FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Deer, TR Prager, J Levy, R Rathmell, J Buchser, E Burton, A Caraway, D Cousins, M De Andres, J Diwan, S Erdek, M Grigsby, E Huntoon, M Jacobs, MS Kim, P Kumar, K Leong, M Liem, L McDowell, GC Panchal, S Rauck, R Saulino, M Sitzman, BT Staats, P Stanton-Hicks, M Stearns, L Wallace, M Willis, KD Witt, W Yaksh, T Mekhail, N AF Deer, Timothy R. Prager, Joshua Levy, Robert Rathmell, James Buchser, Eric Burton, Allen Caraway, David Cousins, Michael De Andres, Jose Diwan, Sudhir Erdek, Michael Grigsby, Eric Huntoon, Marc Jacobs, Marilyn S. Kim, Philip Kumar, Krishna Leong, Michael Liem, Liong McDowell, Gladstone C., II Panchal, Sunil Rauck, Richard Saulino, Michael Sitzman, B. Todd Staats, Peter Stanton-Hicks, Michael Stearns, Lisa Wallace, Mark Willis, K. Dean Witt, William Yaksh, Tony Mekhail, Nagy TI Polyanalgesic Consensus Conference 2012: Recommendations for the Management of Pain by Intrathecal (Intraspinal) Drug Delivery: Report of an Interdisciplinary Expert Panel SO NEUROMODULATION LA English DT Review DE Chronic pain; consensus; intrathecal ID SPINAL-CORD-INJURY; SPASTIC CEREBRAL-PALSY; CHRONIC NONCANCER PAIN; IMPLANTABLE INFUSION SYSTEM; BACLOFEN PUMP IMPLANTATION; CEREBROSPINAL-FLUID FLOW; CATHETER TIP GRANULOMAS; D-ASPARTATE ANTAGONISTS; TRAUMATIC BRAIN-INJURY; LONG-LASTING ALLODYNIA AB Introduction: The use of intrathecal (IT) infusion of analgesic medications to treat patients with chronic refractory pain has increased since its inception in the 1980s, and the need for clinical research in IT therapy is ongoing. The Polyanalgesic Consensus Conference (PACC) panel of experts convened in 2000, 2003, and 2007 to make recommendations on the rational use of IT analgesics based on preclinical and clinical literature and clinical experiences. Methods: The PACC panel convened again in 2011 to update the standard of care for IT therapies to reflect current knowledge gleaned from literature and clinical experience. A thorough literature search was performed, and information from this search was provided to panel members. Analysis of published literature was coupled with the clinical experience of panel members to form recommendations regarding the use of IT analgesics to treat chronic pain. Results: After a review of literature published from 2007 to 2011 and discussions of clinical experience, the panel created updated algorithms for the rational use of IT medications for the treatment of neuropathic pain and nociceptive pain. Conclusions: The advent of new algorithmic tracks for neuropathic and nociceptive pain is an important step in improving patient care. The panel encourages continued research and development, including the development of new drugs, devices, and safety recommendations to improve the care of patients with chronic pain. C1 [Deer, Timothy R.] Ctr Pain Relief, Charleston, WV 25301 USA. [Prager, Joshua; Jacobs, Marilyn S.] Univ Calif Los Angeles, Los Angeles, CA USA. [Levy, Robert] Univ Florida, Jacksonville, FL USA. [Rathmell, James] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rathmell, James] Harvard Univ, Sch Med, Boston, MA USA. [Buchser, Eric] CHUV Univ Hosp, Lausanne, Switzerland. [Buchser, Eric] EHC Hosp, Anaesthesia & Pain Management Dept, Morges, Switzerland. [Burton, Allen] Houston Pain Associates LLC, Houston, TX USA. [Caraway, David] Tri State LLC, Ctr Pain Relief, Huntington, WV USA. [Cousins, Michael] Royal N Shore Hosp, Kolling Inst Med Res, Sydney, NSW, Australia. [De Andres, Jose] Univ Valencia, Sch Med, Valencia, Spain. [De Andres, Jose] Gen Univ Hosp, Valencia, Spain. [Diwan, Sudhir] Suny Downstate Med Ctr, Staten Isl, NY USA. [Diwan, Sudhir] Univ Hosp, New York, NY USA. [Erdek, Michael] Johns Hopkins Univ, Sch Med, Dept Anesthesiol, Baltimore, MD USA. [Erdek, Michael] Johns Hopkins Univ, Sch Med, Dept Crit Care Med, Baltimore, MD USA. [Erdek, Michael] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. [Grigsby, Eric] Napa Pain Inst, Napa, CA USA. [Huntoon, Marc] Vanderbilt Univ, Nashville, TN USA. [Kim, Philip] Christiana Hosp, Newark, DE USA. [Kim, Philip] Bryn Mawr Hosp, Bryn Mawr, PA USA. [Kumar, Krishna] Univ Saskatchewan, Regina, SK, Canada. [Leong, Michael] Stanford Univ, Palo Alto, CA 94304 USA. [Liem, Liong] St Antonius Hosp, Nieuwegein, Netherlands. [McDowell, Gladstone C., II] Integrated Pain Solut, Columbus, OH USA. [Panchal, Sunil] Natl Inst Pain, Lutz, FL USA. [Rauck, Richard] Carolinas Pain Inst, Winston Salem, NC USA. [Rauck, Richard] Wake Forest Univ, Sch Med Baptist Hlth, Winston Salem, NC 27109 USA. [Saulino, Michael] Thomas Jefferson Univ, Jefferson Med Coll, MossRehab, Philadelphia, PA 19107 USA. [Saulino, Michael] Thomas Jefferson Univ, Jefferson Med Coll, Dept Rehabil Med, Philadelphia, PA 19107 USA. [Sitzman, B. Todd] Adv Pain Therapy PLLC, Hattiesburg, MS USA. [Staats, Peter] Premier Pain Management Ctr, Shrewsbury, NJ USA. [Stanton-Hicks, Michael; Mekhail, Nagy] Cleveland Clin, Dept Pain Management, Cleveland, OH 44106 USA. [Stearns, Lisa] Ctr Pain & Support Care, Phoenix, AZ USA. [Wallace, Mark; Yaksh, Tony] Univ Calif San Diego, La Jolla, CA 92093 USA. [Willis, K. Dean] Univ Alabama Birmingham, Sch Nursing, Birmingham, AL USA. [Willis, K. Dean] Alabama Pain Ctr, Huntsville, AL USA. [Witt, William] Univ Kentucky, Lexington, KY USA. [Grigsby, Eric] Neurovat Clin Res & Educ, Napa, CA USA. RP Deer, TR (reprint author), Ctr Pain Relief, 400 Court St,Suite 100, Charleston, WV 25301 USA. EM doctdeer@aol.com FU Medtronic, Inc. (Minneapolis, Minnesota, USA); Azur Pharma Ltd (Dublin, Ireland); Spinal Modulation FX This project was supported by grants from Medtronic, Inc. (Minneapolis, Minnesota, USA) and Azur Pharma Ltd (Dublin, Ireland).; Timothy R. Deer, MD: consulting (Medtronic, Spinal Modulation, St. Jude, Medasys, Bioness, Vertos). Robert Levy, MD, PhD: consulting (Medtronic and Codman & Shurtleff). Joshua Prager, MD: honoraria (Medtronic, Eli Lily, Qutenza). Allen Burton, MD: consulting (Medtronic, BSCIS, Stryker), speaking (Azur, Cadence, Cephalon, NeurogesX, Pricara, Pfizer), stockholder (Vapogenix). Eric Buchser, MD: consulting (Medtronic). David Caraway, MD, PhD: consulting (Medtronic, Spinal Modulation, MedSys, Codman). Sudhir Diwan, MD: speaking (Neurotherm, BSCI). Eric Grigsby, MD: clinical research (Alfred Mann Foundation, Medtronic, NeurogesX, Spinal Restoration), speaking (Azur Pharma), consulting (Medtronic, St. Jude Medical, Spinal Modulation, Vertos, Xalud), stock options (Spinal Modulation, Spinal Restoration, Vertos, Xalud). Marilyn Jacobs, PhD: consulting (Medtronic). Philip Kim, MD: consulting (Medtronic, Biotronik, Stryker, Azur). Krishna Kumar, MD: consulting and research (Medtronic, Boston Scientific). Michael Leong, MD: advisor (Covidien). Liong Liem, MD: grant (Spinal Modulation). Gladstone McDowell, MD: speaking (Azur), consulting (Medtronic, Mysys). Nagy Mekhail, MD, PhD: spe(Endo Pharmaceutical), research (Baylis, Inc., Vertos). Richard Rauck, MD: research (Medtronic, Medasys, Azur, Codman, Al Mann Foundation), consulting (Medtronic, Medasys, Azur), data and safety monitoring board membership (Medtronic, Al Mann Foundation). Michael Saulino, MD, PhD: speaking (Medtronic, Azur), research (Medtronic). Lisa Stearns, MD: research (Medtronic, Insys Therapeutics, Vertos), consulting (Medtronic). Mark Wallace, MD: research and consulting (Medtronic). K. Dean Willis, MD: speaking (Boston Scientific, Medtronic, St. Jude Medical), Implantable Systems Performance Registry participant (Medtronic), advisory committee (Boston Scientific). William Witt, MD: consulting (Medtronic), speaking (Cadence, Pfizer, Medtronic). Jose De Andres, MD, PhD; Michael Erdek, MD; Marc Huntoon, MD, PhD; Sunil J. Panchal, MD; Peter Staats, MD; Michael Stanton-Hicks, MD; B. Todd Sitzman, MD; Michael Cousins, MD: nothing to disclose; and Tony Yaksh, PhD: consulting (Vertex, Adynxx, Solace, Neuroadjuvants, Trevana), research (Adynxx, Johnson & Johnson, Xenome, Torrey Pines, Third Rock Ventures, Advanced Targeting Systems, Nektar Pharma, Endo Pharmaceuticals, Sage Rx, Solstice, Epigen). NR 283 TC 85 Z9 86 U1 1 U2 20 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1094-7159 EI 1525-1403 J9 NEUROMODULATION JI Neuromodulation PD SEP-OCT PY 2012 VL 15 IS 5 BP 436 EP 466 DI 10.1111/j.1525-1403.2012.00476.x PG 31 WC Medicine, Research & Experimental; Clinical Neurology SC Research & Experimental Medicine; Neurosciences & Neurology GA 019MU UT WOS:000309744800004 PM 22748024 ER PT J AU Deer, TR Prager, J Levy, R Rathmell, J Buchser, E Burton, A Caraway, D Cousins, M De Andres, J Diwan, S Erdek, M Grigsby, E Huntoon, M Jacobs, MS Kim, P Kumar, K Leong, M Liem, L McDowell, GC Panchal, S Rauck, R Saulino, M Sitzman, BT Staats, P Stanton-Hicks, M Stearns, L Wallace, M Willis, KD Witt, W Yaksh, T Mekhail, N AF Deer, Timothy R. Prager, Joshua Levy, Robert Rathmell, James Buchser, Eric Burton, Allen Caraway, David Cousins, Michael De Andres, Jose Diwan, Sudhir Erdek, Michael Grigsby, Eric Huntoon, Marc Jacobs, Marilyn S. Kim, Philip Kumar, Krishna Leong, Michael Liem, Liong McDowell, Gladstone C., II Panchal, Sunil Rauck, Richard Saulino, Michael Sitzman, B. Todd Staats, Peter Stanton-Hicks, Michael Stearns, Lisa Wallace, Mark Willis, K. Dean Witt, William Yaksh, Tony Mekhail, Nagy TI Polyanalgesic Consensus Conference-2012: Consensus on Diagnosis, Detection, and Treatment of Catheter-Tip Granulomas (Inflammatory Masses) SO NEUROMODULATION LA English DT Article DE Chronic pain; consensus; granuloma; inflammatory mass; intrathecal ID THERAPY-RELATED GRANULOMAS; INTRATHECAL DRUG INFUSION; SPINAL-CORD DISTRIBUTION; CEREBROSPINAL-FLUID; MORPHINE INFUSION; EXPERT PANEL; CANCER PAIN; SHEEP MODEL; BACLOFEN; MANAGEMENT AB Introduction: Continuous intrathecal infusion of drugs to treat chronic pain and spasticity has become a standard part of the algorithm of care. The use of opioids has been associated with noninfectious inflammatory masses at the tip of the intrathecal catheter, which can result in neurologic complications. Methods: The Polyanalgesic Consensus Conference is a meeting of a group of well-published and experienced practitioners; the purpose of the meeting is to update the standard of care for intrathecal therapies to reflect current knowledge gleaned from literature and clinical experience. An exhaustive literature search was performed, and information from this search was provided to panel members. Analysis of the published literature was coupled with the clinical experience of panel participants to form recommendations regarding intrathecal inflammatory masses or granulomas. Results: The panel has made recommendations for the prevention, diagnosis, and management of intrathecal granulomas. Conclusion: The use of chronic infusions of intrathecal opioids is associated with the formation of inflammatory masses at the intrathecal catheter tip in a small minority of treated patients. Nonetheless, the appearance of these space-occupying lesions can lead to devastating neurologic sequelae. The prevention, early detection, and successful treatment of intraspinal granulomas are important considerations when offering intrathecal drug therapy to patients with chronic intractable pain. C1 [Deer, Timothy R.] Ctr Pain Relief, Charleston, WV 25301 USA. [Prager, Joshua; Jacobs, Marilyn S.] Univ Calif Los Angeles, Los Angeles, CA USA. [Levy, Robert] Univ Florida, Jacksonville, FL USA. [Rathmell, James] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rathmell, James] Harvard Univ, Sch Med, Boston, MA USA. [Buchser, Eric] CHUV Univ Hosp, Lausanne, Switzerland. [Buchser, Eric] EHC Hosp, Anaesthesia & Pain Management Dept, Morges, Switzerland. [Burton, Allen] Houston Pain Associates LLC, Houston, TX USA. [Caraway, David] Tri State, Ctr Pain Relief, Huntington, WV USA. [Cousins, Michael] Royal N Shore Hosp, Kolling Inst Med Res, Sydney, NSW, Australia. [De Andres, Jose] Univ Valencia, Sch Med, Valencia, Spain. [De Andres, Jose] Gen Univ Hosp, Valencia, Spain. [Diwan, Sudhir] Suny Downstate Med Ctr, Staten Isl Univ Hosp, New York, NY USA. [Erdek, Michael] Johns Hopkins Univ, Sch Med, Dept Anesthesiol, Baltimore, MD USA. [Erdek, Michael] Johns Hopkins Univ, Sch Med, Dept Crit Care Med, Baltimore, MD USA. [Erdek, Michael] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. [Grigsby, Eric] Napa Pain Inst, Napa, CA USA. [Grigsby, Eric] Neurovat Clin Res & Educ, Napa, CA USA. [Huntoon, Marc] Vanderbilt Univ, Nashville, TN USA. [Kim, Philip] Christiana Hosp, Newark, DE USA. [Kim, Philip] Bryn Mawr Hosp, Bryn Mawr, PA USA. [Kumar, Krishna] Univ Saskatchewan, Regina, SK, Canada. [Leong, Michael] Stanford Univ, Palo Alto, CA 94304 USA. [Liem, Liong] St Antonius Hosp, Nieuwegein, Netherlands. [McDowell, Gladstone C., II] Integrated Pain Solut, Columbus, OH USA. [Panchal, Sunil] Natl Inst Pain, Lutz, FL USA. [Rauck, Richard] Carolinas Pain Inst, Winston Salem, NC USA. [Rauck, Richard] Wake Forest Univ Baptist Hlth, Winston Salem, NC USA. [Saulino, Michael] Thomas Jefferson Univ, Jefferson Med Coll, MossRehab, Philadelphia, PA 19107 USA. [Saulino, Michael] Thomas Jefferson Univ, Jefferson Med Coll, Dept Rehabil Med, Philadelphia, PA 19107 USA. [Sitzman, B. Todd] Adv Pain Therapy PLLC, Hattiesburg, MS USA. [Staats, Peter] Premier Pain Ctr, Shrewsbury, NJ USA. [Stanton-Hicks, Michael; Mekhail, Nagy] Cleveland Clin, Dept Pain Management, Cleveland, OH 44106 USA. [Stearns, Lisa] Ctr Pain & Support Care, Phoenix, AZ USA. [Wallace, Mark; Yaksh, Tony] Univ Calif San Diego, La Jolla, CA 92093 USA. [Willis, K. Dean] Alabama Pain Ctr, Huntsville, AL USA. [Willis, K. Dean] Univ Alabama Birmingham, Sch Nursing, Birmingham, AL USA. [Witt, William] Univ Kentucky, Lexington, KY USA. RP Deer, TR (reprint author), Ctr Pain Relief, 400 Court St,Suite 100, Charleston, WV 25301 USA. EM doctdeer@aol.com FU Medtronic, Inc. (Minneapolis, Minnesota, USA); Azur Pharma Ltd (Dublin, Ireland); International Neuromodulation Society FX This project was supported by grants from Medtronic, Inc. (Minneapolis, Minnesota, USA) and Azur Pharma Ltd (Dublin, Ireland).; Authors would also like to acknowledge the support provided by the International Neuromodulation Society, the staff at the Journal Neuromodulation for publication support; Audrey J. Suh, PharmD, for contributions to manuscript drafting and preparations; S. William Stuart, RPh; and Linda M. Page, PharmD, from Medtronic Neuromodulation. NR 62 TC 38 Z9 38 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1094-7159 J9 NEUROMODULATION JI Neuromodulation PD SEP-OCT PY 2012 VL 15 IS 5 BP 483 EP 496 DI 10.1111/j.1525-1403.2012.00449.x PG 14 WC Medicine, Research & Experimental; Clinical Neurology SC Research & Experimental Medicine; Neurosciences & Neurology GA 019MU UT WOS:000309744800006 PM 22494332 ER PT J AU Tai, YT Anderson, KC AF Tai, Yu-Tzu Anderson, Kenneth C. TI Bruton's tyrosine kinase: oncotarget in myeloma SO ONCOTARGET LA English DT Editorial Material ID BTK; INHIBITION; CELLS C1 [Tai, Yu-Tzu; Anderson, Kenneth C.] Harvard Univ, Sch Med, LeBow Inst Myeloma Therapeut, Boston, MA 02114 USA. [Tai, Yu-Tzu; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. RP Tai, YT (reprint author), Harvard Univ, Sch Med, LeBow Inst Myeloma Therapeut, Boston, MA 02114 USA. EM yu-tzu_tai@dfci.harvard.edu FU NCI NIH HHS [P50 CA100707] NR 8 TC 9 Z9 9 U1 0 U2 2 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD SEP PY 2012 VL 3 IS 9 BP 913 EP 914 PG 2 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 020MR UT WOS:000309815300004 PM 22989914 ER PT J AU Vina, ER Masi, CM Green, SL Utset, TO AF Vina, Ernest R. Masi, Christopher M. Green, Stephanie L. Utset, Tammy O. TI A study of racial/ethnic differences in treatment preferences among lupus patients SO RHEUMATOLOGY LA English DT Article DE systemic lupus erythematosus; racial inequities; patient decision-making; patient preferences; cyclophosphamide ID 3 ETHNIC-GROUPS; RACIAL-DIFFERENCES; REPLACEMENT SURGERY; JOINT REPLACEMENT; KNEE REPLACEMENT; AFRICAN-AMERICAN; DISEASE-ACTIVITY; ERYTHEMATOSUS; NEPHRITIS; OUTCOMES AB Objectives. To determine whether there are racial/ethnic differences in the willingness of SLE patients to receive CYC or participate in clinical trials, and whether demographic, psychosocial and clinical characteristics contribute to these differences. Methods. Data from 120 African-American and 62 white lupus patients were evaluated. Structured telephone interviews were conducted to determine treatment preferences, as well as to study characteristics and beliefs that may affect these preferences. Data were analysed using serial hierarchical multivariate logistic regression and deviances were calculated from a saturated model. Results. Compared with their white counterparts, African-American SLE patients expressed less willingness to receive CYC (67.0% vs 84.9%, P = 0.02) if their lupus worsened. This racial/ethnic difference remained significant after adjusting for socioeconomic and psychosocial variables. Logistic regression analysis showed that African-American race [odds ratio (OR) 0.29, 95% CI 0.10, 0.80], physician trust (OR 1.05, 95% CI 1.00, 1.12) and perception of treatment effectiveness (OR 1.40, 95% CI 1.22, 1.61) were the most significant determinants of willingness to receive CYC. A trend in difference by race/ethnicity was also observed in willingness to participate in a clinical trial, but this difference was not significant. Conclusion. This study demonstrated reduced likelihood of accepting CYC in African-American lupus patients compared with white lupus patients. This racial/ethnic variation was associated with belief in medication effectiveness and trust in the medical provider, suggesting that education about therapy and improved trust can influence decision-making among SLE patients. C1 [Vina, Ernest R.] Univ Pittsburgh, Div Rheumatol & Clin Immunol, Pittsburgh, PA 15260 USA. [Vina, Ernest R.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. [Masi, Christopher M.] N Shore Univ Hlth Syst, Internal Med Practice Based Improvement Res Netwo, Evanston, IL USA. [Green, Stephanie L.; Utset, Tammy O.] Univ Chicago, Rheumatol Sect, Chicago, IL 60637 USA. RP Vina, ER (reprint author), Arthrit Res Ctr, 3347 Forbes Ave,Ste 220, Pittsburgh, PA 15213 USA. EM evina1@pitt.edu OI Vina, Ernest/0000-0001-8135-1731 FU ACR/Research and Education Foundation Rheumatology Scientist Development Award FX ACR/Research and Education Foundation Rheumatology Scientist Development Award. NR 40 TC 6 Z9 6 U1 1 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-0324 J9 RHEUMATOLOGY JI RHEUMATOLOGY PD SEP PY 2012 VL 51 IS 9 BP 1697 EP 1706 DI 10.1093/rheumatology/kes128 PG 10 WC Rheumatology SC Rheumatology GA 992ME UT WOS:000307779700026 PM 22653381 ER PT J AU Palmer, WE AF Palmer, William E. TI Sports Injuries of the Upper Extremity Preface SO SEMINARS IN MUSCULOSKELETAL RADIOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Musculoskeletal Imaging & Intervent, Boston, MA 02114 USA. RP Palmer, WE (reprint author), Massachusetts Gen Hosp, Dept Musculoskeletal Imaging & Intervent, Yawkey 6 Radiol,55 Fruit St,YAW 6030, Boston, MA 02114 USA. EM wpalmer@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1089-7860 J9 SEMIN MUSCULOSKEL R JI Semin. Musculoskelet. Radiol. PD SEP PY 2012 VL 16 IS 4 BP 267 EP 268 DI 10.1055/s-0032-1327000 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 020XS UT WOS:000309850500001 PM 23047274 ER PT J AU Gyftopoulos, S Bencardino, J Palmer, WE AF Gyftopoulos, Soterios Bencardino, Jenny Palmer, William E. TI MR Imaging of the Shoulder: First Dislocation versus Chronic Instability SO SEMINARS IN MUSCULOSKELETAL RADIOLOGY LA English DT Article DE acute shoulder dislocation; first shoulder dislocation; chronic shoulder instability; glenoid bone loss ID RECURRENT ANTERIOR DISLOCATION; GLENOID BONE LOSS; 3-DIMENSIONAL COMPUTED-TOMOGRAPHY; INFERIOR GLENOHUMERAL LIGAMENT; HILL-SACHS DEFECTS; ROTATOR CUFF TEARS; CORACOID PROCESS; BANKART REPAIR; EXTERNAL ROTATION; HUMERAL AVULSION AB Traumatic dislocation of the shoulder is a frequent injury in the young and active population. An acute shoulder dislocation often denotes a onetime traumatic episode, whereas chronic shoulder instability indicates multiple recurrent dislocations. Imaging, in particular MRI, is a useful tool that can accurately demonstrate the typical soft tissue and osseous markers of shoulder dislocation. However, the ability to differentiate between first time versus recurrent dislocation based on imaging remains in question. In this article, we describe the underlying biomechanics of glenohumeral stability as well as the imaging features and treatment options of shoulder dislocation. A review of current literature is presented, aimed to shed light about the potential role of imaging in distinguishing first dislocation versus chronic instability. C1 [Gyftopoulos, Soterios; Bencardino, Jenny] NYU, Hosp Joint Dis, Dept Radiol, New York, NY 10003 USA. [Palmer, William E.] Massachusetts Gen Hosp, Dept Musculoskeletal Radiol, Boston, MA 02114 USA. RP Gyftopoulos, S (reprint author), NYU, Hosp Joint Dis, Dept Radiol, 301 E 17th St, New York, NY 10003 USA. EM Soterios20@gmail.com NR 100 TC 3 Z9 3 U1 0 U2 5 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1089-7860 J9 SEMIN MUSCULOSKEL R JI Semin. Musculoskelet. Radiol. PD SEP PY 2012 VL 16 IS 4 BP 286 EP 295 DI 10.1055/s-0032-1327003 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 020XS UT WOS:000309850500004 PM 23047277 ER PT J AU Chutinet, A Biffi, A Kanakis, A Fitzpatrick, KM Furie, KL Rost, NS AF Chutinet, A. Biffi, A. Kanakis, A. Fitzpatrick, K. M. Furie, K. L. Rost, N. S. TI Severity of Leukoaraiosis in Large Vessel Atherosclerotic Disease SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID WHITE-MATTER LESIONS; CEREBRAL AMYLOID ANGIOPATHY; ACUTE ISCHEMIC-STROKE; EVA-MRI COHORT; HYPERINTENSITY VOLUME; EXTRACRANIAL ATHEROSCLEROSIS; CARDIOVASCULAR HEALTH; RISK-FACTORS; SUBTYPE; CLASSIFICATION AB BACKGROUND AND PURPOSE: The severity of white matter hyperintensity, or leukoaraiosis, is a marker of cerebrovascular disease. In stroke, WMH burden is strongly linked to lacunar infarction; however, impaired cerebral perfusion due to extracranial or intracranial atherosclerosis may also contribute to WMH burden. We sought to determine whether WMH burden is associated with extracranial or intracranial stenosis in patients with AIS. MATERIALS AND METHODS: Patients with AIS with admission head/neck CTA and brain MR imaging were included in this analysis. "Extracranial stenosis" was defined as >50% stenosis in the extracranial (CA, and "intracranial," as >50% stenosis in either the middle, anterior, or posterior cerebral arteries on CTA, on either side. WMHV was determined by using a validated semiautomated protocol. Multiple regression was used to assess the relationship between WMHV and extracranial/intracranial atherosclerosis. RESULTS: Of 201 subjects, 51 (25.4%) had extracranial and 63 (31.5%) had intracranial stenosis. Mean age was 62 +/- 15 years; 36% were women. Mean WMHV was 12.87 cm(3) in the extracranial and 8.59 cm(3) in the intracranial stenosis groups. In univariate analysis, age (P < .0001), SBP and DBP (P = .004), and HTN (P = .0003) were associated with WMHV. Extracranial stenosis was associated with greater WMHV after adjustment for intracranial stenosis (P = .04). In multivariate analysis including extracranial stenosis, only age (P < .0001) and HTN (P = .03) demonstrated independent effects on WMHV. CONCLUSIONS: In our cohort of patients with AIS, age and HTN were the strongest determinants of the WMHV severity. Future studies are warranted to unravel further association between WMHV and cerebral vessel atherosclerosis. C1 [Chutinet, A.; Biffi, A.; Kanakis, A.; Fitzpatrick, K. M.; Furie, K. L.; Rost, N. S.] Massachusetts Gen Hosp, J Philip Kistler Stroke Res Ctr, Dept Neurol, Boston, MA 02114 USA. [Chutinet, A.] Chulalongkorn Univ, Fac Med, Dept Med, Div Neurol, Bangkok 10330, Thailand. RP Rost, NS (reprint author), Massachusetts Gen Hosp, J Philip Kistler Stroke Res Ctr, Dept Neurol, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM nrost@partners.org FU National Institutes of Health National Institute of Neurological Disorders and Stroke [K23NS064052, P50NS051343]; American Heart Association/Bugher Foundation Centers for Stroke Prevention Research [0775010N]; Deane Institute for Integrative Study of Atrial Fibrillation and Stroke; American Heart Association FX This work was supported by the National Institutes of Health National Institute of Neurological Disorders and Stroke (K23NS064052, N.S.R.; P50NS051343, K.L.F.), the American Heart Association/Bugher Foundation Centers for Stroke Prevention Research (0775010N), and the Deane Institute for Integrative Study of Atrial Fibrillation and Stroke.; Alessandro Biffi-UNRELATED: Grants/Grants Pending: American Heart Association. Karen Furie-UNRELATED: Consultancy: Quintiles. NR 47 TC 12 Z9 12 U1 0 U2 4 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD SEP PY 2012 VL 33 IS 8 BP 1591 EP 1595 DI 10.3174/ajnr.A3015 PG 5 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 016AN UT WOS:000309489800030 PM 22422177 ER PT J AU Kar, S Bhatt, DL AF Kar, Subrata Bhatt, Deepak L. TI Anticoagulants for the treatment of acute coronary syndrome in the era of new oral agents SO CORONARY ARTERY DISEASE LA English DT Review DE acute coronary syndrome; atrial fibrillation; direct thrombin inhibitors; factor Xa inhibitors; warfarin ID ELEVATION MYOCARDIAL-INFARCTION; PHASE-II TRIAL; ATRIAL-FIBRILLATION; ANTIPLATELET THERAPY; DOUBLE-BLIND; FACTOR XA; ANTITHROMBOTIC THERAPY; RANDOMIZED EVALUATION; CONSENSUS DOCUMENT; UNSTABLE ANGINA AB Acute coronary syndromes (ACS) cause cessation of myocardial blood flow leading to coronary ischemia. The standard medical treatment includes heparin or low molecular weight heparin in the hospital, antiplatelet agents in the hospital and long term, and occasionally warfarin long term. All of these therapies are associated with bleeding complications. Furthermore, warfarin, with its narrow therapeutic window and need for frequent laboratory monitoring, poses several disadvantages. The development of novel oral factor Xa inhibitors and oral direct thrombin inhibitors may provide an alternative to warfarin. In this review, we discuss the new agents, rivaroxaban, apixaban, and dabigatran, for the potential treatment of ACS. We also review the relevant clinical trials evaluating their effects in ACS. These novel anticoagulants allow convenience of use with no requirement for laboratory monitoring and limited drug interactions, which may provide multifaceted treatment options for ACS and anticoagulation in the future. Coron Artery Dis 23:380-390 (c) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Bhatt, Deepak L.] Harvard Univ, Sch Med, Dept Cardiol, Brigham & Womens Hosp,VA Boston Healthcare Syst, Boston, MA 02132 USA. [Kar, Subrata] Univ Missouri, Sch Med, Div Cardiovasc Med, Columbia, MO USA. RP Bhatt, DL (reprint author), Harvard Univ, Sch Med, Dept Cardiol, Brigham & Womens Hosp,VA Boston Healthcare Syst, 1400 VFW Pkwy, Boston, MA 02132 USA. EM dlbhattmd@post.harvard.edu NR 37 TC 2 Z9 2 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0954-6928 J9 CORONARY ARTERY DIS JI Coronary Artery Dis. PD SEP PY 2012 VL 23 IS 6 BP 380 EP 390 DI 10.1097/MCA.0b013e328356490a PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 017BM UT WOS:000309563700004 PM 22728913 ER PT J AU Merabet, L Plow, EB AF Merabet, L. Plow, E. B. TI Visual field training for hemianopia with transcranial direct cortical stimulation SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Meeting Abstract CT 16th Congress of the European-Federation-of-Neurological-Societies (EFNS) CY SEP 08-11, 2012 CL Stockholm, SWEDEN SP European Federat Neurol Soc (EFNS) C1 [Merabet, L.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. [Plow, E. B.] Cleveland Clin Fdn, Lerner Res Inst, Cleveland, OH 44195 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 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD SEP PY 2012 VL 19 SU 1 SI SI BP 34 EP 34 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 014FD UT WOS:000309359700068 ER PT J AU Williams, J Atassi, N Nakano, I Mora, JS Drory, V Cudkowicz, M Shefner, J Chio, A Mitsumoto, H Silani, V Zinman, L Weber, M van den Berg, LH Robberecht, W Ronnevi, LO Hardiman, O Bruijn, L Kerr, D AF Williams, J. Atassi, N. Nakano, I. Mora, J. S. Drory, V. Cudkowicz, M. Shefner, J. Chio, A. Mitsumoto, H. Silani, V. Zinman, L. Weber, M. van den Berg, L. H. Robberecht, W. Ronnevi, L-O. Hardiman, O. Bruijn, L. Kerr, D. TI Development of a "red flags" symptom list to assist with early recognition and diagnosis of amyotrophic lateral sclerosis SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Meeting Abstract CT 16th Congress of the European-Federation-of-Neurological-Societies (EFNS) CY SEP 08-11, 2012 CL Stockholm, SWEDEN SP European Federat Neurol Soc (EFNS) C1 [Williams, J.; Kerr, D.] Biogen Idec Inc, Cambridge, MA USA. [Atassi, N.; Cudkowicz, M.] Massachussetts Gen Hosp, Charlestown, MA USA. [Nakano, I.] Jichi Med Univ, Togichi, Japan. [Mora, J. S.] Hosp Carlos III, Madrid, Spain. [Drory, V.] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, IL-69978 Tel Aviv, Israel. [Shefner, J.] UPSTATE Med Univ, Syracuse, NY USA. [Chio, A.] Univ Turin, Turin, Italy. [Mitsumoto, H.] Columbia Univ, Med Ctr, New York, NY USA. [Silani, V.] Univ Milan, Sch Med, Milan, Italy. [Zinman, L.] Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. [Weber, M.] Kantonsspital St Gallen, St Gallen, Switzerland. [van den Berg, L. H.] Univ Med Ctr Utrecht, Utrecht, Netherlands. [Robberecht, W.] Univ Hosp Leuven, Louvain, Belgium. [Ronnevi, L-O.] Karolinska Inst, Stockholm, Sweden. [Hardiman, O.] Trinity Coll Dublin, Dublin, Ireland. [Hardiman, O.] Beaumont Hosp, Dublin 9, Ireland. [Bruijn, L.] ALS Assoc, Tampa, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD SEP PY 2012 VL 19 SU 1 SI SI BP 83 EP 83 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 014FD UT WOS:000309359700156 ER PT J AU Dai, Z Xiao, G Shen, Z Wang, L Sun, PZ Wu, R AF Dai, Z. Xiao, G. Shen, Z. Wang, L. Sun, P. Z. Wu, R. TI Non-invasive pH-weighted magnetic resonance imaging SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Meeting Abstract CT 16th Congress of the European-Federation-of-Neurological-Societies (EFNS) CY SEP 08-11, 2012 CL Stockholm, SWEDEN SP European Federat Neurol Soc (EFNS) C1 [Dai, Z.; Xiao, G.; Shen, Z.; Wang, L.; Sun, P. Z.] Shantou Univ, Coll Med, Shantou, Peoples R China. [Sun, P. Z.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Sun, P. Z.] Harvard Univ, Sch Med, Charlestown, MA USA. [Wu, R.] Shantou Univ, Coll Med, Affiliated Hosp 2, Dept Med Imaging, Shantou, Peoples R China. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD SEP PY 2012 VL 19 SU 1 SI SI BP 404 EP 404 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 014FD UT WOS:000309359702179 ER PT J AU Wang, L Shen, Z Dai, Z Xiao, G Sun, Z Wu, R AF Wang, L. Shen, Z. Dai, Z. Xiao, G. Sun, Z. Wu, R. TI Measurement of extracellular-pH based iopamidol chemical exchange saturation transfer imaging at 7T SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Meeting Abstract CT 16th Congress of the European-Federation-of-Neurological-Societies (EFNS) CY SEP 08-11, 2012 CL Stockholm, SWEDEN SP European Federat Neurol Soc (EFNS) C1 [Wang, L.; Shen, Z.; Dai, Z.; Wu, R.] Shantou Univ, Coll Med, Affiliated Hosp 2, Dept Med Imaging, Shantou, Peoples R China. [Xiao, G.] Hanshan Normal Univ, Dept Math & Informat Technol, Chaozhou, Peoples R China. [Sun, Z.] Massachusetts Gen Hosp, Dept Radiol, Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Sun, Z.] Harvard Univ, Sch Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD SEP PY 2012 VL 19 SU 1 SI SI BP 405 EP 405 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 014FD UT WOS:000309359702181 ER PT J AU Xiao, G Dai, Z Sun, PZ Wu, R AF Xiao, G. Dai, Z. Sun, P. Z. Wu, R. TI Detection of CEST MRI using magnetization transfer pre-saturation sequence at 1.5 T scan SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Meeting Abstract CT 16th Congress of the European-Federation-of-Neurological-Societies (EFNS) CY SEP 08-11, 2012 CL Stockholm, SWEDEN SP European Federat Neurol Soc (EFNS) C1 [Xiao, G.] Hanshan Normal Univ, Dept Math & Informat Technol, Chaozhou, Peoples R China. [Dai, Z.] Shantou Univ, Coll Med, Shantou, Peoples R China. [Sun, P. Z.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Sun, P. Z.] Harvard Univ, Sch Med, Charlestown, MA USA. [Wu, R.] Shantou Univ, Coll Med, Affiliated Hosp 2, Dept Radiol, Shantou, Peoples R China. NR 0 TC 0 Z9 0 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD SEP PY 2012 VL 19 SU 1 SI SI BP 412 EP 412 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 014FD UT WOS:000309359702195 ER PT J AU Muresanu, DF Winkler, T Nozari, A Menon, PK Sharma, A Sharma, HS AF Muresanu, D. F. Winkler, T. Nozari, A. Menon, P. K. Sharma, A. Sharma, H. S. TI Cerebrolysin enhances spinal cord conduction and reduces blood-spinal cord barrier breakdown, oedema formation, immediate early gene expression and cord pathology after injury SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Meeting Abstract CT 16th Congress of the European-Federation-of-Neurological-Societies (EFNS) CY SEP 08-11, 2012 CL Stockholm, SWEDEN SP European Federat Neurol Soc (EFNS) C1 [Muresanu, D. F.] Univ Med & Pharm, Cluj Napoca, Romania. [Winkler, T.] Uppsala Univ, Univ Hosp, Dept Clin Neurophysiol, Uppsala, Sweden. [Nozari, A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Menon, P. K.; Sharma, A.; Sharma, H. S.] Uppsala Univ, Uppsala, Sweden. RI Sharma, Hari/G-4508-2016 NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD SEP PY 2012 VL 19 SU 1 SI SI BP 798 EP 798 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 014FD UT WOS:000309359705202 ER PT J AU Pasquale, LR Wiggs, JL Willett, WC Kang, JH AF Pasquale, Louis R. Wiggs, Janey L. Willett, Walter C. Kang, Jae H. TI The Relationship between Caffeine and Coffee Consumption and Exfoliation Glaucoma or Glaucoma Suspect: A Prospective Study in Two Cohorts SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; RANDOMIZED CONTROLLED-TRIAL; TOTAL-ENERGY-INTAKE; PSEUDOEXFOLIATION SYNDROME; PLASMA HOMOCYSTEINE; INTRAOCULAR-PRESSURE; LOXL1 POLYMORPHISMS; HEALTHY-VOLUNTEERS; OXIDATIVE STRESS; AQUEOUS-HUMOR AB PURPOSE. We examined the association between caffeine and caffeinated beverage consumption in relation to the risk of exfoliation glaucoma or exfoliation glaucoma suspect (EG/EGS). METHODS. We followed 78,977 women from the Nurses' Health Study (NHS) and 41,202 men from the Health Professionals Follow-up Study (HPFS) who were at least 40 years of age, did not have glaucoma, and reported undergoing eye examinations from 1980 (NHS) or 1986 (HPFS) to 2008. Information on consumption of caffeine-containing beverages and potential confounders were repeatedly ascertained in validated follow-up questionnaires. Confirmation with medical record review revealed 360 incident EG/EGS cases. Multivariate rate ratios (RRs) for EG/EGS were calculated in each cohort and then pooled using meta-analytic techniques. RESULTS. Compared with participants whose cumulatively updated total caffeine consumption was <125 mg/day, participants who consumed >= 500 mg/day had a trend toward increased risk of EG/EGS that was not statistically significant (RR = 1.43; 95% confidence interval [CI], 0.98-2.08); P trend = 0.06). Compared to abstainers, those who drank >= 3 cups of caffeinated coffee daily were at increased risk of EG/EGS (RR 1.66; 95% CI, 1.09-2.54; P trend = 0.02). These results were not materially altered after adjustment for total fluid intake. Associations were stronger among women with a family history of glaucoma (P interaction 0.06 for coffee; P interaction = 0.03 for caffeine). We did not find associations with consumption of other caffeinated products (caffeinated soda, caffeinated tea, decaffeinated coffee or chocolate) and risk of EG/EGS (P trend >0.31). CONCLUSIONS. We observed a positive association between heavier coffee consumption with risk of EG/EGS in this large prospective study. (Invest Ophthalmol Vis Sci. 2012;53:6427-6433) DOI:10.1167/iovs.12-10085 C1 [Kang, Jae H.] Brigham & Womens Hosp, Dept Med, Channing Lab, Channing Div Network Med, Boston, MA 02114 USA. [Pasquale, Louis R.; Willett, Walter C.; Kang, Jae H.] Harvard Univ, Sch Med, Boston, MA USA. [Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Pasquale, Louis R.; Wiggs, Janey L.] Massachusetts Eye & Ear Infirm, Glaucoma Serv, Boston, MA 02114 USA. RP Kang, JH (reprint author), Brigham & Womens Hosp, Dept Med, Channing Lab, Channing Div Network Med, 181 Longwood Ave, Boston, MA 02114 USA. EM nhjhk@channing.harvard.edu FU National Institutes of Health; Arthur Ashley Foundation [CA87969, EY009611, CA49449, CA055075, EY020928, EY015473]; Harvard Glaucoma Center of Excellence FX Supported by National Institutes of Health and Arthur Ashley Foundation Grants CA87969, EY009611, CA49449, CA055075, EY020928 (JLW), and EY015473 (LRP) and by the Harvard Glaucoma Center of Excellence (LRP and JLW). NR 55 TC 13 Z9 13 U1 2 U2 13 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 SEP PY 2012 VL 53 IS 10 BP 6427 EP 6433 DI 10.1167/iovs.12-10085 PG 7 WC Ophthalmology SC Ophthalmology GA 016NQ UT WOS:000309526200057 PM 22918628 ER PT J AU Muir, ER Renteria, RC Duong, TQ AF Muir, Eric R. Renteria, Rene C. Duong, Timothy Q. TI Reduced Ocular Blood Flow as an Early Indicator of Diabetic Retinopathy in a Mouse Model of Diabetes SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID STREPTOZOTOCIN-INDUCED CONSTRICTION; RETINAL HEMODYNAMICS; CONTRAST SENSITIVITY; INS2(AKITA) MOUSE; FUNCTIONAL MRI; RAT RETINA; MICE; DYSFUNCTION; THRESHOLD; MELLITUS AB PURPOSE. To investigate ocular blood flow and visual function in the Ins2(Akita) diabetic retinopathy mouse model at early and late time points after onset of hyperglycemia. METHODS. Mice heterozygous for the Ins2(Akita) mutation, which become hyperglycemic at approximately 4 weeks old, were studied at 2.5 and 7.5 months of age, with age-matched wild-type littermates used as controls. Retinal and choroidal blood flows were noninvasively imaged at 42 X 42 X 400 mu m using magnetic resonance imaging. Visual function was measured using optokinetic tracking to determine spatial frequency and contrast thresholds from the same mice. RESULTS. At 2.5 months, choroidal blood flow was significantly reduced (P < 0.01) by 20% in Ins2(Akita) mice (n = 13) compared with age-matched controls (n = 16), whereas retinal blood flow and visual function were not significantly affected (P > 0.05). At 7.5 months, both choroidal and retinal blood flow were significantly reduced (P < 0.05) by 27% and 28%, respectively, in Ins2(Akita) mice (n = 11) compared with age-matched controls (n = 15). Visual functions were also significantly worse (P < 0.05) in Ins2(Akita) mice at 7.5 months, as indicated by a 19% decreased spatial frequency threshold and 135% increased contrast threshold compared with age-matched controls. The magnitudes of the blood flow and vision deficits, however, were not correlated. CONCLUSIONS. Although both choroidal and retinal blood flow and vision were altered after prolonged diabetes in the Ins2(Akita) mouse, choroidal blood flow was reduced even in young diabetic animals, suggesting ocular blood flow deficit could be an early pathological change in diabetic retinopathy. (Invest Ophthalmol Vis Sci. 2012;53:6488-6494) DOI:10.1167/iovs.12-9758 C1 [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Ctr, Res Imaging Inst, San Antonio, TX 78229 USA. [Renteria, Rene C.; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [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. [Renteria, Rene C.] Univ Texas Hlth Sci Ctr San Antonio, Ctr Biomed Neurosci, 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 Ctr, Res Imaging Inst, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. EM duongt@uthscsa.edu RI Muir, Eric/H-8830-2013; OI Renteria, Rene/0000-0002-4490-0735 FU National Institutes of Health/National Eye Institute [R01 EY014211, EY018855]; MERIT Award from the Department of Veterans Affairs; Translational Technology Resources and Pilot Grant programs of the Clinical Translational Science Award Parent [8UL1TR000149]; National Institutes of Health [5T32HL007446-29] FX Supported in part by National Institutes of Health/National Eye Institute Grants R01 EY014211 and EY018855, a MERIT Award from the Department of Veterans Affairs (TQD), Translational Technology Resources and Pilot Grant programs of the Clinical Translational Science Award Parent Grant 8UL1TR000149 (RCR and TQD), and partially supported by National Institutes of Health Grant 5T32HL007446-29 (ERM). NR 50 TC 34 Z9 34 U1 1 U2 10 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 SEP PY 2012 VL 53 IS 10 BP 6488 EP 6494 DI 10.1167/iovs.12-9758 PG 7 WC Ophthalmology SC Ophthalmology GA 016NQ UT WOS:000309526200065 PM 22915034 ER PT J AU Wiecek, E Jackson, ML Dakin, SC Bex, P AF Wiecek, Emily Jackson, Mary Lou Dakin, Steven C. Bex, Peter TI Visual Search with Image Modification in Age-Related Macular Degeneration SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID QUALITY-OF-LIFE; OBJECT RECOGNITION; NATURAL SCENES; FACE RECOGNITION; OLDER-ADULTS; READING PERFORMANCE; SPATIAL-FREQUENCY; EYE-MOVEMENTS; LOW-VISION; ENHANCEMENT AB PURPOSE. AMD results in loss of central vision and a dependence on low-resolution peripheral vision. While many image enhancement techniques have been proposed, there is a lack of quantitative comparison of the effectiveness of enhancement. We developed a natural visual search task that uses patients' eye movements as a quantitative and functional measure of the efficacy of image modification. METHODS. Eye movements of 17 patients (mean age = 77 years) with AMD were recorded while they searched for target objects in natural images. Eight different image modification methods were implemented and included manipulations of local image or edge contrast, color, and crowding. In a subsequent task, patients ranked their preference of the image modifications. RESULTS. Within individual participants, there was no significant difference in search duration or accuracy across eight different image manipulations. When data were collapsed across all image modifications, a multivariate model identified six significant predictors for normalized search duration including scotoma size and acuity, as well as interactions among scotoma size, age, acuity, and contrast (P < 0.05). Additionally, an analysis of image statistics showed no correlation with search performance across all image modifications. Rank ordering of enhancement methods based on participants' preference revealed a trend that participants preferred the least modified images (P < 0.05). CONCLUSIONS. There was no quantitative effect of image modification on search performance. A better understanding of low-and high-level components of visual search in natural scenes is necessary to improve future attempts at image enhancement for low vision patients. Different search tasks may require alternative image modifications to improve patient functioning and performance. (Invest Ophthalmol Vis Sci. 2012;53:6600-6609) DOI:10.1167/iovs.12-10012 C1 [Wiecek, Emily; Jackson, Mary Lou; Bex, Peter] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Wiecek, Emily; Bex, Peter] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Wiecek, Emily; Dakin, Steven C.] UCL, Inst Ophthalmol, London, England. [Dakin, Steven C.] Moorfields Eye Hosp NHS Fdn Trust, NIHR, Biomed Res Ctr, London, England. RP Wiecek, E (reprint author), 20 Staniford St, Boston, MA 02118 USA. EM emily.wiecek@schepens.harvard.edu RI Dakin, Steven/B-7610-2008 OI Dakin, Steven/0000-0002-3548-9104 FU National Institute of Health [R01EY018664, R01EY019281]; NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust FX Supported by National Institute of Health Grants R01EY018664 and R01EY019281, and by the NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust (SCD). NR 64 TC 4 Z9 4 U1 5 U2 17 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 SEP PY 2012 VL 53 IS 10 BP 6600 EP 6609 DI 10.1167/iovs.12-10012 PG 10 WC Ophthalmology SC Ophthalmology GA 016NQ UT WOS:000309526200078 PM 22930725 ER PT J AU Haddadin, RI Oh, DJ Kang, MH Villarreal, G Kang, JH Jin, R Gong, HY Rhee, DJ AF Haddadin, Ramez I. Oh, Dong-Jin Kang, Min Hyung Villarreal, Guadalupe, Jr. Kang, Ja-Heon Jin, Rui Gong, Haiyan Rhee, Douglas J. TI Thrombospondin-1 (TSP1)-Null and TSP2-Null Mice Exhibit Lower Intraocular Pressures SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID HUMAN TRABECULAR MESHWORK; GENE-EXPRESSION PROFILE; GROWTH-FACTOR-BETA; AQUEOUS-HUMOR; MATRIX METALLOPROTEINASES; GLAUCOMATOUS EYES; HUMAN LENS; IN-VIVO; CELLS; SPARC AB PURPOSE. Thrombospondin-1 (TSP1) and TSP2 are matricellular proteins that have been shown to regulate cytoskeleton, cell adhesion, and extracellular matrix remodeling. Both TSP1 and TSP2 are found in the trabecular meshwork (TM). In cadaver eyes with primary open-angle glaucoma (POAG), TSP1 is increased in one third of patients. We hypothesized that TSP1 and TSP2 participate in the regulation of intraocular pressure (IOP). METHODS. IOPs of TSP1-null, TSP2-null mice, and their corresponding wild-type (WT) mice were measured using a commercial rebound tonometer. Fluorophotometric measurements assessed aqueous turnover. Central corneal thickness (CCT) was measured by optical coherence tomography. Iridocorneal angles were examined using light microscopy (LM), immunofluorescence (IF), and transmission electron microscopy (TEM). RESULTS. Average IOPs of TSP1-null and TSP2-null mice were 10% and 7% less than that of the corresponding WT mice, respectively. CCTs were 6.5% less in TSP1-null mice (P < 0.05) and 1.1% less in TSP2-null mice (P > 0.05). Fluorophotometric measurements suggest that aqueous turnover rates in TSP1-null and TSP2-null mice are greater than those of WT mice. LM of the TSP1-null and TSP2-null iridocorneal angles reveals morphology, which is indistinguishable from that of their corresponding WTs. IF revealed possible concurrent underexpression of TSP2 in TSP1-null mice and of TSP1 in TSP2-null mice. TEM revealed larger collagen fibril diameters in TSP1-null and TSP2-null mice compared with WTs. CONCLUSIONS. TSP1-null and TSP2-null mice have lower IOPs than their WT counterparts. The rate of aqueous turnover suggests that the mechanism is enhanced outflow facility. An alteration in the extracellular matrix may contribute to this finding. (Invest Ophthalmol Vis Sci. 2012;53:6708-6717) DOI:10.1167/iovs.11-9013 C1 [Haddadin, Ramez I.; Oh, Dong-Jin; Kang, Min Hyung; Villarreal, Guadalupe, Jr.; Rhee, Douglas J.] Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Sch Med, Boston, MA 02114 USA. [Kang, Ja-Heon] Kyung Hee Univ, Coll Med, Kyung Hee Univ Hosp Gangdong, Dept Ophthalmol, Seoul, South Korea. [Jin, Rui; Gong, Haiyan] Boston Univ, Sch Med, Dept Ophthalmol, Boston, MA 02118 USA. RP Rhee, DJ (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Sch Med, 243 Charles St, Boston, MA 02114 USA. EM DougRhee@aol.com FU National Eye Institute [EY 019654-01, EY 014104]; Fight for Sight; Research to Prevent Blindness; Massachusetts Lions Eye Research Foundation; American Glaucoma Society FX Supported in part by National Eye Institute Grants EY 019654-01 and EY 014104 (Massachusetts Eye and Ear Infirmary Core Grant), Fight for Sight (RIH), Research to Prevent Blindness, Massachusetts Lions Eye Research Foundation, and American Glaucoma Society. NR 54 TC 25 Z9 26 U1 0 U2 7 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 SEP PY 2012 VL 53 IS 10 BP 6708 EP 6717 DI 10.1167/iovs.11-9013 PG 10 WC Ophthalmology SC Ophthalmology GA 016NQ UT WOS:000309526200094 PM 22930728 ER PT J AU Tang, LL Zhou, XH AF Tang, Liansheng Larry Zhou, Xiao-Hua TI A Semiparametric Separation Curve Approach for Comparing Correlated ROC Data From Multiple Markers SO JOURNAL OF COMPUTATIONAL AND GRAPHICAL STATISTICS LA English DT Article DE Confidence band; Empirical distribution function; Least squares ID OPERATING CHARACTERISTIC CURVES AB In this article, we propose a separation curve method to identify the range of false positive rates for which two receiver operating characteristic (ROC) curves differ or one ROC curve is superior to the other. Our method is based on a general multivariate ROC curve model, including interaction terms between discrete covariates and false positive rates. It is applicable with most existing ROC curve models. Furthermore, we introduce a semiparametric least squares ROC estimator and apply the estimator to the separation curve method. We derive a sandwich estimator for the covariance matrix of the semiparametric estimator. We illustrate the application of our separation curve method through two real life examples. The technical proofs, a dataset, and the computer code are available in the online supplementary materials. C1 [Tang, Liansheng Larry] George Mason Univ, Dept Stat, Fairfax, VA 22030 USA. [Zhou, Xiao-Hua] VA Puget Sound Hlth Care Syst, NW HSR & D Ctr Excellence, Seattle, WA 98101 USA. [Zhou, Xiao-Hua] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Zhou, Xiao-Hua] Harbin Med Univ, Dept Biostat, Harbin 150081, Heilongjiang, Peoples R China. RP Tang, LL (reprint author), George Mason Univ, Dept Stat, Fairfax, VA 22030 USA. EM ltang1@gmu.edu; azhou@u.washington.edu FU National Cancer Institute under the American Recovery and Reinvestment Act [R15CA150698]; National Security Agency [H98230-11-1-0196]; Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service [XVA 61-036] FX The authors thank two anonymous referees, the associate editor, and the editor for their constructive comments and useful suggestions. The project described here was supported by Award Number R15CA150698 from the National Cancer Institute under the American Recovery and Reinvestment Act of 2009; by Award Number H98230-11-1-0196 from the National Security Agency; and by Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service, project grant XVA 61-036. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute, the National Institutes of Health, or the Department Of Veterans Affairs. NR 9 TC 3 Z9 3 U1 0 U2 0 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA SN 1061-8600 J9 J COMPUT GRAPH STAT JI J. Comput. Graph. Stat. PD SEP PY 2012 VL 21 IS 3 BP 662 EP 676 DI 10.1080/10618600.2012.663303 PG 15 WC Statistics & Probability SC Mathematics GA 999AR UT WOS:000308282000006 PM 23074360 ER PT J AU Muzykewicz, DA Black, ME Muse, V Numis, AL Rajagopal, J Thiele, EA Sharma, A AF Muzykewicz, David A. Black, Margaux E. Muse, Victorine Numis, Adam L. Rajagopal, Jayaraj Thiele, Elizabeth A. Sharma, Amita TI Multifocal Micronodular Pneumocyte Hyperplasia: Computed Tomographic Appearance and Follow-Up in Tuberous Sclerosis Complex SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE computed tomography; tuberous sclerosis; multifocal micronodular pneumocyte hyperplasia; pulmonary nodules; lung ID LYMPHANGIOLEIOMYOMATOSIS; NODULES AB Objective: To characterize pulmonary nodules in patients with tuberous sclerosis complex (TSC) using computed tomography. Methods: We retrospectively reviewed chest computed tomographic images of 73 patients with TSC (22 males and 51 females; mean +/- SD age, 31.5 +/- 13.2 years; range, 13.8-63.5 years). Results: Multiple pulmonary nodules were identified in 42 (58%) of 73 patients (mean T SD size, 6.6 +/- 3.0 mm; range, 2-14 mm). Solid nodules were present in 11 (26%) of 42 patients, ground-glass nodules were present in 3 (7%) of 42 patients, and both solid and ground-glass nodules were present in 28 (67%) of 42 patients. The presence of multiple nodules was independent of sex and lymphangioleiomyomatosis. Follow-up images were available for 22 patients with multiple nodules (mean T SD follow-up, 2.0 +/- 1.1 years; range, 0.9-4.9 years), none of whom had change in nodule size or number. Conclusions: Most men and women with TSC have multiple pulmonary nodules, which likely represent multifocal micronodular pneumocyte hyperplasia in the absence of known predisposing factors. C1 [Muzykewicz, David A.; Black, Margaux E.; Numis, Adam L.; Thiele, Elizabeth A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Muse, Victorine; Sharma, Amita] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Rajagopal, Jayaraj] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Sharma, A (reprint author), Massachusetts Gen Hosp, Dept Thorac Imaging, 55 Fruit St,FND 202, Boston, MA 02114 USA. EM asharma2@partners.org FU Herscot Center for Tuberous Sclerosis Complex; NIH/NINDS [P01 NS024279] FX This study was supported by the Herscot Center for Tuberous Sclerosis Complex and NIH/NINDS P01 NS024279. NR 21 TC 12 Z9 14 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0363-8715 EI 1532-3145 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD SEP-OCT PY 2012 VL 36 IS 5 BP 518 EP 522 DI 10.1097/RCT.0b013e318264e404 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 016KW UT WOS:000309518100003 PM 22992599 ER PT J AU Li, XH Zhang, D Liu, B AF Li, Xinhua Zhang, Da Liu, Bob TI Equations for CT dose calculations on axial lines based on the principle of symmetry SO MEDICAL PHYSICS LA English DT Article DE computed tomography (CT); dose; calculation; equation; symmetry ID COMPUTED-TOMOGRAPHY; PRACTICAL APPROACH; DOSIMETRY; FEASIBILITY; INFINITY AB Purpose: Radiation dose from CT examination depends on the position relative to the irradiated region in the longitudinal direction. The objective of this work is to present a mechanism for calculating dose at any point on a line parallel to the axis of rotation. Methods: In a medium that is uniform in the z direction, the cumulative dose at the midpoint D-L(0) of the irradiated length (L) increases with L until the equilibrium dose (D-eq) is reached. Using the approach to equilibrium function, H(L) = D-L(0)1 D-eq, the authors formulated equations for calculating dose at an arbitrary point on an axial line. Results: Dose calculation examples are presented for multidetector CT (MDCT) and micro-CT. Conclusions: The new equations are suited for any functional form of H(L), and can be used for dose evaluations in MDCT, micro-CT, cone-beam CT, and other cases with media that are approximately uniform along the z direction. (c) 2012 American Association of Physicists in Medicine. [http://dx.doi.org/10.1118/1.4742070] C1 [Li, Xinhua; Zhang, Da; Liu, Bob] Massachusetts Gen Hosp, Dept Radiol, Div Diagnost Imaging Phys, Boston, MA 02114 USA. RP Liu, B (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Diagnost Imaging Phys, Boston, MA 02114 USA. EM bliu7@bics.bwh.harvard.edu NR 19 TC 6 Z9 6 U1 0 U2 2 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD SEP PY 2012 VL 39 IS 9 BP 5347 EP 5352 DI 10.1118/1.4742070 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 013VR UT WOS:000309334500006 PM 22957602 ER PT J AU Warmerdam, G Steininger, P Neuner, M Sharp, G Winey, B AF Warmerdam, Guy Steininger, Philipp Neuner, Markus Sharp, Gregory Winey, Brian TI Influence of imaging source and panel position uncertainties on the accuracy of 2D/3D image registration of cranial images SO MEDICAL PHYSICS LA English DT Article DE 2D/3D registration; image calibration ID CONE-BEAM CT; COMPUTED-TOMOGRAPHY SYSTEM; GEOMETRIC CALIBRATION; RADIATION-THERAPY; GUIDED RADIOTHERAPY; QUALITY-ASSURANCE; IMPLEMENTATION; GUIDANCE; PHANTOM; ANGLE AB Purpose: To determine the effects of imager source and panel positioning uncertainties on the accuracy of dual intensity-based 2D/3D image registration of cranial images. Methods: An open source 2D/3D image registration algorithm has been developed for registration of two orthogonal x-rays to a 3D volumetric image. The initialization files of the algorithm allow for nine degrees of freedom system calibration including,v, y, z positions of the source and panel, and three rotational degrees of freedom of the panel about each of the three translational axes. A baseline system calibration was established and a baseline 2D/3D registration between two orthogonal x-rays and the volumetric image was determined. The calibration file was manipulated to insert errors into each of the nine calibration variables of both imager geometries. Rigid six degrees of freedom registrations were iterated for each panel or source positional error over a range of predetermined calibration errors to determine the resulting error in the registration versus the baseline registration due to the manipulated error of the panel or source calibration. Results: Panel and source translational errors orthogonal to the imager/panel axis introduced the greatest errors in the registration accuracy (4.0 mm geometric error results in up to 2.7 mm registration error). Panel rotation about the imaging direction also resulted in errors of the registration (2.0 degrees geometric error results in up to 1.7 degrees registration error). Differences in magnification and panel tilt and roll, i.e., source and/or panel translation along the imaging direction and panel rotations about the orthogonal axes had minimal effects on the registration accuracy (below 0.3 mm and 0.2 degrees registration error). Conclusions: While five of the nine imaging system variables were found to have a considerable effect on 2D/3D registration accuracy of cranial images, the other four variables showed minimal effects. Vendors typically provide simplified calibration procedures which aim to remove encountered geometric uncertainties by accounting for two panel translations. This study shows that at least the five relevant positional variables should be separately calibrated, if accurate alignment is required for 2D/3D registration. (c) 2012 American Association of Physicists in Medicine. [http://dx.doi.org/10.1118/1.4742866] C1 [Warmerdam, Guy; Sharp, Gregory; Winey, Brian] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sharp, Gregory; Winey, Brian] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Warmerdam, Guy] Eindhoven Univ Technol, Sch Med Phys & Engn, NL-5600 MB Eindhoven, Netherlands. [Steininger, Philipp; Neuner, Markus] Paracelsus Med Univ, Inst Res & Dev Adv Radiat Technol, A-5020 Salzburg, Austria. RP Winey, B (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM winey.brian@mgh.harvard.edu NR 33 TC 4 Z9 4 U1 1 U2 5 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD SEP PY 2012 VL 39 IS 9 BP 5547 EP 5556 DI 10.1118/1.4742866 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 013VR UT WOS:000309334500025 PM 22957621 ER PT J AU Kimonis, VE Steller, J Sahai, I Grange, DK Shoemaker, J Zelaya, BM Mandell, R Shih, K Shih, V AF Kimonis, V. E. Steller, J. Sahai, I. Grange, D. K. Shoemaker, J. Zelaya, B. M. Mandell, R. Shih, K. Shih, V. TI Mild fumarase deficiency and a trial of low protein diet SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE Fumarase; Fumarate hydratase; Fumaric aciduria; Developmental delay; Hypotonia; Ventriculomegaly AB We report clinical findings in a 12-year-old girl with a mild case of fumarase deficiency who continues to make progress. She has two novel mutations of the fumarase gene [c.521 C>G (p.P174R) and c.908 T>C (p.L303S)]. A trial of low protein diet did not reduce fumaric aciduria. (C) 2012 Elsevier Inc. All rights reserved. C1 [Kimonis, V. E.; Steller, J.] Univ Calif Irvine, Dept Pediat, Div Genet & Metab, Orange, CA 92868 USA. [Sahai, I.] Childrens Hosp, Div Genet & Metab, Boston, MA 02115 USA. [Grange, D. K.] Washington Univ, St Louis Childrens Hosp, Dept Pediat, Div Med Genet, St Louis, MO 63110 USA. [Shoemaker, J.] St Louis Univ, Sch Med, Edward A Doisy Dept Biochem & Mol Biol, St Louis, MO 63104 USA. [Zelaya, B. M.] Univ Coll Med Peoria, Peoria, IL USA. [Mandell, R.; Shih, K.; Shih, V.] Massachusetts Gen Hosp, Amino Acid Lab, Boston, MA 02114 USA. [Kimonis, V. E.] So Illinois Univ, Sch Med, Dept Pediat, Div Genet, Springfield, IL USA. RP Kimonis, VE (reprint author), Univ Calif Irvine, Med Ctr, Dept Pediat, UCI Div Genet & Metab, 101 City Dr S,ZC4482, Orange, CA 92868 USA. EM vkimonis@uci.edu NR 6 TC 1 Z9 1 U1 2 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD SEP-OCT PY 2012 VL 107 IS 1-2 SI SI BP 241 EP 242 DI 10.1016/j.ymgme.2012.04.010 PG 2 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 014KI UT WOS:000309374200034 PM 22595425 ER PT J AU Yan, ZY Shah, PK Amin, SB Samur, MK Huang, N Wang, XJ Misra, V Ji, HB Gabuzda, D Li, C AF Yan, Zhenyu Shah, Parantu K. Amin, Samir B. Samur, Mehmet K. Huang, Norman Wang, Xujun Misra, Vikas Ji, Hongbin Gabuzda, Dana Li, Cheng TI Integrative analysis of gene and miRNA expression profiles with transcription factor-miRNA feed-forward loops identifies regulators in human cancers SO NUCLEIC ACIDS RESEARCH LA English DT Article ID MESSENGER-RNA TARGETS; LUNG-CANCER; HEPATOCELLULAR-CARCINOMA; MICRORNA; NETWORK; PROTEIN; MYC; PROGNOSIS; CIRCUITS; ONCOMIRS AB We describe here a novel method for integrating gene and miRNA expression profiles in cancer using feed-forward loops (FFLs) consisting of transcription factors (TFs), miRNAs and their common target genes. The dChip-GemiNI (Gene and miRNA Network-based Integration) method statistically ranks computationally predicted FFLs by their explanatory power to account for differential gene and miRNA expression between two biological conditions such as normal and cancer. GemiNI integrates not only gene and miRNA expression data but also computationally derived information about TF-target gene and miRNA-mRNA interactions. Literature validation shows that the integrated modeling of expression data and FFLs better identifies cancer-related TFs and miRNAs compared to existing approaches. We have utilized GemiNI for analyzing six data sets of solid cancers (liver, kidney, prostate, lung and germ cell) and found that top-ranked FFLs account for similar to 20% of transcriptome changes between normal and cancer. We have identified common FFL regulators across multiple cancer types, such as known FFLs consisting of MYC and miR-15/miR-17 families, and novel FFLs consisting of ARNT, CREB1 and their miRNA partners. The results and analysis web server are available at ext-link-type="uri" xlink:href="http://www.canevolve.org/dChip-GemiNi" xmlns:xlink="http://www.w3.org/1999/xlink">http://www.canevolve.org/dChip-GemiNi. C1 [Yan, Zhenyu; Shah, Parantu K.; Amin, Samir B.; Samur, Mehmet K.; Huang, Norman; Li, Cheng] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Yan, Zhenyu; Shah, Parantu K.; Amin, Samir B.; Samur, Mehmet K.; Huang, Norman; Li, Cheng] Harvard Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Samur, Mehmet K.] Akdeniz Univ, Dept Biostat & Med Informat, TR-07058 Antalya, Turkey. [Wang, Xujun] Tongji Univ, Dept Bioinformat, Shanghai 200092, Peoples R China. [Misra, Vikas; Gabuzda, Dana] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA. [Ji, Hongbin] Chinese Acad Sci, State Key Lab Cell Biol, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China. RP Li, C (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. EM cli@hsph.harvard.edu OI Amin, Samir/0000-0002-3207-9505 FU National Institutes of Health [R01 GM077122, DP1 DA28994]; Hundred Talents Program of the Chinese Academy of Sciences FX National Institutes of Health [R01 GM077122 to Z.Y., P.K.S. and C.L., DP1 DA28994 to D.G. and V.M.]; Dana Foundation (to Z.Y.). Claudia Adams Barr Program in Innovative Basic Cancer Research and the Multiple Myeloma Career Development award (to P.K.S.); Claudia Adams Barr Program in Innovative Basic Cancer Research (to D.G. and V.M.); H.J. is a scholar of the Hundred Talents Program of the Chinese Academy of Sciences. Funding for open access charge: NIH [R01 GM077122]. NR 49 TC 26 Z9 27 U1 1 U2 19 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD SEP PY 2012 VL 40 IS 17 AR e135 DI 10.1093/nar/gks395 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 015RS UT WOS:000309464300009 PM 22645320 ER PT J AU Carmel, L Koonin, EV Dracheva, S AF Carmel, Liran Koonin, Eugene V. Dracheva, Stella TI Dependencies among Editing Sites in Serotonin 2C Receptor mRNA SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID 5-HT2C RECEPTORS; CONSTITUTIVE ACTIVITY; HUMAN BRAIN; ADAR2; SUICIDE; GENE; IDENTIFICATION; TRANSCRIPTOME; PHARMACOLOGY; SELECTIVITY AB The serotonin 2C receptor (5-HT2CR)-a key regulator of diverse neurological processes-exhibits functional variability derived from editing of its pre-mRNA by site-specific adenosine deamination (A-to-I pre-mRNA editing) in five distinct sites. Here we describe a statistical technique that was developed for analysis of the dependencies among the editing states of the five sites. The statistical significance of the observed correlations was estimated by comparing editing patterns in multiple individuals. For both human and rat 5-HT2CR, the editing states of the physically proximal sites A and B were found to be strongly dependent. In contrast, the editing states of sites C and D, which are also physically close, seem not to be directly dependent but instead are linked through the dependencies on sites A and B, respectively. We observed pronounced differences between the editing patterns in humans and rats: in humans site A is the key determinant of the editing state of the other sites, whereas in rats this role belongs to site B. The structure of the dependencies among the editing sites is notably simpler in rats than it is in humans implying more complex regulation of 5-HT2CR editing and, by inference, function in the human brain. Thus, exhaustive statistical analysis of the 5-HT2CR editing patterns indicates that the editing state of sites A and B is the primary determinant of the editing states of the other three sites, and hence the overall editing pattern. Taken together, these findings allow us to propose a mechanistic model of concerted action of ADAR1 and ADAR2 in 5-HT2CR editing. Statistical approach developed here can be applied to other cases of interdependencies among modification sites in RNA and proteins. C1 [Carmel, Liran] Hebrew Univ Jerusalem, Dept Genet, Alexander Silberman Inst Life Sci, Fac Sci, IL-91904 Jerusalem, Israel. [Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [Dracheva, Stella] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. [Dracheva, Stella] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. RP Carmel, L (reprint author), Hebrew Univ Jerusalem, Dept Genet, Alexander Silberman Inst Life Sci, Fac Sci, J Safra Campus, IL-91904 Jerusalem, Israel. EM Stella.Dracheva@mssm.edu FU European Union Marie Curie International Reintegration Grant [PIRG05-GA-2009-248639]; Lohenstein August and Elza Foundation; Intramural Program of the US Department of Health and Human Services (National Library of Medicine, NIH); VA Merit award; NIMH grant [MH090352]; Hope for Depression Foundation grant; VISN3 Mental Illness Research and Education Clinical Center (MIRECC) FX LC was supported by the European Union Marie Curie International Reintegration Grant (PIRG05-GA-2009-248639), and by the Lohenstein August and Elza Foundation. EVK is supported by the Intramural Program of the US Department of Health and Human Services (National Library of Medicine, NIH). SD is supported by VA Merit award, NIMH MH090352 grant, the Hope for Depression Foundation grant, and by the VISN3 Mental Illness Research and Education Clinical Center (MIRECC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 43 TC 2 Z9 3 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7358 J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD SEP PY 2012 VL 8 IS 9 AR e1002663 DI 10.1371/journal.pcbi.1002663 PG 13 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 016IJ UT WOS:000309510900008 PM 22969417 ER PT J AU Cohen, SP Gallagher, RM Davis, SA Griffith, SR Carragee, EJ AF Cohen, Steven P. Gallagher, Rollin M. Davis, Shelton A. Griffith, Scott R. Carragee, Eugene J. TI Spine-area pain in military personnel: a review of epidemiology, etiology, diagnosis, and treatment SO SPINE JOURNAL LA English DT Review DE Back pain; Neck pain; Nonbattle injury; Soldier; War ID LOW-BACK-PAIN; EPIDURAL STEROID INJECTIONS; POSTTRAUMATIC-STRESS-DISORDER; OPERATION IRAQI FREEDOM; NECK PAIN; MUSCULOSKELETAL DISORDERS; SACROILIAC JOINT; RADIOFREQUENCY DENERVATION; WORKING POPULATION; ENDURING FREEDOM AB BACKGROUND CONTEXT: Nonbattle illnesses and injuries are the major causes of unit attrition in modern warfare. Spine-area pain is a common disabling injury in service members associated with a very low return-to-duty (RTD) rate. PURPOSE: To provide an overview of the current understanding of epidemiology, possible causes, and relative prognosis of spine-area pain syndromes in military personnel, including a discussion of various treatment options available in theaters of operation. STUDY DESIGN: Literature review. METHODS: Search focusing on epidemiology, etiology and associative factors, and treatment of spinal pain using electronic databases, textbooks, bibliographic references, and personal accounts. RESULTS: Spine-area pain is the most common injury or complaint "in garrison" and appears to increase during training and combat deployments. Approximately three-quarters involve low back pain, followed by cervical and midback pain syndromes. Some predictive factors associated with spine-area pain are similar to those observed in civilian cohorts, such as psychosocial distress, heavy physical activity, and more sedentary lifestyle. Risk factors specific to military personnel include concomitant psychological trauma, g-force exposure in pilots and airmen, extreme shock and vibration exposure, heavy combat load requirements, and falls incurred during airborne, air assault, and urban dismounted ground operations. Effective forward-deployed treatment has been difficult to implement, but newer strategies may improve RTD rates. CONCLUSIONS: Spine-area pain syndromes comprise a major source of unit attrition and are often the result of duty-related burdens incurred during combat operations. Current strategies in theaters of operation that may improve the low RTD rates include individual and unit level psychological support, early resumption of at least some forward-area duties, multimodal treatments, and ergonomic modifications. Published by Elsevier Inc. C1 [Cohen, Steven P.] Johns Hopkins Sch Med, Dept Anesthesiol & Crit Care Med, Pain Management Div, Baltimore, MD 21205 USA. [Cohen, Steven P.] Walter Reed Natl Mil Med Ctr, Dept Anesthesiol, Bethesda, MD 20889 USA. [Gallagher, Rollin M.] Philadelphia VA Med Ctr, Dept Psychiat, Philadelphia, PA 19104 USA. [Gallagher, Rollin M.] Philadelphia VA Med Ctr, Dept Anesthesiol, Philadelphia, PA 19104 USA. [Davis, Shelton A.] Walter Reed Natl Mil Med Ctr, Dept Orthoped Surg, Phys Med & Rehabil Serv, Bethesda, MD 20889 USA. [Griffith, Scott R.] Walter Reed Natl Mil Med Ctr, Dept Surg, Anesthesia Serv, Bethesda, MD 20889 USA. [Carragee, Eugene J.] Stanford Univ, Sch Med, Dept Orthoped Surg, Stanford, CA 94305 USA. RP Cohen, SP (reprint author), Johns Hopkins Sch Med, Dept Anesthesiol & Crit Care Med, Pain Management Div, 550 N Broadway,Suite 301, Baltimore, MD 21205 USA. EM scohen40@jhmi.edu FU NIH; OREF; AO Foundation; John P. Murtha Neuroscience and Pain Institute, Johnstown, PA, USA; Defense and Veterans Pain Management Initiative, Washington, DC, USA FX SPC: Nothing to disclose. RMG: Nothing to disclose. SAD: Nothing to disclose. SRG: Nothing to disclose. EJC: Stock Ownership: Intrinsic Spine (B), Bioassetts (B); Private Investments: Simpirica (D); Research Support (Investigator Salary): NIH (C, Paid directly to institution/employer); Trips/Travel: The Spine Journal (A); Other Office: NASS/The Spine Journal (E, Editor in Chief); Fellowship Support: OREF (E, Paid directly to institution/employer), AO Foundation (E, Paid directly to institution/employer).; Funded in part by a congressional grant from the John P. Murtha Neuroscience and Pain Institute, Johnstown, PA, USA, and the Defense and Veterans Pain Management Initiative, Washington, DC, USA. NR 83 TC 17 Z9 20 U1 1 U2 8 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 SEP PY 2012 VL 12 IS 9 SI SI BP 833 EP 842 DI 10.1016/j.spinee.2011.10.010 PG 10 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 016OF UT WOS:000309527900019 PM 22100208 ER PT J AU Cheng, TL Kotelchuck, M Guyer, B AF Cheng, Tina L. Kotelchuck, Milton Guyer, Bernard TI Preconception Women's Health and Pediatrics: An Opportunity to Address Infant Mortality and Family Health SO ACADEMIC PEDIATRICS LA English DT Editorial Material ID OF-THE-LITERATURE; UNINTENDED PREGNANCY; UNITED-STATES; CARE; OUTCOMES; FETAL; CHILD; RISK C1 [Cheng, Tina L.] Johns Hopkins Univ, Dept Pediat, Baltimore, MD 21287 USA. [Cheng, Tina L.; Guyer, Bernard] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Kotelchuck, Milton] MassGen Hosp Children, Boston, MA USA. RP Cheng, TL (reprint author), Johns Hopkins Univ, Dept Pediat, 200 N Wolfe St 2055, Baltimore, MD 21287 USA. EM tcheng2@jhmi.edu FU NICHD NIH HHS [K24 HD052559]; NIMHD NIH HHS [P20 MD000198, P20 MD000165] NR 34 TC 10 Z9 10 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1876-2859 EI 1876-2867 J9 ACAD PEDIATR JI Acad. Pediatr. PD SEP-OCT PY 2012 VL 12 IS 5 BP 357 EP 359 PG 3 WC Pediatrics SC Pediatrics GA 013KV UT WOS:000309305200001 PM 22658953 ER PT J AU Boudreau, ADA Van Cleave, JM Gnanasekaran, SK Kurowski, DS Kuhlthau, KA AF Boudreau, Alexy D. Arauz Van Cleave, Jeanne M. Gnanasekaran, Sangeeth K. Kurowski, Daniel S. Kuhlthau, Karen A. TI The Medical Home: Relationships With Family Functioning for Children With and Without Special Health Care Needs SO ACADEMIC PEDIATRICS LA English DT Article DE children; family impact; health care delivery; medical home; quality of care ID ASSOCIATION; ALLIANCE; ILLNESS; STRESS; ACCESS; IMPACT AB OBJECTIVE: In this study we tested the association of the medical home with family functioning for children without and with special health care needs (CSHCN). METHODS: We used data from the 2007 National Survey of Children's Health to run multivariate logistic regressions to test the association between having a medical home and family functioning (difficulty with parental coping, parental aggravation, childcare/work issues, and missed school days). We further assessed interactions of CSHCN status with having a medical home. RESULTS: In adjusted analysis, parents of children with a medical home were less likely to report difficulty with parental coping (odds ratio [OR] 0.26 [0.19-0.36]), parental aggravation (OR 0.54 [0.45-0.65]), childcare/work issues (OR 0.72 [0.61-0.841), and missed school days (OR 0.87[0.78-0.97]) for their children than those without a medical home. Using interaction terms, we found that for most outcomes, the medical home had a greater association for CSHCN compared with healthy peers, with odds ratios ranging 0.40 (CI 0.22-0.56) for parental aggravation to 0.67 (CI0.52-0.86) for missed school days. CONCLUSIONS: We show that the medical home is associated with better family functioning. All children may benefit from receiving care in a medical home, but CSHCN, who have greater needs, may particularly benefit from this enhanced model of care. C1 [Boudreau, Alexy D. Arauz; Van Cleave, Jeanne M.; Kuhlthau, Karen A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Child & Adolescent Hlth Policy,MassGen Hosp C, Boston, MA 02114 USA. [Kurowski, Daniel S.] Ctr Home Care Policy & Res, New York, NY USA. [Gnanasekaran, Sangeeth K.] Harvard Univ, Sch Med, Cambridge Hlth Alliance, Boston, MA 02114 USA. RP Boudreau, ADA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Child & Adolescent Hlth Policy,MassGen Hosp C, 100 Cambridge St,15th Floor, Boston, MA 02114 USA. EM aarauz@partners.org FU Massachusetts General Hospital Multicultural Affairs Career Development Award FX This work was supported by the Massachusetts General Hospital Multicultural Affairs Career Development Award awarded to Dr. Arauz Boudreau, MD, MPH. NR 36 TC 5 Z9 5 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 SEP-OCT PY 2012 VL 12 IS 5 BP 391 EP 398 PG 8 WC Pediatrics SC Pediatrics GA 013KV UT WOS:000309305200009 ER PT J AU Sheldrick, RC Henson, BS Merchant, S Neger, EN Murphy, JM Perrin, EC AF Sheldrick, R. Christopher Henson, Brandi S. Merchant, Shela Neger, Emily N. Murphy, J. Michael Perrin, Ellen C. TI The Preschool Pediatric Symptom Checklist (PPSC): Development and Initial Validation of a New Social/Emotional Screening Instrument SO ACADEMIC PEDIATRICS LA English DT Article DE behavioral; child behavior; emotional; pediatrics; questionnaire; screening; social; social behavior ID PRIMARY-CARE; PSYCHOSOCIAL DYSFUNCTION; HEALTH-ASSESSMENT; CHILDREN; DISORDERS; VALIDITY; FEASIBILITY; POPULATION; PREVALENCE; SETTINGS AB OBJECTIVE: This article describes the development and initial validation of the Preschool Pediatric Symptom Checklist (PPSC), a social/emotional screening instrument for children 18 to 60 months of age. The PPSC was created as part of a comprehensive screening instrument designed for pediatric primary care and is modeled after the Pediatric Symptom Checklist. METHOD: Items for the PPSC were developed by a team of experts who reviewed existing assessment instruments and relevant research literature. Scale construction and initial validation (including factor analysis and tests of construct validity) were conducted with 292 families from pediatric primary care sites and 354 families from referral clinics. One hundred seventy-one additional families were recruited from primary care sites to obtain an independent replication sample. RESULTS: Exploratory factor analysis revealed 4 dimensions of the PPSC: Externalizing, Internalizing, Attention Problems, and Parenting Challenges. These dimensions were incorporated into a bifactor model that displayed a strong general factor, thus supporting the use of a total score. The PPSC total score shows strong internal and retest reliability, and it identifies children who score in the clinical range of a longer, well-validated, and more comprehensive parent-report instrument (the Child Behavior Checklist), as well as children who are reported to have a range of behavioral diagnoses. Moreover, sensitivity and specificity with respect to these criteria were comparable to those of another well-accepted but longer screener, the Ages & Stages Questionnaire: Social/Emotional. Finally, results for the PPSC total scale remained consistent when replicated in an independent sample. CONCLUSION: The PPSC shows promise as a social/emotional screening instrument for use in pediatric primary care. C1 [Sheldrick, R. Christopher; Henson, Brandi S.; Merchant, Shela; Neger, Emily N.; Perrin, Ellen C.] Floating Hosp Children, Tufts Med Ctr, Div Dev Behav Pediat, Boston, MA 02111 USA. [Murphy, J. Michael] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Sheldrick, RC (reprint author), Floating Hosp Children, Tufts Med Ctr, Div Dev Behav Pediat, 800 Washington St,Box 854, Boston, MA 02111 USA. EM rsheldrick@tuftsmedicalcenter.org FU Commonwealth Fund; National Institutes of Health grant [KM1CA156726] FX We are indebted to The Commonwealth Fund for its support of the larger project of which this is a part. In particular, Dr Ed Schor's vision and imagination motivated us to create a practical instrument to guide surveillance in pediatric primary care settings. Dr Michael Jellinek had the foresight long ago to create a tool to help pediatricians identify children who had unmet needs for mental health attention. We are grateful also for the assistance of Dr Robin Adair, Dr Liz McGowan, and a large number of pediatricians and other child health specialists,* who allowed us to enroll parents through their offices, to Kate Mattern and Robyn Della Giustina for help with data collection and management, and to the Tufts Medical Center CTSI for ongoing support. We acknowledge as well the wise suggestions of anonymous reviewers of an earlier version of this article.; Research support for the development and validation of the Preschool Pediatric Symptom Checklist was provided by The Commonwealth Fund & National Institutes of Health grant KM1CA156726. NR 42 TC 11 Z9 11 U1 5 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1876-2859 EI 1876-2867 J9 ACAD PEDIATR JI Acad. Pediatr. PD SEP-OCT PY 2012 VL 12 IS 5 BP 456 EP 467 PG 12 WC Pediatrics SC Pediatrics GA 013KV UT WOS:000309305200017 PM 22921494 ER PT J AU Lei, HT Rheaume, MA Cui, J Mukai, S Maberley, D Samad, A Matsubara, J Kazlauskas, A AF Lei, Hetian Rheaume, Marc-Andre Cui, Jing Mukai, Shizuo Maberley, David Samad, Arif Matsubara, Joanne Kazlauskas, Andrius TI A Novel Function of p53 A Gatekeeper of Retinal Detachment SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID EXPERIMENTAL PROLIFERATIVE VITREORETINOPATHY; MASSIVE PERIRETINAL PROLIFERATION; COLLAGEN GEL CONTRACTION; CLINICAL RISK-FACTORS; PROTEIN 2 EMP2; EPIRETINAL MEMBRANES; EXPERIMENTAL-MODEL; GROWTH-FACTORS; MDM2; CELLS AB Proliferative vitreoretinopathy (PVR) is a blinding disease associated with rhegmatogenous retinal detachment, for which there is no satisfactory treatment. Surgery helps in many cases, but, to our knowledge, there are no pharmacological approaches to reduce PVR risk. We report that suppressing expression of p53 was a required event in two assays of PVR (namely, platelet-derived growth factor receptor a mediated contraction of cells in a collagen gel and retinal detachment in an animal model of PVR). Furthermore, preventing the decline in the level of p53 with agents such as Nutlin-3 protected from retinal detachment, which is the most vision-compromising component of PVR. Finally, Nutlin-3 may be effective in the clinical setting because it prevented human PVR vitreous-induced contraction of cells isolated from a patient PVR membrane. These studies identify Nutlin-3 as a potential PVR prophylaxis. (Am J Pathol 2012, 181:866-874; http://dx.doi.org/10.1016/j.ajpath.2012.05.036) C1 [Kazlauskas, Andrius] Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. [Lei, Hetian; Rheaume, Marc-Andre; Mukai, Shizuo; Kazlauskas, Andrius] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. [Lei, Hetian; Rheaume, Marc-Andre; Mukai, Shizuo; Kazlauskas, Andrius] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. [Cui, Jing; Maberley, David; Matsubara, Joanne] Univ British Columbia, Dept Ophthalmol & Visual Sci, Vancouver, BC V5Z 1M9, Canada. [Samad, Arif] Dalhousie Univ, Dept Opthalmol & Visual Sci, Halifax, NS, Canada. RP Kazlauskas, A (reprint author), Harvard Univ, Sch Med, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM andrius_kazlauskas@meei.harvard.edu FU NIH [EY012509]; Canadian Institutes of Health Research [IAO 77736, MOP 97806] FX Supported by a grant from the NIH (EY012509 to A.K.) and the Canadian Institutes of Health Research grants IAO 77736 and MOP 97806 (J.M. and J.C.). NR 61 TC 11 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD SEP PY 2012 VL 181 IS 3 BP 866 EP 874 DI 10.1016/j.ajpath.2012.05.036 PG 9 WC Pathology SC Pathology GA 012QH UT WOS:000309251100015 PM 22901751 ER PT J AU Paintlia, AS Paintlia, MK Hollis, BW Singh, AK Singh, I AF Paintlia, Ajaib S. Paintlia, Manjeet K. Hollis, Bruce W. Singh, Avtar K. Singh, Inderjit TI Interference with RhoA-ROCK Signaling Mechanism in Autoreactive CD4(+) T Cells Enhances the Bioavailability of 1,25-Dihydroxyvitamin D-3 in Experimental Autoimmune Encephalomyelitis SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID REMITTING MULTIPLE-SCLEROSIS; VITAMIN-D-RECEPTOR; COA REDUCTASE INHIBITOR; ADD-ON THERAPY; COMBINATION THERAPY; SUPPRESSES SEVERITY; SEASONAL-VARIATION; GENE POLYMORPHISM; HEALTHY-SUBJECTS; CONTROLLED-TRIAL AB Vitamin D deficiency is a major risk factor for central nervous system (CNS) demyelinating diseases including multiple sclerosis (MS) and its animal model, that of experimental autoimmune encephalomyelitis (EAE). Both vitamin D-3 and 1, 25-dihydroxyviatmin-D-3 (calcitriol) had beneficial effects in EAE/MS. However, the exact cause of vitamin D deficiency in EAE/MS is not clear. Previously, we documented that lovastatin (LOV) provides protection in EAE animals via inhibition of RhoA-ROCK signaling. Herein, we demonstrate that LOV prevents the lowering of circulating 25-hydroxyvitamin-D-3 and 1,25-dihydroxyviatmin-D-3 levels including 1,25-dihydroxyviatmin-D-3 levels in the peripheral lymphoid organs and CNS of treated EAE animals. These effects of LOV were attributed to enhanced expression of vitamin D synthesizing enzyme (la-hydroxylase) in kidney and the CNS, with corresponding reduction of vitamin D catabolizing enzyme (24-hydorxylase) expression in the CNS of EAE animals via inhibition of RhoA-ROCK signaling. Ex vivo and in vitro studies established that autoreactive Th1/Th17 cells had higher expression of 24-hydroxylase than Th2/T regulatory cells, that was reverted by LOV or ROCK inhibitor. Interestingly, LOV-mediated regulation of vitamin D metabolism had improved vitamin D-3 efficacy to confer protection in EAE animals and that was ascribed to the LOV- and calcitriol-induced immunomodulatory synergy. Together, these data provide evidence that interfering with RhoA-ROCK signaling in autoreactive Th1/Th17 cells can improve vitamin D-3 efficacy in clinical trials of MS and related neurodegenerative disorders. (Am J Pathol 2012,181:993-1006 http://dx.doi.org/10.1016/j.ajpath.2012.05.028) C1 [Paintlia, Ajaib S.; Paintlia, Manjeet K.; Hollis, Bruce W.; Singh, Inderjit] Med Univ S Carolina, Dept Pediat, Darby Childrens Res Inst, Charleston, SC 29425 USA. [Singh, Avtar K.] Ralph H Johnson VA Med Ctr, Dept Pathol & Lab Med, Charleston, SC USA. RP Singh, I (reprint author), Med Univ S Carolina, Dept Pediat, Darby Childrens Res Inst, 173 Ashley Ave, Charleston, SC 29425 USA. EM singhi@musc.edu OI Paintlia, Ajaib/0000-0003-4525-5333 FU NIH [NS-22576, NS-37766, 1BX001072, C06-RR015455, C06-RR018823] FX Supported by grants from the NIH (NS-22576, NS-37766, 1BX001072, C06-RR015455, and C06-RR018823). NR 64 TC 6 Z9 6 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD SEP PY 2012 VL 181 IS 3 BP 993 EP 1006 DI 10.1016/j.ajpath.2012.05.028 PG 14 WC Pathology SC Pathology GA 012QH UT WOS:000309251100027 PM 22796435 ER PT J AU Wang, C Parmigiani, G Dominici, F AF Wang, Chi Parmigiani, Giovanni Dominici, Francesca TI Bayesian Effect Estimation Accounting for Adjustment Uncertainty SO BIOMETRICS LA English DT Article DE Adjustment uncertainty; Bayesian model averaging; Exposure effects; Treatment effects ID AIR-POLLUTION; VARIABLE SELECTION; PROPENSITY SCORE; MODEL SELECTION; TIME-SERIES; MORTALITY; CONFOUNDERS AB Model-based estimation of the effect of an exposure on an outcome is generally sensitive to the choice of which confounding factors are included in the model. We propose a new approach, which we call Bayesian adjustment for confounding (BAC), to estimate the effect of an exposure of interest on the outcome, while accounting for the uncertainty in the choice of confounders. Our approach is based on specifying two models: (1) the outcome as a function of the exposure and the potential confounders (the outcome model); and (2) the exposure as a function of the potential confounders (the exposure model). We consider Bayesian variable selection on both models and link the two by introducing a dependence parameter, ?, denoting the prior odds of including a predictor in the outcome model, given that the same predictor is in the exposure model. In the absence of dependence (?= 1), BAC reduces to traditional Bayesian model averaging (BMA). In simulation studies, we show that BAC, with ? > 1, estimates the exposure effect with smaller bias than traditional BMA, and improved coverage. We, then, compare BAC, a recent approach of Crainiceanu, Dominici, and Parmigiani (2008, Biometrika 95, 635651), and traditional BMA in a time series data set of hospital admissions, air pollution levels, and weather variables in Nassau, NY for the period 19992005. Using each approach, we estimate the short-term effects of on emergency admissions for cardiovascular diseases, accounting for confounding. This application illustrates the potentially significant pitfalls of misusing variable selection methods in the context of adjustment uncertainty. C1 [Wang, Chi] Univ Kentucky, Markey Canc Ctr, Lexington, KY 40536 USA. [Wang, Chi] Univ Kentucky, Dept Biostatist, Coll Publ Hlth, Lexington, KY 40536 USA. [Parmigiani, Giovanni] Dana Farber Canc Inst, Dept Biostatist & Computat Biol, Boston, MA 02115 USA. [Parmigiani, Giovanni; Dominici, Francesca] Harvard Sch Publ Hlth, Dept Biostatist, Boston, MA 02115 USA. RP Wang, C (reprint author), Univ Kentucky, Markey Canc Ctr, Lexington, KY 40536 USA. EM chi.wang@uky.edu NR 30 TC 28 Z9 28 U1 0 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0006-341X EI 1541-0420 J9 BIOMETRICS JI Biometrics PD SEP PY 2012 VL 68 IS 3 BP 661 EP 671 DI 10.1111/j.1541-0420.2011.01731.x PG 11 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 011RW UT WOS:000309183600001 PM 22364439 ER PT J AU Wang, C Parmigiani, G Dominici, F AF Wang, Chi Parmigiani, Giovanni Dominici, Francesca TI Rejoinder: Bayesian Effect Estimation Accounting for Adjustment Uncertainty SO BIOMETRICS LA English DT Editorial Material ID PROPENSITY SCORE; CAUSAL INFERENCE C1 [Wang, Chi] Univ Kentucky, Markey Canc Ctr, Lexington, KY 40536 USA. [Wang, Chi] Univ Kentucky, Dept Biostatist, Coll Publ Hlth, Lexington, KY 40536 USA. [Parmigiani, Giovanni] Dana Farber Canc Inst, Dept Biostatist & Computat Biol, Boston, MA 02115 USA. [Parmigiani, Giovanni; Dominici, Francesca] Harvard Sch Publ Hlth, Dept Biostatist, Boston, MA 02115 USA. RP Wang, C (reprint author), Univ Kentucky, Markey Canc Ctr, Lexington, KY 40536 USA. EM chi.wang@uky.edu NR 16 TC 3 Z9 3 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 2012 VL 68 IS 3 BP 680 EP 686 DI 10.1111/j.1541-0420.2011.01735.x PG 7 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 011RW UT WOS:000309183600005 ER PT J AU Cronin, CG Scott, J Kambadakone, A Catalano, OA Sahani, D Blake, MA McDermott, S AF Cronin, C. G. Scott, J. Kambadakone, A. Catalano, O. A. Sahani, D. Blake, M. A. McDermott, S. TI Utility of positron emission tomography/CT in the evaluation of small bowel pathology SO BRITISH JOURNAL OF RADIOLOGY LA English DT Review ID GASTROINTESTINAL STROMAL TUMORS; T-CELL LYMPHOMA; ORAL CONTRAST; FDG-PET/CT; SMALL-INTESTINE; CROHNS-DISEASE; NONINVASIVE ASSESSMENT; IMATINIB MESYLATE; F-18-FDG PET; CT AB We describe the management principles and different roles of positron emission tomography (PET)/CT in the evaluation of patients with small bowel tumours (adenocarcinoma, gastrointestinal stromal tumour, lymphoma, metastases) from initial staging, monitoring response to treatment, to detection of recurrent disease. We also discuss the various non-malignant aetiologies of small bowel fludeoxyglucose (FDG) PET uptake, and other pitfalls in FDG PET/CT interpretation. Awareness of the imaging appearances of small bowel tumours, patterns of disease spread and potential PET/CT interpretation pitfalls are of paramount importance to optimise diagnostic accuracy. C1 [Cronin, C. G.; Scott, J.; Kambadakone, A.; Catalano, O. A.; Sahani, D.; Blake, M. A.; McDermott, S.] Massachusetts Gen Hosp, Dept Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. [Catalano, O. A.] SDN IRCCS, Dept Radiol, Naples, Italy. RP Cronin, CG (reprint author), Mater Misericordiae Univ Hosp, Eccles St, Dublin 7, Ireland. EM cgcronin@partners.org NR 47 TC 10 Z9 11 U1 0 U2 4 PU BRITISH INST RADIOLOGY PI LONDON PA 36 PORTLAND PLACE, LONDON W1N 4AT, ENGLAND SN 0007-1285 J9 BRIT J RADIOL JI Br. J. Radiol. PD SEP PY 2012 VL 85 IS 1017 BP 1211 EP 1221 DI 10.1259/bjr/64534573 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 009US UT WOS:000309051300036 PM 22919004 ER PT J AU Seshasai, RK Katz, R de Boer, IH Siscovick, D Shlipak, MG Rifkin, DE Sarnak, MJ AF Seshasai, Rebecca Kurnik Katz, Ronit de Boer, Ian H. Siscovick, David Shlipak, Michael G. Rifkin, Dena E. Sarnak, Mark J. TI Apolipoprotein E and kidney function in older adults SO CLINICAL NEPHROLOGY LA English DT Article DE apolipoprotein E; chronic kidney disease; kidney function; elderly ID GLOMERULAR-FILTRATION-RATE; SERUM CYSTATIN-C; RENAL-DISEASE; RISK; POLYMORPHISM; NEPHROPATHY; ASSOCIATION; PROGRESSION; CREATININE; DECLINE AB Background: Previous studies suggest that the epsilon 4 and epsilon 2 alleles of apolipoprotein E (APOE) may be associated with decreased and increased risks of CKD, respectively, but there are limited data in older adults. We evaluated the associations of apolipoprotein E alleles with kidney function among older adults in the cardiovascular health study (CHS). Methods: Caucasian participants had APOE allelic analysis and serum creatinine and cystatin C measured at baseline (n = 3,844 for cross sectional analysis) and in follow up (n = 3,226 for longitudinal analysis). APOE variation was evaluated as an additive model with number of epsilon 2, epsilon 3 and epsilon 4 alleles. GFR was estimated using the CKD epidemiology equation (eGFRcreat) and the cystatin C demographic equation (eGFRcys). The primary outcome was CKD defined by eGFR < 60 ml/min/1.73 m(2). The secondary outcome was rapid progression defined by annual loss of eGFR > 3 ml/min/1.73 m(2). Results: Mean eGFRcreat was 72 ml/min/1.73 m(2) (25% CKD). Compared with the epsilon 3 allele, the APOE epsilon 4 allele was associated with reduced risk of CKD by eGFRcreat: unadjusted odds ratio (OR) and 95% confidence interval (CI) 0.79 (0.67-0.93) per allele, fully adjusted OR (95% CI) 0.80 (0.68-0.96) per allele. Results were consistent using eGFRcys. There was no association of the epsilon 2 allele with CKD or between the apolipoprotein E gene with rapid progression. Conclusions: The apolipoprotein epsilon 4 allele was associated with lower odds of CKD in elderly Caucasian individuals. Future research should confirm these findings in other races and explore mechanisms to explain these results. C1 [Seshasai, Rebecca Kurnik; Sarnak, Mark J.] Tufts Med Ctr, Div Nephrol, Dept Med, Boston, MA 02111 USA. [Katz, Ronit] Univ Washington, Collaborat Hlth Studies Coordinating Ctr, Seattle, WA 98195 USA. [de Boer, Ian H.] Univ Washington, Dept Med, Div Nephrol, Seattle, WA 98195 USA. [Siscovick, David] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Shlipak, Michael G.] Univ Calif San Francisco, Gen Internal Med Sect, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Rifkin, Dena E.] Univ Calif San Diego, Dept Med, Div Nephrol, San Diego, CA 92103 USA. RP Sarnak, MJ (reprint author), Tufts Med Ctr, Div Nephrol, Dept Med, Box 391,800 Washington St, Boston, MA 02111 USA. EM msarnak@tuftsmedicalcenter.org FU National Heart, Lung, and Blood Institute [HL080295, HL-075366]; National Institute on Aging [AG-023269, AG-15928, AG-20098, AG-027058]; University of Pittsburgh Claude D. Pepper Older Americans Independence Center [P30-AG-024827]; [R01-AG-027002]; [K24DK078204]; [N01-HC-85239]; [N01-HC-85079]; [N01-HC-85086]; [N01-HC-35129]; [N01 HC-15103]; [N01 HC-55222]; [N01-HC-75150]; [N01-HC-45133] FX The research reported in this article was supported by grants R01-AG-027002, K24DK078204 and contract numbers N01-HC-85239, N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, grant number HL080295 from the National Heart, Lung, and Blood Institute and grant number AG-023269 from the National Institute on Aging, with additional contribution from the National Institute of Neurological Disorders and Stroke. Additional support was provided through AG-15928, AG-20098, and AG-027058 from the National Institute on Aging, HL-075366 from the National Heart, Lung and Blood Institute, and the University of Pittsburgh Claude D. Pepper Older Americans Independence Center P30-AG-024827. A full list of principal CHS investigators and institutions can be found at http://www.chs-nhlbi.org/pi.htm. Dr. Katz had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. An abstract representing this work was presented at the American Society of Nephrology Annual Meeting in Denver, Colorado in 2010. NR 25 TC 6 Z9 6 U1 0 U2 0 PU DUSTRI-VERLAG DR KARL FEISTLE PI DEISENHOFEN-MUENCHEN PA BAHNHOFSTRASSE 9 POSTFACH 49, D-82032 DEISENHOFEN-MUENCHEN, GERMANY SN 0301-0430 J9 CLIN NEPHROL JI Clin. Nephrol. PD SEP PY 2012 VL 78 IS 3 BP 174 EP 180 DI 10.5414/CN107427 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 014MC UT WOS:000309378900002 PM 22874105 ER PT J AU Scherz, A Hasan, T AF Scherz, Avigdor Hasan, Tayyaba TI Light-Activated Pharmaceuticals in Therapy and Diagnosis SO ISRAEL JOURNAL OF CHEMISTRY LA English DT Editorial Material C1 [Scherz, Avigdor] Weizmann Inst Sci, IL-76100 Rehovot, Israel. [Hasan, Tayyaba] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Scherz, A (reprint author), Weizmann Inst Sci, IL-76100 Rehovot, Israel. NR 0 TC 0 Z9 0 U1 1 U2 3 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 0021-2148 J9 ISR J CHEM JI Isr. J. Chem. PD SEP PY 2012 VL 52 IS 8-9 SI SI BP 671 EP 672 DI 10.1002/ijch.201210002 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 010BH UT WOS:000309068900002 ER PT J AU Sharma, SK Mroz, P Dai, TH Huang, YY St Denis, TG Hamblin, MR AF Sharma, Sulbha K. Mroz, Pawel Dai, Tianhong Huang, Ying-Ying St Denis, Tyler G. Hamblin, Michael R. TI Photodynamic Therapy for Cancer and for Infections: What Is the Difference? SO ISRAEL JOURNAL OF CHEMISTRY LA English DT Review DE antitumor agents; antimicrobial agents; cancer; photodynamic therapy; sensitizers ID GRAM-NEGATIVE BACTERIA; SELECTIVE ANTIMICROBIAL PHOTOSENSITIZERS; ENDOPLASMIC-RETICULUM STRESS; LIPOPROTEIN RECEPTOR PATHWAY; CHLORIN-TYPE PHOTOSENSITIZER; SINGLET OXYGEN; ACNE-VULGARIS; IN-VITRO; CUTANEOUS LEISHMANIASIS; ANTITUMOR IMMUNITY AB Photodynamic therapy (PDT) was discovered over one hundred years ago when it was observed that certain dyes could kill microorganisms when exposed to light in the presence of oxygen. Since those early days, PDT has mainly been developed as a cancer therapy and as a way to destroy proliferating blood vessels. However, recently it has become apparent that PDT may also be used as an effective antimicrobial modality and a potential treatment for localized infections. This review discusses the similarities and differences between the application of PDT for the treatment of microbial infections and for cancer lesions. Type I and type II photodynamic processes are described, and the structure-function relationships of optimal anticancer and antimicrobial photosensitizers are outlined. The different targeting strategies, intracellular photosensitizer localization, and pharmacokinetic properties of photosensitizers required for these two different PDT applications are compared and contrasted. Finally, the ability of PDT to stimulate an adaptive or innate immune response against pathogens and tumors is also covered. C1 [Sharma, Sulbha K.; Mroz, Pawel; Dai, Tianhong; Huang, Ying-Ying; St Denis, Tyler G.; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Mroz, Pawel; Dai, Tianhong; Huang, Ying-Ying; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Huang, Ying-Ying] Guangxi Med Univ, Aesthet & Plast Ctr, Nanning, Peoples R China. [St Denis, Tyler G.] Columbia Univ, New York, NY USA. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Sharma, SK (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 US NIH [R01AI050875]; US Air Force Medical Free Electron Laser Program [FA9550-04-1-0079]; Genzyme-Partners Translational Research Grant; NIH Dermatology training grant; Bullock Wellman Postdoctoral Fellowship; Airlift Research Foundation [109421]; Columbia University FX Research in the Hamblin laboratory is supported by US NIH grant R01AI050875 to M. R. H. and by the US Air Force Medical Free Electron Laser Program (FA9550-04-1-0079). P. M. was partly supported by a Genzyme-Partners Translational Research Grant and NIH Dermatology training grant. T. D. was supported by the Bullock Wellman Postdoctoral Fellowship and an Airlift Research Foundation grant (#109421). T. G. St. D. was supported by the Columbia University I. I. Rabi Fellows Program. NR 142 TC 21 Z9 21 U1 4 U2 46 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 0021-2148 J9 ISR J CHEM JI Isr. J. Chem. PD SEP PY 2012 VL 52 IS 8-9 SI SI BP 691 EP 705 DI 10.1002/ijch.201100062 PG 15 WC Chemistry, Multidisciplinary SC Chemistry GA 010BH UT WOS:000309068900005 PM 23248387 ER PT J AU Jung, Y Nichols, AJ Klein, OJ Roussakis, E Evans, CL AF Jung, Yookyung Nichols, Alexander J. Klein, Oliver J. Roussakis, Emmanuel Evans, Conor L. TI Label-Free, Longitudinal Visualization of PDT Response In Vitro with Optical Coherence Tomography SO ISRAEL JOURNAL OF CHEMISTRY LA English DT Review DE antitumor agents; cancer; optical coherence tomography; photodynamic therapy; sensitizers ID RAMAN-SCATTERING MICROSCOPY; ENDOTHELIAL GROWTH-FACTOR; BREAST EPITHELIAL-CELLS; PHOTODYNAMIC THERAPY; OVARIAN-CANCER; MACULAR DEGENERATION; LIGHT-SCATTERING; ENDOPLASMIC-RETICULUM; SPECTRAL INTERFEROMETRY; LYSOSOMAL PHOTODAMAGE AB A major challenge in creating and optimizing therapeutics in the fight against cancer is visualizing and understanding the microscale spatiotemporal treatment response dynamics that occur in patients. This is especially true for photodynamic therapy (PDT), where therapeutic optimization relies on understanding the interplay between factors such as photosensitizer localization and uptake, in addition to light dose and delivery rate. In vitro 3D culture systems that recapitulate many of the biological features of human disease are powerful platforms for carrying out detailed studies on PDT response and resistance. Current techniques for visualizing these models, however, often lack accuracy due to the perturbative nature of the sample preparation, with light attenuation complicating the study of intact models. Optical coherence tomography (OCT) is an ideal method for the long-term, non-perturbative study of in vitro models and their response to PDT. Monitoring the response of 3D models to PDT by time-lapse OCT methods promises to provide new perspectives and open the way to cancer treatment methodologies that can be translated towards the clinic. C1 [Nichols, Alexander J.; Evans, Conor L.] Harvard Univ, Program Biophys, Cambridge, MA 02138 USA. [Nichols, Alexander J.