIN-00014 Helsinki, Finland. EM sini.koskinen@helsinki.fi RI Kujala, Teija/G-6704-2016; OI Kujala, Teija/0000-0002-8814-605X; Kaprio, Jaakko/0000-0002-3716-2455 FU National Institute on Alcohol Abuse and Alcoholism [R37AA012502, R01AA08315]; Academy of Finland (Center of Excellence in Complex Disease Genetics) [1211486, 118555, 100499]; Emil Aaltonen Foundation; Finnish Cultural Foundation; Jenny and Antti Wihuri Foundation; Finnish Foundation for Alcohol Studies; Ella and Georg Ehrnrooth Foundation; Yrjo Jahnsson Foundation; NIH [R01MH083744, R01HD040712, R01NS037462, R01NS048279] FX This study was supported by the National Institute on Alcohol Abuse and Alcoholism (R37AA012502 and R01AA08315), the Academy of Finland (Center of Excellence in Complex Disease Genetics, and grants 1211486, 118555, 100499), Emil Aaltonen Foundation, Finnish Cultural Foundation, Jenny and Antti Wihuri Foundation, Finnish Foundation for Alcohol Studies, Ella and Georg Ehrnrooth Foundation, and Yrjo Jahnsson Foundation. NIH Awards R01MH083744, R01HD040712, R01NS037462, and R01NS048279 supported JA. We thank Pasi Piiparinen for help with data acquisition. NR 66 TC 10 Z9 10 U1 3 U2 11 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUL PY 2011 VL 35 IS 7 BP 1339 EP 1350 DI 10.1111/j.1530-0277.2011.01470.x PG 12 WC Substance Abuse SC Substance Abuse GA 783UM UT WOS:000292109500018 PM 21463336 ER PT J AU Smith-Bindman, R McCulloch, CE Ding, A Quale, C Chu, PW AF Smith-Bindman, Rebecca McCulloch, Charles E. Ding, Alex Quale, Christopher Chu, Philip W. TI Diagnostic imaging rates for head injury in the ED and states' medical malpractice tort reforms SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID NEW-ORLEANS CRITERIA; DEFENSIVE MEDICINE; POPULATIONS; PHYSICIANS; SERVICES; CLAIMS; RULE; CARE; FREQUENCY; SEVERITY AB Objective: Physicians' fears of being sued may lead to defensive medical practices, such as ordering nonindicated medical imaging. We investigated the association between states' medical malpractice tort reforms and neurologic imaging rates for patients seen in the emergency department with mild head trauma. Methods: We assessed neurologic imaging among a national sample of 8588 women residing in 10 US states evaluated in an emergency setting for head injury between January 1, 1992, and December 31, 2001. We assessed the odds of imaging as it varied by the enactment of medical liability reform laws. Results: The medical liability reform laws were significantly associated with the likelihood of imaging. States with laws that limited monetary damages (odds ratio [OR], 0.63; 95% confidence interval [CI], 0.40-0.99), mandated periodic award payments (OR, 0.64; 95% CI, 0.43-0.97), or specified collateral source offset rules (OR, 0.62; 95% CI, 0.40-0.96) had an approximately 40% lower odds of imaging, whereas states that had laws that limited attorney's contingency fees had significantly higher odds of imaging (OR, 1.5; 95% CI, 0.99-2.4), compared to states without these laws. When we used a summation of the number of laws in place, the greater the number of laws, the lower the odds of imaging. In the multivariate analysis, after adjusting for individual and community factors, the total number of laws remained significantly associated with the odds of imaging, and the effect of the individual laws was attenuated, but not eliminated. Conclusion: The tort reforms we examined were associated with the propensity to obtain neurologic imaging. If these results are confirmed in larger studies, tort reform might mitigate defensive medical practices. (C) 2011 Elsevier Inc. All rights reserved. C1 [Smith-Bindman, Rebecca; Chu, Philip W.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Smith-Bindman, Rebecca; McCulloch, Charles E.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Smith-Bindman, Rebecca] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA. [Ding, Alex] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Cambridge, MA 02138 USA. [Quale, Christopher] Genom Hlth, Redwood City, CA 94063 USA. RP Smith-Bindman, R (reprint author), Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. EM rebecca.smith-bindman@radiology.ucsf.edu NR 39 TC 10 Z9 10 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 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD JUL PY 2011 VL 29 IS 6 BP 656 EP 664 DI 10.1016/j.ajem.2010.01.038 PG 9 WC Emergency Medicine SC Emergency Medicine GA 786KF UT WOS:000292306100014 PM 20630679 ER PT J AU West, RK Beeri, MS Schmeidler, J Mitchell, DB Carlisle, KR Angelo, G Mavris, R Langhoff, E Rosendorff, C Silverman, JM AF West, Rebecca K. Beeri, Michal Schnaider Schmeidler, James Mitchell, Dara B. Carlisle, Katherine R. Angelo, Gary Mavris, Rizalina Langhoff, Erik Rosendorff, Clive Silverman, Jeremy M. TI Homocysteine and Cognitive Function in Very Elderly Nondemented Subjects SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE Cognitive performance; dementia; homocysteine ID ALZHEIMER-DISEASE; DECLINE; DEMENTIA; RISK; AGE AB Objectives: To examine the association of homocysteine with cognitive functioning in very elderly community-dwelling individuals (80 years or older). Methods: Two hundred twenty-eight nondemented community-dwelling individuals were assessed with a broad neuropsychological battery. Bloods were drawn to measure homocysteine, serum vitamin B(12), and folate levels and APOE genotype. Results: Higher homocysteine levels were associated with poorer executive-language functioning scores (r = -0.311). The association persisted when serum B12 and folate levels were controlled for (r = -0.308). Homocysteine levels were not associated with memory score (r = 0.120). Conclusions: In very elderly, nondemented community dwellers, high homocysteine levels are associated with poorer executive-language functioning but not with memory. This possible differential effect of homocysteine on cognitive functions suggests that it may affect only specific brain regions or mechanisms underlying healthy executive functioning. (Am J Geriatr Psychiatry 2011; 19:673-677) C1 [West, Rebecca K.; Beeri, Michal Schnaider; Schmeidler, James; Mitchell, Dara B.; Carlisle, Katherine R.; Angelo, Gary; Langhoff, Erik; Rosendorff, Clive; Silverman, Jeremy M.] Mt Sinai Sch Med, New York, NY USA. [Mavris, Rizalina; Langhoff, Erik; Rosendorff, Clive; Silverman, Jeremy M.] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. RP West, RK (reprint author), 1 Gustave L Levy Pl,Box 1230, New York, NY 10029 USA. EM rebecca.west@mssm.edu RI Yue, Chunlin/B-3554-2014 OI Yue, Chunlin/0000-0002-2261-6725 FU National Institutes of Health [AG002219, AG023515]; United States Department of Veterans Affairs, Berkman Charitable Trust FX This study was supported by National Institutes of Health (AG002219 [to JMS] and AG023515 [to MSB]) and United States Department of Veterans Affairs, Berkman Charitable Trust (to Vahram Haroutunian). NR 12 TC 7 Z9 7 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD JUL PY 2011 VL 19 IS 7 BP 673 EP 677 DI 10.1097/JGP.0b013e3181faee37 PG 5 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 782SQ UT WOS:000292031900009 PM 21709613 ER PT J AU Banwait, R O'Regan, K Campigotto, F Harris, B Yarar, D Bagshaw, M Leleu, X Leduc, R Ramaiya, N Weller, E Ghobrial, IM AF Banwait, Ranjit O'Regan, Kevin Campigotto, Federico Harris, Brianna Yarar, Dilek Bagshaw, Meghan Leleu, Xavier Leduc, Renee Ramaiya, Nikhil Weller, Edie Ghobrial, Irene M. TI The role of F-18-FDG PET/CT imaging in Waldenstrom macroglobulinemia SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; NON-HODGKINS-LYMPHOMA; CONSENSUS PANEL RECOMMENDATIONS; 2ND INTERNATIONAL WORKSHOP; THERAPEUTIC RESPONSE; FLUORODEOXYGLUCOSE; CHEMOTHERAPY; INDICATOR; CRITERIA; BONE AB Disease assessment in WM is dependent on the quantification of the IgM monoclonal protein and percent involvement of the bone marrow. There is a need for imaging studies that objectively measure tumor load in these patients. In this study, we sought to examine the role of combined FDG-PET/CT imaging in the detection of tumor load and in the assessment of response to therapy. Thirty-five patients were enrolled on a prospective study using bortezomib and rituximab therapy and were included in this study because they completed a pre- and post-treatment FDG-PET/CT imaging at one facility (12 newly diagnosed and 23 relapsed/refractory). The use of combined FDG-PET/CT imaging showed positive findings in 83% of patients with WM, unlike prior studies using conventional imaging that indicate that only 20% of patients have lymphadenopathy or hepatosplenomegaly. Moreover, 43% of patients had abnormal bone marrow uptake on FDG-PET imaging that can potentially help in the assessment of their tumor load, especially with heterogenous sampling of the bone marrow. There was no statistical correlation between EORTC response criteria for FDG-PET/CT and response by monoclonal protein. This is the first study to examine the role of FDG-PET/CT imaging in WM. Future studies should examine the role of FDG-PET/CT in conjunction with monoclonal protein response in the assessment of progression-free survival in patients with WM. Am. J. Hematol. 86:567-572, 2011. (C) 2011 Wiley-Liss, Inc. C1 [Banwait, Ranjit; O'Regan, Kevin; Campigotto, Federico; Harris, Brianna; Yarar, Dilek; Bagshaw, Meghan; Leleu, Xavier; Leduc, Renee; Ramaiya, Nikhil; Weller, Edie; Ghobrial, Irene M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Leleu, Xavier] CHRU, Hop Huriez, Serv Malad Sang, Lille, France. RP Ghobrial, IM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM irene_ghobrial@dfci.harvard.edu FU International Waldenstrom Macroglobulinemia Foundation (IWMF); Kirsch Lab for Waldenstrom; Heje Fellowship FX Contract grant sponsors: The International Waldenstrom Macroglobulinemia Foundation (IWMF); Kirsch Lab for Waldenstrom; Heje Fellowship. NR 23 TC 9 Z9 10 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD JUL PY 2011 VL 86 IS 7 BP 567 EP 572 DI 10.1002/ajh.22044 PG 6 WC Hematology SC Hematology GA 781MX UT WOS:000291938000008 PM 21681781 ER PT J AU Ghobrial, IM Munshi, NC Harris, BN Shi, PP Porter, NM Schlossman, RL Laubach, JP Anderson, KC Desaiah, D Myrand, SP Wooldridge, JE Richardson, PG Abonour, R AF Ghobrial, Irene M. Munshi, Nikhil C. Harris, Brianna N. Shi, Peipei Porter, Nichole M. Schlossman, Robert L. Laubach, Jacob P. Anderson, Kenneth C. Desaiah, Durisala Myrand, Scott P. Wooldridge, James E. Richardson, Paul G. Abonour, Rafat TI A phase I safety study of enzastaurin plus bortezomib in the treatment of relapsed or refractory multiple myeloma SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID PROTEIN-KINASE-C; EXTENDED FOLLOW-UP; AKT PATHWAY; INHIBITOR; APOPTOSIS; CANCER; TRIAL AB The purpose of this study was to assess the safety and identify the recommended doses of enzastaurin and bortezomib in combination for future Phase II studies in patients with relapsed or refractory multiple myeloma. Three dose levels (DLs) of oral enzastaurin and intravenous bortezomib were used according to a conventional "3 + 3'' design. A loading dose of enzastaurin (250 mg twice/day [BID]) on Day 1 was followed by enzastaurin 125 mg BID for 1 week, after which bortezomib was added (Cycle 1, 28 days, 1.0 mg/m(2): Days 8, 11, 15, and 18; seven subsequent 21-day cycles, 1.3 mg/m(2): Days 1, 4, 8, and 11). Twenty-three patients received treatment; all patients received prior systemic therapy. Most patients received >= 3 regimens; 17 patients were bortezomib-refractory. A median of four treatment cycles (range 1-24) was completed. No dose-limiting toxicities were observed; thus, DL 3 was the recommended Phase II dose. The most common drug-related Grade 3/4 toxicities were thrombocytopenia (n = 6) and anemia (n = 2). No patients died on therapy. One patient (DL 1) achieved a very good partial response; three patients (DLs 2 and 3), a partial response; nine patients, stable disease; and four patients, progressive disease. The recommended Phase II doses in patients with relapsed or refractory multiple myeloma are as follows: enzastaurin loading dose of 375 mg three times/day on Day 1 followed by 250 mg BID, with bortezomib 1.3 mg/m(2) on Days 1, 4, 8, and 11 of a 21-day cycle. The combination was well-tolerated and demonstrated some antimyeloma activity. Am. J. Hematol. 86:573-578, 2011. (C) 2011 Wiley-Liss, Inc. C1 [Ghobrial, Irene M.; Munshi, Nikhil C.; Harris, Brianna N.; Schlossman, Robert L.; Laubach, Jacob P.; Anderson, Kenneth C.] Dana Farber Canc Inst, Multiple Myeloma Waldenstroms Macroglobulinemia P, Boston, MA 02115 USA. [Shi, Peipei; Desaiah, Durisala; Myrand, Scott P.; Wooldridge, James E.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Porter, Nichole M.; Abonour, Rafat] Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA. [Richardson, Paul G.] Dana Farber Canc Inst, Jerome Lipper Ctr Multiple Myeloma, Boston, MA 02115 USA. RP Ghobrial, IM (reprint author), Dana Farber Canc Inst, Multiple Myeloma Waldenstroms Macroglobulinemia P, 44 Binney St,Dana Bldg D1B30, Boston, MA 02115 USA. EM irene_ghobrial@dfci.harvard.edu OI Harris, Brianna/0000-0001-6229-9907 FU Eli Lilly and Company, Indianapolis, USA FX Sponsor: Eli Lilly and Company, Indianapolis, USA NR 16 TC 15 Z9 15 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD JUL PY 2011 VL 86 IS 7 BP 573 EP 578 DI 10.1002/ajh.22048 PG 6 WC Hematology SC Hematology GA 781MX UT WOS:000291938000009 PM 21630305 ER PT J AU Singh, H Werner, LL Asali, S DeAngelo, DJ Ballen, KK Amrein, PC Wadleigh, M Galinsky, I Wolpin, B Pidala, J Neuberg, DS Fox, EA Stone, RM Attar, EC AF Singh, Harshabad Werner, Lillian L. Asali, Salma DeAngelo, Daniel J. Ballen, Karen K. Amrein, Philip C. Wadleigh, Martha Galinsky, Ilene Wolpin, Brian Pidala, Joseph Neuberg, Donna S. Fox, Edward A. Stone, Richard M. Attar, Eyal C. TI Comparison of autologous stem cell transplantation versus consolidation chemotherapy for patients with cytogenetically normal acute myeloid leukemia (CN-AML) and FLT3ITD SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID INTERNAL TANDEM DUPLICATION; PROGNOSTIC-SIGNIFICANCE; GROUP-B; POOR-PROGNOSIS; ADULT PATIENTS; MUTATIONS; CANCER; SIZE; D835 AB We retrospectively analyzed clinical outcomes of patients aged 18-59 with cytogenetically normal acute myeloid leukemia (CN-AML) and mutations in the FLT3 receptor according to type of postremission therapy. Specifically, we compared the outcomes of patients who underwent autologous SCT versus consolidation chemotherapy. There were 37 patients with an ITD mutation (seven also had a TKD mutation) and 19 patients with an isolated TKD mutation at diagnosis. In all, patients with an isolated TKD (n = 16) had an improved disease free survival (DFS) and overall survival (OS) (P = 0.031 and 0.014, respectively) compared to ITD patients (n = 21). For individuals with an isolated TKD mutation, survival outcomes were similar irrespective of the type of postremission therapy (n = 7 for SCT and 9 for chemotherapy; P = 0.97 and 0.082, respectively). However, ITD positive patients who underwent an autologous SCT in CR1 (n = 10) had an improved DFS but similar OS compared to those who received consolidation chemotherapy (n = 11; P = 0.05 and 0.27). These results suggest that high-dose chemotherapy with autologous SCT may be a reasonable therapeutic choice over consolidation chemotherapy for young CN-AML patients with a FLT3ITD mutation. C1 [Singh, Harshabad; Asali, Salma; Ballen, Karen K.; Amrein, Philip C.; Attar, Eyal C.] Massachusetts Gen Hosp, Bone Marrow Transplant Unit, Boston, MA 02114 USA. [Werner, Lillian L.; Neuberg, Donna S.] Dept Biostat & Computat Biol, Boston, MA USA. [Pidala, Joseph] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [DeAngelo, Daniel J.; Wadleigh, Martha; Galinsky, Ilene; Wolpin, Brian; Stone, Richard M.] Adult Leukemia Program, Boston, MA USA. [Fox, Edward A.] Dana Farber Canc Inst, Mol Diagnost Lab, Dept Med Oncol, Boston, MA 02115 USA. RP Attar, EC (reprint author), Massachusetts Gen Hosp, Hematol & Oncol Unit, Ctr Canc, 100 Blossom St, Boston, MA 02114 USA. EM rstone@partners.org; eattar@partners.org FU NCI NIH HHS [K23 CA118419] NR 25 TC 4 Z9 4 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD JUL PY 2011 VL 86 IS 7 BP 625 EP 627 DI 10.1002/ajh.22041 PG 3 WC Hematology SC Hematology GA 781MX UT WOS:000291938000023 PM 21681787 ER PT J AU Madero, M Wassel, CL Peralta, CA Najjar, SS Sutton-Tyrrell, K Fried, LF de Boer, IH Shlipak, MG Newman, AB Hausmann, D Sarnak, MJ Kritcheysky, SB Ix, JH AF Madero, Magdalena Wassel, Christina L. Peralta, Carmen A. Najjar, Samer S. Sutton-Tyrrell, Kim Fried, Linda F. de Boer, Ian H. Shlipak, Michael G. Newman, Anne B. Hausmann, Dorothy Sarnak, Mark J. Kritcheysky, Stephen B. Ix, Joachim H. CA Hlth ABC Study TI Markers of Mineral Metabolism Are Not Associated With Aortic Pulse Wave Velocity in Community-Living Elderly Persons: The Health Aging and Body Composition Study SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE arterial stiffness; blood pressure; cardiovascular disease; hypertension; kidney disease; mineral metabolism; PWV ID SERUM PHOSPHORUS LEVELS; VITAMIN-D DEFICIENCY; PARATHYROID-HORMONE; CARDIOVASCULAR-DISEASE; 25-HYDROXYVITAMIN-D LEVELS; ARTERIAL STIFFNESS; MORTALITY RISK; RENAL-FUNCTION; YOUNG-ADULTS; CYSTATIN-C AB BACKGROUND Disorders in mineral metabolism are associated with risk for cardiovascular disease (CVD) events in patients with kidney disease as well as in the general population. This risk is thought to be mediated, in part, through the mechanism of stiffening of the arteries. METHODS The objective of this study was to evaluate the relationships between serum calcium, phosphorus, intact parathyroid hormone (iPTH), and 25-hydroxyvitamin D levels and arterial pulse wave velocity (aPWV) among 2,229 community-dwelling elderly persons participating in the Health Aging and Body Composition (Health ABC) study. RESULTS The mean age of the participants was 72 years; 52% were woman, 39% were black, and 17% had chronic kidney disease (CKD) (estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2)). In parallel unadjusted analyses, the following associations were observed: 2.86% greater aPWV per 12 ng/ml (s.d.) lower 25-hydroxyvitamin D (95% confidence interval -4.38%, -1.31%), 3.04% greater aPWV per 28 pg/ml (s.d.) higher iPTH (95% confidence interval 1.42-4.68%), and 2.37% lower aPWV per 0.5 mg/dl (s.d.) higher phosphorus (95% confidence interval -3.90% to -0.81%). Except for phosphorus, these associations were attenuated and rendered no longer statistically significant after adjustment for demographic risk factors, clinical site, season, medications and other CVD risk factors. The results were similar in men and women and were not dependent on the presence of CKD. CONCLUSIONS Among well-functioning community-dwelling elderly persons, only serum phosphorus was associated with aPWV; and this association was in the opposite direction of the one hypothesized. Factors other than vascular stiffening may mediate the relationship between disordered mineral metabolism and CVD events in community-living elders. C1 [Madero, Magdalena] Inst Nacl Cardiol Ignacio Chavez, Dept Nephrol, Mexico City, DF, Mexico. [Wassel, Christina L.] Univ Calif San Diego, Div Prevent Med, Dept Family & Prevent Med, San Diego, CA 92103 USA. [Peralta, Carmen A.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Peralta, Carmen A.] San Francisco VA Med Ctr, San Francisco, CA USA. [Najjar, Samer S.] Washington Hosp Ctr, MedStar Hlth Res Inst, Washington, DC 20010 USA. [Sutton-Tyrrell, Kim; Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Fried, Linda F.] Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Pittsburgh, PA USA. [Fried, Linda F.] VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. [de Boer, Ian H.] Univ Washington, Kidney Res Inst, Seattle, WA 98195 USA. [de Boer, Ian H.] Univ Washington, Div Nephrol, Seattle, WA 98195 USA. [Shlipak, Michael G.] San Francisco VA Med Ctr, Sect Gen Internal Med, San Francisco, CA USA. [Hausmann, Dorothy] Univ Georgia, Dept Foods & Nutr, Athens, GA 30602 USA. [Sarnak, Mark J.] Tufts Med Ctr, Dept Med, Div Nephrol, Boston, MA USA. [Kritcheysky, Stephen B.] Wake Forest Univ, Bowman Gray Sch Med, Sticht Ctr Aging, Winston Salem, NC USA. [Ix, Joachim H.] Univ Calif San Diego, Dept Med, Div Nephrol & Hypertens, San Diego, CA 92103 USA. [Ix, Joachim H.] Vet Affairs San Diego Healthcare Ctr, San Diego, CA USA. RP Madero, M (reprint author), Inst Nacl Cardiol Ignacio Chavez, Dept Nephrol, Mexico City, DF, Mexico. EM madero.magdalena@gmail.com RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Kritchevsky, Stephen/0000-0003-3336-6781 FU NIH, National Institute on Aging [R01 HL096851, R01 AG029364, N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106] FX This work was supported in part by the Intramural Research Program of the NIH, National Institute on Aging (National Institute on Aging R01 HL096851, R01 AG029364, N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106). NR 33 TC 8 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 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD JUL PY 2011 VL 24 IS 7 BP 755 EP 761 DI 10.1038/ajh.2011.43 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 780ZT UT WOS:000291901100007 PM 21436791 ER PT J AU Click, ES Cox, B Olson, SB Grompe, M Akkari, Y Moreau, LA Shimamura, A Sternen, DL Liu, YJJ Leppig, KA Matthews, DC Parisi, MA AF Click, Eleanor S. Cox, Barbara Olson, Susan B. Grompe, Markus Akkari, Yassmine Moreau, Lisa A. Shimamura, Akiko Sternen, Darci L. Liu, Yajuan J. Leppig, Kathleen A. Matthews, Dana C. Parisi, Melissa A. TI Fanconi Anemia-Like Presentation in an Infant with Constitutional Deletion of 21q Including the RUNX1 Gene SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE chromosome breakage; chromosome 21q; thrombocytopenia; Fanconi anemia; intellectual disability; chromosome microarray; RUNX1 ID ACUTE MYELOGENOUS LEUKEMIA; FAMILIAL PLATELET DISORDER; ACUTE MYELOID-LEUKEMIA; DOWN-SYNDROME; MENTAL-RETARDATION; POINT MUTATIONS; THROMBOCYTOPENIA; PREDISPOSITION; CHROMOSOME-21; PHENOTYPE AB We describe a newborn female with a de novo interstitial deletion of chromosome 21q21.1-22.12 including the RUNX1 gene who had developmental delay, multiple congenital anomalies, tetralogy of Fallot, anemia, and chronic thromobocytopenia requiring frequent platelet transfusions from birth. Because of her physical and hematologic abnormalities, she was tested for Fanconi anemia (FA). Lymphocytes and fibroblasts from this patient demonstrated increased chromosome breakage with exposure to the clastogen mitomycin C, but not, in contrast to most FA patients, to diepoxybutane. Further testing by Western analysis and complementation testing did not show a defect in the function of known Fanconi proteins. Her constitutional deletion was later found to span 13.2Mb by chromosome microarray analysis, encompassing the RUNX1 gene that has been implicated in thrombocytopenia and predisposition to acute myelogenous leukemia (AML) when in the haploinsufficient state. We compare her phenotype to other individuals with similar 21q deletions and thrombocytopenia, as well as those with FA. We suggest that deletion of RUNX1 or another critical gene within the deleted region may result in chromosomal instability similar to that seen in FA. (C) 2011 Wiley-Liss, Inc. C1 [Parisi, Melissa A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Intellectual & Dev Disabil Branch, Ctr Dev Biol & Perinatal Med, Bethesda, MD 20892 USA. [Click, Eleanor S.; Shimamura, Akiko; Sternen, Darci L.; Matthews, Dana C.] Seattle Childrens Hosp, Seattle, WA USA. [Cox, Barbara; Olson, Susan B.; Grompe, Markus] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Akkari, Yassmine] Legacy Hlth, Legacy Lab Serv, Portland, OR USA. [Moreau, Lisa A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Liu, Yajuan J.; Leppig, Kathleen A.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Leppig, Kathleen A.] Grp Hlth Cooperat Puget Sound, Seattle, WA USA. RP Parisi, MA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Intellectual & Dev Disabil Branch, Ctr Dev Biol & Perinatal Med, 6100 Execut Blvd,Room 4B09,MSC 7510, Bethesda, MD 20892 USA. EM parisima@mail.nih.gov FU NCRR NIH HHS [UL1 RR024140] NR 38 TC 11 Z9 11 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD JUL PY 2011 VL 155A IS 7 BP 1673 EP 1679 DI 10.1002/ajmg.a.34024 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 781OZ UT WOS:000291944700027 PM 21626672 ER PT J AU Ghadirivasfi, M Nohesara, S Ahmadkhaniha, HR Eskandari, MR Mostafavi, S Thiagalingam, S Abdolmaleky, HM AF Ghadirivasfi, Mohammad Nohesara, Shabnam Ahmadkhaniha, Hamid-Reza Eskandari, Mohammad-Reza Mostafavi, Siavash Thiagalingam, Sam Abdolmaleky, Hamid Mostafavi TI Hypomethylation of the Serotonin Receptor Type-2A Gene (HTR2A) at T102C Polymorphic Site in DNA Derived From the Saliva of Patients With Schizophrenia and Bipolar Disorder SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE HTR2A; DNA methylation; schizophrenia; bipolar disorder; saliva; biomarker ID MAJOR PSYCHIATRIC-DISORDERS; MESSENGER-RNA EXPRESSION; 2A RECEPTOR; FRONTAL-CORTEX; DIFFERENTIAL EXPRESSION; TARDIVE-DYSKINESIA; PROMOTER; ASSOCIATION; METHYLATION; METAANALYSIS AB Several lines of evidence indicate that dysfunction of serotonin signaling and HTR2A receptor are involved in the pathogenesis of schizophrenia (SCZ) and bipolar disorder (BD). DNA methylation of HTR2A at T102C polymorphic site influences HTR2A expression and aberrant DNA methylation of HTR2A promoter was reported in postmortem brain of patients with SCZ and BD. Hypothesizing that the brain's epigenetic alteration of HTR2A may also exist in peripheral tissues that can be used as a diagnostic/therapeutic biomarker, we analyzed HTR2A promoter DNA methylation in DNA extracted from the saliva of patients with SCZ and BD, and their first degree relatives versus normal controls. Bisulfite sequencing was used to screen DNA methylation status of the HTR2A promoter CpGs and qMSP was used to quantify the degree of cytosine methylation at differentially methylated sites. Most of the cytosines of the HTR2A promoter were unmethylated. However, CpGs of the -1438A/G polymorphism site, -1420 and -1223 were >95% methylated. The CpG at T102C polymorphic site and neighboring CpGs were similar to 70% methylated both in the patients and controls. qMSP analysis revealed that the cytosine of the T102C polymorphic site was significantly hypomethylated in SCZ, BD, and their first degree relatives compared to the controls. Cytosine methylation of HTR2A at T102C polymorphic site in DNA derived from the saliva can potentially be used as a diagnostic, prognostic, and/or therapeutic biomarker in SCZ and BD. However, these preliminary observations need to be replicated in other populations with a larger sample size to be considered for clinical applications. (C) 2011 Wiley-Liss, Inc. C1 [Ghadirivasfi, Mohammad; Nohesara, Shabnam; Ahmadkhaniha, Hamid-Reza; Abdolmaleky, Hamid Mostafavi] Univ Tehran Med Sci, Mental Hlth Res Ctr, Dept Psychiat, Tehran, Iran. [Eskandari, Mohammad-Reza; Abdolmaleky, Hamid Mostafavi] Harvard Univ, Sch Med, Lab Nutr & Metab, BIDMC, Boston, MA USA. [Mostafavi, Siavash] Univ Massachusetts, Dept Biol Sci, Lowell, MA USA. [Thiagalingam, Sam; Abdolmaleky, Hamid Mostafavi] Dept Med Biomed Genet Genet & Genom, Boston, MA USA. [Thiagalingam, Sam; Abdolmaleky, Hamid Mostafavi] Genome Sci Inst, Boston, MA USA. [Thiagalingam, Sam] Boston Univ, Sch Med, Dept Pathol & Lab Med, Boston, MA 02118 USA. RP Thiagalingam, S (reprint author), Boston Univ, Sch Med L320, 72 E Concord St, Boston, MA 02118 USA. EM samthia@bu.edu; hamostafavi@yahoo.com OI Thiagalingam, Sam/0000-0001-5211-266X FU Mental Health Research Center, IUMS; NARSAD FX Grant sponsor: Mental Health Research Center, IUMS.; This work was supported by a grant from Mental Health Research Center, IUMS. Saliva samples for DNA and RNA extraction were donated by the Tehran Psychiatric Institute, IUMS. Dr. Sam Thiagalingam is supported by the NARSAD independent investigator Award with the designation Dr. Walter F. Nichols investigator. We thank Sahar Mostafavi for the editing of the manuscript. NR 48 TC 51 Z9 51 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD JUL PY 2011 VL 156B IS 5 BP 536 EP 545 DI 10.1002/ajmg.b.31192 PG 10 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 781PG UT WOS:000291945400004 PM 21598376 ER PT J AU O'Rourke, JA Scharf, JM Platko, J Stewart, SE Illmann, C Geller, DA King, RA Leckman, JF Pauls, DL AF O'Rourke, Julia A. Scharf, Jeremiah M. Platko, Jill Stewart, S. Evelyn Illmann, Cornelia Geller, Daniel A. King, Robert A. Leckman, James F. Pauls, David L. TI The Familial Association of Tourette's Disorder and ADHD: The Impact of OCD Symptoms SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE Tourette's disorder; ADHD; OCD; comorbidity ID OBSESSIVE-COMPULSIVE DISORDER; DEFICIT HYPERACTIVITY DISORDER; GLOBUS-PALLIDUS DYSFUNCTION; GENETIC-RELATIONSHIP; TIC DISORDERS; LEARNING-DISORDERS; SCHOOL-CHILDREN; PREVALENCE; COMORBIDITY; BEHAVIOR AB Tourette's disorder (TD) frequently co-occurs with attention-deficit/hyperactivity disorder(ADHD) and obsessive compulsive disorder (OCD). While the relationship between TD and OCD suggests that they share etiological factors, the exact relationship between TD and ADHD is less clear. The goal of the current analyses was to understand better the familial relationship between DSM-IV ADHD and TD. Direct interview diagnostic data from a case-control study of 692 relatives of 75 comorbid TD and ADHD(TD+ADHD), 74 TD without ADHD(TD Only), 41 ADHD without TD (ADHD Only), and 49 control probands were analyzed. Hierarchical loglinear modeling was used to explore association patterns between TD, ADHD, and OCD or sub-clinical OCD (OCD/OCDsub) diagnoses among the 190 affected probands and their 538 relatives. The presence of OCD or OCDsub diagnosis in a proband was associated with a significantly increased risk of comorbid TD+ADHD in his/her relatives. The finding of an association between TD, ADHD and a proband OCD/OCDsub diagnosis was unexpected. The current results suggest that TD, ADHD, and OCD symptoms have overlapping neurobiology when occurring in families of TD and/or ADHD probands. (C) 2011 Wiley-Liss, Inc. C1 [O'Rourke, Julia A.; Scharf, Jeremiah M.; Platko, Jill; Stewart, S. Evelyn; Illmann, Cornelia; Geller, Daniel A.; Pauls, David L.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. [O'Rourke, Julia A.; Scharf, Jeremiah M.; Platko, Jill; Stewart, S. Evelyn; Illmann, Cornelia; Geller, Daniel A.; Pauls, David L.] Harvard Univ, Sch Med, Boston, MA USA. [O'Rourke, Julia A.] Tufts Univ, Dept Biomed Engn, Medford, MA 02155 USA. [O'Rourke, Julia A.] Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA 02114 USA. [King, Robert A.; Leckman, James F.] Yale Univ, Sch Med, Ctr Child Study, New Haven, CT 06510 USA. RP Pauls, DL (reprint author), Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, 185 Cambridge St, Boston, MA 02114 USA. EM dpauls@pngu.mgh.harvard.edu RI Stewart, Evelyn/K-6961-2014; OI Stewart, S. Evelyn/0000-0002-0994-6383 FU NINDS [NS-16648, MH-49351, MH076273]; McIngvale Foundation FX Grant sponsor: NINDS; Grant Numbers: NS-16648, MH-49351, MH076273; Grant sponsor: McIngvale Foundation. NR 51 TC 25 Z9 25 U1 1 U2 19 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD JUL PY 2011 VL 156B IS 5 BP 553 EP 560 DI 10.1002/ajmg.b.31195 PG 8 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 781PG UT WOS:000291945400006 PM 21557467 ER PT J AU Sanchez-Mora, C Ribases, M Casas, M Bayes, M Bosch, R Fernandez-Castillo, N Brunso, L Jacobsen, KK Landaas, ET Lundervold, AJ Gross-Lesch, S Kreiker, S Jacob, CP Lesch, KP Buitelaar, JK Hoogman, M Kiemeney, LALM Kooij, JJS Mick, E Asherson, P Faraone, SV Franke, B Reif, A Johansson, S Haavik, J Ramos-Quiroga, JA Cormand, B AF Sanchez-Mora, Cristina Ribases, Marta Casas, Miquel Bayes, Monica Bosch, Rosa Fernandez-Castillo, Noelia Brunso, Lucas Jacobsen, Kaya K. Landaas, Elisabeth T. Lundervold, Astri J. Gross-Lesch, Silke Kreiker, Susanne Jacob, Christian P. Lesch, Klaus-Peter Buitelaar, Jan K. Hoogman, Martine Kiemeney, Lambertus A. L. M. Kooij, J. J. Sandra Mick, Eric Asherson, Phil Faraone, Stephen V. Franke, Barbara Reif, Andreas Johansson, Stefan Haavik, Jan Ramos-Quiroga, Josep Antoni Cormand, Bru TI Exploring DRD4 and Its Interaction With SLC6A3 as Possible Risk Factors for Adult ADHD: A Meta-Analysis in Four European Populations SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE attention-deficit hyperactivity disorder; case-control association study; neurotransmission; dopamine; psychiatric genetics ID DEFICIT HYPERACTIVITY DISORDER; DOPAMINE-D4 RECEPTOR GENE; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; TANDEM DUPLICATION POLYMORPHISM; III REPEAT POLYMORPHISM; 7-REPEAT ALLELE; D-4 RECEPTOR; MOLECULAR-GENETICS; TRANSPORTER GENE; CANDIDATE GENES AB Attention-deficit hyperactivity disorder (ADHD) is a common behavioral disorder affecting about 4-8% of children. ADHD persists into adulthood in around 65% of cases, either as the full condition or in partial remission with persistence of symptoms. Pharmacological, animal and molecular genetic studies support a role for genes of the dopaminergic system in ADHD due to its essential role in motor control, cognition, emotion, and reward. Based on these data, we analyzed two functional polymorphisms within the DRD4 gene (120 bp duplication in the promoter and 48 bp VNTR in exon 3) in a clinical sample of 1,608 adult ADHD patients and 2,352 controls of Caucasian origin from four European countries that had been recruited in the context of the International Multicentre persistent ADHD CollaboraTion (IMpACT). Single-marker analysis of the two polymorphisms did not reveal association with ADHD. In contrast, multiple-marker meta-analysis showed anominal association (P = 0.02) of the L-4R haplotype (dup120bp-48bpVNTR) with adulthood ADHD, especially with the combined clinical subtype. Since we previously described association between adulthood ADHD and the dopamine transporter SLC6A3 9R-6R haplotype (3'UTR VNTR-intron 8 VNTR) in the same dataset, we further tested for gene x gene interaction between DRD4 and SLC6A3. However, we detected no epistatic effects but our results rather suggest additive effects of the DRD4 risk haplotype and the SLC6A3 gene. (C) 2011 Wiley-Liss, Inc. C1 [Sanchez-Mora, Cristina; Fernandez-Castillo, Noelia; Brunso, Lucas; Cormand, Bru] Univ Barcelona, Fac Biol, Dept Genet, E-08028 Barcelona, Catalonia, Spain. [Sanchez-Mora, Cristina; Ribases, Marta; Casas, Miquel; Bosch, Rosa; Ramos-Quiroga, Josep Antoni] Hosp Univ Vall dHebron, Dept Psychiat, Barcelona, Catalonia, Spain. [Sanchez-Mora, Cristina; Ribases, Marta] Hosp Univ Vall dHebron, Psychiat Genet Unit, Barcelona, Catalonia, Spain. [Casas, Miquel; Bosch, Rosa; Ramos-Quiroga, Josep Antoni] Univ Autonoma Barcelona, Dept Psychiat & Legal Med, Catalonia, Spain. [Bayes, Monica] CNAG, Catalonia, Spain. [Fernandez-Castillo, Noelia; Cormand, Bru] CIBER Enfermedades Raras, Barcelona, Catalonia, Spain. [Jacobsen, Kaya K.; Landaas, Elisabeth T.; Johansson, Stefan] Haukeland Hosp, Dept Med Genet & Mol Med, N-5021 Bergen, Norway. [Jacobsen, Kaya K.; Landaas, Elisabeth T.; Johansson, Stefan; Haavik, Jan] Univ Bergen, Dept Biomed, Bergen, Norway. [Lundervold, Astri J.] Univ Bergen, Dept Biol & Med Psychol, Bergen, Norway. [Gross-Lesch, Silke; Jacob, Christian P.; Lesch, Klaus-Peter; Reif, Andreas] Univ Wurzburg, Dept Psychiat Psychosomat & Psychotherapy, Wurzburg, Germany. [Kreiker, Susanne] Univ Wurzburg, Dept Child & Adolescent Psychiat & Psychotherapy, Wurzburg, Germany. [Buitelaar, Jan K.] Radboud Univ Nijmegen, Med Ctr, Dept Cognit Neurosci, Donders Inst Brain Cognit & Behav, NL-6525 ED Nijmegen, Netherlands. [Hoogman, Martine; Franke, Barbara] Radboud Univ Nijmegen, Med Ctr, Dept Psychiat, Donders Inst Brain Cognit & Behav, NL-6525 ED Nijmegen, Netherlands. [Kiemeney, Lambertus A. L. M.; Ramos-Quiroga, Josep Antoni] Radboud Univ Nijmegen, Med Ctr, Dept Epidemiol Biostat & HTA, NL-6525 ED Nijmegen, Netherlands. [Kooij, J. J. Sandra] Program Adult ADHD, Psychomed Programs, The Hague, Netherlands. [Mick, Eric] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Mick, Eric] Harvard Univ, Sch Med, Boston, MA USA. [Asherson, Phil] Inst Psychiat, MRC, Social Genet Dev & Psychiat Ctr, London, England. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat & Neurosci & Physiol, Syracuse, NY USA. [Franke, Barbara] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands. [Haavik, Jan] Haukeland Hosp, Dept Psychiat, N-5021 Bergen, Norway. [Cormand, Bru] Univ Barcelona, Inst Biomed, Catalonia, Spain. RP Cormand, B (reprint author), Univ Barcelona, Fac Biol, Dept Genet, Av Diagonal 645,Edifici Annex,3A Planta, E-08028 Barcelona, Catalonia, Spain. EM bcormand@ub.edu RI Franke, Barbara/D-4836-2009; Buitelaar, Jan/E-4584-2012; Kiemeney, Lambertus/D-3357-2009; Johansson, Stefan/C-4394-2011; Hoogman, Martine/G-8958-2015; Cormand, Bru/H-5338-2015; Fernandez-Castillo, Noelia/F-7395-2016; Lesch, Klaus-Peter/J-4906-2013; OI Franke, Barbara/0000-0003-4375-6572; Buitelaar, Jan/0000-0001-8288-7757; Kiemeney, Lambertus/0000-0002-2368-1326; Johansson, Stefan/0000-0002-2298-7008; Hoogman, Martine/0000-0002-1261-7628; Cormand, Bru/0000-0001-5318-4382; Fernandez-Castillo, Noelia/0000-0001-9948-0312; Ramos-Quiroga, Josep Antoni/0000-0003-1622-0350; Mick, Eric/0000-0001-8505-8145; Lesch, Klaus-Peter/0000-0001-8348-153X; Ribases, Marta/0000-0003-1039-1116; Faraone, Stephen/0000-0002-9217-3982; Haavik, Jan/0000-0001-7865-2808 FU "Institutode SaludCarlos III-FIS," Spain [PI040524PI041267, PI080519]; "Fundacio La Marato de TV3" [092330/31]; "Agencia de Gestio d'Ajuts Univeristaris i de Recerca-AGAUR" [2009SGR-00971]; Obra Social - Fundacio "La Caixa" [2007-2010]; Subdireccio General de Drogodependencies, Departament de Salut; Pla Director de Salut Mental i Addiccions, Catalonia Government (Generalitat de Catalunya); Hersenstichting Nederland (Fonds Psychische Gezondheid); Research Council of Norway; Western Norway Regional Health Authority; National Research Network for ADHD; University of Bergen; DFG [RE1632/1-5, KFO 125 SFB TRR 58/A1, Z02, GRK 1156]; GK Emotions; BMBF [01GV0605]; EC [NEWMOOD LSHM-CT-2003-503474] FX Grant sponsor: "Institutode SaludCarlos III-FIS," Spain; Grant numbers: PI040524PI041267, PI080519; Grant sponsor: "Fundacio La Marato de TV3"; Grant number: 092330/31; Grant sponsor: "Agencia de Gestio d'Ajuts Univeristaris i de Recerca-AGAUR"; Grant number: 2009SGR-00971; Grant sponsor: Obra Social - Fundacio "La Caixa"; Grant number: 2007-2010; Grant sponsor: Subdireccio General de Drogodependencies, Departament de Salut, and Pla Director de Salut Mental i Addiccions, Catalonia Government (Generalitat de Catalunya); Grant sponsor: Hersenstichting Nederland (Fonds Psychische Gezondheid); Grant sponsor: Research Council of Norway; Grant sponsor: Western Norway Regional Health Authority; Grant sponsor: The National Research Network for ADHD; Grant sponsor: The University of Bergen; Grant sponsor: DFG; Grant numbers: RE1632/1-5, KFO 125 SFB TRR 58/A1,5, Z02, GRK 1156; Grant sponsor: GK Emotions; Grant sponsor: BMBF; Grant number: 01GV0605; Grant sponsor: EC; Grant number: NEWMOOD LSHM-CT-2003-503474. NR 83 TC 13 Z9 13 U1 4 U2 17 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD JUL PY 2011 VL 156B IS 5 BP 600 EP 612 DI 10.1002/ajmg.b.31202 PG 13 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 781PG UT WOS:000291945400011 PM 21595008 ER PT J AU Townsend, MK Jura, YH Curhan, GC Resnick, NM Grodstein, F AF Townsend, Mary K. Jura, Ying H. Curhan, Gary C. Resnick, Neil M. Grodstein, Francine TI Fluid intake and risk of stress, urgency, and mixed urinary incontinence SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE fluid intake; urinary incontinence ID FOOD FREQUENCY QUESTIONNAIRE; LIFE-STYLE FACTORS; EPIDEMIOLOGIC SURVEY; OVERACTIVE BLADDER; WOMEN; REPRODUCIBILITY; VALIDITY; VALIDATION AB OBJECTIVE: We investigated the relation between total fluid intake and incident urinary incontinence in the Nurses' Health Study cohorts. STUDY DESIGN: We measured daily fluid intake using food frequency questionnaires among 65,167 women, who were 37-79 years old, without urinary incontinence at study baseline (20002001). Women reported incontinence incidence on questionnaires during 4 years of follow-up evaluation. Multivariable-adjusted hazard ratios and 95% confidence intervals were calculated with Cox proportional hazards models. RESULTS: We found no association between total fluid intake and risk of incident incontinence (hazard ratio, 1.04; 95% confidence interval, 0.98-1.10; comparing top vs bottom quintile of fluid intake). In analyses of incontinence type, total fluid intake was not associated with risks of incident stress, urgency, or mixed incontinence. CONCLUSION: No significant risk of incident urinary incontinence was found with higher fluid intake in women. These findings suggest that women should not restrict their fluid intake to prevent incontinence development. C1 [Townsend, Mary K.; Curhan, Gary C.; Grodstein, Francine] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Curhan, Gary C.] Brigham & Womens Hosp, Dept Med, Div Renal, Boston, MA 02115 USA. [Townsend, Mary K.; Jura, Ying H.; Curhan, Gary C.; Grodstein, Francine] Harvard Univ, Sch Med, Boston, MA USA. [Townsend, Mary K.; Curhan, Gary C.; Grodstein, Francine] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Jura, Ying H.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Resnick, Neil M.] Univ Pittsburgh, Sch Med, Dept Med, Div Geriatr Med, Pittsburgh, PA USA. RP Townsend, MK (reprint author), 181 Longwood Ave, Boston, MA 02115 USA. EM nhmkt@channing.harvard.edu FU National Institutes of Health [DK62438, CA87969, CA50385]; Harvard School of Public Health FX Supported by Grant nos. DK62438, CA87969, and CA50385 from the National Institutes of Health and by the Yerby Postdoctoral Fellowship Program, Harvard School of Public Health (M.K.T.). NR 25 TC 1 Z9 1 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JUL PY 2011 VL 205 IS 1 AR 73.e1 DI 10.1016/j.ajog.2011.02.054 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 783KX UT WOS:000292082400039 PM 21481835 ER PT J AU Routray, C Liu, CS Yaqoob, U Billadeau, DD Bloch, KD Kaibuchi, K Shah, VH Kang, NL AF Routray, Chittaranjan Liu, Chunsheng Yaqoob, Usman Billadeau, Daniel D. Bloch, Kenneth D. Kaibuchi, Kozo Shah, Vijay H. Kang, Ningling TI Protein kinase G signaling disrupts Rac1-dependent focal adhesion assembly in liver specific pericytes SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE nitric oxide; vasodilator-stimulated phosphoprotein; cGMP-dependent kinase; hepatic stellate cells ID VASCULAR SMOOTH-MUSCLE; NITRIC-OXIDE SYNTHASE; VASODILATOR-STIMULATED PHOSPHOPROTEIN; CIRRHOTIC RAT LIVERS; CELL-MIGRATION; ENDOTHELIAL DYSFUNCTION; HEPATIC-FIBROSIS; TUMOR-GROWTH; RAC1; VASP AB Routray C, Liu C, Yaqoob U, Billadeau DD, Bloch KD, Kaibuchi K, Shah VH, Kang N. Protein kinase G signaling disrupts Rac1-dependent focal adhesion assembly in liver specific pericytes. Am J Physiol Cell Physiol 301: C66-C74, 2011. First published March 30, 2011; doi:10.1152/ajpcell.00038.2011.-Nitric oxide (NO) regulates the function of perivascular cells (pericytes), including hepatic stellate cells (HSC), mainly by activating cGMP and cGMP-dependent kinase (PKG) via NO/cGMP paracrine signaling. Although PKG is implicated in integrin-mediated cell adhesion to extracellular matrix, whether or how PKG signaling regulates the assembly of focal adhesion complexes (FA) and migration of HSC is not known. With the help of complementary molecular and cell biological approaches, we demonstrate here that activation of PKG signaling in HSC inhibits vascular tubulogenesis, migration/chemotaxis, and assembly of mature FA plaques, as assessed by vascular tubulogenesis assays and immunofluorescence localization of FA markers such as vinculin and vasodilator-stimulated phosphoprotein (VASP). To determine whether PKG inhibits FA assembly by phosphorylation of VASP at Ser-157, Ser-239, and Thr-278, we mutated these putative phosphorylation sites to alanine (VASP3A, phosphoresistant mutant) or aspartic acid (VASP3D, phosphomimetic), respectively. Data generated from these two mutants suggest that the effect of PKG on FA is independent of these three phosphorylation sites. In contrast, activation of PKG inhibits the activity of small GTPase Rac1 and its association with the effector protein IQGAP1. Moreover, PKG activation inhibits the formation of a trimeric protein complex containing Rac1, IQGAP1, and VASP. Finally, we found that expression of a constitutively active Rac1 mutant abolishes the inhibitory effects of PKG on FA formation. In summary, our data suggest that activation of PKG signaling in pericytes inhibits FA formation by inhibiting Rac1. C1 [Routray, Chittaranjan; Liu, Chunsheng; Yaqoob, Usman; Shah, Vijay H.; Kang, Ningling] Mayo Clin, GI Res Unit, Rochester, MN 55905 USA. [Routray, Chittaranjan; Liu, Chunsheng; Yaqoob, Usman; Shah, Vijay H.; Kang, Ningling] Mayo Clin, Canc Cell Biol Program, Rochester, MN 55905 USA. [Billadeau, Daniel D.] Mayo Clin, Dept Immunol, Rochester, MN 55905 USA. [Bloch, Kenneth D.] Massachusetts Gen Hosp, Anesthesia Ctr Crit Care Res, Boston, MA 02114 USA. [Kaibuchi, Kozo] Nagoya Univ, Grad Sch Med, Dept Cell Pharmacol, Nagoya, Aichi 4648601, Japan. RP Kang, NL (reprint author), Mayo Clin, GI Res Unit, 200 1st St SW, Rochester, MN 55905 USA. EM kang.ningling@mayo.edu RI Kaibuchi, Kozo/M-4887-2014 OI Kaibuchi, Kozo/0000-0003-0714-1992 FU Howard Temin Award [K01 CA]; Mayo Clinic; NIDDK Center FX These studies were supported through The Howard Temin Award (K01 CA), 2009 Research Early Career Development Award (Mayo Clinic), and P/F Award (P30 NIDDK Center Grant). NR 54 TC 9 Z9 9 U1 1 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD JUL PY 2011 VL 301 IS 1 BP C66 EP C74 DI 10.1152/ajpcell.00038.2011 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 783LN UT WOS:000292084300009 PM 21451103 ER PT J AU Shum, WW Da Silva, N Belleannee, C Mckee, M Brown, D Breton, S AF Shum, Winnie Waichi Da Silva, Nicolas Belleannee, Clemence McKee, Mary Brown, Dennis Breton, Sylvie TI Regulation of V-ATPase recycling via a RhoA- and ROCKII-dependent pathway in epididymal clear cells SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE actin; proton pump; luminal acidification; proton ATPase; epididymis ID VACUOLAR H+-ATPASE; MALE REPRODUCTIVE-TRACT; TRANSCRIPTION FACTOR FOXI1; RAT CAUDA-EPIDIDYMIDIS; ACTIN-BINDING SITE; LUMINAL ACIDIFICATION; APICAL MEMBRANE; B1 SUBUNIT; F-ACTIN; VESICLE TRAFFICKING AB Shum WW, Da Silva N, Belleannee C, McKee M, Brown D, Breton S. Regulation of V-ATPase recycling via a RhoA-and ROCKII-dependent pathway in epididymal clear cells. Am J Physiol Cell Physiol 301: C31-C43, 2011. First published March 16, 2011; doi:10.1152/ajpcell.00198.2010.-Luminal acidification in the epididymis is critical for sperm maturation and storage. Clear cells express the vacuolar H+-ATPase (V-ATPase) in their apical membrane and are major contributors to proton secretion. We showed that this process is regulated via recycling of V-ATPase-containing vesicles. We now report that RhoA and its effector ROCKII are enriched in rat epididymal clear cells. In addition, cortical F-actin was detected beneath the apical membrane and along the lateral membrane of "resting" clear cells using a pan-actin antibody or phalloidin-TRITC. In vivo luminal perfusion of the cauda epididymal tubule with the ROCK inhibitors Y27632 (10-30 mu M) and HA1077 (30 mu M) or with the cell-permeable Rho inhibitor Clostridium botulinum C3 transferase (3.75 mu g/ml) induced the apical membrane accumulation of V-ATPase and extension of V-ATPase-labeled microvilli in clear cells. However, these newly formed microvilli were devoid of ROCKII. In addition, Y27632 (30 mu M) or HA1077 (30 mu M) decreased the ratio of F-actin to G-actin detected by Western blot analysis in epididymal epithelial cells, and Y27632 also decreased the ratio of F-actin to G-actin in clear cells isolated by fluorescence activated cell sorting from B1-enhanced green fluorescence protein (EGFP) transgenic mice. These results provide evidence that depolymerization of the cortical actin cytoskeleton via inhibition of RhoA or its effector ROCKII favors the recruitment of V-ATPase from the cytosolic compartment into the apical membrane in clear cells. In addition, our data suggest that the RhoA-ROCKII pathway is not locally involved in the elongation of apical microvilli. We propose that inhibition of RhoA-ROCKII might be part of the intracellular signaling cascade that is triggered upon agonist-induced apical membrane V-ATPase accumulation. C1 [Shum, Winnie Waichi; Da Silva, Nicolas; Belleannee, Clemence; McKee, Mary; Brown, Dennis; Breton, Sylvie] Massachusetts Gen Hosp, Program Membrane Biol, Ctr Syst Biol, Div Nephrol, Boston, MA 02114 USA. [Shum, Winnie Waichi; Da Silva, Nicolas; Belleannee, Clemence; Brown, Dennis; Breton, Sylvie] Harvard Univ, Sch Med, Boston, MA USA. RP Breton, S (reprint author), Massachusetts Gen Hosp, Program Membrane Biol, Ctr Syst Biol, Div Nephrol, Simches Bldg,185 Cambridge St,Suite 8-204, Boston, MA 02114 USA. EM sbreton@partners.org FU National Institutes of Health [HD-40793, DK-38452] FX This study was supported by National Institutes of Health Grants HD-40793 (to S. Breton) and DK-38452 (to D. Brown and S. Breton). NR 70 TC 15 Z9 15 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD JUL PY 2011 VL 301 IS 1 BP C31 EP C43 DI 10.1152/ajpcell.00198.2010 PG 13 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 783LN UT WOS:000292084300006 PM 21411727 ER PT J AU Jessen, N An, D Lihn, AS Nygren, J Hirshman, MF Thorell, A Goodyear, LJ AF Jessen, Niels An, Ding Lihn, Aina S. Nygren, Jonas Hirshman, Michael F. Thorell, Anders Goodyear, Laurie J. TI Exercise increases TBC1D1 phosphorylation in human skeletal muscle SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE glucose transport; adenosine 5 '-monophosphate-activated protein kinase ID GTPASE-ACTIVATING-PROTEIN; SITE-SPECIFIC PHOSPHORYLATION; AS160 PHOSPHORYLATION; GLUCOSE-TRANSPORT; GLUT4 TRANSLOCATION; INSULIN; CONTRACTION; AMPK; KINASE; BINDING AB Jessen N, An D, Lihn AS, Nygren J, Hirshman MF, Thorell A, Goodyear LJ. Exercise increases TBC1D1 phosphorylation in human skeletal muscle. Am J Physiol Endocrinol Metab 301: E164-E171, 2011. First published April 19, 2011; doi: 10.1152/ajpendo.00042.2011.-Exercise and weight loss are cornerstones in the treatment and prevention of type 2 diabetes, and both interventions function to increase insulin sensitivity and glucose uptake into skeletal muscle. Studies in rodents demonstrate that the underlying mechanism for glucose uptake in muscle involves site-specific phosphorylation of the Rab-GTPase-activating proteins AS160 (TBC1D4) and TBC1D1. Multiple kinases, including Akt and AMPK, phosphorylate TBC1D1 and AS160 on distinct residues, regulating their activity and allowing for GLUT4 translocation. In contrast to extensive rodent-based studies, the regulation of AS160 and TBC1D1 in human skeletal muscle is not well understood. In this study, we determined the effects of dietary intervention and a single bout of exercise on TBC1D1 and AS160 site-specific phosphorylation in human skeletal muscle. Ten obese (BMI 33.4 +/- 2.4, M-value 4.3 +/- 0.5) subjects were studied at baseline and after a 2-wk dietary intervention. Muscle biopsies were obtained from the subjects in the resting (basal) state and immediately following a 30-min exercise bout (70% (V)over dotO(2 max)). Muscle lysates were analyzed for AMPK activity and Akt phosphorylation and for TBC1D1 and AS160 phosphorylation on known or putative AMPK and Akt sites as follows: AS160 Ser(711) (AMPK), TBC1D1 Ser(231) (AMPK), TBC1D1 Ser(660) (AMPK), TBC1D1 Ser(700) (AMPK), and TBC1D1 Thr(590) (Akt). The diet intervention that consisted of a major shift in the macronutrient composition resulted in a 4.2 +/- 0.4 kg weight loss (P < 0.001) and a significant increase in insulin sensitivity (M value 5.6 +/- 0.6), but surprisingly, there was no effect on expression or phosphorylation of any of the muscle-signaling proteins. Exercise increased muscle AMPK alpha 2 activity but did not increase Akt phosphorylation. Exercise increased phosphorylation on AS160 Ser(711), TBC1D1 Ser(231), and TBC1D1 Ser(660) but had no effect on TBC1D1 Ser(700). Exercise did not increase TBC1D1 Thr(590) phosphorylation or TBC1D1/AS160 PAS phosphorylation, consistent with the lack of Akt activation. These data demonstrate that a single bout of exercise regulates TBC1D1 and AS160 phosphorylation on multiple sites in human skeletal muscle. C1 [Jessen, Niels; An, Ding; Hirshman, Michael F.; Goodyear, Laurie J.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Jessen, Niels] Aarhus Univ Hosp, Dept Clin Pharmacol, DK-8000 Aarhus, Denmark. [Lihn, Aina S.] Aarhus Univ Hosp, Dept Endocrinol & Metab, DK-8000 Aarhus, Denmark. [Nygren, Jonas; Thorell, Anders] Karolinska Inst, Dept Clin Sci, Danderyds Hosp, Stockholm, Sweden. [Nygren, Jonas; Thorell, Anders] Ersta Hosp, Dept Surg, Stockholm, Sweden. RP Goodyear, LJ (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM laurie.goodyear@joslin.harvard.edu RI Jessen, Niels/E-1731-2011; OI Jessen, Niels/0000-0001-5613-7274 FU National Institute of Arthritis and Musculoskeletal and Skin Diseases [R01-AR-42238, R01-AR-45670]; Joslin Diabetes Center; American Diabetes Association; Diabetes and Endocrinology Research Center [P30-DK-36836]; Danish Agency for Science Technology and Innovation [271-07-0719] FX This work was supported by funding from National Institute of Arthritis and Musculoskeletal and Skin Diseases Grants R01-AR-42238 and R01-AR-45670 (L. J. Goodyear), the Graetz Challenge Grant from the Joslin Diabetes Center (L. J. Goodyear), the American Diabetes Association Mentor-based Award (L. J. Goodyear), and Diabetes and Endocrinology Research Center Grant P30-DK-36836 (Joslin Diabetes Center). Additional funds to support this work were provided by the Danish Agency for Science Technology and Innovation to N. Jessen (grant no. 271-07-0719). NR 38 TC 31 Z9 31 U1 0 U2 10 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD JUL PY 2011 VL 301 IS 1 BP E164 EP E171 DI 10.1152/ajpendo.00042.2011 PG 8 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 783MA UT WOS:000292085900018 PM 21505148 ER PT J AU Luo, NL Wang, XD Chung, BH Lee, MH Klein, RL Garvey, WT Fu, YC AF Luo, Nanlan Wang, Xiangdong Chung, B. Hong Lee, Mi-Hye Klein, Richard L. Garvey, W. Timothy Fu, Yuchang TI Effects of macrophage-specific adiponectin expression on lipid metabolism in vivo SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE metabolic disorder; type 2 diabetes; atherosclerosis ID HIGH-DENSITY-LIPOPROTEIN; REVERSE CHOLESTEROL TRANSPORT; MONOCYTE-DERIVED MACROPHAGES; PIMA INDIAN POPULATION; INSULIN-RESISTANCE; ADIPOSE-TISSUE; SERUM ADIPONECTIN; LIVER-TRANSPLANTATION; APOLIPOPROTEIN-B; PLASMA-PROTEIN AB Luo N, Wang X, Chung BH, Lee M, Klein RL, Garvey WT, Fu Y. Effects of macrophage-specific adiponectin expression on lipid metabolism in vivo. Am J Physiol Endocrinol Metab 301: E180-E186, 2011. First published April 19, 2011; doi: 10.1152/ajpendo.00614.2010.-Epidemiological studies have associated low circulating levels of the adipokine adiponectin with multiple metabolic disorders, including metabolic syndrome, obesity, insulin resistance, type II diabetes, and cardiovascular disease. Recently, we reported that adiponectin selectively overexpressed in mouse macrophages can improve insulin sensitivity and protect against inflammation and atherosclerosis. To further investigate the role of adiponectin and macrophages on lipid and lipometabolism in vivo, we engineered the expression of adiponectin in mouse macrophages (Ad-TG mice) and examined effects on plasma lipoproteins and on the expression levels of genes involved in lipoprotein metabolism in tissues. Compared with the wild-type (WT) mice, Ad-TG mice exhibited significantly lower levels of plasma total cholesterol (-21%, P < 0.05) due to significantly decreased LDL (-34%, P < 0.05) and VLDL (-32%, P < 0.05) cholesterol concentrations together with a significant increase in HDL cholesterol (+41%, P < 0.05). Further studies investigating potential mechanisms responsible for the change in lipoprotein cholesterol profile revealed that adiponectin-producing macrophages altered expression of key genes in liver tissue, including apoA1, apoB, apoE, the LDL receptor, (P < 0.05), and ATP-binding cassette G1 (P < 0.01). In addition, Ad-TG mice also exhibited higher total and high-molecular-weight adipnection levels in plasma and increased expression of the anti-inflammatory cytokine IL-10 as well as a decrease in the proinflammatory cytokine IL-6 in adipose tissue. These results indicate that macrophages engineered to produce adiponectin can influence in vivo gene expression in adipose tissue in a manner that reduces inflammation and macrophage infiltration and in liver tissue in a manner that alters the circulating lipoprotein profile, resulting in a decrease in VLDL and LDL and an increase in HDL cholesterol. The data support further study addressing the use of genetically manipulated macrophages as a novel therapeutic approach for treatment of cardiometabolic disease. C1 [Luo, Nanlan; Chung, B. Hong; Garvey, W. Timothy; Fu, Yuchang] Univ Alabama, Dept Nutr Sci, Birmingham, AL 35294 USA. [Garvey, W. Timothy] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Wang, Xiangdong] Shandong Univ, Sch Med, Inst Cell Biol, Jinan 250100, Peoples R China. [Lee, Mi-Hye; Klein, Richard L.