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Jung, Yookyung; Nichols, Alexander J.; Klein, Oliver J.; Roussakis, Emmanuel; Evans, Conor L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. RP Evans, CL (reprint author), BAR410,40 Blossom St, Boston, MA 02214 USA. EM evans.conor@mgh.harvard.edu FU National Science Foundation (NSF) Graduate Fellowship; National Defense and Science Engineering Graduate (NDSEG) Fellowship; National Institutes of Health through the NIH Director's New Innovator Award Program [1DP2 OD007096-01] FX The authors would like to thank Professor Tayyaba Hasan, Dr. Imran Rizvi, and Professor Jon Celli for their guidance and assistance in the collection of some of the data presented in this review. The authors would also like to acknowledge Nicole Devoe and Sam Patterson for their help editing this manuscript. AJN wishes to acknowledge the National Science Foundation (NSF) Graduate Fellowship and National Defense and Science Engineering Graduate (NDSEG) Fellowship for their support. This work was partially funded by the National Institutes of Health through the NIH Director's New Innovator Award Program, grant number 1DP2 OD007096-01. Information on the New Innovator Award Program is available at http://nihroadmap.nih.gov/newinnovator/. NR 157 TC 11 Z9 11 U1 1 U2 11 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA POSTFACH 101161, 69451 WEINHEIM, GERMANY SN 0021-2148 EI 1869-5868 J9 ISR J CHEM JI Isr. J. Chem. PD SEP PY 2012 VL 52 IS 8-9 SI SI BP 728 EP 744 DI 10.1002/ijch.201200009 PG 17 WC Chemistry, Multidisciplinary SC Chemistry GA 010BH UT WOS:000309068900008 PM 23316088 ER PT J AU Maytin, EV Honari, G Khachemoune, A Taylor, CR Ortel, B Pogue, BW Sznycer-Taub, N Hasan, T AF Maytin, Edward V. Honari, Golara Khachemoune, Amor Taylor, Charles R. Ortel, Bernhard Pogue, Brian W. Sznycer-Taub, Nathaniel Hasan, Tayyaba TI The Vitamin D Analog Calcipotriol Combined with Aminolevulinate-Mediated Photodynamic Therapy for Human Psoriasis: A Proof-of-Principle Study SO ISRAEL JOURNAL OF CHEMISTRY LA English DT Article DE antitumor agents; fluorescence; photochemistry; prodrugs; vitamins ID PROTOPORPHYRIN-IX ACCUMULATION; NONMELANOMA SKIN-CANCER; 5-AMINOLEVULINIC ACID; PLAQUE PSORIASIS; EPIDERMAL DIFFERENTIATION; HUMAN KERATINOCYTES; ACTINIC KERATOSES; CARCINOMA-CELLS; IN-VITRO; FLUORESCENCE AB We previously showed that select agents (methotrexate or vitamin D), when administered as a preconditioning regimen, are capable of promoting cellular differentiation of epithelial cancer cells while simultaneously enhancing the efficacy of 5-aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT). In solid tumors, pretreatment with vitamin D simultaneously promotes cellular differentiation and leads to selective accumulation of target porphyrins (mainly protoporphyrin IX, PpIX) within diseased tissue. However, questions of whether or not the effects upon cellular differentiation are inexorably linked to PpIX accumulation, and whether these effects might occur in hyperproliferative noncancerous tissues, have remained unanswered. In this paper, we reasoned that psoriasis, a human skin disease in which abnormal cellular proliferation and differentiation play a major role, could serve as a useful model to test the effects of prodifferentiating agents upon PpIX levels in a nonneoplastic setting. In particular, vitamin D, a treatment for psoriasis that restores (i.e., increases) differentiation, might increase PpIX levels in psoriatic lesions and facilitate their responsiveness to ALA-PDT. This concept was tested in a pilot study of seven patients with bilaterally matched psoriatic plaques. A regimen in which calcipotriol 0.005?% ointment was applied for six days prior to ALA-PDT using blue light led to preferential increases in PpIX (ca. 50?%), and reductions in thickness, redness, scaling, and itching in the pretreated plaques. The results suggest that a larger clinical trial is warranted to confirm a role for combination treatments with vitamin D and ALA-PDT for psoriasis. C1 [Maytin, Edward V.] Cleveland Clin, Lerner Res Inst, Cleveland, OH 44195 USA. [Maytin, Edward V.; Honari, Golara] Cleveland Clin, Dept Dermatol, Cleveland, OH 44195 USA. [Pogue, Brian W.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. [Ortel, Bernhard] Univ Chicago, Dept Dermatol, Chicago, IL 60637 USA. [Maytin, Edward V.; Khachemoune, Amor; Taylor, Charles R.; Sznycer-Taub, Nathaniel; Hasan, Tayyaba] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Maytin, EV (reprint author), Cleveland Clin, Lerner Res Inst, ND 20,9500 Euclid Ave, Cleveland, OH 44195 USA. EM maytine@ccf.org FU National Institutes of Health [P01-CA084203] FX This study was funded by National Institutes of Health grant P01-CA084203 (T. Hasan). NR 53 TC 10 Z9 11 U1 0 U2 13 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 0021-2148 J9 ISR J CHEM JI Isr. J. Chem. PD SEP PY 2012 VL 52 IS 8-9 SI SI BP 767 EP 775 DI 10.1002/ijch.201200005 PG 9 WC Chemistry, Multidisciplinary SC Chemistry GA 010BH UT WOS:000309068900011 PM 23264699 ER PT J AU Rizvi, I Dinh, TA Yu, WP Chang, YC Sherwood, ME Hasan, T AF Rizvi, Imran Dinh, Tri A. Yu, Weiping Chang, Yuchiao Sherwood, Margaret E. Hasan, Tayyaba TI Photoimmunotherapy and Irradiance Modulation Reduce Chemotherapy Cycles and Toxicity in a Murine Model for Ovarian Carcinomatosis: Perspective and Results SO ISRAEL JOURNAL OF CHEMISTRY LA English DT Review DE antitumor agents; cancer; epidermal growth factor receptor; photodynamic therapy; photoimmunoconjugates ID GROWTH-FACTOR RECEPTOR; FALLOPIAN-TUBE CANCER; INTERNALIZING MONOCLONAL-ANTIBODIES; TARGETED PHOTODYNAMIC THERAPY; E(6) MONOETHYLENE DIAMINE; MULTICELL TUMOR SPHEROIDS; PHASE-II CONSORTIA; EPITHELIAL OVARIAN; IN-VIVO; RECURRENT OVARIAN AB Significant toxicities from multiple cycles of chemotherapy often cause delays or early termination of treatment, leading to poor outcomes in ovarian cancer patients. Complementary modalities that potentiate the efficacy of traditional agents and lead to fewer cycles and less toxicity are needed. Photodynamic therapy is a mechanistically distinct modality that synergizes with chemical and biological agents. Here, a combination regimen with a clinically relevant chemotherapy cocktail (cisplatin and paclitaxel) and epidermal growth factor receptor?targeted photoimmunotherapy (PIT) is evaluated in a murine model for ovarian carcinomatosis. Mice received either one or two cycles of chemotherapy followed by PIT with a chlorine6-Erbitux photoimmunoconjugate and 25 J/cm2 light. PIT plus a single cycle of chemotherapy significantly reduced tumor burden, comparable to multiple chemotherapy cycles. Relative to one cycle of chemotherapy, the addition of PIT did not cause significant mouse weight loss, whereas two cycles of chemotherapy led to a significant reduction in weight. Irradiance-dependence on PIT efficacy was a function of the conjugation chemistry, providing an additional variable for optimization of PIT outcome. C1 [Hasan, Tayyaba] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed Bartlett 314, Boston, MA 02114 USA. [Rizvi, Imran; Dinh, Tri A.; Yu, Weiping; Sherwood, Margaret E.; Hasan, Tayyaba] Massachusetts Gen Hosp, Dept Dermatol, Wellman Ctr Photomed, Boston, MA 02114 USA. [Dinh, Tri A.] Massachusetts Gen Hosp, Gillette Ctr Gynecol Oncol, Boston, MA 02114 USA. [Chang, Yuchiao] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. RP Hasan, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed Bartlett 314, 40 Blossom St, Boston, MA 02114 USA. EM thasan@partners.org OI Rizvi, Imran/0000-0001-9673-4700 FU National Cancer Institute, National Institutes of Health, US Department of Health and Human Services [5R01CA160998, 1R01CA158415]; Department of Energy Massachusetts General Hospital Laser Center Fellowship in Gynecologic Oncology from Vincent Memorial Obstetrics and Gynecology Service FX This work was supported by grant numbers 5R01CA160998 and 1R01CA158415 from the National Cancer Institute, National Institutes of Health, US Department of Health and Human Services. Tri A. Dinh, MD, was supported by a Department of Energy Massachusetts General Hospital Laser Center Fellowship in Gynecologic Oncology from Vincent Memorial Obstetrics and Gynecology Service. We thank Imclone Systems Inc. (New York, NY) for the mAb Erbitux. NR 143 TC 11 Z9 11 U1 3 U2 19 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 0021-2148 EI 1869-5868 J9 ISR J CHEM JI Isr. J. Chem. PD SEP PY 2012 VL 52 IS 8-9 SI SI BP 776 EP 787 DI 10.1002/ijch.201200016 PG 12 WC Chemistry, Multidisciplinary SC Chemistry GA 010BH UT WOS:000309068900012 PM 23626376 ER PT J AU Rao, SV Dai, D Subherwal, S Weintraub, WS Brindis, RS Messenger, JC Lopes, RD Peterson, ED AF Rao, Sunil V. Dai, David Subherwal, Sumeet Weintraub, William S. Brindis, Ralph S. Messenger, John C. Lopes, Renato D. Peterson, Eric D. TI Association Between Periprocedural Bleeding and Long-Term Outcomes Following Percutaneous Coronary Intervention in Older Patients SO JACC-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE elderly patients; percutaneous coronary intervention; periprocedural bleeding ID CARDIOVASCULAR DATA REGISTRY; ACUTE MYOCARDIAL-INFARCTION; BLOOD-TRANSFUSION; CLINICAL-OUTCOMES; MORTALITY; RISK; CLOPIDOGREL; IMPACT; THERAPY; ASPIRIN AB Objectives The authors sought to describe the association between post-procedural bleeding and long-term recurrent bleeding, major adverse cardiac events (MACE), and mortality among older patients undergoing percutaneous coronary intervention (PCI). Background Bleeding complications after PCI are associated with an increased risk for acute morbidity and long-term mortality, but the association of these bleeding complications with other events is unknown. Methods Patients entered into the National Cardiovascular Data Registry (NCDR) CathPCI Registry (n = 461,311; 946 sites) from January 2004 to December 2008 were linked with claims from the Centers for Medicare & Medicaid Services and grouped according to in-hospital post-PCI bleeding. The association between post-PCI bleeding and 1-, 12-, and 30-month readmission for bleeding, MACE, and all-cause mortality was examined with Cox regression that included patient and procedural characteristics using no bleeding as the reference. Results Overall, 3.1% (n = 14,107) of patients experienced post-PCI bleeding. Patients who bled were older, more often female, had more medical comorbidities, less often received bivalirudin, and more often underwent PCI via the femoral approach. After adjustment, bleeding after the index procedure was significantly associated with readmission for bleeding (adjusted hazard ratios [95% confidence interval]: 1 month, 1.54 [1.42 to 1.67]; 12 months, 1.52 [1.40 to 1.66]; 30 months, 1.29 [1.11 to 1.50]), MACE (1 month, 1.11 [1.07 to 1.15]; 12 months, 1.17 [1.13 to 1.21]; 30 months, 1.12 [1.06 to 1.19]) and all-cause mortality (1 month, 1.32 [1.26 to 1.38]; 12 months, 1.33 [1.27 to 1.40]); 30 months, 1.22 [1.15 to 1.30]). Conclusions Post-PCI bleeding complications are associated with an increased risk for short-and long-term recurrent bleeding, MACE, and all-cause mortality. These data underscore the prognostic importance of periprocedural bleeding and the need for identifying strategies to reduce long-term bleeding risk among patients undergoing PCI. (J Am Coll Cardiol Intv 2012;5:958-65) (C) 2012 by the American College of Cardiology Foundation C1 [Rao, Sunil V.; Dai, David; Subherwal, Sumeet; Lopes, Renato D.; Peterson, Eric D.] Durham Vet Affairs Med Ctr, Duke Clin Res Inst, Durham, NC 27705 USA. [Weintraub, William S.] Christiana Care Hlth Syst, Newark, DE USA. [Brindis, Ralph S.] San Francisco Kaiser Permanente Hosp, San Francisco, CA USA. [Messenger, John C.] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Rao, SV (reprint author), Durham Vet Affairs Med Ctr, Duke Clin Res Inst, 508 Fulton St 111A, Durham, NC 27705 USA. EM sunil.rao@duke.edu FU American College of Cardiology; Medicines Company, Parsippany, New Jersey; Ikaria and Sanofi-Aventis; Medicines Company, Terumo, Zoll; Bristol-Myers Squibb; Eli Lilly; Johnson Johnson FX This analysis was supported by the American College of Cardiology and The Medicines Company, Parsippany, New Jersey. The Medicines Company did not have input into the design of the study nor in the preparation of the paper. Dr. Rao has received research funding from Ikaria and Sanofi-Aventis (<$ 10,000), and consulting fees from The Medicines Company, Terumo, and Zoll (<$ 10,000). Dr. Lopes has received research grant support from Bristol-Myers Squibb (<$ 10,000). Dr. Peterson has received research grant support from Eli Lilly and Johnson & Johnson (<$ 10,000). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 29 TC 30 Z9 33 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-8798 J9 JACC-CARDIOVASC INTE JI JACC-Cardiovasc. Interv. PD SEP PY 2012 VL 5 IS 9 BP 958 EP 965 DI 10.1016/j.jcin.2012.05.010 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 014CB UT WOS:000309351600010 PM 22995883 ER PT J AU Wu, O Lu, J Mandeville, JB Murata, Y Egi, Y Dai, GP Marota, JJ Diwan, I Dijkhuizen, RM Kwong, KK Lo, EH Singhal, AB AF Wu, Ona Lu, Jie Mandeville, Joseph B. Murata, Yoshihiro Egi, Yasu Dai, Guangping Marota, John J. Diwan, Izzuddin Dijkhuizen, Rick M. Kwong, Kenneth K. Lo, Eng H. Singhal, Aneesh B. TI Dynamic functional cerebral blood volume responses to normobaric hyperoxia in acute ischemic stroke SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE acute stroke; brain imaging; BOLD contrast; cerebral hemodynamics; focal ischemia ID ARTERY OCCLUSION; OXYGEN-THERAPY; FOCAL ISCHEMIA; MRI; RAT; DIFFUSION; FLOW; EVOLUTION; PERFUSION; DEPOLARIZATIONS AB Studies suggest that neuroprotective effects of normobaric oxygen (NBO) therapy in acute stroke are partly mediated by hemodynamic alterations. We investigated cerebral hemodynamic effects of repeated NBO exposures. Serial magnetic resonance imaging (MRI) was performed in Wistar rats subjected to focal ischemic stroke. Normobaric oxygen-induced functional cerebral blood volume (fCBV) responses were analyzed. All rats had diffusion-weighted MRI (DWI) lesions within larger perfusion deficits, with DWI lesion expansion after 3 hours. Functional cerebral blood volume responses to NBO were spatially and temporally heterogeneous. Contralateral healthy tissue responded consistently with vasoconstriction that increased with time. No significant responses were evident in the acute DWI lesion. In hypoperfused regions surrounding the acute DWI lesion, tissue that remained viable until the end of the experiment showed relative preservation of mean fCBV at early time points, with some rats showing increased fCBV (vasodilation); however, these regions later exhibited significantly decreased fCBV (vasoconstriction). Tissue that became DWI abnormal by study-end initially showed marginal fCBV changes that later became moderate fCBV reductions. Our results suggest that a reverse-steal hemodynamic effect may occur in peripheral ischemic zones during NBO treatment of focal stroke. In addition, CBV responses to NBO challenge may have potential as an imaging marker to distinguish ischemic core from salvageable tissues. Journal of Cerebral Blood Flow & Metabolism (2012) 32, 1800-1809; doi:10.1038/jcbfm.2012.87; published online 27 June 2012 C1 [Wu, Ona; Mandeville, Joseph B.; Dai, Guangping; Diwan, Izzuddin; Kwong, Kenneth K.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Lu, Jie; Murata, Yoshihiro; Egi, Yasu; Lo, Eng H.] Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Lab, Charlestown, MA 02129 USA. [Marota, John J.] Massachusetts Gen Hosp, Dept Anesthesiol, Boston, MA 02114 USA. [Dijkhuizen, Rick M.] Univ Med Ctr Utrecht, Image Sci Inst, Biomed MR Imaging & Spect Grp, Utrecht, Netherlands. [Singhal, Aneesh B.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Wu, O (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St CNY 2301, Charlestown, MA 02129 USA. EM ona@nmr.mgh.harvard.edu OI Dijkhuizen, Rick/0000-0002-4623-4078 FU US National Institutes of Health [R01NS051412, R01NS59775, P50NS051343]; Royal Netherlands Academy of Arts and Sciences; US National Institutes of Health (NCRR) [R03 EB008134, P41RR14075] FX This study was supported in part by grants from the US National Institutes of Health (R01NS051412, R01NS59775, P50NS051343, and NCRR grants R03 EB008134 and P41RR14075), and the Royal Netherlands Academy of Arts and Sciences. NR 41 TC 5 Z9 8 U1 1 U2 14 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 SEP PY 2012 VL 32 IS 9 BP 1800 EP 1809 DI 10.1038/jcbfm.2012.87 PG 10 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 000MR UT WOS:000308390900014 PM 22739619 ER PT J AU Sarma, J AF Sarma, Jaydev TI Sinus arrest during insertion of a Laryngeal Mask Airway SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Letter C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Sarma, J (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. EM jsarma@partners.org NR 1 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 0952-8180 J9 J CLIN ANESTH JI J. Clin. Anesth. PD SEP PY 2012 VL 24 IS 6 BP 507 EP 508 DI 10.1016/j.jclinane.2011.08.011 PG 2 WC Anesthesiology SC Anesthesiology GA 015FQ UT WOS:000309432200015 PM 22986323 ER PT J AU Venkataramani, AS AF Venkataramani, Atheendar S. TI Early life exposure to malaria and cognition in adulthood: Evidence from Mexico SO JOURNAL OF HEALTH ECONOMICS LA English DT Article DE Malaria; Cognition; Early childhood; Education; Mexico; Eradication; Flynn Effect; Parental investments ID LABOR-MARKET OUTCOMES; PLASMODIUM-FALCIPARUM; EARLY-CHILDHOOD; BIRTH-WEIGHT; HEALTH; ERADICATION; IMPACT; SCHOOLCHILDREN; CONSEQUENCES; EDUCATION AB This study examines the impact of early life malaria exposure on cognition in sample of Mexican adults, using the nationwide introduction of malaria eradication efforts to identify causal impacts. The core findings are that birth year exposure to malaria eradication was associated with increases in Raven Progressive Matrices test scores and consumption expenditures, but not schooling. Additionally, cohorts born after eradication both entered and exited school earlier than their pre-eradication counterparts. These effects were only seen for men and explanations for this are assessed. Collectively, these findings suggest that improvements in infant health help explain secular increases in cognitive test scores, that better cognition may link early life health to adulthood earnings, and that human capital investments through childhood and young adulthood respond sensitively to market returns to early life endowment shocks. (C) 2012 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Charlestown HealthCare Ctr, Dept Med, Charlestown, MA 02129 USA. RP Venkataramani, AS (reprint author), Massachusetts Gen Hosp, Charlestown HealthCare Ctr, Dept Med, 73 High St, Charlestown, MA 02129 USA. EM avenkataramani@partners.org NR 65 TC 15 Z9 15 U1 0 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-6296 EI 1879-1646 J9 J HEALTH ECON JI J. Health Econ. PD SEP PY 2012 VL 31 IS 5 BP 767 EP 780 DI 10.1016/j.jhealeco.2012.06.003 PG 14 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 011ED UT WOS:000309146600007 PM 22906550 ER PT J AU Michailidou, M Velmahos, GC van der Wilden, G Alam, HB de Moya, M Chang, YC AF Michailidou, Maria Velmahos, George C. van der Wilden, Gwen Alam, Hasan B. de Moya, Marc Chang, Yuchiao TI "Blush" on trauma computed tomography: Not as bad as we think! SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Article DE Computed tomography; contrast extravasation; blush; trauma ID BLUNT ABDOMINAL-TRAUMA; ANGIOGRAPHIC EMBOLIZATION; MULTIDETECTOR CT; NONOPERATIVE MANAGEMENT; EXTRAVASATION; SPLEEN; INJURY; HEMORRHAGE; SURGERY AB INTRODUCTION: Intravenous contrast extravasation (IVCE) on a trauma computed tomography has been quoted as a reason for intervention (angiographic embolization or operation). The new-generation computed tomographic (CT) scanners identify IVCE with increasing frequency. We hypothesized that most IVCEs do not require an intervention. METHODS: This study was a retrospective evaluation of trauma patients with IVCE on abdomen or pelvis CT scan (January 2005-December 2009). Along with demographic and hemodynamic variables, the following characteristics of IVCE were examined as potential risk factors for intervention: maximal dimension, small (<= 1.5 cm) versus large (>1.5 cm), contained versus free, and single versus multiple and location. RESULTS: Sixty-nine patients with 81 IVCEs were identified: 48 IVCEs occurred in intra-abdominal solid organs, 18 IVCEs in the pelvic retroperitoneal space, and 15 IVCEs in the soft tissues or other locations. Thirty patients (43.5%) were managed without an intervention, and 39 patients (56.5%) required either an immediate (30 patients) or a delayed (9 patients) intervention. Multivariate analysis identified three independent predictors of an intervention: an admission systolic blood pressure of 100 mm Hg or lower, a large ICVE, and an Abbreviated Injury Score of the abdomen of 3 or higher. If all three independent predictors were present, 100% of patients received an intervention. CONCLUSION: Nearly half of IVCEs on CT scan did not require an intervention. A hypotension at admission, a severe abdominal trauma, and a blush diameter of 1.5 cm or greater predicted the need for intervention. (J Trauma Acute Care Surg. 2012;73: 580-586. Copyright (C) 2012 by Lippincott Williams & Wilkins) C1 [Velmahos, George C.] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Biostat & Epidemiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Velmahos, GC (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM gvelmahos@partners.org NR 20 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 2163-0755 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD SEP PY 2012 VL 73 IS 3 BP 580 EP 586 DI 10.1097/TA.0b013e318265cbd4 PG 7 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 009TK UT WOS:000309047900007 PM 22929487 ER PT J AU Dai, TH Murray, CK Vrahas, MS Baer, DG Tegos, GP Hamblin, MR AF Dai, Tianhong Murray, Clinton K. Vrahas, Mark S. Baer, David G. Tegos, George P. Hamblin, Michael R. TI Ultraviolet C light for Acinetobacter baumannii wound infections in mice: Potential use for battlefield wound decontamination? SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Article DE Skin abrasion; burn; Acinetobacter baumannii; ultraviolet C; combat-related infection ID MULTIDRUG-RESISTANT ACINETOBACTER; INTERSTITIAL PHOTODYNAMIC THERAPY; EXTREMITY INJURIES; BURN INFECTIONS; INACTIVATION; PREVENTION; BACTERIA; MANAGEMENT; OPERATIONS; RADIATION AB BACKGROUND: Since the beginning of the conflicts in the Middle East, US Army physicians have noted a high rate of multidrug-resistant Acinetobacter baumannii infections among US soldiers wounded and initially treated in Iraq. In this study, we investigated the use of ultraviolet C (UVC) light for prevention of multidrug-resistant A. baumannii wound infections using mouse models. METHODS: Partial-thickness skin abrasions and full-thickness burns in mice were infected with a multidrug-resistant A. baumannii isolate recovered from a wounded US soldier deployed to Iraq. The luxCDABE operon, which was contained in plasmid pMF 385, was cloned into the A. baumannii strain. This allowed real-time monitoring of the extent of infection in mice using bioluminescence imaging. UVC light was delivered to the mouse wounds at 30 minutes after the inoculation of A. baumannii. Groups of infected mouse wounds without being exposed to UVC served as the controls. RESULTS: In vitro studies demonstrated that A. baumannii cells were inactivated at UVC exposures much lower than those needed for a similar effect on mammalian cells. It was observed in animal studies that UVC (3.24 J/cm(2) for abrasions and 2.59 J/cm(2) for burns) significantly reduced the bacterial burdens in UVC-treated wounds by approximately 10-fold compared with nontreated controls (p = 0.004 for abrasions, p = 0.019 for burns). DNA lesions were observed by immunofluorescence in mouse skin abrasions immediately after a UVC exposure of 3.24 J/cm(2); however, the lesions were extensively repaired within 72 hours. CONCLUSION: These results suggested that UVC may be useful in preventing combat-related wound infections. (J Trauma Acute Care Surg. 2012; 73: 661-667. Copyright (C) 2012 by Lippincott Williams & Wilkins) C1 [Dai, Tianhong; Tegos, George P.; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Dai, Tianhong; Tegos, George P.; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Murray, Clinton K.] Brooke Army Med Ctr, Infect Dis Serv, Ft Sam Houston, TX 78234 USA. [Vrahas, Mark S.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Baer, David G.] USA, Inst Surg Res, Ft Sam Houston, TX 78234 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, 40 Blossom St,BAR 414, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 FU Airlift Research Foundation Extremity Trauma Research Grant [109421]; COTA/Smith Nephew Grant [2012-16]; National Institutes of Health [RO1AI050875, 5U54MH084690-02] FX The authors declare no conflicts of interest. This study was supported in part by an Airlift Research Foundation Extremity Trauma Research Grant (grant 109421 to T. D.), a COTA/Smith & Nephew Grant (Grant 2012-16 to T. D.), and the National Institutes of Health (grant RO1AI050875 to M. R. H.). G. P. T. was supported by the National Institutes of Health (grant 5U54MH084690-02). NR 29 TC 7 Z9 7 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 2163-0755 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD SEP PY 2012 VL 73 IS 3 BP 661 EP 667 DI 10.1097/TA.0b013e31825c149c PG 7 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 009TK UT WOS:000309047900019 PM 22929495 ER PT J AU Kuehne, AJC Gather, MC Sprakel, J AF Kuehne, Alexander J. C. Gather, Malte C. Sprakel, Joris TI Monodisperse conjugated polymer particles by Suzuki-Miyaura dispersion polymerization SO NATURE COMMUNICATIONS LA English DT Article ID AQUEOUS-MEDIA; NANOPARTICLES; LASER; MICROPARTICLES; FILMS; GAIN; DOTS AB The self-assembly of colloidal building blocks into complex and hierarchical structures offers a versatile and powerful toolbox for the creation of new photonic and optoelectronic materials. However, well-defined and monodisperse colloids of semiconducting polymers, which would form excellent building blocks for such self-assembled materials, are not readily available. Here we report the first demonstration of a Suzuki-Miyaura dispersion polymerization; this method produces highly monodisperse submicrometer particles of a variety of semiconducting polymers. Moreover, we show that these monodisperse particles readily self-assemble into photonic crystals that exhibit a pronounced photonic stopgap. C1 [Kuehne, Alexander J. C.; Sprakel, Joris] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Kuehne, Alexander J. C.] Rhein Westfal TH Aachen, DWI, D-52056 Aachen, Germany. [Gather, Malte C.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Gather, Malte C.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Gather, Malte C.] Tech Univ Dresden, Inst Angew Photophys, D-01062 Dresden, Germany. [Sprakel, Joris] Wageningen Univ, Lab Phys Chem & Colloid Sci, NL-6703 HB Wageningen, Netherlands. RP Kuehne, AJC (reprint author), Harvard Univ, Sch Engn & Appl Sci, 9 Oxford St, Cambridge, MA 02138 USA. EM kuehne@dwi.rwth-aachen.de RI Kuehne, Alexander/L-1333-2015; OI Kuehne, Alexander/0000-0003-0142-8001; Gather, Malte/0000-0002-4857-5562 FU German Academic Exchange Service (DAAD); Netherlands Organization for Scientic Research (NWO); NSF [DMR-1006546, ECS-0335765]; Harvard MRSEC [DMR-0820484] FX A.J.C.K. thanks the German Academic Exchange Service (DAAD) and J.S. thanks the Netherlands Organization for Scientic Research (NWO) and all authors thank NSF (DMR-1006546) and the Harvard MRSEC (DMR-0820484) for financial support.; We gratefully acknowledge Dr Kai Zhang for performing GPC and elemental analysis, Rodrigo Guerra for assistance with 1H-NMR experiments and fluorescence spectroscopy, Sofia Magkiriadou for assistance with reflectance experiments, Dr Markus Kaiser and Dr Kim- Ho Phan for assistance with SEM and Professor David A. Weitz for support. We thank the Meerholz Group at the University of Cologne for access to an integrating sphere, the Xie Group at Harvard for providing access to the fluorescence spectrometer and the Harvard Center for Nanoscale Systems (CNS), a member of the National Nanotechnology Infrastructure Network (NNIN), which is supported by the NSF (ECS-0335765), for granting access to SEMs. NR 37 TC 32 Z9 32 U1 9 U2 119 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 SEP PY 2012 VL 3 AR 1088 DI 10.1038/ncomms2085 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 013XA UT WOS:000309338100055 PM 23011142 ER PT J AU Lee, S Vinegoni, C Feruglio, PF Fexon, L Gorbatov, R Pivoravov, M Sbarbati, A Nahrendorf, M Weissleder, R AF Lee, Sungon Vinegoni, Claudio Feruglio, Paolo Fumene Fexon, Lyuba Gorbatov, Rostic Pivoravov, Misha Sbarbati, Andrea Nahrendorf, Matthias Weissleder, Ralph TI Real-time in vivo imaging of the beating mouse heart at microscopic resolution SO NATURE COMMUNICATIONS LA English DT Article ID INTRAVITAL MICROSCOPY; MOTION; MICE AB Real-time imaging of moving organs and tissues at microscopic resolutions represents a major challenge in studying the complex biology of live animals. Here we present a technique based on a novel stabilizer setup combined with a gating acquisition algorithm for the imaging of a beating murine heart at the single-cell level. The method allows serial in vivo fluorescence imaging of the beating heart in live mice in both confocal and nonlinear modes over the course of several hours. We demonstrate the utility of this technique for in vivo optical sectioning and dual-channel time-lapse fluorescence imaging of cardiac ischaemia. The generic method could be adapted to other moving organs and thus broadly facilitate in vivo microscopic investigations. C1 [Lee, Sungon; Vinegoni, Claudio; Feruglio, Paolo Fumene; Fexon, Lyuba; Gorbatov, Rostic; Pivoravov, Misha; Nahrendorf, Matthias; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Lee, Sungon; Vinegoni, Claudio; Feruglio, Paolo Fumene; Fexon, Lyuba; Gorbatov, Rostic; Pivoravov, Misha; Nahrendorf, Matthias; Weissleder, Ralph] Harvard Univ, Sch Med, Richard B Simches Res Ctr, Boston, MA 02114 USA. [Lee, Sungon] Korea Inst Sci & Technol, Interact & Robot Res Ctr, Seoul 136791, South Korea. [Feruglio, Paolo Fumene; Sbarbati, Andrea] Univ Verona, Dept Neurol Neuropsychol Morphol & Movement Sci, I-37134 Verona, Italy. RP Vinegoni, C (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA. EM cvinegoni@mgh.harvard.edu FU Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services [HHSN26820100004xC]; Institute of Biomedical Engineering [R01EB006432] FX We gratefully acknowledge the help of Brena Sena. This project was funded in part by Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services (under Contract No. HHSN26820100004xC) and from the Institute of Biomedical Engineering (under R01EB006432). NR 25 TC 46 Z9 46 U1 4 U2 34 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 SEP PY 2012 VL 3 AR 1054 DI 10.1038/ncomms2060 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 013XA UT WOS:000309338100021 PM 22968700 ER PT J AU Patrician, PA Dolansky, M Estrada, C Brennan, C Miltner, R Newsom, J Olds, D Splaine, M Moore, S AF Patrician, Patricia A. Dolansky, Mary Estrada, Carlos Brennan, Caitlin Miltner, Rebecca Newsom, Jeremiah Olds, Danielle Splaine, Mark Moore, Shirley TI Interprofessional Education in Action: The VA Quality Scholars Fellowship Program SO NURSING CLINICS OF NORTH AMERICA LA English DT Article DE Quality improvement; Interprofessional education; Patient safety; VA Quality Scholars Fellowship Program ID IMPROVEMENT; SAFETY; CARE AB Although there are many examples of interprofessional education activities that focus on quality and safety, few include longitudinal experiences of teams working together over time. One exception is the Veterans Affairs Quality Scholars (VAQS) fellowship program. This article describes the integration of interprofessional education into the VAQS fellowship program, offers 2 examples of interprofessional projects conducted by the fellows, and discusses the VAQS program as a model for others to consider in developing interprofessional training programs in safety and quality improvement. C1 [Patrician, Patricia A.; Miltner, Rebecca] Univ Alabama Birmingham, Sch Nursing, Dept Community Hlth Outcomes & Syst, Birmingham, AL 35294 USA. [Patrician, Patricia A.; Estrada, Carlos; Miltner, Rebecca; Newsom, Jeremiah] Birmingham VA Med Ctr, Vet Affairs VA Natl Qual Scholars Program, Birmingham, AL 35233 USA. [Dolansky, Mary; Brennan, Caitlin; Olds, Danielle] Case Western Reserve Univ, Frances Payne Bolton Sch Nursing, Cleveland, OH 44106 USA. [Dolansky, Mary] Cleveland VA Med Ctr, VA Natl Qual Scholars Program, Cleveland, OH 44106 USA. [Estrada, Carlos; Miltner, Rebecca; Newsom, Jeremiah] Univ Alabama Birmingham, Div Gen Internal Med, Birmingham, AL 35294 USA. [Brennan, Caitlin; Olds, Danielle] Case Western Reserve Univ, VA Natl Qual Scholar Program, Louis Stokes Cleveland VA Med Ctr, Cleveland, OH 44106 USA. [Splaine, Mark] Dartmouth Inst Hlth Policy & Clin Practice, VA Natl Qual Scholars Fellowship Program, Ctr Leadership & Improvement, Lebanon, NH 03766 USA. [Splaine, Mark] Dartmouth Med Sch, Geisel Sch Med, Hanover, NH 03766 USA. RP Patrician, PA (reprint author), Birmingham VA Med Ctr, Vet Affairs VA Natl Qual Scholars Program, Birmingham, AL 35233 USA. EM ppatrici@uab.edu OI Miltner, Rebecca/0000-0002-4653-0328 NR 25 TC 5 Z9 5 U1 1 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 0029-6465 J9 NURS CLIN N AM JI Nurs. Clin. North Am. PD SEP PY 2012 VL 47 IS 3 BP 347 EP + DI 10.1016/j.cnur.2012.05.006 PG 9 WC Nursing SC Nursing GA 013PJ UT WOS:000309317000004 PM 22920425 ER PT J AU Miao, B Skidan, I Yang, J You, Z Fu, X Famulok, M Schaffhausen, B Torchilin, V Yuan, J Degterev, A AF Miao, B. Skidan, I. Yang, J. You, Z. Fu, X. Famulok, M. Schaffhausen, B. Torchilin, V. Yuan, J. Degterev, A. TI Inhibition of cell migration by PITENINs: the role of ARF6 SO ONCOGENE LA English DT Article DE ARF6 guanine nucleotide exchange factor; ARNO/GRP1 membrane translocation; lamellipodia suppression; anti-angiogenesis; anti-metastasis ID GUANINE-NUCLEOTIDE-EXCHANGE; RIBOSYLATION FACTOR 6; PLECKSTRIN-HOMOLOGY DOMAINS; PLASMA-MEMBRANE; MAMMALIAN-CELLS; PATHWAY; PROTEINS; BINDING; SEC7; ARNO AB We have reported previously the development of small-molecule phosphatidylinositol-3,4,5-trisphosphate (PIP3) antagonists (PITs) that block pleckstrin homology (PH) domain interaction, including activation of Akt, and show anti-tumor potential. Here we show that the same molecules inhibit growth factor-induced actin remodeling, lamellipodia formation and, ultimately, cell migration and invasion, consistent with an important role of PIP3 in these processes. In vivo, a PIT-1 analog displays significant inhibition on tumor angiogenesis and metastasis. ADP ribosylation factor 6 (ARF6) was recently identified as an important mediator of cytoskeleton and cell motility, which is regulated by PIP3-dependent membrane translocation of the guanine nucleotide exchange factors (GEFs), such as ADP-ribosylation factor nucleotide binding site opener (ARNO) and general receptor for 3-phosphoinositides (GRP1). We demonstrate that PITs inhibit PIP3/ARNO or GRP1 PH domain binding and membrane localization, resulting in the inhibition of ARF6 activation. Importantly, we show that expression of the constitutively active mutant of ARF6 attenuates inhibition of lamellipodia formation and cell migration by PITs, confirming that inhibition of ARF6 contributes to inhibition of these processes by PITs. Overall, our studies demonstrate the feasibility of developing specific small-molecule targeting PIP3 binding by PH domains as potential anticancer agents that can simultaneously interfere with cancer development at multiple points. Oncogene (2012) 31, 4317-4332; doi:10.1038/onc.2011.593; published online 19 December 2011 C1 [Miao, B.; You, Z.; Schaffhausen, B.; Degterev, A.] Tufts Univ, Sch Med, Dept Biochem, Boston, MA 02111 USA. [Skidan, I.; Torchilin, V.] Northeastern Univ, Dept Pharmaceut Sci, Ctr Pharmaceut Biotechnol & Nanomed, Boston, MA 02115 USA. [Skidan, I.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurosci Ctr, Charlestown, MA USA. [Fu, X.] Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Famulok, M.] Univ Bonn, Program Unit Chem Biol & Med Chem, LIMES Inst, Bonn, Germany. [Yuan, J.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. RP Degterev, A (reprint author), Tufts Univ, Sch Med, Dept Biochem, Boston, MA 02111 USA. EM alexei.degterev@tufts.edu FU Smith Family Award for Excellence in Biomedical Research; National Institute on Aging Mentored Research Scientist Career Development Award; US Army [DAMD17-02-1-0403]; National Cancer Institute [RO1 CA34722/PO1-50661]; National Institute on Aging [R37 AG012859] FX We thank Dr Joan Brugge (Harvard Medical School), Dr Tamas Balla (National Institutes of Health) and Dr Philippe Chavrier (Institut Curie) for the gifts of plasmids and cells. We thank Dr Jeff Peterson (Fox Chase Cancer Center, Philadelphia, PA, USA) for providing valuable comments. This work was supported by Smith Family Award for Excellence in Biomedical Research and National Institute on Aging Mentored Research Scientist Career Development Award (to AD), an Innovator Award from US Army (DAMD17-02-1-0403), National Cancer Institute (RO1 CA34722/PO1-50661) (to BSS) and the National Institute on Aging (R37 AG012859) (to JY). NR 38 TC 9 Z9 9 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP PY 2012 VL 31 IS 39 BP 4317 EP 4332 DI 10.1038/onc.2011.593 PG 16 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 016LP UT WOS:000309520200006 PM 22179837 ER PT J AU Mouw, KW Harris, JR AF Mouw, Kent W. Harris, Jay R. TI Irradiation in Early-Stage Breast Cancer: Conventional Whole-Breast, Accelerated Partial-Breast, and Accelerated Whole-Breast Strategies Compared SO ONCOLOGY-NEW YORK LA English DT Review ID CONFORMAL RADIATION-THERAPY; 20-YEAR FOLLOW-UP; PHASE-II TRIAL; RANDOMIZED-TRIAL; CONSERVING SURGERY; RADIOTHERAPY HYPOFRACTIONATION; PATHOLOGICAL FINDINGS; CONSERVATIVE SURGERY; UK STANDARDIZATION; AMERICAN SOCIETY AB Whole-breast irradiation (WBI) following breast-conserving surgery (BCS) has been used for several decades as an alternative to mastectomy in the treatment of localized breast cancer, and it has been shown to decrease rates of local-regional recurrence and improve survival rates compared with BCS alone. WBI is delivered using high-energy external beam radiation and typically consists of approximately 5 weeks of daily treatments to the entire breast, with or without inclusion of a "boost" to the primary site. Accelerated partial-breast irradiation (APBI) and accelerated whole-breast irradiation (AWBI) have been developed as alternatives to conventional WBI for selected patients with early-stage breast cancer. Given its large size and long follow-up, the Canadian trial of AWBI has been widely considered as practice-changing, and additional studies of AWBI are maturing or newly-launched. Use of APBI is based on the observation that the majority of local recurrences occur near the primary tumor site. Because a smaller portion of the breast is irradiated, treatment courses can often be abbreviated, and techniques such as conformal external beam, catheter- or balloon-based brachytherapy, and intra-operative radiation have been developed. Data from early APBI randomized trials and retrospective studies report mixed results. However, given the protracted time to local recurrence and complications following breast-conserving therapy, definitive results from contemporary randomized clinical trials comparing conventional WBI against AWBI or APBI are still limited. C1 [Harris, Jay R.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Harris, Jay R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Mouw, Kent W.] Harvard Radiat Oncol Program, Boston, MA USA. RP Harris, JR (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, 450 Brookline Ave,Room D1622, Boston, MA 02115 USA. EM JHarris@lroc.harvard.edu NR 60 TC 6 Z9 6 U1 0 U2 7 PU UBM MEDICA PI NORWALK PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD SEP PY 2012 VL 26 IS 9 BP 820 EP 830 PG 11 WC Oncology SC Oncology GA 008XG UT WOS:000308989300007 PM 23061336 ER PT J AU Fay, A Santiago, YMB AF Fay, Aaron Santiago, Yvette Marie B. TI A Modified Levine Palpebral Spring for the Treatment of Myogenic Ptosis SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID MANAGEMENT AB Purpose: Surgical treatment of myogenic ptosis usually requires a form of frontalis suspension. Complications can include entropion, headache, contour abnormalities, and poor eyelid excursion. The Levine palpebral spring has been used successfully to augment eyelid closure in more than 2,000 patients. The authors present a modified Levine spring to correct ptosis in a patient with poor levator function. Methods: Interventional case report. A 55-year-old man with profound myogenic ptosis was treated with bilateral modified Levine palpebral springs. Eyelid position, contour and excursion, blink reflex, lagophthalmos, and ocular surface were evaluated. Results: The Levine palpebral spring functioned well to open both eyelids. Margin reflex distance improved from -3 mm to 3 m postoperatively. Excellent contour and excursion were observed. Orbicularis action, including blink reflex, was preserved, and ocular surface was not compromised. Conclusion: The modified Levine palpebral spring is an alternative to frontalis suspension in treating select patients with eyelid ptosis with poor levator function. (Ophthal Plast Reconstr Surg 2012; 28: 372-375) C1 [Fay, Aaron] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Fay, Aaron] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Santiago, Yvette Marie B.] St Lukes Med Ctr, Int Eye Inst, Quezon City, Philippines. RP Fay, A (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM aaron_fay@meei.harvard.edu NR 9 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD SEP-OCT PY 2012 VL 28 IS 5 BP 372 EP 375 DI 10.1097/IOP.0b013e318263ded7 PG 4 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 006HN UT WOS:000308810200024 PM 22965015 ER PT J AU Jakobiec, FA Zakka, FR Kim, N AF Jakobiec, Frederick A. Zakka, Fouad R. Kim, Nancy TI Basaloid Follicular Hamartoma of the Eyelid SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID CELL CARCINOMAS; FIBROEPITHELIOMA; EXPRESSION; PINKUS AB An 86-year-old woman slowly developed a solitary 0.3 x 0.2-cm papule on the left lower eyelid. Complete excision disclosed a honeycombed lesion composed of interlacing basaloid strands unattached to the epidermis but rather extending into the dermis from a dilated hair follicle. The diagnosis was a solitary basaloid follicular hamartoma that can also occur in multiple, generalized, and inherited forms, sometimes with an associated systemic disease. The lesion exhibited a distinctive CD34-positive, mildly cellular myxoid stroma with many CK20-positive Merkel cells scattered within the basaloid cellular strands, which exhibited BCL-2 positivity only within the outermost cells bordering the stroma. These immunohistochemical features are the opposite of those displayed by basal cell carcinomas, which require more aggressive surgical management. Besides basal cell carcinomas, the differential diagnosis of basaloid follicular hamartoma includes fibrofolliculoma, tumor of the follicular infundibulum, poroma, and trabecular (Merkel cell) carcinoma. C1 [Jakobiec, Frederick A.; Zakka, Fouad R.; Kim, Nancy] Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Boston, MA 02114 USA. [Jakobiec, Frederick A.; Zakka, Fouad R.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Suite 321,243 Charles St, Boston, MA 02114 USA. EM Fred_Jakobiec@meei.harvard.edu NR 21 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD SEP-OCT PY 2012 VL 28 IS 5 BP E127 EP E130 DI 10.1097/IOP.0b013e3182467dfc PG 4 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 006HN UT WOS:000308810200011 PM 22460674 ER PT J AU Kirzhner, M Jakobiec, FA Borodic, G AF Kirzhner, Maria Jakobiec, Frederick A. Borodic, Gary TI Desmoplastic Trichoepithelioma: Report of a Unique Periocular Case SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID MICROCYSTIC ADNEXAL CARCINOMA; BASAL-CELL CARCINOMAS; MERKEL CELLS; DIFFERENTIATION; CRITERIA; CD34; SKIN AB In a 58-year-old woman with blepharospasm, a slowly enlarging left inferomedial eyelid lesion developed. It measured 3 3 5 mm and was nonulcerated, well-circumscribed, whitish, upraised, and firm. An initial incomplete excision followed by a total repeated excision revealed small squamous microcysts, often exhibiting calcifications and cords of nonclefting basaloid cells embedded in a scirrhous stroma characteristic of desmoplastic trichoepithelioma (DTE). Immunohistochemical investigations disclosed CD34-positive stromal fibroblasts and many CK20-positive Merkel cells located among the epithelial cells, features absent in mimicking sclerosing basal cell carcinoma (BCC). The tumor has not recurred during 6 months of follow up. Besides BCC, the differential diagnosis chiefly concerns syringoma and microcystic adnexal carcinoma. Surgical therapy should aim at complete excision but does not have to be as extensive or aggressive as that used for morpheic or sclerosing BCC because of its lack of diffusely infiltrating margins. C1 [Kirzhner, Maria; Jakobiec, Frederick A.] Massachusetts Eye & Ear Infirm, David G Cogan Ophthalm Pathol Lab, Boston, MA 02114 USA. [Kirzhner, Maria; Jakobiec, Frederick A.; Borodic, Gary] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Kirzhner, Maria; Jakobiec, Frederick A.; Borodic, Gary] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, David G Cogan Ophthalm Pathol Lab, 243 Charles St,Room 321, Boston, MA 02114 USA. EM Fred_Jakobiec@meei.harvard.edu NR 19 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0740-9303 EI 1537-2677 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD SEP-OCT PY 2012 VL 28 IS 5 BP E121 EP E124 DI 10.1097/IOP.0b013e318245535a PG 5 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 006HN UT WOS:000308810200009 PM 22366669 ER PT J AU Brigham, KS Woods, ER Steltz, SK Sandora, TJ Blood, EA AF Brigham, Kathryn S. Woods, Elizabeth R. Steltz, Sarah K. Sandora, Thomas J. Blood, Emily A. TI Randomized Controlled Trial of an Immunization Recall Intervention for Adolescents SO PEDIATRICS LA English DT Article DE immunization; vaccination; diphtheria-tetanus-acellular pertussis vaccines; chickenpox vaccine; meningococcal vaccines; adolescent; pediatrics; humans; reminder systems; intervention studies; randomized controlled trial ID UNDERIMMUNIZED CHILDREN; INFLUENZA VACCINATION; TELEPHONE MESSAGES; ADVISORY-COMMITTEE; PRACTICES ACIP; RATES; REMINDER/RECALL; RECOMMENDATIONS; VISITS; SYSTEM AB OBJECTIVE: Determine if adolescent immunization rates can be improved by contacting the parents or by contacting both the parents and adolescents. METHODS: Thirteen-to 17-year-olds overdue for at least 1 of 3 immunizations were randomized to (1) a control arm (Control), (2) telephone calls to the parent/guardian (Parent Only), or (3) telephone calls to the parent/guardian and the adolescent (Parent/Adol). Immunization records were assessed 4 weeks and 1 year after the intervention. Two-sided chi(2) tests and logistic regression models were used to compare receipt of immunizations by study arm. RESULTS: The intention-to-treat analysis showed improved immunization rates at 4 weeks (adjusted odds ratio 2.27, 95% confidence interval 1.00-5.18), but not at 1 year, in the Parent/Adol group compared with controls. There was a trend toward increased immunization in the Parent Only group (odds ratio 2.02, 95% confidence interval 0.89-4.56). However, phone contact was not achieved for many parents and adolescents in the intervention groups. A post hoc analysis of the impact of actual phone contact showed significant improvement in immunization rates both 4 weeks and 1 year after the intervention among those who were reached successfully. CONCLUSIONS: Improvement in immunization rates was seen in the short term but not the long term after contacting both the parent and adolescent. Although telephone interventions may be effective when rapid immunization is necessary, the difficulty in reaching parents and adolescents by phone highlights the importance of up-to-date contact information and a need to assess the effectiveness of alternative means of communication. Pediatrics 2012;130:507-514 C1 [Brigham, Kathryn S.; Woods, Elizabeth R.; Blood, Emily A.] Boston Childrens Hosp, Dept Med, Div Adolescent Young Adult Med, Boston, MA USA. [Steltz, Sarah K.; Blood, Emily A.] Boston Childrens Hosp, Clin Res Program, Boston, MA USA. [Sandora, Thomas J.] Boston Childrens Hosp, Dept Med, Div Infect Dis, Boston, MA USA. [Sandora, Thomas J.] Boston Childrens Hosp, Dept Lab Med, Div Infect Dis, Boston, MA USA. RP Brigham, KS (reprint author), MassGen Hosp Children, 175 Cambridge St,CPZS 509, Boston, MA 02114 USA. EM kbrigham@partners.org FU Maternal and Child Health Bureau, Health Resources and Services Administration [T71MC00009] FX This work was supported by the Leadership Education in Adolescent Health Training grant T71MC00009 from the Maternal and Child Health Bureau, Health Resources and Services Administration. NR 29 TC 6 Z9 6 U1 0 U2 3 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD SEP PY 2012 VL 130 IS 3 BP 507 EP 514 DI 10.1542/peds.2012-0471 PG 8 WC Pediatrics SC Pediatrics GA 014XO UT WOS:000309409300053 PM 22908112 ER PT J AU Camargo, CA Ganmaa, D Frazier, AL Kirchberg, FF Stuart, JJ Kleinman, K Sumberzul, N Rich-Edwards, JW AF Camargo, Carlos A., Jr. Ganmaa, Davaasambuu Frazier, A. Lindsay Kirchberg, Franca F. Stuart, Jennifer J. Kleinman, Ken Sumberzul, Nyamjav Rich-Edwards, Janet W. TI Randomized Trial of Vitamin D Supplementation and Risk of Acute Respiratory Infection in Mongolia SO PEDIATRICS LA English DT Article DE vitamin D; nutritional supplements; respiratory infections; randomized controlled trial ID 25-HYDROXYVITAMIN D LEVELS; D-DEFICIENCY; FORTIFIED MILK; CHILDREN; CATHELICIDIN; SCHOOLCHILDREN; PREVALENCE; CHILDHOOD; INFLUENZA; PREGNANCY AB OBJECTIVE: Observational studies suggest that serum levels of 25-hydroxyvitamin D (25[OH]D) are inversely associated with acute respiratory infections (ARIs). We hypothesized that vitamin D supplementation of children with vitamin D deficiency would lower the risk of ARIs. METHODS: By using cluster randomization, classrooms of 744 Mongolian schoolchildren were randomly assigned to different treatments in winter (January-March). This analysis focused on a subset of 247 children who were assigned to daily ingestion of unfortified regular milk (control; n = 104) or milk fortified with 300 IU of vitamin D-3 (n = 143). This comparison was double-blinded. The primary outcome was the number of parent-reported ARIs over the past 3 months. RESULTS: At baseline, the median serum 25(OH)D level was 7 ng/mL (interquartile range: 5-10 ng/mL). At the end of the trial, follow-up was 99% (n = 244), and the median 25(OH)D levels of children in the control versus vitamin D groups was significantly different (7 vs 19 ng/mL; P < .001). Compared with controls, children receiving vitamin D reported significantly fewer ARIs during the study period (mean: 0.80 vs 0.45; P = .047), with a rate ratio of 0.52 (95% confidence interval: 0.31-0.89). Adjusting for age, gender, and history of wheezing, vitamin D continued to halve the risk of ARI (rate ratio: 0.50 [95% confidence interval: 0.28-0.88]). Similar results were found among children either below or above the median 25(OH)D level at baseline (rate ratio: 0.41 vs 0.57; P-interaction = .27). CONCLUSIONS: Vitamin D supplementation significantly reduced the risk of ARIs in winter among Mongolian children with vitamin D deficiency. Pediatrics 2012;130:e561-e567 C1 [Camargo, Carlos A., Jr.; Kirchberg, Franca F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Camargo, Carlos A., Jr.; Ganmaa, Davaasambuu; Frazier, A. Lindsay; Kleinman, Ken; Rich-Edwards, Janet W.] Harvard Univ, Sch Med, Boston, MA USA. [Camargo, Carlos A., Jr.; Ganmaa, Davaasambuu; Frazier, A. Lindsay; Stuart, Jennifer J.; Rich-Edwards, Janet W.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Ganmaa, Davaasambuu; Sumberzul, Nyamjav] Hlth Sci Univ Mongolia, Ulaanbaatar, Mongol Peo Rep. [Frazier, A. Lindsay] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kleinman, Ken] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Stuart, Jennifer J.; Rich-Edwards, Janet W.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Camargo, CA (reprint author), Massachusetts Gen Hosp, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM ccamargo@partners.org OI Kirchberg, Franca Fabiana/0000-0001-6863-1202 FU Massachusetts General Hospital Center for D-receptor Activation Research, Boston, Massachusetts FX The Blue Sky Study was supported by a grant from an anonymous foundation. Additional support for the current analysis came from the Massachusetts General Hospital Center for D-receptor Activation Research, Boston, Massachusetts. NR 32 TC 99 Z9 103 U1 0 U2 6 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD SEP PY 2012 VL 130 IS 3 BP E561 EP E567 DI 10.1542/peds.2011-3029 PG 7 WC Pediatrics SC Pediatrics GA 014XO UT WOS:000309409300012 PM 22908115 ER PT J AU Mansbach, JM Piedra, PA Stevenson, MD Sullivan, AF Forgey, TF Clark, S Espinola, JA Camargo, CA AF Mansbach, Jonathan M. Piedra, Pedro A. Stevenson, Michelle D. Sullivan, Ashley F. Forgey, Tate F. Clark, Sunday Espinola, Janice A. Camargo, Carlos A., Jr. CA MARC-30 Investigators TI Prospective Multicenter Study of Children With Bronchiolitis Requiring Mechanical Ventilation SO PEDIATRICS LA English DT Article DE bronchiolitis; continuous positive airway pressure; intubation; ICU; respiratory syncytial virus; human rhinovirus ID RESPIRATORY SYNCYTIAL VIRUS; INTENSIVE-CARE-UNIT; INVESTIGATORS COLLABORATIVE NETWORK; REAL-TIME PCR; RISK-FACTORS; LUNG-FUNCTION; ENDOTRACHEAL INTUBATION; MATERNAL SMOKING; YOUNG-CHILDREN; HOSPITALIZED INFANTS AB OBJECTIVE: To identify factors associated with continuous positive airway pressure (CPAP) and/or intubation for children with bronchiolitis. METHODS: We performed a 16-center, prospective cohort study of hospitalized children aged <2 years with bronchiolitis. For 3 consecutive years from November 1 until March 31, beginning in 2007, researchers collected clinical data and a nasopharyngeal aspirate from study participants. We oversampled children from the ICU. Samples of nasopharyngeal aspirate were tested by polymerase chain reaction for 18 pathogens. RESULTS: There were 161 children who required CPAP and/or intubation. The median age of the overall cohort was 4 months; 59% were male; 61% white, 24% black, and 36% Hispanic. In the multivariable model predicting CPAP/intubation, the significant factors were: age <2 months (odds ratio [OR] 4.3; 95% confidence interval [CI] 1.7-11.5), maternal smoking during pregnancy (OR 1.4; 95% CI 1.1-1.9), birth weight <5 pounds (OR 1.7; 95% CI 1.0-2.6), breathing difficulty began <1 day before admission (OR 1.6; 95% CI 1.2-2.1), presence of apnea (OR 4.8; 95% CI 2.5-8.5), inadequate oral intake (OR 2.5; 95% CI 1.3-4.3), severe retractions (OR 11.1; 95% CI 2.4-33.0), and room air oxygen saturation <85% (OR 3.3; 95% CI 2.0-4.8). The optimism-corrected c-statistic for the final model was 0.80. CONCLUSIONS: In this multicenter study of children hospitalized with bronchiolitis, we identified several demographic, historical, and clinical factors that predicted the use of CPAP and/or intubation, including children born to mothers who smoked during pregnancy. We also identified a novel subgroup of children who required mechanical respiratory support <1 day after respiratory symptoms began. Pediatrics 2012;130:e492-e500 C1 [Mansbach, Jonathan M.] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Med, Boston, MA 02115 USA. [Piedra, Pedro A.] Baylor Coll Med, Dept Mol Virol, Houston, TX 77030 USA. [Piedra, Pedro A.] Baylor Coll Med, Dept Microbiol, Houston, TX 77030 USA. [Piedra, Pedro A.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Stevenson, Michelle D.] Univ Louisville, Kosair Childrens Hosp, Dept Pediat, Louisville, KY 40292 USA. [Sullivan, Ashley F.; Forgey, Tate F.; Espinola, Janice A.; Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Clark, Sunday] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. RP Mansbach, JM (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Med, 300 Longwood Ave,Main Clin Bldg 9 S,9157, Boston, MA 02115 USA. EM jonathan.mansbach@childrens.harvard.edu FU National Institutes of Health (Bethesda, MD) [U01 AI-67693, K23 AI-77801]; National Institutes of Health (NIH) FX This study was supported by the grants U01 AI-67693 and K23 AI-77801 from the National Institutes of Health (Bethesda, MD). The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health. Funded by the National Institutes of Health (NIH). NR 67 TC 34 Z9 37 U1 0 U2 9 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD SEP PY 2012 VL 130 IS 3 BP E492 EP E500 DI 10.1542/peds.2012-0444 PG 9 WC Pediatrics SC Pediatrics GA 014XO UT WOS:000309409300004 PM 22869823 ER PT J AU Lau, KS Cortez-Retamozo, V Philips, SR Pittet, MJ Lauffenburger, DA Haigis, KM AF Lau, Ken S. Cortez-Retamozo, Virna Philips, Sarah R. Pittet, Mikael J. Lauffenburger, Douglas A. Haigis, Kevin M. TI Multi-Scale In Vivo Systems Analysis Reveals the Influence of Immune Cells on TNF-alpha-Induced Apoptosis in the Intestinal Epithelium SO PLOS BIOLOGY LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; PLASMACYTOID DENDRITIC CELLS; MONOCYTE-CHEMOATTRACTANT PROTEIN-1; INNATE LYMPHOID-CELLS; CCR2 EXPRESSION; GOBLET CELLS; COLITIS; CYTOKINES; MUCOSA; MICE AB Intestinal epithelial cells exist within a complex environment that affects how they interpret and respond to stimuli. We have applied a multi-scale in vivo systems approach to understand how intestinal immune cells communicate with epithelial cells to regulate responses to inflammatory signals. Multivariate modeling analysis of a large dataset composed of phospho-signals, cytokines, and immune cell populations within the intestine revealed an intimate relationship between immune cells and the epithelial response to TNF-alpha. Ablation of lymphocytes in the intestine prompted a decrease in the expression of MCP-1, which in turn increased the steady state number of intestinal plasmacytoid dendritic cells (pDCs). This change in the immune compartment affected the intestinal cytokine milieu and subsequent epithelial cell signaling network, with cells becoming hypersensitive to TNF-alpha-induced apoptosis in a way that could be predicted by mathematical modeling. In summary, we have uncovered a novel cellular network that regulates the response of intestinal epithelial cells to inflammatory stimuli in an in vivo setting. C1 [Lau, Ken S.; Philips, Sarah R.; Haigis, Kevin M.] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA. [Lau, Ken S.; Philips, Sarah R.; Haigis, Kevin M.] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA USA. [Lau, Ken S.; Cortez-Retamozo, Virna; Philips, Sarah R.; Pittet, Mikael J.; Haigis, Kevin M.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Lau, Ken S.; Haigis, Kevin M.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Lau, Ken S.; Lauffenburger, Douglas A.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Lau, Ken S.; Lauffenburger, Douglas A.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. RP Lau, KS (reprint author), Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA. EM khaigis@partners.org OI Lau, Ken/0000-0001-8438-0319 FU National Institute of General Medical Sciences [R01-GM088827]; National Cancer Institute [U54-CA112967] FX This work was supported by grants from the National Institute of General Medical Sciences (R01-GM088827 to K. M. H., D. A. L.) and the National Cancer Institute (U54-CA112967 to D. A. L.). K. S. L. is a Robert Black Fellow of the Damon Runyon Cancer Research Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 44 TC 21 Z9 22 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1545-7885 J9 PLOS BIOL JI PLoS. Biol. PD SEP PY 2012 VL 10 IS 9 AR e1001393 DI 10.1371/journal.pbio.1001393 PG 14 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 016LO UT WOS:000309520100006 PM 23055830 ER PT J AU Curtin, HD AF Curtin, Hugh D. TI Posttreatment CT and MR Imaging in Head and Neck Cancer: What the Radiologist Needs to Know Commentary SO RADIOGRAPHICS LA English DT Editorial Material C1 Harvard Univ, Sch Med, Dept Radiol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. RP Curtin, HD (reprint author), Harvard Univ, Sch Med, Dept Radiol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. NR 1 TC 0 Z9 0 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 SEP-OCT PY 2012 VL 32 IS 5 BP 1282 EP 1284 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 003SZ UT WOS:000308632900005 ER PT J AU Kobayashi, K Bhargava, P Raja, S Nasseri, F Al-Balas, HA Smith, DD George, SP Vij, MS AF Kobayashi, Katsuhiro Bhargava, Peeyush Raja, Shanker Nasseri, Farbod Al-Balas, Hassan A. Smith, Darryl D. George, Sharad P. Vij, Meena S. TI Image-guided Biopsy: What the Interventional Radiologist Needs to Know about PET/CT SO RADIOGRAPHICS LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; FDG UPTAKE; INTRATUMORAL DISTRIBUTION; CANCER-CELLS; ELECTROMAGNETIC TRACKING; INDETERMINATE BIOPSY; METABOLIC BIOPSY; LESIONS; SPECTRUM; FLUORINE-18-FLUORODEOXYGLUCOSE AB Positron emission tomography (PET)/computed tomography (CT) with fluorine 18 fluorodeoxyglucose (FDG) is increasingly used in evaluation of oncology patients. Because PET/CT can demonstrate malignancy before morphologic changes are evident, application of PET/CT information to image-guided biopsy can facilitate early histologic diagnosis and staging. However, because FDG uptake is not specific to cancer, PET/CT findings may raise questions about whether uptake in a lesion is an indication for biopsy. To properly select patients for image-guided biopsy, interventional radiologists should be familiar with the biologic significance of FDG uptake and various causes of false-positive uptake. PET/CT images may also become a source of confusion in the interpretation of biopsy results. Various causes of false-positive and false-negative FDG uptake need to be considered, especially when there is a discrepancy between biopsy results and PET/CT findings. False-negative FDG uptake can result from cancers that are too small to be observed or not FDG avid. False-positive FDG uptake can be due to underlying inflammation from recent treatment. Conversely, complete resolution of FDG uptake in a treated lesion does not necessarily indicate absence of viable cells. When questions about PET/CT findings arise in the context of image-guided biopsy, discussion with experienced nuclear imaging physicians is essential. (C)RSNA, 2012 . radiographics.rsna.org C1 [Kobayashi, Katsuhiro; Al-Balas, Hassan A.; Smith, Darryl D.; Vij, Meena S.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Sect Radiol, Unit 114, Houston, TX 77030 USA. [Nasseri, Farbod] Baylor Coll Med, Dept Radiol, Houston, TX 77030 USA. RP Kobayashi, K (reprint author), Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Sect Radiol, Unit 114, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM Katsuhiro.Kobayashi@va.gov NR 34 TC 22 Z9 22 U1 0 U2 1 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 SEP-OCT PY 2012 VL 32 IS 5 BP 1483 EP 1501 DI 10.1148/rg.325115159 PG 19 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 003SZ UT WOS:000308632900023 PM 22977031 ER PT J AU Drukteinis, JS Gombos, EC Raza, S Chikarmane, SA Swami, A Birdwell, RL AF Drukteinis, Jennifer S. Gombos, Eva C. Raza, Sughra Chikarmane, Sona A. Swami, Arpita Birdwell, Robyn L. TI Fat Necrosis: BI-RADS 2 or 3? respond SO RADIOGRAPHICS LA English DT Letter ID BREAST-CONSERVATION THERAPY C1 [Drukteinis, Jennifer S.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Gombos, Eva C.; Raza, Sughra; Chikarmane, Sona A.; Swami, Arpita; Birdwell, Robyn L.] Brigham & Womens Hosp, Dept Radiol, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Drukteinis, JS (reprint author), H Lee Moffitt Canc Ctr & Res Inst, 12902 Magnolia Dr, Tampa, FL 33612 USA. EM jennifer.drukteinis@moffitt.org NR 5 TC 0 Z9 0 U1 0 U2 3 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 SEP-OCT PY 2012 VL 32 IS 5 BP 1562 EP 1562 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 003SZ UT WOS:000308632900032 ER PT J AU Sharma, A Abtin, F Shepard, JAO AF Sharma, Amita Abtin, Fereidoun Shepard, Jo-Anne O. TI Image-Guided Ablative Therapies for Lung Cancer SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article DE Ablation; Radiofrequency ablation; Cryoablation; Microwave ablation; Lung tumors; Thoracic; Lung cancer; Treatment; Image-guided ID PERCUTANEOUS RADIOFREQUENCY ABLATION; PULMONARY MALIGNANT-TUMORS; POSITIVE AIRWAY PRESSURE; MICROWAVE ABLATION; THERMAL ABLATION; TISSUE ABLATION; RABBIT LUNG; IN-VIVO; NONSURGICAL CANDIDATES; INITIAL-EXPERIENCE AB Lung cancer is the commonest cause of cancer death in adults. Although the treatment of choice is surgical resection with lobectomy, many patients are nonsurgical candidates because of medical comorbidities. Patients may also have recurrent disease after resection or radiotherapy and some patients refuse surgical options. Image-guided ablation has been recently introduced as a safe, alternative treatment of localized disease in carefully selected patients. This article discusses the principles, technique, and follow-up of the 3 main ablative therapies currently used in the lung, radiofrequency ablation, microwave ablation, and percutaneous cryotherapy. C1 [Sharma, Amita; Shepard, Jo-Anne O.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Abtin, Fereidoun] Univ Calif Los Angeles, Med Ctr, Dept Radiol, Los Angeles, CA 90095 USA. RP Shepard, JAO (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM jshepard@partners.org NR 92 TC 11 Z9 11 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD SEP PY 2012 VL 50 IS 5 BP 975 EP + DI 10.1016/j.rcl.2012.06.004 PG 26 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 016CV UT WOS:000309495800009 PM 22974782 ER PT J AU Liapakis, IE Paschalis, EI Vrentzos, NP AF Liapakis, Ioannis E. Paschalis, Eleftherios I. Vrentzos, Nikolaos P. TI SECONDARY RHINOPLASTY FIXATIONS WITH HYALURONIC ACID SO WOUND REPAIR AND REGENERATION LA English DT Meeting Abstract C1 [Liapakis, Ioannis E.; Vrentzos, Nikolaos P.] Therissos, OpsisClin Plast & Reconstruct Surg, Iraklion, Crete, Greece. [Paschalis, Eleftherios I.] Harvard Univ, Massachusetts Eye & Ear Infirm, Boston, MA 02114 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 1067-1927 J9 WOUND REPAIR REGEN JI Wound Repair Regen. PD SEP-OCT PY 2012 VL 20 IS 5 BP A100 EP A100 PG 1 WC Cell Biology; Dermatology; Medicine, Research & Experimental; Surgery SC Cell Biology; Dermatology; Research & Experimental Medicine; Surgery GA 008GI UT WOS:000308945000179 ER PT J AU Peck, JS Benneyan, JC Nightingale, DJ Gaehde, SA AF Peck, Jordan S. Benneyan, James C. Nightingale, Deborah J. Gaehde, Stephan A. TI Predicting Emergency Department Inpatient Admissions to Improve Same-day Patient Flow SO ACADEMIC EMERGENCY MEDICINE LA English DT Article ID AMBULANCE DIVERSION; ADMITTED PATIENTS AB ACADEMIC EMERGENCY MEDICINE 2012; 19:10451054 (C) 2012 by the Society for Academic Emergency Medicine Abstract Objectives: The objectives were to evaluate three models that use information gathered during triage to predict, in real time, the number of emergency department (ED) patients who subsequently will be admitted to a hospital inpatient unit (IU) and to introduce a new methodology for implementing these predictions in the hospital setting. Methods: Three simple methods were compared for predicting hospital admission at ED triage: expert opinion, naive Bayes conditional probability, and a generalized linear regression model with a logit link function (logit-linear). Two months of data were gathered from the Boston VA Healthcare Systems 13-bed ED, which receives approximately 1,100 patients per month. Triage nurses were asked to estimate the likelihood that each of 767 triaged patients from that 2-month period would be admitted after their ED treatment, by placing them into one of six categories ranging from low to high likelihood. Logit-linear regression and naive Bayes models also were developed using retrospective data and used to estimate admission probabilities for each patient who entered the ED within a 2-month time frame, during triage hours (1,160 patients). Predictors considered included patient age, primary complaint, provider, designation (ED or fast track), arrival mode, and urgency level (emergency severity index assigned at triage). Results: Of the three methods considered, logit-linear regression performed the best in predicting total bed need, with a receiver operating characteristic (ROC) area under the curve (AUC) of 0.887, an R2 of 0.58, an average estimation error of 0.19 beds per day, and on average roughly 3.5 hours before peak demand occurred. Significant predictors were patient age, primary complaint, bed type designation, and arrival mode (p < 0.0001 for all factors). The naive Bayesian model had similar positive predictive value, with an AUC of 0.841 and an R2 of 0.58, but with average difference in total bed need of approximately 2.08 per day. Triage nurse expert opinion also had some predictive capability, with an R2 of 0.52 and an average difference in total bed need of 1.87 per day. Conclusions: Simple probability models can reasonably predict ED-to-IU patient volumes based on basic data gathered at triage. This predictive information could be used for improved real-time bed management, patient flow, and discharge processes. Both statistical models were reasonably accurate, using only a minimal number of readily available independent variables. C1 [Peck, Jordan S.; Benneyan, James C.] New England Vet Engn Resource Ctr, Boston, MA USA. [Gaehde, Stephan A.] Boston VA Healthcare Syst, Emergency Med Serv, Boston, MA USA. [Peck, Jordan S.; Nightingale, Deborah J.] MIT, Engn Syst Div, Cambridge, MA 02139 USA. [Benneyan, James C.] Northeastern Univ, Healthcare Syst Engn Inst, Boston, MA 02115 USA. RP Peck, JS (reprint author), New England Vet Engn Resource Ctr, Boston, MA USA. EM jspeck@mit.edu FU Department of Veterans Affairs through the Veterans Integrated Service Network 1 (New England) Veterans Engineering Resource Center; VA Office of Systems Redesign FX This research was supported by the Department of Veterans Affairs through the Veterans Integrated Service Network 1 (New England) Veterans Engineering Resource Center and the VA Office of Systems Redesign. Any views expressed herein represent those of the authors and do not necessarily reflect those of the Veterans Health Administration. The authors have no potential conflicts of interest to disclose. NR 29 TC 12 Z9 12 U1 0 U2 20 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD SEP PY 2012 VL 19 IS 9 BP E1045 EP E1054 DI 10.1111/j.1553-2712.2012.01435.x PG 10 WC Emergency Medicine SC Emergency Medicine GA 007EQ UT WOS:000308872000007 PM 22978731 ER PT J AU Sorensen, PM Iacob, RE Fritzsche, M Engen, JR Brieher, WM Charras, G Eggert, US AF Soerensen, Pia M. Iacob, Roxana E. Fritzsche, Marco Engen, John R. Brieher, William M. Charras, Guillaume Eggert, Ulrike S. TI The Natural Product Cucurbitacin E Inhibits Depolymerization of Actin Filaments SO ACS CHEMICAL BIOLOGY LA English DT Article ID F-ACTIN; HEAVY-MEROMYOSIN; BINDING; POLYMERIZATION; ORGANIZATION; CYTOSKELETON; CYTOKINESIS; PHALLOIDIN; PROTEINS; DYNAMICS AB Although small molecule actin modulators have been widely used as research tools, only one cell-permeable small molecule inhibitor of actin depolymerization (jasplakinolide) is commercially available. We report that the natural product cucurbitacin E inhibits actin depolymerization and show that its mechanism of action is different from jasplakinolide. In assays using pure fluorescently labeled actin, cucurbitacin E specifically affects depolymerization without affecting polymerization. It inhibits actin depolymerization at substoichiometric concentrations up to 1:6 cucurbitacin E:actin. Cucurbitacin E specifically binds to filamentous actin (F-actin) forming a covalent bond at residue Cys257, but not to monomeric actin (G-actin). On the basis of its compatibility with phalloidin staining, we show that cucurbitacin E occupies a different binding site on actin filaments. Using loss of fluorescence after localized photoactivation, we found that cucurbitacin E inhibits actin depolymerization in live cells. Cucurbitacin E is a widely available plant-derived natural product, making it a useful tool to study actin dynamics in cells and actin-based processes such as cytokinesis. C1 [Soerensen, Pia M.; Eggert, Ulrike S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Soerensen, Pia M.; Eggert, Ulrike S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Iacob, Roxana E.; Engen, John R.] Northeastern Univ, Dept Chem & Chem Biol, Boston, MA 02115 USA. [Fritzsche, Marco; Charras, Guillaume] UCL, London Ctr Nanotechnol, London, England. [Fritzsche, Marco] UCL, Dept Phys & Astron, London, England. [Brieher, William M.] Univ Illinois, Dept Cell & Dev Biol, Urbana, IL 61801 USA. [Charras, Guillaume] UCL, Dept Cell & Dev Biol, London, England. [Eggert, Ulrike S.] Kings Coll London, Dept Chem, London WC2R 2LS, England. [Eggert, Ulrike S.] Kings Coll London, Randall Div Cell & Mol Biophys, London WC2R 2LS, England. RP Eggert, US (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM ulrike.eggert@kcl.ac.uk RI Charras, Guillaume/F-8571-2014 OI Charras, Guillaume/0000-0002-7902-0279 FU NIH [R01 GM082834, R01 GM086507]; Harvard Chemical Biology PhD program; Dana-Farber Cancer Institute; Human Frontier Science Program; UCL Comprehensive Biomedical Research Centre FX We thank the staff at the Nikon Imaging Center at Harvard Medical School for assistance and H. Y. Kueh and T. Mitchison for helpful discussions. Cucurbitacin F was originally isolated from plant extracts by K. Maloney and M. Fujita in J. Clardy's lab. P.M.S. and U.S.E. were supported by NIH grant R01 GM082834, the Harvard Chemical Biology PhD program, and the Dana-Farber Cancer Institute. R.E.I. and J.R.E. acknowledge NIH grant R01 GM086507 and a research collaboration with the Waters Corporation. G.C. and M.F. gratefully acknowledge funding from the Human Frontier Science Program through a Young Investigator grant to G.C. and the UCL Comprehensive Biomedical Research Centre for generous funding of microscopy equipment. G.C. is a Royal Society University Research Fellow. NR 34 TC 19 Z9 21 U1 0 U2 27 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1554-8929 J9 ACS CHEM BIOL JI ACS Chem. Biol. PD SEP PY 2012 VL 7 IS 9 BP 1502 EP 1508 DI 10.1021/cb300254s PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 010NA UT WOS:000309099900005 PM 22724897 ER PT J AU McLellan, CA Whitesell, L King, OD Lancaster, AK Mazitschek, R Lindquist, S AF McLellan, Catherine A. Whitesell, Luke King, Oliver D. Lancaster, Alex K. Mazitschek, Ralph Lindquist, Susan TI Inhibiting GPI Anchor Biosynthesis in Fungi Stresses the Endoplasmic Reticulum and Enhances Immunogenicity SO ACS CHEMICAL BIOLOGY LA English DT Article ID UNFOLDED PROTEIN RESPONSE; BROAD-SPECTRUM ANTIFUNGAL; CANDIDA-ALBICANS; SACCHAROMYCES-CEREVISIAE; INOSITOL ACYLATION; DRUG-RESISTANCE; YEAST; E1210; LOCALIZATION; MECHANISM AB In fungi, the anchoring of proteins to the plasma membrane via their covalent attachment to glycosylphosphatidylinositol (GPI) is essential and thus provides a valuable point of attack for the development of antifungal therapeutics. Unfortunately, studying the underlying biology of GPI-anchor synthesis is difficult, especially in medically relevant fungal pathogens because they are not genetically tractable. Compounding difficulties, many of the genes in this pathway are essential in Saccharomyces cerevisiae. Here, we report the discovery of a new small molecule christened gepinacin (for GPI acylation inhibitor) which selectively inhibits Gwt1, a critical acyltransferase required for the biosynthesis of fungal GPI anchors. After delineating the target specificity of gepinacin using genetic and biochemical techniques, we used it to probe key, therapeutically relevant consequences of disrupting GPI anchor metabolism in fungi. We found that, unlike all three major classes of antifungals in current use, the direct antimicrobial activity of this compound results predominantly from its ability to induce overwhelming stress to the endoplasmic reticulum. Gepinacin did not affect the viability of mammalian cells nor did it inhibit their orthologous acyltransferase. This enabled its use in co-culture experiments to examine Gwt1's effects on host-pathogen interactions. In isolates of Candida albicans, the most common fungal pathogen in humans, exposure to gepinacin at sublethal concentrations impaired filamentation and unmasked cell wall beta-glucan to stimulate a pro-inflammatory cytokine response in macrophages. Gwt1 is a promising antifungal drug target, and gepanacin is a useful probe for studying how disrupting GPI-anchor synthesis impairs viability and alters host-pathogen interactions in genetically intractable fungi. C1 [McLellan, Catherine A.; Whitesell, Luke; Lancaster, Alex K.; Lindquist, Susan] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [McLellan, Catherine A.; Lindquist, Susan] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA. [Lindquist, Susan] MIT, Dept Biol, Cambridge, MA 02139 USA. [King, Oliver D.] Boston Biomed Res Inst, Watertown, MA 02472 USA. [Mazitschek, Ralph] Massachusetts Gen Hosp, Richard B Simches Res Ctr, Ctr Syst Biol, Boston, MA 02114 USA. RP Lindquist, S (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. EM Lindquist_admin@wi.mit.edu RI Mazitschek, Ralph/E-3741-2013; Lancaster, Alex/K-2855-2013 OI Mazitschek, Ralph/0000-0002-1105-689X; Lancaster, Alex/0000-0002-0002-9263 FU Howard Hughes Medical Institute FX We thank S. Agarwala for help with filamentation assays and V. Vyas for advice on beta-glucan and TNF alpha assays. D. Tardiff, L. Cowen, B. Vincent, and P. Auluck provided advice on manuscript preparation. This work was supported by the Howard Hughes Medical Institute. NR 41 TC 21 Z9 22 U1 1 U2 13 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1554-8929 EI 1554-8937 J9 ACS CHEM BIOL JI ACS Chem. Biol. PD SEP PY 2012 VL 7 IS 9 BP 1520 EP 1528 DI 10.1021/cb300235m PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 010NA UT WOS:000309099900008 PM 22724584 ER PT J AU Tracy, JJ Lombardo, TW Bentley, JP AF Tracy, Josie J. Lombardo, Thomas W. Bentley, John P. TI A Smoker Identity Measure for Experimental, Intermittent, and Daily College Student Smokers SO AMERICAN JOURNAL OF HEALTH PROMOTION LA English DT Article DE College Students; Smoker Identity; Cigarette Smoking; Light and Intermittent Smokers; Experimental Smokers; Scale Development; Psychometrics; Prevention Research ID BEHAVIOR SURVEY QUESTIONNAIRE; SMOKING-CESSATION; PLANNED BEHAVIOR; EXTENDED VERSION; SOCIAL-INFLUENCE; RISK BEHAVIOR; UNITED-STATES; SELF-IDENTITY; QUIT SMOKING; NICOTINE DEPENDENCE AB Purpose. To provide initial tests of internal consistency reliability, and both structural and concurrent validity of a smoker identity (SI) scale for college student populations. Design. Cross-sectional design. Setting. Midsouth university. Participants. Undergraduates in a random sample of university classes completed surveys (92.3% response rate). Method. items derived from a literature review and clinical expertise, lifetime and current tobacco use, cigarette purchasing patterns, and quitting variables. Analysis. Current (some days or eve?), day) cigarette users (n = 362) were divided into daily, intermittent, and experimental smoker groups. After principal components analysis was conducted on the SI items, analysis of variance (ANOVA) was used to assess SI differentiation of smoker groups, and correlational analysis or ANOVA was used to assess SI relationships with smoking and quitting variables. Results. Eight SI items produced a high-internal-consistency, single-factor structure (alpha = .93) and clearly differentiated the three smoker groups. Higher SI scores indicated greater smoking rate, smoking within 30 minutes of awakening, larger purchased quantities, and both greater interest and lower confidence in quitting. Conclusions. The scale demonstrated good reliability and validity. Other SI measures exist, but this is the first scale to establish utility with experimental and intermittent smokers-substantial groups among college students. The extent to which cigarette users identify as smokers may provide useful information beyond behavioral measures, especially among college students. (Am J Health Promot 2012;27[1]:55-62.) C1 [Tracy, Josie J.] Dept Vet Affairs Med Ctr, Portland, OR USA. [Tracy, Josie J.; Lombardo, Thomas W.] Univ Mississippi, Dept Psychol, University, MS 38677 USA. [Bentley, John P.] Univ Mississippi, Dept Pharm Adm, University, MS 38677 USA. RP Tracy, JJ (reprint author), Portland VA Med Ctr, 3710 SW US Vet Hosp Rd,POB 1035,V3SATP, Portland, OR 97207 USA. EM josie.tracy@va.gov NR 52 TC 3 Z9 3 U1 2 U2 26 PU AMER JOURNAL HEALTH PROMOTION INC PI TROY PA PO BOX 1254, TROY, MI 48099-1254 USA SN 0890-1171 J9 AM J HEALTH PROMOT JI Am. J. Health Promot. PD SEP-OCT PY 2012 VL 27 IS 1 BP 55 EP 62 DI 10.4278/ajhp.110401-QUAN-146 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 004MI UT WOS:000308685400010 PM 22950927 ER PT J AU Wu, X Yu, T Bullard, DC Kucik, DF AF Wu, Xing Yu, Tao Bullard, Daniel C. Kucik, Dennis F. TI SDF-1 alpha (CXCL12) regulation of lateral mobility contributes to activation of LFA-1 adhesion SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE chemokines; integrins; avidity; lateral mobility; single particle tracking ID INTEGRIN AFFINITY; AVIDITY REGULATION; FLOW; CELLS; CHEMOKINES; MOVEMENTS; MIGRATION; ICAM-1 AB Wu X, Yu T, Bullard DC, Kucik DF. SDF-1 alpha (CXCL12) regulation of lateral mobility contributes to activation of LFA-1 adhesion. Am J Physiol Cell Physiol 303: C666-C672, 2012. First published August 8, 2012; doi:10.1152/ajpcell.00190.2012.-Regulation of integrin activity enables leukocytes to circulate freely, avoiding inappropriate adhesion while maintaining the ability to adhere quickly at sites of infection or inflammation. This regulation involves at least two components: affinity for ligand and affinity-independent avidity effects such as lateral mobility. Using lymphocyte function associated antigen-1 (LFA-1) as a model, we investigated the role of integrin release from cytoskeletal motion constraints in response to the chemokine stromal cell-derived factor-1 (SDF-1 alpha) in this process. All experiments were done in primary T cells to avoid nonphysiological activation processes often seen with the use of cell lines. We found that SDF-1 alpha releases LFA-1 from cytoskeletal constraints as effectively as does cytochalasin D. The resultant increased diffusion is correlated with a robust increase in LFA-1-mediated adhesion under physiological shear stress. We further investigated the role of the highly conserved GFFKR sequence in the LFA-1 cytoplasmic domain. We report that the GFFKR sequence is both necessary and sufficient for regulation of the SDF-1 alpha-triggered proadhesive release from cytoskeleton interactions. While this does not address the role of transient SDF-1 alpha-induced conformational changes in the activation process, these results strongly suggest that any model of chemokine-induced LFA-1 activation must take into account chemokine-induced integrin lateral mobility. In addition, these results have ramifications for models of differential binding of LFA-1 to surface-bound vs. soluble intercellular adhesion molecule-1. C1 [Wu, Xing; Yu, Tao; Kucik, Dennis F.] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Bullard, Daniel C.] Univ Alabama Birmingham, Dept Genet, Birmingham, AL 35294 USA. [Kucik, Dennis F.] Univ Alabama Birmingham, Dept Biomed Engn, Birmingham, AL 35294 USA. [Kucik, Dennis F.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Kucik, DF (reprint author), Univ Alabama Birmingham, Dept Pathol, Kaul Bldg,Rm 640A,619 S 19th St, Birmingham, AL 35294 USA. EM kucik@uab.edu FU Department of Veterans Affairs Merit Award FX This work was supported by a Department of Veterans Affairs Merit Award. NR 22 TC 4 Z9 4 U1 0 U2 2 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 SEP PY 2012 VL 303 IS 6 BP C666 EP C672 DI 10.1152/ajpcell.00190.2012 PG 7 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 012RU UT WOS:000309255000010 PM 22875786 ER PT J AU Stubbs, ND Geraci, SA Stephenson, PL Jones, DB Sanders, S AF Stubbs, Nancy D. Geraci, Stephen A. Stephenson, Priscilla L. Jones, Dianne B. Sanders, Suzanne TI Methods to Reduce Outpatient Non-attendance SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Review DE Mail reminders; Telephone reminders; Text message reminders; Short message service reminders; Non-attendance ID RANDOMIZED CONTROLLED-TRIAL; TEXTING APPOINTMENT REMINDERS; ACCESS SCHEDULING SYSTEM; PRIMARY-CARE; TELEPHONE REMINDERS; INCREASE ATTENDANCE; IMPROVE ATTENDANCE; SMS REMINDERS; HEALTH-CARE; SHOW RATES AB Non-attendance reduces clinic and provider productivity and efficiency, compromises access and increases cost of health care. This systematic review of the English language literature (November 1999-November 2009) compares telephone, mail, text/short message service, electronic mail and open-access scheduling to determine which is best at reducing outpatient non-attendance and providing net financial benefit. Telephone, mail and text/short message service interventions all improved attendance modestly but at varying costs. Text messaging was the most cost-effective of the 3, but its applicability may be limited. Few data are available regarding electronic mail reminders, whereas open-access scheduling is an area of active research. C1 [Sanders, Suzanne] GV Sonny Montgomery Vet Affairs Med Ctr, Med Serv, Jackson, MS USA. [Jones, Dianne B.] GV Sonny Montgomery Vet Affairs Med Ctr, Lib Serv, Jackson, MS USA. [Geraci, Stephen A.; Sanders, Suzanne] Univ Mississippi, Div Rheumatol, Dept Med, Sch Med, Jackson, MS 39216 USA. [Stephenson, Priscilla L.] Philadelphia Vet Affairs Med Ctr, Lib Serv, Philadelphia, PA USA. RP Sanders, S (reprint author), Med Serv 111, 1500 E Woodrow Wilson Dr, Jackson, MS 39216 USA. EM Suzanne.Sanders@va.gov NR 57 TC 17 Z9 19 U1 0 U2 21 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD SEP PY 2012 VL 344 IS 3 BP 211 EP 219 DI 10.1097/MAJ.0b013e31824997c6 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 003LQ UT WOS:000308613400009 PM 22475731 ER PT J AU Badrane, H Nguyen, MH Blankenship, JR Cheng, SJ Hao, BH Mitchell, AP Clancy, CJ AF Badrane, Hassan Nguyen, M. Hong Blankenship, Jill R. Cheng, Shaoji Hao, Binghua Mitchell, Aaron P. Clancy, Cornelius J. TI Rapid Redistribution of Phosphatidylinositol-(4,5)-Bisphosphate and Septins during the Candida albicans Response to Caspofungin SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID WALL DAMAGE RESPONSE; CELL-WALL; SACCHAROMYCES-CEREVISIAE; HYPHAL FORMATION; BUDDING YEAST; INVASIVE GROWTH; GENE DISRUPTION; VIRULENCE; PROTEINS; KINASE AB We previously showed that phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P2] and septin regulation play major roles in maintaining Candida albicans cell wall integrity in response to caspofungin and other stressors. Here, we establish a link between P1(4,5)P2 signaling and septin localization and demonstrate that rapid redistribution of PI(4,5)P2 and septins is part of the natural response of C. albicans to caspofungin. First, we studied caspofungin-hypersusceptible C. albicans irs4 and inp51 mutants, which have elevated PI(4,5)P2 levels due to loss of PI(4,5)P2-specific 5'-phosphatase activity. PI(4,5)P2 accumulated in discrete patches, rather than uniformly, along surfaces of mutants in yeast and filamentous morphologies, as visualized with a green fluorescent protein (GFP)-pleckstrin homology domain. The patches also contained chitin (calcofluor white staining) and cell wall protein Rbt5 (Rbt5-GFP). By transmission electron microscopy, patches corresponded to plasma membrane invaginations that incorporated cell wall material. Fluorescently tagged septins Cdc10 and Sep7 colocalized to these sites, consistent with well-described PI(4,5)P2-septin physical interactions. Based on expression patterns of cell wall damage response genes, irs4 and inp51 mutants were firmly positioned within a group of caspofungin-hypersusceptible, septin-regulatory protein kinase mutants. irs4 and inp51 were linked most closely to the gin4 mutant by expression profiling, PI(4,5)P2-septin-chitin redistribution and other phenotypes. Finally, sublethal 5-min exposure of wild-type C. albicans to caspofungin resulted in redistribution of P1(4,5)P2 and septins in a manner similar to those of irs4, inp51, and gin4 mutants. Taken together, our data suggest that the C. albicans Irs4-Inp51 5'-phosphatase complex and Gin4 function upstream of PI(4,5)P2 and septins in a pathway that helps govern responses to caspofungin. C1 [Badrane, Hassan; Nguyen, M. Hong; Cheng, Shaoji; Hao, Binghua; Clancy, Cornelius J.] Univ Pittsburgh, Dept Med, Div Infect Dis, Pittsburgh, PA 15260 USA. [Blankenship, Jill R.; Mitchell, Aaron P.] Carnegie Mellon Univ, Dept Biol Sci, Pittsburgh, PA 15213 USA. [Clancy, Cornelius J.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Clancy, CJ (reprint author), Univ Pittsburgh, Dept Med, Div Infect Dis, Pittsburgh, PA 15260 USA. EM cjc76@pitt.edu OI Mitchell, Aaron/0000-0002-0868-4000 FU US Department of Veterans Affairs; National Institutes of Health [R56DE020831] FX This project was funded in part by grant support from the US Department of Veterans Affairs (Merit Review to C. J. Clancy) and the National Institutes of Health (R56DE020831 to C. J. Clancy). NR 61 TC 13 Z9 22 U1 0 U2 5 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 SEP PY 2012 VL 56 IS 9 BP 4614 EP 4624 DI 10.1128/AAC.00112-12 PG 11 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 994CN UT WOS:000307908600006 PM 22687514 ER PT J AU Shrestha, A Hamblin, MR Kishere, A AF Shrestha, Annie Hamblin, Michael R. Kishere, Anil TI Characterization of a Conjugate between Rose Bengal and Chitosan for Targeted Antibiofilm and Tissue Stabilization Effects as a Potential Treatment of Infected Dentin SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID PHOTODYNAMIC THERAPY; CROSS-LINKING; ENTEROCOCCUS-FAECALIS; DRUG-DELIVERY; IN-VITRO; COLLAGEN; CELLS; PHOTOSENSITIZERS; DISINFECTION; CANALS AB Bacterial biofilms and dentin structural changes are some of the major challenges in the management of infected dentin tissue. This study characterized a photosensitizer-conjugated chitosan with enhanced photodynamic efficacy against dental biofilms, as well as the ability to reinforce the postinfected dentin matrix in order to improve its mechanical and chemical stability. Rose Bengal-conjugated chitosan (CSRB) was synthesized using a chemical cross-linking method and characterized for photophysical, photobiological, and cytotoxicity properties. Its potential as an antibacterial and matrix-reinforcing agent on dentin collagen was also evaluated. Enterococcus faecalis as planktonic and in vitro biofilms was treated with CSRB and photodynamically activated with 5 to 60 J/cm(2) green light. Dentin collagen was used for the CSRB cross-linking experiments and evaluated for chemical changes, resistance to enzymatic degradation, and mechanical properties. CSRB was a photosensitizer with efficient singlet oxygen yield. In vitro photoactivation gave higher fibroblast cell survival than did RB alone. CSRB showed significant antibiofilm photoinactivation (P < 0.01). The CSRB-cross-linked dentin collagen showed higher resistance to collagenase degradation and superior mechanical properties (P < 0.05). In summary, the photoactivated CSRB particles synthesized in this study may be a synergistic multifunctional treatment approach with lower cytotoxicity and effective antibiofilm activity as well as the ability to reinforce the dentin collagen to enhance resistance to degradation and improve mechanical properties. This may be a targeted treatment strategy to deal with infected dentin hard tissues in a clinical scenario, where both disinfection and structural integrity need to be addressed concomitantly. C1 [Shrestha, Annie; Kishere, Anil] Univ Toronto, Dent Res Inst, Fac Dent, Discipline Endodont, Toronto, ON, Canada. [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 Kishere, A (reprint author), Univ Toronto, Dent Res Inst, Fac Dent, Discipline Endodont, Toronto, ON, Canada. EM anil.kishen@dentistry.utoronto.ca OI Hamblin, Michael/0000-0001-6431-4605 FU University of Toronto; Canadian Foundation of Innovation; CIHR Training Fellowship [TGF-53877]; U.S. NIH [R01A1050875] FX Funding from the University of Toronto and the Canadian Foundation of Innovation and a CIHR Training Fellowship, TGF-53877, are gratefully acknowledged. Michael R. Hamblin was supported by the U.S. NIH (grant R01A1050875). NR 48 TC 20 Z9 20 U1 0 U2 17 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 SEP PY 2012 VL 56 IS 9 BP 4876 EP 4884 DI 10.1128/AAC.00810-12 PG 9 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 994CN UT WOS:000307908600042 PM 22777042 ER PT J AU Lu, X Agasti, SS Vinegoni, C Waterman, P DePinho, RA Weissleder, R AF Lu, Xin Agasti, Sarit S. Vinegoni, Claudio Waterman, Peter DePinho, Ronald A. Weissleder, Ralph TI Optochemogenetics (OCG) Allows More Precise Control of Genetic Engineering in Mice with CreER regulators SO BIOCONJUGATE CHEMISTRY LA English DT Article ID IN-VIVO; CELLS; RECOMBINATION; MOUSE; EXPRESSION; MODEL AB New approaches that allow precise spatiotemporal control of gene expression in model organisms at the single cell level are necessary to better dissect the role of specific genes and cell populations in development, disease, and therapy. Here, we describe a new optochemogenetic switch (OCG switch) to control CreER/loxP-mediated recombination via photoactivatable ("caged") tamoxifen analogues in individual cells in cell culture, organoid culture, and in vivo in adult mice. This approach opens opportunities to more fully exploit existing CreER transgenic mouse strains to achieve more precise temporal- and location-specific regulation of genetic events and gene expression. C1 [Lu, Xin; DePinho, Ronald A.] UT MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77054 USA. [Agasti, Sarit S.; Vinegoni, Claudio; Waterman, Peter; Weissleder, Ralph] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02114 USA. [Lu, Xin; DePinho, Ronald A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Lu, Xin; DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Lu, Xin; DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP DePinho, RA (reprint author), UT MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77054 USA. EM rdepinho@mdanderson.org; rweissleder@mgh.harvard.edu FU Jane Coffin Childs Memorial Fund; NIH [HHSN268201000044C]; [PO1CA117969]; [U01CA141508]; [P50-CA86355]; [U24CA092782] FX We are grateful to Rujuta Narurkar, Emma Labrot, Eliot Fletcher-Sananikone, Zhou Shan, and Shan Jiang for assistance in the animal facility. We thank Y. Alan Wang and other colleagues in our laboratories for helpful advice and discussion. We thank Joshua Dunham, Alex Zaltsman, and Lisa Cameron for help with imaging. This work was supported in part by grants PO1CA117969 (R.A.D.), U01CA141508 (R.A.D.), P50-CA86355 (R.W.), and U24CA092782 (R.W.). X.L. is supported by a postdoctoral fellowship from Jane Coffin Childs Memorial Fund. S.S.A. is supported by an NIH fellowship (HHSN268201000044C). NR 29 TC 8 Z9 8 U1 2 U2 15 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD SEP PY 2012 VL 23 IS 9 BP 1945 EP 1951 DI 10.1021/bc300319c PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 006QJ UT WOS:000308833600026 PM 22917215 ER PT J AU Musolino, PL Rapalino, O Caruso, P Caviness, VS Eichler, FS AF Musolino, Patricia Leonor Rapalino, Otto Caruso, Paul Caviness, Verne Strudwick Eichler, Florian Sebald TI Hypoperfusion predicts lesion progression in cerebral X-linked adrenoleukodystrophy SO BRAIN LA English DT Article DE MRI perfusion; demyelination; neuroinflammation; adrenoleukodystrophy; leukodystrophy ID MULTIPLE-SCLEROSIS; MRI; PATHOGENESIS; ABNORMALITY AB Magnetic resonance imaging sequences such as diffusion and spectroscopy have been well studied in X-linked adrenoleukodystrophy, but no data exist on magnetic resonance perfusion imaging. Since inflammation is known to modulate the microcirculation, we investigated the hypothesis that changes in the local perfusion might be one of the earliest signs of lesion development. Twenty patients with different phenotypes of adrenoleukodystrophy and seven age-matched controls were evaluated between 2006 and 2011. Fluid attenuated inversion recovery, post-contrast T-1-weighted and normalized dynamic susceptibility contrast magnetic resonance perfusion cerebral blood volume maps were co-registered, segmented when cerebral lesion was present, and normalized cerebral blood volume values were analysed using a Food and Drug Association approved magnetic resonance perfusion software (NordicICE). Clinical and imaging data were reviewed to determine phenotype and status of progression. All eight patients with cerebral adrenoleukodystrophy had an average 80% decrease in normalized cerebral blood volume at the core of the lesion (P < 0.0001). Beyond the leading edge of contrast enhancement cerebral perfusion varied, patients with progressive lesions showed an average 60% decrease in normalized cerebral blood volume (adults P < 0.05; children P < 0.001), while one child with arrested progression normalized cerebral blood volume in this region. In six of seven patients with cerebral adrenoleukodystrophy lesions and follow-up imaging (2-24 month interval period), we found progression of contrast enhancement into the formerly hypoperfused perilesional zone. Asymptomatic, adrenomyeloneuropathy and female heterozygote patients had no significant changes in cerebral perfusion. Our data indicate that decreased brain magnetic resonance perfusion precedes leakage of the blood-brain barrier as demonstrated by contrast enhancement in cerebral adrenoleukodystrophy and is an early sign of lesion progression. C1 [Musolino, Patricia Leonor; Caviness, Verne Strudwick; Eichler, Florian Sebald] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Rapalino, Otto; Caruso, Paul] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Caviness, Verne Strudwick; Eichler, Florian Sebald] Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. RP Eichler, FS (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St,WAC 708, Boston, MA 02114 USA. EM feichler@partners.org FU National Institutes of Health [K08NS52550, R01 NS072446, R25NS065743] FX This work was supported by the National Institutes of Health: K08NS52550 and R01 NS072446 to F. S. E. and R25NS065743 to P.L.M. NR 22 TC 11 Z9 11 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD SEP PY 2012 VL 135 BP 2676 EP 2683 DI 10.1093/brain/aws206 PN 9 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 007FG UT WOS:000308873600010 PM 22961546 ER PT J AU Pascual, B Prieto, E Arbizu, J Marti-Climent, JM Penuelas, I Quincoces, G Zarauza, R Pappata, S Masdeu, JC AF Pascual, Belen Prieto, Elena Arbizu, Javier Marti-Climent, Josep M. Penuelas, Ivan Quincoces, Gemma Zarauza, Rosina Pappata, Sabina Masdeu, Joseph C. TI Decreased carbon-11-flumazenil binding in early Alzheimer's disease SO BRAIN LA English DT Article DE Alzheimer's disease; flumazenil PET; MRI; GABA(A) receptors ID POSITRON-EMISSION-TOMOGRAPHY; MILD COGNITIVE IMPAIRMENT; ARTERIAL INPUT FUNCTION; C-11 FLUMAZENIL PET; BENZODIAZEPINE-RECEPTORS; ENTORHINAL CORTEX; I-123 IOMAZENIL; NEURONAL LOSS; BRAIN; VOLUME AB Neuronal loss in Alzheimer's disease, a better correlate of cognitive impairment than amyloid deposition, is currently gauged by the degree of regional atrophy. However, functional markers, such as GABA(A) receptor density, a marker of neuronal integrity, could be more sensitive. In post-mortem hippocampus, GABA(A) messenger RNA expression is reduced even in mild cognitive impairment. We measured whole-brain GABA(A) binding potential in vivo using [C-11]-flumazenil positron emission tomography and compared GABA(A) binding with metabolic and volumetric measurements. For this purpose, we studied 12 subjects, six patients with early Alzheimer's disease and six healthy controls, with [C-11]-flumazenil and [F-18]-fluorodeoxyglucose positron emission tomography, as well as with high-resolution magnetic resonance imaging. Data were evaluated with both voxel-based parametric methods and volume of interest methods. We found that in early Alzheimer's disease, with voxel-based analysis, [C-11]-flumazenil binding was decreased in infero-medial temporal cortex, retrosplenial cortex and posterior perisylvian regions. Inter-group differences reached corrected significance when using an arterial input function. Metabolism measured with positron emission tomography and volumetric measurements obtained with magnetic resonance imaging showed changes in regions affected in early Alzheimer's disease, but, unlike with [C-11]-flumazenil binding and probably due to sample size, the voxel-based findings failed to reach corrected significance in any region of the brain. With volume of interest analysis, hippocampi and posterior cingulate gyrus showed decreased [C-11]-flumazenil binding. In addition, [C-11]-flumazenil hippocampal binding correlated with memory performance. Remarkably, [C-11]-flumazenil binding was decreased precisely in the regions showing the greatest degree of neuronal loss in post-mortem studies of early Alzheimer's disease. From these data, we conclude that [C-11]-flumazenil binding could be a useful marker of neuronal loss in early Alzheimer's disease. C1 [Pascual, Belen; Masdeu, Joseph C.] Univ Navarra, Ctr Appl Med Res, Div Neurosci, Pamplona 31008, Spain. [Pascual, Belen; Arbizu, Javier; Marti-Climent, Josep M.; Masdeu, Joseph C.] CIBERNED, Pamplona 31008, Spain. [Prieto, Elena; Arbizu, Javier; Marti-Climent, Josep M.; Penuelas, Ivan; Quincoces, Gemma] Univ Navarra, Dept Nucl Med, Pamplona 31008, Spain. [Zarauza, Rosina] Univ Navarra, Dept Anaesthesiol & Crit Care, Pamplona 31008, Spain. [Pappata, Sabina] CNR, Inst Biostruct & Bioimaging, I-80131 Naples, Italy. RP Pascual, B (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Frontotemporal Dementia Unit, 149 13th St,149-2691, Charlestown, MA 02129 USA. EM belen@nmr.mgh.harvard.edu RI Penuelas, Ivan/I-6292-2013; Prieto, Elena/N-2142-2014 OI Penuelas, Ivan/0000-0001-8008-976X; Prieto, Elena/0000-0002-3609-1210 FU European Community [LSHB-CT-2005-512146]; 'Union Temporal de Empresas (UTE): Centro de Investigacion Medica Aplicada,' University of Navarra; 'Fundacion Mutua Madrilena'; Government of Navarra [13255308-53-GN]; 'Centro de Investigacion Biomedica en Red de Enfermedades Neurodegenerativas (CIBERNED) of the Spanish Ministry of Health FX The EC-FP6-project DiMI of the European Community [LSHB-CT-2005-512146], the 'Union Temporal de Empresas (UTE): Centro de Investigacion Medica Aplicada,' University of Navarra, the 'Fundacion Mutua Madrilena', the Government of Navarra [13255308-53-GN], and the 'Centro de Investigacion Biomedica en Red de Enfermedades Neurodegenerativas (CIBERNED) of the Spanish Ministry of Health. NR 48 TC 14 Z9 14 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD SEP PY 2012 VL 135 BP 2817 EP 2825 DI 10.1093/brain/aws210 PN 9 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 007FG UT WOS:000308873600022 PM 22961552 ER PT J AU Vasterling, JJ Brailey, K Proctor, SP Kane, R Heeren, T Franz, M AF Vasterling, Jennifer J. Brailey, Kevin Proctor, Susan P. Kane, Robert Heeren, Timothy Franz, Molly TI Neuropsychological outcomes of mild traumatic brain injury, post-traumatic stress disorder and depression in Iraq-deployed US Army soldiers SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID UK MILITARY PERSONNEL; PERSIAN-GULF-WAR; SYMPTOMS; VETERANS; HEALTH; COHORT; AFGHANISTAN; SEQUELAE; TBI; INFORMATION AB Background Traumatic brain injury (TBI) is a concern of contemporary military deployments. Whether milder TBI leads to enduring impairment remains controversial. Aims To determine the influence of deployment TBI, and post-traumatic stress disorder (PTSD) and depression symptoms on neuropsychological and functional outcomes. Method A sample of 760 US Army soldiers were assessed pre- and post-deployment. Outcomes included neuropsychological performances and subjective functional impairment. Results In total, 9% of the participants reported (predominantly mild) TBI with loss of consciousness between pre- and post-deployment. At post-deployment, 17.6% of individuals with TBI screened positive for PTSD and 31.3% screened positive for depression. Before and after adjustment for psychiatric symptoms, TBI was significantly associated only with functional impairment. Both PTSD and depression symptoms adjusted for TBI were significantly associated with several neuropsychological performance deficits and functional impairment. Conclusions Milder TBI reported by deployed service members typically has limited lasting neuropsychological consequences; PTSD and depression are associated with more enduring cognitive compromise. C1 [Vasterling, Jennifer J.; Proctor, Susan P.] USA, VA Boston Healthcare Syst, Environm Med Res Inst, Mil Performance Div,Res Serv, Boston, MA 02130 USA. [Vasterling, Jennifer J.; Brailey, Kevin] Boston Univ, Sch Med, Boston, MA 02118 USA. [Proctor, Susan P.] Boston Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA. [Kane, Robert] Def & Vet Brain Injury Ctr, Washington, DC USA. [Heeren, Timothy] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. RP Vasterling, JJ (reprint author), USA, VA Boston Healthcare Syst, Environm Med Res Inst, Mil Performance Div,Res Serv, 150 S Huntington Ave, Boston, MA 02130 USA. EM jennifer.vasterling@va.gov OI Heeren, Timothy/0000-0001-5643-3559 FU US Department of Defense CDMRP [W81XWH-08-2-0035]; US Army Medical Research and Materiel Command [DAMD 17-03-0020]; US Veterans Affairs Clinical Sciences Research and Development FX Funding was provided by the US Department of Defense CDMRP (W81XWH-08-2-0035), US Army Medical Research and Materiel Command (DAMD 17-03-0020); and US Veterans Affairs Clinical Sciences Research and Development. The primary funding organisation had no role in the scientific aspects of the study or the preparation of the manuscript. The manuscript underwent scientific and administrative review within the US Army Research Institute for Environmental Medicine and US Army Medical Research and Materiel Command. The content of this article does not necessarily reflect the position or policy of the US government, and no official endorsement should be inferred. NR 36 TC 54 Z9 54 U1 5 U2 22 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON SW1X 8PG, ENGLAND SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD SEP PY 2012 VL 201 IS 3 BP 186 EP 192 DI 10.1192/bjp.bp.111.096461 PG 7 WC Psychiatry SC Psychiatry GA 007OR UT WOS:000308898500006 PM 22743844 ER PT J AU Biederman, J Petty, CR Hammerness, P Batchelder, H Faraone, SV AF Biederman, Joseph Petty, Carter R. Hammerness, Paul Batchelder, Holly Faraone, Stephen V. TI Cigarette smoking as a risk factor for other substance misuse: 10-year study of individuals with and without attention-deficit hyperactivity disorder SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID ILLICIT DRUG-USE; FOLLOW-UP; DEFICIT/HYPERACTIVITY DISORDER; FAMILIAL TRANSMISSION; UNITED-STATES; ADHD; ADOLESCENTS; CHILDREN; ALCOHOL; ADULTS AB Background We previously documented that cigarette smoking is a risk factor for subsequent alcohol and drug misuse and dependence in adolescent girls with attention-deficit hyperactivity disorder (ADHD). Aims To revisit this hypothesis with a large longitudinal sample of both genders followed up for 10 years into young adulthood. Method We used data from two identically designed, longitudinal, case-control family studies of boys and girls with and without ADHD ascertained from psychiatric and paediatric sources. We studied 165 individuals with ADHD and 374 controls followed up longitudinally and masked for 10 years. We assessed ADHD, smoking and substance use status using structured diagnostic interviews. We tested the association between cigarette smoking and subsequent substance use outcomes using Cox proportional hazard regression models. Results Youth with ADHD who smoked cigarettes (n = 27) were significantly more likely to subsequently develop drug misuse and dependence compared with youth with ADHD who did not smoke (n = 138, P<0.05). Conclusions These results confirm that cigarette smoking increases the risk for subsequent drug and alcohol use disorders among individuals with ADHD. These findings have important public health implications, and underscore the already pressing need to prevent smoking in children with ADHD. C1 [Biederman, Joseph] Massachusetts Gen Hosp, Pediat Psychopharmacol Program, Dept Psychiat, Boston, MA 02114 USA. [Biederman, Joseph] Harvard Univ, Sch Med, Boston, MA USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Program, Dept Psychiat, Yawkey 6A,55 Fruit St, Boston, MA 02114 USA. EM jbiederman@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU Elminda; Janssen; McNeil; Shire; Massachusetts General Hospital (MGH) Psychiatry Academy; Abbott; Alza; AstraZeneca; Boston University; Bristol-Myers Squibb; Celltech; Cephalon; Eli Lilly and Co.; Esai; Fundacion Areces (Spain); Forest; GlaxoSmithKline; Gliatech; Hastings Center; Medice Pharmaceuticals (Germany); Merck; MMC Pediatric; NARSAD; NIDA; New River; NICHD; NIMH; Novartis; Noven; Neurosearch; Organon; Otsuka; Pfizer; Pharmacia; Phase V Communications; Physicians Academy; Prechter Foundation; Quantia Communications; Reed Exhibitions; Spanish Child Psychiatry Association; Stanley Foundation; UCB Pharma; Veritas; Wyeth; Shire Pharmaceuticals; Johnson Johnson; Ortho-McNeil Janssen; Takeda Pharmaceuticals; Alcobra; National Institutes of Health; Eli Lilly; USPHS (NIMH) [R01 MH-41314-01A2]; Pediatric Psychopharmacology Council FX J.B. is currently receiving research support from: Elminda, Janssen, McNeil and Shire. He has received: honoraria from the Massachusetts General Hospital (MGH) Psychiatry Academy for a tuition-funded continuing medical education (CME) course on ADHD; departmental royalties from a copyrighted rating scale used for ADHD diagnoses, paid to the Department of Psychiatry at MGH by Eli Lilly, Shire and AstraZeneca; a speaker's fee for a talk given at Fundacion Dr. Manuel Camelo A.C. in Monterrey, Mexico; honoraria for consultations for Shionogi Pharma and Cipher Pharmaceuticals, paid to the Department of Psychiatry at the MGH; research support, consultation fees, or speaker's fees for/from: Abbott, Alza, AstraZeneca, Boston University, Bristol-Myers Squibb, Celltech, Cephalon, Eli Lilly and Co., Esai, Fundacion Areces (Spain), Forest, GlaxoSmithKline, Gliatech, Hastings Center, Janssen, McNeil, Medice Pharmaceuticals (Germany), Merck, MMC Pediatric, NARSAD, NIDA, New River, NICHD, NIMH, Novartis, Noven, Neurosearch, Organon, Otsuka, Pfizer, Pharmacia, Phase V Communications, Physicians Academy, The Prechter Foundation, Quantia Communications, Reed Exhibitions, Shire, the Spanish Child Psychiatry Association, The Stanley Foundation, UCB Pharma, Veritas, and Wyeth. In the past 12 months, P.H. has participated in CME activities/writing supported by Shire Pharmaceuticals and, as an investigator/principal investigator, in research funded by: Cephalon, Forest, GlaxoSmithKline, Johnson & Johnson, McNeil, Novartis, Ortho-McNeil Janssen, Shire, Takeda Pharmaceuticals and Elminda. P.H. has also received honoraria from commercial entities supporting the MGH Psychiatry Academy (www.mghcme.org). In the past year, S.V.F. received consulting income and research support from Shire, Otsuka and Alcobra and research support from the National Institutes of Health. He has also received consulting fees or was on advisory boards or participated in CME programmes sponsored by: Shire, McNeil, Janssen, Novartis, Pfizer and Eli Lilly.; This work was supported, in part, by USPHS (NIMH) grant R01 MH-41314-01A2 (JB) and the Pediatric Psychopharmacology Council Fund. NR 47 TC 9 Z9 10 U1 2 U2 3 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON SW1X 8PG, ENGLAND SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD SEP PY 2012 VL 201 IS 3 BP 207 EP 214 DI 10.1192/bjp.bp.111.100339 PG 8 WC Psychiatry SC Psychiatry GA 007OR UT WOS:000308898500009 PM 22844023 ER PT J AU Baehring, JM Batchelor, TT AF Baehring, Joachim M. Batchelor, Tracy T. TI Diagnosis and Management of Neurolymphomatosis SO CANCER JOURNAL LA English DT Review DE Neurolymphomatosis; NHL; MRI ID CENTRAL-NERVOUS-SYSTEM; PRIMARY CNS LYMPHOMA; B-CELL LYMPHOMA; MALIGNANT-LYMPHOMA; CAUDA-EQUINA; FDG-PET/CT; L-SELECTIN; INVOLVEMENT; PATIENT; POLYNEUROPATHY AB Invasion of cranial nerves and peripheral nerve roots, plexus, or nerves by non-Hodgkin lymphoma is denoted as neurolymphomatosis (NL). Four clinical patterns are recognized. Most commonly, NL presents as a painful polyneuropathy or polyradiculopathy, followed by cranial neuropathy, painless polyneuropathy, and peripheral mononeuropathy. Diagnosis of NL is challenging and requires integration of clinical information, imaging findings, and histopathologic examination of involved nerves or nonneural tissue and cerebrospinal fluid analysis. In the rare cases of primary NL, the diagnosis is often delayed. Successful therapy is contingent upon recognition of the disease and its exact neuroanatomic localization without delay. Treatment options include systemic chemotherapy and localized irradiation of bulky disease sites. Concomitant involvement of cerebrospinal fluid and systemic disease sites requires more complex regimens. C1 [Baehring, Joachim M.] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06514 USA. [Baehring, Joachim M.] Yale Univ, Sch Med, Dept Med, New Haven, CT 06514 USA. [Baehring, Joachim M.] Yale Univ, Sch Med, Dept Neurosurg, New Haven, CT 06514 USA. [Batchelor, Tracy T.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Batchelor, Tracy T.] Massachusetts Gen Hosp, Dept Radiat Oncol, Div Hematol & Oncol, Boston, MA 02114 USA. [Batchelor, Tracy T.] Harvard Univ, Sch Med, Boston, MA USA. RP Baehring, JM (reprint author), Yale Univ, Sch Med, Dept Neurol, 15 York St, New Haven, CT 06514 USA. EM Joachim.baehring@yale.edu NR 34 TC 24 Z9 25 U1 3 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD SEP-OCT PY 2012 VL 18 IS 5 BP 463 EP 468 DI 10.1097/PPO.0b013e31826c5ad5 PG 6 WC Oncology SC Oncology GA 012EP UT WOS:000309218600014 PM 23006953 ER PT J AU Somma, KA Bhatt, DL Fonarow, GC Cannon, CP Cox, M Laskey, W Peacock, WF Hernandez, AF Peterson, ED Schwamm, L Saxon, LA AF Somma, Keith A. Bhatt, Deepak L. Fonarow, Gregg C. Cannon, Christopher P. Cox, Margueritte Laskey, Warren Peacock, W. Frank Hernandez, Adrian F. Peterson, Eric D. Schwamm, Lee Saxon, Leslie A. TI Guideline Adherence After ST-Segment Elevation Versus Non-ST-Segment Elevation Myocardial Infarction SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE acute myocardial infarction; coronary artery disease; myocardial infarction; non-ST-segment elevation acute coronary syndromes; ST-segment elevation myocardial infarction ID ACUTE CORONARY SYNDROMES; ASSOCIATION TASK-FORCE; HEART-ASSOCIATION; MANAGEMENT STRATEGIES; FOCUSED UPDATE; OUTCOMES; REGISTRY; RISK; ATHEROTHROMBOSIS; OUTPATIENTS AB Background-Clinical guidelines recommend similar medical therapy for patients with ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation MI (NSTEMI). Methods and Results-Using the Get with the Guidelines-Coronary Artery Disease registry (GWTG-CAD), we analyzed data including 72 352 patients (48 966, NSTEMI; 23 386, STEMI) from 237 US sites between May 1, 2006 and March 21, 2010. Performance and quality measures were compared between NSTEMI and STEMI patients. NSTEMI patients were older and had a higher rate of medical comorbidities compared with STEMI patients, including prior coronary artery disease (38.5% versus 24.7%; P<0.0001), heart failure (17.5% versus 6.2%; P<0.0001), hypertension (70.8% versus 59.1%; P<0.0001) and diabetes mellitus (34.9 versus 23.3%; P<0.0001). Adjusting for confounding variables, STEMI patients were more likely to receive aspirin within 24 hours 98.5% versus 97.1% (adjusted odds ratio [AOR], 1.63; 95% confidence interval [CI], 1.32-2.02), be discharged on aspirin 98.5% versus 97.3% (AOR, 1.33; 95% CI, 1.19-1.49), beta-blockers 98.2% versus 96.9% (AOR, 1.48; 95% CI, 1.35-1.63), or lipid-lowering medication for low-density lipoprotein level >100 mg/dL 96.8% versus 91.0% (AOR, 1.85; 95% CI, 1.61-2.13). STEMI patients were also more likely to receive beta-blockers within 24 hours of hospital arrival 93.9% versus 90.8% (AOR, 1.57; 95% CI, 1.37-1.79) and the following discharge medications: angiotensin-converting enzyme inhibitors or angiotensin receptor blocking agents 85.3% versus 77.4% (AOR, 1.62; 95% CI, 1.51-1.75), clopidogrel 85.6% versus 67.0% (AOR, 2.42; 95% CI, 2.23-2.61) or lipid-lowering medications 94.8% versus 88.0% (AOR, 1.71; 95% CI, 1.56-1.86). Conclusions-Among hospitals participating in GWTG-CAD, adherence with guideline-based medical therapy was high for patients with both STEMI and NSTEMI. Yet, there is still room for further improvement, particularly in the care of NSTEMI patients. (Circ Cardiovasc Qual Outcomes. 2012;5:654-661.) C1 [Somma, Keith A.; Saxon, Leslie A.] Univ So Calif, Div Cardiovasc Med, Keck Sch Med, Los Angeles, CA 90033 USA. [Bhatt, Deepak L.; Cannon, Christopher P.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Bhatt, Deepak L.; Cannon, Christopher P.; Schwamm, Lee] Harvard Univ, Sch Med, Boston, MA USA. [Fonarow, Gregg C.] Ronald Reagan UCLA Med Ctr, Ahmanson UCLA Cardiomyopathy Ctr, Los Angeles, CA USA. [Cox, Margueritte; Hernandez, Adrian F.; Peterson, Eric D.] Duke Clin Res Inst, Durham, NC USA. [Laskey, Warren] Univ New Mexico, Div Cardiol, Albuquerque, NM 87131 USA. [Peacock, W. Frank] Cleveland Clin, Cleveland, OH 44106 USA. [Schwamm, Lee] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Saxon, LA (reprint author), Univ So Calif, Div Cardiovasc Med, Keck Sch Med, 1510 San Pablo St,Suite 322, Los Angeles, CA 90033 USA. EM saxon@usc.edu RI Hernandez, Adrian F./A-7818-2016 OI Schwamm, Lee/0000-0003-0592-9145; Hernandez, Adrian F./0000-0003-3387-9616 FU Amarin; AstraZeneca; Bristol-Myers Squibb; Eisai; Ethicon; Medtronic; Sanofi-aventis; Medicines Company; Boston Scientific Corp; St. Jude Medical and Medtronic, Inc; St Jude Medical; National Heart, Lung, and Blood Institute; Agency for Healthcare Research and Quality; Novartis; Pfizer; Accumetrics; Glaxo Smith Kline; Intekrin Therapeutics; Merck; Takada; Johnson Johnson; Proventys; Amylin; Bristol-Meyers Squibb; Eli Lilly; Ortho McNeil Pharmaceuticals; Alere; Brams; Electrocore; Medicines Co FX Dr Bhatt receives research grants from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi-aventis, and The Medicines Company. Dr Saxon receives institutional grant support and or institutional fellowship support from Boston Scientific Corp, St. Jude Medical and Medtronic, Inc, and consultant fees from Boston Scientific Corp and St Jude Medical. Dr Fonarow received research grants from the National Heart, Lung, and Blood Institute and Agency for Healthcare Research and Quality, consultant fees from Novartis and Pfizer, and honorarium from Medtronic. Dr Cannon receives research grants from Accumetrics, AstraZeneca, Glaxo Smith Kline, Intekrin Therapeutics, Merck, and Takada and received honorarium for development of independent educational symposia from Pfizer and AstraZeneca. Dr Cannon serves on the advisory board for Bristol-Meyers Squibb/Sanofi, Novartis, Alnylam and donates these funds to charity. He also serves as clinical advisor and holds equity in Automedics Medical Systems. Dr Hernandez reported receiving research support from Johnson & Johnson, Proventys, and Amylin; and honoraria from Amgen and Corthera. Dr Peterson serves as the principal investigator for the American Heart Association (AHA) Get with the Guidelines (GWTG) data analytic center at Duke Clinical Research Institute. He also receives research funding from Bristol-Meyers Squibb, Sanofi-Aventis, Eli Lilly, and Ortho McNeil Pharmaceuticals. Dr Schwamm serves as chair of the AHA GWTG steering committee, and is a consultant to Medtronic. Dr Peacock serves on the advisory board of Abbot, Alere, Lily, and the Medicines Co, receives a research grant from Alere, Brams, Electrocore, Novartis, and the Medicines Co, is on the Speakers Bureau of Abbot, Alere, and EKR. Dr Peacock has Ownership Interest in Research Associates, Emergencies in Medicine, and the Medicines Co. The other authors report no conflicts. NR 20 TC 21 Z9 22 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7705 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD SEP PY 2012 VL 5 IS 5 BP 654 EP 661 DI 10.1161/CIRCOUTCOMES.111.963959 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 010QK UT WOS:000309109000012 PM 22949493 ER PT J AU Husted, S James, S Becker, RC Horrow, J Katus, H Storey, RF Cannon, CP Heras, M Lopes, RD Morais, J Mahaffey, KW Bach, RG Wojdyla, D Wallentin, L AF Husted, Steen James, Stefan Becker, Richard C. Horrow, Jay Katus, Hugo Storey, Robert F. Cannon, Christopher P. Heras, Magda Lopes, Renato D. Morais, Joao Mahaffey, Kenneth W. Bach, Richard G. Wojdyla, Daniel Wallentin, Lars CA PLATO Study Grp TI Ticagrelor Versus Clopidogrel in Elderly Patients With Acute Coronary Syndromes A Substudy From the Prospective Randomized PLATelet Inhibition and Patient Outcomes (PLATO) Trial SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE acute coronary syndrome; age factors; platelets; P2Y(12) receptor; thrombosis; bleeding ID ST-SEGMENT-ELEVATION; HEART-ASSOCIATION COUNCIL; HEALTH-CARE PROFESSIONALS; MYOCARDIAL-INFARCTION; INTRACRANIAL HEMORRHAGE; SCIENTIFIC STATEMENT; GERIATRIC-CARDIOLOGY; CLINICAL CARDIOLOGY; ATRIAL-FIBRILLATION; GLOBAL REGISTRY AB Background-Elderly patients with acute coronary syndrome are at high risk of recurrent ischemic events and death, and for both antithrombotic therapy and catheter-based complications. This prespecified analysis investigates the effect and treatment-related complications of ticagrelor versus clopidogrel in elderly patients (>= 75 years of age) with acute coronary syndrome compared with those < 75 years of age. Methods and Results-The association between age and the primary composite outcome, as well as major bleeding were evaluated in the PLATelet inhibition and patient Outcomes (PLATO) trial using Cox proportional hazards. Similar models were used to evaluate the interaction of age with treatment effects. Hazard ratios were adjusted for baseline characteristics. The clinical benefit of ticagrelor over clopidogrel was not significantly different between patients aged >= 75 years of age (n=2878) and those < 75 years of age (n=15744) with respect to the composite of cardiovascular death, myocardial infarction, or stroke (interaction P=0.56), myocardial infarction (P=0.33), cardiovascular death (P=0.47), definite stent thrombosis (P=0.81), or all-cause mortality (P=0.76). No increase in PLATO-defined overall major bleeding with ticagrelor versus clopidogrel was observed in patients aged >= 75 years (hazard ratio, 1.02; 95% confidence interval, 0.82-1.27) or patients aged < 75 years (hazard ratio, 1.04; 95% confidence interval, 0.94-1.15). Dyspnea and ventricular pauses were more common during ticagrelor than clopidogrel treatment, with no evidence of an age-by-treatment interaction. Conclusions-The significant clinical benefit and overall safety of ticagrelor compared with clopidogrel in acute coronary syndrome patients in the PLATO cohort were not found to depend on age. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00391872. (Circ Cardiovasc Qual Outcomes. 2012;5:680-688.) C1 [Husted, Steen] Arhus Univ Hosp, Dept Cardiol, Aarhus, Denmark. [James, Stefan; Wallentin, Lars] Uppsala Univ, Uppsala Clin Res Ctr, Uppsala, Sweden. [Becker, Richard C.; Lopes, Renato D.; Mahaffey, Kenneth W.; Wojdyla, Daniel] Duke Clin Res Inst, Durham, NC USA. [Katus, Hugo] Univ Klinikum Heidelberg, Med Klin, Heidelberg, Germany. [Horrow, Jay] AstraZeneca R&D, Wilmington, DE USA. [Storey, Robert F.] Univ Sheffield, Dept Cardiovasc Sci, Sheffield, S Yorkshire, England. [Cannon, Christopher P.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Heras, Magda] Univ Barcelona, Dept Cardiol, Hosp Clin, Barcelona, Spain. [Morais, Joao] Santo Andres Hosp, Leiria, Portugal. [Bach, Richard G.] Washington Univ, Sch Med, Div Cardiovasc, St Louis, MO 63110 USA. RP Husted, S (reprint author), Arhus Univ Hosp, Dept Cardiol, Aarhus, Denmark. EM steehust@rm.dk RI Katus, Hugo/P-1712-2016 FU AZ; BMS; Pf; Bay; SA; EL; MSD; RB; JJ; Roche; Novartis; EL/DS alliance; MSD/SP; Nov; Accumetrics; Eisai; Intekrin therapeutics; Takeda; Menarini; BI; Rovi; Momenta Pharmaceutical; Portola Pharmaceutical; Pozen; SP; TMC; DS; GSK; Ortho/McNeill; Polymedix; F. Hoffmann-La Roche Ltd; Athera; CSL Behring; Evolva; Portola FX Dr Husted has received research grants from AZ, BMS, Pf, and Bay and consultant fees from SA, Pf, and AZ. Dr James has received research grants from AZ, EL, MSD and honoraria from AZ, EL, Merck and MSD. Dr Becker has received research grants from AZ, RB, JJ, and Bay and consultant fees from AZ, RB, and BMS. Dr Horrow is an employee of AZ with equity ownership in AZ. Dr Katus has received consulting/lecture fees from AZ, Roche, and Novartis. Dr Storey has received research grants from AZ, EL/DS alliance, and MSD/SP and honoraria from AZ, EL/DS alliance, Medscape, Nov, GSK, MSD/SP, Eisai, SA/BMS, TMC, Accumetrics, and Iroko and consultant fees from AZ, Nov, Accumetrics, and Eisai. Dr Cannon has received research grants from Accumetrics, AZ, GSK, Intekrin therapeutics, MSD, and Takeda and is on the advisory boards for BMS/SA, Nov, and Alnyam and received honoraria from AZ, Pf and equity from Automedics Medical Systems. Dr Heras is on the advisory boards for AZ, Menarini, and Nov and has received research grant from GSK and honoraria from AZ, EL, Menarini, BI, and Rovi. Dr Lopes has received research grant from BMS and is on the advisory boards for Pfizer and BI. Dr Morais has received research grants from SA and is on the speakers' bureau/advisory boards for AZ, Bay, MSC, and EL. Dr Mahaffey has received research grants from AZ, Bay, BI, BMS, DS, EL, GSK, JJ, MSD, Momenta Pharmaceutical, Nov, Portola Pharmaceutical, Pozen, RB, SA, SP, and TMC and consultant fees from AZ, Bay, BI, BMS, DS, EL, GSK, JJ, MSD, Nov, Ortho/McNeill, Pf, Polymedix, SA, and SP. Dr Bach has received research grants from AZ, BMS, EL, MSD, and SP and consultant fees (CEC activity) from F. Hoffmann-La Roche Ltd, EL, and Pf. D. W. has nothing to disclose. Dr Wallentin has received research grants from AZ, BI, BMS/Pf, GSK, and MSD/SP and honoraria from AZ, Athera, RB, CSL Behring, Evolva, Bay, BMS, GSK, and SP and consultant fees from RB, Athera, AZ, BI, GSK, EL, Portola, CSL Behring, BI, AZ, and BMS/Pf and lecture fees from AZ, BI, BMS/Pf, GSK, and SP. NR 28 TC 46 Z9 49 U1 0 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7705 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD SEP PY 2012 VL 5 IS 5 BP 680 EP 688 DI 10.1161/CIRCOUTCOMES.111.964395 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 010QK UT WOS:000309109000015 PM 22991347 ER PT J AU Murthy, VL Desai, NR Vora, A Bhatt, DL AF Murthy, Venkatesh L. Desai, Nihar R. Vora, Amit Bhatt, Deepak L. TI Increasing Proportion of Clinical Trials Using Noninferiority End Points SO CLINICAL CARDIOLOGY LA English DT Editorial Material ID EQUIVALENCE RANDOMIZED-TRIALS; ACUTE MYOCARDIAL-INFARCTION; ASSENT-2 AB This study was funded in part by grants from the National Institutes of Health (T32 HL094301-01A1 and T32 HL007604-27). Dr. Bhatt discloses the following relationships - Advisory Board: Medscape Cardiology; Board of Directors: Boston VA Research Institute, Society of Chest Pain Centers; Chair: American Heart Association Get With The Guidelines Science Subcommittee; Honoraria: American College of Cardiology (Editor, Clinical Trials, Cardiosource), Duke Clinical Research Institute (clinical trial steering committees), Slack Publications (Chief Medical Editor, Cardiology Today Intervention), WebMD (CME steering committees); Research Grants: Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi Aventis, The Medicines Company; Unfunded Research: FlowCo, PLx Pharma, Takeda. Drs. Murthy and Desai have received consulting fees from Novo Nordisk. The authors have no other funding, financial relationships, or conflicts of interest to disclose. C1 [Murthy, Venkatesh L.; Desai, Nihar R.; Bhatt, Deepak L.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Murthy, Venkatesh L.; Desai, Nihar R.; Vora, Amit; Bhatt, Deepak L.] Brigham & Womens Hosp, Dept Internal Med, Boston, MA 02115 USA. [Murthy, Venkatesh L.] Brigham & Womens Hosp, Cardiovasc Imaging Program, Boston, MA 02115 USA. [Desai, Nihar R.; Bhatt, Deepak L.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA USA. RP Murthy, VL (reprint author), Brigham & Womens Hosp, Div Cardiovasc Med, ASB L1 037B,75 Francis St, Boston, MA 02115 USA. EM vlmurthy@partners.org RI Murthy, Venkatesh/B-3448-2013 OI Murthy, Venkatesh/0000-0002-7901-1321 FU NHLBI NIH HHS [T32 HL007604, T32 HL007604-27, T32 HL094301, T32 HL094301-01A1] NR 8 TC 2 Z9 2 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0160-9289 J9 CLIN CARDIOL JI Clin. Cardiol. PD SEP PY 2012 VL 35 IS 9 BP 522 EP 523 DI 10.1002/clc.22040 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 002ZZ UT WOS:000308579200001 PM 22806427 ER PT J AU Kandzari, DE Bhatt, DL Sobotka, PA O'Neill, WW Esler, M Flack, JM Katzen, BT Leon, MB Massaro, JM Negoita, M Oparil, S Rocha-Singh, K Straley, C Townsend, RR Bakris, G AF Kandzari, David E. Bhatt, Deepak L. Sobotka, Paul A. O'Neill, William W. Esler, Murray Flack, John M. Katzen, Barry T. Leon, Martin B. Massaro, Joseph M. Negoita, Manuela Oparil, Suzanne Rocha-Singh, Krishna Straley, Craig Townsend, Raymond R. Bakris, George TI Catheter-Based Renal Denervation for Resistant Hypertension: Rationale and Design of the SYMPLICITY HTN-3 Trial SO CLINICAL CARDIOLOGY LA English DT Review ID SYMPATHETIC-NERVOUS-SYSTEM; BLOOD-PRESSURE RESEARCH; SCIENTIFIC STATEMENT; PREVALENCE; METABOLISM; PREVENTION; MANAGEMENT; CARDIOLOGY; THERAPY; FAILURE AB Hypertension represents a significant global public health concern, contributing to vascular and renal morbidity, cardiovascular mortality, and economic burden. The opportunity to influence clinical outcomes through hypertension management is therefore paramount. Despite adherence to multiple available medical therapies, a significant proportion of patients have persistent blood pressure elevation, a condition termed resistant hypertension. Recent recognition of the importance of the renal sympathetic and somatic nerves in modulating blood pressure and the development of a novel procedure that selectively removes these contributors to resistant hypertension represents an opportunity to provide clinically meaningful benefit across wide and varied patient populations. Early clinical evaluation with catheter-based, selective renal sympathetic denervation in patients with resistant hypertension has mechanistically correlated sympathetic efferent denervation with decreased renal norepinephrine spillover and renin activity, increased renal plasma flow, and has demonstrated clinically significant, sustained reductions in blood pressure. The SYMPLICITY HTN-3 Trial is a pivotal study designed as a prospective, randomized, masked procedure, single-blind trial evaluating the safety and effectiveness of catheter-based bilateral renal denervation for the treatment of uncontrolled hypertension despite compliance with at least 3 antihypertensive medications of different classes (at least one of which is a diuretic) at maximal tolerable doses. The primary effectiveness endpoint is measured as the change in office-based systolic blood pressure from baseline to 6 months. This manuscript describes the design and methodology of a regulatory trial of selective renal denervation for the treatment of hypertension among patients who have failed pharmacologic therapy. Clin. Cardiol. 2012. doi: 10.1002/clc.22008 Dr. Kandzari receives research/grant support and consulting honoraria from Medtronic CardioVascular, Abbott Vascular and Boston Scientific; Dr. Bhatt receives honoraria from WebMD and research grants from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi Aventis, and The Medicines Company. Dr. Oparil receives research/grant support from Merck and Co., NHLBI, Novartis, and Takeda, honoraria from Daiichi Sankyo and Pfizer, and is a consultant for Bayer, Medtronic, Novartis, Pfizer, and Daiichi Sankyo. Dr. Rocha-Singh is a consultant for Medtronic, Covidien, and Cardiosonic. Dr. Flack receives grant/research support from NIH, Daiichi Sankyo, sanofi aventis, and Novartis. He is on the Speaker Bureau for Novartis, Daiichi Sankyo, and Boehringer Ingleheim, and is a consultant for Glaxo-Smith-Kline, Novartis, NIH, Daiichi Sankyo, and Boehringer Ingleheim, Medtronic, and Back Beat Hypertension. Dr. Katzen is a consultant for Abbott, CRBard, Boston Scientific, WL Gore, and Medtronic. Dr. Massaro is a member of the Data Safety Monitoring Board and will no longer participate as a member of the SYMPLICITY HTN-3 Steering Committee. Dr. Leon, Dr. O'Neill, and Dr. Esler have nothing to disclose. Dr. Negoita, Dr. Sobotka, and Craig Straley are employees of Medtronic, Inc. Dr. Bakris receives grant/clinical trial support (paid directly to University of Chicago) from Forest Laboratories, Medtronic, and Relapysa, and is a consultant to Takeda, Abbott, CVRx, Johnson & Johnson, Eli Lilly, and the Food and Drug Administration. Dr. Bakris is on the Speaker Bureau for Takeda, and the Boards of the National Kidney Foundation and the American Society of Hypertension. He is Editor for the American Journal of Nephrology and Associate Editor for Diabetes Care and Nephrology Dialysis and Transplantation. C1 [Kandzari, David E.] Piedmont Heart Inst, Atlanta, GA 30309 USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. [Sobotka, Paul A.] Ohio State Univ, Columbus, OH 43210 USA. [O'Neill, William W.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Esler, Murray] Baker IDI Heart & Diabet Inst, Melbourne, Vic, Australia. [Flack, John M.] Wayne State Univ, Detroit, MI USA. [Flack, John M.] Detroit Med Ctr, Detroit, MI USA. [Katzen, Barry T.] Baptist Cardiac & Vasc Inst, Miami, FL USA. [Leon, Martin B.] Columbia Univ, New York Presbyterian Hosp, Med Ctr, New York, NY USA. [Leon, Martin B.] Cardiovasc Res Fdn, New York, NY USA. [Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Sobotka, Paul A.; Negoita, Manuela; Straley, Craig] Medtron CardioVasc, Santa Rosa, CA USA. [Oparil, Suzanne] Univ Alabama Birmingham, Birmingham, AL USA. [Rocha-Singh, Krishna] Prairie Educ & Res Cooperat, Springfield, IL USA. [Townsend, Raymond R.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Bakris, George] Univ Chicago Med, Chicago, IL USA. RP Kandzari, DE (reprint author), Piedmont Heart Inst, Suite 300,275 Collier Rd, Atlanta, GA 30309 USA. EM david.kandzari@piedmont.org FU Medtronic Cardio Vascular; Abbott Vascular; Boston Scientific; Amarin; AstraZeneca; Bristol-Myers Squibb; Eisai; Ethicon; Medtronic; Sanofi Aventis; Medicines Company; Merck and Co.; NHLBI; Novartis; Takeda; NIH; Daiichi Sankyo; Forest Laboratories; Relapysa FX Dr. Kandzari receives research/grant support and consulting honoraria from Medtronic Cardio Vascular, Abbott Vascular and Boston Scientific; Dr. Bhatt receives honoraria from WebMD and research grants from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi Aventis, and The Medicines Company. Dr. Oparil receives research/grant support from Merck and Co., NHLBI, Novartis, and Takeda, honoraria from Daiichi Sankyo and Pfizer, and is a consultant for Bayer, Medtronic, Novartis, Pfizer, and Daiichi Sankyo. Dr. Rocha-Singh is a consultant for Medtronic, Covidien, and Cardiosonic. Dr. Flack receives grant/research support from NIH, Daiichi Sankyo, sanofi aventis, and Novartis. He is on the Speaker Bureau for Novartis, Daiichi Sankyo, and Boehringer Ingleheim, and is a consultant for Glaxo-Smith-Kline, Novartis, NIH, Daiichi Sankyo, and Boehringer Ingleheim, Medtronic, and Back Beat Hypertension. Dr. Katzen is a consultant for Abbott, CRBard, Boston Scientific, WL Gore, and Medtronic. Dr. Massaro is a member of the Data Safety Monitoring Board and will no longer participate as a member of the SYMPLICITY HTN-3 Steering Committee. Dr. Leon, Dr. O'Neill, and Dr. Esler have nothing to disclose. Dr. Negoita, Dr. Sobotka, and Craig Straley are employees of Medtronic, Inc. Dr. Bakris receives grant/clinical trial support (paid directly to University of Chicago) from Forest Laboratories, Medtronic, and Relapysa, and is a consultant to Takeda, Abbott, CVRx, Johnson & Johnson, Eli Lilly, and the Food and Drug Administration. Dr. Bakris is on the Speaker Bureau for Takeda, and the Boards of the National Kidney Foundation and the American Society of Hypertension. He is Editor for the American Journal of Nephrology and Associate Editor for Diabetes Care and Nephrology Dialysis and Transplantation. NR 35 TC 163 Z9 172 U1 6 U2 43 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0160-9289 J9 CLIN CARDIOL JI Clin. Cardiol. PD SEP PY 2012 VL 35 IS 9 BP 528 EP 535 DI 10.1002/clc.22008 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 002ZZ UT WOS:000308579200002 PM 22573363 ER PT J AU Vasaiwala, S Cannon, CP Fonarow, GC Peacock, WF Laskey, W Schwamm, LH Liang, L Hernandez, AF Peterson, ED Rosas, SE Bhatt, DL AF Vasaiwala, Samip Cannon, Christopher P. Fonarow, Gregg C. Peacock, W. Frank Laskey, Warren Schwamm, Lee H. Liang, Li Hernandez, Adrian F. Peterson, Eric D. Rosas, Sylvia E. Bhatt, Deepak L. CA Get Guidelines Steering Comm Inves TI Quality of Care and Outcomes Among Patients With Acute Myocardial Infarction by Level of Kidney Function at Admission: Report From the Get With The Guidelines Coronary Artery Disease Program SO CLINICAL CARDIOLOGY LA English DT Article ID STAGE RENAL-DISEASE; CARDIOVASCULAR OUTCOMES; RISK-FACTOR; INTERVENTION; IMPACT; INSUFFICIENCY; THERAPY; TRIALS; HEALTH AB Background: Many patients admitted for acute myocardial infarction (AMI) have chronic renal insufficiency. We studied the impact of chronic renal insufficiency on mortality and quality of inpatient care for AMI from the American Heart Association's Get With The GuidelinesCoronary Artery Disease Program. Hypothesis: We hypothesized that mortality and quality of inpatient care would not vary with renal function. Methods: We examined in-hospital AMI performance measures by renal function based on glomerular filtration rate (GFR). Severity of renal insufficiency was categorized as normal (GFR = 90 mL/min/1.73 m2), mild (GFR 6090 mL/min/1.73 m2), moderate (GFR 3060 mL/min/1.73 m2), severe (GFR 1530 mL/min/1.73 m2), and kidney failure (GFR = 15 mL/min/1.73 m2 or dialysis). A total of 21721 patients from 291 sites were studied, with most data collected in 2008 to 2009. Multivariable regression analysis after adjusting for patient characteristics was performed and generalized estimating equations were used to account for within-hospital clustering. In-hospital mortality and quality of inpatient care were assessed. Results: Renal insufficiency was present in 82.0 percent of AMI patients. The adjusted odds ratio vs normal renal function for mortality increased with worsening renal function: 1.45 for mild renal insufficiency (95% confidence interval [CI]: 1.032.05, P = 0.03); 3.36 for moderate renal insufficiency (95% CI: 2.314.89, P < 0.0001); 5.43 for severe renal insufficiency (95% CI: 3.707.95, P < 0.0001); and 6.35 for kidney failure (95% CI: 4.489.01, P < 0.0001). Patients with renal insufficiency received less inpatient and discharge guideline-recommended therapy for AMI. Conclusions: Among AMI patients, mortality and guideline-recommended inpatient therapy correlated inversely with renal function. Adjusted mortality was equally poor among patients with severe renal dysfunction and on dialysis. Clin. Cardiol. 2012 doi: 10.1002/clc.22021 Christopher P. Cannon, MD, has received research grants/support from Accumetrics, AstraZeneca, GlaxoSmithKline, Intekrin Therapeutics, Merck, and Takeda; is a member of the advisory board (funds donated to charity) of Bristol-Myers Squibb/Sanofi, Novartis, and Alnylam; received an honorarium for development of independent educational symposia from Pfizer and AstraZeneca; and is a clinical advisor with equity in Automedics Medical Systems. Gregg C. Fonarow, MD, is a consultant for Novartis and Pfizer. W. Frank Peacock, MD, has received research grants (>$10000) from Abbott, Alere, Brahms, Corthera, EKR, Nanosphere, and The Medicines Company; is a consultant (<$10000) for Abbott, Alere, Beckman Coulter, Electrocore, and The Medicines Company; participates in the speakers' bureau (<$10000) with Abbott and Alere; and has an ownership interest (<$10000) in Comprehensive Research Associates LLC, Vital Sensors, and Emergencies in Medicine LLC. Lee H. Schwamm, MD, is a consultant for Stroke Systems and Medtronic. Deepak L. Bhatt, MD, MPH, discloses the following relationships - Advisory Board: Medscape Cardiology; Board of Directors: Boston VA Research Institute, Society of Chest Pain Centers; Chair: American Heart Association Get With The Guidelines Science Subcommittee; Honoraria: American College of Cardiology (Editor, Clinical Trials, Cardiosource), Duke Clinical Research Institute (clinical trial steering committees), Slack Publications (Chief Medical Editor, Cardiology Today Intervention), WebMD (CME steering committees); Research Grants: Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi Aventis, The Medicines Company; Unfunded Research: FlowCo, PLx Pharma, Takeda. Sylvia E. Rosas has received a research grant from Abbott Laboratories and honorarium from Genzyme. The Get With The Guidelines-Coronary Artery Disease (GWTG-CAD) program was provided by the American Heart Association. The GWTG-CAD program was supported in part through the American Heart Association Pharmaceutical Roundtable and an unrestricted educational grant from Merck. The authors have no other funding, financial relationships, or conflicts of interest to disclose. Additional Supporting Information may be found in the online version of this article. C1 [Vasaiwala, Samip; Cannon, Christopher P.; Bhatt, Deepak L.] Brigham & Womens Hosp, Div Cardiol, Boston, MA 02115 USA. [Bhatt, Deepak L.] Vet Affairs Boston Healthcare, Boston, MA USA. [Cannon, Christopher P.; Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. [Fonarow, Gregg C.] Ronald Reagan UCLA Med Ctr, Div Cardiol, Los Angeles, CA USA. [Peacock, W. Frank] Cleveland Clin, Cleveland, OH 44106 USA. [Laskey, Warren] Univ New Mexico, Sch Med, Div Cardiol, Albuquerque, NM 87131 USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Div Neurol, Boston, MA 02114 USA. [Liang, Li; Hernandez, Adrian F.; Peterson, Eric D.] Duke Clin Res Inst, Div Cardiol, Durham, NC USA. [Rosas, Sylvia E.] Univ Penn, Renal Elect & Hypertens Div, Philadelphia, PA 19104 USA. [Rosas, Sylvia E.] Philadelphia VA Med Ctr, Dept Med, Philadelphia, PA USA. RP Bhatt, DL (reprint author), VA Boston Healthcare Syst, Cardiol Sect, 1400 VFW Pkwy, Boston, MA 02132 USA. EM dlbhattmd@post.harvard.edu RI Hernandez, Adrian F./A-7818-2016 OI Schwamm, Lee/0000-0003-0592-9145; Hernandez, Adrian F./0000-0003-3387-9616 FU Accumetrics; AstraZeneca; GlaxoSmithKline; Intekrin Therapeutics; Merck; Takeda; Abbott; Alere; Brahms; Corthera; EKR; Nanosphere; Medicines Company; Amarin; Bristol-Myers Squibb; Eisai; Ethicon; Medtronic; Sanofi Aventis; Abbott Laboratories; American Heart Association Pharmaceutical Roundtable FX Christopher P. Cannon, MD, has received research grants/support from Accumetrics, AstraZeneca, GlaxoSmithKline, Intekrin Therapeutics, Merck, and Takeda; is a member of the advisory board (funds donated to charity) of Bristol-Myers Squibb/Sanofi, Novartis, and Alnylam; received an honorarium for development of independent educational symposia from Pfizer and AstraZeneca; and is a clinical advisor with equity in Automedics Medical Systems. Gregg C. Fonarow, MD, is a consultant for Novartis and Pfizer. W. Frank Peacock, MD, has received research grants (>$10000) from Abbott, Alere, Brahms, Corthera, EKR, Nanosphere, and The Medicines Company; is a consultant (<$10000) for Abbott, Alere, Beckman Coulter, Electrocore, and The Medicines Company; participates in the speakers' bureau (<$10000) with Abbott and Alere; and has an ownership interest (<$10000) in Comprehensive Research Associates LLC, Vital Sensors, and Emergencies in Medicine LLC. Lee H. Schwamm, MD, is a consultant for Stroke Systems and Medtronic. Deepak L. Bhatt, MD, MPH, discloses the following relationships - Advisory Board: Medscape Cardiology; Board of Directors: Boston VA Research Institute, Society of Chest Pain Centers; Chair: American Heart Association Get With The Guidelines Science Subcommittee; Honoraria: American College of Cardiology (Editor, Clinical Trials, Cardiosource), Duke Clinical Research Institute (clinical trial steering committees), Slack Publications (Chief Medical Editor, Cardiology Today Intervention), WebMD (CME steering committees); Research Grants: Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi Aventis, The Medicines Company; Unfunded Research: FlowCo, PLx Pharma, Takeda. Sylvia E. Rosas has received a research grant from Abbott Laboratories and honorarium from Genzyme.; The Get With The Guidelines-Coronary Artery Disease (GWTG-CAD) program was provided by the American Heart Association. The GWTG-CAD program was supported in part through the American Heart Association Pharmaceutical Roundtable and an unrestricted educational grant from Merck. The authors have no other funding, financial relationships, or conflicts of interest to disclose. NR 18 TC 12 Z9 12 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0160-9289 J9 CLIN CARDIOL JI Clin. Cardiol. PD SEP PY 2012 VL 35 IS 9 BP 541 EP 547 DI 10.1002/clc.22021 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 002ZZ UT WOS:000308579200004 PM 22744797 ER PT J AU Mell, LK Lau, SK Rose, BS Jeong, JH AF Mell, Loren K. Lau, Steven K. Rose, Brent S. Jeong, Jong-Hyeon TI Reporting of cause-specific treatment effects in cancer clinical trials with competing risks: A systematic review SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Randomized trials; Oncology; Competing risks; Cause-specific ID COMPOSITE END-POINTS; RANDOMIZED-TRIALS; NECK-CANCER; OUTCOMES; MORTALITY; SELECTION; ISSUES; TESTS; HEAD AB Background: Separate analysis of cause-specific treatment effects is important for interpreting results of randomized trials. We sought to determine the extent to which cause-specific effects on primary events are reported in contemporary randomized controlled trials in oncology. Methods: We screened 833 randomized trials published in eight leading medical journals between January 2006 and December 2009. We excluded prevention studies (n = 52). secondary reports (n = 100), and one retracted study. Analysis was further restricted to 116 trials in non-metastatic/recurrent cancer that used an event-free survival primary endpoint. For each study included in the analysis, we evaluated whether treatment effects on both cancer and non-cancer events comprising the primary endpoint were reported separately and whether statistical analysis was provided. Results: Of the 116 randomized trials, 47 (40%; 95% confidence interval (CI), 32-50%) reported effects on both cancer and non-cancer events comprising the primary endpoint, with statistical analysis provided in 13(11%: 95% CI, 7-19%). Twenty-six trials (22%; 95% CI, 15-31%) reported effects on cancer but not non-cancer events, with statistical analysis provided in 11 (9%; 95% CI, 5-17%). In 43 studies (37%; 95% CI, 28-47%), no effects on cancer-specific components of the primary endpoint were given. Of these, 33 studies (28%; 95% CI 21-38%) did report effects on some cancer-specific event, while ten (9%; 95% CI, 4-16%) did not report effects of treatment on any cancer event. Discussion: Many randomized trials in oncology do not report cause-specific effects on primary events. Increased specificity is needed in the design and reporting of cancer clinical trials. (c) 2012 Elsevier Inc. All rights reserved. C1 [Mell, Loren K.; Lau, Steven K.] Univ Calif San Diego, Dept Radiat Oncol, La Jolla, CA 92093 USA. [Rose, Brent S.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Rose, Brent S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Jeong, Jong-Hyeon] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA. RP Mell, LK (reprint author), Univ Calif San Diego, Dept Radiat Oncol, 3855 Hlth Sci Dr,MC0843, La Jolla, CA 92093 USA. EM lmell@ucsd.edu OI Lau, Steven/0000-0002-6433-8735; Jeong, Jong/0000-0003-0596-2201; Mell, Loren/0000-0003-2277-6080 FU U.S. National Institutes of Health FX U.S. National Institutes of Health NR 28 TC 4 Z9 4 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD SEP PY 2012 VL 33 IS 5 BP 920 EP 924 DI 10.1016/j.cct.2012.05.013 PG 5 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 995XY UT WOS:000308049800009 PM 22664646 ER PT J AU Henninger, H Hsieh, DT Eskandar, EN Cole, AJ AF Henninger, H. Hsieh, D. T. Eskandar, E. N. Cole, A. J. TI LATERALIZATION AND LOCALIZATION OF POST-TRAUMATIC EPILEPSY WITH DUAL PATHOLOGY USING FORAMEN OVALE ELECTRODES: A CASE REPORT SO EPILEPSIA LA English DT Meeting Abstract CT 10th European Congress on Epileptology CY SEP 30-OCT 04, 2012 CL London, ENGLAND C1 [Henninger, H.] Maine Med Partners Neurol, Scarborough, ME USA. [Eskandar, E. N.; Cole, A. J.] Massachusetts Gen Hosp, MGH Epilepsy Serv, Boston, MA 02114 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 0013-9580 J9 EPILEPSIA JI Epilepsia PD SEP PY 2012 VL 53 SU 5 SI SI BP 30 EP 30 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 007GD UT WOS:000308875900100 ER PT J AU Karakis, I Leeman, B Leveroni, C Kilbride, RR Cash, S Eskandar, EN Simon, MV AF Karakis, I. Leeman, B. Leveroni, C. Kilbride, R. R. Cash, S. Eskandar, E. N. Simon, M. V. TI THE SIGNIFICANCE OF INTRA-STIMULATION DISCHARGES DURING NEUROPHYSIOLOGIC LANGUAGE MAPPING FOR EPILEPSY SURGERY SO EPILEPSIA LA English DT Meeting Abstract CT 10th European Congress on Epileptology CY SEP 30-OCT 04, 2012 CL London, ENGLAND C1 [Karakis, I.; Leveroni, C.; Kilbride, R. R.; Cash, S.; Eskandar, E. N.; Simon, M. V.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Leeman, B.] Emory Univ, Atlanta, GA 30322 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 0013-9580 J9 EPILEPSIA JI Epilepsia PD SEP PY 2012 VL 53 SU 5 SI SI BP 128 EP 128 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 007GD UT WOS:000308875900437 ER PT J AU Kabir, A Hegde, M Santos-Sanchez, C Hess, C Garcia, P AF Kabir, A. Hegde, M. Santos-Sanchez, C. Hess, C. Garcia, P. TI WORSENING OF SEIZURES FOLLOWING ABRUPT DISCONTINUATION OF MARIJUANA IN AN EPILEPSY MONITORING UNIT SO EPILEPSIA LA English DT Meeting Abstract CT 10th European Congress on Epileptology CY SEP 30-OCT 04, 2012 CL London, ENGLAND C1 [Kabir, A.] San Francisco VA Med Ctr, San Francisco, CA USA. [Hegde, M.; Santos-Sanchez, C.; Hess, C.; Garcia, P.] Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD SEP PY 2012 VL 53 SU 5 SI SI BP 156 EP 156 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 007GD UT WOS:000308875900536 ER PT J AU Kravljanac, R Staropoli, J Sims, K Jovic, NJ Djuric, M AF Kravljanac, R. Staropoli, J. Sims, K. Jovic, N. J. Djuric, M. TI CLINICAL AND EEG CHARACTERISTICS OF EPILEPSY IN PATIENTS WITH NEURONAL CEROID LIPOFUSCINOSIS SO EPILEPSIA LA English DT Meeting Abstract CT 10th European Congress on Epileptology CY SEP 30-OCT 04, 2012 CL London, ENGLAND C1 [Kravljanac, R.; Djuric, M.] Univ Belgrade, Fac Med, Inst Mother & Child Healthcare Serbia, Belgrade, Serbia. [Staropoli, J.; Sims, K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Jovic, N. J.] Sch Med, Dept Neurol & Psychiat Children & Youth, Belgrade, Serbia. 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 0013-9580 J9 EPILEPSIA JI Epilepsia PD SEP PY 2012 VL 53 SU 5 SI SI BP 221 EP 221 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 007GD UT WOS:000308875900762 ER PT J AU Gallagher, A Tanaka, N Suzuki, N Liu, HS Thiele, EA Stufflebeam, SM AF Gallagher, Anne Tanaka, Naoaki Suzuki, Nao Liu, Hesheng Thiele, Elizabeth A. Stufflebeam, Steven M. TI Decreased language laterality in tuberous sclerosis complex: A relationship between language dominance and tuber location as well as history of epilepsy SO EPILEPSY & BEHAVIOR LA English DT Article DE TSC; Language lateralization; History of epilepsy; Cortical lesions; MEG; Minimum-norm estimate (MNE); Presurgical work-up ID SURFACE-BASED ANALYSIS; FUNCTIONAL MRI; CORTICAL ACTIVITY; WORD RECOGNITION; MEG; RECONSTRUCTION; CHILDREN; EEG; LOCALIZATION; MAGNETOENCEPHALOGRAPHY AB Nearly 90% of patients with tuberous sclerosis complex (TSC) have epilepsy. Epilepsy surgery can be considered, which often requires a presurgical assessment of language lateralization. This is the first study to investigate language lateralization in TSC patients using magnetoencephalography. Fifteen patients performed a language task during magnetoencephalography recording. Cerebral generators of language-evoked fields (EF) were identified in each patient. Laterality indices (LI) were computed using magnetoencephalography data extracted from the inferior frontal as well as middle and superior temporal gyri from both hemispheres between 250 and 550 ms. Source analysis demonstrated a fusiform gyrus activation, followed by an activation located in the basal temporal language area and middle and superior temporal gyri responses, ending with an inferior frontal activation. Eleven patients (73.3%) had left-hemisphere language dominance, whereas four patients (26.7%) showed a bilateral language pattern, which was associated with a history of epilepsy and presence of tubers in language-related areas. (c) 2012 Elsevier Inc. All rights reserved. C1 [Gallagher, Anne; Tanaka, Naoaki; Suzuki, Nao; Liu, Hesheng; Stufflebeam, Steven M.] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Gallagher, Anne; Tanaka, Naoaki; Suzuki, Nao; Liu, Hesheng; Thiele, Elizabeth A.; Stufflebeam, Steven M.] Harvard Univ, Sch Med, Boston, MA USA. [Gallagher, Anne; Thiele, Elizabeth A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Gallagher, A (reprint author), Univ Montreal, Dept Psychol, CP 6128,Succursale Ctr Ville, Montreal, PQ H3C 3J7, Canada. EM anneg@nmr.mgh.harvard.edu OI Liu, Hesheng/0000-0002-7233-1509 FU National Center for Research Resources [S10RR031599]; National Institutes of Health [P41RR14075, RO1NS037462-07, R01NS069696]; Canadian Institute of Health Research (CIHR); Carol and James Herscot Center for Tuberous Sclerosis Complex FX This work was supported by award number S10RR031599 from the National Center for Research Resources and the National Institutes of Health (P41RR14075, RO1NS037462-07, R01NS069696). 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. This research was also supported by a scholarship by the Canadian Institute of Health Research (CIHR) awarded to Anne Gallagher, Ph.D. as well as by the Carol and James Herscot Center for Tuberous Sclerosis Complex. NR 38 TC 4 Z9 4 U1 2 U2 8 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 SEP PY 2012 VL 25 IS 1 BP 36 EP 41 DI 10.1016/j.yebeh.2012.06.013 PG 6 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA 009BE UT WOS:000308999500007 PM 22980079 ER PT J AU Januzzi, JL Filippatos, G Nieminen, M Gheorghiade, M AF Januzzi, James L., Jr. Filippatos, Gerasimos Nieminen, Markku Gheorghiade, Mihai TI Troponin elevation in patients with heart failure: on behalf of the third Universal Definition of Myocardial Infarction Global Task Force: Heart Failure Section SO EUROPEAN HEART JOURNAL LA English DT Review DE Troponin; Heart failure; Prognosis ID ACUTE CORONARY SYNDROME; BRAIN NATRIURETIC PEPTIDE; CARDIAC TROPONIN; AMBULATORY PATIENTS; PROGNOSTIC VALUE; SENSITIVE ASSAY; SERIAL CHANGES; I ELEVATION; CIRCULATING CONCENTRATIONS; RISK STRATIFICATION AB Cardiac troponin testing is commonly performed in patients with heart failure (HF). Despite being strongly linked to spontaneous (Type I) acute myocardial infarction (MI)a common cause of acute HF syndromesit is well recognized that concentrations of circulating troponins above the 99th percentile of a normal population in the context of both acute and chronic HF are highly prevalent, and frequently unrelated to Type I MI. Other mechanism(s) leading to troponin elevation in HF syndromes remain elusive in many cases but prominently includes supplydemand inequity (Type II MI), which may be associated with coronary artery obstruction and endothelial dysfunction, or may occur in the absence of coronary obstruction due to increased oxygen demand related to increased wall tension, anaemia, or other factors provoking subendocardial injury. Non-coronary triggers, such as cellular necrosis, apoptosis, or autophagy in the context of wall stress may explain the troponin release in HF, as can toxic effects of circulating neurohormones, toxins, inflammation, and infiltrative processes, among others. Nonetheless, across a wide spectrum of HF syndromes, when troponin elevation occurs, independent of mechanism, it is strongly predictive of an adverse outcome. Clinicians should be aware of the high frequency of troponin elevation when measuring the marker in patients with HF, should keep in mind the possible causes of this phenomenon, and, independent of a diagnosis of oacute MI', should recognize the considerable ramifications of troponin elevation in this setting. C1 [Januzzi, James L., Jr.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Filippatos, Gerasimos] Univ Athens, Hosp Attikon, Dept Cardiol, Heart Failure Unit, Athens, Greece. [Nieminen, Markku] Univ Helsinki, Cent Hosp, Div Cardiol, Helsinki, Finland. [Gheorghiade, Mihai] Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, Chicago, IL 60611 USA. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Div Cardiol, Yawkey 5984,32 Fruit St, Boston, MA 02114 USA. EM jjanuzzi@partners.org RI Lainscak, Mitja/F-3237-2015 FU Roche Diagnostics; Siemens; Critical Diagnostics; BRAHMS, GMBH FX J.L.J. reports grant support from Roche Diagnostics, Siemens, Critical Diagnostics, and BRAHMS, GMBH. NR 67 TC 84 Z9 86 U1 1 U2 18 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2012 VL 33 IS 18 BP 2265 EP + DI 10.1093/eurheartj/ehs191 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 007KF UT WOS:000308886500005 PM 22745356 ER PT J AU Mebazaa, A Vanpoucke, G Thomas, G Verleysen, K Cohen-Solal, A Vanderheyden, M Bartunek, J Mueller, C Launay, JM Van Landuyt, N D'hondt, F Verschuere, E Vanhaute, C Tuytten, R Vanneste, L De Cremer, K Wuyts, J Davies, H Moerman, P Logeart, D Collet, C Lortat-Jacob, B Tavares, M Laroy, W Januzzi, JL Samuel, JL Kas, K AF Mebazaa, Alexandre Vanpoucke, Griet Thomas, Gregoire Verleysen, Katleen Cohen-Solal, Alain Vanderheyden, Marc Bartunek, Jozef Mueller, Christian Launay, Jean-Marie Van Landuyt, Natalie D'hondt, Filip Verschuere, Elisabeth Vanhaute, Caroline Tuytten, Robin Vanneste, Lies De Cremer, Koen Wuyts, Jan Davies, Huw Moerman, Piet Logeart, Damien Collet, Corinne Lortat-Jacob, Brice Tavares, Miguel Laroy, Wouter Januzzi, James L. Samuel, Jane-Lise Kas, Koen TI Unbiased plasma proteomics for novel diagnostic biomarkers in cardiovascular disease: identification of quiescin Q6 as a candidate biomarker of acutely decompensated heart failure SO EUROPEAN HEART JOURNAL LA English DT Article DE Diagnosis; Acute decompensated heart failure; Biomarker; Proteomics ID SULFHYDRYL OXIDASE; INDUCED APOPTOSIS; CELLS; HYPERTROPHY; VALIDATION; PEPTIDES; QSOX1 AB Biochemical marker testing has improved the evaluation and management of patients with cardiovascular diseases over the past decade. Natriuretic peptides (NPs), used in clinical practice to assess cardiac dysfunction, exhibit many limitations, however. We used an unbiased proteomics approach for the discovery of novel diagnostic plasma biomarkers of heart failure (HF). A proteomics pipeline adapted for very low-abundant plasma proteins was applied to clinical samples from patients admitted with acute decompensated HF (ADHF). Quiescin Q6 (QSOX1), a protein involved in the formation of disulfide bridges, emerged as the best performing marker for ADHF (with an area under the receiver operator characteristic curve of 0.86, 95 confidence interval: 0.790.92), and novel isoforms of NPs were also identified. Diagnostic performance of QSOX1 for ADHF was confirmed in 267 prospectively collected subjects of whom 76 had ADHF. Combining QSOX1 to B-type NP (BNP) significantly improved diagnostic accuracy for ADHF by particularly improving specificity. Using thoracic aortic constriction in rats, QSOX1 was specifically induced within both left atria and ventricles at the time of HF onset. The novel biomarker QSOX1 accurately identifies ADHF, particularly when combined with BNP. Through both clinical and experimental studies we provide lines of evidence for a link between ADHF and cardiovascular production of QSOX1. C1 [Mebazaa, Alexandre; Cohen-Solal, Alain; Launay, Jean-Marie; Logeart, Damien; Collet, Corinne; Lortat-Jacob, Brice; Samuel, Jane-Lise] Paris Diderot Univ, Lariboisiere Hosp, Dept Anesthesia & Intens Care, INSERM,U942, F-75010 Paris, France. [Mebazaa, Alexandre; Cohen-Solal, Alain; Logeart, Damien; Lortat-Jacob, Brice; Samuel, Jane-Lise] Univ Paris Diderot, Paris, France. [Mebazaa, Alexandre; Cohen-Solal, Alain; Launay, Jean-Marie; Logeart, Damien; Collet, Corinne; Lortat-Jacob, Brice; Samuel, Jane-Lise] Hop Lariboisiere, AP HP, Dept Anaesthesia & Crit Care Cardiol & Biochem, F-75475 Paris, France. [Mebazaa, Alexandre] DHU Neurovasc Sorbonne Paris Cite, Paris, France. [Vanpoucke, Griet; Thomas, Gregoire; Verleysen, Katleen; Van Landuyt, Natalie; D'hondt, Filip; Verschuere, Elisabeth; Vanhaute, Caroline; Tuytten, Robin; Vanneste, Lies; De Cremer, Koen; Wuyts, Jan; Davies, Huw; Moerman, Piet; Laroy, Wouter; Kas, Koen] Pronota NV, B-9052 Zwijnaarde, Belgium. [Vanderheyden, Marc; Bartunek, Jozef] Onze Lieve Vrouw Hosp, Ctr Cardiovasc, Aalst, Belgium. [Mueller, Christian] Kantonsspital Basel, Basel, Switzerland. [Launay, Jean-Marie; Collet, Corinne] Univ R Descartes, Paris, France. [Tavares, Miguel] Hosp Geral Santo Antonio, Oporto, Portugal. [Januzzi, James L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Mebazaa, A (reprint author), Paris Diderot Univ, Lariboisiere Hosp, Dept Anesthesia & Intens Care, INSERM,U942, 2 Rue Ambroise Pare, F-75010 Paris, France. EM alexandre.mebazaa@lrb.aphp.fr OI Tuytten, Robin/0000-0002-8734-7335; Samuel, Jane-Lise/0000-0002-7346-2404 FU Inserm [AAP 2009/RRC]; AP-HP (CI/JLS); Agency for Innovation through Science and Technology in Flanders (IWT, Belgium); Alere; BRAHMS; Pronota; Bayer Pharma; Abbott; Roche FX This work was supported by the Inserm (AAP 2009/RRC), AP-HP (CI/JLS), and the Agency for Innovation through Science and Technology in Flanders (IWT, Belgium).; A.M. and A.C.S. received speakers' fees from Alere and BRAHMS; A.M. received consulting fees from Pronota and Bayer Pharma. C.M. received research support from Pronota, Brahms, Alere, Abbott, and Roche and speakers' honoraria from Brahms, Alere, Abbott, and Roche. A financial collaboration exists between Pronota and U942 and Cardiovascular-Center-Aalst, respectively. No funding bodies had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 28 TC 25 Z9 26 U1 1 U2 20 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2012 VL 33 IS 18 BP 2317 EP 2324 DI 10.1093/eurheartj/ehs162 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 007KF UT WOS:000308886500012 PM 22733835 ER PT J AU Fedorowski, A Franceschini, N Brody, J Liu, CY Verwoert, GC Boerwinkle, E Couper, D Rice, KM Rotter, JI Mattace-Raso, F Uitterlinden, A Hofman, A Almgren, P Sjogren, M Hedblad, B Larson, MG Newton-Cheh, C Wang, TJ Rose, KM Psaty, BM Levy, D Witteman, J Melander, O AF Fedorowski, Artur Franceschini, Nora Brody, Jennifer Liu, Chunyu Verwoert, Germaine C. Boerwinkle, Eric Couper, David Rice, Kenneth M. Rotter, Jerome I. Mattace-Raso, Francesco Uitterlinden, Andre Hofman, Albert Almgren, Peter Sjogren, Marketa Hedblad, Bo Larson, Martin G. Newton-Cheh, Christopher Wang, Thomas J. Rose, Kathryn M. Psaty, Bruce M. Levy, Daniel Witteman, Jacqueline Melander, Olle TI Orthostatic hypotension and novel blood pressure-associated gene variants: Genetics of Postural Hemodynamics (GPH) Consortium SO EUROPEAN HEART JOURNAL LA English DT Article DE Orthostatic hypotension; Genetics; Single nucleotide polymorphism; Steroid 17-alpha-hydroxylase; Natriuretic peptides; Adrenomedullin ID GENOME-WIDE ASSOCIATION; PRIMARY SJOGRENS-SYNDROME; MALMO PREVENTIVE PROJECT; ATHEROSCLEROSIS RISK; PREDICTS MORTALITY; HYPERTENSION; COMMUNITIES; DIAGNOSIS; HEART; DISEASE AB Orthostatic hypotension (OH), an independent predictor of mortality and cardiovascular events, strongly correlates with hypertension. Recent genome-wide studies have identified new loci influencing blood pressure (BP) in populations, but their impact on OH remains unknown. A total of 38 970 men and women of European ancestry from five population-based cohorts were included, of whom 2656 (6.8) met the diagnostic criteria for OH (systolic/diastolic BP drop epsilon 20/10 mmHg within 3 min of standing). Thirty-one recently discovered BP-associated single nucleotide polymorphisms (SNPs) were examined using an additive genetic model and the major allele as referent. Relations between OH, orthostatic systolic BP response, and genetic variants were assessed by inverse variance-weighted meta-analysis. We found Bonferroni adjusted (P 0.0016) significant evidence for association between OH and the EBF1 locus (rs11953630, per-minor-allele odds ratio, 95 confidence interval: 0.90, 0.850.96; P 0.001), and nominal evidence (P 0.05) for CYP17A1 (rs11191548: 0.85, 0.750.95; P 0.005), and NPR3-C5orf23 (rs1173771: 0.92, 0.870.98; P 0.009) loci. Among subjects not taking BP-lowering drugs, three SNPs within the NPPA/NPPB locus were nominally associated with increased risk of OH (rs17367504: 1.13, 1.021.24; P 0.02, rs198358: 1.10, 1.011.20; P 0.04, and rs5068: 1.22, 1.041.43; P 0.01). Moreover, an ADM variant was nominally associated with continuous orthostatic systolic BP response in the adjusted model (P 0.04). The overall association between common gene variants in BP loci and OH was generally weak and the direction of effect inconsistent with resting BP findings. These results suggest that OH and resting BP share few genetic components. C1 [Fedorowski, Artur; Melander, Olle] Skane Univ Hosp, Ctr Emergency Med, S-20502 Malmo, Sweden. [Fedorowski, Artur; Almgren, Peter; Sjogren, Marketa; Hedblad, Bo; Melander, Olle] Lund Univ, Clin Res Ctr, Dept Clin Sci, Malmo, Sweden. [Franceschini, Nora; Rose, Kathryn M.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Brody, Jennifer; Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Brody, Jennifer; Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Brody, Jennifer; Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Liu, Chunyu; Larson, Martin G.; Wang, Thomas J.; Levy, Daniel] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Liu, Chunyu; Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Verwoert, Germaine C.; Mattace-Raso, Francesco; Uitterlinden, Andre; Hofman, Albert; Witteman, Jacqueline] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Verwoert, Germaine C.; Mattace-Raso, Francesco; Uitterlinden, Andre] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Verwoert, Germaine C.; Uitterlinden, Andre; Witteman, Jacqueline] Netherlands Genome Initiat NGI, Netherlands Consortium Healthy Aging NCHA, The Hague, Netherlands. [Boerwinkle, Eric] Univ Texas Houston, Sch Publ Hlth, Human Genet Ctr, Houston, TX USA. [Couper, David] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. [Rice, Kenneth M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Larson, Martin G.] Boston Univ, Dept Math, Boston, MA 02215 USA. [Newton-Cheh, Christopher; Wang, Thomas J.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Newton-Cheh, Christopher; Wang, Thomas J.] Harvard Univ, Sch Med, Boston, MA USA. [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Ctr Human Genet Res, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Newton-Cheh, Christopher] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. RP Fedorowski, A (reprint author), Skane Univ Hosp, Ctr Emergency Med, Entrance 35,Floor 2, S-20502 Malmo, Sweden. EM artur.fedorowski@med.lu.se RI Rice, Kenneth/A-4150-2013; Mattace- Raso, Francesco/L-2541-2015; OI Rice, Kenneth/0000-0001-5779-4495; Larson, Martin/0000-0002-9631-1254 FU Lund University; Zoll FX Detailed information on the sources of funding can be found in the Supplementary material online (Funding and Acknowledgements Section). Funding to pay the Open Access publication charges for this article was provided by Lund University.; B.M.P. serves on a DSMB for a clinical trial of a device funded by the manufacturer (Zoll). NR 40 TC 12 Z9 12 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2012 VL 33 IS 18 BP 2331 EP 2341 DI 10.1093/eurheartj/ehs058 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 007KF UT WOS:000308886500014 PM 22504314 ER PT J AU Ueno, T Yeung, MY McGrath, M Yang, SM Zaman, N Snawder, B Padera, RF Magee, CN Gorbatov, R Hashiguchi, M Azuma, M Freeman, GJ Sayegh, MH Najafian, N AF Ueno, Takuya Yeung, Melissa Y. McGrath, Martina Yang, Sunmi Zaman, Nadia Snawder, Benjamin Padera, Robert F. Magee, Ciara N. Gorbatov, Rostic Hashiguchi, Masaaki Azuma, Miyuki Freeman, Gordon J. Sayegh, Mohamed H. Najafian, Nader TI Intact B7-H3 signaling promotes allograft prolongation through preferential suppression of Th1 effector responses SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE Costimulatory molecules; Transplantation; T helper cells ID T-CELL-ACTIVATION; IN-VIVO; IMMUNE-RESPONSES; PD-1 PATHWAY; EXPRESSION; TRANSPLANTATION; SURVIVAL; CANCER; MOUSE; AUTOIMMUNITY AB Ligands of the B7 family provide both positive and negative costimulatory signals to the CD28 family of receptors on T lymphocytes, the balance of which determines the immune response. B7-H3 is a member of the B7 family whose function in T-cell activation has been the subject of some controversy: in autoimmunity and tumor immunity, it has been described as both costimulatory and coinhibitory, while in transplantation, B7-H3 signaling is thought to contribute to graft rejection. However, we now demonstrate results to the contrary. Signaling through a putative B7-H3 receptor prolonged allograft survival in a fully MHC-mismatched cardiac model and promoted a shift toward a Th2 milieu; conversely, B7-H3 blockade, achieved by use of a blocking antibody, resulted in accelerated rejection, an effect associated with enhanced IFN-? production. Finally, graft prolongation achieved by CTLA4 Ig was shortened both by B7-H3 blockade and the absence of recipient B7-H3. These findings suggest a coinhibitory role for B7-H3. However, experience with other CD28/B7 family members suggests that immune redundancy plays a crucial role in determining the functions of various pathways. Given the abundance of conflicting data, it is plausible that, under differing conditions, B7-H3 may have both positive and negative costimulatory functions. C1 [Ueno, Takuya; Yeung, Melissa Y.; McGrath, Martina; Yang, Sunmi; Zaman, Nadia; Snawder, Benjamin; Magee, Ciara N.; Sayegh, Mohamed H.; Najafian, Nader] Harvard Univ, Sch Med, Transplantat Res Ctr, Brigham & Womens Hosp,Renal Div, Boston, MA 02115 USA. [Ueno, Takuya; Gorbatov, Rostic] Harvard Univ, Sch Med, Ctr Syst Biol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Padera, Robert F.] Harvard Univ, Sch Med, Deparment Pathol, Brigham & Womens Hosp, Boston, MA 02115 USA. [Hashiguchi, Masaaki; Azuma, Miyuki] Tokyo Med & Dent Univ, Dept Mol Immunol, Tokyo, Japan. [Freeman, Gordon J.] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Najafian, N (reprint author), Harvard Univ, Sch Med, Transplantat Res Ctr, Brigham & Womens Hosp,Renal Div, 221 Longwood Ave, Boston, MA 02115 USA. EM nnajafian@rics.bwh.harvard.edu FU American Heart Association; National Kidney Foundation; American Society of Transplantation; NIH [R01 AI070820, AI41521, R01 A1051559, P01 AI56299, R56 AI089777] FX T. Ueno is supported by a scientist development grant from the American Heart Association. M.Y. Yeung is supported by a postdoctoral fellowship from the National Kidney Foundation and a fellow-to-faculty transition grant from the American Heart Association. M. M. and C.N.M are supported by postdoctoral fellowships from the American Society of Transplantation. This work was supported by NIH grants R01 AI070820 and AI41521 (to M. H. S.), R01 A1051559 and P01 AI56299 (to G. F. and M. H. S), and R56 AI089777 (to N.N.) NR 30 TC 10 Z9 14 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD SEP PY 2012 VL 42 IS 9 BP 2343 EP 2353 DI 10.1002/eji.201242501 PG 11 WC Immunology SC Immunology GA 000RH UT WOS:000308404800017 PM 22733595 ER PT J AU Scheffel, H Stolzmann, P Leschka, S Desbiolles, L Seifert, B Marincek, B Alkadhi, H AF Scheffel, Hans Stolzmann, Paul Leschka, Sebastian Desbiolles, Lotus Seifert, Burkhardt Marincek, Borut Alkadhi, Hatem TI Ventricular short-axis measurements in patients with pulmonary embolism: Effect of ECG-gating on variability, accuracy, and risk prediction SO EUROPEAN JOURNAL OF RADIOLOGY LA English DT Article DE Pulmonary embolism; Computed tomography; Electrocardiography; Short axis; Ventricular function; Prognostic value ID MULTIDETECTOR ROW CT; CHEST COMPUTED-TOMOGRAPHY; HELICAL CT; INITIAL-EXPERIENCE; DYSFUNCTION; MORTALITY; ECHOCARDIOGRAPHY; ANGIOGRAPHY; DIAGNOSIS; ENLARGEMENT AB Objective: To assess prospectively the intra-and interobserver variability, accuracy, and prognostic value of right and left ventricular short-axis diameter (RVd and LVd) measurements for risk stratification in patients with pulmonary embolism (PE) using ECG-gated compared to non-gated CT. Materials and methods: Sixty consecutive patients (33 women; mean age 58.7 +/- 10.3 years) with suspicion of PE underwent both non-gated and ECG-gated chest CT. RVd and LVd on four-chamber views and intra- and interobserver agreements were calculated for both protocols. RVd/LVd ratios were calculated and were related to 30-days adverse clinical events using receiver operating characteristics with area-under-the-curve (AUC) analyses. Results: Both inter-and intraobserver variability showed narrower limits of agreement for all measurements with ECG-gated as compared to non-gated CT. Diameter measurements were significantly lower using non-ECG-gated CT as compared to ECG-gated CT for RVd and LVd (both p < .05). The AUC for the RVd/LVd ratio from ECG-gated CT was significantly larger than that from non-gated CT (0.956, 95% CI: 0.768-0.999 versus 0.675, 95% CI: 0.439-0.860; p = .048). Conclusion: RVd and LVd measurements from ECG-gated chest CT show less intra-and interobserver variability and more accurately reflect ventricular function. In our patient cohort ECG-gated chest CT allows better prediction of short-term outcome of patients with acute PE that needs to be validated in a larger outcome study. (C) 2011 Published by Elsevier Ireland Ltd. C1 [Scheffel, Hans] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Scheffel, Hans; Stolzmann, Paul; Leschka, Sebastian; Desbiolles, Lotus; Marincek, Borut; Alkadhi, Hatem] Univ Zurich Hosp, Inst Diagnost Radiol, Zurich, Switzerland. [Seifert, Burkhardt] Univ Zurich, Inst Social & Prevent Med, Biostat Unit, CH-8006 Zurich, Switzerland. [Scheffel, Hans; Stolzmann, Paul; Alkadhi, Hatem] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Scheffel, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM hscheffel@partners.org OI Seifert, Burkhardt/0000-0002-5829-2478 NR 29 TC 5 Z9 6 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0720-048X J9 EUR J RADIOL JI Eur. J. Radiol. PD SEP PY 2012 VL 81 IS 9 BP 2195 EP 2202 DI 10.1016/j.ejrad.2011.03.067 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 990ZG UT WOS:000307670000045 PM 21978773 ER PT J AU Kurusu, S Sapirstein, A Bonventre, JV AF Kurusu, Shiro Sapirstein, Adam Bonventre, Joseph V. TI Group IVA phospholipase A(2) optimizes ovulation and fertilization in rodents through induction of and metabolic coupling with prostaglandin endoperoxide synthase 2 SO FASEB JOURNAL LA English DT Article DE PLA(2) isoforms; prostaglandin E-2; preovulatory follicle; female reproduction ID HUMAN CHORIONIC-GONADOTROPIN; PRIMED IMMATURE RATS; CYCLOOXYGENASE-2 EXPRESSION; ARACHIDONIC-ACID; GENE DISRUPTION; GRANULOSA-CELLS; EICOSANOID GENERATION; REDUCED FERTILITY; FEEDBACK-CONTROL; MICE LACKING AB Female mice lacking group IVA phospholipase A(2) (Pla2g4a(-/-)) have a smaller litter size, which is due, in part, to defective implantation. We examined PLA(2)G4A dependence of the processes of ovulation and fertilization. Following induction of ovulation by equine chorionic gonadotropin (eCG)/human CG (hCG) treatment and mating, ovulation and fertilization rates were reduced significantly in Pla2g4a(-/-) mice as compared to wild-type littermates. Human CG triggered robust ovarian prostaglandin (PG) E-2 production in the preovulatory period that was significantly attenuated in Pla2g4a(-/-) mice. Human CG transiently enhanced ovarian expression of PLA(2)G4A and prostaglandin endoperoxide synthase 2 (PTGS2) in wild-type mice. This PTGS2 induction was decreased in Pla2g4a(-/-) mice and also in immature rats treated with the PLA(2)G4A inhibitor, archidonyl trifluoromethyl ketone. A close spatiotemporal association of PLA(2)G4A with PTGS2 was found in mouse and rat preovulatory follicles examined by immunohistochemistry. Less association was observed with 4 other forms of PLA(2). Our data strongly suggest that PLA(2)G4A amplifies hCG induction of PTGS2 and colocalizes with the induced PTGS2, thus contributing to robust PG production required for optimal ovulation and fertilization in rodents.-Kurusu, S., Sapirstein, A., Bonventre, J. V. Group IVA phospholipase A(2) optimizes ovulation and fertilization in rodents through induction of and metabolic coupling with prostaglandin endoperoxide synthase 2. FASEB J. 26, 3800-3810 (2012). www.fasebj.org C1 [Kurusu, Shiro; Bonventre, Joseph V.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Sapirstein, Adam] Harvard Univ, Sch Med, Dept Anesthesia & Crit Care, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Bonventre, Joseph V.] Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp, Boston, MA 02115 USA. [Kurusu, Shiro] Kitasato Univ, Sch Vet Med, Vet Physiol Lab, Towada, Aomori 034, Japan. [Sapirstein, Adam] Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21205 USA. [Bonventre, Joseph V.] Harvard Stem Cell Inst, Boston, MA USA. RP Bonventre, JV (reprint author), Harvard Inst Med, Div Renal, 4 Blackfan Cir,Rm 576, Boston, MA 02115 USA. EM joseph_bonventre@hms.harvard.edu FU U.S. National Institute of Health [DK39773, DK38452]; Japanese Society for the Promotion of Science; Kieikai Research Foundation; Nakayama Foundation for Human Science FX The authors greatly thank E. O'Leary and X.-M. Sun and other members of the J.V.B. laboratory for technical assistance and useful suggestions; H. Satoh and M. Jinno for experimental help; Dr. M. Kawaminami (Kitasato University, Towada, Japan) for supplying experimental materials; Drs. A. Cybulsky (McGill University, Montreal, QC, Canada), K. Nomura (Shionogi Research Laboratories, Osaka, Japan), and I. Kudo (Showa University, Tokyo, Japan) and Wyeth Co. (Cambridge, MA, USA) for antibodies; and M. Nakata for assistance with manuscript preparation. The work with mice was supported by U.S. National Institute of Health grants DK39773 and DK38452 (to J.V.B.) and that with rats was by grants-in-aid for scientific research from the Japanese Society for the Promotion of Science and the Kieikai Research Foundation (to S. K.). S. K. received a fellowship for studies abroad from the Nakayama Foundation for Human Science. The authors declare no conflicts of interest. NR 57 TC 7 Z9 7 U1 2 U2 5 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD SEP PY 2012 VL 26 IS 9 BP 3800 EP 3810 DI 10.1096/fj.12-203968 PG 11 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 000MY UT WOS:000308391600020 PM 22673578 ER PT J AU Merritt, MA Kotsopoulos, J Cramer, DW Hankinson, SE Terry, KL Tworoger, SS AF Merritt, Melissa A. Kotsopoulos, Joanne Cramer, Daniel W. Hankinson, Susan E. Terry, Kathryn L. Tworoger, Shelley S. TI Duarte galactose-1-phosphate uridyl transferase genotypes are not associated with ovarian cancer risk SO FERTILITY AND STERILITY LA English DT Article DE Duarte GALT; ovarian cancer; dairy foods; lactose ID GALACTOSE CONSUMPTION; GALT GENE; METABOLISM; WOMEN; METAANALYSIS; PRODUCTS; MUTATION; DELETION; PROMOTER; ALLELES AB Objective: To investigate whether galactose-1-phosphate uridyl transferase (GALT) variant genotypes were associated with epithelial ovarian cancer risk, and to determine if this association was modified by lactose intake. Design: Two prospective cohort studies and a case-control study. Setting: Academic institution. Patient(s): A total of 992 cases and 1,050 population-based control samples from a New England case-control study and 240 cases and 900 control samples from the Nurses' Health Studies. Intervention(s): None. Main Outcome Measure(s): Genotyping of the N314D variant and the 4-bp deletion (-119delGTCA) of GALT with the use of the Taqman 5' nuclease assay. Duarte1 (D1) genotype individuals have a missense mutation (N314D) associated with normal GALT activity unless it occurs together with an associated 4-bp deletion leading to reduced GALT activity (Duarte2 or D2). Result(s): Logistic regression analysis identified no association between D1/D2 genotypes and ovarian cancer risk (pooled risk ratio 1.1 [95% confidence interval (CI) 0.8-1.5] for D1 and 1.0 [95% CI 0.7-1.4] for D2). We did not observe a significant interaction between D1 and D2 genotypes in analyses stratified by level of lactose intake. Conclusion(s): D1 and D2 genotypes do not appear to play a role in the association between galactose intake, possible ovarian dysfunction, and the link with ovarian cancer. (Fertil Steril (R) 2012; 98: 687-91. (C) 2012 by American Society for Reproductive Medicine.) C1 [Merritt, Melissa A.; Cramer, Daniel W.; Hankinson, Susan E.; Terry, Kathryn L.; Tworoger, Shelley S.] Harvard Univ, Dept Epidemiol, Sch Publ Hlth, Boston, MA 02115 USA. [Merritt, Melissa A.; Cramer, Daniel W.; Terry, Kathryn L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, OB GYN Epidemiol Ctr, Boston, MA 02115 USA. [Hankinson, Susan E.; Tworoger, Shelley S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab, Boston, MA 02115 USA. [Merritt, Melissa A.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Kotsopoulos, Joanne] Univ Toronto, Womens Coll Res Inst, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. [Hankinson, Susan E.] Univ Massachusetts, Div Biostat & Epidemiol, Amherst, MA 01003 USA. RP Merritt, MA (reprint author), Harvard Univ, Dept Epidemiol, Sch Publ Hlth, 221 Longwood Ave, Boston, MA 02115 USA. EM merritt@jimmy.harvard.edu OI Tworoger, Shelley/0000-0002-6986-7046 FU National Cancer Institute, National Institutes of Health [P50 CA105009, P01 CA87969, R01 CA49449, R01 CA50385, R01 CA67262, R01 CA054419, R25 CA098566] FX Supported by the National Cancer Institute, National Institutes of Health: grants P50 CA105009, P01 CA87969, R01 CA49449, R01 CA50385, R01 CA67262, and R01 CA054419 and training grant R25 CA098566. NR 25 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2012 VL 98 IS 3 BP 687 EP 691 DI 10.1016/j.fertnstert.2012.05.045 PG 5 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 000QO UT WOS:000308402400036 PM 22749219 ER PT J AU Ananthakrishnan, AN Chan, AT AF Ananthakrishnan, Ashwin N. Chan, Andrew T. TI Association Between Higher Predicted Serum Vitamin D Levels and Reduced Incidence of Inflammatory Bowel Diseases Reply SO GASTROENTEROLOGY LA English DT Letter C1 [Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. NR 4 TC 0 Z9 0 U1 1 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD SEP PY 2012 VL 143 IS 3 BP E28 EP E29 DI 10.1053/j.gastro.2012.07.100 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 000PO UT WOS:000308399300020 ER PT J AU Brown, AD Kuznetsova, MS Spain, WJ Stecker, GC AF Brown, Andrew D. Kuznetsova, Marina S. Spain, William J. Stecker, G. Christopher TI Frequency-specific, location-nonspecific adaptation of interaural time difference sensitivity SO HEARING RESEARCH LA English DT Article ID SOUND LOCALIZATION; POTASSIUM CURRENTS; COCHLEAR NUCLEUS; LEVEL; LATERALIZATION; INHIBITION; CUES AB Human listeners' sensitivity to interaural time differences (ITD) was assessed for 1000 Hz tone bursts (500 ms duration) preceded by trains of 500-ms "adapter" tone bursts (7 s total adapter duration, frequencies of 200, 665, 1000, or 1400 Hz) carrying random ITD, or by an equal-duration period of silence. Presentation of the adapter burst train reduced ITD sensitivity in a frequency-specific manner. The observed effect differs from previously described forms of location-specific psychophysical adaptation, as it was produced using a binaurally diffuse sequence of tone bursts (i.e., a location-nonspecific adapter stimulus). Results are discussed in the context of pre-binaural adaptation. (C) 2012 Elsevier B.V. All rights reserved. C1 [Brown, Andrew D.; Stecker, G. Christopher] Univ Washington, Dept Speech & Hearing Sci, Seattle, WA 98105 USA. [Kuznetsova, Marina S.] Univ Washington, Interdisciplinary Grad Program Neurobiol & Behav, Seattle, WA 98105 USA. [Spain, William J.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Brown, AD (reprint author), Univ Washington, Dept Speech & Hearing Sci, 1417 NE 42nd St, Seattle, WA 98105 USA. EM andrewdb@uw.edu; msk@uw.edu; spain@uw.edu; cstecker@uw.edu FU National Institute on Deafness and Other Communication Disorders [NIH] [T32-DC000033, F31-DC010543, F31-DC091763, R03-DC009482]; VA Merit Review FX The authors thank Anna Mamiya and Shiboney Dumo for help with data collection. This work was supported by the National Institute on Deafness and Other Communication Disorders [NIH Grant Nos. T32-DC000033, F31-DC010543 (ADB), F31-DC091763 (MSK), R03-DC009482 (GCS)] and a VA Merit Review (WJS). NR 27 TC 1 Z9 1 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD SEP PY 2012 VL 291 IS 1-2 BP 52 EP 56 DI 10.1016/j.heares.2012.06.002 PG 5 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 004MA UT WOS:000308684600006 PM 22732693 ER PT J AU Jones, J McDermott, CM Nowels, CT Matlock, DD Bekelman, DB AF Jones, Jacqueline McDermott, Carrie M. Nowels, Carolyn T. Matlock, Daniel D. Bekelman, David B. TI The experience of fatigue as a distressing symptom of heart failure SO HEART & LUNG LA English DT Article DE Fatigue; Heart failure; Patient experiences; Qualitative research; Patient-centered care ID QUALITY-OF-LIFE; PALLIATIVE CARE; PREDICTORS; BURDEN AB OBJECTIVE: We explored the perceptions, experience, and meaning of fatigue as a distressing symptom of chronic heart failure (HP). BACKGROUND: Fatigue, a common symptom of HF, may indicate worsening condition. Patients interpret their symptoms to determine the need for assistance. The meaning of fatigue in everyday life for HF patients in the United States is not well understood. METHODS: We performed an interpretive study of in-depth interviews with HF patients (n = 26) who reported fatigue as a symptom, using a thematic analysis of transcripts within an iterative group framework. RESULTS: Fatigue is characterized by patient values related to their self-identity, their body, their experience of time, their environment, and their relationships with others, including the healthcare system. CONCLUSIONS: Fatigue influences perceived proximity to death and how patients try to preserve what they can do. A patient's HF management plan should be tailored and responsive to that patient's experience of fatigue as communicated by the patient. C1 [Jones, Jacqueline; McDermott, Carrie M.] Univ Colorado, Coll Nursing, Aurora, CO 80045 USA. [Nowels, Carolyn T.; Matlock, Daniel D.] Univ Colorado, Sch Med, Aurora, CO 80045 USA. [Nowels, Carolyn T.; Bekelman, David B.] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Jones, J (reprint author), Univ Colorado, Coll Nursing, Anchutz Med Campus,13120 E 19th Ave,Campus Box C-, Aurora, CO 80045 USA. EM jacqueline.jones@ucdenver.edu OI Jones, Jacqueline/0000-0001-9714-995X FU University of Colorado Hartford/Jahnigen Center for Excellence in Geriatric Medicine; Department of Veterans Affairs Career Development Award (Health Services Research & Development Service Career Development Award [HSRD CDA] [08-022]; Mordecai Palliative Care Grants Fund FX This research was funded by the University of Colorado Hartford/Jahnigen Center for Excellence in Geriatric Medicine and the Mordecai Palliative Care Grants Fund. D.B.B. is funded by a Department of Veterans Affairs Career Development Award (Health Services Research & Development Service Career Development Award [HSR&D CDA] 08-022). The funding organizations had no role in any part of the study. The views expressed in this paper are those of the authors, and do not necessarily reflect the views of the Department of Veterans Affairs. The authors thank Jessica Haxton Retrum, PhD, LCSW, for her contributions to early analytic discussions. NR 43 TC 8 Z9 8 U1 3 U2 9 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0147-9563 J9 HEART LUNG JI Heart Lung PD SEP-OCT PY 2012 VL 41 IS 5 BP 484 EP 491 DI 10.1016/j.hrtlng.2012.04.004 PG 8 WC Cardiac & Cardiovascular Systems; Nursing; Respiratory System SC Cardiovascular System & Cardiology; Nursing; Respiratory System GA 011DP UT WOS:000309145200008 PM 22652166 ER PT J AU Wesemann, D Portuguese, A Magee, J Cluff, K Panchakshari, R Gallagher, M Alt, F AF Wesemann, D. Portuguese, A. Magee, J. Cluff, K. Panchakshari, R. Gallagher, M. Alt, F. TI Primary B cell development in the gut lamina propria SO IMMUNOLOGY LA English DT Meeting Abstract CT European Congress of Immunology CY SEP 05-08, 2012 CL Glasgow, SCOTLAND C1 [Wesemann, D.] Harvard Univ, Sch Med, Boston, MA USA. [Portuguese, A.; Magee, J.; Cluff, K.; Panchakshari, R.; Gallagher, M.; Alt, F.] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 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 0019-2805 J9 IMMUNOLOGY JI Immunology PD SEP PY 2012 VL 137 SU 1 SI SI BP 38 EP 38 PG 1 WC Immunology SC Immunology GA 011TW UT WOS:000309189100092 ER PT J AU Gmyrek, GB Graham, DB Sandoval, G Blaufuss, GS Akilesh, HM Fujikawa, K Xavier, RJ Swat, W AF Gmyrek, G. B. Graham, D. B. Sandoval, G. Blaufuss, G. S. Akilesh, H. M. Fujikawa, K. Xavier, R. J. Swat, W. TI Discs large protein 1 regulates endogenous T cell response: implications for generation of memory T cells SO IMMUNOLOGY LA English DT Meeting Abstract CT European Congress of Immunology CY SEP 05-08, 2012 CL Glasgow, SCOTLAND C1 [Gmyrek, G. B.; Graham, D. B.; Sandoval, G.; Blaufuss, G. S.; Akilesh, H. M.; Swat, W.] Washington Univ, Sch Med, St Louis, MO USA. [Fujikawa, K.] Hokkaido Univ, Sch Med, Sapporo, Hokkaido 060, Japan. [Xavier, R. J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 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 0019-2805 J9 IMMUNOLOGY JI Immunology PD SEP PY 2012 VL 137 SU 1 SI SI BP 136 EP 137 PG 2 WC Immunology SC Immunology GA 011TW UT WOS:000309189101051 ER PT J AU Berberich-Siebelt, F Vaeth, M Schliesser, U Reissig, S Satoh, K Jonuleit, H Muller, G Waisman, A Serfling, E Sawitzki, B Tuttenberg, A Muller, MR AF Berberich-Siebelt, F. Vaeth, M. Schliesser, U. Reissig, S. Satoh, K. Jonuleit, H. Mueller, G. Waisman, A. Serfling, E. Sawitzki, B. Tuettenberg, A. Mueller, M. R. TI The dependence on NFAT levels discriminates conventional T cells from Foxp3(+) regulatory T cells SO IMMUNOLOGY LA English DT Meeting Abstract CT European Congress of Immunology CY SEP 05-08, 2012 CL Glasgow, SCOTLAND C1 [Berberich-Siebelt, F.; Vaeth, M.; Serfling, E.] Univ Wurzburg, Inst Pathol, D-8700 Wurzburg, Germany. [Schliesser, U.; Sawitzki, B.] CCM, Inst Med Immunol, Berlin, Germany. [Reissig, S.; Waisman, A.] Univ Med Ctr, Inst Mol Med, Mainz, Germany. [Satoh, K.; Jonuleit, H.; Tuettenberg, A.] Univ Med Ctr, Dept Dermatol, Mainz, Germany. [Mueller, G.] MDC, Dept Tumor Genet & Immunogenet, Berlin, Germany. [Mueller, M. R.] Harvard, Program Cellular & Mol Med, Boston, MA USA. RI Jonuleit, Helmut/D-8059-2011; Waisman, Ari/C-7383-2015 OI Jonuleit, Helmut/0000-0002-5672-9365; Waisman, Ari/0000-0003-4304-8234 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 0019-2805 J9 IMMUNOLOGY JI Immunology PD SEP PY 2012 VL 137 SU 1 SI SI BP 416 EP 416 PG 1 WC Immunology SC Immunology GA 011TW UT WOS:000309189103118 ER PT J AU Smith, K Willberg, C Ussher, J O'Callaghan, C Freeman, GJ Klenerman, P AF Smith, K. Willberg, C. Ussher, J. O'Callaghan, C. Freeman, G. J. Klenerman, P. TI Impact of cross-linking CD161 on human T cells SO IMMUNOLOGY LA English DT Meeting Abstract CT European Congress of Immunology CY SEP 05-08, 2012 CL Glasgow, SCOTLAND C1 [Smith, K.; Willberg, C.; Ussher, J.; O'Callaghan, C.; Klenerman, P.] Nuffield Dept Med, Oxford, England. [Freeman, G. J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. 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 0019-2805 J9 IMMUNOLOGY JI Immunology PD SEP PY 2012 VL 137 SU 1 SI SI BP 476 EP 476 PG 1 WC Immunology SC Immunology GA 011TW UT WOS:000309189104034 ER PT J AU Conlan, T Sivakumaran, J Fallah-Arani, F Zhang, L Means, T Geissman, F Chakraverty, R Bennett, C AF Conlan, T. Sivakumaran, J. Fallah-Arani, F. Zhang, L. Means, T. Geissman, F. Chakraverty, R. Bennett, C. TI Investigating the role of cutaneous dendritic cells in T-cell mediated immunopathology SO IMMUNOLOGY LA English DT Meeting Abstract CT European Congress of Immunology CY SEP 05-08, 2012 CL Glasgow, SCOTLAND C1 [Conlan, T.; Sivakumaran, J.; Fallah-Arani, F.; Zhang, L.; Chakraverty, R.; Bennett, C.] UCL Canc Inst, London, England. [Means, T.] Massachusetts Gen Hosp, Charlestown, MA USA. [Geissman, F.] Kings Coll London, Ctr Mol & Cellular Biol Inflammat Biol, London WC2R 2LS, England. RI bennett, clare/J-5249-2013 OI bennett, clare/0000-0001-9146-2347 NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD SEP PY 2012 VL 137 SU 1 SI SI BP 479 EP 479 PG 1 WC Immunology SC Immunology GA 011TW UT WOS:000309189104043 ER PT J AU Wellman, TJ Winkler, T Costa, ELV Musch, G Harris, RS Venegas, JG Melo, MFV AF Wellman, Tyler J. Winkler, Tilo Costa, Eduardo L. V. Musch, Guido Harris, R. Scott Venegas, Jose G. Melo, Marcos F. Vidal TI Effect of regional lung inflation on ventilation heterogeneity at different length scales during mechanical ventilation of normal sheep lungs SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE positron emission tomography; tracer kinetics; aeration; airway closure ID END-EXPIRATORY PRESSURE; ANESTHETIZED-PARALYZED MAN; ACUTE RESPIRATORY-FAILURE; PULMONARY BLOOD-FLOW; AIRWAY-CLOSURE; TIDAL VOLUME; GAS-EXCHANGE; GENERAL-ANESTHESIA; NORMAL RABBITS; NITRIC-OXIDE AB Wellman TJ, Winkler T, Costa ELV, Musch G, Harris RS, Venegas JG, Vidal Melo MF. Effect of regional lung inflation on ventilation heterogeneity at different length scales during mechanical ventilation of normal sheep lungs. J Appl Physiol 113: 947-957, 2012. First published June 7, 2012; doi:10.1152/japplphysiol.01631.2011.-Heterogeneous, small-airway diameters and alveolar derecruitment in poorly aerated regions of normal lungs could produce ventilation heterogeneity at those anatomic levels. We modeled the washout kinetics of (NN)-N-13 with positron emission tomography to examine how specific ventilation (s(V) over dot) heterogeneity at different length scales is influenced by lung aeration. Three groups of anesthetized, supine sheep were studied: high tidal volume (VT; 18.4 +/- 4.2 ml/kg) and zero end-expiratory pressure (ZEEP) (n = 6); low VT (9.2 +/- 1.0 ml/kg) and ZEEP (n = 6); and low VT (8.2 +/- 0.2 ml/kg) and positive end-expiratory pressure (PEEP; 19 +/- 1 cmH(2)O) (n = 4). We quantified fractional gas content with transmission scans, and s(V) over dot with emission scans of infused (NN)-N-13-saline. Voxel (NN)-N-13-washout curves were fit with one-or two-compartment models to estimate s(V) over dot. Total heterogeneity, measured as SD[ log(10)(s(V) over dot)], was divided into length-scale ranges by measuring changes in variance of log(10)(s(V) over dot), resulting from progressive filtering of s(V) over dot images. High-VT ZEEP showed higher s(V) over dot heterogeneity at <12- (P < 0.01), 12- to 36- (P < 0.01), and 36- to 60-mm (P < 0.05) length scales compared with low-VT PEEP, with low-VT ZEEP in between. Increased heterogeneity was associated with the emergence of low s(V) over dot units in poorly aerated regions, with a high correlation (r = 0.95, P < 0.001) between total heterogeneity and the fraction of lung with slow washout. Regional mean fractional gas content was inversely correlated with regional s(V) over dot heterogeneity at <12- (r = -0.67), 12- to 36-(r = -0.74), and >36-mm (r = -0.72) length scales (P < 0.001). We conclude that s(V) over dot heterogeneity at length scales <60 mm increases in poorly aerated regions of mechanically ventilated normal lungs, likely due to heterogeneous small-airway narrowing and alveolar derecruitment. PEEP reduces s(V) over dot heterogeneity by maintaining lung expansion and airway patency at those small length scales. C1 [Melo, Marcos F. Vidal] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Wellman, Tyler J.; Winkler, Tilo; Costa, Eduardo L. V.; Musch, Guido; Harris, R. Scott; Venegas, Jose G.; Melo, Marcos F. Vidal] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Wellman, Tyler J.] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Harris, R. Scott] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Melo, MFV (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM mvidalmelo@partners.org RI Winkler, Tilo/B-5337-2009 OI Winkler, Tilo/0000-0002-7276-5550 FU National Heart, Lung, and Blood Institute [5R01HL086827]; [R01 HL-094639] FX This work was supported by grant 5R01HL086827 from the National Heart, Lung, and Blood Institute. G. Musch was supported in part by grant R01 HL-094639. NR 75 TC 27 Z9 27 U1 1 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD SEP PY 2012 VL 113 IS 6 BP 947 EP 957 DI 10.1152/japplphysiol.01631.2011 PG 11 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 010QQ UT WOS:000309109600014 PM 22678958 ER PT J AU Singh, JA Jensen, MR Lewallen, DG AF Singh, Jasvinder A. Jensen, Matthew R. Lewallen, David G. TI Patient Factors Predict Periprosthetic Fractures After Revision Total Hip Arthroplasty SO JOURNAL OF ARTHROPLASTY LA English DT Article DE total hip arthroplasty; periprosthetic fracture; predictors; risk factors; comorbidity; primary THA ID PERI-PROSTHETIC FRACTURE; KNEE ARTHROPLASTY; FEMORAL FRACTURES; FEMUR; FALLS; RISK; REPLACEMENT; MORBIDITY; MORTALITY; OUTCOMES AB We assessed important patient risk factors for postoperative periprosthetic fractures after revision total hip arthroplasty (THA) using prospectively collected Institutional Joint Registry data. We used univariate and multivariable-adjusted Cox regression analyses. There were 330 postoperative periprosthetic fractures after 6281 revision THAs. In multivariable-adjusted analyses, hazard ratio (95% confidence interval) of periprosthetic fracture was higher for women (1.66 [1.32-2.080], P < .001), a higher Deyo-Charlson comorbidity index of 2 (1.46 [1.03-2.07]) and index of 3+ (2.01 [1.48-2.73]; overall, P < .001), and operative diagnosis, especially previous nonunion (5.76 [2.55-13.02]; overall, P < .001). Hazard ratio was lower in patients 61 to 70 years old (0.64 [0.49-0.84]) and 71 to 80 years old (0.57 [0.43-0.76]) compared with those younger than 60 years (overall, P < .0001). Our study identified important modifiable and unmodifiable risk factors for fractures after revision THA. C1 [Singh, Jasvinder A.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL USA. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Ctr Surg Med Acute Care Res & Transit C SMART, Birmingham, AL USA. [Singh, Jasvinder A.; Lewallen, David G.] Univ Alabama Birmingham, Sch Publ Hlth, Div Epidemiol, Birmingham, AL 35294 USA. [Singh, Jasvinder A.; Lewallen, David G.] Mayo Clin, Coll Med, Dept Orthoped Surg, Rochester, MN USA. [Jensen, Matthew R.] Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN USA. RP Singh, JA (reprint author), Univ Alabama Birmingham, Dept Med, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. OI singh, jasvinder/0000-0003-3485-0006 FU National Institutes of Health Clinical Translational Science Award [1 KL2 RR024151-01] FX This material is the result of work supported with the National Institutes of Health Clinical Translational Science Award 1 KL2 RR024151-01 (Mayo Clinic Center for Clinical and Translational Research) and the resources and the use of facilities at the Birmingham VA Medical Center, Birmingham, Ala. NR 30 TC 10 Z9 11 U1 0 U2 4 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD SEP PY 2012 VL 27 IS 8 BP 1507 EP 1512 DI 10.1016/j.arth.2011.12.010 PG 6 WC Orthopedics SC Orthopedics GA 003NH UT WOS:000308618100015 PM 22342128 ER PT J AU Filkins, LM Hampton, TH Gifford, AH Gross, MJ Hogan, DA Sogin, ML Morrison, HG Paster, BJ O'Toole, GA AF Filkins, L. M. Hampton, T. H. Gifford, A. H. Gross, M. J. Hogan, D. A. Sogin, M. L. Morrison, H. G. Paster, B. J. O'Toole, G. A. TI Prevalence of Streptococci and Increased Polymicrobial Diversity Associated with Cystic Fibrosis Patient Stability SO JOURNAL OF BACTERIOLOGY LA English DT Article ID LUNG-INFECTIONS; BACTERIAL DIVERSITY; DISEASE; SPUTUM; PCR; IDENTIFICATION; SAMPLES; GENE AB Diverse microbial communities chronically colonize the lungs of cystic fibrosis patients. Pyrosequencing of amplicons for hypervariable regions in the 16S rRNA gene generated taxonomic profiles of bacterial communities for sputum genomic DNA samples from 22 patients during a state of clinical stability (outpatients) and 13 patients during acute exacerbation (inpatients). We employed quantitative PCR (qPCR) to confirm the detection of Pseudomonas aeruginosa and Streptococcus by the pyrosequencing data and human oral microbe identification microarray (HOMIM) analysis to determine the species of the streptococci identified by pyrosequencing. We show that outpatient sputum samples have significantly higher bacterial diversity than inpatients, but maintenance treatment with tobramycin did not impact overall diversity. Contrary to the current dogma in the field that Pseudomonas aeruginosa is the dominant organism in the majority of cystic fibrosis patients, Pseudomonas constituted the predominant genera in only half the patient samples analyzed and reported here. The increased fractional representation of Streptococcus in the outpatient cohort relative to the inpatient cohort was the strongest predictor of clinically stable lung disease. The most prevalent streptococci included species typically associated with the oral cavity (Streptococcus salivarius and Streptococcus parasanguis) and the Streptococcus milleri group species. These species of Streptococcus may play an important role in increasing the diversity of the cystic fibrosis lung environment and promoting patient stability. C1 [Filkins, L. M.; Hampton, T. H.; Gross, M. J.; Hogan, D. A.; O'Toole, G. A.] Geisel Sch Med Dartmouth, Hanover, NH USA. [Gifford, A. H.] Dartmouth Hitchcock Med Ctr, Sect Pulm & Crit Care Med, Lebanon, NH 03766 USA. [Sogin, M. L.; Morrison, H. G.] Marine Biol Lab, Josephine Bay Paul Ctr Comparat Mol Biol & Evolut, Woods Hole, MA 02543 USA. [Paster, B. J.] Forsyth Inst, Dept Mol Genet, Cambridge, MA USA. [Paster, B. J.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. RP O'Toole, GA (reprint author), Geisel Sch Med Dartmouth, Hanover, NH USA. EM georgeo@dartmouth.edu OI Morrison, Hilary/0000-0003-0281-326X FU National Center for Research Resources [5P20RR018787]; National Institute of General Medical Sciences from the National Institutes of Health [8 P20 GM 103413]; Cystic Fibrosis Foundation [STANTO011RO]; Hitchcock Foundation; National Institutes of Health [4UH3DK083993-02, R01-HL074175-09]; National Institute of Dental and Craniofacial Research [DE11443]; National Institute of General Medical Sciences [T32GM008704] FX The TRC is supported by grants from the National Center for Research Resources (5P20RR018787) and the National Institute of General Medical Sciences (8 P20 GM 103413) from the National Institutes of Health to B.A.S. This work was also supported by a pilot grant from the Cystic Fibrosis Foundation Research Development Program (STANTO011RO), a grant from the Hitchcock Foundation to G.A.O., grants from the National Institutes of Health to M.L.S. (4UH3DK083993-02) and to B.A.S. (R01-HL074175-09), and a grant from the National Institute of Dental and Craniofacial Research (DE11443) to B.J.P. The project described was supported by award number T32GM008704 from the National Institute of General Medical Sciences. NR 32 TC 61 Z9 62 U1 2 U2 31 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 SEP PY 2012 VL 194 IS 17 BP 4709 EP 4717 DI 10.1128/JB.00566-12 PG 9 WC Microbiology SC Microbiology GA 991EA UT WOS:000307683100024 PM 22753064 ER PT J AU Aizer, AA Paly, JJ Zietman, AL Nguyen, PL Beard, CJ Rao, SK Kaplan, ID Niemierko, A Hirsch, MS Wu, CL Olumi, AF Michaelson, MD D'Amico, AV Efstathiou, JA AF Aizer, Ayal A. Paly, Jonathan J. Zietman, Anthony L. Nguyen, Paul L. Beard, Clair J. Rao, Sandhya K. Kaplan, Irving D. Niemierko, Andrzej Hirsch, Michelle S. Wu, Chin-Lee Olumi, Aria F. Michaelson, M. Dror D'Amico, Anthony V. Efstathiou, Jason A. TI Multidisciplinary Care and Pursuit of Active Surveillance in Low-Risk Prostate Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID MEN; EXPERIENCE; MORBIDITY; TRENDS AB Purpose Multidisciplinary clinics offer a unique approach to the management of patients with cancer. Yet, limited data exist to show that such clinics affect management. The purpose of this study was to determine whether consultation at a multidisciplinary clinic is associated with selection of active surveillance in patients with low-risk prostate cancer. Patients and Methods The study comprised 701 men with low-risk prostate cancer managed at three tertiary care centers in Boston, MA in 2009. Patients either obtained consultation at a multidisciplinary prostate cancer clinic, at which they were seen by a combination of urologic, radiation, and medical oncologists in a concurrent setting, or they were seen by individual practitioners in sequential settings. The primary outcome was selection of active surveillance. Results Crude rates of selection of active surveillance in patients seen at a multidisciplinary clinic were double that of patients seen by individual practitioners (43% v 22%), whereas the proportion of men treated with prostatectomy or radiation decreased by approximately 30% (P < .001). On multivariate logistic regression, older age (odds ratio [OR], 1.09; 95% CI, 1.05 to 1.12; P < .001), unmarried status (OR, 1.66; 95% CI, 1.01 to 2.72; P = .04), increased Charlson comorbidity index (OR, 1.37; 95% CI, 1.06 to 1.77; P = .02), fewer positive cores (OR, 0.92; 95% CI, 0.90 to 0.94; P < .001), and consultation at a multidisciplinary clinic (OR, 2.15; 95% CI, 1.13 to 4.10; P = .02) were significantly associated with pursuit of active surveillance. Conclusion Multidisciplinary care is associated with increased selection of active surveillance in men with low-risk prostate cancer. This finding may have an important clinical, social, and economic impact. J Clin Oncol 30: 3071-3076. (C) 2012 by American Society of Clinical Oncology C1 [Aizer, Ayal A.] Massachusetts Gen Hosp, Harvard Radiat Oncol Program, Dept Radiat Oncol, Boston, MA 02114 USA. [Nguyen, Paul L.; Hirsch, Michelle S.; D'Amico, Anthony V.