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Lee, Mi-Hye; Klein, Richard L.] Med Univ S Carolina, Ralph H Johnson Dept Veteran Affairs Med Ctr, Charleston, SC 29425 USA. RP Fu, YC (reprint author), Univ Alabama, Dept Nutr Sci, Shelby Bldg 1213,1825 Univ Blvd, Birmingham, AL 35294 USA. EM yfu@uab.edu RI e-, a/F-9947-2012 FU National Institute of Diabetes and Digestive and Kidney Diseases [DK-083562, DK-038764]; Medical Research Service of the Department of Veterans Affairs; University of Alabama Birmingham Diabetes Research and Training Center; American Diabetes Association [1-07-RA-49]; University of Alabama at Birmingham Diabetes Research Center [DK-079626] FX This work was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (DK-083562, DK-038764) and the Merit Review Program of the Medical Research Service of the Department of Veterans Affairs to W. T. Garvey and R. L. Klein and by grants from the University of Alabama Birmingham Diabetes Research and Training Center and American Diabetes Association (1-07-RA-49) to Y. Fu. We further acknowledge the University of Alabama at Birmingham Diabetes Research Center (DK-079626) for research core support. NR 46 TC 12 Z9 12 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD JUL PY 2011 VL 301 IS 1 BP E180 EP E186 DI 10.1152/ajpendo.00614.2010 PG 7 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 783MA UT WOS:000292085900020 PM 21505149 ER PT J AU Cawley, SM Kolodziej, S Ichinose, F Brouckaert, P Buys, ES Bloch, KD AF Cawley, Sharon M. Kolodziej, Starsha Ichinose, Fumito Brouckaert, Peter Buys, Emmanuel S. Bloch, Kenneth D. TI sGC alpha(1) mediates the negative inotropic effects of NO in cardiac myocytes independent of changes in calcium handling SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE cyclic-3 ',5 '-guanosine monophosphate; beta(3)-adrenergic receptor; cardiac contractility; nitric oxide; soluble guanylate cyclase ID NITRIC-OXIDE SYNTHASE; SOLUBLE GUANYLATE-CYCLASE; CYCLIC-GMP; VENTRICULAR MYOCYTES; PROTEIN-KINASE; CONTRACTILE RESPONSE; HEART-FAILURE; SARCOPLASMIC-RETICULUM; ADRENERGIC-STIMULATION; MYOCARDIAL-INFARCTION AB Cawley SM, Kolodziej S, Ichinose F, Brouckaert P, Buys ES, Bloch KD. sGC alpha(1) mediates the negative inotropic effects of NO in cardiac myocytes independent of changes in calcium handling. Am J Physiol Heart Circ Physiol 301: H157-H163, 2011. First published May 2, 2011; doi:10.1152/ajpheart.01273.2010.-In the heart, nitric oxide (NO) modulates contractile function; however, the mechanisms responsible for this effect are incompletely understood. NO can elicit effects via a variety of mechanisms including S-nitrosylation and stimulation of cGMP synthesis by soluble guanylate cyclase (sGC). sGC is a heterodimer comprised of a beta(1)- and an alpha(1)- or alpha(2)-subunit. sGC alpha(1)beta(1) is the predominant isoform in the heart. To characterize the role of sGC in the regulation of cardiac contractile function by NO, we compared left ventricular cardiac myocytes (CM) isolated from adult mice deficient in the sGC alpha(1)-subunit (sGC alpha(-/-)(1)) and from wild-type (WT) mice. Sarcomere shortening under basal conditions was less in sGC alpha(-/-)(1) CM than in WT CM. To activate endogenous NO synthesis from NO synthase 3, CM were incubated with the beta(3)-adrenergic receptor (beta(3)-AR) agonist BRL 37344. BRL 37344 decreased cardiac contractility in WT CM but not in sGC alpha(-/-)(1) myocytes. Administration of spermine NONOate, an NO donor compound, did not affect sarcomeric shortening in CM of either genotype; however, in the presence of isoproterenol, addition of spermine NONOate reduced sarcomere shortening in WT but not in sGC alpha(-/-)(1) CM. Neither BRL 37344 nor spermine NONOate altered calcium handling in CM of either genotype. These findings suggest that sGC alpha(1) exerts a positive inotropic effect under basal conditions, as well as mediates the negative inotropic effect of beta(3)-AR signaling. Additionally, our work demonstrates that sGC alpha(1)beta(1) is required for NO to depress beta(1)/beta(2)-AR-stimulated cardiac contractility and that this modulation is independent of changes in calcium handling. C1 [Cawley, Sharon M.; Bloch, Kenneth D.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Cawley, Sharon M.; Kolodziej, Starsha; Ichinose, Fumito; Buys, Emmanuel S.; Bloch, Kenneth D.] Massachusetts Gen Hosp, Anesthesia Ctr Crit Care Res, Boston, MA 02114 USA. [Brouckaert, Peter] Univ Ghent, Dept Biomed Mol Biol, B-9000 Ghent, Belgium. [Brouckaert, Peter] VIB, Dept Mol Biomed Res, Ghent, Belgium. RP Cawley, SM (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 505 Thier Bldg, Boston, MA 02114 USA. EM Scawley@partners.org FU Ruth L. Kirschtein National Research Service [HL-07208-29]; American Heart Association [10SDG2610313]; National Institute of General Medical Sciences [RO1-GM-079360]; National Heart, Lung, and Blood Institute [R01 HL74352] FX S. M. Cawley was supported by a Ruth L. Kirschtein National Research Service Award Grant HL-07208-29, E. S. Buys was supported by a Scientist Development Grant 10SDG2610313 from the American Heart Association, F. Ichinose was supported by National Institute of General Medical Sciences Grant RO1-GM-079360, and K. D. Bloch was supported by National Heart, Lung, and Blood Institute R01 HL74352. NR 51 TC 11 Z9 11 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD JUL PY 2011 VL 301 IS 1 BP H157 EP H163 DI 10.1152/ajpheart.01273.2010 PG 7 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 784ZL UT WOS:000292197100018 PM 21536853 ER PT J AU Rush, AJ Trivedi, MH Stewart, JW Nierenberg, AA Fava, M Kurian, BT Warden, D Morris, DW Luther, JF Husain, MM Cook, IA Shelton, RC Lesser, IM Kornstein, SG Wisniewski, SR AF Rush, A. John Trivedi, Madhukar H. Stewart, Jonathan W. Nierenberg, Andrew A. Fava, Maurizio Kurian, Benji T. Warden, Diane Morris, David W. Luther, James F. Husain, Mustafa M. Cook, Ian A. Shelton, Richard C. Lesser, Ira M. Kornstein, Susan G. Wisniewski, Stephen R. TI Combining Medications to Enhance Depression Outcomes (CO-MED): Acute and Long-Term Outcomes of a Single-Blind Randomized Study SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID STAR-ASTERISK-D; MEASUREMENT-BASED CARE; CLINICAL-PRACTICE; MAJOR DEPRESSION; RATING-SCALE; BUPROPION-SR; COMBINATION; DISORDER; TRIAL; AUGMENTATION AB Objective: Two antidepressant medication combinations were compared with selective serotonin reuptake inhibitor monotherapy to determine whether either combination produced a higher remission rate in first-step acute-phase (12 weeks) and long-term (7 months) treatment. Method: The single-blind, prospective, randomized trial enrolled 665 outpatients at six primary and nine psychiatric care sites. Participants had at least moderately severe nonpsychotic chronic and/or recurrent major depressive disorder. Escitalopram (up to 20 mg/day) plus placebo, sustained-release bupropion (up to 400 mg/day) plus escitalopram (up to 20 mg/day), or extended-release venlafaxine (up to 300 mg/day) plus mirtazapine (up to 45 mg/day) was delivered (1: 1: 1 ratio) by using measurement-based care. The primary outcome was remission, defined as ratings of less than 8 and less than 6 on the last two consecutive applications of the 16-item Quick Inventory of Depressive Symptomatology-Self-Report. Secondary outcomes included side effect burden, adverse events, quality of life, functioning, and attrition. Results: Remission and response rates and most secondary outcomes were not different among treatment groups at 12 weeks. The remission rates were 38.8% for escitalopram-placebo, 38.9% for bupropion-escitalopram, and 37.7% for venlafaxine-mirtazapine, and the response rates were 51.6%-52.4%. The mean number of worsening adverse events was higher for venlafaxine-mirtazapine (5.7) than for escitalopram-placebo (4.7). At 7 months, remission rates (41.8%-46.6%), response rates (57.4%-59.4%), and most secondary outcomes were not significantly different. Conclusions: Neither medication combination outperformed monotherapy. The combination of extended-release venlafaxine plus mirtazapine may have a greater risk of adverse events. C1 [Trivedi, Madhukar H.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. Duke Natl Univ Singapore, Grad Sch Med, Singapore, Singapore. Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA 15260 USA. Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. Columbia Univ, Coll Phys & Surg, New York State Psychiat Inst, New York, NY USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Depress Res & Clin Program, Los Angeles, CA 90024 USA. Vanderbilt Univ, Dept Psychiat, Nashville, TN USA. Harbor UCLA Med Ctr, Dept Psychiat, Torrance, CA 90509 USA. Los Angeles Biomed Res Inst, Torrance, CA USA. Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA USA. RP Trivedi, MH (reprint author), Univ Texas SW Med Ctr Dallas, Dept Psychiat, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM madhukar.trive-di@utsouthwestern.edu OI Wisniewski, Stephen/0000-0002-3877-9860; Rush, Augustus/0000-0003-2004-2382 FU Neuromodulation Systems; Best Practice Project Management; Brain Resource; Otsuka; University of Michigan; Forest; Pfizer; Guilford Publications; Healthcare Technology Systems; University of Texas Southwestern Medical Center; National Institute of Mental Health [N01 MH-90003]; Agency for Healthcare Research and Quality; Corcept; Cyberonics; Merck; NARSAD; National Institute on Drug Abuse; Novartis; Pharmacia Upjohn; Predix (EPIX); Solvay; Targacept; Abbott; Abdi Ibrahim; Akzo (Organon); AstraZeneca; Bristol-Myers Squibb; Cephalon; Eli Lilly; Evotec; Fabre Kramer; GlaxoSmithKline; Janssen; Johnson Johnson; Meade Johnson; Medtronic; Neuronetics; Parke-Davis; Sepracor; Shire Development; VantagePoint; Wyeth; Alkermes; Aspect Medical Systems; BioResearch; BrainCells; CeNeRx BioPharma; Clinical Trials Solutions; Clintara; Covidien; EnVivo; Euthymics Bioscience; Ganeden Biotech; Icon Clinical Research; i3 Innovus/Ingenix; Lichtwer; Lorex; National Center for Complementary and Alternative Medicine; Organon; Pamlab; Pharmavite; Photothera; RCT Logic; Roche; Sanofi-Aventis; Shire; Synthelabo; Adamed; Advanced Meeting Partners; American Psychiatric Association; American Society of Clinical Psychopharmacology; Belvoir Media Group; Boehringer Ingelheim; CME Institute/Physicians Postgraduate Press; Imedex; MGH Psychiatry Academy/Primedia; MGH Psychiatry Academy/Reed Elsevier; PharmaStar; United BioSource; Magstim; NIH/NIMH; Stanley Foundation; St. Jude Medical; Aspect Medical Systems/Covidien; NIH; Sanofi; Boehringer-Ingelheim; Rexahn; Takeda; Guilford Press; University of Texas Southwestern Medical Center at Dallas; U.S. Department of Health and Human Services; U.S. government FX Dr. Rush has received consulting fees from Advanced Neuromodulation Systems, Best Practice Project Management, Brain Resource, Otsuka, and the University of Michigan; he has received consultant/speaker fees from Forest; he has received consultant fees from and owns stock in Pfizer; he has received author royalties from Guilford Publications, Healthcare Technology Systems, and the University of Texas Southwestern Medical Center; and he has received research support from the National Institute of Mental Health. Dr. Trivedi has received research support from the Agency for Healthcare Research and Quality, Corcept, Cyberonics, Merck, NARSAD, the National Institute of Mental Health, the National Institute on Drug Abuse, Novartis, Pharmacia & Upjohn, Predix (EPIX), Solvay, and Targacept; he has received consulting and speaker fees from Abbott, Abdi Ibrahim, Akzo (Organon), AstraZeneca, Bristol-Myers Squibb, Cephalon, Eli Lilly, Evotec, Fabre Kramer, Forest, GlaxoSmithKline, Janssen, Johnson & Johnson, Meade Johnson, Medtronic, Neuronetics, Otsuka, Parke-Davis, Pfizer, Sepracor, Shire Development, VantagePoint, and Wyeth. Dr.; Fava has received research support from Abbott, Alkermes, Aspect Medical Systems, AstraZeneca, BioResearch, BrainCells, Bristol-Myers Squibb, CeNeRx BioPharma, Cephalon, Clinical Trials Solutions, Clintara, Covidien, Eli Lilly, EnVivo, Euthymics Bioscience, Forest, Ganeden Biotech, GlaxoSmithKline, Icon Clinical Research, i3 Innovus/Ingenix, Johnson & Johnson, Lichtwer, Lorex, NARSAD, the National Center for Complementary and Alternative Medicine, the National Institute on Drug Abuse, NIMH, Novartis, Organon, Pamlab, Pfizer, Pharmavite, Photothera, RCT Logic, Roche, Sanofi-Aventis, Shire, Solvay, Synthelabo, and Wyeth; he has served as adviser or consultant to Abbott, Affectis, Alkermes, Amarin, Aspect Medical Systems, AstraZeneca, Auspex, Bayer, Best Practice Project Management, BioMarin, Biovail, BrainCells, Bristol-Myers Squibb, CeNeRx BioPharma, Cephalon, Clinical Trials Solutions, CNS Response, Compellis, Cypress, DiagnoSearch Life Sciences, Dinippon Sumitomo, DOV, Edgemont, Eisai, Eli Lilly, ePharmaSolutions, EPIX, Euthymics Bioscience, Fabre-Kramer, Forest, GenOmind, GlaxoSmithKline, Grunenthal, i3 Innovus/Ingenix, Janssen, Jazz, Johnson & Johnson, Knoll, Labopharm, Lorex, Lundbeck, MedAvante, Merck, MSI Methylation Sciences, Naurex, Neuronetics, NextWave, Novartis, Nutrition 21, Orexigen, Organon, Otsuka, Pamlab, Pfizer, PharmaStar, Pharmavite, PharmoRx, Precision Human Biolaboratory, Prexa, PsychoGenics, Psylin Neurosciences, Puretech Ventures, RCT Logic, Rexahn, Ridge Diagnostics, Roche, Sanofi-Aventis, Schering-Plough, Sepracor, Servier, Solvay, Somaxon, Somerset, Sunovion, Synthelabo, Takeda, Tal Medical, Tetragenex, Transcept, TransForm, and Vanda; he has received speaking or publishing fees from Adamed, Advanced Meeting Partners, the American Psychiatric Association, the American Society of Clinical Psychopharmacology, AstraZeneca, Belvoir Media Group, Boehringer Ingelheim, Bristol-Myers Squibb, Cephalon, CME Institute/Physicians Postgraduate Press, Eli Lilly, Forest, GlaxoSmithKline, Imedex, MGH Psychiatry Academy/Primedia, MGH Psychiatry Academy/Reed Elsevier, Novartis, Organon, Pfizer, PharmaStar, United BioSource, and Wyeth; he owns stock in Compellis; he has a patent for SPCD, a patent application for a combination of azapirones and bupropion in major depressive disorder, and a patent for research and licensing of SPCD with RCT Logic and Lippincott, Williams & Wilkins; and he receives copyright royaltes for the MGH CPFQ, SFI, ATRQ, DESS, and SAFER. Dr. Kurian has received research support from Evotec, Pfizer, and Targacept. Dr. Warden has owned stock in Bristol-Myers Squibb and Pfizer in the past 5 years. Dr. Husain has received research support from Cyberonics, Magstim, Neuronetics, NIH/NIMH, the Stanley Foundation, and St. Jude Medical; he has also served on advisory boards for AstraZeneca, BMS, Forest, and Novartis. Dr. Cook has served as an adviser and consultant for Ascend Media, Bristol-Myers Squibb, Cyberonics, Janssen, NeuroSigma, and the U.S. Departments of Defense and of Justice; he has served on the speakers bureaus for Bristol-Myers Squibb, Neuronetics, and Wyeth/Pfizer; he has received research support from Aspect Medical Systems/Covidien, Cyberonics, Eli Lilly, Neuronetics, NIH, Novartis, Pfizer, and Sepracor; his patents on biomedical devices are assigned to the Regents of the University of California. Dr.; Shelton has received grant/research support from Abbott, AstraZeneca, Eli Lilly, GlaxoSmithKline, Janssen, Pamlab, Pfizer, Sanofi, and Wyeth; he has been a paid consultant to Evotec, Janssen, and Sirra Neuropharmaceuticals; and he has served on speakers bureaus for Abbott, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, and Wyeth. Dr. Lesser has received research support from Aspect Medical Systems and NIMH. Dr. Kornstein has received grants/research support from Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, Forest, the National Institute of Mental Health, Novartis, Pfizer, Rexahn, Takeda, and Wyeth; she has served on advisory boards for Bristol-Myers Squibb, Dey, Eli Lilly, Forest, Pfizer, PGx Health, Takeda, and Wyeth; and she has received book royalties from Guilford Press. Dr. Wisniewski reports financial relationships with Cyberonics (2005-2009), ImaRx Therapeutics (2006), Bristol-Myers Squibb (2007-2008), Organon (2007), Case-Western University (2007), Singapore Clinical Research Institute (2009), Dey (2010), and Venebio (2010). The other authors report no financial relationships with commercial interests. Funded by NIMH under contract N01 MH-90003 to the University of Texas Southwestern Medical Center at Dallas (principal investigators, A.J. Rush and M. H. Trivedi). Forest Pharmaceuticals, GlaxoSmithKline, Organon, and Wyeth Pharmaceuticals provided medications for this trial at no cost.; The content of this publication does not necessarily reflect the views or policies of the U.S. Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government. NIMH had no role in the drafting or review of the manuscript or in the collection or analysis of the data. NR 47 TC 130 Z9 138 U1 1 U2 12 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JUL PY 2011 VL 168 IS 7 BP 689 EP 701 DI 10.1176/appi.ajp.2011.10111645 PG 13 WC Psychiatry SC Psychiatry GA 786HX UT WOS:000292296200009 PM 21536692 ER PT J AU Abujudeh, H Kaewlai, R Shah, B Thrall, J AF Abujudeh, Hani Kaewlai, Rathachai Shah, Baiju Thrall, James TI Characteristics of Falls in a Large Academic Radiology Department: Occurrence, Associated Factors, Outcomes, and Quality Improvement Strategies SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE fall characteristics; fall reduction strategies; falls; outcomes; predisposing factors of fall; radiology department ID INPATIENT FALLS; INJURIES; PREVENTION; RISK; CIRCUMSTANCES AB OBJECTIVE. The objective of our study was to describe the characteristics of falls in a radiology department. MATERIALS AND METHODS. The departmental incident report database was retrospectively searched for fall incidents that occurred from March 2006 through October 2008. During that period, 1,801,275 radiologic examinations were performed in our department and there were 82 falls, yielding an incidence of 0.46 per 10,000 examinations. We collected patient information, associated factors, specific circumstances surrounding each incident, the location of each incident, and patient outcome. RESULTS. Eighty-two falls occurred involving 82 patients (35 males, 47 females; mean age, 58.2 years; range, 3-92 years): 66 falls (80%) involved outpatients; 11, inpatients; and five, visitors accompanying a patient. Radiography and CT-MRI units were the top two most common locations of falls (45/82, 55%). Thirty-six events (36/82, 44%) were directly related to a radiologic examination. Most falls were witnessed (61/82, 74%) and unassisted (50/82, 61%), and a majority occurred while the patient was standing or ambulating (59/82, 72%). Most patients (70/82, 85%) had at least one predisposing factor for falling. Sixteen patients (16/82, 20%) had fallen within the previous 3 months. Twenty-four falls (24/82, 29%) resulted in a documented injury (17 minor, seven moderate or severe) with one patient dying. Patients were more likely to be injured if they fell while ambulating (p = 0.0257, univariate analysis) or if they were taking antihypertensive medication (p = 0.02, multivariate analysis). CONCLUSION. Falls were uncommon in the radiology department studied; however, they can result in significant morbidity and mortality. C1 [Abujudeh, Hani; Kaewlai, Rathachai; Shah, Baiju; Thrall, James] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Abujudeh, H (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,Founders 213D, Boston, MA 02114 USA. EM habujudeh@partners.org OI Kaewlai, Rathachai/0000-0002-0650-9380 NR 35 TC 6 Z9 7 U1 1 U2 6 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUL PY 2011 VL 197 IS 1 BP 154 EP 159 DI 10.2214/AJR.10.4994 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 782EO UT WOS:000291991200037 PM 21701024 ER PT J AU Gee, MS Nimkin, K Hsu, M Israel, EJ Biller, JA Katz, AJ Mino-Kenudson, M Harisinghani, MG AF Gee, Michael S. Nimkin, Katherine Hsu, Maylee Israel, Esther J. Biller, Jeffrey A. Katz, Aubrey J. Mino-Kenudson, Mari Harisinghani, Mukesh G. TI Prospective Evaluation of MR Enterography as the Primary Imaging Modality for Pediatric Crohn Disease Assessment SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE children; Crohn disease; inflammatory bowel disease; MRI ID INFLAMMATORY-BOWEL-DISEASE; MULTIDETECTOR ROW CT; COMPUTED-TOMOGRAPHY; CANCER-RISKS; FOLLOW-THROUGH; RADIATION; DIAGNOSIS; CHILDREN; FISTULAS; TOOL AB OBJECTIVE. The objectives of this study were prospective evaluation of MR enterographic accuracy for detecting Crohn disease imaging features in pediatric patients, compared with a CT reference standard, as well as determination of MR enterographic accuracy for detecting active bowel inflammation and fibrosis using a histologic reference standard. SUBJECTS AND METHODS. The study group for this blinded prospective study included 21 pediatric subjects with known Crohn disease scheduled for clinical CT and histologic bowel sampling for symptomatic exacerbation. All subjects and their parents gave informed consent to also undergo MR enterography. CT and MR enterography examinations were independently reviewed by two radiologists and were scored for Crohn disease features. All bowel histology specimens were reviewed by a single pathologist for the presence of active mucosal inflammation and mural fibrosis, followed by correlation of imaging and histologic findings. RESULTS. All 21 subjects underwent MR enterography and histologic sampling, 18 of whom also underwent CT. MR enterography had high sensitivity for detecting Crohn disease imaging features (e. g., bowel wall thickening, mesenteric inflammation, lymphadenopathy, fistula, and abscess) compared with CT, with individual sensitivity values ranging from 85.1% to 100%. Of a total of 53 abnormal bowel segments with correlation of MRI and histologic findings, MR enterography showed 86.7% accuracy (90.0% sensitivity and 82.6% specificity) for detecting active inflammation (p < 0.001). The accuracy of MR enterography for detecting mural fibrosis overall was 64.9%, compared with histology, but increased to 83.3% (p < 0.05) for detecting fibrosis without superimposed active inflammation. CONCLUSION. MR enterography can substitute for CT as the first-line imaging modality in pediatric patients with Crohn disease, on the basis of its ability to detect intestinal pathologic abnormalities in both small and large bowel as well as extraintestinal disease manifestations. Additionally, MR enterography provides an accurate noninvasive assessment of Crohn disease activity and mural fibrosis and can aid in formulating treatment strategies for symptomatic patients and assessing therapy response. C1 [Gee, Michael S.; Nimkin, Katherine; Harisinghani, Mukesh G.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Hsu, Maylee; Mino-Kenudson, Mari] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Israel, Esther J.; Biller, Jeffrey A.; Katz, Aubrey J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. RP Gee, MS (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,Ellison 237, Boston, MA 02114 USA. EM msgee@partners.org FU National Institutes of Health, National Center for Research Resources; Harvard Medical School [UL1 RR025758-02] FX This work was supported by a Catalyst award from National Institutes of Health, National Center for Research Resources, and Harvard Medical School (grant UL1 RR025758-02 to M. S. Gee). NR 36 TC 60 Z9 61 U1 0 U2 3 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUL PY 2011 VL 197 IS 1 BP 224 EP 231 DI 10.2214/AJR.10.5970 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 782EO UT WOS:000291991200055 PM 21701034 ER PT J AU Cronin, CG Gervais, DA Fernandez-Del Castillo, C Mueller, PR Arellano, RS AF Cronin, Carmel G. Gervais, Debra A. Fernandez-Del Castillo, Carlos Mueller, Peter R. Arellano, Ronald S. TI Interventional Radiology in the Management of Abdominal Collections After Distal Pancreatectomy: A Retrospective Review SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE distal pancreatectomy; interventional radiology; pancreatic cancer; percutaneous drainage ID RISK-FACTORS; SINGLE INSTITUTION; FISTULA; CLOSURE; DRAINAGE; LEAK AB OBJECTIVE. The purpose of this study was to assess the technical and clinical success and complications of imaging-guided percutaneous catheter drainage of peripancreatic fluid collections after distal pancreatectomy. MATERIALS AND METHODS. Between January 2001 and February 2009, the cases of patients who underwent distal pancreatectomy were selected from a surgical database, and the cases of those who underwent subsequent interventional radiologic percutaneous drainage were identified. Details of percutaneous catheter drainage were recorded, and technical and clinical success was determined. Technical success was defined as successful percutaneous imaging-guided placement of a drainage catheter. Primary clinical success was defined as resolution of peripancreatic fluid collection with percutaneous drainage only. Secondary clinical success was defined as resolution of peripancreatic fluid collection with percutaneous drainage and additional manipulations (i.e., tube repositioning, additional catheter drainage) and no surgical debridement. Multifactor logistic regression analysis was used to identify predictors of drain failure. RESULTS. Between January 2001 and February 2009, 365 patients underwent distal pancreatectomy. Of these, 51 patients (14%; 25 men, 26 women; mean age, 53.4 years; range, 18-81 years) underwent 57 CT-guided percutaneous procedures for drainage of postsurgical peripancreatic fluid collection. The mean interval between surgery and drainage was 23.5 days (median, 17 days; range, 2-120 days), and the mean collection size was 7.3 cm in transverse dimension (median, 6.9 cm; range, 2.3-16 cm). The mean duration of catheter drainage was 39.7 days (median, 24 days; range, 3-220 days). The technical success rate was 100%, primary clinical success rate was 60%, and primary and secondary clinical success rates together were 95%. Three of the 51 patients (6%) needed surgery for definitive management of the collection. One of 51 patients (2%) had a complication of the interventional radiologic procedure. Catheter size and the need for additional catheter manipulation were significantly associated with drainage failure (p < 0.05). CONCLUSION. Catheter drainage of peripancreatic fluid collections after distal pancreatectomy is a technically safe and clinically effective procedure. Although extra manipulations may be needed to achieve clinical success, the combined primary and secondary clinical success rates are high. C1 [Cronin, Carmel G.; Gervais, Debra A.; Fernandez-Del Castillo, Carlos; Mueller, Peter R.; Arellano, Ronald S.] Massachusetts Gen Hosp, Dept Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. RP Cronin, CG (reprint author), Massachusetts Gen Hosp, Dept Abdominal Imaging & Intervent Radiol, 55 Fruit St,White 270, Boston, MA 02114 USA. EM cgcronin@partners.org NR 21 TC 8 Z9 8 U1 0 U2 3 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUL PY 2011 VL 197 IS 1 BP 241 EP 246 DI 10.2214/AJR.10.5447 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 782EO UT WOS:000291991200059 PM 21701036 ER PT J AU Ackman, JB Wu, CC AF Ackman, Jeanne B. Wu, Carol C. TI MRI of the Thymus SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Editorial Material DE chemical shift imaging; cyst; MRI; thymic hyperplasia; thymoma; thymus ID THYMOMA; TUMORS; CT C1 [Ackman, Jeanne B.; Wu, Carol C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Thorac Radiol & Intervent,Dept Radiol, Boston, MA 02214 USA. RP Ackman, JB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Thorac Radiol & Intervent,Dept Radiol, Founders House 202,55 Fruit St, Boston, MA 02214 USA. EM jackman@partners.org NR 14 TC 12 Z9 12 U1 0 U2 6 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUL PY 2011 VL 197 IS 1 BP W15 EP W20 DI 10.2214/AJR.10.4703 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 782EO UT WOS:000291991200003 PM 21700977 ER PT J AU O'Regan, K Hall, M Jagannathan, J Giardino, A Kelly, PJ Butrynski, J Ramaiya, N AF O'Regan, Kevin Hall, Matthew Jagannathan, Jyothipriya Giardino, Angela Kelly, Paul J. Butrynski, James Ramaiya, Nikhil TI Imaging of Radiation-Associated Sarcoma SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE imaging; postradiation sarcomas; radiation complications; radiation-induced sarcomas; radiation therapy ID POSTRADIATION SARCOMAS; SOFT-TISSUE; CERVICAL-CANCER; 2ND CANCERS; BONE; RADIOTHERAPY; CARCINOMA; FEATURES; BREAST; NECK AB OBJECTIVE. The objective of this article is to show the imaging features of radiation-associated sarcoma arising after radiation therapy using multiple imaging modalities. CONCLUSION. A multimodality imaging strategy and collaboration between multidisciplinary teams are important for the management of radiation-associated sarcoma. Because radiation-associated sarcoma often displays locally aggressive behavior and may metastasize, resulting in a poor prognosis, it is important to consider this diagnosis in any patient previously treated with radiation therapy and to recognize the imaging findings. C1 [O'Regan, Kevin; Hall, Matthew; Jagannathan, Jyothipriya; Giardino, Angela; Ramaiya, Nikhil] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. [Kelly, Paul J.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Butrynski, James] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP O'Regan, K (reprint author), Dana Farber Canc Inst, Dept Imaging, 44 Binney St, Boston, MA 02115 USA. EM knoregan@partners.org NR 16 TC 0 Z9 0 U1 0 U2 3 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUL PY 2011 VL 197 IS 1 BP W30 EP W36 DI 10.2214/AJR.10.5558 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 782EO UT WOS:000291991200008 PM 21700992 ER PT J AU O'Regan, KN Jagannathan, J Krajewski, K Zukotynski, K Souza, F Wagner, AJ Ramaiya, N AF O'Regan, Kevin N. Jagannathan, Jyothi Krajewski, Katherine Zukotynski, Katherine Souza, Frederico Wagner, Andrew J. Ramaiya, Nikhil TI Imaging of Liposarcoma: Classification, Patterns of Tumor Recurrence, and Response to Treatment SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE CT; liposarcoma; MRI ID MYXOID LIPOSARCOMAS; SARCOMAS AB OBJECTIVE. The purpose of this study was to illustrate the subtypes of liposarcoma (LPS) and the significance of the nonlipomatous tumor components using multiple imaging modalities. CONCLUSION. The subtypes of LPS with greater nonlipomatous soft-tissue components on imaging studies tend to show less differentiation and are usually more aggressive both histologically and clinically. Imaging plays an important role in the diagnosis, surveillance, and response assessment of LPS. C1 [O'Regan, Kevin N.; Jagannathan, Jyothi; Krajewski, Katherine; Zukotynski, Katherine; Souza, Frederico; Wagner, Andrew J.; Ramaiya, Nikhil] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02215 USA. RP O'Regan, KN (reprint author), Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA. EM kevin.oregan1@hse.ie FU Certificate of Merit FX This work was presented as an electronic exhibit at the 2010 annual meeting of the American Roentgen Ray Society San Diego, CA, and was awarded a Certificate of Merit. NR 12 TC 16 Z9 18 U1 0 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUL PY 2011 VL 197 IS 1 BP W37 EP W43 DI 10.2214/AJR.10.5824 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 782EO UT WOS:000291991200009 PM 21700993 ER PT J AU Sahani, DV Sainani, NI Blake, MA Crippa, S Mino-Kenudson, M del-Castillo, CF AF Sahani, Dushyant V. Sainani, Nisha I. Blake, Michael A. Crippa, Stefano Mino-Kenudson, Mari del-Castillo, Carlos Fernandez TI Prospective Evaluation of Reader Performance on MDCT in Characterization of Cystic Pancreatic Lesions and Prediction of Cyst Biologic Aggressiveness SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE aggressiveness; characterization; cyst biology; cyst size; MDCT; pancreas ID PAPILLARY-MUCINOUS TUMORS; 539 CONSECUTIVE PATIENTS; SELECTIVE APPROACH; PATHOLOGICAL CORRELATION; SINGLE INSTITUTION; RELATIVE ACCURACY; HELICAL CT; FOLLOW-UP; NEOPLASMS; MANAGEMENT AB OBJECTIVE. Our objective was to evaluate the accuracy of MDCT features of pancreatic cystic lesions in cyst characterization and in predicting cyst biologic aggressiveness. SUBJECTS AND METHODS. In this prospective study, 114 patients (40 men and 74 women; age range, 23-89 years) with 130 cystic lesions (size range, 31-160 mm) in the pancreas underwent contrast-enhanced dual-phase (n = 92) and portal phase (n = 22) examinations with 16- or 64-MDCT scanners. Using defined morphologic features of cystic lesions on MDCT, two readers performed blinded evaluations for cystic characterization and predicting biologic aggressiveness (invasive lesions, carcinoma in situ, and moderate grade dysplasias) before pancreatic surgery. Receiver operating characteristic analysis was performed to assess the accuracy of MDCT using pathologic evaluation of the surgical specimen as a reference standard. RESULTS. On the basis of MDCT features, the radiologic accuracy (reader 1 and reader 2) for stratifying lesions into mucinous and nonmucinous subtypes was 85% and 82% and for recognizing cysts with aggressive biology was 86% and 85%, respectively. Predictive values of MDCT were superior for lesions > 30 mm and nonmucinous lesions. Features favoring aggressive biology were main pancreatic duct dilation > 10 mm (p < 0.0001), biliary obstruction (p=0.01), mural nodule (p < 0.0001), main-duct intraductal papillary mucinous neoplasm (p < 0.0001), and advanced age (p = 0.0001). Sensitivity of detecting morphologic features was higher with the dual-phase pancreatic protocol CT. CONCLUSION. Morphologic features of pancreatic cystic lesions on MDCT allow reliable characterization into mucinous and nonmucinous subtypes and enable prediction of biologic aggressiveness. C1 [Sahani, Dushyant V.; Sainani, Nisha I.; Blake, Michael A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Radiol, Div Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. [Crippa, Stefano; del-Castillo, Carlos Fernandez] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Mino-Kenudson, Mari] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Sahani, DV (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Radiol, Div Abdominal Imaging & Intervent Radiol, 55 Fruit St,White 270, Boston, MA 02114 USA. EM dsahani@partners.org NR 55 TC 29 Z9 31 U1 1 U2 4 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUL PY 2011 VL 197 IS 1 BP W53 EP W61 DI 10.2214/AJR.10.5866 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 782EO UT WOS:000291991200019 PM 21700995 ER PT J AU Marchie, A Panuncialman, I McCarthy, JC AF Marchie, Anthony Panuncialman, Ian McCarthy, Joseph C. TI Efficacy of Hip Arthroscopy in the Management of Synovial Chondromatosis SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article DE hip arthroscopy; synovial chondromatosis; loose body removal; hip joint ID LOOSE BODIES; SYNOVECTOMY; OSTEOCHONDROMATOSIS; DISORDERS; ARTHRITIS; SURGERY; BONE; KNEE AB Background: Synovial chondromatosis can result in intra-articular loose bodies. Open arthrotomy has been the conventional treatment for this condition in the hip. Hip arthroscopy, however, is a minimally invasive approach and avoids potential problems with open arthrotomy. Purpose: This series was described to evaluate the role of arthroscopy in treatment and outcome of synovial chondromatosis of the hip at early to intermediate follow-up. Study Design: Case series; Level of evidence, 4. Methods: Twenty-nine patients had arthroscopic treatment for synovial chondromatosis of the hip. All loose bodies were intracapsular and smaller than 10 mm. Radiographs of the painful hip, computed tomography (CT), and gadolinium-enhanced magnetic resonance imaging (MRI) were obtained preoperatively. Intraoperatively, loose bodies were removed, and partial synovectomy, partial labrectomy, chondroplasty, and microfracture were done as needed. Results: There were 14 women and 15 men (mean age, 41 years; mean duration of symptoms, 52 months). All patients had hip pain and 63% reported mechanical hip symptoms. Twenty-three patients were followed for at least 12 months (mean, 64 months). Loose bodies could be seen in the imaging studies of 52% of patients: 8 on radiographs and 7 with CT or gadolinium-enhanced MRI. At surgery, 23 of the 29 (79%) patients had torn labra and femoral head changes. There were an average of 35 loose bodies per patient. Twenty-five of the 29 (86%) had acetabular chondral findings. Five of the 29 patients (17%) eventually underwent total hip reconstruction surgery at a mean of 52 months; 5 of these patients had grade III/IV lesions at the time of arthroscopy. Eleven of the 23 patients (48%) had good to excellent outcomes at an average of 60 months. Recurrent symptoms were seen in 7 patients, and revision arthroscopy was done for 1 patient at 1-year follow-up, 2 patients at 4 years, 1 at 5 years, and 1 at 7-year follow-up. Complications included transient perineal and pedal paresthesia in 2 patients. Conclusion: Patients with synovial chondromatosis with hip central compartment loose bodies that were less than 10 mm benefited from hip arthroscopy. Imaging studies alone failed to establish the diagnosis in 14 of 29 patients (48%). Diagnosis was made by direct visualization via arthroscopy. For patients with grade I/II cartilage change, early diagnosis and treatment via arthroscopy helped. It is a valid and effective treatment at early to intermediate follow-up. C1 [Marchie, Anthony; Panuncialman, Ian; McCarthy, Joseph C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP McCarthy, JC (reprint author), Newton Wellesley Hosp, Joint Reconstruct Ctr, 2000 Washington St,Suite 361 GR, Newton, MA 02162 USA. EM jcmccarthy1@partners.org NR 36 TC 12 Z9 14 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0363-5465 J9 AM J SPORT MED JI Am. J. Sports Med. PD JUL PY 2011 VL 39 SU 1 BP 126S EP 131S DI 10.1177/0363546511414014 PG 6 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 784OU UT WOS:000292167400018 PM 21709042 ER PT J AU Farris, AB Taheri, D Kawai, T Fazlollahi, L Wong, W Tolkoff-Rubin, N Spitzer, TR Iafrate, AJ Preffer, FI LoCascio, SA Sprangers, B Saidman, S Smith, RN Cosimi, AB Sykes, M Sachs, DH Colvin, RB AF Farris, A. B. Taheri, D. Kawai, T. Fazlollahi, L. Wong, W. Tolkoff-Rubin, N. Spitzer, T. R. Iafrate, A. J. Preffer, F. I. LoCascio, S. A. Sprangers, B. Saidman, S. Smith, R. N. Cosimi, A. B. Sykes, M. Sachs, D. H. Colvin, R. B. TI Acute Renal Endothelial Injury During Marrow Recovery in a Cohort of Combined Kidney and Bone Marrow Allografts SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Bone marrow transplant; engraftment syndrome; renal transplant ID STEM-CELL TRANSPLANTATION; VERSUS-HOST-DISEASE; NONLETHAL PREPARATIVE REGIMEN; HIGH-DOSE CHEMOTHERAPY; MIXED CHIMERISM; THROMBOTIC MICROANGIOPATHY; ENGRAFTMENT SYNDROME; CYNOMOLGUS MONKEYS; RESPIRATORY-FAILURE; LYMPHOCYTE RECOVERY AB An idiopathic capillary leak syndrome ('engraftment syndrome') often occurs in recipients of hematopoietic cells, manifested clinically by transient azotemia and sometimes fever and fluid retention. Here, we report the renal pathology in 10 recipients of combined bone marrow and kidney allografts. Nine developed graft dysfunction on day 10-16 and renal biopsies showed marked acute tubular injury, with interstitial edema, hemorrhage and capillary congestion, with little or no interstitial infiltrate (<= 10%) and marked glomerular and peritubular capillary (PTC) endothelial injury and loss by electron microscopy. Two had transient arterial endothelial inflammation; and 2 had C4d deposition. The cells in capillarieswere primarily CD68(+) MPO(+) mononuclear cells and CD3(+) CD8(+) T cells, the latter with a high proliferative index (Ki67(+)). B cells (CD20(+)) and CD4(+) T cells were not detectable, and NK cells were rare. XY FISH showed that CD45(+) cells in PTCs were of recipient origin. Optimal treatment remains to be defined; two recovered without additional therapy, six were treated with anti-rejection regimens. Except for one patient, who later developed thrombotic microangiopathy and one with acute humoral rejection, all fully recovered within 2-4 weeks. Graft endothelium is the primary target of this process, attributable to as yet obscure mechanisms, arising during leukocyte recovery. C1 [Farris, A. B.; Taheri, D.; Fazlollahi, L.; Iafrate, A. J.; Preffer, F. I.; Saidman, S.; Smith, R. N.; Colvin, R. B.] Massachusetts Gen Hosp, Pathol Serv, Boston, MA 02114 USA. [Farris, A. B.] Emory Univ, Dept Pathol, Atlanta, GA 30322 USA. [Farris, A. B.; Taheri, D.; Kawai, T.; Fazlollahi, L.; Wong, W.; Tolkoff-Rubin, N.; Spitzer, T. R.; Iafrate, A. J.; Preffer, F. I.; Saidman, S.; Smith, R. N.; Cosimi, A. B.; Sykes, M.; Sachs, D. H.; Colvin, R. B.] Harvard Univ, Sch Med, Boston, MA USA. [Kawai, T.; Cosimi, A. B.] Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. [Wong, W.; Tolkoff-Rubin, N.; Spitzer, T. R.] Massachusetts Gen Hosp, Med Serv, Boston, MA 02114 USA. [LoCascio, S. A.; Sykes, M.; Sachs, D. H.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. [LoCascio, S. A.; Sprangers, B.; Sykes, M.] Columbia Univ, Dept Med Surg & Microbiol & Immunol, Columbia Ctr Translat Immunol, New York, NY USA. RP Farris, AB (reprint author), Massachusetts Gen Hosp, Pathol Serv, Boston, MA 02114 USA. EM abfarri@emory.edu FU NIH/ITN; National Institute of Allergy and Infectious Diseases [N01-AI-15416]; National Institute of Diabetes and Digestive and Kidney Diseases [N01-AI-15416]; Juvenile Diabetes Research Foundation [N01-AI-15416]; National Institutes of Health [RO1-AI-084074] FX The authors are grateful for the review of the pathology of this study and manuscript by Charles E. Alpers, MD, Anthony J. Demetris, MD and Lorraine C. Racusen, MD, done as a part of the NIH/ITN sponsored clinical trial.; Supported by a grants from the Immune Tolerance Network (N01-AI-15416), a collaborative clinical research project supported by the National Institute of Allergy and Infectious Diseases, the National Institute of Diabetes and Digestive and Kidney Diseases, and the Juvenile Diabetes Research Foundation, and the National Institutes of Health (RO1-AI-084074). NR 50 TC 33 Z9 37 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUL PY 2011 VL 11 IS 7 BP 1464 EP 1477 DI 10.1111/j.1600-6143.2011.03572.x PG 14 WC Surgery; Transplantation SC Surgery; Transplantation GA 785WR UT WOS:000292264000018 PM 21668634 ER PT J AU Batki, SL Canfield, KM Ploutz-Snyder, R AF Batki, Steven L. Canfield, Kelly M. Ploutz-Snyder, Robert TI Psychiatric and Substance Use Disorders among Methadone Maintenance Patients with Chronic Hepatitis C Infection: Effects on Eligibility for Hepatitis C Treatment SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID OPIOID-DEPENDENT PATIENTS; INJECTION-DRUG USERS; INTERFERON-ALPHA; COOCCURRING DISORDERS; VIRUS-INFECTION; ABUSE TREATMENT; PUBLIC-HEALTH; PREVALENCE; COMORBIDITY; CARE AB We set out to describe the prevalence and severity of psychiatric and substance use disorders (SUDs) in methadone maintenance treatment (MMT) patients with chronic hepatitis C virus (HCV) infection and to measure the impact on HCV-treatment eligibility. Psychiatric disorders, SUDs, and HCV-treatment eligibility were assessed in 111 MMT patients prior to a controlled trial of HCV treatment. Lifetime and current diagnosis rates, respectively were.. any non-SUD Axis I disorder 82% and 57%, any mood disorder: 67% and 35%, any anxiety disorder: 63% and 22%, any psychotic disorder: 11% and 9%. Antisocial personality disorder was present in 40%. A total of 56% met criteria for current SUDs. A total of 66% received psychiatric medications prior to HCV treatment; over half were receiving antidepressants. Despite psychiatric and substance use comorbidity, only 15% of patients were ineligible for HCV treatment: 10% clue to failure to complete the evaluation, and 5% due to psychiatric severity. Substance use did not lead to ineligibility in any participant. Multiple logistic regression showed the Beck Depression Inventory contributed significantly to predicting HCV treatment eligibility. Most MMT patients were ineligible for HCV treatment despite current SUD and non-SUD diagnoses. Depression severity may be a more significant predictor of HCV treatment eligibility than is substance use. (Am J Addict 2011;20:312-318) C1 [Batki, Steven L.] UCSF, Addict Psychiat Res Program, Dept Psychiat, San Francisco VA Med Ctr 116P, San Francisco, CA 94121 USA. [Batki, Steven L.] San Francisco VA Med Ctr, San Francisco, CA USA. [Canfield, Kelly M.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. [Ploutz-Snyder, Robert] Univ Space Res Assoc, Houston, TX USA. RP Batki, SL (reprint author), UCSF, Addict Psychiat Res Program, Dept Psychiat, San Francisco VA Med Ctr 116P, 4150 Clement St, San Francisco, CA 94121 USA. EM steven.batki@ucsf.edu FU NIDA NIH HHS [R01 DA 016764, R01 DA016764, R01 DA016764-06] NR 52 TC 9 Z9 9 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD JUL-AUG PY 2011 VL 20 IS 4 BP 312 EP 318 DI 10.1111/j.1521-0391.2011.00139.x PG 7 WC Substance Abuse SC Substance Abuse GA 781CT UT WOS:000291908900002 PM 21679262 ER PT J AU Wilens, TE Adler, LA Tanaka, Y Xiao, F D'Souza, DN Gutkin, SW Upadhyaya, HP AF Wilens, Timothy E. Adler, Lenard A. Tanaka, Yoko Xiao, Feng D'Souza, Deborah N. Gutkin, Stephen W. Upadhyaya, Himanshu P. TI Correlates of Alcohol Use in Adults with Attention-Deficit/Hyperactivity Disorder (ADHD) and Comorbid Alcohol Use Disorders SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Meeting Abstract C1 [Wilens, Timothy E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Adler, Lenard A.] NYU, Sch Med, New York, NY 10003 USA. [Tanaka, Yoko; D'Souza, Deborah N.; Upadhyaya, Himanshu P.] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD JUL-AUG PY 2011 VL 20 IS 4 MA 6 BP 375 EP 376 PG 2 WC Substance Abuse SC Substance Abuse GA 781CT UT WOS:000291908900015 ER PT J AU Yule, A Wilens, TE Martelon, MK Simon, A Biederman, J AF Yule, Amy Wilens, Timothy E. Martelon, Mary Kate Simon, Andrew Biederman, Joseph TI Impact of Exposure to Parental Substance Use Disorders (SUD) on SUD Risk in Girls and Their Siblings SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Meeting Abstract C1 [Yule, Amy; Wilens, Timothy E.; Martelon, Mary Kate; Simon, Andrew; Biederman, Joseph] 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 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD JUL-AUG PY 2011 VL 20 IS 4 MA 5 BP 375 EP 375 PG 1 WC Substance Abuse SC Substance Abuse GA 781CT UT WOS:000291908900014 ER PT J AU Meszaros, ZS Dimmock, JA Abdul-Malak, Y Ploutz-Snyder, R Batki, SL AF Meszaros, Zsuzsa Szombathyne Dimmock, Jacqueline A. Abdul-Malak, Ynesse Ploutz-Snyder, Robert Batki, Steven L. TI Alcohol Use Is Associated with Impaired Decision Making in Patients with Schizophrenia and Schizoaffective Disorder SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Meeting Abstract C1 [Batki, Steven L.] SUNY Upstate Med Univ, Dept Psychiat, UCSF Dept Psychiat, Syracuse, NY USA. [Batki, Steven L.] San Francisco VA Med Ctr, San Francisco, CA 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 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD JUL-AUG PY 2011 VL 20 IS 4 MA 7 BP 376 EP 376 PG 1 WC Substance Abuse SC Substance Abuse GA 781CT UT WOS:000291908900016 ER PT J AU Silverman, BC Connery, HS AF Silverman, Benjamin C. Connery, Hilary Smith TI What Is "Internet Addiction?"-A Review of the Literature, Phenotype Diversity, and Portal Hypothesis SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Meeting Abstract C1 [Silverman, Benjamin C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, McLean Hosp,Adult Psychiat Residency Training Pro, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD JUL-AUG PY 2011 VL 20 IS 4 MA 14 BP 379 EP 379 PG 1 WC Substance Abuse SC Substance Abuse GA 781CT UT WOS:000291908900022 ER PT J AU Ward, N Barmash, J Stathoupolou, G Czarnecki, K Kane, M AF Ward, Nalan Barmash, Jennifer Stathoupolou, Georgia Czarnecki, Kristen Kane, Martha TI Does Wait Time to Intake Influence Initial "No Show" Rates? SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Meeting Abstract C1 [Ward, Nalan; Barmash, Jennifer; Stathoupolou, Georgia; Czarnecki, Kristen; Kane, Martha] Massachusetts Gen Hosp, Dept Psychiat, 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 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD JUL-AUG PY 2011 VL 20 IS 4 MA 32 BP 385 EP 385 PG 1 WC Substance Abuse SC Substance Abuse GA 781CT UT WOS:000291908900037 ER PT J AU Schuman-Olivier, Z Albanese, M Carlini, S Shaffer, HJ AF Schuman-Olivier, Zev Albanese, Mark Carlini, Sara Shaffer, Howard J. TI Effects of Trait Mindfulness During Buprenorphine Treatment for Heroin Dependence: A Pilot Study SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Meeting Abstract C1 [Schuman-Olivier, Zev] Harvard Univ, Sch Med, Dept Psychiat, Div Addict,Massachusetts Gen Hosp,Ctr Addict Med, Cambridge, MA 02138 USA. NR 0 TC 3 Z9 3 U1 2 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD JUL-AUG PY 2011 VL 20 IS 4 MA 36 BP 386 EP 386 PG 1 WC Substance Abuse SC Substance Abuse GA 781CT UT WOS:000291908900041 ER PT J AU Smith, DZ Hernandez, E Renner, J AF Smith, Dwight Zach Hernandez, Elvin Renner, John TI Getting Away with It: An Analysis of Methods Used in Defeating Drug Testing SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Meeting Abstract C1 [Hernandez, Elvin; Renner, John] VA Boston Healthcare Syst, 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 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD JUL-AUG PY 2011 VL 20 IS 4 MA 43 BP 388 EP 388 PG 1 WC Substance Abuse SC Substance Abuse GA 781CT UT WOS:000291908900045 ER PT J AU Atassi, N Cudkowicz, ME Schoenfeld, DA AF Atassi, Nazem Cudkowicz, Merit E. Schoenfeld, David A. TI Advanced statistical methods to study the effects of gastric tube and non-invasive ventilation on functional decline and survival in amyotrophic lateral sclerosis SO AMYOTROPHIC LATERAL SCLEROSIS LA English DT Article DE G-tube; PEG; NIV; Bipap; ALS; marginal structural models ID PERCUTANEOUS ENDOSCOPIC GASTROSTOMY; QUALITY STANDARDS SUBCOMMITTEE; PULMONARY-FUNCTION; PRACTICE PARAMETER; AMERICAN ACADEMY; ALS; NEUROLOGY; PATIENT; DISEASE; TRIAL AB A few studies suggest that non-invasive ventilation (1) and gastric tube (G-tube) may have a positive impact on survival but the effect on functional decline is unclear. Confounding by indication may have produced biased estimates of the benefit seen in some of these retrospective studies. The objective of this study was to evaluate the effects of G-tube and NIV on survival and functional decline using advanced statistical models that adjust for confounding by indications. A database of 331 subjects enrolled in previous clinical trials in ALS was available for analysis. Marginal structural models (MSM) were used to compare the mortality hazards and ALSFRS-R slopes between treatment and non-treatment groups, after adjusting for confounding by indication. Results showed that the placement of a G-tube was associated with an additional 1.42 units/month decline in the ALSFRS-R slope (p < 0.0001) and increased mortality hazard of 0.28 (p = 0.02). The use of NIV had no significant effect on ALSFRS-R decline or mortality. In conclusion, marginal structural models can be used to adjust for confounding by indication in retrospective ALS studies. G-tube placement could be followed by a faster rate of functional decline and increased mortality. Our results may suffer from some of the limitations of retrospective analyses. C1 [Atassi, Nazem] Harvard Univ, Massachusetts Gen Hosp, Sch Med, NCTU, Charlestown, MA 02129 USA. RP Atassi, N (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, NCTU, 13th St,Bldg 149,Room 2274, Charlestown, MA 02129 USA. EM NATASSI@PARTNERS.ORG FU Muscular Dystrophy Association (MDA) [CRTG160611]; NIH [T32NS048005] FX We would like to thank the Northeast ALS Consortium (NEALS) for providing the data. This work was conducted with support from a Muscular Dystrophy Association (MDA) clinical research training grant (CRTG160611) and NIH training grant (T32NS048005). NR 23 TC 6 Z9 6 U1 0 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1748-2968 J9 AMYOTROPH LATERAL SC JI Amyotroph. Lateral. Scler. PD JUL PY 2011 VL 12 IS 4 BP 272 EP 277 DI 10.3109/17482968.2011.577786 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 783WJ UT WOS:000292114500005 PM 21554030 ER PT J AU Pan, CX Xu, ZP Dong, YL Zhang, YY Zhang, J McAuliffe, S Yue, Y Li, TZ Xie, ZC AF Pan, Chuxiong Xu, Zhipeng Dong, Yuanlin Zhang, Yiying Zhang, Jun McAuliffe, Sayre Yue, Yun Li, Tianzuo Xie, Zhongcong TI The Potential Dual Effects of Anesthetic Isoflurane on Hypoxia-Induced Caspase-3 Activation and Increases in beta-Site Amyloid Precursor Protein-Cleaving Enzyme Levels SO ANESTHESIA AND ANALGESIA LA English DT Article ID ALZHEIMERS-DISEASE; INDUCED APOPTOSIS; VOLATILE ANESTHETICS; NEURONAL APOPTOSIS; BACE1 EXPRESSION; ISCHEMIC-STROKE; SH-SY5Y CELLS; UP-REGULATION; CYTOCHROME-C; BRAIN-INJURY AB BACKGROUND: beta-Amyloid protein (A beta) accumulation, caspase activation, apoptosis, and hypoxia-induced neurotoxicity have been suggested to be involved in Alzheimer disease neuropathogenesis. A beta is produced from amyloid precursor protein through proteolytic processing by the aspartyl protease beta-site amyloid precursor protein-cleaving enzyme (BACE) and gamma-secretase. Inhaled anesthetics have long been considered to protect against neurotoxicity. However, recent studies have suggested that the inhaled anesthetic isoflurane may promote neurotoxicity by inducing caspase activation and apoptosis, and by increasing levels of BACE and A beta. We therefore sought to determine whether isoflurane can induce concentration-dependent dual effects on hypoxia-induced caspase-3 activation and increases in BACE levels: protection versus promotion. METHODS: H4 human neuroglioma cells were treated with hypoxia (3% O(2)) alone, different concentrations of isoflurane (0.5% and 2%), and the combination of hypoxia and 0.5% or 2% isoflurane. The levels of caspase-3 cleavage (activation), BACE, and Bcl-2 were determined by Western blot analysis. RESULTS: We show for the first time that treatment with 0.5% isoflurane for 8 hours attenuated, whereas treatment with 2% isoflurane for 8 hours enhanced, hypoxia-induced caspase-3 activation and increases in BACE levels. The 2% isoflurane treatment also enhanced a hypoxia-induced decrease in Bcl-2 levels. CONCLUSIONS: These results suggest a potential concept that isoflurane has dual effects (protection versus promotion) on hypoxia-induced toxicity, which may act through Bcl-2 family proteins. These findings could lead to more systematic studies to determine the potential dual effects of anesthetics on Alzheimer disease-associated neurotoxicity. (Anesth Analg 2011;113:145-52) C1 [Pan, Chuxiong; Xu, Zhipeng; Dong, Yuanlin; Zhang, Yiying; Zhang, Jun; McAuliffe, Sayre; Xie, Zhongcong] Massachusetts Gen Hosp, Geriatr Anesthesia Res Unit, Dept Anesthesia Crit Care & Pain Med, Charlestown, MA 02129 USA. [Pan, Chuxiong; Xu, Zhipeng; Dong, Yuanlin; Zhang, Yiying; Zhang, Jun; McAuliffe, Sayre; Xie, Zhongcong] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Pan, Chuxiong; Xu, Zhipeng; Dong, Yuanlin; Zhang, Yiying; Zhang, Jun; McAuliffe, Sayre; Xie, Zhongcong] Massachusetts Gen Hosp, Genet & Aging Res Unit, MassGeneral Inst Neurodegenerat Dis, Dept Neurol, Charlestown, MA 02129 USA. [Yue, Yun] Capital Med Univ, Beijing Chaoyang Hosp, Dept Anesthesia, Beijing, Peoples R China. [Li, Tianzuo] Capital Med Univ, Beijing Tongren Hosp, Dept Anesthesia, Beijing, Peoples R China. RP Xie, ZC (reprint author), Massachusetts Gen Hosp, Geriatr Anesthesia Res Unit, Dept Anesthesia Crit Care & Pain Med, 149 13th St,Room 4310, Charlestown, MA 02129 USA. EM zxie@partners.org FU National Institutes of Health [K08NS048140, R21AG029856, R01 GM088801]; American Geriatrics Society; Alzheimer's Association FX Supported by grants K08NS048140, R21AG029856, and R01 GM088801 (National Institutes of Health), the Jahnigen Career Development Award (American Geriatrics Society), and the Investigator Initiated Research Grant (Alzheimer's Association) (to ZX). NR 51 TC 15 Z9 17 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD JUL PY 2011 VL 113 IS 1 BP 145 EP 152 DI 10.1213/ANE.0b013e3182185fee PG 8 WC Anesthesiology SC Anesthesiology GA 781XT UT WOS:000291971900025 PM 21519046 ER PT J AU Jiang, YD Bao, FP Liang, YF Kimball, WR Liu, YH Zapol, WM Kacmarek, RM AF Jiang, Yandong Bao, Fang Ping Liang, Yafen Kimball, William R. Liu, Yanhong Zapol, Warren M. Kacmarek, Robert M. TI Effectiveness of Breathing through Nasal and Oral Routes in Unconscious Apneic Adult Human Subjects A Prospective Randomized Crossover Trial SO ANESTHESIOLOGY LA English DT Article ID MOUTH-TO-MOUTH; ONLY CARDIOPULMONARY-RESUSCITATION; AMERICAN-HEART-ASSOCIATION; HOSPITAL CARDIAC-ARREST; EMERGENCY CARDIOVASCULAR CARE; CHEST-COMPRESSION; MASK VENTILATION; UPPER AIRWAY; CPR; SLEEP AB Background: The authors hypothesized that mouth ventilation by a resuscitator via the nasal route ensures a more patent airway and more effective ventilation than does ventilation via the oral route and therefore would be the optimal manner to ventilate adult patients in emergencies, such as during cardiopulmonary resuscitation. They tested the hypothesis by comparing the effectiveness of mouth-to-nose breathing (MNB) and mouth-to-mouth breathing (MMB) in anesthetized, apneic, adult subjects without muscle paralysis. Methods: Twenty subjects under general anesthesia randomly received MMB and MNB with their heads placed first in a neutral position and then an extended position. A single operator performed MNB and MMB at the target breathing rate of 10 breaths/min, inspiratory: expiratory ratio 1:2 and peak inspiratory airway pressure 24 cm H(2)O. A plethysmograph was used to measure the amplitude change during MMB and MNB. The inspiratory and expiratory tidal volumes during MMB and MNB were calculated retrospectively using the calibration curve. Results: All data are presented as medians (interquartile ranges). The rates of effective ventilation (expired volume > estimated anatomic dead space) during MNB and MMB were 91.1% (42.4-100%) and 43.1% (42.5-100%) (P < 0.001), and expired tidal volume with MMB 130.5 ml (44.0-372.8 ml) was significantly lower than with MNB 324.5 ml (140.8-509.0 ml), regardless of the head position (P < 0.001). Conclusions: Direct mouth ventilation delivered exclusively via the nose is significantly more effective than that delivered via the mouth in anesthetized, apneic adult subjects without muscle paralysis. Additional studies are needed to establish whether using this breathing technique during emergency situations will improve patient outcomes. C1 [Jiang, Yandong; Bao, Fang Ping; Liang, Yafen; Kimball, William R.; Liu, Yanhong; Zapol, Warren M.; Kacmarek, Robert M.