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Nguyen, Paul L.; D'Amico, Anthony V.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kaplan, Irving D.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Aizer, AA (reprint author), Massachusetts Gen Hosp, Harvard Radiat Oncol Program, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM aaaizer@partners.org OI Michaelson, Dror/0000-0001-9249-6338 FU Department of Radiation Oncology at Massachusetts General Hospital FX Supported by the Department of Radiation Oncology at Massachusetts General Hospital. NR 28 TC 47 Z9 47 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 SEP 1 PY 2012 VL 30 IS 25 BP 3071 EP 3076 DI 10.1200/JCO.2012.42.8466 PG 6 WC Oncology SC Oncology GA 002TM UT WOS:000308558800012 PM 22851571 ER PT J AU Smith, MR Li, HL Gordon, L Gascoyne, RD Paietta, E Forero-Torres, A Kahl, BS Advani, R Hong, FX Horning, SJ AF Smith, Mitchell R. Li, Hailun Gordon, Leo Gascoyne, Randy D. Paietta, Elisabeth Forero-Torres, Andres Kahl, Brad S. Advani, Ranjana Hong, Fangxin Horning, Sandra J. TI Phase II Study of Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone Immunochemotherapy Followed by Yttrium-90-Ibritumomab Tiuxetan in Untreated Mantle-Cell Lymphoma: Eastern Cooperative Oncology Group Study E1499 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PROGRESSION-FREE SURVIVAL; PROSPECTIVE RANDOMIZED-TRIAL; STUDY-GROUP GLSG; FOLLICULAR LYMPHOMA; INITIAL THERAPY; TUMOR BURDEN; MAINTENANCE; CHOP; CHEMOIMMUNOTHERAPY; RADIOIMMUNOTHERAPY AB Purpose To test the hypothesis that consolidation therapy with yttrium-90 (Y-90) -ibritumomab tiuxetan after brief initial therapy with four cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with previously untreated mantle-cell lymphoma would be a well-tolerated regimen that would improve outcomes compared with historical R-CHOP data. Patients and Methods Patients >= 18 years old with histologically confirmed mantle-cell lymphoma expressing CD20 and cyclin D1 who had not received any previous therapy and had an Eastern Cooperative Oncology Group performance status of 0 to 2 and adequate organ function were eligible. The study enrolled and treated 57 patients, of whom 56 patients were eligible. Fifty-two patients (50 eligible patients) received 90Y-ibritumomab tiuxetan. The study design required 52 eligible patients to detect a 50% improvement in the median time to treatment failure (TTF) compared with that reported for six cycles of R-CHOP. Results With 56 analyzed patients (median age, 60 years; men, 73%), the overall response rate was 82% (55% complete response/complete response-unconfirmed). With a median follow-up of 72 months, the median TTF was 34.2 months. The median overall survival (OS) has not been reached, with an estimated 5-year OS of 73% (79% for patients <= age 65 years v 62% for patients > age 65 years; P = .08 [log-rank test]). There were no unexpected toxicities. Conclusion R-CHOP given for four cycles followed by Y-90-ibritumomab tiuxetan compared favorably with historical results with six cycles of R-CHOP in patients with previously untreated mantle-cell lymphoma. This regimen was well tolerated and should be applicable to most patients with this disease. J Clin Oncol 30: 3119-3126. (C) 2012 by American Society of Clinical Oncology C1 [Smith, Mitchell R.] Fox Chase Canc Ctr, Lymphoma Serv, Philadelphia, PA 19111 USA. [Li, Hailun; Hong, Fangxin] Dana Farber Canc Ctr, Boston, MA USA. [Gordon, Leo] Northwestern Univ, Chicago, IL 60611 USA. [Gascoyne, Randy D.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [Paietta, Elisabeth] Montefiore Canc Ctr, Bronx, NY USA. [Forero-Torres, Andres] Univ Alabama Birmingham, Birmingham, AL USA. [Kahl, Brad S.] Univ Wisconsin, Madison, WI USA. [Advani, Ranjana; Horning, Sandra J.] Stanford Univ, Stanford, CA 94305 USA. RP Smith, MR (reprint author), Fox Chase Canc Ctr, Lymphoma Serv, Room C307,333 Cottman Ave, Philadelphia, PA 19111 USA. EM m_smith@fccc.edu OI Smith, Mitchell/0000-0003-1428-8765; Gordon, Leo/0000-0003-1666-7064 FU National Cancer Institute, National Institutes of Health, Department of Health and Human Services [CA21115, CA23318, CA66636, CA17145, CA27525, CA14958, CA21076]; Biogen-IDEC; Genentech FX Supported in part by Public Health Service Grants No. CA21115, CA23318, CA66636, CA17145, CA27525, CA14958, and CA21076 from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services.; Although all authors completed the disclosure declaration, the following author(s) and/or an author's immediate family member(s) indicated a financial or other interest that is relevant to the subject matter under consideration in this article. Certain relationships marked with a "U" are those for which no compensation was received; those relationships marked with a "C" were compensated. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors. Employment or Leadership Position: Sandra J. Horning, Genentech (C) Consultant or Advisory Role: Leo Gordon, Spectrum Pharmaceuticals (C); Randy D. Gascoyne, Roche/Genentech (C); Brad S. Kahl, Genentech (C); Ranjana Advani, Genentech (C) Stock Ownership: Sandra J. Horning, Roche Honoraria: Mitchell R. Smith, Genentech, Spectrum Pharmaceuticals; Randy D. Gascoyne, Roche/Genentech Research Funding: Andres Forero-Torres, Biogen-IDEC; Brad S. Kahl, Genentech; Ranjana Advani, Genentech Expert Testimony: None Other Remuneration: None NR 34 TC 38 Z9 39 U1 0 U2 5 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 SEP 1 PY 2012 VL 30 IS 25 BP 3119 EP 3126 DI 10.1200/JCO.2012.42.2444 PG 8 WC Oncology SC Oncology GA 002TM UT WOS:000308558800018 PM 22851557 ER PT J AU Davids, MS Letai, A AF Davids, Matthew S. Letai, Anthony TI Targeting the B-Cell Lymphoma/Leukemia 2 Family in Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; BCL-2 ANTISENSE OLIGONUCLEOTIDE; ACUTE MYELOID-LEUKEMIA; BH3 MIMETIC ABT-737; PHASE-I; CHROMOSOME-TRANSLOCATION; MITOCHONDRIAL-MEMBRANE; OBLIMERSEN SODIUM; CYTOCHROME-C; OBATOCLAX MESYLATE AB The B-cell lymphoma/leukemia 2 (BCL-2) family of proteins has attracted the attention of cancer biologists since the cloning of BCL-2 more than 25 years ago. In the intervening decades, the way the BCL-2 family controls commitment to programmed cell death has been greatly elucidated. Several drugs directed at inhibiting BCL-2 and related antiapoptotic proteins have been tested clinically, with some showing considerable promise, particularly in lymphoid malignancies. A better understanding of the BCL-2 family has also provided insight into how conventional chemotherapy selectively kills cancer cells and why some cancers are more chemosensitive than others. Further exploitation of our understanding of the BCL-2 family promises to offer improved predictive biomarkers for oncologists and improved therapies for patients with cancer. J Clin Oncol 30: 3127-3135. (C) 2012 by American Society of Clinical Oncology C1 [Davids, Matthew S.; Letai, Anthony] Dana Farber Canc Inst, Boston, MA 02215 USA. RP Letai, A (reprint author), Dana Farber Canc Inst, Mayer 429,450 Brookline Ave, Boston, MA 02215 USA. EM anthony_letai@dfci.harvard.edu FU NCI NIH HHS [T32 CA009172] NR 72 TC 114 Z9 118 U1 1 U2 17 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 SEP 1 PY 2012 VL 30 IS 25 BP 3127 EP 3135 DI 10.1200/JCO.2011.37.0981 PG 9 WC Oncology SC Oncology GA 002TM UT WOS:000308558800019 PM 22649144 ER PT J AU Hudis, CA Citron, ML Muss, H Norton, L Winer, EP AF Hudis, Clifford A. Citron, Marc L. Muss, Hy Norton, Larry Winer, Eric P. TI Can We Really Use Retrospective Subset Analyses and Surveillance, Epidemiology, and End Results Data to Drive Clinical Practice? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID BREAST-CANCER; CHEMOTHERAPY C1 [Hudis, Clifford A.; Norton, Larry] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Citron, Marc L.] ProHEALTH Care Associates, Lake Success, NY USA. [Muss, Hy] Univ N Carolina, Chapel Hill, NC USA. [Winer, Eric P.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Hudis, CA (reprint author), Mem Sloan Kettering Canc Ctr, New York, NY USA. OI Norton, Larry/0000-0003-3701-9250 NR 7 TC 3 Z9 3 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 SEP 1 PY 2012 VL 30 IS 25 BP 3148 EP 3149 DI 10.1200/JCO.2012.43.4746 PG 2 WC Oncology SC Oncology GA 002TM UT WOS:000308558800026 PM 22851555 ER PT J AU Velez, NF Ishizawar, RC Dellaripa, PF Saavedra, AP Laga, AC Murphy, GF Fisher, DC Kupper, TS Vleugels, RA AF Velez, Nicole F. Ishizawar, Rumey C. Dellaripa, Paul F. Saavedra, Arturo P. Laga, Alvaro C. Murphy, George F. Fisher, David C. Kupper, Thomas S. Vleugels, Ruth Ann TI Full Facial Edema: A Novel Presentation of Subcutaneous Panniculitis-Like T-Cell Lymphoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID LYMPHOCYTIC LOBULAR PANNICULITIS; LUPUS-ERYTHEMATOSUS PANNICULITIS; HEMOPHAGOCYTIC SYNDROME; CUTANEOUS LYMPHOMAS; CLASSIFICATION; DYSCRASIA; TISSUE C1 [Velez, Nicole F.; Ishizawar, Rumey C.; Dellaripa, Paul F.; Saavedra, Arturo P.; Laga, Alvaro C.; Murphy, George F.; Kupper, Thomas S.; Vleugels, Ruth Ann] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Saavedra, Arturo P.; Kupper, Thomas S.] Dana Farber Brigham & Womens Canc Ctr, Ctr Cutaneous Oncol, Boston, MA USA. RP Velez, NF (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. NR 22 TC 3 Z9 3 U1 1 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 SEP 1 PY 2012 VL 30 IS 25 BP E233 EP E236 DI 10.1200/JCO.2011.40.7684 PG 4 WC Oncology SC Oncology GA 002TM UT WOS:000308558800002 PM 22826278 ER PT J AU Capp, R Soremekun, OA Biddinger, PD White, BA Sweeney, LM Chang, YC Brown, DFM AF Capp, Roberta Soremekun, Olan A. Biddinger, Paul D. White, Benjamin A. Sweeney, Linda M. Chang, Yuchiao Brown, David F. M. TI IMPACT OF PHYSICIAN-ASSISTED TRIAGE ON TIMING OF ANTIBIOTIC DELIVERY IN PATIENTS ADMITTED TO THE HOSPITAL WITH COMMUNITY-ACQUIRED PNEUMONIA (CAP) SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE community-acquired pneumonia (CAP); physician-assisted triage; antibiotic delivery; core quality measures ID EMERGENCY-DEPARTMENT AB Background: Time to antibiotic delivery in patients with diagnosis of pneumonia is a publicly reported quality measure. Objective: We aim to describe the impact of emergency department (ED) physician-assisted triage (PAT) on The Joint Commission (TJC) and Centers for Medicare and Medicaid Services (CMS) pneumonia core quality measures of timing to antibiotic delivery. Methods: Retrospective case series studies of patients admitted to the hospital through the ED with diagnosis of community-acquired pneumonia were identified over a period of 48 months. Patients were included in the study if they met TJC/CMS PN-5 (antibiotic timing) criteria. We compared antibiotic delivery timing before and after implementation of PAT in moderate-acuity patients using Wilcoxon rank sum tests. A linear regression analysis was done to account for age, sex, ED volume, and acuity level. Results: A total of 659 patients were identified: 497 patients and 162 patients enrolled pre- and post-implementation of a PAT, respectively. The median antibiotic delivery times for moderate-acuity patients during open hours of operation of PAT were 180 min (pre) and 195 min (post), p = 0.027; this was unchanged when ED volume, age, sex, and acuity level were accounted. for. A total of 43 patients (9%) and 13 patients (8%) failed to receive antibiotics within 6 h of ED presentation before and after implementation of PAT, respectively. Conclusion: In this study, implementation of PAT did not result in overall decrease in antibiotic delivery time in patients admitted to the hospital with CAP. We postulate several explanations for this delay in antibiotic delivery time. (C) 2012 Elsevier Inc. C1 [Capp, Roberta; Soremekun, Olan A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Capp, Roberta; Soremekun, Olan A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Capp, Roberta; Soremekun, Olan A.; Biddinger, Paul D.; White, Benjamin A.; Sweeney, Linda M.; Chang, Yuchiao; Brown, David F. M.] Harvard Univ, Sch Med, Div Emergency Med, Boston, MA USA. [Biddinger, Paul D.; White, Benjamin A.; Sweeney, Linda M.; Chang, Yuchiao; Brown, David F. M.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Capp, R (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. NR 11 TC 0 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD SEP PY 2012 VL 43 IS 3 BP 502 EP 508 DI 10.1016/j.jemermed.2011.08.016 PG 7 WC Emergency Medicine SC Emergency Medicine GA 011GR UT WOS:000309153600025 PM 22244295 ER PT J AU Soremekun, OA Capp, R Biddinger, PD White, BA Chang, YC Carignan, SB Brown, DFM AF Soremekun, Olanrewaju A. Capp, Roberta Biddinger, Paul D. White, Benjamin A. Chang, Yuchiao Carignan, Sarah B. Brown, David F. M. TI IMPACT OF PHYSICIAN SCREENING IN THE EMERGENCY DEPARTMENT ON PATIENT FLOW SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE emergency department; physician triage ID SATISFACTION; ANTIBIOTICS; THROUGHPUT; OUTCOMES; TRIAGE; TIMES AB Background: Physician triage is one of many front-end interventions being implemented to improve emergency department (ED) efficiency. Study Objective: We aim to determine the impact of this intervention on some key components of ED patient flow, including time to physician evaluation, treatment order entry, diagnostic order entry, and disposition time for admitted patients. Methods: We conducted a 2-year before-after analysis of a physician triage system at an urban tertiary academic center with 90,000 annual visits. The goal of the physician in triage was to arrange safe disposition of straightforward patients as well as to initiate work-ups. All medium-acuity patients arriving during the hours of the intervention were impacted and thus included in the analysis. Our primary outcome was the time to disposition decision. In addition to before-after analysis, comparison was made with high-acuity patients, a group not impacted by this intervention. Patient flow data were extracted from the ED information system. Outcomes were summarized with medians and interquartiles. Multivariable regression analysis was performed to investigate the intervention effect controlling for potential confounding variables. Results: The median time to disposition decision decreased by 6 min, and the time to physician evaluation, analgesia, antiemetic, antibiotic, and radiology order decreased by 16, 70, 66, 36, and 16 min, respectively. These findings were all statistically significant. Similar results were observed from the multivariable regression models after controlling for potential confounding factors. Conclusions: Physician triage led to earlier evaluation, physician orders, and a decrease in the time to disposition decision. (C) 2012 Elsevier Inc. C1 [Soremekun, Olanrewaju A.] Univ Penn, Dept Emergency Med, Philadelphia, PA 19104 USA. [Capp, Roberta] Brigham & Womens Hosp, Harvard Affiliated Emergency Med Residency Progra, Boston, MA 02115 USA. [Biddinger, Paul D.; White, Benjamin A.; Carignan, Sarah B.; Brown, David F. M.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Chang, Yuchiao] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Soremekun, OA (reprint author), Hosp Univ Penn, Dept Emergency Med, 3400 Spruce St, Philadelphia, PA 19104 USA. NR 17 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 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD SEP PY 2012 VL 43 IS 3 BP 509 EP 515 DI 10.1016/j.jemermed.2012.01.025 PG 7 WC Emergency Medicine SC Emergency Medicine GA 011GR UT WOS:000309153600026 PM 22445677 ER PT J AU Premereur, E Vanduffel, W Roelfsema, PR Janssen, P AF Premereur, Elsie Vanduffel, Wim Roelfsema, Pieter R. Janssen, Peter TI Frontal eye field microstimulation induces task-dependent gamma oscillations in the lateral intraparietal area SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE saccades; spatial attention; macaque ID SELECTIVE VISUAL-ATTENTION; SPATIAL ATTENTION; PARIETAL CORTEX; ELECTRICAL MICROSTIMULATION; NEURAL MECHANISMS; NEURONAL-ACTIVITY; OCCIPITAL CORTEX; MACAQUE MONKEYS; TOP-DOWN; MODULATION AB Premereur E, Vanduffel W, Roelfsema PR, Janssen P. Frontal eye field microstimulation induces task-dependent gamma oscillations in the lateral intraparietal area. J Neurophysiol 108: 1392-1402, 2012. First published June 6, 2012; doi:10.1152/jn.00323.2012.-Macaque frontal eye fields (FEF) and the lateral intraparietal area (LIP) are high-level oculomotor control centers that have been implicated in the allocation of spatial attention. Electrical microstimulation of macaque FEF elicits functional magnetic resonance imaging (fMRI) activations in area LIP, but no study has yet investigated the effect of FEF microstimulation on LIP at the single-cell or local field potential (LFP) level. We recorded spiking and LFP activity in area LIP during weak, subthreshold microstimulation of the FEF in a delayed-saccade task. FEF microstimulation caused a highly time-and frequency-specific, task-dependent increase in gamma power in retinotopically corresponding sites in LIP: FEF microstimulation produced a significant increase in LIP gamma power when a saccade target appeared and remained present in the LIP receptive field (RF), whereas less specific increases in alpha power were evoked by FEF microstimulation for saccades directed away from the RF. Stimulating FEF with weak currents had no effect on LIP spike rates or on the gamma power during memory saccades or passive fixation. These results provide the first evidence for task-dependent modulations of LFPs in LIP caused by top-down stimulation of FEF. Since the allocation and disengagement of spatial attention in visual cortex have been associated with increases in gamma and alpha power, respectively, the effects of FEF microstimulation on LIP are consistent with the known effects of spatial attention. C1 [Janssen, Peter] Katholieke Univ Leuven, O&N 2, Lab Neuro & Psychofysiol, B-3000 Louvain, Belgium. [Vanduffel, Wim] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Vanduffel, Wim] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Roelfsema, Pieter R.] Netherlands Inst Neurosci, Amsterdam, Netherlands. [Roelfsema, Pieter R.] Vrije Univ Amsterdam, Ctr Neurogen & Cognit Res, Dept Integrat Neurophysiol, Amsterdam, Netherlands. RP Janssen, P (reprint author), Katholieke Univ Leuven, O&N 2, Lab Neuro & Psychofysiol, Herestr 49,Bus 1021, B-3000 Louvain, Belgium. EM peter.janssen@med.kuleuven.be RI Roelfsema, Pieter/J-6903-2013 OI Roelfsema, Pieter/0000-0002-1625-0034 FU Geneeskundige Stichting Koningin Elisabeth; Fonds voor Wetenschappelijk Onderzoek [G.0713.09, G.0622.08, G.0831.11]; National Science Foundation (NSF) [BCS-0745436]; Inter-university Attraction Poles [P6/29]; Excellentie Financiering [EF/05/014]; Programma Financiering [PFV/10/008]; Geconcerteerde onderzoeksacties [GOA/10/19] FX This work was supported by Geneeskundige Stichting Koningin Elisabeth, Fonds voor Wetenschappelijk Onderzoek (G.0713.09, G.0622.08, and G.0831.11), National Science Foundation (NSF) Grant BCS-0745436, Inter-university Attraction Poles (P6/29), Excellentie Financiering (EF/05/014), Programma Financiering (PFV/10/008), and Geconcerteerde onderzoeksacties (GOA/10/19). NR 57 TC 10 Z9 10 U1 1 U2 11 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD SEP PY 2012 VL 108 IS 5 BP 1392 EP 1402 DI 10.1152/jn.00323.2012 PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 003JQ UT WOS:000308608100016 PM 22673327 ER PT J AU Lewis, RF Haburcakova, C Gong, WS Karmali, F Merfeld, DM AF Lewis, Richard F. Haburcakova, Csilla Gong, Wangsong Karmali, Faisal Merfeld, Daniel M. TI Spatial and temporal properties of eye movements produced by electrical stimulation of semicircular canal afferents SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE vestibular nerve; velocity storage; spatial orientation ID ANGULAR VESTIBULOOCULAR REFLEX; OPTOKINETIC AFTER-NYSTAGMUS; VESTIBULAR PROSTHESIS; RHESUS-MONKEYS; INERTIAL REPRESENTATION; SQUIRREL-MONKEYS; NERVE; ORIENTATION; FREQUENCY; MOTION AB Lewis RF, Haburcakova C, Gong W, Karmali F, Merfeld DM. Spatial and temporal properties of eye movements produced by electrical stimulation of semicircular canal afferents. J Neurophysiol 108: 1511-1520, 2012. First published June 6, 2012; doi:10.1152/jn.01029.2011.-To investigate the characteristics of eye movements produced by electrical stimulation of semicircular canal afferents, we studied the spatial and temporal features of eye movements elicited by short-term lateral canal stimulation in two squirrel monkeys with plugged lateral canals, with the head upright or statically tilted in the roll plane. The electrically induced vestibuloocular reflex (eVOR) evoked with the head upright decayed more quickly than the stimulation signal provided by the electrode, demonstrating an absence of the classic velocity storage effect that improves the dynamics of the low-frequency VOR. When stimulation was provided with the head tilted in roll, however, the eVOR decayed more rapidly than when the head was upright, and a cross-coupled vertical response developed that shifted the eye's rotational axis toward alignment with gravity. These results demonstrate that rotational information provided by electrical stimulation of canal afferents interacts with otolith inputs (or other graviceptive cues) in a qualitatively normal manner, a process that is thought to be mediated by the velocity storage network. The observed interaction between the eVOR and graviceptive cues is of critical importance for the development of a functionally useful vestibular prosthesis. Furthermore, the presence of gravity-dependent effects (dumping, spatial orientation) despite an absence of low-frequency augmentation of the eVOR has not been previously described in any experimental preparation. C1 [Lewis, Richard F.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Jenks Vestibular Physiol Lab, Boston, MA 02114 USA. [Lewis, Richard F.; Haburcakova, Csilla; Karmali, Faisal; Merfeld, Daniel M.] Harvard Univ, Sch Med, Dept Otolaryngol, Boston, MA 02115 USA. [Lewis, Richard F.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Lewis, RF (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Jenks Vestibular Physiol Lab, 243 Charles St, Boston, MA 02114 USA. EM richard_lewis@meei.harvard.edu OI Karmali, Faisal/0000-0002-1140-4954 FU National Institute on Deafness and Other Communication Disorders [DC-6909, DC-8362, DC-8167] FX This work was supported by National Institute on Deafness and Other Communication Disorders Grants DC-6909 and DC-8362 to R. F. Lewis and DC-8167 to D. M. Merfeld. NR 42 TC 5 Z9 5 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD SEP PY 2012 VL 108 IS 5 BP 1511 EP 1520 DI 10.1152/jn.01029.2011 PG 10 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 003JQ UT WOS:000308608100024 PM 22673321 ER PT J AU Holland, JP Cumming, P Vasdev, N AF Holland, Jason P. Cumming, Paul Vasdev, Neil TI PET of Signal Transduction Pathways in Cancer SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE PET; cellular signaling; pharmacodynamic biomarkers; surrogate imaging; cancer ID POSITRON-EMISSION-TOMOGRAPHY; MEMBRANE ANTIGEN; IN-VIVO; LUNG; BIOMARKER; TARGETS AB In this era of systems biology, the tide of information derived from "omic" technologies (genomics, proteomics, etc.) has sparked a revolution in drug design, with many industrial and academic programs now embracing the concepts of molecular medicine (i.e., targeting changes in specific proteins or pathways) as measures of treatment efficacy and outcome. This approach has yielded a plethora of new preclinical therapeutics directed at novel targets within oncology. In many ways, the evolution of molecular imaging agents as diagnostic probes mirrors that of chemotherapeutics; yet despite an increasing number of PET and SPECT radiotracers being evaluated in human trials, relatively few agents have found widespread use in clinical oncology. In light of this observation, is it time to reevaluate our strategies for radiopharmaceutical design and use? In this article, we argue that PET has enormous potential to deliver clinically relevant information on disease dynamics that extends beyond mapping the density and spatial distribution of a target. Recent developments in targeting pharmacodynamic biomarkers aim to exploit better the advantages of functional PET by detecting changes in signal transduction pathways, particularly in response to disease progression or treatment in cancer. C1 [Holland, Jason P.; Vasdev, Neil] Harvard Univ, Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Sch Med, Boston, MA 02114 USA. [Holland, Jason P.; Vasdev, Neil] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Holland, Jason P.] ETH, Inst Pharmaceut Sci, Dept Chem & Appl Biosci, Zurich, Switzerland. [Cumming, Paul] ABX GmbH, Radeberg, Germany. RP Holland, JP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Sch Med, 55 Fruit St,White 427, Boston, MA 02114 USA. EM jholland@pet.mgh.harvard.edu OI Holland, Jason/0000-0002-0066-219X FU ETH Fellowship Program [FEL-01-10-1] FX We thank Prof. Jason Lewis, Dr. Nagavarakishore Pillarsetty, Dr. Michael Evans, and Dr. David Ulmert for helpful discussions. This work was funded in part by the ETH Fellowship Program (FEL-01-10-1). No other potential conflict of interest relevant to this article was reported. NR 24 TC 9 Z9 9 U1 0 U2 8 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 SEP PY 2012 VL 53 IS 9 BP 1333 EP 1336 DI 10.2967/jnumed.112.105387 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 004MF UT WOS:000308685100014 PM 22879078 ER PT J AU Dodson, TB Cheifetz, ID Nelson, WJ Rafetto, LK AF Dodson, Thomas B. Cheifetz, Ira D. Nelson, William J. Rafetto, Louis K. TI Summary of the Proceeding of the Third Molar Multidisciplinary Conference SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Editorial Material C1 [Dodson, Thomas B.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Dodson, Thomas B.] Massachusetts Gen Hosp, Ctr Appl Clin Invest, Boston, MA 02114 USA. [Dodson, Thomas B.] Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. RP Dodson, TB (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 55 Fruit St,Warren 1201, Boston, MA 02114 USA. EM tbdodson@partners.org NR 4 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 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD SEP PY 2012 VL 70 IS 9 SU 1 BP S66 EP S69 DI 10.1016/j.joms.2012.05.001 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 999NN UT WOS:000308320800014 PM 22916701 ER PT J AU Dodson, TB AF Dodson, Thomas B. TI How Many Patients Have Third Molars and How Many Have One or More Asymptomatic, Disease-Free Third Molars? SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID PATHOLOGY AB The purpose of this report was to summarize the frequencies of third molars (M3s) in general and asymptomatic, disease-free M3s specifically. Estimates of M3 prevalence range so widely (ie, 6.0% to 96%) as to be of little use. The estimates vary depending on definitions, age, clinical versus radiographic assessment, and patient versus population samples. For patient management, it may be more valuable to estimate the prevalence of M3s grouped by clinical rather than anatomic status. Many times, however, M3s are categorized simply as asymptomatic. In many pathologic processes, from cancer to cardiovascular disease, the term asymptomatic does not equal an absence of disease. As such, M3s should be categorized based on symptom and disease status. Subjects with all M3s asymptomatic and absent of disease ranged from 12% in a sample of patients referred for M3 evaluation to 29% in a nonpatient volunteer sample. In the patient sample, 37% of the M3s evaluated were asymptomatic and free of disease. (c) 2012 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 70:4-7, 2012, Suppl 1 C1 [Dodson, Thomas B.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Ctr Appl Clin Invest, Boston, MA 02114 USA. [Dodson, Thomas B.] Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. RP Dodson, TB (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Ctr Appl Clin Invest, 55 Fruit St,Warren Bldg,Suite 1201, Boston, MA 02114 USA. EM tbdodson@partners.org FU Center for Applied Clinical Investigation; Department of Oral and Maxillofacial Surgery; Massachusetts General Hospital; Massachusetts General Physicians' Organization FX This work was supported in part by the Center for Applied Clinical Investigation, Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital and the Massachusetts General Physicians' Organization. NR 9 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 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD SEP PY 2012 VL 70 IS 9 SU 1 BP S4 EP S7 DI 10.1016/j.joms.2012.04.038 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 999NN UT WOS:000308320800003 PM 22916698 ER PT J AU Dodson, TB AF Dodson, Thomas B. TI Surveillance as a Management Strategy for Retained Third Molars: Is It Desirable? SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID REMOVAL; DISEASE; RETENTION; 3RD-MOLAR; MEDICINE; SURGERY AB The purpose of the present report was to define and advocate active surveillance compared with follow-up as needed (prn follow-up), as the preferred management strategy for patients who elect to retain their third molars (M3s). Active surveillance, a nonoperative management strategy for retained M3s, is characterized as a prescribed, regularly scheduled set of follow-up visits that include both clinical and radiographic examinations. Given that the risk of complications with M3 removal are age related, the rationale for recommending active surveillance instead of "prn follow-up" is that the frequency of future disease among retained M3s is sufficiently high to warrant routine scheduled follow-up visits to detect and treat disease before it becomes symptomatic. Symptomatic disease is a late finding. Patients electing active surveillance as their preferred management strategy might not avoid operative treatment in the future, but it should increase their chances of being diagnosed at the youngest age possible, thus minimizing the age-related operative complications. The author recommends that the frequency of follow-up visits be approximately every 24 months and the examination be completed by a specialist or general dentist. Active surveillance as a management strategy is based on level 5 evidence (ie, expert opinion). (c) 2012 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 70:20-24, 2012, Suppl 1 C1 [Dodson, Thomas B.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Ctr Appl Clin Invest, Boston, MA 02114 USA. [Dodson, Thomas B.] Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. RP Dodson, TB (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Ctr Appl Clin Invest, 55 Fruit St,Warren Bldg,Suite 1201, Boston, MA 02114 USA. EM tbdodson@partners.org FU Center for Applied Clinical Investigation, Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital; Massachusetts General Physicians Organization FX This manuscript was funded in part by the Center for Applied Clinical Investigation, Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital and Massachusetts General Physicians Organization. NR 22 TC 4 Z9 4 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 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD SEP PY 2012 VL 70 IS 9 SU 1 BP S20 EP S24 DI 10.1016/j.joms.2012.04.026 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 999NN UT WOS:000308320800007 PM 22916696 ER PT J AU Marciani, RD AF Marciani, Robert D. TI Is There Pathology Associated With Asymptomatic Third Molars? SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID PERIODONTAL PATHOLOGY; YOUNG-ADULTS; CARIES EXPERIENCE; MICROBIAL COMPLEXES; 3RD-MOLARS; TIME; REGION; PROGRESSION; PREVALENCE; POSITION AB Purpose: The purpose of this article was to estimate the proportion of patients with asymptomatic third molars (M3s) and evidence of disease at baseline and to measure the health risks of retained M3s in the long term. Materials and Methods: A literature search was conducted using Google Scholar. Search terms included third molars and periodontitis, pericoronitis, caries, odontogenic cysts or tumors, and infections. To be included in this review, studies were limited to prospective studies with samples of at least 50 subjects and a follow-up longer than 1 year. Results: Periodontal pathology was associated with asymptomatic M3s. At baseline, 25% of 329 asymptomatic subjects enrolled in studies had at least 1 probing depth (PD) of at least 5 mm in the M3 region, distal of the second molars, or around the M3s, with at least 1-mm attachment lost in each patient. PDs deeper than 5 mm were associated with an attachment loss of at least 2 mm in 80 of 82 subjects. The clinical findings of increased periodontal PDs and periodontal attachment loss coupled with the colonization of periodontal pathogens supported the concept that clinical and microbial changes associated with the initiation of periodontitis may present first in the M3 region in young adults. For subjects with a baseline PD of at least 4 mm in the M3 region or baseline "orange and red" complex periodontal bacteria of at least 105, the odds were significantly increased for the progression of periodontal disease in the M3 region. The visible presence of M3s in young adults was significantly associated with periodontal inflammatory disease in non-M3s. Conclusion: The data suggest that the absence of symptoms associated with retained M3s does not equal the absence of disease or pathology. The clinical implications of these findings suggest that patients who elect to retain their M3s should have regular periodic clinical and radiographic examinations to detect disease before it becomes symptomatic. (c) 2012 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 70:15-19, 2012, Suppl 1 C1 [Marciani, Robert D.] Univ Cincinnati, Div Oral & Maxillofacial Surg, Cincinnati, OH USA. RP Marciani, RD (reprint author), Care of Dodson TB, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 55 Fruit St,Warren 1201, Boston, MA 02114 USA. EM tbdodson@partners.org NR 25 TC 6 Z9 6 U1 1 U2 5 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 SEP PY 2012 VL 70 IS 9 SU 1 BP S15 EP S19 DI 10.1016/j.joms.2012.04.025 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 999NN UT WOS:000308320800006 PM 22717377 ER PT J AU Renton, T Al-Haboubi, M Pau, A Shepherd, J Gallagher, JE AF Renton, Tara Al-Haboubi, Mustafa Pau, Allan Shepherd, Jonathan Gallagher, Jennifer E. TI What Has Been the United Kingdom's Experience With Retention of Third Molars? SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID NICE GUIDANCE; REMOVAL; SURGERY; COMPLICATIONS; 3RD-MOLAR; POLICY; TIME; AGE AB Background: In 2000, the first National Institute of Clinical Excellence (NICE) guidelines related to third molar (M3) surgery, a commonly performed operation in the United Kingdom, were published. This followed research publications and professional guidelines in the 1990s that advised against prophylactic surgery and provided specific therapeutic indications for M3 surgery. The aim of the present report was to summarize the available evidence on the effects of guidelines on M3 surgery within the United Kingdom. Materials and Methods: Data from primary care dental services and hospital admissions in England and Wales during a 20-year period (Hospital Episode Statistics 1989/1990 to 2009/2010), and from private medical insurance companies were analyzed. The volume and, where possible, the nature of the M3 surgery activity over time were assessed together, as were the collateral effects of the guidelines, including patient age at surgery and the indications for surgery. Results: The volume of M3 removal decreased in all sectors during the 1990s before the introduction of the NICE guidelines. During the 20-year period, the proportion of impacted M3 surgery decreased from 80% to 50% of admitted hospital cases. Furthermore, an increase occurred in the mean age for surgical admissions from 25.5 to 31.8 years. The change in age correlated with a change in the indications for M3 surgery during that period, with a reduction in "impaction," but an increase in "caries" and "pericoronitis" as etiologic factors, in accordance with the NICE guidelines. Conclusion: The significant decrease in M3 surgery activity occurred before the NICE guidelines. Thus, M3 surgery has been performed at a later age, with indications for surgery increasingly in accordance with the NICE guidelines. The importance of clinical monitoring of the retained M3s is discussed. c 2012 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 70: 48-57, 2012, Suppl 1 C1 [Renton, Tara] Kings Coll London, Dept Oral Surg, Inst Dent, London WC2R 2LS, England. [Al-Haboubi, Mustafa; Pau, Allan; Gallagher, Jennifer E.] Guys Hosp, London SE1 9RT, England. [Al-Haboubi, Mustafa; Pau, Allan; Gallagher, Jennifer E.] Kings Coll Hosp London, London, England. [Al-Haboubi, Mustafa; Pau, Allan; Gallagher, Jennifer E.] St Thomas Hosp, London, England. [Shepherd, Jonathan] Cardiff Univ, Sch Dent, Cardiff, S Glam, Wales. RP Renton, T (reprint author), Care of Dodson, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 55 Fruit St,Warren 1201, Boston, MA 02114 USA. EM tbdodson@partners.org RI Gallagher, Jennifer/F-9019-2013 NR 39 TC 9 Z9 9 U1 0 U2 10 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 SEP PY 2012 VL 70 IS 9 SU 1 BP S48 EP S57 DI 10.1016/j.joms.2012.04.040 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 999NN UT WOS:000308320800012 PM 22762969 ER PT J AU Teles, FR Teles, RP Sachdeo, A Uzel, NG Song, XQ Torresyap, G Singh, M Papas, A Haffajee, AD Socransky, SS AF Teles, F. R. Teles, R. P. Sachdeo, A. Uzel, N. G. Song, X. Q. Torresyap, G. Singh, M. Papas, A. Haffajee, A. D. Socransky, S. S. TI Comparison of Microbial Changes in Early Redeveloping Biofilms on Natural Teeth and Dentures SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE Bacteria; biofilms; dental plaque; dentures; tooth ID DNA-DNA HYBRIDIZATION; NOVO PLAQUE-FORMATION; SURFACE-FREE-ENERGY; DENTAL PLAQUE; EXPERIMENTAL GINGIVITIS; SUPRAGINGIVAL PLAQUE; PERIODONTAL HEALTH; SUBGINGIVAL PLAQUE; ORAL HYGIENE; DISEASE AB Background: Surfaces and fluids can affect oral bacterial colonization. The aim of this study is to compare redeveloping biofilms on natural teeth and dentures. Methods: Supragingival plaque samples were taken from 55 dentate individuals and the denture teeth of 62 edentulous individuals before and after professional cleaning. Also, samples from seven "teeth" (samples included dentures) in randomly selected quadrants were collected after 1, 2, 4, and 7 days of no oral hygiene. Samples were analyzed using checkerboard DNA-DNA hybridization. Counts and proportions of 41 bacterial taxa were determined at each time point, and significant differences were determined using the Mann-Whitney U test. Ecological succession was determined using a modified moving window analysis. Results: Mean total DNA probe counts were similar pre-cleaning but were higher in dentate individuals at all post-cleaning visits (P <0.01). Precleaning edentate biofilms had higher counts and proportions of Streptococcus mitis, Streptococcus oralis, and Streptococcus mutans, whereas dentate individuals had higher proportions of Tannerella forsythia, Selenomonas noxia, and Neisseria mucosa. By day 2, mean counts of all taxa were higher in natural teeth, and most remained higher at day 7 (P <0.01). Succession was more rapid and complex in dentate individuals. Both groups demonstrated increased proportions of S. mitis and S. oralis by day 1. N. mucosa, Veillonella parvula, and Eikenella corrodens increased in both groups, but later in samples from edentate individuals. Conclusions: "Mature" natural and denture teeth biofilms have similar total numbers of bacteria but different species proportions. Post-cleaning biofilm redevelopment is more rapid and more complex on natural teeth than on denture teeth. J Periodontol 2012;83:1139-1148. C1 [Teles, F. R.; Teles, R. P.; Song, X. Q.; Torresyap, G.; Haffajee, A. D.; Socransky, S. S.] Forsyth Inst, Dept Periodontol, Cambridge, MA 02142 USA. [Teles, F. R.; Teles, R. P.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Sachdeo, A.] Tufts Univ, Sch Dent Med, Dept Prosthodont, Boston, MA 02111 USA. [Singh, M.; Papas, A.] Tufts Univ, Sch Dent Med, Div Publ Hlth Res & Oral Med, Boston, MA 02111 USA. RP Teles, FR (reprint author), Forsyth Inst, Dept Periodontol, 245 1st St, Cambridge, MA 02142 USA. EM fteles@forsyth.org FU NIH/NIDCR [R01-DE-14368, R03-DE-021742, U01-DE-021127]; Eleanor and Miles Shore Fellowship Program for Scholars in Medicine (The Forsyth Institute/Harvard Medical School) FX This work was supported in part by NIH/NIDCR grants R01-DE-14368 (SS), R03-DE-021742 (FT), and U01-DE-021127 (RT) and the Eleanor and Miles Shore Fellowship Program for Scholars in Medicine (The Forsyth Institute/Harvard Medical School) (FT). The authors report no conflicts of interest related to this study. NR 36 TC 20 Z9 20 U1 1 U2 17 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 SEP PY 2012 VL 83 IS 9 BP 1139 EP 1148 DI 10.1902/jop.2012.110506 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 010JU UT WOS:000309091500009 PM 22443543 ER PT J AU Teles, FR Teles, RP Martin, L Socransky, SS Haffajee, AD AF Teles, Flavia R. Teles, Ricardo P. Martin, Lynn Socransky, Sigmund S. Haffajee, Anne D. TI Relationships Among Interleukin-6, Tumor Necrosis Factor-alpha, Adipokines, Vitamin D, and Chronic Periodontitis SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE Adipokines; biofilms; calcitriol; periodontal debridement; periodontitis ID C-REACTIVE PROTEIN; SERUM INFLAMMATORY MARKERS; GINGIVAL CREVICULAR FLUID; CORONARY-HEART-DISEASE; DNA-DNA HYBRIDIZATION; AGGRESSIVE PERIODONTITIS; CALCIUM SUPPLEMENTATION; SYSTEMIC INFLAMMATION; CLINICAL-PARAMETERS; POTENTIAL ROLE AB Background: The aim of this study is to explore relationships among serum adipokines, vitamin D, and clinical and microbial parameters of chronic periodontitis before and after treatment. Methods: Weight, height, and smoking status were recorded for 56 patients with chronic periodontitis. Plaque, gingivitis, bleeding on probing, suppuration, probing depth, and clinical attachment level were measured at all teeth present. Subgingival biofilm samples from each tooth were analyzed for levels of 40 bacterial species using checkerboard DNA DNA hybridization. Serum levels of interleukin-6 (IL-6), tumor necrosis factor-a, adiponectin, leptin, resistin, and vitamin D were measured at baseline. Sample collection was then performed in a subset of the population 6 months after therapy (n = 17). Serum samples were analyzed using enzyme-linked immunosorbent assay and immunoassays. Differences in clinical, microbial, and serum factors among groups were sought using the Mann-Whitney U test. Correlations among factors were evaluated using regression analysis. Effects of therapy were sought using the Wilcoxon signed rank test. Results: There were positive correlations between adiponectin/vitamin D and between IL-6/leptin, negative correlations between IL-6/vitamin D and leptin/vitamin D, but no associations between serum analytes and clinical or microbial parameters. Sex and body mass index were associated with levels of adipokines. Periodontal therapy improved clinical and microbiologic parameters but did not influence the levels of serum analytes. Conclusion: Adipokines and IL-6 levels were affected by sex and body mass index. Serum analytes were not influenced by periodontal therapy. J Periodontol 2012;83:1183-1191. C1 [Teles, Flavia R.; Teles, Ricardo P.; Martin, Lynn; Socransky, Sigmund S.; Haffajee, Anne D.] Forsyth Inst, Dept Periodontol, Cambridge, MA 02142 USA. [Teles, Flavia R.; Teles, Ricardo P.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. RP Teles, FR (reprint author), Forsyth Inst, Dept Periodontol, 245 1st St, Cambridge, MA 02142 USA. EM fteles@forsyth.org FU National Institutes of Health/National Institute of Dental and Craniofacial Research [R01-DE014242, R03 DE021742, U01-DE021127]; Harvard Medical School; Forsyth Institute/Harvard Medical School FX This work was supported in part by National Institutes of Health/National Institute of Dental and Craniofacial Research Grants R01-DE014242 (awarded to Dr. Haffajee), R03 DE021742 (awarded to Dr. F. Teles), and U01-DE021127 (awarded to Dr. R. Teles), the Participant and Clinical Interactions Resources Junior Investigator Laboratory Support Award (Harvard Medical School), and the Eleanor and Miles Shore Fellowship Program for Scholars in Medicine (The Forsyth Institute/Harvard Medical School) (both awarded to Dr. F. Teles). The authors report no conflicts of interest related to this study. NR 50 TC 14 Z9 15 U1 1 U2 18 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 SEP PY 2012 VL 83 IS 9 BP 1183 EP 1191 DI 10.1902/jop.2011.110346 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 010JU UT WOS:000309091500014 PM 22181684 ER PT J AU Nguyen, JT Buchanan, IA Patel, PP Aljinovic, N Lee, BT AF Nguyen, John T. Buchanan, Ian A. Patel, Priti P. Aljinovic, Nika Lee, Bernard T. TI Intercostal neuroma as a source of pain after aesthetic and reconstructive breast implant surgery SO JOURNAL OF PLASTIC RECONSTRUCTIVE AND AESTHETIC SURGERY LA English DT Article DE Intercostal neuroma; Breast implant; Breast reconstruction; Breast augmentation ID CHRONIC POSTOPERATIVE BREAST; NERVE AB The development of persistent post-operative pain after implant placement for aesthetic or reconstructive breast surgery can lead to significant patient morbidity. Although there are many etiologies for post-operative pain, the diagnosis of an intercostal neuroma is important as this can be treated surgically. We describe three cases of an intercostal neuroma in patients with breast implants. A Tinel's sign can be elicited along the lateral chest wall and a local anesthetic block temporarily alleviates this pain. Surgical management with identification and clipping of the intercostal neuroma and burying into the underlying muscle significantly decreases post-operative pain long term. In patients with persistent pain after breast implant placement, plastic surgeons must be aware of this treatable cause of pain. (C) 2012 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved. C1 [Nguyen, John T.; Buchanan, Ian A.; Patel, Priti P.; Lee, Bernard T.] Harvard Univ, Dept Surg, Div Plast & Reconstruct Surg, Beth Israel Deaconess Med Ctr,Med Sch, Boston, MA 02215 USA. [Aljinovic, Nika] Harvard Univ, Dept Pathol, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. RP Lee, BT (reprint author), Harvard Univ, Dept Surg, Div Plast & Reconstruct Surg, Beth Israel Deaconess Med Ctr,Med Sch, 110 Francis St,Suite 5A, Boston, MA 02215 USA. EM blee3@bidmc.harvard.edu RI Lee, Bernard/K-1106-2016; OI Lee, Bernard/0000-0002-5533-3166; Buchanan, Ian /0000-0001-6674-4924 NR 5 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1748-6815 J9 J PLAST RECONSTR AES JI J. Plast. Reconstr. Aesthet. Surg. PD SEP PY 2012 VL 65 IS 9 BP 1199 EP 1203 DI 10.1016/j.bjps.2012.04.003 PG 5 WC Surgery SC Surgery GA 990UO UT WOS:000307657500021 PM 22542703 ER PT J AU Litz, BT Salters-Pedneault, K Steenkamp, MM Hermos, JA Bryant, RA Otto, MW Hofmann, SG AF Litz, Brett T. Salters-Pedneault, Kristalyn Steenkamp, Maria M. Hermos, John A. Bryant, Richard A. Otto, Michael W. Hofmann, Stefan G. TI A randomized placebo-controlled trial of D-cycloserine and exposure therapy for posttraumatic stress disorder SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE PTSD; DCS; Exposure therapy; Veterans; Imaginal ID OBSESSIVE-COMPULSIVE DISORDER; COGNITIVE-BEHAVIORAL THERAPY; SOCIAL ANXIETY DISORDER; FEAR EXTINCTION; CONDITIONED FEAR; MEMORY RECONSOLIDATION; PTSD; AUGMENTATION; FACILITATION; METAANALYSIS AB D-Cycloserine (DCS) is a partial NMDA receptor agonist that has been shown to enhance therapeutic response to exposure-based treatments for anxiety disorders, but has not been tested in the treatment of combat-related posttraumatic stress disorder (PTSD). The aim of this randomized, double-blind, placebo-controlled trial was to determine whether DCS augments exposure therapy for PTSD in veterans returning from Iraq and Afghanistan and to test whether a brief six-session course of exposure therapy could effectively reduce PTSD symptoms in returning veterans. In contrast to previous trials using DCS to enhance exposure therapy, results indicated that veterans in the exposure therapy plus DCS condition experienced significantly less symptom reduction than those in the exposure therapy plus placebo condition over the course of the treatment. Possible reasons for why DCS was associated with poorer outcome are discussed. C1 [Litz, Brett T.; Steenkamp, Maria M.; Hermos, John A.] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA 02130 USA. [Litz, Brett T.] Natl Ctr PTSD, Boston, MA USA. [Litz, Brett T.; Hermos, John A.] Boston Univ, Sch Med, Boston, MA 02215 USA. [Salters-Pedneault, Kristalyn] Eastern Connecticut State Univ, Willimantic, CT 06226 USA. [Bryant, Richard A.] Univ New S Wales, Sydney, NSW 2052, Australia. RP Litz, BT (reprint author), VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, 150 S Huntington Ave 116B-5, Boston, MA 02130 USA. EM Brett.Litz@va.gov RI Hofmann, Stefan/B-8769-2014; OI Hofmann, Stefan/0000-0002-3548-9681; Bryant, Richard/0000-0002-9607-819X FU VA as part of VA/NIMH; Merck (Organon); NIMH [MH078308] FX This randomized controlled trial was funded by the VA as part of a joint VA/NIMH solicitation for R-34 type PTSD trials.; Drs. Litz, Salters-Pedneault, Steenkamp, Hermos, and Bryant reported no biomedical financial interests or potential conflicts of interest. In the last 2 years, Dr. Otto has received research support from Merck (Organon). Dr. Otto is also a recipient of an NIMH grant to study the effects of D-cycloserine in combination with exposure-based therapy for panic disorder. Dr. Hofmann is a paid consultant by Schering-Plough for research unrelated to this study, and he is supported by NIMH grant MH078308. NR 46 TC 71 Z9 71 U1 4 U2 32 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 SEP PY 2012 VL 46 IS 9 BP 1184 EP 1190 DI 10.1016/j.jpsychires.2012.05.006 PG 7 WC Psychiatry SC Psychiatry GA 993MN UT WOS:000307863900011 PM 22694905 ER PT J AU Holsen, LM Lawson, EA Blum, J Ko, E Makris, N Fazeli, PK Klibanski, A Goldstein, JM AF Holsen, Laura M. Lawson, Elizabeth A. Blum, Justine Ko, Eunice Makris, Nikos Fazeli, Pouneh K. Klibanski, Anne Goldstein, Jill M. TI Food motivation circuitry hypoactivation related to hedonic and nonhedonic aspects of hunger and satiety in women with active anorexia nervosa and weight-restored women with anorexia nervosa SO JOURNAL OF PSYCHIATRY & NEUROSCIENCE LA English DT Article ID HIGH-CALORIE FOODS; EATING-DISORDERS; ADOLESCENT GIRLS; SUSCEPTIBILITY ARTIFACTS; HEALTHY ADOLESCENTS; SYMPTOM PROVOCATION; SECRETORY DYNAMICS; BRAIN ACTIVITY; STIMULI; CORTEX AB Background: Previous studies have provided evidence of food motivation circuitry dysfunction in individuals with anorexia nervosa. However, methodological limitations present challenges to the development of a cohesive neurobiological model of anorexia nervosa. Our goal was to investigate the neural circuitry of appetite dysregulation across states of hunger and satiety in active and weight-restored phases of anorexia nervosa using robust methodology to advance our understanding of potential neural circuitry abnormalities related to hedonic and nonhedonic state and trait. Methods: We scanned women with active anorexia nervosa, weight-restored women with anorexia nervosa and healthy-weight controls on a 3-T Siemens magnetic resonance scanner while they viewed images of high- and low-calorie foods and objects before (premeal) and after (postmeal) eating a 400 kcal meal. Results: We enrolled 12 women with active disease, 10 weight-restored women with anorexia nervosa and 11 controls in our study. Compared with controls, both weight-restored women and those with active disease demonstrated hypoactivity premeal in the hypothalamus, amygdala and anterior insula in response to high-calorie foods (v. objects). Postmeal, hypoactivation in the anterior insula persisted in women with active disease. Percent signal change in the anterior insula was positively correlated with food stimuli ratings and hedonic and nonhedonic appetite ratings in controls, but not women with active disease. Limitations: Our findings are limited by a relatively small sample size, which prevented the use of an analysis of variance model and exploration of interaction effects, although our substantial effect sizes of between-group differences suggest adequate power for our statistical analysis approach. Participants taking psychotropic medications were included. Conclusion: Our data provide evidence of potential state and trait hypoactivations in food motivation regions involved in the assessment of food's reward value and integration of these with interoceptive signalling of one's internal state of well-being, with important relations between brain activity and homeostatic and hedonic aspects of appetite. Our findings give novel evidence of disruption in neurobiological circuits and stress the importance of examining both state and trait characteristics in the investigation of brain phenotypes in individuals with anorexia nervosa. C1 [Holsen, Laura M.; Ko, Eunice; Goldstein, Jill M.] Brigham & Womens Hosp, Div Womens Hlth, Dept Med, Boston, MA 02120 USA. [Holsen, Laura M.; Goldstein, Jill M.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02120 USA. [Holsen, Laura M.; Lawson, Elizabeth A.; Fazeli, Pouneh K.; Klibanski, Anne; Goldstein, Jill M.] Harvard Univ, Sch Med, Boston, MA USA. [Lawson, Elizabeth A.; Blum, Justine; Fazeli, Pouneh K.; Klibanski, Anne] Massachusetts Gen Hosp, Dept Med, Neuroendocrine Unit, Boston, MA 02114 USA. [Makris, Nikos; Goldstein, Jill M.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr, Charlestown, MA USA. [Makris, Nikos; Goldstein, Jill M.] MIT, Charlestown, MA USA. [Makris, Nikos] Harvard Univ, Sch Med, Dept Neurol, Ctr Morphometr Anal,Massachusetts Gen Hosp, Charlestown, MA USA. [Makris, Nikos] Harvard Univ, Sch Med, Dept Psychiat, Ctr Morphometr Anal,Massachusetts Gen Hosp, Charlestown, MA USA. [Makris, Nikos] Harvard Univ, Sch Med, Dept Radiol Serv, Ctr Morphometr Anal,Massachusetts Gen Hosp, Charlestown, MA USA. Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. RP Holsen, LM (reprint author), Brigham & Womens Hosp, Div Womens Hlth, Dept Med, BC 3,1620 Tremont St, Boston, MA 02120 USA. EM lholsen@partners.org FU National Institutes of Health Office of Research in Women's Health; Harvard Catalyst \ The Harvard Clinical and Translational Science Center (NIH) [UL1 RR025758]; Davis Foundation; National Institutes of Health; Harvard Building Interdisciplinary Research Careers in Women's Health Program [K12 HD051959] FX L.M. Holsen and E.A. Lawson were funded by the Harvard K12 HD051959 Building Interdisciplinary Research Careers in Women's Health Program supported by National Institutes of Health Office of Research in Women's Health. The research was conducted with support from Harvard Catalyst vertical bar The Harvard Clinical and Translational Science Center (NIH Award #UL1 RR025758) and the Davis Foundation (P.K. Fazeli). We thank Daniel Donoho, Lauren Ogden and Tara Minaker for help in earlier phases of the study and David Herzog, MD, Kamryn Eddy, PhD, and Erinne Meenaghan, NP, for clinical assessment of the participants.; As above for L.M. Holsen, E.A. Lawson and P.K. Fazeli. None declared for J. Blum. E. Ko, N. Makris, A. Klibanski and J.M. Goldstein declare having received grant support from the National Institutes of Health through their respective insitutions. NR 68 TC 37 Z9 39 U1 3 U2 16 PU CMA-CANADIAN MEDICAL ASSOC PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 5W8, CANADA SN 1180-4882 J9 J PSYCHIATR NEUROSCI JI J. Psychiatry Neurosci. PD SEP PY 2012 VL 37 IS 5 BP 322 EP 332 DI 10.1503/jpn.110156 PG 11 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 012BG UT WOS:000309209800006 PM 22498079 ER PT J AU Newcomb, ME Heinz, AJ Mustanski, B AF Newcomb, Michael E. Heinz, Adrienne J. Mustanski, Brian TI Examining Risk and Protective Factors for Alcohol Use in Lesbian, Gay, Bisexual, and Transgender Youth: A Longitudinal Multilevel Analysis SO JOURNAL OF STUDIES ON ALCOHOL AND DRUGS LA English DT Article ID PERCEIVED SOCIAL SUPPORT; ADOLESCENT SUBSTANCE USE; SEXUAL ORIENTATION; DRUG-USE; PSYCHIATRIC COMORBIDITY; MULTIDIMENSIONAL SCALE; SCHOOL VICTIMIZATION; RACIAL-DIFFERENCES; DRINKING PATTERNS; MENTAL-HEALTH AB Objective: Lesbian, gay, bisexual, and transgender (LGBT) youth are at increased risk for alcohol misuse, but little is known about the psychosocial and demographic factors that are associated with these differences over time. The purpose of this study was to investigate change in alcohol use across development. We aimed to describe group/demographic differences in alcohol use, the effects of psychosocial variables on drinking within persons (i.e., psychological distress, sexual orientation based victimization, and perceived family support), and the interactions between demographic differences and longitudinal psychosocial variables in predicting rates of alcohol use. Method: The current study used data from the longest running longitudinal study of LGBT youth. Hierarchical linear modeling was used to examine both demographic differences and psychosocial predictors of alcohol use in an ethnically diverse sample of 246 LGBT youth (ages 16-20 years at baseline) across five time points over 2.5 years. Results: Drinking increased significantly over time in a linear fashion, although it tended to increase more rapidly among male LGBT youth compared with females. Analyses of group differences revealed lower average rates of drinking for African American and female LGBT youth, and there were no differences between bisexual youth and gay/lesbian youth. Psychological distress and sexual orientation based victimization were associated with increased alcohol use at each wave of data collection for female LGBT youth only. Perceived family support at each wave was negatively associated with alcohol use for all LGBT youth. Conclusions: Findings indicate that there is significant heterogeneity in the etiological pathways that lead to alcohol use in LGBT youth and that correlates of drinking are similar to those found in general populations. These crucial findings indicate that existing alcohol interventions also may be effective for LGBT youth and open up a wider array of prevention and treatment options for this at-risk population. (J. Stud. Alcohol Drugs, 73, 783-793, 2012) C1 [Newcomb, Michael E.] Northwestern Univ, Feinberg Sch Med, Dept Med & Social Sci, Chicago, IL 60611 USA. [Newcomb, Michael E.; Heinz, Adrienne J.] Univ Illinois, Dept Psychol, Chicago, IL 60680 USA. [Newcomb, Michael E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Heinz, Adrienne J.] Vet Affairs Med Ctr, San Francisco, CA 94121 USA. RP Newcomb, ME (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Med & Social Sci, 625 N Michigan Ave,Suite 2700, Chicago, IL 60611 USA. EM michael@impactprogram.org FU American Foundation for Suicide Prevention grant; William T. Grant Foundation Scholars Award; David Bohnett Foundation; National Research Service Award from the National Institute of Mental Health [F31MH088942]; National Research Service Award from the National Institute on Alcohol Abuse and Alcoholism [F31AA018918] FX This research was supported by an American Foundation for Suicide Prevention grant (to principal investigator Brian Mustanski), the William T. Grant Foundation Scholars Award (to principal investigator Brian Mustanski), and the David Bohnett Foundation (to principal investigator Brian Mustanski). Michael E. Newcomb was supported by a National Research Service Award from the National Institute of Mental Health (Grant F31MH088942), and Adrienne J. Heinz was supported by a National Research Service Award from the National Institute on Alcohol Abuse and Alcoholism (Grant F31AA018918). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies. NR 64 TC 36 Z9 36 U1 7 U2 32 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA SN 1937-1888 EI 1938-4114 J9 J STUD ALCOHOL DRUGS JI J. Stud. Alcohol Drugs PD SEP PY 2012 VL 73 IS 5 BP 783 EP 793 PG 11 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA 009PL UT WOS:000309037600009 PM 22846242 ER PT J AU Salanitro, AH Hovater, M Hearld, KR Roth, DL Sawyer, P Locher, JL Bodner, E Brown, CJ Allman, RM Ritchie, CS AF Salanitro, Amanda H. Hovater, Martha Hearld, Kristine R. Roth, David L. Sawyer, Patricia Locher, Julie L. Bodner, Eric Brown, Cynthia J. Allman, Richard M. Ritchie, Christine S. TI Symptom Burden Predicts Hospitalization Independent of Comorbidity in Community-Dwelling Older Adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE healthcare utilization; symptom; older adults; comorbidity ID MEDICAL CONDITIONS; HEALTH; PREVALENCE; DISTRESS; PROFILE; ELDERS AB Objectives To determine whether cumulative symptom burden predicts hospitalization or emergency department (ED) visits in a cohort of older adults. Design Prospective, observational study with a baseline in-home assessment of symptom burden. Setting Central Alabama. Participants Nine hundred eighty community-dwelling adults aged 65 and older (mean 75.3 +/- 6.7) recruited from a random sample of Medicare beneficiaries stratified according to sex, race, and urban/rural residence. Measurements Symptom burden score (range 010). One point was given for each symptom reported: shortness of breath, tiredness or fatigue, problems with balance or dizziness, leg weakness, poor appetite, pain, stiffness, constipation, anxiety, and loss of interest in activities. Dependent variables were hospitalizations and ED visits, assessed every 6 months during the 8.5-year follow-up period. Using Cox proportional hazards models, time from the baseline in-home assessment to the first hospitalization and first hospitalization or ED visit was determined. Results During the 8.5-year follow-up period, 545 (55.6%) participants were hospitalized or had an ED visit. Participants with greater symptom burden had higher risk of hospitalization (hazard ratio (HR) = 1.09, 95% confidence interval (CI) = 1.051.14) and hospitalization or ED visit (HR = 1.10, 95% CI = 1.061.14) than those with lower scores. Participants living in rural areas had significantly lower risk of hospitalization (HR = 0.83, 95% CI = 0.690.99) and hospitalization or ED visit (HR = 0.80, 95% CI = 0.700.95) than individuals in urban areas, independent of symptom burden and comorbidity. Conclusion Greater symptom burden was associated with higher risk of hospitalization and ED visits in community-dwelling older adults. Healthcare providers treating older adults should consider symptom burden to be an additional risk factor for subsequent hospital utilization. C1 [Salanitro, Amanda H.] Vet Affairs Tennessee Valley Healthcare, Geriatr Res Educ & Clin Ctr, Nashville, TN USA. [Salanitro, Amanda H.] Vanderbilt Univ, Sect Hosp Med, Nashville, TN USA. [Hovater, Martha; Hearld, Kristine R.] Univ Alabama Birmingham, Dept Biostat, Birmingham, AL 35294 USA. [Roth, David L.] Johns Hopkins Univ, Ctr Aging & Hlth, Baltimore, MD USA. [Sawyer, Patricia; Locher, Julie L.; Bodner, Eric; Brown, Cynthia J.; Allman, Richard M.] Univ Alabama Birmingham, Div Gerontol Geriatr & Palliat Care, Birmingham, AL USA. [Brown, Cynthia J.; Allman, Richard M.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Brown, Cynthia J.; Allman, Richard M.] Atlanta Dept Vet Affairs, Geriatr Res Educ & Clin Ctr, Birmingham, AL USA. [Ritchie, Christine S.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Ritchie, Christine S.] Jewish Home San Francisco, Ctr Res Aging, San Francisco, CA USA. RP Salanitro, AH (reprint author), Room A-414,1310 24th Ave S, Nashville, TN 37212 USA. EM Amanda.Salanitro@Vanderbilt.Edu FU National Institutes of Health [R01-AG015062, P30AG031054, 1UL 1RR025777]; National Institute on Aging K07 award FX This study was funded in part by Grants R01-AG015062, P30AG031054, and 1UL 1RR025777 from the National Institutes of Health. Dr. Ritchie is supported by a National Institute on Aging K07 award. The content is solely the responsibility of the authors and does not necessarily reflect the policy of the National Institute on Aging or the National Institutes of Health. NR 21 TC 9 Z9 9 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 2012 VL 60 IS 9 BP 1632 EP 1637 DI 10.1111/j.1532-5415.2012.04121.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 008ER UT WOS:000308940700005 PM 22985139 ER PT J AU Eicken, JJ Wilcox, SR Liteplo, AS AF Eicken, John J. Wilcox, Susan R. Liteplo, Andrew S. TI Bedside Sonographic Diagnosis of Tracheal Stenosis SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Letter C1 [Eicken, John J.; Wilcox, Susan R.; Liteplo, Andrew S.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Eicken, JJ (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. NR 9 TC 3 Z9 3 U1 0 U2 0 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD SEP PY 2012 VL 31 IS 9 BP 1468 EP 1470 PG 3 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 001HT UT WOS:000308451900020 PM 22922630 ER PT J AU Ulmer, WD Prasad, SM Kowalczyk, KJ Gu, XM Dodgion, C Lipsitz, S Palapattu, GS Choueiri, TK Hu, JC AF Ulmer, William D. Prasad, Sandip M. Kowalczyk, Keith J. Gu, Xiangmei Dodgion, Christopher Lipsitz, Stuart Palapattu, Ganesh S. Choueiri, Toni K. Hu, Jim C. TI Factors Associated with the Adoption of Minimally Invasive Radical Prostatectomy in the United States SO JOURNAL OF UROLOGY LA English DT Article DE surgical procedures; minimally invasive; prostatic neoplasms; referral and consultation; choice behavior ID CANCER; PHYSICIAN; SURGERY; COMORBIDITY; IMPACT; AGE AB Purpose: Minimally invasive radical prostatectomy has supplanted radical retropubic prostatectomy in popularity despite the absence of strong comparative effectiveness data demonstrating its superiority. We examined the influence of patient, surgeon and hospital characteristics on the use of minimally invasive radical prostatectomy vs radical retropubic prostatectomy. Materials and Methods: Using SEER (Surveillance, Epidemiology and End Results)-Medicare linked data we identified 11,732 men who underwent radical prostatectomy from 2003 to 2007. We assessed the contribution of patient, surgeon and hospital characteristics to the likelihood of undergoing minimally invasive radical prostatectomy vs radical retropubic prostatectomy using multi-level logistic regression mixed models. Results: Patient factors (36.7%) contributed most to the use of minimally invasive radical prostatectomy vs radical retropubic prostatectomy, followed by surgeon (19.1%) and hospital (11.8%) factors. Among patient specific factors Asian race (OR 1.86, 95% CI 1.27-2.72, p = 0.001), clinically organ confined tumors (OR 2.71, 95% CI 1.60-4.57, p <0.001) and obtaining a second opinion from a urologist (OR 3.41, 95% CI 2.67-4.37, p <0.001) were associated with the highest use of minimally invasive radical prostatectomy while lower income was associated with decreased use of minimally invasive radical prostatectomy. Among surgeon and hospital specific factors, higher surgeon volume (OR 1.022, 95% CI 1.015-1.028, p <0.001), surgeon age younger than 50 years (OR 2.68, 95% CI 1.69-4.24, p <0.001) and greater hospital bed size (OR 1.001, 95% CI 1.001-1.002, p <0.001) were associated with increased use of minimally invasive radical prostatectomy, while solo or 2 urologist practices were associated with decreased use of minimally invasive radical prostatectomy (OR 0.48, 95% CI 0.27-0.86, p = 0.013). Conclusions: The adoption of minimally invasive radical prostatectomy vs radical retropubic prostatectomy is multifactorial, and associated with specific patient, surgeon and hospital related factors. Obtaining a second opinion from another urologist was the strongest factor associated with opting for minimally invasive radical prostatectomy. C1 [Hu, Jim C.] Univ Calif Los Angeles, Dept Urol, Los Angeles, CA 90024 USA. [Ulmer, William D.] Brigham & Womens Hosp, Div Urol Surg, Boston, MA 02115 USA. [Gu, Xiangmei; Dodgion, Christopher; Lipsitz, Stuart] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Choueiri, Toni K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Prasad, Sandip M.] Med Univ S Carolina, Dept Urol, Charleston, SC 29425 USA. [Kowalczyk, Keith J.] Georgetown Univ Hosp, Dept Urol, Washington, DC 20007 USA. [Palapattu, Ganesh S.] Methodist Hosp, Weill Cornell Med Coll, Dept Urol, New York, NY USA. RP Hu, JC (reprint author), Univ Calif Los Angeles, Dept Urol, 924 Westwood Blvd, Los Angeles, CA 90024 USA. RI Dodgion, Chris/A-2877-2016 OI Dodgion, Chris/0000-0002-5789-7731 FU Department of Defense Prostate Cancer Physician Training Award [W81XWH-08-1-0283] FX Supported by a Department of Defense Prostate Cancer Physician Training Award (W81XWH-08-1-0283) (JCH). NR 30 TC 8 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD SEP PY 2012 VL 188 IS 3 BP 775 EP 780 DI 10.1016/j.juro.2012.05.014 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 989HP UT WOS:000307551200025 PM 22818134 ER PT J AU Tarnoki, AD Tarnoki, DL Bata, P Littvay, L Osztovits, J Jermendy, G Karlinger, K Lannert, A Preda, I Kiss, RG Molnar, AA Garami, Z Baffy, G Berczi, V AF Tarnoki, Adam D. Tarnoki, David L. Bata, Pal Littvay, Levente Osztovits, Janos Jermendy, Gyorgy Karlinger, Kinga Lannert, Agnes Preda, Istvan Kiss, Robert G. Molnar, Andrea A. Garami, Zsolt Baffy, Gyorgy Berczi, Viktor TI Heritability of non-alcoholic fatty liver disease and association with abnormal vascular parameters: A twin study SO LIVER INTERNATIONAL LA English DT Article DE arterial stiffness; genetics; heritability; intima media thickness; steatosis ID INTIMA-MEDIA THICKNESS; INCREASED ARTERIAL STIFFNESS; RISK-FACTORS; METABOLIC SYNDROME; CORONARY ATHEROSCLEROSIS; COMPUTED-TOMOGRAPHY; STEATOHEPATITIS; ULTRASOUND; STEATOSIS AB Background: Non-alcoholic fatty liver disease (NAFLD) has been linked to increased cardiovascular morbidity. However, genetic factors have an unclear role in this condition. Aims: To analyse heritability of NAFLD and its association with abnormal vascular parameters in a large twin cohort. Methods: Anthropometric and lipid metabolic parameters were obtained from 208 adult Hungarian twins (63 monozygotic and 41 dizygotic pairs; 58 men and 150 women; age 43.7 +/- 16.7 years). B-mode ultrasonography was performed to detect steatosis and categorize severity. Brachial and aortic augmentation indices and aortic pulse wave velocity were assessed using oscillometry (TensioMed Arteriograph). Carotid intima media thickness (IMT) was measured using ultrasonography on the proximal common, distal common and internal carotid arteries. Results: NAFLD was identified in 47 subjects (22.6%), of which 44 (93.6%) had mild and 3 (6.4%) had moderate steatosis. These subjects were older (age: 50.9 +/- 14.3 vs. 41.5 +/- 16.7 years, P < 0.001) and had a higher body mass index (BMI; 30.1 +/- 5.2 vs. 24.6 +/- 4.1 km/m(2), P < 0.001) than non-NAFLD twins. Based on 91 same-sex twin pairs, heritability analysis indicated no discernible role for genetic components in the presence of NAFLD (95% confidence interval, 0.0-36.0%), while shared and unshared environmental effects accounted for 74.2% and 25.8% of variations adjusted for age and BMI. Augmentation indices and carotid IMT in twins with NAFLD were increased at most examined locations (P < 0.05-P < 0.001). Conclusion: These findings do not support heritability of NAFLD, although it coexists with vascular parameters linked to increased cardiovascular risk, underscoring the importance and value of prevention in this very common disorder. C1 [Tarnoki, Adam D.; Tarnoki, David L.; Bata, Pal; Karlinger, Kinga; Berczi, Viktor] Semmelweis Univ, Dept Radiol & Oncotherapy, H-1082 Budapest, Hungary. [Littvay, Levente] Cent European Univ, Budapest, Hungary. [Osztovits, Janos; Jermendy, Gyorgy] Bajcsy Zsilinszky Hosp III, Dept Internal Med, Budapest, Hungary. [Lannert, Agnes] Semmelweis Univ, Sch Pharm, H-1082 Budapest, Hungary. [Preda, Istvan; Kiss, Robert G.; Molnar, Andrea A.] Semmelweis Univ, Hungarian Acad Sci, Res Grp Inflammat Biol & Immunogen, H-1082 Budapest, Hungary. [Preda, Istvan; Kiss, Robert G.; Molnar, Andrea A.] Mil Hosp, Natl Hlth Ctr, Dept Cardiol, Budapest, Hungary. [Garami, Zsolt] Methodist Hosp, DeBakey Heart & Vasc Ctr, Houston, TX 77030 USA. [Baffy, Gyorgy] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Baffy, Gyorgy] VA Boston Healthcare Syst, Boston, MA USA. RP Tarnoki, AD (reprint author), Semmelweis Univ, Dept Radiol & Oncotherapy, 78-A Ulloi St, H-1082 Budapest, Hungary. EM tarnoki4@gmail.com FU Medexpert Ltd. FX The authors would like to disclose the financial support provided by Medexpert Ltd. in this study. The help of Andrea Kovacs and Katalin Csizmadia in the laboratory work is gratefully acknowledged. NR 38 TC 11 Z9 11 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1478-3223 J9 LIVER INT JI Liver Int. PD SEP PY 2012 VL 32 IS 8 BP 1287 EP 1293 DI 10.1111/j.1478-3231.2012.02823.x PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 991SN UT WOS:000307722000013 PM 22651705 ER PT J AU Adams, SG Pitts, J Wynne, J Yawn, BP Diamond, EJ Lee, S Dellert, E Hanania, NA AF Adams, Sandra G. Pitts, Jennifer Wynne, JoEllen Yawn, Barbara P. Diamond, Edward J. Lee, Shuko Dellert, Ed Hanania, Nicola A. TI Effect of a Primary Care Continuing Education Program on Clinical Practice of Chronic Obstructive Pulmonary Disease: Translating Theory Into Practice SO MAYO CLINIC PROCEEDINGS LA English DT Article ID MEDICAL-EDUCATION; AMERICAN-COLLEGE; GUIDELINES; COMMITMENT; MODEL AB Objectives: To describe the development and implementation process and assess the effect on self-reported clinical practice changes of a multidisciplinary, collaborative, interactive continuing medical education (CME)/continuing education (CE) program on chronic obstructive pulmonary disease (CORD). Methods: Multidisciplinary subject matter experts and education specialists used a systematic instructional design approach and collaborated with the American College of Chest Physicians and American Academy of Nurse Practitioners to develop, deliver, and reproduce a 1-day interactive COPD CME/CE program for 351 primary care clinicians in 20 US cities from September 23, 2009, through November 13, 2010. Results: We recorded responses to demographic, self-confidence, and knowledge/comprehension questions by using an audience response system. Before the program, 173 of 320 participants (54.1%) had never used the Global Initiative for Chronic Obstructive Lung Disease recommendations for COPD. After the program, clinician self-confidence improved in all areas measured. In addition, participant knowledge and comprehension significantly improved (mean score, 77.1%-94.7%; P<.001). We implemented the commitment-to-change strategy in courses 6 through 20. A total of 271 of 313 participants (86.6%) completed 971 commitment-to-change statements, and 132 of 271 (48.7%) completed the follow-up survey. Of the follow-up survey respondents, 92 of 132 (69.7%) reported completely implementing at least one clinical practice change, and only 8 of 132 (6.1%) reported inability to make any clinical practice change after the program. Conclusion: A carefully designed, interactive, flexible, dynamic, and reproducible COPD CME/CE program tailored to clinicians' needs that involves diverse instructional strategies and media can have short-term and long-term improvements in clinician self-confidence, knowledge/comprehension, and clinical practice. (C) 2012 Mayo Foundation for Medical Education and Research rectangle Mayo Clin Proc. 2012;87:(9),862-870 C1 [Adams, Sandra G.; Lee, Shuko] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Adams, Sandra G.; Lee, Shuko] Univ Texas Hlth Sci Ctr San Antonio, Div Pulm Dis Crit Care Med, San Antonio, TX 78229 USA. [Pitts, Jennifer; Dellert, Ed] Amer Coll Chest Phys, Northbrook, IL USA. [Wynne, JoEllen] Amer Acad Nurse Practitioners, Austin, TX USA. [Yawn, Barbara P.] Univ Minnesota, Dept Family & Community Hlth, Minneapolis, MN USA. [Diamond, Edward J.] Suburban Lung Associates, Elk Grove Village, IL USA. [Hanania, Nicola A.] Baylor Coll Med, Dept Med, Pulm Crit Care Div, Houston, TX 77030 USA. RP Adams, SG (reprint author), Audie L Murphy Mem Vet Adm Med Ctr, Pulm Dis Sect 111E, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM adamssg@uthscsa.edu FU National Institute of Health; Veterans Affairs Cooperative Studies Program; Bayer Pharmaceuticals Corp; Boehringer Ingelheim Pharmaceuticals Inc; Centocor Inc; GlaxoSmithKline; Novartis Pharmaceuticals AG; Pfizer Inc; Schering-Plough Corp; Aerocrine; Boehringer Ingelheim; Forrest GlaxoSmithKline; Novartis; Astra Zeneca; MedImmune; Pfizer; Sunovion; Pearl; ACCP; AANP; Wilmington, DE; Ridgefield, CT; Philadelphia, PA FX Dr Adams discloses the following: investigator/grant research: National Institute of Health, Veterans Affairs Cooperative Studies Program, Bayer Pharmaceuticals Corp, Boehringer Ingelheim Pharmaceuticals Inc, Centocor Inc, GlaxoSmithKline, Novartis Pharmaceuticals AG, Pfizer Inc, and Schering-Plough Corp; honoraria for speaking at CE programs (unrestricted grants for CE): AstraZeneca Pharmaceuticals LP, Bayer Pharmaceuticals Corp, Boehringer Ingelheim Pharmaceuticals Inc, GlaxoSmithKline, Novartis Pharmaceuticals AG, Pfizer Inc, and Schering-Plough Corp. Ms Pitts and Mr Dellert are both employees of the ACCP. Ms Wynn is employed by the AANP. Dr Yawn discloses the following: research support from Aerocrine, Boehringer Ingelheim, Forrest GlaxoSmithKline, and Novartis. Dr Hanania discloses the following: investigator/research support from Astra Zeneca, Boehringer Ingelheim, GlaxoSmitfiKline, MedImmune, Novartis, Pfizer, and Sunovion; speaker bureau of Boehringer Ingelheim, GlaxoSmithKline, and Pfizer; advisory board/consultancy for Dey Inc, GlaxoSmithKline, Navartis, Pearl, and Pfizer. The programs described were conducted and sponsored by the ACCP and the AANP, Which received unrestricted grants from AstraZeneca Pharmaceuticals LP, Wilmington, DE, Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, CT, and GlaxoSmithKline Pharmaceuticals Ltd, Philadelphia, PA. The funders of the unrestricted grants were not involved in the development or implementation of these programs, in the interpretation of the data, or in the preparation, review, or any part of the manuscript. NR 28 TC 4 Z9 4 U1 0 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD SEP PY 2012 VL 87 IS 9 BP 862 EP 870 DI 10.1016/j.mayocp.2012.02.028 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 009MT UT WOS:000309030600008 PM 22958990 ER PT J AU Slocum, AH Cervantes, TM Seldin, EB Varanasi, KK AF Slocum, Alexander H., Jr. Cervantes, Thomas M. Seldin, Edward B. Varanasi, Kripa K. TI Analysis and design of rolling-contact joints for evaluating bone plate performance SO MEDICAL ENGINEERING & PHYSICS LA English DT Article DE Rolling contact; Bone plate; Fracture fixation; Fatigue life ID MANDIBULAR ANGLE FRACTURES; RIGID FIXATION; STRENGTH; REPAIR AB An apparatus for testing maxillofacial bone plates has been designed using a rolling contact joint. First, a free-body representation of the fracture fixation techniques utilizing bone plates is used to illustrate how rolling contact joints accurately simulate in vivo biomechanics. Next, a deterministic description of machine functional requirements is given, and is then used to drive the subsequent selection and design of machine elements. Hertz contact stress and fatigue analysis for two elements are used to ensure that the machine will both withstand loads required to deform different plates, and maintain a high cycle lifetime for testing large numbers of plates. Additionally, clinically relevant deformations are presented to illustrate how stiffness is affected after a deformation is applied, and to highlight improvements made by the machine over current testing standards, which do not adequately re-create in vivo loading conditions. The machine performed as expected and allowed for analysis of bone plates in both deformed and undeformed configurations to be conducted. Data for deformation experiments is presented to show that the rolling-contact testing machine leads to improved loading configurations, and thus a more accurate description of plate performance. A machine for evaluation of maxillofacial bone plates has been designed, manufactured, and used to accurately simulate in vivo loading conditions to more effectively evaluate the performance of both new and existing bone plates. (C) 2012 IPEM. Published by Elsevier Ltd. All rights reserved. C1 [Slocum, Alexander H., Jr.; Cervantes, Thomas M.; Varanasi, Kripa K.] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Slocum, Alexander H., Jr.] Marshall Univ, Joan C Edwards Sch Med, Huntington, WV 25755 USA. [Seldin, Edward B.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Slocum, AH (reprint author), MIT, Dept Mech Engn, Cambridge, MA 02139 USA. EM ahslocum@mit.edu FU CIMIT FX The authors are grateful to CIMIT for funding this work in part; to Prof. Alexander Slocum, PhD, for his technical guidance on various aspects of this project; to Mark Belanger in the Edgerton Center student shop; to Ken Stone and Hayami Arakawa at the MIT Hobby Shop; Bill Buckley and Pat McAtemney in the LMP shop; and to Pierce Hayward for his invaluable assistance in the Materials Testing Laboratory in the Department of Mechanical Engineering. NR 26 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1350-4533 J9 MED ENG PHYS JI Med. Eng. Phys. PD SEP PY 2012 VL 34 IS 7 BP 1009 EP 1018 DI 10.1016/j.medengphy.2012.06.016 PG 10 WC Engineering, Biomedical SC Engineering GA 000LK UT WOS:000308387600025 PM 22809676 ER PT J AU Bromberger, JT Schott, LL Matthews, KA Kravitz, HM Randolph, JF Harlow, S Crawford, S Green, R Joffe, H AF Bromberger, Joyce T. Schott, Laura L. Matthews, Karen A. Kravitz, Howard M. Randolph, John F., Jr. Harlow, Sioban Crawford, Sybil Green, Robin Joffe, Hadine TI Association of past and recent major depression and menstrual characteristics in midlife: Study of Women's Health Across the Nation SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE Major depression; Bleeding; Menstrual cycle; Midlife ID STRUCTURED CLINICAL INTERVIEW; CARDIOVASCULAR-DISEASE; PREMENSTRUAL-SYNDROME; PSYCHIATRIC-DISORDER; BLOOD-LOSS; FOLLOW-UP; SYMPTOMS; STRESS; MENORRHAGIA; EPIDEMIOLOGY AB Objective: The aim of this study was to examine the association of a history of major depression (MD) with menstrual problems in a multiethnic sample of midlife women. Methods: Participants were 934 women enrolled in the Study of Women's Health Across the Nation, a multisite study of menopause and aging. The outcomes were menstrual bleeding problems and premenstrual symptoms in the year before study entry. The Structured Clinical Interview for the Diagnosis of DSM-IV Axis I Disorders was conducted to determine recent and past psychiatric diagnoses. Covariates included sociodemographic, behavioral, and gynecologic factors. Results: One third of the participants reported heavy bleeding, 20% reported other abnormal bleeding, and 18% reported premenstrual symptoms. One third had past and 11% had recent MD. Past MD was associated with an increased likelihood of heavy bleeding (odds ratio, 1.89; 95% CI, 1.25-2.85), adjusting for recent MD, menopause status, and other covariates. Past MD was not associated with other abnormal bleeding or premenstrual symptoms in the final analysis that adjusted for recent MD. Conclusions: Midlife women with a history of MD are more likely to report heavy bleeding. C1 [Bromberger, Joyce T.; Schott, Laura L.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Bromberger, Joyce T.; Matthews, Karen A.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Matthews, Karen A.] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. [Kravitz, Howard M.] Rush Univ, Med Ctr, Dept Psychiat, Chicago, IL 60612 USA. [Kravitz, Howard M.] Rush Univ, Med Ctr, Dept Prevent Med, Chicago, IL 60612 USA. [Randolph, John F., Jr.] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA. [Harlow, Sioban] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Crawford, Sybil] Univ Massachusetts, Med Ctr, Dept Epidemiol & Biostat, Worcester, MA USA. [Green, Robin] Albert Einstein Coll Med, Dept Obstet Gynecol & Womens Hlth, Jersey City, NJ USA. [Joffe, Hadine] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Womens Mental Hlth,Dept Psychiat, Boston, MA USA. RP Bromberger, JT (reprint author), 3811 OHara St, Pittsburgh, PA 15213 USA. EM brombergerjt@upmc.edu FU National Institutes of Health (NIH) [NR004061, AG012505, AG012535, AG012531, AG012539, AG012546, AG012553, AG012554, AG012495, AG029216]; National Institute of Mental Health [MH59689, MH59770, MH59688]; Cephalon; University of Pittsburgh, Pittsburgh FX This work was supported by National Institutes of Health (NIH) Grants NR004061, AG012505, AG012535, AG012531, AG012539, AG012546, AG012553, AG012554, AG012495, and AG029216. Supplemental funding was provided by National Institute of Mental Health Grants MH59689, MH59770, and MH59688.; Dr. Joffe has had research support from Cephalon and provided advisory/consulting services to Sunovion and Noven.; We thank the National Institute of Mental Health for supplemental funding: University of Pittsburgh, Pittsburgh, PA- Joyce T. Bromberger, Principal Investigator (PI) (R01 MH59689); Rush University, Medical Center, Chicago, IL-Howard M. Kravitz, PI (R01 MH59770); and New Jersey Medical School, Newark, NJ-Adriana Cordal, PI (R01 MH59688). NR 40 TC 6 Z9 6 U1 1 U2 4 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 SEP PY 2012 VL 19 IS 9 BP 959 EP 966 DI 10.1097/gme.0b013e318248f2d5 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 000UR UT WOS:000308415500005 PM 22510936 ER PT J AU Deshpande, V Zen, Y Chan, JKC Yi, EE Sato, Y Yoshino, T Kloppel, G Heathcote, JG Khosroshahi, A Ferry, JA Aalberse, RC Bloch, DB Brugge, WR Bateman, AC Carruthers, MN Chari, ST Cheuk, W Cornell, LD Fernandez-Del Castillo, C Forcione, DG Hamilos, DL Kamisawa, T Kasashima, S Kawa, S Kawano, M Lauwers, GY Masaki, Y Nakanuma, Y Notohara, K Okazaki, K Ryu, JK Saeki, T Sahani, DV Smyrk, TC Stone, JR Takahira, M Webster, GJ Yamamoto, M Zamboni, G Umehara, H Stone, JH AF Deshpande, Vikram Zen, Yoh Chan, John K. Yi, Eunhee E. Sato, Yasuharu Yoshino, Tadashi Kloeppel, Guenter Heathcote, J. Godfrey Khosroshahi, Arezou Ferry, Judith A. Aalberse, Rob C. Bloch, Donald B. Brugge, William R. Bateman, Adrian C. Carruthers, Mollie N. Chari, Suresh T. Cheuk, Wah Cornell, Lynn D. Fernandez-Del Castillo, Carlos Forcione, David G. Hamilos, Daniel L. Kamisawa, Terumi Kasashima, Satomi Kawa, Shigeyuki Kawano, Mitsuhiro Lauwers, Gregory Y. Masaki, Yasufumi Nakanuma, Yasuni Notohara, Kenji Okazaki, Kazuich Ryu, Ji Kon Saeki, Takako Sahani, Dushyant V. Smyrk, Thomas C. Stone, James R. Takahira, Masayuki Webster, George J. Yamamoto, Motohisa Zamboni, Giuseppe Umehara, Hisanori Stone, John H. TI Consensus statement on the pathology of IgG4-related disease SO MODERN PATHOLOGY LA English DT Review DE consensus statement; IgG4; IgG4-related disease ID IGG4-POSITIVE PLASMA-CELLS; HEPATIC INFLAMMATORY PSEUDOTUMOR; AUTOIMMUNE PANCREATITIS; SCLEROSING DISEASE; SYSTEMIC-DISEASE; TUBULOINTERSTITIAL NEPHRITIS; DIAGNOSTIC-CRITERIA; CLINICOPATHOLOGICAL-ENTITY; RETROPERITONEAL FIBROSIS; IMMUNOGLOBULIN G4 AB IgG4-related disease is a newly recognized fibro-inflammatory condition characterized by several features: a tendency to form tumefactive lesions in multiple sites; a characteristic histopathological appearance; and-often but not always-elevated serum IgG4 concentrations. An international symposium on IgG4-related disease was held in Boston, MA, on 4-7 October 2011. The organizing committee comprising 35 IgG4-related disease experts from Japan, Korea, Hong Kong, the United Kingdom, Germany, Italy, Holland, Canada, and the United States, including the clinicians, pathologists, radiologists, and basic scientists. This group represents broad subspecialty expertise in pathology, rheumatology, gastroenterology, allergy, immunology, nephrology, pulmonary medicine, oncology, ophthalmology, and surgery. The histopathology of IgG4-related disease was a specific focus of the international symposium. The primary purpose of this statement is to provide practicing pathologists with a set of guidelines for the diagnosis of IgG4-related disease. The diagnosis of IgG4-related disease rests on the combined presence of the characteristic histopathological appearance and increased numbers of IgG4(+) plasma cells. The critical histopathological features are a dense lymphoplasmacytic infiltrate, a storiform pattern of fibrosis, and obliterative phlebitis. We propose a terminology scheme for the diagnosis of IgG4-related disease that is based primarily on the morphological appearance on biopsy. Tissue IgG4 counts and IgG4:IgG ratios are secondary in importance. The guidelines proposed in this statement do not supplant careful clinicopathological correlation and sound clinical judgment. As the spectrum of this disease continues to expand, we advocate the use of strict criteria for accepting newly proposed entities or sites as components of the IgG4-related disease spectrum. Modern Pathology (2012) 25, 1181-1192; doi:10.1038/modpathol.2012.72; published online 18 May 2012 C1 [Deshpande, Vikram; Ferry, Judith A.; Lauwers, Gregory Y.; Stone, James R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Zen, Yoh] Kings Coll Hosp London, Inst Liver Studies, London SE5 8RX, England. [Chan, John K.; Cheuk, Wah] Queen Elizabeth Hosp, Dept Pathol, Kowloon, Hong Kong, Peoples R China. [Yi, Eunhee E.] Mayo Clin, Div Anat Pathol, Rochester, MN USA. [Sato, Yasuharu; Yoshino, Tadashi] Okayama Univ, Dept Pathol, Grad Sch Med Dent & Pharmaceut Sci, Okayama 7008530, Japan. [Kloeppel, Guenter] Tech Univ Munich, Dept Pathol, Munich, Germany. [Heathcote, J. Godfrey] Dalhousie Univ, Dept Pathol, Halifax, NS, Canada. [Khosroshahi, Arezou; Bloch, Donald B.; Carruthers, Mollie N.; Stone, John H.] Massachusetts Gen Hosp, Rheumatol Unit, Boston, MA 02114 USA. [Aalberse, Rob C.] Univ Amsterdam, Dept Immunol, Amsterdam, Netherlands. [Brugge, William R.; Forcione, David G.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Bateman, Adrian C.] Southampton Gen Hosp, Dept Cellular Pathol, Southampton SO9 4XY, Hants, England. [Chari, Suresh T.] Mayo Clin Fdn, Div Gastroenterol, Rochester, MN USA. [Cornell, Lynn D.; Smyrk, Thomas C.] Mayo Clin Fdn, Dept Pathol, Rochester, MN USA. [Fernandez-Del Castillo, Carlos] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Kamisawa, Terumi] Tokyo Metropolitan Komagome Hosp, Div Gastroenterol, Tokyo, Japan. [Kasashima, Satomi] Kanazawa Med Ctr, Dept Pathol, Kanazawa, Ishikawa, Japan. [Kawa, Shigeyuki] Shinshu Univ, Ctr Hlth Safety & Environm, Shinshu, Japan. [Kawano, Mitsuhiro] Kanazawa Univ, Div Nephrol, Grad Sch Med, Kanazawa, Ishikawa, Japan. [Hamilos, Daniel L.] Massachusetts Gen Hosp, Div Allergy & Immunol, Boston, MA 02114 USA. [Masaki, Yasufumi; Umehara, Hisanori] Kanazawa Med Univ, Div Hematol & Immunol, Kanazawa, Ishikawa, Japan. [Nakanuma, Yasuni] Kanazawa Univ, Dept Pathol, Kanazawa, Ishikawa, Japan. [Notohara, Kenji] Kurashiki Cent Hosp, Dept Pathol, Kurashiki, Okayama, Japan. [Okazaki, Kazuich] Kansai Med Univ, Div Gastroenterol & Hepatol, Kansai, Japan. [Ryu, Ji Kon] Seoul Natl Univ, Coll Med, Div Gastroenterol, Seoul, South Korea. [Saeki, Takako] Nagaoka Red Cross Hosp, Div Nephrol, Nagaoka, Niigata, Japan. [Sahani, Dushyant V.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Takahira, Masayuki] Kanazawa Univ, Grad Sch Med Sci, Dept Ophthalmol, Kanazawa, Ishikawa, Japan. [Webster, George J.] Univ Coll London Hosp, Div Gastroenterol, London, England. [Yamamoto, Motohisa] Sapporo Med Univ, Sch Med, Dept Internal Med 1, Sapporo, Hokkaido, Japan. [Zamboni, Giuseppe] Univ Verona, Dept Pathol, I-37100 Verona, Italy. RP Deshpande, V (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 2,55 Fruit St, Boston, MA 02114 USA. EM vdeshpande@partners.org RI Ryu, Ji Kon/J-5462-2012; Giuseppe, Zamboni/A-5991-2016; OI Giuseppe, Zamboni/0000-0001-7428-4673; Kloppel, Gunter/0000-0002-6688-086X; Bateman, Adrian/0000-0003-2222-4104 NR 64 TC 537 Z9 583 U1 13 U2 79 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD SEP PY 2012 VL 25 IS 9 BP 1181 EP 1192 DI 10.1038/modpathol.2012.72 PG 12 WC Pathology SC Pathology GA 004MN UT WOS:000308685900001 PM 22596100 ER PT J AU Lovera, JF Kim, E Heriza, E Fitzpatrick, M Hunziker, J Turner, AP Adams, J Stover, T Sangeorzan, A Sloan, A Howieson, D Wild, K Haselkorn, J Bourdette, D AF Lovera, Jesus F. Kim, Edward Heriza, Elizabeth Fitzpatrick, Mary Hunziker, James Turner, Aaron P. Adams, Joshua Stover, Thomas Sangeorzan, Adam Sloan, Alicia Howieson, Diane Wild, Katherine Haselkorn, Jodie Bourdette, Dennis TI Ginkgo biloba does not improve cognitive function in MS A randomized placebo-controlled trial SO NEUROLOGY LA English DT Article ID MULTIPLE-SCLEROSIS PATIENTS; L-AMPHETAMINE SULFATE; MEMORY IMPAIRMENT; DYSFUNCTION; PERFORMANCE; EXPRESSION; MEMANTINE; GLUTAMATE AB Objective: To determine whether Ginkgo biloba extract (ginkgo) improves cognitive function in persons with multiple sclerosis (MS). Methods: Persons with MS from the Seattle and Portland VA clinics and adjacent communities who scored 1 SD or more below the mean on one of 4 neuropsychological tests (Stroop Test, California Verbal Learning Test II [CVLT-II], Controlled Oral Word Association Test [COWAT], and Paced Auditory Serial Addition Task [PASAT]) were randomly assigned to receive either one 120-mg tablet of ginkgo (EGb-761; Willmar Schwabe GmbH & Co, Germany) or one placebo tablet twice a day for 12 weeks. As the primary outcome, we compared the performance of the 2 groups on the 4 tests at exit after adjusting for baseline performance. Results: Fifty-nine subjects received placebo and 61 received ginkgo; 1 participant receiving placebo and 3 receiving ginkgo were lost to follow-up. Two serious adverse events (AEs) (myocardial infarction and severe depression) believed to be unrelated to the treatment occurred in the ginkgo group; otherwise, there were no significant differences in AEs. The differences (ginkgo - placebo) at exit in the z scores for the cognitive tests were as follows: PASAT -0.2 (95% confidence interval [CI] -0.5 to 0.1); Stroop Test -0.5 (95% CI -0.9 to -0.1); COWAT 0.0 (95% CI -0.2 to 0.3); and CVLT-II 0.0 (95% CI -0.3 to 0.3); none was statistically significant. Conclusions: Treatment with ginkgo 120 mg twice a day did not improve cognitive performance in persons with MS. Classification of evidence: This study provides Class I evidence that treatment with ginkgo 120 mg twice a day for 12 weeks does not improve cognitive performance in people with MS. Neurology (R) 2012; 79: 1278-1284 C1 [Lovera, Jesus F.] Louisiana State Univ, Dept Neurol, Hlth Sci Ctr New Orleans, New Orleans, LA USA. [Kim, Edward; Heriza, Elizabeth; Fitzpatrick, Mary; Hunziker, James; Bourdette, Dennis] Portland VA Med Ctr, MS Ctr Excellence W & Neurol Serv, Portland, OR USA. [Hunziker, James; Turner, Aaron P.; Stover, Thomas; Sangeorzan, Adam; Sloan, Alicia; Haselkorn, Jodie] Puget Sound Hlth Care Syst, MS Ctr Excellence W, Seattle, WA USA. [Turner, Aaron P.; Haselkorn, Jodie] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Haselkorn, Jodie] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Kim, Edward; Howieson, Diane; Wild, Katherine; Bourdette, Dennis] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. RP Lovera, JF (reprint author), Louisiana State Univ, Dept Neurol, Hlth Sci Ctr New Orleans, New Orleans, LA USA. EM jlover@lsuhsc.edu OI sloan, alicia/0000-0003-4891-3266; Turner, Aaron/0000-0001-6897-8003 FU Department of Veterans Affair, Office of Research and Development, Rehabilitation Research and Development; NIH NCCAM [K23AT004433]; Rehabilitation Research and Development Service Career Development Award [B4927W]; VA RRD [I01 RX000223-01A1]; NSF BCS [0826654]; NIH/NIA [P30 AG008017]; VA Merit Review Grants [112705, 05-2706, B4368R, RDIS 01104]; VA Cooperative Studies [558]; Biogen Idec; Serono; Teva Neurosciences; Department of Veterans Affairs/BLRD Merit Review; Department of Veterans Affairs/RRD [B4368R]; National MS Society [CA 1055-A-3]; [NIH/NINDS 1P30 NS069346-01]; [NIH/NINDS 1R01 NS057433] FX Supported by the Department of Veterans Affair, Office of Research and Development, Rehabilitation Research and Development. The contents of this manuscript do not represent the views of the Department of Veterans Affairs or the US government.; J. Lovera is funded by NIH NCCAM K23AT004433 and has received compensation from EMD Serono and TEVA Pharmaceuticals for conducting educational activities for physicians. He is on the speakers' bureau for Biogen Idec and EMD Serono. E. Kim has received honoraria from Biogen Idec for conducting educational activities for physicians. E. Heriza, M. Fitzpatrick, and J. Hunziker report no disclosures. A. Turner is funded by a Rehabilitation Research and Development Service Career Development Award (B4927W) and by VA RR&D I01 RX000223-01A1. J. Adams, T. Stover, and A. Sangeorzan report no disclosures. A. Sloan received travel expenses from Paralyzed Veterans of America and Consortium of MS Centers for serving as faculty in conferences. D. Howieson is funded by NSF BCS 0826654 and NIH/NIA P30 AG008017 grants. K. Wild is funded by NIH/NIA grants P30 AG008017 and R01 AG024059. J. Haselkorn received compensation from Paralyzed Veterans of America for travel to their Education Planning Committee and to the MS Summit conference; she is funded by VA Merit Review Grants 112705, 05-2706, B4368R, and RDIS 01104 and VA Cooperative Studies 558. D. Bourdette has received honoraria and travel expenses for speaking and serving as faculty at company sponsored meetings from Biogen Idec, Serono, and Teva Neurosciences. He is funded by the following grants: NIH/NINDS 1P30 NS069346-01, NIH/NINDS 1R01 NS057433, Department of Veterans Affairs/BLR&D Merit Review, Department of Veterans Affairs/RR&D B4368R; and National MS Society, CA 1055-A-3. Go to Neurology.org for full disclosures. NR 28 TC 14 Z9 14 U1 1 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP PY 2012 VL 79 IS 12 BP 1278 EP 1284 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 009WK UT WOS:000309055900020 PM 22955125 ER PT J AU Mehta, BP Nogueira, RG AF Mehta, Brijesh P. Nogueira, Raul G. TI Should clot composition affect choice of endovascular therapy? SO NEUROLOGY LA English DT Article ID TISSUE-PLASMINOGEN-ACTIVATOR; ACUTE ISCHEMIC-STROKE; THROMBOLYSIS; THROMBI; TRIAL; ASSOCIATION; ARTERIES AB Endovascular therapy has become a promising alternative for patients who are ineligible for IV thrombolysis or for whom it has failed. Greater knowledge about the composition of thromboembolic material underlying the vascular occlusion in stroke patients may provide the means for improving existing endovascular therapies and developing new treatment strategies. The objective of this article is to provide a review of clinical and experimental animal studies on the histology, imaging correlation, and ultrastructure of thromboemboli retrieved during acute ischemic stroke. Neurology (R) 2012; 79 (Suppl 1): S63-S67 C1 [Nogueira, Raul G.] Emory Univ, Grady Hosp, Dept Neurol, Atlanta, GA 30322 USA. [Nogueira, Raul G.] Emory Univ, Grady Hosp, Dept Neurosurg, Atlanta, GA 30322 USA. [Nogueira, Raul G.] Emory Univ, Grady Hosp, Dept Radiol, Atlanta, GA 30322 USA. [Mehta, Brijesh P.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Nogueira, RG (reprint author), Emory Univ, Grady Hosp, Dept Neurol, Atlanta, GA 30322 USA. EM raul.g.nogueira@emory.edu NR 26 TC 9 Z9 9 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP PY 2012 VL 79 IS 13 SU 1 BP S63 EP S67 DI 10.1212/WNL.0b013e3182695859 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 012TA UT WOS:000309258300012 PM 23008415 ER PT J AU Nguyen, TN Zaidat, OO Edgell, RC Janjua, N Yavagal, DR Xavier, AR Kirmani, JF Liebeskind, DS Nogueira, RG Vora, NA Sims, JR Lynch, JR Fitzsimmons, BF Wolfe, TJ Chen, M Badruddin, A Zahuranec, DB McDonagh, DL Janardhan, V Bastan, B Madden, JA Sanossian, N Gupta, R Lazzaro, MA Jovin, TG Abou-Chebl, A Linfante, I Hussain, SI AF Nguyen, Thanh N. Zaidat, Osama O. Edgell, Randall C. Janjua, Nazli Yavagal, Dileep R. Xavier, Andrew R. Kirmani, Jawad F. Liebeskind, David S. Nogueira, Raul G. Vora, Nirav A. Sims, John R. Lynch, John R. Fitzsimmons, Brian-Fred Wolfe, Thomas J. Chen, Michael Badruddin, Aamir Zahuranec, Darin B. McDonagh, David L. Janardhan, Vallabh Bastan, Birgul Madden, Jane A. Sanossian, Nerses Gupta, Rishi Lazzaro, Marc A. Jovin, Tudor G. Abou-Chebl, Alex Linfante, Italo Hussain, Syed I. TI Vascular neurologists and neurointerventionalists on endovascular stroke care Polling results SO NEUROLOGY LA English DT Article C1 [Zaidat, Osama O.; Lynch, John R.; Fitzsimmons, Brian-Fred; Badruddin, Aamir; Madden, Jane A.; Lazzaro, Marc A.