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Kacmarek, RM (reprint author), Massachusetts Gen Hosp, Dept Resp Care, 55 Fruit St,EL 404, Boston, MA 02114 USA. EM rkacmarek@partners.org FU Covidien (Boulder, Colorado); Cardinal Medical (Woburn, Massachusetts); Drager (Telford, Pennsylvania); Newport Medical (Newport Beach, California); General Electric (Waukesha, Wisconsin); Hamilton Medical (Reno, Nevada) FX Received from the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts. Submitted for publication August 16, 2010. Accepted for publication March 8, 2011. Support was provided solely from institutional and/or departmental sources. Potential conflict of interest: Dr. Kacmarek has received research grants from Covidien (Boulder, Colorado), Cardinal Medical (Woburn, Massachusetts), Drager (Telford, Pennsylvania), Newport Medical (Newport Beach, California), General Electric (Waukesha, Wisconsin), and Hamilton Medical (Reno, Nevada), has received honorarium for lecturing from Hamilton Medical and Maquet (Danvers, Massachusetts), and is a consultant for Newport Medical and KCI (San Antonio, Texas). Drs. Zapol and Kacmarek contributed equally as senior authors. NR 33 TC 4 Z9 6 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JUL PY 2011 VL 115 IS 1 BP 129 EP 135 DI 10.1097/ALN.0b013e31821d6c69 PG 7 WC Anesthesiology SC Anesthesiology GA 781IX UT WOS:000291925400019 PM 21572315 ER PT J AU Sarma, J Eikermann, M AF Sarma, Jaydev Eikermann, Matthias TI Images in Anesthesiology: A Large Gastric Bezoar: Preanesthetic Considerations SO ANESTHESIOLOGY LA English DT Editorial Material C1 [Sarma, Jaydev] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Sarma, Jaydev] Harvard Univ, Sch Med, Boston, MA USA. RP Sarma, J (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM jsarma@partners.org NR 2 TC 1 Z9 1 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JUL PY 2011 VL 115 IS 1 BP 175 EP 175 DI 10.1097/ALN.0b013e31820b8a29 PG 1 WC Anesthesiology SC Anesthesiology GA 781IX UT WOS:000291925400024 PM 21694514 ER PT J AU Manion, SC Brennan, TJ AF Manion, Smith C. Brennan, Timothy J. TI Thoracic Epidural Analgesia and Acute Pain Management SO ANESTHESIOLOGY LA English DT Article ID ARTERY-BYPASS SURGERY; POSTOPERATIVE ANALGESIA; COLORECTAL SURGERY; SURGICAL-PATIENTS; ANESTHESIA; COMPLICATIONS; METAANALYSIS; CATHETERIZATION; ROPIVACAINE; MORTALITY C1 [Brennan, Timothy J.] Univ Iowa Hosp & Clin, Dept Anesthesia, Iowa City, IA 52242 USA. RP Manion, SC (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Wang Ambulatory Care Ctr, Suite 340,15 Parkman St, Boston, MA 02114 USA. EM smanion@partners.org NR 45 TC 27 Z9 29 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JUL PY 2011 VL 115 IS 1 BP 181 EP 188 DI 10.1097/ALN.0b013e318220847c PG 8 WC Anesthesiology SC Anesthesiology GA 781IX UT WOS:000291925400025 PM 21606825 ER PT J AU Donnell-Fink, L Reichmann, WM Arbelaez, C Case, AL Katz, JN Losina, E Walensky, RP AF Donnell-Fink, Laurel Reichmann, William M. Arbelaez, Christian Case, Amy L. Katz, Jeffrey N. Losina, Elena Walensky, Rochelle P. TI Patient Satisfaction With Rapid HIV Testing in the Emergency Department SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID SEVERITY INDEX; CARE; SERVICES AB Objective: Patient satisfaction with HIV screening is crucial for sustainable implementation of the Centers for Disease Control and Prevention (CDC) HIV testing recommendations. This investigation assesses patient satisfaction with rapid HIV testing in the emergency department (ED) of an urban tertiary academic medical center. Methods: After receiving HIV test results, participants in the Universal Screening for HIV Infection in the Emergency Room (USHER) randomized controlled trial were offered a patient satisfaction survey. Questions concerned overall satisfaction with ED visit, time spent on primary medical problem, time spent on HIV testing, and test provider's ability to answer HIV-related questions. Responses were reported on a 4-point Likert scale, ranging from very dissatisfied to very satisfied (defined as optimal satisfaction). Results: Of 4,860 USHER participants, 2,025 completed testing and were offered the survey: 1,616 (79.8%) completed the survey. Overall, 1,478 (91.5%) were very satisfied. Satisfaction was less than optimal for 34.5% (10 of 29) of participants with reactive results and for 7.5% (115 of 1,542) with nonreactive results. The independent factors associated with less than optimal satisfaction were reactive test result, aged 60 years or older, black race, Hispanic/Latino ethnicity, and testing by ED provider instead of HIV counselor. Conclusion: Most participants were very satisfied with the ED-based rapid HIV testing program. Identification of independent factors that correlate with patient satisfaction will help guide best practices as EDs implement CDC recommendations. It is critical to better understand whether patients with reactive results were negatively affected by their results or truly had concerns about the testing process. [Ann Emerg Med. 2011;58:S49-S52.] C1 [Donnell-Fink, Laurel; Reichmann, William M.; Katz, Jeffrey N.; Losina, Elena] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Arbelaez, Christian; Case, Amy L.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Walensky, Rochelle P.] Brigham & Womens Hosp, Dept Infect Dis, Dept Med, Boston, MA 02115 USA. [Reichmann, William M.; Losina, Elena] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Arbelaez, Christian; Katz, Jeffrey N.; Losina, Elena; Walensky, Rochelle P.] Harvard Univ, Sch Med, Boston, MA USA. [Katz, Jeffrey N.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Walensky, Rochelle P.] Massachusetts Gen Hosp, Div Gen Med, Dept Med, Boston, MA 02114 USA. [Walensky, Rochelle P.] Massachusetts Gen Hosp, Div Infect Dis, Dept Med, Boston, MA 02114 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 OI Walensky, Rochelle P./0000-0002-8795-379X FU National Institute of Mental Health [R01 MH073445, R01 MH65869]; Doris Duke Charitable Foundation FX By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article per ICMJE conflict of interest guidelines (see www.icmje.org). This work was funded by the National Institute of Mental Health (R01 MH073445, R01 MH65869) and the Doris Duke Charitable Foundation, Clinical Scientist Development Award, to Rochelle P. Walensky. No authors have conflicts of interest to disclose. NR 10 TC 12 Z9 12 U1 0 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD JUL PY 2011 VL 58 IS 1 SU S BP S49 EP S52 DI 10.1016/j.annemergmed.2011.03.024 PG 4 WC Emergency Medicine SC Emergency Medicine GA 786XM UT WOS:000292341200010 PM 21684408 ER PT J AU Hsu, H Walensky, RP AF Hsu, Heather Walensky, Rochelle P. TI Cost-effectiveness Analysis and HIV Screening: The Emergency Medicine Perspective SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HEALTH-CARE SETTINGS; WILLINGNESS-TO-PAY; ADJUSTED LIFE-YEAR; ANTIRETROVIRAL THERAPY; PREVENTIVE SERVICES; PREVALENCE AREA; BLOOD-DONATIONS; UNITED-STATES; DEPARTMENTS AB Cost-effectiveness analysis is a useful tool for decisionmakers charged with prioritizing of the myriad medical interventions in the emergency department (ED). This analytic approach may be especially helpful for ranking programs that are competing for scarce resources while attempting to maximize net health benefits. In this article, we review the health economics literature on HIV screening in EDs and introduce the methods of cost-effectiveness analysis for medical interventions. We specifically describe the incremental cost-effectiveness ratio-its calculation, the derivation of ratio components, and the interpretation of these ratios. [Ann Emerg Med. 2011;58:S145-S150.] C1 [Hsu, Heather; Walensky, Rochelle P.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Walensky, Rochelle P.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Walensky, Rochelle P.] Harvard Univ, Sch Med, Ctr AIDS Res, Boston, MA USA. [Walensky, Rochelle P.] Brigham & Womens Hosp, Dept Med, Div Infect Dis, Boston, MA 02115 USA. RP Walensky, RP (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM rwalensky@partners.org OI Walensky, Rochelle P./0000-0002-8795-379X FU National Institute of Mental Health [R01 MH073445, R01 MH65869]; Doris Duke Charitable Foundation; Centers for Disease Control and Prevention, Atlanta, GA FX By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article as per ICMJE conflict of interest guidelines (see www.icmje.org). This work was funded by the National Institute of Mental Health (R01 MH073445, R01 MH65869) and the Doris Duke Charitable Foundation, Clinical Scientist Development Award, to Dr. Walensky. No authors have conflicts of interest to disclose.; Publication of this article was supported by Centers for Disease Control and Prevention, Atlanta, GA. NR 40 TC 8 Z9 8 U1 1 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD JUL PY 2011 VL 58 IS 1 SU S BP S145 EP S150 DI 10.1016/j.annemergmed.2011.03.039 PG 6 WC Emergency Medicine SC Emergency Medicine GA 786XM UT WOS:000292341200026 PM 21684394 ER PT J AU Walensky, RP Reichnnann, WM Arbelaez, C Wright, E Katz, JN Seage, GR Safren, SA Hare, AQ Novais, A Losina, E AF Walensky, Rochelle P. Reichnnann, William M. Arbelaez, Christian Wright, Elizabeth Katz, Jeffrey N. Seage, George R., III Safren, Steven A. Hare, Anna Q. Novais, Anna Losina, Elena TI Counselor- Versus Provider-Based HIV Screening in the Emergency Department: Results From the Universal Screening for HIV Infection in the Emergency Room (USHER) Randomized Controlled Trial SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID PREVENTION GUIDELINES; SEVERITY INDEX; DISEASE; ROUTINE; IMPLEMENTATION; VIOLENCE AB Objective: We compare rates of rapid HIV testing, test offer, and acceptance in an urban emergency department (ED) when conducted by dedicated HIV counselors versus current members of the ED staff. Methods: The Universal Screening for HIV Infection in the Emergency Room [USHER] trial is a prospective randomized controlled trial that implemented an HIV screening program in the ED of an urban tertiary medical center. ED patients were screened and consented for trial enrollment by an USHER research assistant. Eligible subjects were randomized to rapid HIV testing (oral Ora Quick) offered by a dedicated counselor (counselor arm) or by an ED provider (provider arm). In the counselor arm, counselors-without other clinical responsibilities-assumed nearly all testing-related activities (consent, counseling, delivery of test results). In the provider arm, trained ED emergency service assistants (nursing assistants) consented and tested the participant in the context of other ED-related responsibilities. In this arm, ED house officers, physician assistants, or attending physicians provided HIV test results to trial participants. Outcome measures were rates of HIV testing and test offer among individuals consenting for study participation. Among individuals offered the test, test acceptance was also measured. Results: From February 2007 through July 2008, 8,187 eligible patients were approached in the ED, and 4,855 (59%) consented and were randomized to trial participation. The mean age was 37 years, 65% were women, and 42% were white. The overall testing rate favored the counselor arm (57% versus 27%; P<.001); 80% (1,959/2,446) of subjects in the counselor arm were offered an HIV test compared with 36% (861/2,409) in the provider arm (P<.001). HIV test acceptance was slightly higher in the provider arm (counselor arm 71% versus provider arm 75%; P=.025). Conclusion: Routine rapid HIV testing in the ED was accomplished more frequently by dedicated HIV counselors than by ED staff in the course of routine clinical work. Without dedicated staff, HIV testing in this setting may not be truly routine. [Ann Emerg Med. 2011;58:S126-S132.] C1 [Walensky, Rochelle P.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Walensky, Rochelle P.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Safren, Steven A.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Safren, Steven A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Walensky, Rochelle P.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Katz, Jeffrey N.] Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Reichnnann, William M.; Wright, Elizabeth; Katz, Jeffrey N.; Losina, Elena] Brigham & Womens Hosp, Dept Med, Dept Orthoped Surg, Boston, MA 02115 USA. [Arbelaez, Christian; Hare, Anna Q.; Novais, Anna] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Walensky, Rochelle P.; Losina, Elena] Brigham & Womens Hosp, Ctr AIDS Res, Boston, MA 02115 USA. [Katz, Jeffrey N.; Seage, George R., III] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Sch Med, Boston, MA 02115 USA. [Losina, Elena] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. RP Walensky, RP (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM rwalensky@partners.org OI Walensky, Rochelle P./0000-0002-8795-379X FU National Institute of Mental Health [R01 MH073445, R01 MH65869]; Doris Duke Charitable Foundation FX By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article as per ICMJE conflict of interest guidelines (see www.icmje.org). This research was funded by the National Institute of Mental Health (R01 MH073445, R01 MH65869) and the Doris Duke Charitable Foundation, Clinical Scientist Development Award to Rochelle P. Walensky. No authors have conflicts of interest to disclose. NR 26 TC 18 Z9 18 U1 0 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD JUL PY 2011 VL 58 IS 1 SU S BP S126 EP S132 DI 10.1016/j.annemergmed.2011.03.023 PG 7 WC Emergency Medicine SC Emergency Medicine GA 786XM UT WOS:000292341200023 PM 21684391 ER PT J AU Jacobsen, ED Kim, HT Ho, VT Cutler, CS Koreth, J Fisher, DC Armand, P Alyea, EP Freedman, AS Soiffer, RJ Antin, JH AF Jacobsen, E. D. Kim, H. T. Ho, V. T. Cutler, C. S. Koreth, J. Fisher, D. C. Armand, P. Alyea, E. P. Freedman, A. S. Soiffer, R. J. Antin, J. H. TI A large single-center experience with allogeneic stem-cell transplantation for peripheral T-cell non-Hodgkin lymphoma and advanced mycosis fungoides/Sezary syndrome SO ANNALS OF ONCOLOGY LA English DT Article DE allogeneic transplant; CTCL; GVHD; mycosis fungoides; NK lymphoma; T-cell lymphoma ID COMPETING RISK; SURVIVAL AB Background: The prognosis for patients with most forms of T-cell lymphoma is poor. Allogeneic hematopoietic stem-cell transplantation (HSCT) may improve the outcome. Patients and methods: This study examines the outcome of 52 patients who underwent ablative or nonablative allogeneic HSCT for peripheral T-cell lymphoma (PTCL) or advanced mycosis fungoides/Sezary syndrome over a 12-year period at a single institution. We divided the patients into those with predominantly nodal histologies: peripheral T-cell not otherwise specified (PTCL NOS), angioimmunoblastic (AITL), or anaplastic large cell lymphoma, T/null type (systemic) (ALCL), and predominantly extranodal histologies: natural killer (NK)/T cell, enteropathy type, hepatosplenic, subcutaneous panniculitic, mycosis fungoides, or T cell or NK cell other. Results: Median follow-up of survivors is 49 months. Non-relapse mortality and relapse at 3 years was 27% and 43%, respectively. The incidence of grade II-IV acute graft-versus-host disease (GVHD) was 21%. The incidence of extensive chronic GVHD at 2 years was 27%. The 3-year progression-free survival was 30%: 45% in patients with predominantly nodal histologies (PTCL NOS, AITL, and ALCL) and 6% in patients with predominantly extranodal histologies (P = 0.016). Overall survival at 3 years was 41% for all patients. Conclusion: Allogeneic HSCT can produce long-term remissions in relapsed/refractory T-cell lymphoma, especially those with nodal histologies. C1 [Jacobsen, E. D.; Ho, V. T.; Cutler, C. S.; Koreth, J.; Fisher, D. C.; Armand, P.; Alyea, E. P.; Freedman, A. S.; Soiffer, R. J.; Antin, J. H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Kim, H. T.] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. RP Jacobsen, ED (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM edjacobsen@partners.org FU Jock and Bunny Adams Education and Research Endowment; National Cancer Institute [CA142106] FX Jock and Bunny Adams Education and Research Endowment; National Cancer Institute (CA142106). NR 14 TC 38 Z9 38 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JUL PY 2011 VL 22 IS 7 BP 1608 EP 1613 DI 10.1093/annonc/mdq698 PG 6 WC Oncology SC Oncology GA 782YK UT WOS:000292048500018 PM 21252059 ER PT J AU Jacobs, JP Edwards, FH Shahian, DM Prager, RL Wright, CD Puskas, JD Morales, DLS Gammie, JS Sanchez, JA Haan, CK Badhwar, V George, KM O'Brien, SM Dokholyan, RS Sheng, SB Peterson, ED Shewan, CM Feehan, KM Han, JM Jacobs, ML Williams, WG Mayer, JE Chitwood, WR Murray, GF Grover, FL AF Jacobs, Jeffrey Phillip Edwards, Fred H. Shahian, David M. Prager, Richard L. Wright, Cameron D. Puskas, John D. Morales, David L. S. Gammie, James S. Sanchez, Juan A. Haan, Constance K. Badhwar, Vinay George, Kristopher M. O'Brien, Sean M. Dokholyan, Rachel S. Sheng, Shubin Peterson, Eric D. Shewan, Cynthia M. Feehan, Kelly M. Han, Jane M. Jacobs, Marshall Lewis Williams, William G. Mayer, John E., Jr. Chitwood, W. Randolph, Jr. Murray, Gordon F. Grover, Frederick L. TI Successful Linking of The Society of Thoracic Surgeons Database to Social Security Data to Examine Survival After Cardiac Operations SO ANNALS OF THORACIC SURGERY LA English DT Article ID CORONARY-ARTERY-BYPASS; LONG-TERM SURVIVAL; VALVE-REPLACEMENT; REVASCULARIZATION; MORTALITY; PUMP; MEDICARE; OUTCOMES AB Background. Long-term evaluation of cardiothoracic surgical outcomes is a major goal of The Society of Thoracic Surgeons (STS). Linking the STS Database to the Social Security Death Master File (SSDMF) allows for the verification of "life status." This study demonstrates the feasibility of linking the STS Database to the SSDMF and examines longitudinal survival after cardiac operations. Methods. For all operations in the STS Adult Cardiac Surgery Database performed in 2008 in patients with an available Social Security Number, the SSDMF was searched for a matching Social Security Number. Survival probabilities at 30 days and 1 year were estimated for nine common operations. Results. A Social Security Number was available for 101,188 patients undergoing isolated coronary artery bypass grafting, 12,336 patients undergoing isolated aortic valve replacement, and 6,085 patients undergoing isolated mitral valve operations. One-year survival for isolated coronary artery bypass grafting was 88.9% (6,529 of 7,344) with all vein grafts, 95.2% (84,696 of 88,966) with a single mammary artery graft, 97.4% (4,422 of 4,540) with bilateral mammary artery grafts, and 95.6% (7,543 of 7,890) with all arterial grafts. One-year survival was 92.4% (11,398 of 12,336) for isolated aortic valve replacement (95.6% [2,109 of 2,206] with mechanical prosthesis and 91.7% [9,289 of 10,130] with biologic prosthesis), 86.5% (2,312 of 2,674) for isolated mitral valve replacement (91.7% [923 of 1,006] with mechanical prosthesis and 83.3% [1,389 of 1,668] with biologic prosthesis), and 96.0% (3,275 of 3,411) for isolated mitral valve repair. Conclusions. Successful linkage to the SSDMF has substantially increased the power of the STS Database. These longitudinal survival data from this large multi-institutional study provide reassurance about the durability and long-term benefits of cardiac operations and constitute a contemporary benchmark for survival after cardiac operations. (Ann Thorac Surg 2011;92:32-9) (C) 2011 by The Society of Thoracic Surgeons C1 [Jacobs, Jeffrey Phillip] Univ S Florida, Coll Med, All Childrens Hosp, CHIF,CSAoF, St Petersburg, FL 33701 USA. Univ S Florida, Coll Med, All Childrens Hosp, CHIF,CSAoF, Tampa, FL USA. Univ S Florida, Coll Med, Jacksonville, FL USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Univ Michigan, Ann Arbor, MI 48109 USA. Emory Univ, Emory Univ Hosp Midtown, Atlanta, GA 30322 USA. Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA. Univ Maryland, Med Ctr, Baltimore, MD 21201 USA. Univ Connecticut, Ctr Hlth, Farmington, CT USA. Cardiac Surg Associates Florida, Orlando, FL USA. Duke Univ, Med Ctr, DCRI, Durham, NC USA. Soc Thorac Surg, Chicago, IL USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Harvard Univ, Sch Med, Childrens Hosp Boston, Boston, MA USA. E Carolina Univ, Brody Sch Med, Greenville, NC USA. W Virginia Univ, Morgantown, WV 26506 USA. Univ Colorado Denver, Sch Med, Aurora, CO USA. RP Jacobs, JP (reprint author), Univ S Florida, Coll Med, All Childrens Hosp, CHIF,CSAoF, 625 6th Ave S,Ste 475, St Petersburg, FL 33701 USA. EM jeffjacobs@msn.com RI O'Brien, Sean/H-6268-2013; Sanchez, Juan/I-1936-2016 OI Sanchez, Juan/0000-0002-6789-3208 NR 21 TC 38 Z9 38 U1 2 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JUL PY 2011 VL 92 IS 1 BP 32 EP 39 DI 10.1016/j.athoracsur.2011.02.029 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 784WO UT WOS:000292189400013 PM 21718828 ER PT J AU Henstrom, DK Malo, JS Cheney, ML Hadlock, TA AF Henstrom, Douglas K. Malo, Juan S. Cheney, Mack L. Hadlock, Tessa A. TI Platysmectomy An Effective Intervention for Facial Synkinesis and Hypertonicity SO ARCHIVES OF FACIAL PLASTIC SURGERY LA English DT Article ID QUALITY-OF-LIFE; PARALYSIS; EMOTION; EXPRESSIONS; REANIMATION; COMPLEX; FACE AB Objectives: To describe a procedure to permanently address platysmal synkinesis and hypertonicity and to report changes in quality of life associated with platysmectomy using the Facial Clinimetric Evaluation instrument. Methods: Chemodenervation significantly relieves platysmal synkinesis in almost all patients with significant face and neck synkinesis associated with dynamic facial expressions. We recently began to offer platysmectomy as part of a permanent solution to chronic superficial torticollis-like neck symptoms. For a 10-month period, 24 patients underwent the procedure, and preoperative and postoperative Facial Clinimetric Evaluation data were obtained from 21 patients (88%). Results: In 19 patients, platysmectomy was performed using local anesthesia without sedation. In the remaining 5 patients, platysmectomy was performed using general anesthesia concurrent with free gracilis transfer for smile reanimation. No intraoperative or postoperative complications occurred. Overall, the patients' quality of life significantly improved after platysmectomy (P=.02). Conclusion: Platysmectomy is straightforward and seems effective in treating neck synkinesis associated with chronic hypertonic platysmal activity. C1 [Henstrom, Douglas K.; Malo, Juan S.; Cheney, Mack L.; Hadlock, Tessa A.] Massachusetts Eye & Ear Infirm, Facial Nerve Ctr, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. RP Henstrom, DK (reprint author), Massachusetts Eye & Ear Infirm, Facial Nerve Ctr, Dept Otolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA. EM douglas_henstrom@meei.harvard.edu NR 16 TC 19 Z9 19 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 1521-2491 J9 ARCH FACIAL PLAST S JI Arch. Facial Plast. Surg. PD JUL-AUG PY 2011 VL 13 IS 4 BP 239 EP 243 PG 5 WC Surgery SC Surgery GA 793QU UT WOS:000292839000003 PM 21768558 ER PT J AU Gunderson, JG Zanarini, MC Choi-Kain, LW Mitchell, KS Jang, KL Hudson, JI AF Gunderson, John G. Zanarini, Mary C. Choi-Kain, Lois W. Mitchell, Karen S. Jang, Kerry L. Hudson, James I. TI Family Study of Borderline Personality Disorder and Its Sectors of Psychopathology SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID BINGE-EATING DISORDER; DSM-IV BORDERLINE; GENETIC EPIDEMIOLOGY; PSYCHIATRIC-DISORDERS; COVARIANCE STRUCTURE; HISTORY METHOD; COMORBIDITY; CRITERIA; TWIN; HERITABILITY AB Context: The familiality of borderline personality disorder (BPD) and its sectors of psychopathology are incompletely understood. Objectives: To assess the familial aggregation of BPD and its 4 major sectors (affective, interpersonal, behavioral, and cognitive) and test whether the relationship of the familial and nonfamilial associations among these sectors can be accounted for by a latent BPD construct. Design: Family study, with direct interviews of probands and relatives. Setting: A psychiatric hospital (McLean Hospital) and the Boston-area community. Participants: A total of 368 probancls (132 with BPD, 134 without BPD, and 102 with major depressive disorder) and 885 siblings and parents of probands. Main Assessments: The Diagnostic Interview for DSM-IV Personality Disorders and the Revised Diagnostic Interview for Borderlines (DIB-R) were used to assess borderline psychopathology, and the Structured Clinical Interview for DSM-IV was used to assess major depressive disorder. Results: Borderline personality disorder meeting both DSM-IV and DIB-R criteria showed substantial familial aggregation for BPD in individuals with a family member with BPD vs those without a family, member with BPD, using proband-relative pairs (risk ratio, 2.9; 95% confidence interval, 1.5-5.5) as well as using all pairs of family members (3.9; 1.7-9.0). All 4 sectors of BPD psychopathology aggregated significantly, in families, using both DSM-IV and DIB-R definitions (correlation of traits among all pairs of family members ranged from 0.07 to 0.27), with the affective and interpersonal sectors showing the highest levels; however, the level of familial aggregation of BPD was higher than that of the individual sectors. The relationship among the sectors was best explained by a common pathway model in which the sectors represent manifestations of a latent BPD construct. Conclusions: Familial factors contribute to BPD and its sectors of psychopathology. Borderline personality, disorder may arise from a unitary liability that finds expression in its sectors of psychopathology,. C1 [Gunderson, John G.; Zanarini, Mary C.; Choi-Kain, Lois W.; Hudson, James I.] Harvard Univ, McLean Hosp, Sch Med, Dept Psychiat, Belmont, MA 02478 USA. [Mitchell, Karen S.] Vet Affairs Boston Healthcare Syst, Womens Hlth Sci Div, Natl Ctr Posttraumat Stress Disorder, Boston, MA USA. [Mitchell, Karen S.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Jang, Kerry L.] Univ British Columbia, Dept Psychiat, Vancouver, BC, Canada. RP Gunderson, JG (reprint author), Harvard Univ, McLean Hosp, Sch Med, Dept Psychiat, 115 Mill St, Belmont, MA 02478 USA. EM jgunderson@mclean.harvard.edu FU National Institute of Mental Health [MH 400130 (R01)] FX This study was supported by grant MH 400130 (R01) from the National Institute of Mental Health. NR 84 TC 25 Z9 25 U1 3 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JUL PY 2011 VL 68 IS 7 BP 753 EP 762 PG 10 WC Psychiatry SC Psychiatry GA 787DK UT WOS:000292356600011 PM 21727257 ER PT J AU Lugea, A Waldron, RT French, SW Pandol, SJ AF Lugea, Aurelia Waldron, Richard T. French, Samuel W. Pandol, Stephen J. TI Drinking and driving pancreatitis Links between endoplasmic reticulum stress and autophagy SO AUTOPHAGY LA English DT Editorial Material DE acinar cell; alcohol abuse; pancreas; ERAD; UPR; XBP1 AB Alcohol abuse is the leading etiologic factor of pancreatitis, although many heavy drinkers do not develop pancreatic damage. Alcohol promotes pancreatitis through a combination of remote (e.g., increased gut permeability to bacterial products such as lipopolysaccharide) and more proximal effects (e.g., altered pancreatic cholinergic inputs), including oxidative damage at the level of the pancreatic acinar cell. Recent evidence indicates that alcohol exposure to rodents disturbs proteostasis in the exocrine pancreas, an effect counterbalanced by homeostatic processes that include both the unfolded protein response (UPR) and autophagy. A corollary to this notion is that pancreatitis results when adaptive responses are insufficiently robust to alleviate the cellular stress caused by alcohol. C1 [Lugea, Aurelia; Waldron, Richard T.; Pandol, Stephen J.] VA Greater Los Angeles Healthcare Syst, So Calif Res Ctr ALPD & Cirrhosis, Los Angeles, CA USA. [Lugea, Aurelia; Waldron, Richard T.; Pandol, Stephen J.] Univ Calif Los Angeles, Los Angeles, CA USA. [French, Samuel W.] Harbor UCLA Med Ctr, Dept Pathol, Torrance, CA 90509 USA. RP Lugea, A (reprint author), VA Greater Los Angeles Healthcare Syst, So Calif Res Ctr ALPD & Cirrhosis, Los Angeles, CA USA. EM alugea@ucla.edu FU NCCIH NIH HHS [1P01AT003960, P01 AT003960]; NIAAA NIH HHS [R01 AA019954, R21AA016010, R21 AA016010]; PHS HHS [P50-A11999] NR 0 TC 9 Z9 10 U1 0 U2 3 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1554-8627 J9 AUTOPHAGY JI Autophagy PD JUL PY 2011 VL 7 IS 7 BP 783 EP 785 DI 10.4161/auto.7.7.15594 PG 3 WC Cell Biology SC Cell Biology GA 786JA UT WOS:000292300600017 PM 21460613 ER PT J AU Da Silva, N Hill, E Breton, S AF Da Silva, Nicolas Hill, Eric Breton, Sylvie TI The Epididymal Dendritic Cell Network Is Affected by Efferent Duct Ligation and Vasectomy. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 44th Annual Meeting of the Society-for-the-Study-of-Reproduction (SSR) CY 2011 CL Portland, OR SP Soc Study Reproduct C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD JUL PY 2011 VL 85 SI SI MA 43 PG 2 WC Reproductive Biology SC Reproductive Biology GA 032VC UT WOS:000310746200236 ER PT J AU Fiedler, SE Carr, DW AF Fiedler, Sarah E. Carr, Daniel W. TI ROPN1, a Protein Kinase A-Like (R2D2) Protein, Regulates Sperm Motility SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 44th Annual Meeting of the Society-for-the-Study-of-Reproduction (SSR) CY 2011 CL Portland, OR SP Soc Study Reproduct C1 Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD JUL PY 2011 VL 85 SI SI MA 804 PG 1 WC Reproductive Biology SC Reproductive Biology GA 032VC UT WOS:000310746200193 ER PT J AU Lee, GY Liu, J Lawitts, J Toner, M Biggers, JD AF Lee, Gloria Y. Liu, Jie Lawitts, Joel Toner, Mehmet Biggers, John D. TI Desiccation at Ambient Temperature and Storage of Mouse Sperm in 3-O-methyl-D-glucose Medium Without Freezing SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 44th Annual Meeting of the Society-for-the-Study-of-Reproduction (SSR) CY 2011 CL Portland, OR SP Soc Study Reproduct C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Isreal Deaconess Med Ctr, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU SOC STUDY REPRODUCTION PI MADISON PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD JUL PY 2011 VL 85 SI SI MA 732 PG 1 WC Reproductive Biology SC Reproductive Biology GA 032VC UT WOS:000310746200403 ER PT J AU Liu, J Lee, GY Lawitts, J Toner, M Biggers, JD AF Liu, Jie Lee, Gloria Y. Lawitts, Joel Toner, Mehmet Biggers, John D. TI Mice Produced by ICSI Using a Conventional Injection Pipette Without Piezo. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 44th Annual Meeting of the Society-for-the-Study-of-Reproduction (SSR) CY 2011 CL Portland, OR SP Soc Study Reproduct C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Isreal Deaconess Med Ctr, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD JUL PY 2011 VL 85 SI SI MA 731 PG 1 WC Reproductive Biology SC Reproductive Biology GA 032VC UT WOS:000310746200098 ER PT J AU Rueda, BR Attaman, JA Stanic-Kostic, A Kim, M Styer, AK AF Rueda, Bo R. Attaman, Jill A. Stanic-Kostic, Aleksandar Kim, Minji Styer, Aaron K. TI Defining the Antagonistic Role of Omega-3 Polyunsaturated Fatty Acid in the Establishment and Early Maintenance of Endometriosis-Like Lesions in a Murine Model SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 44th Annual Meeting of the Society-for-the-Study-of-Reproduction (SSR) CY 2011 CL Portland, OR SP Soc Study Reproduct C1 [Rueda, Bo R.; Attaman, Jill A.; Stanic-Kostic, Aleksandar; Kim, Minji; Styer, Aaron K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD JUL PY 2011 VL 85 SI SI MA 379 PG 2 WC Reproductive Biology SC Reproductive Biology GA 032VC UT WOS:000310746200626 ER PT J AU Shioda, T Rosenthal, N Ellis, H Shioda, K AF Shioda, Toshi Rosenthal, Noel Ellis, Haley Shioda, Keiko TI Selective Repair of Epigenetic Aberrations at the Gtl2/Meg3 Imprinted Locus in Mouse Induced Primordial Germ Cells SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 44th Annual Meeting of the Society-for-the-Study-of-Reproduction (SSR) CY 2011 CL Portland, OR SP Soc Study Reproduct C1 [Shioda, Toshi; Rosenthal, Noel; Ellis, Haley; Shioda, Keiko] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD JUL PY 2011 VL 85 SI SI MA 120 PG 2 WC Reproductive Biology SC Reproductive Biology GA 032VC UT WOS:000310746200497 ER PT J AU Shum, WW Da Silva, N Hill, E Brown, D Breton, S AF Shum, Winnie Waichi Da Silva, Nicolas Hill, Eric Brown, Dennis Breton, Sylvie TI Characterization of the Novel Apical-Reaching Property of Basal Cells in the Epididymis SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 44th Annual Meeting of the Society-for-the-Study-of-Reproduction (SSR) CY 2011 CL Portland, OR SP Soc Study Reproduct C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD JUL PY 2011 VL 85 SI SI MA 565 PG 2 WC Reproductive Biology SC Reproductive Biology GA 032VC UT WOS:000310746200662 ER PT J AU Tanwar, PS Zhang, LH Teixeira, J AF Tanwar, Pradeep S. Zhang, LiHua Teixeira, Jose TI APC (Adenomatous Polyposis Coli), a Tumor Suppressor Gene, Is Required for Maintenance of Sertoli Cell Polarity and Microtubules Integrity. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 44th Annual Meeting of the Society-for-the-Study-of-Reproduction (SSR) CY 2011 CL Portland, OR SP Soc Study Reproduct C1 [Tanwar, Pradeep S.; Zhang, LiHua; Teixeira, Jose] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD JUL PY 2011 VL 85 SI SI MA 44 PG 1 WC Reproductive Biology SC Reproductive Biology GA 032VC UT WOS:000310746200232 ER PT J AU White, YAR Johnson, AL Woods, DC AF White, Yvonne A. R. Johnson, Alan L. Woods, Dori C. TI TRAIL-Induced Cell Death Is Independent of NFKB in Ovarian Granulosa Tumor Cell Lines SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 44th Annual Meeting of the Society-for-the-Study-of-Reproduction (SSR) CY 2011 CL Portland, OR SP Soc Study Reproduct C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Penn State Univ, University Pk, PA 16802 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD JUL PY 2011 VL 85 SI SI MA 820 PG 2 WC Reproductive Biology SC Reproductive Biology GA 032VC UT WOS:000310746200705 ER PT J AU White, YAR Johnson, AL Woods, DC AF White, Yvonne A. R. Johnson, Alan L. Woods, Dori C. TI TRAIL-Induced Cell Death Is Independent of NFKB in Ovarian Granulosa Tumor Cell Lines. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 44th Annual Meeting of the Society-for-the-Study-of-Reproduction (SSR) CY 2011 CL Portland, OR SP Soc Study Reproduct C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Penn State Univ, University Pk, PA 16802 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD JUL PY 2011 VL 85 SI SI MA 820 PG 2 WC Reproductive Biology SC Reproductive Biology GA 032VC UT WOS:000310746200463 ER PT J AU Kang, JX AF Kang, Jing X. TI Omega-3: A link between global climate change and human health SO BIOTECHNOLOGY ADVANCES LA English DT Review DE Global climate change; Phytoplankton; Photosynthesis; Omega-3 polyunsaturated fatty acids; Omega-6/omega-3 ratio; Ocean sustainability; Human nutrition; Public health; Human diseases; Biotechnology ID FATTY-ACID COMPOSITION; ULTRAVIOLET-RADIATION; OZONE DEPLETION; UV-B; MARINE-PHYTOPLANKTON; OMEGA-3-FATTY-ACIDS; MICROALGAE; AQUACULTURE; FAT-1; FISH AB In recent years, global climate change has been shown to detrimentally affect many biological and environmental factors, including those of marine ecosystems. In particular, global climate change has been linked to an increase in atmospheric carbon dioxide, UV irradiation, and ocean temperatures, resulting in decreased marine phytoplankton growth and reduced synthesis of omega-3 polyunsaturated fatty acids (PUFAs). Marine phytoplankton are the primary producers of omega-3 PUFAs, which are essential nutrients for normal human growth and development and have many beneficial effects on human health. Thus, these detrimental effects of climate change on the oceans may reduce the availability of omega-3 PUFAs in our diets, exacerbating the modern deficiency of omega-3 PUFAs and imbalance of the tissue omega-6/omega-3 PUFA ratio, which have been associated with an increased risk for cardiovascular disease, cancer, diabetes, and neurodegenerative disease. This article provides new insight into the relationship between global climate change and human health by identifying omega-3 PUFA availability as a potentially important link, and proposes a biotechnological strategy for addressing the potential shortage of omega-3 PUFAs in human diets resulting from global climate change. (C) 2011 Elsevier Inc. All rights reserved. C1 [Kang, Jing X.] Massachusetts Gen Hosp, Lab Lipid Med & Technol, Boston, MA 02114 USA. [Kang, Jing X.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Kang, JX (reprint author), 149 13th St,Room 4433, Charlestown, MA 02129 USA. EM jxkang@partners.org FU NIH [CA113605] FX This work was partly supported by NIH grant CA113605. I thank Marina Kang for discussing and assisting in the preparation of this manuscript. NR 30 TC 14 Z9 15 U1 6 U2 36 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0734-9750 J9 BIOTECHNOL ADV JI Biotechnol. Adv. PD JUL-AUG PY 2011 VL 29 IS 4 BP 388 EP 390 DI 10.1016/j.biotechadv.2011.02.003 PG 3 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 783JI UT WOS:000292076900002 PM 21406222 ER PT J AU Thulin, H Kreicbergs, U Onelov, E Ahlstrand, C Carringer, M Holmang, S Ljungberg, B Malmstrom, PU Robinsson, D Wijkstrom, H Wiklund, NP Steineck, G Henningsohn, L AF Thulin, Helena Kreicbergs, Ulrika Onelov, Erik Ahlstrand, Christer Carringer, Malcolm Holmang, Sten Ljungberg, Borje Malmstrom, Per-Uno Robinsson, David Wijkstrom, Hans Wiklund, N. Peter Steineck, Gunnar Henningsohn, Lars TI Defecation disturbances after cystectomy for urinary bladder cancer SO BJU INTERNATIONAL LA English DT Article DE cystectomy; urinary diversion; faecal straining capacity ID BILE-ACID MALABSORPTION; CERVICAL-CANCER; RADICAL HYSTERECTOMY; ILEAL RESERVOIR; SEXUAL FUNCTION; BOWEL FUNCTION; DYSFUNCTION; DIVERSION; SURVIVORS; SYMPTOMS AB OBJECTIVE To describe and compare long-term defecation disturbances in patients who had undergone a cystectomy due to urinary bladder cancer with non-continent urostomies, continent reservoirs and orthotopic neobladder urinary diversions. PATIENTS AND METHODS During their follow-up we attempted to contact all men and women aged 30-80 years who had undergone cystectomy and urinary diversion at seven Swedish hospitals. During a qualitative phase we identified defecation disturbances as a distressful symptom and included this item in a study-specific questionnaire together with freehand comments. The patients completed the questionnaire at home. Outcome variables were dichotomized and the results are presented as relative risks with 95% confidence interval. RESULTS The questionnaire was returned from 452 (92%) of 491 identified patients. Up to 30% reported problems with the physiological emptying process of stool (bowel movement, sensory rectal function, awareness of need for defecation, motoric rectal and anal function, straining ability). A sense of decreased straining capacity was reported by 20% of the men and women with non-continent urostomy and 14% and 8% of those with continent reservoirs and orthotopic neobladders, respectively. CONCLUSIONS Of the cystectomized individuals 30% reported problems with the physiological emptying process of stool (bowel movement, sensory rectal function, awareness of need for defecation, motoric rectal and anal function, straining ability). Those wanting to improve the situation for bladder cancer survivors may consider communicating before surgery the possibility of stool-emptying problems, and asking about them after surgery. C1 [Thulin, Helena; Onelov, Erik; Steineck, Gunnar; Henningsohn, Lars] Karolinska Inst, Dept Pathol & Oncol, Div Clin Canc Epidemiol, Stockholm, Sweden. [Kreicbergs, Ulrika] Karolinska Inst, Dept Woman & Child Hlth, Stockholm, Sweden. [Wiklund, N. Peter; Henningsohn, Lars] Karolinska Inst, Dept Mol Med & Surg, Urol Sect, Stockholm, Sweden. [Wijkstrom, Hans] Karolinska Univ, Huddinge Hosp, Karolinska Inst, Surg Sci Ctr, Stockholm, Sweden. [Ahlstrand, Christer] Linkoping Univ Hosp, Fac Hlth Sci, Div Urol, S-58185 Linkoping, Sweden. [Carringer, Malcolm] Univ Hosp Orebro, Dept Urol, Orebro, Sweden. [Holmang, Sten] Sahlgrens Univ Hosp, Dept Urol, Gothenburg, Sweden. [Steineck, Gunnar] Sahlgrens Acad, Dept Oncol, Div Clin Canc Epidemiol, Gothenburg, Sweden. [Ljungberg, Borje] Norrlands Univ Hosp, Umea, Sweden. [Malmstrom, Per-Uno] Uppsala Univ, Dept Surg Sci, Uppsala, Sweden. [Robinsson, David] Ryhov Cty Hosp, Dept Urol, Jonkoping, Sweden. [Kreicbergs, Ulrika] Dana Farber Canc Inst, Phyllis F Cantor Ctr, Boston, MA 02115 USA. RP Thulin, H (reprint author), Z5 U1 Karolinska Univ Hosp, SE-14176 Stockholm, Sweden. EM helena.thulin@ki.se OI Steineck, Gunnar/0000-0002-0787-3969 NR 29 TC 4 Z9 4 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1464-4096 J9 BJU INT JI BJU Int. PD JUL PY 2011 VL 108 IS 2 BP 196 EP 203 DI 10.1111/j.1464-410X.2010.09815.x PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 786SS UT WOS:000292328800014 PM 21050359 ER PT J AU Okera, M Bae, K Bernstein, E Cheng, L Lawton, C Wolkov, H Pollack, A Dicker, A Sandler, H Sweeney, CJ AF Okera, Meena Bae, Kyoungwha Bernstein, Eric Cheng, Liang Lawton, Colleen Wolkov, Harvey Pollack, Alan Dicker, Adam Sandler, Howard Sweeney, Christopher J. TI Evaluation of nuclear factor kappa B and chemokine receptor CXCR4 co-expression in patients with prostate cancer in the Radiation Therapy Oncology Group (RTOG) 8610 SO BJU INTERNATIONAL LA English DT Article DE Nf kappa B; CXCR4; prostate cancer; radiation ID ALPHA-INDUCED APOPTOSIS; NECROSIS-FACTOR-ALPHA; CONSTITUTIVE ACTIVATION; INDEPENDENT GROWTH; BREAST-CANCER; UP-REGULATION; CELLS; PROGRESSION; INHIBITION; EXPRESSION AB OBJECTIVE To determine the frequency of nuclear factor kappa B (NF kappa B) and the chemokine receptor CXCR4 co-expression in prostate cancer specimens from men with locally advanced disease. PATIENTS AND METHODS Paraffin-embedded samples from patients enrolled on the Radiation Therapy Oncology Group (RTOG) 8610 trial underwent immunohistochemical staining for NF kappa B and CXCR4. The amount of NF kappa B and CXCR4 was scored by a 'blinded' pathologist for the percentage of cells stained (0-100%) and staining intensity (0-3 +). Cox proportional hazard models were used for overall survival and disease-free survival to examine if NF kappa B and/or CXCR4 expression were associated with patient outcomes with and without adjustment for covariates. RESULTS Available material and successful staining allowed NF kappa B and CXCR4 status to be determined for 55 and 63 patients, respectively. Both NF kappa B and CXCR4 status were available for 51 patients. Of these, 53% were 2/3 + for cytoplasmic NF kappa B staining and 56% were 2/3 + for CXCR4. In all, 18 of the 51 patients were 2/3 + for both NF kappa B and CXCR4 (P = 0.129). Ten of 11 patients with 3 + NF kappa B had 2/3 + CXCR4 (P = 0.004). In this small study, neither NF kappa B nor CXCR4 were associated with prostate cancer outcomes. CONCLUSIONS High NF kappa B expression is associated with CXCR4 expression and they are co-expressed in about one third of patients with clinically localized prostate cancer. Larger studies to accurately determine the frequency of co-expression and prognostic utility of NF kappa B and CXCR4 alone and in combination are warranted. C1 [Sweeney, Christopher J.] Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. [Okera, Meena] Royal Adelaide Hosp, Dept Med, Adelaide, SA 5000, Australia. [Bae, Kyoungwha] RTOG, Dept Stat, Philadelphia, PA USA. [Bernstein, Eric] Providence Canc Ctr, Portland, OR USA. [Cheng, Liang] Indiana Univ, Dept Pathol & Lab Med, Indianapolis, IN 46204 USA. [Lawton, Colleen] Med Coll Wisconsin, Dept Radiat Oncol, Milwaukee, WI 53226 USA. [Wolkov, Harvey] Radiol Associates Sacramento, Sacramento, CA USA. [Pollack, Alan] Univ Miami, Miller Sch Med, Dept Radiat Oncol, Miami, FL 33136 USA. [Dicker, Adam] Thomas Jefferson Univ, Dept Radiat Oncol, Philadelphia, PA 19107 USA. [Sandler, Howard] Cedars Sinai Med Ctr, Dept Radiat Oncol, Los Angeles, CA 90048 USA. RP Sweeney, CJ (reprint author), Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, 44 Binney St,Rm 1230, Boston, MA 02115 USA. EM christopher_sweeney@dfci.harvard.edu OI Dicker, Adam/0000-0003-0733-3337 FU RTOG; National Cancer Institute and Pennysylvania Department of Health [CA-006927, CA-101984-01] FX Source of Funding: RTOG.; Financial support: This publication was supported in part by Grants CA-006927 and CA-101984-01 from the National Cancer Institute and Pennysylvania Department of Health. NR 29 TC 11 Z9 11 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1464-4096 J9 BJU INT JI BJU Int. PD JUL PY 2011 VL 108 IS 2B SI SI BP E51 EP E58 DI 10.1111/j.1464-410X.2010.09884.x PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 789EO UT WOS:000292497000008 PM 21156016 ER PT J AU Devic, I Hwang, HJ Edgar, JS Izutsu, K Presland, R Pan, C Goodlett, DR Wang, Y Armaly, J Tumas, V Zabetian, CP Leverenz, JB Shi, M Zhang, J AF Devic, Ivana Hwang, HyeJin Edgar, John Scott Izutsu, Kenneth Presland, Richard Pan, Catherine Goodlett, David R. Wang, Yu Armaly, Jeff Tumas, Vitor Zabetian, Cyrus P. Leverenz, James B. Shi, Min Zhang, Jing TI Salivary alpha-synuclein and DJ-1: potential biomarkers for Parkinson's disease SO BRAIN LA English DT Letter ID CARDIAC SYMPATHETIC-NERVE; LEWY BODY DISEASE; DEGENERATION; PATHOLOGY; SYSTEM; SECRETION C1 [Devic, Ivana; Hwang, HyeJin; Pan, Catherine; Wang, Yu; Armaly, Jeff; Shi, Min; Zhang, Jing] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98104 USA. [Devic, Ivana; Izutsu, Kenneth; Presland, Richard] Univ Washington, Sch Dent, Dept Oral Biol, Seattle, WA 98195 USA. [Edgar, John Scott; Goodlett, David R.] Univ Washington, Sch Pharm, Dept Med Chem, Seattle, WA 98195 USA. [Presland, Richard] Univ Washington, Sch Med, Dept Med Dermatol, Seattle, WA 98104 USA. [Wang, Yu] Huazhong Univ Sci & Technol, Dept Neurosurg, Tongji Hosp, Tongji Med Coll, Wuhan 430074, Peoples R China. [Tumas, Vitor] Univ Sao Paulo, Dept Neurosci & Behav, Ribeirao Preto Sch Med, BR-05508 Sao Paulo, Brazil. [Zabetian, Cyrus P.; Leverenz, James B.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98104 USA. [Zabetian, Cyrus P.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Leverenz, James B.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Leverenz, James B.] Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA 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; Tumas, Vitor/C-9949-2014 OI Shi, Min/0000-0002-6901-2558; FU NIA NIH HHS [AG033398, R01 AG033398]; NIDCR NIH HHS [DE17634]; NIEHS NIH HHS [ES004696, P42 ES004696]; NINDS NIH HHS [P30 NS055088, NS057567, NS062684, NS065070, P50 NS062684, P50 NS062684-02, R01 NS057567, R01 NS065070, R01 NS065070-02, R01 NS065070-03] NR 25 TC 66 Z9 69 U1 0 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD JUL PY 2011 VL 134 AR e178 DI 10.1093/brain/awr015 PN 7 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 782YV UT WOS:000292049600001 PM 21349902 ER PT J AU Ng, AK AF Ng, Andrea K. TI Review of the cardiac long-term effects of therapy for Hodgkin lymphoma SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Review DE Hodgkin lymphoma; cardiology; radiotherapy ID CORONARY-ARTERY-DISEASE; INTENSITY-MODULATED RADIOTHERAPY; INVOLVED-FIELD RADIOTHERAPY; MEDIASTINAL IRRADIATION; RADIATION-THERAPY; HEART-DISEASE; AORTIC REGURGITATION; NODE RADIOTHERAPY; DOSE CONSTRAINTS; VIRTUAL VOLUMES AB Patients diagnosed with Hodgkin lymphoma have a high cure rate. However, long-term survivors of the disease are at significantly increased risk for a number of late effects, with cardiovascular disease being the most common non-malignant cause of death in these patients. This review summarizes the available data regarding the types of cardiac complications, timing of their onset in relationship to initial treatment, associated risk factors, and available studies on the role of screening for subclinical cardiac disease. Given the known correlation between the extent of Hodgkin lymphoma therapy and subsequent cardiac risks, current trials investigating treatment reduction, including using lower radiation dose, smaller radiation field size and abbreviated chemotherapy will hopefully help in limiting cardiac toxicity. Screening for and aggressive management of traditional cardiac risk factors are also important strategies in reducing risks of cardiac disease in long-term Hodgkin lymphoma survivors. C1 [Ng, Andrea K.] Harvard Univ, Dept Radiat Oncol, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. [Ng, Andrea K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Ng, AK (reprint author), Harvard Univ, Dept Radiat Oncol, Dana Farber Canc Inst, Sch Med, 75 Francis St,ASB1-L2, Boston, MA 02115 USA. EM ang@lroc.harvard.edu NR 64 TC 34 Z9 38 U1 1 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUL PY 2011 VL 154 IS 1 BP 23 EP 31 DI 10.1111/j.1365-2141.2011.08713.x PG 9 WC Hematology SC Hematology GA 786RV UT WOS:000292326500003 PM 21539537 ER PT J AU Treon, SP Yang, G Hanzis, C Ioakimidis, L Verselis, SJ Fox, EA Xu, L Hunter, ZR Tseng, HY Manning, RJ Patterson, CJ Sheehy, P Turnbull, B AF Treon, Steven P. Yang, Guang Hanzis, Christine Ioakimidis, Leukothea Verselis, Sigitas J. Fox, Edward A. Xu, Lian Hunter, Zachary R. Tseng, Hsiuyi Manning, Robert J. Patterson, Christopher J. Sheehy, Patricia Turnbull, Barry TI Attainment of complete/very good partial response following rituximab-based therapy is an important determinant to progression-free survival, and is impacted by polymorphisms in FCGR3A in Waldenstrom macroglobulinaemia SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE Waldenstrom macroglobulinemia; complete response; very good partial response; FCGR3A; rituximab ID FC-GAMMA-RIIIA; PROGNOSTIC SCORING SYSTEM; MONOCLONAL-ANTIBODY; FOLLICULAR LYMPHOMA; RECEPTOR-II; INTERNATIONAL WORKSHOP; CLINICAL-RESPONSE; MULTIPLE-MYELOMA; HUMAN IGG2; RECOMMENDATIONS AB The incorporation of rituximab into various regimens has improved depth of response in Waldenstrom macroglobulinaemia (WM), though the impact of achieving better responses remains to be determined. We examined response depth on progression-free survival (PFS) in 159 rituximab-naive WM patients who received rituximab-based therapy. The median follow-up was 33 5 months, and categorical responses were as follows: complete response (CR, 8.8%); very good partial response (VGPR, 13.2%); partial response (50%); minor response (18.9%); Non-Responders (8.8%). Sequencing for polymorphic variants of FCGR2A, FCGR2B, and FCGR3A was performed, and impact on response depth determined. Achievement of better categorical responses was incrementally associated with improved PFS (P < 0 0001). No separation was observed between CR and VGPR, and attainment of at least a VGPR was associated with improved time-to-progression. Neither age, serum IgM, haematocrit, platelet count, serum beta(2)microglobulin, WM International Prognostic Scoring System score, and treatment group predicted for CR/VGPR. Polymorphisms at FCGR3A-48 and -158 were associated with improved categorical responses, particularly attainment of CR/VGPR (P <= 0 03). The attainment of CR/VGPR was associated with significantly longer PFS in rituximab-naive WM patients undergoing rituximab-based therapy, and was predicted by polymorphisms in FCGR3A. C1 [Treon, Steven P.; Yang, Guang; Hanzis, Christine; Ioakimidis, Leukothea; Xu, Lian; Hunter, Zachary R.; Tseng, Hsiuyi; Manning, Robert J.; Patterson, Christopher J.; Sheehy, Patricia] Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinaemia, Boston, MA 02115 USA. [Treon, Steven P.; Yang, Guang; Fox, Edward A.] Harvard Univ, Sch Med, Boston, MA USA. [Verselis, Sigitas J.; Fox, Edward A.] Dana Farber Canc Inst, Mol Diagnost Ctr, Boston, MA 02115 USA. [Turnbull, Barry] BioBridges, Boston, MA USA. RP Treon, SP (reprint author), Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinaemia, M547,44 Binney St, Boston, MA 02115 USA. EM steven_treon@dfci.harvard.edu RI Hunter, Zachary/H-3018-2013 OI Hunter, Zachary/0000-0002-1689-1691 FU Bing Fund for Waldenstrom's Macroglobulinaemia; Bailey Family Fund for Waldenstrom's Research; Linda and Edward Nelson Fund for Waldenstrom's Macroglobulinaemia; National Institutes of Health [K23CA087977-03] FX Supported by the Bing Fund for Waldenstrom's Macroglobulinaemia, the Bailey Family Fund for Waldenstrom's Research, the Linda and Edward Nelson Fund for Waldenstrom's Macroglobulinaemia, a gift from the Bauman Family Trust, and a National Institutes of Health Career Development Award (K23CA087977-03) to SPT. NR 45 TC 23 Z9 23 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUL PY 2011 VL 154 IS 2 BP 223 EP 228 DI 10.1111/j.1365-2141.2011.08726.x PG 6 WC Hematology SC Hematology GA 786QW UT WOS:000292324000007 PM 21564078 ER PT J AU Giulino, L Guinan, EC Gillio, AP Drachtman, RA Teruya-Feldstein, J Boulad, F AF Giulino, Lisa Guinan, Eva C. Gillio, Alfred P. Drachtman, Richard A. Teruya-Feldstein, Julie Boulad, Farid TI Sweet syndrome in patients with Fanconi anaemia: association with extracutaneous manifestations and progression of haematological disease SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Letter DE Fanconi anaemia; Sweet syndrome C1 [Giulino, Lisa; Teruya-Feldstein, Julie; Boulad, Farid] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Guinan, Eva C.] Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Gillio, Alfred P.] Hackensack Univ Med Ctr, Hackensack, NJ USA. [Drachtman, Richard A.] UMDNJ, Robert Wood Johnson Med Sch, New Brunswick, NJ USA. RP Giulino, L (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. EM bouladf@mskcc.org NR 10 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUL PY 2011 VL 154 IS 2 BP 278 EP 281 DI 10.1111/j.1365-2141.2011.08604.x PG 4 WC Hematology SC Hematology GA 786QW UT WOS:000292324000015 PM 21501135 ER PT J AU Cooley, ME Emmons, KM Haddad, R Wang, Q Posner, M Bueno, R Cohen, TJ Johnson, BE AF Cooley, Mary E. Emmons, Karen M. Haddad, Robert Wang, Qian Posner, Marshall Bueno, Raphael Cohen, Tiffany-Jen Johnson, Bruce E. TI Patient-Reported Receipt of and Interest in Smoking-Cessation Interventions After a Diagnosis of Cancer SO CANCER LA English DT Article DE cancer; smoking-cessation programs; evidence-based tobacco treatment; smoking-related malignancies; patient preference ID CELL LUNG-CANCER; NICOTINE DEPENDENCE; TOBACCO-CESSATION; CLINICAL-PRACTICE; NARRATIVE COMMUNICATION; PREDICTIVE-VALIDITY; CIGARETTE-SMOKING; CONSUMER DEMAND; ONCOLOGY NURSES; NATIONAL-SURVEY AB BACKGROUND: Smoking cessation is essential after the diagnosis of cancer to enhance clinical outcomes. Although effective smoking-cessation treatments are available, <50% of smokers with cancer report receiving treatment. Reasons for the low dissemination of such treatment are unclear. METHODS: Data were collected from questionnaires and medical record reviews from 160 smokers or recent quitters with lung or head and neck cancer. Descriptive statistics, Cronbach alpha coefficients, and logistic regression were used in the analyses. The median age of participants was 57 years, 63% (n = 101) were men, 93% (n = 149) were white, and 57% (n = 91) had lung cancer. RESULTS: Eight-six percent (n = 44) of smokers and 75% (n = 82) of recent quitters reported that healthcare providers gave advice to quit smoking. Sixty-five percent (n = 33) of smokers and 47% (n = 51) of recent quitters reported that they were offered assistance from their healthcare providers to quit smoking. Fifty-one percent (n = 26) of smokers and 20% (n = 22) of recent quitters expressed an interest in a smoking-cessation program. An individualized smoking-cessation program was the preferred type of program. Among smokers, younger patients with early stage disease and those with partners who were smokers were more interested in programs. CONCLUSIONS: Although the majority of patients received advice and were offered assistance to quit smoking, approximately 50% of smokers were interested in cessation programs. Innovative approaches to increase interest in cessation programs need to be developed and tested in this population. Cancer 2011;117:2961-9. (C) 2011 American Cancer Society C1 [Cooley, Mary E.] Dana Farber Canc Inst, Phyllis F Cantor Ctr Res Nursing & Patient Care S, Boston, MA 02115 USA. [Cooley, Mary E.] Univ Massachusetts, Coll Nursing & Hlth Sci, Boston, MA 02125 USA. [Emmons, Karen M.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Emmons, Karen M.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Haddad, Robert] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Haddad, Robert; Posner, Marshall; Johnson, Bruce E.] Bringham & Womens Hosp, Dept Med, Boston, MA USA. [Wang, Qian] Dana Farber Canc Inst, Dept Biostat & Computat Sci, Boston, MA 02115 USA. [Posner, Marshall] Dana Farber Canc Inst, Head & Neck Oncol Program, Boston, MA 02115 USA. [Bueno, Raphael] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Thorac Surg, Boston, MA 02115 USA. [Cohen, Tiffany-Jen] Univ Massachusetts, Coll Nursing, Worcester, MA 01605 USA. [Johnson, Bruce E.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. RP Cooley, ME (reprint author), Dana Farber Canc Inst, Phyllis F Cantor Ctr Res Nursing & Patient Care S, 44 Binney St,CP-301, Boston, MA 02115 USA. EM mary_cooley@dfci.harvard.edu FU National Cancer Institute [1 K07 CA92696-02]; Dana-Farber Cancer Institute FX Supported by National Cancer Institute grant 1 K07 CA92696-02 and by the James B. Gillen Thoracic Oncology Research Fund, Dana-Farber Cancer Institute. NR 52 TC 26 Z9 26 U1 3 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD JUL 1 PY 2011 VL 117 IS 13 BP 2961 EP 2969 DI 10.1002/cncr.25828 PG 9 WC Oncology SC Oncology GA 783BJ UT WOS:000292056200018 PM 21692055 ER PT J AU Kirchhoff, AC Krull, KR Ness, KK Park, ER Oeffinger, KC Hudson, MM Stovall, M Robison, LL Wickizer, T Leisenring, W AF Kirchhoff, Anne C. Krull, Kevin R. Ness, Kirsten K. Park, Elyse R. Oeffinger, Kevin C. Hudson, Melissa M. Stovall, Marilyn Robison, Leslie L. Wickizer, Thomas Leisenring, Wendy TI Occupational Outcomes of Adult Childhood Cancer Survivors SO CANCER LA English DT Article DE neoplasms; occupations; survivors; socioeconomic factors; late effects; female ID LONG-TERM SURVIVORS; PHYSICAL PERFORMANCE; COHORT; HEALTH; UNEMPLOYMENT; DISPARITIES; LIMITATIONS; EDUCATION; RISK AB BACKGROUND: The authors examined whether survivors from the Childhood Cancer Survivor Study were less likely to be in higher-skill occupations than a sibling comparison and whether certain survivors were at higher risk for lower-skill jobs. METHODS: The authors created 3 mutually exclusive occupational categories for participants aged >= 25 years: Managerial/Professional, Nonphysical Service/Blue Collar, and Physical Service/Blue Collar. The authors examined currently employed survivors (4845) and their siblings (1727) in multivariable generalized linear models to evaluate the likelihood of being in 1 of the 3 occupational categories. Multinomial logistic regression was used among all participants to examine the likelihood of these outcomes compared to being unemployed (survivors, 6671; siblings, 2129). Multivariable linear models were used to assess survivor occupational differences by cancer- and treatment-related variables. Personal income was compared by occupation. RESULTS: Employed survivors were less often in higher-skilled Managerial/Professional occupations (relative risk, 0.93; 95% confidence interval 0.89-0.98) than their siblings. Survivors who were black, were diagnosed at a younger age, or had high-dose cranial radiation were less likely to hold Managerial/Professional occupations than other survivors. In multinomial models, female survivors' likelihood of being in full-time Managerial/Professional occupations (27%) was lower than male survivors (42%) and female (41%) and male (50%) siblings. Survivors' personal income was lower than siblings within each of the 3 occupational categories in models adjusted for sociodemographic variables. CONCLUSIONS: Adult childhood cancer survivors are employed in lower-skill jobs than siblings. Survivors with certain treatment histories are at higher risk for lower-skill jobs and may require vocational assistance throughout adulthood. Cancer 2011;117:3033-44. (C) 2011 American Cancer Society. C1 [Kirchhoff, Anne C.; Leisenring, Wendy] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Kirchhoff, Anne C.] Univ Washington, Dept Hlth Sci, Seattle, WA 98195 USA. [Krull, Kevin R.; Ness, Kirsten K.; Hudson, Melissa M.; Robison, Leslie L.] St Jude Childrens Hosp, Dept Epidemiol & Canc Control, Memphis, TN 38105 USA. [Park, Elyse R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mongan Inst Hlth Policy, Boston, MA USA. [Park, Elyse R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. [Oeffinger, Kevin C.] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. [Oeffinger, Kevin C.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [Hudson, Melissa M.] St Jude Childrens Hosp, Dept Oncol, Memphis, TN 38105 USA. [Stovall, Marilyn] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA. [Wickizer, Thomas] Ohio State Univ, Coll Publ Hlth, Columbus, OH 43210 USA. [Leisenring, Wendy] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Leisenring, Wendy] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. RP Kirchhoff, AC (reprint author), 1100 Fairview Ave N,M3-B232, Seattle, WA 98109 USA. EM akirchho@fhcrc.org FU National Cancer Institute [U24 CA55727]; Cancer Center [CA 21,765]; American, Syrian, Lebanese Associated Charities (ALSAC) FX The Childhood Cancer Survivor Study is funded by the National Cancer Institute (U24 CA55727, principal investigator: L. L. Robison). Support to St. Jude Children's Research Hospital also provided by the Cancer Center Support (CORE) grant (CA 21,765) and by the American, Syrian, Lebanese Associated Charities (ALSAC). NR 30 TC 27 Z9 27 U1 1 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD JUL 1 PY 2011 VL 117 IS 13 BP 3033 EP 3044 DI 10.1002/cncr.25867 PG 12 WC Oncology SC Oncology GA 783BJ UT WOS:000292056200025 PM 21246530 ER PT J AU Catenacci, DVT Cervantes, G Yala, S Nelson, EA El-Hashani, E Kanteti, R El Dinali, M Hasina, R Bragelmann, J Seiwert, T Sanicola, M Henderson, L Grushko, TA Olopade, O Karrison, T Bang, YJ Kim, WH Tretiakova, M Vokes, E Frank, DA Kindler, HL Huet, H Salgia, R AF Catenacci, Daniel V. T. Cervantes, Gustavo Yala, Soheil Nelson, Erik A. El-Hashani, Essam Kanteti, Rajani El Dinali, Mohamed Hasina, Rifat Braegelmann, Johannes Seiwert, Tanguy Sanicola, Michele Henderson, Les Grushko, Tatyana A. Olopade, Olufunmilayo Karrison, Theodore Bang, Yung-Jue Kim, Woo Ho Tretiakova, Maria Vokes, Everett Frank, David A. Kindler, Hedy L. Huet, Heather Salgia, Ravi TI RON (MST1R) is a novel prognostic marker and therapeutic target for gastroesophageal adenocarcinoma SO CANCER BIOLOGY & THERAPY LA English DT Article DE RON; MST1R; MET; MSP; HGF; STAT3; stomach cancer; gastroesophageal adenocarcinoma; R1018G mutation ID RECEPTOR TYROSINE KINASE; MACROPHAGE-STIMULATING PROTEIN; GROWTH-FACTOR RECEPTOR; CELL LUNG-CANCER; LYMPH-NODE METASTASIS; GENE COPY NUMBER; C-MET; GASTRIC-CANCER; BREAST-CANCER; ANTITUMOR-ACTIVITY AB RON (MST1R) is one of two members of the MET receptor tyrosine kinase family, along with parent receptor MET. RON has a putative role in several cancers, but its expression and function is poorly characterized in gastroesophageal adenocarcinoma. A recognized functional role of MET tyrosine kinase in gastroesophageal cancer has led to early phase clinical trials using MET inhibitors, with unimpressive results. Therefore, the role of RON in gastroesophageal cancer, as well as its role in cooperative signaling with MET and as a mechanism of resistance to MET inhibition, was studied in gastroesophageal tissues and cell lines. By IHC, RON was highly overexpressed in 74% of gastroesophageal samples (n = 94) and overexpression was prognostic of poor survival (p = 0.008); RON and MET co-expression occurred in 43% of samples and was prognostic of worst survival (p = 0.03). High MST1R gene copy number by quantitative polymerase chain reaction and confirmed by fluorescence in situ hybridization and/or array comparative genomic hybridization, was seen in 35.5% (16/45) of cases. High MST1R gene copy number correlated with poor survival (p = 0.01), and was associated with high MET and ERBB2 gene copy number. A novel somatic MST1R juxtamembrane mutation R1018G was found in 11% of samples. RON signaling was functional in cell lines, activating downstream effector STAT3, and resulted in increased viability over controls. RON and MET co-stimulation assays led to enhanced malignant phenotypes over stimulation of either receptor alone. Growth inhibition as evidenced by viability and apoptosis assays was optimal using novel blocking monoclonal antibodies to both RON and MET, versus either alone. SU11274, a classic MET small molecule tyrosine kinase inhibitor, blocked signaling of both receptors and proved synergistic when combined with STAT3 inhibition (combination index <1). These preclinical studies define RON as an important novel prognostic marker and therapeutic target for gastroesophageal cancer warranting further investigation. C1 [Catenacci, Daniel V. T.; Cervantes, Gustavo; Yala, Soheil; El-Hashani, Essam; Kanteti, Rajani; El Dinali, Mohamed; Hasina, Rifat; Braegelmann, Johannes; Seiwert, Tanguy; Henderson, Les; Grushko, Tatyana A.; Olopade, Olufunmilayo; Vokes, Everett; Kindler, Hedy L.; Salgia, Ravi] Univ Chicago, Med Ctr, Dept Med, Sect Hematol Oncol, Chicago, IL 60637 USA. [Nelson, Erik A.; Frank, David A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Sanicola, Michele; Huet, Heather] Biogen Idec Inc, Cambridge, MA USA. [Karrison, Theodore] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. [Bang, Yung-Jue] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 151, South Korea. [Kim, Woo Ho] Seoul Natl Univ, Coll Med, Dept Pathol, Seoul 151, South Korea. [Tretiakova, Maria] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. RP Salgia, R (reprint author), Univ Chicago, Med Ctr, Dept Med, Sect Hematol Oncol, Chicago, IL 60637 USA. EM rsalgia@medicine.bsd.uchicago.edu RI Kim, Wooho/G-3703-2011; Seoul National University, Pathology/B-6702-2012; Bang, Yung Jue/J-2759-2012 FU NIH; ASCO; Cancer Research Foundation; CTSA-ITM; US National Institute of Health [5R01CA100750-07, 5R01CA125541-04, 5R01CA129501-03, 3R01CA129501-02S1, 3R01CA125541-03S1, 1R21CA140003-01]; ACS; NIH/NCI [T32 CA009566] FX This work was supported by a NIH K12 award, an ASCO 2009 Young Investigator Award, Cancer Research Foundation 2010 Young Investigator Award "The Role of RON (MST1R) Receptor Tyrosine Kinase in Gastroesophageal Cancers as a Therapeutic Target," Amgen Hematology and Oncology Research Fellowship Grant Award 2008 "The Role of RON (MST1R) in gastroesophageal malignancies," and a CTSA-ITM Core Subsidies Fellow Grant 2009 (to D. V. T. C.); US National Institute of Health grants (5R01CA100750-07, 5R01CA125541-04, 5R01CA129501-03, 3R01CA129501-02S1, 3R01CA125541-03S1 to R. S., 1R21CA140003-01, to R. S., H. L. K., D. V. T. C.); an ACS Professorship Grant and a Basic Research Training Grant in Medical Oncology (NIH/NCI T32 CA009566 to O.O.); an ASCO Translational Research Professorship Award (to E. V.). NR 87 TC 45 Z9 46 U1 0 U2 4 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD JUL 1 PY 2011 VL 12 IS 1 BP 9 EP 46 DI 10.4161/cbt.12.1.15747 PG 38 WC Oncology SC Oncology GA 786GG UT WOS:000292290900004 PM 21543897 ER PT J AU Ramsey, MR He, L Forster, N Ory, B Ellisen, LW AF Ramsey, Matthew R. He, Lei Forster, Nicole Ory, Benjamin Ellisen, Leif W. TI Physical Association of HDAC1 and HDAC2 with p63 Mediates Transcriptional Repression and Tumor Maintenance in Squamous Cell Carcinoma SO CANCER RESEARCH LA English DT Article ID GENE-EXPRESSION; APOPTOSIS; HEAD; P73; DELTA-NP63-ALPHA; VORINOSTAT; SURVIVAL; TARGETS; PROTEIN; CANCER AB Squamous cell carcinoma (SCC) is a treatment-refractory subtype of human cancer arising from stratified epithelium of the skin, lung, esophagus, oropharynx, and other tissues. A unifying feature of SCC is high-level expression of the p53-related protein p63 (TP63) in 80% of cases. The major protein isoform of p63 expressed in SCC is Delta Np63 alpha, an N-terminally truncated form which functions as a key SCC cell survival factor by mechanisms that are unclear. In this study, we show that Delta Np63 alpha associates with histone deacetylase 1 (HDAC1) and HDAC2 to form an active transcriptional repressor complex that can be targeted to therapeutic advantage. Repression of proapoptotic Bcl-2 family member genes including p53 upregulated modulator of apoptosis (PUMA) by p63/HDAC is required for survival of SCC cells. Cisplatin chemotherapy, a mainstay of SCC treatment, promotes dissociation of p63 and HDAC from the PUMA promoter, leading to increased histone acetylation, PUMA activation, and apoptosis. These effects are recapitulated upon targeting the p63/HDAC complex selectively with class I/II HDAC inhibitors using both in vitro and in vivo models. Sensitivity to HDAC inhibition is directly correlated with p63 expression and is abrogated in tumor cells that overexpress endogenous Bcl-2. Together, our results elucidate a mechanism of p63-mediated transcriptional repression and they identify the Delta Np63 alpha/HDAC complex as an essential tumor maintenance factor in SCC. In addition, our findings offer a rationale to apply HDAC inhibitors for SCC treatment. Cancer Res; 71(13); 4373-9. (C) 2011 AACR. C1 [Ellisen, Leif W.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Ellisen, LW (reprint author), Massachusetts Gen Hosp, Ctr Canc, GRJ 904,55 Fruit St, Boston, MA 02114 USA. EM ellisen@helix.mgh.harvard.edu RI He, Lei/G-6018-2011; ory, benjamin/K-8231-2015; OI Ramsey, Matthew/0000-0003-2402-8502 FU ACS/Mass Biotech Council Cancer Research Challenge-AstraZeneca Pharmaceuticals [PF-09-100-01]; Tracey Davis Memorial; Fondation pour la Recherche Medicale FX NIH R01 DE-015945 (L.W. Ellisen and L. He); ACS/Mass Biotech Council Cancer Research Challenge-AstraZeneca Pharmaceuticals LP Fellowship PF-09-100-01 MGO (M.R. Ramsey); Tracey Davis Memorial Fund (N. Forster); and Fondation pour la Recherche Medicale (B. Ory). NR 20 TC 37 Z9 38 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 2011 VL 71 IS 13 BP 4373 EP 4379 DI 10.1158/0008-5472.CAN-11-0046 PG 7 WC Oncology SC Oncology GA 786EY UT WOS:000292287300008 PM 21527555 ER PT J AU Perentes, JY Kirkpatrick, ND Nagano, S Smith, EY Shaver, CM Sgroi, D Garkavtsev, I Munn, LL Jain, RK Boucher, Y AF Perentes, Jean Y. Kirkpatrick, Nathaniel D. Nagano, Satoshi Smith, Eve Y. Shaver, Christine M. Sgroi, Dennis Garkavtsev, Igor Munn, Lance L. Jain, Rakesh K. Boucher, Yves TI Cancer Cell-Associated MT1-MMP Promotes Blood Vessel Invasion and Distant Metastasis in Triple-Negative Mammary Tumors SO CANCER RESEARCH LA English DT Article ID MEMBRANE TRANSMIGRATION PROGRAM; BREAST-CANCER; MATRIX METALLOPROTEINASES; BASEMENT-MEMBRANE; PROSTATE-CANCER; EXTRACELLULAR-MATRIX; IN-VIVO; EXPRESSION; MIGRATION; CLEAVES AB Functional roles for the cancer cell-associated membrane type I matrix metalloproteinase (MT1-MMP) during early steps of the metastatic cascade in primary tumors remain unresolved. In an effort to determine its significance, we determined the in vivo effects of RNAi-mediated downregulation in mammary cancer cells on the migration, blood and lymphatic vessel invasion (LVI), and lymph node and lung metastasis. We also correlated the expression of cancer cell MT1-MMP with blood vessel invasion (BVI) in 102 breast cancer biopsies. MT1-MMP downregulation in cancer cells decreased lung metastasis without affecting primary tumor growth. The inhibition of lung metastasis correlated with reduced cancer cell migration and BVI. Furthermore, cancer cell-expressed MT1-MMP upregulated the expression of MT1-MMP in vascular endothelial cells, but did not affect MT1-MMP expression in lymphatic endothelial cells, LVI, or lymph node metastasis. Of clinical importance, we observed that elevated MT1-MMP expression correlated with BVI in biopsies from triple-negative breast cancers (TNBC), which have a poor prognosis and high incidence of distant metastasis, relative to other breast cancer subtypes. Together, our findings established that MT1-MMP activity in breast tumors is essential for BVI, but not LVI, and that MT1-MMP should be further explored as a predictor and therapeutic target of hematogenous metastasis in TNBC patients. Cancer Res; 71(13); 4527-38. (C) 2011 AACR. C1 [Perentes, Jean Y.; Kirkpatrick, Nathaniel D.; Nagano, Satoshi; Smith, Eve Y.; Shaver, Christine M.; Garkavtsev, Igor; Munn, Lance L.; Jain, Rakesh K.; Boucher, Yves] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab Tumor Biol, Boston, MA 02114 USA. [Sgroi, Dennis] Massachusetts Gen Hosp, MGH Canc Ctr, Mol Pathol Unit, Boston, MA 02114 USA. [Perentes, Jean Y.] CHU Vaudois, Dept Thorac & Vasc Surg, CH-1011 Lausanne, Switzerland. RP Boucher, Y (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, 100 Blossom St, Boston, MA 02114 USA. EM yves@steele.mgh.harvard.edu RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 FU NIH [PO1-CA80124, RO1-CA115767]; DOD [BC-095991, RO1-CA98706, T32-CA073479]; Swiss National Funding for young scientists [107362]; Fond Decker; Fond de Pefectionement du CHUV; bourse de la faculte de Biologie et de Medecine; Japan Society for the Promotion of Science; Dyax; AstraZeneca; MedImmune; Roche; Astellas; Genzyme; Noxxon Pharma FX This work was supported by NIH grants PO1-CA80124 and RO1-CA115767 and a DOD Breast Cancer Research Program grant (BC-095991) (R.K. Jain); RO1-CA98706 (Y. Boucher); T32-CA073479 (N.D. Kirkpatrick); the Swiss National Funding for young scientists no 107362, Fond Decker, Fond de Pefectionement du CHUV and the bourse de la faculte de Biologie et de Medecine (jeunes chercheurs; J.Y. Perentes); and Japan Society for the Promotion of Science (S. Nagano).; R.K. Jain received commercial research grants from Dyax, AstraZeneca, MedImmune, and Roche; consultant fees from AstraZeneca, Dyax, Astellas, Genzyme, and Noxxon Pharma; and a speaker honorarium from MPM Capital. R. K. Jain owns stock in SynDevRx. No reagents or funding from these companies were used in these studies. There is no significant financial or other competing interest in the work. NR 45 TC 42 Z9 47 U1 1 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 2011 VL 71 IS 13 BP 4527 EP 4538 DI 10.1158/0008-5472.CAN-10-4376 PG 12 WC Oncology SC Oncology GA 786EY UT WOS:000292287300023 PM 21571860 ER PT J AU Orth, JD Kohler, RH Foijer, F Sorger, PK Weissleder, R Mitchison, TJ AF Orth, James D. Kohler, Rainer H. Foijer, Floris Sorger, Peter K. Weissleder, Ralph Mitchison, Timothy J. TI Analysis of Mitosis and Antimitotic Drug Responses in Tumors by In Vivo Microscopy and Single-Cell Pharmacodynamics SO CANCER RESEARCH LA English DT Article ID PACLITAXEL-INDUCED APOPTOSIS; MITOTIC ARREST; SKIN-FOLD; CANCER; TAXOL; MICROTUBULES; CHECKPOINT; KINESIN-5; CHAMBER; MAMMARY AB Cancer relies upon frequent or abnormal cell division, but how the tumor microenvironment affects mitotic processes in vivo remains unclear, largely due to the technical challenges of optical access, spatial resolution, and motion. We developed high-resolution in vivo microscopy methods to visualize mitosis in a murine xenograft model of human cancer. Using these methods, we determined whether the single-cell response to the antimitotic drug paclitaxel (Ptx) was the same in tumors as in cell culture, observed the impact of Ptx on the tumor response as a whole, and evaluated the single-cell pharmacodynamics (PD) of Ptx (by in vivo PD microscopy). Mitotic initiation was generally less frequent in tumors than in cell culture, but subsequently it proceeded normally. Ptx treatment caused spindle assembly defects and mitotic arrest, followed by slippage from mitotic arrest, multinucleation, and apoptosis. Compared with cell culture, the peak mitotic index in tumors exposed to Ptx was lower and the tumor cells survived longer after mitotic arrest, becoming multinucleated rather than dying directly from mitotic arrest. Thus, the tumor microenvironment was much less proapoptotic than cell culture. The morphologies associated with mitotic arrest were dose and time dependent, thereby providing a semiquantitative, single-cell measure of PD. Although many tumor cells did not progress through Ptx-induced mitotic arrest, tumor significantly regressed in the model. Our findings show that in vivo microscopy offers a useful tool to visualize mitosis during tumor progression, drug responses, and cell fate at the single-cell level. Cancer Res; 71(13); 4608-16. (C)2011 AACR. C1 [Orth, James D.; Foijer, Floris; Sorger, Peter K.; Weissleder, Ralph; Mitchison, Timothy J.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Kohler, Rainer H.; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Foijer, Floris] Wellcome Trust Sanger Inst, Hinxton, England. RP Orth, JD (reprint author), Harvard Univ, Sch Med, Dept Syst Biol, WAB541,200 Longwood Ave, Boston, MA 02115 USA. EM james_orth@hms.harvard.edu OI Foijer, Floris/0000-0003-0989-3127 FU NIH [CA139980, CA084179, CA86355, CA092782] FX This study was funded by NIH grants CA139980 (to T.J. Mitchison), CA084179 (to P.K. Sorger), and CA86355 and CA092782 (to R. Weissleder). NR 41 TC 59 Z9 60 U1 0 U2 16 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 2011 VL 71 IS 13 BP 4608 EP 4616 DI 10.1158/0008-5472.CAN-11-0412 PG 9 WC Oncology SC Oncology GA 786EY UT WOS:000292287300030 PM 21712408 ER PT J AU Mayes, DA Rizvi, TA Cancelas, JA Kolasinski, NT Ciraolo, GM Stemmer-Rachamimov, AO Ratner, N AF Mayes, Debra A. Rizvi, Tilat A. Cancelas, Jose A. Kolasinski, Nathan T. Ciraolo, Georgianne M. Stemmer-Rachamimov, Anat O. Ratner, Nancy TI Perinatal or Adult Nf1 Inactivation Using Tamoxifen-Inducible PlpCre Each Cause Neurofibroma Formation SO CANCER RESEARCH LA English DT Article ID SCHWANN-CELL DEVELOPMENT; CREST STEM-CELLS; PERIPHERAL-NERVE; BONE-MARROW; MYELOMONOCYTIC LEUKEMIA; BENIGN NEUROFIBROMAS; SELF-RENEWAL; TYPE-1; TUMORS; GENE AB Plexiform neurofibromas are peripheral nerve sheath tumors initiated by biallelic mutation of the NF1 tumor suppressor gene in the Schwann cell lineage. To understand whether neurofibroma formation is possible after birth, we induced Nf1 loss of function with an inducible proteolipid protein Cre allele. Perinatal loss of Nf1 resulted in the development of small plexiform neurofibromas late in life, whereas loss in adulthood caused large plexiform neurofibromas and morbidity beginning 4 months after onset of Nf1 loss. A conditional EGFP reporter allele identified cells showing recombination, including peripheral ganglia satellite cells, peripheral nerve S100 beta+ myelinating Schwann cells, and peripheral nerve p75+ cells. Neurofibromas contained cells with Remak bundle disruption but no recombination within GFAP+ nonmyelinating Schwann cells. Extramedullary lymphohematopoietic expansion was also observed in PlpCre;Nf1fl/fl mice. These tumors contained EGFP+/Sca-1+ stromal cells among EGFP-negative lympho-hematopoietic cells indicating a noncell autonomous effect and unveiling a role of Nf1-deleted microenvironment on lympho-hematopoietic proliferation in vivo. Together these findings define a tumor suppressor role for Nf1 in the adult and narrow the range of potential neurofibroma-initiating cell populations. Cancer Res; 71(13); 4675-85. (C)2011 AACR. C1 [Mayes, Debra A.; Rizvi, Tilat A.; Cancelas, Jose A.; Kolasinski, Nathan T.; Ciraolo, Georgianne M.; Ratner, Nancy] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. [Cancelas, Jose A.] Univ Cincinnati, Hoxworth Blood Ctr, Cincinnati, OH USA. [Stemmer-Rachamimov, Anat O.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Stemmer-Rachamimov, Anat O.] Harvard Univ, Sch Med, Boston, MA USA. RP Ratner, N (reprint author), Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. EM nancy.ratner@cchmc.org FU DAMD [W81XWH-06-1-0114]; NIH [R01-NS28840]; NIH NRSA [T32CA117846]; National Multiple Sclerosis Society [FG1762A1/1] FX The DAMD Program on Neurofibromatosis (W81XWH-06-1-0114 to T.A. Rizvi and N. Ratner) and NIH R01-NS28840 (N. Ratner) supported this work. NIH NRSA (T32CA117846) and National Multiple Sclerosis Society (FG1762A1/1) supported D.A. Mayes. NR 39 TC 24 Z9 25 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 2011 VL 71 IS 13 BP 4675 EP 4685 DI 10.1158/0008-5472.CAN-10-4558 PG 11 WC Oncology SC Oncology GA 786EY UT WOS:000292287300036 PM 21551249 ER PT J AU Elmariah, S Lubitz, SA Shah, AM Miller, MA Kaplish, D Kothari, S Moreno, PR Kini, AS Sharma, SK AF Elmariah, Sammy Lubitz, Steven A. Shah, Amil M. Miller, Marc A. Kaplish, Dheeraj Kothari, Sharad Moreno, Pedro R. Kini, Annapoorna S. Sharma, Samin K. TI A Novel Clinical Prediction Rule for 30-day Mortality Following Balloon Aortic Valuloplasty: The CRRAC the AV Score SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE aortic valve stenosis; EuroSCORE; percutaneous ID CHRONIC KIDNEY-DISEASE; EUROSCORE MULTINATIONAL DATABASE; EUROPEAN CARDIAC-SURGERY; VALVE-REPLACEMENT; RISK-FACTORS; VALVULOPLASTY REGISTRY; LOGISTIC EUROSCORE; OPERATIVE RISK; STENOSIS; CORONARY AB Objectives: We seek to identify predictors of 30-day mortality after balloon aortic valvuloplasty (BAV). Background: To date, there is no validated method of predicting patient outcomes after percutaneous aortic valve interventions. Methods: Data for consecutive patients with severe aortic stenosis who underwent BAV at the Mount Sinai Medical Center from January 2001 to July 2007 were retrospectively reviewed. Cox-proportional hazards regression was used to identify significant predictors of 30-day mortality, and the resultant model was compared to the EuroSCORE using Akaike's Information Criterion and area under the receiver-operating curve (AUC). Results: The analysis included 281 patients (age 83 +/- 9 years, 61% women, aortic valve area: 0.64 +/- 0.2 cm(2)) and 36 (12.8%) of whom died within 30 days of BAV. With identified risk factors for 30-day mortality, critical status, renal dysfunction, right atrial pressure, and cardiac output, we constructed the CRRAC the AV risk score. Thirty-day survival was 72% in the highest tertile versus 94% in the lower two tertiles of the score. Compared to the additive and logistic EuroSCORE, the risk score demonstrated superior discrimination (AUC = 0.75 vs. 0.60 and 0.63, respectively). Conclusion: We derived a risk score, the CRRAC the AV score that identifies patients at high-risk of 30-day mortality after BAV. Validation of the developed risk prediction score, the CRRAC the AV score, is needed in other cohorts of post-BAV patients and potentially in patients undergoing other catheter-based valve interventions. (C) 2011 Wiley-Liss, Inc. C1 [Elmariah, Sammy; Miller, Marc A.; Kaplish, Dheeraj; Kothari, Sharad; Moreno, Pedro R.; Kini, Annapoorna S.; Sharma, Samin K.] Mt Sinai Sch Med, Dept Cardiol, Zena & Michael A Wiener Cardiovasc Inst, New York, NY USA. [Elmariah, Sammy; Lubitz, Steven A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Shah, Amil M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc, Boston, MA 02115 USA. RP Sharma, SK (reprint author), 1 Gustave L Levy Pl,Box 1030, New York, NY 10029 USA. EM samin.sharma@mountsinai.org OI Sharma, Sanjeev Kumar/0000-0002-3273-0708 FU National Heart, Lung, and Blood Institute [T32 HL007824, T32 HL007575] FX Grant sponsor: National Heart Lung, and Blood Institute; Grant number: T32 HL007824; Grant sponsor: National Heart, Lung, and Blood Institute; Grant number: T32 HL007575 NR 34 TC 9 Z9 9 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD JUL 1 PY 2011 VL 78 IS 1 BP 112 EP 118 DI 10.1002/ccd.22912 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 783OY UT WOS:000292094800027 PM 21413131 ER PT J AU Goldstein, NE May, CW Meier, DE AF Goldstein, Nathan E. May, Christopher W. Meier, Diane E. TI Comprehensive Care for Mechanical Circulatory Support A New Frontier for Synergy With Palliative Care SO CIRCULATION-HEART FAILURE LA English DT Article DE ventricular assist device; communication; palliative care; decision making; heart failure ID ADVANCED HEART-FAILURE; RANDOMIZED CONTROLLED-TRIAL; VENTRICULAR ASSIST DEVICE; INTERMACS ANNUAL-REPORT; OF-LIFE CARE; PROGNOSIS COMMUNICATION; ADVANCE DIRECTIVES; DECISION-MAKING; ADVANCED CANCER; END C1 [Goldstein, Nathan E.; Meier, Diane E.] Mt Sinai Sch Med, Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Goldstein, Nathan E.] James J Peters Vet Affairs Med Ctr, GRECC, Bronx, NY USA. [May, Christopher W.] Inova Heart & Vasc Inst, Heart Failure Cardiac Transplant Program, Falls Church, VA USA. RP Goldstein, NE (reprint author), Mt Sinai Sch Med, Dept Geriatr & Palliat Med, Box 1070, New York, NY 10029 USA. EM Nathan.Goldstein@mssm.edu FU National Institute of Aging [K23 AG025933]; Mount Sinai Claude D Pepper Older Americans Independence Center from the National Institute on Aging [P30AG028741-01A2]; National Heart, Lung, and Blood Institute [1R01HL102084-01A1]; Greenwall Foundation; Kornfeld Program in Bioethics and Patient Care; National Cancer Institute [5R01CA116227] FX Dr Goldstein was supported by a Mentored Patient-Oriented Research Career Development Award for the National Institute of Aging (K23 AG025933), a grant from the Mount Sinai Claude D Pepper Older Americans Independence Center from the National Institute on Aging (P30AG028741-01A2), a grant from the National Heart, Lung, and Blood Institute (1R01HL102084-01A1), and a grant jointly provided by the Greenwall Foundation and the Kornfeld Program in Bioethics and Patient Care. Dr Meier was supported by a grant from the National Cancer Institute (5R01CA116227). NR 49 TC 19 Z9 19 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD JUL PY 2011 VL 4 IS 4 BP 519 EP + DI 10.1161/CIRCHEARTFAILURE.110.957241 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 794BX UT WOS:000292871300018 PM 21772016 ER PT J AU Lai, KKY Jin, M Yuan, S Larson, MF Dominitz, JA Bankson, DD AF Lai, Keane K. Y. Jin, Ming Yuan, Shan Larson, Meaghan F. Dominitz, Jason A. Bankson, Daniel D. TI Improved Reflexive Testing Algorithm for Hepatitis C Infection Using Signal-to-Cutoff Ratios of a Hepatitis C Virus Antibody Assay SO CLINICAL CHEMISTRY LA English DT Article ID UNITED-STATES; PREVALENCE AB BACKGROUND: Chemiluminescence immunoassay (CIA) is used to detect hepatitis C virus (HCV) antibody status on the basis of signal-to-cutoff (S/Co) ratios. Positive results of antibody to HCV (anti-HCV) are followed by either recombinant immunoblot assay (RIBA) to confirm anti-HCV positivity or reverse transcription (RT)-PCR to detect viremia. We hypothesized that by analyzing S/Co ratios, we could determine a strategy to reduce unnecessary supplementary testing in our population. METHODS: CIA was performed to screen for anti-HCV, and positive results were followed up with RT-PCR testing. Negative RT-PCR results were followed up with RIBA, whereas positive RT-PCR results were assumed to be RIBA positive. ROC curves were analyzed to determine the optimal S/Co ratios to predict HCV infection. RESULTS: We determined the S/Co ratios on 34 243 veteran patient samples. We found that with the CIA method 9.0% of patients had positive test results for anti-HCV. An S/Co ratio < 3.0 ruled out active HCV infection and exposure with 100% negative predictive value. When the S/Co ratio was >= 20.0, positive predictive values were 98.5% compared with RIBA results, and 81.0% compared with RT-PCR results. CONCLUSIONS: RIBA is not necessary to confirm negative or positive CIA anti-HCV if the S/Co ratio is < 3.0 or > 20.0, respectively. To confirm HCV exposure, samples with an S/Co ratio between 3.0 and 19.9 should be followed up with RIBA unless PCR testing has been performed and the result is positive. Samples with an S/Co ratio >= 20.0 or positive RIBA results should be further tested by RT-PCR to determine HCV viremia status. (C) 2011 American Association for Clinical Chemistry C1 [Jin, Ming] Temple Univ, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19140 USA. [Lai, Keane K. Y.] Univ So Calif, Dept Pathol, So Calif Res Ctr Alcohol Liver & Pancreat Dis & C, Los Angeles, CA 90089 USA. [Lai, Keane K. Y.] Cedars Sinai Med Ctr, Dept Pathol & Lab Med, Los Angeles, CA 90048 USA. [Yuan, Shan] Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA USA. [Larson, Meaghan F.; Dominitz, Jason A.] Vet Affairs Puget Sound Hlth Care Syst, NW Hepatitis Resource Ctr C, Seattle, WA USA. [Dominitz, Jason A.] Univ Washington, Dept Med, Div Gastroenterol, Seattle, WA USA. [Bankson, Daniel D.] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. [Bankson, Daniel D.] Vet Affairs Puget Sound Hlth Care Syst, Pathol & Lab Med Serv, Seattle, WA USA. RP Jin, M (reprint author), Temple Univ, Sch Med, Dept Pathol & Lab Med, 3401 N Broad St, Philadelphia, PA 19140 USA. EM mjin@temple.edu OI Dominitz, Jason/0000-0002-8070-7086 FU Department of Veterans Affairs; VAPSHCS Liver Research Enhancement Award Program; NIH [P50AA011999, T32AA007578] FX This material is based upon work supported by the National Hepatitis C Program, Department of Veterans Affairs. K.K.Y. Lai, VAPSHCS Liver Research Enhancement Award Program and NIH grants P50AA011999 and T32AA007578. NR 13 TC 13 Z9 13 U1 0 U2 5 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUL PY 2011 VL 57 IS 7 BP 1050 EP 1056 DI 10.1373/clinchem.2010.158691 PG 7 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 784DL UT WOS:000292134400020 PM 21566071 ER PT J AU Braunwald, E Sacks, FM Pfeffer, MA Ridker, PM AF Braunwald, Eugene Sacks, Frank M. Pfeffer, Marc A. Ridker, Paul M. TI Citation Classic HMG CoA Reduction in Patients with Average Cholesterol Concentrations SO CLINICAL CHEMISTRY LA English DT Editorial Material ID CORONARY-HEART-DISEASE; RECURRENT EVENTS CARE; C-REACTIVE PROTEIN; MYOCARDIAL-INFARCTION; PRAVASTATIN; TRIAL; PREVENTION; MEN C1 [Braunwald, Eugene] Harvard Univ, Brigham & Womens Hosp, Dept Med, TIMI Study Grp,Cardiovasc Div,Sch Med, Boston, MA 02115 USA. [Sacks, Frank M.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Sacks, Frank M.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. RP Braunwald, E (reprint author), Harvard Univ, Brigham & Womens Hosp, Dept Med, TIMI Study Grp,Cardiovasc Div,Sch Med, 350 Longwood Ave, Boston, MA 02115 USA. EM ebraunwald@partners.org NR 11 TC 1 Z9 1 U1 0 U2 2 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUL PY 2011 VL 57 IS 7 BP 1072 EP 1073 DI 10.1373/clinchem.2011.164038 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 784DL UT WOS:000292134400023 PM 21519035 ER PT J AU Li, YX Tafti, BA Shaba, W Berenji, GR AF Li, Yuxin Tafti, Bashir A. Shaba, Wisam Berenji, Gholam R. TI Extraosseus Uptake of F-18 Fluoride in the Primary Malignancy and Cerebral Metastasis in a Case of Non-Small-Cell Lung Cancer SO CLINICAL NUCLEAR MEDICINE LA English DT Editorial Material DE F-18 fluoride; lung cancer; positron emission tomography; bone scan ID TC-99M MDP; CARCINOMA; TRACER; BREAST AB A 68-year-old man with history of heavy smoking was admitted for increasing falls during the past 4 weeks. Chest x-ray revealed a right upper lobe mass. Biopsy demonstrated poorly differentiated non-small-cell carcinoma. F-18 fluoride positron emission tomography/computer tomography (PET/CT) was performed to evaluate bone metastasis. Review of the sectional PET images demonstrated extraosseous fluoride uptake in the primary lung mass, as well as ring-shaped fluoride uptake in the cerebral metastatic lesion. Neither of these lesions demonstrated calcifications on CT images. The patient received radiation treatment of the brain metastasis after F-18 fluoride PET/CT study. C1 [Berenji, Gholam R.] VA Greater Los Angeles Healthcare Syst, Nucl Med Serv 115, Dept Nucl Med, Los Angeles, CA 90073 USA. RP Berenji, GR (reprint author), VA Greater Los Angeles Healthcare Syst, Nucl Med Serv 115, Dept Nucl Med, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM Gholam.Berenji@va.gov NR 12 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-9762 J9 CLIN NUCL MED JI Clin. Nucl. Med. PD JUL PY 2011 VL 36 IS 7 BP 609 EP 611 DI 10.1097/RLU.0b013e318217af49 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 772XH UT WOS:000291271000035 PM 21637076 ER PT J AU Tatonetti, NP Denny, JC Murphy, SN Fernald, GH Krishnan, G Castro, V Yue, P Tsau, PS Kohane, I Roden, DM Altman, RB AF Tatonetti, N. P. Denny, J. C. Murphy, S. N. Fernald, G. H. Krishnan, G. Castro, V. Yue, P. Tsau, P. S. Kohane, I. Roden, D. M. Altman, R. B. TI Detecting Drug Interactions From Adverse-Event Reports: Interaction Between Paroxetine and Pravastatin Increases Blood Glucose Levels SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID SEROTONIN TRANSPORTER; METABOLIC SYNDROME; DIABETES-MELLITUS; SURVEILLANCE; RISK; INHIBITORS; OBESITY; HEALTH; ADULTS; RAC1 AB The lipid-lowering agent pravastatin and the antidepressant paroxetine are among the most widely prescribed drugs in the world. Unexpected interactions between them could have important public health implications. We mined the US Food and Drug Administration's (FDA's) Adverse Event Reporting System (AERS) for side-effect profiles involving glucose homeostasis and found a surprisingly strong signal for comedication with pravastatin and paroxetine. We retrospectively evaluated changes in blood glucose in 104 patients with diabetes and 135 without diabetes who had received comedication with these two drugs, using data in electronic medical record (EMR) systems of three geographically distinct sites. We assessed the mean random blood glucose levels before and after treatment with the drugs. We found that pravastatin and paroxetine, when administered together, had a synergistic effect on blood glucose. The average increase was 19 mg/dl (1.0 mmol/l) overall, and in those with diabetes it was 48 mg/dl (2.7 mmol/l). In contrast, neither drug administered singly was associated with such changes in glucose levels. An increase in glucose levels is not a general effect of combined therapy with selective serotonin reuptake inhibitors (SSRIs) and statins. C1 [Tatonetti, N. P.; Fernald, G. H.; Altman, R. B.] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA. [Tatonetti, N. P.; Fernald, G. H.] Stanford Univ, Biomed Informat Training Program, Stanford, CA 94305 USA. [Tatonetti, N. P.; Fernald, G. H.; Altman, R. B.] Stanford Univ, Dept Genet, Stanford, CA 94305 USA. [Denny, J. C.] Vanderbilt Univ, Dept Biomed Informat, Nashville, TN USA. [Denny, J. C.; Roden, D. M.] Vanderbilt Univ, Dept Med, Nashville, TN USA. [Murphy, S. N.; Castro, V.] Massachusetts Gen Hosp, Lab Comp Sci, Boston, MA 02114 USA. [Murphy, S. N.; Kohane, I.] Harvard Univ, Sch Med, Boston, MA USA. [Krishnan, G.] Stanford Univ, Stanford Ctr Clin Informat, Stanford, CA 94305 USA. [Yue, P.; Tsau, P. S.] Stanford Univ, Dept Med Cardiovasc Med, Stanford, CA 94305 USA. [Kohane, I.] Childrens Hosp, Boston, MA 02115 USA. [Kohane, I.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Altman, RB (reprint author), Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA. EM russ.altman@stanford.edu RI Kohane, Isaac Kohane/K-3716-2012; OI Kohane, Isaac Kohane/0000-0003-2192-5160; Tatonetti, Nicholas/0000-0002-2700-2597 FU National Library of Medicine [NIH LM007033]; DOE SCGF; NHGRI Electronic Medical Records and Genomics network [U01 HG04603]; NIH/NIGMS Pharmacogenetics Research Network [U01 HL65962]; NIH [NIH U54LM008758, R01MH085542]; FNIH [MURPHY09OMOP0]; NIH/NIGMS PharmGKB resource [NIH R24GM61374] FX The authors thank the statistics reviewers at Clinical Pharmacology & Therapeutics for their valuable insights. N.P.T. and G.H.F. are supported by a training grant from the National Library of Medicine (NIH LM007033). N.P.T. is supported by an award from DOE SCGF. J.C.D. and D.M.R. are supported in part by the NHGRI Electronic Medical Records and Genomics network (U01 HG04603) and the NIH/NIGMS Pharmacogenetics Research Network (U01 HL65962). S.N.M. and I.K. are supported by the NIH Roadmap for Medical Research grant (NIH U54LM008758). S.N.M. is supported by FNIH MURPHY09OMOP0. V.C. is supported by NIH R01MH085542. R.B.A. is supported by NIH/NIGMS PharmGKB resource (NIH R24GM61374). NR 33 TC 91 Z9 93 U1 1 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JUL PY 2011 VL 90 IS 1 BP 133 EP 142 DI 10.1038/clpt.2011.83 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 780KD UT WOS:000291853800023 PM 21613990 ER PT J AU Roshanaei-Moghaddam, B Pauly, MC Atkins, DC Baldwin, SA Stein, MB Roy-Byrne, P AF Roshanaei-Moghaddam, Babak Pauly, Michael C. Atkins, David C. Baldwin, Scott A. Stein, Murray B. Roy-Byrne, Peter TI RELATIVE EFFECTS OF CBT AND PHARMACOTHERAPY IN DEPRESSION VERSUS ANXIETY: IS MEDICATION SOMEWHAT BETTER FOR DEPRESSION, AND CBT SOMEWHAT BETTER FOR ANXIETY? SO DEPRESSION AND ANXIETY LA English DT Review DE meta-analysis; CBT; pharmacotherapy; depression; anxiety ID COGNITIVE-BEHAVIORAL THERAPY; PLACEBO-CONTROLLED TRIAL; RANDOMIZED CONTROLLED-TRIAL; OBSESSIVE-COMPULSIVE DISORDER; GENERALIZED SOCIAL PHOBIA; COLLABORATIVE RESEARCH-PROGRAM; MENTAL-HEALTH TREATMENT; PANIC DISORDER; PRIMARY-CARE; ANTIDEPRESSANT MEDICATION AB Background: Little is known about whether cognitive behavioral therapy (CBT) or pharmacotherapy is relatively more advantageous for depressive versus anxiety disorders. Methods: We conducted a meta-analysis wherein we searched electronic databases and references to select randomized controlled studies comparing CBT and pharmacotherapy, with or without placebo, in adults with major depressive or anxiety disorders. The primary effect size was calculated from disorder-specific outcome measures as the difference between CBT and pharmacotherapy outcomes (i.e., positive effect size favors CBT; negative effect size favors pharmacotherapy). Results: Twenty-one anxiety (N = 1,266) and twenty-one depression (N = 2,027) studies comparing medication to CBT were included. Including all anxiety disorders, the overall effect size was .25 (95% CI: -0.02, 0.55, P = .07). Effects for panic disorder significantly favored CBT over medications (.50, 95% CI: 0.02, 0.98). Obsessive-compulsive disorder showed similar effects-sizes, though not statistically significant (.49, 95% CI: -0.11, 1.09). Medications showed a nonsignificant advantage for social anxiety disorder (-.22, 95% CI: -0.50, 0.06). The overall effect size for depression studies was .05 (95% CI: -0.09, 0.19), with no advantage for medications or CBT. Pooling anxiety disorder and depression studies, the omnibus comparison of the relative difference between anxiety and depression in effectiveness for CBT versus pharmacotherapy pointed to a nonsignificant advantage for CBT in anxiety versus depression (B = .14, 95% CI: -0.14, 0.43). Conclusions: On balance, the evidence presented here indicates that there are at most very modest differences in effects of CBT versus pharmacotherapy in the treatment of anxiety versus depressive disorders. There seems to be larger differences between the anxiety disorders in terms of their relative responsiveness to pharmacotherapy versus CBT. Depression and Anxiety 28: 560-567, 2011. (C) 2011 Wiley-Liss, Inc. C1 [Roshanaei-Moghaddam, Babak; Pauly, Michael C.; Atkins, David C.; Baldwin, Scott A.; Stein, Murray B.; Roy-Byrne, Peter] VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Roshanaei-Moghaddam, B (reprint author), VA Puget Sound Hlth Care Syst, S-116 ATC,1660 S Columbian Wy, Seattle, WA USA. EM babakr@uw.edu OI Atkins, David/0000-0002-5781-9880 NR 68 TC 34 Z9 36 U1 6 U2 46 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PD JUL PY 2011 VL 28 IS 7 BP 560 EP 567 DI 10.1002/da.20829 PG 8 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 784JR UT WOS:000292153900002 PM 21608087 ER PT J AU Jing, LL Zon, LI AF Jing, Lili Zon, Leonard I. TI Zebrafish as a model for normal and malignant hematopoiesis SO DISEASE MODELS & MECHANISMS LA English DT Article ID RIBOSOMAL-PROTEIN S19; ZINC-FINGER NUCLEASES; BLOOD STEM-CELLS; AORTIC ENDOTHELIUM; TRANSGENIC ZEBRAFISH; GENE; TRANSPLANTATION; MUTANTS; FATE; REGENERATION AB Zebrafish studies in the past two decades have made major contributions to our understanding of hematopoiesis and its associated disorders. The zebrafish has proven to be a powerful organism for studies in this area owing to its amenability to large-scale genetic and chemical screening. In addition, the externally fertilized and transparent embryos allow convenient genetic manipulation and in vivo imaging of normal and aberrant hematopoiesis. This review discusses available methods for studying hematopoiesis in zebrafish, summarizes key recent advances in this area, and highlights the current and potential contributions of zebrafish to the discovery and development of drugs to treat human blood disorders. C1 [Jing, Lili; Zon, Leonard I.] Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. [Jing, Lili; Zon, Leonard I.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Jing, Lili; Zon, Leonard I.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Zon, LI (reprint author), Childrens Hosp, Stem Cell Program, 300 Longwood Ave, Boston, MA 02115 USA. EM zon@enders.tch.harvard.edu FU Howard Hughes Medical Institute NR 62 TC 63 Z9 64 U1 2 U2 11 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 1754-8403 J9 DIS MODEL MECH JI Dis. Model. Mech. PD JUL PY 2011 VL 4 IS 4 BP 433 EP 438 DI 10.1242/dmm.006791 PG 6 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 783LO UT WOS:000292084500004 PM 21708900 ER PT J AU Seal, KH Cohen, G Waldrop, A Cohen, BE Maguen, S Ren, L AF Seal, Karen H. Cohen, Greg Waldrop, Angela Cohen, Beth E. Maguen, Shira Ren, Li TI Substance use disorders in Iraq and Afghanistan veterans in VA healthcare, 2001-2010: Implications for screening, diagnosis and treatment SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Alcohol use disorders; Drug use disorders; Posttraumatic stress disorder; Comorbidity; Veterans ID POSTTRAUMATIC-STRESS-DISORDER; NATIONAL EPIDEMIOLOGIC SURVEY; COMORBIDITY SURVEY REPLICATION; ALCOHOL-RELATED PROBLEMS; MENTAL-HEALTH; VIETNAM VETERANS; SERVICE UTILIZATION; MILITARY PERSONNEL; COMBAT DEPLOYMENT; EXPOSURE THERAPY AB Background: The prevalence and correlates of alcohol use disorder (AUD) and drug use disorder (DUD) diagnoses in Iraq and Afghanistan veterans who are new users of Department of Veterans Affairs (VA) healthcare nationwide has not been evaluated. Methods: VA administrative data were used in retrospective cross-sectional descriptive and multivariable analyses to determine the prevalence and independent correlates of AUD and DUD in 456,502 Iraq and Afghanistan veterans who were first-time users of VA healthcare between October 15, 2001 and September 30, 2009 and followed through January 1, 2010. Results: Over 11% received substance use disorder diagnoses: AUD, DUD or both; 10% received AUD diagnoses, 5% received DUD diagnoses and 3% received both. Male sex, age <25 years, being never married or divorced, and proxies for greater combat exposure were independently associated with AUD and DUD diagnoses. Of those with AUD, DUD or both diagnoses, 55-75% also received PTSD or depression diagnoses. AUD, DUD or both diagnoses were 3-4.5 times more likely in veterans with PTSD and depression (p < 0.001). Conclusions: Post-deployment AUD and DUD diagnoses were more prevalent in subgroups of Iraq and Afghanistan veterans and were highly comorbid with PTSD and depression. Stigma and lack of universal screening may have reduced the number of DUD diagnoses reported. There is a need for improved screening and diagnosis of substance use disorders and increased availability of integrated treatments that simultaneously address AUD and DUD in the context of PTSD and other deployment-related mental health disorders. Published by Elsevier Ireland Ltd. C1 [Seal, Karen H.; Cohen, Greg; Waldrop, Angela; Cohen, Beth E.; Maguen, Shira; Ren, Li] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Seal, Karen H.; Waldrop, Angela; Cohen, Beth E.; Maguen, Shira] Univ Calif San Francisco, San Francisco, CA 94121 USA. RP Seal, KH (reprint author), San Francisco VA Med Ctr, 4150 Clement St,Box 111A-1, San Francisco, CA 94121 USA. EM Karen.Seal@va.gov RI Schueter, nicos/A-3625-2014 FU VA Health Services Research and Development (HSRD); Department of Defense [W81XWH-05-2-0094]; VA HSR&D Career Development Award; San Francisco VA Medical Center; [K23 DA018718]; [K23 HL 094765-01] FX This study was funded by a VA Health Services Research and Development (HSR&D) Career Development Award and by a Department of Defense Award (W81XWH-05-2-0094). Dr. Waldrop was supported by a K23 DA018718. Dr. Cohen was supported by a K23 HL 094765-01. Dr. Maguen was supported by a VA HSR&D Career Development Award. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review or approval of the manuscript.; The authors wish to acknowledge the service and courage of the men and women who have served in Iraq, Afghanistan and surrounding areas. We also wish to acknowledge Mr. Daniel Bertenthal of the San Francisco VA Medical Center HSR&D Research Enhancement Award Program who provided consultation on the use of VA national-level data. NR 86 TC 114 Z9 114 U1 6 U2 19 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JUL 1 PY 2011 VL 116 IS 1-3 BP 93 EP 101 DI 10.1016/j.drugalcdep.2010.11.027 PG 9 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 784SY UT WOS:000292179700015 PM 21277712 ER PT J AU Banks, WA AF Banks, William A. TI Extrahypothalamic Effects of Leptin: A Therapeutic for Depression and Dementia? SO ENDOCRINOLOGY LA English DT Editorial Material ID HIGH-FAT DIET; RECEPTOR EXPRESSION; MEMORY C1 [Banks, William A.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Banks, William A.] Univ Washington, Sch Med, Dept Internal Med, Div Gerontol & Geriatr Med, Seattle, WA 98108 USA. RP Banks, WA (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Room 810A,Bldg 1,1660 S Columbian Way, Seattle, WA 98108 USA. EM wabanks1@uw.edu NR 14 TC 6 Z9 6 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JUL PY 2011 VL 152 IS 7 BP 2539 EP 2541 DI 10.1210/en.2011-1161 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 781IZ UT WOS:000291925700001 PM 21697453 ER PT J AU Madrigano, J Baccarelli, A Mittleman, MA Wright, RO Sparrow, D Vokonas, PS Tarantini, L Schwartz, J AF Madrigano, Jaime Baccarelli, Andrea Mittleman, Murray A. Wright, Robert O. Sparrow, David Vokonas, Pantel S. Tarantini, Letizia Schwartz, Joel TI Prolonged Exposure to Particulate Pollution, Genes Associated with Glutathione Pathways, and DNA Methylation in a Cohort of Older Men SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE air pollution; DNA methylation; epigenetics; gene-environment ID HEART-RATE-VARIABILITY; AIR-POLLUTION; ENVIRONMENT INTERACTION; L1 RETROTRANSPOSONS; US CITIES; BLOOD DNA; DISEASE; PARTICLES; HYPOMETHYLATION; MORTALITY AB BACKGROUND: DNA methylation is a potential pathway linking environmental exposures to disease. Exposure to particulate air pollution has been associated with increased cardiovascular morbidity and mortality, and lower blood DNA methylation has been found in processes related to cardiovascular morbidity. OBJECTIVE: We hypothesized that prolonged exposure to particulate pollution would be associated with hypomethylation of repetitive DNA elements and that this association would be modified by genes involved in glutathione metabolism and other host characteristics. METHODS: DNA methylation of the long interspersed nucleotide element-1 (LINE-1) and the short interspersed nucleotide element Alu were measured by quantitative polymerase chain reaction pyrosequencing in 1,406 blood samples from 706 elderly participants in the Normative Aging Study. We estimated changes in repetitive element DNA methylation associated with ambient particles (particulate matter <= 2.5 mu m in aerodynamic diameter), black carbon (BC), and sulfates (SO4), with mixed models. We examined multiple exposure windows (1-6 months) before DNA methylation measurement. We investigated whether this association was modified by genotype and phenotype. RESULTS: An interquartile range (IQR) increase in BC over a 90-day period was associated with a decrease of 0.31% 5-methylcytosine (5mC) (95% confidence interval, 0.12-0.50%) in Alu. An IQR increase in SO4 over a 90-day period was associated with a decrease of 0.27% 5mC (0.02-0.52%) in LINE-1. The glutathione S-transferase mu-1-null genotype strengthened the association between BC and Alu hypomethylation. CONCLUSION: Prolonged exposure to BC and SO4 particles was associated with hypomethylation of two types of repetitive elements. C1 [Madrigano, Jaime] Harvard Univ, Sch Publ Hlth, Exposure Epidemiol & Risk Program, Landmark Ctr W,Dept Epidemiol, Boston, MA 02215 USA. [Madrigano, Jaime; Baccarelli, Andrea; Wright, Robert O.; Schwartz, Joel] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02215 USA. [Mittleman, Murray A.] Beth Israel Deaconess Med Ctr, Cardiovasc Epidemiol Res Unit, Boston, MA 02215 USA. [Wright, Robert O.] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Pediat, Boston, MA 02215 USA. [Sparrow, David; Vokonas, Pantel S.] Boston Univ, Sch Med, Vet Adm Normat Aging Study, VA Boston Healthcare Syst, Boston, MA 02118 USA. [Sparrow, David; Vokonas, Pantel S.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Sparrow, David] Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab, Boston, MA 02215 USA. [Tarantini, Letizia] Univ Milan, Ctr Mol & Genet Epidemiol, Ist Ricovero & Cura Carattere Sci, Ca Granda Maggiore Policlin Hosp Fdn, Milan, Italy. [Tarantini, Letizia] Univ Milan, Dept Environm & Occupat Hlth, Milan, Italy. RP Madrigano, J (reprint author), Harvard Univ, Sch Publ Hlth, Exposure Epidemiol & Risk Program, Landmark Ctr W,Dept Epidemiol, Suite 415,401 Pk Dr, Boston, MA 02215 USA. EM jmadriga@post.harvard.edu OI Baccarelli, Andrea/0000-0002-3436-0640 FU Epidemiology Research and Information Center of the U.S. Department of Veterans Affairs; Massachusetts Veterans Epidemiology Research and Information Center, Boston, Massachusetts; National Institute of Environmental Health Sciences [T32ES07069, ES0002, ES015172-01, ES014663, T32ES016645]; U.S. Environmental Protection Agency [R832416] FX The Veterans Administration Normative Aging Study is supported by the Cooperative Studies Program/Epidemiology Research and Information Center of the U.S. Department of Veterans Affairs and is a component of the Massachusetts Veterans Epidemiology Research and Information Center, Boston, Massachusetts. This work was also supported by National Institute of Environmental Health Sciences grants T32ES07069, ES0002, ES015172-01, ES014663, and T32ES016645 and U.S. Environmental Protection Agency grant R832416. NR 56 TC 85 Z9 90 U1 2 U2 21 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUL PY 2011 VL 119 IS 7 BP 977 EP 982 DI 10.1289/ehp.1002773 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 786IT UT WOS:000292299300031 PM 21385671 ER PT J AU Davis, ME Hart, JE Laden, F Garshick, E Smith, TJ AF Davis, Mary E. Hart, Jaime E. Laden, Francine Garshick, Eric Smith, Thomas J. TI A Retrospective Assessment of Occupational Exposure to Elemental Carbon in the US Trucking Industry SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE air pollution; diesel; lung cancer; occupational health; traffic exposure; trucking industry ID NONMETAL MINING FACILITIES; DIESEL EXHAUST EXPOSURES; LUNG-CANCER RISK; RAILROAD WORKERS; PARTICULATE MATTER; HISTORICAL EXPOSURES; PARTICLES; MINERS; EPIDEMIOLOGY; TERMINALS AB BACKGROUND: Despite considerable epidemiologic evidence about the health effects of chronic exposure to vehicle exhaust, efforts at defining the extent of risk have been limited by the lack of historical exposure measurements suitable for use in epidemiologic studies and for risk assessment. OBJECTIVES: We sought to reconstruct exposure to elemental carbon (EC), a marker of diesel and other vehicle exhaust exposure, in a large national cohort of U. S. trucking industry workers. METHODS: We identified the predictors of measured exposures based on a statistical model and used this information to extrapolate exposures across the cohort nationally. These estimates were adjusted for changes in work-related conditions over time based on a previous exposure assessment of this industry, and for changes in background levels based on a trend analysis of historical air pollution data, to derive monthly estimates of EC exposure for each job and trucking terminal combination between 1971 and 2000. RESULTS: Occupational exposure to EC declined substantially over time, and we found significant variability in estimated exposures both within and across job groups, trucking terminals, and regions of the United States. Average estimated EC exposures during a typical work shift ranged from < 1 mu g/m(3) in the lowest exposed category in the 1990s to > 40 mu g/m(3) for workers in the highest exposed jobs in the 1970s. CONCLUSIONS: Our results provide a framework for understanding changes over time in exposure to EC in the U. S. trucking industry. Our assessment should minimize exposure misclassification by capturing variation among terminals and across U. S. regions, and changes over time. C1 [Davis, Mary E.] Tufts Univ, Dept Urban & Environm Policy & Planning, Medford, MA 02115 USA. [Davis, Mary E.; Laden, Francine; Smith, Thomas J.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Exposure Epidemiol & Risk Program, Boston, MA 02115 USA. [Hart, Jaime E.; Laden, Francine; Garshick, Eric] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Hart, Jaime E.; Laden, Francine; Garshick, Eric] Harvard Univ, Sch Med, Boston, MA USA. [Hart, Jaime E.; Laden, Francine] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Garshick, Eric] VA Boston Healthcare Syst, Pulm & Crit Care Med Sect, Med Serv, W Roxbury, MA USA. RP Davis, ME (reprint author), Tufts Univ, Dept Urban & Environm Policy & Planning, Medford, MA 02115 USA. EM mary.davis@tufts.edu FU National Institutes of Health, National Cancer Institute [R01 CA90792]; Health Effects Institute [4705-RFA03-1/04-1] FX This work was supported by a grant from the National Institutes of Health, National Cancer Institute (R01 CA90792) and by a grant from the Health Effects Institute (4705-RFA03-1/04-1). NR 36 TC 13 Z9 13 U1 1 U2 16 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUL PY 2011 VL 119 IS 7 BP 997 EP 1002 DI 10.1289/ehp.1002981 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 786IT UT WOS:000292299300034 PM 21447452 ER PT J AU Meeker, JD Maity, A Missmer, SA Williams, PL Mahalingaiah, S Ehrlich, S Berry, KF Altshul, L Perry, MJ Cramer, DW Hauser, R AF Meeker, John D. Maity, Arnab Missmer, Stacey A. Williams, Paige L. Mahalingaiah, Shruthi Ehrlich, Shelley Berry, Katharine F. Altshul, Larisa Perry, Melissa J. Cramer, Daniel W. Hauser, Russ TI Serum Concentrations of Polychlorinated Biphenyls in Relation to in Vitro Fertilization Outcomes SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE environment; epidemiology; female; organochlorine; reproduction ID PERSISTENT ORGANOCHLORINE COMPOUNDS; MENSTRUAL-CYCLE CHARACTERISTICS; CONTAMINATED SPORT FISH; HUMAN FOLLICULAR-FLUID; HUMAN HEALTH; REPRODUCTIVE TOXICITY; ENVIRONMENTAL CONTAMINANTS; POLYBROMINATED BIPHENYLS; CHLORINATED HYDROCARBONS; PREIMPLANTATION EMBRYOS AB BACKGROUND: Human exposure to polychlorinated biphenyls (PCBs) remains widespread. PCBs have been associated with adverse reproductive health outcomes including reduced fecundability and increased risk of pregnancy loss, although the human data remain largely inconclusive. OBJECTIVE: Our goal was to explore the relationship between serum PCB concentrations and early pregnancy loss among a large cohort of women undergoing in vitro fertilization (IVF) between 1994 and 2003. METHODS: Concentrations of 57 PCB congeners were measured in serum samples collected during 827 IVF/intracytoplasmic sperm injection cycles from 765 women. Joint statistical models that accommodate multiple outcomes and multiple cycles per woman were used to assess the relationship between serum PCB quartiles and implantation failure, chemical pregnancies (human chorionic gonadotropin level > 5.0 mIU/mL) that did not result in clinical pregnancy, or spontaneous abortion, while also adjusting for confounders. RESULTS: PCB-153 was the congener present in the highest concentration (median, 46.2 ng/g lipid). Increasing quartiles of PCB-153 and the sum of all measured PCB congeners (Sigma PCBs) were associated with significantly elevated dose-dependent odds of failed implantation. Adjusted odds ratios (95% confidence interval) for highest versus lowest quartile were 2.0 (1.2-3.4) for PCB-153 and 1.7 (1.0-2.9) for Sigma PCBs. There were suggestive trends for increased odds of implantation failure for PCB-118 and cytochrome P450-inducing congeners (p-values for trend = 0.06). No statistically significant associations between PCBs and chemical pregnancy or spontaneous abortion were found. CONCLUSIONS: Serum PCB concentrations at levels similar to the U. S. general population were associated with failed implantation among women undergoing IVF. These findings may help explain previous reports of reduced fecundability among women exposed to PCBs. C1 [Meeker, John D.] Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA. [Maity, Arnab] N Carolina State Univ, Dept Stat, Raleigh, NC 27695 USA. [Missmer, Stacey A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Missmer, Stacey A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab,Dept Med, Boston, MA 02115 USA. [Williams, Paige L.