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Nguyen, Thanh N.] Boston Med Ctr, Boston, MA USA. [Edgell, Randall C.; Vora, Nirav A.] St Louis Univ, St Louis, MO 63103 USA. [Janjua, Nazli] Asia Pacific Comprehens Stroke Inst, Pahoa, HI USA. [Yavagal, Dileep R.] Univ Miami, Miami, FL USA. [Xavier, Andrew R.] Wayne State Univ, Detroit, MI USA. [Kirmani, Jawad F.] JFK Neurosci Ctr, Lake Worth, FL USA. [Liebeskind, David S.; Sanossian, Nerses] Univ Calif Los Angeles, Los Angeles, CA USA. [Nogueira, Raul G.; Gupta, Rishi] Emory Univ, Atlanta, GA 30322 USA. [Sims, John R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chen, Michael] Rush Univ, Chicago, IL 60612 USA. [Zahuranec, Darin B.] Univ Michigan, Ann Arbor, MI 48109 USA. [McDonagh, David L.] Duke Univ, Durham, NC USA. [Janardhan, Vallabh] Texas Stroke Inst, Plano, TX USA. [Bastan, Birgul] Univ Massachusetts, Boston, MA 02125 USA. [Jovin, Tudor G.] Univ Pittsburgh, Pittsburgh, PA USA. [Abou-Chebl, Alex] Univ Louisville, Louisville, KY 40292 USA. [Linfante, Italo] Baptist Vasc Inst, Miami, FL USA. [Hussain, Syed I.] Michigan State Univ, E Lansing, MI 48824 USA. RP Zaidat, OO (reprint author), Med Coll Wisconsin, Milwaukee, WI 53226 USA. FU NINDS NIH HHS [K24 NS072272] NR 4 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD SEP PY 2012 VL 79 IS 13 SU 1 BP S5 EP S15 DI 10.1212/WNL.0b013e31826957b3 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA 012TA UT WOS:000309258300003 PM 23008412 ER PT J AU Sheth, KN Sims, JR AF Sheth, Kevin N. Sims, John R. TI Neurocritical care and periprocedural blood pressure management in acute stroke SO NEUROLOGY LA English DT Article ID ACUTE ISCHEMIC-STROKE; TISSUE-PLASMINOGEN ACTIVATOR; FOCAL CEREBRAL-ISCHEMIA; 1ST 24 HOURS; HEMORRHAGIC TRANSFORMATION; INDUCED HYPERTENSION; PROGNOSTIC VALUE; AUTO-REGULATION; ECASS-II; TRIAL AB The purpose of this article is to review the literature on periprocedural blood pressure (BP) management in acute ischemic stroke and to establish guidelines regarding management of BP. These guidelines are drawn from available evidence and expert opinion. This article reviews the pathophysiologic considerations of BP in ischemic stroke. It also examines the natural history of BP changes during stroke, as well as data on induced BP reduction and hypertension, particularly in light of reperfusion therapy. Finally, the article reviews major ongoing clinical trials for BP management in this setting. Recommendations made in this article may serve as a benchmark for future research in BP management in this patient population. Neurology (R) 2012;79 (Suppl 1):S199-S204 C1 [Sheth, Kevin N.] Univ Maryland, Sch Med, Dept Neurol,R Adams Cowley Shock Trauma Ctr, Program Shock Trauma & Anesthesiol Res STAR, Baltimore, MD 21201 USA. [Sims, John R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Sheth, KN (reprint author), Univ Maryland, Sch Med, Dept Neurol,R Adams Cowley Shock Trauma Ctr, Program Shock Trauma & Anesthesiol Res STAR, Baltimore, MD 21201 USA. EM kshethmd@gmail.com FU American Academy of Neurology Clinical Research Award; NIH [K08 NS049241]; NIH; American Academy of Neurology; American Heart Association; Remedy Pharmaceuticals; Brainscope, Inc.; US Army FX This work was supported by an American Academy of Neurology Clinical Research Award to Dr. Sheth and by an NIH grant, K08 NS049241, to Dr. Sims. Dr. Sims has received research support from the NIH.; Dr. Sheth receives research support from the American Academy of Neurology, American Heart Association, Remedy Pharmaceuticals, Brainscope, Inc., and the US Army; served as a paid consultant to Verimed; received compensation for a lecture to the Research Foundation and Kansas City Stroke Symposium; receives royalties from publishing Blueprints Clinical Cases in Neurology; and serves on the editorial board or as section editor for Neurology Today, Frontiers in Hospitalist Neurology, and the Neuro-Critical Care Section for Current Treatment Options in Neurology. Go to Neurology.org for full disclosures. NR 52 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP PY 2012 VL 79 IS 13 SU 1 BP S199 EP S204 DI 10.1212/WNL.0b013e31826958f4 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 012TA UT WOS:000309258300033 PM 23008398 ER PT J AU Cade, L Reyon, D Hwang, WY Tsai, SQ Patel, S Khayter, C Joung, JK Sander, JD Peterson, RT Yeh, JRJ AF Cade, Lindsay Reyon, Deepak Hwang, Woong Y. Tsai, Shengdar Q. Patel, Samir Khayter, Cyd Joung, J. Keith Sander, Jeffry D. Peterson, Randall T. Yeh, Jing-Ruey Joanna TI Highly efficient generation of heritable zebrafish gene mutations using homo- and heterodimeric TALENs SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ZINC-FINGER NUCLEASES; DOUBLE-STRAND BREAKS; EMBRYO MICROINJECTION; TARGETED MUTAGENESIS; EFFECTOR NUCLEASES; KNOCKOUT RATS; TRANSCRIPTION; CELLS; DROSOPHILA; CONSTRUCTION AB Transcription activator-like effector nucleases (TALENs) are powerful new research tools that enable targeted gene disruption in a wide variety of model organisms. Recent work has shown that TALENs can induce mutations in endogenous zebrafish genes, but to date only four genes have been altered, and larger-scale tests of the success rate, mutation efficiencies and germline transmission rates have not been described. Here, we constructed homodimeric TALENs to 10 different targets in various endogenous zebrafish genes and found that 7 nuclease pairs induced targeted indel mutations with high efficiencies ranging from 2 to 76%. We also tested obligate heterodimeric TALENs and found that these nucleases induce mutations with comparable or higher frequencies and have better toxicity profiles than their homodimeric counterparts. Importantly, mutations induced by both homodimeric and heterodimeric TALENs are passed efficiently through the germline, in some cases reaching 100% transmission. For one target gene sequence, we observed substantially reduced mutagenesis efficiency for a variant site bearing two mismatched nucleotides, raising the possibility that TALENs might be used to perform allele-specific gene disruption. Our results suggest that construction of one to two heterodimeric TALEN pairs for any given gene will, in most cases, enable researchers to rapidly generate knockout zebrafish. C1 [Cade, Lindsay; Hwang, Woong Y.; Patel, Samir; Peterson, Randall T.; Yeh, Jing-Ruey Joanna] Harvard Univ, Sch Med, Dept Med, Cardiovasc Res Ctr,Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Reyon, Deepak; Tsai, Shengdar Q.; Khayter, Cyd; Joung, J. Keith; Sander, Jeffry D.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Charlestown, MA 02129 USA. [Reyon, Deepak; Tsai, Shengdar Q.; Khayter, Cyd; Joung, J. Keith; Sander, Jeffry D.] Massachusetts Gen Hosp, Ctr Canc Res, Mol Pathol Unit, Charlestown, MA 02129 USA. [Reyon, Deepak; Tsai, Shengdar Q.; Joung, J. Keith; Sander, Jeffry D.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Peterson, Randall T.] Broad Inst, Cambridge, MA 02142 USA. RP Yeh, JRJ (reprint author), Harvard Univ, Sch Med, Dept Med, Cardiovasc Res Ctr,Massachusetts Gen Hosp, Charlestown, MA 02129 USA. EM jsander@partners.org; peterson@cvrc.mgh.harvard.edu; jyeh1@partners.org RI Tsai, Shengdar/G-4600-2012 FU National Institutes of Health (NIH) [R01 GM088040, DP1 OD006862, T32 CA009216, K01 AG031300]; Jim and Ann Orr MGH Research Scholar award; Charles and Ann Sanders MGH Research Scholar award; National Science Foundation [DBI-0923827] FX National Institutes of Health (NIH) [R01 GM088040 to J.K.J. and R. T. P.]; NIH Director's Pioneer Award [DP1 OD006862 to J.K.J., T32 CA009216 to J.D.S. and K01 AG031300 to J.-R.J.Y.]; Jim and Ann Orr MGH Research Scholar award (to J.K.J.); Charles and Ann Sanders MGH Research Scholar award (to R. T. P.); National Science Foundation [DBI-0923827 to D. R.]. Funding for open access charge: NIH. NR 42 TC 139 Z9 149 U1 1 U2 56 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 SEP PY 2012 VL 40 IS 16 BP 8001 EP 8010 DI 10.1093/nar/gks518 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 008LZ UT WOS:000308959800042 PM 22684503 ER PT J AU Kofonow, JM Adappa, ND AF Kofonow, Jennifer M. Adappa, Nithin D. TI In vitro Antimicrobial Activity of SinuSurf (TM) SO ORL-JOURNAL FOR OTO-RHINO-LARYNGOLOGY HEAD AND NECK SURGERY LA English DT Article DE Sinusitis; Biofilm; Mupirocin; Gentamicin; Irrigations; Surfactants; Staphylococcus; Pseudomonas ID ENDOSCOPIC SINUS SURGERY; IRRIGATION BOTTLE CONTAMINATION; CHRONIC RHINOSINUSITIS; STAPHYLOCOCCUS-AUREUS; BACTERIAL BIOFILMS; CLINICAL-OUTCOMES; SHEEP MODEL; BIOTECHNOLOGY; MICROBIOLOGY; SURFACTANTS AB Background: Topical surfactant therapy has been found to be effective in the management of recalcitrant chronic rhinosinusitis. Objective: To determine in vitro the antibacterial potential of SinuSurf (TM), a previously commercially available sinonasal surfactant. Methods: Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PA) cultures were grown in the presence or absence of serial dilutions of mupirocin or gentamicin with and without SinuSurf and quantified by colony-forming units (CFUs). Biofilm formation was also assessed. Finally, bacterial growth was evaluated in sinus irrigation bottles inoculated with MRSA or PA and rinsed daily with SinuSurf. Results: SinuSurf alone evinced a 3-log (1,000-fold) and 6-log (10(6)-fold) reduction in CFUs for MRSA and PA, respectively. The combination of SinuSurf with a 1:10 dilution mupirocin and 1:100 dilution gentamicin demonstrated complete bacterial eradication. Similar concentrations of antibiotic dilutions alone demonstrated bacterial growth. SinuSurf averaged an 83% MRSA and 76% PA reduction in biofilm formation. Bottle contamination evaluation demonstrated reduction of MRSA and PA (p < 0.05) with SinuSurf. Conclusion: Biofilms have been demonstrated in chronic rhinosinusitis patients and implicated in recalcitrant disease. Our in vitro data demonstrates the addition of SinuSurf improved the effectiveness of a lower concentration of topical antibiotics in biofilm mass and viability. Copyright (C) 2012 S. Karger AG, Basel C1 [Kofonow, Jennifer M.; Adappa, Nithin D.] Univ Penn, Dept Otorhinolaryngol, Div Rhinol, Philadelphia, PA 19104 USA. [Kofonow, Jennifer M.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Adappa, ND (reprint author), Hosp Univ Penn, Ravdin Bldg,5th Floor,3400 Spruce St, Philadelphia, PA 19104 USA. EM Nithin.Adappa@uphs.upenn.edu NR 23 TC 7 Z9 7 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-1569 J9 ORL J OTO-RHINO-LARY JI ORL-J. Oto-Rhino-Laryngol. Head Neck Surg. PD SEP PY 2012 VL 74 IS 4 BP 179 EP 184 DI 10.1159/000339585 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA 011DI UT WOS:000309143800001 PM 22814356 ER PT J AU Kuhn, MA Friedmann, DR Winata, LS Eubig, J Pramanik, BK Kveton, J Kohan, D Merchant, SN Lalwani, AK AF Kuhn, Maggie A. Friedmann, David R. Winata, Leon S. Eubig, Jan Pramanik, Bidyut K. Kveton, John Kohan, Darius Merchant, Saumil N. Lalwani, Anil K. TI Large Jugular Bulb Abnormalities Involving the Middle Ear SO OTOLOGY & NEUROTOLOGY LA English DT Article DE High-riding jugular bulb; Jugular bulb; Jugular bulb diverticulum ID TEMPORAL BONE; DIVERTICULUM AB Objective: Jugular bulb abnormalities (JBA), such as jugular bulb diverticula (JBD) or large jugular bulbs, rarely present in the middle ear. We review a large series of temporal bone histopathologic specimens to determine their prevalence and present a series of cases of JB abnormalities involving the middle ear (JBME) that shed light on the probable mechanism for their development. Patients: 1,579 unique temporal bone specimens and individuals with radiographically-diagnosed JBME. Intervention: Histopathologic and clinical review of temporal bone specimens and patient presentations, radiographic findings, treatments and outcomes. Main Outcome Measure: Shared characteristics of JBME. Results: There were 17 cases of JBME in 1,579 temporal bone (1.1%), of which, 15 involved the inferior mesotympanum below the level of the round window membrane (RWM), whereas 2 encroached upon the RWM or ossicles. In addition, 4 clinical cases of large JBME extending above RWM were encountered; these occurred in both sexes with ages spanning from young to old (7-66 yr). They presented with conductive hearing loss (n = 3), ear canal mass (n = 1), and intraoperative bleeding (n = 1). Radiologically, they had multiple diverticula of the JB on the side with JBME, with 1 patient demonstrating growth on serial imaging studies. All patients who underwent additional imaging had marked hypoplastic contralateral transverse sinus. Conclusion: JBME abnormalities are rare, present across age groups, and may demonstrate serial growth over time. They are usually associated with multiple other diverticula within the same JB. Our clinical series suggests that JBME's development and uniquely aggressive behavior results from contralateral transverse sinus outflow obstruction. C1 [Lalwani, Anil K.] Columbia Univ Coll Phys & Surg, Dept Otolaryngol, Div Otol & Neurotol, New York, NY 10032 USA. [Kuhn, Maggie A.; Friedmann, David R.; Kohan, Darius] NYU, Sch Med, Dept Otolaryngol, New York, NY USA. [Winata, Leon S.; Merchant, Saumil N.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, Boston, MA USA. [Eubig, Jan; Pramanik, Bidyut K.] NYU, Sch Med, Dept Radiol, New York, NY USA. [Kveton, John] Yale Univ, Sch Med, Dept Surg, New Haven, CT 06510 USA. RP Lalwani, AK (reprint author), Columbia Univ Coll Phys & Surg, Dept Otolaryngol, Div Otol & Neurotol, 180 Ft Washington Ave,Harkness Pavil,8th Floor, New York, NY 10032 USA. EM akl2144@columbia.edu NR 20 TC 5 Z9 5 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1531-7129 EI 1537-4505 J9 OTOL NEUROTOL JI Otol. Neurotol. PD SEP PY 2012 VL 33 IS 7 BP 1201 EP 1206 DI 10.1097/MAO.0b013e31825d97fa PG 6 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 996MH UT WOS:000308092200022 PM 22772004 ER PT J AU Rowe, S Tearney, GJ AF Rowe, Steven Tearney, Guillermo J. TI FUNCTIONAL ANATOMIC IMAGING USING ONE MICRON RESOLUTION OPTICAL COHERENCE TOMOGRAPHY SO PEDIATRIC PULMONOLOGY LA English DT Meeting Abstract ID CYSTIC-FIBROSIS; TRANSPORT; SECRETION C1 [Rowe, Steven] Univ Alabama Birmingham, Birmingham, AL USA. [Tearney, Guillermo J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. NR 7 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 8755-6863 J9 PEDIATR PULM JI Pediatr. Pulmonol. PD SEP PY 2012 VL 47 SU 35 SI SI BP 189 EP 190 PG 2 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA 007IM UT WOS:000308882000064 ER PT J AU Liu, L Wilsterman, E Shastry, S Houser, G Smith, A Boylan, N Hanes, J Tearney, G Rowe, SM AF Liu, L. Wilsterman, E. Shastry, S. Houser, G. Smith, A. Boylan, N. Hanes, J. Tearney, G. Rowe, S. M. TI MEASURING MUCUS VISCOSITY USING MICRO-OPTICAL COHERENCE TOMOGRAPHY DEVELOPED MICRORHEOLOGY TECHNIQUES SO PEDIATRIC PULMONOLOGY LA English DT Meeting Abstract C1 [Liu, L.; Wilsterman, E.; Tearney, G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Boylan, N.; Hanes, J.] Johns Hopkins Univ, Baltimore, MD USA. [Shastry, S.; Houser, G.; Smith, A.; Rowe, S. M.] Univ Alabama Birmingham, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 8755-6863 J9 PEDIATR PULM JI Pediatr. Pulmonol. PD SEP PY 2012 VL 47 SU 35 SI SI BP 313 EP 314 PG 2 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA 007IM UT WOS:000308882000342 ER PT J AU Madan, J Koestler, D O'Toole, GA Stanton, B Davidson, L Moore, JH Sogin, M Karagas, MR Hampton, T Palumbo, P Morrison, H Guill, M Hibberd, PL AF Madan, J. Koestler, D. O'Toole, G. A. Stanton, B. Davidson, L. Moore, J. H. Sogin, M. Karagas, M. R. Hampton, T. Palumbo, P. Morrison, H. Guill, M. Hibberd, P. L. TI SERIAL ANALYSIS OF THE INTERACTION BETWEEN GUT AND LUNG MICROBIOME IN CF IN INFANCY SO PEDIATRIC PULMONOLOGY LA English DT Meeting Abstract C1 [Madan, J.; Guill, M.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Koestler, D.; O'Toole, G. A.; Stanton, B.; Moore, J. H.; Karagas, M. R.] Geisel Sch Med Dartmouth, Hanover, NH USA. [Davidson, L.] Tufts Univ, Sch Med, Ctr Global Hlth Res, Boston, MA 02111 USA. [Sogin, M.; Morrison, H.] Marine Biol Lab, Woods Hole, MA 02543 USA. [Palumbo, P.] Dartmouth Hitchcock Med Ctr, Hanover, NH USA. [Hibberd, P. L.] Massachusetts Gen Hosp, Global Hlth, Boston, MA 02114 USA. RI Koestler, Devin /D-7902-2015 OI Koestler, Devin /0000-0002-0598-0146 NR 0 TC 0 Z9 0 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 8755-6863 J9 PEDIATR PULM JI Pediatr. Pulmonol. PD SEP PY 2012 VL 47 SU 35 SI SI BP 322 EP 323 PG 2 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA 007IM UT WOS:000308882000365 ER PT J AU Filkins, LM Hampton, T Gifford, AH Gross, M Hogan, D Sogin, M Morrison, H Paster, B O'Toole, G AF Filkins, L. M. Hampton, T. Gifford, A. H. Gross, M. Hogan, D. Sogin, M. Morrison, H. Paster, B. O'Toole, G. TI POLYMICROBIAL DIVERSITY IN CYSTIC FIBROSIS PATIENT SPUTUM SAMPLES SO PEDIATRIC PULMONOLOGY LA English DT Meeting Abstract C1 [Filkins, L. M.; Hampton, T.; Gifford, A. H.; Gross, M.; Hogan, D.; O'Toole, G.] Dartmouth Coll, Hanover, NH 03755 USA. [Paster, B.] Forsyth Inst, Dept Mol Genet, Cambridge, MA USA. [Sogin, M.; Morrison, H.] Marine Biol Lab, Josephine Bay Paul Ctr Comparat Mol Biol & Evolut, Woods Hole, MA 02543 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 8755-6863 J9 PEDIATR PULM JI Pediatr. Pulmonol. PD SEP PY 2012 VL 47 SU 35 SI SI BP 326 EP 326 PG 1 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA 007IM UT WOS:000308882000374 ER PT J AU Stalvey, MS Clines, KL Chung, WJ Clines, GA AF Stalvey, M. S. Clines, K. L. Chung, W. J. Clines, G. A. TI CYSTIC FIBROSIS BONE DISEASE: INTERACTIONS BETWEEN OSTEOBLASTS AND OSTEOCLASTS MAY BE THE KEY TO INCREASED BONE LOSS SO PEDIATRIC PULMONOLOGY LA English DT Meeting Abstract C1 [Stalvey, M. S.; Clines, K. L.; Chung, W. J.] Univ Alabama Birmingham, Birmingham, AL USA. [Clines, G. A.] Birmingham VA Med Ctr, Birmingham, AL 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 8755-6863 J9 PEDIATR PULM JI Pediatr. Pulmonol. PD SEP PY 2012 VL 47 SU 35 SI SI BP 422 EP 422 PG 1 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA 007IM UT WOS:000308882000626 ER PT J AU Verhoef, TI Redekop, WK van Schie, RMF Bayat, S Daly, AK Geitona, M Haschke-Becher, E Hughes, DA Kamali, F Levin, LA Manolopoulos, VG Pirmohamed, M Siebert, U Stingl, JC Wadelius, M de Boer, A Maitland-van der Zee, AH AF Verhoef, Talitha I. Redekop, William K. van Schie, Rianne M. F. Bayat, Samira Daly, Ann K. Geitona, Mary Haschke-Becher, Elisabeth Hughes, Dyfrig A. Kamali, Farhad Levin, Lars-Ake Manolopoulos, Vangelis G. Pirmohamed, Munir Siebert, Uwe Stingl, Julia C. Wadelius, Mia de Boer, Anthonius Maitland-van der Zee, Anke-Hilse CA EU-PACT Grp TI Cost-effectiveness of pharmacogenetics in anticoagulation: international differences in healthcare systems and costs SO PHARMACOGENOMICS LA English DT Review DE acenocoumarol; atrial fibrillation; cost analysis; coumarins; health; economics; healthcare system; phenprocoumon; warfarin ID NONVALVULAR ATRIAL-FIBRILLATION; DEEP VENOUS THROMBOSIS; ORAL ANTICOAGULATION; SELF-MANAGEMENT; WARFARIN THERAPY; BLEEDING COMPLICATIONS; INTRACEREBRAL HEMORRHAGE; DABIGATRAN ETEXILATE; COUMARIN DERIVATIVES; ECONOMIC OUTCOMES AB Genotyping patients for CYP2C9 and VKORC1 polymorphisms can improve the accuracy of dosing during the initiation of anticoagulation with vitamin K antagonists (coumarin derivatives). The anticipated degree of improvement in the safety of anticoagulation with coumarins through genotyping may vary depending on the quality of patient care, which varies both with and among countries. The management and the cost of anticoagulant care can therefore influence the cost effectiveness of genotyping within any given country. In this article, we provide an overview of the cost effectiveness of pharmacogenetics-guided dosing of coumarin derivatives. We describe the organization of anticoagulant care in the UK, Sweden, The Netherlands, Greece, Germany and Austria, where a genotype-guided dosing algorithm is currently being investigated as part of the EU-PACT trial. We also explore the costs of anticoagulant care for the treatment of atrial fibrillation in these countries. C1 [Verhoef, Talitha I.; van Schie, Rianne M. F.; Bayat, Samira; de Boer, Anthonius; Maitland-van der Zee, Anke-Hilse] Univ Utrecht, Dept Pharmaceut Sci, Div Pharmacoepidemiol & Clin Pharmacol, NL-3508 TB Utrecht, Netherlands. [Redekop, William K.] Erasmus Univ, Inst Med Technol Assessment, Rotterdam, Netherlands. [Daly, Ann K.] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Geitona, Mary] Univ Peloponnese, Sch Social Policy, Corinth, Greece. [Haschke-Becher, Elisabeth] Elisabethinen Hosp Linz, Inst Med & Chem Lab Diagnost, Ctr Mol Diagnost & Genet, Linz, Austria. [Hughes, Dyfrig A.] Bangor Univ, Ctr Hlth Econ & Med Evaluat, Bangor, Gwynedd, Wales. [Kamali, Farhad] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Levin, Lars-Ake] Linkoping Univ, Ctr Med Technol Assessment, Linkoping, Sweden. [Manolopoulos, Vangelis G.] Democritus Univ Thrace, Alexandroupolis, Greece. [Pirmohamed, Munir] Univ Liverpool, Liverpool L69 3BX, Merseyside, England. [Siebert, Uwe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA USA. [Siebert, Uwe] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Siebert, Uwe] ONCOTYROL Ctr Personalized Canc Med, Innsbruck, Austria. [Siebert, Uwe] UMIT Univ Hlth Sci Med Informat & Technol, Dept Publ Hlth, Hall In Tirol, Austria. [Siebert, Uwe] UMIT Univ Hlth Sci Med Informat & Technol, HTA, Hall In Tirol, Austria. [Stingl, Julia C.] Univ Ulm, Ulm, Germany. [Wadelius, Mia] Uppsala Univ, Dept Med Sci, Uppsala, Sweden. RP Maitland-van der Zee, AH (reprint author), Univ Utrecht, Dept Pharmaceut Sci, Div Pharmacoepidemiol & Clin Pharmacol, POB 80 082, NL-3508 TB Utrecht, Netherlands. EM a.h.maitland@uu.nl RI Daly, Ann/H-3144-2011; Hughes, Dyfrig/H-5252-2012; Stingl, Julia/H-2410-2013; Pirmohamed, Munir/H-6004-2011; Wadelius, Mia/C-7740-2016 OI Daly, Ann/0000-0002-7321-0629; Hughes, Dyfrig/0000-0001-8247-7459; Stingl, Julia/0000-0002-1566-8156; Pirmohamed, Munir/0000-0002-7534-7266; Wadelius, Mia/0000-0002-6368-2622 FU EU [HEALTH-F2-2009-223062]; Netherlands Organisation for Health Research and Development (ZonMW); Dutch Health Care Insurance Board (CVZ); Royal Dutch Pharmacists Association (KNMP); private public funded Top Institute Pharma; EU Innovative Medicines Initiative (IMI); FP7; Dutch Medicines Evaluation Board; Dutch Ministry of Health and industry FX This project is funded by the EU's Seventh Framework Programme (FP7) under grant agreement number HEALTH-F2-2009-223062. The division of Pharmacoepidemiology & Clinical Pharmacology employing authors TI Verhoef, AH Maitland-van der Zee, RMF van Schie, S Bayat and A de Boer, has received unrestricted research funding from the Netherlands Organisation for Health Research and Development (ZonMW), the Dutch Health Care Insurance Board (CVZ), the Royal Dutch Pharmacists Association (KNMP), the private public funded Top Institute Pharma (www.tipharma.nl, includes co-funding from universities, government and industry), the EU Innovative Medicines Initiative (IMI), FP7, the Dutch Medicines Evaluation Board, the Dutch Ministry of Health and industry (including GlaxoSmithKline, Pfizer and others). 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 98 TC 11 Z9 11 U1 0 U2 14 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1462-2416 EI 1744-8042 J9 PHARMACOGENOMICS JI Pharmacogenomics PD SEP PY 2012 VL 13 IS 12 BP 1405 EP 1417 DI 10.2217/PGS.12.124 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 005UR UT WOS:000308776100016 PM 22966889 ER PT J AU Katiyar, SK Singh, T Prasad, R Sun, Q Vaid, M AF Katiyar, Santosh K. Singh, Tripti Prasad, Ram Sun, Qian Vaid, Mudit TI Epigenetic Alterations in Ultraviolet Radiation-Induced Skin Carcinogenesis: Interaction of Bioactive Dietary Components on Epigenetic Targets SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Review ID TUMOR-SUPPRESSOR GENES; GREEN TEA POLYPHENOLS; PROSTATE-CANCER CELLS; CPG BINDING-PROTEIN; SKH-1 HAIRLESS MICE; DNA METHYLATION; HISTONE ACETYLATION; ANTICANCER AGENTS; HYDROPHILIC CREAM; HUMAN-DISEASE AB The importance of epigenetic alterations in the development of various diseases including the cancers has been realized. As epigenetic changes are reversible heritable changes, these can be utilized as an effective strategy for the prevention of cancers. DNA methylation is the most characterized epigenetic mechanism that can be inherited without changing the DNA sequence. Although limited available data suggest that silencing of tumor suppressor genes in ultraviolet (UV) radiation-exposed epidermis leads to photocarcinogenesis and is associated with a network of epigenetic modifications including alterations in DNA methylation, DNA methyltransferases and histone acetylations. Various bioactive dietary components have been shown to protect skin from UV radiation-induced skin tumors in animal models. The role of bioactive dietary components, such as, (-)-epicatechins from green tea and proanthocyanidins from grape seeds has been assessed in chemoprevention of UV-induced skin carcinogenesis and underlying epigenetic mechanism in vitro and in vivo animal models. These bioactive components have the ability to block UV-induced DNA hypermethylation and histone modifications in the skin required for the silencing of tumor suppressor genes (e.g. Cip1/p21, p16INK4a). This information is of importance for understanding the role of epigenetic modulation in UV-induced skin tumor and the chemopreventive mechanism of bioactive dietary components. C1 [Katiyar, Santosh K.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Katiyar, Santosh K.; Singh, Tripti; Prasad, Ram; Sun, Qian; Vaid, Mudit] Univ Alabama Birmingham, Dept Dermatol, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Univ Alabama Birmingham, Obes Res Ctr, Dept Nutr, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Univ Alabama Birmingham, Dept Comprehens Canc Ctr, Birmingham, AL 35294 USA. RP Katiyar, SK (reprint author), Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. EM skatiyar@uab.edu FU National Cancer Institute/NCCAM/NIH [CA140197, AT2536, CA140832]; Veterans Affairs Merit Review Award FX The work reported from Dr. Katiyar's laboratory was supported by funds from National Cancer Institute/NCCAM/NIH (CA140197, AT2536, CA140832,) and Veterans Affairs Merit Review Award (S. K. K.). The content of this article does not necessarily reflect the views or policies of the funding sources. NR 69 TC 21 Z9 21 U1 0 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD SEP-OCT PY 2012 VL 88 IS 5 BP 1066 EP 1074 DI 10.1111/j.1751-1097.2011.01020.x PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 000OM UT WOS:000308396000004 PM 22017262 ER PT J AU Dittrich, R Kurth, J Decelle, EA Defeo, EM Taupitz, M Wu, S Wu, CI McDougal, WS Cheng, LL AF Dittrich, R. Kurth, J. Decelle, E. A. DeFeo, E. M. Taupitz, M. Wu, S. Wu, C-I McDougal, W. S. Cheng, L. L. TI Assessing prostate cancer growth with citrate measured by intact tissue proton magnetic resonance spectroscopy SO PROSTATE CANCER AND PROSTATIC DISEASES LA English DT Article DE citrate; PSA velocity; PSA density; percent-free PSA; magnetic resonance spectroscopy; high-resolution magic angle spinning ID EPITHELIAL-CELLS; IN-VITRO; ZINC; ANTIGEN; BIOMARKERS; DIAGNOSIS; HZIP1; INTERVENTION; RECURRENCE; PROGNOSIS AB BACKGROUND: Annual PSA tests have led to a significant increase in the number of prostate cancer (PCa) cases diagnosed. This increased incidence has led to overtreatment of many patients, as current pathology often cannot distinguish latent from aggressive PCa. Studies have shown that the depletion of zinc in prostate cells correlated with cell-line growth rates, and may therefore relate to the progression of PCa. Furthermore, as zinc is normally an inhibitor of citrate oxidation, the reduction of zinc in PCa may cause a decrease in citrate secretion levels in the glandular epithelia of PCa patients. METHODS: Using high-resolution magic angle spinning proton magnetic resonance spectroscopy followed by quantitative histopathology, we investigate unit histo-benign prostate epithelial citrate concentrations in intact tissue samples obtained from 18 patients with pre-surgical PSA values less than 20 ng/ml. Using these data, we evaluate correlations between citrate concentrations and PSA velocities, densities and blood percent-free PSA. RESULTS: We observe different linear patterns between citrate concentrations and histo-benign glandular epithelia from patients of different PSA velocities. More importantly, we obtain a significant correlation between PSA velocity, density and percent-free PSA, and citrate concentrations in unit volume of histo-benign epithelial glands of the peripheral zone. CONCLUSIONS: Low levels of citrate in unit volume represent rapidly increasing PSA values, and, therefore, may be used as an indicator of fast-growing PCa. Thus, tissue samples obtained at the time of biopsy may be evaluated for their citrate concentrations for the prediction of PCa growth rates, allowing for the implementation of alternative treatment options and reducing overtreatment. C1 [Dittrich, R.; Kurth, J.; Decelle, E. A.; DeFeo, E. M.; Wu, S.; Wu, C-I; McDougal, W. S.; Cheng, L. L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. [Dittrich, R.; Kurth, J.; Decelle, E. A.; DeFeo, E. M.; Wu, S.; Wu, C-I; McDougal, W. S.; Cheng, L. L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Charlestown, MA 02129 USA. [Dittrich, R.; Kurth, J.; Decelle, E. A.; DeFeo, E. M.; Wu, S.; Wu, C-I; McDougal, W. S.; Cheng, L. L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Urol, Charlestown, MA 02129 USA. [Dittrich, R.; Kurth, J.; Taupitz, M.] Charite, D-13353 Berlin, Germany. RP Cheng, LL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, 149 13th St,CNY 6, Charlestown, MA 02129 USA. EM cheng@nmr.mgh.harvard.edu FU PHS/NIH [CA115746, CA115746S2, CA162959, CA141139]; MGH A.A. Martinos Center for Biomedical Imaging FX This work was supported by PHS/NIH grants CA115746, CA115746S2, CA162959, and CA141139 (LLC), and MGH A.A. Martinos Center for Biomedical Imaging. NR 36 TC 5 Z9 5 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1365-7852 J9 PROSTATE CANCER P D JI Prostate Cancer Prostatic Dis. PD SEP PY 2012 VL 15 IS 3 BP 278 EP 282 DI 10.1038/pcan.2011.70 PG 5 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 992SF UT WOS:000307799300011 PM 22289782 ER PT J AU Egerdie, RB Saad, F Smith, MR Tammela, TLJ Heracek, J Sieber, P Ke, C Leder, B Dansey, R Goessl, C AF Egerdie, R. B. Saad, F. Smith, M. R. Tammela, T. L. J. Heracek, J. Sieber, P. Ke, C. Leder, B. Dansey, R. Goessl, C. TI Responder analysis of the effects of denosumab on bone mineral density in men receiving androgen deprivation therapy for prostate cancer SO PROSTATE CANCER AND PROSTATIC DISEASES LA English DT Article DE androgen deprivation; bone mineral density; bone loss; antiresorptive therapy; responder analysis ID WOMEN; RISK; FRACTURES; CARCINOMA; PREVENT AB BACKGROUND: Denosumab, a fully human monoclonal antibody against RANK ligand, increased bone mineral density (BMD) and reduced fracture risk vs placebo in a phase 3 trial in men with prostate cancer on androgen deprivation therapy (ADT). The present analysis of this study evaluated BMD changes after 36 months in responder subgroups and in individual patients for three key skeletal sites (lumbar spine (LS), femoral neck (FN) and total hip (TH)) and the distal radius. METHODS: Men with nonmetastatic prostate cancer receiving ADT were treated with subcutaneous denosumab 60 mg (n=734) or placebo (n=734) every 6 months for up to 36 months in a phase 3, randomized, double-blind study. Patients were instructed to take supplemental calcium and vitamin D. For this BMD responder analysis, the primary outcome measure was the percentage change in BMD from baseline to month 36 at the LS, FN and TH as measured by dual-energy X-ray absorptiometry. BMD at the distal 1/3 radius at 36 months was measured in a substudy of 309 patients. RESULTS: At 36 months, significantly more patients in the denosumab arm had increases of >3% BMD from baseline at each site studied compared with placebo (LS, 78 vs 17%; FN, 48 vs 13%; TH, 48 vs 6%; distal 1/3 radius, 40 vs 7% (P<0.0001 for all)). BMD loss at the LS, FN and TH occurred in 1% of denosumab-treated patients vs 42% of placebo patients, and BMD gain at all three sites occurred in 69% of denosumab patients vs 8% of placebo patients. Lower baseline BMD was associated with higher-magnitude BMD responses to denosumab at the LS, FN and TH. CONCLUSIONS: In men with prostate cancer receiving ADT, significantly higher BMD response rates were observed with denosumab vs placebo. Patients with lower baseline T-scores benefited the most from denosumab treatment. C1 [Egerdie, R. B.] Urol Associates Urol Med Res, Kitchener, ON N2N 2B9, Canada. [Saad, F.] Ctr Hosp Univ Montreal, Dept Chirurg, Montreal, PQ, Canada. [Smith, M. R.] Massachusetts Gen Hosp, Ctr Canc, Dept Hematol Oncol, Boston, MA USA. [Smith, M. R.] Massachusetts Gen Hosp, Dept Med, Ctr Canc, Boston, MA 02114 USA. [Tammela, T. L. J.] Tampere Univ Hosp, Dept Urol, Tampere, Finland. [Heracek, J.] Androgeos, Prague, Czech Republic. [Sieber, P.] Urol Associates Lancaster, Lancaster, PA USA. [Ke, C.; Dansey, R.; Goessl, C.] Amgen Inc, Thousand Oaks, CA USA. [Leder, B.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Egerdie, RB (reprint author), Urol Associates Urol Med Res, Unit 18,450 Westhts Dr, Kitchener, ON N2N 2B9, Canada. EM blairegerdie@mac.com FU Amgen, Thousand Oaks, CA, USA; Amgen; Bayer; Pfizer; Sanofi-Aventis; Novartis; GTx; Orion Pharma; AstraZeneca; New England Research Institutes FX The research was funded by Amgen, Thousand Oaks, CA, USA. Dr RB Egerdie has received consulting fees and honoraria from Amgen, Bayer and Pfizer. Dr F Saad has received grant support from Sanofi-Aventis, Novartis and Amgen, and consulting fees and honoraria from Sanofi-Aventis, Novartis and Amgen. Dr MR Smith has received consulting fees from Amgen, GTx and Novartis, and honoraria from Amgen and GTx. Dr TLJ Tammela has received consulting fees from Orion Pharma and AstraZeneca, and honoraria from AstraZeneca and Astellas. Dr J Heracek has received consulting fees from Amgen. Dr P Sieber has received consulting fees from Amgen and GTx. Drs C Ke, R Dansey and C Goessl are Amgen employees and own Amgen stock. Dr B Leder has received consulting fees from Amgen and New England Research Institutes, and honoraria from Merck and Novartis. NR 26 TC 3 Z9 4 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1365-7852 EI 1476-5608 J9 PROSTATE CANCER P D JI Prostate Cancer Prostatic Dis. PD SEP PY 2012 VL 15 IS 3 BP 308 EP 312 DI 10.1038/pcan.2012.18 PG 5 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 992SF UT WOS:000307799300016 PM 22641239 ER PT J AU Hansen, RA Maciejewski, M Yu-Isenberg, K Farley, JF AF Hansen, Richard A. Maciejewski, Matthew Yu-Isenberg, Kristina Farley, Joel F. TI Adherence to Antipsychotics and Cardiometabolic Medication: Association With Health Care Utilization and Costs SO PSYCHIATRIC SERVICES LA English DT Article ID ADMINISTRATIVE CLAIMS DATA; PSYCHOTIC DISORDERS; RISK-FACTORS; EXCESS MORTALITY; OLDER PATIENTS; UNITED-STATES; SCHIZOPHRENIA; NONADHERENCE; HOSPITALIZATION; HYPERTENSION AB Objective: This study examined the association between adherence to antipsychotic and cardiometabolic medication and annual use of health care services and expenditures. Methods: MarketScan Medicaid files from 2004 to 2008 were used to evaluate annual cross-sections of patients with schizophrenia and diabetes, hypertension, or hyperlipidemia. Annual adherence to antipsychotic and cardiometabolic medication was defined as a score of at least 80% on proportion of days covered. Logistic regression was used to examine the association between antipsychotic adherence and adherence to cardiometabolic medications. Count data models and generalized linear models estimated health care utilization and health care expenditures, respectively, for outpatient, emergency, inpatient, and overall health services. Results: A total of 87,015 unique patients with schizophrenia received at least one antipsychotic medication. The overall prevalence of any comorbid cardiometabolic condition was 42.9% in 2004 and increased to 52.5% in 2008. Adherence to cardiometabolic medications was significantly greater among patients who were adherent to antipsychotic medications (adjusted odds ratio=6.9). Adjusted annual expenditures for emergency and inpatient care were higher for patients who were nonadherent to either antipsychotics or cardiometabolic medications than for patients who were adherent to antipsychotic and cardiometabolic medications. They were highest for patients who were nonadherent to both groups of medications. Outpatient, medication, and overall expenditures were lower for patients who were nonadherent to antipsychotic medications, regardless of cardiometabolic medication adherence. Conclusions: Among Medicaid patients with schizophrenia, cardiometabolic conditions are common, and adherence to antipsychotics and adherence to cardiometabolic medications are strongly related. Interventions that can improve medication adherence to treatment of both schizophrenia and comorbid cardiometabolic conditions may reduce emergency visits and hospitalizations. (Psychiatric Services 63:920-928, 2012; doi: 10.1176/appi.ps.201100328) C1 [Hansen, Richard A.] Auburn Univ, Dept Pharm Care Syst, Auburn, AL 36849 USA. [Maciejewski, Matthew] Duke Univ, Div Gen Internal Med, Durham, NC 27706 USA. [Maciejewski, Matthew] US Dept Vet Affairs, Med Ctr, Durham, NC USA. [Yu-Isenberg, Kristina] Novartis Pharmaceut, E Hanover, NJ USA. [Farley, Joel F.] Univ N Carolina, UNC Eshelman Sch Pharm, Chapel Hill, NC USA. RP Hansen, RA (reprint author), Auburn Univ, Dept Pharm Care Syst, 207 Dunstan Hall, Auburn, AL 36849 USA. EM rah0019@auburn.edu OI Hansen, Richard/0000-0002-4578-6698 FU Novartis Pharmaceuticals Corporation; U.S. Department of Veterans Affairs [RCS 10-391]; Pfizer; Robert Wood Johnson Foundation FX This study was funded by Novartis Pharmaceuticals Corporation. Dr. Maciejewski is a recipient of Research Career Scientist award RCS 10-391 from the U.S. Department of Veterans Affairs. The authors acknowledge the helpful comments of Christopher Zacker, Ph.D., during the early stages of manuscript preparation.; Dr. Hansen, Dr. Maciejewski, and Dr. Farley have served as consultants to Takeda Pharmaceuticals, Inc., and Novartis. Dr. Maciejewski owns stock in Amgen. Dr. Farley has received unrestricted grant support from Pfizer and the Robert Wood Johnson Foundation. At the time of this research, Dr. Yu-Isenberg was with Novartis Pharmaceutical Corporation and is now with GlaxoSmithKline. NR 43 TC 9 Z9 9 U1 3 U2 10 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD SEP PY 2012 VL 63 IS 9 BP 920 EP 928 DI 10.1176/appi.ps.201100328 PG 9 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 006TK UT WOS:000308841700013 PM 22706887 ER PT J AU Naragon-Gainey, K Hoerster, KD Malte, CA Jakupcak, M AF Naragon-Gainey, Kristin Hoerster, Katherine D. Malte, Carol A. Jakupcak, Matthew TI Distress Symptoms and High-Risk Behaviors Prospectively Associated With Treatment Use Among Returning Veterans SO PSYCHIATRIC SERVICES LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; MENTAL-HEALTH DIAGNOSES; AFGHANISTAN VETERANS; PRIMARY-CARE; IRAQ; SERVICES AB Objective: Distress symptoms and high-risk behaviors among Iraq and Afghanistan veterans were examined as predictors of treatment utilization. Methods: Veterans (N=618) completed self-report measures upon treatment enrollment (2005-2008). Two-year utilization data were obtained for five settings: primary care, mental health within primary care, outpatient mental health, emergency room, and inpatient psychiatric. Results: Pain was associated with primary care use; depression, panic, post-traumatic stress disorder (PTSD), alcohol misuse, and aggression were associated with use of other settings. After adjustment for comorbidity, veterans with high levels of PTSD and depression symptoms had more treatment visits across several settings than veterans with lower levels. Specialty mental health utilization was low among those reporting elevated psychiatric symptoms (for example, a mean of 8.8 outpatient visits over two years). Conclusions: Symptoms and high-risk behaviors were differentially associated with treatment settings; PTSD and depression predicted greater treatment use. Veterans may have overutilized emergency care while underutilizing specialty mental health services. (Psychiatric Services 63:942-944, 2012; doi: 10.1176/appi.ps.201100349) C1 [Naragon-Gainey, Kristin; Hoerster, Katherine D.; Malte, Carol A.; Jakupcak, Matthew] US Dept Vet Affairs VA Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA 98108 USA. [Hoerster, Katherine D.; Jakupcak, Matthew] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Malte, Carol A.] VA Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA USA. RP Naragon-Gainey, K (reprint author), US Dept Vet Affairs VA Puget Sound Hlth Care Syst, Seattle Div, 1660 S Columbian Way, Seattle, WA 98108 USA. EM kristin.piney@gmail.com FU VA Puget Sound Health Care System, Seattle FX This report is the result of work supported by the VA Puget Sound Health Care System, Seattle. NR 12 TC 9 Z9 9 U1 0 U2 2 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 EI 1557-9700 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD SEP PY 2012 VL 63 IS 9 BP 942 EP 944 DI 10.1176/appi.ps.201100349 PG 3 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 006TK UT WOS:000308841700017 PM 22810211 ER PT J AU Gross, AF Stern, TW Silverman, BC Stern, TA AF Gross, Anne F. Stern, Thomas W. Silverman, Benjamin C. Stern, Theodore A. TI Portrayals of Professionalism by the Media: Trends in Etiquette and Bedside Manners as Seen on Television SO PSYCHOSOMATICS LA English DT Article ID MEDICINE AB Background: Critics of current healthcare argue that professionalism, as manifest by etiquette and bedside manners, has been eroding, in part as a consequence of portrayals on television (TV) and in the media. Objective: We sought to identify changing patterns of physicians' behaviors as shown on TV (as these interactions have often served as models for physicians-in-training) over the last 30 years. Method: We selected popular TV shows that portrayed practicing physicians and analyzed doctor-family, doctor-doctor, and doctor-nurse interactions as well as methods of disclosing errors to identify changing behavioral trends. Results: We found that difficult news was more commonly delivered while standing, and that handshakes were rarely offered to patients. Male physicians were seen raising their voices toward, disclosing errors to, as well as inappropriately touching, peers or subordinates. In comparison, female physicians were identified as raising their voices toward, disclosing errors to, as well as inappropriately touching, their supervisors. Over the past several decades, official salutations between physicians and nurses have become less common; physicians have started to address nurses solely by their first names. More recently, sexual banter and sexual activity have been portrayed as occurring predominantly between male physicians and female nurses. Conclusions: While shifts in behavioral patterns (in etiquette, bedside manners, and professionalism) of physicians as seen on television have not been radical, potentially concerning trends were identified. Media portrayals may change patients' perceptions of physicians, hospitals, and the health care profession as well as influence behaviors of medical trainees. Moreover, TV and the media can be used as teaching tools about professionalism in healthcare providers. (Psychosomatics 2012; 53:452-455) C1 [Gross, Anne F.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97239 USA. [Stern, Thomas W.; Stern, Theodore A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Silverman, Benjamin C.] McLean Hosp, Dept Psychiat, Belmont, MA 02178 USA. RP Gross, AF (reprint author), Oregon Hlth & Sci Univ, Dept Psychiat, Mail Code UHN 80,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM gross@ohsu.edu NR 15 TC 0 Z9 1 U1 0 U2 11 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 SEP-OCT PY 2012 VL 53 IS 5 BP 452 EP 455 PG 4 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 009MN UT WOS:000309030000006 PM 22902087 ER PT J AU Sahani, DV Agarwal, S Chung, RT AF Sahani, Dushyant V. Agarwal, Sheela Chung, Raymond T. TI The Double-edged Sword of Functional Liver Imaging SO RADIOLOGY LA English DT Editorial Material ID GD-EOB-DTPA; FOCAL NODULAR HYPERPLASIA; HEPATOCELLULAR-CARCINOMA; CONTRAST AGENT; PHASE-III; ENHANCEMENT; LESIONS; SAFETY; IMAGES; MRI C1 [Sahani, Dushyant V.; Agarwal, Sheela] Harvard Univ, Sch Med, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. [Chung, Raymond T.] Harvard Univ, Sch Med, Dept Gastroenterol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Sahani, DV (reprint author), Harvard Univ, Sch Med, Div Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02114 USA. EM dsahani@partners.org NR 23 TC 1 Z9 2 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD SEP PY 2012 VL 264 IS 3 BP 621 EP 623 DI 10.1148/radiol.12121416 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 003XU UT WOS:000308645500002 PM 22919034 ER PT J AU Nance, JW Schlett, CL Schoepf, UJ Oberoi, S Leisy, HB Barraza, JM Headden, GF Nikolaou, K Bamberg, F AF Nance, John W., Jr. Schlett, Christopher L. Schoepf, U. Joseph Oberoi, Shane Leisy, Heather B. Barraza, J. Michael, Jr. Headden, Gary F. Nikolaou, Konstantin Bamberg, Fabian TI Incremental Prognostic Value of Different Components of Coronary Atherosclerotic Plaque at Cardiac CT Angiography beyond Coronary Calcification in Patients with Acute Chest Pain SO RADIOLOGY LA English DT Article ID COMPUTED-TOMOGRAPHY ANGIOGRAPHY; ARTERY-DISEASE; INTRAVASCULAR ULTRASOUND; NONINVASIVE ASSESSMENT; MYOCARDIAL-INFARCTION; EMERGENCY-DEPARTMENT; COST-EFFECTIVENESS; CALCIUM; PREDICTION; 64-SLICE AB Purpose: To systematically evaluate the incremental predictive value of cardiac computed tomographic (CT) angiography beyond the assessment of coronary artery calcium (CAC) in patients who present with acute chest pain but without evidence of acute coronary syndrome (ACS). Materials and Methods: The human research committee approved this study and waived the need for individual written informed consent. The study was HIPAA compliant. A total of 458 patients (36% male; mean age, 55 years 6 11) with acute chest pain at low to intermediate risk for coronary artery disease underwent coronary calcification assessment with cardiac CT angiography. All patients who did not experience ACS at index hospitalization were followed for instances of a major adverse cardiac event (MACE), such as a myocardial infarct, revascularization, cardiac death, or angina requiring hospitalization. CAC score and cardiac CT angiography were used to derive the presence and extent of atherosclerotic plaque (calcified, noncalcified, or mixed), and obstructive lesions (>50% luminal narrowing) were related to outcomes by using univariate and adjusted Cox proportional hazards models. Results: Of the 458 patients, 70 (15%) experienced MACE (median follow-up, 13 months). Patients with no plaque at cardiac CT angiography remained free of events during the follow-up period, while 11 (5%) of 215 patients with no CAC had MACE. The extent of plaque was the strongest predictor of MACE independent of traditional risk factors (hazard ratio [HR], 151.77 for four or more segments containing plaque as compared with those containing no plaque; P < .001). Patients with mixed plaque were more likely to experience MACE (HR, 86.96; P = .002) than those with exclusively noncalcified plaque (HR, 58.06; P = .005) or exclusively calcified plaque (HR, 32.94; P = .02). Conclusion: The strong prognostic value of cardiac CT angiography is incremental to its known diagnostic value in patients with acute chest pain without ACS and is independent of traditional risk factors and CAC. (C) RSNA, 2012 C1 [Nance, John W., Jr.; Schoepf, U. Joseph; Oberoi, Shane; Leisy, Heather B.; Barraza, J. Michael, Jr.; Headden, Gary F.] Med Univ S Carolina, Heart & Vasc Ctr, Charleston, SC 29401 USA. [Schlett, Christopher L.; Bamberg, Fabian] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MR PET CT Program,Dept Radiol, Boston, MA USA. [Nikolaou, Konstantin; Bamberg, Fabian] Univ Munich, Dept Radiol, Munich, Germany. [Bamberg, Fabian] Munich Heart Alliance, Munich, Germany. RP Schoepf, UJ (reprint author), Med Univ S Carolina, Heart & Vasc Ctr, Ashley River Tower,25 Courtenay Dr,MSC 226, Charleston, SC 29401 USA. EM schoepf@musc.edu OI Nikolaou, Konstantin/0000-0003-2668-7325 FU Bayer; Bracco; GE Healthcare; Siemens FX No potential conflicts of interest to disclose. C. L. S. No potential conflicts of interest to disclose. U.J.S. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: consultant to Bayer, Bracco, GE Healthcare, and Siemens; institution has grants pending with Bayer, Bracco, GE Healthcare, and Siemens; performed lectures for Bayer, Bracco, GE Healthcare, and Siemens; institution developed educational presentations for GE Healthcare. Other relationships: none to disclose. S.O. No potential conflicts of interest to disclose. H. B. L. No potential conflicts of interest to disclose. J.M.B. No potential conflicts of interest to disclose. G. F. H. No potential conflicts of interest to disclose. K.N. No potential conflicts of interest to disclose. F. B. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: institution has a grant pending with Bayer Healthcare; served as a lecturer for Siemens Healthcare. Other relationships: none to disclose. NR 46 TC 21 Z9 21 U1 0 U2 3 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD SEP PY 2012 VL 264 IS 3 BP 679 EP 690 DI 10.1148/radiol.12112350 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 003XU UT WOS:000308645500009 PM 22820732 ER PT J AU Hunter, GJ Schellingerhout, D Vu, TH Perrier, ND Hamberg, LM AF Hunter, George J. Schellingerhout, Dawid Vu, Thinh H. Perrier, Nancy D. Hamberg, Leena M. TI Accuracy of Four-dimensional CT for the Localization of Abnormal Parathyroid Glands in Patients with Primary Hyperparathyroidism SO RADIOLOGY LA English DT Article ID MINIMALLY INVASIVE SURGERY; ADENOMAS; NECK; EXPLORATION; TOMOGRAPHY; MANAGEMENT; MDCT AB Purpose: To investigate multiphase multidetector four-dimensional computed tomography (CT) as a technique to correctly localize abnormal parathyroid glands in patients with primary hyperparathyroidism. Materials and Methods: Informed consent was waived by the institutional review body for this retrospective, chart review study. Radiology reports from four-dimensional CT and surgical notes were reviewed in 143 patients with primary hyperparathyroidism (35 men, 108 women; median ages, 58 and 60 years, respectively) who underwent parathyroid surgery between August 2004 and January 2007 and in whom four-dimensional CT predicted a single lesion. Accuracy of four-dimensional CT was stratified by patient and was determined separately for localization to the correct side and quadrant (upper and lower for each side), with surgical findings serving as standard of reference. Results: In 143 patients, 148 abnormal parathyroid glands were found at surgery; 137 (93%) of these were weighed, with mean and median weights of 757 and 417 mg, respectively. Four-dimensional CT lateralized the abnormal glands with 93.7% accuracy (134 of 143). For localization according to quadrant, the accuracy was 86.6% (116 of 134). Conclusion: Four-dimensional CT has sufficiently high accuracy in presurgical localization to allow confident performance of unilateral parathyroidectomy in patients with sporadic primary hyperparathyroidism. The superior accuracy compared with that of ultrasonography and technetium 99m sestamibi scanning may be sufficient to allow four-dimensional CT to be used as the sole presurgical localization method. (C) RSNA, 2012 C1 [Hunter, George J.; Hamberg, Leena M.] Massachusetts Gen Hosp, Dept Neuroradiol, Boston, MA 02114 USA. [Schellingerhout, Dawid; Vu, Thinh H.] Univ Texas MD Anderson Canc Ctr, Dept Neuroradiol, Houston, TX 77030 USA. [Perrier, Nancy D.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. RP Hunter, GJ (reprint author), Massachusetts Gen Hosp, Dept Neuroradiol, 55 Fruit St,Gray 273A, Boston, MA 02114 USA. EM gjhunter@partners.org NR 21 TC 40 Z9 41 U1 0 U2 6 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD SEP PY 2012 VL 264 IS 3 BP 789 EP 795 DI 10.1148/radiol.12110852 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 003XU UT WOS:000308645500020 PM 22798226 ER PT J AU Anzueto, A Miravitlles, M Ewig, S Legnani, D Heldner, S Stauch, K AF Anzueto, Antonio Miravitlles, Marc Ewig, Santiago Legnani, Delfino Heldner, Stephanie Stauch, Kathrin TI Identifying patients at risk of late recovery (>= 8 days) from acute exacerbation of chronic bronchitis and COPD SO RESPIRATORY MEDICINE LA English DT Article DE Exacerbation; AECOPD; AECB; Moxifloxacin; Observational; Non-interventional ID OBSTRUCTIVE PULMONARY-DISEASE; PRIMARY-CARE; ANTIBIOTIC-TREATMENT; SPIROMETRY; DIAGNOSIS; OUTCOMES AB Objectives: To identify factors associated with late recovery (>= 8 days from exacerbation start) in patients with acute exacerbations of chronic bronchitis/COPD (AECB/AECOPD). Methods: An international, observational, non-interventional study in outpatients with AECB/AECOPD who received treatment for their exacerbation with the antibiotic moxifioxacin. Factors analyzed for late recovery included patient demographic characteristics, geographic region and disease severity. Additionally, logistic regression analysis was undertaken to identify factors associated with late recovery. Results: The analysis population was 40,435 patients aged >= 35 years, from Asia-Pacific, Europe, the Americas and Middle East/Africa. Most were male (63.1%), mean age 60.4 years and current or ex-smokers (60.6%) with history of >= 2 exacerbations in the previous year. Patients who underwent spirometry (n = 6408, 19.7%) had moderate airflow obstruction (mean FEV1 1.7 L). Both clinicians and patients reported that moxifloxacin provided clinical improvement in a mean of 3 days and recovery in 6 days. Clinical factors significantly associated with late recovery were: age >= 65 years, duration of chronic bronchitis >10 years, cardiac comorbidity, >3 exacerbations in the previous 12 months, current exacerbation type (Anthonisen I/II) and hospitalization in the last 12 months. Conclusions: In a large cohort of patients, all treated with the same antibiotic for an exacerbation of chronic bronchitis or COPD, the main factors associated with late recovery (>= 8 days) were: older age, history of frequent exacerbations, current exacerbation type of Anthonisen I/II, history of prior hospitalizations and cardiac comorbid conditions. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Anzueto, Antonio] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Miravitlles, Marc] Hosp Clin Barcelona, Ciber Enfermedades Resp CIBERES, Inst Invest Biomed August Pi i Sunyer IDIBAPS, Barcelona, Spain. [Ewig, Santiago] EVK Herne & Augusta Kranken Anstalt Bochum, Kliniken Pneumol & Infektiol, Thoraxzentrum Ruhrgebiet, Bochum, Germany. [Legnani, Delfino] Osped L Sacco, I-20157 Milan, Italy. [Heldner, Stephanie] Bayer HealthCare, D-13342 Berlin, Germany. [Stauch, Kathrin] Bayer HealthCare Germany GmbH, D-51368 Leverkusen, Germany. RP Anzueto, A (reprint author), Univ Texas Hlth Sci Ctr San Antonio, 111E,7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM anzueto@uthscsa.edu OI Miravitlles, Marc/0000-0002-9850-9520 FU Bayer Schering Pharma (BSP); Bayer Schering Pharma; Boehringer Ingelheim; Pfizer; GlaxoSmithKline; Schering Plough Corporation; University of Texas Health Science Center at San Antonio; C R Bard; Lilly; GSK; National Institutes of Health, National Heart, Lung and Blood Institute; Novartis; AstraZeneca; Wyeth; MSD; Sanofi Aventis FX This study was supported by a research grant from Bayer Schering Pharma (BSP). Project Management including the set-up and conduct of the study was supervised by Kathrin Stauch and Stephanie Heldner from Global Non-Interventional Studies at BSP. The contract research organisation (CRO) Institute Dr. Schauerte (Oberhaching, Germany) was responsible for data capture and data management. The CRO Kantar Health (Munich, Germany) was responsible for statistical analysis and reporting of study results. Highfield Communication Consultancy (funded by Bayer Schering Pharma) provided editorial assistance in the preparation of this manuscript.; Antonio Anzueto has participated as a speaker in scientific meetings or courses organized and financed by pharmaceutical companies including: Boehringer Ingelheim, Bayer Schering Pharma, Pfizer, GlaxoSmithKline, and the Schering Plough Corporation. He has also provided consultancy services to Boehringer Ingelheim, Bayer Schering Pharma, Pfizer, GlaxoSmithKline and the Schering Plough Corporation. He has been the principal investigator for research grants and the University of Texas Health Science Center at San Antonio was paid for participating in multicenter clinical trials sponsored by: C R Bard, Lilly, GSK, Pfizer, and the National Institutes of Health, National Heart, Lung and Blood Institute.; Marc Miravitlles has participated as a speaker in scientific meetings or courses organized and financed by pharmaceutical companies including: Boehringer Ingelheim, Bayer Schering Pharma, Pfizer, Novartis, and AstraZeneca. He has been a consultant for Boehringer Ingelheim, Bayer Schering Pharma, Pfizer, AstraZeneca and Novartis.; Santiago Ewig has participated as a speaker in scientific meetings or courses organized and financed by pharmaceutical companies including: GlaxoSmithKline, Boehringer Ingelheim, Bayer Schering Pharma, Pfizer, Wyeth, Novartis, AstraZeneca and MSD.; Delfino Legnani has participated as a speaker in scientific meetings or courses organized and financed by pharmaceutical companies including Bayer Schering Pharma, Sanofi Aventis and GSK. NR 31 TC 5 Z9 6 U1 0 U2 8 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0954-6111 EI 1532-3064 J9 RESP MED JI Respir. Med. PD SEP PY 2012 VL 106 IS 9 BP 1258 EP 1267 DI 10.1016/j.rmed.2012.06.002 PG 10 WC Cardiac & Cardiovascular Systems; Respiratory System SC Cardiovascular System & Cardiology; Respiratory System GA 005RT UT WOS:000308768300007 PM 22749710 ER PT J AU Moy, ML Weston, NA Wilson, EJ Hess, ML Richardson, CR AF Moy, Marilyn L. Weston, Nicole A. Wilson, Elizabeth J. Hess, Michael L. Richardson, Caroline R. TI A pilot study of an Internet walking program and pedometer in COPD SO RESPIRATORY MEDICINE LA English DT Article DE Physical activity; Daily step counts; Pedometer; COPD; Outcomes ID OBSTRUCTIVE PULMONARY-DISEASE; RANDOMIZED CONTROLLED-TRIAL; PHYSICAL-ACTIVITY; REHABILITATION; POPULATION; EXERCISE; HEALTH; EFFICACY; INDIVIDUALS; MORTALITY AB Background: Higher levels of physical activity are associated with better functional status, fewer hospital admissions, and lower mortality. In this pilot study, we examined the feasibility and safety of a novel program that combines a pedometer with a website to increase walking. Methods: 27 persons with stable COPD wore the Omron HJ-720ITC pedometer and used the website for 90 days. They uploaded step-count data to the study server using their home computer and received an email each week with their individualized step-count goal. The website provided step-count feedback, education, and motivational content. Subjects participated in a monthly semi-structured interview by telephone. Subjects reported changes in medical condition by telephone or on the website. Paired T-tests assessed change in daily step counts. Results: Subjects were males, mean age 72 +/- 8 years, with moderate COPD, FEV1, 1.57 +/- 0.48 L (55 +/- 16% predicted). 87% and 65% reported no problems using the pedometer and website, respectively. At month 3, 96% reported it was true that they knew their step count goal every day, and 52% reported that they were able to reach their goal. 95% of participants said they would recommend the walking program to another person with COPD. Eight subjects experienced breathing problems unrelated to the intervention. In 24 subjects with step counts at baseline and month 3, there was a significant increase of 1263 steps per day (approximately 1.0 km), p = 0.0054. Conclusions: The use of a website and pedometer was feasible and safe, and persons increased their daily walking. Registration Site and Registration Number: ClinicalTrials.gov Identifier NCT01564043. Published by Elsevier Ltd. C1 [Moy, Marilyn L.; Weston, Nicole A.] VA Boston Healthcare Syst, Pulm & Crit Care Sect, Boston, MA USA. [Moy, Marilyn L.] Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care Med, Boston, MA 02115 USA. [Moy, Marilyn L.] Harvard Univ, Sch Med, Boston, MA USA. [Wilson, Elizabeth J.; Hess, Michael L.; Richardson, Caroline R.] Univ Michigan, Sch Med, Dept Family Med, Ann Arbor, MI 48109 USA. [Richardson, Caroline R.] Ann Arbor VA Med Ctr, Ann Arbor, MI USA. RP Moy, ML (reprint author), VA Boston Healthcare Syst, Pulm & Crit Care Sect, 1400 VFW Pkwy,Mail Code 111PI, W Roxbury, MA 02132 USA. EM marilyn.moy@va.gov FU Department of Veteran Affairs, Veterans Health Administration, Rehabilitation Research and Development Service through a VA Career Development Award; CIMIT: Center for Integration of Medicine and Innovative Technology; Robert Wood Johnson Foundation; National Institutes of Health [1 K23 HL075098]; Center for Health Communications Research - University of Michigan; Michigan Diabetes Research and Training Center FX The research reported here was supported by the Department of Veteran Affairs, Veterans Health Administration, Rehabilitation Research and Development Service through a VA Career Development Award to Dr. Moy.; Supported in part by CIMIT: Center for Integration of Medicine and Innovative Technology (Dr. Moy).; Supported in part by the Robert Wood Johnson Foundation, National Institutes of Health [Grant 1 K23 HL075098], and Center for Health Communications Research - University of Michigan, and Michigan Diabetes Research and Training Center (Dr. Richardson). NR 41 TC 40 Z9 41 U1 1 U2 18 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0954-6111 J9 RESP MED JI Respir. Med. PD SEP PY 2012 VL 106 IS 9 BP 1342 EP 1350 DI 10.1016/j.rmed.2012.06.013 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System SC Cardiovascular System & Cardiology; Respiratory System GA 005RT UT WOS:000308768300018 PM 22795984 ER PT J AU Bromley, E Mikesell, L Mates, A Smith, M Brekke, JS AF Bromley, Elizabeth Mikesell, Lisa Mates, Andrea Smith, Michael Brekke, John S. TI A Video Ethnography Approach to Assessing The Ecological Validity of Neurocognitive and Functional Measures in Severe Mental Illness: Results From A Feasibility Study SO SCHIZOPHRENIA BULLETIN LA English DT Article DE schizophrenia; neurocognition; functional performance ID NEUROPSYCHOLOGICAL ASSESSMENT; PSYCHOSOCIAL REHABILITATION; PART 1; SCHIZOPHRENIA; COMMUNITY; SKILLS; INDIVIDUALS; PERFORMANCE; PREDICTORS; DEMENTIA AB Background. The ecological validity of neurocognitive and functional measures in severe mental illness is poorly understood because of a lack of validated research methods to study community life-as-lived. We describe the development of a video ethnography method that measures naturalistic behaviors with codes called community performance indicators (CPIs). The method could provide a strategy to test the ecological validity of neurocognitive and functional assessments. Methods. We gathered up to 18.5 hours of video ethnography data on each of 9 subjects with schizophrenia selected for high or low composite scores on the MATRICS Consensus Cognitive Battery (MCCB). We used video ethnography to capture subjects' everyday behaviors in their usual environments. We established 4 CPIs that showed excellent inter-rater and promising test-retest reliability: (1) behavioral activity level, (2) goal pursuit, (3) social interaction, and (4) problem solving. Results. (1) High and low MCCB subjects showed statistically significantly differences on all 4 CPIs. (2) MCCB composite scores were correlated with all 4 CPIs (r = .54 to -.77, P < .01 to .07). (3) The MCCB domain scores demonstrated some specificity in their correlations with the CPIs; eg, verbal learning, reasoning/problem solving, and social cognition were correlated with CPI domains of social interaction and problem solving. Conclusions. We present a method for reliably measuring everyday functional performance in schizophrenia. Results from a small select sample suggest that CPIs capture skills associated with neurocognition, supporting their use in a larger study of ecological validity. C1 [Bromley, Elizabeth; Mikesell, Lisa] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Semel Inst, Ctr Hlth Serv & Soc, Los Angeles, CA 90024 USA. [Bromley, Elizabeth; Mikesell, Lisa] W Los Angeles VA Healthcare Ctr, Desert Pacific Mental Illness Res Educ & Clin Ctr, Los Angeles, CA USA. [Mates, Andrea; Smith, Michael] Univ Calif Los Angeles, Dept Appl Linguist, Neurobiol Language Res Grp, Los Angeles, CA USA. [Brekke, John S.] Univ So Calif, Sch Social Work, Los Angeles, CA 90089 USA. RP Bromley, E (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Semel Inst, Ctr Hlth Serv & Soc, Los Angeles, CA 90024 USA. EM ebromley@ucla.edu FU VA Desert Pacific Mental Illness Research, Education and Clinical Center; University of California, Los Angeles Faculty Senate Council on Research; University of Southern California Clinical and Translational Science Institute FX VA Desert Pacific Mental Illness Research, Education and Clinical Center to E.B; University of California, Los Angeles Faculty Senate Council on Research to E.B.; University of Southern California Clinical and Translational Science Institute to J.S.B. NR 51 TC 6 Z9 6 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD SEP PY 2012 VL 38 IS 5 BP 981 EP 991 DI 10.1093/schbul/sbr002 PG 11 WC Psychiatry SC Psychiatry GA 009LS UT WOS:000309027900016 PM 21402723 ER PT J AU Ehrlich, S Brauns, S Yendiki, A Ho, BC Calhoun, V Schulz, SC Gollub, RL Sponheim, SR AF Ehrlich, Stefan Brauns, Stefan Yendiki, Anastasia Ho, Beng-Choon Calhoun, Vince Schulz, S. Charles Gollub, Randy L. Sponheim, Scott R. TI Associations of Cortical Thickness and Cognition in Patients With Schizophrenia and Healthy Controls SO SCHIZOPHRENIA BULLETIN LA English DT Article DE gray matter thickness; cognitive dysfunction; working memory; structural MRI ID HEMISPHERIC LANGUAGE DOMINANCE; 1ST EPISODE SCHIZOPHRENIA; REGIONAL BRAIN VOLUMES; SURFACE-BASED ANALYSIS; HUMAN CEREBRAL-CORTEX; PREFRONTAL CORTEX; NEUROPSYCHOLOGICAL PERFORMANCE; ONSET SCHIZOPHRENIA; EXECUTIVE FUNCTION; COORDINATE SYSTEM AB Previous studies have found varying relationships between cognitive functioning and brain volumes in patients with schizophrenia. However, cortical thickness may more closely reflect cytoarchitectural characteristics than gray matter density or volume estimates. Here, we aimed to compare associations between regional variation in cortical thickness and executive functions, memory, as well as verbal and spatial processing in patients with schizophrenia and healthy controls (HCs). We obtained magnetic resonance imaging and neuropsychological data for 131 patients and 138 matched controls. Automated cortical pattern matching methods allowed testing for associations with cortical thickness estimated as the shortest distance between the gray/white matter border and the pial surface at thousands of points across the entire cortical surface. Two independent measures of working memory showed robust associations with cortical thickness in lateral prefrontal cortex in HCs, whereas patients exhibited associations between working memory and cortical thickness in the right middle and superior temporal lobe. This study provides additional evidence for a disrupted structure-function relationship in schizophrenia. In line with the prefrontal inefficiency hypothesis, schizophrenia patients may engage a larger compensatory network of brain regions other than frontal cortex to recall and manipulate verbal material in working memory. C1 [Ehrlich, Stefan] Harvard Univ, Athinoula A Martinos Ctr Biomed Imaging, Psychiat Neuroimaging Res Program,Med Sch, Massachusetts Gen Hosp,Massachusetts Inst Technol, Charlestown, MA 02129 USA. [Ehrlich, Stefan; Gollub, Randy L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. [Ehrlich, Stefan] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dept Child & Adolescent Psychiat, Dresden, Germany. [Ho, Beng-Choon] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA. [Calhoun, Vince] Image Anal & MR Res, Mind Res Network, Albuquerque, NM USA. [Calhoun, Vince] Univ New Mexico, Dept Elect & Comp Engn, Albuquerque, NM 87131 USA. [Schulz, S. Charles; Sponheim, Scott R.] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA. [Schulz, S. Charles; Sponheim, Scott R.] Univ Minnesota, Ctr Magnet Resonance Res, Minneapolis, MN USA. [Sponheim, Scott R.] Vet Affairs Med Ctr, Minneapolis, MN USA. RP Ehrlich, S (reprint author), Harvard Univ, Athinoula A Martinos Ctr Biomed Imaging, Psychiat Neuroimaging Res Program,Med Sch, Massachusetts Gen Hosp,Massachusetts Inst Technol, CNY Bldg 120,Suite 100, Charlestown, MA 02129 USA. EM stefan@nmr.mgh.harvard.edu RI Ho, Beng-Choon/D-6959-2011; Calhoun, Vince/H-7146-2013; OI Ho, Beng-Choon/0000-0003-3976-1555; Calhoun, Vince/0000-0001-9058-0747; Ehrlich, Stefan/0000-0003-2132-4445; Gollub, Randy L./0000-0002-9434-4044 FU National Institutes of Health (NIH)/National Center for Research Resources (NCRR) [P41RR14075, 1U24 RR021382A, U24RR021992-01, MO1 RR025758-01]; Department of Energy for the Mental Illness and Neuroscience Discovery (MIND) Research Network [DE-FG02-99ER62764]; National Institute of Mental Health; Deutsche Forschungsgemeinschaft Research Fellowship FX National Institutes of Health (NIH)/National Center for Research Resources (NCRR) [P41RR14075, Morphometry BIRN NIH/NCRR 1U24 RR021382A, Function BIRN NIH/NCRR U24RR021992-01, NIH/NCRR MO1 RR025758-01]; Department of Energy for the Mental Illness and Neuroscience Discovery (MIND) Research Network [DE-FG02-99ER62764]; National Institute of Mental Health-Clinical Scholar Training to S.C.S.; Deutsche Forschungsgemeinschaft Research Fellowship to S.E. NR 117 TC 51 Z9 53 U1 1 U2 16 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD SEP PY 2012 VL 38 IS 5 BP 1050 EP 1062 DI 10.1093/schbul/sbr018 PG 13 WC Psychiatry SC Psychiatry GA 009LS UT WOS:000309027900023 PM 21436318 ER PT J AU Avruch, J Zhou, DW Fitamant, J Bardeesy, N Mou, F Barrufet, LR AF Avruch, Joseph Zhou, Dawang Fitamant, Julien Bardeesy, Nabeel Mou, Fan Barrufet, Laura Regue TI Protein kinases of the Hippo pathway: Regulation and substrates SO SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY LA English DT Review DE Protein kinase; Hippo; Mst1/2; Mob1; Lats1/2; ndr1/2 ID DROSOPHILA TUMOR-SUPPRESSOR; HUMAN NDR KINASES; ORGAN SIZE CONTROL; CELL-CYCLE EXIT; STE20-LIKE KINASE; PROMOTES APOPTOSIS; SIGNALING PATHWAY; MST1 KINASE; CASPASE CLEAVAGE; FISSION YEAST AB The "Hippo" signaling pathway has emerged as a major regulator of cell proliferation and survival in metazoans. The pathway, as delineated by genetic and biochemical studies in Drosophila, consists of a kinase cascade regulated by cell-cell contact and cell polarity that inhibits the transcriptional coactivator Yorkie and its proliferative, anti-differentiation, antiapoptotic transcriptional program. The core pathway components are the GC kinase Hippo, which phosphorylates the noncatalytic polypeptide Mats/Mob1 and, with the assistance of the scaffold protein Salvador, phosphorylates the ndr-family kinase Lats. In turn phospho-Lats, after binding to phospho-Mats, autoactivates and phosphorylates Yorkie, resulting in its nuclear exit. Hippo also uses the scaffold protein Furry and a different Mob protein to control another ndr-like kinase, the morphogenetic regulator Tricornered. Architecturally homologous kinase cascades consisting of a GC kinase, a Mob protein, a scaffolding polypeptide and an ndr-like kinase are well described in yeast; in Saccharomyces cerevisiae, e. g., the MEN pathway promotes mitotic exit whereas the RAM network, using a different GC kinase, Mob protein, scaffold and ndr-like kinase, regulates cell polarity and morphogenesis. In mammals, the Hippo orthologs Mst1 and Mst2 utilize the Salvador ortholog WW45/Sav1 and other scaffolds to regulate the kinases Lats1/Lats2 and ndr1/ndr2. As in Drosophila, murine Mst1/Mst2, in a redundant manner, negatively regulate the Yorkie ortholog YAP in the epithelial cells of the liver and gut; loss of both Mst1 and Mst2 results in hyperproliferation and tumorigenesis that can be largely negated by reduction or elimination of YAP. Despite this conservation, considerable diversification in pathway composition and regulation is already evident; in skin, e. g., YAP phosphorylation is independent of Mst1Mst2 and Lats1Lats2. Moreover, in lymphoid cells, Mst1/Mst2, under the control of the Rap1 GTPase and independent of YAP, promotes integrin clustering, actin remodeling and motility while restraining the proliferation of naive T cells. This review will summarize current knowledge of the structure and regulation of the kinases Hippo/Mst1&2, their noncatalytic binding partners, Salvador and the Rassf polypeptides, and their major substrates Warts/Lats1&2, Trc/ndr1&2, Mats/Mob1 and FOXO. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Avruch, Joseph; Mou, Fan; Barrufet, Laura Regue] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Avruch, Joseph; Mou, Fan; Barrufet, Laura Regue] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. [Fitamant, Julien; Bardeesy, Nabeel] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Avruch, Joseph; Fitamant, Julien; Bardeesy, Nabeel; Mou, Fan; Barrufet, Laura Regue] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Zhou, Dawang] Xiamen Univ, Sch Life Sci, State Key Lab Stress Cell Biol, Xiamen 361005, Fujian, Peoples R China. RP Avruch, J (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Simches Res Bldg 6408,185 Cambridge St, Boston, MA 02114 USA. EM avruch@molbio.mgh.harvard.edu RI han, jing/A-2527-2015; OI Zhou, Dawang/0000-0002-9053-5249 FU NIH [DK17776, CA136567]; Sidney Kimmel Foundation for Cancer Research; Linda J. Verville Cancer Research Foundation; 111 Project of Education of China [B06016]; Fundamental Research Funds for the Central Universities of China [2010111079]; National Natural Science Foundation of China [81101503]; Natural Science Foundation of Fujian [2011J05096] FX The work described herein from the author's laboratories was supported by NIH grants DK17776 (JA) and CA136567 (to JA and NB), the Sidney Kimmel Foundation for Cancer Research (NB), the Linda J. Verville Cancer Research Foundation (NB), 111 Project of Education of China (No. B06016, DZ), the Fundamental Research Funds for the Central Universities of China (No. 2010111079, DZ), National Natural Science Foundation of China (No. 81101503, DZ) and Natural Science Foundation of Fujian (No. 2011J05096, DZ). NR 169 TC 68 Z9 72 U1 1 U2 46 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1084-9521 J9 SEMIN CELL DEV BIOL JI Semin. Cell Dev. Biol. PD SEP PY 2012 VL 23 IS 7 BP 770 EP 784 DI 10.1016/j.semcdb.2012.07.002 PG 15 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 012VI UT WOS:000309264300008 PM 22898666 ER PT J AU Menon, BK Saver, JL Prabhakaran, S Reeves, M Liang, L Olson, DM Peterson, ED Hernandez, AF Fonarow, GC Schwamm, LH Smith, EE AF Menon, Bijoy K. Saver, Jeffrey L. Prabhakaran, Shyam Reeves, Mathew Liang, Li Olson, DaiWai M. Peterson, Eric D. Hernandez, Adrian F. Fonarow, Gregg C. Schwamm, Lee H. Smith, Eric E. TI Risk Score for Intracranial Hemorrhage in Patients With Acute Ischemic Stroke Treated With Intravenous Tissue-Type Plasminogen Activator SO STROKE LA English DT Article DE acute ischemic stroke; intravenous tPA; risk score; symptomatic intracranial hemorrhage ID SYMPTOMATIC INTRACEREBRAL HEMORRHAGE; SAFE IMPLEMENTATION; THROMBOLYTIC THERAPY; SITS-MOST; HAT SCORE; ALTEPLASE; TRIALS; REGISTRY AB Background and Purpose-There are few validated models for prediction of risk of symptomatic intracranial hemorrhage (sICH) after intravenous tissue-type plasminogen activator treatment for ischemic stroke. We used data from Get With The Guidelines-Stroke (GWTG-Stroke) to derive and validate a prediction tool for determining sICH risk. Methods-The population consisted of 10 242 patients from 988 hospitals who received intravenous tissue-type plasminogen activator within 3 hours of symptom onset from January 2009 to June 2010. This sample was randomly divided into derivation (70%) and validation (30%) cohorts. Multivariable logistic regression identified predictors of intravenous tissue-type plasminogen activator-related sICH in the derivation sample; model beta coefficients were used to assign point scores for prediction. Results-sICH within 36 hours was noted in 496 patients (4.8%). Multivariable adjusted independent predictors of sICH were increasing age (17 points), higher baseline National Institutes of Health Stroke Scale (42 points), higher systolic blood pressure (21 points), higher blood glucose (8 points), Asian race (9 points), and male sex (4 points). The C-statistic was 0.71 in the derivation sample and 0.70 in the independent internal validation sample. Plots of observed versus predicted sICH showed good model calibration in the derivation and validation cohorts. The model was externally validated in National Institute of Neurological Disorders and Stroke trial patients with a C-statistic of 0.68. Conclusions-The GWTG-Stroke sICH risk "GRASPS" score provides clinicians with a validated method to determine the risk of sICH in patients treated with intravenous tissue-type plasminogen activator within 3 hours of stroke symptom onset. (Stroke. 2012; 43: 2293-2299.) C1 [Menon, Bijoy K.; Smith, Eric E.] Univ Calgary, Dept Clin Neurosci, Hotchkiss Brain Inst, Calgary Stroke Program, Calgary, ON, Canada. [Saver, Jeffrey L.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA USA. [Prabhakaran, Shyam] Northwestern Univ, Feinberg Sch Med, Dept Neurol, Chicago, IL 60611 USA. [Reeves, Mathew] Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA. [Liang, Li; Olson, DaiWai M.; Peterson, Eric D.; Hernandez, Adrian F.] Duke Univ, Duke Clin Res Inst, Durham, NC USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Menon, BK (reprint author), 1079 A,29th St NW, Calgary, AB T3H 4J2, Canada. EM Bijoy.Menon@Albertahealthservices.ca RI MENON, BIJOY/B-7718-2014; Hernandez, Adrian F./A-7818-2016; OI Saver, Jeffrey/0000-0001-9141-2251; Schwamm, Lee/0000-0003-0592-9145; Hernandez, Adrian F./0000-0003-3387-9616; Smith, Eric/0000-0003-3956-1668 FU Pfizer, Inc, New York, NY; Merck-Schering Plough Partnership (North Wales, PA); Lundbeck; National Institutes of Health FX The American Heart Association and the American Stroke Association fund Get With the Guidelines-Stroke. The program is also supported in part by unrestricted educational grants to the American Heart Association by Pfizer, Inc, New York, NY, and the Merck-Schering Plough Partnership (North Wales, PA), who did not participate in the design, analysis, article preparation, or approval.; Dr Schwamm is a member of the Steering Committee for the Desmoteplase in Acute Ischemic Stroke Trial (DIAS)-3 trial funded by Lundbeck and is employed by Massachusetts General Hospital, which has received IV tPA from Genentech as part of a National Institutes of Health-sponsored clinical trial. NR 21 TC 59 Z9 59 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD SEP PY 2012 VL 43 IS 9 BP 2293 EP + DI 10.1161/STROKEAHA.112.660415 PG 9 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 000UX UT WOS:000308416300020 PM 22811458 ER PT J AU Song, SS Latour, LL Ritter, CH Wu, O Tighiouart, M Hernandez, DA Ku, KD Luby, M Warach, S AF Song, Shlee S. Latour, Lawrence L. Ritter, Carsten H. Wu, Ona Tighiouart, Mourad Hernandez, Daymara A. Ku, Katherine D. Luby, Marie Warach, Steven TI A Pragmatic Approach Using Magnetic Resonance Imaging to Treat Ischemic Strokes of Unknown Onset Time in a Thrombolytic Trial SO STROKE LA English DT Article DE diffusion-weighted imaging; fluid-attenuated inversion recovery; stroke; thrombolysis ID TISSUE-PLASMINOGEN ACTIVATOR; WAKE-UP; SYMPTOM ONSET; ABESTT-II; HEMIANESTHESIA; EXPERIENCE; HEMIANOPIA; THERAPY; NEGLECT; MRI AB Background and Purpose-Toward the goal of designing a clinical trial using imaging parameters to treat stroke patients with unknown onset time, we investigated the timing of changes on MRI in patients with well-defined stroke onset. Methods-Hypothesis-generating (n=85) and confirmatory (n=111) samples were scored by blinded readers for fluid-attenuated inversion recovery (FLAIR) hyperintensity in diffusion-positive regions. Reader-measured signal intensity ratio (SIR) of the lesion to contralateral tissue was compared with SIR measured by coregistration. Results-Lesion conspicuity increased with time on FLAIR (P=0.006). Qualitative assessment of FLAIR-negative vs FLAIR hyperintensity (k=0.7091; 95% CI, 0.61-0.81) showed good interrater agreement. Subtle hyperintensity was less reliably categorized (k=0.59; 95% CI, 0.47-0.71). Reader-measured SIR <1.15 can identify patients within the treatable time window of 4.5 hours (positive predictive value=0.90). The SIR was greater for right hemisphere lesions (P=0.04) for a given reported time from stroke symptom onset. Conclusion-The SIR on FLAIR provides a quantitative tool to identify early ischemic strokes. In developing SIR thresholds, right hemisphere lesions may confound the accurate estimate of stroke onset time. Image coregistration for thrombolytic trial enrollment is not necessary. A SIR <1.15 on FLAIR yields a practical estimate of stroke onset within 4.5 hours. (Stroke. 2012;43:2331-2335.) C1 [Song, Shlee S.] Cedars Sinai Med Ctr, Dept Neurol, Stroke Program, Los Angeles, CA 90048 USA. [Song, Shlee S.; Latour, Lawrence L.; Ritter, Carsten H.; Hernandez, Daymara A.; Ku, Katherine D.; Luby, Marie; Warach, Steven] NINDS, Sect Stroke Diagnost & Therapeut, NIH, Bethesda, MD 20892 USA. [Wu, Ona] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA USA. [Tighiouart, Mourad] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst3, Los Angeles, CA 90048 USA. [Warach, Steven] Univ Texas Austin, SW Med Ctr, Clin Res Inst, Austin Programs, Austin, TX 78712 USA. RP Song, SS (reprint author), Cedars Sinai Med Ctr, Dept Neurol, Stroke Program, 8730 Alden Dr,Thalians E-216, Los Angeles, CA 90048 USA. EM shlee.song@cshs.org FU National Institutes of Health, National Institutes of Neurological Diseases and Stroke FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Institutes of Neurological Diseases and Stroke. NR 18 TC 21 Z9 21 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD SEP PY 2012 VL 43 IS 9 BP 2331 EP 2335 DI 10.1161/STROKEAHA.111.630947 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 000UX UT WOS:000308416300026 PM 22693129 ER PT J AU Chandra, RV Leslie-Mazwi, TM Oh, DC Chaudhry, ZA Mehta, BP Rost, NS Rabinov, JD Hirsch, JA Gonzalez, G Schwamm, LH Yoo, AJ AF Chandra, Ronil V. Leslie-Mazwi, Thabele M. Oh, Daniel C. Chaudhry, Zeshan A. Mehta, Brijesh P. Rost, Natalia S. Rabinov, James D. Hirsch, Joshua A. Gonzalez, Gilberto Schwamm, Lee H. Yoo, Albert J. TI Elderly Patients Are at Higher Risk for Poor Outcomes After Intra-Arterial Therapy SO STROKE LA English DT Article DE elderly; stroke; thrombolysis ID ACUTE ISCHEMIC-STROKE; INTERVENTIONAL MANAGEMENT; MECHANICAL THROMBECTOMY; SCALE SCORE; THROMBOLYSIS; TRIAL; OLDER; AGE; OCTOGENARIANS; DETERMINANTS AB Background and Purpose-Conflicting data exist regarding outcomes after intra-arterial therapy (IAT) in elderly stroke patients. We compare safety and clinical outcomes of multimodal IAT in elderly versus nonelderly patients and investigate differences in baseline health and disability as possible explanatory factors. Methods-Data from a prospectively collected institutional IAT database were analyzed comparing elderly (80 years or older) versus nonelderly patients. Baseline demographics, angiographic reperfusion (Thrombolysis in Cerebral Infarction scale score 2-3), rate of parenchymal hematoma type 2, and 90-day modified Rankin Scale scores were compared in univariate and multivariate analyses. Results-There were 49 elderly and 130 nonelderly patients treated between 2005 and 2010. Between the 2 cohorts, there was no significant difference in Thrombolysis in Cerebral Infarction 2 to 3 reperfusion (71% vs 75%; P=0.57), time to reperfusion (P=0.77), or rate of parenchymal hematoma type 2 (4% vs 7%; P=0.73) after IAT. However, elderly patients had significantly lower rates of good outcome (modified Rankin Scale score 0-2: 2% vs 33%; P<0.0001) and higher mortality (59% vs 24%; P<0.0001) at 90 days. Atrial fibrillation, coronary artery disease, hypertension, hyperlipidema, and baseline disability were significantly more common in elderly patients. Adjusting for baseline disability, stroke severity, and reperfusion, elderly patients were 29-times more likely to be dependent or dead at 90 days (odds ratio, 28.7; 95% confidence interval, 3.2-255.7; P=0.003). Conclusions-Despite comparable rates of reperfusion and significant hemorrhage, elderly patients had worse clinical outcomes after IAT, which may relate, in part, to worse baseline health and disability. The use of IAT in the elderly should be performed after a careful analysis of the potential risks and benefits. (Stroke. 2012;43:2356-2361.) C1 [Chandra, Ronil V.; Leslie-Mazwi, Thabele M.; Oh, Daniel C.; Chaudhry, Zeshan A.; Rabinov, James D.; Hirsch, Joshua A.; Yoo, Albert J.] Massachusetts Gen Hosp, Dept Radiol, Div Intervent, Boston, MA 02114 USA. [Chaudhry, Zeshan A.; Yoo, Albert J.] Massachusetts Gen Hosp, Div Diagnost Neuroradiol, Boston, MA 02114 USA. [Leslie-Mazwi, Thabele M.; Mehta, Brijesh P.; Rost, Natalia S.; Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Yoo, AJ (reprint author), 55 Fruit St,Gray 241, Boston, MA 02114 USA. EM ajyoo@partners.org OI Schwamm, Lee/0000-0003-0592-9145 FU Neuroradiology Education and Research Foundation/Boston Scientific Fellowship in Cerebrovascular Disease Research; Penumbra, Inc FX Dr Yoo was the 2007 recipient of the Neuroradiology Education and Research Foundation/Boston Scientific Fellowship in Cerebrovascular Disease Research.; Dr Hirsch is on the MERCI Registry Steering Committee but receives no financial compensation. Dr Yoo has received a research grant from Penumbra, Inc and modest honoraria from Codman Neurovascular. NR 24 TC 22 Z9 23 U1 4 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD SEP PY 2012 VL 43 IS 9 BP 2356 EP + DI 10.1161/STROKEAHA.112.650713 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 000UX UT WOS:000308416300030 PM 22744644 ER PT J AU Willey, JZ Ortega-Gutierrez, S Petersen, N Khatri, P Ford, AL Rost, NS Ali, LK Gonzales, NR Merino, JG Meyer, BC Marshall, RS AF Willey, Joshua Z. Ortega-Gutierrez, Santiago Petersen, Nils Khatri, Pooja Ford, Andria L. Rost, Natalia S. Ali, Latisha K. Gonzales, Nichole R. Merino, Jose G. Meyer, Brett C. Marshall, Randolph S. TI Impact of Acute Ischemic Stroke Treatment in Patients > 80 Years of Age The Specialized Program of Translational Research in Acute Stroke (SPOTRIAS) Consortium Experience SO STROKE LA English DT Article DE acute Rx; acute stroke; interventional neuroradiology ID TISSUE-PLASMINOGEN ACTIVATOR; RANDOMIZED CONTROLLED-TRIAL; 80 YEARS OLD; INTRAVENOUS THROMBOLYSIS; RT-PA; INTRAARTERIAL THROMBOLYSIS; ALTEPLASE; GREATER-THAN-OR-EQUAL-TO-80; OCTOGENARIANS; REGISTRY AB Background and Purpose-Few studies have addressed outcomes among patients >= 80 years treated with acute stroke therapy. In this study, we outline in-hospital outcomes in (1) patients >= 80 years compared with their younger counterparts; and (2) those over >80 years receiving intra-arterial therapy (IAT) compared with those treated with intravenous recombinant tissue-type plasminogen activator (IV rtPA). Methods-Stroke centers within the Specialized Program of Translational Research in Acute Stroke (SPOTRIAS) prospectively collected data on all patients treated with IV rtPA or IAT from January 1, 2005, to December 31, 2010. IAT was defined as receiving any endovascular therapy; IAT was further divided into bridging therapy when the patient received both IAT and IV rtPA and endovascular therapy alone. In-hospital mortality was compared in (1) all patients aged >= 80 years versus younger counterparts; and (2) IAT, bridging therapy, and endovascular therapy alone versus IV rtPA only among those age >= 80 years using multivariable logistic regression. An age-stratified analysis was also performed. Results-A total of 3768 patients were included in the study; 3378 were treated with IV rtPA alone and 808 with IAT (383 with endovascular therapy alone and 425 with bridging therapy). Patients >= 80 years (n=1182) had a higher risk of in-hospital mortality compared with younger counterparts regardless of treatment modality (OR, 2.13; 95% CI, 1.60-2.84). When limited to those aged >= 80 years, IAT (OR, 0.95; 95% CI, 0.60-1.49), bridging therapy (OR, 0.82; 95% CI, 0.47-1.45), or endovascular therapy alone (OR, 1.15; 95% CI, 0.64-2.08) versus IV rtPA were not associated with increased in-hospital mortality. Conclusions-IAT does not appear to increase the risk of in-hospital mortality among those aged >80 years compared with IV thrombolysis alone. (Stroke. 2012;43:2369-2375.) C1 [Willey, Joshua Z.; Ortega-Gutierrez, Santiago; Petersen, Nils; Marshall, Randolph S.] Columbia Univ, Dept Neurol, New York, NY 10032 USA. [Khatri, Pooja] Univ Cincinnati, Dept Neurol, Cincinnati, OH USA. [Ford, Andria L.] Washington Univ, Dept Neurol, St Louis, MO USA. [Rost, Natalia S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Ali, Latisha K.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Gonzales, Nichole R.] Univ Texas Houston, Dept Neurol, Houston, TX USA. [Merino, Jose G.] NIH, Div Intramural Res, Bethesda, MD 20892 USA. [Meyer, Brett C.] Univ Calif San Diego, Dept Neurol, San Diego, CA 92103 USA. RP Willey, JZ (reprint author), Columbia Univ, Dept Neurol, 710 W 168th St,Box 30, New York, NY 10032 USA. EM jzw2@columbia.edu OI Merino, Jose/0000-0002-6676-0008 FU National Institutes of Neurological Diseases and Stroke [NINDS P50 NS049060]; NINDS [1K23 NS 073104-01A1]; National Institutes of Health (NIH) [AG 31009]; Intramural Division of the National Institute of Neurological Disorders and Stroke/NIH FX SPOTRIAS is funded by the National Institutes of Neurological Diseases and Stroke (NINDS P50 NS049060). Dr Willey was funded by NINDS 1K23 NS 073104-01A1 and the National Institutes of Health (NIH) Loan Repayment Program (AG 31009). This work was funded in part by the Intramural Division of the National Institute of Neurological Disorders and Stroke/NIH. NR 34 TC 14 Z9 15 U1 3 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD SEP PY 2012 VL 43 IS 9 BP 2369 EP 2375 DI 10.1161/STROKEAHA.112.660993 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 000UX UT WOS:000308416300032 PM 22798327 ER PT J AU Depta, JP Fowler, J Novak, E Katzan, I Bakdash, S Kottke-Marchant, K Bhatt, DL AF Depta, Jeremiah P. Fowler, Jeffrey Novak, Eric Katzan, Irene Bakdash, Suzanne Kottke-Marchant, Kandice Bhatt, Deepak L. TI Clinical Outcomes Using a Platelet Function-Guided Approach for Secondary Prevention in Patients With Ischemic Stroke or Transient Ischemic Attack SO STROKE LA English DT Article DE aspirin; clopidogrel; ischemic stroke; nonresponse; platelet function testing; resistance; transient ischemic attack ID ACUTE CORONARY SYNDROMES; ADENOSINE-DIPHOSPHATE; ASPIRIN RESISTANCE; RECURRENT STROKE; CONTROLLED-TRIAL; FUNCTION ASSAYS; CLOPIDOGREL; DIPYRIDAMOLE; ASSOCIATION; INTERVENTION AB Background and Purpose-Antiplatelet therapy nonresponse is associated with worse clinical outcomes. We studied the clinical outcomes associated with platelet function-guided modifications in antiplatelet therapy in patients with ischemic stroke or transient ischemic attack. Methods-From January 2005 to August 2007, 324 patients with ischemic stroke underwent platelet function testing using platelet aggregometry. Aspirin nonresponse was defined as a mean platelet aggregation >= 20% with 0.5 mg/mL arachidonic acid and/or >= 70% with 5 mu mol/L adenosine diphosphate. Clopidogrel nonresponse was defined as a mean platelet aggregation >= 40% with 5 mu mol/L adenosine diphosphate. A modification was any increase in antiplatelet therapy occurring after testing. Clinical outcomes were compared between patients with and without platelet function-guided antiplatelet therapy modifications using univariate and propensity score-adjusted analyses. Results-In patients with ischemic stroke or transient ischemic attack, 43% (n=128) and 35% (n=54) were nonresponders to aspirin and clopidogrel, respectively. After platelet function testing, antiplatelet therapy was increased in 23% of patients (n=73). After propensity score matching (n=61 in each group), antiplatelet therapy modification was associated with significantly increased rates of death, ischemic events, or bleeding (hazard ratio, 2.24; 95% CI, 1.12-4.47; P=0.02) compared with no modification in antiplatelet therapy and a trend toward increased bleeding (hazard ratio, 3.56; 95% CI, 0.98-12.95; P=0.05). No differences in ischemic events were observed. Conclusions-Platelet function-guided modification in antiplatelet therapy after an ischemic stroke or transient ischemic attack was associated with significantly higher rates of adverse clinical outcomes. (Stroke. 2012;43:2376-2381.) C1 [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02132 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. [Fowler, Jeffrey; Katzan, Irene; Bakdash, Suzanne; Kottke-Marchant, Kandice] Cleveland Clin, Cleveland, OH 44106 USA. [Depta, Jeremiah P.; Novak, Eric] Washington Univ, Sch Med, St Louis, MO 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 FU Amarin; AstraZeneca; Bristol-Myers Squibb; Eisai; Ethicon; Medtronic; Sanofi Aventis; Medicines Company FX Dr Bhatt is on the Advisory Board of Medscape Cardiology; the Board of Directors of the Boston VA Research Institute, Society of Chest Pain Centers; Chair of the American Heart Association Get With The Guidelines Science Subcommittee; received honoraria from the American College of Cardiology (Editor, Clinical Trials, Cardiosource), Duke Clinical Research Institute (clinical trial steering committees), Slack publications (Chief Medical Editor, Cardiology Today Intervention), and WebMD (CME steering committees); has received research grants from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi Aventis, and The Medicines Company; and received unfunded research from FlowCo, PLx Pharma and Takeda. NR 31 TC 12 Z9 14 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD SEP PY 2012 VL 43 IS 9 BP 2376 EP + DI 10.1161/STROKEAHA.112.655084 PG 12 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 000UX UT WOS:000308416300033 PM 22713488 ER PT J AU Perry, LJP Jakobiec, FA Zakka, FR Rubin, PAD AF Perry, Lynn J. P. Jakobiec, Frederick A. Zakka, Fouad R. Rubin, Peter A. D. TI Giant Dacryocystomucopyocele in an Adult: A Review of Lacrimal Sac Enlargements With Clinical and Histopathologic Differential Diagnoses SO SURVEY OF OPHTHALMOLOGY LA English DT Review DE amniotocele; canaliculus; dacryocystitis; dacryocystocele; dacryostenosis; lacrimal sac; mucocele; nasolacrimal duct; orbit; Peptostreptococcus; Prevotella; valves of Rosenmuller and Hasner ID NASOLACRIMAL DUCT OBSTRUCTION; EFFERENT TEAR-DUCTS; CANALICULAR OBSTRUCTION; CONGENITAL DACRYOCELE; MALIGNANT-MELANOMA; LYMPHOID-TISSUE; DACRYOCYSTOCELE; MANAGEMENT; DISEASE; CYST AB Dacryocystocele is an umbrella term that refers to any diffuse, centrifugal enlargement of the lacrimal sac that results from combined proximal and distal obstructions in the tear drainage system. In adults, the presence of mucus in the cyst's contents leads to the modified term of dacryocystomucocele. If infection supervenes, which almost always occurs in protracted cases and adds the clinical dimension of a dacryocystitis, then a dacryocystomucopyocele is created. Dacryocystocele and its congeners are much rarer in adults than in children. We describe a 95-year-old woman with an acquired, enormous dacryocystomucopyocele, larger than any previously reported, that developed over 25 years and produced globe displacement with an associated conspicuous enlargement of the nasolacrimal duct. The aspirated sac fluid was mucopurulent and harbored low-virulence bacterial organisms of the Prevotella and Petosteptococcus species. In infants, dacryocystoceles are transitory as the result of spontaneously reversible factors. In adults, secondary proximal irreversible fibrotic strictures or bony changes around the nasolacrimal duct typically arise from chronic inflammation or low grade infection. Other possible causations of duct obstruction, in addition to florid mucosal edema, include encroachment on the duct by enlarged contiguous ethmoid air cells; a sinus mucocele or sinusitis; idiopathic, post-traumatic or dysplastic bony remodeling of the wall of the duct; and a neoplasm-all of which require some form of surgical intervention, typically dacryocystorhinostomy. The differential diagnosis of medial canthal swellings centered on the lacrimal sac spans malformations, diverticula, dermoid/epidermoid cysts, sac inflammations/infections causing swelling without generalized sac enlargement, encephaloceles and primary epithelial tumors, as well as extrinsic tumors impinging on the sac. (Surv Ophthalmol 57:474-485, 2012. (c) 2012 Elsevier Inc. All rights reserved.) C1 [Jakobiec, Frederick A.] Harvard Univ, Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Sch Med,Dept Ophthalmol, Boston, MA 02114 USA. [Perry, Lynn J. P.; Jakobiec, Frederick A.; Zakka, Fouad R.] Massachusetts Eye & Ear Infirm, Cogan Eye Pathol Lab, Boston, MA 02114 USA. [Rubin, Peter A. D.] Ophthalm Plast & Orbital Surg, W Palm Beach, FL USA. [Rubin, Peter A. D.] Univ Tennessee, Dept Ophthalmol, Knoxville, TN USA. RP Jakobiec, FA (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Sch Med,Dept Ophthalmol, Suite 321,243 Charles St, Boston, MA 02114 USA. EM Fred_Jakobiec@meei.harvard.edu FU Heed Foundation, Cleveland, Ohio FX The authors reported no proprietary or commercial interest in any product mentioned or any concept discussed in the article. Lynn J. Poole Perry is supported in part by the Heed Foundation, Cleveland, Ohio. NR 80 TC 9 Z9 11 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6257 EI 1879-3304 J9 SURV OPHTHALMOL JI Surv. Ophthalmol. PD SEP-OCT PY 2012 VL 57 IS 5 BP 474 EP 485 DI 10.1016/j.survophthal.2012.02.003 PG 12 WC Ophthalmology SC Ophthalmology GA 994DF UT WOS:000307910400006 PM 22784678 ER PT J AU Crescente, M Thomas, GM Demers, M Voorhees, JR Wong, SL Ho-Tin-Noe, B Wagner, DD AF Crescente, Marilena Thomas, Grace M. Demers, Melanie Voorhees, Jaymie R. Wong, Siu Ling Ho-Tin-Noe, Benoit Wagner, Denisa D. TI ADAMTS13 exerts a thrombolytic effect in microcirculation SO THROMBOSIS AND HAEMOSTASIS LA English DT Article DE ADAMS/ADAMTS 13; thrombolysis / thrombolytic agents; plasminogen activators; intravital microscopy ID VON-WILLEBRAND-FACTOR; CATHETER-DIRECTED THROMBOLYSIS; DEEP VENOUS THROMBOSIS; MASSIVE PULMONARY-EMBOLISM; DORSAL SKINFOLD CHAMBER; ACUTE ISCHEMIC-STROKE; PLASMINOGEN-ACTIVATOR; INTRAVITAL MICROSCOPY; POOLED ANALYSIS; THERAPY AB Recombinant tissue plasminogen activator (r-tPA) is the drug of choice for thrombolysis, but it is associated with a significant risk of bleeding and is not always successful. By cleaving von Willebrand factor (VWF), the metalloprotease ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type I repeats-13) down-regulates thrombus formation in injured vessels. We investigated whether recombinant ADAMTS13 (r-ADAMTS13) induces thrombolysis in vivo in mice. Thrombosis was produced by ferric chloride-induced (FeCl3) injury in the venules of a dorsal skinfold chamber. Phosphate-buffered saline (PBS, vehicle), r-tPA or r-ADAMTS13, supplemented with hirudin (to stop ongoing thrombin generation), was directly applied onto the occluded vessel, and thrombus dissolution was evaluated by intravital microscopy. The incidence of blood flow restoration significantly increased 30 minutes (min) after r-ADAMTS13 vs. PBS treatment (60% vs. 0%, p<0.05) and 60 min after r-tPA treatment (75% vs. 17%, p<0.05). Both r-tPA and r-ADAMTS13 significantly reduced thrombus size 60 min after their superfusion (53.2% and 62.3% of the initial thrombus size, p<0.05 and p<0.01, respectively). Bleeding occurred in all r-tPA-treated chambers, while it was absent in mice treated with r-ADAMTS13 or PBS. We observed that, similar to r-tPA, r-ADAMTS13 can dissolve occlusive thrombi induced by FeCl3 injury in venules. In contrast to r-tPA, the in vivo thrombolytic effect of ADAMTS13 was not associated with any signs of haemorrhage. ADAMTS13 could represent a new therapeutic option for thrombolysis. C1 [Crescente, Marilena; Thomas, Grace M.; Demers, Melanie; Voorhees, Jaymie R.; Wong, Siu Ling; Wagner, Denisa D.] Childrens Hosp, Immune Dis Inst, Boston, MA 02115 USA. [Crescente, Marilena; Thomas, Grace M.; Demers, Melanie; Voorhees, Jaymie R.; Wong, Siu Ling; Wagner, Denisa D.] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Crescente, Marilena; Thomas, Grace M.; Demers, Melanie; Wong, Siu Ling; Wagner, Denisa D.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Ho-Tin-Noe, Benoit] Univ Paris Diderot, INSERM, UMR698, Paris, France. [Ho-Tin-Noe, Benoit] AP HP Bichat Claude Bernard Hosp, Paris, France. RP Wagner, DD (reprint author), Childrens Hosp, Immune Dis Inst, 3 Blackfan Circle, Boston, MA 02115 USA. EM wagner@idi.harvard.edu RI Thomas, Grace/G-1020-2011 OI Thomas, Grace/0000-0003-4502-7154 FU National Heart, Lung, and Blood Institute of the National Institutes of Health [HL041002] FX This work was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health grant HL041002 (to D.D.W.) NR 38 TC 14 Z9 14 U1 0 U2 3 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD SEP PY 2012 VL 108 IS 3 BP 527 EP 532 DI 10.1160/TH12-01-0046 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 006SO UT WOS:000308839300019 PM 22782575 ER PT J AU Xu, NN Yu, S Moniot, S Weyand, M Blankenfeldt, W AF Xu, Ningna Yu, Shen Moniot, Sebastien Weyand, Michael Blankenfeldt, Wulf TI Crystallization and preliminary crystal structure analysis of the ligand-binding domain of PqsR (MvfR), the Pseudomonas quinolone signal (PQS) responsive quorum-sensing transcription factor of Pseudomonas aeruginosa SO ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY AND CRYSTALLIZATION COMMUNICATIONS LA English DT Article DE LysR; LTTR; quorum sensing; virulence; infectious diseases; signal transduction ID MOLECULAR-REPLACEMENT; ANALYSIS REVEALS; DATA QUALITY; PROTEIN; SYSTEM; DNA; COMMUNICATION; REGULATOR; VIRULENCE; GENE AB The opportunistic bacterial pathogen Pseudomonas aeruginosa employs three transcriptional regulators, LasR, RhlR and PqsR, to control the transcription of a large subset of its genes in a cell-density-dependent process known as quorum sensing. Here, the recombinant production, crystallization and structure solution of the ligand-binding domain of PqsR (MvfR), the LysR-type transcription factor that responds to the Pseudomonas quinolone signal (PQS), a quinolone-based quorum-sensing signal that is unique to P.aeruginosa and possibly a small number of other bacteria, is reported. PqsR regulates the expression of many virulence genes and may therefore be an interesting drug target. The ligand-binding domain (residues 91319) was produced as a fusion with SUMO, and hexagonal-shaped crystals of purified PqsR_91319 were obtained using the vapour-diffusion method. Crystallization in the presence of a PQS precursor allowed data collection to 3.25 angstrom resolution on a synchrotron beamline, and initial phases have been obtained using single-wavelength anomalous diffraction data from seleno-l-methionine-labelled crystals, revealing the space group to be P6522, with unit-cell parameters a = b = 116120, c = 115117 angstrom. C1 [Xu, Ningna; Moniot, Sebastien; Weyand, Michael; Blankenfeldt, Wulf] Univ Bayreuth, Lehrstuhl Biochem, D-95447 Bayreuth, Germany. [Yu, Shen] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Xu, Ningna; Yu, Shen; Blankenfeldt, Wulf] Max Planck Inst Mol Physiol, D-44227 Dortmund, Germany. RP Blankenfeldt, W (reprint author), Univ Bayreuth, Lehrstuhl Biochem, Univ Str 30, D-95447 Bayreuth, Germany. EM wulf.blankenfeldt@uni-bayreuth.de RI Blankenfeldt, Wulf/F-8877-2010 OI Blankenfeldt, Wulf/0000-0001-9886-9668 NR 38 TC 4 Z9 4 U1 1 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1744-3091 J9 ACTA CRYSTALLOGR F JI Acta Crystallogr. F-Struct. Biol. Cryst. Commun. PD SEP PY 2012 VL 68 BP 1034 EP 1039 DI 10.1107/S1744309112032538 PN 9 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 000SA UT WOS:000308407200008 PM 22949189 ER PT J AU Schakman, O Dehoux, M Bouchuari, S Delaere, S Lause, P Decroly, N Shoelson, SE Thissen, JP AF Schakman, O. Dehoux, M. Bouchuari, S. Delaere, S. Lause, P. Decroly, N. Shoelson, S. E. Thissen, J. -P. TI Role of IGF-I and the TNF alpha/NF-kappa B pathway in the induction of muscle atrogenes by acute inflammation SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE insulin-like growth factor I; tumor necrosis factor-alpha; nuclear factor-kappa B; proteolysis; autophagy system; ubiquitin-proteasome system; glucocorticoids; sepsis; skeletal muscle ID GROWTH-FACTOR-I; NECROSIS-FACTOR-ALPHA; STIMULATED PROTEIN-SYNTHESIS; GLUCOCORTICOID-TREATED RATS; ENDOTOXIN-INDUCED DECREASE; SKELETAL-MUSCLE; DEPENDENT PROTEOLYSIS; ATROPHY INVOLVE; GENE-TRANSFER; SEPTIC RATS AB Several catabolic states (sepsis, cancer, etc.) associated with acute inflammation are characterized by a loss of skeletal muscle due to accelerated proteolysis. The main proteolytic systems involved are the autophagy and the ubiquitin-proteasome (UPS) pathways. Among the signaling pathways that could mediate proteolysis induced by acute inflammation, the transcription factor NF-kappa B, induced by TNF alpha, and the transcription factor forkhead box O (FOXO), induced by glucocorticoids (GC) and inhibited by IGF-I, are likely to play a key role. The aim of this study was to identify the nature of the molecular mediators responsible for the induction of these muscle proteolytic systems in response to acute inflammation caused by LPS injection. LPS injection robustly stimulated the expression of several components of the autophagy and the UPS pathways in the skeletal muscle. This induction was associated with a rapid increase of circulating levels of TNF alpha together with a muscular activation of NF-kappa B followed by a decrease in circulating and muscle levels of IGF-I. Neither restoration of circulating IGF-I nor restoration of muscle IGF-I levels prevented the activation of autophagy and UPS genes by LPS. The inhibition of TNF alpha production and muscle NF-kappa B activation, respectively by using pentoxifilline and a repressor of NF-kappa B, did not prevent the activation of autophagy and UPS genes by LPS. Finally, inhibition of GC action with RU-486 blunted completely the activation of these atrogenes by LPS. In conclusion, we show that increased GC production plays a more crucial role than decreased IGF-I and increased TNF alpha/NF-kappa B pathway for the induction of the proteolytic systems caused by acute inflammation. C1 [Thissen, J. -P.] Catholic Univ Louvain, Pole Endocrinol Diabet & Nutr EDIN, IREC, B-1200 Brussels, Belgium. [Schakman, O.] Catholic Univ Louvain, Lab Cell Physiol, Inst Neurosci, B-1200 Brussels, Belgium. [Shoelson, S. E.