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Ehrlich, Shelley; Altshul, Larisa; Perry, Melissa J.; Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Hauser, Russ] Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Androl Lab, Boston, MA 02114 USA. [Hauser, Russ] Massachusetts Gen Hosp, In Vitro Fertilizat Unit, Boston, MA 02114 USA. RP Meeker, JD (reprint author), Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, 6635 SPH Tower,109 S Observ St, Ann Arbor, MI 48109 USA. EM meekerj@umich.edu RI Ehrlich , Shelley/L-6991-2015; MAITY, ARNAB/M-8142-2016; OI MAITY, ARNAB/0000-0002-3364-8933; Mahalingaiah, Shruthi/0000-0002-5527-5787; Meeker, John/0000-0001-8357-5085 FU National Institute of Environmental Health Sciences [R01-ES013967]; Eunice Kennedy Shriver National Institute of Child Health and Human Development [R01-HD32153] FX This work was supported by grant R01-ES013967 from the National Institute of Environmental Health Sciences and grant R01-HD32153 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 85 TC 26 Z9 27 U1 3 U2 21 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUL PY 2011 VL 119 IS 7 BP 1010 EP 1016 DI 10.1289/ehp.1002922 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 786IT UT WOS:000292299300036 PM 21345762 ER PT J AU Restrepo, MI Mortensen, EM Anzueto, A AF Restrepo, M. I. Mortensen, E. M. Anzueto, A. TI Are COPD patients with pneumonia who are taking inhaled corticosteroids at higher risk of dying? SO EUROPEAN RESPIRATORY JOURNAL LA English DT Editorial Material ID OBSTRUCTIVE PULMONARY-DISEASE; COMMUNITY-ACQUIRED PNEUMONIA; METERED-DOSE INHALER; SALMETEROL/FLUTICASONE PROPIONATE; CLINICAL-TRIAL; BUDESONIDE; EXACERBATIONS; PREVENTION; SALMETEROL; FORMOTEROL C1 [Restrepo, M. I.; Mortensen, E. M.] Vet Evidence Based Res Disseminat & Implementat C, San Antonio, TX USA. [Restrepo, M. I.; Mortensen, E. M.; Anzueto, A.] S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. [Restrepo, M. I.; Anzueto, A.] Div Pulm & Crit Care Med, San Antonio, TX USA. [Mortensen, E. M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Hosp Med, San Antonio, TX 78229 USA. RP Restrepo, MI (reprint author), S Texas Vet Hlth Care Syst ALMD, VERDICT 11C6, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM restrepom@uthscsa.edu RI Restrepo, Marcos/H-4442-2014; OI Mortensen, Eric/0000-0002-3880-5563 FU NHLBI NIH HHS [K23 HL096054, K23HL096054] NR 15 TC 7 Z9 7 U1 0 U2 3 PU EUROPEAN RESPIRATORY SOC JOURNALS LTD PI SHEFFIELD PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND SN 0903-1936 J9 EUR RESPIR J JI Eur. Resp. J. PD JUL PY 2011 VL 38 IS 1 BP 1 EP 3 DI 10.1183/09031936.00028711 PG 3 WC Respiratory System SC Respiratory System GA 785RW UT WOS:000292247700001 PM 21719494 ER PT J AU Gerits, A Ruff, CC Guipponi, O Wenderoth, N Driver, J Vanduffel, W AF Gerits, Annelies Ruff, Christian C. Guipponi, Olivier Wenderoth, Nicole Driver, Jon Vanduffel, Wim TI Transcranial magnetic stimulation of macaque frontal eye fields decreases saccadic reaction time SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE Frontal eye field; Macaque; Saccades; Theta burst; TMS ID THETA-BURST STIMULATION; MEMORY-GUIDED SACCADES; HUMAN MOTOR CORTEX; VISUAL-CORTEX; CORTICAL CONTROL; HAND-AREA; MONKEY; TMS; EXCITABILITY; LESIONS AB Transcranial magnetic stimulation (TMS) is increasingly used to perturb targeted human brain sites non-invasively, to test for causal effects on performance of cognitive tasks. TMS might also be used in non-human primates to complement invasive work and compare with human studies. Here, we targeted the frontal eye fields (FEF) in two macaques with a continuous theta-burst (cTBS) protocol, testing the impact on visually guided saccades. After unilateral cTBS over the FEF in either hemisphere, a small (mean 7 ms) but highly consistent decrease in saccadic reaction times (RTs) was observed. Lower latencies arose for saccades both contra-and ipsilateral to the stimulated FEF after cTBS. These results provide the first demonstration that TMS can be used to affect saccadic behavior in non-human primates. The unexpectedly bilateral impact on RTs may reflect an impact on 'fixation' neurons in the FEF and/or transcallosal modulation of both FEFs induced by unilateral cTBS. In either case, this study demonstrates a clear behavioral effect induced by TMS in awake behaving monkeys performing a cognitive task. This opens new opportunities for investigating the causal roles of targeted brain areas in behavior, for measuring physiological consequences of TMS in the primate brain, and ultimately for human-monkey comparisons. C1 [Gerits, Annelies; Vanduffel, Wim] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Gerits, Annelies; Guipponi, Olivier; Vanduffel, Wim] KU Leuven Med Sch, Lab Neuro & Psychophysiol, Leuven, Belgium. [Gerits, Annelies; Vanduffel, Wim] Harvard Univ, Sch Med, Dept Radiol, Charlestown, MA USA. [Wenderoth, Nicole] Katholieke Univ Leuven, Lab Movement Control & Neuroplast, Leuven, Belgium. [Ruff, Christian C.] Lab Social & Neural Syst Res SNS Lab, Zurich, Switzerland. [Ruff, Christian C.; Driver, Jon] UCL Inst Cognit Neurosci, London, England. [Ruff, Christian C.; Driver, Jon] UCL, Wellcome Trust Ctr Neuroimaging, London, England. RP Vanduffel, W (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM Wim@nmr.mgh.harvard.edu RI Wenderoth, Nicole/D-7262-2015; OI Wenderoth, Nicole/0000-0002-3246-9386; Ruff, Christian/0000-0002-3964-2364 FU Human Frontiers Science Program [HFSPO RGP7/2007]; Medical Foundation Queen Elisabeth [2008-10]; Inter University Attraction Pole6/29; Fonds voor Wetenschappelijk onderzoek, VLaanderen (FWO) [G.0622.08, FWO G.0593.09]; National Science Foundation [BCS-0745436]; European Union (EU) [FP7 HEALTH-F2-2008-200728]; BrainSynch; FWO-Flanders FX The authors are indebted to A. Coeman, C. Fransen, M. Depaep, W. Depuydt, M. Deforche, P. Kayenbergh, G. Meulemans, C. Van Eupen, S. Verstraeten for help with the experiments. The work was supported by Human Frontiers Science Program (HFSPO RGP7/2007), Medical Foundation Queen Elisabeth (2008-10), Inter University Attraction Pole6/29, Program Financing 2010-15, Fonds voor Wetenschappelijk onderzoek, VLaanderen (FWO) G.0622.08; FWO G.0593.09, National Science Foundation BCS-0745436 and European Union (EU) grant (FP7 HEALTH-F2-2008-200728), BrainSynch. JD is a Royal Society Anniversary Research Professor. AG has an Aspirant fellowship of FWO-Flanders. NR 50 TC 7 Z9 7 U1 2 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD JUL PY 2011 VL 212 IS 1 BP 143 EP 152 DI 10.1007/s00221-011-2710-3 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 782YL UT WOS:000292048600012 PM 21544509 ER PT J AU Wang, Q Yan, JQ Chen, XH Li, J Yang, Y Weng, JP Deng, C Yenari, MA AF Wang, Qing Yan, Junqiang Chen, Xiaohong Li, Jin Yang, Yu Weng, JianPing Deng, Chao Yenari, Midori A. TI Statins: Multiple neuroprotective mechanisms in neurodegenerative diseases SO EXPERIMENTAL NEUROLOGY LA English DT Review DE Statins; Inflammation; Ischemia; Alzheimer's disease; Parkinson's disease; Neuroprotection ID NITRIC-OXIDE SYNTHASE; COA REDUCTASE INHIBITORS; CEREBRAL VASOMOTOR REACTIVITY; MILD COGNITIVE IMPAIRMENT; D-2 RECEPTOR EXPRESSION; BRAIN-BARRIER BREAKDOWN; SMOOTH-MUSCLE-CELLS; ALZHEIMERS-DISEASE; BLOOD-PRESSURE; PARKINSONS-DISEASE AB Statins have been widely used for the treatment of a variety of conditions beyond their original role in lowering cholesterol. Since statins have relatively few side effects, they have been recognized as useful medicine to ameliorate neurodegenerative disorders. Current studies on the applications of statins have demonstrated their neuroprotective and clinical significance among neurodegenerative diseases like cerebral ischemic stroke, vascular dementia, Alzheimer's disease, and Parkinson's disease, though the neuroprotective mechanisms are not completely understood. This review will discuss recent development in the use of statins in slowing down the progression of these neurodegenerative diseases. It will summarize the potential mechanisms for statin-mediated neuroprotective effects in neurodegenerative diseases. In detail, this review discuss the roles of statins in lowering cholesterol, reducing reactive oxygen species, impairing beta-amyloid production and serum apolipoprotein E levels, enhancing the levels of endothelial nitric oxide synthase and cerebral blood flow, and modulating cognitive related receptors and matrix metalloproteases. Finally, different alterations of various receptors in brain regions following statin treatment and their correlations with cognitive dysfunction in Parkinson's disease will also be reviewed, as well as the potential for therapy in ameliorating the progression of Parkinson's disease. This article is part of a Special Issue entitled "Interaction between repair, disease, & inflammation." (C) 2010 Elsevier Inc. All rights reserved. C1 [Wang, Qing] Sun Yat Sen Univ, Affiliated Hosp 3, Neurol Res Lab, Dept Neurol, Guangzhou 510630, Guangdong, Peoples R China. [Weng, JianPing] Sun Yat Sen Univ, Affiliated Hosp 3, Dept Endocrinol, Guangzhou 510630, Guangdong, Peoples R China. [Wang, Qing; Deng, Chao] Univ Wollongong, Sch Hlth Sci, Ctr Translat Neurosci, Wollongong, NSW 2522, Australia. [Yenari, Midori A.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. [Yenari, Midori A.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Wang, Q (reprint author), Sun Yat Sen Univ, Affiliated Hosp 3, Neurol Res Lab, Dept Neurol, 600 Tianhe Rd, Guangzhou 510630, Guangdong, Peoples R China. EM denniswq@yahoo.com RI Deng, Chao/F-4417-2016 OI Deng, Chao/0000-0003-1147-5741 FU Third Affiliated Hospital of Sun Yat-Sen University; Sun Yat-Sen University [A77, 10ykzd08]; Ministry of Education (PR China); Australia National Health and Medical Research Council (NHMRC) [514640] FX This work was supported by Grant-In-Aid of the Third Affiliated Hospital of Sun Yat-Sen University and Sun Yat-Sen University (grant no. A77 and 10ykzd08), Distinguished Young Investigator Supporting Grant of the Ministry of Education (PR China), and Australia National Health and Medical Research Council Grant (NHMRC, ID: 514640) from Q.W. We would like to thank Dr. Mandy Reid for critical reading of this manuscript. NR 116 TC 46 Z9 49 U1 1 U2 24 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD JUL PY 2011 VL 230 IS 1 SI SI BP 27 EP 34 DI 10.1016/j.expneurol.2010.04.006 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 781BT UT WOS:000291906300004 PM 20406638 ER PT J AU Greenawalt, DM Dobrin, R Chudin, E Hatoum, IJ Suver, C Beaulaurier, J Zhang, B Castro, V Zhu, J Sieberts, SK Wang, S Molony, C Heymsfield, SB Kemp, DM Reitman, ML Lum, PY Schadt, EE Kaplan, LM AF Greenawalt, Danielle M. Dobrin, Radu Chudin, Eugene Hatoum, Ida J. Suver, Christine Beaulaurier, John Zhang, Bin Castro, Victor Zhu, Jun Sieberts, Solveig K. Wang, Susanna Molony, Cliona Heymsfield, Steven B. Kemp, Daniel M. Reitman, Marc L. Lum, Pek Yee Schadt, Eric E. Kaplan, Lee M. TI A survey of the genetics of stomach, liver, and adipose gene expression from a morbidly obese cohort SO GENOME RESEARCH LA English DT Article ID GENOME-WIDE ASSOCIATION; TRIGLYCERIDE LEVELS; FASTING GLUCOSE; WEIGHT-LOSS; TYPE-2; LOCI; RISK; POPULATION; DISEASE; RESISTANCE AB To map the genetics of gene expression in metabolically relevant tissues and investigate the diversity of expression SNPs (eSNPs) in multiple tissues from the same individual, we collected four tissues from approximately 1000 patients undergoing Roux-en-Y gastric bypass (RYGB) and clinical traits associated with their weight loss and co-morbidities. We then performed high-throughput genotyping and gene expression profiling and carried out a genome-wide association analyses for more than 100,000 gene expression traits representing four metabolically relevant tissues: liver, omental adipose, subcutaneous adipose, and stomach. We successfully identified 24,531 eSNPs corresponding to about 10,000 distinct genes. This represents the greatest number of eSNPs identified to our knowledge by any study to date and the first study to identify eSNPs from stomach tissue. We then demonstrate how these eSNPs provide a high-quality disease map for each tissue in morbidly obese patients to not only inform genetic associations identified in this cohort, but in previously published genome-wide association studies as well. These data can aid in elucidating the key networks associated with morbid obesity, response to RYGB, and disease as a whole. C1 [Greenawalt, Danielle M.; Molony, Cliona] Merck Res Labs, Boston, MA 02115 USA. [Dobrin, Radu; Heymsfield, Steven B.; Kemp, Daniel M.; Reitman, Marc L.] Merck Res Labs, Rahway, NJ 07065 USA. [Chudin, Eugene; Suver, Christine; Beaulaurier, John; Zhang, Bin; Zhu, Jun; Sieberts, Solveig K.; Wang, Susanna; Lum, Pek Yee; Schadt, Eric E.] Rosetta Inpharmat LLC, Genet, Seattle, WA 98109 USA. [Hatoum, Ida J.; Castro, Victor; Kaplan, Lee M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Greenawalt, DM (reprint author), Merck Res Labs, Boston, MA 02115 USA. EM danielle_greenawalt@merck.com; RDobrin@ITS.JNJ.COM; eric.schadt@gmail.com; lmkaplan@partners.org RI Reitman, Marc/B-4448-2013; OI Reitman, Marc/0000-0002-0426-9475; Suver, Christine/0000-0002-2986-385X; Dobrin, Radu/0000-0002-3336-0091 FU NIDDK NIH HHS [F32 DK093257] NR 49 TC 94 Z9 95 U1 0 U2 5 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 EI 1549-5469 J9 GENOME RES JI Genome Res. PD JUL PY 2011 VL 21 IS 7 BP 1008 EP 1016 DI 10.1101/gr.112821.110 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 786IM UT WOS:000292298000002 PM 21602305 ER PT J AU Russell, AH AF Russell, Anthony H. TI Base Two? SO GYNECOLOGIC ONCOLOGY LA English DT Editorial Material C1 Harvard Univ, Dept Radiat Oncol, Med Sch Chief, Gynecol Radiat Oncol Serv,Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Russell, AH (reprint author), Harvard Univ, Dept Radiat Oncol, Med Sch Chief, Gynecol Radiat Oncol Serv,Massachusetts Gen Hosp, 100 Blossom St, Boston, MA 02114 USA. EM ahrussell@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JUL PY 2011 VL 122 IS 1 BP 1 EP 2 DI 10.1016/j.ygyno.2011.05.005 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 781BW UT WOS:000291906600001 PM 21621705 ER PT J AU Singh, M Kindelberger, D Nagymanyoki, Z Ng, SW Quick, CM Elias, KM Yamamoto, H Fichorova, R Fulop, V Berkowitz, RS AF Singh, Margit Kindelberger, David Nagymanyoki, Zoltan Ng, Shu-Wing Quick, Charles M. Elias, Kevin M. Yamamoto, Hidemi Fichorova, Raina Fulop, Vilmos Berkowitz, Ross S. TI Matrix metalloproteinases and their inhibitors and inducer in gestational trophoblastic diseases and normal placenta SO GYNECOLOGIC ONCOLOGY LA English DT Article DE MMP; TIMP; CD 147; Gestational trophoblastic disease; Placental site trophoblastic tumor ID BREAST-CANCER; PROTEASE INHIBITORS; CELLS; EXPRESSION; NEOPLASIA; INVASION; TUMORS; CD147; CHEMOTHERAPY; MECHANISMS AB Objectives: This study aimed to investigate the expression of recently identified matrix metalloproteinases (MMPs), their inhibitors (TIMPs), and inducer (CD147) in a wide range of gestational trophoblastic diseases (GTD) thereby expanding our understanding of the potential role of MMPs in GTD. Methods: Paraffin sections of 10 normal first-trimester placentas (NP), 10 partial moles (PM), 10 complete moles (CM), 5 choriocarcinomas (CCA) and 5 placental site trophoblastic tumors (PSTT) were studied immunohistochemically for expression of MMP-7, MMP-14, MMP-21, MMP-28, TIMP-3, TIMP-4 and CD147. Immunolocalization of MMP-1, MMP-2, MMP-3, MMP-9, MMP-13 and TIMP-1 was performed on 5 CCA and 5 PSTTs. Results: CCA showed stronger intensity for MMP-14 and MMP-28 than PSTT (p<0.05, p<0.05). CCA and PSTT had stronger expression of MMP-21 than NP, PM and CM (p<0.05, p<0.05, p<0.01). PSTT (p<0.05, p<0.05), NP (p<0.01, p<0.01) and CM (p<0.01, p<0.05) showed stronger staining for TIMP-3 and TIMP-4 than CCA. Conclusion: Choriocarcinoma's high expression of MMPs and low expression of MMP inhibitors may contribute to its invasiveness and metastatic potential. Similarly, PSTT's lower expression of MMPs and high expression of MMP inhibitors may partly explain its lower invasiveness. Agents that inhibit MMP may prove useful in treating GTD. (C) 2011 Elsevier Inc. All rights reserved. C1 [Berkowitz, Ross S.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Sch Med,Div Gynecol Oncol,New England Trophoblast, Boston, MA 02115 USA. [Singh, Margit] Univ Szeged, Dept Obstet & Gynecol, Szeged, Hungary. [Kindelberger, David; Nagymanyoki, Zoltan; Quick, Charles M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Womens & Perinatal Pathol,Dept Pathol, Boston, MA 02115 USA. [Ng, Shu-Wing] Harvard Univ, Brigham & Womens Hosp, Sch Med, Lab Gynecol Oncol,Div Gynecol Oncol,Dept Obstet &, Boston, MA 02115 USA. [Elias, Kevin M.] Massachusetts Gen Hosp, Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. [Yamamoto, Hidemi; Fichorova, Raina] Harvard Univ, Brigham & Womens Hosp, Sch Med, Lab Genital Tract Biol,Dept Obstet Gynecol & Repr, Boston, MA 02115 USA. [Fulop, Vilmos] Natl Hlth Ctr, Dept Obstet & Gynecol, Budapest, Hungary. [Fulop, Vilmos] Semmelweis Univ, Budapest, Hungary. RP Berkowitz, RS (reprint author), Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Sch Med,Div Gynecol Oncol,New England Trophoblast, Boston, MA 02115 USA. EM rberkowitz@partners.org RI Fichorova, Raina/G-9969-2014; OI Elias, Kevin/0000-0003-1502-5553 NR 30 TC 12 Z9 17 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JUL PY 2011 VL 122 IS 1 BP 178 EP 182 DI 10.1016/j.ygyno.2011.03.025 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 781BW UT WOS:000291906600033 PM 21514631 ER PT J AU May, T Rabinowe, SN Berkowitz, RS Goldstein, DP AF May, Taymaa Rabinowe, Susan N. Berkowitz, Ross S. Goldstein, Donald P. TI Cerebral venous sinus thrombosis presenting as cerebral metastasis in a patient with choriocarcinoma following a non-molar gestation SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Choriocarcinoma; Non-molar gestation; Cerebral metastasis; Cerebral venous sinus thrombosis; Combination chemotherapy C1 [May, Taymaa; Berkowitz, Ross S.; Goldstein, Donald P.] Harvard Univ, Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol,New England Trophoblas Dis Ctr,, Boston, MA 02115 USA. [May, Taymaa; Berkowitz, Ross S.; Goldstein, Donald P.] Harvard Univ, Dana Farber Canc Inst, Dept Obstet & Gynecol, Div Gynecol Oncol,New England Trophoblas Dis Ctr,, Boston, MA 02115 USA. [Rabinowe, Susan N.] St Francis Reg Canc Ctr, Hartford, CT USA. RP Berkowitz, RS (reprint author), Harvard Univ, Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol,New England Trophoblas Dis Ctr,, 75 Francis St, Boston, MA 02115 USA. EM rberkowitz@partners.org NR 4 TC 0 Z9 1 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JUL PY 2011 VL 122 IS 1 BP 199 EP 200 DI 10.1016/j.ygyno.2011.04.001 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 781BW UT WOS:000291906600036 PM 21514630 ER PT J AU Sawaya, H Plana, JC Scherrer-Crosbie, M AF Sawaya, Heloisa Plana, Juan Carlos Scherrer-Crosbie, Marielle TI Newest Echocardiographic Techniques for the Detection of Cardiotoxicity and Heart Failure During Chemotherapy SO HEART FAILURE CLINICS LA English DT Article DE Echocardiography; Cardiotoxicity; Chemotherapy ID ACUTE MYOCARDIAL-INFARCTION; VENTRICULAR EJECTION FRACTION; METASTATIC BREAST-CANCER; ANTHRACYCLINE-INDUCED CARDIOTOXICITY; TIME 3-DIMENSIONAL ECHOCARDIOGRAPHY; LIPOSOME-ENCAPSULATED DOXORUBICIN; RISK-FACTOR BURDEN; CONVENTIONAL DOXORUBICIN; CARDIAC TOXICITY; QUANTITATIVE ASSESSMENT AB Chemotherapy-induced cardiotoxicity has become a significant public health issue. Left ventricular ejection fraction is routinely used to monitor cardiotoxicity but fails to detect subtle alterations in cardiac function. Improvements in the measurement of left ventricular ejection fraction, physical or pharmacologic stressors, and novel cardiac functional indices may be useful in the detection of cardiotoxicity. The improvements in the detection and therapy of cancer have led to the emergence of chemotherapy-induced cardiotoxicity. New echocardiographic techniques may be useful in the detection of patients undergoing chemotherapy treatments who could benefit from alternative cancer treatments, therefore decreasing the incidence of cardiotoxicity. C1 [Sawaya, Heloisa; Scherrer-Crosbie, Marielle] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab,Div Cardiol, Boston, MA 02114 USA. [Plana, Juan Carlos] Cleveland Clin Fdn, Sect Imaging, Dept Cardiovasc Med, Cleveland, OH 44195 USA. RP Scherrer-Crosbie, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab,Div Cardiol, 55 Fruit St, Boston, MA 02114 USA. EM marielle@crosbie.com FU investigator-initiated grant from Susan G. Komen for the Cure Foundation; Caflin Distinguished Scholar Award; Clinical Innovation Award FX This work was supported by an investigator-initiated grant from Susan G. Komen for the Cure Foundation and Caflin Distinguished Scholar Award and a Clinical Innovation Award. NR 64 TC 8 Z9 8 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7136 J9 HEART FAIL CLIN JI Heart Fail. Clin. PD JUL PY 2011 VL 7 IS 3 BP 313 EP + DI 10.1016/j.hfc.2011.03.003 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 988MI UT WOS:000307494700004 PM 21749883 ER PT J AU Hayward, RM Upadhyay, GA Mela, T Ellinor, PT Barrett, CD Heist, EK Verma, A Choudhry, NK Singh, JP AF Hayward, Robert M. Upadhyay, Gaurav A. Mela, Theofanie Ellinor, Patrick T. Barrett, Conor D. Heist, E. Kevin Verma, Atul Choudhry, Niteesh K. Singh, Jagmeet P. TI Pulmonary vein isolation with complex fractionated atrial electrogram ablation for paroxysmal and nonparoxysmal atrial fibrillation: A meta-analysis SO HEART RHYTHM LA English DT Article DE Atrial fibrillation; Catheter ablation; Complex fractionated atrial electrogram; Pulmonary vein isolation ID GUIDED SUBSTRATE ABLATION; CATHETER ABLATION; RADIOFREQUENCY ABLATION; ANTIARRHYTHMIC-DRUGS; RANDOMIZED-TRIAL; EFFICACY; RISK; MULTICENTER; TERMINATION; STRATEGIES AB BACKGROUND: Pulmonary vein isolation (PVI) is recognized as a potentially curative treatment for atrial fibrillation (AF). Ablation of complex fractionated atrial electrograms (CFAEs) in addition to PVI has been advocated as a means to improve procedural outcomes, but the benefit remains unclear. OBJECTIVE: This study sought t synthesize the available data testing the incremental benefit of adding CFAE ablation to PVI. METHODS: We performed a meta-analysis of controlled studies comparing the effect of PVI with CFAE ablation vs. PVI alone in patients with paroxysmal and nonparoxysmal AF. RESULTS: Of the 481 reports identified, 8 studies met our inclusion criteria. There was a statistically significant increase in freedom from atrial tachyarrhythmia (AT) with the addition of CFAE ablation (relative risk [RR] 1.15, P = .03). In the 5 reports of nonparoxysmal AF (3 randomized controlled trials, 1 controlled clinical trial, and 1 trial using matched historical controls), addition of CFAE ablation resulted in a statistically significant increase in freedom from AT (n = 112 of 181 [62%] for PVI + CFAE vs. n = 84 of 179 [47%] for PVI alone; RR 1.32, P = .02). In trials of paroxysmal AF (3 randomized controlled trials and 1 trial using matched historical controls), addition of CFAE ablation did not result in a statistically significant increase in freedom from AT (n = 131 of 166 [79%] for PVI + CFAE vs. n = 122 of 164 [74%] for PVI alone; RR 1.04, P = .52). CONCLUSION: In these studies of patients with nonparoxysmal AF, addition of CFAE ablation to PVI results in greater improvement in freedom from AF. No additional benefit of this combined approach was observed in patients with paroxysmal AF. C1 [Singh, Jagmeet P.] Massachusetts Gen Hosp, Ctr Heart, Cardiac Arrhythmia Serv, Div Cardiol, Boston, MA 02114 USA. [Hayward, Robert M.; Upadhyay, Gaurav A.; Mela, Theofanie; Ellinor, Patrick T.; Barrett, Conor D.; Heist, E. Kevin; Singh, Jagmeet P.] Massachusetts Gen Hosp, Ctr Heart, Dept Med, Boston, MA 02114 USA. [Choudhry, Niteesh K.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Singh, JP (reprint author), Massachusetts Gen Hosp, Ctr Heart, Cardiac Arrhythmia Serv, Div Cardiol, Gray Bldg 109,55 Fruit St, Boston, MA 02114 USA. EM jsingh@partners.org FU Harvard Catalyst; Harvard Clinical and Translational Science Center (National Institutes of Health) [UL1 RR 025758]; Biotronik; Boston Scientific; Medtronic; St. Jude Medical; Biosense Webster FX This work was conducted with support from Harvard Catalyst, The Harvard Clinical and Translational Science Center (National Institutes of Health Award UL1 RR 025758 and financial contributions from Harvard University and its 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 National Institutes of Health. Dr. Mela is a consultant to Biotronik and has lectured for Medtronic, St. Jude Medical, and Biotronik. Dr. Heist is a consultant to St. Jude Medical; has received research support from Boston Scientific and St. Jude Medical; and has lectured for Biotronik, Boston Scientific, Medtronic, St. Jude Medical, and Sorin. Dr. Verma is a consultant to Biosense Webster, Medtronic, Sanofi Aventis, Astra Zeneca, and Servier; has lectured for Biosense Webster, Medtronic, and St. Jude Medical; and has received research grants from Biosense Webster, Medtronic, and St. Jude Medical. Dr. Singh is a consultant to Biotronik, Boston Scientific, Biosense Webster, CardioInsight, Medtronic, St. Jude Medical, CardioInsight, Thoratec, and the Sorin Group; has lectured for Biotronik, Boston Scientific, Medtronic, St. Jude Medical, and the Sorin Group; and has received research grants from Biotronik, Boston Scientific, Medtronic, and St. Jude Medical. Address reprint requests and correspondence: Dr. Jagmeet P. Singh, Cardiac Arrhythmia Service, Cardiology Division, Gray Building 109, Massachusetts General Hospital Heart Center, 55 Fruit Street, Boston, MA 02114. E-mail address: jsingh@partners.org. (Received January 23, 2011; accepted February 22, 2011.) NR 28 TC 61 Z9 62 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD JUL PY 2011 VL 8 IS 7 BP 994 EP 1000 DI 10.1016/j.hrthm.2011.02.033 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 785QJ UT WOS:000292243400011 PM 21397045 ER PT J AU Dubin, R Owens, C Gasper, W Ganz, P Johansen, K AF Dubin, Ruth Owens, Christopher Gasper, Warren Ganz, Peter Johansen, Kirsten TI Associations of endothelial dysfunction and arterial stiffness with intradialytic hypotension and hypertension SO HEMODIALYSIS INTERNATIONAL LA English DT Article DE Endothelial dysfunction; arterial stiffness; intradialytic hypotension; intradialytic hypertension; phosphorus ID HEMODIALYSIS-ASSOCIATED HYPOTENSION; STAGE RENAL-DISEASE; FLOW-MEDIATED DILATION; CHRONIC KIDNEY-DISEASE; ASYMMETRIC DIMETHYLARGININE; CARDIOVASCULAR EVENTS; OXIDATIVE STRESS; VITAMIN-E; DIALYSIS; FAILURE AB Intradialytic hypotension and hypertension are both independently associated with mortality among persons with end-stage renal disease on hemodialysis. Endothelial dysfunction and arterial stiffness are two possible mechanisms underlying these phenomena, but their association with hemodynamic instability during dialysis has not been evaluated. Thirty patients were recruited from chronic dialysis units at San Francisco General Hospital and San Francisco Veterans Affairs Medical Center. Endothelial dysfunction was assessed with flow-mediated dilation of the brachial artery after upper arm occlusion. Arterial stiffness was assessed using carotid-femoral pulse wave velocity measured by tonometry. Intradialytic hypotension and hypertension were defined as the average decrease in systolic blood pressure (SBP) over 1 week, as well as the frequency over 1 month of hypotension or hypertension. Every 5% decrease in flow-mediated dilation was associated with a 7.5 mmHg decrease in SBP after adjustment for phosphorus, body mass index, atherosclerosis, and ultrafiltration (P=0.02). Every 5 m/s increase in pulse wave velocity was associated with an 8 mmHg increase in SBP after adjustment for predialysis SBP and ultrafiltration (P=0.03). Over 1 month, every 5% lower flow-mediated dilation was associated with a 10% higher frequency of hypotension (P=0.09), and every 5 m/s increase in pulse wave velocity was associated with an 15% higher frequency of hypertension (P=0.02). In a cross-sectional analysis of 30 dialysis patients, endothelial dysfunction and arterial stiffness were independently associated with intradialytic hypotension and intradialytic hypertension, respectively. Elucidating these potential mechanisms of hemodynamic instability during dialysis may facilitate development of treatment strategies specific to this pathophysiology. C1 [Dubin, Ruth; Johansen, Kirsten] Univ Calif San Francisco, Dept Med, Div Nephrol, San Francisco, CA 94143 USA. [Owens, Christopher; Gasper, Warren] Univ Calif San Francisco, Dept Vasc & Endovasc Surg, San Francisco, CA 94143 USA. [Owens, Christopher; Johansen, Kirsten] San Francisco VA Med Ctr, San Francisco, CA USA. [Ganz, Peter] Univ Calif San Francisco, Div Cardiol, San Francisco, CA 94143 USA. RP Dubin, R (reprint author), Univ Calif San Francisco, Dept Med, Div Nephrol, 521 Parnassus Ave,C443, San Francisco, CA 94143 USA. EM ruth.dubin@ucsf.edu FU Clinical and Translational Science Institute, University of California, San Francisco FX This research is funded through the Clinical and Translational Science Institute by the Resource Allocation Program of the University of California, San Francisco. The authors have no conflicts of interest to declare. NR 48 TC 17 Z9 18 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1492-7535 J9 HEMODIAL INT JI Hemodial. Int. PD JUL PY 2011 VL 15 IS 3 BP 350 EP 358 DI 10.1111/j.1542-4758.2011.00560.x PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 786NJ UT WOS:000292314900008 PM 21658174 ER PT J AU Bonmasser, G AF Bonmasser, George TI The MGH/HST Athinoula A. Martinos Center SO IEEE PULSE LA English DT Article ID VISUAL-CORTEX C1 [Bonmasser, George] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Bonmasser, George] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Bonmasser, G (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. EM giorgio@nmr.mgh.harvard.edu NR 8 TC 0 Z9 0 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 2154-2287 J9 IEEE PULSE JI IEEE Pulse PD JUL-AUG PY 2011 VL 2 IS 4 BP 39 EP 42 DI 10.1109/MPUL.2011.941454 PG 4 WC Engineering, Biomedical SC Engineering GA 992GC UT WOS:000307762600009 PM 21791398 ER PT J AU Caldwell, A Young, A Gomez-Marquez, J Olson, KR AF Caldwell, Aya Young, Anna Gomez-Marquez, Jose Olson, Kristian R. TI Global Health Technology 2.0 SO IEEE PULSE LA English DT Article C1 [Caldwell, Aya; Olson, Kristian R.] Massachusetts Gen Hosp, Ctr Global Hlth, CIMITs Global Hlth Initiat, Boston, MA 02114 USA. [Young, Anna; Gomez-Marquez, Jose] Massachusetts Inst Technol MIT Innovat Int Hlth, Cambridge, MA USA. RP Caldwell, A (reprint author), Massachusetts Gen Hosp, Ctr Global Hlth, CIMITs Global Hlth Initiat, Boston, MA 02114 USA. EM acaldwell1@partners.org; annakyoung@gmail.com; jose.gomez.marquez@gmail.com; krolson@partners.org NR 12 TC 6 Z9 6 U1 0 U2 5 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 2154-2287 J9 IEEE PULSE JI IEEE Pulse PD JUL-AUG PY 2011 VL 2 IS 4 BP 63 EP 67 DI 10.1109/MPUL.2011.941459 PG 5 WC Engineering, Biomedical SC Engineering GA 992GC UT WOS:000307762600015 PM 21791404 ER PT J AU Schillace, RV Miller, CL Carr, DW AF Schillace, Robynn V. Miller, Casey L. Carr, Daniel W. TI AKAPs in lipid rafts are required for optimal antigen presentation by dendritic cells SO IMMUNOLOGY AND CELL BIOLOGY LA English DT Article DE AKAP; antigen presentation; human dendritic cell; lipid raft; signal transduction ID PROTEIN-KINASE-A; CLASS-II MOLECULES; MEMBRANE RAFTS; CYTOKINE PRODUCTION; KEY FACTOR; T-CELLS; EZRIN; ACTIVATION; RECEPTOR; MATURATION AB Dendritic cell (DC) maturation and antigen presentation are regulated by activation of protein kinase A (PKA) signaling pathways, through unknown mechanisms. We have recently shown that interfering with PKA signaling through the use of anchoring inhibitor peptides hinders antigen presentation and DC maturation. These experiments provide evidence that DC maturation and antigen presentation are regulated by A-kinase anchoring proteins (AKAPs). Herein, we determine that the presence of AKAPs and PKA in lipid rafts regulates antigen presentation. Using a combination of western blotting and immuno-cytochemistry, we illustrate the presence of AKAP149, AKAP79, Ezrin and the regulatory subunits of PKA in DC lipid rafts. Incubation of DCs with the type II anchoring inhibitor, AKAP-in silico (AKAP-IS), removes Ezrin and RII from the lipid raft without disrupting raft formation. Addition of a lipid raft disruptor, methyl-beta-cyclodextrin, blocks the efficacy of AKAP-IS, suggesting that the lipid raft must be intact for AKAP-IS to inhibit antigen presentation. Ezrin and AKAP79 are present in the lipid raft of stimulated KG1 cells, but Ezrin is not present in the lipid raft of unstimulated KG1 cells and AKAP79 levels are greatly diminished, suggesting that Ezrin and AKAP79 may be the key AKAPs responsible for regulating antigen presentation. Immunology and Cell Biology (2011) 89, 650-658; doi:10.1038/icb.2010.148; published online 11 January 2011 C1 [Schillace, Robynn V.; Miller, Casey L.; Carr, Daniel W.] Portland VA Med Ctr, Portland, OR 97239 USA. [Schillace, Robynn V.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Carr, Daniel W.] Oregon Hlth & Sci Univ, Dept Endocrinol, Portland, OR 97201 USA. RP Carr, DW (reprint author), Portland VA Med Ctr, VAMC RD 8,3710 US Vet Hosp Rd, Portland, OR 97239 USA. EM carrd@ohsu.edu FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development Service FX This research was supported by Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development Service (DWC). We thank Sarah Fiedler and Dr Sonemany Salinthone for helpful comments during paper preparation. NR 51 TC 8 Z9 9 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0818-9641 J9 IMMUNOL CELL BIOL JI Immunol. Cell Biol. PD JUL PY 2011 VL 89 IS 5 BP 650 EP 658 DI 10.1038/icb.2010.148 PG 9 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 786PK UT WOS:000292320200011 PM 21221125 ER PT J AU Villar, J Cabrera, NE Casula, M Valladares, F Flores, C Lopez-Aguilar, J Blanch, L Zhang, HB Kacmarek, RM Slutsky, AS AF Villar, Jesus Cabrera, Nuria E. Casula, Milena Valladares, Francisco Flores, Carlos Lopez-Aguilar, Josefina Blanch, Lluis Zhang, Haibo Kacmarek, Robert M. Slutsky, Arthur S. TI WNT/beta-catenin signaling is modulated by mechanical ventilation in an experimental model of acute lung injury SO INTENSIVE CARE MEDICINE LA English DT Article DE Acute lung injury; WNT/beta-catenin pathway; Ventilator-induced lung injury; Metalloproteinase ID IDIOPATHIC PULMONARY-FIBROSIS; RESPIRATORY-DISTRESS-SYNDROME; BETA-CATENIN; CONSTITUTIVE ACTIVATION; GENE-EXPRESSION; WNT PATHWAY; DISEASE; HUMANS; REPAIR; CELLS AB The mechanisms involved in lung injury progression during acute lung injury (ALI) are still poorly understood. Because WNT/beta-catenin signaling has been shown to be involved in epithelial cell injury and hyperplasia during inflammation and sepsis, we hypothesized that it would be modulated by mechanical ventilation (MV) in an experimental model of sepsis-induced ALI. This study was a prospective, randomized, controlled animal study performed using adult male Sprague-Dawley rats. Sepsis was induced by cecal ligation and perforation. At 18 h, surviving animals were randomized to spontaneous breathing or two strategies of MV for 4 h: low tidal volume (V (T)) (6 ml/kg) plus 10 cmH(2)O of positive end-expiratory pressure (PEEP) versus high (20 ml/kg) tidal volume (V (T)) with zero PEEP. Histological evaluation, measurements of WNT5A, total beta-catenin, and matrix metalloproteinase-7 (MMP7) protein levels by Western blot, and their immunohistochemical localization in the lungs were analyzed. Sepsis and high-V (T) MV caused lung inflammation and perivascular edema with cellular infiltrates and collagen deposition. Protein levels of WNT5A, beta-catenin, and MMP7 in the lungs were increased in animals with sepsis-induced ALI. High-V (T) MV was associated with higher levels of WNT5A, beta-catenin, and MMP7 protein levels (p < 0.001), compared to healthy control animals. By contrast, low-V (T) MV markedly reduced WNT5A, beta-catenin, and MMP7 protein levels (p < 0.001). Our findings demonstrate that the WNT/beta-catenin signaling pathway is modulated early during sepsis and ventilator-induced lung injury, suggesting that activation of this pathway could play an important role in both lung injury progression and repair. C1 [Villar, Jesus; Cabrera, Nuria E.; Casula, Milena] Hosp Univ Dr Negrin, Multidisciplinary Organ Dysfunct Evaluat Res Netw, Res Unit, Las Palmas Gran Canaria 35010, Spain. [Villar, Jesus; Cabrera, Nuria E.; Casula, Milena; Valladares, Francisco; Flores, Carlos; Lopez-Aguilar, Josefina; Blanch, Lluis] Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain. [Villar, Jesus; Zhang, Haibo; Slutsky, Arthur S.] St Michaels Hosp, Keenan Res Ctr, Li Ka Shing Knowledge Inst, Toronto, ON M5B 1W8, Canada. [Valladares, Francisco] Univ La Laguna, Dept Anat Pathol & Histol, Tenerife, Spain. [Flores, Carlos] Hosp Univ NS Candelaria, Res Unit, Tenerife, Spain. [Lopez-Aguilar, Josefina; Blanch, Lluis] Corp Sanitaria Parc Tauli, Crit Care Ctr, Barcelona, Spain. [Kacmarek, Robert M.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. [Slutsky, Arthur S.] Univ Toronto, Interdepartmental Div Crit Care Med, Toronto, ON, Canada. [Slutsky, Arthur S.] King Saud Univ, Riyadh, Saudi Arabia. RP Villar, J (reprint author), Hosp Univ Dr Negrin, Multidisciplinary Organ Dysfunct Evaluat Res Netw, Res Unit, S-N 4th Floor,S Wing, Las Palmas Gran Canaria 35010, Spain. EM jesus.villar54@gmail.com FU Ministry of Science of Spain [SAF 2004-06833]; Instituto de Salud Carlos III of Spain [PI 10/0393]; Canadian Institutes of Health Research; Instituto de Salud Carlos III [EMER07/001]; FUNCIS [EMER07/001, 53/04] FX Supported by grants from Ministry of Science of Spain (SAF 2004-06833), Instituto de Salud Carlos III of Spain (PI 10/0393), the Canadian Institutes of Health Research, FUNCIS (53/04), and by a specific agreement between Instituto de Salud Carlos III and FUNCIS (EMER07/001) under the ENCYT 2015 framework. NR 36 TC 17 Z9 20 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD JUL PY 2011 VL 37 IS 7 BP 1201 EP 1209 DI 10.1007/s00134-011-2234-0 PG 9 WC Critical Care Medicine SC General & Internal Medicine GA 786ET UT WOS:000292286800022 PM 21567117 ER PT J AU Mulligan, JK Mulligan, RM Atkinson, C Schlosser, RJ AF Mulligan, Jennifer K. Mulligan, Ryan M. Atkinson, Carl Schlosser, Rodney J. TI Human sinonasal epithelial cells direct dendritic function and T-cell T helper 1/T helper 2 skewing following Aspergillus exposure SO INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY LA English DT Article; Proceedings Paper CT 69th Annual Meeting of the American-Academy-of-Otolaryngic-Allergy (AAOA) CY SEP 24-25, 2010 CL Boston, MA SP Amer Acad Otolaryng Allergy (AAOA) DE allergic fungal rhinosinusitis; chronic rhinosinusitis without nasal polyps; chronic rhinosinusitis; dendritic cells; human sinonasal epithelial cells ID CHRONIC RHINOSINUSITIS; NASAL POLYPOSIS; HOST-DEFENSE; ASTHMA; SINUSITIS; DISEASE; CYTOKINES; IMMUNITY; PERSPECTIVES; EXPRESSION AB Background: In lower airway disease such as asthma, epithelial cells have been shown to be potent regulators of dendritic cell (DC) functions. However, it is unclear how human sinonasal epithelial cells (HSNECs) from patients with sinusitis regulate DC functions. Therefore, in these studies we investigated the ability of Aspergillus fumigatus exposed HSNECs to regulate DC antigen uptake, maturation, and direction of T-cell T helper 1 (Th1)/Th2 skewing. Methods: Primary HSNECs were cultured from control (n = 8), chronic sinusitis without nasal polyps (CRSsNP) (n = 9), and chronic sinusitis with nasal polyps (CRSwNP) (n = 7) patients and exposed to Aspergillus. Conditioned media was placed upon monocyte-derived DCs from healthy controls. DC antigen uptake was assessed by dextran-fluorescein isothiocyanate (FITC) uptake. DC differentiation and maturation was assessed by immunostaining for CD209, CD80, and CD86 followed by flow cytometric analysis. DC direction of T-cell Th1/Th2 skewing was evaluated by immunostaining followed by intracellular flow cytometric analysis for interferon (IFN)-gamma and interleukin (IL)-5. Results: Control and CRSsNP HSNECs have the capacity to stimulate DC antigen uptake, differentiation, and maturation following Aspergillus exposure. CRSwNP HSNECs stimulate DC activation independent of Aspergillus exposure. Furthermore, Aspergillus-exposed CRSwNP HSNECs skew T-cells toward a Th2 phenotype. Conclusion: CRSwNP-derived HSNECs stimulate DC maturation and Th2 skewing independent of Aspergillus exposure. However, control and CRSsNP HSNECs induce DC maturation and Th2 skewing after Aspergillus exposure. These in vitro studies demonstrate that HSNECs are key regulators of DC functions in the sinus microenvironment. (C) 2011 ARS-AAOA, LLC. C1 [Mulligan, Jennifer K.; Mulligan, Ryan M.; Schlosser, Rodney J.] Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA. [Mulligan, Jennifer K.; Mulligan, Ryan M.; Schlosser, Rodney J.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Atkinson, Carl] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. RP Mulligan, JK (reprint author), MSC 550,135 Rutledge Ave, Charleston, SC 29425 USA. EM konopa@musc.edu NR 35 TC 9 Z9 9 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2042-6976 J9 INT FORUM ALLERGY RH JI Int. Forum Allergy Rhinol. PD JUL-AUG PY 2011 VL 1 IS 4 BP 268 EP 274 DI 10.1002/alr.20055 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA 007XS UT WOS:000308922300007 PM 22287430 ER PT J AU Ayers, CM Schlosser, RJ O'Connell, BP Atkinson, C Mulligan, RM Casey, SE Bleier, BS Wang, EW Sansoni, ER Kuhlen, JL Mulligan, JK AF Ayers, Chris M. Schlosser, Rodney J. O'Connell, Brendan P. Atkinson, Carl Mulligan, Ryan M. Casey, Sarah E. Bleier, Benjamin S. Wang, Eric W. Sansoni, Eugene R. Kuhlen, James L. Mulligan, Jennifer K. TI Increased presence of dendritic cells and dendritic cell chemokines in the sinus mucosa of chronic rhinosinusitis with nasal polyps and allergic fungal rhinosinusitis SO INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY LA English DT Article DE allergic fungal rhinosinusitis; chemokine; chronic rhinosinusitis without nasal polyps; chronic rhinosinusitis; dendritic cells ID EPITHELIAL-CELLS; BRONCHIAL EPITHELIUM; EXPRESSION; IMMUNITY; INFLAMMATION; RELEASE; DISEASE; ASTHMA; RECRUITMENT; RECEPTORS AB Background: The aim of this study was to determine if there is a link between local dendritic cells (DCs) and various sub-types of chronic rhinosinusitis (CRS): CRS with nasal polyposis (CRSwNP), CRS without nasal polyposis (CRSsNP), and allergic fungal rhinosinusitis (AFRS). Once DC presence was established we considered possible mechanisms for DC recruitment to the sinuses. Methods: Biopsy specimens were taken from the osteomeatal complex during endoscopic sinus surgery in patients with AFRS (n >= 5), CRSsNP (n >= 6), and CRSwNP (n >= 6). Control patients (n >= 5) were undergoing either tumor resection or repair of cerebrospinal fluid leak and had no radiographic or endoscopic evidence of inflammatory sinus disease. Tissue samples were immunohistochemically stained for DC marker, CD209, costimulatory molecules, CD80 and CD86, and chemokine receptors, CCR2 and CCR6. Sinus tissue lysates were examined for levels of the DC chemoattractants, chemokine ligand 2 (CCL2) and CCL20. Results: Analysis of sinus tissue from AFRS and CRSwNP revealed elevated numbers of cells staining positive for CD209, CD80, CD86, CCR2, and CCR6 compared to controls. CCL2 and CCL20 levels were elevated in AFRS and CRSwNP compared to controls, similar to increases in their receptors, CCR2 and CCR6, respectively. While there were trends toward increases in all markers in CRSsNP, none was statistically significant compared to control. Conclusion: AFRS and CRSwNP have increased numbers of DCs displaying costimulatory molecules, DC chemoattractants, and their corresponding receptors in the sinus mucosa compared to controls. These differences represent a possible mechanism for increased numbers of DCs with a T helper 2 (Th2)-skewed profile seen in CRSwNP and AFRS. (C) 2011 ARS-AAOA, LLC. C1 [Ayers, Chris M.; Schlosser, Rodney J.; O'Connell, Brendan P.; Mulligan, Ryan M.; Bleier, Benjamin S.; Wang, Eric W.; Sansoni, Eugene R.; Kuhlen, James L.; Mulligan, Jennifer K.] Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA. [Schlosser, Rodney J.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Atkinson, Carl; Casey, Sarah E.] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. [Bleier, Benjamin S.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. RP Mulligan, JK (reprint author), MSC 550,135 Rutledge Ave, Charleston, SC 29425 USA. EM konopa@musc.edu OI Wang, Eric/0000-0002-1180-5854 FU American Academy of Otolaryngic Allergy; Flight Attendant Medical Research Institute FX American Academy of Otolaryngic Allergy (to B.O.C.) and the Flight Attendant Medical Research Institute (to R.J.S. and J.K.M.). NR 38 TC 23 Z9 23 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2042-6976 J9 INT FORUM ALLERGY RH JI Int. Forum Allergy Rhinol. PD JUL-AUG PY 2011 VL 1 IS 4 BP 296 EP 302 DI 10.1002/alr.20046 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA 007XS UT WOS:000308922300012 PM 22287435 ER PT J AU Keszei, M Latchman, YE Vanguri, VK Brown, DR Detre, C Morra, M Arancibia-Carcamo, CV Paul, E Calpe, S Castro, W Wang, NH Terhorst, C Sharpe, AH AF Keszei, Marton Latchman, Yvette E. Vanguri, Vijay K. Brown, Daniel R. Detre, Cynthia Morra, Massimo Arancibia-Carcamo, Carolina V. Paul, Elahna Calpe, Silvia Castro, Wilson Wang, Ninghai Terhorst, Cox Sharpe, Arlene H. TI Auto-antibody production and glomerulonephritis incongenic Slamf1(-/-) and Slamf2(-/-) [B6.129] but not in Slamf1(-/-) and Slamf2(-/-) [BALB/c.129] mice (vol 23, pg 149, 2011) SO INTERNATIONAL IMMUNOLOGY LA English DT Correction C1 [Keszei, Marton] Harvard Univ, Sch Med, Div Immunol, Beth Israel Deaconess Med Ctr,Ctr Life Sci, Boston, MA 02115 USA. [Latchman, Yvette E.; Vanguri, Vijay K.; Brown, Daniel R.; Arancibia-Carcamo, Carolina V.; Sharpe, Arlene H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Paul, Elahna] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. RP Keszei, M (reprint author), Harvard Univ, Sch Med, Div Immunol, Beth Israel Deaconess Med Ctr,Ctr Life Sci, Room CLS 928,3 Blackfan Circle, Boston, MA 02115 USA. EM mkeszei@bidmc.harvard.edu NR 1 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD JUL PY 2011 VL 23 IS 7 BP 463 EP 463 DI 10.1093/intimm/dxr030 PG 1 WC Immunology SC Immunology GA 786NO UT WOS:000292315400007 ER PT J AU Landeck, L Schalock, P Baden, L Gonzalez, E AF Landeck, Lilla Schalock, Peter Baden, Lynn Gonzalez, Ernesto TI Contact sensitization pattern in 172 atopic subjects SO INTERNATIONAL JOURNAL OF DERMATOLOGY LA English DT Article ID PATCH-TEST REACTIONS; DERMATITIS; SENSITIVITY; ALLERGY; IVDK AB Background Some authors have claimed a decreased cell-mediated immunity among atopic individuals, which would lead to observations of decreased rates of allergic contact dermatitis (ACD). Objectives The purpose of our study was to investigate contact sensitization patterns in atopic subjects compared with non-atopic subjects. Methods Patch test data for 1247 patients undergoing patch testing at Massachusetts General Hospital between 1990 and 2006 were reviewed. Using accepted criteria, 172 subjects were classified as atopic individuals (AIs), and 1075 were classified as non-atopic individuals (NAIs). Sensitization rates were compared between these two groups. Results Sensitization rates (65.0% and 57.4% in the AI and NAI groups, respectively) and average numbers of positive responses (1.5 and 1.2 in the AI and NAI groups, respectively) were higher in AIs. Leading allergens observed were similar for both groups. Sensitization to potassium dichromate and phenylmercuric acetate was significantly greater in the AI group. The most frequent diagnosis in both groups was ACD (41.9% and 45.5% in the AI and NAI groups, respectively). In addition, more NAIs who were employed in occupations with exposure to wet and/or irritant conditions had hand eczema (P < 0.005). Conclusions Atopic individuals were shown to be at least as likely to have ACD as NAIs. The most common sensitizers were similar in both groups, suggesting common sources of sensitization. C1 [Landeck, Lilla; Schalock, Peter; Gonzalez, Ernesto] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA USA. [Baden, Lynn] Ctr Dermatol & Aesthet Med, Newton, MA USA. RP Gonzalez, E (reprint author), Massachusetts Gen Hosp, Dept Dermatol BAR610, 55 Fruit St, Boston, MA 02114 USA. EM egonzalez1@partners.org OI Schalock, Peter/0000-0001-8953-4639 NR 16 TC 10 Z9 10 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0011-9059 J9 INT J DERMATOL JI Int. J. Dermatol. PD JUL PY 2011 VL 50 IS 7 BP 806 EP 810 DI 10.1111/j.1365-4632.2010.04754.x PG 5 WC Dermatology SC Dermatology GA 785YL UT WOS:000292269000006 PM 21699515 ER PT J AU Goodman, E Must, A AF Goodman, Elizabeth Must, Aviva TI Depressive Symptoms in Severely Obese Compared With Normal Weight Adolescents: Results From a Community-Based Longitudinal Study SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article DE Obesity; Depression; Adolescence; Race/ethnicity ID QUALITY-OF-LIFE; YOUNG ADULTHOOD; EXTREME OBESITY; OVERWEIGHT; HEALTH; CHILDREN; TRAJECTORIES; ASSOCIATION; DISORDER; CHILDHOOD AB Purpose: Little is known about the relationship between severe obesity and depressive symptoms, particularly in community as opposed to clinic-based samples. This study determined the relationship of severe obesity and depressive symptoms over 3 years in a community-based sample of non-Hispanic black and white adolescents in grades 7-12 at baseline. Methods: The nested matched cohort study using data from a longitudinal school-based study of youth followed up for 3 years. A total of 51 severely obese participants (body mass index-for-age >= 99% and a body mass index >= 40 at one or more study visit) were identified and paired with an age-, gender-, and race-matched normal weight subject. Depressive symptoms (Center for Epidemiological Studies Depression [CES-D] scale) were assessed at baseline, 2 and 3 years later. High-depressive symptoms were defined by CES-D score above cut points predictive of major depressive disorder or use of antidepressant medication. Results: Pairs were 73% non-Hispanic black, 67% females. There was no relationship between weight status and high-depressive symptoms at any assessment point. However, a positive association between weight status and CES-D scores, while not present at baseline or at 2 years, emerged at 3 years (p = .02). This relationship was present only among non-Hispanic whites (p = .006 whites, p = .25 blacks) and did not differ by gender. Conclusion: Severely obese youth in this community sample did not have increased likelihood of high levels of depressive symptoms. However, significantly increased depressive symptoms among non-Hispanic white youth at the end of the follow-up period suggests that this racial/ethnic group may be particularly vulnerable to the psychological effects of obesity in late adolescence and/or early adulthood. (C) 2011 Society for Adolescent Health and Medicine. All rights reserved. C1 [Goodman, Elizabeth] Harvard Univ, Sch Med, Dept Pediat, Ctr Child & Adolescent Hlth Policy,Massachusetts, Boston, MA 02115 USA. [Must, Aviva] Tufts Univ, Sch Med, Dept Publ Hlth & Community Med, Boston, MA 02111 USA. RP Goodman, E (reprint author), MassGen Hosp Children, Ctr Child & Adolescent Hlth Policy, 50 Staniford St,Suite 901, Boston, MA 02114 USA. EM egoodman3@partners.org OI Goodman, Elizabeth/0000-0002-9640-9884 FU NIH [HD041527, DK59183, DL46200]; Richard Salton-stall Fund FX The authors thank Minghua Chen, MD, MPH, for assistance with data analysis. The present study was supported by NIH grants HD041527, DK59183, DL46200 and the Richard Salton-stall Fund. NR 34 TC 12 Z9 12 U1 6 U2 18 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 JUL PY 2011 VL 49 IS 1 BP 64 EP 69 DI 10.1016/j.jadohealth.2010.10.015 PG 6 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA 782AA UT WOS:000291978400013 PM 21700159 ER PT J AU Kahn, JA Huang, B Ding, LL Geller, A Frazier, AL AF Kahn, Jessica A. Huang, Bin Ding, Lili Geller, Alan Frazier, A. Lindsay TI Impact of Maternal Communication About Skin, Cervical, and Lung Cancer Prevention on Adolescent Prevention Behaviors SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article DE Cervical cancer; Skin cancer; Lung cancer; Prevention; Adolescent; Sunscreen; Papanicolaou test; Smoking cessation ID INTERGENERATIONAL TRANSMISSION; SMOKING; HEALTH AB Purpose: To explore whether maternal communication about behaviors that prevent skin, cervical, and lung cancer is associated with adolescent cancer prevention behaviors. Methods: The study sample consisted of 10,409 girls and boys (14-21 years) who participated in a longitudinal survey study of U. S. adolescents. The independent variables were adolescent report of how often mothers had spoken with them (never, once, occasionally, sometimes, often) about sunscreen use, Pap screening, and quitting smoking. Outcome variables included adolescent self-report of sunscreen use, Pap screening, and quitting smoking (among past-year smokers). We used multivariate logistic regression models to determine whether maternal communication in 2001 was associated independently with the three adolescent cancer prevention behaviors in 2001 and 2003. Results: In adjusted logistic regression models, maternal communication about sunscreen use and Pap screening was positively associated with adolescent behaviors in 2001 and 2003, and maternal communication about quitting smoking was positively associated with adolescent behavior in 2001. Conclusions: In a national sample, maternal communication encouraging sunscreen use, Pap screening, and quitting smoking was associated with the corresponding behaviors in their adolescent children. The findings suggest that intergenerational interventions could enhance adolescent practice of cancer prevention behaviors. (C) 2011 Society for Adolescent Health and Medicine. All rights reserved. C1 [Kahn, Jessica A.] Cincinnati Childrens Hosp Med Ctr, Div Adolescent Med, Cincinnati, OH 45229 USA. [Huang, Bin; Ding, Lili] Cincinnati Childrens Hosp Med Ctr, Ctr Epidemiol & Biostat, Cincinnati, OH 45229 USA. [Geller, Alan] Harvard Univ, Sch Publ Hlth, Dept Soc, Boston, MA 02115 USA. [Frazier, A. Lindsay] Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp, Boston, MA 02115 USA. [Frazier, A. Lindsay] Harvard Univ, Brigham & Womens Hosp, Channing Lab, Sch Med, Boston, MA 02115 USA. RP Kahn, JA (reprint author), Cincinnati Childrens Hosp Med Ctr, Div Adolescent Med, MLC 4000,3333 Burnet Ave, Cincinnati, OH 45229 USA. EM jessica.kahn@cchmc.org RI Ding, Lili/E-8018-2012; Huang, bin/G-2468-2014 FU American Cancer Society [RSGPB-04-009-01-CPPB] FX Supported by American Cancer Society # RSGPB-04-009-01-CPPB (Frazier, PI). NR 10 TC 1 Z9 1 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-139X EI 1879-1972 J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD JUL PY 2011 VL 49 IS 1 BP 93 EP 96 DI 10.1016/j.jadohealth.2010.11.247 PG 4 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA 782AA UT WOS:000291978400019 PM 21700165 ER PT J AU Palmer, KL Whiteley, M AF Palmer, Kelli L. Whiteley, Marvin TI DMS3-42: the Secret to CRISPR-Dependent Biofilm Inhibition in Pseudomonas aeruginosa SO JOURNAL OF BACTERIOLOGY LA English DT Editorial Material ID BACTERIA; ARCHAEA; PROKARYOTES; INFECTIONS; REPEATS C1 [Whiteley, Marvin] Univ Texas Austin, Sect Mol Genet & Microbiol, Inst Cellular & Mol Biol, Austin, TX 78712 USA. [Palmer, Kelli L.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Palmer, Kelli L.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Whiteley, M (reprint author), Univ Texas Austin, Sect Mol Genet & Microbiol, Inst Cellular & Mol Biol, Austin, TX 78712 USA. EM mwhiteley@mail.utexas.edu FU NEI NIH HHS [F32 EY020734-02, EY020734, F32 EY020734, F32 EY020734-01]; NIAID NIH HHS [5R01AI075068, R01 AI075068, R01 AI075068-04] NR 13 TC 8 Z9 9 U1 1 U2 10 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 JUL PY 2011 VL 193 IS 14 BP 3431 EP 3432 DI 10.1128/JB.05066-11 PG 2 WC Microbiology SC Microbiology GA 784DQ UT WOS:000292134900001 PM 21551309 ER PT J AU Bouxsein, ML AF Bouxsein, Mary L. TI Bone Structure and Fracture Risk: Do They Go Arm in Arm? SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Editorial Material ID POSTMENOPAUSAL WOMEN; DISTAL RADIUS; HR-PQCT; VERTEBRAL FRACTURES; MINERAL DENSITY; EPIDEMIOLOGY; OSTEOPOROSIS; TIBIA; MICROARCHITECTURE; ARCHITECTURE C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Ctr Adv Orthoped Studies,Endocrine Unit, Beth Israel Deaconess Med Ctr,Dept Orthopaed Surg, Boston, MA 02215 USA. RP Bouxsein, ML (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Ctr Adv Orthoped Studies,Endocrine Unit, Beth Israel Deaconess Med Ctr,Dept Orthopaed Surg, 330 Brookline Ave,RN 115, Boston, MA 02215 USA. EM mbouxsei@bidmc.harvard.edu NR 34 TC 6 Z9 6 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JUL PY 2011 VL 26 IS 7 BP 1389 EP 1391 DI 10.1002/jbmr.442 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 783DJ UT WOS:000292061400002 PM 21695731 ER PT J AU Powe, CE Ricciardi, C Berg, AH Erdenesanaa, D Collerone, G Ankers, E Wenger, J Karumanchi, SA Thadhani, R Bhan, I AF Powe, Camille E. Ricciardi, Catherine Berg, Anders H. Erdenesanaa, Delger Collerone, Gina Ankers, Elizabeth Wenger, Julia Karumanchi, S. Ananth Thadhani, Ravi Bhan, Ishir TI Vitamin D-Binding Protein Modifies the Vitamin D-Bone Mineral Density Relationship SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE VITAMIN D; VITAMIN D-BINDING PROTEIN; BONE MINERAL DENSITY; FREE HORMONE HYPOTHESIS; VITAMIN D DEFICIENCY ID RANDOMIZED CONTROLLED-TRIAL; NUTRITION EXAMINATION SURVEY; D SUPPLEMENTATION; ELDERLY-WOMEN; SERUM 25-HYDROXYVITAMIN-D; PLASMA-CONCENTRATIONS; POSITIVE ASSOCIATION; POSTMENOPAUSAL WOMEN; PREMENOPAUSAL WOMEN; PARATHYROID-HORMONE AB Studies examining the relationship between total circulating 25-hydroxyvitamin D [25(OH)D] levels and bone mineral density (BMD) have yielded mixed results. Vitamin D-binding protein (DBP), the major carrier protein for 25(OH)D, may alter the biologic activity of circulating vitamin D. We hypothesized that free and bioavailable 25(OH)D, calculated from total 25(OH)D, DBP, and serum albumin levels, would be more strongly associated with BMD than levels of total 25(OH)D. We measured total 25(OH)D, DBP, and serum albumin levels in 49 healthy young adults enrolled in the Metabolic Abnormalities in College-Aged Students (MACS) study. Lumbar spine BMD was measured in all subjects using dual-energy X-ray absorptiometry. Clinical, diet, and laboratory information also was gathered at this time. We determined free and bioavailable (free + albumin-bound) 25(OH)D using previously validated formulas and examined their associations with BMD. BMD was not associated with total 25(OH)D levels (r=0.172, p=.236). In contrast, free and bioavailable 25(OH)D levels were positively correlated with BMD (r=0.413, p=.003 for free, r=0.441, p=.002 for bioavailable). Bioavailable 25(OH)D levels remained independently associated with BMD in multivariate regression models adjusting for age, sex, body mass index, and race (p=.03). It is concluded that free and bioavailable 25(OH)D are more strongly correlated with BMD than total 25(OH)D. These findings have important implications for vitamin D supplementation in vitamin D-deficient states. Future studies should continue to explore the relationship between free and bioavailable 25(OH)D and health outcomes. (C) 2011 American Society for Bone and Mineral Research. C1 [Powe, Camille E.; Erdenesanaa, Delger; Collerone, Gina; Ankers, Elizabeth; Wenger, Julia; Thadhani, Ravi; Bhan, Ishir] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. [Powe, Camille E.; Erdenesanaa, Delger; Collerone, Gina; Ankers, Elizabeth; Wenger, Julia; Thadhani, Ravi; Bhan, Ishir] Harvard Univ, Sch Med, Boston, MA USA. [Ricciardi, Catherine] MIT, Clin Res Ctr, Boston, MA USA. [Berg, Anders H.] Beth Israel Deaconess Med Ctr, Dept Clin Chem, Div Clin Pathol, Boston, MA 02215 USA. [Karumanchi, S. Ananth] Howard Hughes Med Inst, Boston, MA 02115 USA. [Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Dept Med, Div Nephrol, Boston, MA 02215 USA. [Karumanchi, S. Ananth] Harvard Univ, Sch Med, Boston, MA USA. RP Thadhani, R (reprint author), Massachusetts Gen Hosp, Dept Med, Div Nephrol, Bullfinch 127, Boston, MA 02114 USA. EM thadhani.r@mgh.harvard.edu FU Abbott; National Center for Research Resources [M01-(RR-01066)] FX The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. RT has grant support from Abbott. All the other authors state that they have no conflicts of interest.; The project described herein, conducted at the Clinical Research Center (CRC) of the Massachusetts Institute of Technology, was supported by Grant Number M01-(RR-01066)-Harvard Clinical and Translational Science Center, from the National Center for Research Resources. NR 51 TC 132 Z9 134 U1 0 U2 14 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 JUL PY 2011 VL 26 IS 7 BP 1609 EP 1616 DI 10.1002/jbmr.387 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 783DJ UT WOS:000292061400024 PM 21416506 ER PT J AU Gordon, CM Gordon, LB Snyder, BD Nazarian, A Quinn, N Huh, S Giobbie-Hurder, A Neuberg, D Cleveland, R Kleinman, M Miller, DT Kieran, MW AF Gordon, Catherine M. Gordon, Leslie B. Snyder, Brian D. Nazarian, Ara Quinn, Nicolle Huh, Susanna Giobbie-Hurder, Anita Neuberg, Donna Cleveland, Robert Kleinman, Monica Miller, David T. Kieran, Mark W. TI Hutchinson-Gilford Progeria Is a Skeletal Dysplasia SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE BONE QCT; CLINICAL/PEDIATRICS; BONE DENSITOMETRY; OSTEOPOROSIS; BONE MINERALIZATION ID MOUSE MODEL; COMPUTED-TOMOGRAPHY; BONE; CHILDREN; DEFECTS; DISEASE AB Hutchinson-Gilford progeria syndrome (HGPS) is a rare segmental premature aging disorder that affects bone and body composition, among other tissues. We sought to determine whether bone density and structural geometry are altered in children with HGPS and whether relationships exist among these parameters and measures of skeletal anthropometry, body composition, and nutrition. We prospectively enrolled 26 children with HGPS (ages 3.1 to 16.2 years). Outcomes included anthropometric data; bone age; areal bone mineral density (aBMD) and body composition by dual-energy X-ray absorptiometry (DXA); volumetric bone mineral density (vBMD), strength-strain index (SSI), and bone structural rigidity calculated from radial transaxial peripheral quantitative computed tomographic (pQCT) images; serum bone biomarkers and hormonal measures; and nutrition assessments. Children with HGPS had low axial aBMD Z-scores by DXA, which improved after adjustment for height age, whereas differences in radial vBMD by pQCT were less striking. However, pQCT revealed distinct abnormalities in both novel measures of bone structural geometry and skeletal strength at the radius compared with healthy controls. Dietary intake was adequate, confirming that HGPS does not represent a model of malnutrition-induced bone loss. Taken together, these findings suggest that the phenotype of HGPS represents a unique skeletal dysplasia. 2011 American Society for Bone and Mineral Research. C1 [Gordon, Catherine M.] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Adolescent Med, Boston, MA 02115 USA. [Gordon, Catherine M.] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Endocrinol, Boston, MA 02115 USA. [Gordon, Leslie B.] Brown Univ, Dept Pediat, Hasbro Childrens Hosp, Warren Alpert Med Sch, Providence, RI 02912 USA. [Gordon, Leslie B.; Kleinman, Monica] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Anesthesia, Boston, MA 02115 USA. [Snyder, Brian D.] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Orthoped, Boston, MA 02115 USA. [Snyder, Brian D.; Nazarian, Ara] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Orthopaed Surg,Ctr Adv Orthopaed Studies, Boston, MA 02115 USA. [Quinn, Nicolle] Childrens Hosp, Clin & Translat Study Unit, Boston, MA 02115 USA. [Huh, Susanna] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Gastroenterol & Nutr, Boston, MA 02115 USA. [Giobbie-Hurder, Anita] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Neuberg, Donna] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Cleveland, Robert] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Radiol, Boston, MA 02115 USA. [Miller, David T.] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Genet, Boston, MA 02115 USA. [Kieran, Mark W.] Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. RP Gordon, CM (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Div Adolescent Med, 300 Longwood Ave, Boston, MA 02115 USA. EM catherine.gordon@childrens.harvard.edu OI Kieran, Mark/0000-0003-2184-7692 FU Progeria Research Foundation [PRFCLIN2007-01]; NIH [MO1-RR02172]; Harvard Catalyst Clinical and Translational Study Unit (CTSU) [UL1 RR025758-01] FX The study was funded by the Progeria Research Foundation (PRFCLIN2007-01), by NIH grants to the Children's Hospital Boston GCRC (MO1-RR02172), and by the Harvard Catalyst Clinical and Translational Study Unit (CTSU; UL1 RR025758-01). Additional support was provided by the Stop&Shop Family Pediatric Brain Tumor Program. NR 28 TC 21 Z9 23 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JUL PY 2011 VL 26 IS 7 BP 1670 EP 1679 DI 10.1002/jbmr.392 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 783DJ UT WOS:000292061400031 PM 21445982 ER PT J AU Halliburton, SS Abbara, S Chen, MY Gentry, R Mahesh, M Raff, GL Shaw, LJ Hausleiter, J AF Halliburton, Sandra S. Abbara, Suhny Chen, Marcus Y. Gentry, Ralph Mahesh, Mahadevappa Raff, Gilbert L. Shaw, Leslee J. Hausleiter, Joerg TI SCCT guidelines on radiation dose and dose-optimization strategies in cardiovascular CT SO JOURNAL OF CARDIOVASCULAR COMPUTED TOMOGRAPHY LA English DT Article DE Practice guideline; Radiation dose; Radiation protection; Radiation monitoring; Tomography, x-ray computed; Cardiac-gated imaging techniques; Coronary CT angiography; Coronary calcium scanning; Algorithms ID DUAL-SOURCE CT; NONINVASIVE CORONARY-ANGIOGRAPHY; CARDIAC COMPUTED-TOMOGRAPHY; TUBE CURRENT MODULATION; STATISTICAL ITERATIVE RECONSTRUCTION; AMERICAN-HEART-ASSOCIATION; BISMUTH BREAST SHIELDS; IMPROVED IMAGE QUALITY; MULTISLICE HELICAL CT; MULTIDETECTOR ROW CT AB Over the last few years, computed tomography (CT) has developed into a standard clinical test for a variety of cardiovascular conditions. The emergence of cardiovascular CT during a period of dramatic increase in radiation exposure to the population from medical procedures and heightened concern about the subsequent potential cancer risk has led to intense scrutiny of the radiation burden of this new technique. This has hastened the development and implementation of dose reduction tools and prompted closer monitoring of patient dose. In an effort to aid the cardiovascular CT community in incorporating patient-centered radiation dose optimization and monitoring strategies into standard practice, the Society of Cardiovascular Computed Tomography has produced a guideline document to review available data and provide recommendations regarding interpretation of radiation dose indices and predictors of risk, appropriate use of scanner acquisition modes and settings, development of algorithms for dose optimization, and establishment of procedures for dose monitoring. (C) 2011 Society of Cardiovascular Computed Tomography. All rights reserved. C1 [Halliburton, Sandra S.] Cleveland Clin, Inst Heart & Vasc, Imaging Inst, Cleveland, OH 44195 USA. [Abbara, Suhny] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chen, Marcus Y.] NIH, Bethesda, MD 20892 USA. [Gentry, Ralph; Raff, Gilbert L.] William Beaumont Hosp, Royal Oak, MI 48072 USA. [Mahesh, Mahadevappa] Johns Hopkins Univ, Baltimore, MD USA. [Shaw, Leslee J.] Emory Univ, Atlanta, GA 30322 USA. [Hausleiter, Joerg] Deutsch Herzzentrum Munich, Munich, Germany. RP Halliburton, SS (reprint author), Cleveland Clin, Inst Heart & Vasc, Imaging Inst, 9500 Euclid Ave,J1-4, Cleveland, OH 44195 USA. EM hallibs@ccf.org FU Intramural NIH HHS [Z99 HL999999] NR 140 TC 191 Z9 204 U1 2 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-5925 J9 J CARDIOVASC COMPUT JI J. Cardiovasc. Comput. Tomogr. PD JUL-AUG PY 2011 VL 5 IS 4 BP 198 EP 224 DI 10.1016/j.jcct.2011.06.001 PG 27 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 035HF UT WOS:000310933300002 PM 21723512 ER PT J AU Ghoshhajra, BB Engel, LC Major, GP Verdini, D Sidhu, M Karolyi, M Abbara, S Hoffmann, U Kalra, M Brady, TJ AF Ghoshhajra, Brian B. Engel, Leif-Christopher Major, Gyoengyi Petra Verdini, Dan Sidhu, Manavjot Karolyi, Mihaly Abbara, Suhny Hoffmann, Udo Kalra, Manudeep Brady, Thomas J. TI Direct chest area measurement: A potential anthropometric replacement for BMI to inform cardiac CT dose parameters? SO JOURNAL OF CARDIOVASCULAR COMPUTED TOMOGRAPHY LA English DT Article DE Radiation dose; Cardiac CT angiography; Tube voltage; Contrast-to-noise ratio; Image quality; Linear regression; Second-generation dual-source CT ID BODY-FAT DISTRIBUTION; COMPUTED-TOMOGRAPHY; CORONARY-ANGIOGRAPHY; PEDIATRIC CT; RADIATION; CONTRAST; EXPOSURE; PROTOCOLS; IMPACT AB BACKGROUND: Significant dose reductions for coronary CT angiography (CTA) can be achieved with reduced tube potential (kV); however, the potential effect on image quality is unknown. OBJECTIVE: We sought to evaluate anthropometric measures (chest area, chest circumference, and chest attenuation) as potentially better predictors of the appropriate tube potential versus body mass index (BMI). METHODS: Consecutive patients (n = 183) who underwent routine coronary CTA (with standard department protocols, whereby tube potential was selected according to BMI) between April 2010 and October 2010 were included. All anthropometric measures were obtained by tracing a region of interest encompassing an entire axial full field-of-view image at the mid left atrial level. Linear regression was used to stratify patients into 4 chest area classes (very small to large). Patients were also stratified by standard BMI classes (underweight to obese). Qualitative and quantitative image quality parameters were compared between concordant and discordant chest area and BM I classes. RESULTS: A strong correlation was observed between patients' BMI and chest area (r = 0.84; P < 0.001) and between BMI and chest circumference (r = 0.82, P < 0.001). Concordance between chest area class and BMI class was found in 61%, whereas 17.6% of patients were "potentially underdosed" (chest area class > BMI class) and 21.4% were "potentially overdosed" (chest area class < BMI class). Signal and contrast of the proximal coronaries and left ventricle were significantly different between the groups. CONCLUSION: Patients' chest area and BMI classes were frequently discordant, potentially leading to overdosing or underdosing when using BMI to select tube potential. (C) 2011 Society of Cardiovascular Computed Tomography. All rights reserved. C1 [Major, Gyoengyi Petra; Verdini, Dan; Sidhu, Manavjot; Karolyi, Mihaly; Abbara, Suhny; Hoffmann, Udo; Kalra, Manudeep; Brady, Thomas J.] Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, Boston, MA 02114 USA. RP Engel, LC (reprint author), Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, 165 Cambridge St,Ste 400, Boston, MA 02114 USA. EM lengel@partners.org NR 24 TC 12 Z9 13 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-5925 J9 J CARDIOVASC COMPUT JI J. Cardiovasc. Comput. Tomogr. PD JUL-AUG PY 2011 VL 5 IS 4 BP 240 EP 246 DI 10.1016/j.jcct.2011.06.003 PG 7 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 035HF UT WOS:000310933300005 PM 21723515 ER PT J AU Techasith, T Ghoshhajra, BB Truong, QA Pale, R Nasir, K Bolen, MA Hoffmann, U Cury, RC Abbara, S Brady, TJ Blankstein, R AF Techasith, Tust Ghoshhajra, Brian B. Truong, Quynh A. Pale, Rodrigo Nasir, Khurram Bolen, Michael A. Hoffmann, Udo Cury, Ricardo C. Abbara, Suhny Brady, Thomas J. Blankstein, Ron TI The effect of heart rhythm on patient radiation dose with dual-source cardiac computed tomography SO JOURNAL OF CARDIOVASCULAR COMPUTED TOMOGRAPHY LA English DT Article DE Heart rhythm; Cardiac CT; Radiation dose ID 64-MDCT CORONARY-ANGIOGRAPHY; ATRIAL-FIBRILLATION; IMAGE QUALITY; DIAGNOSTIC-ACCURACY; INITIAL-EXPERIENCE; ARTERY-DISEASE; CT ANGIOGRAPHY; CHEST-PAIN; EXPOSURE; RISK AB BACKGROUND: To lower the radiation exposure associated with cardiac CT, it is essential to identify all factors that influence radiation dose. OBJECTIVES: We explored the effect of heart rhythm during scan acquisition on radiation dose with a 64-slice dual-source cardiac CT. METHODS: Patient and scan data were collected prospectively in 302 consecutive patients referred for a clinical dual-source cardiac CT. Electrocardiograms recorded during acquisition were interpreted by a cardiologist and categorized as (I) normal sinus rhythm (NSR), (2) premature atrial contraction (PAC) or premature ventricular contraction (PVC), or (3) atrial fibrillation or flutter. RESULTS: Of the 302 patients, 227 (75.2%) were in NSR and had no ectopy, 55 (18.2%) had PAC/PVC, and 20 (6.6%) had atrial fibrillation or flutter during the scan. Patients with irregular rhythm (PAC/PVC and atrial fibrillation or flutter) were older than patients with regular rhythm (61.0 vs 54.8 years; P = 0.006). Patients with NSR had the lowest estimated radiation dose, followed by PAC/PVC and atrial fibrillation/flutter (9.4, 14.5, 20.9 mSv: P < 0.001). The difference remained significant after adjustments for differences in examination type, tube current and voltage, scan length, pitch, and use of tube current modulation (9.8, 14.1, 17.9 mSv; P < 0.001). No significant association was observed between heart rhythm and subjective image quality although scans with regular rhythm and no ectopy had higher signal-to-noise and contrast-to-noise ratios (P < 0.01). CONCLUSION: Compared to patients with NSR, patients with atrial fibrillation/flutter had the highest radiation exposure, followed by those with PAC/PVC. Even after adjustment for factors associated with radiation exposure, a significant difference in radiation dose persisted. These findings can be used to identify patients who are more likely to receive higher radiation dose when undergoing cardiac CT and to develop future more-efficient scanner algorithms for use in patients with arrhythmias. (C) 2011 Society of Cardiovascular Computed Tomography. All rights reserved. C1 [Techasith, Tust; Ghoshhajra, Brian B.; Truong, Quynh A.; Hoffmann, Udo; Cury, Ricardo C.; Abbara, Suhny; Brady, Thomas J.; Blankstein, Ron] Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Techasith, Tust; Ghoshhajra, Brian B.; Truong, Quynh A.; Hoffmann, Udo; Cury, Ricardo C.; Abbara, Suhny; Brady, Thomas J.; Blankstein, Ron] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Techasith, Tust; Ghoshhajra, Brian B.; Truong, Quynh A.; Hoffmann, Udo; Cury, Ricardo C.; Abbara, Suhny; Brady, Thomas J.; Blankstein, Ron] Harvard Univ, Sch Med, Boston, MA USA. [Pale, Rodrigo] Inst Nacl Cardiol Ignacio Chavez, CT Dept, Mexico City, DF, Mexico. [Nasir, Khurram] Yale New Haven Med Ctr, Dept Cardiol, New Haven, CT 06504 USA. [Bolen, Michael A.] Cleveland Clin, Imaging Inst, Cardiovasc Div, Cleveland, OH 44106 USA. [Cury, Ricardo C.] Baptist Cardiac & Vasc Inst, Miami, FL USA. [Blankstein, Ron] Brigham & Womens Hosp, Dept Med & Radiol, Noninvas Cardiovasc Imaging Program, Boston, MA 02115 USA. RP Blankstein, R (reprint author), Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, Boston, MA 02114 USA. EM rblankstein@partners.org FU National Institutes of Health [1T32 HL076136-02] FX R.B., B.B.G., and Q.A.T. received support from the National Institutes of Health (grant 1T32 HL076136-02). NR 30 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 1934-5925 J9 J CARDIOVASC COMPUT JI J. Cardiovasc. Comput. Tomogr. PD JUL-AUG PY 2011 VL 5 IS 4 BP 255 EP 263 DI 10.1016/j.jcct.2011.05.003 PG 9 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 035HF UT WOS:000310933300007 PM 21723517 ER PT J AU Hoffmann, U Lee, JH Qin, T Eikermann-Haerter, K Ayata, C AF Hoffmann, Ulrike Lee, Jeong Hyun Qin, Tao Eikermann-Haerter, Katharina Ayata, Cenk TI Gabapentin reduces infarct volume but does not suppress peri-infarct depolarizations SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE gabapentin; peri-infarct depolarization; spreading depression; stroke ID CORTICAL SPREADING DEPRESSION; ISCHEMIA; RATS; NEUROPROTECTION; MODELS AB Spreading depression (SD) is an intense depolarization wave implicated in brain injury. In focal ischemia, recurrent peri-infarct depolarization (PID) waves akin to SD worsen the ischemic injury by exacerbating the blood flow-metabolism mismatch. We recently showed that gabapentin suppresses SD. We, therefore, tested gabapentin on PIDs and stroke outcome. Gabapentin pretreatment (200 mg/kg, intravenously) reduced the infarct volume by 23% after transient focal ischemia in mice. However, the frequency and duration of PIDs were not suppressed when recorded for 2 hours during ischemia, suggesting that gabapentin reduces infarct volume independent of PID suppression. Journal of Cerebral Blood Flow & Metabolism (2011) 31, 1578-1582; doi: 10.1038/jcbfm.2011.50; published online 20 April 2011 C1 [Hoffmann, Ulrike; Lee, Jeong Hyun; Qin, Tao; Eikermann-Haerter, Katharina; Ayata, Cenk] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurovasc Res Lab,Dept Radiol, Charlestown, MA 02129 USA. [Ayata, Cenk] Harvard Univ, Massachusetts Gen Hosp, Stroke Serv & Neurosci Intens Care Unit, Sch Med,Dept Neurol, Charlestown, MA 02129 USA. RP Ayata, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurovasc Res Lab,Dept Radiol, 149 13th St,Room 6408, Charlestown, MA 02129 USA. EM cayata@partners.org RI Lee, Jeong Hyun/G-1676-2013 OI Lee, Jeong Hyun/0000-0003-0504-0119 FU National Institute of Health [NS061505, NS055104]; Deutsche Forschungsgemeinschaft [HO 4211/1-1]; American Heart Association [10SDG2610275] FX This work was supported by the National Institute of Health (NS061505, NS055104), Deutsche Forschungsgemeinschaft (HO 4211/1-1) and the American Heart Association (10SDG2610275). NR 15 TC 3 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 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUL PY 2011 VL 31 IS 7 BP 1578 EP 1582 DI 10.1038/jcbfm.2011.50 PG 5 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 786FD UT WOS:000292287800009 PM 21505480 ER PT J AU Woods, DW Piacentini, JC Scahill, L Peterson, AL Wilhelm, S Chang, S Deckersbach, T McGuire, J Specht, M Conelea, CA Rozenman, M Dzuria, J Liu, HB Levi-Pearl, S Walkup, JT AF Woods, Douglas W. Piacentini, John C. Scahill, Lawrence Peterson, Alan L. Wilhelm, Sabine Chang, Susanna Deckersbach, Thilo McGuire, Joseph Specht, Matt Conelea, Christine A. Rozenman, Michelle Dzuria, James Liu, Haibei Levi-Pearl, Sue Walkup, John T. TI Behavior Therapy for Tics in Children: Acute and Long-Term Effects on Psychiatric and Psychosocial Functioning SO JOURNAL OF CHILD NEUROLOGY LA English DT Article DE Tourette disorder; tics; behavior therapy; secondary outcomes ID DEFICIT HYPERACTIVITY DISORDER; TOURETTE-SYNDROME; DOUBLE-BLIND; COMMUNITY SAMPLE; CONTROLLED-TRIAL; SELF-REPORT; PIMOZIDE; RISPERIDONE; PLACEBO; SCALE AB Children (n - 126) ages 9 to 17 years with chronic tic or Tourette disorder were randomly assigned to receive either behavior therapy or a control treatment over 10 weeks. This study examined acute effects of behavior therapy on secondary psychiatric symptoms and psychosocial functioning and long-term effects on these measures for behavior therapy responders only. Baseline and end point assessments conducted by a masked independent evaluator assessed several secondary psychiatric symptoms and measures of psychosocial functioning. Responders to behavior therapy at the end of the acute phase were reassessed at 3-month and 6-month follow-up. Children in the behavior therapy and control conditions did not differentially improve on secondary psychiatric or psychosocial outcome measures at the end of the acute phase. At 6-month posttreatment, positive response to behavior therapy was associated with decreased anxiety, disruptive behavior, and family strain and improved social functioning. Behavior therapy is a tic-specific treatment for children with tic disorders. C1 [Woods, Douglas W.; Conelea, Christine A.] Univ Wisconsin, Milwaukee, WI 53211 USA. [Piacentini, John C.; Chang, Susanna; Rozenman, Michelle] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA USA. [Scahill, Lawrence; McGuire, Joseph; Dzuria, James; Liu, Haibei] Yale Child Study Ctr, New Haven, CT USA. [Peterson, Alan L.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Wilhelm, Sabine; Deckersbach, Thilo] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wilhelm, Sabine; Deckersbach, Thilo] Harvard Univ, Sch Med, Boston, MA USA. [Specht, Matt; Walkup, John T.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. [Levi-Pearl, Sue] Tourette Syndrome Assoc, Bayside, NY USA. RP Woods, DW (reprint author), Univ Wisconsin, 2441 E Hartford Ave, Milwaukee, WI 53211 USA. EM dwoods@uwm.edu OI Conelea, Christine/0000-0003-2791-9802; Scahill, Lawrence/0000-0001-5073-1707 FU National Institute of Mental Health [R01MH070802]; Yale University; National Center for Research Resources, NIH [UL1 RR 024139] FX The authors disclosed receipt of the following financial support for the research and/or authorship of this article: This work was supported by grant R01MH070802 from the National Institute of Mental Health to Dr Piacentini, with subcontracts to Drs Woods, Scahill, Wilhelm, Peterson, and Walkup. Drs. Scahill, Dzuria, and Liu receive support from the Yale University Clinical and Translational Sciences Award grant UL1 RR 024139 from the National Center for Research Resources, NIH. NR 41 TC 24 Z9 24 U1 1 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0883-0738 J9 J CHILD NEUROL JI J. Child Neurol. PD JUL PY 2011 VL 26 IS 7 BP 858 EP 865 DI 10.1177/0883073810397046 PG 8 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 785DK UT WOS:000292207400010 PM 21555779 ER PT J AU Jones, D Glimcher, LH Aliprantis, AO AF Jones, Dallas Glimcher, Laurie H. Aliprantis, Antonios O. TI Osteoimmunology at the nexus of arthritis, osteoporosis, cancer, and infection SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID OSTEOCLAST DIFFERENTIATION FACTOR; DIRECTLY INDUCE OSTEOCLASTOGENESIS; BONE-MINERAL DENSITY; TOLL-LIKE RECEPTORS; T-CELL-ACTIVATION; RHEUMATOID-ARTHRITIS; MULTIPLE-MYELOMA; ZOLEDRONIC ACID; TNF-ALPHA; KAPPA-B AB Over the past decade and a half, the biomedical community has uncovered a previously unappreciated reciprocal relationship between cells of the immune and skeletal systems. Work in this field, which has been termed "osteoimmunology," has resulted in the development of clinical therapeutics for seemingly disparate diseases linked by the common themes of inflammation and bone remodeling. Here, the important concepts and discoveries in osteoimmunology are discussed in the context of the diseases bridging these two organ systems, including arthritis, osteoporosis, cancer, and infection, and the targeted treatments used by clinicians to combat them. C1 [Jones, Dallas; Glimcher, Laurie H.; Aliprantis, Antonios O.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Jones, Dallas; Glimcher, Laurie H.; Aliprantis, Antonios O.] Brigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. [Jones, Dallas; Glimcher, Laurie H.; Aliprantis, Antonios O.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Glimcher, Laurie H.] Harvard Univ, Massachusetts Gen Hosp, Ragon Inst, Boston, MA 02115 USA. [Glimcher, Laurie H.] MIT, Boston, MA USA. RP Aliprantis, AO (reprint author), Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, 651 Huntington Ave,FXB 205, Boston, MA 02115 USA. EM aaliprantis@partners.org FU Merck and Co. Inc.; Burroughs Wellcome Fund; National Institute of Arthritis and Musculoskeletal and Skin Diseases [K08AR054859]; NIH [HD055601, K99AR055668] FX Laurie H. Glimcher is a director of the Bristol-Myers Squibb Pharmaceutical Co. and holds equity therein. Laurie H. Glimcher is supported by a sponsored research grant From Merck and Co. Inc.; Antonios O. Aliprantis holds a Career Award for Medical Scientists from the Burroughs Wellcome Fund and is supported by award number K08AR054859 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. This work was also supported by NIH grants HD055601 (to L.H. Glimcher) and K99AR055668 (to D. Jones). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Arthritis and Musculoskeletal and Skin Diseases or the NIH. NR 127 TC 34 Z9 35 U1 1 U2 7 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 2011 VL 121 IS 7 BP 2534 EP 2542 DI 10.1172/JCI46262 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 787YQ UT WOS:000292413000003 PM 21737885 ER PT J AU Marotta, LLC Almendro, V Marusyk, A Shipitsin, M Schemme, J Walker, SR Bloushtain-Qimron, N Kim, JJ Choudhury, SA Maruyama, R Wu, Z Gonen, M Mulvey, LA Bessarabova, MO Huh, SJ Silver, SJ Kim, SY Park, SY Lee, HE Anderson, KS Richardson, AL Nikolskaya, T Nikolsky, Y Liu, XS Root, DE Hahn, WC Frank, DA Polyak, K AF Marotta, Lauren L. C. Almendro, Vanessa Marusyk, Andriy Shipitsin, Michail Schemme, Janina Walker, Sarah R. Bloushtain-Qimron, Noga Kim, Jessica J. Choudhury, Sibgat A. Maruyama, Reo Wu, Zhenhua Goenen, Mithat Mulvey, Laura A. Bessarabova, Marina O. Huh, Sung Jin Silver, Serena J. Kim, So Young Park, So Yeon Lee, Hee Eun Anderson, Karen S. Richardson, Andrea L. Nikolskaya, Tatiana Nikolsky, Yuri Liu, X. Shirley Root, David E. Hahn, William C. Frank, David A. Polyak, Kornelia TI The JAK2/STAT3 signaling pathway is required for growth of CD44(+)CD24(-) stem cell-like breast cancer cells in human tumors SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID GENE-EXPRESSION SIGNATURE; STAT3 ACTIVATION; IN-SITU; METASTASIS; SURVIVAL; CARCINOMA; IL-6; THERAPY; IDENTIFICATION; HETEROGENEITY AB Intratumor heterogeneity is a major clinical problem because tumor cell subtypes display variable sensitivity to therapeutics and may play different roles in progression. We previously characterized 2 cell populations in human breast tumors with distinct properties: CD44(+)CD24(-) cells that have stem cell-like characteristics, and CD44(-)CD24(+) cells that resemble more differentiated breast cancer cells. Here we identified 15 genes required for cell growth or proliferation in CD44(+)CD24(-) human breast cancer cells in a large-scale loss-of-function screen and found that inhibition of several of these (IL6, PTGIS, HAS1, CXCL3, and PFKFB3) reduced Stat3 activation. We found that the IL-6/JAK2/Stat3 pathway was preferentially active in CD44(+)CD24(-) breast cancer cells compared with other tumor cell types, and inhibition of JAK2 decreased their number and blocked growth of xenografts. Our results highlight the differences between distinct breast cancer cell types and identify targets such as JAK2 and Stat3 that may lead to more specific and effective breast cancer therapies. C1 [Marotta, Lauren L. C.; Almendro, Vanessa; Marusyk, Andriy; Shipitsin, Michail; Schemme, Janina; Walker, Sarah R.; Bloushtain-Qimron, Noga; Kim, Jessica J.; Choudhury, Sibgat A.; Maruyama, Reo; Mulvey, Laura A.; Huh, Sung Jin; Kim, So Young; Anderson, Karen S.; Hahn, William C.; Frank, David A.; Polyak, Kornelia] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Marotta, Lauren L. C.; Kim, Jessica J.; Frank, David A.; Polyak, Kornelia] Harvard Univ, Sch Med, Program Biol & Biomed Sci, Boston, MA USA. [Almendro, Vanessa; Marusyk, Andriy; Shipitsin, Michail; Walker, Sarah R.; Choudhury, Sibgat A.; Maruyama, Reo; Huh, Sung Jin; Kim, So Young; Anderson, Karen S.; Hahn, William C.; Frank, David A.; Polyak, Kornelia] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Almendro, Vanessa; Marusyk, Andriy; Shipitsin, Michail; Walker, Sarah R.; Choudhury, Sibgat A.; Maruyama, Reo; Huh, Sung Jin; Kim, So Young; Hahn, William C.; Frank, David A.; Polyak, Kornelia] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Almendro, Vanessa] Hosp Clin Barcelona, Inst Invest Biomed August Pi & Sunyer, Barcelona, Spain. [Wu, Zhenhua; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Wu, Zhenhua; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Goenen, Mithat] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Bessarabova, Marina O.; Hahn, William C.] Russian Acad Sci, Vavilov Inst Gen Genet, Moscow, Russia. [Silver, Serena J.; Kim, So Young; Root, David E.; Hahn, William C.] MIT, Broad Inst, Cambridge, MA 02139 USA. [Park, So Yeon; Lee, Hee Eun] Seoul Natl Univ, Coll Med, Dept Pathol, Seoul 151, South Korea. [Park, So Yeon; Lee, Hee Eun] Seoul Natl Univ, Bundang Hosp, Dept Pathol, Songnam, Gyeonggi, South Korea. [Richardson, Andrea L.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA USA. [Richardson, Andrea L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Nikolskaya, Tatiana; Nikolsky, Yuri] GeneGo Inc, St Joseph, MI USA. RP Polyak, K (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St D740C, Boston, MA 02115 USA. EM Kornelia_Polyak@dfci.harvard.edu RI Park, So Yeon/A-2621-2012; Lee, Hee Eun/G-6372-2011; Seoul National University, Pathology/B-6702-2012; Gonen, Mithat/E-4826-2012; Nikolskaya, Tatiana/M-5008-2013 FU Novartis Oncology; Novartis Pharmaceuticals Inc.; National Cancer Institute [P50 CA89383-07, NS50830, MH079826, R33 CA12862]; American Cancer Society [RSG-05-154-01-MGO]; US Army [W81XWH-07-1-04-8, BC087579]; Breast Cancer Research Foundation; Snyder Medical Foundation; Susan G. Komen Foundation; Tern Brodeur Foundation; Cellex Foundation FX Kornelia Polyak and William C. Hahn receive research support from Novartis Oncology and are consultants to Novartis Oncology. Kornelia Polyak serves on the Scientific Advisory Board of Metamark Genetics Inc. and Theracrine Inc. and holds AVEO Pharmaceuticals Inc. stocks.; We thank the members of the Broad RNAi Platform, the DFCI RNAi Screening Facility, and the Wistar Institute who provided technical assistance with this work, and we thank A. Partridge and J. Bahen for their help with collecting tissue samples. We also thank M. Brown, J. Brugge, and D. Pellman and members of the Polyak lab for their critical reading of the manuscript and advice during the course of this project. We thank C. Pissot-Soldermann, F. Baffert, and T. Radimerski (Novartis Institutes for BioMedical Research, Basel, Switzerland) for providing BSK805 compound and advice on its use. This work was supported by Novartis Pharmaceuticals Inc. (to K. Polyak), the National Cancer Institute (P50 CA89383-07 to K. Polyak and A.L. Richardson; NS50830 and MH079826 to D.A. Frank; and R33 CA12862 to W.C. Hahn), the American Cancer Society (RSG-05-154-01-MGO to K. Polyak), US Army Congressionally Directed Medical Research Program (W81XWH-07-1-04-8 to W.C. Hahn; BC087579 to A. Marusyk), the Breast Cancer Research Foundation (to K. Polyak, A.L. Richardson, and D.A. Frank), the Snyder Medical Foundation (to W.C. Hahn), the Susan G. Komen Foundation (to D.A. Frank, M. Shipitsin, and R. Maruyama), the Tern Brodeur Foundation (to S.A. Choudhury), and the Cellex Foundation (to V. Almendro). We thank the late Candice Maxwell Bahen for her donation. NR 63 TC 281 Z9 285 U1 3 U2 44 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 JUL PY 2011 VL 121 IS 7 BP 2723 EP 2735 DI 10.1172/JCI44745 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 787YQ UT WOS:000292413000022 PM 21633165 ER PT J AU Vlantis, K Wullaert, A Sasaki, Y Schmidt-Supprian, M Rajewsky, K Roskams, T Pasparakis, M AF Vlantis, Katerina Wullaert, Andy Sasaki, Yoshiteru Schmidt-Supprian, Marc Rajewsky, Klaus Roskams, Tania Pasparakis, Manolis TI Constitutive IKK2 activation in intestinal epithelial cells induces intestinal tumors in mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID NF-KAPPA-B; COLITIS-ASSOCIATED CANCER; ADULT STEM-CELLS; BETA-CATENIN; COLON-CANCER; APC GENE; TRANSCRIPTION FACTOR; MOUSE MODEL; COLORECTAL-CANCER; NEMO/IKK-GAMMA AB Many cancers display increased NF-kappa B activity, and NF-kappa B inhibition is known to diminish tumor development in multiple mouse models, supporting an important role of NF-kappa B in carcinogenesis. NF-kappa B activation in premalignant or cancer cells is believed to promote tumor development mainly by protecting these cells from apoptosis. However, it remains unclear to what extent NF-kappa B activation exhibits additional protumorigenic functions in premalignant cells that could be sufficient to induce spontaneous tumor development. Here we show that expression of constitutively active I kappa B kinase 2 (IKK2ca) in mouse intestinal epithelial cells (IECs) induced spontaneous tumors in aged mice and also strongly enhanced chemical- and Apc mutation-mediated carcinogenesis. IECs expressing IKK2ca displayed altered Wnt signaling and increased proliferation and elevated expression of genes encoding intestinal stem cell-associated factors including Ascl2, Olfm4, DLK1, and Bmi-1, indicating that increased IKK2/NF-kappa B activation synergized with Wnt signaling to drive intestinal tumorigenesis. Moreover, IECs expressing IKK2ca produced cytokines and chemokines that induced the recruitment of myeloid cells and activated stromal fibroblasts to become myofibroblasts, thus creating a tumor-promoting microenvironment. Taken together, our results show that constitutively increased activation of IKK2/NF-kappa B signaling in the intestinal epithelium is sufficient to induce the full spectrum of cell-intrinsic and stromal alterations required for intestinal tumorigenesis. C1 [Vlantis, Katerina; Wullaert, Andy; Pasparakis, Manolis] Univ Cologne, Inst Genet, Ctr Mol Med CMMC, D-50674 Cologne, Germany. [Vlantis, Katerina; Wullaert, Andy; Pasparakis, Manolis] Univ Cologne, Cologne Excellence Cluster Cellular Stress Respon, D-50674 Cologne, Germany. [Sasaki, Yoshiteru; Schmidt-Supprian, Marc; Rajewsky, Klaus] Immune Dis Inst, Boston, MA USA. [Sasaki, Yoshiteru] RIKEN Ctr Dev Biol, Lab Stem Cell Biol, Kobe, Hyogo, Japan. [Schmidt-Supprian, Marc] Max Planck Inst Biochem, D-82152 Martinsried, Germany. [Roskams, Tania] Univ Leuven, Univ Hosp, Dept Pathol, Louvain, Belgium. RP Pasparakis, M (reprint author), Univ Cologne, Inst Genet, Ctr Mol Med CMMC, Zulpicher Str 47A, D-50674 Cologne, Germany. EM pasparakis@uni-koeln.de RI Schmidt-Supprian, Marc/F-5893-2011; OI Schmidt-Supprian, Marc/0000-0002-8543-6166; Wullaert, Andy/0000-0001-5012-654X; Pasparakis, Manolis/0000-0002-9870-0966 FU European Commission [INFLA-CARE, 223151]; Deutsche Forschungsgemeinschaft FX We wish to thank C. Uthoff-Hachenberg, J. Pfeiffer, E. Mahlberg, D. Beier, J. Buchholz, B. Huelser, and B. Wolff for excellent technical assistance. We also thank Alan Clarke for valuable discussions. This work was supported by the European Commission FP7 program grant INFLA-CARE (EC contract number 223151) and by grants from the Deutsche Forschungsgemeinschaft to M. Pasparakis. NR 67 TC 42 Z9 42 U1 1 U2 10 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 JUL PY 2011 VL 121 IS 7 BP 2781 EP 2793 DI 10.1172/JCI45349 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 787YQ UT WOS:000292413000026 PM 21701067 ER PT J AU Lockhart, SR Wagner, D Iqbal, N Pappas, PG Andes, DR Kauffman, CA Brumble, LM Hadley, S Walker, R Ito, JI Baddley, JW Chiller, T Park, BJ AF Lockhart, Shawn R. Wagner, Debra Iqbal, Naureen Pappas, Peter G. Andes, David R. Kauffman, Carol A. Brumble, Lisa M. Hadley, Susan Walker, Randall Ito, James I. Baddley, John W. Chiller, Tom Park, Benjamin J. TI Comparison of In Vitro Susceptibility Characteristics of Candida Species from Cases of Invasive Candidiasis in Solid Organ and Stem Cell Transplant Recipients: Transplant-Associated Infections Surveillance Network (TRANSNET), 2001 to 2006 SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID GLOBAL ANTIFUNGAL SURVEILLANCE; BONE-MARROW-TRANSPLANTATION; STANDARDIZED DISK DIFFUSION; FUNGAL-INFECTIONS; IMMUNOCOMPROMISED PATIENTS; FLUCONAZOLE PROPHYLAXIS; ACTIVE SURVEILLANCE; UNITED-STATES; EPIDEMIOLOGY; KRUSEI AB Invasive fungal infections (IFI) are a major cause of morbidity and mortality among both solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients. Candida is the most common cause of IFI in SOT recipients and the second most common cause of IFI in HSCT recipients. We determined susceptibilities to fluconazole, voriconazole, itraconazole, posaconazole, amphotericin B, and caspofungin for 383 invasive Candida sp. isolates from SOT and HSCT recipients enrolled in the Transplant-Associated Infection Surveillance Network and correlated these results to clinical data. Fluconazole resistance in C. albicans, C. tropicalis, and C. parapsilosis isolates was low (1%), but the high percentage of C. glabrata and C. krusei isolates within this group of patients increased the overall percentage of fluconazole resistance to 16%. Voriconazole resistance was 3% overall but was 8% among C. glabrata isolates. On multivariable analysis, among HSCT recipients fluconazole nonsusceptibility was independently associated with C. glabrata, non-Hodgkin's lymphoma, cytomegalovirus (CMV) antigenemia, diabetes active at the time of the IFI, and any prior amphotericin B use; among SOT recipients, fluconazole nonsusceptibility was independently associated with any fluconazole use in the 3 months prior to the IFI, C. glabrata, ganciclovir use in the 3 months prior to the IFI, diabetes acquired since the transplant, and gender. C1 [Lockhart, Shawn R.; Wagner, Debra; Iqbal, Naureen; Chiller, Tom; Park, Benjamin J.] Ctr Dis Control & Prevent, Mycot Dis Branch, Atlanta, GA 30333 USA. [Pappas, Peter G.; Baddley, John W.] Univ Alabama, Dept Med, Div Infect Dis & Prevent Med, Birmingham, AL 35294 USA. [Andes, David R.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. [Kauffman, Carol A.] Univ Michigan, Ann Arbor, MI 48109 USA. [Kauffman, Carol A.] Vet Affairs Ann Arbor Healthcare Syst, Ann Arbor, MI USA. [Brumble, Lisa M.] Mayo Clin, Jacksonville, FL 32224 USA. [Hadley, Susan] Tufts Med Ctr, Boston, MA USA. [Walker, Randall] Mayo Clin, Coll Med, Rochester, MN USA. [Ito, James I.] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Baddley, John W.] Birmingham Vet Affairs Med Ctr, Dept Med, Div Infect Dis, Birmingham, AL USA. RP Lockhart, SR (reprint author), Ctr Dis Control & Prevent, Mycot Dis Branch, 1600 Clifton Rd NE,Mailstop G-11, Atlanta, GA 30333 USA. EM gyi2@cdc.gov FU Astellas; Pfizer; Merck; Schering-Plough FX TRANSNET was sponsored by Astellas, Pfizer, Merck, and Schering-Plough.; Potential conflicts of interest are as follows: P.G.P. receives research support from and is an ad hoc advisor for Merck, Pfizer, and Astellas; J.W.B. received research support from Pfizer and is a consultant/advisor for Merck and Pfizer; J.I.I. received honoraria for speaker activities from Astellas, Cubist, and Pfizer; D.R.A. has received grants from and is a consultant for Merck, Astellas, and Pfizer; and C.A.K. receives research support from Merck and chairs a data adjudication committee for Pfizer. All other authors have no conflicts. NR 34 TC 17 Z9 17 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUL PY 2011 VL 49 IS 7 BP 2404 EP 2410 DI 10.1128/JCM.02474-10 PG 7 WC Microbiology SC Microbiology GA 786BC UT WOS:000292276200004 PM 21562099 ER PT J AU Walcott, BP Pisapia, JM Nahed, BV Kahle, KT Ogilvy, CS AF Walcott, Brian P. Pisapia, Jared M. Nahed, Brian V. Kahle, Kristopher T. Ogilvy, Christopher S. TI Early experience with flow diverting endoluminal stents for the treatment of intracranial aneurysms SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Review DE Blood vessel prosthesis; Intracranial aneurysm; Stents; Subarachnoid hemorrhage; Surgical procedures; Therapeutic embolization; Vascular review ID PIPELINE EMBOLIZATION DEVICE; WIDE-NECKED ANEURYSMS; ENDOVASCULAR TREATMENT; SUBARACHNOID HEMORRHAGE; CLINICAL-EXPERIENCE; SACCULAR ANEURYSMS; CAROTID-ARTERY; RECONSTRUCTION; IMPLANTATION; BYPASS AB We aimed to identify the initial preliminary experience with flow diverting stents (FDS) for the treatment of intracranial aneurysms (IA). A PubMed search was performed to identify studies reporting patients treated with FDS. Selection was made for studies that provided either immediate or short term follow-up data. For each study, the number of patients and IA were identified. Details regarding the aneurysm itself were recorded; such as aneurysm morphology (saccular or fusiform), location, and rupture status. The primary treatment modality and the number of stents used to treat each aneurysm was recorded along with the antiplatelet regimen used. Outcomes such as aneurysm occlusion and complications, including stroke, in-stent thrombosis and stenosis, and death were identified. The average length of follow-up was calculated in weeks. A total of 10 manuscripts reporting 206 IA in 190 patients were identified in the literature. Occlusion rates were variably reported, ranging from 58% to 94% in the larger series. Major complications of treatment included stroke (6.0%), in-stent thrombosis and stenosis (4.9%), and death (3.3%). A phenomenon of delayed aneurysm rupture was also identified. We concluded that flow diverting stents have proven effective in a variety of scenarios. The major complications with FDS have related to perforator artery stroke, aneurysm re-rupture, and in-stent stenosis and thrombosis. Long-term efficacy, optimal antithrombotic agent regimen, and perforator stroke risk are yet to be determined. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Walcott, Brian P.; Nahed, Brian V.; Kahle, Kristopher T.; Ogilvy, Christopher S.] Massachusetts Gen Hosp, Dept Neurol Surg, Boston, MA 02114 USA. [Walcott, Brian P.; Nahed, Brian V.; Kahle, Kristopher T.; Ogilvy, Christopher S.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Pisapia, Jared M.] Univ Penn, Sch Med, Dept Neurol Surg, Philadelphia, PA 19104 USA. RP Walcott, BP (reprint author), Massachusetts Gen Hosp, Dept Neurol Surg, White Bldg,Room 502,55 Fruit St, Boston, MA 02114 USA. EM Walcott.brian@mgh.harvard.edu NR 41 TC 18 Z9 19 U1 0 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-5868 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD JUL PY 2011 VL 18 IS 7 BP 891 EP 894 DI 10.1016/j.jocn.2011.01.002 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 783FK UT WOS:000292066700004 PM 21571535 ER PT J AU Houvras, Y Wirth, LJ AF Houvras, Yariv Wirth, Lori J. TI Cabozantinib in Medullary Thyroid Carcinoma: Time to Focus the Spotlight on This Rare Disease SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID STANDARDIZED SURGICAL APPROACH; 80 CONSECUTIVE PATIENTS; PHASE-II; ALTERNATING COMBINATION; CONTEMPORARY SERIES; CANCER; GUIDELINES; MANAGEMENT C1 [Houvras, Yariv; Wirth, Lori J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Houvras, Y (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 22 TC 1 Z9 1 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 JUL 1 PY 2011 VL 29 IS 19 BP 2616 EP 2618 DI 10.1200/JCO.2010.34.0505 PG 4 WC Oncology SC Oncology GA 785EP UT WOS:000292210500012 PM 21606409 ER PT J AU Wo, JY Chen, K Neville, BA Lin, NU Punglia, RS AF Wo, Jennifer Y. Chen, Kun Neville, Bridget A. Lin, Nancy U. Punglia, Rinaa S. TI Effect of Very Small Tumor Size on Cancer-Specific Mortality in Node-Positive Breast Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT Breast Cancer Symposium of the American-Society-of-Clinical-Oncology CY OCT 08-10, 2009 CL San Francisco, CA SP Amer Soc Clin Oncol ID AXILLARY METASTASES; ADJUVANT THERAPY; CLINICAL-TRIALS; SURVIVAL; INVASION; AGE; CELLS AB Purpose Traditionally, larger tumor size and increasing lymph node (LN) involvement have been considered independent predictors of increased breast cancer-specific mortality (BCSM). We sought to characterize the interaction between tumor size and LN involvement in determination of BCSM. In particular, we evaluated whether very small tumor size may predict for increased BCSM relative to larger tumors in patients with extensive LN involvement. Patients and Methods Using Surveillance, Epidemiology and End Results registry data, we identified 50,949 female patients diagnosed between 1990 and 2002 with nonmetastatic T1/T2 invasive breast cancer treated with surgery and axillary LN dissection. Primary study variables were tumor size, degree of LN involvement, and their corresponding interaction term. Kaplan-Meier methods, adjusted Cox proportional hazards models with interaction terms, and a linear trend test across nodal categories were performed. Results Median follow-up was 99 months. In multivariable analysis, there was significant interaction between tumor size and LN involvement (P < .001). Using T1aN0 as reference, T1aN2 + conferred significantly higher BCSM compared with T1bN2 + (hazard ratio [HR], 20.66 v 12.53; P = .02). A similar pattern was seen among estrogen receptor (ER) -negative patients with T1aN2+ compared with T1bN2+ (HR, 24.16 v 12.67; P = .03), but not ER-positive patients (P = .52). The effect of very small tumor size on BCSM was intermediate among N1 cancers, between that of N0 and N2+ cancers. Conclusion Very small tumors with four positive LNs may predict for higher BCSM compared with larger tumors. In extensive node-positive disease, very small tumor size may be a surrogate for biologically aggressive disease. These results should be validated in future database studies. J Clin Oncol 29:2619-2627. (C) 2011 by American Society of Clinical Oncology C1 Harvard Univ, Harvard Radiat Oncol Program, Sch Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Punglia, RS (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM rpunglia@lroc.harvard.edu FU NCI NIH HHS [1K07 CA118629] NR 29 TC 46 Z9 46 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 JUL 1 PY 2011 VL 29 IS 19 BP 2619 EP 2627 DI 10.1200/JCO.2010.29.5907 PG 9 WC Oncology SC Oncology GA 785EP UT WOS:000292210500013 PM 21606424 ER PT J AU de Groot, JF Lamborn, KR Chang, SM Gilbert, MR Cloughesy, TF Aldape, K Yao, J Jackson, EF Lieberman, F Robins, HI Mehta, MP Lassman, AB DeAngelis, LM Yung, WKA Chen, A Prados, MD Wen, PY AF de Groot, John F. Lamborn, Kathleen R. Chang, Susan M. Gilbert, Mark R. Cloughesy, Timothy F. Aldape, Kenneth Yao, Jun Jackson, Edward F. Lieberman, Frank Robins, H. Ian Mehta, Minesh P. Lassman, Andrew B. DeAngelis, Lisa M. Yung, W. K. Alfred Chen, Alice Prados, Michael D. Wen, Patrick Y. TI Phase II Study of Aflibercept in Recurrent Malignant Glioma: A North American Brain Tumor Consortium Study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; GLIOBLASTOMA-MULTIFORME; VEGF TRAP; ANGIOGENESIS; EXPRESSION; BEVACIZUMAB; IRINOTECAN; INHIBITOR; THERAPY; SAMPLES AB Purpose Antivascular endothelial growth factor (anti-VEGF) therapy is a promising treatment approach for patients with recurrent glioblastoma. This single-arm phase II study evaluated the efficacy of aflibercept (VEGF Trap), a recombinantly produced fusion protein that scavenges both VEGF and placental growth factor in patients with recurrent malignant glioma. Patients and Methods Forty-two patients with glioblastoma and 16 patients with anaplastic glioma who had received concurrent radiation and temozolomide and adjuvant temozolomide were enrolled at first relapse. Aflibercept 4 mg/kg was administered intravenously on day 1 of every 2-week cycle. Results The 6-month progression-free survival rate was 7.7% for the glioblastoma cohort and 25% for patients with anaplastic glioma. Overall radiographic response rate was 24% (18% for glioblastoma and 44% for anaplastic glioma). The median progression-free survival was 24 weeks for patients with anaplastic glioma (95% CI, 5 to 31 weeks) and 12 weeks for patients with glioblastoma (95% CI, 8 to 16 weeks). A total of 14 patients (25%) were removed from the study for toxicity, on average less than 2 months from treatment initiation. The main treatment-related National Cancer Institute Common Terminology Criteria grades 3 and 4 adverse events (38 total) included fatigue, hypertension, and lymphopenia. Two grade 4 CNS ischemias and one grade 4 systemic hemorrhage were reported. Aflibercept rapidly decreases permeability on dynamic contrast enhanced magnetic resonance imaging, and molecular analysis of baseline tumor tissue identified tumor-associated markers of response and resistance. Conclusion Aflibercept monotherapy has moderate toxicity and minimal evidence of single-agent activity in unselected patients with recurrent malignant glioma. J Clin Oncol 29:2689-2695. (C) 2011 by American Society of Clinical Oncology C1 [de Groot, John F.] Univ Texas MD Anderson Canc Ctr, Unit 431, Houston, TX 77030 USA. [Lamborn, Kathleen R.; Chang, Susan M.; Prados, Michael D.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Cloughesy, Timothy F.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Lieberman, Frank] Univ Pittsburgh, Pittsburgh, PA USA. [Robins, H. Ian] Univ Wisconsin Comprehens Canc Ctr, Madison, WI USA. [Mehta, Minesh P.] Northwestern Univ, Evanston, IL USA. [Lassman, Andrew B.; DeAngelis, Lisa M.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Chen, Alice] NCI, Canc Treatment Expt Program, Bethesda, MD 20892 USA. [Wen, Patrick Y.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wen, Patrick Y.] Brigham & Womens Canc Ctr, Boston, MA USA. RP de Groot, JF (reprint author), Univ Texas MD Anderson Canc Ctr, Unit 431, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM jdegroot@mdanderson.org RI Jackson, Edward/L-5159-2013; Gilbert, Mark/J-7494-2016; OI Gilbert, Mark/0000-0003-2556-9722; Jackson, Edward/0000-0002-5958-0076; mehta, minesh/0000-0002-4812-5713 FU North American Brain Tumor Coalition, National Institutes of Health [U01-CA62399]; National Cancer Institute [1R21A126127]; AstraZeneca; Adnexus Therapeutics; Exelixis; Novartis; Schering-Plough; Genentech; Keryx Biopharmaceuticals; Sigma Tau Pharmaceuticals; NovoCure FX Supported by Grants No. U01-CA62399 from the North American Brain Tumor Coalition, National Institutes of Health and No. 1R21A126127 from the National Cancer Institute (J.D.G.).; Research Funding: John F. de Groot, AstraZeneca, Adnexus Therapeutics, Exelixis; Susan M. Chang, Novartis, Schering-Plough; Mark R. Gilbert, Genentech; Andrew B. Lassman, Keryx Biopharmaceuticals, Genentech, Sigma Tau Pharmaceuticals, Schering-Plough, Exelixis, NovoCure, AstraZeneca, Adnexus Therapeutics; W.K. Alfred Yung, Novartis NR 33 TC 103 Z9 104 U1 0 U2 9 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 JUL 1 PY 2011 VL 29 IS 19 BP 2689 EP 2695 DI 10.1200/JCO.2010.34.1636 PG 7 WC Oncology SC Oncology GA 785EP UT WOS:000292210500022 PM 21606416 ER PT J AU Bass, A AF Bass, Adam TI Impact of KRAS and BRAF Gene Mutations on Targeted Therapies in Colorectal Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID CETUXIMAB; RAS C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Bass, A (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 12 TC 6 Z9 6 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 JUL 1 PY 2011 VL 29 IS 19 BP 2728 EP 2729 DI 10.1200/JCO.2011.36.1816 PG 2 WC Oncology SC Oncology GA 785EP UT WOS:000292210500028 PM 21646605 ER PT J AU Van Allen, EM AF Van Allen, Eliezer M. TI The Paradox of Positive Thinking SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID CANCER C1 [Van Allen, Eliezer M.] Dana Farber Canc Ctr, Boston, MA USA. RP Van Allen, EM (reprint author), Dana Farber Canc Ctr Partners, 450 Brookline Ave, Boston, MA 02115 USA. EM evanallen@partners.org OI Van Allen, Eliezer/0000-0002-0201-4444 NR 3 TC 0 Z9 0 U1 0 U2 4 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 JUL 1 PY 2011 VL 29 IS 19 BP 2730 EP 2731 DI 10.1200/JCO.2011.34.7450 PG 2 WC Oncology SC Oncology GA 785EP UT WOS:000292210500029 PM 21422410 ER PT J AU Rhodes, KV Dichter, ME Kothari, CL Marcus, SC Cerulli, C AF Rhodes, Karin Verlaine Dichter, Melissa E. Kothari, Catherine L. Marcus, Steven C. Cerulli, Catherine TI The Impact of Children on Legal Actions Taken by Women Victims of Intimate Partner Violence SO JOURNAL OF FAMILY VIOLENCE LA English DT Article DE Intimate partner violence; Children; Prosecution; Personal protection order; Help seeking ID ABUSIVE RELATIONSHIPS; DECISION-MAKING; PROSECUTION; PROTECTION AB Successful criminal or civil legal system response to assaults against intimate partners (intimate partner violence; IPV) usually rely on the victim's participation in the legal process, including having contact with the prosecutor, filing charges, and/or applying for an order of personal protection. Using data abstracted from criminal and civil legal system records for a county-wide cohort of 990 female IPV victims over a 4-year period, we examine the impact of having children, and of specific child factors, on victims' engagement with the criminal prosecution of their abusive partners and/or seeking a personal protection order (PPO) in the civil court system. Having children increased victim's contact with the prosecutor and applications for PPOs, but did not increase her likelihood of wanting to file or drop charges. Findings support prior work suggesting both the importance and complexity of children on mothers' decision-making. Policy makers and service providers may want to assess survivors' thoughts about the role children play in their decision-making. Additionally, by offering survivors interventions to help their children address the impact of IPV exposure, survivors may be more willing to engage with services. C1 [Rhodes, Karin Verlaine] Univ Penn, Div Emergency Care Policy Res, Dept Emergency Med, Philadelphia, PA 19104 USA. [Rhodes, Karin Verlaine; Dichter, Melissa E.; Marcus, Steven C.] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19104 USA. [Rhodes, Karin Verlaine] Univ Penn, Sch Med, Dept Emergency Med, Philadelphia, PA 19104 USA. [Dichter, Melissa E.; Marcus, Steven C.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Kothari, Catherine L.] Michigan State Univ, Kalamazoo Ctr Med Studies, Kalamazoo, MI USA. [Rhodes, Karin Verlaine; Marcus, Steven C.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Cerulli, Catherine] Univ Rochester, Med Ctr, Dept Psychiat, Rochester, NY 14642 USA. RP Rhodes, KV (reprint author), Univ Penn, Div Emergency Care Policy Res, Dept Emergency Med, 3815 Walnut St, Philadelphia, PA 19104 USA. EM kvr@sp2.upenn.edu OI Kothari, Catherine/0000-0001-8072-8920 NR 39 TC 8 Z9 8 U1 1 U2 4 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-7482 J9 J FAM VIOLENCE JI J. Fam. Violence PD JUL PY 2011 VL 26 IS 5 BP 355 EP 364 DI 10.1007/s10896-011-9370-8 PG 10 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA 782WY UT WOS:000292044600003 ER PT J AU Jordan, TH Talarico, RH Schuberth, JM AF Jordan, Thomas H. Talarico, Ross H. Schuberth, John M. TI The Radiographic Fate of the Syndesmosis after Trans-syndesmotic Screw Removal in Displaced Ankle Fractures SO JOURNAL OF FOOT & ANKLE SURGERY LA English DT Article DE ankle fracture; open reduction; syndesmosis ID DISTAL TIBIOFIBULAR SYNDESMOSIS; FIXATION; INSTABILITY; ROTATION; CADAVER; OSSIFICATION; BIMALLEOLAR; DIASTASIS; INJURIES; MODEL AB The purpose of this study was to evaluate the radiographic changes of the tibiofibular position and the ankle mortise after removal of trans-syndesmotic fixation to determine if there is loss or maintenance of correction. In addition, the effect of the type of rotational injury, early weight bearing, and the number of trans-syndesmotic screws used on the integrity of the inferior tibiofibular articulation or ankle mortise after screw removal were evaluated. An analysis was conducted of 86 patients, with an unstable rotational ankle fracture requiring open reduction with syndesmosis screw stabilization. Routine radiographic parameters were measured just after open reduction and just before syndesmotic screw removal. There was a high correlation of loss of the integrity of the syndesmotic parameters after screw removal. However, the medial clear space of the ankle changed an insignificant amount, suggesting that although there appears to be some loss of maintenance, the talus did not shift laterally at the expense of a mobile syndesmosis. Ankle injuries requiring stabilization of syndesmotic instability with use of temporary trans-syndesmotic fixation achieve a stable ankle mortise after removal. Tibiofibular diastasis is commonplace upon removal of the syndesmotic hardware, but the ankle mortise remains unchanged. Based on the radiographic criteria described in this study, the postoperative change in medial clear space or tibiofibular diastasis has no bearing on fracture type, deltoid injury, or the use of 1 or 2 cortical screws. As such, other unknown mechanisms affecting the integrity of the syndesmosis after screw removal are in place. (C) 2011 by the American College of Foot and Ankle Surgeons. All rights reserved. C1 [Schuberth, John M.] Kaiser Fdn Hosp, Dept Orthoped Surg, San Francisco, CA 94118 USA. [Jordan, Thomas H.] Kaiser Permanente Med Grp, Santa Rosa, CA USA. [Talarico, Ross H.