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Shoelson, S. E.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Thissen, JP (reprint author), Catholic Univ Louvain, Pole Endocrinol Diabet & Nutr EDIN, IREC, Ave Hippocrate 55 Bte B1-55-06, B-1200 Brussels, Belgium. EM jeanpaul.thissen@uclouvain.be FU Fonds de la Recherche Scientifique Medicale (Belgium); National Fund for Scientific Research (Belgium); Association Belge contre les Maladies Neuro-Musculaires (Belgium); Fonds Speciaux de Recherche (Universite Catholique de Louvain, Belgium) FX This work was supported by grants from the Fonds de la Recherche Scientifique Medicale (Belgium), the National Fund for Scientific Research (Belgium), the Association Belge contre les Maladies Neuro-Musculaires (Belgium), and the Fonds Speciaux de Recherche (Universite Catholique de Louvain, Belgium). NR 64 TC 24 Z9 26 U1 0 U2 12 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 SEP PY 2012 VL 303 IS 6 BP E729 EP E739 DI 10.1152/ajpendo.00060.2012 PG 11 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 009BB UT WOS:000308999200005 PM 22739109 ER PT J AU Lunardon, L Tsai, KJ Propert, KJ Fett, N Stanley, JR Werth, VP Tsai, DE Payne, AS AF Lunardon, Luisa Tsai, Kathleen J. Propert, Kathleen J. Fett, Nicole Stanley, John R. Werth, Victoria P. Tsai, Donald E. Payne, Aimee S. TI Adjuvant Rituximab Therapy of Pemphigus A Single-Center Experience With 31 Patients SO ARCHIVES OF DERMATOLOGY LA English DT Article ID MYCOPHENOLATE-MOFETIL; VULGARIS; RESPONSES; DISEASE; TRIAL AB Background: We conducted a retrospective study of patients with pemphigus vulgaris (n = 24) and foliaceus (n = 7) treated with adjuvant rituximab to determine efficacy and adverse events. The end point for efficacy was complete remission of disease taking no or minimal therapy. Observations: Eighteen patients (58%) achieved the study end point. Of these, 13 patients achieved complete remission off systemic therapy. Patients achieving the study end point had a median disease duration before rituximab therapy of 19 months vs 86 months in those not achieving the end point (P =. 01). For the 18 patients achieving the end point, the median (SD) duration of remission was 19 (2) months. Eight of these 18 patients (44%) relapsed from 6 to 17 months after treatment. Serious adverse events attributed to rituximab treatment (osteomyelitis or phlegmon) occurred in 2 patients (6%). In paired serum samples from 10 patients before and after rituximab treatment, the percent change in serum desmoglein index value (median, -80%) was unrelated to the percent change in pneumococcal antibodies (median, +8%) (Spearman rank correlation coefficient r =-0.2). Conclusions: Patients treated with rituximab earlier in the course of disease may have better outcomes. A discussion of rituximab's mechanism of action supports the rationale for early therapy. Prospective clinical studies are necessary to substantiate this observation. C1 [Lunardon, Luisa; Fett, Nicole; Stanley, John R.; Werth, Victoria P.; Payne, Aimee S.] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. [Tsai, Kathleen J.; Tsai, Donald E.] Univ Penn, Dept Hematol Oncol, Philadelphia, PA 19104 USA. [Propert, Kathleen J.] Univ Penn, Dept Biostat, Philadelphia, PA 19104 USA. [Fett, Nicole; Werth, Victoria P.] Vet Affairs Med Ctr, Philadelphia, PA USA. RP Payne, AS (reprint author), Univ Penn, Dept Dermatol, 217A Clin Res Bldg,415 Curie Blvd, Philadelphia, PA 19104 USA. EM paynea@mail.med.upenn.edu FU Department of Dermatology, University of Milan, Milan, Italy; CTSA [UL1-RR-024134]; Skin Disease Research Center grant from the National Institutes of Health, Bethesda, Maryland [AR057217]; [AR052672]; [AR002207]; [AR053505]; [AR057001] FX This work was supported by the Department of Dermatology, University of Milan, Milan, Italy (Dr Lunardon), and grants AR052672 (Dr Stanley), AR002207 (Dr Werth), AR053505 and AR057001 (Dr Payne), CTSA UL1-RR-024134 (Dr Propert), and Skin Disease Research Center grant AR057217 (Drs Stanley and Payne) from the National Institutes of Health, Bethesda, Maryland. NR 17 TC 37 Z9 38 U1 0 U2 1 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 SEP PY 2012 VL 148 IS 9 BP 1031 EP 1036 PG 6 WC Dermatology SC Dermatology GA 007JB UT WOS:000308883500010 PM 22710375 ER PT J AU Danczyk, RC Mitchell, EL Petersen, BD Edwards, J Liem, TK Landry, GJ Moneta, GL AF Danczyk, Rachel C. Mitchell, Erica L. Petersen, Bryan D. Edwards, James Liem, Timothy K. Landry, Gregory J. Moneta, Gregory L. TI Outcomes of Open Operation for Aortoiliac Occlusive Disease After Failed Endovascular Therapy SO ARCHIVES OF SURGERY LA English DT Article ID CRITICAL LIMB ISCHEMIA; CONSENSUS-CLASS-C; RANDOMIZED-TRIALS; EVENTS; ANGIOPLASTY; ASPIRIN; LESIONS; INTERVENTION; METAANALYSIS; CLOPIDOGREL AB Objectives: To compare patient outcomes of primary open operation for aortoiliac occlusive disease (AIOD) with those of secondary open operations for failed endovascular therapy (ET) of AIOD. Design: A retrospective cohort study was performed analyzing demographic characteristics, comorbidities, and outcomes. Setting: Affiliated Veterans Affairs Hospital from January 1, 1998, through March 31, 2010. Patients: Patients who underwent primary open operation for AIOD or secondary open operation for failed ET of AIOD. Main Outcome Measures: Overall survival and limb salvage. Results: Primary open operations (n=153) were 67 aortobifemoral grafts (43.8%), 38 axillobifemoral grafts (24.8%), and 48 femoral-femoral grafts (31.4%). Secondary open operations (n=35) were 28 aortobifemoral grafts (80.0%), 5 axillobifemoral grafts (14.3%), and 2 femoral-femoral grafts (5.7%). Mean (SD) 5-year survival was 48.2%(5.6%) and 66.8%(10.0%), respectively, for patients undergoing primary vs secondary open surgery for AIOD (P=.01). There were 7 amputations during a mean follow-up of 3 years, all in the primary open surgery group. Conclusions: Despite a higher proportion of coronary artery disease and a 20% conversion of claudication to critical limb ischemia after failed ET for AIOD, survival was longer in patients undergoing secondary vs primary open surgery. Patients who underwent open surgery after failed ET for AIOD did not require amputation. Failed ET for AIOD does not lead to worse outcomes for patients undergoing open surgery for AIOD. C1 [Danczyk, Rachel C.; Mitchell, Erica L.; Liem, Timothy K.; Landry, Gregory J.; Moneta, Gregory L.] Oregon Hlth & Sci Univ, Div Vasc Surg, Portland, OR 97239 USA. [Petersen, Bryan D.] Oregon Hlth & Sci Univ, Dotter Inst, Portland, OR 97239 USA. [Petersen, Bryan D.; Edwards, James] Portland VA Med Ctr, Portland, OR USA. RP Mitchell, EL (reprint author), Oregon Hlth & Sci Univ, Div Vasc Surg, 3181 Sam Jackson Pk Rd SW,Mail Stop OP 11, Portland, OR 97239 USA. EM mitcheer@ohsu.edu NR 17 TC 5 Z9 8 U1 0 U2 2 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 SEP PY 2012 VL 147 IS 9 BP 841 EP 845 PG 5 WC Surgery SC Surgery GA 007JD UT WOS:000308883700017 PM 22987177 ER PT J AU Wang, K Liu, TM Wu, JW Horton, NG Lin, CP Xu, C AF Wang, Ke Liu, Tzu-Ming Wu, Juwell Horton, Nicholas G. Lin, Charles P. Xu, Chris TI Three-color femtosecond source for simultaneous excitation of three fluorescent proteins in two-photon fluorescence microscopy SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID SELF-FREQUENCY SHIFT; SOLITON PULSE GENERATION; OPTICAL-FIBERS; SYSTEM; EXPRESSION; TRACKING; CELLS AB We demonstrate a fiber-based, three-color femtosecond source for simultaneous imaging of three fluorescent proteins (FPs) using two-photon fluorescence microscopy (2PM). The three excitation wavelengths at 775 nm, 864 nm and 950 nm, are obtained through second harmonic generation (SHG) of the 1550-nm pump laser and the 1728-nm and 1900-nm solitons generated through soliton self-frequency shift (SSFS) in a large-mode-area (LMA) fiber. These energetic pulses are well matched to the two-photon excitation peaks of red, cyan and yellow fluorescent proteins (TagRFPs, TagCFPs, and TagYFPs) for efficient excitation. We demonstrate simultaneous 2PM of human melanoma cells expressing a "rainbow" combination of these three fluorescent proteins. (c) 2012 Optical Society of America C1 [Wang, Ke; Horton, Nicholas G.; Xu, Chris] Cornell Univ, Sch Appl & Engn Phys, Ithaca, NY 14853 USA. [Liu, Tzu-Ming; Wu, Juwell; Lin, Charles P.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Liu, Tzu-Ming; Wu, Juwell; Lin, Charles P.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Liu, Tzu-Ming] Natl Taiwan Univ, Mol Imaging Ctr, Taipei 10617, Taiwan. [Liu, Tzu-Ming] Natl Taiwan Univ, Inst Biomed Engn, Taipei 10617, Taiwan. RP Wang, K (reprint author), Cornell Univ, Sch Appl & Engn Phys, Ithaca, NY 14853 USA. EM charles_lin@hms.harvard.edu; chris.xu@cornell.edu RI Liu, Tzu-Ming/M-9331-2016 FU National Science Council, Taiwan [101-2918-I-002-022]; NIH [R21RR032392, P50 CA086355, U01HL100402]; NSF Graduate Research Fellowship [DGE-0707428] FX We acknowledge Hensin Tsao's Laboratory at the Wellman Center for Photomedicine for giving us the amelanotic melanoma cells. This work is supported in part by National Science Council, Taiwan, under Grant No. 101-2918-I-002-022 to T. Liu, NIH R21RR032392 to C. Xu, and NIH P50 CA086355 and U01HL100402 to C. P. Lin. N. G. Horton is supported by NSF Graduate Research Fellowship (Grant No. DGE-0707428). NR 17 TC 23 Z9 23 U1 3 U2 23 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 2156-7085 J9 BIOMED OPT EXPRESS JI Biomed. Opt. Express PD SEP 1 PY 2012 VL 3 IS 9 BP 1972 EP 1977 PG 6 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 007AM UT WOS:000308861100002 PM 23024893 ER PT J AU Pettersson, A Graff, RE Bauer, SR Pitt, MJ Lis, RT Stack, EC Martin, NE Kunz, L Penney, KL Ligon, AH Suppan, C Flavin, R Sesso, HD Rider, JR Sweeney, C Stampfer, MJ Fiorentino, M Kantoff, PW Sanda, MG Giovannucci, EL Ding, EL Loda, M Mucci, LA AF Pettersson, Andreas Graff, Rebecca E. Bauer, Scott R. Pitt, Michael J. Lis, Rosina T. Stack, Edward C. Martin, Neil E. Kunz, Lauren Penney, Kathryn L. Ligon, Azra H. Suppan, Catherine Flavin, Richard Sesso, Howard D. Rider, Jennifer R. Sweeney, Christopher Stampfer, Meir J. Fiorentino, Michelangelo Kantoff, Philip W. Sanda, Martin G. Giovannucci, Edward L. Ding, Eric L. Loda, Massimo Mucci, Lorelei A. TI The TMPRSS2:ERG Rearrangement, ERG Expression, and Prostate Cancer Outcomes: A Cohort Study and Meta-analysis SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID TMPRSS2-ERG GENE FUSION; IN-SITU HYBRIDIZATION; TRANSITION ZONE; RADICAL PROSTATECTOMY; FAVORABLE PROGNOSIS; PSA RECURRENCE; GLEASON SCORE; UNITED-STATES; TUMOR-CELLS; ADENOCARCINOMAS AB Background: Whether the genomic rearrangement transmembrane protease, serine 2 (TMPRSS2):v-ets erythroblastosis virus E26 oncogene homolog (ERG) has prognostic value in prostate cancer is unclear. Methods: Among men with prostate cancer in the prospective Physicians' Health and Health Professionals Follow-Up Studies, we identified rearrangement status by immunohistochemical assessment of ERG protein expression. We used Cox models to examine associations of ERG overexpression with biochemical recurrence and lethal disease (distant metastases or cancer-specific mortality). In a meta-analysis including 47 additional studies, we used random-effects models to estimate associations between rearrangement status and outcomes. Results: The cohort consisted of 1,180 men treated with radical prostatectomy between 1983 and 2005. During a median follow-up of 12.6 years, 266 men experienced recurrence and 85 men developed lethal disease. We found no significant association between ERG overexpression and biochemical recurrence [hazard ratio (HR), 0.99; 95% confidence interval (CI), 0.78-1.26] or lethal disease (HR, 0.93; 95% CI, 0.61-1.43). The meta-analysis of prostatectomy series included 5,074 men followed for biochemical recurrence (1,623 events), and 2,049 men followed for lethal disease (131 events). TMPRSS2: ERG was associated with stage at diagnosis [ risk ratio (RR)(>T3 vs. T2), 1.23; 95% CI, 1.16-1.30) but not with biochemical recurrence (RR, 1.00; 95% CI, 0.86-1.17) or lethal disease (RR, 0.99; 95% CI, 0.47-2.09). Conclusions: These results suggest that TMPRSS2: ERG, or ERG overexpression, is associated with tumor stage but does not strongly predict recurrence or mortality among men treated with radical prostatectomy. Impact: This is the largest prospective cohort study to examine associations of ERG overexpression and lethal prostate cancer among men treated with radical prostatectomy. Cancer Epidemiol Biomarkers Prev; 21(9); 1497-509. (C) 2012 AACR. C1 [Pettersson, Andreas; Graff, Rebecca E.; Bauer, Scott R.; Pitt, Michael J.; Penney, Kathryn L.; Rider, Jennifer R.; Stampfer, Meir J.; Fiorentino, Michelangelo; Giovannucci, Edward L.; Ding, Eric L.; Mucci, Lorelei A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Pettersson, Andreas; Graff, Rebecca E.; Pitt, Michael J.; Penney, Kathryn L.; Suppan, Catherine; Rider, Jennifer R.; Stampfer, Meir J.; Giovannucci, Edward L.; Ding, Eric L.; Mucci, Lorelei A.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Sesso, Howard D.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. [Kunz, Lauren] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Stampfer, Meir J.; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Lis, Rosina T.; Stack, Edward C.; Ligon, Azra H.; Loda, Massimo] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Lis, Rosina T.; Stack, Edward C.; Martin, Neil E.; Ligon, Azra H.; Flavin, Richard; Fiorentino, Michelangelo; Loda, Massimo] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Martin, Neil E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Sweeney, Christopher; Kantoff, Philip W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. [Sanda, Martin G.] Beth Israel Deaconess Med Ctr, Dept Surg, Div Urol, Boston, MA 02215 USA. [Bauer, Scott R.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Flavin, Richard] Natl Univ Ireland, Dept Pathol, Galway, Ireland. [Fiorentino, Michelangelo] St Orsola Marcello Malpighi Hosp, Addarii Inst, Pathol Unit, Bologna, Italy. RP Pettersson, A (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA. EM apetters@hsph.harvard.edu; rgraff@hsph.harvard.edu RI Sanda, Martin/A-6202-2013; Sanda, Martin/B-2023-2015; Martin, Neil/E-2193-2014; OI Martin, Neil/0000-0002-8164-8516; Ding, Eric/0000-0002-5881-8097; Rider, Jennifer/0000-0002-2637-6036 FU Dana-Farber/Harvard Cancer Center Specialized Programs of Research Excellence program in prostate cancer [5P50CA090381-08]; National Cancer Institute [T32 CA009001, CA-55075, CA-141298, CA-13389, CA-34944, CA-40360, CA-097193, EDRN U01 CA-113913, PO1 CA-055075]; National Heart, Lung, and Blood Institute [HL-26490, HL-34595]; Prostate Cancer Foundation; National Institute of Health [R25 CA-098566]; Swedish Research Council [2009-7309]; Birgit and Hellmuth Hertz' Foundation FX This work was supported by the Dana-Farber/Harvard Cancer Center Specialized Programs of Research Excellence program in prostate cancer (5P50CA090381-08); and the National Cancer Institute (T32 CA009001 to K. L. Penney, CA-55075, CA-141298, CA-13389, CA-34944, CA-40360, CA-097193, EDRN U01 CA-113913, and PO1 CA-055075); and the National Heart, Lung, and Blood Institute (HL-26490 and HL-34595); and the Prostate Cancer Foundation (to L. A. Mucci and N.E. Martin); and the National Institute of Health (R25 CA-098566 to R. E. Graff); and the Swedish Research Council (Reg. No. 2009-7309 to A. Pettersson); and the Birgit and Hellmuth Hertz' Foundation (to A. Pettersson) NR 84 TC 105 Z9 109 U1 1 U2 13 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 2012 VL 21 IS 9 BP 1497 EP 1509 DI 10.1158/1055-9965.EPI-12-0042 PG 13 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 000NC UT WOS:000308392000014 PM 22736790 ER PT J AU Rathinam, V Vanaja, SK Waggoner, L Sokolovska, A Becker, C Stuart, L Leong, J Fitzgerald, K AF Rathinam, V. Vanaja, S. Kailasan Waggoner, L. Sokolovska, A. Becker, C. Stuart, L. Leong, J. Fitzgerald, K. TI Type I interferons license caspase-11-dependent NLRP3 inflammasome activation by Gram-negative bacteria SO CYTOKINE LA English DT Meeting Abstract CT 10th Joint Meeting of the International-Cytokine-Society (ICS) / Meeting of the International-Society-for-Interferon-and-Cytokine-Research (ISICR) CY SEP 11-14, 2012 CL Geneva, SWITZERLAND SP Int Cytokine Soc (ICS), Int Soc Interferon & Cytokine Res (ISICR) C1 [Rathinam, V.; Waggoner, L.; Fitzgerald, K.] Univ Massachusetts, Sch Med, Div Infect Dis & Immunol, Worcester, MA USA. [Vanaja, S. Kailasan; Leong, J.] Tufts Univ, Sch Med, Medford, MA 02155 USA. [Sokolovska, A.; Becker, C.; Stuart, L.] Mass Gen Hosp, Boston, MA USA. NR 1 TC 0 Z9 0 U1 0 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD SEP PY 2012 VL 59 IS 3 SI SI BP 500 EP 500 DI 10.1016/j.cyto.2012.06.035 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 005FG UT WOS:000308735300038 ER PT J AU Clark, K MacKenzie, K Zhang, J Kristariyanto, Y Petkevicius, K Peggie, M Arthur, S Pedrioli, PG Gray, N McIver, E Cohen, P AF Clark, K. MacKenzie, K. Zhang, J. Kristariyanto, Y. Petkevicius, K. Peggie, M. Arthur, S. Pedrioli, P. G. Gray, N. McIver, E. Cohen, P. TI Identification of the first protein kinase inhibitors that switch macrophages from pro-inflammatory to anti-inflammatory cytokine production SO CYTOKINE LA English DT Meeting Abstract CT 10th Joint Meeting of the International-Cytokine-Society (ICS) / Meeting of the International-Society-for-Interferon-and-Cytokine-Research (ISICR) CY SEP 11-14, 2012 CL Geneva, SWITZERLAND SP Int Cytokine Soc (ICS), Int Soc Interferon & Cytokine Res (ISICR) C1 [Clark, K.; MacKenzie, K.; Zhang, J.; Kristariyanto, Y.; Petkevicius, K.; Peggie, M.; Arthur, S.; Cohen, P.] Univ Dundee, MRC, Prot Phosphorylat Unit, Dundee DD1 4HN, Scotland. [Pedrioli, P. G.] Univ Dundee, SCILLS, Dundee, Scotland. [Gray, N.] Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. [McIver, E.] MRC Technol, London, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD SEP PY 2012 VL 59 IS 3 SI SI BP 547 EP 548 DI 10.1016/j.cyto.2012.06.177 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 005FG UT WOS:000308735300161 ER PT J AU Franklin, TR Shin, J Jagannathan, K Suh, JJ Detre, JA O'Brien, CP Childress, AR AF Franklin, Teresa R. Shin, Joshua Jagannathan, Kanchana Suh, Jesse J. Detre, John A. O'Brien, Charles P. Childress, Anna Rose TI Acute baclofen diminishes resting baseline blood flow to limbic structures: A perfusion fMRI study SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Addiction; fMRI; GABA B agonist; Cerebral blood flow; Smoking cessation; Treatment; Baclofen ID PLACEBO-CONTROLLED TRIAL; SMOKING-CESSATION; ALCOHOL INTAKE; DOUBLE-BLIND; ORBITOFRONTAL CORTEX; NICOTINE REPLACEMENT; TARGETED NALTREXONE; CIGARETTE-SMOKING; NUCLEUS-ACCUMBENS; PROBLEM DRINKERS AB Background: Preclinical and clinical evidence show that the GABA B agonist, baclofen is a promising treatment for addictive disorders; however, until recently its mechanism of action in the human brain was unknown. In previous work we utilized a laboratory model that included a medication versus placebo regimen to examine baclofen's actions on brain circuitry. Perfusion fMRI [measure of cerebral blood flow (CBF)] data acquired 'at rest' before and on the last day of the 21-day medication regimen showed that baclofen diminished CBF bilaterally in the VS, insula and medial orbitofrontal cortex (mOFC). In the present study, we hypothesized that a single dose of baclofen would have effects similar to repeated dosing. Methods: To test our hypothesis, in a crossover design, CBF data were acquired using pseudo continuous arterial spin labeled (pCASL) perfusion fMRI. Subjects were either un-medicated or were administered a 20 mg dose of baclofen approximately 110 min prior to scanning. Results: Acute baclofen diminished mOFC, amygdala, and ventral anterior insula CBF without causing sedation (family-wise error corrected at p = 0.001). Conclusions: Results demonstrate that similar to repeated dosing, an acute dose of baclofen blunts the 'limbic' substrate that is hyper-responsive to drugs and drug cues. Smokers often manage their craving and can remain abstinent for extended periods after quitting, however the risk of eventual relapse approaches 90%. Given that chronic medication may not be a practical solution to the long-term risk of relapse, acute baclofen may be useful on an 'as-needed' basis to block craving during 'at risk' situations. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Franklin, Teresa R.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Detre, John A.] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. [Detre, John A.] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Suh, Jesse J.; O'Brien, Charles P.; Childress, Anna Rose] Univ Penn, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. RP Franklin, TR (reprint author), Univ Penn, Sch Med, Dept Psychiat, 3900 Chestnut St, Philadelphia, PA 19104 USA. EM franklin_t@mail.trc.upenn.edu FU NIH [5-P60-DA-005186-18, 1R21DA025882 - 01A1, MH080729, EB015893] FX Work supported by NIH grants 5-P60-DA-005186-18, 1R21DA025882 - 01A1, MH080729 and EB015893. NR 73 TC 10 Z9 10 U1 0 U2 10 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD SEP 1 PY 2012 VL 125 IS 1-2 BP 60 EP 66 DI 10.1016/j.drugalcdep.2012.03.016 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 004ZS UT WOS:000308720700008 PM 22513380 ER PT J AU Uihlein, AV Leder, BZ AF Uihlein, Alexander V. Leder, Benjamin Z. TI Anabolic Therapies for Osteoporosis SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Article DE Teriparatide; Osteoporosis; Bone mineral density; Parathyroid hormone; Anabolic therapy ID HUMAN PARATHYROID-HORMONE; BONE-MINERAL DENSITY; GROWTH-FACTOR-I; POSTMENOPAUSAL WOMEN; TERIPARATIDE RHPTH(1-34); SCLEROSTIN ANTIBODY; VERTEBRAL FRACTURE; OVARIECTOMIZED RATS; ESTROGEN DEFICIENCY; RANDOMIZED-TRIAL AB As the first FDA-approved anabolic agent for osteoporosis, teriparatide has proven effective for people at highest risk of fracture, despite limitations of expense, route of delivery, and length of treatment. Available data show that combination therapy with teriparatide and antiresorptive agents does not offer a therapeutic advantage. However, treatment with an antiresorptive agent after teriparatide discontinuation is essential to prevent the ensuing bone loss. Although pretreatment with bisphosphonates may somewhat attenuate the anabolic effect of teriparatide, significant gains in bone mineral density are still achieved and prior bisphosphonate use should not dissuade clinicians from using teriparatide in select patients. C1 [Uihlein, Alexander V.; Leder, Benjamin Z.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Leder, BZ (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St,Thier 1051, Boston, MA 02114 USA. EM bzleder@partners.org NR 81 TC 13 Z9 14 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 0889-8529 J9 ENDOCRIN METAB CLIN JI Endocrinol. Metabol. Clin. North Amer. PD SEP PY 2012 VL 41 IS 3 BP 507 EP + DI 10.1016/j.ecl.2012.05.002 PG 20 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 000IO UT WOS:000308380100005 PM 22877427 ER PT J AU Marchetti, R Lanzetta, R Michelow, IC Molinaro, A Silipo, A AF Marchetti, Roberta Lanzetta, Rosa Michelow, Ian C. Molinaro, Antonio Silipo, Alba TI Structural Study of Binding of alpha-Mannosides to Mannan-Binding Lectins SO EUROPEAN JOURNAL OF ORGANIC CHEMISTRY LA English DT Article DE Medicinal chemistry; Natural products; Carbohydrates; Protein design; Chimeric proteins; Lectins; Ebola virus ID TRANSFER DIFFERENCE NMR; PROTEIN-CARBOHYDRATE; DEFICIENT MICE; EBOLA-VIRUS; DC-SIGN; SPECTROSCOPY; RECOGNITION; COMPLEMENT; INFECTION; MBL AB Mannan-binding lectin (MBL) is a soluble, collagen-like C-type lectin that shows the ability to bind certain N-glycosylated carbohydrates through calcium-dependent CRDs. It is composed of three identical polypeptides that form a helical homotrimer further arranged in octadecameric and larger oligomers with a very complex quaternary structure. Several studies have revealed that this protein modulates the immune response, being able to mediate phagocytosis. Unsuitable for industrial-scale production, due to the costs and the difficulties inherent in its extremely complex quaternary structure, its potential for use in successful anti-infective therapy is limited. To produce better, less expensive therapeutic agents, less complex chimeric fusion proteins with similar ligand recognition and enhanced effector functions have been developed. In a previous study, recombinant human MBL (rhMBL) and three L-ficolin (L-FCN) variants containing the MBL carbohydrate recognition domain and varying lengths of the collagenous domain with potential clinical application against glycosylated enveloped viruses such as Ebola and Marburg were produced. It was also demonstrated that one of these chimeras L-FCN/MBL76 had superior effector activity that appeared to be mediated by greater structural flexibility. In this work we have used an NMR-based approach to study, at the atomic level, the mannose-binding activities both of rhMBL and of the chimeric molecule L-FCN/MBL76. Our findings indicate that the analysis of the binding dynamics of immune effector molecules could be useful for the design and optimization of new therapeutic proteins. C1 [Marchetti, Roberta; Lanzetta, Rosa; Molinaro, Antonio; Silipo, Alba] Univ Naples Federico II, Dept Chem Sci, I-80126 Naples, Italy. [Michelow, Ian C.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. RP Silipo, A (reprint author), Univ Naples Federico II, Dept Chem Sci, Via Cintia 4, I-80126 Naples, Italy. EM silipo@unina.it RI Molinaro, Antonio/J-1866-2012; Silipo, Alba/L-5929-2014; OI LANZETTA, Rosa/0000-0002-1472-5825; Molinaro, Antonio/0000-0002-3456-7369 FU National Institutes of Health (NIH) (NIAID) [U01 AI070330] FX This work was funded by the National Institutes of Health (NIH) (NIAID grant U01 AI070330, to I. C. M.). NR 44 TC 3 Z9 3 U1 0 U2 11 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1434-193X J9 EUR J ORG CHEM JI Eur. J. Org. Chem. PD SEP PY 2012 IS 27 BP 5275 EP 5281 DI 10.1002/ejoc.201200697 PG 7 WC Chemistry, Organic SC Chemistry GA 003AP UT WOS:000308580800018 ER PT J AU DaSilva, AF Mendonca, ME Zaghi, S Lopes, M DosSantos, MF Spierings, EL Bajwa, Z Datta, A Bikson, M Fregni, F AF DaSilva, Alexandre F. Mendonca, Mariana E. Zaghi, Soroush Lopes, Mariana DosSantos, Marcos Fabio Spierings, Egilius L. Bajwa, Zahid Datta, Abhishek Bikson, Marom Fregni, Felipe TI tDCS-Induced Analgesia and Electrical Fields in Pain-Related Neural Networks in Chronic Migraine SO HEADACHE LA English DT Article DE transcranial direct current stimulation; chronic migraine; motor cortex; neuromodulation; brain stimulation; chronic pain ID DIRECT-CURRENT STIMULATION; POSITRON-EMISSION-TOMOGRAPHY; TRANSCRANIAL DC STIMULATION; CHRONIC NEUROPATHIC PAIN; VOXEL-BASED MORPHOMETRY; GREY-MATTER CHANGES; HUMAN MOTOR CORTEX; CORTICAL STIMULATION; CUTANEOUS ALLODYNIA; BRAIN-STIMULATION AB Objective. We investigated in a sham-controlled trial the analgesic effects of a 4-week treatment of transcranial direct current stimulation (tDCS) over the primary motor cortex in chronic migraine. In addition, using a high-resolution tDCS computational model, we analyzed the current flow (electric field) through brain regions associated with pain perception and modulation. Methods. Thirteen patients with chronic migraine were randomized to receive 10 sessions of active or sham tDCS for 20 minutes with 2 mA over 4 weeks. Data were collected during baseline, treatment and follow-up. For the tDCS computational analysis, we adapted a high-resolution individualized model incorporating accurate segmentation of cortical and subcortical structures of interest. Results. There was a significant interaction term (time vs group) for the main outcome (pain intensity) and for the length of migraine episodes (ANOVA, P < .05 for both analyses). Post-hoc analysis showed a significant improvement in the follow-up period for the active tDCS group only. Our computational modeling studies predicted electric current flow in multiple cortical and subcortical regions associated with migraine pathophysiology. Significant electric fields were generated, not only in targeted cortical regions but also in the insula, cingulate cortex, thalamus, and brainstem regions. Conclusions. Our findings give preliminary evidence that patients with chronic migraine have a positive, but delayed, response to anodal tDCS of the primary motor cortex. These effects may be related to electrical currents induced in pain-related cortical and subcortical regions. C1 [Mendonca, Mariana E.; Zaghi, Soroush; Datta, Abhishek; Fregni, Felipe] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Lab Neuromodulat, Boston, MA 02114 USA. [DaSilva, Alexandre F.; DosSantos, Marcos Fabio] Univ Michigan, Sch Dent, Dept Biol & Mat Sci, HOPE, Ann Arbor, MI 48109 USA. [Mendonca, Mariana E.; Fregni, Felipe] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA 02114 USA. [Mendonca, Mariana E.; Fregni, Felipe] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Zaghi, Soroush; Lopes, Mariana; Fregni, Felipe] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Berenson Allen Ctr Noninvas Brain Stimulat, Boston, MA 02114 USA. [Spierings, Egilius L.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurol, Boston, MA 02114 USA. [Bajwa, Zahid] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Arnold Pain Ctr, Boston, MA 02114 USA. [Bikson, Marom] CUNY City Coll, Dept Biomed Engn, New York, NY 10031 USA. RP Fregni, F (reprint author), Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Lab Neuromodulat, 125 Nashua St 727, Boston, MA 02114 USA. EM fregni.felipe@mgh.harvard.edu RI DosSantos, Marcos/E-8913-2014 OI DosSantos, Marcos/0000-0002-5997-9693 FU NCRR NIH HHS [UL1 RR024986]; NINDS NIH HHS [K23 NS062946] NR 65 TC 75 Z9 75 U1 1 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0017-8748 J9 HEADACHE JI Headache PD SEP PY 2012 VL 52 IS 8 BP 1283 EP 1295 DI 10.1111/j.1526-4610.2012.02141.x PG 13 WC Clinical Neurology SC Neurosciences & Neurology GA 000RM UT WOS:000308405500008 PM 22512348 ER PT J AU Braun, SE Taube, R Zhu, Q Wong, FE Murakami, A Kamau, E Dwyer, M Qiu, G Daigle, J Carville, A Johnson, RP Marasco, WA AF Braun, Stephen E. Taube, Ran Zhu, Quan Wong, Fay Eng Murakami, Akikazu Kamau, Erick Dwyer, Markryan Qiu, Gang Daigle, Janet Carville, Angela Johnson, R. Paul Marasco, Wayne A. TI In Vivo Selection of CD4(+) T Cells Transduced with a Gamma-Retroviral Vector Expressing a Single-Chain Intrabody Targeting HIV-1 Tat SO HUMAN GENE THERAPY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; MARROW CD34(+) CELLS; GENE-THERAPY; INFECTED PATIENTS; LENTIVIRAL VECTOR; PROGENITOR CELLS; INTRACELLULAR ANTIBODIES; MONONUCLEAR-CELLS; GROWTH ADVANTAGE; RNA INTERFERENCE AB We evaluated the potential of an anti-human immunodeficiency virus (HIV) Tat intrabody (intracellular antibody) to promote the survival of CD4(+) cells after chimeric simian immunodeficiency virus (SIV)/HIV (SHIV) infection in rhesus macaques. Following optimization of stimulation and transduction conditions, purified CD4(+) T cells were transduced with GaLV-pseudotyped retroviral vectors expressing either an anti-HIV-1 Tat or a control single-chain intrabody. Ex vivo intrabody-gene marking was highly efficient, averaging four copies per CD4(+) cell. Upon reinfusion of engineered autologous CD4(+) cells into two macaques, high levels of gene marking (peak of 0.6% and 6.8% of peripheral blood mononuclear cells (PBMCs) and 0.3% or 2.2% of the lymph node cells) were detected in vivo. One week post cell infusion, animals were challenged with SHIV 89.6p and the ability of the anti-HIV Tat intrabody to promote cell survival was evaluated. The frequency of genetically modified CD4(+) T cells progressively decreased, concurrent with loss of CD4(+) cells and elevated viral loads in both animals. However, CD4(+) T cells expressing the therapeutic anti-Tat intrabody exhibited a relative survival advantage over an 8- and 21-week period compared with CD4(+) cells expressing a control intrabody. In one animal, this survival benefit of anti-Tat transduced cells was associated with a reduction in viral load. Overall, these results indicate that a retrovirus-mediated anti-Tat intrabody provided significant levels of gene marking in PBMCs and peripheral tissues and increased relative survival of transduced cells in vivo. C1 [Taube, Ran; Zhu, Quan; Murakami, Akikazu; Kamau, Erick; Dwyer, Markryan; Daigle, Janet; Marasco, Wayne A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Braun, Stephen E.; Wong, Fay Eng; Qiu, Gang; Carville, Angela; Johnson, R. Paul] Harvard Univ, Sch Med, New England Primate Res Ctr, Southborough, MA 01772 USA. [Johnson, R. Paul] Massachusetts Gen Hosp, Ragon Inst Massachusetts Gen Hosp MIT & Harvard, Charlestown, MA 02129 USA. [Johnson, R. Paul] Massachusetts Gen Hosp, Infect Dis Unit, Charlestown, MA 02129 USA. RP Marasco, WA (reprint author), Dana Farber Canc Inst, 44 Binney St,Mailstop Jimmy Fund 824, Boston, MA 02115 USA. EM wayne_marasco@dfci.harvard.edu FU National Institutes of Health (NIH) [RR14447, AI 61797, CA 73473, RR00164, RR00168]; developmental award from the Partners/Fenway/Shattuck Center for AIDS Research (CFAR); NIH-funded program [AI 42851] FX These studies were supported by National Institutes of Health (NIH) grants RR14447, AI 61797, CA 73473, RR00164, and RR00168, and by a developmental award from the Partners/Fenway/Shattuck Center for AIDS Research (CFAR), an NIH-funded program (AI 42851). We thank Johnson Wong (Massachusetts General Hospital) for the 6G12 anti-CD3 hybridoma, Dr. M. Gately (Hoffman-La Roche) for the IL-2, Keith Reimann (Beth Israel Deaconess Medical Center, Harvard Medical School) for the SHIV 89.6p challenge stock, Richard C. Mulligan (Harvard Medical School) for the U2OS human osteosarcoma cell line, David A. Williams (Children's Hospital Boston) for the HEL-GFP cell line, and Garry Nolan (Stanford University School of Medicine) for the LZRS vector and the Phoenix packaging cell line. We also thank Lynda Fernsten and the NEPRC Primate Medicine staff for expert care of the animals, Jackie Gillis and Michelle Connole for assistance with flow cytometry. NR 67 TC 7 Z9 7 U1 0 U2 6 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD SEP PY 2012 VL 23 IS 9 BP 917 EP 931 DI 10.1089/hum.2011.184 PG 15 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 007VM UT WOS:000308916500002 PM 22734618 ER PT J AU Lorenzo, LS Vazquez, GH Zaratiegui, RM Tondo, L Baldessarini, RJ AF Lorenzo, Laura S. Vazquez, Gustavo H. Zaratiegui, Rodolfo M. Tondo, Leonardo Baldessarini, Ross J. TI Characteristics of bipolar disorder patients given antidepressants SO HUMAN PSYCHOPHARMACOLOGY-CLINICAL AND EXPERIMENTAL LA English DT Article DE antidepressants; bipolar disorders; depression ID I DISORDER; DEPRESSION; PATTERNS; PHARMACOTHERAPY; PRESCRIPTION; MORTALITY; RISKS AB Evidence concerning efficacy of antidepressants in bipolar disorder remains inconsistent and inconclusive. As the appropriate clinical use for such patients remains unclear, we characterized outpatients with bipolar disorders who were or were not treated with antidepressants. Clinical data were collected systematically from consecutive outpatients in 11 participating Argentine mood-disorder clinics in 20072008. Diagnoses met DSM-IV criteria, supported by structured interviews based on the MINI-500. Of 338 outpatients diagnosed with bipolar I (45.0%), II (29.3%), or not-otherwise-specified (NOS) (25.7%) disorder, 128 (37.9%) received antidepressants. Subjects given antidepressants or not did not differ significantly by presence or severity of current depression or being suicidal but were more likely to be women. Bipolar I disorder patients were three times less likely than types II or NOS to receive an antidepressant, with or without a mood-stabilizer or antimanic agent. Despite inconclusive evidence for efficacy and safety of antidepressants in various phases of bipolar disorders, 37.9% of such patients were receiving an antidepressant in 11 Argentine outpatient clinics. Antidepressant treatment was least likely with type I disorder and was independent of current depression and not associated with more use of mood-stabilizing or antimanic agents. Copyright (c) 2012 John Wiley & Sons, Ltd. C1 [Vazquez, Gustavo H.] Univ Palermo, Dept Neurosci, RA-1425 Buenos Aires, DF, Argentina. [Lorenzo, Laura S.; Zaratiegui, Rodolfo M.] Psinapsys Psychiat Ctr, La Plata, Buenos Aires, Argentina. [Vazquez, Gustavo H.; Tondo, Leonardo; Baldessarini, Ross J.] Massachusetts Gen Hosp, McLean Div, Int Consortium Bipolar Disorder Res, Boston, MA 02114 USA. [Vazquez, Gustavo H.; Tondo, Leonardo; Baldessarini, Ross J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Tondo, Leonardo] Lucio Bini Mood Disorders Ctr, Cagliari, Sardinia, Italy. RP Vazquez, GH (reprint author), Univ Palermo, Dept Neurosci, Mario Bravo 1259, RA-1425 Buenos Aires, DF, Argentina. EM gvazquez@palermo.edu FU Bruce J. Anderson Foundation; McLean Private Donors Psychopharmacology Research Fund FX This study was supported in part by a grant from the Bruce J. Anderson Foundation and by the McLean Private Donors Psychopharmacology Research Fund (to R.J.B.). No author or immediate family member has current financial relations with corporate organizations that might present potential conflicts of interest in the work presented. NR 35 TC 9 Z9 9 U1 2 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-6222 J9 HUM PSYCHOPHARM CLIN JI Hum. Psychopharmacol.-Clin. Exp. PD SEP PY 2012 VL 27 IS 5 BP 486 EP 491 DI 10.1002/hup.2253 PG 6 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry; Psychology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry; Psychology GA 008BE UT WOS:000308931300007 PM 22927134 ER PT J AU Scofield, AK Radfar, L Ice, JA Vista, E Anaya, JM Houston, G Lewis, D Stone, DU Chodosh, J Hefner, K Lessard, CJ Moser, KL Scofield, RH AF Scofield, Amanda Kyle Radfar, Lida Ice, John A. Vista, Evan Anaya, Juan-Manuel Houston, Glen Lewis, David Stone, Donald U. Chodosh, James Hefner, Kimberly Lessard, Christopher J. Moser, Kathy L. Scofield, Robert Hal TI Relation of Sensory Peripheral Neuropathy in Sjogren Syndrome to Anti-Ro/SSA SO JCR-JOURNAL OF CLINICAL RHEUMATOLOGY LA English DT Article DE Sjogren syndrome; autoantibodies; peripheral neuropathy; vitamin B-12 ID SALIVARY-GLAND BIOPSY; SYSTEMIC LUPUS; COBALAMIN DEFICIENCY; MANIFESTATIONS AB Background: Sjogren syndrome is a common, chronic autoimmune disease that typically produces inflammation and poor function of the salivary and lacrimal glands. Other organs can be affected, including the nervous system. Sensory peripheral neuropathy is a common manifestation of the disease. Methods: Eight-eight patients attending a dry eyes dry mouth clinic were diagnosed to have primary Sjogren syndrome and underwent a neurological examination. Anti-Ro (or SSA) and anti-La (or SSB) were determined using immunodiffusion as well as Inno-Lia and BioPlex ANA screen. Serum vitamin 1312 levels were determined using an enzyme-linked microtiter plate assay. Results: Twenty-seven (31%) of the 88 patients had peripheral neuropathy as defined by loss of light touch, proprioception, or vibratory sensation. Anti-Ro and anti-La were found by immunodiffusion in 12 patients, and 8 of these 12 had neuropathy (chi(2) = 8.46, P = 0.0036, odds ratio = 6.0 compared to those without precipitating anti-Ro and anti-La). Of the 27 patients with only anti-Ro by immunodiffusion, 13 (48.1%) had neuropathy (chi(2) = 5.587, P = 0.018, compared to those without anti-Ro). There was no relationship of the other, more sensitive measures of anti-Ro and anti-La to neuropathy. In addition, we found no association of serum vitamin B-12 levels to neuropathy among these patients with Sjogren syndrome. Conclusions: Sensory peripheral neuropathy is common among patients with Sjogren syndrome and is associated with the presence of anti-Ro and anti-La when determined by immunodiffusion. C1 [Scofield, Amanda Kyle; Ice, John A.; Hefner, Kimberly; Lessard, Christopher J.; Moser, Kathy L.; Scofield, Robert Hal] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Program, Oklahoma City, OK 73104 USA. [Scofield, Robert Hal] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA. [Moser, Kathy L.] Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA. Univ Oklahoma, Hlth Sci Ctr, Dept Ophthalmol, Oklahoma City, OK USA. [Radfar, Lida; Houston, Glen; Lewis, David; Stone, Donald U.] Univ Oklahoma, Hlth Sci Ctr, Coll Dent, Oklahoma City, OK 73190 USA. [Stone, Donald U.] Dean McGee Eye Inst, Oklahoma City, OK USA. [Scofield, Robert Hal] Dept Vet Affairs Med Ctr, Oklahoma City, OK USA. [Chodosh, James] Harvard Univ, Sch Med, Boston, MA USA. [Chodosh, James] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Univ Nacl Rosario, Sch Med & Hlth Sci, Ctr Autoimmune Dis Res, Bogota, Colombia. RP Scofield, RH (reprint author), 825 NE 13th St,MS24, Oklahoma City, OK 73104 USA. EM hal-scofield@omrf.ouhsc.edu RI Anaya, Juan-Manuel/J-1960-2016; OI Anaya, Juan-Manuel/0000-0002-6444-1249; Universidad del Rosario, Biblioteca/0000-0003-3491-9392; Houston, Graeme/0000-0002-9786-7975 FU Center of Research Translation award from the National Institute of Arthritis, Musculoskeletal, and Skin Diseases; Research to Prevent Blindness grant FX This work was supported in part by a Center of Research Translation award from the National Institute of Arthritis, Musculoskeletal, and Skin Diseases. D.U.S. and J.C. were supported by a Research to Prevent Blindness grant to the OUHSC Department of Ophthalmology and the Dean McGee Eye Institute. NR 27 TC 5 Z9 5 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-1608 J9 JCR-J CLIN RHEUMATOL JI JCR-J. Clin. Rheumatol. PD SEP PY 2012 VL 18 IS 6 BP 290 EP 293 DI 10.1097/RHU.0b013e3182675e4f PG 4 WC Rheumatology SC Rheumatology GA 009GW UT WOS:000309015200003 PM 22955477 ER PT J AU Lieberman, JR Freiberg, AA Lavernia, CJ AF Lieberman, Jay R. Freiberg, Andrew A. Lavernia, Carlos J. TI Practice Management Strategies Among Members of the American Association of Hip and Knee Surgeons SO JOURNAL OF ARTHROPLASTY LA English DT Article DE practice management; total hip arthroplasty; total knee arthroplasty AB A survey was conducted at the 2011 Annual Meeting of the American Association of Hip and Knee Surgeons to determine current practice management strategies among its members. This article summarizes the audience responses to a number of different questions. related to type of practice, use of physician extenders, potential sources of ancillary income, consulting activity, royalties, emergency department call, and the use of the electronic medical record. C1 [Lieberman, Jay R.] Univ Connecticut, Ctr Hlth, Dept Orthopaed Surg, New England Musculoskeletal Inst, Farmington, CT 06030 USA. [Freiberg, Andrew A.] Massachusetts Gen Hosp, Orthopaed Associates, Boston, MA 02114 USA. [Lavernia, Carlos J.] Inst Orthoped, Miami, FL USA. RP Lieberman, JR (reprint author), Univ Connecticut, Ctr Hlth, Dept Orthopaed Surg, New England Musculoskeletal Inst, 263 Farmington Ave,MC 5456, Farmington, CT 06030 USA. NR 2 TC 2 Z9 2 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD SEP PY 2012 VL 27 IS 8 SU 1 BP 17 EP 19 DI 10.1016/j.arth.2012.02.030 PG 3 WC Orthopedics SC Orthopedics GA 004HD UT WOS:000308671100005 PM 22503334 ER PT J AU Kwon, YM Jacobs, JJ MacDonald, SJ Potter, HG Fehring, TK Lombardi, AV AF Kwon, Young-Min Jacobs, Joshua J. MacDonald, Steven J. Potter, Hollis G. Fehring, Thomas K. Lombardi, Adolph V. TI Evidence-Based Understanding of Management Perils for Metal-on-Metal Hip Arthroplasty Patients SO JOURNAL OF ARTHROPLASTY LA English DT Article DE metal-on-metal hip arthroplasty; MoM bearing; pseudotumors ID INFLAMMATORY PSEUDOTUMOR; VOLUMETRIC WEAR; REPLACEMENT; COBALT; RESURFACINGS; CHROMIUM; HYPERSENSITIVITY; PROSTHESES; INFECTION; RESPONSES AB Adverse biological reactions causing failures of metal-on-metal (MoM) hip arthroplasty can be local or systemic. Both dose-dependent cytotoxicity of wear debris leading to subsequent necrosis of periprosthetic soft tissues and adaptive immunity may play an important role in pathogenesis in susceptible patients. There appears to be a spectrum of clinical presentations of adverse soft tissue reactions, reflecting a complex interplay of implant, surgical, and patient factors. A systematic treatment approach is helpful in optimizing evidence-based management of MoM patients. Although specialized tests such as metal ion levels are a useful diagnostic tool for evaluating MoM hip arthroplasty patients, overreliance on any single investigative tool in clinical decision-making process should be avoided. Future research focusing on diagnostic tools for detecting adverse periprosthetic soft tissue necrosis as well as optimization of MoM bearings and modular connections to further diminish wear and corrosion is warranted. C1 [Kwon, Young-Min] Harvard Univ, Dept Orthopaed Surg, Massachusetts Gen Hosp, Med Sch,Adult Reconstruct Surg Unit, Boston, MA 02114 USA. [Jacobs, Joshua J.] Rush Univ, Med Ctr, Dept Orthopaed Surg, Chicago, IL 60612 USA. [MacDonald, Steven J.] Univ Western Ontario, Dept Orthopaed Surg, London, ON, Canada. [Potter, Hollis G.] Cornell Univ, Weill Med Coll, Hosp Special Surg, Dept Radiol & Imaging, New York, NY 10021 USA. [Fehring, Thomas K.] Ortho Carolina Hip & Knee Ctr, Charlotte, NC USA. [Lombardi, Adolph V.] Ohio State Univ, Joint Implant Surg Inc, New Albany, OH USA. RP Kwon, YM (reprint author), Harvard Univ, Dept Orthopaed Surg, Massachusetts Gen Hosp, Med Sch,Adult Reconstruct Surg Unit, Boston, MA 02114 USA. RI MacDonald, Steven/B-6173-2015 NR 39 TC 16 Z9 16 U1 1 U2 11 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD SEP PY 2012 VL 27 IS 8 SU 1 BP 20 EP 25 DI 10.1016/j.arth.2012.03.029 PG 6 WC Orthopedics SC Orthopedics GA 004HD UT WOS:000308671100006 PM 22608691 ER PT J AU Bozic, KJ Lau, EC Ong, KL Vail, TP Rubash, HE Berry, DJ AF Bozic, Kevin J. Lau, Edmund C. Ong, Kevin L. Vail, Thomas P. Rubash, Harry E. Berry, Daniel J. TI Comparative Effectiveness of Metal-On-Metal and Metal-On-Polyethylene Bearings in Medicare Total Hip Arthroplasty Patients SO JOURNAL OF ARTHROPLASTY LA English DT Article DE THA bearings; comparative effectiveness; Medicare ID FOLLOW-UP; AGE AB The purpose of this study was to compare the risk of complication and revision total hip arthroplasty (THA) in Medicare THA patients with different bearings. Using the 100% Medicare database (2005-2009), the adjusted risk of complication and revision THA was calculated for 148 827 THA patients (93 929 metal-on-polyethylene, 49 646 metal-on-metal, 5252 ceramic-on ceramic). Adjusted risk of deep vein thrombosis, dislocation, periprosthetic joint infection (PJI), mechanical loosening, periprosthetic fracture, and revision THA at up to 4 years postoperatively was compared using Cox regression. After adjusting for patient and hospital factors, metal-on-metal bearings were associated with higher risk of PJI (P = .001), mechanical loosening (P < .001), and deep vein thrombosis (P = .031) than metal-on-polyethylene bearings and higher risk of PH (P = .014) than ceramic-on-ceramic bearings. Overall short-term revision rates did not vary significantly across bearing types, consistent with registry data. The benefits of hard-on-hard bearings in Medicare patients remain unproven, and further study is needed to compare long-term complication and revision rates in Medicare THA patients with different bearing types. C1 [Bozic, Kevin J.; Vail, Thomas P.] Univ Calif San Francisco, Dept Orthopaed Surg, San Francisco, CA 94143 USA. [Bozic, Kevin J.] Univ Calif San Francisco, Philip R Lee Inst Hlth Policy Studies, San Francisco, CA 94143 USA. [Lau, Edmund C.] Exponent Inc, Menlo Pk, CA USA. [Ong, Kevin L.] Exponent Inc, Philadelphia, PA USA. [Rubash, Harry E.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Berry, Daniel J.] Mayo Clin, Dept Orthopaed Surg, Rochester, MN USA. RP Bozic, KJ (reprint author), Univ Calif San Francisco, Dept Orthopaed Surg, 500 Parnassus,MU 320W, San Francisco, CA 94143 USA. NR 16 TC 14 Z9 14 U1 0 U2 7 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD SEP PY 2012 VL 27 IS 8 SU 1 BP 37 EP 40 DI 10.1016/j.arth.2012.03.031 PG 4 WC Orthopedics SC Orthopedics GA 004HD UT WOS:000308671100009 PM 22608689 ER PT J AU Carter, EA Paul, KW Barrow, SA Fischman, AJ Tompkins, RG AF Carter, Edward A. Paul, Kasie W. Barrow, Sandra A. Fischman, Alan J. Tompkins, Ronald G. TI Previous Burn Injury Predisposes Mice to Lipopolysaccharide-Induced Changes in Glucose Metabolism SO JOURNAL OF BURN CARE & RESEARCH LA English DT Article ID MULTIPLE ORGAN FAILURE; BROWN ADIPOSE-TISSUE; THERMAL-INJURY; INSULIN-RESISTANCE; SEPSIS; EPIDEMIOLOGY; REACTIVITY; POSTBURN; PATIENT; MUSCLE AB In mice, it has been demonstrated that at 7 days after burn injury, injection of lipopolysaccharide (LPS) is more lethal than the same dose at 1 day after injury. In the present study, we examined the effect of LPS injection to mice burned 7 days previously on glucose metabolism ([F-18] 2-fluoro-2-deoxy-D-glucose [(18)FDG] uptake) in vivo. CD-1 male mice (25-28 g, Charles River Breeding Laboratories, Wilmington, MA) were anesthetized, backs shaven, and subjected to dorsal full thickness burn on 25% TBSA. Sham-treated animals were used as controls. Six days after burn injury, all mice were fasted overnight. One half of the burned and sham controls were subsequently injected IP with LPS (10 mg/kg; Escherichia coli). The remaining animals were injected with saline IP. Two hours later, all mice were injected IV with 50 mu Ci of F-18 FDG. One hour later, the animals were euthanized, and biodistribution was measured. Tissues were weighed, and radioactivity was measured with a well-type gamma counter. Results were expressed as %dose/g tissue, mean +/- SEM. The combination of burn 7 days previously and LPS significantly increased mortality compared to animals with burn alone, LPS alone, or sham controls. Burn injury 7 days previously caused a significant decrease in (18)FDG uptake by the brain compared to sham controls. The combination of LPS and burn injury 7 days previously produced a significant increase in (18)FDG uptake by brown adipose tissue and heart compared with either treatment separately. LPS produced a significant increase in (18)FDG uptake by lung, spleen, and gastrointestinal tract of the sham animals, changes that were different in mice burned 7 days previously and injected with LPS. The present results suggest that burn injury 7 days previously predisposes mice to alterations in (18)FDG uptake produced by LPS. These changes may relate, in part, to the increased lethality of LPS injection in previously burned mice. (J Burn Care Res 2012;33:683-689) C1 [Carter, Edward A.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Carter, Edward A.; Fischman, Alan J.; Tompkins, Ronald G.] Harvard Univ, Sch Med, Boston, MA USA. [Paul, Kasie W.; Barrow, Sandra A.; Fischman, Alan J.; Tompkins, Ronald G.] Shriners Hosp Children, Boston, MA USA. [Barrow, Sandra A.; Tompkins, Ronald G.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Carter, EA (reprint author), Massachusetts Gen Hosp, Pediat Gastrointestinal Unit, 114 16th St, Charlestown, MA 02129 USA. FU National Institutes of Health; Shriners Hospitals for Children FX Supported in part by grants from the National Institutes of Health and Shriners Hospitals for Children. NR 28 TC 0 Z9 1 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1559-047X J9 J BURN CARE RES JI J. Burn Care Res. PD SEP-OCT PY 2012 VL 33 IS 5 BP 683 EP 689 DI 10.1097/BCR.0b013e31825d6a86 PG 7 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA 004VG UT WOS:000308708700023 PM 22961012 ER PT J AU Hsia, E Seggelke, S Gibbs, J Hawkins, RM Cohlmia, E Rasouli, N Wang, C Kam, I Draznin, B AF Hsia, Elisa Seggelke, Stacey Gibbs, Joanna Hawkins, R. Matthew Cohlmia, Elizabeth Rasouli, Neda Wang, Cecilia Kam, Igal Draznin, Boris TI Subcutaneous Administration of Glargine to Diabetic Patients Receiving Insulin Infusion Prevents Rebound Hyperglycemia SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GLYCEMIC CONTROL; INTRAVENOUS INSULIN; BASAL INSULIN; MANAGEMENT; PROTOCOL; TRANSITION; SURGERY; ORDERS; US AB Context: Transition of diabetic patients from iv insulin infusion to sc insulin frequently results in rebound hyperglycemia. Objectives: We hypothesized that initiation of a long-acting insulin therapy concurrently with iv insulin infusion would decrease the rate of rebound hyperglycemia after discontinuation of the insulin infusion. Design and Intervention: Sixty-one diabetic patients receiving iv insulin therapy participated in this prospective randomized study. Subjects in the intervention group received daily injections of glargine sc (0.25 U/kg body weight) starting within 12 h of initiation of iv insulin infusion. Capillary blood glucose measurements were obtained up to 12 h after discontinuation of insulin infusion. Rebound hyperglycemia was defined as a blood glucose level greater than 180 mg/dl. Setting: The study was conducted at the University of Colorado Hospital. Patients: Sixty-one hospitalized patients with known type 1 or type 2 diabetes receiving iv insulin infusion participated in the study. Main Outcome: The primary outcome of this study was to compare the rates of rebound hyperglycemia between the control and the intervention groups after iv insulin infusion is discontinued. Results: Overall, 29 subjects in the control group (93.5%) had at least one glucose value above 180 mg/dl during the 12-h follow-up period. This was significantly greater than the rate of rebound hyperglycemia in the intervention group (10 subjects or 33.3%, P < 0.001). The effect of the intervention was apparent in subjects who presented with diabetic ketoacidosis, after solid organ transplantation, and in patients with other surgical and medical diagnoses. There were three hypoglycemic measurements in two control subjects (68, 62, and 58 mg/dl) and none in the intervention group. Conclusions: Once-daily sc insulin glargine administered during iv insulin infusion is a safe method for preventing future rebound hyperglycemia, without increased risk of hypoglycemia. (J Clin Endocrinol Metab 97: 3132-3137, 2012) C1 [Hsia, Elisa; Seggelke, Stacey; Gibbs, Joanna; Hawkins, R. Matthew; Cohlmia, Elizabeth; Rasouli, Neda; Wang, Cecilia; Draznin, Boris] Univ Colorado, Sch Med, Div Endocrinol, Dept Med,Div Transplant Surg, Denver, CO 80045 USA. [Kam, Igal] Univ Colorado, Sch Med, Dept Surg, Denver, CO 80045 USA. [Rasouli, Neda; Wang, Cecilia] Denver Vet Affairs Med Ctr, Denver, CO 80045 USA. RP Draznin, B (reprint author), Univ Colorado, Sch Med, Div Endocrinol Metab & Diabet, MS 8106,12801 E 17th Ave,RC1 S RM 7103, Aurora, CO 80045 USA. EM boris.draznin@ucdenver.edu FU Sanofi-Aventis; Veterans Affairs Career Development Award FX This work was supported by a grant from Sanofi-Aventis. C.W. is a recipient of the Veterans Affairs Career Development Award. NR 26 TC 15 Z9 15 U1 0 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2012 VL 97 IS 9 BP 3132 EP 3137 DI 10.1210/jc.2012-1244 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 004PF UT WOS:000308692900050 PM 22685233 ER PT J AU Joffe, H Deckersbach, T Lin, NU Makris, N Skaar, TC Rauch, SL Dougherty, DD Hall, JE AF Joffe, Hadine Deckersbach, Thilo Lin, Nancy U. Makris, Nikos Skaar, Todd C. Rauch, Scott L. Dougherty, Darin D. Hall, Janet E. TI Metabolic Activity in the Insular Cortex and Hypothalamus Predicts Hot Flashes: An FDG-PET Study SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; BREAST-CANCER; POSTMENOPAUSAL WOMEN; TAMOXIFEN; SYMPTOMS; ACTIVATION; DEPRESSION; MENOPAUSE; LIFE; THERMOREGULATION AB Context: Hot flashes are a common side effect of adjuvant endocrine therapies (AET; leuprolide, tamoxifen, aromatase inhibitors) that reduce quality of life and treatment adherence in breast cancer patients. Because hot flashes affect only some women, preexisting neurobiological traits might predispose to their development. Previous studies have implicated the insula during the perception of hot flashes and the hypothalamus in thermoregulatory dysfunction. Objective: The aim of the study was to understand whether neurobiological factors predict hot flashes. Design: [18F]-Fluorodeoxyglucose (FDG) positron emission tomography (PET) brain scans coregistered with structural magnetic resonance imaging were used to determine whether metabolic activity in the insula and hypothalamic thermoregulatory and estrogen-feedback regions measured before and in response to AET predict hot flashes. Findings were correlated with CYP2D6 genotype because of CYP2D6 polymorphism associations with tamoxifen-induced hot flashes. Outcome Measures: We measured regional cerebral metabolic rate of glucose uptake (rCMRglu) in the insula and hypothalamus on FDG-PET. Results: Of 18 women without hot flashes who began AET, new-onset hot flashes were reported by 10 (55.6%) and were detected objectively in nine (50%) participants. Prior to the use of all AET, rCMRglu in the insula (P <= 0.01) and hypothalamic thermoregulatory (P = 0.045) and estrogen-feedback (P = 0.007) regions was lower in women who reported developing hot flashes. In response to AET, rCMRglu was further reduced in the insula in women developing hot flashes (P <= 0.02). Insular and hypothalamic rCMRglu levels were lower in intermediate than extensive CYP2D6 metabolizers. Conclusions: Trait neurobiological characteristics predict hot flashes. Genetic variability in CYP2D6 may underlie the neurobiological predisposition to hot flashes induced by AET. (J Clin Endocrinol Metab 97: 3207-3215, 2012) C1 [Joffe, Hadine] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Womens Mental Hlth,Dept Psychiat, Boston, MA 02114 USA. [Deckersbach, Thilo; Makris, Nikos; Dougherty, Darin D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Psychiat Neuroimaging Res Program, Boston, MA 02114 USA. [Lin, Nancy U.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Makris, Nikos] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Morphometr Anal,Dept Neurol, Boston, MA 02114 USA. [Skaar, Todd C.] Indiana Univ, Sch Med, Dept Med, Div Clin Pharmacol, Indianapolis, IN 46202 USA. [Rauch, Scott L.] Harvard Univ, McLean Hosp, Sch Med, Belmont, MA 02478 USA. [Hall, Janet E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Reprod Endocrine Unit, Boston, MA 02114 USA. RP Joffe, H (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Womens Mental Hlth,Dept Psychiat, Simches Res Bldg,185 Cambridge St,Suite 2000, Boston, MA 02114 USA. EM hjoffe@partners.org FU Harvard Medical School Fund for Women's Health, Friends of Dana-Farber Cancer Institute; Massachusetts General Hospital Claflin Distinguished Scholar Award; NIMH; NIH; Cephalon; Tufts University; Janssen Pharmaceuticals; Forest Research Institute; Shire Development Inc.; Medtronic; Cyberonics; Northstar; MGH Psychiatry Academy; BrainCells Inc.; Systems Research and Applications Corporation; Boston University; National Association of Social Workers Massachusetts; Massachusetts Medical Society; Oxford University Press FX This work was supported by the Harvard Medical School Fund for Women's Health, Friends of Dana-Farber Cancer Institute, and the Massachusetts General Hospital Claflin Distinguished Scholar Award.; N.U.L., N.M., T. C. S., S. L. R., D. D. D., and J.E.H. have nothing to declare. H.J. has received grant support from the Harvard Medical School Fund for Women's Health, Friends of the Dana Farber Cancer Institute, and the Massachusetts General Hospital Claflin Distinguished Scholar Award to support this study. H.J. currently receives research support from NIMH, NIH, and Cephalon, and consults for Sunovion, Pfizer, and Noven. T. D. has received research support from NIH, Tufts University, Janssen Pharmaceuticals, Forest Research Institute, Shire Development Inc., Medtronic, Cyberonics, and Northstar. T. D. has received honoraria, consultant fees, and/or royalties from MGH Psychiatry Academy, BrainCells Inc., Systems Research and Applications Corporation, Boston University, Tufts University, National Association of Social Workers Massachusetts, Massachusetts Medical Society, and Oxford University Press. NR 41 TC 7 Z9 7 U1 0 U2 4 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 SEP PY 2012 VL 97 IS 9 BP 3207 EP 3215 DI 10.1210/jc.2012-1413 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 004PF UT WOS:000308692900059 PM 22723326 ER PT J AU Namkung, J Song, JY Jo, HH Kim, MR Lew, YO Donahoe, PK MacLaughlin, DT Kim, JH AF Namkung, Jeong Song, Jae Yen Jo, Hyun Hee Kim, Mee Ran Lew, Young Oak Donahoe, Patricia K. MacLaughlin, David T. Kim, Jang Heub TI Mullerian Inhibiting Substance Induces Apoptosis of Human Endometrial Stromal Cells in Endometriosis SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HUMAN OVARIAN-CANCER; IN-VIVO; EPITHELIAL-CELLS; CYCLE ARREST; II RECEPTOR; GROWTH; EXPRESSION; HORMONE; MECHANISM; PATHOGENESIS AB Context: Mullerian inhibiting substance (MIS) is produced in Sertoli cells of fetal testis and causes regression of Mullerian ducts in male embryos. MIS also can induce the cell cycle arrest and apoptosis in Mullerian duct-derived tumors in vivo and in vitro. Objective: Our objective was to investigate the expression of MIS type II receptor (MISR II) and whether MIS can inhibit the proliferation and induce apoptosis in primary cultures of endometrial stromal cells (ESC) of endometriosis. Design and Settings: In vitro experiments were performed in the university research laboratory. Participants: Tissue samples from 12 patients who had undergone evisceration for ovarian endometrial cysts were included in this study. Interventions and Main Outcome Measures: The expression of MISR II in ESC was investigated by immunohistochemistry. The cell viability and apoptosis in ESC treated with MIS was measured by methylthiazoletetrazolium assay and annexin V analysis. The expression of regulatory proteins in ESC treated with MIS was shown by Western blotting. Results: ESC showed specific immunostaining for the MISR II. ESC treated with MIS exhibited 32% growth inhibition (P = 0.0001). The changes in cell cycle distribution after MIS exposure at 72 h demonstrated that S and G(2)M phases were decreased; G(0)G(1) and sub-G(0)G(1) phases were increased. ESC treated with MIS showed 13.72% annexin V-fluorescein isothiocyanate positivity. In the ESCs, which contain defective p16, MIS increased the expression of pocket proteins p107 and p130 and decreased E2F transcription factor 1. Conclusions: The results support a central role for MIS in endometriosis. Although the precise mechanism of MIS-mediated inhibition of ESC growth has not been fully defined, these data suggest that MIS has activity against ESC in vitro and may also be an effective targeted therapy for endometriosis. (J Clin Endocrinol Metab 97: 3224-3230, 2012) C1 [Namkung, Jeong; Song, Jae Yen; Jo, Hyun Hee; Kim, Mee Ran; Lew, Young Oak; Kim, Jang Heub] Catholic Univ Korea, Dept Obstet & Gynecol, Coll Med, Seoul 137701, South Korea. [Donahoe, Patricia K.; MacLaughlin, David T.] Harvard Univ, Pediat Surg Res Labs, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Kim, JH (reprint author), Catholic Univ Korea, Dept Obstet & Gynecol, Coll Med, 505 Banpo Dong, Seoul 137701, South Korea. EM janghkim@catholic.ac.kr NR 35 TC 11 Z9 11 U1 1 U2 4 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 SEP PY 2012 VL 97 IS 9 BP 3224 EP 3230 DI 10.1210/jc.2012-1538 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 004PF UT WOS:000308692900061 PM 22761458 ER PT J AU Gianetti, E Hall, JE Au, MG Kaiser, UB Quinton, R Stewart, JA Metzger, DL Pitteloud, N Mericq, V Merino, PM Levitsky, LL Izatt, L Lang-Muritano, M Fujimoto, VY Dluhy, RG Chase, ML Crowley, WF Plummer, L Seminara, SB AF Gianetti, Elena Hall, Janet E. Au, Margaret G. Kaiser, Ursula B. Quinton, Richard Stewart, Jane A. Metzger, Daniel L. Pitteloud, Nelly Mericq, Veronica Merino, Paulina M. Levitsky, Lynne L. Izatt, Louise Lang-Muritano, Mariarosaria Fujimoto, Victor Y. Dluhy, Robert G. Chase, Matthew L. Crowley, William F., Jr. Plummer, Lacey Seminara, Stephanie B. TI When Genetic Load Does Not Correlate with Phenotypic Spectrum: Lessons from the GnRH Receptor (GNRHR) SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM; FUNCTIONAL HYPOTHALAMIC AMENORRHEA; KALLMANN-SYNDROME; PEPTIDE LOCALIZATION; LUTEINIZING-HORMONE; PUBERTAL CHANGES; MUTATIONS; EXPRESSION; DEFICIENCY AB Context: A broad spectrum of GnRH-deficient phenotypes has been identified in individuals with both mono-and biallelic GNRHR mutations. Objective: The objective of the study was to determine the correlation between the severity of the reproductive phenotype(s) and the number and functional severity of rare sequence variants in GNRHR. Subjects: Eight hundred sixty-three probands with different forms of GnRH deficiency, 46 family members and 422 controls were screened for GNRHR mutations. The 70 subjects (32 patients and 38 family members) harboring mutations were divided into four groups (G1-G4) based on the functional severity of the mutations (complete or partial loss of function) and the number of affected alleles (monoallelic or biallelic) with mutations, and these classes were mapped on their clinical phenotypes. Results: The prevalence of heterozygous rare sequence variants in GNRHR was significantly higher in probands vs. controls (P < 0.01). Among the G1-G3 groups (homozygous subjects with successively decreasing severity and number of mutations), the hypogonadotropic phenotype related to their genetic load. In contrast, subjects in G4, with only monoallelic mutations, demonstrated a greater diversity of clinical phenotypes. Conclusions: In patients with GnRH deficiency and biallelic mutations in GNRHR, genetic burden defined by severity and dose is associated with clinical phenotype. In contrast, for patients with monoallelic GNRHR mutations this correlation does not hold. Taken together, these data indicate that as-yet-unidentified genetic and/or environmental factors may combine with singly mutated GNRHR alleles to produce reproductive phenotypes. (J Clin Endocrinol Metab 97: E1798-E1807, 2012) C1 [Gianetti, Elena; Hall, Janet E.; Au, Margaret G.; Chase, Matthew L.; Crowley, William F., Jr.; Plummer, Lacey; Seminara, Stephanie B.] Massachusetts Gen Hosp, Harvard Ctr Reprod Sci, Dept Med, Boston, MA 02114 USA. [Gianetti, Elena; Hall, Janet E.; Au, Margaret G.; Chase, Matthew L.; Crowley, William F., Jr.; Plummer, Lacey; Seminara, Stephanie B.] Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, Boston, MA 02114 USA. [Seminara, Stephanie B.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Levitsky, Lynne L.] Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. [Kaiser, Ursula B.] Brigham & Womens Hosp, Harvard Ctr Reprod Sci, Boston, MA 02115 USA. [Kaiser, Ursula B.; Dluhy, Robert G.] Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. [Quinton, Richard] Newcastle Univ, Endocrine Res Grp, Inst Med Genet, Newcastle Upon Tyne Hosp, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England. [Quinton, Richard] Newcastle Upon Tyne Hosp, Dept Endocrinol, Newcastle Upon Tyne, Tyne & Wear, England. [Stewart, Jane A.] Int Ctr Life, Newcastle Fertil Ctr LIFE, Biosci Ctr, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England. [Metzger, Daniel L.] British Columbia Childrens Hosp, Dept Endocrinol, Vancouver, BC V6H 3V4, Canada. [Metzger, Daniel L.] British Columbia Childrens Hosp, Diabet Unit, Vancouver, BC V6H 3V4, Canada. [Pitteloud, Nelly] CHU Vaudois, Dept Endocrinol Diabet & Metab, CH-1011 Lausanne, Switzerland. [Mericq, Veronica] Univ Chile, Fac Med, Inst Maternal & Child Res, Santiago 8389100, Chile. [Merino, Paulina M.] Univ Chile, Fac Med, Dept Pediat, Santiago 8389100, Chile. [Izatt, Louise] Guys Hosp, Dept Clin Genet, London SE1 9RT, England. [Lang-Muritano, Mariarosaria] Univ Childrens Hosp, Dept Endocrinol & Diabetol, CH-8032 Zurich, Switzerland. [Fujimoto, Victor Y.] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA. RP Seminara, SB (reprint author), Massachusetts Gen Hosp, Harvard Ctr Reprod Sci, Dept Med, 55 Fruit St,BHX 504, Boston, MA 02114 USA. EM sseminara@partners.org RI Mericq, Veronica/F-3927-2010; PITTELOUD, Nelly/K-2709-2014; OI Mericq, Veronica/0000-0003-2287-0181 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development/National Institutes of Health, Specialized Cooperative Centers Program in Reproduction and Infertility Research [U54 5U54HD028138]; [R01-HD-15788]; [R01-HD-19938]; [R01-HD-42708]; [R01-HD-043341] FX This work was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development/National Institutes of Health through Cooperative Agreement U54 5U54HD028138 as part of the Specialized Cooperative Centers Program in Reproduction and Infertility Research, and Grants R01-HD-15788, R01-HD-19938, R01-HD-42708, and R01-HD-043341. NR 56 TC 12 Z9 12 U1 2 U2 4 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 SEP PY 2012 VL 97 IS 9 BP E1798 EP E1807 DI 10.1210/jc.2012-1264 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 004PF UT WOS:000308692900023 PM 22745237 ER PT J AU Spatz, JM Fields, EE Yu, EW Pajevic, PD Bouxsein, ML Sibonga, JD Zwart, SR Smith, SM AF Spatz, J. M. Fields, E. E. Yu, E. W. Pajevic, P. Divieti Bouxsein, M. L. Sibonga, J. D. Zwart, S. R. Smith, S. M. TI Serum Sclerostin Increases in Healthy Adult Men during Bed Rest SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID NUTRITIONAL-STATUS; BONE-FORMATION; EXPRESSION; SOST AB Context: Animal models and human studies suggest that osteocytes regulate the skeleton's response to mechanical unloading in part by an increase in sclerostin. However, few studies have reported changes in serum sclerostin in humans exposed to reduced mechanical loading. Objective: We determined changes in serum sclerostin and bone turnover markers in healthy adult men undergoing controlled bed rest. Design, Setting, and Participants: Seven healthy adult men (31 +/- 3 yr old) underwent 90 d of 6 head down tilt bed rest at the University of Texas Medical Branch Institute for Translational Sciences-Clinical Research Center. Outcomes: Serum sclerostin, PTH, vitamin D, bone resorption and formation markers, urinary calcium and phosphorus excretion, and 24-h pooled urinary markers of bone resorption were evaluated before bed rest [baseline (BL)] and at bed rest d 28 (BR-28), d 60 (BR-60), and d 90 (BR-90). Bone mineral density was measured at BL, BR-60, and 5 d after the end of the study (BR+5). Data are reported as mean +/- SD. Results: Consistent with prior reports, bone mineral density declined significantly (1-2% per month) at weight-bearing skeletal sites. Serum sclerostin was elevated above BL at BR-28 (+29 +/- 20%; P = 0.003) and BR-60 (+42 +/- 31%; P < 0.001), with a lesser increase at BR-90 (+22 +/- 21%; P = 0.07). Serum PTH levels were reduced at BR-28 (-17 +/- 16%; P = 0.02) and BR-60 (-24 +/- 14%; P = 0.03) and remained lower than BL at BR-90 (-21 +/- 21%; P = 0.14), but did not reach statistical significance. Serum bone turnover markers were unchanged; however, urinary bone resorption markers and calcium were significantly elevated at all time points after bed rest (P < 0.01). Conclusions: In healthy men subjected to controlled bed rest for 90 d, serum sclerostin increased, with a peak at 60, whereas serum PTH declined, and urinary calcium and bone resorption markers increased. (J Clin Endocrinol Metab 97: E1736-E1740, 2012) C1 [Spatz, J. M.; Bouxsein, M. L.] Beth Israel Deaconess Med Ctr, Ctr Adv Orthoped Studies, Boston, MA 02215 USA. [Spatz, J. M.; Bouxsein, M. L.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Spatz, J. M.] Harvard Massachusetts Inst Technol, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Sibonga, J. D.; Smith, S. M.] NASA, Lyndon B Johnson Space Ctr, Human Adaptat & Countermeasures Div, Houston, TX 77058 USA. [Spatz, J. M.; Yu, E. W.; Pajevic, P. Divieti; Bouxsein, M. L.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Fields, E. E.] Enterprise Advisory Serv Inc, Houston, TX 77058 USA. [Zwart, S. R.] Univ Space Res Assoc, Houston, TX 77058 USA. RP Spatz, JM (reprint author), Beth Israel Deaconess Med Ctr, Ctr Adv Orthoped Studies, RN 118,330 Brookline Ave, Boston, MA 02215 USA. EM jspatz@bidmc.harvard.edu FU NASA's Human Research Program [NASA NNX10AE39G]; National Institutes of Health [R21 AR057522, UH2AR059655]; Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology Bioastronautics Ph.D. Program; Northrop Grumman Aerospace Systems Ph.D. Training Fellowship FX The authors acknowledge NASA's Human Research Program (NASA NNX10AE39G), the National Institutes of Health (R21 AR057522, UH2AR059655), Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology Bioastronautics Ph.D. Program, and Northrop Grumman Aerospace Systems Ph.D. Training Fellowship for providing support for this work. NR 19 TC 43 Z9 43 U1 0 U2 4 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 SEP PY 2012 VL 97 IS 9 BP E1736 EP E1740 DI 10.1210/jc.2012-1579 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 004PF UT WOS:000308692900014 PM 22767636 ER PT J AU Wildman, RP Tepper, PG Crawford, S Finkelstein, JS Sutton-Tyrrell, K Thurston, RC Santoro, N Sternfeld, B Greendale, GA AF Wildman, Rachel P. Tepper, Ping G. Crawford, Sybil Finkelstein, Joel S. Sutton-Tyrrell, Kim Thurston, Rebecca C. Santoro, Nanette Sternfeld, Barbara Greendale, Gail A. TI Do Changes in Sex Steroid Hormones Precede or Follow Increases in Body Weight during the Menopause Transition? Results from The Study of Women's Health Across the Nation SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; ESTROGEN-RECEPTOR-ALPHA; BINDING GLOBULIN; REPRODUCTIVE HORMONES; INSULIN-RESISTANCE; ESTRADIOL; MICE; ADIPOSITY; OBESITY; FAT AB Context: Whether menopause-related changes in sex steroids account for midlife weight gain in women or whether weight drives changes in sex steroids remains unanswered. Objective: The objective of the study was to characterize the potential reciprocal nature of the associations between sex hormones and their binding protein with waist circumference in midlife women. Design, Setting, and Participants: The study included 1528 women (mean age 46 yr) with 9 yr of follow-up across the menopause transition from the observational Study of Women's Health Across the Nation. Main Outcome Measures: Waist circumference, SHBG, testosterone, FSH, and estradiol were measured. Results: Current waist circumference predicted future SHBG, testosterone, and FSH but not vice versa. For each (SD) higher current waist circumference, at the subsequent visit SHBG was lower by 0.04-0.15 (SD), testosterone was higher by 0.08-0.13 (SD), and log(2) FSH was lower by 0.15-0.26 (SD). Estradiol results were distinct from those above, changing direction across the menopause transition. Estradiol and waist circumference were negatively associated in early menopausal transition stages and positively associated in later transition stages (for each (SD) higher current waist circumference, future estradiol was lower by 0.15 (SD) in pre- and early perimenopause and higher by 0.38 (SD) in late peri- and postmenopause; P for interaction <0.001). In addition, they appeared to be reciprocal, with current waist circumference associated with future estradiol and current estradiol associated with future waist circumference. However, associations in the direction of current waist circumference predicting future estradiol levels were of considerably larger magnitude than the reverse. Conclusions: These Study of Women's Health Across the Nation data suggest that the predominant temporal sequence is that weight gain leads to changes in sex steroids rather than vice versa. (J Clin Endocrinol Metab 97: E1695-E1704, 2012) C1 [Wildman, Rachel P.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA. [Tepper, Ping G.; Sutton-Tyrrell, Kim] Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. [Crawford, Sybil] Univ Massachusetts, Div Prevent & Behav Med, Worcester, MA 01655 USA. [Finkelstein, Joel S.] Massachusetts Gen Hosp, Endocrine Unit, Dept Med, Boston, MA 02114 USA. [Thurston, Rebecca C.] Univ Pittsburgh, Dept Psychiat, Sch Med, Pittsburgh, PA 15213 USA. [Santoro, Nanette] Univ Colorado, Dept Obstet & Gynecol, Sch Med, Aurora, CO 80045 USA. [Sternfeld, Barbara] Kaiser Permanente, Div Res, Oakland, CA 94612 USA. [Greendale, Gail A.] Univ Calif Los Angeles, David Geffen Sch Med, Div Geriatr, Los Angeles, CA 90095 USA. RP Wildman, RP (reprint author), Albert Einstein Coll Med, Dept Epidemiol, 1300 Morris Pk Ave,Belfer Room 1309, Bronx, NY 10461 USA. EM rachel.wildman@einstein.yu.edu FU National Institutes of Health, Department of Health and Human Services through National Institute on Aging, the National Institute of Nursing Research; National Institutes of Health Office of Research on Women's Health [NR004061, AG012505, AG012535, AG012531, AG012539, AG012546, AG012553, AG012554, AG012495] FX The Study of Women's Health Across the Nation has grant support from the National Institutes of Health, Department of Health and Human Services through the National Institute on Aging, the National Institute of Nursing Research, and the National Institutes of Health Office of Research on Women's Health (Grants NR004061; AG012505, AG012535, AG012531, AG012539, AG012546, AG012553, AG012554, and AG012495). NR 37 TC 21 Z9 22 U1 0 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2012 VL 97 IS 9 BP E1695 EP E1704 DI 10.1210/jc.2012-1614 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 004PF UT WOS:000308692900008 PM 22723312 ER PT J AU Hoggatt, J Scadden, DT AF Hoggatt, Jonathan Scadden, David T. TI The stem cell niche: tissue physiology at a single cell level SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID BONE-MARROW NICHE; HEMATOPOIETIC PROGENITOR CELLS; COLONY-STIMULATING FACTOR; SELF-RENEWAL; OSTEOBLAST PROLIFERATION; ENDOTHELIAL-CELLS; NERVOUS-SYSTEM; MOBILIZATION; MICROENVIRONMENT; RECEPTOR AB Stem cells are the critical unit affecting tissue maintenance, regeneration, and repair, with particular relevance to the tissues with high cell turnover. Stem cell regulation accommodates the conflicting needs of prompt responsiveness to injury and long-term preservation through quiescence. They are, in essence, the fundamental unit by which a tissue handles changing physiologic needs throughout the lifetime of the organism. As such, they are the focal point of dynamic tissue function, and their governance is physiology expressed at a cellular and molecular level. Here, we discuss the multiple components representing the stem cell niche in hematopoiesis and argue for a unbiased mapping of the niche constituents under different conditions as the first step in developing systems physiology. C1 [Hoggatt, Jonathan; Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Hoggatt, Jonathan; Scadden, David T.] Harvard Univ, Dept Stem Cells & Regenerat Biol, Cambridge, MA 02138 USA. [Hoggatt, Jonathan; Scadden, David T.] Harvard Stem Cell Inst, Cambridge, MA USA. RP Scadden, DT (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, 185 Cambridge St,CPZN-4265A, Boston, MA 02114 USA. EM david_scadden@harvard.edu FU NIH training grant [HL087735]; NIH [HL44851, HL100402, HL97794, HL108655, CA1631910]; Ellison Medical Foundation; Peabody Foundation FX J. Hoggart is supported by NIH training grant HL087735 and is a consultant for Fate Therapeutics. D.T. Scadden is supported by the NIH (HL44851, HL100402, HL97794, HL108655, and CA1631910), the Ellison Medical Foundation, and the Peabody Foundation and is a consultant for Fate Therapeutics, Hospira, GSK, and Bone Therapeutics. NR 70 TC 21 Z9 21 U1 0 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 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 2012 VL 122 IS 9 BP 3029 EP 3034 DI 10.1172/JCI60238 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 002EC UT WOS:000308513100002 PM 22945635 ER PT J AU Brent, GA AF Brent, Gregory A. TI Mechanisms of thyroid hormone action SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID RECEPTOR-ALPHA GENE; MONOCARBOXYLATE TRANSPORTER 8; RETINOIC ACID RECEPTORS; CELL-SURFACE RECEPTOR; EMBRYONIC STEM-CELLS; V-ERBA ONCOGENE; ACTION IN-VIVO; TYPE-3 DEIODINASE; RESPONSE ELEMENT; PROTEIN-KINASE AB Our understanding of thyroid hormone action has been substantially altered by recent clinical observations of thyroid signaling defects in syndromes of hormone resistance and in a broad range of conditions, including profound mental retardation, obesity, metabolic disorders, and a number of cancers. The mechanism of thyroid hormone action has been informed by these clinical observations as well as by animal models and has influenced the way we view the role of local ligand availability; tissue and cell-specific thyroid hormone transporters, corepressors, and coactivators; thyroid hormone receptor (TR) isoform-specific action; and cross-talk in metabolic regulation and neural development. In some cases, our new understanding has already been translated into therapeutic strategies, especially for treating hyperlipidemia and obesity, and other drugs are in development to treat cardiac disease and cancer and to improve cognitive function. C1 [Brent, Gregory A.] VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA 90073 USA. [Brent, Gregory A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Brent, Gregory A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90095 USA. RP Brent, GA (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Med, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM gbrent@ucla.edu FU Veterans Affairs Merit Review Funds; NIH [R01 CA89364] FX This work was supported by Veterans Affairs Merit Review Funds and NIH grant R01 CA89364. NR 135 TC 129 Z9 134 U1 9 U2 55 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 2012 VL 122 IS 9 BP 3035 EP 3043 DI 10.1172/JCI60047 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 002EC UT WOS:000308513100003 PM 22945636 ER PT J AU Butovsky, O Siddiqui, S Gabriely, G Lanser, AJ Dake, B Murugaiyan, G Doykan, CE Wu, PM Gali, RR Iyer, LK Lawson, R Berry, J Krichevsky, AM Cudkowicz, ME Weiner, HL AF Butovsky, Oleg Siddiqui, Shafiuddin Gabriely, Galina Lanser, Amanda J. Dake, Ben Murugaiyan, Gopal Doykan, Camille E. Wu, Pauline M. Gali, Reddy R. Iyer, Lakshmanan K. Lawson, Robert Berry, James Krichevsky, Anna M. Cudkowicz, Merit E. Weiner, Howard L. TI Modulating inflammatory monocytes with a unique microRNA gene signature ameliorates murine ALS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; NF-KAPPA-B; REGULATORY T-CELLS; CENTRAL-NERVOUS-SYSTEM; HEXANUCLEOTIDE REPEAT; TRANSCRIPTION FACTOR; SIGNALING PATHWAY; DENDRITIC CELLS; INHERITED ALS; BREAST-CANCER AB Amyotrophic lateral sclerosis (ALS) is a progressive disease associated with neuronal cell death that is thought to involve aberrant immune responses. Here we investigated the role of innate immunity in a mouse model of ALS. We found that inflammatory monocytes were activated and that their progressive recruitment to the spinal cord, but not brain, correlated with neuronal loss. We also found. a decrease in resident microglia in the spinal cord with disease progression. Prior to disease onset, splenic Ly6C(hi) monocytes expressed a polarized macrophage phenotype (M1 signature), which included increased levels of chemokine receptor CCR2. As disease onset neared, microglia expressed increased CCL2 and other chemotaxis-associated molecules, which led to the recruitment of monocytes to the CNS by spinal cord-derived microglia. Treatment with anti-Ly6C mAb modulated the Ly6Chi monocyte cytokine profile, reduced monocyte recruitment to the spinal cord, diminished neuronal loss, and extended survival. In humans with ALS, the analogous monocytes (CD14(+)CD16(-)) exhibited an ALS-specific microRNA inflammatory signature similar to that observed in the ALS mouse model, linking the animal model and the human disease. Thus, the profile of monocytes in ALS patients may serve as a bio-marker for disease stage or progression. Our results suggest that recruitment of inflammatory monocytes plays an important role in disease progression and that modulation of these cells is a potential therapeutic approach. C1 [Butovsky, Oleg; Siddiqui, Shafiuddin; Gabriely, Galina; Lanser, Amanda J.; Dake, Ben; Murugaiyan, Gopal; Doykan, Camille E.; Wu, Pauline M.; Krichevsky, Anna M.; Weiner, Howard L.] Harvard Univ, Brigham & Womens Hosp, Ctr Neurol Dis, Sch Med,Dept Neurol, Boston, MA 02115 USA. [Gali, Reddy R.] Harvard Univ, Harvard Clin & Translat Sci Ctr, Sch Med, Boston, MA 02115 USA. [Iyer, Lakshmanan K.] Tufts Sch Med, Dept Neurosci, Boston, MA USA. [Lawson, Robert; Berry, James; Cudkowicz, Merit E.] Harvard Univ, Dept Neurol, Massachusetts Gen Hosp, Sch Med,Neurol Clin Trial Unit, Boston, MA 02115 USA. RP Weiner, HL (reprint author), Harvard Univ, Brigham & Womens Hosp, Ctr Neurol Dis, Sch Med,Dept Neurol, 77 Ave Louis Pasteur,HIM 730, Boston, MA 02115 USA. EM hweiner@rics.bwh.harvard.edu OI Iyer, Lakshmanan/0000-0001-9167-6396 FU Amyotrophic Lateral Sclerosis Association; NIH [AG027437]; Tufts Center for Neuroscience Research [P30 NS047243] FX This work was supported in part by the Amyotrophic Lateral Sclerosis Association; NIH grant AG027437; Tufts Center for Neuroscience Research P30 NS047243. The Harvard NeuroDiscovery Center provided CSF specimens (Biomarker Study). We thank Prize4Life for providing SOD I mice; V. Kuchroo and D. Selkoe for critical discussions; N. Kassam for technical support. NR 81 TC 135 Z9 136 U1 1 U2 17 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 2012 VL 122 IS 9 BP 3063 EP 3087 DI 10.1172/JCI62636 PG 25 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 002EC UT WOS:000308513100011 PM 22863620 ER PT J AU Carracedo, A Weiss, D Leliaert, AK Bhasin, M de Boer, VCJ Laurent, G Adams, AC Sundvall, M Song, SJ Ito, K Finley, LS Egia, A Libermann, T Gerhart-Hines, Z Puigserver, P Haigis, MC Maratos-Flier, E Richardson, AL Schafer, ZT Pandolfi, PP AF Carracedo, Arkaitz Weiss, Dror Leliaert, Amy K. Bhasin, Manoj de Boer, Vincent C. J. Laurent, Gaelle Adams, Andrew C. Sundvall, Maria Song, Su Jung Ito, Keisuke Finley, Lydia S. Egia, Ainara Libermann, Towia Gerhart-Hines, Zachary Puigserver, Pere Haigis, Marcia C. Maratos-Flier, Elefteria Richardson, Andrea L. Schafer, Zachary T. Pandolfi, Pier P. TI A metabolic prosurvival role for PML in breast cancer SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID FATTY-ACID OXIDATION; DIET-INDUCED OBESITY; BASEMENT-MEMBRANE CULTURES; GENE-EXPRESSION PATTERNS; LEUKEMIA NUCLEAR-BODIES; LIPID-METABOLISM; PPAR-ALPHA; TRANSCRIPTIONAL COACTIVATOR; CELLULAR SENESCENCE; MOLECULAR SUBTYPES AB Cancer cells exhibit an aberrant metabolism that facilitates more efficient production of biomass and hence tumor growth and progression. However, the genetic cues modulating this metabolic switch remain largely undetermined. We identified a metabolic function for the promyelocytic leukemia (PML) gene, uncovering an unexpected role for this bona fide tumor suppressor in breast cancer cell survival. We found that PML acted. as both a negative regulator of PPAR gamma coactivator 1A (PGC1A) acetylation and a potent activator of PPAR signaling and fatty acid oxidation. We further showed that PML promoted ATP production and inhibited anoikis. Importantly, PML expression allowed luminal filling in 3D basement membrane breast culture models, an effect that was reverted by the pharmacological inhibition of fatty acid oxidation. Additionally, immunohistochemical analysis of breast cancer biopsies revealed that PML was overexpressed in a subset of breast cancers and enriched in triple-negative cases. Indeed, PML expression in breast cancer correlated strikingly with reduced time to recurrence, a gene signature of poor prognosis, and activated PPAR signaling. These findings have important therapeutic implications, as PML and its key role in fatty acid oxidation metabolism are amenable to pharmacological suppression, a potential future mode of cancer prevention and treatment. C1 [Carracedo, Arkaitz; Weiss, Dror; Sundvall, Maria; Song, Su Jung; Ito, Keisuke; Egia, Ainara; Pandolfi, Pier P.] Harvard Univ, Beth Israel Deaconess Med Ctr, Canc Genet Program, Sch Med,Beth Israel Deaconess Canc Ctr,Dept Med, Boston, MA 02215 USA. [Carracedo, Arkaitz; Weiss, Dror; Sundvall, Maria; Song, Su Jung; Ito, Keisuke; Egia, Ainara; Pandolfi, Pier P.] Harvard Univ, Beth Israel Deaconess Med Ctr, Canc Genet Program, Sch Med,Beth Israel Deaconess Canc Ctr,Dept Patho, Boston, MA 02215 USA. [Carracedo, Arkaitz] Basque Fdn Sci, CIC BioGUNE, Bizkaia, Spain. [Carracedo, Arkaitz] Basque Fdn Sci, IKERBASQUE, Bizkaia, Spain. [Leliaert, Amy K.; Schafer, Zachary T.] Univ Notre Dame, Dept Biol Sci, Notre Dame, IN 46556 USA. [Bhasin, Manoj; Libermann, Towia] Harvard Univ, Beth Israel Deaconess Med Ctr, Div Interdisciplinary Med & Biotechnol, Sch Med, Boston, MA 02215 USA. [de Boer, Vincent C. J.; Laurent, Gaelle; Finley, Lydia S.; Haigis, Marcia C.] Harvard Univ, Sch Med, Dept Pathol, Paul F Glenn Labs Biol Mech Aging, Boston, MA 02115 USA. [Adams, Andrew C.; Maratos-Flier, Elefteria] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Adams, Andrew C.; Maratos-Flier, Elefteria] Beth Israel Deaconess Med Ctr, Dept Endocrinol, Boston, MA 02215 USA. [Gerhart-Hines, Zachary; Puigserver, Pere] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Richardson, Andrea L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Pandolfi, PP (reprint author), 330 Brookline Ave,CLS-401, Boston, MA 02215 USA. EM ppandolf@bidmc.harvard.edu RI cancer, biogune/H-7276-2012; Carracedo, Arkaitz/F-7029-2011; de Boer, Vincent/F-4879-2010; de Boer, Vincent/L-2196-2016; OI Carracedo, Arkaitz/0000-0001-5957-1260; de Boer, Vincent/0000-0001-9928-1698; Libermann, Towia/0000-0002-4006-8179 FU NIH; NCI Harvard SPORE in breast cancer [2P50 CA089393]; Breast Cancer Research Foundation; EMBO; Ramon y Cajal award (Spanish Ministry of Education); ISCIII [PI10/01484]; Marie Curie IRG grant [277043]; Basque Government of Education [PI2012-03] FX We thank P. Hemmerich and I. Kitabayashi for sharing valuable reagents. We thank all members of the Pandolfi lab, in particular, R.M. Hobbs, D. Sciaranghella, M.S. Song, and L. Salmena as well as J. Brugge, A. Grassian, and M. Serrano for advice and technical support. This work was supported by NIH grants to P.P. Pandolfi and partially supported by the NCI Harvard SPORE in breast cancer (2P50 CA089393) and the Breast Cancer Research Foundation (to A.L. Richardson). The work of A. Carracedo was supported by EMBO, the Ramon y Cajal award (Spanish Ministry of Education), the ISCIII (PI10/01484), the Marie Curie IRG grant (277043), and the Basque Government of Education (PI2012-03). NR 82 TC 70 Z9 77 U1 1 U2 22 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 2012 VL 122 IS 9 BP 3088 EP 3100 DI 10.1172/JCI62129 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 002EC UT WOS:000308513100012 PM 22886304 ER PT J AU Liu, YQ Berendsen, AD Jia, SD Lotinun, S Baron, R Ferrara, N Olsen, BR AF Liu, Yanqiu Berendsen, Agnes D. Jia, Shidong Lotinun, Sutada Baron, Roland Ferrara, Napoleone Olsen, Bjorn R. TI Intracellular VEGF regulates the balance between osteoblast and adipocyte differentiation SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID MESENCHYMAL STEM-CELLS; ENDOTHELIAL GROWTH-FACTOR; COLONY-STIMULATING FACTOR; BONE-MARROW; LAMIN A/C; ADIPOGENIC DIFFERENTIATION; TRANSCRIPTION FACTOR; OSTEOGENIC CELLS; OSTEOPOROSIS; MICE AB Osteoporotic bones have reduced spongy bone mass, altered bone architecture, and increased marrow fat. Bone marrow stem cells from osteoporotic patients are more likely to differentiate into adipocytes than control cells, suggesting that adipocyte differentiation may play a role in osteoporosis. VEGF is highly expressed in osteoblastic precursor cells and is known to stimulate bone formation. Here we tested the hypothesis that VEGF is also an important regulator of cell fate, determining whether differentiation gives rise to osteoblasts or adipocytes. Mice with conditional VEGF deficiency in osteoblastic precursor cells exhibited an osteoporosis-like phenotype characterized by reduced bone mass and increased bone marrow fat. In addition, reduced VEGF expression in mesenchymal stem cells resulted in reduced osteoblast and increased adipocyte differentiation. Osteoblast differentiation was reduced when VEGF receptor 1 or 2 was knocked down but was unaffected by treatment with recombinant VEGF or neutralizing antibodies against VEGF. Our results suggested that VEGF controls differentiation in mesenchymal stem cells by regulating the transcription factors RUNX2 and PPAR gamma 2 as well as through a reciprocal interaction with nuclear envelope proteins lamin A/C. Importantly, our data support a model whereby VEGF regulates differentiation through an intracrine mechanism that is distinct from the role of secreted VEGF and its receptors. C1 [Liu, Yanqiu; Berendsen, Agnes D.; Olsen, Bjorn R.] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. [Jia, Shidong] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Lotinun, Sutada; Baron, Roland] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Ferrara, Napoleone] Genentech Inc, San Francisco, CA 94080 USA. RP Olsen, BR (reprint author), Harvard Univ, Sch Dent Med, Dept Dev Biol, 188 Longwood Ave, Boston, MA 02115 USA. EM yanqiu_liu@post.harvard.edu; olsen@hms.harvard.edu OI Lotinun, Sutada/0000-0002-5127-3039 FU NIH [AR36819, AR36820, AR48564]; Harvard School of Dental Medicine FX We thank Hiroki Suemoto for help with isolation of bone marrow cells, Yulia Pittel for secretarial assistance, Naomi Fukai and Sofiya Plotkina for technical support, and Carl Walkly and Louise Purton for helpful discussions. We thank Nicholas Brady and Antonios Aliprantis for microCT analysis and the Nikon Imaging Center at Harvard Medical School for help with light and fluorescence microscopy. This work was supported by NIH grants AR36819, AR36820, and AR48564 (to B.R. Olsen) and partially supported by a Harvard School of Dental Medicine Dean's Scholarship (to Y. Liu). Received for publication September 28, 2011, and accepted in revised form July 5, 2012. NR 65 TC 117 Z9 123 U1 1 U2 26 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 2012 VL 122 IS 9 BP 3101 EP 3113 DI 10.1172/JCI61209 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 002EC UT WOS:000308513100013 PM 22886301 ER PT J AU Crequer, A Troeger, A Patin, E Ma, CS Picard, C Pedergnana, V Fieschi, C Lim, A Abhyankar, A Gineau, L Mueller-Fleckenstein, I Schmidt, M Taieb, A Krueger, J Abel, L Tangye, SG Orth, G Williams, DA Casanova, JL Jouanguy, E AF Crequer, Amandine Troeger, Anja Patin, Etienne Ma, Cindy S. Picard, Capucine Pedergnana, Vincent Fieschi, Claire Lim, Annick Abhyankar, Avinash Gineau, Laure Mueller-Fleckenstein, Ingrid Schmidt, Monika Taieb, Alain Krueger, James Abel, Laurent Tangye, Stuart G. Orth, Gerard Williams, David A. Casanova, Jean-Laurent Jouanguy, Emmanuelle TI Human RHOH deficiency causes T cell defects and susceptibility to EV-HPV infections SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ABERRANT SOMATIC HYPERMUTATION; GTP-BINDING PROTEIN; EPIDERMODYSPLASIA-VERRUCIFORMIS; HUMAN PAPILLOMAVIRUSES; LYMPHOCYTE SUBSETS; JAPANESE PATIENT; DOCK8 DEFICIENCY; EVER1/TMC6 GENE; MUTATION; ACTIVATION AB Epidermodysplasia verruciformis (EV) is a rare genetic disorder characterized by increased susceptibility to specific human papillomaviruses, the betapapillomaviruses. These EV-HPVs cause warts and increase the risk of skin carcinomas in otherwise healthy individuals. Inactivating mutations in epidermodysplasia verruciformis 1 (EVER1) or EVER2 have been identified in most, but not all, patients with autosomal recessive EV. We found that 2 young adult siblings presenting with T cell deficiency and various infectious diseases, including persistent EV-HPV infections, were homozygous for a mutation creating a stop codon in the ras homolog gene family member H (RHOH) gene. RHOH encodes an atypical Rho GTPase expressed predominantly in hematopoietic cells. Patients' circulating T cells contained predominantly effector memory T cells, which displayed impaired TCR signaling. Additionally, very few circulating T cells expressed the beta(7) integrin subunit, which homes T cells to specific tissues. Similarly, Rhoh-null mice exhibited a severe overall T cell defect and abnormally small numbers of circulating beta(7)-positive cells. Expression of the WT, but not of the mutated RHOH, allele in Rhoh(-/-) hematopoietic stem cells corrected the T cell lymphopenia in mice after bone marrow transplantation. We conclude that RHOH deficiency leads to T cell defects and persistent EV-HPV infections, suggesting that T cells play a role in the pathogenesis of chronic EV-HPV infections. C1 [Picard, Capucine; Pedergnana, Vincent; Gineau, Laure; Abel, Laurent; Casanova, Jean-Laurent; Jouanguy, Emmanuelle] INSERM, Lab Human Genet Infect Dis, Necker Branch, U980, Paris, France. [Crequer, Amandine; Abhyankar, Avinash; Abel, Laurent; Casanova, Jean-Laurent; Jouanguy, Emmanuelle] Rockefeller Univ, St Giles Lab Human Genet Infect Dis, Rockefeller Branch, New York, NY 10021 USA. [Crequer, Amandine; Picard, Capucine; Pedergnana, Vincent; Gineau, Laure; Abel, Laurent; Casanova, Jean-Laurent; Jouanguy, Emmanuelle] Paris Descartes Univ, Fac Med Necker, Paris, France. [Troeger, Anja; Williams, David A.