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Schuberth, JM (reprint author), Kaiser Fdn Hosp, Dept Orthoped Surg, 450 6th Ave, San Francisco, CA 94118 USA. EM Jmfoot@aol.com NR 35 TC 15 Z9 15 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1067-2516 J9 J FOOT ANKLE SURG JI J. Foot Ankle Surg. PD JUL-AUG PY 2011 VL 50 IS 4 BP 407 EP 412 DI 10.1053/j.jfas.2011.03.014 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 782TY UT WOS:000292036100009 PM 21596590 ER PT J AU Lamont, EB Landrum, MB Keating, NL Bozeman, SR McNeil, BJ AF Lamont, Elizabeth B. Landrum, Mary Beth Keating, Nancy L. Bozeman, Samuel R. McNeil, Barbara J. TI Evaluating colorectal cancer care in the Veterans Health Administration: How good are the data? SO JOURNAL OF GERIATRIC ONCOLOGY LA English DT Article DE Administrative data; Veterans' Health Administration; Medicare; Cancer Registry Data; Colorectal cancer; Chemotherapy; Radiation therapy; Elderly cancer patients ID TRIAL PARTICIPANTS; CLAIMS; BREAST AB Objective: Longitudinal observational data sources can be useful for studies of health care use and outcomes among patients treated in the usual care setting. In this study, we sought to determine the quality of a Veterans Health Administration (VHA) observational dataset for ascertaining of colorectal cancer (CRC) diagnoses and selected therapies among veterans. Materials and methods: We determined (1) the completeness of Veterans Affairs Central Cancer Registry (VACCR) CRC case ascertainment by determining the proportion of 7224 probable CRC cases identified from VHA administrative data who also appeared in the VACCR; and (2) the accuracy of VHA administrative data regarding CRC patients' utilization of chemotherapy and radiation therapy (RT) through comparison to gold-standard medical record data on a different sample of patients (N=295). Results: Among probable cases of CRC identified through administrative data, the proportion ascertained by the VACCR was 0.89 (95% confidence interval [CI]: 0.88-0.90). The VACCR-Administrative data were highly accurate in measuring chemotherapy (sensitivity = 0.99, 95% CI: 0.96-1.00; specificity=0.92, 95% CI: 0.86-0.96) and RT (sensitivity = 1.00, 95% CI: 0.96-1.00; specificity = 0.88, 95% CI 0.80-0.94) use among veterans with CRC. Conclusions: The clinically rich patient-level longitudinal VACCR-Administrative dataset is appropriate for empirical studies of chemotherapy and RT-related processes of care for veterans with CRC. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Lamont, Elizabeth B.; Landrum, Mary Beth; Keating, Nancy L.; McNeil, Barbara J.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Lamont, Elizabeth B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Keating, Nancy L.; McNeil, Barbara J.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Lamont, Elizabeth B.; Keating, Nancy L.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [McNeil, Barbara J.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Bozeman, Samuel R.] ABT Associates Inc, Cambridge, MA 02138 USA. RP Lamont, EB (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180A Longwood Ave, Boston, MA 02115 USA. EM lamont@hcp.med.harvard.edu FU Department of Veterans Affairs through the Office of Policy and Planning as part of a larger evaluation of oncology care FX This work was supported by the Department of Veterans Affairs through the Office of Policy and Planning as part of a larger evaluation of oncology care. NR 8 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1879-4068 J9 J GERIATR ONCOL JI J. Geriatr. Oncol. PD JUL PY 2011 VL 2 IS 3 BP 187 EP 193 DI 10.1016/j.jgo.2011.02.001 PG 7 WC Oncology; Geriatrics & Gerontology SC Oncology; Geriatrics & Gerontology GA 783BT UT WOS:000292057200004 ER PT J AU Coakley, E Ananian, L Keeley, A AF Coakley, Edward Ananian, Lillian Keeley, Adele TI Untitled SO JOURNAL OF HOSPICE & PALLIATIVE NURSING LA English DT Letter C1 [Coakley, Edward; Ananian, Lillian; Keeley, Adele] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Coakley, E (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1522-2179 J9 J HOSP PALLIAT NURS JI J. Hosp. Palliat. Nurs. PD JUL-AUG PY 2011 VL 13 IS 4 BP 194 EP 194 DI 10.1097/NJH.0b013e318223bb36 PG 1 WC Nursing SC Nursing GA 782PQ UT WOS:000292022000002 ER PT J AU Lee, SM Coakley, EE AF Lee, Susan M. Coakley, Edward E. TI Geropalliative Care A Concept Synthesis SO JOURNAL OF HOSPICE & PALLIATIVE NURSING LA English DT Article DE concept synthesis; geriatric palliative care; geropalliative ID LONG-TERM-CARE; PALLIATIVE CARE; GERIATRIC SYNDROMES; PAIN MANAGEMENT; CORE AB The aging demography of the United States and other first-world countries is increasing the demands for palliative care. Palliative care is a philosophical stance as well as an interdisciplinary model of care delivery, the goals of which are to prevent and relieve suffering and to support the best quality of life for patients and their families, regardless of the stage of the disease or the need for other therapies. The palliative care needs of older adults are not unlike those of younger adults but are confounded by a variety of phenomena related to aging. The purpose of this article was to describe a concept synthesis of geropalliative care. Using Walker and Avant's method of concept synthesis, an electronic database search yielded 68 articles, the synthesis of which along with other evidence yielded 9 attributes of geropalliative care. To date, geropalliative care has been described from a disease perspective. The findings of this article begin to explicate the unique philosophical stance of geropalliative care as well as critical attributes that must be considered to provide the safest and best quality care to older adults and their families during the last 2 to 5 years of life. C1 [Lee, Susan M.] Massachusetts Gen Hosp, Yvonne L Munn Ctr Nursing Res, Boston, MA 02114 USA. RP Lee, SM (reprint author), Massachusetts Gen Hosp, Yvonne L Munn Ctr Nursing Res, 275 Cambridge St,4th Floor, Boston, MA 02114 USA. EM slee40@partners.org FU Division of Nursing (DN); Bureau of Health Professions (BHPr); Health Resources and Services Administration (HRSA); Department of Health and Human Services (DHHS) [D11HP08359]; Nurse Education, Practice, and Retention FX This project was supported by funds from the Division of Nursing (DN), Bureau of Health Professions (BHPr), Health Resources and Services Administration (HRSA), Department of Health and Human Services (DHHS) under D11HP08359, Nurse Education, Practice, and Retention. The information or content and conclusions are those of the authors and should not be construed as the official position or policy of, nor should any official endorsement be inferred by, the DN, BHPr, HRSA, DHHS, or the US Government. NR 44 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1522-2179 J9 J HOSP PALLIAT NURS JI J. Hosp. Palliat. Nurs. PD JUL-AUG PY 2011 VL 13 IS 4 BP 242 EP 248 DI 10.1097/NJH.0b013e318214b6cc PG 7 WC Nursing SC Nursing GA 782PQ UT WOS:000292022000007 ER PT J AU Benarafa, C LeCuyer, TE Baumann, M Stolley, JM Cremona, TP Remold-O'Donnell, E AF Benarafa, Charaf LeCuyer, Tessa E. Baumann, Mathias Stolley, James Michael Cremona, Tiziana P. Remold-O'Donnell, Eileen TI SerpinB1 protects the mature neutrophil reserve in the bone marrow SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE neutropenia; granulopoiesis; apoptosis; serine protease; MNEI ID COLONY-STIMULATING FACTOR; HEMATOPOIETIC PROGENITOR MOBILIZATION; SEVERE CONGENITAL NEUTROPENIA; SERINE-PROTEASE INHIBITOR-6; STEM-CELL MOBILIZATION; ELASTASE INHIBITOR; DEFICIENT MICE; GRANULOCYTE; DIFFERENTIATION; EXPRESSION AB SerpinB1 is among the most efficient inhibitors of neutrophil serine proteases-NE, CG, and PR-3-and we investigated here its role in neutrophil development and homeostasis. We found that serpinB1 is expressed in all human bone marrow leukocytes, including stem and progenitor cells. Expression levels were highest in the neutrophil lineage and peaked at the promyelocyte stage, coincident with the production and packaging of the target proteases. Neutrophil numbers were decreased substantially in the bone marrow of serpinB1(-/-) mice. This cellular deficit was associated with an increase in serum G-CSF levels. On induction of acute pulmonary injury, neutrophils were recruited to the lungs, causing the bone marrow reserve pool to be completely exhausted in serpinB1(-/-) mice. Numbers of myeloid progenitors were normal in serpinB1(-/-) bone marrow, coincident with the absence of target protease expression at these developmental stages. Maturation arrest of serpinB1(-/-) neutrophils was excluded by the normal CFU-G growth in vitro and the normal expression in mature neutrophils of early and late differentiation markers. Normal absolute numbers of proliferating neutrophils and pulse-chase kinetic studies in vivo showed that the bone marrow deficit in serpinB1(-/-) mice was largely restricted to mature, postmitotic neutrophils. Finally, upon overnight culture, apoptosis and necrosis were greater in purified bone marrow neutrophils from serpinB1(-/-) compared with WT mice. Collectively, these findings demonstrate that serpinB1 sustains a healthy neutrophil reserve that is required in acute immune responses. J. Leukoc. Biol. 90: 21-29; 2011. C1 [Benarafa, Charaf; Baumann, Mathias; Cremona, Tiziana P.] Univ Bern, Theodor Kocher Inst, CH-3006 Bern, Switzerland. [LeCuyer, Tessa E.; Stolley, James Michael; Remold-O'Donnell, Eileen] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [LeCuyer, Tessa E.; Stolley, James Michael; Remold-O'Donnell, Eileen] Harvard Univ, Sch Med, Program Cellular & Mol Med, Boston, MA 02115 USA. [LeCuyer, Tessa E.; Stolley, James Michael; Remold-O'Donnell, Eileen] Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. [LeCuyer, Tessa E.; Stolley, James Michael; Remold-O'Donnell, Eileen] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Benarafa, C (reprint author), Univ Bern, Theodor Kocher Inst, Freiestr 1, CH-3006 Bern, Switzerland. EM charaf.benarafa@tki.unibe.ch; remold@idi.harvard.edu OI Benarafa, Charaf/0000-0002-2049-7769 FU National Institutes of Health [HL66548]; Swiss National Fonds [310030-127464]; European Union FX This study was supported by the National Institutes of Health (HL66548; E.R-O.), the Swiss National Fonds (310030-127464; C. B.), and the European Union 7th Framework Program Marie Curie International Reintegration Grant (C. B.). C. B. was a fellow of the Parker B. Francis Foundation in Pulmonary Research. We thank Drs. Sherwin Kevy and May Jacobson (Harvest Technologies) for providing human bone marrow samples. We thank Drs. Natasha Barteneva and Ken Ketman for expert help in cell sorting and Dr. Myriam Armant for help in setting up colony-forming cell assays. We thank Isabelle Oswald and Svetlozar Tsonev for animal husbandry, Elisabeth Frei, and Dolores A. Fici for excellent technical assistance. NR 53 TC 25 Z9 27 U1 1 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD JUL PY 2011 VL 90 IS 1 BP 21 EP 29 DI 10.1189/jlb.0810461 PG 9 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 785QQ UT WOS:000292244200004 PM 21248149 ER PT J AU Kogiso, M Nishiyama, A Shinohara, T Nakamura, M Mizoguchi, E Misawa, Y Guinet, E Nouri-Shirazi, M Dorey, CK Henriksen, RA Shibata, Y AF Kogiso, Mari Nishiyama, Akihito Shinohara, Tsutomu Nakamura, Masataka Mizoguchi, Emiko Misawa, Yoshinori Guinet, Elisabeth Nouri-Shirazi, Mahyar Dorey, C. Kathleen Henriksen, Ruth Ann Shibata, Yoshimi TI Chitin particles induce size-dependent but carbohydrate-independent innate eosinophilia SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE M2; IL-10; phagocytosis; CRTH2 ID ACETYL-D-GLUCOSAMINE; PROSTAGLANDIN D-2; ALTERNATIVE ACTIVATION; BONE-MARROW; MAST-CELLS; INTRACELLULAR PATHOGENS; PERITONEAL-MACROPHAGES; ALLERGIC INFLAMMATION; AIRWAY INFLAMMATION; HELMINTH INFECTION AB Murine M phi that phagocytose CMP develop into M1; this response depends on the size and the chemical composition of the particles. In contrast, recent studies concluded that chitin particles induce M2 and eosinophil migration, promoting acquired Th2 immune responses against chitin-containing microbes or allergens. This study examined whether these apparently inconsistent responses to chitin could be induced by variation in the size and chemical composition of the chitin particles. We compared the responses of M phi with CMP, LCB, and Sephadex G-100 beads (>40 mu m). Beads were given i.p. to WT mice and to mice deficient in a CRTH2, a receptor for the eosinophil chemoattractant PGD(2). In contrast to the M1 activation induced by CMP, i.p. administration of LCB or Sephadex beads induced within 24 h a CRTH2-dependent peritoneal eosinophilia, as well as CRTH2-independent activation of peritoneal M phi that expressed Arg I, an M2 phenotype. LCB-induced M phi exhibited elevated Arg I and a surface MR, reduced surface TLR2 levels, and no change in the levels of CHI3L1 or IL-10 production. Our results indicate that the effects of chitin in vivo are highly dependent on particle size and that large, nonphagocytosable beads, independent of their chemical composition, induce innate eosinophilia and activate M phi expressing several M2, but not M1, phenotypes. J. Leukoc. Biol. 90: 167-176; 2011. C1 [Kogiso, Mari; Nishiyama, Akihito; Shinohara, Tsutomu; Guinet, Elisabeth; Nouri-Shirazi, Mahyar; Shibata, Yoshimi] Florida Atlantic Univ, Charles E Schmidt Coll Med, Boca Raton, FL 33431 USA. [Nakamura, Masataka] Tokyo Med & Dent Univ, Human Gene Sci Ctr, Tokyo, Japan. [Mizoguchi, Emiko] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Misawa, Yoshinori] Yaizu Suisankagaku, Yaizu, Japan. [Dorey, C. Kathleen] Virginia Tech Caril Sch Med & Res Inst, Roanoke, VA USA. [Henriksen, Ruth Ann] E Carolina Univ, Brody Sch Med, Dept Physiol, Greenville, NC USA. RP Shibata, Y (reprint author), Florida Atlantic Univ, Charles E Schmidt Coll Med, 777 Glades Rd, Boca Raton, FL 33431 USA. EM yshibata@fau.edu FU National Institutes of Health [RO1 HL71711]; DOD DAMD [17-03-1-0004]; Bankhead-Coley Cancer Research Program [06BS-04-9615]; Charles E. Schmidt Biomedical Foundation FX This work was supported by National Institutes of Health RO1 HL71711, DOD DAMD 17-03-1-0004, Bankhead-Coley Cancer Research Program 06BS-04-9615, and the Charles E. Schmidt Biomedical Foundation. The authors thank Traci Pantuso for her technical assistance. NR 71 TC 20 Z9 20 U1 0 U2 5 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD JUL PY 2011 VL 90 IS 1 BP 167 EP 176 DI 10.1189/jlb.1110624 PG 10 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 785QQ UT WOS:000292244200018 PM 21447645 ER PT J AU Larauche, M Mulak, A Tache, Y AF Larauche, Muriel Mulak, Agata Tache, Yvette TI Stress-Related Alterations of Visceral Sensation: Animal Models for Irritable Bowel Syndrome Study SO JOURNAL OF NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Review DE Irritable bowel syndrome; Models, animal; Pain AB Stressors of different psychological, physical or immune origin play a critical role in the pathophysiology of irritable bowel syndrome participating in symptoms onset, clinical presentation as well as treatment outcome. Experimental stress models applying a variety of acute and chronic exteroceptive or interoceptive stressors have been developed to target different periods throughout the lifespan of animals to assess the vulnerability, the trigger and perpetuating factors determining stress influence on visceral sensitivity and interactions within the brain-gut axis. Recent evidence points towards adequate construct and face validity of experimental models developed with respect to animals' age, sex, strain differences and specific methodological aspects such as non-invasive monitoring of visceromotor response to colorectal distension as being essential in successful identification and evaluation of novel therapeutic targets aimed at reducing stress-related alterations in visceral sensitivity. Underlying mechanisms of stress-induced modulation of visceral pain involve a combination of peripheral, spinal and supraspinal sensitization based on the nature of the stressors and dysregulation of descending pathways that modulate nociceptive transmission or stress-related analgesic response. C1 Univ Calif Los Angeles, David Geffen Sch Med, CURE Digest Dis Res Ctr, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Ctr Neurobiol Stress, Digest Dis Div,Dept Med, Los Angeles, CA 90095 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Larauche, M (reprint author), West Los Angeles VA Med Ctr, CURE Digest Dis Res Ctr, 11301 Wilshire Blvd,Bldg 115 Rm 111, Los Angeles, CA 90073 USA. EM mlarauche@mednet.ucla.edu OI Larauche, Muriel/0000-0003-3320-3675 FU VA Research Career Scientist Award; NIH [R01 DK-57238, DK 33061, P50 DK-64539, K01 DK088937] FX This review is part of studies supported by the VA Research Career Scientist Award, NIH grants R01 DK-57238 and DK 33061 and P50 DK-64539 (YT) and K01 DK088937 (ML). NR 310 TC 28 Z9 33 U1 2 U2 9 PU KOREAN SOC NEUROGASTERONTEROL & MOTILITY PI GANGNAM-GU PA RM 305, LOTTE GOLD ROSE VILL II, 31 SEOLLEUNG-RO 86-GIL, GANGNAM-GU, SEOUL 135-839, SOUTH KOREA SN 2093-0879 J9 J NEUROGASTROENTEROL JI J. Neurogastroenterol. Motil. PD JUL PY 2011 VL 17 IS 3 BP 213 EP 234 DI 10.5056/jnm.2011.17.3.213 PG 22 WC Gastroenterology & Hepatology; Clinical Neurology SC Gastroenterology & Hepatology; Neurosciences & Neurology GA V29WV UT WOS:000208779400003 PM 21860814 ER PT J AU Cai, CS Ren, QS Desai, NJ Rizzo, JF Fried, SI AF Cai, Changsi Ren, Qiushi Desai, Neal J. Rizzo, Joseph F., III Fried, Shelley I. TI Response variability to high rates of electric stimulation in retinal ganglion cells SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE retinal prosthesis; initial segment ID AXON INITIAL SEGMENT; ACTION-POTENTIAL INITIATION; RABBIT RETINA; MAMMALIAN RETINA; IN-VITRO; CHANNELS; MICROELECTRODE; SENSITIVITY; PROSTHESIS; ACTIVATION AB Cai C, Ren Q, Desai NJ, Rizzo JF 3rd, Fried SI. Response variability to high rates of electric stimulation in retinal ganglion cells. J Neurophysiol 106: 153-162, 2011. First published April 13, 2011; doi:10.1152/jn.00956.2010.-To improve the quality of prosthetic vision, it is important to understand how retinal neurons respond to electric stimulation. Previous studies present conflicting reports as to the maximum rate at which retinal ganglion cells can "follow" pulse trains, i.e., generate one spike for each pulse of the train. In the present study, we measured the response of 5 different types of rabbit retinal ganglion cells to pulse trains of 100-700 Hz. Surprisingly, we found significant heterogeneity in the ability of different types to follow pulse trains. For example, brisk transient (BT) ganglion cells could reliably follow pulse rates up to 600 pulses per second (PPS). In contrast, other types could not even follow rates of 200 PPS. There was additional heterogeneity in the response patterns across those types that could not follow high-rate trains. For example, some types generated action potentials in response to approximately every other pulse, whereas other types generated one spike per pulse for a few consecutive pulses and then did not generate any spikes in response to the next few pulses. Interestingly, in the types that could not follow high-rate trains, we found a second type of response: many pulses of the train elicited a biphasic waveform with an amplitude much smaller than that of standard action potentials. This small waveform was often observed following every pulse for which a standard spike was not elicited. A possible origin of the small waveform and its implication for effective retinal stimulation are discussed. C1 [Cai, Changsi; Desai, Neal J.; Fried, Shelley I.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. [Cai, Changsi; Ren, Qiushi] Shanghai Jiao Tong Univ, Dept Biomed Engn, Inst Laser Med & Biophoton, Shanghai 200030, Peoples R China. [Cai, Changsi; Rizzo, Joseph F., III; Fried, Shelley I.] Boston Vet Adm Healthcare Syst, Ctr Innovat Visual Rehabil, Boston, MA USA. [Rizzo, Joseph F., III] Massachusetts Eye & Ear Infirm, Dept NeuroOphthalmol, Boston, MA 02114 USA. RP Fried, SI (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, 165 Cambridge St,Simches 3600, Boston, MA 02114 USA. EM fried.shelley@mgh.harvard.edu RI Ren, Qiushi/D-1451-2012 FU VA Healthcare System (Center for Innovative Visual Rehabilitation); Department of Defense [W81XWH-07-1-0474]; NIH [1 R0IEY019967-01] FX This work was funded in part by the VA Healthcare System (Center for Innovative Visual Rehabilitation), the Department of Defense (W81XWH-07-1-0474), and the NIH (1 R0IEY019967-01). NR 37 TC 20 Z9 20 U1 1 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JUL PY 2011 VL 106 IS 1 BP 153 EP 162 DI 10.1152/jn.00956.2010 PG 10 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 786PC UT WOS:000292319400017 PM 21490287 ER PT J AU Seo, Y Aparici, CM Chen, CP Hsu, C Kased, N Schreck, C Costouros, N Hawkins, R Shinohara, K Roach, M AF Seo, Youngho Aparici, Carina Mari Chen, Chien Peter Hsu, Charles Kased, Norbert Schreck, Carole Costouros, Nick Hawkins, Randall Shinohara, Katsuto Roach, Mack, III TI Mapping of Lymphatic Drainage from the Prostate Using Filtered Tc-99m-Sulfur Nanocolloid and SPECT/CT SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE prostate cancer; sulfur colloid; SPECT/CT; lymphatic mapping; sentinel node ID RADIATION-THERAPY; NODE DISSECTION; WHOLE-PELVIS; GAMMA-PROBE; CANCER; RADIOTHERAPY; LYMPHOSCINTIGRAPHY; INJECTION; INVASION AB We have developed a practice procedure for prostate lymphoscintigraphy using SPECT/CT and filtered Tc-99m-sulfur nanocolloid, as an alternative to the proprietary product Tc-99m-Nanocoll, which is not approved in the United States. Methods: Ten patients were enrolled for this study, and all received radiotracer prepared using a 100-nm membrane filter at a commercial radiopharmacy. Whole-body scans and SPECT/CT studies were performed within 1.5-3 h after the radiotracer had been administered directly into 6 locations of the prostate gland under transrectal ultrasound guidance. The radiation dose was estimated from the first 3 patients. Lymphatic drainage mapping was performed, and lymph nodes were identified. Results: The estimated radiation dose ranged from 3.9 to 5.2 mSv/MBq. The locations of lymph nodes draining the prostate gland were similar to those found using the proprietary product. Conclusion: When the proprietary radiolabeled nanocolloid indicated for lymphoscintigraphy is not available, prostate lymph node mapping and identification are still feasible using filtered Tc-99m-sulfur nanocolloid. C1 [Seo, Youngho; Aparici, Carina Mari; Schreck, Carole; Costouros, Nick; Hawkins, Randall] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94107 USA. [Seo, Youngho; Chen, Chien Peter; Hsu, Charles; Kased, Norbert; Shinohara, Katsuto; Roach, Mack, III] Univ Calif San Francisco, Helen Diller Family Comprehens Ctr, Dept Radiat Oncol, San Francisco, CA 94107 USA. [Seo, Youngho; Hawkins, Randall] Univ Calif San Francisco, Joint Grad Grp Bioengn, San Francisco, CA 94107 USA. [Aparici, Carina Mari] San Francisco VA Med Ctr, San Francisco, CA USA. [Shinohara, Katsuto; Roach, Mack, III] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94107 USA. RP Seo, Y (reprint author), Univ Calif San Francisco, Dept Radiol & Biomed Imaging, 185 Berry St,Ste 350, San Francisco, CA 94107 USA. EM youngho.seo@ucsf.edu FU National Cancer Institute [K25 CA114254] FX We thank Marilyn Robinson at the University of California, San Francisco, for her help with coordinating the clinical study. We also thank Chang-Lae Lee, who helped with radiation dose calculations using biokinetic data. This study was partially funded by National Cancer Institute grant K25 CA114254. No other potential conflict of interest relevant to this article was reported. NR 20 TC 7 Z9 7 U1 0 U2 1 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 JUL 1 PY 2011 VL 52 IS 7 BP 1068 EP 1072 DI 10.2967/jnumed.110.085944 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 786IL UT WOS:000292297900011 PM 21680690 ER PT J AU Salinthone, S Schillace, RV Tsang, C Regan, JW Bourdette, DN Carr, DW AF Salinthone, Sonemany Schillace, Robynn V. Tsang, Catherine Regan, John W. Bourdette, Dennis N. Carr, Daniel W. TI Lipoic acid stimulates cAMP production via G protein-coupled receptor-dependent and -independent mechanisms SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY LA English DT Article DE G protein-coupled receptors; Adenylyl cyclase; cAMP; Lipoic acid ID SOLUBLE ADENYLYL-CYCLASE; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; T-CELL MIGRATION; ADENOSINE-MEDIATED INHIBITION; PROSTANOID RECEPTORS; CYTOKINE PRODUCTION; THIOCTIC ACID; NK CELLS; SIGNAL-TRANSDUCTION; MULTIPLE-SCLEROSIS AB Lipoic acid (LA) is a naturally occurring fatty acid that exhibits anti-oxidant and anti-inflammatory properties and is being pursued as a therapeutic for many diseases including multiple sclerosis, diabetic polyneuropathy and Alzheimer's disease. We previously reported on the novel finding that racemic LA (50:50 mixture of R-LA and S-LA) stimulates CAMP production, activates prostanoid EP2 and EP4 receptors and adenylyl cyclases (AC), and suppresses activation and cytotoxicity in NK cells. In this study, we present evidence that furthers our understanding of the mechanisms of action of LA. Using various LA derivatives, such as dihydrolipoic acid (DHLA),S,S-dimethyl lipoic acid (DMLA) and lipoamide (LPM), we discovered that only LA is capable of stimulating CAMP production in NK cells. Furthermore, there is no difference in cAMP production after stimulation with either R-LA, S-LA or racemic LA. Competition and synergistic studies indicate that LA may also activate AC independent of the EP2 and EP4 receptors. Pretreatment of PBMCs with KH7 (a specific peptide inhibitor of soluble AC) and the calcium inhibitor (Bapta) prior to LA treatment resulted in reduced cAMP levels, suggesting that soluble AC and calcium signaling mediate LA stimulation of cAMP production. In addition, pharmacological inhibitor studies demonstrate that LA also activates other G protein-coupled receptors, including histamine and adenosine but not the beta-adrenergic receptors. These novel findings provide information to better understand the mechanisms of action of LA, which can help facilitate the use of LA as a therapeutic for various diseases. (C) Published by Elsevier Inc. C1 [Salinthone, Sonemany; Schillace, Robynn V.; Tsang, Catherine; Bourdette, Dennis N.; Carr, Daniel W.] Portland VA Med Ctr, Portland, OR 97239 USA. [Salinthone, Sonemany; Schillace, Robynn V.; Bourdette, Dennis N.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Regan, John W.] Univ Arizona, Dept Pharmacol & Toxicol, Tucson, AZ 85721 USA. [Carr, Daniel W.] Oregon Hlth & Sci Univ, Dept Endocrinol, Portland, OR 97239 USA. RP Carr, DW (reprint author), Portland VA Med Ctr, Portland, OR 97239 USA. EM carrd@ohsu.edu FU Department of Veterans Affairs Biomedical Laboratory Research & Development Service; NIH [P50AT00066-01]; The National MS Society [CRG CA1055-A-3]; Laura Fund for Innovation in Multiple Sclerosis Research; Nancy Davis Center Without Walls; Collins Medical Trust FX This research was supported by the Department of Veterans Affairs Biomedical Laboratory Research & Development Service (D.W.C. and D.N.B.), NIH Grant P50AT00066-01 (D.N.B.), The National MS Society CRG CA1055-A-3 (D.N.B.), the Laura Fund for Innovation in Multiple Sclerosis Research (D.N.B.), the Nancy Davis Center Without Walls (D.N.B.), and the Collins Medical Trust (S.S.). NR 69 TC 17 Z9 17 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0955-2863 EI 1873-4847 J9 J NUTR BIOCHEM JI J. Nutr. Biochem. PD JUL PY 2011 VL 22 IS 7 BP 681 EP 690 DI 10.1016/j.jnutbio.2010.05.008 PG 10 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 787CR UT WOS:000292354700010 PM 21036588 ER PT J AU Bekelman, DB Nowels, CT Allen, LA Shakar, S Kutner, JS Matlock, DD AF Bekelman, David B. Nowels, Carolyn T. Allen, Larry A. Shakar, Simon Kutner, Jean S. Matlock, Daniel D. TI Outpatient Palliative Care for Chronic Heart Failure: A Case Series SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID SYMPTOM ASSESSMENT SCALE; QUALITY-OF-LIFE; DEPRESSION; MANAGEMENT; SURVIVAL; CANCER; PREVALENCE; DISEASE; END; HOSPITALIZATION AB Background/Objectives: Although the palliative care needs of outpatients with chronic heart failure (HF) are numerous, there is limited published experience in providing outpatient HF palliative care. This article describes the patients seen and the issues addressed in an outpatient palliative care program for patients with HF. Methods: Case series involving a retrospective medical record review using descriptive quantitative and qualitative analysis. Results: Over a 3 1/2 year time period, 50 patients were seen, resulting in 228 total visits. Fifty percent of patients were seen only once. Fifty-eight percent of patients had New York Heart Association (NYHA) Class III-IV HF. Within a year of the initial palliative care visit, 14% of patients died. Depression, anxiety, pain, fatigue, breathlessness, and sleep disturbance were common symptoms addressed during visits. Advance care planning topics were discussed with 48% of patients; hospice and resuscitation status were each discussed with 16% of patients. Fears or concerns about the future arose in 34% of patients. Care coordination was commonly addressed with patients' other health care providers (58%). The most common referrals were to social work (26%) and rehabilitation/physical therapy (20%). Conclusions: Several findings reflect how outpatient HF palliative care differs from that of inpatient hospital-based palliative care. Many of the issues addressed, including care coordination, advance care planning, and psychosocial issues, imply that palliative HF care is complementary to standard HF care at all stages of the disease process and that future programs should consider dedicating a nurse and/or social worker. Research is needed to test how such a care model affects patient-centered outcomes, utilization, and cost. C1 [Bekelman, David B.] Dept Vet Affairs Med Ctr, Denver, CO USA. [Bekelman, David B.; Nowels, Carolyn T.; Allen, Larry A.; Shakar, Simon; Kutner, Jean S.; Matlock, Daniel D.] Univ Colorado, Denver Sch Med, Aurora, CO USA. [Bekelman, David B.; Allen, Larry A.; Matlock, Daniel D.] Colorado Cardiovasc Outcomes Res, Denver, CO USA. [Allen, Larry A.; Shakar, Simon; Kutner, Jean S.; Matlock, Daniel D.] Univ Colorado Hosp, Aurora, CO USA. RP Bekelman, DB (reprint author), Denver VA Med Ctr, 1055 Clermont St, Denver, CO 80220 USA. EM david.bekelman@va.gov FU University of Colorado; Department of Veterans Affairs (HSRD) [CDA 08-022]; University of Colorado Hartford/Jahnigen Center for Excellence in Geriatric Medicine; Division of General Internal Medicine FX This research was funded by the University of Colorado Program in Palliative Care Research Fund. Dr. Bekelman is funded through the Department of Veterans Affairs (HSR&D CDA 08-022) and was also funded by University of Colorado Hartford/Jahnigen Center for Excellence in Geriatric Medicine and the Division of General Internal Medicine while running the Supportive Care Program. The funding organizations had no role in any part of the study. The views in this article are those of the authors and do not necessarily reflect the views of the Department of Veterans Affairs. NR 48 TC 17 Z9 17 U1 1 U2 6 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 JUL PY 2011 VL 14 IS 7 BP 815 EP 821 DI 10.1089/jpm.2010.0508 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 782PP UT WOS:000292021900007 PM 21554021 ER PT J AU Chittenden, EH Ritchie, CS AF Chittenden, Eva H. Ritchie, Christine S. TI Work-Life Balancing: Challenges and Strategies SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID PART-TIME CAREERS; INTERNAL-MEDICINE; PHYSICAL-ACTIVITY; HEALTH; SATISFACTION; ATTITUDES AB Background: Balancing the personal and the professional is an ongoing struggle for most professionals, and palliative care clinicians are no exception. A sustained lack of balance can lead to feelings of frustration, inadequacy, and guilt. Palliative care physicians may find this balance particularly difficult due to the nature of their work: caring for patients and families who are often suffering and in crisis. Discussion: In this article, we describe challenges to work-life balancing and strategies that may promote balance, including "timeshifting," goal setting, cognitive reframing, and self-care. We argue that the search for balance is a lifelong endeavor that entails self-reflection and continuing examination of one's values and goals. C1 [Chittenden, Eva H.] Massachusetts Gen Hosp, Boston, MA 02115 USA. [Ritchie, Christine S.] Univ Alabama, Birmingham, AL USA. [Ritchie, Christine S.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Chittenden, EH (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Founders 600, Boston, MA 02115 USA. EM echittenden@partners.org NR 21 TC 10 Z9 10 U1 0 U2 12 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 JUL PY 2011 VL 14 IS 7 BP 870 EP 874 DI 10.1089/jpm.2011.0095 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 782PP UT WOS:000292021900015 PM 21651342 ER PT J AU Fernandez-Pineda, I Parida, L Jenkins, JJ Davidoff, AM Rao, BN Rodriguez-Galindo, C AF Fernandez-Pineda, Israel Parida, Lalit Jenkins, Jesse J. Davidoff, Andrew M. Rao, Bhaskar N. Rodriguez-Galindo, Carlos TI Childhood Hemangiopericytoma: Review of St Jude Children's Research Hospital SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE hemangiopericytoma; infants; children; intracranial ID OF-THE-LITERATURE; INTRACRANIAL HEMANGIOPERICYTOMA; CONGENITAL HEMANGIOPERICYTOMA; INFANTILE HEMANGIOPERICYTOMA; PREOPERATIVE CHEMOTHERAPY; FIBROUS TUMOR; SKULL BASE; RADIOTHERAPY; MANAGEMENT; SPECTRUM AB Background: Hemangiopericytoma (HPC) is a heterogeneous, highly vascularized malignant soft-tissue neoplasm with 2 different clinical presentations: adult-type and infantile-type HPC. Intracranial HPC represents a special subtype with a high proclivity toward recurrence and metastasis. Methods: The authors have reviewed the clinical features, response to treatment, and outcomes of 17 patients with HPC treated at St Jude Children's Research Hospital from 1962 to 2009. Results: At diagnosis, 11 patients were older than 1 year (subgroup A) and 6 patients were younger than 1 year (subgroup B). Subgroup A: median age at diagnosis 13.5 years, (range, 4 to 20 y). Primary sites were intracranial (n = 5), thigh (n = 3), calf (n = 1), foot (n = 1), and scalp (n = 1). One patient who presented with a thigh HPC had metastatic disease at diagnosis, and 3 patients with head location had unresectable tumors. Two patients with thigh location experienced objective responses to chemotherapy. Six patients died of disease progression, 4 of them had an intracranial location. The remaining 5 children are alive at follow-up of 12 to 32 years. Subgroup B: median age at diagnosis 0.5 months (range, 0 to 3 mo). Primary sites were thigh (n = 2), calf (n = 1), perianal (n = 1), forearm (n = 1), and lung (n = 1). Three patients with limb location had unresectable disease at diagnosis, 2 of them experienced excellent responses to neoadjuvant chemotherapy and 1 did not show any response to chemotherapy and a staged resection was performed. All 6 infants are alive without evidence of disease at follow-up of 2 to 27 years. Conclusions: Infantile HPC is characterized by a better clinical behavior than the adult type, which requires an aggressive multimodality therapy. Chemoresponsiveness and spontaneous regression have been reported in children younger than 1 year, suggesting that a more conservative surgical approach should be used. Intracranial HPC is considered as an aggressive tumor because of its propensity for recurrence and metastasis. C1 [Fernandez-Pineda, Israel; Parida, Lalit; Davidoff, Andrew M.; Rao, Bhaskar N.] St Jude Childrens Hosp, Dept Surg, Memphis, TN 38105 USA. [Jenkins, Jesse J.] St Jude Childrens Hosp, Dept Pathol, Memphis, TN 38105 USA. [Rodriguez-Galindo, Carlos] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Rodriguez-Galindo, Carlos] Childrens Hosp, Boston, MA 02115 USA. RP Fernandez-Pineda, I (reprint author), St Jude Childrens Hosp, Dept Surg, 262 Danny Thomas Pl,Mail Stop 133, Memphis, TN 38105 USA. EM israel.fernandez@stjude.org RI IBIS, MALFORMACIONES/H-7372-2016 NR 32 TC 8 Z9 10 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD JUL PY 2011 VL 33 IS 5 BP 356 EP 359 DI 10.1097/MPH.0b013e318214e667 PG 4 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 781IS UT WOS:000291924700019 PM 21602721 ER PT J AU Wang, Y AF Wang, Ying TI Battle Hymn of the Tiger Mother SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Book Review C1 [Wang, Ying] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Wang, Y (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM Yingwang_1@yahoo.com NR 1 TC 0 Z9 0 U1 0 U2 4 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 JUL PY 2011 VL 50 IS 7 BP 726 EP 727 DI 10.1016/j.jaac.2011.05.003 PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 786CC UT WOS:000292279100013 ER PT J AU Prager, LM AF Prager, Laura M. TI Battle Hymn of the Tiger Mother SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Book Review C1 [Prager, Laura M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Prager, LM (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM lmprager@partners.org NR 1 TC 0 Z9 0 U1 0 U2 4 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 JUL PY 2011 VL 50 IS 7 BP 727 EP 728 DI 10.1016/j.jaac.2011.05.004 PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 786CC UT WOS:000292279100014 ER PT J AU Patti, JA AF Patti, John A. TI The National Radiology Data Registry: A Necessary Component of Quality Health Care SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Patti, JA (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,FND 202, Boston, MA 02114 USA. EM jpatti@partners.org NR 2 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD JUL PY 2011 VL 8 IS 7 BP 453 EP 453 DI 10.1016/j.jacr.2011.05.014 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 971JZ UT WOS:000306201500001 PM 21723477 ER PT J AU Bennett, GL Andreotti, RF Lee, SI Allison, SOD Brown, DL Dubinsky, T Glanc, P Mitchell, DG Podrasky, AE Shipp, TD Siegel, CL Wong-You-Cheong, JJ Zelop, CM AF Bennett, Genevieve L. Andreotti, Rochelle F. Lee, Susanna I. Allison, Sandra O. DeJesus Brown, Douglas L. Dubinsky, Theodore Glanc, Phyllis Mitchell, Donald G. Podrasky, Ann E. Shipp, Thomas D. Siegel, Cary Lynn Wong-You-Cheong, Jade J. Zelop, Carolyn M. TI ACR Appropriateness Criteria (R) on Abnormal Vaginal Bleeding SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Appropriateness Criteria (R); vaginal bleeding; endometrium; transvaginal ultrasound; hysterosonography; MRI ID TRANSVAGINAL ULTRASONOGRAPHY; ENDOMETRIAL THICKNESS; POSTMENOPAUSAL WOMEN; ENDOVAGINAL SONOGRAPHY; PREMENOPAUSAL WOMEN; DOPPLER SONOGRAPHY; UTERINE CAVITY; SONOHYSTEROGRAPHY; CARCINOMA; DIAGNOSIS AB In evaluating a woman with abnormal vaginal bleeding, imaging cannot replace definitive histologic diagnosis but often plays an important role in screening, characterization of structural abnormalities, and directing appropriate patient care. Transvaginal ultrasound (TVUS) is generally the initial imaging modality of choice, with endometrial thickness a well-established predictor of endometrial disease in postmenopausal women. Endometrial thickness measurements of <= 5 mm and <= 4 mm have been advocated as appropriate upper threshold values to reasonably exclude endometrial carcinoma in postmenopausal women with vaginal bleeding; however, the best upper threshold endometrial thickness in the asymptomatic postmenopausal patient remains a subject of debate. Endometrial thickness in a premenopausal patient is a less reliable indicator of endometrial pathology since this may vary widely depending on the phase of menstrual cycle, and an upper threshold value for normal has not been well-established. Transabdominal ultrasound is generally an adjunct to TVUS and is most helpful when TVUS is not feasible or there is poor visualization of the endometrium. Hysterosonography may also allow for better delineation of both the endometrium and focal abnormalities in the endometrial cavity, leading to hysteroscopically directed biopsy or resection. Color and pulsed Doppler may provide additional characterization of a focal endometrial abnormality by demonstrating vascularity. MRI may also serve as an important problem-solving tool if the endometrium cannot be visualized on TVUS and hysterosonography is not possible, as well as for pretreatment planning of patients with suspected endometrial carcinoma. CT is generally not warranted for the evaluation of patients with abnormal bleeding, and an abnormal endometrium incidentally detected on CT should be further evaluated with TVUS. C1 [Bennett, Genevieve L.] NYU Med Ctr, New York, NY 10016 USA. [Andreotti, Rochelle F.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Lee, Susanna I.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Allison, Sandra O. DeJesus] Georgetown Univ Hosp, Washington, DC 20007 USA. [Brown, Douglas L.] Mayo Clin, Rochester, MN USA. [Dubinsky, Theodore] Univ Washington, Sch Med, Seattle, WA USA. [Glanc, Phyllis] Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. [Mitchell, Donald G.] Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. [Podrasky, Ann E.] Baptist Hosp Miami, S Miami Ctr Women & Infants, Miami, FL USA. [Shipp, Thomas D.] Diagnost Ultrasound Associates, Boston, MA USA. [Shipp, Thomas D.; Zelop, Carolyn M.] Amer Coll Obstetricians & Gynecologists, Washington, DC USA. [Siegel, Cary Lynn] Mallinckrodt Inst Radiol, St Louis, MO USA. [Wong-You-Cheong, Jade J.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Zelop, Carolyn M.] Univ Connecticut, Sch Med, Farmington, CT USA. RP Bennett, GL (reprint author), Amer Coll Radiol, 1891 Preston White Dr, Reston, VA 20191 USA. EM Genevieve.Bennett@nyumc.org NR 60 TC 8 Z9 8 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD JUL PY 2011 VL 8 IS 7 BP 460 EP 468 DI 10.1016/j.jacr.2011.03.011 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 971JZ UT WOS:000306201500006 PM 21723482 ER PT J AU Zondervan, RL Hahn, PF Sadow, CA Liu, B Lee, SI AF Zondervan, Robert L. Hahn, Peter F. Sadow, Cheryl A. Liu, Bob Lee, Susanna I. TI Frequent Body CT Scanning of Young Adults: Indications, Outcomes, and Risk for Radiation-Induced Cancer SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Radiation safety; radiation effects; computed tomography; health policy and practice; physics ID COMPUTED-TOMOGRAPHY; DIAGNOSTIC-RADIOLOGY; IONIZING-RADIATION; UNITED-STATES; EXPOSURE; PROTOCOLS; REPEAT; TRAUMA; SCANS AB Purpose: The aims of this study were to define the magnitude of frequent body CT scanning of young adults and to determine associated patient diagnoses, examination indications, short-term outcomes, and estimated radiation-induced cancer risk. Methods: Patients aged 18 to 35 years who underwent chest or abdominopelvic CT between 2003 and 2007 at any of 3 hospitals were identified and categorized by total number of scans per body part as rarely (<5), intermediately (>5 and <15), or frequently (>15) scanned. Medical records of the frequently scanned were reviewed. Cumulative radiation exposure, calculated from typical effective doses, was used to estimate cancer risk. Cancer incidence and mortality were estimated using the Biological Effects of Ionizing Radiation method. Results: A total of 25,104 patients underwent 45,632 scans, of whom 23,851 (95%) and 70 (0.3%) were rarely and frequently scanned, respectively. Among frequently scanned patients, the most common diagnoses were cancer (19 of 36 [52.8%]) and cystic fibrosis with lung transplantation (11 of 36 [30.5%]) for chest CT and cancer (25 of 34 [73.5%]) for abdominopelvic CT. During the mean 5.4 years (range, 0.9-7.6 years) of follow-up, 46% of frequently scanned patients (32 of 70) died. Of the 47 cancers predicted in the entire cohort, 36 (77%) and 2 (3%) were expected in the rarely and frequently scanned. Conclusions: The majority of CT-induced cancers are predicted to result from sporadic rather than frequent scanning. Frequent scanning confers a significant cancer risk but occurs in severely ill patients, a large proportion of who die before any radiation-induced cancer would be a factor in their health. C1 [Zondervan, Robert L.; Hahn, Peter F.; Liu, Bob] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Lee, Susanna I.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp,Webster Ctr Radiat Res & E, Boston, MA 02115 USA. [Sadow, Cheryl A.] Harvard Univ, Brigham & Womens Hosp, Dept Radiol, Sch Med, Boston, MA 02115 USA. RP Zondervan, RL (reprint author), Massachusetts Gen Hosp, Dept Radiol, 25 New Chardon, Boston, MA 02114 USA. EM robert.zondervan@gmail.com NR 42 TC 16 Z9 17 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD JUL PY 2011 VL 8 IS 7 BP 501 EP 507 DI 10.1016/j.jacr.2010.12.025 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 971JZ UT WOS:000306201500012 PM 21723488 ER PT J AU Helmer, KG Ambite, JL Ames, J Ananthakrishnan, R Burns, G Chervenak, AL Foster, I Liming, L Keator, D Macciardi, F Madduri, R Navarro, JP Potkin, S Rosen, B Ruffins, S Schuler, R Turner, JA Toga, A Williams, C Kesselman, C AF Helmer, Karl G. Ambite, Jose Luis Ames, Joseph Ananthakrishnan, Rachana Burns, Gully Chervenak, Ann L. Foster, Ian Liming, Lee Keator, David Macciardi, Fabio Madduri, Ravi Navarro, John-Paul Potkin, Steven Rosen, Bruce Ruffins, Seth Schuler, Robert Turner, Jessica A. Toga, Arthur Williams, Christina Kesselman, Carl CA Biomed Informatics Res Network TI Enabling collaborative research using the Biomedical Informatics Research Network (BIRN) SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID MULTICENTER FMRI; VARIABILITY; INTEGRATION; ACTIVATION; DATABASE AB Objective As biomedical technology becomes increasingly sophisticated, researchers can probe ever more subtle effects with the added requirement that the investigation of small effects often requires the acquisition of large amounts of data. In biomedicine, these data are often acquired at, and later shared between, multiple sites. There are both technological and sociological hurdles to be overcome for data to be passed between researchers and later made accessible to the larger scientific community. The goal of the Biomedical Informatics Research Network (BIRN) is to address the challenges inherent in biomedical data sharing. Materials and methods BIRN tools are grouped into 'capabilities' and are available in the areas of data management, data security, information integration, and knowledge engineering. BIRN has a user-driven focus and employs a layered architectural approach that promotes reuse of infrastructure. BIRN tools are designed to be modular and therefore can work with pre-existing tools. BIRN users can choose the capabilities most useful for their application, while not having to ensure that their project conforms to a monolithic architecture. Results BIRN has implemented a new software-based data-sharing infrastructure that has been put to use in many different domains within biomedicine. BIRN is actively involved in outreach to the broader biomedical community to form working partnerships. Conclusion BIRN's mission is to provide capabilities and services related to data sharing to the biomedical research community. It does this by forming partnerships and solving specific, user-driven problems whose solutions are then available for use by other groups. C1 [Helmer, Karl G.; Rosen, Bruce] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. [Helmer, Karl G.; Rosen, Bruce] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Ambite, Jose Luis; Burns, Gully; Chervenak, Ann L.; Schuler, Robert; Williams, Christina; Kesselman, Carl] Univ So Calif, Inst Informat Sci, Marina Del Rey, CA 90292 USA. [Ames, Joseph; Keator, David; Macciardi, Fabio; Potkin, Steven] Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92717 USA. [Ananthakrishnan, Rachana; Foster, Ian; Liming, Lee; Madduri, Ravi; Navarro, John-Paul] Argonne Natl Lab, Math & Comp Sci MCS Div, Argonne, IL 60439 USA. [Ananthakrishnan, Rachana; Foster, Ian; Liming, Lee; Madduri, Ravi; Navarro, John-Paul] Univ Chicago, Computat Inst, Chicago, IL 60637 USA. [Potkin, Steven] Univ Calif Irvine, Brain Imaging Ctr, Irvine, CA USA. [Ruffins, Seth; Toga, Arthur] Univ Calif Los Angeles, Sch Med, Dept Neurol, Lab Neuro Imaging, Los Angeles, CA 90024 USA. [Ruffins, Seth] CALTECH, Biol Imaging Ctr, Pasadena, CA 91125 USA. [Turner, Jessica A.] Mind Res Network, Albuquerque, NM USA. RP Helmer, KG (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, 149-13th St Room 2301, Boston, MA 02129 USA. EM helmer@nmr.mgh.harvard.edu RI Turner, Jessica/H-7282-2015; Macciardi, Fabio/N-3768-2014; OI Kesselman, Carl/0000-0003-0917-1562; Turner, Jessica/0000-0003-0076-8434; Macciardi, Fabio/0000-0003-0537-4266; Potkin, Steven/0000-0003-1028-1013; Burns, Gully/0000-0003-1493-865X FU National Center for Research Resources (NCRR) [U24-RR025736, U24-RR021992, U24-RR021760]; National Institute of General Medical Sciences (NIGMS [RO1 GM083871]; National Science Foundation and through the Kinetics and Michael J. Fox Foundations [0849977]; [U24-RR026057-01] FX BIRN is supported by grants from the National Center for Research Resources (NCRR) through the following grants: U24-RR025736, U24-RR021992, and U24-RR021760. The outreach portion of BIRN is supported through U24-RR026057-01. Some of the knowledge engineering work is supported though a grant from the National Institute of General Medical Sciences (NIGMS; RO1 GM083871) and the National Science Foundation (grant 0849977), and through the Kinetics and Michael J. Fox Foundations. NR 37 TC 24 Z9 24 U1 0 U2 10 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD JUL PY 2011 VL 18 IS 4 BP 416 EP 422 DI 10.1136/amiajnl-2010-000032 PG 7 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics SC Computer Science; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics GA 783DM UT WOS:000292061700012 PM 21515543 ER PT J AU Jones, RN Manly, J Glymour, MM Rentz, DM Jefferson, AL Stern, Y AF Jones, Richard N. Manly, Jennifer Glymour, M. Maria Rentz, Dorene M. Jefferson, Angela L. Stern, Yaakov TI Conceptual and Measurement Challenges in Research on Cognitive Reserve SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article DE Cognitive reserve; Brain reserve; Latent variable; Aging; Cognition; Neuronal plasticity; Multivariate Analysis; Environment; Social Environment; Education; Social Class; Intelligence ID QUALITY-OF-LIFE; ALZHEIMERS-DISEASE; OLDER-ADULTS; TRAINING TRIAL; BRAIN RESERVE; DEMENTIA; HEALTH; EDUCATION; INTELLIGENCE; PLASTICITY AB Cognitive reserve, broadly conceived, encompasses aspects of brain structure and function that optimize individual performance in the presence of injury or pathology. Reserve is defined as a feature of brain structure and/or function that modifies the relationship between injury or pathology and performance on neuropsychological tasks or clinical outcomes. Reserve is challenging to study for two reasons. The first is: reserve is a hypothetical construct, and direct measures of reserve are not available. Proxy variables and latent variable models are used to attempt to operationalize reserve. The second is: in vivo measures of neuronal pathology are not widely available. It is challenging to develop and test models involving a risk factor (injury or pathology), a moderator (reserve) and an outcome (performance or clinical status) when neither the risk factor nor the moderator are measured directly. We discuss approaches for quantifying reserve with latent variable models, with emphasis on their application in the analysis of data from observational studies. Increasingly latent variable models are used to generate composites of cognitive reserve based on multiple proxies. We review the theoretical and ontological status of latent variable modeling approaches to cognitive reserve, and suggest research strategies for advancing the field. (JINS, 2011, 17, 593-601) C1 [Jones, Richard N.] Harvard Univ, Beth Israel Deaconess Med Ctr, Inst Aging Res, Sch Med,Div Gerontol,Hebrew SeniorLife,Dept Med, Boston, MA 02131 USA. [Manly, Jennifer; Stern, Yaakov] Columbia Univ, Med Ctr, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY USA. [Manly, Jennifer; Stern, Yaakov] Columbia Univ, Dept Neurol, Med Ctr, New York, NY USA. [Glymour, M. Maria] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02131 USA. [Rentz, Dorene M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02131 USA. [Rentz, Dorene M.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Jefferson, Angela L.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Stern, Yaakov] Columbia Univ Coll Phys & Surg, Dept Neurol, New York, NY 10032 USA. [Stern, Yaakov] Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. RP Jones, RN (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Inst Aging Res, Sch Med,Div Gerontol,Hebrew SeniorLife,Dept Med, 1200 Ctr St, Boston, MA 02131 USA. EM jones@hrca.harvard.edu RI Jones, Richard/J-3488-2013 OI Jones, Richard/0000-0002-1049-218X FU NIH/NIA [P01AG031720]; [R13AG030995] FX Collaborative work on this project by the co-authors was partially supported by a conference grant on Advanced Psychometric Methods in Cognitive Aging Research (R13AG030995). Dr. Jones was also supported by NIH/NIA grant P01AG031720. The authors have no conflict of interest. NR 62 TC 51 Z9 54 U1 2 U2 19 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 JUL PY 2011 VL 17 IS 4 BP 593 EP 601 DI 10.1017/S1355617710001748 PG 9 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 781NL UT WOS:000291939900003 PM 21411036 ER PT J AU Burstein, HJ AF Burstein, Harold J. TI The Fifth "C" Is Cost: Highlights From ASCO 2011 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 02115 USA. [Burstein, Harold J.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Burstein, Harold J.] Harvard Univ, Cambridge, MA USA. [Burstein, Harold J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Burstein, HJ (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 2 TC 0 Z9 0 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 JUL PY 2011 VL 9 IS 7 BP 691 EP 691 PG 1 WC Oncology SC Oncology GA 785WT UT WOS:000292264200002 PM 21715720 ER PT J AU Streiff, MB Bockenstedt, PL Cataland, SR Chesney, C Eby, C Fanikos, J Fogarty, PF Gao, SW Garcia-Aguilar, J Goldhaber, SZ Hassoun, H Hendrie, P Holmstrom, B Jones, KA Kuderer, N Lee, JT Millenson, MM Neff, AT Ortel, TL Smith, JL Yee, GC Zakarija, A AF Streiff, Michael B. Bockenstedt, Paula L. Cataland, Spero R. Chesney, Carolyn Eby, Charles Fanikos, John Fogarty, Patrick F. Gao, Shuwei Garcia-Aguilar, Julio Goldhaber, Samuel Z. Hassoun, Hani Hendrie, Paul Holmstrom, Bjorn Jones, Kimberly A. Kuderer, Nicole Lee, Jason T. Millenson, Michael M. Neff, Anne T. Ortel, Thomas L. Smith, Judy L. Yee, Gary C. Zakarija, Anaadriana CA NCCN Clinical Practice Guidelines TI Venous Thromboembolic Disease SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review DE NCCN Clinical Practice Guidelines; NCCN Guidelines; venous thromboembolism; superficial vein thrombosis; cancer; deep venous thrombosis; pulmonary embolism; anticoagulation; heparin; prophylaxis; treatment; low-molecular-weight heparin; warfarin ID HEPARIN-INDUCED-THROMBOCYTOPENIA; MOLECULAR-WEIGHT HEPARIN; DEEP-VEIN THROMBOSIS; BUDD-CHIARI-SYNDROME; ACUTE PULMONARY-EMBOLISM; RANDOMIZED CONTROLLED-TRIAL; ENDOSCOPIC VARICEAL LIGATION; SINGLE-CENTER EXPERIENCE; VENA-CAVA FILTERS; INTERNATIONAL NORMALIZED RATIO C1 [Bockenstedt, Paula L.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Cataland, Spero R.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Cataland, Spero R.] Solove Res Inst, Columbus, OH USA. [Chesney, Carolyn] Univ Tennessee, Inst Canc, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Eby, Charles] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Eby, Charles] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Fanikos, John; Goldhaber, Samuel Z.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Gao, Shuwei] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Garcia-Aguilar, Julio] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Hassoun, Hani] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Hendrie, Paul] Univ Washington Seattle Canc Care Alliance, Washington, DC USA. [Jones, Kimberly A.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Lee, Jason T.] Stanford Comprehens Canc Ctr, Stanford, CA USA. [Millenson, Michael M.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Neff, Anne T.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Smith, Judy L.] Roswell Pk Canc Inst, Buffalo, NY USA. [Yee, Gary C.] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. [Zakarija, Anaadriana] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. FU NCI NIH HHS [KM1 CA156687, UC2 CA148041]; NHLBI NIH HHS [R01 HL095109] NR 384 TC 43 Z9 45 U1 0 U2 2 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD JUL PY 2011 VL 9 IS 7 BP 714 EP 777 PG 64 WC Oncology SC Oncology GA 785WT UT WOS:000292264200005 PM 21715723 ER PT J AU Kuter, DJ AF Kuter, D. J. TI TPO mimetics in ITP SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 [Kuter, D. J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Hematol, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1538-7933 EI 1538-7836 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD JUL PY 2011 VL 9 SU 2 SI SI MA SY-TU-003 BP 251 EP 251 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA V33AX UT WOS:000208992800003 ER PT J AU Springer, TA AF Springer, T. A. TI Biology and physics of von Willebrand factor concatamers SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 [Springer, T. A.] Immune Dis Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1538-7933 EI 1538-7836 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD JUL PY 2011 VL 9 SU 2 SI SI MA SA-TU-004 BP 254 EP 254 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA V33AX UT WOS:000208992800014 ER PT J AU Grabowski, EF Cheung, M Skaria, A Kushak, RI Ingelfinger, JR AF Grabowski, E. F. Cheung, M. Skaria, A. Kushak, R., I Ingelfinger, J. R. TI Shiga toxin upregulates tissue factor gene expression in endothelium while reducing secretion and cell-surface association of tissue factor pathway inhibitor SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Pediat Hematol Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1538-7933 EI 1538-7836 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD JUL PY 2011 VL 9 SU 2 SI SI MA O-TU-047 BP 275 EP 275 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA V33AX UT WOS:000208992800079 ER PT J AU Frelinger, AL Jakubowski, JA Sugidachi, A Barnard, MR Michelson, AD AF Frelinger, A. L. Jakubowski, J. A. Sugidachi, A. Barnard, M. R. Michelson, A. D. TI The active metabolite of prasugrel augments GPIIb-IIIa antagonist inhibition of platelet activation and aggregation: complementary roles for inhibition of P2Y(12) and GPIIb-IIIa SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 [Frelinger, A. L.; Barnard, M. R.; Michelson, A. D.] Childrens Hosp Boston, Dana Farber Canc Inst, Div Hematol Oncol, Ctr Platelet Res Studies, Boston, MA USA. [Frelinger, A. L.; Barnard, M. R.; Michelson, A. D.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Jakubowski, J. A.] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN USA. [Sugidachi, A.] Daiichi Sankyo Co Ltd, Biol Res Labs, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1538-7933 EI 1538-7836 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD JUL PY 2011 VL 9 SU 2 SI SI MA P-TU-099 BP 339 EP 339 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA V33AX UT WOS:000208992800269 ER PT J AU Kim, B Viel, KR Marder, VJ Howard, TE AF Kim, B. Viel, K. R. Marder, V. J. Howard, T. E. TI ADAMTS13 single-nucleotide polymorphisms in geographically-diverse populations SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 [Kim, B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol Oncol, Los Angeles, CA 90024 USA. [Viel, K. R.; Marder, V. J.] St Josephs Hosp, St Josephs Translat Res Inst, Phoenix, AZ USA. [Howard, T. E.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Pathol & Lab Med, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1538-7933 EI 1538-7836 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD JUL PY 2011 VL 9 SU 2 SI SI MA P-TU-473 BP 456 EP 456 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA V33AX UT WOS:000208992801255 ER PT J AU Lewis, KB Nguyen, PCT Norby-Slycord, C Howard, TE Key, NS Pratt, KP AF Lewis, K. B. Nguyen, P-C T. Norby-Slycord, C. Howard, T. E. Key, N. S. Pratt, K. P. TI Phenotypes of allo- and auto-immune antibody responses to FVIII characterized by surface plasmon resonance SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 [Lewis, K. B.; Nguyen, P-C T.; Norby-Slycord, C.; Pratt, K. P.] Puget Sound Blood Ctr, Res Dept, Seattle, WA USA. [Howard, T. E.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Key, N. S.] Univ N Carolina, Hemophilia & Thrombosis Ctr, Chapel Hill, NC 27515 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1538-7933 EI 1538-7836 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD JUL PY 2011 VL 9 SU 2 SI SI MA P-WE-184 BP 578 EP 578 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA V33AX UT WOS:000208992802092 ER PT J AU Wagner, DD AF Wagner, D. D. TI How platelets safeguard vascular integrity SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 [Wagner, D. D.] Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. [Wagner, D. D.] Immune Dis Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1538-7933 EI 1538-7836 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD JUL PY 2011 VL 9 SU 2 SI SI MA SA-TH-004 BP 714 EP 714 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA V33AX UT WOS:000208992803012 ER PT J AU Kuter, DJ Gerstenberger, E Konkle, BA Uhl, L Assmann, SF Ortel, TL AF Kuter, D. J. Gerstenberger, E. Konkle, B. A. Uhl, L. Assmann, S. F. Ortel, T. L. TI Heparin-induced thrombocytopenia (HIT)retrospective analysis of data on incidence and outcomes (HIT-RADIO Study) SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 [Kuter, D. J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Hematol, Cambridge, MA 02138 USA. [Gerstenberger, E.; Assmann, S. F.] Univ Washington, Sch Med, New England Res Inst, Seattle, WA 98195 USA. [Konkle, B. A.] Univ Washington, Sch Med, Puget Sound Blood Ctr, Seattle, WA 98195 USA. [Uhl, L.] Harvard Univ, Sch Med, Beth Israel Hosp, Cambridge, MA 02138 USA. [Ortel, T. L.] Duke Univ, Sch Med, Durham, NC 27706 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1538-7933 EI 1538-7836 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD JUL PY 2011 VL 9 SU 2 SI SI MA P-LB-001 BP 960 EP 960 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA V33AX UT WOS:000208992804381 ER PT J AU Gheuens, S Bord, E Kesari, S Simpson, DM Gandhi, RT Clifford, DB Berger, JR Ngo, L Koralnik, IJ AF Gheuens, Sarah Bord, Evelyn Kesari, Santosh Simpson, David M. Gandhi, Rajesh T. Clifford, David B. Berger, Joseph R. Ngo, Long Koralnik, Igor J. TI Role of CD4(+) and CD8(+) T-Cell Responses against JC Virus in the Outcome of Patients with Progressive Multifocal Leukoencephalopathy (PML) and PML with Immune Reconstitution Inflammatory Syndrome SO JOURNAL OF VIROLOGY LA English DT Article ID HEPATITIS-C; NATALIZUMAB; LYMPHOCYTES; RESTORATION; ASSOCIATION; INFECTION; FREQUENCY; SURVIVAL; DISEASE; EPITOPE AB Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating disease of the brain caused by JC virus (JCV). To assess the role of CD4(+) and CD8(+) T-cells against JCV in the clinical outcome of PML and PML in the setting of immune reconstitution inflammatory syndrome (IRIS), we tested gamma interferon (IFN-gamma) response by enzyme-linked immunosorbent spot (ELISpot) and intracellular cytokine staining (ICS) in 117 subjects, including 66 PML patients with different clinical outcomes. Both assays were concordant and demonstrated that the cellular immune response against JCV is associated with better clinical outcome. PML survivors had an early CD8(+) T-cell response more frequently than PML progressors (100% versus 27.3%; P = 0.001), while only a trend was observed for the early CD4(+) T-cell response between these two groups (80% versus 45.5%; P = 0.18). Although IRIS itself was more frequent in the PML survivor group, there was no difference in IFN-gamma-producing CD4(+) and CD8(+) T-cells between IRIS and non-IRIS PML patients, suggesting that T-cells expressing other cytokines likely have a role in the immunopathogenesis of IRIS. ELISpot and ICS assays are useful prognostic markers of PML evolution and may help in the clinical management of these patients. C1 [Gheuens, Sarah; Bord, Evelyn; Koralnik, Igor J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div NeuroVirol,Div Viral Pathogenesis, Boston, MA 02215 USA. [Kesari, Santosh] UC San Diego Sch Med, Moores Canc Ctr, Dept Neurosci, Div Neurooncol, La Jolla, CA USA. [Simpson, David M.] Mt Sinai Med Ctr, Dept Neurol, New York, NY 10029 USA. [Gandhi, Rajesh T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02215 USA. [Gandhi, Rajesh T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ragon Inst, Boston, MA 02215 USA. [Clifford, David B.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Berger, Joseph R.] Univ Kentucky, Coll Med, Dept Neurol, Lexington, KY USA. [Ngo, Long] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med, Boston, MA 02215 USA. RP Koralnik, IJ (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div NeuroVirol,Div Viral Pathogenesis, E CLS 1005,330 Brookline Ave, Boston, MA 02215 USA. EM ikoralni@bidmc.harvard.edu RI Kesari, Santosh/E-8461-2013 FU Harvard University CFAR; NIH [P30 AI60354, R01, R56 NS 041198,, 01 NS 047029, K24 NS 060950, T32 CA09031-32]; Belgian-American Foundation; The Harvard Clinical and Translational Science Center (NIH) [UL1 RR 025758] FX This study was supported in part by a grant from Harvard University CFAR and NIH grant P30 AI60354. I. J. K. was supported by NIH grants R01 and R56 NS 041198, R01 NS 047029, and K24 NS 060950, and S. G. was supported by NIH grant T32 CA09031-32 and a Belgian-American Foundation grant. S. G. is a fellow of the Clinical Investigator Training Program, Beth Israel Deaconess Medical Center-Harvard/MIT Health Sciences and Technology, in collaboration with Pfizer Inc. and Merck & Co. L.N. is supported by The Harvard Clinical and Translational Science Center (NIH Award UL1 RR 025758). NR 32 TC 48 Z9 48 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 JUL PY 2011 VL 85 IS 14 BP 7256 EP 7263 DI 10.1128/JVI.02506-10 PG 8 WC Virology SC Virology GA 781LA UT WOS:000291932400041 PM 21543472 ER PT J AU Blackburn, JS Liu, S Langenau, DM AF Blackburn, Jessica S. Liu, Sali Langenau, David M. TI Quantifying the Frequency of Tumor-propagating Cells Using Limiting Dilution Cell Transplantation in Syngeneic Zebrafish SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Developmental Biology; Issue 53; cancer stem cell; T-cell acute lymphoblastic leukemia; microinjection; fluorescence; self-renewal AB Self-renewing cancer cells are the only cell types within a tumor that have an unlimited ability to promote tumor growth, and are thus known as tumor-propagating cells, or tumor-initiating cells. It is thought that targeting these self-renewing cells for destruction will block tumor progression and stop relapse, greatly improving patient prognosis(1). The most common way to determine the frequency of self-renewing cells within a tumor is a limiting dilution cell transplantation assay, in which tumor cells are transplanted into recipient animals at increasing doses; the proportion of animals that develop tumors is used the calculate the number of self-renewing cells within the original tumor sample(2,3). Ideally, a large number of animals would be used in each limiting dilution experiment to accurately determine the frequency of tumor-propagating cells. However, large scale experiments involving mice are costly, and most limiting dilution assays use only 10-15 mice per experiment. Zebrafish have gained prominence as a cancer model, in large part due to their ease of genetic manipulation and the economy by which large scale experiments can be performed. Additionally, the cancer types modeled in zebrafish have been found to closely mimic their counterpart human disease(4). While it is possible to transplant tumor cells from one fish to another by sub-lethal irradiation of recipient animals, the regeneration of the immune system after 21 days often causes tumor regression(5). The recent creation of syngeneic zebrafish has greatly facilitated tumor transplantation studies (6-8). Because these animals are genetically identical, transplanted tumor cells engraft robustly into recipient fish, and tumor growth can be monitored over long periods of time. Syngeneic zebrafish are ideal for limiting dilution transplantation assays in that tumor cells do not have to adapt to growth in a foreign microenvironment, which may underestimate self-renewing cell frequency(9,10). Additionally, one-cell transplants have been successfully completed using syngeneic zebrafish(8) and several hundred animals can be easily and economically transplanted at one time, both of which serve to provide a more accurate estimate of self-renewing cell frequency. Here, a method is presented for creating primary, fluorescently-labeled T-cell acute lymphoblastic leukemia (T-ALL) in syngeneic zebrafish, and transplanting these tumors at limiting dilution into adult fish to determine self-renewing cell frequency. While leukemia is provided as an example, this protocol is suitable to determine the frequency of tumor-propagating cells using any cancer model in the zebrafish. C1 [Blackburn, Jessica S.; Liu, Sali] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Mol Pathol, Cambridge, MA 02138 USA. [Langenau, David M.] Massachusetts Gen Hosp, Ctr Canc, Harvard Stem Cell Inst, Dept Mol Pathol, Boston, MA 02114 USA. RP Langenau, DM (reprint author), Massachusetts Gen Hosp, Ctr Canc, Harvard Stem Cell Inst, Dept Mol Pathol, Boston, MA 02114 USA. EM dlangenau@partners.org FU NIH [5T32CA09216-26, K01 AR055619-01A1, 3 K01 AR055619-03S1]; Alex's Lemonade Stand Foundation; Harvard Stem Cell Institute; American Cancer Society FX Funding has been provided by NIH grants 5T32CA09216-26 (for J.S.B.), and K01 AR055619-01A1 and 3 K01 AR055619-03S1 (for D.M.L.), as well as by the Alex's Lemonade Stand Foundation, the Harvard Stem Cell Institute and the American Cancer Society. NR 17 TC 4 Z9 4 U1 0 U2 2 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 JUL PY 2011 IS 53 AR e2790 DI 10.3791/2790 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V36MC UT WOS:000209215000014 PM 21775966 ER PT J AU Pinne, M Haake, D AF Pinne, Marija Haake, David TI Immuno-fluorescence Assay of Leptospiral Surface-exposed Proteins SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article C1 [Pinne, Marija] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Pinne, Marija] Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA. [Haake, David] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Haake, David] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA. [Haake, David] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Gent, Los Angeles, CA 90095 USA. [Haake, David] Vet Affairs Greater Angeles Hlth Care Syst, Div Infect Dis, Los Angeles, CA USA. RP Pinne, M (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. EM mpinne@ucla.edu NR 17 TC 0 Z9 0 U1 0 U2 0 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 JUL PY 2011 IS 53 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V36MC UT WOS:000209215000019 ER PT J AU Tam, JM Castro, CE Heath, RJW Mansour, MK Cardenas, ML Xavier, RJ Lang, MJ Vyas, JM AF Tam, Jenny M. Castro, Carlos E. Heath, Robert J. W. Mansour, Michael K. Cardenas, Michael L. Xavier, Ramnik J. Lang, Matthew J. Vyas, Jatin M. TI Use of an Optical Trap for Study of Host-Pathogen Interactions for Dynamic Live Cell Imaging SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Immunology; Issue 53; Optical trapping; optical tweezers; T-cell; pathogen; live cell imaging; spinning disk confocal microscopy; Aspergillus fumigatus; Candida albicans; fungi AB Dynamic live cell imaging allows direct visualization of real-time interactions between cells of the immune system(1, 2); however, the lack of spatial and temporal control between the phagocytic cell and microbe has rendered focused observations into the initial interactions of host response to pathogens difficult. Historically, intercellular contact events such as phagocytosis(3) have been imaged by mixing two cell types, and then continuously scanning the field-of-view to find serendipitous intercellular contacts at the appropriate stage of interaction. The stochastic nature of these events renders this process tedious, and it is difficult to observe early or fleeting events in cell-cell contact by this approach. This method requires finding cell pairs that are on the verge of contact, and observing them until they consummate their contact, or do not. To address these limitations, we use optical trapping as a non-invasive, non-destructive, but fast and effective method to position cells in culture. Optical traps, or optical tweezers, are increasingly utilized in biological research to capture and physically manipulate cells and other micron-sized particles in three dimensions(4). Radiation pressure was first observed and applied to optical tweezer systems in 1970(5, 6), and was first used to control biological specimens in 1987(7). Since then, optical tweezers have matured into a technology to probe a variety of biological phenomena(8-13). We describe a method(14) that advances live cell imaging by integrating an optical trap with spinning disk confocal microscopy with temperature and humidity control to provide exquisite spatial and temporal control of pathogenic organisms in a physiological environment to facilitate interactions with host cells, as determined by the operator. Live, pathogenic organisms like Candida albicans and Aspergillus fumigatus, which can cause potentially lethal, invasive infections in immunocompromised individuals(15, 16) (e.g. AIDS, chemotherapy, and organ transplantation patients), were optically trapped using non-destructive laser intensities and moved adjacent to macrophages, which can phagocytose the pathogen. High resolution, transmitted light and fluorescence-based movies established the ability to observe early events of phagocytosis in living cells. To demonstrate the broad applicability in immunology, primary T-cells were also trapped and manipulated to form synapses with anti-CD3 coated microspheres in vivo, and time-lapse imaging of synapse formation was also obtained. By providing a method to exert fine spatial control of live pathogens with respect to immune cells, cellular interactions can be captured by fluorescence microscopy with minimal perturbation to cells and can yield powerful insight into early responses of innate and adaptive immunity. C1 [Tam, Jenny M.; Mansour, Michael K.; Cardenas, Michael L.; Vyas, Jatin M.] Harvard Univ, Massachusetts Gen Hosp, Div Infect Dis, Dept Med,Med Sch, Cambridge, MA 02138 USA. [Castro, Carlos E.] Ohio State Univ, Dept Mech & Aerosp Engn, Columbus, OH 43210 USA. [Heath, Robert J. W.; Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Sch Med, Cambridge, MA 02138 USA. [Lang, Matthew J.] Vanderbilt Univ, Dept Chem & Biomol Engn, Nashville, TN USA. RP Vyas, JM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Div Infect Dis, Dept Med,Med Sch, Cambridge, MA 02138 USA. EM jvyas@partners.org RI Vyas, Jatin/Q-1627-2016 OI Vyas, Jatin/0000-0002-9985-9565 FU Massachusetts General Hospital Department of Medicine Internal Funds; National Institute of Biomedical Imaging and Bioengineering grant [T32EB006348]; Massachusetts General Hospital's Center for Computational and Integrative Biology development fund; NSF [0643745]; NIH [R21CA133576]; National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) [AI057999]; [AI062773]; [DK83756]; [DK 043351] FX This work was supported by Massachusetts General Hospital Department of Medicine Internal Funds (J.M.T., M.K.M, M.L.C., J.M.V.), National Institute of Biomedical Imaging and Bioengineering grant T32EB006348 (C.E.C.), Massachusetts General Hospital's Center for Computational and Integrative Biology development fund and AI062773 (R.J.H.), grants AI062773, DK83756, and DK 043351 (R.J.X.), NSF 0643745 (M.J.L.), NIH R21CA133576 (M.J.L.), and National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) AI057999 (J.M.V.). We thank Nicholas C. Yoder for helpful discussions, and Charles Felts (RPI, Inc.) for technical assistance. NR 16 TC 4 Z9 4 U1 0 U2 2 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 JUL PY 2011 IS 53 AR UNSP e3123 DI 10.3791/3123 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V36MC UT WOS:000209215000050 ER PT J AU Lane, AA Mcafee, SL Kennedy, J Dube, C Attar, EC Ballen, KK Dey, BR Spitzer, TR Chen, YB AF Lane, Andrew A. Mcafee, Steven L. Kennedy, Joanne Dube, Christine Attar, Eyal C. Ballen, Karen K. Dey, Bimalangshu R. Spitzer, Thomas R. Chen, Yi-Bin TI High-dose chemotherapy with busulfan and cyclophosphamide and autologous stem cell rescue in patients with Hodgkin lymphoma SO LEUKEMIA & LYMPHOMA LA English DT Letter ID CONDITIONING REGIMEN; INTRAVENOUS BUSULFAN; RANDOMIZED-TRIAL; TRANSPLANTATION; ETOPOSIDE; DISEASE; BU; CY C1 [Lane, Andrew A.] Harvard Univ, Massachusetts Gen Hosp, Dana Farber Harvard Canc Ctr, Sch Med,Canc Ctr,Dept Hematol Oncol,Div Bone Marr, Boston, MA 02114 USA. RP Lane, AA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dana Farber Harvard Canc Ctr, Sch Med,Canc Ctr,Dept Hematol Oncol,Div Bone Marr, 55 Fruit St, Boston, MA 02114 USA. EM aalane@partners.org; ychen6@partners.org FU NCI NIH HHS [T32 CA009172] NR 14 TC 5 Z9 5 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD JUL PY 2011 VL 52 IS 7 BP 1363 EP 1366 DI 10.3109/10428194.2011.572324 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA 782EY UT WOS:000291992400028 PM 21612379 ER PT J AU Bickel, CS Cross, JM Bamman, MM AF Bickel, C. Scott Cross, James M. Bamman, Marcas M. TI Exercise Dosing to Retain Resistance Training Adaptations in Young and Older Adults SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE MUSCLE FIBER; SARCOPENIA; EXERCISE DOSE; HYPERTROPHY; AGING; ATROPHY ID SKELETAL-MUSCLE ADAPTATIONS; MYOFIBER HYPERTROPHY; GENE-EXPRESSION; STRENGTH; MEN; WOMEN; FORCE; AGE; INTENSITY; PEOPLE AB BICKEL, C. S., J. M. CROSS, and M. M. BAMMAN. Exercise Dosing to Retain Resistance Training Adaptations in Young and Older Adults. Med. Sci. Sports Exerc., Vol. 43, No. 7, pp. 1177-1187, 2011. Resistance training (RT) is a proven sarcopenia countermeasure with a high degree of potency. However, sustainability remains a major issue that could limit the appeal of RT as a therapeutic approach without well-defined dosing requirements to maintain gains. Purpose: To test the efficacy of two maintenance prescriptions on muscle mass, myofiber size and type distribution, and strength. We hypothesized the minimum dose required to maintain RT-induced adaptations would be greater in the old (60-75 yr) versus young (20-35 yr). Methods: Seventy adults participated in a two-phase exercise trial that consisted of RT 3 d.wk(-1) for 16 wk (phase 1) followed by a 32-wk period (phase 2) with random assignment to detraining or one of two maintenance prescriptions (reducing the dose to one-third or one-ninth of that during phase 1). Results: Phase 1 resulted in expected gains in strength, myofiber size, and muscle mass along with the typical IIx-to-IIa shift in myofiber-type distribution. Both maintenance prescriptions preserved phase 1 muscle hypertrophy in the young but not the old. In fact, the one-third maintenance dose led to additional myofiber hypertrophy in the young. In both age groups, detraining reversed the phase 1 IIx-to-IIa myofiber-type shift, whereas a dose response was evident during maintenance training with the one-third dose better maintaining the shift. Strength gained during phase 1 was largely retained throughout detraining with only a slight reduction at the final time point. Conclusions: We conclude that older adults require a higher dose of weekly loading than the young to maintain myofiber hypertrophy attained during a progressive RT program, yet gains in specific strength among older adults were well preserved and remained at or above levels of the untrained young. C1 [Bickel, C. Scott] Univ Alabama, Dept Physiol & Biophys, Core Muscle Res Lab, Birmingham, AL 35294 USA. [Bickel, C. Scott] Univ Alabama, Dept Phys Therapy, Birmingham, AL 35294 USA. [Cross, James M.] Univ Alabama, Dept Surg, Birmingham, AL 35294 USA. [Bamman, Marcas M.] Birmingham Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Birmingham, AL USA. [Bickel, C. Scott; Bamman, Marcas M.] UAB Ctr Exercise Med, Birmingham, AL USA. RP Bamman, MM (reprint author), Univ Alabama, Dept Physiol & Biophys, Core Muscle Res Lab, MCLM 966,1530 3rd Ave S, Birmingham, AL 35294 USA. EM mbamman@uab.edu FU National Institute on Aging [1R01 AG017896, 1R01 AG027084-S1]; VA Merit Review grant FX This work was sponsored by National Institute on Aging grants 1R01 AG017896 (MMB) and 1R01 AG027084-S1 (CSB), and a VA Merit Review grant (MMB). NR 42 TC 25 Z9 25 U1 3 U2 14 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 JUL PY 2011 VL 43 IS 7 BP 1177 EP 1187 DI 10.1249/MSS.0b013e318207c15d PG 11 WC Sport Sciences SC Sport Sciences GA 781IQ UT WOS:000291924500007 PM 21131862 ER PT J AU Kan, IP Keane, MM Martin, E Parks-Stamm, EJ Lewis, L Verfaellie, M AF Kan, Irene P. Keane, Margaret M. Martin, Elizabeth Parks-Stamm, Elizabeth J. Lewis, Lindsay Verfaellie, Mieke TI Implicit memory for novel associations between pictures: effects of stimulus unitization and aging SO MEMORY & COGNITION LA English DT Article DE Implicit memory; Novel associations; Priming; Aging ID ADULT AGE-DIFFERENCES; AMNESIC SUBJECTS; OLDER-ADULTS; ALZHEIMERS-DISEASE; EXPLICIT MEMORY; RECOGNITION; TESTS; FAMILIARITY; NONWORDS; DEFICIT AB Studies of implicit memory for novel associations have focused primarily on verbal materials and have highlighted the contribution of conceptually unitized representations to such priming. Using pictorial stimuli in a perceptual identification task, we examined whether new association priming can occur at a purely perceptual level. By manipulating the spatial contiguity of stimuli, we also evaluated whether such priming requires the creation of perceptually unitized representations. Finally, we examined the status of such priming in aging. In Experiment 1, we found that spatial contiguity of stimuli is not necessary for novel pictorial association priming to emerge, although such contiguity does enhance the magnitude of associative priming. In Experiment 2, we found that new association priming is age invariant, regardless of spatial contiguity. In Experiment 3, we provide additional evidence that pictorial association priming is perceptually based. These findings expand the scope and delineate the conditions of novel association priming and inform theories about the nature of implicit memory for new associations. C1 [Kan, Irene P.] Villanova Univ, Dept Psychol, Villanova, PA 19085 USA. [Kan, Irene P.; Keane, Margaret M.; Martin, Elizabeth; Parks-Stamm, Elizabeth J.; Verfaellie, Mieke] Boston VA Healthcare Syst, Memory Disorders Res Ctr, Boston, MA USA. [Kan, Irene P.; Keane, Margaret M.; Martin, Elizabeth; Parks-Stamm, Elizabeth J.; Verfaellie, Mieke] Boston Univ, Sch Med, Boston, MA 02118 USA. [Keane, Margaret M.; Lewis, Lindsay] Wellesley Coll, Dept Psychol, Wellesley, MA 02181 USA. RP Kan, IP (reprint author), Villanova Univ, Dept Psychol, 800 Lancaster Ave, Villanova, PA 19085 USA. EM irene.kan@villanova.edu OI Verfaellie, Mieke/0000-0001-5535-4584 FU NIMH NIH HHS [MH 57681, MH 070830, R01 MH070830, R01 MH057681-10, R01 MH057681] NR 50 TC 4 Z9 4 U1 0 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0090-502X EI 1532-5946 J9 MEM COGNITION JI Mem. Cogn. PD JUL PY 2011 VL 39 IS 5 BP 778 EP 790 DI 10.3758/s13421-011-0071-6 PG 13 WC Psychology, Experimental SC Psychology GA 782JB UT WOS:000292003200004 PM 21286899 ER PT J AU Styer, AK AF Styer, Aaron K. TI Building the bridge between lifestyle intervention, physical function, and cardiovascular risk in middle-aged women: lessons learned from the Women on the Move Through Activity and Nutrition study SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material ID HEALTHY C1 Massachusetts Gen Hosp, Massachusetts Gen Hosp Fertil Ctr, Vincent Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Styer, AK (reprint author), Massachusetts Gen Hosp, Massachusetts Gen Hosp Fertil Ctr, Vincent Dept Obstet & Gynecol, Boston, MA 02114 USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD JUL PY 2011 VL 18 IS 7 BP 725 EP 726 DI 10.1097/gme.0b013e31821e42ca PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 781IO UT WOS:000291924300002 PM 21587087 ER PT J AU Bailey, A AF Bailey, Allison TI Exercise as a treatment of gait dysfunction in postmenopausal women SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; HORMONE REPLACEMENT THERAPY; PLANTAR PRESSURE; RISK-FACTORS; OLDER WOMEN; PHYSICAL PERFORMANCE; FOOT PAIN; HEALTH; MENOPAUSE; COMMUNITY C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Bailey, A (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 36 TC 0 Z9 0 U1 1 U2 3 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 JUL PY 2011 VL 18 IS 7 BP 730 EP 731 DI 10.1097/gme.0b013e31821d689f PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 781IO UT WOS:000291924300004 PM 21587088 ER PT J AU Aronis, KN Joseph, RJ Blackburn, GL Mantzoros, C AF Aronis, Konstantinos N. Joseph, Richard J. Blackburn, George L. Mantzoros, Christos TI trans-Fatty acids, insulin resistance/diabetes, and cardiovascular disease risk: should policy decisions be based on observational cohort studies, or should we be waiting for results from randomized placebo-controlled trials? SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Editorial Material ID CORONARY-HEART-DISEASE; TYPE-2 DIABETES-MELLITUS; SERUM-LIPIDS; DIETARY-FAT; LIFE-STYLE; INDUSTRIAL SOURCES; METABOLIC SYNDROME; METROPOLITAN-AREA; HEALTHY-SUBJECTS; WOMEN C1 [Aronis, Konstantinos N.; Mantzoros, Christos] Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. [Joseph, Richard J.; Blackburn, George L.] Beth Israel Deaconess Med Ctr, Ctr Study Nutr Med, Dept Surg, Boston, MA 02215 USA. [Mantzoros, Christos] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Cambridge, MA 02138 USA. [Mantzoros, Christos] Boston VA Healthcare Syst, Endocrinol Sect, Boston, MA USA. RP Aronis, KN (reprint author), Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. EM karonis@bidmc.harvard.edu; rjoseph1@bidmc.harvard.edu; gblackbu@bidmc.harvard.edu; cmantzor@bidmc.harvard.edu RI Aronis, Konstantinos/F-3586-2012 OI Aronis, Konstantinos/0000-0001-7189-8434 NR 49 TC 5 Z9 5 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 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD JUL PY 2011 VL 60 IS 7 BP 901 EP 905 DI 10.1016/j.metabol.2011.04.003 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 786XC UT WOS:000292340200001 PM 21684360 ER PT J AU Hamnvik, OPR Liu, XM Petrou, M Gong, HZ Chamberland, JP Kim, EH Christophi, CA Kales, SN Christiani, DC Mantzoros, CS AF Hamnvik, Ole-Petter R. Liu, Xiamen Petrou, Michael Gong, Huizhi Chamberland, John P. Kim, Esther H. Christophi, Costas A. Kales, Stefanos N. Christiani, David C. Mantzoros, Christos S. TI Soluble leptin receptor and leptin are associated with baseline adiposity and metabolic risk factors, and predict adiposity, metabolic syndrome, and glucose levels at 2-year follow-up: the Cyprus Metabolism Prospective Cohort Study SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID TUMOR-NECROSIS-FACTOR; BINDING-PROTEIN; EXPRESSION; WEIGHT; HUMANS; TISSUE AB We examined the relationship between serum levels of leptin-binding protein (soluble leptin receptor [sOB-R]) and leptin with metabolic parameters at baseline and prospectively at 2-year follow-up in young healthy men. A total of 916 eighteen-year-old men were examined at baseline, with a subgroup of 91 participants examined again 2 years later. Anthropometric and metabolic measurements were performed at baseline and at follow-up. In the cross-sectional study, levels of sOB-R were significantly inversely correlated with all baseline measures of obesity and metabolic risk factors (blood pressure, total and low-density lipoprotein cholesterol, and fasting glucose), and significantly positively correlated with high-density lipoprotein cholesterol. After correcting for age, smoking status, and waist-to-hip ratio, the inverse correlation remained statistically significant for all measures of adiposity, fasting glucose, and the metabolic syndrome score. Correlations for leptin were similar in magnitude but opposite in direction to correlations for sOB-R. In prospective analyses, baseline levels of sOB-R were predictive at 2-year follow-up of fasting glucose, the metabolic syndrome score, and measures of adiposity in both unadjusted and adjusted models. Similarly, leptin was predictive of fasting glucose, the metabolic syndrome score, adiposity, and systolic blood pressure. We confirm correlations of leptin and sOB-R levels with measures of adiposity and metabolic risk factors at baseline, and demonstrate for the first time prospectively the role of sOB-R as an independent, although weak, predictor of metabolic syndrome and fasting glucose in young men. (C) 2011 Elsevier Inc. All rights reserved. C1 [Hamnvik, Ole-Petter R.] Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Dept Med, Boston, MA 02215 USA. [Hamnvik, Ole-Petter R.; Liu, Xiamen; Gong, Huizhi; Chamberland, John P.; Kim, Esther H.] Harvard Univ, Sch Med, Boston, MA USA. [Liu, Xiamen; Gong, Huizhi; Chamberland, John P.; Kim, Esther H.] Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. [Petrou, Michael; Christophi, Costas A.] Cyprus Univ Technol, Harvard Univ, Sch Publ Hlth, Cyprus Int Inst Environm & Publ Hlth, Limassol, Cyprus. [Christophi, Costas A.; Kales, Stefanos N.; Christiani, David C.; Mantzoros, Christos S.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Mantzoros, Christos S.] Boston VA Healthcare Syst, Endocrinol Sect, Boston, MA 02130 USA. RP Hamnvik, OPR (reprint author), Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Dept Med, Boston, MA 02215 USA. EM ohamnvik@partners.org RI Hamnvik, Ole-Petter/D-1719-2011; OI Chamberland, John/0000-0002-7862-1371 NR 25 TC 25 Z9 27 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 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD JUL PY 2011 VL 60 IS 7 BP 987 EP 993 DI 10.1016/j.metabol.2010.09.009 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 786XC UT WOS:000292340200013 PM 21056886 ER PT J AU Fletcher, CE Copeland, LA Lowery, JC Reeves, PJ AF Fletcher, Carol E. Copeland, Laurel A. Lowery, Julie C. Reeves, Pamela J. TI Nurse Practitioners as Primary Care Providers Within the VA SO MILITARY MEDICINE LA English DT Article ID INSTITUTIONAL REORGANIZATION; COMORBIDITY INDEX; AMBULATORY CARE; PILOT PROGRAM; PHYSICIANS; OUTCOMES; VETERANS; QUALITY; DISEASE; TRIAL AB We examined the perceptions of nurse practitioners (NPs) and physicians regarding NPs' roles as primary care providers within the Department of Veterans Affairs, thus suggesting possible reasons for the variation of NPs use. NPs and physicians from 7 Veterans Affairs hospitals were surveyed regarding perceptions and concerns about NPs' responsibilities. Quality of care was verified through outpatient services, laboratory results, and medications prescribed for 104,226 hypertensive or diabetic patients. Clinical findings suggest primary care for diabetic and hypertensive patients was comparable. Survey findings suggest physicians tended to underestimate what NPs do on their own for acute patients. Both groups expressed some concerns about expectations for NPs. To successfully integrate NPs into the primary care environment, health systems need to pay increased attention to differences in role perceptions among primary care providers. C1 [Fletcher, Carol E.; Lowery, Julie C.] VA Ann Arbor Med Ctr, Ann Arbor, MI 48108 USA. [Copeland, Laurel A.] S Texas Vet Healthcare Syst, San Antonio, TX 78229 USA. [Reeves, Pamela J.] John D Dingell Vet Med Ctr, Detroit, MI 48201 USA. RP Fletcher, CE (reprint author), VA Ann Arbor Med Ctr, 2215 Fuller Rd 127, Ann Arbor, MI 48108 USA. OI Copeland, Laurel/0000-0002-9478-0209 FU VISN 11 in Ann Arbor, Michigan; Veterans Evidence-based Research Dissemination; South Texas Veterans Health Care System, San Antonio, Texas; Health Services Research and Development Service of the Department of VA; VA Health Services [MRP-05-145] FX This article is based on the work supported by VISN 11 in Ann Arbor, Michigan, Veterans Evidence-based Research Dissemination and Implementation Cen-Ter (VERDICT) research program at the South Texas Veterans Health Care System, San Antonio, Texas, and the Health Services Research and Development Service of the Department of VA. Dr. Copeland was funded by VA Health Services Research and Development award MRP-05-145. NR 40 TC 3 Z9 3 U1 0 U2 15 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 J9 MIL MED JI Milit. Med. PD JUL PY 2011 VL 176 IS 7 BP 791 EP 797 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 792XO UT WOS:000292783900010 PM 22128721 ER PT J AU Wilbertz, T Wagner, P Petersen, K Stiedl, AC Scheble, VJ Maier, S Reischl, M Mikut, R Altorki, NK Moch, H Fend, F Staebler, A Bass, AJ Meyerson, M Rubin, MA Soltermann, A Lengerke, C Perner, S AF Wilbertz, Theresia Wagner, Patrick Petersen, Karen Stiedl, Ann-Cathrin Scheble, Veit J. Maier, Sebastian Reischl, Markus Mikut, Ralf Altorki, Nasser K. Moch, Holger Fend, Falko Staebler, Annette Bass, Adam J. Meyerson, Matthew Rubin, Mark A. Soltermann, Alex Lengerke, Claudia Perner, Sven TI SOX2 gene amplification and protein overexpression are associated with better outcome in squamous cell lung cancer SO MODERN PATHOLOGY LA English DT Article DE amplification; expression; lung cancer; SOX2; squamous cell carcinoma ID NONSMALL CELL; 3Q AMPLIFICATION; EXPRESSION; CARCINOMAS; ADENOCARCINOMA; ONCOGENE; SURVIVAL; DIFFERENTIATION AB The transcription factor SOX2 (3q26.3-q27) is a key regulator of foregut development and an embryonic stem cell factor cooperating during induction of pluripotency in terminally differentiated somatic cells. Recently, we found SOX2 to be amplified in a subset of squamous cell lung and esophageal cancers. The aim of this study was to explore the prognostic role of SOX2 in a large series of squamous cell carcinomas and adenocarcinomas of the lung. A total of 891 samples from two independent population-based cohorts were assessed by fluorescence in situ hybridization and immunohistochemistry. Furthermore, we assessed for associations between SOX2 amplification/upregulation and clinicopathological features. Similar results were found in the two cohorts. Within squamous cell carcinoma cases, 8% high-level as well as 68 and 65% low-level SOX2 amplifications occurred in the two cohorts, respectively. In adenocarcinomas, no high-level amplification was found and low-level amplification occurred in 6% of the two cohorts. Within squamous cell carcinomas of one cohort, SOX2 amplification was associated with lower tumor grade, while higher levels of SOX2 expression were related to younger age, smaller tumor size, and lower probability of angiolymphatic invasion and metastasis. High SOX2 expression levels proved to be a marker for prolonged overall survival among patients with squamous cell carcinomas. In conclusion, SOX2 amplification and upregulation are frequent events in squamous cell carcinomas of the lung and are associated with indicators of favorable prognosis. Modern Pathology (2011) 24, 944-953; doi: 10.1038/modpathol.2011.49; published online 1 April 2011 C1 [Wilbertz, Theresia; Petersen, Karen; Stiedl, Ann-Cathrin; Scheble, Veit J.; Maier, Sebastian; Fend, Falko; Staebler, Annette; Perner, Sven] Univ Tubingen Hosp, Ctr Comprehens Canc, Inst Pathol, Tubingen, Germany. [Wagner, Patrick; Rubin, Mark A.] Weill Cornell Med Ctr, Dept Pathol & Lab Med, New York, NY USA. [Reischl, Markus; Mikut, Ralf] Karlsruhe Inst Technol, Inst Appl Comp Sci, Karlsruhe, Germany. [Moch, Holger; Soltermann, Alex] Univ Zurich Hosp, Inst Surg Pathol, CH-8091 Zurich, Switzerland. [Bass, Adam J.; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Bass, Adam J.; Meyerson, Matthew] Broad Inst, Cambridge, MA USA. [Bass, Adam J.; Meyerson, Matthew] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Meyerson, Matthew] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Lengerke, Claudia] Univ Tubingen, Med Ctr 2, Div Hematol & Oncol, Tubingen, Germany. RP Perner, S (reprint author), Univ Hosp Bonn, Inst Pathol, Sigmund Freud Str 25, D-53127 Bonn, Germany. EM sven.perner1972@googlemail.com RI Meyerson, Matthew/E-7123-2012; Mikut, Ralf /A-5949-2013; Reischl, Markus/H-6970-2013; OI Mikut, Ralf /0000-0001-9100-5496; Rubin, Mark/0000-0002-8321-9950; Lengerke, Claudia/0000-0001-5442-2805 FU Deutsche Forschungsgemeinschaft [SFB773] FX The work of C.L. was supported by the Deutsche Forschungsgemeinschaft (SFB773). NR 31 TC 86 Z9 90 U1 2 U2 7 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 JUL PY 2011 VL 24 IS 7 BP 944 EP 953 DI 10.1038/modpathol.2011.49 PG 10 WC Pathology SC Pathology GA 786PF UT WOS:000292319700008 PM 21460799 ER PT J AU Dias-Santagata, D Lam, Q Bergethon, K Baker, GM Iafrate, AJ Rakheja, D Hoang, MP AF Dias-Santagata, Dora Quynh Lam Bergethon, Kristin Baker, Gabrielle M. Iafrate, A. John Rakheja, Dinesh Hoang, Mai P. TI A potential role for targeted therapy in a subset of metastasizing adnexal carcinomas SO MODERN PATHOLOGY LA English DT Article DE adnexal neoplasm; EGFR; gene mutation; metastasis; PIK3CA; TP53 ID IN-SITU HYBRIDIZATION; CELL LUNG-CANCER; TYROSINE KINASE INHIBITORS; FACTOR RECEPTOR MUTATIONS; SWEAT GLAND CARCINOMAS; BREAST-CANCER; GENE AMPLIFICATION; PULMONARY ADENOCARCINOMA; HIGH-FREQUENCY; P53 MUTATIONS AB Metastasizing adnexal carcinomas are rare; thus, currently there is no uniform treatment guideline. Chemotherapeutic drugs that selectively target cancer-promoting pathways may complement conventional therapeutic approaches. We performed immunohistochemistry (epidermal growth factor receptor (EGFR), HER2, and CD117), EGFR and ERBB2 fluorescence in situ hybridization (FISH), and multiplexed SNaPshots (R) genotyping (testing for recurrent mutations in 15 cancer genes including BRAF, EGFR, KRAS, PIK3CA, and TP53) on primary tumors and corresponding metastases of 14 metastasizing adnexal carcinomas (three apocrine, six eccrine, two hidradenocarcinomas, two porocarcinomas, and one aggressive digital papillary adenocarcinoma). Metastasis to regional lymph node was most common, followed by skin and then lungs. Follow-up was available in 12 patients (5 months to 8 years) with 1 died of widespread metastases. Although EGFR overexpression was a prevalent feature in this cohort, seen in 7/11 (64%) primary tumors and 10/14 (71%) metastases; FISH for EGFR gene amplification was negative in 9 tested primary tumors and 12 metastases. FISH of the one primary tumor and three metastases with 2 + HER2 overexpression revealed a low level of ERBB2 gene amplification in one apocrine carcinoma and corresponding metastasis. CD117 expression was seen only in rare cases. PIK3CA (2/12, 17%) and TP53 (3/12, 25%) mutations were detected in two (one hidradenocarcinoma, one porocarcinoma) and three (one eccrine, one hidradenocarcinoma, and one aggressive digital papillary adenocarcinoma) cases, respectively. The role of EGFR inhibitor therapy in metastasizing adnexal carcinomas with protein overexpression remains unclear. Targeted therapy including PI3K pathway inhibitors might be a potential treatment for rare cases of adnexal carcinomas with metastases. Modern Pathology (2011) 24, 974-982; doi: 10.1038/modpathol.2011.48; published online 18 March 2011 C1 [Hoang, Mai P.] Massachusetts Gen Hosp, Dermatopathol Unit, Dept Pathol, Boston, MA 02114 USA. [Dias-Santagata, Dora; Quynh Lam; Bergethon, Kristin; Baker, Gabrielle M.; Iafrate, A. John; Hoang, Mai P.] Harvard Univ, Sch Med, Boston, MA USA. [Rakheja, Dinesh] Univ Texas SW Med Sch, Dept Pathol, Dallas, TX USA. [Rakheja, Dinesh] Childrens Med Ctr, Dallas, TX 75235 USA. RP Hoang, MP (reprint author), Massachusetts Gen Hosp, Dermatopathol Unit, Dept Pathol, 55 Fruit St,Warren 820, Boston, MA 02114 USA. EM mhoang@partners.org NR 46 TC 12 Z9 12 U1 0 U2 1 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 JUL PY 2011 VL 24 IS 7 BP 974 EP 982 DI 10.1038/modpathol.2011.48 PG 9 WC Pathology SC Pathology GA 786PF UT WOS:000292319700011 PM 21423156 ER PT J AU Ekim, B Magnuson, B Acosta-Jaquez, HA Keller, JA Feener, EP Fingar, DC AF Ekim, Bilgen Magnuson, Brian Acosta-Jaquez, Hugo A. Keller, Jennifer A. Feener, Edward P. Fingar, Diane C. TI mTOR Kinase Domain Phosphorylation Promotes mTORC1 Signaling, Cell Growth, and Cell Cycle Progression SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TUBEROUS SCLEROSIS COMPLEX-1; RICH AKT SUBSTRATE; 40 KDA PRAS40; MAMMALIAN TARGET; RAPAMYCIN MTOR; FKBP12-RAPAMYCIN-ASSOCIATED PROTEIN; GENE-PRODUCTS; RAG GTPASES; S6 KINASE; TOS MOTIF AB The mammalian target of rapamycin complex 1 (mTORC1) functions as an environmental sensor to promote critical cellular processes such as protein synthesis, cell growth, and cell proliferation in response to growth factors and nutrients. While diverse stimuli regulate mTORC1 signaling, the direct molecular mechanisms by which mTORC1 senses and responds to these signals remain poorly defined. Here we investigated the role of mTOR phosphorylation in mTORC1 function. By employing mass spectrometry and phospho-specific antibodies, we demonstrated novel phosphorylation on S2159 and T2164 within the mTOR kinase domain. Mutational analysis of these phosphorylation sites indicates that dual S2159/T2164 phosphorylation cooperatively promotes mTORC1 signaling to S6K1 and 4EBP1. Mechanistically, S2159/T2164 phosphorylation modulates the mTOR-raptor and raptor-PRAS40 interactions and augments mTORC1-associated mTOR S2481 autophosphorylation. Moreover, mTOR S2159/T2164 phosphorylation promotes cell growth and cell cycle progression. We propose a model whereby mTOR kinase domain phosphorylation modulates the inter-action of mTOR with regulatory partner proteins and augments intrinsic mTORC1 kinase activity to promote biochemical signaling, cell growth, and cell cycle progression. C1 [Ekim, Bilgen; Magnuson, Brian; Acosta-Jaquez, Hugo A.; Keller, Jennifer A.; Fingar, Diane C.] Univ Michigan, Sch Med, Div Metab Endocrinol & Diabet, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA. [Fingar, Diane C.] Univ Michigan, Sch Med, Div Metab Endocrinol & Diabet, Dept Med, Ann Arbor, MI 48109 USA. [Feener, Edward P.] Joslin Diabet Ctr, Boston, MA 02215 USA. RP Fingar, DC (reprint author), Univ Michigan, Sch Med, Div Metab Endocrinol & Diabet, Dept Cell & Dev Biol, 109 Zina Pitcher Pl, Ann Arbor, MI 48109 USA. EM dfingar@umich.edu FU NIH [R01-DK078135]; American Diabetes Association; Michigan Diabetes Research and Training Center (MDRTC); American Heart Association; NIDDK at the University of Michigan [NIH5P60 DK20572] FX This work was supported by the NIH (R01-DK078135), the American Diabetes Association, and the Michigan Diabetes Research and Training Center (MDRTC) (D. C. F.) and by the American Heart Association (B.E.). This work utilized the Cell and Molecular Biology Core(s) of the MDRTC funded by NIH5P60 DK20572 from NIDDK at the University of Michigan. NR 72 TC 48 Z9 56 U1 0 U2 6 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 JUL PY 2011 VL 31 IS 14 BP 2787 EP 2801 DI 10.1128/MCB.05437-11 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 784IC UT WOS:000292149300002 PM 21576368 ER PT J AU Nakamura, Y Inloes, JB Katagiri, T Kobayashi, T AF Nakamura, Yukio Inloes, Jennifer B. Katagiri, Takenobu Kobayashi, Tatsuya TI Chondrocyte-Specific MicroRNA-140 Regulates Endochondral Bone Development and Targets Dnpep To Modulate Bone Morphogenetic Protein Signaling SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SYSTEMATIC IDENTIFICATION; MESSENGER-RNAS; IN-VIVO; BMP; DIFFERENTIATION; MICE; GROWTH; CHONDROGENESIS; PROLIFERATION; RECOGNITION AB MicroRNAs (miRNAs) play critical roles in a variety of biological processes in diverse organisms, including mammals. In the mouse skeletal system, a global reduction of miRNAs in chondrocytes causes a lethal skeletal dysplasia. However, little is known about the physiological roles of individual miRNAs in chondrocytes. The miRNA-encoding gene, Mir140, is evolutionarily conserved among vertebrates and is abundantly and almost exclusively expressed in chondrocytes. In this paper, we show that loss of Mir140 in mice causes growth defects of endochondral bones, resulting in dwarfism and craniofacial deformities. Endochondral bone development is mildly advanced due to accelerated hypertrophic differentiation of chondrocytes in Mir140-null mice. Comparison of profiles of RNA associated with Argonaute 2 (Ago2) between wild-type and Mir140-null chondrocytes identified Dnpep as a Mir140 target. As expected, Dnpep expression was increased in Mir140-null chondrocytes. Dnpep overexpression showed a mild antagonistic effect on bone morphogenetic protein (BMP) signaling at a position downstream of Smad activation. Mir140-null chondrocytes showed lower-than-normal basal BMP signaling, which was reversed by Dnpep knockdown. These results demonstrate that Mir140 is essential for normal endochondral bone development and suggest that the reduced BMP signaling caused by Dnpep upregulation plays a causal role in the skeletal defects of Mir140-null mice. C1 [Inloes, Jennifer B.; Kobayashi, Tatsuya] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Inloes, Jennifer B.; Kobayashi, Tatsuya] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Katagiri, Takenobu] Saitama Med Univ, Res Ctr Genom Med, Div Pathophysiol, Hidaka, Saitama 3501241, Japan. [Nakamura, Yukio] Murayama Med Ctr, Clin Res Ctr, Tokyo 2080011, Japan. RP Kobayashi, T (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St, Boston, MA 02114 USA. EM kobayash@helix.mgh.harvard.edu FU National Institutes of Health [AR054500, AR056645]; American Society for Bone and Mineral Research [CEA0811] FX This work was supported by the National Institutes of Health (grants AR054500 and AR056645 to T. K.) and the American Society for Bone and Mineral Research (grant CEA0811 to T.K.). NR 42 TC 69 Z9 76 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 2011 VL 31 IS 14 BP 3019 EP 3028 DI 10.1128/MCB.05178-11 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 784IC UT WOS:000292149300021 PM 21576357 ER PT J AU Miranda-Carboni, GA Guemes, M Bailey, S Anaya, E Corselli, M Peault, B Krum, SA AF Miranda-Carboni, Gustavo A. Guemes, Miriam Bailey, Shannon Anaya, Edgar Corselli, Mirko Peault, Bruno Krum, Susan A. TI GATA4 Regulates Estrogen Receptor-alpha-Mediated Osteoblast Transcription SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID GENE-EXPRESSION; BONE-FORMATION; ER-ALPHA; BREAST-CANCER; CELL FATE; BINDING; BETA; MOUSE; DIFFERENTIATION; GATA-4,-5 AB Estrogens regulate osteoblast differentiation and mineralization. We identified GATA4 as a transcription factor expressed in osteoblasts and directly regulated by 17 beta-estradiol in this cell type but not in breast cancer cells, another estrogen-responsive tissue. Chromatin immuno-precipitation sequencing (chromatin immunoprecipitation sequencing) reveals that estrogen receptor alpha (ER alpha) binds to chromatin near GATA4 at five different enhancers. GATA4 and ER alpha are both recruited to ER alpha binding sites near genes that are specifically expressed in osteoblasts and control osteoblast differentiation. Maximal binding of GATA4 precedes ER alpha binding, and GATA4 is necessary for histone 3 lysine 4 dimethylation at ER alpha binding sites, suggesting that GATA4 is a pioneer factor for ER alpha. As such, knockdown of GATA4 reduced recruitment of ER alpha to DNA. Our study illustrates that GATA4 is a pioneer factor for ER alpha recruitment to osteoblast-specific enhancers. (Molecular Endocrinology 25: 1126-1136, 2011) C1 [Miranda-Carboni, Gustavo A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90095 USA. [Guemes, Miriam; Anaya, Edgar; Corselli, Mirko; Peault, Bruno; Krum, Susan A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. [Guemes, Miriam; Anaya, Edgar; Corselli, Mirko; Peault, Bruno; Krum, Susan A.] Univ Calif Los Angeles, Orthopaed Hosp, Dept Orthopaed Surg, Res Ctr,David Geffen Sch Med, Los Angeles, CA 90095 USA. [Bailey, Shannon] Dana Farber Canc Inst, Dept Med Oncol, Div Mol & Cellular Oncol, Boston, MA 02115 USA. RP Krum, SA (reprint author), 615 Charles E Young Dr S,OHRC 410, Los Angeles, CA 90095 USA. EM skrum@mednet.ucla.edu RI krum, susan/D-7282-2013; Bailey, Shannon/B-8045-2014 FU National Institutes of Health Office of Research on Women's Health [K12 BIRCWH, HD001400-08]; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [1R56DK090231-01]; National Cancer Institute [K22, CA137168-01A1] FX This work was supported by a K12 BIRCWH Grant from the National Institutes of Health Office of Research on Women's Health (HD001400-08) and 1R56DK090231-01 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) to S. A. K. G. M. C. is currently supported by a K22 Grant from the National Cancer Institute (CA137168-01A1). NR 47 TC 23 Z9 25 U1 1 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD JUL PY 2011 VL 25 IS 7 BP 1126 EP 1136 DI 10.1210/me.2010-0463 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 784DF UT WOS:000292133500005 PM 21566084 ER PT J AU Tolar, J Adair, JE Antoniou, M Bartholomae, CC Becker, PS Blazar, BR Bueren, J Carroll, T Cavazzana-Calvo, M Clapp, DW Dalgleish, R Galy, A Gaspar, HB Hanenberg, H Von Kalle, C Kiem, HP Lindeman, D Naldini, L Navarro, S Renella, R Rio, P Sevilla, J Schmidt, M Verhoeyen, E Wagner, JE Williams, DA Thrasher, AJ AF Tolar, Jakub Adair, Jennifer E. Antoniou, Michael Bartholomae, Cynthia C. Becker, Pamela S. Blazar, Bruce R. Bueren, Juan Carroll, Thomas Cavazzana-Calvo, Marina Clapp, D. Wade Dalgleish, Robert Galy, Anne Gaspar, H. Bobby Hanenberg, Helmut Von Kalle, Christof Kiem, Hans-Peter Lindeman, Dirk Naldini, Luigi Navarro, Susana Renella, Raffaele Rio, Paula Sevilla, Julian Schmidt, Manfred Verhoeyen, Els Wagner, John E. Williams, David A. Thrasher, Adrian J. TI Stem Cell Gene Therapy for Fanconi Anemia: Report from the 1st International Fanconi Anemia Gene Therapy Working Group Meeting SO MOLECULAR THERAPY LA English DT Review ID SEVERE COMBINED IMMUNODEFICIENCY; CHRONIC GRANULOMATOUS-DISEASE; CANINE REPOPULATING CELLS; IN-VIVO INFUSION; WILD-TYPE CELLS; VECTOR INTEGRATION; LENTIVIRAL VECTORS; SOMATIC MOSAICISM; PERIPHERAL-BLOOD; MARROW-TRANSPLANTATION AB Survival rates after allogeneic hematopoietic cell transplantation (HCT) for Fanconi anemia (FA) have increased dramatically since 2000. However, the use of autologous stem cell gene therapy, whereby the patient's own blood stem cells are modified to express the wild-type gene product, could potentially avoid the early and late complications of allogeneic HCT. Over the last decades, gene therapy has experienced a high degree of optimism interrupted by periods of diminished expectation. Optimism stems from recent examples of successful gene correction in several congenital immunodeficiencies, whereas diminished expectations come from the realization that gene therapy will not be free of side effects. The goal of the 1st International Fanconi Anemia Gene Therapy Working Group Meeting was to determine the optimal strategy for moving stem cell gene therapy into clinical trials for individuals with FA. To this end, key investigators examined vector design, transduction method, criteria for large-scale clinical-grade vector manufacture, hematopoietic cell preparation, and eligibility criteria for FA patients most likely to benefit. The report summarizes the roadmap for the development of gene therapy for FA. Received 8 February 2011; accepted 23 March 2011; published online 3 May 2011. doi: 10.1038/mt.2011.78 C1 [Tolar, Jakub] Univ Minnesota, Sch Med, Div Blood & Marrow Transplantat, Minneapolis, MN 55455 USA. [Adair, Jennifer E.; Kiem, Hans-Peter] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Antoniou, Michael] Kings Coll London, Sch Med, Dept Med Genet, Gene Express & Therapy Grp,Guys Hosp, London, England. [Bartholomae, Cynthia C.; Von Kalle, Christof; Schmidt, Manfred] Natl Ctr Tumor Dis, Heidelberg, Germany. [Bartholomae, Cynthia C.; Von Kalle, Christof; Schmidt, Manfred] German Canc Res Ctr, Dept Translat Oncol, D-6900 Heidelberg, Germany. [Becker, Pamela S.] Univ Washington, Sch Med, Seattle, WA USA. [Bueren, Juan; Navarro, Susana; Rio, Paula; Sevilla, Julian] CIBERER, CIEMAT, Hematopoiesis & Gene Therapy Div, Madrid, Spain. [Carroll, Thomas] Univ Sheffield Sheffield Teaching Hosp NHS Fdn Tr, Royal Hallamshire Hosp, Dept Neurosurg, Sheffield, S Yorkshire, England. [Cavazzana-Calvo, Marina] Univ Paris 05, Dept Biotherapy, Paris, France. [Cavazzana-Calvo, Marina] Hop Necker Enfants Malad, AP HP, Ctr Invest Clin Biotherapie, Paris, France. [Cavazzana-Calvo, Marina] INSERM, Paris, France. [Clapp, D. Wade] Indiana Univ Sch Med, Riley Hosp Children, Indianapolis, IN USA. [Galy, Anne] INSERM, U951, Genethon, France. [Galy, Anne] Univ Evry Val dEssonne, UMR S951, Evry, France. [Gaspar, H. Bobby; Thrasher, Adrian J.] UCL Inst Child Hlth, Mol Immunol Unit, Ctr Immunodeficiency, London, England. [Gaspar, H. Bobby; Thrasher, Adrian J.] Great Ormond St Hosp NHS Trust, Dept Immunol, London, England. [Hanenberg, Helmut] Univ Dusseldorf, Sch Med, Dept Otorhinolaryngol, Dusseldorf, Germany. [Hanenberg, Helmut; Lindeman, Dirk] Tech Univ Dresden, Inst Virol, Dresden, Germany. [Lindeman, Dirk] CRTD DFG Ctr Regenerat Therapies Dresden Cluster, Ctr Biotechnol, Dresden, Germany. [Naldini, Luigi] San Raffaele Telethon Inst Gene Therapy, Milan, Italy. [Naldini, Luigi] Univ Vita Salute San Raffaele, San Raffaele Sci Inst, Milan, Italy. [Renella, Raffaele; Williams, David A.] Childrens Hosp Boston, Dana Farber Canc Inst, Div Hematol Oncol, Boston, MA USA. [Renella, Raffaele; Williams, David A.] Harvard Univ, Sch Med, Boston, MA USA. [Sevilla, Julian] Hosp Infantil Univ Nino Jesus, Madrid, Spain. [Verhoeyen, Els] Univ Lyon 1, Ecole Normale Super Lyon, Human Virol Dept, INSERM,EVIR,U758, F-69365 Lyon, France. RP Tolar, J (reprint author), Univ Minnesota, Sch Med, Div Blood & Marrow Transplantat, MMC 366,420 Delaware St SE, Minneapolis, MN 55455 USA. EM tolar003@umn.edu RI Naldini, Luigi/E-9083-2012; Galy, Anne/J-4439-2013; Navarro, Susana/L-9300-2014; Bueren, Juan/L-6112-2014; Verhoeyen, Els/H-6360-2016; Rio, Paula/G-8681-2015; OI Sevilla, Julian/0000-0002-6852-1860; Tolar, Jakub/0000-0002-0957-4380; Galy, Anne/0000-0002-0153-4392; Navarro, Susana/0000-0002-0764-5384; Bueren, Juan/0000-0002-3228-7013; Rio, Paula/0000-0002-5424-5543; Renella, Raffaele/0000-0002-5041-2308; ORCIDDD, TESSST/0000-0002-2970-3987 FU Fanconi Anemia Research Fund; Children's Cancer Research Fund, Minnesota; Albert D. and Eva J. Corniea Chair; European Commision (Ministries of Science and Innovation and Health, Genoma Espana, and Fundacion Botin); DFG [SPP1230]; BMBF; Foamyviral Network for Genetic Therapy of FANCA; STTR [R41HL099150]; Genoma Espana, Madrid, Spain; AFM (French Muscular Dystrophy Association), Evry, France; Assistance Publique-Hopitaux de Paris Direction de la Recherche Clinique; National Institutes of Health [HL85693, DK56465, HL36444]; Telethon; European Research Council; European 7th Framework Program for Life Sciences; Italian Ministries of Health and of Scientific Research; ANR; Wellcome Trust; Great Ormond Street Children's Charity; [R01 CA155294-01] FX The authors would like to thank the Fanconi Anemia Research Fund, the Fanconi Hope Charitable Trust, the Spanish Association on FA, and the Children's Cancer Research Fund, Minnesota. We thank Grover C. Bagby for useful comments on the manuscript. J.T. is supported by the Fanconi Anemia Research Fund, Children's Cancer Research Fund, Minnesota, and the Albert D. and Eva J. Corniea Chair for clinical research. J. A. B. and P. R. are supported by grants from European Commision (FP7, Ministries of Science and Innovation and Health, Genoma Espana, and Fundacion Botin). H. H. is supported by the DFG SPP1230, the BMBF networks for Inherited Bone Marrow Failure Syndromes, the Foamyviral Network for Genetic Therapy of FANCA, and R01 CA155294-01 and STTR R41HL099150. A. G. is supported by a grant from Genoma Espana, Madrid, Spain and by AFM (French Muscular Dystrophy Association), Evry, France. M. C. C. is supported by the Association Francaise contre les Myopathies (AFM) and Assistance Publique-Hopitaux de Paris Direction de la Recherche Clinique. H. P. K. is supported by National Institutes of Health grants HL85693, DK56465, and HL36444. H. P. K. is a Markey Molecular Medicine Investigator and recipient of Jose Carreras/E. Donnall Thomas Endowed Chair for Cancer Research. Research in L.N. lab is supported by Telethon, the European Research Council, the European 7th Framework Program for Life Sciences, and the Italian Ministries of Health and of Scientific Research. E. V. is supported by grants from the European 7th Framework Program for Life Sciences and French grants (AFM and ANR). A. J. T. receives funding from The Wellcome Trust and Great Ormond Street Children's Charity. NR 67 TC 16 Z9 16 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD JUL PY 2011 VL 19 IS 7 BP 1193 EP 1198 DI 10.1038/mt.2011.78 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 786HU UT WOS:000292295900005 PM 21540837 ER EF