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Troeger, Anja; Williams, David A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Harvard Stem Cell Inst, Boston, MA 02115 USA. [Patin, Etienne] Inst Pasteur, CNRS, URA 3012, Genomes & Genet Dept, Paris, France. [Ma, Cindy S.; Tangye, Stuart G.] Garvan Inst Med Res, Program Immunol, Sydney, NSW, Australia. [Ma, Cindy S.; Tangye, Stuart G.] Univ New S Wales, St Vincents Clin Sch, Fac Med, Sydney, NSW, Australia. [Picard, Capucine] Hop Necker Enfants Malad, AP HP, Study Ctr Primary Immunodeficiencies, Paris, France. [Casanova, Jean-Laurent] Hop Necker Enfants Malad, AP HP, Pediat Immunohematol Unit, Paris, France. [Orth, Gerard] Inst Pasteur, Dept Virol, Paris, France. [Krueger, James] Rockefeller Univ, Invest Dermatol Lab, New York, NY 10021 USA. [Taieb, Alain] Univ Bordeaux Segalen, INSERM 1035, Bordeaux, France. [Taieb, Alain] CHU Bordeaux, Pediat Dermatol Unit, Bordeaux Childrens Hosp, Bordeaux, France. [Mueller-Fleckenstein, Ingrid; Schmidt, Monika] Univ Erlangen Nurnberg, Inst Klin & Mol Virol, Erlangen, Germany. [Fieschi, Claire] Hop St Louis, AP HP, Dept Clin Immunol, Paris, France. [Fieschi, Claire] Paris Diderot Univ, EA3963, Paris, France. [Lim, Annick] Inst Pasteur, Dept Immunol, F-75724 Paris, France. RP Jouanguy, E (reprint author), INSERM, Lab Human Genet Infect Dis, Necker Branch, U980, Paris, France. EM emmanuelle.jouanguy@inserm.fr RI Tangye, Stuart/H-4023-2014; Gineau, Laure/G-2446-2016; OI Picard, Capucine/0000-0001-8788-5056; Patin, Etienne/0000-0002-9911-4459 FU INSERM; University Paris Descartes; Rockefeller University; Rockefeller University Clinical and Translational Science Awards (CTSA) [5UL1RR024143]; St. Giles Foundation; National Health and Medical Research Council of Australia; Deutsche Forschungsgemeinschaft [TR 1005/1-1]; William Lawrence and Blanche Hughes Foundation; NIH [5R01CA113969-08]; Akademie der Wissenschaften und der Literatur, Mainz, Germany FX We thank the members of both branches of the Saint Giles Laboratory of Human Genetics of Infectious Diseases, in particular Shen-Ying Zhang for her very helpful suggestions; Lazar Lorenzo for the preliminary screening of blood samples from the patients; Tatiana Kochetkov for her patience in maintaining saimiri T cells in culture; Corinne Jacques, Chantal Harre, and Stephanie N'Daga for excellent technical assistance; Svetlana Mazel, Gaelle Breton, Dusan Bogunovic, Vanessa Bryant, and Guillaume Vogt for their suggestions regarding the flow cytometry and expression assays; Tiffany Nivare and Carolina Prando for the recruitment of healthy volunteers; and Yelena Nemirovskaya and Eric Anderson for logistical assistance. We thank Minji Byun, Sophie Cypowyj, Michael Ciancanelli, and Ruben Martinez-Barricarte for critical reading. We thank Laurence Fiette for the histologic pictures. We warmly thank the patients and their family for their participation. This work was supported by grants from INSERM, University Paris Descartes, the Rockefeller University, the Rockefeller University Clinical and Translational Science Awards (CTSA) (5UL1RR024143), the St. Giles Foundation, the National Health and Medical Research Council of Australia, the Deutsche Forschungsgemeinschaft (TR 1005/1-1), the William Lawrence and Blanche Hughes Foundation, the NIH (5R01CA113969-08), and the Akademie der Wissenschaften und der Literatur, Mainz, Germany. NR 61 TC 35 Z9 35 U1 0 U2 16 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 2012 VL 122 IS 9 BP 3239 EP 3247 DI 10.1172/JCI62949 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 002EC UT WOS:000308513100024 PM 22850876 ER PT J AU Lindqvist, M van Lunzen, J Soghoian, DZ Kuhl, BD Ranasinghe, S Kranias, G Flanders, MD Cutler, S Yudanin, N Muller, MI Davis, I Farber, D Hartjen, P Haag, F Alter, G zur Wiesch, JS Streeck, H AF Lindqvist, Madelene van Lunzen, Jan Soghoian, Damien Z. Kuhl, Bjorn D. Ranasinghe, Srinika Kranias, Gregory Flanders, Michael D. Cutler, Samuel Yudanin, Naomi Muller, Matthias I. Davis, Isaiah Farber, Donna Hartjen, Philip Haag, Friedrich Alter, Galit zur Wiesch, Julian Schulze Streeck, Hendrik TI Expansion of HIV-specific T follicular helper cells in chronic HIV infection SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID IMMATURE/TRANSITIONAL B-CELLS; IMMUNODEFICIENCY-VIRUS TYPE-1; ACTIVE-ANTIRETROVIRAL-THERAPY; SYSTEMIC-LUPUS-ERYTHEMATOSUS; IMMUNE-DEFICIENCY-SYNDROME; ANTIBODY-RESPONSES; CUTTING EDGE; LYMPH-NODES; DIFFERENTIATION; IL-21 AB HIV targets CD4 T cells, which are required for the induction of high-affinity antibody responses and the formation of long-lived B cell memory. The depletion of antigen-specific CD4 T cells during HIV infection is therefore believed to impede the development of protective B cell immunity. Although several different HIV-related B cell dysfunctions have been described, the role of CD4 T follicular helper (TFH) cells in HIV infection remains unknown. Here, we assessed HIV-specific TFH responses in the lymph nodes of treatment-naive and antiretroviral-treated HIV-infected individuals. Strikingly, both the bulk TFH and HIV-specific TFH cell populations were significantly expanded in chronic HIV infection and were highly associated with viremia. In particular, GAG-specific TFH cells were detected at significantly higher levels in the lymph nodes compared with those of GP120-specific TFH cells and showed preferential secretion of the helper cytokine IL-21. In addition, TFH cell expansion was associated with an increase of germinal center B cells and plasma cells as well as IgG1 hypersecretion. Thus, our study suggests that high levels of HIV viremia drive the expansion of TFH cells, which in turn leads to perturbations of B cell differentiation, resulting in dysregulated antibody production. C1 [Lindqvist, Madelene; Soghoian, Damien Z.; Kuhl, Bjorn D.; Ranasinghe, Srinika; Kranias, Gregory; Flanders, Michael D.; Cutler, Samuel; Muller, Matthias I.; Davis, Isaiah; Alter, Galit; Streeck, Hendrik] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ragon Inst MGH MIT & Harvard, Boston, MA USA. [van Lunzen, Jan; Hartjen, Philip; zur Wiesch, Julian Schulze] Univ Med Ctr Eppendorf, Infect Dis Unit, Hamburg, Germany. [Yudanin, Naomi; Farber, Donna] Columbia Univ, Columbia Ctr Translat Immunol, New York, NY USA. [Haag, Friedrich] Univ Med Ctr Eppendorf, Dept Immunol, Hamburg, Germany. RP Streeck, H (reprint author), US Mil HIV Res Program, 6720-A Rockledge Dr, Bethesda, MD 20817 USA. EM hstreeck@hivresearch.org RI Yudanin, Naomi/D-1809-2014 OI Yudanin, Naomi/0000-0002-5019-2851 FU NIH [1R01-AI091450-01, 1R01-AI094602-01]; German Ministry for Education and Research; University Medical Center Eppendorf; Werner-Otto foundation; Deutsches Zentrum fur Infektionsforschung; German Research Agency [SFB841] FX We thank all individuals whose participation enabled this study. This study was funded by the NIH (1R01-AI091450-01 and 1R01-AI094602-01). P. Hartjen and J. Schulze zur Wiesch were supported by the German Ministry for Education and Research and the intramural funding program of the University Medical Center Eppendorf, the Werner-Otto foundation, Deutsches Zentrum fur Infektionsforschung, and the German Research Agency (SFB841 project A6) (to J. Schulze zur Wiesch). NR 51 TC 167 Z9 173 U1 1 U2 8 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 2012 VL 122 IS 9 BP 3271 EP 3280 DI 10.1172/JCI64314 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 002EC UT WOS:000308513100027 PM 22922259 ER PT J AU Ananthakrishnan, AN Zadvornova, Y Naik, AS Issa, M Perera, LP AF Ananthakrishnan, Ashwin N. Zadvornova, Yelena Naik, Amar S. Issa, Mazen Perera, Lilani P. TI Impact of pregnancy on health-related quality of life of patients with inflammatory bowel disease SO JOURNAL OF DIGESTIVE DISEASES LA English DT Article DE Crohn's disease; inflammatory bowel disease; pregnancy; quality of life; ulcerative colitis AB Objective To examine the impact of pregnancy on health-related quality of life (HRQoL) of women with inflammatory bowel disease (IBD). Methods This was a retrospective study in a tertiary referral center and included women with?=2 short inflammatory bowel disease questionnaire (SIBDQ) scores obtained during their pregnancy. Regression models were used to identify independent factors influencing SIBDQ scores and changes of SIBDQ scores at different time points. Results A total of 32 women (23 CD, 9 UC) with a mean age at pregnancy of 29.4 years and a mean disease duration of 7.8 years were included in the study. The mean pre-pregnancy SIBDQ score in our cohort was 49, which was significantly lower than the values during (55, P?= 20% TBSA) burns. The most profound impact of hand burns was noted in fine and gross motor function during the 4 years of follow-up. CONCLUSION: Children with hand burns have significantly worse outcomes than do children with burns in other areas. (J Trauma Acute Care Surg. 2012;73: S197-S204. Copyright (C) 2012 by Lippincott Williams & Wilkins) LEVEL OF EVIDENCE: Epidemiologic/prognostic study, level III. C1 [Palmieri, Tina L.; Nelson-Mooney, Kate] Shriners Hosp Children No Calif, Sacramento, CA 95817 USA. [Kagan, Richard J.; Stubbs, Teresa K.] Shriners Hosp Children, Cincinnati, OH USA. [Meyer, Walter J., III; Herndon, David N.] Shriners Hosp Children, Galveston, TX 77550 USA. [Hinson, Michelle I.; Tompkins, Ronald G.] Univ Calif Davis, Med Ctr, Shriners Hosp Children Boston, Boston, MA USA. [Lee, Austin F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Li, Nien-Chen; Kazis, Lewis E.] Boston Univ, Sch Publ Hlth, Boston, MA USA. RP Palmieri, TL (reprint author), Shriners Hosp Children No Calif, 2425 Stockton Blvd,Suite 718, Sacramento, CA 95817 USA. EM tpalmieri@shrinenet.org OI Kazis, Lewis/0000-0003-1800-5849 FU Shriners Hospitals for Children FX This study is supported by unrestricted grants from Shriners Hospitals for Children. NR 19 TC 9 Z9 12 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 2163-0755 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD SEP PY 2012 VL 73 SU 2 BP S197 EP S204 DI 10.1097/TA.0b013e318265c7ff PG 8 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 009UE UT WOS:000309049900004 PM 22929547 ER PT J AU Sheridan, RL Lee, AF Kazis, LE Liang, MH Li, NC Hinson, MI Bauk, H Meyer, WJ Stubbs, TK Palmieri, TL Tompkins, RG AF Sheridan, Robert L. Lee, Austin F. Kazis, Lewis E. Liang, Matthew H. Li, Nien-Chen Hinson, Michelle I. Bauk, Helena Meyer, Walter J., III Stubbs, Teresa K. Palmieri, Tina L. Tompkins, Ronald G. CA Multi-Ctr Benchmarking Study TI The effect of family characteristics on the recovery of burn injuries in children SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Article DE Pediatric burns; Multi-Center Benchmarking Study; Burn Outcome Questionnaire (BOQ); health outcomes; family functioning ID ASSOCIATION/SHRINERS-HOSPITALS; ADJUSTMENT; SURVIVORS; QUESTIONNAIRE AB BACKGROUND: Interactions between family members and characteristics of family life and function may affect a child's recovery from burn injury. We prospectively examined the relationship between family characteristics and physical and psychosocial recovery from burns. METHODS: The families of 399 burned children aged 5 years to 18 years admitted to one of four Shriners Hospitals for Children for management of acute burns completed the Family Environment Scale within 7 days of admission and then the American Burn Association/Shriners Hospitals for Children Burn Outcome Questionnaire (BOQ) at baseline, 3, 6, 12, 18, 24, 36, and 48 months. Generalized estimating equations with random effects for the time since burn were used to track recovery of the BOQ patient-centered domains associated with baseline family characteristics during the course of the study. RESULTS: The children had a mean age of 11 years and burn size of 32% total body surface area burned. Higher Family Environment Scale scores in cohesion, independence, organization, and active recreational orientation were associated with significantly better rates of recovery in multiple BOQ domains of health-related quality of life. Higher scores in conflict and achievement orientation predicted statistically significant impaired recovery. Higher expressiveness predicted greater difficulty with school reentry. CONCLUSION: Family characteristics affect the recovery of children after serious burns. Some of these may be amenable to focused anticipatory family interventions to help optimize outcomes. In particular, those characteristics that impair school reentry should be targeted. (J Trauma Acute Care Surg. 2012;73: S205-S212. Copyright (C) 2012 by Lippincott Williams & Wilkins) LEVEL OF EVIDENCE: Epidemiologic/prognostic study, level III. C1 [Sheridan, Robert L.; Lee, Austin F.; Liang, Matthew H.; Tompkins, Ronald G.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Kazis, Lewis E.; Li, Nien-Chen] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Liang, Matthew H.] Massachusetts Vet Epidemiol & Res Ctr, Boston, MA USA. [Stubbs, Teresa K.] Shriners Hosp Children, Cincinnati, OH USA. [Meyer, Walter J., III] Shriners Hosp Children, Galveston, TX 77550 USA. [Palmieri, Tina L.] Shriners Hosp Children, Sacramento, CA USA. RP Tompkins, RG (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,GRB1302, Boston, MA 02114 USA. EM rtompkins@partners.org OI Kazis, Lewis/0000-0003-1800-5849 FU Ruzan Avetisyan, Boston University School of Public Health, Boston, Massachusetts; Helena Bauk, Shriners Hospitals for Children-Boston, Boston, Massachusetts; Patricia Blakeney, Shriners Hospitals for Children-Galveston, Galveston, Texas; Catherine Calvert, North Carolina Jaycee Burn Center, Chapel Hill, North Carolina; Kathleen Carey, Boston University School of Public Health, Boston, Massachusetts; Grace Chan, Shriners Hospitals for Children-Northern California, Sacramento, California; Marc Cullen, Detroit Children's Hospital, Detroit, Michigan; Lawren Daltroy (deceased); Mary Beth Daugherty, Shriners Hospitals for Children-Cincinnati, Cincinnati, Ohio; Jing Deng, Shriners Hospitals for Children-Boston, Boston, Massachusetts; Christine Duval, Shriners Hospitals for Children-Galveston, Galveston, Texas; Kathryn Epperson, Shriners Hospitals for Children-Galveston, Galveston, Texas; Eileen Evans, Boston University School of Public Health, Boston, Massachusetts; Frank Pidcock, Kennedy Krieger, Baltimore, Maryland; Sylvia Garma, University of California at Davis, Sacramento, California; Cleon Goodwin, Western States Burn Center, Greeley, Colorado; David Herndon, Shriners Hospitals for Children-Galveston, Galveston, Texas; Michelle Hinson, Shriners Hospitals for Children-Boston, Boston, Massachusetts; Kelli M. Jarrett, Boston University School of Public Health, Boston, Massachusetts; Marilyn Jenkins (deceased), Richard Kagan, Shriners Hospitals for Children-Cincinnati, Cincinnati, Ohio; Lewis Kazis, Boston University School of Public Health, Boston, Massachusetts; Kathy Korte, Shriners Hospitals for Children-Cincinnati, Cincinnati, Ohio; Austin Lee, Massachusetts General Hospital, Boston, Massachusetts; Karen Lenkus, Shriners Hospitals for Children-Northern California, Sacramento, California; Janet Gilroy-Lewis, Shriners Hospitals for Children-Boston, Boston, Massachusetts; Nien-Chen Li, Boston University School of Public Health, Boston, Massachusetts; Matthew Liang, Shriners Hospitals for Children-Boston, Boston, Massachusetts; Martha Lydon, Shriners Hospitals for Children-Boston, Boston, Massachusetts; Robert McCauley; Shriners Hospitals for Children-Galveston, Galveston, Texas; Walter Meyer III, Shriners Hospitals for Children-Galveston, Galveston, Texas; Andrew Munster, (deceased); J. Michael Murphy, Shriners Hospitals for Children-Boston, Boston, Massachusetts; Kate Nelson Mooney, Shriners Hospitals for Children-Northern California, Sacramento, California; Marc Nicolai, Shriners Hospitals for Children-Galveston, Galveston, Texas; Tina Palmieri, Shriners Hospitals for Children-Northern California, Sacramento, California; Charlotte Phillips, Hospital for Special Surgery, New York, New York; Debra Reilly, Nebraska Medical Center, Omaha, Nebraska; Steven Ren, Boston University School of Public Health, Boston, Massachusetts; Mary Rose, University of Texas Medical Branch, Galveston, Texas; Gabriel D. Shapiro, Boston University School of Public Health, Boston, Omaha, Nebraska; Robert Sheridan, Shriners Hospitals for Children-Boston, Boston, Massachusetts; Michelle Skornicki, Boston University School of Public Health, Boston, Massachusetts; Frederick J. Stoddard Jr., Shriners Hospitals for Children-Boston, Boston, Massachusetts; T. Kim Stubbs, Shriners Hospitals for Children-Cincinnati, Cincinnati, Ohio; William Tunell, (retired) Oklahoma City, Oklahoma; Glenn Warden, Shriners Hospitals for Children-Cincinnati, Cincinnati, Warden, Shriners Hospitals for Children-Cincinnati, Cincinnati, Ohio; Petra Warner, Shriners Hospitals for Children-Cincinnati, Cincinnati, Ohio; Gwyne White, Rutgers University, Camden, New Jersey; David Wood, Department of Health-Pediatrics, Jacksonville, Florida; Mengyao Zhao, Shriners Hospital for Children-Boston, Boston, Massachusetts; Ronald G. Tompkins, Shriners Hospitals for Children-Boston, Boston, Massachusetts FX The magnitude of the clinical and outcomes data reported here required the efforts of many individuals at participating institutions. In particular, we wish to acknowledge the supportive research environment created and sustained by the participants in the outcomes program: Ruzan Avetisyan, Boston University School of Public Health, Boston, Massachusetts; Helena Bauk, Shriners Hospitals for Children-Boston, Boston, Massachusetts; Patricia Blakeney, Shriners Hospitals for Children-Galveston, Galveston, Texas; Catherine Calvert, North Carolina Jaycee Burn Center, Chapel Hill, North Carolina; Kathleen Carey, Boston University School of Public Health, Boston, Massachusetts; Grace Chan, Shriners Hospitals for Children-Northern California, Sacramento, California; Marc Cullen, Detroit Children's Hospital, Detroit, Michigan; Lawren Daltroy (deceased); Mary Beth Daugherty, Shriners Hospitals for Children-Cincinnati, Cincinnati, Ohio; Jing Deng, Shriners Hospitals for Children-Boston, Boston, Massachusetts; Christine Duval, Shriners Hospitals for Children-Galveston, Galveston, Texas; Kathryn Epperson, Shriners Hospitals for Children-Galveston, Galveston, Texas; Eileen Evans, Boston University School of Public Health, Boston, Massachusetts; Frank Pidcock, Kennedy Krieger, Baltimore, Maryland; Sylvia Garma, University of California at Davis, Sacramento, California; Cleon Goodwin, Western States Burn Center, Greeley, Colorado; David Herndon, Shriners Hospitals for Children-Galveston, Galveston, Texas; Michelle Hinson, Shriners Hospitals for Children-Boston, Boston, Massachusetts; Kelli M. Jarrett, Boston University School of Public Health, Boston, Massachusetts; Marilyn Jenkins (deceased), Richard Kagan, Shriners Hospitals for Children-Cincinnati, Cincinnati, Ohio; Lewis Kazis, Boston University School of Public Health, Boston, Massachusetts; Kathy Korte, Shriners Hospitals for Children-Cincinnati, Cincinnati, Ohio; Austin Lee, Massachusetts General Hospital, Boston, Massachusetts; Karen Lenkus, Shriners Hospitals for Children-Northern California, Sacramento, California; Janet Gilroy-Lewis, Shriners Hospitals for Children-Boston, Boston, Massachusetts; Nien-Chen Li, Boston University School of Public Health, Boston, Massachusetts; Matthew Liang, Shriners Hospitals for Children-Boston, Boston, Massachusetts; Martha Lydon, Shriners Hospitals for Children-Boston, Boston, Massachusetts; Robert McCauley; Shriners Hospitals for Children-Galveston, Galveston, Texas; Walter Meyer III, Shriners Hospitals for Children-Galveston, Galveston, Texas; Andrew Munster, (deceased); J. Michael Murphy, Shriners Hospitals for Children-Boston, Boston, Massachusetts; Kate Nelson Mooney, Shriners Hospitals for Children-Northern California, Sacramento, California; Marc Nicolai, Shriners Hospitals for Children-Galveston, Galveston, Texas; Tina Palmieri, Shriners Hospitals for Children-Northern California, Sacramento, California; Charlotte Phillips, Hospital for Special Surgery, New York, New York; Debra Reilly, Nebraska Medical Center, Omaha, Nebraska; Steven Ren, Boston University School of Public Health, Boston, Massachusetts; Mary Rose, University of Texas Medical Branch, Galveston, Texas; Gabriel D. Shapiro, Boston University School of Public Health, Boston, Omaha, Nebraska; Robert Sheridan, Shriners Hospitals for Children-Boston, Boston, Massachusetts; Michelle Skornicki, Boston University School of Public Health, Boston, Massachusetts; Frederick J. Stoddard Jr., Shriners Hospitals for Children-Boston, Boston, Massachusetts; T.; Kim Stubbs, Shriners Hospitals for Children-Cincinnati, Cincinnati, Ohio; William Tunell, (retired) Oklahoma City, Oklahoma; Glenn Warden, Shriners Hospitals for Children-Cincinnati, Cincinnati, Warden, Shriners Hospitals for Children-Cincinnati, Cincinnati, Ohio; Petra Warner, Shriners Hospitals for Children-Cincinnati, Cincinnati, Ohio; Gwyne White, Rutgers University, Camden, New Jersey; David Wood, Department of Health-Pediatrics, Jacksonville, Florida; Mengyao Zhao, Shriners Hospital for Children-Boston, Boston, Massachusetts; Ronald G. Tompkins, Shriners Hospitals for Children-Boston, Boston, Massachusetts. NR 10 TC 8 Z9 8 U1 3 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 2163-0755 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD SEP PY 2012 VL 73 SU 2 BP S205 EP S212 DI 10.1097/TA.0b013e318265c81f PG 8 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 009UE UT WOS:000309049900005 PM 22929548 ER PT J AU Tompkins, RG Liang, MH Lee, AF Kazis, LE AF Tompkins, Ronald G. Liang, Matthew H. Lee, Austin F. Kazis, Lewis E. CA Multi-Ctr Benchmarking Study TI The American Burn Association/Shriners Hospitals for Children Burn Outcomes Program: A progress report at 15 years SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Editorial Material DE Multi-Center Benchmarking Study; Burn Outcome Questionnaire (BOQ); health outcomes; recovery curves ID HEALTH OUTCOMES; QUESTIONNAIRE; RELIABILITY; VALIDITY AB The American Burn Association and the Shriners Hospitals for Children Outcomes Program has been in development for more than 15 years. Many of the tools and important findings are described in this special issue of The Journal of Trauma. This unique program in outcomes research introduces a model for outcome assessments from the patient-centered perspective with a cohort of 1,140 children with burn injury after hospitalization for up to 4 years. The findings represent a fundamental contribution to the field of burn care for monitoring outcomes from the perspective of the parent or child/adolescent. The Multi-Center Benchmarking Study of four burn centers serve as a model for collecting empiric scientific data on the variation and the expected trajectories of recovery in the most important domains of patient outcomes and can inform clinical decisions and the conduct of health service research. The dramatic progress in survival of children with severe burn injury and other advances in burn management can now move into a new phase of understanding the most cost-effective components of this care. (J Trauma Acute Care Surg. 2012; 73: S173-S178. Copyright (C) 2012 by Lippincott Williams & Wilkins) C1 [Tompkins, Ronald G.; Lee, Austin F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tompkins, Ronald G.] Shriners Hosp Children, Boston, MA USA. [Liang, Matthew H.] Massachusetts Vet Epidemiol & Res Ctr, Boston, MA USA. [Kazis, Lewis E.] Boston Univ, Sch Publ Hlth, Boston, MA USA. RP Tompkins, RG (reprint author), Massachusetts Gen Hosp, 55 Fruit St,GRB1302, Boston, MA 02114 USA. EM rtompkins@partners.org OI Kazis, Lewis/0000-0003-1800-5849 NR 20 TC 13 Z9 13 U1 3 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 2163-0755 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD SEP PY 2012 VL 73 SU 2 BP S173 EP S178 DI 10.1097/TA.0b013e318265c53e PG 6 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 009UE UT WOS:000309049900001 PM 22929544 ER PT J AU Warner, P Stubbs, TK Kagan, RJ Herndon, DN Palmieri, TL Kazis, LE Li, NC Lee, AF Meyer, WJ Tompkins, RG AF Warner, Petra Stubbs, Teresa K. Kagan, Richard J. Herndon, David N. Palmieri, Tina L. Kazis, Lewis E. Li, Nien-Chen Lee, Austin F. Meyer, Walter J., III Tompkins, Ronald G. CA Multi-Ctr Benchmarking Study TI The effects of facial burns on health outcomes in children aged 5 to 18 years SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Article DE Facial burns; Multi-Center Benchmarking Study; Burn Outcomes Questionnaire; recovery ID QUALITY-OF-LIFE; ASSOCIATION/SHRINERS-HOSPITALS; PEDIATRIC BURNS; ADJUSTMENT; INJURY; QUESTIONNAIRE; SEQUELAE AB BACKGROUND: There are many potential longterm effects of facial burns in children and young adults. We evaluated the outcomes of children and young adults with and without facial burns with respect to physical, psychological, and social domains of health-related quality of life (HRQoL). In addition, we examined the role of sex and socioeconomic status on HRQoL in these patients. METHODS: Parents of children aged from 5 to 18 years with burn injury completed the American Burn Association/Shriners Hospitals for Children Burn Outcomes Questionnaire when survival was ensured at their original burn center admission and at regular 6-month intervals during the first 2 years and annually up to 4 years after their acute care discharge. Generalized estimating equations with mixed models were used to evaluate the course of recovery with risk adjustments for time since burn, presence of facial burns, and clinical and other sociodemographic characteristics. RESULTS: Patients with facial burns paralleled the recovery of patients without facial burns, but their mean scores remained lower during the 4 years, with the lowest scores in the domains of appearance, emotional health, and parental concern. Teenagers had improved recovery rates when compared with younger children. Males scored lower with respect to family disruption but recovered at faster rates than females over time, and parents with higher education scored lower for parental concern during the 4 years of follow-up. CONCLUSION: Psychosocial concerns predominate in the recovery of children who sustain facial burns and are significantly greater than those observed in children in whom the face is not involved by burn injury (J Trauma Acute Care Surg. 2012;73: S189-S196. Copyright (C) 2012 by Lippincott Williams & Wilkins). LEVEL OF EVIDENCE: Prognostic study, level III. C1 [Lee, Austin F.; Tompkins, Ronald G.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Lee, Austin F.; Tompkins, Ronald G.] Shriners Hosp Children, Boston, MA USA. [Kazis, Lewis E.; Li, Nien-Chen] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Palmieri, Tina L.] Shriners Hosp Children No Calif, Sacramento, CA USA. [Herndon, David N.; Meyer, Walter J., III] Shriners Hosp Children, Galveston, TX 77550 USA. [Warner, Petra; Stubbs, Teresa K.; Kagan, Richard J.] Shriners Hosp Children, Cincinnati, OH USA. RP Tompkins, RG (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,GRB1302, Boston, MA 02114 USA. EM rtompkins@partners.org OI Kazis, Lewis/0000-0003-1800-5849 FU Shriners Hospitals for Children FX Supported by unrestricted grants from Shriners Hospitals for Children. NR 23 TC 6 Z9 7 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 2163-0755 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD SEP PY 2012 VL 73 SU 2 BP S189 EP S196 DI 10.1097/TA.0b013e318265c7df PG 8 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 009UE UT WOS:000309049900003 PM 22929546 ER PT J AU Wolf, AR Mootha, VK AF Wolf, Ashley R. Mootha, Vamsi K. TI A systematic search for mitochondrial RNA processing components SO MITOCHONDRION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA 02141 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1567-7249 J9 MITOCHONDRION JI Mitochondrion PD SEP PY 2012 VL 12 IS 5 MA 48 BP 568 EP 568 DI 10.1016/j.mito.2012.07.046 PG 1 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 009KC UT WOS:000309023700054 ER PT J AU Lieber, DS Calvo, SE Slate, NG Liu, S Borowsky, ML Hershman, SG Gold, NB Berry, GT Mueller, DM Schmahmann, JD Sims, KB Mootha, VK AF Lieber, Daniel S. Calvo, Sarah E. Slate, Nancy G. Liu, Shangtao Borowsky, Mark L. Hershman, Steven G. Gold, Nina B. Berry, Gerard T. Mueller, David M. Schmahmann, Jeremy D. Sims, Katherine B. Mootha, Vamsi K. TI Targeted exome sequencing of suspected mitochondrial disorders in a hospital-based cohort SO MITOCHONDRION LA English DT Meeting Abstract C1 [Lieber, Daniel S.; Calvo, Sarah E.; Slate, Nancy G.; Liu, Shangtao; Borowsky, Mark L.; Hershman, Steven G.; Gold, Nina B.; Mootha, Vamsi K.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Lieber, Daniel S.; Calvo, Sarah E.; Slate, Nancy G.; Liu, Shangtao; Hershman, Steven G.; Gold, Nina B.; Sims, Katherine B.; Mootha, Vamsi K.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Lieber, Daniel S.; Calvo, Sarah E.; Hershman, Steven G.; Mootha, Vamsi K.] Harvard Univ, Dept Syst Biol, Sch Med, Boston, MA 02115 USA. [Lieber, Daniel S.; Calvo, Sarah E.; Hershman, Steven G.; Mootha, Vamsi K.] Broad Inst Harvard & MIT, Cambridge, MA 02141 USA. [Berry, Gerard T.] Childrens Hosp, Manton Ctr Orphan Dis Res, Boston, MA 02115 USA. [Mueller, David M.] Rosalind Franklin Univ Med & Sci, Chicago Med Sch, Dept Biochem & Mol Biol, N Chicago, IL 60064 USA. [Schmahmann, Jeremy D.; Sims, Katherine B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1567-7249 J9 MITOCHONDRION JI Mitochondrion PD SEP PY 2012 VL 12 IS 5 MA 71 BP 575 EP 576 DI 10.1016/j.mito.2012.07.065 PG 2 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 009KC UT WOS:000309023700073 ER PT J AU Strittmatter, L Leoni, V Zorzi, G Zibordi, F Dusi, S Garavaglia, B Venco, P Caccia, C Souza, AL Deik, A Clish, CB Rimoldi, M Ciusani, E Bertini, E Nardocci, N Mootha, VK Tiranti, V AF Strittmatter, Laura Leoni, Valerio Zorzi, Giovanna Zibordi, Federica Dusi, Sabrina Garavaglia, Barbara Venco, Paola Caccia, Claudio Souza, Amanda L. Deik, Amy Clish, Clary B. Rimoldi, Marco Ciusani, Emilio Bertini, Enrico Nardocci, Nardo Mootha, Vamsi K. Tiranti, Valeria TI Global metabolic profiling reveals metabolic consequences of mitochondrial coenzyme A deficiency in patients with PANK2 mutations SO MITOCHONDRION LA English DT Meeting Abstract C1 [Strittmatter, Laura; Mootha, Vamsi K.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02114 USA. [Strittmatter, Laura; Mootha, Vamsi K.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. [Strittmatter, Laura; Mootha, Vamsi K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Strittmatter, Laura; Souza, Amanda L.; Deik, Amy; Clish, Clary B.; Mootha, Vamsi K.] Broad Inst, Cambridge, MA 02142 USA. [Leoni, Valerio; Caccia, Claudio; Rimoldi, Marco; Ciusani, Emilio] IRCCS Fdn Neurol Inst C Besta, Lab Clin Pathol & Med Genet, Milan, Italy. [Zorzi, Giovanna; Zibordi, Federica; Nardocci, Nardo] IRCCS Fdn Neurol Inst C Besta, Unit Child Neurol, Milan, Italy. [Dusi, Sabrina; Garavaglia, Barbara; Venco, Paola; Tiranti, Valeria] IRCCS Fdn Neurol Inst C Besta, Unit Mol Neurogenet, Pierfranco & Luisa Mariani Ctr Study Mitochondria, Milan, Italy. [Bertini, Enrico] Bambino Gesu Pediat Res Hosp, Dept Neurosci, Unit Mol Med, Rome, Italy. RI Tiranti, Valeria/J-8233-2016 OI Tiranti, Valeria/0000-0002-3584-7338 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1567-7249 J9 MITOCHONDRION JI Mitochondrion PD SEP PY 2012 VL 12 IS 5 MA 75 BP 577 EP 577 DI 10.1016/j.mito.2012.07.069 PG 1 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 009KC UT WOS:000309023700077 ER PT J AU Hershman, SG Tucker, EJ Kohrer, C Belcher-Timme, CA Patel, J Goldberger, OA Christodoulou, J Silberstein, JM McKenzie, M Ryan, MT Compton, AG Garone, C Garcia-Diaz, B DiMauro, S Jaffe, JD Carr, SA Calvo, SE RajBhandary, UL Thorburn, DR Mootha, VK AF Hershman, Steven G. Tucker, Elena J. Koehrer, Caroline Belcher-Timme, Casey A. Patel, Jinal Goldberger, Olga A. Christodoulou, John Silberstein, Jonathon M. McKenzie, Matthew Ryan, Michael T. Compton, Alison G. Garone, Caterina Garcia-Diaz, Beatriz DiMauro, Salvatore Jaffe, Jacob D. Carr, Steven A. Calvo, Sarah E. RajBhandary, Uttam L. Thorburn, David R. Mootha, Vamsi K. TI Mutations in MTFMT underlie a human disorder of formylation causing impaired mitochondrial translation SO MITOCHONDRION LA English DT Meeting Abstract C1 [Hershman, Steven G.; Belcher-Timme, Casey A.; Goldberger, Olga A.; Calvo, Sarah E.; Mootha, Vamsi K.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Hershman, Steven G.; Belcher-Timme, Casey A.; Goldberger, Olga A.; Calvo, Sarah E.; Mootha, Vamsi K.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Hershman, Steven G.; Belcher-Timme, Casey A.; Patel, Jinal; Goldberger, Olga A.; Jaffe, Jacob D.; Carr, Steven A.; Calvo, Sarah E.; Mootha, Vamsi K.] Broad Inst, Cambridge, MA 02142 USA. [Tucker, Elena J.; Compton, Alison G.; Thorburn, David R.] Royal Childrens Hosp, Murdoch Childrens Res Inst, Melbourne, Vic 3052, Australia. [Thorburn, David R.] Royal Childrens Hosp, Genet Hlth Serv Victoria, Melbourne, Vic 3052, Australia. [Tucker, Elena J.; Thorburn, David R.] Univ Melbourne, Dept Paediat, Melbourne, Vic 3052, Australia. [Koehrer, Caroline; RajBhandary, Uttam L.] MIT, Dept Biol, Cambridge, MA 02142 USA. [Christodoulou, John] Childrens Hosp Westmead, Genet Metab Disorders Res Unit, Sydney, NSW 2006, Australia. [Christodoulou, John] Univ Sydney, Discipline Paediat & Child Hlth, Sydney, NSW 2006, Australia. [Christodoulou, John] Univ Sydney, Discipline Genet Med, Sydney, NSW 2006, Australia. [Silberstein, Jonathon M.] Princess Margaret Hosp Children, Dept Neurol, Perth, WA 6008, Australia. [McKenzie, Matthew] Monash Univ, Monash Inst Med Res, Ctr Reprod & Dev, Melbourne, Vic 3168, Australia. [Ryan, Michael T.] La Trobe Univ, Dept Biochem, Melbourne, Vic 3086, Australia. [Ryan, Michael T.] La Trobe Univ, ARC Ctr Excellence Coherent Xray Sci, Melbourne, Vic 3086, Australia. [Garone, Caterina; Garcia-Diaz, Beatriz; DiMauro, Salvatore] Columbia Univ Coll Phys & Surg, Dept Neurol, New York, NY 10032 USA. [Garone, Caterina] Univ Turin, Human Genet Joint PhD Programme, I-10125 Turin, Italy. [Garone, Caterina] Univ Bologna, Human Genet Joint PhD Programme, I-40125 Bologna, Italy. RI Ryan, Michael/C-6673-2011; Christodoulou, John/E-5866-2015 OI Ryan, Michael/0000-0003-2586-8829; NR 0 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1567-7249 J9 MITOCHONDRION JI Mitochondrion PD SEP PY 2012 VL 12 IS 5 MA 93 BP 583 EP 583 DI 10.1016/j.mito.2012.07.084 PG 1 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 009KC UT WOS:000309023700092 ER PT J AU Mao, YD Wang, LP Gu, C Herschhorn, A Xiang, SH Haim, H Yang, XZ Sodroski, J AF Mao, Youdong Wang, Liping Gu, Christopher Herschhorn, Alon Xiang, Shi-Hua Haim, Hillel Yang, Xinzhen Sodroski, Joseph TI Subunit organization of the membrane-bound HIV-1 envelope glycoprotein trimer SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; NEUTRALIZATION EPITOPE; CONFORMATIONAL-CHANGES; VARIABLE LOOPS; AIDS PATIENTS; CD4 BINDING; GP120 CORE; HTLV-III; GP41; ANTIBODY AB The trimeric human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) spike is a molecular machine that mediates virus entry into host cells and is the sole target for virus-neutralizing antibodies. The mature Env spike results from cleavage of a trimeric glycoprotein precursor, gp160, into three gp120 and three gp41 subunits. Here, we describe an similar to 11-angstrom cryo-EM structure of the trimeric HIV-1 Env precursor in its unliganded state. The three gp120 and three gp41 subunits form a cage-like structure with an interior void surrounding the trimer axis. Interprotomer contacts are limited to the gp41 transmembrane region, the torus-like gp41 ectodomain and a trimer-association domain of gp120 composed of the V1, V2 and V3 variable regions. The cage-like architecture, which is unique among characterized viral envelope proteins, restricts antibody access, reflecting requirements imposed by HIV-1 persistence in the host. C1 [Mao, Youdong; Wang, Liping; Gu, Christopher; Herschhorn, Alon; Xiang, Shi-Hua; Haim, Hillel; Sodroski, Joseph] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Microbiol & Immunobiol,Dept Canc Immunol & A, Boston, MA 02115 USA. [Yang, Xinzhen] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Div Viral Pathogenesis, Boston, MA 02115 USA. [Sodroski, Joseph] Massachusetts Gen Hosp, MIT, Ragon Inst, Boston, MA 02114 USA. [Sodroski, Joseph] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Mao, YD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Microbiol & Immunobiol,Dept Canc Immunol & A, 44 Binney St, Boston, MA 02115 USA. EM youdong_mao@dfci.harvard.edu; joseph_sodroski@dfci.harvard.edu FU US National Science Foundation under NSF [ECS-0335765]; US National Institutes of Health (NIH) [AI93256, AI67854, AI24755]; Ragon Institute of MGH, MIT and Harvard; International AIDS Vaccine Initiative FX The authors thank J. Mascola and P. Kwong (NIH Vaccine Research Center, Bethesda, Maryland, USA) and D. Burton (Scripps Institute, La Jolla, California, USA) for kindly providing antibodies; M. Ericsson, L. Trakimas and E. Benecchi for help in initial sample screening by conventional electron microscopy; D. Bell, E. Hodges and D. Wei for assistance and coordination in data collection; J. Faltskog, S. Doktor and B. Battle for laboratory coordination and assistance in building a high-performance computing system; and Y. McLaughlin and E. Carpelan for assistance in manuscript preparation. The experiments and data processing were performed in part at the Center for Nanoscale Systems at Harvard University, a member of National Nanotechnology Infrastructure Network (NNIN), which is supported by the US National Science Foundation under NSF award no. ECS-0335765. This work was funded by the US National Institutes of Health (NIH) (AI93256, AI67854 and AI24755 to J.S.), by an Innovation Award (J.S.) and a Fellowship Award (Y.M.) from the Ragon Institute of MGH, MIT and Harvard, by the International AIDS Vaccine Initiative, and by a gift from the late William F. McCarty-Cooper (J.S.). NR 54 TC 88 Z9 90 U1 3 U2 52 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 SEP PY 2012 VL 19 IS 9 BP 893 EP 899 DI 10.1038/nsmb.2351 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 003SF UT WOS:000308630900009 PM 22864288 ER PT J AU McManus, DD Lyass, A Ingelsson, E Massaro, JM Meigs, JB Aragam, J Benjamin, EJ Vasan, RS AF McManus, David D. Lyass, Asya Ingelsson, Erik Massaro, Joseph M. Meigs, James B. Aragam, Jayashri Benjamin, Emelia J. Vasan, Ramachandran S. TI Relations of Circulating Resistin and Adiponectin and Cardiac Structure and Function: The Framingham Offspring Study SO OBESITY LA English DT Article ID CONGESTIVE-HEART-FAILURE; LEFT ATRIAL SIZE; LEFT-VENTRICULAR HYPERTROPHY; M-MODE ECHOCARDIOGRAPHY; INSULIN-RESISTANCE; MYOCARDIAL-INFARCTION; INFLAMMATORY MARKERS; PLASMA ADIPONECTIN; SERUM RESISTIN; ADIPOSE-TISSUE AB Obesity is associated with pathological cardiac remodeling and risk of heart failure (HF). Adipocytokines (ADKs) may mediate the increased risk of cardiovascular disease associated with excess adiposity. Yet data relating ADKs to cardiac remodeling phenotypes are sparse. We related two circulating ADKs, resistin and adiponectin, to three important echocardiographic markers of cardiac remodeling, left ventricular mass (LVM), left atrial diameter (LAD), and LV fractional shortening (LVFS) in 2,615 participants (mean age 61 years, 55% women) in the Framingham Offspring Study. Adiponectin concentrations were inversely related to LVM in multivariable linear regression models adjusting for key clinical correlates including BMI (regression coefficient per s.d.-increment in In-adiponectin = -3.37, P = 0.02; P for trend across quartiles = 0.02). Adiponectin was not associated with LAD or LVFS (P > 0.56). Resistin concentrations were inversely related to LVFS (regression coefficient per s.d.-increment in In-resistin = -0.01, P = 0.03; P for trend across quartiles = 0.04). Resistin was not associated with LVM or LAD (P > 0.05). In our moderate-sized, community-based sample, higher circulating concentrations of adiponectin and resistin were associated with lower LVM and lower LVFS, respectively. In conclusion, these associations identify potential mechanisms by which excess adiposity may mediate adverse cardiac remodeling and HF risk. C1 [McManus, David D.; Lyass, Asya; Massaro, Joseph M.; Aragam, Jayashri; Benjamin, Emelia J.; Vasan, Ramachandran S.] NHLBI, Framingham, MA USA. [McManus, David D.; Lyass, Asya; Massaro, Joseph M.; Aragam, Jayashri; Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Framingham Heart Study, Framingham, MA USA. [Lyass, Asya; Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Ingelsson, Erik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Massaro, Joseph M.] Boston Univ, Dept Math, Sch Publ Hlth, Boston, MA 02215 USA. [Meigs, James B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Meigs, James B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Aragam, Jayashri] Vet Adm Hosp, W Roxbury, MA USA. [Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Prevent Med Sect, Boston, MA 02118 USA. [Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. RP Vasan, RS (reprint author), NHLBI, Framingham, MA USA. EM vasan@bu.edu OI Massaro, Joseph/0000-0002-2682-4812; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, MA [N01-HC-25195, 6R01-NS 17950, 2 K24 HL04334, RO1HL080124, RO1DK80739] FX This work was supported by the National Heart, Lung and Blood Institute's Framingham Heart Study (contract no. N01-HC-25195), 6R01-NS 17950, 2 K24 HL04334, RO1HL080124, RO1DK80739 (R.S.V.), Framingham, MA. NR 45 TC 24 Z9 26 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 EI 1930-739X J9 OBESITY JI Obesity PD SEP PY 2012 VL 20 IS 9 BP 1882 EP 1886 DI 10.1038/oby.2011.32 PG 5 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 998ZO UT WOS:000308279100020 PM 21350435 ER PT J AU Hsu, I Saha, S Korthuis, PT Sharp, V Cohn, J Moore, RD Beach, MC AF Hsu, Ian Saha, Somnath Korthuis, Phillip Todd Sharp, Victoria Cohn, Jonathon Moore, Richard D. Beach, Mary Catherine TI Providing support to patients in emotional encounters: A new perspective on missed empathic opportunities SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE Empathy; Patient-physician communication; Emotion; Physician-patient relations ID COMMUNICATION; CARE; REASSURANCE; CANCER; DOCTOR AB Objective: Studies have repeatedly found that providers miss 70-90% of opportunities to express empathy. Our study sought to characterize provider responses to patients' emotions, with the overall goal of better understanding reasons for lack of empathic response. Methods: We analyzed 47 visits between patients and their providers. We defined empathic opportunities as instances where patients expressed a strong negative emotion. We then developed thematic categories to describe provider response. Results: We found a total of 29 empathic opportunities within 21 visits. Provider responses were categorized as ignore, dismiss, elicit information, problem-solve, or empathize. An empathic statement occurred at some point in the response sequence in 13/29 opportunities (45%). When problem-solving was the initial response, empathic statements rarely occurred in subsequent dialogue. Among the 16 instances with no empathic statements, providers engaged in problem-solving in 8 (50%). Conclusion: Similar to other studies, we found providers missed most opportunities to respond empathically to patient emotion. Yet contrary to common understanding, providers often addressed the problem underlying the emotion, especially when the problem involved logistical or biomedical issues, as opposed to grief. Practice implications: With enhanced awareness, providers may better recognize situations where they cans offer empathy in addition to problem-solving. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Hsu, Ian; Moore, Richard D.; Beach, Mary Catherine] Johns Hopkins Univ, Baltimore, MD 21287 USA. [Saha, Somnath; Korthuis, Phillip Todd] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Saha, Somnath] Portland VA Med Ctr, Portland, OR USA. [Sharp, Victoria] St Lukes Roosevelt Hosp, New York, NY USA. [Cohn, Jonathon] Wayne State Univ, Detroit, MI USA. RP Beach, MC (reprint author), Johns Hopkins Univ, 2024 E Monument St,Room 2-511, Baltimore, MD 21287 USA. EM mcbeach@jhmi.edu FU Health Resources Service Administration; Agency for Healthcare Research and Quality [AHRQ 290-01-0012, K08 HS013903-05]; National Institute of Drug Abuse [K23 DA019809]; Department of Veterans Affairs; Robert Wood Johnson Generalist Physician Faculty Scholars Awards FX This research was supported by a contract from the Health Resources Service Administration and the Agency for Healthcare Research and Quality (AHRQ 290-01-0012). In addition, Dr. Korthuis was supported by the National Institute of Drug Abuse (K23 DA019809), 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 26 TC 10 Z9 10 U1 4 U2 9 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD SEP PY 2012 VL 88 IS 3 SI SI BP 436 EP 442 DI 10.1016/j.pec.2012.06.015 PG 7 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 005SD UT WOS:000308769300013 PM 22818767 ER PT J AU Kelly, NR Mitchell, KS Gow, RW Trace, SE Lydecker, JA Bair, CE Mazzeo, S AF Kelly, Nichole R. Mitchell, Karen S. Gow, Rachel W. Trace, Sara E. Lydecker, Janet A. Bair, Carrie E. Mazzeo, Suzanne TI An Evaluation of the Reliability and Construct Validity of Eating Disorder Measures in White and Black Women SO PSYCHOLOGICAL ASSESSMENT LA English DT Article DE eating disorder measures; Black; validity; reliability; psychometric properties ID BODY-IMAGE; AFRICAN-AMERICAN; OBJECTIFICATION THEORY; ETHNIC-DIFFERENCES; EUROPEAN-AMERICAN; DIAGNOSTIC SCALE; COLLEGE-STUDENTS; COMMUNITY SAMPLE; NATIONAL-SURVEY; ATTITUDES TEST AB Most measures of eating disorder symptoms and risk factors were developed in predominantly White female samples. Yet eating disorders affect individuals of all racial and ethnic backgrounds. Black women appear more vulnerable to certain forms of eating pathology, such as binge eating, and less susceptible to other eating disorder symptoms and risk factors, such as body dissatisfaction, compared with their White peers. Despite concern that extant measures do not adequately assess eating concerns among Black women, the construct validity of scores on most of these measures has not been adequately examined within this population. This study included 2,208 Black and White women who completed the following: the Binge Eating Scale (BES), the Eating Disorder Diagnostic Scale (EDDS), the Eating Attitudes Test-26 (EAT-26), the Eating Disorder Inventory Body Dissatisfaction and Drive for Thinness subscales, the Bulimia Test Revised (BULIT-R), the Multidimensional Body Self Relations Questionnaire Appearance Evaluation subscale (MBSRQ-AE), and the Objectified Body Consciousness Scale (OBCS). Most measures yielded internally consistent scores in both races. Confirmatory factor analyses indicated that loadings for some measures, including the EAT-26 and EDDS, were not invariant across groups and thus do not assess equivalent constructs in White and Black women. However, others, including the BULIT-R, BES, OBCS, and MBSRQ-AE, exhibited factorial invariance in both races. Results suggest scores are likely not equivalent across races for several popular measures of eating disorder symptoms and risk factors. Thus, it is recommended that researchers and clinicians obtain additional information regarding racial/cultural factors when using these instruments with Black women. C1 [Kelly, Nichole R.; Gow, Rachel W.; Lydecker, Janet A.; Bair, Carrie E.; Mazzeo, Suzanne] Virginia Commonwealth Univ, Dept Psychol, Richmond, VA 23284 USA. [Mazzeo, Suzanne] Virginia Commonwealth Univ, Dept Pediat, Richmond, VA 23284 USA. [Mitchell, Karen S.] VA Boston Healthcare Syst, Womens Hlth Sci Div, Natl Ctr PTSD, Boston, MA USA. [Mitchell, Karen S.] Boston Univ, Dept Psychiat, Boston, MA 02215 USA. [Trace, Sara E.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. RP Mazzeo, S (reprint author), Virginia Commonwealth Univ, Dept Psychol, Box 2018, Richmond, VA 23284 USA. EM semazzeo@vcu.edu RI Lydecker, Janet/B-3349-2016 OI Lydecker, Janet/0000-0001-6425-514X NR 75 TC 12 Z9 12 U1 7 U2 33 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1040-3590 EI 1939-134X J9 PSYCHOL ASSESSMENT JI Psychol. Assess. PD SEP PY 2012 VL 24 IS 3 BP 608 EP 617 DI 10.1037/a0026457 PG 10 WC Psychology, Clinical SC Psychology GA 999AI UT WOS:000308281100008 PM 22149327 ER PT J AU Burguete, SR Levine, SM Restrepo, MI Angel, LF Levine, DJ Coalson, JJ Peters, JI AF Burguete, S. Rodrigo Levine, Stephanie M. Restrepo, Marcos I. Angel, Luis F. Levine, Deborah J. Coalson, Jacqueline J. Peters, Jay I. TI Lung Transplantation for Williams-Campbell Syndrome With a Probable Familial Association SO RESPIRATORY CARE LA English DT Article DE Williams-Campbell syndrome; bronchiectasis; lung transplantation; bronchial cartilage deficiency ID CONGENITAL BRONCHIECTASIS; CARTILAGE DEFICIENCY; COMPUTED-TOMOGRAPHY; CT AB Williams-Campbell syndrome is a rare disorder characterized by deficiency of subsegmental bronchial cartilage and development of airway collapse and bronchiectasis that may subsequently progress to respiratory failure and death. There are only 2 published reports suggesting a familial association, and only one report of lung transplantation being used as a therapeutic modality. Due to postoperative airway complications, transplantation has not been recommended for this disease. We report the first lung transplant with prolonged survival, approaching 10 years, in a patient with Williams-Campbell syndrome, and provide further evidence to support a familial association. C1 [Burguete, S. Rodrigo; Levine, Stephanie M.; Restrepo, Marcos I.; Angel, Luis F.; Levine, Deborah J.; Coalson, Jacqueline J.; Peters, Jay I.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Pulm & Crit Care Med, San Antonio, TX 78229 USA. [Burguete, S. Rodrigo; Levine, Stephanie M.; Restrepo, Marcos I.; Angel, Luis F.; Levine, Deborah J.; Coalson, Jacqueline J.; Peters, Jay I.] S Texas Vet Hlth Care Syst, Vet Evidence Res Disseminat & Implementat Ctr, San Antonio, TX USA. RP Burguete, SR (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Pulm & Crit Care Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM burguete@uthscsa.edu RI Restrepo, Marcos/H-4442-2014 FU National Heart, Lung, and Blood Institute [K23HL096054] FX The authors have disclosed no conflicts of interest. Dr Restrepo was partly supported by grant K23HL096054 from the National Heart, Lung, and Blood Institute. NR 20 TC 2 Z9 3 U1 0 U2 1 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 EI 1943-3654 J9 RESP CARE JI Respir. Care PD SEP PY 2012 VL 57 IS 9 BP 1505 EP 1508 DI 10.4187/respcare.01484 PG 4 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 007PX UT WOS:000308901700018 PM 22348466 ER PT J AU Mallipattu, SK He, JC Uribarri, J AF Mallipattu, Sandeep K. He, John C. Uribarri, Jaime TI Role of Advanced Glycation Endproducts and Potential Therapeutic Interventions in Dialysis Patients SO SEMINARS IN DIALYSIS LA English DT Review ID GLYCOSYLATION END-PRODUCTS; HEMODIALYSIS-ASSOCIATED AMYLOIDOSIS; AMBULATORY PERITONEAL-DIALYSIS; OXIDATION PROTEIN PRODUCTS; RENAL REPLACEMENT THERAPY; CHRONIC KIDNEY-DISEASE; DIABETIC-NEPHROPATHY; CARBONYL STRESS; IN-VIVO; VASCULAR-DISEASE AB It has been nearly 100 years since the first published report of advanced glycation end products (AGEs) by the French chemist Maillard. Since then, our understanding of AGEs in diseased states has dramatically changed. Especially in the last 25 years, AGEs have been implicated in complications related to aging, neurodegenerative diseases, diabetes, and chronic kidney disease. Although AGE formation has been well characterized by both in vitro and in vivo studies, few prospective human studies exist demonstrating the role of AGEs in patients on chronic renal replacement therapy. As the prevalence of end-stage renal disease (ESRD) in the United States rises, it is essential to identify therapeutic strategies that either delay progression to ESRD or improve morbidity and mortality in this population. This article reviews the role of AGEs, especially those of dietary origin, in ESRD patients as well as potential therapeutic anti-AGE strategies in this population. C1 [Mallipattu, Sandeep K.; He, John C.; Uribarri, Jaime] Mt Sinai Sch Med, Dept Med, Div Nephrol, New York, NY 10029 USA. [He, John C.] James J Peters VA Med Ctr, Dept Med, Renal Sect, New York, NY USA. RP Uribarri, J (reprint author), Mt Sinai Sch Med, Dept Med Nephrol, 1 Gustave L Levy Pl,Box 1243, New York, NY 10029 USA. EM jaime.uribarri@mssm.edu RI Mallipattu , Sandeep/M-7009-2014 NR 146 TC 7 Z9 7 U1 0 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-0959 EI 1525-139X J9 SEMIN DIALYSIS JI Semin. Dial. PD SEP-OCT PY 2012 VL 25 IS 5 BP 529 EP 538 DI 10.1111/j.1525-139X.2012.01081.x PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 008OQ UT WOS:000308966800011 PM 22548330 ER PT J AU Silva, PS Walia, S Cavallerano, JD Sun, JK Dunn, C Bursell, SE Aiello, LM Aiello, LP AF Silva, Paolo S. Walia, Saloni Cavallerano, Jerry D. Sun, Jennifer K. Dunn, Cheri Bursell, Sven-Erik Aiello, Lloyd M. Aiello, Lloyd Paul TI Comparison of Low-Light Nonmydriatic Digital Imaging with 35-mm ETDRS Seven-Standard Field Stereo Color Fundus Photographs and Clinical Examination SO TELEMEDICINE AND E-HEALTH LA English DT Article DE ophthalmology; telehealth; technology ID DIABETIC-RETINOPATHY; COST-EFFECTIVENESS; EYE CARE; PROGRAM; CAMERA AB Purpose:To compare agreement between diagnosis of clinical level of diabetic retinopathy (DR) and diabetic macular edema (DME) derived from nonmydriatic fundus images using a digital camera back optimized for low-flash image capture (MegaVision) compared with standard seven-field Early Treatment Diabetic Retinopathy Study (ETDRS) photographs and dilated clinical examination. Subject comfort and image acquisition time were also evaluated. Subjects and Methods:In total, 126 eyes from 67 subjects with diabetes underwent Joslin Vision Network nonmydriatic retinal imaging. ETDRS photographs were obtained after pupillary dilation, and fundus examination was performed by a retina specialist. Results:There was near-perfect agreement between MegaVision and ETDRS photographs (kappa = 0.81, 95% confidence interval [CI] 0.73-0.89) for clinical DR severity levels. Substantial agreement was observed with clinical examination (kappa = 0.71, 95% CI 0.62-0.80). For DME severity level there was near-perfect agreement with ETDRS photographs (kappa = 0.92, 95% CI 0.87-0.98) and moderate agreement with clinical examination (kappa = 0.58, 95% CI 0.46-0.71). The wider MegaVision 45 degrees field led to identification of nonproliferative changes in areas not imaged by the 30 degrees field of ETDRS photos. Field area unique to ETDRS photographs identified proliferative changes not visualized with MegaVision. Mean MegaVision acquisition time was 9:52 min. After imaging, 60% of subjects preferred the MegaVision lower flash settings. Conclusions:When evaluated using a rigorous protocol, images captured using a low-light digital camera compared favorably with ETDRS photography and clinical examination for grading level of DR and DME. Furthermore, these data suggest the importance of more extensive peripheral images and suggest that utilization of wide-field retinal imaging may further improve accuracy of DR assessment. C1 [Silva, Paolo S.; Walia, Saloni; Cavallerano, Jerry D.; Sun, Jennifer K.; Dunn, Cheri; Aiello, Lloyd M.; Aiello, Lloyd Paul] Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. [Silva, Paolo S.; Cavallerano, Jerry D.; Sun, Jennifer K.; Aiello, Lloyd M.; Aiello, Lloyd Paul] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Bursell, Sven-Erik] Univ Hawaii, Telehlth Res Inst, Honolulu, HI 96822 USA. RP Aiello, LP (reprint author), Joslin Diabet Ctr, Beetham Eye Inst, 1 Joslin Pl, Boston, MA 02215 USA. EM lpaiello@joslin.harvard.edu FU Department of the Army [DAMD 17-03-2-0062]; Massachusetts Lions Eye Research Fund for the Joslin Vision Network FX This work was funded in part by Department of the Army by means of Cooperative Agreement DAMD 17-03-2-0062 and the Massachusetts Lions Eye Research Fund for the Joslin Vision Network. NR 25 TC 9 Z9 9 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 SEP PY 2012 VL 18 IS 7 BP 492 EP 499 DI 10.1089/tmj.2011.0232 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 004TF UT WOS:000308703300002 PM 22827402 ER PT J AU Hayden, EM Navedo, DD Gordon, JA AF Hayden, Emily M. Navedo, Deborah D. Gordon, James A. TI Web-Conferenced Simulation Sessions: A Satisfaction Survey of Clinical Simulation Encounters via Remote Supervision SO TELEMEDICINE AND E-HEALTH LA English DT Article DE Web conference; simulation; direct observation; video; medical education ID MEDICAL-EDUCATION AB Purpose: A critical barrier to expanding simulation-based instruction in medicine is the availability of clinical instructors. Allowing instructors to remotely observe and debrief simulation sessions may make simulation-based instruction more convenient, thus expanding the pool of instructors available. This study compared the impact of simulation sessions facilitated by in-person (IP) faculty versus those supervised remotely using Web-conferencing software (WebEx (R), Cisco [www.webex.com/]). Subjects and Methods: A convenience sample of preclinical medical students volunteered to "care for" patients in a simulation laboratory. Students received either standard IP or Web-conferenced (WC) instruction. WC sessions were facilitated by off-site instructors. A satisfaction survey (5-point Likert scale, where 1 = strongly disagree and 5 = strongly agree) was completed immediately following the sessions. Results: Forty-four surveys were analyzed (WC n = 25, IP n = 19). In response to the question "Was the communication between faculty and students a barrier to understanding the case?," the average student responses were 2.8 (95% confidence interval [CI] 2.4-3.2) for WC and 4.5 (95% CI 4.0-5.0) for IP (p < 0.0001). In response to the question "Would you participate again in such a session?," the average student responses were 4.2 (95% CI 4.0-4.5) for WC and 4.9 (95% CI 4.6-5.2) for IP (p = 0.0003). Both groups agreed that they acquired new skills (4.2 for WC, 4.5 for IP; p = 0.39) and new knowledge (4.6 for WC, 4.7 for IP; p = 0.41). Conclusions: Telecommunication can successfully enhance access to simulation-based instruction. In this study, a Web interface downgraded the quality of student-faculty communication. Future investigation is needed to better understand the impact of such an effect on the learning process and to reduce barriers that impede implementation of technology-facilitated supervision. C1 [Hayden, Emily M.; Gordon, James A.] Massachusetts Gen Hosp, Dept Emergency Med, Div Med Simulat, Boston, MA 02114 USA. [Hayden, Emily M.; Gordon, James A.] Harvard Univ, Sch Med, Gilbert Program Med Simulat, Boston, MA USA. [Hayden, Emily M.; Navedo, Deborah D.; Gordon, James A.] Massachusetts Gen Hosp, MGH Learning Lab, Boston, MA 02114 USA. [Navedo, Deborah D.] MGH Inst Hlth Profess, Boston, MA USA. RP Hayden, EM (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Div Med Simulat, 0 Emerson Pl,Suite 3B, Boston, MA 02114 USA. EM emhayden@partners.org NR 10 TC 4 Z9 4 U1 2 U2 5 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 SEP PY 2012 VL 18 IS 7 BP 525 EP 529 DI 10.1089/tmj.2011.0217 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 004TF UT WOS:000308703300007 PM 22827475 ER PT J AU Jibson, MD Broquet, KE Anzia, JM Beresin, EV Hunt, JI Kaye, D Rao, NR Rostain, AL Sexson, SB Summers, RF AF Jibson, Michael D. Broquet, Karen E. Anzia, Joan Meyer Beresin, Eugene V. Hunt, Jeffrey I. Kaye, David Rao, Nyapati Raghu Rostain, Anthony Leon Sexson, Sandra B. Summers, Richard F. TI Clinical Skills Verification in General Psychiatry: Recommendations of the ABPN Task Force on Rater Training SO ACADEMIC PSYCHIATRY LA English DT Article ID BOARD CERTIFICATION EXAMINATION; MINI-CEX; RELIABILITY; TRIAL AB Objective: The American Board of Psychiatry and Neurology (ABPN) announced in 2007 that general psychiatry training programs must conduct Clinical Skills Verification (CSV), consisting of observed clinical interviews and case presentations during residency, as one requirement to establish graduates' eligibility to sit for the written certification examination. To facilitate implementation of these requirements, the ABPN convened a task force to prepare training materials for faculty and programs to guide them in the CSV process. This article reviews the specific requirements for the CSV experience within general residency programs, and briefly describes the recommendations of the task force for faculty training and program implementation. Methods: Materials prepared by the ABPN Task Force include background information on the intent of the observed interview, a literature review on assessment methods, aids to train faculty in direct observation of clinical work, directions for effective feedback, notes regarding special issues for cross-cultural trainees, clarification of performance standards, and recommendations for structuring and conducting the assessments. Results: Recommendations of the task force include the use of a variety of clinical settings for CSV assessments, flexibility in the duration of CSV interviews, use of formative and summative feedback after each CSV assessment, and frequent use of the CSV across all years of training. Formal faculty training is recommended to help establish performance parameters, increase inter-rater reliability, and improve the quality of feedback. Conclusions: The implementation of the CSV process provides psychiatry training programs with an excellent opportunity to assess how interviewing skills are taught and evaluated. In the process, psychiatry educators have an opportunity to establish performance parameters that will guide the training of residents in patient interaction and evaluation. C1 [Jibson, Michael D.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. So Illinois Univ, Sch Med, Dept Psychiat, Springfield, IL USA. Northwestern Univ, Dept Psychiat, Feinberg Sch Med, Chicago, IL 60611 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Brown Univ, Dept Psychiat, Providence, RI 02912 USA. SUNY Buffalo, Dept Psychiat, Buffalo, NY 14260 USA. Nassau Univ, Med Ctr, Dept Psychiat & Behav Sci, E Meadow, NY USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Georgia Hlth Sci Univ, Dept Psychiat, Augusta, GA USA. RP Jibson, MD (reprint author), Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. EM mdjibson@umich.edu NR 15 TC 1 Z9 1 U1 0 U2 6 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 SEP-OCT PY 2012 VL 36 IS 5 BP 363 EP 368 PG 6 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 001IR UT WOS:000308454500005 PM 22983466 ER PT J AU Griswold, T Bullock, C Gaufberg, E Albanese, M Bonilla, P Dvorak, R Epelbaum, C Givon, L Kueppenbender, K Joseph, R Boyd, JW Shtasel, D AF Griswold, Todd Bullock, Christopher Gaufberg, Elizabeth Albanese, Mark Bonilla, Pedro Dvorak, Ramona Epelbaum, Claudia Givon, Lior Kueppenbender, Karsten Joseph, Robert Boyd, J. Wesley Shtasel, Derri TI Psychiatry in the Harvard Medical School-Cambridge Integrated Clerkship: An Innovative, Year-Long Program SO ACADEMIC PSYCHIATRY LA English DT Article ID LEARNING COMMUNITIES; CLINICAL EDUCATION; ACADEMIC MEDICINE; STUDENTS; PERFORMANCE; CONTINUITY; EROSION AB Objective: The authors present what is to their knowledge the first description of a model for longitudinal third-year medical student psychiatry education. Method: A longitudinal, integrated psychiatric curriculum was developed, implemented, and sustained within the Harvard Medical School-Cambridge Integrated Clerkship. Curriculum elements include longitudinal mentoring by attending physicians in an outpatient psychiatry clinic, exposure to the major psychotherapies, psychopharmacology training, acute psychiatry "immersion" experiences, and a variety of clinical and didactic teaching sessions. Results: The longitudinal psychiatry curriculum has been sustained for 8 years to-date, providing effective learning as demonstrated by OSCE scores, NBME shelf exam scores, written work, and observed clinical work The percentage of students in this clerkship choosing psychiatry as a residency specialty is significantly greater than those in traditional clerkships at Harvard Medical School and greater than the U.S. average. Conclusion: Longitudinal integrated clerkship experiences are effective and sustainable: they offer particular strengths and opportunities for psychiatry education, and may influence student choice of specialty. C1 [Griswold, Todd; Bullock, Christopher; Gaufberg, Elizabeth; Albanese, Mark; Bonilla, Pedro; Dvorak, Ramona; Epelbaum, Claudia; Givon, Lior; Joseph, Robert; Boyd, J. Wesley] Cambridge Hlth Alliance, Cambridge, MA USA. [Griswold, Todd; Bullock, Christopher; Gaufberg, Elizabeth; Albanese, Mark; Bonilla, Pedro; Dvorak, Ramona; Epelbaum, Claudia; Givon, Lior; Kueppenbender, Karsten; Joseph, Robert; Boyd, J. Wesley; Shtasel, Derri] Harvard Univ, Sch Med, Boston, MA USA. [Kueppenbender, Karsten; Shtasel, Derri] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Griswold, T (reprint author), Cambridge Hlth Alliance, Somerville, MA USA. EM tgriswold@calliance.org NR 24 TC 3 Z9 3 U1 0 U2 6 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 SEP-OCT PY 2012 VL 36 IS 5 BP 380 EP 387 PG 8 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 001IR UT WOS:000308454500008 PM 22983469 ER PT J AU Camm, AJ Al-Khatib, SM Calkins, H Halperin, JL Kirchhof, P Lip, GYH Nattel, S Ruskin, J Banerjee, A Blendea, D Guasch, E Needleman, M Savelieva, I Viles-Gonzalez, J Williams, ES AF Camm, A. John Al-Khatib, Sana M. Calkins, Hugh Halperin, Jonathan L. Kirchhof, Paulus Lip, Gregory Y. H. Nattel, Stanley Ruskin, Jeremy Banerjee, Amitava Blendea, Dan Guasch, Eduard Needleman, Matthew Savelieva, Irina Viles-Gonzalez, Juan Williams, Eric S. TI A proposal for new clinical concepts in the management of atrial fibrillation SO AMERICAN HEART JOURNAL LA English DT Article ID FOLLOW-UP; ATHEROSCLEROSIS RISK; EUROPEAN-SOCIETY; PULMONARY VEINS; HEART-FAILURE; SLEEP-APNEA; MECHANISMS; MORTALITY; ARRHYTHMIAS; OUTCOMES AB Atrial fibrillation (AF) represents a growing public health burden. It is a complex condition, involving a number of etiologic factors and arrhythmia mechanisms associated with atrial remodeling. Greater understanding of these mechanisms may improve therapy. Current AF classification schemes are limited by simplicity. A number of risk factors predict AF onset, and additional factors are being evaluated in registry studies. Doppler imaging and Holter monitoring in high-risk patients to predict the onset of AF and progression from paroxysmal to permanent AF are promising. There is a need for a novel multifactorial classification model encompassing AF duration, symptoms, markers of atrial remodeling, and a risk score for AF onset, persistence, progression, and complications to guide treatment and prognostication. Preventing AF onset with upstream therapy is of great interest, but current data are conflicting. More study is needed to optimize rhythm control with antiarrhythmic drugs and targeted ablation to specific patient populations at an earlier stage. There is little consensus on optimal rate control and no information relating to optimum rate control in specific populations. This article highlights new concepts in AF and directions for future research. (Am Heart J 2012;164:292-302.e1.) C1 [Camm, A. John; Savelieva, Irina] Univ London, London SW17 0RE, England. [Al-Khatib, Sana M.] Duke Univ, Med Ctr, Durham, NC USA. [Calkins, Hugh; Needleman, Matthew] Johns Hopkins Univ, Baltimore, MD USA. [Halperin, Jonathan L.; Viles-Gonzalez, Juan] Mt Sinai Sch Med, New York, NY USA. [Kirchhof, Paulus; Lip, Gregory Y. H.; Banerjee, Amitava] Univ Birmingham, Ctr Cardiovasc Sci, City Hosp, Birmingham, W Midlands, England. [Kirchhof, Paulus] Univ Hosp Munster, Dept Cardiol Angiol, Munster, Germany. [Nattel, Stanley; Blendea, Dan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ruskin, Jeremy; Guasch, Eduard] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. [Williams, Eric S.] Univ Washington, Med Ctr, Seattle, WA 98195 USA. RP Camm, AJ (reprint author), Univ London, Cranmer Terrace, London SW17 0RE, England. EM jcamm@sgul.ac.uk RI Guasch, Eduard/D-1243-2013; Banerjee, Amitava/D-4381-2014; OI Guasch, Eduard/0000-0003-4238-5319; Banerjee, Amitava/0000-0001-8741-3411; Kirchhof, Paulus/0000-0002-1881-0197 FU Sanofi; Bristol Myers Squibb; Astellas Pharma, US; Atricure/Boston Biomedical Associates; AstraZeneca; Bayer AG HealthCare; Boehringer Ingelheim; Pharmaceuticals, Inc; Bristol Meyers-Squibb; Daiichi Sankyo; Ortho-McNeil-Janssen Pharmaceuticals, Inc; Johnson Johnson; Pfizer, Inc; Biotronik, Inc.; 3M Medica; MEDA Pharma; Bayer Healthcare; Daicchi-Sankyo; Medtronic; Merck; MSD; Otsuka Pharma; Pfizer/ BMS; Servier; Siemens; TAKEDA; 3M Medica/MEDA Pharma; Cardiovascular Therapeutics; OMRON; Sanofi, St.; Xention Labs; Pfizer; Boehringer-Ingelheim; Biosense-Webster; St. Jude; Biosense Webster, Inc; Boston Scientific Corp; Medtronic, Inc; St. Jude Medical; Best Doctors, Inc; Web MD; Morgan Stanley; Smith Barney; Merrill Lynch; Mckensie Co; Gerson Lehrman Group; Daiichi Sankyo Co, LTD; Boston Scientific; Biotronik FX Logistical and editorial support was provided by Healthcare21 Communications Ltd and was paid for by an unrestricted grant from Sanofi.; Sana M Al-Khatib, MD, received research funding from Bristol Myers Squibb; Jonathon L Halperin, MD, received consulting fees from Astellas Pharma, US, Atricure/Boston Biomedical Associates, AstraZeneca, Bayer AG HealthCare, Boehringer Ingelheim, Pharmaceuticals, Inc, Bristol Meyers-Squibb, Daiichi Sankyo, Ortho-McNeil-Janssen Pharmaceuticals, Inc, Johnson & Johnson, Pfizer, Inc, Sanofi, and Biotronik, Inc.; Paulus Kirchhof, MD, received consulting fees and honoraria from 3M Medica, MEDA Pharma, AstraZeneca, Bayer Healthcare, Boehringer Ingelheim, Daicchi-Sankyo, MEDA Pharma, Medtronic, Merck, MSD, Otsuka Pharma, Pfizer/ BMS, Sanofi, Servier, Siemens and TAKEDA; research grants from 3M Medica/MEDA Pharma, Cardiovascular Therapeutics, Medtronic, OMRON, Sanofi, St.; Stanley Nattel, MD, has patents awarded or pending to the Montreal Heart Institute, which lists Dr Nattel as inventor or coinventor: (1) Preventing atrial fibrillation with the use of statin drugs (EU patent awarded); (2) TRPC3 channels are critical for regulating fibroblast proliferation in the heart; (3) MiR21 as a target in prevention of atrial fibrillation. He received research funding from AstraZeneca and Xention Labs. He is a consultant for Pierre Fabre, Cardiome, Merck, Bayer, Nyken. He received honoraria for scientific lectures from Sanofi, Pfizer, Boehringer-Ingelheim, Biosense-Webster, and St. Jude.; Jeremy Ruskin, MD, is a consultant to Atricure, Inc, Arrhythmia Education, Inc, Astellas/Cardiome, Biosense Webster, Inc, Bristol Myers Squibb, CardioInsight, Info-Bionic (equity), Medtronic, Inc, Pfizer, Portola (equity), Sanofi Aventis, and Third Rock Ventures; He received fellowship support from Biosense Webster, Inc, Boston Scientific Corp, Medtronic, Inc, and St. Jude Medical.; Juan Viles-Gonzalez, MD, received consulting fees from Best Doctors, Inc, Web MD, Morgan Stanley, Smith Barney, Merrill Lynch, Mckensie & Co, Gerson Lehrman Group, Daiichi Sankyo Co, LTD, Boehringer Ingelheim, Sanofi; educational grants from Medtronic, Boston Scientific, St. Jude Medical, and Biotronik. NR 63 TC 15 Z9 16 U1 0 U2 9 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 SEP PY 2012 VL 164 IS 3 BP 292 EP U193 DI 10.1016/j.ahj.2012.05.017 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 004OD UT WOS:000308690100004 PM 22980294 ER PT J AU Shah, RV Altman, RK Park, MY Zilinski, J Leyton-Mange, J Orencole, M Picard, MH Barrett, CD Heist, EK Upadhyay, G Das, R Singh, JP Das, S AF Shah, Ravi V. Altman, Robert K. Park, Mi Young Zilinski, Jodi Leyton-Mange, Jordan Orencole, Mary Picard, Michael H. Barrett, Conor D. Heist, E. Kevin Upadhyay, Gaurav Das, Ranendra Singh, Jagmeet P. Das, Saumya TI Usefulness of Hemoglobin A(1c) to Predict Outcome After Cardiac Resynchronization Therapy in Patients With Diabetes Mellitus and Heart Failure SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID MORTALITY; MORBIDITY; DEFIBRILLATOR AB Patients with diabetes and heart failure (HF) have worse clinical outcomes compared to patients with HF without diabetes after cardiac resynchronization therapy (CRT). Patients with I-IF and diabetes represent a growing population at high risk for cardiovascular events and are increasingly treated with CRT. Although patients with diabetes and HF appear to benefit from CRT, their clinical outcomes are worse than those of patients without diabetes after CRT. The aim of this study was to identify clinical predictors that explain the differential hazard in patients with diabetes. We studied 442 patients (169 with diabetes) with systolic HF referred to the Massachusetts General Hospital CRT clinic from 2003 to 2010 to identify predictors of outcomes after CRT in patients with HF and diabetes. Patients with diabetes were more likely to have ischemic causes of HF than those without diabetes, but there was no difference in the left ventricular ejection fraction or HF classification at implantation. Patients with diabetes had poorer event-free survival (death or HF hospitalization) compared to those without diabetes (log-rank p = 0.04). The presence of diabetes was the most important independent predictor of differential outcomes in the entire population (hazard ratio 1.65, 95% confidence interval 1.10 to 2.51). Patients with diabetes receiving insulin therapy had poorer survival, whereas those not receiving insulin therapy had similar survival to patients without diabetes. Patients with pen-implantation glycosylated hemoglobin >7% had worse outcomes, whereas patients with glycosylated hemoglobin <= 7% had improved survival (hazard ratio 0.36, 95% confidence interval 0.15.to 0.86) equivalent to that of patients without diabetes. In conclusion, although the presence of diabetes, independent of other variables, increases the hazard of worse outcomes after CRT, there is additional risk conferred by insulin use and suboptimal poi-implantation glycemic control. (c) 2012 Elsevier Inc. All rights reserved. (Am J Cardiol 2012;110:683-688) C1 [Das, Saumya] Beth Israel Deaconess Med Ctr, Dept Cardiol & Med, Boston, MA 02215 USA. [Shah, Ravi V.; Zilinski, Jodi; Leyton-Mange, Jordan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiol Div,Dept Med, Boston, MA USA. [Altman, Robert K.; Orencole, Mary; Barrett, Conor D.; Heist, E. Kevin; Upadhyay, Gaurav; Singh, Jagmeet P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Unit,Dept Med, Boston, MA USA. [Park, Mi Young; Picard, Michael H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Echocardiog Lab,Dept Med, Boston, MA USA. [Das, Ranendra] Johns Hopkins Univ, Dept Anthropol, Baltimore, MD USA. RP Das, S (reprint author), Beth Israel Deaconess Med Ctr, Dept Cardiol & Med, Boston, MA 02215 USA. EM sdas@bidmc.harvard.edu OI Altman, Robert/0000-0002-1612-3561; Picard, Michael/0000-0002-9264-3243 FU Post-Doctoral Fellowship Award from the American Heart Association, Dallas, Texas [11POST000002]; Heart Failure NIH-NHLBI Clinical Research Network, Bethesda, Maryland [U01-HL084877]; Max Schaldach Fellowship in Cardiac Pacing and Electrophysiology from the Heart Rhythm Society, Washington, District of Columbia; National Institutes of Health, Bethesda, Maryland [KO8HL089319] FX Dr. Shah is supported by Post-Doctoral Fellowship Award 11POST000002 from the American Heart Association, Dallas, Texas, and training grant U01-HL084877 from the Heart Failure NIH-NHLBI Clinical Research Network, Bethesda, Maryland. Dr. Upadhyay is supported by a Max Schaldach Fellowship in Cardiac Pacing and Electrophysiology from the Heart Rhythm Society, Washington, District of Columbia. Dr. Dan is supported by grant KO8HL089319 from the National Institutes of Health, Bethesda, Maryland. NR 10 TC 7 Z9 7 U1 0 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD SEP 1 PY 2012 VL 110 IS 5 BP 683 EP 688 DI 10.1016/j.amjcard.2012.04.056 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 003NI UT WOS:000308618200012 PM 22632827 ER PT J AU Tsai, CL Sullivan, AF Gordon, JA Kaushal, R Magid, DJ Blumenthal, D Camargo, CA AF Tsai, Chu-Lin Sullivan, Ashley F. Gordon, James A. Kaushal, Rainu Magid, David J. Blumenthal, David Camargo, Carlos A., Jr. TI Quality of care for joint dislocation in 47 US EDs SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID RANDOMIZED CLINICAL-TRIAL; LONG-BONE FRACTURES; EMERGENCY-DEPARTMENT; PROCEDURAL SEDATION; SHOULDER DISLOCATION; ACUTE PAIN; ANALGESIA; PROPOFOL; MANAGEMENT; ETHNICITY AB Background: Little is known about emergency department (ED) quality of care for joint dislocation. We sought to determine concordance of ED management of dislocation with guideline recommendations and to assess whether higher concordance was associated with better patient outcomes. Methods: We conducted a retrospective chart review study of joint dislocation as part of the National ED Safety Study (www.emnet-usa.org). We identified all charts with a primary ED or hospital discharge diagnosis of joint dislocation in 47 EDs across 19 US states between 2003 and 2005. Concordance with guideline recommendations was evaluated using 5 individual quality measures and composite guideline concordance scores. Concordance scores were calculated as the percentage of eligible patients receiving guidelines-recommended care. These percentage scores were rescaled from 0 to 100, with 100 indicating perfect concordance. Results: The cohort consisted of 1980 ED patients; the patients' median age was 38 years, and 63% were men. Care for dislocation was excellent, with a concordance score of more than 85 across all quality measures. The median ED composite guideline concordance score was 93 (interquartile range, 90-95). In multivariable analyses, receiving treatment in EDs with the highest (fourth quartile) composite guideline concordance scores was independently associated with a significantly higher likelihood of successful joint reduction (adjusted odds ratio, 3.28; 95% confidence interval, 1.38-7.81), as compared with treatment in EDs with the lowest (first quartile) scores. Conclusions: Concordance of ED management of joint dislocation with guideline recommendations was high. Greater concordance with guideline-recommended care may increase the likelihood of successful joint reduction. (C) 2012 Elsevier Inc. All rights reserved. C1 [Tsai, Chu-Lin; Sullivan, Ashley F.; Gordon, James A.; Camargo, Carlos A., Jr.] Harvard Univ, Dept Emergency Med, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Gordon, James A.; Blumenthal, David; Camargo, Carlos A., Jr.] Harvard Univ, Mongan Inst Hlth Policy, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Kaushal, Rainu] Weill Cornell Med Coll, New York, NY 10065 USA. [Kaushal, Rainu] New York Presbyterian Hosp, New York, NY 10065 USA. [Magid, David J.] Univ Colorado Denver, Kaiser Permanente Colorado, Dept Emergency Med, Aurora, CO 80231 USA. [Magid, David J.] Univ Colorado Denver, Kaiser Permanente Colorado, Inst Hlth Res, Aurora, CO 80231 USA. [Magid, David J.] Univ Colorado Denver, Kaiser Permanente Colorado, Dept Prevent Med, Aurora, CO 80231 USA. [Magid, David J.] Univ Colorado Denver, Kaiser Permanente Colorado, Dept Biometr, Aurora, CO 80231 USA. [Blumenthal, David] Off Natl Coordinator Hlth Informat Technol, Dept Hlth & Human Serv, Washington, DC 20201 USA. RP Camargo, CA (reprint author), Harvard Univ, Dept Emergency Med, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. EM ccamargo@partners.org OI TSAI, CHU-LIN/0000-0003-4639-1513 FU Agency for Healthcare Research and Quality (Rockville, MD) [R01 HS013099] FX This study was supported by grant R01 HS013099 from the Agency for Healthcare Research and Quality (Rockville, MD). NR 44 TC 2 Z9 2 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 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD SEP PY 2012 VL 30 IS 7 BP 1105 EP 1113 DI 10.1016/j.ajem.2011.07.012 PG 9 WC Emergency Medicine SC Emergency Medicine GA 002OI UT WOS:000308541100014 PM 22030182 ER PT J AU Ballard, DW Reed, ME Huang, J Kramer, BJ Hsu, J Chettipally, U AF Ballard, Dustin W. Reed, Mary E. Huang, Jie Kramer, Barbara J. Hsu, John Chettipally, Uli TI Does primary stroke center certification change ED diagnosis, utilization, and disposition of patients with acute stroke? SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID ACUTE ISCHEMIC-STROKE; TISSUE-PLASMINOGEN ACTIVATOR; QUALITY-OF-CARE; PERFORMANCE-MEASURES; OUTCOMES; PREVENTION; MORTALITY; ALTEPLASE; DISEASE; SAFETY AB Background and Purpose: We examined the impact of primary stroke center (PSC) certification on emergency department (ED) use and outcomes within an integrated delivery system in which EDs underwent staggered certification. Methods: A retrospective cohort study of 30 461 patients seen in 17 integrated delivery system EDs with a primary diagnosis of transient ischemic attack (TIA), intracranial hemorrhage, or ischemic stroke between 2005 and 2008 was conducted. We compared ED stroke patient visits across hospitals for (1) temporal trends and (2) pre- and post-PSC certification-using logistic and linear regression models to adjust for comorbidities, patient characteristics, and calendar time, to examine major outcomes (ED throughput time, hospital admission, radiographic imaging utilization and throughput, and mortality) across certification stages. Results: There were 15 687 precertification ED visits and 11 040 postcertification visits. Primary stroke center certification was associated with significant changes in care processes associated with PSC certification process, including (1) ED throughput for patients with intracranial hemorrhage (55 minutes faster), (2) increased utilization of cranial magnetic resonance imaging for patients with ischemic stroke (odds ratio, 1.88; 95% confidence interval, 1.36-2.60), and (3) decrease in time to radiographic imaging for most modalities, including cranial computed tomography done within 6 hours of ED arrival (TIA: 12 minutes faster, ischemic stroke: 11 minutes faster), magnetic resonance imaging for patients with ischemic stroke (197 minutes faster), and carotid Doppler sonography for TIA patients (138 minutes faster). There were no significant changes in survival. Conclusions: Stroke center certification was associated with significant changes in ED admission and radiographic utilization patterns, without measurable improvements in survival. (C) 2012 Elsevier Inc. All rights reserved. C1 [Ballard, Dustin W.; Chettipally, Uli] Kaiser Permanente, Dept Emergency Med, San Rafael, CA 94901 USA. [Ballard, Dustin W.; Chettipally, Uli] Kaiser Permanente, Dept Emergency Med, San Francisco, CA 94901 USA. [Ballard, Dustin W.; Reed, Mary E.; Huang, Jie; Kramer, Barbara J.; Hsu, John; Chettipally, Uli] Kaiser Permanente, Div Res, Oakland, CA 94612 USA. [Ballard, Dustin W.; Reed, Mary E.; Huang, Jie; Kramer, Barbara J.; Hsu, John; Chettipally, Uli] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mongan Inst Hlth Policy,Dept Hlth Care Policy, Boston, MA 02114 USA. RP Ballard, DW (reprint author), Kaiser Permanente San Rafael, Dept Emergency Med, Fairfax, CA 94930 USA. EM dballard30@yahoo.com FU Kaiser Foundation Research Institute FX Supported by a Community Benefit grant from the Kaiser Foundation Research Institute (2007-2008). NR 46 TC 5 Z9 5 U1 2 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 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD SEP PY 2012 VL 30 IS 7 BP 1152 EP 1162 DI 10.1016/j.ajem.2011.08.015 PG 11 WC Emergency Medicine SC Emergency Medicine GA 002OI UT WOS:000308541100022 PM 22100484 ER PT J AU Rex, DK Ahnen, DJ Baron, JA Batts, KP Burke, CA Burt, RW Goldblum, JR Guillem, JG Kahi, CJ Kalady, MF O'Brien, MJ Odze, RD Ogino, S Parry, S Snover, DC Torlakovic, EE Wise, PE Young, J Church, J AF Rex, Douglas K. Ahnen, Dennis J. Baron, John A. Batts, Kenneth P. Burke, Carol A. Burt, Randall W. Goldblum, John R. Guillem, Jose G. Kahi, Charles J. Kalady, Matthew F. O'Brien, Michael J. Odze, Robert D. Ogino, Shuji Parry, Susan Snover, Dale C. Torlakovic, Emina Emilia Wise, Paul E. Young, Joanne Church, James TI Serrated Lesions of the Colorectum: Review and Recommendations From an Expert Panel SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Review ID ISLAND METHYLATOR PHENOTYPE; HYPERPLASTIC POLYPOSIS SYNDROME; SOCIETY-TASK-FORCE; LIFE-STYLE FACTORS; LARGE-BOWEL CANCER; MICROSATELLITE INSTABILITY; LARGE-INTESTINE; RISK-FACTORS; ADENOMATOUS POLYPS; BRAF MUTATION AB Serrated lesions of the colorectum are the precursors of perhaps one-third of colorectal cancers (CRCs). Cancers arising in serrated lesions are usually in the proximal colon, and account for a disproportionate fraction of cancer identified after colonoscopy. We sought to provide guidance for the clinical management of serrated colorectal lesions based on current evidence and expert opinion regarding definitions, classification, and significance of serrated lesions. A consensus conference was held over 2 days reviewing the topic of serrated lesions from the perspectives of histology, molecular biology, epidemiology, clinical aspects, and serrated polyposis. Serrated lesions should be classified pathologically according to the World Health Organization criteria as hyperplastic polyp, sessile serrated adenoma/polyp (SSA/P) with or without cytological dysplasia, or traditional serrated adenoma (TSA). SSA/P and TSA are premalignant lesions, but SSA/P is the principal serrated precursor of CRCs. Serrated lesions have a distinct endoscopic appearance, and several lines of evidence suggest that on average they are more difficult to detect than conventional adenomatous polyps. Effective colonoscopy requires an endoscopist trained in the endoscopic appearance of serrated lesions. We recommend that all serrated lesions proximal to the sigmoid colon and all serrated lesions in the rectosigmoid >5 mm in size, be completely removed. Recommendations are made for post-polypectomy surveillance of serrated lesions and for surveillance of serrated polyposis patients and their relatives. C1 [Rex, Douglas K.] Indiana Univ, Indianapolis, IN 46204 USA. [Ahnen, Dennis J.] Denver VA Med Ctr, Denver, CO USA. [Ahnen, Dennis J.] Univ Colorado, Sch Med, Denver, CO USA. [Baron, John A.] Univ N Carolina, Chapel Hill, NC USA. [Batts, Kenneth P.] Abbott NW Hosp, Minneapolis, MN 55407 USA. [Burke, Carol A.] Cleveland Clin, Inst Digest Dis, Dept Gastroenterol & Hepatol, Cleveland, OH 44106 USA. [Burt, Randall W.] Univ Utah, Sch Med, Dept Internal Med, Div Gastroenterol, Salt Lake City, UT USA. [Guillem, Jose G.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Kahi, Charles J.] Indiana Univ Sch Med, Richard L Roudebush VA Med Ctr, Indianapolis, IN USA. [O'Brien, Michael J.] Boston Univ, Med Ctr, Boston, MA USA. [Odze, Robert D.; Ogino, Shuji] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Parry, Susan] Auckland City Hosp, New Zealand Familial GI Canc Registry, Auckland, New Zealand. [Parry, Susan] Middlemore Hosp, Dept Gastroenterol, Auckland 6, New Zealand. [Snover, Dale C.] Fairview Southdale Hosp, Dept Pathol, Edina, MN USA. [Torlakovic, Emina Emilia] Univ Toronto, Univ Hlth Network, Dept Lab Med & Pathobiol, Toronto, ON, Canada. [Wise, Paul E.] Vanderbilt Univ, Med Ctr, Dept Surg, Nashville, TN USA. RP Church, J (reprint author), Cleveland Clin Fdn, Dept Colorectal Surg, Inst Digest Dis, Desk A-30,9500 Euclid Ave, Cleveland, OH 44195 USA. EM churchj@ccf.org OI O'Brien, Michael J/0000-0003-1124-3537; Wise, Paul/0000-0003-3798-7913 FU National Cancer Institute; Sanford R. Weiss Center for Hereditary Colorectal Neoplasia at the Cleveland Clinic; [R01 CA151993] FX This work was supported by a Grant from the National Cancer Institute and by the Sanford R. Weiss Center for Hereditary Colorectal Neoplasia at the Cleveland Clinic.; Douglas K. Rex: research support and consultant, Olympus America. Shuji Ogino: supported by the R01 CA151993, listed (on colorectal neoplasia epigenetics). Dennis J. Ahnen, John A. Baron, Kenneth P. Batts, Carol A. Burke, Randall W. Burt, John R. Goldblum, Jose G. Guillem, Charles J. Kahi, Matthew F. Kalady, Michael J O'Brien, Robert D. Odze, Susan Parry, Dale C. Snover, Emina Emilia Torlakovic, Paul E. Wise, Joanne Young, and James Church: none. NR 154 TC 334 Z9 348 U1 2 U2 36 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 SEP PY 2012 VL 107 IS 9 BP 1315 EP 1330 DI 10.1038/ajg.2012.161 PG 16 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 004NU UT WOS:000308689200007 PM 22710576 ER PT J AU Morishima, C Shiffman, ML Dienstag, JL Lindsay, KL Szabo, G Everson, GT Lok, AS Di Bisceglie, AM Ghany, MG Naishadham, D Morgan, TR Wright, EC AF Morishima, Chihiro Shiffman, Mitchell L. Dienstag, Jules L. Lindsay, Karen L. Szabo, Gyongyi Everson, Gregory T. Lok, Anna S. Di Bisceglie, Adrian M. Ghany, Marc G. Naishadham, Deepa Morgan, Timothy R. Wright, Elizabeth C. CA HALT-C Trial Grp TI Reduction in Hepatic Inflammation Is Associated With Less Fibrosis Progression and Fewer Clinical Outcomes in Advanced Hepatitis C SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID INTERFERON; THERAPY; PEGINTERFERON; RIBAVIRIN; METAANALYSIS; TRIALS; VIRUS AB OBJECTIVES: During the Hepatitis C Antiviral Long-term Treatment against Cirrhosis Trial, 3.5 years of maintenance peginterferon-alfa-2a therapy did not affect liver fibrosis progression or clinical outcomes among 1,050 previous interferon nonresponders with advanced fibrosis or cirrhosis. We investigated whether reduced hepatic inflammation was associated with clinical benefit in 834 patients with a baseline and follow-up biopsy 1.5 years after randomization to peginterferon or observation. METHODS: Relationships between change in hepatic inflammation (Ishak hepatic activity index, (HAI)) and serum alanine aminotransferase level, fibrosis progression and clinical outcomes after randomization, and hepatitis C virus (HCV) RNA decline before and after randomization were evaluated. Histological change was defined as a >= 2-point difference in HAI or Ishak fibrosis score between biopsies. RESULTS: Among 657 patients who received full-dose peginterferon/ribavirin "lead-in" therapy before randomization, year-1.5 HAI improvement was associated with lead-in HCV RNA suppression in both the randomized treated (P<0.0001) and control (P=0.0001) groups, even in the presence of recurrent viremia. This relationship persisted at year 3.5 in both the treated (P=0.001) and control (P=0.01) groups. Among 834 patients followed for a median of 6 years, fewer clinical outcomes occurred in patients with improved HAI at year 1.5 compared with those without such improvement in both the treated (P=0.03) and control (P=0.05) groups. Among patients with Ishak 3-4 fibrosis at baseline, those with improved HAI at year 1.5 had less fibrosis progression at year 1.5 in both the treated (P=0.0003) and control (P=0.02) groups. CONCLUSIONS: Reduced hepatic inflammation (measured 1.5 and 3.5 years after randomization) was associated with profound virological suppression during lead-in treatment with full-dose peginterferon/ribavirin and with decreased fibrosis progression and clinical outcomes, independent of randomized treatment. C1 [Morishima, Chihiro] Univ Washington, Dept Lab Med, Seattle, WA 98109 USA. [Shiffman, Mitchell L.] Bon Secours Hlth Syst, Liver Inst Virginia, Newport News, VA USA. [Dienstag, Jules L.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Dienstag, Jules L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Lindsay, Karen L.] Univ So Calif, Keck Sch Med, Div Gastrointestinal & Liver Dis, Los Angeles, CA 90033 USA. [Szabo, Gyongyi] Univ Massachusetts, Sch Med, Dept Med, Div Gastroenterol,Hepatol & Liver Ctr, Worcester, MA USA. [Everson, Gregory T.] Univ Colorado Denver, Sch Med, Sect Hepatol, Div Gastroenterol & Hepatol, Aurora, CO USA. [Lok, Anna S.] Univ Michigan, Sch Med, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI USA. [Di Bisceglie, Adrian M.] St Louis Univ, Sch Med, Div Gastroenterol & Hepatol, St Louis, MO USA. [Ghany, Marc G.; Wright, Elizabeth C.] NIDDKD, Dept Hlth & Human Serv, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. [Naishadham, Deepa] New England Res Inst, Watertown, MA 02172 USA. [Morgan, Timothy R.] Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA. [Morgan, Timothy R.] VA Long Beach Healthcare Syst, Gastroenterol Serv, Long Beach, CA USA. [Wright, Elizabeth C.] NIH, Dept Hlth & Human Serv, Off Director, Bethesda, MD 20892 USA. RP Morishima, C (reprint author), Univ Washington, Dept Lab Med, Box 358050,850 Republican St, Seattle, WA 98109 USA. EM chihiro@u.washington.edu OI Yang, Shuman/0000-0002-9638-0890 FU National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK); National Institute of Allergy and Infectious Diseases (NIAID); National Cancer Institute; National Center for Minority Health and Health Disparities; General Clinical Research Center and Clinical and Translational Science Center from National Center for Research Resources, National Institutes of Health (NIH); NIH, NIDDK; Genentech; Tibotec, Inc. FX This study was supported by the National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK contract numbers are listed below). Additional support was provided by the National Institute of Allergy and Infectious Diseases (NIAID); the National Cancer Institute; the National Center for Minority Health and Health Disparities; by General Clinical Research Center and Clinical and Translational Science Center grants from the National Center for Research Resources, National Institutes of Health (NIH grant numbers are listed below); and by the Intramural Research Program of the NIH, NIDDK (M. G. Ghany). 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. Additional funding to conduct this study was supplied by Hoffmann-La Roche, Inc. (now Genentech), through a Cooperative Research and Development Agreement (CRADA) with the National Institutes of Health.; Financial relationships of the authors with Hoffmann-La Roche, Inc. (now Genentech), are as follows: M. L. Shiffman is a consultant, on the speaker's bureau, and receives research support; K. L. Lindsay was a consultant and received research support from Hoffmann-La Roche, Inc. (now Genentech), during this study and is now an employee of Tibotec, Inc. (a subsidiary of Johnson and Johnson), Titusville, NJ; G. Szabo receives research support; G. T. Everson is a consultant and receives research support; A. S. Lok is a consultant and receives research support; A. M. Di Bisceglie is a consultant and receives research support; and T. R. Morgan receives research support. Authors with no financial relationships related to this project are: C. Morishima, J. L. Dienstag, M. G. Ghany, D. Naishadham, and E. C. Wright. NR 19 TC 5 Z9 5 U1 0 U2 0 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 SEP PY 2012 VL 107 IS 9 BP 1388 EP 1398 DI 10.1038/ajg.2012.137 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 004NU UT WOS:000308689200016 PM 22688849 ER PT J AU Higuchi, LM Khalili, H Chan, AT Richter, JM Bousvaros, A Fuchs, CS AF Higuchi, Leslie M. Khalili, Hamed Chan, Andrew T. Richter, James M. Bousvaros, Athos Fuchs, Charles S. TI A Prospective Study of Cigarette Smoking and the Risk of Inflammatory Bowel Disease in Women SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID ULCERATIVE-COLITIS; CROHNS-DISEASE; LIFE-STYLE; ORAL-CONTRACEPTION; DIABETES-MELLITUS; OLMSTED COUNTY; NURSES HEALTH; TOBACCO-SMOKE; CANCER; METAANALYSIS AB OBJECTIVES: Long-term data on the influence of cigarette smoking, especially cessation, on the risk of Crohn's disease (CD) and ulcerative colitis (UC) are limited. METHODS: We conducted a prospective study of 229,111 women in the Nurses' Health Study (NHS) and Nurses' Health Study II (NHS II). Biennially, we collected updated data on cigarette smoking, other risk factors, and diagnoses of CD or UC confirmed by medical record review. RESULTS: Over 32 years in NHS and 18 years in NHS II, we documented 336 incident cases of CD and 400 incident cases of UC. Compared with never smokers, the multivariate hazard ratio (HR) of CD was 1.90 (95 % confidence interval (CI), 1.42-2.53) among current smokers and 1.35 (95 % CI, 1.05-1.73) among former smokers. Increasing pack-years was associated with increasing risk of CD (Ptrend < 0.0001), whereas smoking cessation was associated with an attenuation of risk. By contrast, the multivariate HR of UC was 0.86 (95 % CI, 0.61-1.20) among current smokers and 1.56 (95 % CI, 1.26-1.93) among former smokers. The risk of UC was significantly increased within 2-5 years of smoking cessation (HR, 3.06; 95 % CI, 2.00-4.67) and remained persistently elevated over 20 years. CONCLUSIONS: Current smoking is associated with an increased risk of CD, but not UC. By contrast, former smoking is associated with an increased risk of UC, with risk persisting over two decades after cessation. C1 [Higuchi, Leslie M.; Bousvaros, Athos] Childrens Hosp, Div Gastroenterol & Nutr, Boston, MA 02115 USA. [Higuchi, Leslie M.; Khalili, Hamed; Chan, Andrew T.; Richter, James M.; Bousvaros, Athos; Fuchs, Charles S.] Harvard Univ, Sch Med, Boston, MA USA. [Khalili, Hamed; Chan, Andrew T.; Richter, James M.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Chan, Andrew T.; Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Higuchi, LM (reprint author), Childrens Hosp, Div Gastroenterol & Nutr, Hunnewell Ground Floor,300 Longwood Ave, Boston, MA 02115 USA. EM leslie.higuchi@childrens.harvard.edu FU National Institute of Diabetes and Digestive and Kidney Diseases [K08DK064256]; National Institutes of Health; Crohn's and Colitis Foundation of America, Research Fellowship Award; Broad Medical Research Program of the Broad Foundation; National Cancer Institute [P01 CA87969, P01 CA55075, P50 CA127003]; Merck Co.; UCB FX This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (K08DK064256), the National Institutes of Health (L. M. H.); Crohn's and Colitis Foundation of America, Research Fellowship Award (L. M. H., H. K.); Broad Medical Research Program of the Broad Foundation (A. T. C.); the National Cancer Institute (P01 CA87969 to S. Hankinson, P01 CA55075 to W. Willett, P50 CA127003 to C. S. F.), the National Institutes of Health. The research presented in this manuscript is original. The contents of this article are solely the responsibility of the authors. The National Institute of Diabetes and Digestive and Kidney Diseases, the National Institutes of Health, the Crohn's and Colitis Foundation of America, the Broad Foundation and the National Cancer Institute, the National Institutes of Health had no role in the collection, management, analysis, or interpretation of the data and had no role in the preparation, review, or approval of the manuscript.; Andrew T. Chan has previously served as a consultant for Bayer HealthCare and Millennium Pharmaceuticals. James M. Richter is a consultant for Policy Analysis, and Aptalis Pharmaceuticals. Athos Bousvaros has received research support from Merck & Co., and UCB; he is a consultant for Millennium Pharmaceuticals. Leslie M. Higuchi, Hamed Khalili, and Charles S. Fuchs have no financial disclosures. NR 39 TC 54 Z9 55 U1 0 U2 5 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 SEP PY 2012 VL 107 IS 9 BP 1399 EP 1406 DI 10.1038/ajg.2012.196 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 004NU UT WOS:000308689200017 PM 22777340 ER PT J AU Crocker, JB Crocker, JT Greenwald, JL AF Crocker, J. Benjamin Crocker, Jonathan T. Greenwald, Jeffrey L. TI Telephone Follow-up as a Primary Care Intervention for Postdischarge Outcomes Improvement: A Systematic Review SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Health care delivery; Primary care; Systematic reviews; Technology assessment; Telephone follow-up ID RANDOMIZED CONTROLLED-TRIAL; PATIENTS AFTER-DISCHARGE; HOSPITAL DISCHARGE; ADVERSE EVENTS; EMERGENCY-DEPARTMENT; MEDICAL PATIENTS; OLDER PATIENTS; HIGH-RISK; POSTHOSPITAL CARE; PAYMENT SYSTEM AB OBJECTIVE: Postdischarge telephone follow-up plays an integral part in transitional care efforts in many regions. We systematically reviewed the literature to evaluate the evidence regarding the impact of primary care-based telephone follow-up on postdischarge emergency department visits and hospital readmissions. METHODS: We performed an electronic database search for relevant telephone follow-up studies originating in adult primary care settings. RESULTS: Only 3 studies (N = 1765) met entry criteria for this review. None of the studies demonstrated evidence of reduced admissions or emergency department visits from primary care-based telephone follow-ups. All 3 studies reported improved primary care office contact as a result of telephone follow-up intervention. CONCLUSIONS: Despite the growing use of primary care-based telephone follow-up in the postdischarge period, there are no high-quality studies demonstrating its benefit. However, its positive impact on patient engagement holds potentially meaningful implications. In light of recent national health care legislation, the primary care field is ripe for high-quality studies to evaluate the effectiveness of telephone follow-up for patients in the postdischarge period. Particular areas of research focus are discussed. (C) 2012 Elsevier Inc. All rights reserved. The American Journal of Medicine (2012) 125, 915-921 C1 [Crocker, J. Benjamin] Harvard Univ, Div Primary Care, Dept Med, Massachusetts Gen Hosp,Med Sch,Ambulatory Practic, Boston, MA 02114 USA. [Crocker, Jonathan T.] Harvard Univ, Program Hosp Med, Div Primary Care & Gen Med, Dept Med,Beth Israel Deaconess Med Ctr,Med Sch, Boston, MA 02114 USA. [Greenwald, Jeffrey L.] Harvard Univ, Inpatient Clinician Educ Serv, Dept Med, Massachusetts Gen Hosp,Med Sch, Boston, MA 02114 USA. RP Crocker, JB (reprint author), Harvard Univ, Div Primary Care, Dept Med, Massachusetts Gen Hosp,Med Sch,Ambulatory Practic, 101 Merrimac St,10th Floor,Suite 1000, Boston, MA 02114 USA. EM jbcrocker@partners.org FU Massachusetts General Hospital FX Dr J. Benjamin Crocker thanks the Richard Winickoff Primary Care Fellowship at Massachusetts General Hospital. NR 66 TC 18 Z9 21 U1 3 U2 12 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 SEP PY 2012 VL 125 IS 9 BP 915 EP 921 DI 10.1016/j.amjmed.2012.01.035 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 004PG UT WOS:000308693000022 PM 22938927 ER PT J AU Daniels, KM Arena, R Lavie, CJ Forman, DE AF Daniels, Karla M. Arena, Ross Lavie, Carl J. Forman, Daniel E. TI Cardiac Rehabilitation for Women across the Lifespan SO AMERICAN JOURNAL OF MEDICINE LA English DT Review DE Aging; Cardiac rehabilitation; Cardiovascular disease; Coronary artery disease; Women ID CORONARY-HEART-DISEASE; CLINICAL CARDIOLOGY SUBCOMMITTEE; CARDIOVASCULAR-DISEASE; METABOLISM SUBCOMMITTEE; MYOCARDIAL-INFARCTION; SECONDARY PREVENTION; PHYSICAL-ACTIVITY; HORMONE-THERAPY; ARTERY-DISEASE; HEALTH-CARE AB Cardiac rehabilitation improves function and compliance and also reduces morbidity and mortality in female and male cardiovascular disease patients but remains significantly underutilized. At every age, and especially in their senior years, female cardiovascular disease patients are under-referred relative to men. Lack of standardized referral processes, misconceptions by physicians and patients, and idiosyncrasies of female pathophysiology contribute to this pattern. Moreover, confounding factors of age, socioeconomic status, and sex-specific roles and responsibilities exacerbate the problem. This review summarizes barriers to cardiac rehabilitation for female cardiac patients, and highlights opportunities for increased participation and benefit. (C) 2012 Elsevier Inc. All rights reserved. The American Journal of Medicine (2012) 125, 937.e1-937.e7 C1 [Forman, Daniel E.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Forman, Daniel E.] Harvard Univ, Sch Med, Boston, MA USA. [Daniels, Karla M.; Forman, Daniel E.] VA Boston Healthcare Syst, New England Geriatr Res Educ & Clin Ctr, Boston, MA USA. [Arena, Ross] Univ New Mexico, Dept Internal Med, Div Cardiol, Albuquerque, NM 87131 USA. [Arena, Ross] Univ New Mexico, Dept Orthopaed & Rehabil, Phys Therapy Program, Albuquerque, NM 87131 USA. [Lavie, Carl J.] Univ Queensland, Ochsner Clin Sch, Sch Med, John Ochsner Heart & Vasc Inst, New Orleans, LA USA. RP Forman, DE (reprint author), Brigham & Womens Hosp, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA. EM deforman@partners.org RI Arena, Ross/A-3141-2008; Lavie, Carl/A-6014-2011 OI Arena, Ross/0000-0002-6675-1996; NR 58 TC 2 Z9 2 U1 1 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 SEP PY 2012 VL 125 IS 9 AR 937.e1 DI 10.1016/j.amjmed.2011.10.028 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 004PG UT WOS:000308693000025 PM 22748403 ER PT J AU Burris, HH Rifas-Shiman, SL Kleinman, K Litonjua, AA Huh, SY Rich-Edwards, JW Camargo, CA Gillman, MW AF Burris, Heather H. Rifas-Shiman, Sheryl L. Kleinman, Ken Litonjua, Augusto A. Huh, Susanna Y. Rich-Edwards, Janet W. Camargo, Carlos A., Jr. Gillman, Matthew W. TI Vitamin D deficiency in pregnancy and gestational diabetes mellitus SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE 25-hydroxyvitamin D; gestational diabetes mellitus (GDM); pregnancy; vitamin D ID 25-HYDROXYVITAMIN D; PHYSICAL-ACTIVITY; MATERNAL OBESITY; NUTRITION; INSUFFICIENCY; DETERMINANTS; FREQUENCY; OUTCOMES; CALCIUM; HEALTH AB OBJECTIVE: We examined the association of second-trimester maternal plasma 25-hydroxyvitamin D (25[OH] D) during pregnancy with gestational diabetes mellitus (GDM). STUDY DESIGN: Among 1314 pregnant women who participated in Project Viva, a birth cohort study, we measured 25(OH) D levels at 26-28 weeks gestation during GDM screening using a 1-hour 50-g glucose challenge test. RESULTS: We found 25(OH) D levels of <25 nmol/L in 44 of 1087 women (4.0%) with normal glucose tolerance, 9 of 159 women (5.7%) with impaired glucose tolerance, and 9 of 68 women (13.2%) with GDM. Analyses that were adjusted for sociodemographics, season, maternal body mass index, gestational weight gain, and dietary factors suggested that women with 25(OH) D levels of <25 vs >= 25 nmol/L may have higher odds of experiencing GDM (odds ratio, 2.2; 95% confidence interval, 0.8 -5.5). Glucose levels after the glucose challenge test were associated inversely with 25(OH) D levels (P < .01). CONCLUSION: Second-trimester 25(OH) D levels were associated inversely with glucose levels after 1-hour 50-g glucose challenge test; low 25(OH) D levels may be associated with increased risk of GDM. C1 [Burris, Heather H.] Childrens Hosp, Beth Israel Deaconess Med Ctr, Dept Neonatol, Boston, MA 02115 USA. [Burris, Heather H.] Childrens Hosp, Dept Pediat, Div Newborn Med, Boston, MA 02115 USA. [Huh, Susanna Y.] Childrens Hosp, Dept Pediat, Div Gastroenterol & Nutr, Boston, MA 02115 USA. [Rich-Edwards, Janet W.] Brigham & Womens Hosp, Dept Med, Div Womens Hlth, Boston, MA 02115 USA. [Litonjua, Augusto A.; Camargo, Carlos A., Jr.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Litonjua, Augusto A.] Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Populat Med, Obes Prevent Program, Boston, MA USA. [Rifas-Shiman, Sheryl L.; Kleinman, Ken; Gillman, Matthew W.] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Rich-Edwards, Janet W.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Gillman, Matthew W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Burris, HH (reprint author), BIDMC Neonatol, 330 Brookline Ave,RO 318, Boston, MA 02215 USA. EM heburris@bidmc.harvard.edu OI Burris, Heather/0000-0003-4510-9547; Litonjua, Augusto/0000-0003-0422-5875 FU National Institutes of Health [R01 HD034568, R01 HD064925, K24 HL 06804]; Harvard Pilgrim Health Care Foundation; Klarman Scholars Program at Beth Israel Deaconess Medical Center FX Supported by the National Institutes of Health (grant numbers R01 HD034568, R01 HD064925, and K24 HL 06804), the Harvard Pilgrim Health Care Foundation, and the Klarman Scholars Program at Beth Israel Deaconess Medical Center. NR 42 TC 10 Z9 14 U1 1 U2 11 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 2012 VL 207 IS 3 AR 182.e1 DI 10.1016/j.ajog.2012.05.022 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 003BL UT WOS:000308583100018 PM 22717271 ER PT J AU Flanagan, JE Landa, R Bhat, A Bauman, M AF Flanagan, Joanne E. Landa, Rebecca Bhat, Anjana Bauman, Margaret TI Head Lag in Infants at Risk for Autism: A Preliminary Study SO AMERICAN JOURNAL OF OCCUPATIONAL THERAPY LA English DT Article DE autistic disorder; infants; motor skills disorders; postural balance; risk factor ID MUSCLE POWER DEVELOPMENT; HIGH-FUNCTIONING AUTISM; SPECTRUM DISORDERS; POSTURAL CONTROL; PRETERM INFANTS; DEVELOPMENTAL DISORDERS; MOTOR DEVELOPMENT; 1ST YEAR; CHILDREN; IDENTIFICATION AB OBJECTIVE. Poor postural control during pull-to-sit is a predictor of developmental disruption in cerebral palsy and preterm populations but has not been examined in infants at risk for autism. We examined the association between head lag during pull-to-sit at age 6 mo and autism risk status. METHOD. High-risk participants were siblings of children with autism. We studied one sample of 40 high-risk infants prospectively from 6-36 mo and obtained diagnostic classifications of autism or no autism. We conducted a subsequent between-group comparison with a new sample of 20 high-risk and 21 low-risk infants. RESULTS. Head lag was significantly associated with autism spectrum disorder at 36 mo (p=.020) and was more frequently observed in high-risk than in low-risk infants (p=.018). CONCLUSION. Head lag with other alterations in early development may be associated with autism risk and may serve as an early indicator of neurodevelopmental disruption. Results have clinical implications for occupational therapists in early intervention practice. C1 [Flanagan, Joanne E.; Landa, Rebecca] Kennedy Krieger Inst, Ctr Autism & Related Disorders, Baltimore, MD 21211 USA. [Landa, Rebecca] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Bhat, Anjana] Univ Connecticut, Neag Sch Educ, Dept Kinesiol, Storrs, CT USA. [Bauman, Margaret] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lurie Ctr Autism, Cambridge, MA 02138 USA. [Bauman, Margaret] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat & Neurol, Cambridge, MA 02138 USA. RP Flanagan, JE (reprint author), Kennedy Krieger Inst, Ctr Autism & Related Disorders, 3901 Greenspring Ave, Baltimore, MD 21211 USA. EM landa@kennedykrieger.org FU NIMH NIH HHS [R01 MH59630] NR 57 TC 61 Z9 63 U1 0 U2 16 PU AMER OCCUPATIONAL THERAPY ASSOC, INC PI BETHESDA PA 4720 MONTGOMERY LANE, BETHESDA, MD 20814-3425 USA SN 0272-9490 J9 AM J OCCUP THER JI Am. J. Occup. Ther. PD SEP-OCT PY 2012 VL 66 IS 5 SI SI BP 577 EP 585 DI 10.5014/ajot.2012.004192 PG 9 WC Rehabilitation SC Rehabilitation GA 006RJ UT WOS:000308836200010 PM 22917124 ER PT J AU Best, SR Friedman, AD Landau-Zemer, T Barbu, AM Burns, JA Freeman, MW Halvorsen, YD Hillman, RE Zeitels, SM AF Best, Simon R. Friedman, Aaron D. Landau-Zemer, Tali Barbu, Anca M. Burns, James A. Freeman, Mason W. Halvorsen, Yuan-Di Hillman, Robert E. Zeitels, Steven M. TI Safety and Dosing of Bevacizumab (Avastin) for the Treatment of Recurrent Respiratory Papillomatosis SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE Avastin; bevacizumab; glottis; KTP laser; larynx; papilloma; respiratory papillomatosis; toxicity; vocal cord; voice ID KTP LASER TREATMENT; PULSED DYE-LASER; LARYNGEAL PAPILLOMATOSIS; INTERFERON ALFA-N1; INJECTIONS; CIDOFOVIR; INDOLE-3-CARBINOL; ANESTHESIA; DYSPLASIA; CANCER AB Objectives: Increasing evidence supports the use of laryngeal injections of the antiangiogenic agent bevacizumab (Avastin) for the adjuvant treatment of recurrent respiratory papillomatosis (RRP). A recent prospective open-label investigation, approved by the US Food and Drug Administration, employing 12.5 mg of sublesional bevacizumab demonstrated single-site efficacy without complications; however, the safety of multiple-site injections and higher dosing has not yet been reported. The primary objective of this study was to report on the safety of increased doses of bevacizumab for the treatment of RRP. Methods: Two cohorts of adult patients were evaluated. In the first group, a prospective analysis was performed on patients with a diagnosis of laryngeal RRP after their participation in the initial clinical trial with a single-site lower dose (7.5 to 12.5 mg). They received higher doses of sublesional laryngeal bevacizumab (15 to 50 mg total) with detailed physiologic, hematologic, and serum chemistry measurements performed before and after each bevacizumab injection. A second cohort of patients received sublesional laryngeal injections of bevacizumab (15 to 88 mg total) without physiologic measurements and underwent a retrospective analysis of reported complications. Results: One hundred consecutive laryngeal injection sessions (office, 87; operating room, 13) with bevacizumab were performed in 43 patients, with a mean dose of 30 mg total per treatment (range, 15 to 88 mg). Sixty-three of the 100 sessions were accompanied by KTP laser photoangiolysis of the papilloma prior to bevacizumab injections. Eighteen patients (cohort 1) underwent detailed physiologic assessment, and no dysfunction was observed. There were no local or systemic complications of bevacizumab administration. The second group of 25 patients (cohort 2) also reported no significant local or systemic complications. Neither patient group was observed to have a local wound problem in the larynx. Conclusions: This investigation provides evidence that higher doses of bevacizumab are relatively safe in adult patients with laryngeal RRP. Further refinements in pharmacologic concentration and drug delivery will determine the optimal treatment regimens in the future. C1 [Best, Simon R.; Friedman, Aaron D.; Landau-Zemer, Tali; Barbu, Anca M.; Burns, James A.; Hillman, Robert E.; Zeitels, Steven M.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. [Best, Simon R.; Friedman, Aaron D.; Landau-Zemer, Tali; Barbu, Anca M.; Burns, James A.; Hillman, Robert E.; Zeitels, Steven M.] Harvard Univ, Sch Med, Dept Surg, Cambridge, MA 02138 USA. [Freeman, Mason W.; Halvorsen, Yuan-Di] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. [Freeman, Mason W.; Halvorsen, Yuan-Di] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Translat Med Grp, Boston, MA 02114 USA. [Hillman, Robert E.] Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. RP Zeitels, SM (reprint author), Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, 1 Bowdoin Sq,11th Floor, Boston, MA 02114 USA. FU Eugene B. Casey Foundation; V Foundation; Institute of Laryngology and Voice Restoration; Harvard Catalyst Program FX From the Departments of Surgery (Best, Friedman, Landau-Zemer, Barbu, Burns, Hillman, Zeitels) and Medicine (Freeman, Halvorsen), Harvard Medical School, and the Center for Laryngeal Surgery and Voice Rehabilitation (Best, Friedman, Landau-Zemer, Barbu, Burns, Hillman, Zeitels), the Translational Medicine Group, Center for Computational and Integrative Biology (Freeman, Halvorsen), and the MGH Institute of Health Professions (Hillman), Massachusetts General Hospital, Boston, Massachusetts. This work was supported in part by the Eugene B. Casey Foundation, the V Foundation, the Institute of Laryngology and Voice Restoration, and the Harvard Catalyst Program. NR 29 TC 9 Z9 9 U1 1 U2 4 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD SEP PY 2012 VL 121 IS 9 BP 587 EP 593 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA 006WZ UT WOS:000308851800005 PM 23012897 ER PT J AU Clavien, PA Lillemoe, KD AF Clavien, Pierre-Alain Lillemoe, Keith D. TI Note From the Editors on the ALPPS e-Letters-to-the-Editor SO ANNALS OF SURGERY LA English DT Editorial Material C1 [Clavien, Pierre-Alain] Univ Zurich Hosp, Dept Visceral & Transplantat Surg, CH-8091 Zurich, Switzerland. [Lillemoe, Keith D.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Clavien, PA (reprint author), Univ Zurich Hosp, Dept Visceral & Transplantat Surg, Ramistr, CH-8091 Zurich, Switzerland. EM clavien@access.uzh.ch NR 2 TC 9 Z9 9 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD SEP PY 2012 VL 256 IS 3 BP 552 EP 552 DI 10.1097/SLA.0b013e318266fa1f PG 1 WC Surgery SC Surgery GA 004HB UT WOS:000308670900028 PM 22895352 ER PT J AU Yaffe, K Falvey, C Hamilton, N Schwartz, AV Simonsick, EM Satterfield, S Cauley, JA Rosano, C Launer, LJ Strotmeyer, ES Harris, TB AF Yaffe, Kristine Falvey, Cherie Hamilton, Nathan Schwartz, Ann V. Simonsick, Eleanor M. Satterfield, Suzanne Cauley, Jane A. Rosano, Caterina Launer, Lenore J. Strotmeyer, Elsa S. Harris, Tamara B. TI Diabetes, Glucose Control, and 9-Year Cognitive Decline Among Older Adults Without Dementia SO ARCHIVES OF NEUROLOGY LA English DT Article ID MIDDLE-AGED ADULTS; MELLITUS; RISK; IMPAIRMENT; COHORT; ASSOCIATION; DISEASE; WOMEN AB Objectives: To determine if prevalent and incident diabetes mellitus (DM) increase risk of cognitive decline and if, among elderly adults with DM, poor glucose control is related to worse cognitive performance. Design: Prospective cohort study. Setting: Health, Aging, and Body Composition Study at 2 community clinics. Participants: A total of 3069 elderly adults (mean age, 74.2 years; 42% black; 52% female). Main Outcome Measures: Participants completed the Modified Mini-Mental State Examination (3MS) and Digit Symbol Substitution Test (DSST) at baseline and selected intervals over 10 years. Diabetes mellitus status was determined at baseline and during follow-up visits. Glycosylated hemoglobin A(1c) level was measured at years 1 (baseline), 4, 6, and 10 from fasting whole blood. Results: At baseline, 717 participants (23.4%) had prevalent DM and 2352 (76.6%) were without DM, 159 of whom developed incidentDMduring follow-up. Participants with prevalent DM had lower baseline test scores than participants without DM(3MS: 88.8 vs 90.9; DSST: 32.5 vs 36.3, respectively; t = 6.09; P =. 001 for both tests). Results from mixed-effects models showed a similar pattern for 9-year decline (3MS: -6.0-vs -4.5-point decline; t = 2.66; P =. 008; DSST: -7.9-vs -5.7-point decline; t = 3.69; P =. 001, respectively). Participants with incident DM tended to have baseline and 9-year decline scores between the other 2 groups but were not statistically different from the group without DM. Multivariate adjustment for demographics and medical comorbidities produced similar results. Among participants with prevalent DM, glycosylated hemoglobin A1c level was associated with lower average mean cognitive scores (3MS: F = 8.2; P for overall =. 003; DSST: F = 3.4; P for overall =. 04), even after multivariate adjustment. Conclusion: Among well-functioning older adults, DM and poor glucose control among those with DM are associated with worse cognitive function and greater decline. This suggests that severity of DM may contribute to accelerated cognitive aging. Arch Neurol. 2012; 69(9): 1170-1175. Published online June 18, 2012. doi: 10.1001/archneurol.2012.1117 C1 [Yaffe, Kristine; Falvey, Cherie] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. [Yaffe, Kristine; Schwartz, Ann V.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94121 USA. [Yaffe, Kristine; Falvey, Cherie; Hamilton, Nathan] San Francisco VA Med Ctr, San Francisco, CA USA. [Satterfield, Suzanne] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. [Simonsick, Eleanor M.] NIA, Clin Res Branch, Baltimore, MD 21224 USA. [Launer, Lenore J.; Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA. [Cauley, Jane A.; Rosano, Caterina; Strotmeyer, Elsa S.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. RP Yaffe, K (reprint author), Univ Calif San Francisco, Dept Psychiat, Box 181,4150 Clement St, San Francisco, CA 94121 USA. EM kristine.yaffe@ucsf.edu RI Strotmeyer, Elsa/F-3015-2014; OI Rosano, Caterina/0000-0002-0909-1506; Strotmeyer, Elsa/0000-0002-4093-6036; Rosano, Caterina/0000-0002-4271-6010; Cauley, Jane A/0000-0003-0752-4408 FU NIH (NIA, National Institute of Diabetes and Digestive and Kidney Diseases, and National Institute of Mental Health); Department of Defense; American Health Assistance Foundation; Anonymous Foundation; Alzheimer's Association; Amgen; Merck Serono; GlaxoSmithKline; NIH (National Institute of Diabetes and Digestive and Kidney Diseases and NIA); NIH/NIA; NIH/NIA Intramural Research Program; NIH; NIA [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, R01-AG028050]; National Institute of Nursing Research [R01-NR012459]; Intramural Research Program of the NIH, NIA; American Health Assistance Foundation [A201-0029] FX Dr Yaffe has served on data safety monitoring boards for Pfizer Inc, Medivation Inc, and the National Institutes of Health (NIH) (National Institute of Mental Health and National Institute on Aging [NIA] trials) and has received research support from the NIH (NIA, National Institute of Diabetes and Digestive and Kidney Diseases, and National Institute of Mental Health), the Department of Defense, American Health Assistance Foundation, Anonymous Foundation, and the Alzheimer's Association. Dr Schwartz serves on a scientific advisory board for GlaxoSmithKline; has received speaker honoraria from Amgen and Merck Serono; has received funding for travel from Amgen; and receives research support from Merck Serono, GlaxoSmithKline, and the NIH (National Institute of Diabetes and Digestive and Kidney Diseases and NIA). Dr Simonsick serves as an associate editor for the Journal of Gerontology Medical Sciences. Dr Satterfield receives research support from the NIH/NIA. Dr Cauley receives research support from Novartis. Dr Launer receives research support from the NIH/NIA Intramural Research Program. Dr Harris receives research support from the NIH.; This work was supported by NIA contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106; NIA grant R01-AG028050; and National Institute of Nursing Research grant R01-NR012459. This research was supported in part by the Intramural Research Program of the NIH, NIA, and grant A201-0029 from the American Health Assistance Foundation. Dr Yaffe is supported in part by NIA grant K24AG031155. NR 32 TC 89 Z9 93 U1 0 U2 13 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 SEP PY 2012 VL 69 IS 9 BP 1170 EP 1175 DI 10.1001/archneurol.2012.1117 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 002UB UT WOS:000308560600011 PM 22710333 ER PT J AU Caplan, LR Mohr, JP Ackerman, RH AF Caplan, Louis R. Mohr, Jay P. Ackerman, Robert H. TI In Memoriam: Charles Miller Fisher, MD (1913-2012) SO ARCHIVES OF NEUROLOGY LA English DT Biographical-Item C1 [Caplan, Louis R.] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. [Ackerman, Robert H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Mohr, Jay P.] Columbia Univ, Med Ctr, Neurol Inst, Doris & Stanley Tananbaum Stroke Ctr, New York, NY USA. RP Caplan, LR (reprint author), Beth Israel Deaconess Med Ctr, Dept Neurol, 330 Brookline Ave,Palmer 127 W Campus, Boston, MA 02215 USA. EM lcaplan@bidmc.harvard.edu NR 1 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 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD SEP PY 2012 VL 69 IS 9 BP 1208 EP 1209 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 002UB UT WOS:000308560600021 PM 23753916 ER PT J AU Sohn, EH He, SK Kim, LA Salehi-Had, H Javaheri, M Spee, C Dustin, L Hinton, DR Eliott, D AF Sohn, Elliott H. He, Shikun Kim, Leo A. Salehi-Had, Hani Javaheri, Michael Spee, Christine Dustin, Laurie Hinton, David R. Eliott, Dean TI Angiofibrotic Response to Vascular Endothelial Growth Factor Inhibition in Diabetic Retinal Detachment Report No. 1 SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID INTRAVITREAL BEVACIZUMAB AVASTIN; VITREORETINAL DISORDERS; PREOPERATIVE ADJUNCT; AQUEOUS-HUMOR; RETINOPATHY; EXPRESSION; VITRECTOMY; EYES; INJECTION; FIBROSIS AB Objectives: To assess the effect of bevacizumab injection on connective tissue growth factor (CTGF) and vascular endothelial growth factor (VEGF) in the ocular fluids of patients with diabetic traction retinal detachment, and to determine whether intraoperative and postoperative complications are decreased in eyes given adjunctive preoperative bevacizumab injection. Methods: Twenty eyes of 19 patients were randomized to receive intravitreal bevacizumab or sham injection 3 to 7 days before vitrectomy for severe proliferative diabetic retinopathy. We collected aqueous samples before injection and at the time of vitrectomy and extracted undiluted vitreous samples. Results: Five eyes had decreased vascularization of membranes from preinjection to the time of vitrectomy (all in the bevacizumab treatment arm). Median visual acuities were 20/400 in control eyes at baseline and postoperative month 3 (POM3) and 8/200 in the bevacizumab-treated group at baseline and 20/100 at POM3 (P=.30 between control and bevacizumab-treated groups at POM3). All retinas were attached at POM3. Vitreous levels of VEGF were significantly lower in the bevacizumab group than in the control group (P=.03). Vitreous levels of CTGF were slightly lower in the bevacizumab group compared with the control group, but this difference was not statistically significant (P=.38). Levels of CTGF in the aqueous were strongly correlated with CTGF levels in the vitreous of controls (Spearman correlation coefficient, 0.95 [P<.001]). Conclusions: Intravitreal bevacizumab injection reduces vitreous levels of VEGF and produces a clinically observable alteration in diabetic fibrovascular membranes. Ocular fluid levels of CTGF are not significantly affected within the week after VEGF inhibition. Retinal reattachment rates and visual acuity are not significantly altered by preoperative intravitreal bevacizumab injection at POM3. C1 [Sohn, Elliott H.] Univ Iowa Hosp & Clin, Dept Ophthalmol, Iowa City, IA 52242 USA. [Sohn, Elliott H.; He, Shikun; Kim, Leo A.; Salehi-Had, Hani; Javaheri, Michael; Spee, Christine; Dustin, Laurie; Hinton, David R.; Eliott, Dean] Univ So Calif, Doheny Eye Inst, Los Angeles, CA USA. [Sohn, Elliott H.; He, Shikun; Kim, Leo A.; Salehi-Had, Hani; Javaheri, Michael; Spee, Christine; Dustin, Laurie; Hinton, David R.; Eliott, Dean] Los Angeles Cty Hosp, Los Angeles, CA USA. [He, Shikun; Spee, Christine; Hinton, David R.] Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90033 USA. [Kim, Leo A.; Eliott, Dean] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. [He, Shikun; Spee, Christine; Hinton, David R.] Univ So Calif, Keck Sch Med, Dept Ophthalmol, Los Angeles, CA 90033 USA. RP Sohn, EH (reprint author), Univ Iowa Hosp & Clin, Dept Ophthalmol, 200 Hawkins Dr, Iowa City, IA 52242 USA. EM Elliott.Sohn@gmail.com FU Eugene de Juan Jr Award for Innovation; Heed Foundation; National Eye Institute, National Institutes of Health [K12-EY16335]; Arnold and Mabel Beckman Foundation; Research to Prevent Blindness (Department of Ophthalmology, University of Iowa Hospitals and Clinics); National Eye Institute (Doheny Eye Institute) [EY03040] FX This study was supported by the Eugene de Juan Jr Award for Innovation (Dr Sohn); by the Heed Foundation (Drs Kim and Javaheri); by grant K12-EY16335 from the National Eye Institute, National Institutes of Health (Dr Kim); by The Arnold and Mabel Beckman Foundation (Dr Hinton); by Research to Prevent Blindness (Department of Ophthalmology, University of Iowa Hospitals and Clinics); and by core grant EY03040 from the National Eye Institute (Doheny Eye Institute). NR 47 TC 10 Z9 10 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD SEP PY 2012 VL 130 IS 9 BP 1127 EP 1134 PG 8 WC Ophthalmology SC Ophthalmology GA 002TQ UT WOS:000308559200003 PM 22965588 ER PT J AU Gentile, RC Eliott, D AF Gentile, Ronald C. Eliott, Dean TI Modification of Silicone Oil Retention Sutures in Aphakic Eyes With Iris Loss reply SO ARCHIVES OF OPHTHALMOLOGY LA English DT Letter C1 [Gentile, Ronald C.] New York Eye & Ear Infirm, Dept Ophthalmol, New York, NY 10003 USA. [Gentile, Ronald C.] New York Med Coll, Valhalla, NY 10595 USA. [Eliott, Dean] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Gentile, RC (reprint author), New York Eye & Ear Infirm, Dept Ophthalmol, 310 E 14th St, New York, NY 10003 USA. EM rgentile@nyee.edu NR 1 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 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD SEP PY 2012 VL 130 IS 9 BP 1232 EP 1232 PG 1 WC Ophthalmology SC Ophthalmology GA 002TQ UT WOS:000308559200030 ER PT J AU Holmes, LB Westgate, MN AF Holmes, Lewis B. Westgate, Marie-Noel TI Letter to the editor: Frequency of congenital malformations in newborn children SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Letter ID PRENATAL-DIAGNOSIS; INFANTS C1 MassGen Hosp Children, Genet Unit, Boston, MA USA. [Westgate, Marie-Noel] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Holmes, LB (reprint author), 801 55 Fruit St, Boston, MA USA. EM holmes.lewis@mgh.harvard.edu NR 5 TC 0 Z9 0 U1 0 U2 0 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 SEP PY 2012 VL 94 IS 9 BP 744 EP 744 DI 10.1002/bdra.23044 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 001PY UT WOS:000308473800010 PM 22806999 ER PT J AU Orio, PF Merrick, GS Galbreath, RW Butler, WM Lief, J Wallner, KE AF Orio, Peter F., III Merrick, Gregory S. Galbreath, Robert W. Butler, Wayne M. Lief, Jonathan Wallner, Kent E. TI Patient-reported long-term rectal function after permanent interstitial brachytherapy for clinically localized prostate cancer SO BRACHYTHERAPY LA English DT Article DE Prostate cancer; Brachytherapy; Rectal function; Quality of life ID QUALITY-OF-LIFE; OUTCOMES AB PURPOSE: To evaluate the effect of permanent interstitial brachytherapy with or without supplemental therapies on long-term rectal function using a patient-administered quality-of-life instrument. METHODS AND MATERIALS: One hundred thirty four of the initial 219 prostate brachytherapy patients who remain alive and have participated in a prospective evaluation of rectal function were mailed the rectal function assessment score (R-FAS). Of the 134 patients, 3 have a colostomy because of colorectal cancer, 2 failed to respond, and 129 (99.2% of eligible patients) returned a completed R-FAS. R-FAS ranges from 0 to 27 with lower scores indicative of better bowel function. Median followup was 14 years. Multiple clinical, treatment, and dosimetric parameters were evaluated for impact on bowel function. RESULTS: For the current cohort, R-FAS was 3.35, which was comparable to the 1999 (4.29), 2002 (3.92), and 2006 (4.00) surveys. In the 2011 survey, 10 (7.8%), 17 (13.1%), and 102 (78.3%) patients reported bowel function to be worse, improved, or unchanged after brachytherapy. No patient has developed a rectal ulcer or fistula. The number of preimplant bowel movements, tobacco, and diabetes mellitus correlated with R-FAS. Consistent with the previous thee surveys, patient's perception of overall rectal quality of life was inversely related to the use of supplemental external beam radiation. CONCLUSIONS: Long-term rectal function after prostate brachytherapy is favorable with a small number of patients reporting deterioration in bowel function. The judicious use of supplemental external beam radiation with particular attention to rectal doses may further improve long-term function. (C) 2012 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved. C1 [Orio, Peter F., III] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Merrick, Gregory S.; Galbreath, Robert W.; Butler, Wayne M.; Lief, Jonathan] Wheeling Jesuit Univ, Schiffler Canc Ctr, Wheeling, WV USA. [Wallner, Kent E.] Univ Washington, Grp Hlth Cooperat, Puget Sound Healthcare Corp, Seattle, WA 98195 USA. RP Merrick, GS (reprint author), Wheeling Hosp, Schiffler Canc Ctr, 1 Med Pk, Wheeling, WV 26003 USA. EM gmerrick@urologicresearchinstitute.org NR 18 TC 3 Z9 3 U1 0 U2 3 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 SEP-OCT PY 2012 VL 11 IS 5 BP 341 EP 347 DI 10.1016/j.brachy.2012.02.005 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 003QM UT WOS:000308626400003 PM 22561216 ER PT J AU Dominici, L Liao, GS Brock, J Iglehart, JD Lotfi, P Meyer, J Pandalai, P Golshan, M AF Dominici, Laura Liao, Guo-Shiou Brock, Jane Iglehart, James D. Lotfi, Parisa Meyer, Jack Pandalai, Prakash Golshan, Mehra TI Large Needle Core Biopsy of Atypical Ductal Hyperplasia: Results of Surgical Excision SO BREAST JOURNAL LA English DT Letter ID ASSISTED BREAST BIOPSY; 11-GAUGE C1 [Dominici, Laura; Iglehart, James D.; Pandalai, Prakash; Golshan, Mehra] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Liao, Guo-Shiou] Triserv Gen Hosp, Natl Def Med Ctr, Dept Surg, Taipei, Taiwan. [Brock, Jane] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Lotfi, Parisa; Meyer, Jack] Faulkner Hosp, Brigham & Womens Hosp, Dept Radiol, Boston, MA USA. RP Golshan, M (reprint author), Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, 75 Francis St, Boston, MA 02115 USA. EM mgolshan@partners.org NR 7 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1075-122X J9 BREAST J JI Breast J. PD SEP-OCT PY 2012 VL 18 IS 5 BP 506 EP 508 DI 10.1111/j.1524-4741.2012.01296.x PG 3 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 003EB UT WOS:000308589900028 PM 22897750 ER PT J AU Jirawatnotai, S Hu, YD Livingston, DM Sicinski, P AF Jirawatnotai, Siwanon Hu, Yiduo Livingston, David M. Sicinski, Piotr TI Proteomic Identification of a Direct Role for Cyclin D1 in DNA Damage Repair SO CANCER RESEARCH LA English DT Review ID SQUAMOUS-CELL CARCINOMA; BREAST-CANCER CELLS; HOMOLOGOUS RECOMBINATION; IONIZING-RADIATION; END RESECTION; ACQUIRED RADIORESISTANCE; RETINOBLASTOMA-PROTEIN; REGULATORY PROTEINS; DEPENDENT KINASES; PHOSPHORYLATION AB The human CCND1 gene, which encodes the cell-cycle protein cyclin D1, is one of the most frequently amplified genes in human cancers. Cyclin D1 activates the cyclin-dependent kinases CDK4 and CDK6 and drives cell proliferation. Beyond the cell-cycle role, the full repertoire of cyclin D1 functions in cancer cells is still unclear. Emerging evidence indicates that cyclin D1 may play a role in DNA damage response. In this review, we discuss observations linking cyclin D1 to DNA damage repair and summarize our recent findings, which show a cyclin D1 function in homologous recombination-mediated DNA repair. Cancer Res; 72(17); 4289-93. (c) 2012 AACR. C1 [Jirawatnotai, Siwanon; Hu, Yiduo; Livingston, David M.; Sicinski, Piotr] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Jirawatnotai, Siwanon; Hu, Yiduo; Livingston, David M.; Sicinski, Piotr] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Jirawatnotai, Siwanon] Mahidol Univ, Inst Mol Biosci, Salaya, Nakhon Prathom, Thailand. RP Sicinski, P (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Smith Res Bldg,Room 922,450 Brookline Ave, Boston, MA 02115 USA. EM peter_sicinski@dfci.harvard.edu FU National Institutes of Health [P01 CA080111] FX National Institutes of Health (P01 CA080111 to D.M. Livingston and P. Sicinski). NR 53 TC 23 Z9 26 U1 0 U2 14 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 SEP 1 PY 2012 VL 72 IS 17 BP 4289 EP 4293 DI 10.1158/0008-5472.CAN-11-3549 PG 5 WC Oncology SC Oncology GA 002VS UT WOS:000308565600001 PM 22915759 ER PT J AU Dulak, AM Schumacher, SE van Lieshout, J Imamura, Y Fox, C Shim, B Ramos, AH Saksena, G Baca, SC Baselga, J Tabernero, J Barretina, J Enzinger, PC Corso, G Roviello, F Lin, L Bandla, S Luketich, JD Pennathur, A Meyerson, M Ogino, S Shivdasani, RA Beer, DG Godfrey, TE Beroukhim, R Bass, AJ AF Dulak, Austin M. Schumacher, Steven E. van Lieshout, Jasper Imamura, Yu Fox, Cameron Shim, Byoungyong Ramos, Alex H. Saksena, Gordon Baca, Sylvan C. Baselga, Jose Tabernero, Josep Barretina, Jordi Enzinger, Peter C. Corso, Giovanni Roviello, Franco Lin, Lin Bandla, Santhoshi Luketich, James D. Pennathur, Arjun Meyerson, Matthew Ogino, Shuji Shivdasani, Ramesh A. Beer, David G. Godfrey, Tony E. Beroukhim, Rameen Bass, Adam J. TI Gastrointestinal Adenocarcinomas of the Esophagus, Stomach, and Colon Exhibit Distinct Patterns of Genome Instability and Oncogenesis SO CANCER RESEARCH LA English DT Article ID COPY-NUMBER ALTERATION; COLORECTAL-CANCER; LINEAGE-SURVIVAL; GENE-EXPRESSION; GASTRIC-CANCER; CHROMOSOMAL-ABERRATIONS; THERAPEUTIC TARGETS; BARRETTS-ESOPHAGUS; MUTATIONS; TUMORIGENESIS AB A more detailed understanding of the somatic genetic events that drive gastrointestinal adenocarcinomas is necessary to improve diagnosis and therapy. Using data from high-density genomic profiling arrays, we conducted an analysis of somatic copy-number aberrations in 486 gastrointestinal adenocarcinomas including 296 esophageal and gastric cancers. Focal amplifications were substantially more prevalent in gastric/esophageal adenocarcinomas than colorectal tumors. We identified 64 regions of significant recurrent amplification and deletion, some shared and others unique to the adenocarcinoma types examined. Amplified genes were noted in 37% of gastric/esophageal tumors, including in therapeutically targetable kinases such as ERBB2, FGFR1, FGFR2, EGFR, and MET, suggesting the potential use of genomic amplifications as biomarkers to guide therapy of gastric and esophageal cancers where targeted therapeutics have been less developed compared with colorectal cancers. Amplified loci implicated genes with known involvement in carcinogenesis but also pointed to regions harboring potentially novel cancer genes, including a recurrent deletion found in 15% of esophageal tumors where the Runt transcription factor subunit RUNX1 was implicated, including by functional experiments in tissue culture. Together, our results defined genomic features that were common and distinct to various gut-derived adenocarcinomas, potentially informing novel opportunities for targeted therapeutic interventions. Cancer Res; 72(17); 4383-93. (C) 2012 AACR. C1 [Dulak, Austin M.; van Lieshout, Jasper; Imamura, Yu; Fox, Cameron; Shim, Byoungyong; Baca, Sylvan C.; Barretina, Jordi; Enzinger, Peter C.; Meyerson, Matthew; Ogino, Shuji; Shivdasani, Ramesh A.; Beroukhim, Rameen; Bass, Adam J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Schumacher, Steven E.; Meyerson, Matthew; Beroukhim, Rameen] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Barretina, Jordi; Meyerson, Matthew; Beroukhim, Rameen; Bass, Adam J.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02215 USA. [Shivdasani, Ramesh A.; Beroukhim, Rameen; Bass, Adam J.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Baca, Sylvan C.; Baselga, Jose; Shivdasani, Ramesh A.; Beroukhim, Rameen; Bass, Adam J.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Meyerson, Matthew; Ogino, Shuji] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Dulak, Austin M.; Schumacher, Steven E.; Ramos, Alex H.; Saksena, Gordon; Baca, Sylvan C.; Barretina, Jordi; Meyerson, Matthew; Beroukhim, Rameen; Bass, Adam J.] Broad Inst, Cambridge, MA USA. [Beer, David G.] Univ Michigan, Dept Surg, Thorac Surg Sect, Ann Arbor, MI 48109 USA. [Lin, Lin] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. [Bandla, Santhoshi; Godfrey, Tony E.] Univ Rochester, Dept Surg, Rochester, NY USA. [Luketich, James D.; Pennathur, Arjun] Univ Pittsburgh, Dept Cardiothorac Surg, Pittsburgh, PA USA. [Tabernero, Josep] Hosp Valle dHebron, Dept Med Oncol, Barcelona, Spain. [Corso, Giovanni; Roviello, Franco] Univ Siena, Dept Human Pathol & Oncol, I-53100 Siena, Italy. [Baselga, Jose] Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. [Ogino, Shuji] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Bass, AJ (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM Rameen_beroukhim@dfci.harvard.edu; Adam_Bass@dfci.harvard.edu RI Godfrey, Tony/A-5572-2013; Schumacher, Steven/E-9821-2013 OI Godfrey, Tony/0000-0002-3283-6983; Schumacher, Steven/0000-0002-6819-5647 FU Novartis; Laboratory Corporation of America; Accuray; Novartis Oncology; Novartis Institutes for BioMedical Research and ownership interest; Astrazeneca stock; National Institute of Health-National Cancer Institute [5R01CA090665]; National Cancer Institute [K08CA134931, K08CA122833, U54CA143798]; GI SPORE Developmental Project [P50CA127003]; DeGregorio Family Foundation; V Foundation Scholarship; Istituto Toscano Tumori FX R. Beroukhim, M. Meyerson, and R. A. Shivdasani are consultants for Novartis. M. Meyerson is a founder of Foundation Medicine and Microgenomica, has commercial research grant from Novartis, is a consultant/advisory board member for Novartis and Foundation Medicine, and has patent royalties from Laboratory Corporation of America. J.D. Luketich has commercial research grant from Accuray. R. A. Shivdasani has commercial research grant from Novartis Oncology. R. Beroukhim has commercial research grant from Novartis Institutes for BioMedical Research and ownership interest (including patents) from Astrazeneca stock. No potential conflicts of interest were disclosed by the other authors.; This work was supported in part by the National Institute of Health-National Cancer Institute grant 5R01CA090665 (PI: J.D. Luketich). A.J. Bass is supported by the National Cancer Institute (K08CA134931) and GI SPORE Developmental Project award-P50CA127003) and the DeGregorio Family Foundation. R. Beroukhim is supported by the National Cancer Institute (K08CA122833 and U54CA143798) and a V Foundation Scholarship. F. Roviello is supported by a grant from Istituto Toscano Tumori. NR 48 TC 110 Z9 113 U1 0 U2 23 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 2012 VL 72 IS 17 BP 4383 EP 4393 DI 10.1158/0008-5472.CAN-11-3893 PG 11 WC Oncology SC Oncology GA 002VS UT WOS:000308565600012 PM 22751462 ER PT J AU Hibbert, K Rice, M Malhotra, A AF Hibbert, Kathryn Rice, Mary Malhotra, Atul TI Obesity and ARDS SO CHEST LA English DT Article ID ACUTE LUNG INJURY; OBSTRUCTIVE SLEEP-APNEA; RESPIRATORY-DISTRESS-SYNDROME; POSITIVE-PRESSURE VENTILATION; END-EXPIRATORY PRESSURE; CHEST-WALL MECHANICS; INTENSIVE-CARE-UNIT; AIRWAY PRESSURE; MORBID-OBESITY; TRACHEAL INTUBATION AB Obesity prevalence continues to increase globally, with figures exceeding 30% of some populations. Patients who are obese experience alterations in baseline pulmonary mechanics, including airflow obstruction, decreased lung volumes, and impaired gas exchange. These physiologic changes have implications in many diseases, including ARDS. The unique physiology of patients who are obese affects the presentation and pathophysiology of ARDS, and patients who are obese who have respiratory failure present specific management challenges. Although more study is forthcoming, ventilator strategies that focus on transpulmonary pressure as a measure of lung stress show promise in pilot studies. Given the increasing prevalence of obesity and the variable effects of obesity on respiratory mechanics and ARDS pathophysiology, we recommend an individualized approach to the management of the obese patient with ARDS. CHEST 2012; 142(3):785-790 C1 [Hibbert, Kathryn; Rice, Mary] Massachusetts Gen Hosp, Div Pulm & Crit Care, Boston, MA 02114 USA. [Malhotra, Atul] Brigham & Womens Hosp, Div Pulm, Boston, MA 02115 USA. [Malhotra, Atul] Brigham & Womens Hosp, Div Sleep, Boston, MA 02115 USA. [Malhotra, Atul] Brigham & Womens Hosp, Div Crit Care, Boston, MA 02115 USA. RP Hibbert, K (reprint author), Massachusetts Gen Hosp, Div Pulm, 55 Fruit St, Boston, MA 02114 USA. EM kahibbert@partners.org OI Rice, Mary/0000-0003-2538-391X FU NHLBI NIH HHS [R01 HL085188, R01 HL090897, P01 HL095491, K24 HL093218] NR 47 TC 13 Z9 18 U1 1 U2 3 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD SEP PY 2012 VL 142 IS 3 BP 785 EP 790 DI 10.1378/chest.12-0117 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 003PE UT WOS:000308623000035 PM 22948584 ER PT J AU Falade-Nwulia, OO Dhaliwal, G Schreiber, MP Saint, S Shorr, AF AF Falade-Nwulia, Oluwaseun O. Dhaliwal, Gurpreet Schreiber, Matthew P. Saint, Sanjay Shorr, Andrew F. TI A 36-Year-Old Haitian Man With Coma, Acute Kidney Injury, Lactic Acidosis, and Respiratory Failure SO CHEST LA English DT Editorial Material ID FALCIPARUM-MALARIA; UNITED-STATES C1 [Falade-Nwulia, Oluwaseun O.] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. Johns Hopkins Sch Med, Div Infect Dis, Baltimore, MD USA. Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA. [Dhaliwal, Gurpreet] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. [Schreiber, Matthew P.; Shorr, Andrew F.] Washington Hosp Ctr, Div Pulm & Crit Care Med, Washington, DC 20010 USA. Georgetown Univ, Washington, DC USA. [Saint, Sanjay] Univ Michigan, Ann Arbor VA Med Ctr, Ann Arbor, MI 48109 USA. [Saint, Sanjay] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. RP Falade-Nwulia, OO (reprint author), NIH, Dept Crit Care Med, 10 Ctr Dr,Rm 2C145, Bethesda, MD 20892 USA. EM ofalade1@jhmi.edu NR 10 TC 1 Z9 2 U1 1 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD SEP PY 2012 VL 142 IS 3 BP 798 EP 801 DI 10.1378/chest.11-3209 PG 4 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 003PE UT WOS:000308623000037 PM 22948586 ER PT J AU Morse, MA Hanks, BA Suhocki, P Doan, PL Liu, EA Frost, P Bernard, SA Tsai, A Moore, DT O'Neil, BH AF Morse, Michael A. Hanks, Brent A. Suhocki, Paul Doan, Phuong L. Liu, Emily A. Frost, Patricia Bernard, Stephen A. Tsai, Andrea Moore, Dominic T. O'Neil, Bert H. TI Improved Time to Progression for Transarterial Chemoembolization Compared With Transarterial Embolization for Patients With Unresectable Hepatocellular Carcinoma SO CLINICAL COLORECTAL CANCER LA English DT Article DE Cirrhosis; Doxorubicin; Lipiodol; Mitomycin C; Polyvinyl alcohol particles ID RANDOMIZED CONTROLLED-TRIALS; ARTERIAL EMBOLIZATION AB In a retrospective nonrandomized comparison of patients with unresectable hepatocellular carcinoma (HCC), transarterial chemoembolization (TACE) increases time to progression and progression-free survival (PFS) when compared with transarterial embolization (TAE). Overall survival was not increased by TACE. Background: Embolizing branches of the hepatic artery lengthens survival for patients with unresectable hepatocellular carcinoma (HCC), but the benefit of combining chemotherapy with the embolizing particles remains controversial. Methods: A retrospective review was undertaken of sequential patients with advanced HCC undergoing embolization in the past 10 years at 2 neighboring institutions and with 2 years of follow-up data. TACE was generally performed with doxorubicin plus mitomycin C. Results: One hundred twenty-four patients were included; 77 received TACE and 47 received TAE. On multivariable analysis stratified by institution, type of embolization and CLIP score significantly predicted PFS and time to progression (TTP), whereas CLIP score and AFP independently predicted overall survival (OS). TACE significantly prolonged PFS and TTP (P = .0004 and P = .001, respectively), but not OS (P = .83). Conclusions: The addition of chemotherapy to TAE prolongs PFS and TTP. Future efforts should focus on adjunctive therapies after the embolization to increase survival. C1 [Morse, Michael A.; Hanks, Brent A.; Suhocki, Paul; Doan, Phuong L.; Liu, Emily A.; Frost, Patricia] Duke Univ, Med Ctr, Durham, NC 27710 USA. [Bernard, Stephen A.; Moore, Dominic T.; O'Neil, Bert H.] Univ N Carolina Hosp, Chapel Hill, NC USA. [Tsai, Andrea] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Morse, MA (reprint author), Duke Univ, Med Ctr, POB 3233, Durham, NC 27710 USA. EM morse004@mc.duke.edu NR 19 TC 8 Z9 9 U1 0 U2 3 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1533-0028 EI 1938-0674 J9 CLIN COLORECTAL CANC JI Clin. Colorectal Canc. PD SEP PY 2012 VL 11 IS 3 BP 185 EP 190 DI 10.1016/j.clcc.2011.11.003 PG 6 WC Oncology SC Oncology GA 003OY UT WOS:000308622400004 PM 22280845 ER PT J AU Axelrad, JE Fowler, SA Friedman, S Ananthakrishnan, AN Yajnik, V AF Axelrad, Jordan E. Fowler, Sharyle A. Friedman, Sonia Ananthakrishnan, Ashwin N. Yajnik, Vijay TI Effects of Cancer Treatment on Inflammatory Bowel Disease Remission and Reactivation SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE Retrospective Database Analysis; Correlation; Cancer Therapy; Side Effect ID CROHNS-DISEASE; ULCERATIVE-COLITIS; RISK; METAANALYSIS; PREDICTORS; TAMOXIFEN; THERAPY; RAT AB BACKGROUND & AIMS: Little is known about the effects of cancer therapy for extraintestinal malignancy in patients with inflammatory bowel diseases (IBDs). METHODS: We analyzed data from the Massachusetts General Hospital and the Brigham and Women's Hospital on 84 patients diagnosed with Crohn's disease, ulcerative colitis, or indeterminate colitis found to have a solid malignant extraintestinal neoplasm between January 15, 1993, and December 15, 2011. We investigated the incidence of remission with cancer treatment (cytotoxic chemotherapy, hormone therapy, or both) among patients with active IBD (n = 15) and time to disease activation after cancer treatment of those with inactive disease (n = 69). Cox proportional hazards models and survival curves were constructed to identify independent predictors of these outcomes. RESULTS: Among patients with active IBD at cancer diagnosis, 66.7% (n = 10/15) achieved remission during cancer treatment; the median duration of remission was 27 months. Ninety percent of these patients had received cytotoxic chemotherapy. For patients with IBD in remission at cancer diagnosis, 17.4% (n = 12/69) developed active IBD; the type of treatment was the strongest predictor of IBD reactivation. The risk of IBD reactivation was greatest among patients who received a combination of cytotoxic chemotherapy and adjuvant hormone therapy (hazard ratio, 12.25; 95% confidence interval, 1.51-99.06) or only hormone therapy (hazard ratio, 11.56; 95% confidence interval, 1.39-96.43). Ninety percent of patients who received cytotoxic chemotherapy remained in remission at 5 years compared with 64% of those who received only hormone therapy or the combination of cytotoxic chemotherapy and adjuvant hormone therapy (log rank, P = .02). CONCLUSIONS: IBD is more likely to remit among patients who receive cytotoxic chemotherapy for solid malignancies than those who receive only hormone therapy or the combination of cytotoxic chemotherapy and adjuvant hormone therapy. Among patients with inactive IBD at the time of cancer diagnosis, hormonal therapy, alone or in combination with cytotoxic chemotherapy, increases the risk of IBD reactivation. C1 [Axelrad, Jordan E.; Fowler, Sharyle A.; Ananthakrishnan, Ashwin N.; Yajnik, Vijay] Massachusetts Gen Hosp, Crohns & Colitis Ctr, Gastrointestinal Unit, Boston, MA 02114 USA. [Friedman, Sonia] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. RP Yajnik, V (reprint author), Massachusetts Gen Hosp, Crohns & Colitis Ctr, Gastrointestinal Unit, 165 Cambridge St, Boston, MA 02114 USA. EM vyajnik@partners.org RI Abu Laban , Dr. Nidal /E-5809-2011; OI Axelrad, Jordan/0000-0003-1951-7790 NR 31 TC 10 Z9 10 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD SEP PY 2012 VL 10 IS 9 BP 1021 EP + DI 10.1016/j.cgh.2012.06.016 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 002ZR UT WOS:000308578400016 PM 22732273 ER PT J AU Burchardt, H Tomford, WW AF Burchardt, Hans Tomford, William W. TI Allograft Research and Transplantation: Editorial Comment SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Editorial Material C1 [Tomford, William W.] Massachusetts Gen Hosp, Orthopaed Serv, Boston, MA 02114 USA. [Burchardt, Hans] Musculoskeletal Transplant Fdn, Edison, NJ 08837 USA. RP Tomford, WW (reprint author), Massachusetts Gen Hosp, Orthopaed Serv, 55 Fruit St,YAW 3B, Boston, MA 02114 USA. EM hans_burchardt@mtf.org; wtomford@partners.org NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD SEP PY 2012 VL 470 IS 9 BP 2476 EP 2477 DI 10.1007/s11999-012-2441-1 PG 2 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 987FK UT WOS:000307402300015 PM 22744204 ER PT J AU Fletcher, GF Berra, K Fletcher, BJ Gilstrap, L Wood, MJ AF Fletcher, Gerald F. Berra, Kathy Fletcher, Barbara J. Gilstrap, Lauren Wood, Malissa J. TI The Integrated Team Approach to the Care of the Patient with Cardiovascular Disease SO CURRENT PROBLEMS IN CARDIOLOGY LA English DT Review ID RANDOMIZED-CONTROLLED-TRIAL; RECENT MYOCARDIAL-INFARCTION; CORONARY-ARTERY DISEASE; HEALTH LITERACY; HEART-DISEASE; HOSPITAL ADMISSION; EXERCISE PROGRAM; CLINICAL-TRIALS; HIGH-RISK; MANAGEMENT AB Cardiovascular disease (CVD) is a costly, worldwide problem with significant annual morbidity and mortality. Guideline-based primary and secondary prevention is effective in preventing and controlling CVD. Such prevention must be implemented by an integrated team of physician-directed health professionals, during both the inpatient and the outpatient phases of care. Appropriate team members may include, but are not limited to, nurses, advanced practice nurses, physician assistants, dietitians, physical therapists, psychologists, pharmacists, cardiac fellows, exercise physiologists, and case managers. During the acute phase of care, various teams are activated as appropriate to specific needs of the patient in the medical (invasive and noninvasive) and surgical specialties. The outpatient phase varies with diagnosis and condition of the patient and team members are involved as needed. An integrated team effort is essential to the best care for each patient regarding individual management and will assure that evidence-based guidelines, in both treatment and secondary prevention, are implemented. (Curr Probl Cardiol 2012;37:369-397.) C1 [Fletcher, Gerald F.] Mayo Clin, Jacksonville, FL 32224 USA. [Fletcher, Gerald F.] Grady Mem Hosp, Atlanta, GA USA. [Fletcher, Gerald F.] Univ Calif San Diego, Sch Med, La Jolla, CA 92093 USA. [Gilstrap, Lauren] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wood, Malissa J.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Wood, Malissa J.] Univ N Florida, Sch Nursing, Brooks Coll Hlth, Jacksonville, FL USA. RP Fletcher, GF (reprint author), Mayo Clin, Jacksonville, FL 32224 USA. NR 51 TC 5 Z9 5 U1 9 U2 23 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0146-2806 EI 1535-6280 J9 CURR PROB CARDIOLOGY JI Curr. Probl. Cardiol. PD SEP PY 2012 VL 37 IS 9 BP 369 EP 397 DI 10.1016/j.cpcardiol.2012.04.001 PG 29 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 004LD UT WOS:000308682300002 PM 22884247 ER PT J AU Reichert, JM Dhimolea, E AF Reichert, Janice M. Dhimolea, Eugen TI The future of antibodies as cancer drugs SO DRUG DISCOVERY TODAY LA English DT Review ID GROWTH-FACTOR RECEPTOR; FC-GAMMA-RIIIA; MONOCLONAL-ANTIBODY; PHASE-I; BISPECIFIC ANTIBODIES; CLINICAL DEVELOPMENT; ANTI-CD20 ANTIBODY; SOLID TUMORS; HUMAN CD20; CELL AB Targeted therapeutics such as monoclonal antibodies (mAbs) have proven successful as cancer drugs. To profile products that could be marketed in the future, we examined the current commercial clinical pipeline of mAb candidates for cancer. Our analysis revealed trends toward development of a variety of noncanonical mAbs, including antibody-drug conjugates (ADCs), bispecific antibodies, engineered antibodies and antibody fragments and/or domains. We found substantial diversity in the antibody sequence source, isotype, carbohydrate residues, targets and mechanisms of action (MOA). Although well-validated targets, such as epidermal growth factor receptor (EGFR) and CD20, continue to provide opportunities for companies, we found notable trends toward targeting less-well-validated antigens and exploration of innovative MOA such as the generation of anticancer immune responses or recruitment of cytotoxic T cells. C1 [Reichert, Janice M.] Tufts Univ, Ctr Study Drug Dev, Sch Med, Boston, MA 02111 USA. [Dhimolea, Eugen] Harvard Univ, Sch Med, Harvard Inst Med, Dept Med Oncol,Dana Farber Canc Inst, Boston, MA 02215 USA. RP Reichert, JM (reprint author), Tufts Univ, Ctr Study Drug Dev, Sch Med, 75 Kneeland St,Suite 1100, Boston, MA 02111 USA. EM janice.reichert@tufts.edu OI Reichert, Janice/0000-0003-0400-1951 FU CSDD's unrestricted grants; contract grant from Bayer Healthcare FX Tuft University's Center for the Study of Drug Development (CSDD) is funded by unrestricted and contract grants from commercial sponsors. This study was funded through CSDD's unrestricted grants and a contract grant from Bayer Healthcare. Dr Reichert has received honoraria from Bayer Healthcare, Merck & Co. and Merrimack Pharmaceuticals. NR 71 TC 60 Z9 65 U1 3 U2 53 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 SEP PY 2012 VL 17 IS 17-18 BP 954 EP 963 DI 10.1016/j.drudis.2012.04.006 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 003OI UT WOS:000308620800005 PM 22561895 ER PT J AU Borsook, D Upadhyay, J Klimas, M Schwarz, AJ Coimbra, A Baumgartner, R George, E Potter, WZ Large, T Bleakman, D Evelhoch, J Iyengar, S Becerra, L Hargreaves, RJ AF Borsook, David Upadhyay, Jaymin Klimas, Michael Schwarz, Adam J. Coimbra, Alexandre Baumgartner, Richard George, Edward Potter, William Z. Large, Thomas Bleakman, David Evelhoch, Jeffrey Iyengar, Smriti Becerra, Lino Hargreaves, Richard J. TI Decision-making using fMRI in clinical drug development: revisiting NK-1 receptor antagonists for pain SO DRUG DISCOVERY TODAY LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; MAJOR DEPRESSIVE DISORDER; CENTRAL-NERVOUS-SYSTEM; P NK1 RECEPTOR; SUBSTANCE-P; NEUROPATHIC PAIN; NEUROKININ-1 ANTAGONIST; TACHYKININ NK1; HUMAN BRAIN; GUINEA-PIG AB Substance P (SP) and neurokinin-1 receptors (NK-1R) are localized within central and peripheral sensory pain pathways. The roles of SP and NK-1R in pain processing, the anatomical distribution of NK-1R and efficacy observed in preclinical pain studies involving pain and sensory sensitization models, suggested that NK-1R antagonists (NK-1RAs) would relieve pain in patient populations. Despite positive data available in preclinical tests for a role of NK-1RAs in pain, clinical studies across several pain conditions have been negative. In this review, we discuss how functional imaging-derived information on activity in pain-processing brain regions could have predicted that NK-1RAs would have a low probability of success in this therapeutic domain. C1 [Borsook, David; Upadhyay, Jaymin; George, Edward; Becerra, Lino] McLean Hosp, PAIN Grp, Brain Imaging Ctr, Belmont, MA 02478 USA. [Borsook, David; Becerra, Lino] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Klimas, Michael; Coimbra, Alexandre; Baumgartner, Richard; Potter, William Z.; Evelhoch, Jeffrey; Hargreaves, Richard J.] Merck Res Labs, West Point, PA 19486 USA. [Schwarz, Adam J.; Bleakman, David; Iyengar, Smriti] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. [Large, Thomas] Sunov Pharmaceut Inc, Marlborough, MA 01752 USA. EM David.Borsook@childrens.harvard.edu NR 85 TC 20 Z9 21 U1 1 U2 13 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 SEP PY 2012 VL 17 IS 17-18 BP 964 EP 973 DI 10.1016/j.drudis.2012.05.004 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 003OI UT WOS:000308620800006 PM 22579743 ER PT J AU Bhatt, DL Pare, G Eikelboom, JW Simonsen, KL Emison, ES Fox, KAA Steg, PG Montalescot, G Bhakta, N Hacke, W Flather, MD Mak, KH Cacoub, P Creager, MA Berger, PB Steinhubl, SR Murugesan, G Mehta, SR Kottke-Marchant, K Lincoff, AM Topol, EJ AF Bhatt, Deepak L. Pare, Guillaume Eikelboom, John W. Simonsen, Katy L. Emison, Eileen S. Fox, Keith A. A. Steg, Ph Gabriel Montalescot, Gilles Bhakta, Nihar Hacke, Werner Flather, Marcus D. Mak, Koon-Hou Cacoub, Patrice Creager, Mark A. Berger, Peter B. Steinhubl, Steven R. Murugesan, Gurunathan Mehta, Shamir R. Kottke-Marchant, Kandice Lincoff, A. Michael Topol, Eric J. CA CHARISMA Investigators TI The relationship between CYP2C19 polymorphisms and ischaemic and bleeding outcomes in stable outpatients: the CHARISMA genetics study SO EUROPEAN HEART JOURNAL LA English DT Article DE Coronary disease; Genetics; Peripheral Vascular disease; Platelets; Thrombosis ID PERCUTANEOUS CORONARY INTERVENTION; CLOPIDOGREL-TREATED PATIENTS; OF-FUNCTION POLYMORPHISM; ST-SEGMENT ELEVATION; MYOCARDIAL-INFARCTION; ANTIPLATELET THERAPY; PLATELET-FUNCTION; STENT THROMBOSIS; CONTROLLED TRIAL; ASPIRIN AB Aims Clinical trials have established the value of clopidogrel therapy in a wide spectrum of patients with cardiovascular diseases. Both loss- and gain-of-function single nucleotide variants of CYP2C19 genes have been identified that affect clopidogrel metabolism and anti-platelet response. We sought to determine the impact of CYP2C19 polymorphisms on ischaemic and bleeding events. Methods and results A subset of patients from the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial who consented to genotyping was analysed. Patients with clinically evident cardiovascular disease or multiple risk factors were enrolled in the trial. The rates of ischaemic and bleeding events were compared between carriers and non-carriers of loss-of-function and gain-of-function alleles in patients randomized to clopidogrel vs. placebo. A total of 4819 patients were genotyped and available for the analysis. Carriers of CYP2C19 loss-of-function alleles did not have an increased rate of ischaemic events. However, clopidogrel-treated patients did have a significantly lower rate of any bleeding in carriers: 36.1% (240/665) vs. 42.5% (681/1601) in non-carriers, HR: 0.80, 95% CI: 0.69-0.93, P = 0.003 (genotype/treatment interaction, P-value = 0.023). The CYP2C19 gain-of-function alleles did not affect ischaemic or bleeding endpoints. Conclusion No relationship was seen between CYP2C19 status and ischaemic outcomes in stable patients treated with clopidogrel. There was, however, significantly less bleeding with clopidogrel in carriers of the loss-of-function allele, suggesting less anti-platelet response. Although several prior studies, including mainly stented patients, have emphasized the relationship between CYP2C19 loss-of-function alleles and efficacy of clopidogrel, this study of stable patients establishes a potential link with reduced bleeding complications. C1 [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02132 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA 02132 USA. [Pare, Guillaume; Eikelboom, John W.; Mehta, Shamir R.] McMaster Univ, Hamilton, ON, Canada. [Simonsen, Katy L.] Purdue Univ, Dept Stat, W Lafayette, IN 47907 USA. [Simonsen, Katy L.] Bristol Myers Squibb Co, Global Biometr Sci, Princeton, NJ USA. [Emison, Eileen S.] Bristol Myers Squibb Co, Clin Biomarkers, Pharmacogenet, Princeton, NJ USA. [Fox, Keith A. A.] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Fox, Keith A. A.] Royal Infirm Edinburgh NHS Trust, Edinburgh, Midlothian, Scotland. [Steg, Ph Gabriel] INSERM, U698, Paris, France. [Steg, Ph Gabriel] Univ Paris 07, Paris, France. [Steg, Ph Gabriel] Assistance Publ Hop Paris, Paris, France. [Montalescot, Gilles] CHU Pitie Salpetriere, AP HP, Inst Cardiol, INSERM,U937, Paris, France. [Montalescot, Gilles] Univ Paris 06, Paris, France. [Hacke, Werner] Heidelberg Univ, Dept Neurol, Heidelberg, Germany. [Flather, Marcus D.] Royal Brompton Hosp, Clin Trials & Evaluat Unit, London SW3 6LY, England. [Flather, Marcus D.] Univ London Imperial Coll Sci Technol & Med, London, England. [Mak, Koon-Hou] Mak Heart Clin, Singapore, Singapore. [Cacoub, Patrice] Univ Paris 06, Hop La Pitie Salpetriere, AP HP, Dept Internal Med, Paris, France. [Cacoub, Patrice] Univ Paris 06, UPMC, CNRS, INSERM,UMR 7211,U959, Paris, France. [Creager, Mark A.] Brigham & Womens Hosp, Div Cardiovascular Med, Boston, MA 02132 USA. [Berger, Peter B.; Steinhubl, Steven R.] Geisinger Med Ctr, Div Cardiol, Danville, PA 17822 USA. [Murugesan, Gurunathan; Kottke-Marchant, Kandice; Lincoff, A. Michael] Cleveland Clin, Cleveland, OH 44106 USA. [Topol, Eric J.] Scripps Clin, La Jolla, CA USA. [Topol, Eric J.] Scripps Translat Sci Inst, 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 RI Walker, Philip/F-3034-2010; OI Eikelboom, John/0000-0003-4126-1285; Topol, Eric/0000-0002-1478-4729 FU Sanofi Aventis; Bristol-Myers Squibb; Amarin; AstraZeneca; Eisai; Ethicon; Medtronic; Sanofi-Aventis; Medicines Company; BMS; Eli Lilly; Bayer/JJ; Boehringher Ingelheim; Servier; Astellas; Bayer; Daiichi Sankyo/Eli Lilly alliance; GlaxoSmithKline; Merck; Otsuka Pharmaceutical; Roche; Abbott Vascular; Boston Scientific; Centocor; Cordis; Federation Francaise de Cardiologie; Fondation de France; Guerbet Medical; INSERM; ITC Edison; Pfizer; Societe Francaise de Cardiologie; Stago; Thrombovision; Helena; Accumetrics; Haemoscope; Corgenix/Aspirinworks; Lilly/Daiichi-Sankyo; [NCT00050817] FX The CHARISMA trial was supported by Sanofi Aventis and Bristol-Myers Squibb. They had the right to review this manuscript, but not to make any changes. Three authors are employees of Bristol-Myers Squibb. No compensation was received by any of the authors to write this article. Dr Bhatt had full access to the data and final responsibility to submit it. All statistical analyses were performed by Dr Pare (grant number NCT00050817).; D.L.B. received grants from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi-Aventis, and The Medicines Company. G. P. receives a consulting fee/honorarium from Sanofi-Aventis and Bristol-Myers Squibb. J.W.E. received a grant from Bristol-Myers Squibb and Sanofi Aventis; is a paid consultant for Bristol-Myers Squibb, Sanofi Aventis, Eli Lilly, Astra, and Novartis; has received speaker fees from BMS, Sanofi Aventis, Eli Lilly, and AstraZeneca. K. L. S. and E. S. E. are employed by and have stock options with Bristol-Myers Squibb. K. A. A. F. has received grants from Sanofi-Aventis, Bayer/J&J, and Eli Lilly; has received speaker fees from Sanofi-Aventis and Bayer/J & J; and has received support from Boehringher Ingelheim for travel unrelated to activities listed. P. G. S. has received research grants from Servier; has received fees for consultancy or participation in advisory board meetings from Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo/Eli Lilly alliance, GlaxoSmithKline, Medtronic, Merck, Otsuka Pharmaceutical, Roche, Sanofi-Aventis, Servier, and the Medicines Company; has received payment for development of educational presentations from Boehringer Ingelheim, AstraZeneca, and Merck; and has equity ownership in Aterovax. G. M. is a paid consultant for AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Daiichi-Sankyo, Eisai, Eli-Lilly, Menarini, Novartis, Pfizer, Portola, Sanofi-Aventis, Schering-Plough, and The Medicines Company; has received grants from Abbott Vascular, BMS, Boston Scientific, Centocor, Cordis, Eli-Lilly, Federation Francaise de Cardiologie, Fondation de France, Guerbet Medical, INSERM, ITC Edison, Medtronic, Pfizer, Sanofi-Aventis, Societe Francaise de Cardiologie, and Stago; and received honoraria from Abbott Vascular, Accumetrics AstraZeneca, BMS, Cordis, Daiichi, Eli-Lilly, GlaxoSmithKline, Menarini, Merck Sharpe & Dohme, Pfizer, Sanofi-Aventis, and Schering-Plough. N.B. is employed by and has stock options with Bristol-Myers Squibb. W. H. reported receiving a consultant fee/honorarium and support for travel from Bayer, and is a paid consultant for Bayer, Boehringer, Photothera, and Sanofi. M. D. F. reported receiving a grant and support for travel from Sanofi-Aventis and is a paid consultant for Eisai and Eli Lilly. K.-H. M. reported receiving support for travel and payment for lectures from Sanofi-Aventis. P. C. is a paid consultant for Servier, Bristol-Myers Squibb, and Sanofi-Aventis and received a grant from Servier. M. A. C. is a paid consultant for Merck (via TIMI Group) and Genzyme; and has also reported a grant received from Sanofi-Aventis. P. B. B. serves as a paid consultant for AstraZeneca, Boehringer Ingelheim, Eli Lilly/Daiichi -Sankyo, and Ortho McNeil and has research grants/grants pending from Thrombovision, Helena, Accumetrics, AstraZeneca, Haemoscope, The Medicines Company, Corgenix/Aspirinworks, and Lilly/Daiichi-Sankyo. S. R. S. is a recent former employee of The Medicines Company. G. M. has no relevant disclosures. S. R. M. is a paid consultant for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Novartis, and Sanofi-Aventis and has grants/grants pending from Sanofi-Aventis and Bristol-Myers Squibb. K. K.-M. has an unpaid board membership with Nanomimetics; has received payment for lectures and grants/grant pending from Siemens; has reported receiving royalties for a publication from College of American Pathologists; and is a non-paid consultant for Coagulation Sciences. A. M. L.; reported receiving a grant from Sanofi-Aventis and Schering Plough and support for travel from Sanofi-Aventis; and is a paid consultant for Bristol-Myers Squibb, Schering Plough, and Baxter. E. J. T. received a grant from Sanofi-Aventis and is a paid consultant for Sanofi-Aventis, Quest Diagnostics, and Daiichi-Sankyo. NR 25 TC 40 Z9 43 U1 0 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2012 VL 33 IS 17 BP 2143 EP 2150 DI 10.1093/eurheartj/ehs059 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 002JV UT WOS:000308529100013 PM 22450429 ER PT J AU Altman, RK Parks, KA Schlett, CL Orencole, M Park, MY Truong, QA Deeprasertkul, P Moore, SA Barrett, CD Lewis, GD Das, S Upadhyay, GA Heist, EK Picard, MH Singh, JP AF Altman, Robert K. Parks, Kimberly A. Schlett, Christopher L. Orencole, Mary Park, Mi-Young Truong, Quynh A. Deeprasertkul, Peerawut Moore, Stephanie A. Barrett, Conor D. Lewis, Gregory D. Das, Saumya Upadhyay, Gaurav A. Heist, E. Kevin Picard, Michael H. Singh, Jagmeet P. TI Multidisciplinary care of patients receiving cardiac resynchronization therapy is associated with improved clinical outcomes SO EUROPEAN HEART JOURNAL LA English DT Article DE Cardiac resynchronization therapy; Heart failure; Integrated clinic; Multidisciplinary care ID LEFT-VENTRICULAR DYSFUNCTION; HEART-FAILURE PATIENTS; DEVICE DIAGNOSTICS; MANAGEMENT; SURVIVAL; TRIAL; PREVENTION; MORBIDITY; MORTALITY; SYMPTOMS AB Aims Although cardiac resynchronization therapy (CRT) reduces morbidity and mortality in patients with heart failure, a significant minority of patients do not respond adequately to this therapy. The objective of this study was to examine the impact of a 'multidisciplinary care' (MC) approach on the clinical outcome in CRT patients. Methods and results The clinical outcome in patients prospectively receiving MC (n = 254) was compared with a control group of patients who received conventional care (CC, n = 173). The MC group was followed prospectively in an integrated clinic setting by a team of subspecialists from the heart failure, electrophysiology, and echocardiography service at 1-, 3-, and 6- months post-implant. All patients had echocardiographic-guided optimization at their 1- month visit. The proportional hazards model (adjusting for all covariates) and Kaplan-Meier time to first event curves were compared between the two groups, over a 2-year follow-up. The long-term outcome was measured as a combined endpoint of heart failure hospitalization, cardiac transplantation, or all-cause mortality. The clinical characteristics between the MC and CC groups at baseline were comparable (age, 68 +/- 13 vs. 69 +/- 12; NYHA III, 90 vs. 82%; ischaemic cardiomyopathy 55 vs. 64%, P = NS, respectively). The event-free survival was significantly higher in the multidisciplinary vs. the CC group (P = 0.0015). A significant reduction in clinical events was noted in the MC group vs. the CC group (hazard ratio: 0.62, 95% CI: 0.46-0.83, P = 0.001). Conclusion Integrated MC may improve 2-year event-free survival in patients receiving cardiac resynchronization therapy. Prospective randomized studies are needed to validate our findings. C1 [Altman, Robert K.; Orencole, Mary; Barrett, Conor D.; Das, Saumya; Upadhyay, Gaurav A.; Heist, E. Kevin; Singh, Jagmeet P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv,Heart Ctr, Boston, MA 02114 USA. [Parks, Kimberly A.; Moore, Stephanie A.; Lewis, Gregory D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Heart Failure Serv, Boston, MA 02114 USA. [Schlett, Christopher L.; Truong, Quynh A.; Deeprasertkul, Peerawut] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MR PET CT Program,Div Cardiol,Dept Radiol, Boston, MA 02114 USA. [Park, Mi-Young; Picard, Michael H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, Boston, MA 02114 USA. RP Singh, JP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv,Heart Ctr, Boston, MA 02114 USA. EM jsingh@partners.org OI Altman, Robert/0000-0002-1612-3561; Picard, Michael/0000-0002-9264-3243 FU St Jude Medical; Biotronik; Sorin Group; Boston Scientific; NIH [K23HL098370]; Medtronic Inc.; Boston Scientific Corp. FX This study was supported in part by a research grant from St Jude Medical.; E.K.H. reports receiving research grants from St Jude Medical, Biotronik, Sorin Group and Boston Scientific, lecture fees from Boston Scientific Corp and St Jude Medical and consulting fees from Boston Scientific, St Jude Medical, Biotronik and Sorin group. C. D. B. reports receiving research grants from St Jude Medical and Medtronic and consulting fees from St Jude Medical. Q. A. T. reports receiving research grant support from NIH (grant K23HL098370). K. A. P. reports receiving lecture fees from Biotronik and Sorin Group and has served as a consultant for Thoratec, Inc. J.P.S. reports receiving research grants from St Jude Medical, Medtronic Inc., Boston Scientific Corp. and Biotronik, consulting from Boston Scientific Corp., Medtronic Inc, Sorin Group, St Jude Medical, Biosense Webster, Thoratec Inc. and Respicardia Inc. and receiving lecture fees from Boston Scientific Corp., St Jude Medical and Sorin Group. NR 26 TC 31 Z9 32 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2012 VL 33 IS 17 BP 2181 EP 2188 DI 10.1093/eurheartj/ehs107 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 002JV UT WOS:000308529100017 PM 22613342 ER PT J AU Shah, RV Truong, QA Gaggin, HK Pfannkuche, J Hartmann, O Januzzi, JL AF Shah, Ravi V. Truong, Quynh A. Gaggin, Hanna K. Pfannkuche, Jens Hartmann, Oliver Januzzi, James L., Jr. TI Mid-regional pro-atrial natriuretic peptide and pro-adrenomedullin testing for the diagnostic and prognostic evaluation of patients with acute dyspnoea SO EUROPEAN HEART JOURNAL LA English DT Article DE Diagnosis; Prognosis; Biomarker; Heart failure ID ACUTE HEART-FAILURE; LONG-TERM MORTALITY; EMERGENCY-DEPARTMENT; BACH BIOMARKERS; PREDICTION; TRIAL AB Aims The aim of this study was to assess diagnostic and prognostic value of mid-regional pro-atrial natriuretic peptide (MR-proANP) and adrenomedullin (MR-proADM) for the evaluation of patients presenting to the emergency department with acute dyspnoea. Methods and results A total of 560 patients from the pro-B type natriuretic peptide Investigation of Dyspnoea in the Emergency Department were evaluated; 180 had acutely decompensated heart failure (ADHF). Concentrations of amino-terminal pro-B type natriuretic peptide (NT-proBNP), MR-proADM, and MR-proANP were measured, and patients were followed to 4 years for survival. Logistic regression evaluated utility of MR-proANP in ADHF diagnosis. Area under the curve (AUC), multivariate Cox regression, net reclassification improvement, and Kaplan-Meier survival analyses were used for mortality analyses. Mid-regional pro-atrial natriuretic peptide was higher in patients with ADHF (median 329 vs. 58 pmol/L; P < 0.001), and remained an independent predictor of HF diagnosis even when NT-proBNP was included as a covariate (odds ratio = 4.34, 95% CI = 2.11-8.92; P < 0.001). In time-dependent analyses, MR-proADM had the highest AUC for death during the first year; after 1 year, MR-proANP and NT-proBNP had a higher AUC. Both mid-regional peptides were independently prognostic and reclassified risk at 1 year [MR-proANP, hazard ratio (HR) = 2.99, MR-proADM, HR = 2.70; both P < 0.001] and at 4 years (MR-proANP, HR = 3.12, P < 0.001; MR-proADM, HR = 1.51, P = 0.03) and in Kaplan-Meier curves both mid-regional peptides were associated with death out to 4 years, individually or in a multimarker strategy. Conclusion Among patients with acute dyspnoea, MR-proANP is accurate for diagnosis of ADHF, while both MR-proANP and MR-proADM are independently prognostic to 4 years of the follow-up. C1 [Shah, Ravi V.; Truong, Quynh A.; Gaggin, Hanna K.; Januzzi, James L., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiol Div,Dept Med, Boston, MA 02114 USA. [Pfannkuche, Jens; Hartmann, Oliver] BRAHMS GmBH, Hennigsdorf, Germany. RP Januzzi, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiol Div,Dept Med, 32 Fruit St,Yawkey 5984, Boston, MA 02114 USA. EM jjanuzzi@partners.org FU BRAHMS GmBH; American Heart Association [11POST000002]; Heart Failure National Institutes of Health Clinical Research Network [U01-HL084877]; Dennis and Marilyn Barry Clinical Research Fellowship; National Institutes of Health [K23HL098370, L30HL093896]; Balson Clinical Scholar Fund; Roche Diagnostics; Siemens Diagnostics; Critical Diagnostics FX This work was supported by a grant from BRAHMS GmBH. R.V.S. is supported by an American Heart Association Post-Doctoral Fellowship Award (11POST000002) and a training grant from the Heart Failure National Institutes of Health Clinical Research Network (U01-HL084877). H.K.G. is supported by the Dennis and Marilyn Barry Clinical Research Fellowship. Q.A.T. is supported by National Institutes of Health grant K23HL098370 and L30HL093896. J.L.J. is supported by a grant from the Balson Clinical Scholar Fund.; J.L.J. has received grants from Roche Diagnostics, Siemens Diagnostics, Critical Diagnostics, and BRAHMS, GmBH. NR 15 TC 38 Z9 42 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2012 VL 33 IS 17 BP 2197 EP 2205 DI 10.1093/eurheartj/ehs136 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 002JV UT WOS:000308529100019 PM 22645194 ER PT J AU Thomas, RM Gerstel, PAF Williams, EC Sun, HL Bryson, CL Au, DH Bradley, KA AF Thomas, Rachel M. Gerstel, Patricia A. Francis Williams, Emily C. Sun, Haili Bryson, Chris L. Au, David H. Bradley, Katharine A. TI Association Between Alcohol Screening Scores and Diabetic Self-care Behaviors SO FAMILY MEDICINE LA English DT Article ID NATIONAL EPIDEMIOLOGIC SURVEY; IDENTIFICATION TEST AUDIT; AT-RISK DRINKING; USE DISORDERS; MEDICATION ADHERENCE; GENERAL-POPULATION; GLYCEMIC CONTROL; GLUCOSE CONTROL; BLOOD-GLUCOSE; MALE VETERANS AB BACKGROUND AND OBJECTIVES: Alcohol misuse is associated with poor adherence to recommended self-care behaviors, which are critical for diabetes management. This study investigated whether scores on a validated brief alcohol misuse screen are associated with diabetes self-care. METHODS: Male outpatients (n=3,930) from seven Veterans Affairs sites returned the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) alcohol screen on mailed surveys and indicated they had diabetes. Patients were divided into five alcohol screening groups: no past year alcohol use (AUDIT-C 0), low-level alcohol use (AUDIT-C 1-3); and mild (AUDIT-C 4-5), moderate (AUDIT-C 6-7), and severe (AUDIT-C 8-12) misuse. Outcomes included self-report of monitoring blood glucose, maintaining normal blood glucose levels, inspecting feet, following a meal plan, not smoking, and laboratory data indicating that glycosylated hemoglobin A1c (HbA1c) had been tested in the past year. For each group, the proportion of patients adherent to each behavior were estimated from logistic regression models adjusted for demographics, comorbidity, and depressive symptoms. RESULTS: Patients who did not drink were most likely to report adherence to self-care behaviors, except for past-year HbA1c testing. Compared to patients who did not drink, patients with AUDIT-C scores were significantly less likely to report maintaining normal blood glucose levels (eg, AUDIT-C 6-7 44% versus AUDIT-C 0 59%) or following a meal plan (48% versus 58%), and were more likely to smoke (71% abstained versus 85%) in adjusted analyses. CONCLUSIONS: Results of this study indicate that higher alcohol screening scores are associated with poorer diabetes self-care. C1 [Thomas, Rachel M.; Williams, Emily C.; Sun, Haili; Bryson, Chris L.; Au, David H.; Bradley, Katharine A.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev NW Ctr Excellence, Seattle, WA 98101 USA. [Bryson, Chris L.; Au, David H.] VA Puget Sound Hlth Care Syst, Hosp & Specialty Med Serv, Seattle, WA 98101 USA. [Bradley, Katharine A.] VA Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA 98101 USA. [Bryson, Chris L.; Au, David H.; Bradley, Katharine A.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Williams, Emily C.; Bradley, Katharine A.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Gerstel, Patricia A. Francis] Univ Hosp Geneva, Qual Care Unit, Geneva, Switzerland. [Bradley, Katharine A.] Grp Hlth Res Inst, Seattle, WA USA. RP Thomas, RM (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev NW Ctr Excellence, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM rachel.thomas3@va.gov FU Veterans Affairs (VA) Health Services Research & Development (HSRD) IIR Grant [IAC 05-206-1]; VA [RCD 03-177, RCD 00-018]; VA Ambulatory Care Quality Improvement Project (ACQUIP); VA HSRD [SDR 96-002, BR 99-376] FX This project was funded by Veterans Affairs (VA) Health Services Research & Development (HSR&D) IIR Grant IAC 05-206-1, VA Career Development Awards RCD 03-177 (to Dr Bryson) and RCD 00-018 (to Dr Au), and the VA Ambulatory Care Quality Improvement Project (ACQUIP) was funded by VA HSR&D Grants SDR 96-002 and BR 99-376. 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 US government. A portion of this work was presented at the 2009 Addiction Health Services Research Conference in San Francisco as a poster. NR 57 TC 8 Z9 8 U1 5 U2 11 PU SOC TEACHERS FAMILY MEDICINE PI LEAWOOD PA 11400 TOMAHAWK CREEK PARKWAY, STE 540, LEAWOOD, KS 66207 USA SN 0742-3225 J9 FAM MED JI Fam. Med. PD SEP PY 2012 VL 44 IS 8 BP 555 EP 563 PG 9 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 002HS UT WOS:000308523300005 PM 22930120 ER PT J AU Bichara, DA Henn, RF Theodore, GH AF Bichara, David A. Henn, R. Frank, III Theodore, George H. TI Sesamoidectomy for Hallux Sesamoid Fractures SO FOOT & ANKLE INTERNATIONAL LA English DT Article DE Sesamoidectomy; Hallucal Sesamoid Fracture; Athletic Patients AB Background: Hallux sesamoid fractures are challenging to treat. Symptomatic nonunion is a common problem after nonoperative treatment. Surgical fixation of the fracture can result in successful union, but is technically challenging and can be associated with prolonged return to activities (RTA). Sesamoidectomy is an alternative surgical option that may provide reliable outcomes and allow an earlier RTA in athletes. The purpose of this case-series study was to evaluate a cohort of athletic patients with a hallucal sesamoid fracture treated with sesamoidectomy. Methods: A total of 24 patients with 24 sesamoid fractures that failed to respond to nonoperative measures were treated surgically with sesamoidectomy. Patients' age, level of activity, fractured bone, surgical approach, time required to RTA, and postoperative complications were recorded. Pre- and postoperative pain was assessed with a visual analog scale ranging from zero (no pain) to 10 (intense pain). Five patients were classified as elite athletes playing at an intercollegiate level and 19 were classified as active individuals performing an athletic activity at least three times per week. The mean patient age was 32.2 +/- 10.4 (range, 17 to 54) years. The 24 patients were reviewed at a mean follow-up of 35 21 (range, 8 to 70) months. Results: A total of 22/24 patients (91.6%) returned to activities at a mean time of 11.6 +/- 3.87 (range, 8 to 24) weeks. Mean preoperative pain level was 6.2 +/- 1.4 and the pain level improved after treatment to a mean of 0.7 +/- 1. One patient developed a symptomatic hallux valgus deformity after the resection of the medial sesamoid. Conclusions: This case series demonstrates good results after sesamoidectomy for sesamoid fractures in athletic individuals with reliable pain relief and RTA within 11.6 weeks. Progressive hallux valgus remains a concern after medial sesamoidectomy, with an incidence of 1 in 24 cases in this study. C1 [Bichara, David A.; Henn, R. Frank, III; Theodore, George H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Theodore, GH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 175 Cambridge St,4th Floor, Boston, MA 02114 USA. EM GTheodore@Partners.org NR 9 TC 6 Z9 6 U1 0 U2 3 PU AMER ORTHOPAEDIC FOOT & ANKLE SOC, INC PI SEATTLE PA 2517 EASTLAKE AVE EAST, STE 200, SEATTLE, WA 98102 USA SN 1071-1007 J9 FOOT ANKLE INT JI Foot Ankle Int. PD SEP PY 2012 VL 33 IS 9 BP 704 EP 706 DI 10.3113/FAI.2012.0704 PG 3 WC Orthopedics SC Orthopedics GA 998XF UT WOS:000308273000004 PM 22995255 ER PT J AU Forrester, MT Foster, MW AF Forrester, Michael T. Foster, Matthew W. TI Response to "Is flavohemoglobin a nitric oxide dioxygenase?" SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Letter ID NITROSATIVE STRESS; HEMOGLOBINS C1 [Forrester, Michael T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. [Foster, Matthew W.] Duke Univ, Med Ctr, Div Pulm Allergy & Crit Care Med, Durham, NC 27710 USA. RP Forrester, MT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, 55 Fruit St, Boston, MA 02114 USA. EM michael.forrester@me.com NR 8 TC 2 Z9 2 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD SEP 1 PY 2012 VL 53 IS 5 BP 1211 EP 1212 DI 10.1016/j.freeradbiomed.2012.06.038 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 003PV UT WOS:000308624700019 ER PT J AU Werner, RM Dudley, RA AF Werner, Rachel M. Dudley, R. Adams TI Medicare's New Hospital Value-Based Purchasing Program Is Likely To Have Only A Small Impact On Hospital Payments SO HEALTH AFFAIRS LA English DT Article ID PAY-FOR-PERFORMANCE; QUALITY IMPROVEMENT; INCENTIVES; MORTALITY; CARE AB Medicare's new hospital pay-for-performance program for all acute care hospitals will begin in October 2012. It will be the largest Medicare quality improvement initiative for hospitals to date. Using 2009 data on hospital performance, we calculated hospital performance scores and projected payments under the new program for all eligible hospitals. Despite differences across hospitals in terms of performance, expected changes in payments were small, even for hospitals with the best and worst performance scores. Almost two-thirds of hospitals would experience changes of just a fraction of 1 percent. Although the program will in effect redistribute resources among hospitals, our data suggest that the redistribution is not likely to cause major problems because the amount being redistributed is also small. These results raise questions about whether the new pay-for-performance program will substantially alter the quality of hospital care, and they highlight the challenges of designing effective quality improvement incentives. C1 [Werner, Rachel M.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Werner, Rachel M.] Univ Penn, Philadelphia, PA 19104 USA. [Dudley, R. Adams] Univ Calif San Francisco, Philip R Lee Inst Hlth Policy Studies, San Francisco, CA 94143 USA. RP Werner, RM (reprint author), Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. EM rwerner@upenn.edu FU Agency for Healthcare Research and Quality [R01 HS018409]; Veterans Affairs Health Services Research and Development Career Development Award FX This project was supported by a grant from the Agency for Healthcare Research and Quality (R01 HS018409). Rachel Werner was supported in part by a Veterans Affairs Health Services Research and Development Career Development Award. NR 18 TC 29 Z9 29 U1 5 U2 15 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 SEP PY 2012 VL 31 IS 9 BP 1932 EP 1940 DI 10.1377/hlthaff.2011.0990 PG 9 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 002NU UT WOS:000308539700005 PM 22949441 ER PT J AU Shakil, O Josephson, ME Matyal, R Khabbaz, KR Mahmood, F AF Shakil, Omair Josephson, Mark E. Matyal, Robina Khabbaz, Kamal R. Mahmood, Feroze TI Traumatic right ventricular aneurysm and ventricular tachycardia SO HEART RHYTHM LA English DT Article DE Right ventricle; Ventricular tachycardia; Nonsustained ventricular tachycardia; Aneurysm; Ablation; Blunt chest trauma C1 [Shakil, Omair; Matyal, Robina; Mahmood, Feroze] Beth Israel Deaconess Med Ctr, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02215 USA. [Josephson, Mark E.] Beth Israel Deaconess Med Ctr, Div Cardiovasc Med, Boston, MA 02215 USA. [Khabbaz, Kamal R.] Beth Israel Deaconess Med Ctr, Div Cardiac Surg, Boston, MA 02215 USA. [Shakil, Omair; Josephson, Mark E.; Matyal, Robina; Khabbaz, Kamal R.; Mahmood, Feroze] Harvard Univ, Sch Med, Boston, MA USA. RP Shakil, O (reprint author), Beth Israel Deaconess Med Ctr, Dept Anesthesia Crit Care & Pain Med, 1 Deaconess Rd,CC-470, Boston, MA 02215 USA. EM oshakil@bidmc.harvard.edu RI Mahmood, Feroze/B-1383-2008 OI Mahmood, Feroze/0000-0002-7071-0476 NR 14 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD SEP PY 2012 VL 9 IS 9 BP 1501 EP 1503 DI 10.1016/j.hrthm.2012.04.005 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 001ZR UT WOS:000308499900029 PM 22484649 ER PT J AU Bastepe, M AF Bastepe, M. TI Relative Functions of Gas and its Extra-large Variant XL alpha s in the Endocrine System SO HORMONE AND METABOLIC RESEARCH LA English DT Review DE bone; parathyroid hormone; hypothyroidism; hypocalcemia; hypogonadism ID STIMULATORY-G-PROTEIN; PSEUDOHYPOPARATHYROIDISM TYPE-IB; ALBRIGHT HEREDITARY OSTEODYSTROPHY; PROGRESSIVE OSSEOUS HETEROPLASIA; INDUCED SUBCELLULAR REDISTRIBUTION; INCREASED INSULIN SENSITIVITY; GRADIENT GEL-ELECTROPHORESIS; SIGNAL-TRANSDUCTION PROTEIN; IMPRINTING CONTROL ELEMENT; G(S)ALPHA KNOCKOUT MICE AB G alpha s is a ubiquitous signaling protein necessary for the actions of many neurotransmitters, hormones, and autocrine/paracrine factors. Loss-of-function mutations within the gene encoding G alpha s, GNAS, are responsible for multiple human diseases, including Albright's Hereditary Osteodystrophy, progressive osseous heteroplasia, and pseudohypoparathyroidism. Gain-of-function mutations in the same gene are found in various endocrine and nonendocrine tumors and in patients with McCune-Albright Syndrome and fibrous dysplasia of bone. In addition to G alpha s, GNAS gives rise to multiple additional coding and noncoding transcripts. Among those, XL alpha s is a paternally expressed product that is partially identical to G alpha s. This article reviews the cellular actions of G alpha s and XL alpha s, focusing on the significance of XL alpha s relative to G alpha s in mammalian physiology and human disease. C1 [Bastepe, M.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Bastepe, M.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Bastepe, M (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 55 Fruit St,Thier 10, Boston, MA 02114 USA. EM bastepe@helix.mgh.harvard.edu FU NIH/NIDDK [R01DK073911]; March of Dimes Foundation [6-FY10-336] FX The work in the author's own laboratory has been funded by research grants from NIH/NIDDK (R01DK073911) and the March of Dimes Foundation (#6-FY10-336). NR 118 TC 9 Z9 9 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 SEP PY 2012 VL 44 IS 10 BP 732 EP 740 DI 10.1055/s-0032-1316331 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 007CI UT WOS:000308866000004 PM 22730013 ER PT J AU Nagatani, K Wang, S Llado, V Lau, CW Li, ZX Mizoguchi, A Nagler, CR Shibata, Y Reinecker, HC Mora, JR Mizoguchi, E AF Nagatani, Katsuya Wang, Sen Llado, Victoria Lau, Cindy W. Li, Zongxi Mizoguchi, Atsushi Nagler, Cathryn R. Shibata, Yoshimi Reinecker, Hans-Christian Mora, J. Rodrigo Mizoguchi, Emiko TI Chitin microparticles for the control of intestinal inflammation SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE chitin; chitinase; colitis; cytokine; animal model ID ALPHA-MUTANT MICE; COLONIC EPITHELIAL-CELLS; IFN-GAMMA-PRODUCTION; INTERFERON-GAMMA; T-CELLS; YERSINIA-ENTEROCOLITICA; BACTERIAL ADHESION; BOWEL-DISEASE; CUTTING EDGE; B-CELLS AB Background: Chitin is a polymer of N-acetylglucosamine with the ability to regulate innate and adaptive immune responses. However, the detailed mechanisms of chitin-mediated regulation of intestinal inflammation are only partially known. Methods: In this study chitin microparticles (CMPs) or phosphate-buffered saline (PBS) were orally administered to acute and chronic colitis models every 3 days for 6 consecutive weeks beginning at weaning age. The effects of this treatment were evaluated by histology, cytokine production, coculture study, and enteric bacterial analysis in dextran sodium sulfate (DSS)-induced colitis or T-cell receptor alpha (TCR alpha) knockout chronic colitis models. Results: Histologically, chitin-treated mice showed significantly suppressed colitis as compared with PBS-treated mice in both animal models. The production of interferon-gamma (IFN-gamma) was upregulated in the mucosa of chitin-treated mice compared with control mice. The major source of IFN-gamma-producing cells was CD4+ T cells. In mouse dendritic cells (DCs) we found that CMPs were efficiently internalized and processed within 48 hours. Mesenteric lymph nodes (MLNs) CD4+ T cells isolated from chitin-treated mice produced a 7-fold higher amount of IFN-gamma in the culture supernatant after being cocultured with DCs and chitin as compared with the control. Proliferation of carboxyfluorescein succinimidyl ester (CFSE)low CD4+ T cells in MLNs and enteric bacterial translocation rates were significantly reduced in chitin-treated mice when compared with the control. In addition, CMPs improved the imbalance of enteric bacterial compositions and significantly increased interleukin (IL)-10-producing cells in noninflamed colon, indicating the immunoregulatory effects of CMPs in intestinal mucosa. Conclusions: CMPs significantly suppress the development of inflammation by modulating cytokine balance and microbial environment in colon. (Inflamm Bowel Dis 2012;) C1 [Nagatani, Katsuya; Wang, Sen; Llado, Victoria; Lau, Cindy W.; Li, Zongxi; Reinecker, Hans-Christian; Mora, J. Rodrigo; Mizoguchi, Emiko] Massachusetts Gen Hosp, Gastrointestinal Unit, Dept Med, Boston, MA 02114 USA. [Lau, Cindy W.; Mizoguchi, Atsushi] Massachusetts Gen Hosp, Mol Pathol Unit, Dept Pathol, Boston, MA 02114 USA. [Lau, Cindy W.; Mizoguchi, Atsushi] Harvard Univ, Sch Med, Boston, MA USA. [Li, Zongxi] China Med Univ, Dept Immunol, Shenyang, Liaoning, Peoples R China. [Mizoguchi, Atsushi; Reinecker, Hans-Christian; Mora, J. Rodrigo; Mizoguchi, Emiko] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Nagler, Cathryn R.] Univ Chicago, Dept Pathol, Comm Immunol, Chicago, IL 60637 USA. [Shibata, Yoshimi] Florida Atlantic Univ, Charles E Schmidt Coll Med, Boca Raton, FL 33431 USA. RP Mizoguchi, E (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Dept Med, GRJ 702,55 Fruit St, Boston, MA 02114 USA. EM emizoguchi@partners.org FU National Institutes of Health [DK 80070, DK74454, DK64289, DK43351]; Eli and Edythe L. Broad Medical Foundation; American Gastroenterological Association Foundation FX Supported by National Institutes of Health (DK 80070, DK74454, DK64289, and DK43351), and grants from the Eli and Edythe L. Broad Medical Foundation and American Gastroenterological Association Foundation (to E.M.). NR 45 TC 16 Z9 19 U1 0 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD SEP PY 2012 VL 18 IS 9 BP 1698 EP 1710 DI 10.1002/ibd.22874 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 986YH UT WOS:000307383100015 PM 22241684 ER PT J AU Mizoguchi, A AF Mizoguchi, Atsushi TI Healing of intestinal inflammation by IL-22 SO INFLAMMATORY BOWEL DISEASES LA English DT Review DE epithelial defense; mucin 1; antibacterial proteins; epithelial regeneration; susceptibility genes; inflammatory bowel disease ID INNATE LYMPHOID-CELLS; NATURAL-KILLER-CELLS; BOWEL-DISEASE; CROHNS-DISEASE; ULCERATIVE-COLITIS; T-CELLS; TH17 CELLS; AIRWAY INFLAMMATION; BACTERICIDAL LECTIN; MUCOSAL IMMUNITY AB An interleukin (IL)-10 family cytokine, IL-22 is characterized by several unique biological properties, including 1) the target restricted to innate cells; 2) the distinct expression pattern between large and small intestines; 3) alteration of the cellular source depending on several factors; 4) the dual abilities to serve as protective versus proinflammatory mediators in inflammatory responses; and 5) the close association with some major inflammatory bowel disease (IBD) susceptibility genes. The major functions of IL-22 in the intestine are the stimulation of epithelial cells to produce a wide variety of antibacterial proteins, the reinforcement of mucus barrier through stimulation of mucin 1 production under intestinal inflammatory conditions, and the enhancement of epithelial regeneration with goblet cell restitution. Through these beneficial functions, IL-22 contributes to the improvement of some types of experimental chronic colitis, which are mediated by T helper (Th)1 or Th2 responses. Most important, studies using both loss-of-function and gain-of-function approaches have clearly demonstrated the ability of IL-22 to promote intestinal wound healing from acute intestinal injury. These findings highlight IL-22 as an attractive and promising target for future IBD therapy. Alternatively, the enormous progress in the field of IL-22 biology has also suggested more complicated mechanisms with the IL-22 pathway than previously predicted. This review article briefly summarizes previous and current knowledge on IL-22 particularly associated with intestinal inflammation. (Inflamm Bowel Dis 2012;) C1 [Mizoguchi, Atsushi] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA USA. [Mizoguchi, Atsushi] Harvard Univ, Dept Pathol, Sch Med, Charlestown, MA USA. RP Mizoguchi, A (reprint author), 149 CNY 6024,13th St, Charlestown, MA 02129 USA. EM amizoguchi@partners.org FU Crohn's and Colitis Foundation of America; Harry B. and Leona Helmsley Charitable Trust; National Institutes of Health (NIH) [RC1DK086242] FX Supported by Crohn's and Colitis Foundation of America, the Harry B. and Leona Helmsley Charitable Trust, and National Institutes of Health (NIH) RC1DK086242. NR 95 TC 30 Z9 31 U1 0 U2 20 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD SEP PY 2012 VL 18 IS 9 BP 1777 EP 1784 DI 10.1002/ibd.22929 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 986YH UT WOS:000307383100022 PM 22359410 ER PT J AU Sauk, J AF Sauk, Jenny TI CT Scans: Bad habit or necessity? SO INFLAMMATORY BOWEL DISEASES LA English DT Editorial Material ID ATOMIC-BOMB SURVIVORS; CROHNS-DISEASE; COMPUTED-TOMOGRAPHY; MAGNETIC-RESONANCE; CANCER-RISKS; RADIATION C1 Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. RP Sauk, J (reprint author), Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD SEP PY 2012 VL 18 IS 9 BP 1797 EP 1798 DI 10.1002/ibd.22894 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 986YH UT WOS:000307383100025 PM 22275340 ER PT J AU van de Veerdonk, FL Smeekens, SP Conway, KL Gresnigt, MS Begun, J Plantinga, TS Joosten, LAB van der Meer, JWM Chamilos, G Xavier, RJ Netea, MG AF van de Veerdonk, F. L. Smeekens, S. P. Conway, K. L. Gresnigt, M. S. Begun, J. Plantinga, T. S. Joosten, L. A. B. van der Meer, J. W. M. Chamilos, G. Xavier, R. J. Netea, M. G. TI CHRONIC GRANULOMATOUS DISEASE IS CHARACTERIZED BY DEFECTIVE AUTOPHAGY AND SUBSEQUENT INCREASED INTERLEUKIN-1B PRODUCTION SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 15th Biennial Meeting European-Society-for-Immunodeficiency (ESID) CY OCT 03-06, 2012 CL Florence, ITALY SP European Soc Immunodeficiency (ESID), Int Nursing Grp Immunodeficiencies (INGID), Int Patient Org Primary Immunodeficiencies (IPOPI) C1 [van de Veerdonk, F. L.; Smeekens, S. P.; Gresnigt, M. S.; Plantinga, T. S.; Joosten, L. A. B.; van der Meer, J. W. M.; Netea, M. G.] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands. [van de Veerdonk, F. L.; Smeekens, S. P.; Gresnigt, M. S.; Plantinga, T. S.; Joosten, L. A. B.; van der Meer, J. W. M.; Netea, M. G.] Nijmegen Inst Infect Inflammat & Immun N4I, Nijmegen, Netherlands. [Conway, K. L.; Begun, J.; Xavier, R. J.] Harvard Univ, Sch Med, Ctr Computat & Integrat Biol, Boston, MA USA. [Conway, K. L.; Begun, J.; Xavier, R. J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA USA. [Chamilos, G.] Univ Crete, Sch Med, Dept Internal Med, Iraklion, Greece. [Xavier, R. J.] Broad Inst MIT & Harvard, Cambridge, MA USA. RI van der Meer, Jos/C-8521-2013; Plantinga, Theo/A-6895-2015; Joosten, Leo/H-3138-2015; Netea, Mihai/N-5155-2014; Smeekens, Sanne/G-8307-2011; van de Veerdonk, Frank/C-7256-2008 OI van der Meer, Jos/0000-0001-5120-3690; Smeekens, Sanne/0000-0002-7835-914X; van de Veerdonk, Frank/0000-0002-1121-4894 NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD SEP PY 2012 VL 32 SU 1 BP 5 EP 5 PG 1 WC Immunology SC Immunology GA 005CU UT WOS:000308728900007 ER PT J AU Walter, JE Recher, M Kis-Toth, K Matthew, D Volpi, S Rucci, F Szabo, A Walter, O Csizmadia, E Alt, F Tsokos, GC Notarangelo, LD AF Walter, J. E. Recher, M. Kis-Toth, K. Matthew, D. Volpi, S. Rucci, F. Szabo, A. Walter, O. Csizmadia, E. Alt, F. Tsokos, G. C. Notarangelo, L. D. TI TOLL-LIKE RECEPTOR ENGAGEMENT CONVERTS INNATE DYSREGULATION INTO OVERT CYTOKINE STORM AND PROMOTES AUTOIMMUNITY IN MURINE MODEL OF LEAKY SCID SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 15th Biennial Meeting European-Society-for-Immunodeficiency (ESID) CY OCT 03-06, 2012 CL Florence, ITALY SP European Soc Immunodeficiency (ESID), Int Nursing Grp Immunodeficiencies (INGID), Int Patient Org Primary Immunodeficiencies (IPOPI) C1 [Walter, J. E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp Children, Sect Pediat Allergy & Immunol, Boston, MA USA. [Walter, J. E.; Matthew, D.; Volpi, S.; Rucci, F.; Notarangelo, L. D.] Childrens Hosp Boston, Dept Pediat, Div Immunol, Boston, MA USA. [Recher, M.] Univ Basel Hosp, Dept Internal Med, CH-4031 Basel, Switzerland. [Kis-Toth, K.; Tsokos, G. C.] Beth Israel Deaconess Med Ctr, Div Rheumatol, Boston, MA 02215 USA. [Szabo, A.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Walter, O.] Univ Massachusetts, Dept Pathol, Worcester, MA USA. [Alt, F.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA USA. RI Notarangelo, Luigi/F-9718-2016 OI Notarangelo, Luigi/0000-0002-8335-0262 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD SEP PY 2012 VL 32 SU 1 BP 15 EP 15 PG 1 WC Immunology SC Immunology GA 005CU UT WOS:000308728900025 ER PT J AU Recher, M Deenick, E Al-Herz, W Frugoni, F Lee, Y Delmonte, OM Giliani, S Walter, JE Berger, CT Nobre, R Roscioli, T Buckley, MF Ziegler, JB Wong, M Megarbane, A Chouery, E Lefranc, G Hess, C Tangye, S Notarangelo, LD Bloch, D AF Recher, M. Deenick, E. Al-Herz, W. Frugoni, F. Lee, Y. Delmonte, O. M. Giliani, S. Walter, J. E. Berger, C. T. Nobre, R. Roscioli, T. Buckley, M. F. Ziegler, J. B. Wong, M. Megarbane, A. Chouery, E. Lefranc, G. Hess, C. Tangye, S. Notarangelo, L. D. Bloch, D. TI SP110 REGULATES NUCLEAR ORPHAN RECEPTOR NUR77-DRIVEN APOPTOSIS IN T CELLS SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 15th Biennial Meeting European-Society-for-Immunodeficiency (ESID) CY OCT 03-06, 2012 CL Florence, ITALY SP European Soc Immunodeficiency (ESID), Int Nursing Grp Immunodeficiencies (INGID), Int Patient Org Primary Immunodeficiencies (IPOPI) C1 [Recher, M.; Berger, C. T.; Hess, C.] Univ Basel Hosp, CH-4031 Basel, Switzerland. [Frugoni, F.; Lee, Y.; Delmonte, O. M.; Walter, J. E.; Notarangelo, L. D.] Harvard Univ, Sch Med, Childrens Hosp Boston, Boston, MA USA. [Deenick, E.; Tangye, S.] St Vincents Hosp, Garvan Inst Med Res, Darlinghurst, NSW 2010, Australia. [Al-Herz, W.] Kuwait Univ, Kuwait, Kuwait. [Giliani, S.] A Nocivelli Inst Mol Med, Brescia, Italy. [Nobre, R.; Bloch, D.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [Roscioli, T.; Buckley, M. F.] Nijmegen Med Ctr, Nijmegen, Neth Antilles. [Ziegler, J. B.] Childrens Hosp, Sydney, NSW, Australia. [Wong, M.] Childrens Hosp Westmead, Sydney, NSW, Australia. [Megarbane, A.; Chouery, E.] Univ St Joseph, Paris, France. [Lefranc, G.] Univ Montpellier, Inst Genet Humaine, F-34059 Montpellier, France. RI Notarangelo, Luigi/F-9718-2016 OI Notarangelo, Luigi/0000-0002-8335-0262 NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD SEP PY 2012 VL 32 SU 1 BP 20 EP 21 PG 2 WC Immunology SC Immunology GA 005CU UT WOS:000308728900036 ER PT J AU Henderson, LA Frugoni, F Hopkins, G Alherz, W Weinacht, K Comeau, AM Bonilla, FA Notarangelo, LD Pai, SY AF Henderson, L. A. Frugoni, F. Hopkins, G. Alherz, W. Weinacht, K. Comeau, A. M. Bonilla, F. A. Notarangelo, L. D. Pai, S-Y TI FIRST REPORTED CASE OF OMENN SYNDROME IN A PATIENT WITH RETICULAR DYSGENESIS SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 15th Biennial Meeting European-Society-for-Immunodeficiency (ESID) CY OCT 03-06, 2012 CL Florence, ITALY SP European Soc Immunodeficiency (ESID), Int Nursing Grp Immunodeficiencies (INGID), Int Patient Org Primary Immunodeficiencies (IPOPI) C1 [Henderson, L. A.; Frugoni, F.; Bonilla, F. A.; Notarangelo, L. D.] Childrens Hosp, Div Immunol, Boston, MA 02115 USA. [Hopkins, G.; Weinacht, K.; Pai, S-Y] Childrens Hosp, Div Hematol & Oncol, Boston, MA 02115 USA. [Alherz, W.] Kuwait Univ, Fac Med, Al Sabah Hosp, Pediat Dept,Allergy & Clin Immunol Unit, Kuwait, Kuwait. [Weinacht, K.; Pai, S-Y] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Comeau, A. M.] Univ Massachusetts, Med Ctr, New England Newborn Screening Program, Worcester, MA USA. [Notarangelo, L. D.] Manton Ctr Orphan Dis Res, Boston, MA USA. RI Notarangelo, Luigi/F-9718-2016 OI Notarangelo, Luigi/0000-0002-8335-0262 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD SEP PY 2012 VL 32 SU 1 BP 71 EP 71 PG 1 WC Immunology SC Immunology GA 005CU UT WOS:000308728900135 ER PT J AU Eisner, BH Kulkarni, N Pinho, D Uppot, R Desai, G Sahani, D AF Eisner, Brian Howard Kulkarni, Naveen Pinho, Daniella Uppot, Raul Desai, Guarav Sahani, Dushyant TI SUBMILISIEVERT COMPUTED TOMOGRAPHY FOR THE EVALUATION OF UROLITHIASIS SO JOURNAL OF ENDOUROLOGY LA English DT Meeting Abstract C1 [Eisner, Brian Howard] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA USA. [Kulkarni, Naveen; Pinho, Daniella; Uppot, Raul; Desai, Guarav; Sahani, Dushyant] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. NR 0 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 SEP PY 2012 VL 26 SU 1 BP A199 EP A200 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 001VM UT WOS:000308488202165 ER PT J AU Lange, D Arsovska, O Ross, M Eisner, BH Kurtz, MP Gershman, B Paterson, RF Chew, BH AF Lange, Dirk Arsovska, Olga Ross, Michael Eisner, Brian H. Kurtz, Michael P. Gershman, Boris Paterson, Ryan F. Chew, Ben H. TI ARE POSTOPERATIVE ANTIBIOTICS NECESSARY AFTER UNCOMPLICATED URETEROSCOPY? SO JOURNAL OF ENDOUROLOGY LA English DT Meeting Abstract C1 [Lange, Dirk; Arsovska, Olga; Ross, Michael; Paterson, Ryan F.; Chew, Ben H.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Eisner, Brian H.; Kurtz, Michael P.; Gershman, Boris] Harvard Univ, Sch Med, Dept Urol, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0892-7790 J9 J ENDOUROL JI J. Endourol. PD SEP PY 2012 VL 26 SU 1 BP A276 EP A276 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 001VM UT WOS:000308488203076 ER PT J AU Shoag, J Eisner, BH AF Shoag, Jonathan Eisner, Brian Howard TI INCREASING PREVALENCE OF NEPHROLITHIASIS IN THE UNITED STATES OVER THE PAST TWO DECADES SO JOURNAL OF ENDOUROLOGY LA English DT Meeting Abstract C1 [Shoag, Jonathan; Eisner, Brian Howard] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0892-7790 J9 J ENDOUROL JI J. Endourol. PD SEP PY 2012 VL 26 SU 1 BP A100 EP A100 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 001VM UT WOS:000308488201188 ER PT J AU Kadzielski, JJ Bot, AGJ Ring, D AF Kadzielski, John J. Bot, Arjan G. J. Ring, David TI The Influence of Job Satisfaction, Burnout, Pain, and Worker's Compensation Status on Disability After Finger Injuries SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Disability; finger injuries; job satisfaction; burnout; worker's compensation ID LOW-BACK-PAIN; MUSCULOSKELETAL PAIN; POPULATION; DISORDERS; RETURN; HAND; ASSOCIATION; PREDICTORS; ILLNESS; TRAUMA AB Purpose Motivation, job satisfaction, burnout, and secondary gain are factors that can influence return to work and disability after orthopedic injuries. The current study evaluated the separate effects of job satisfaction, burnout, and secondary gain on arm-specific disability after a finger injury. Methods Ninety-three employed patients with finger injuries were enrolled in this prospective study, and 51 completed the follow-up. Burnout (measured with Shirom-Melamed's Burnout Measure), job satisfaction (measured with the Job Descriptive Index questionnaire), and demographics were assessed at the initial visit. After 6 months, arm-specific disability was measured with the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire, and general health status was measured with the Short Form-36 (SF-36) survey, mental component summary (MCS) and physical component summary (PCS). Results In the 51 patients with complete follow-up, the mean DASH score was 12, the mean SF-36 PCS was 48, the mean SF-36 MCS was 49, and the mean pain rating was 2.1. In multivariable analysis, pain and worker's compensation status explained 52% of the variability in DASH scores (pain alone accounted for 49%); pain accounted for 14% of the variability in SF-36 PCS scores; and worker's compensation accounted for 11% of the variation in the SF-36 MCS scores. Conclusions The majority of variation in the SF-36 PCS and MCS scores remained unaccounted for by the models, but pain and worker's compensation were more important than job burnout or job satisfaction. Pain and worker's compensation were also significant predictors of the DASH. Clinical relevance Worker's compensation and pain were more important than job satisfaction and burnout in explaining variations in arm-specific disability in patients with finger injuries. (J Hand Surg 2012;37A:1812-1819. Copyright (C) 2012 by the American Society for Surgery of the Hand. All rights reserved.) C1 [Ring, David] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey Ctr, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org FU Stichting Anna Fonds; VSB-fonds; Prins Bernhard Cultuurfonds; Banning-de Jong fonds FX A.G.J.B. is supported by Dutch research grants from Stichting Anna Fonds, VSB-fonds, Prins Bernhard Cultuurfonds, and Banning-de Jong fonds. NR 38 TC 7 Z9 8 U1 2 U2 12 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD SEP PY 2012 VL 37A IS 9 BP 1812 EP 1819 DI 10.1016/j.jhsa.2012.05.023 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 002CV UT WOS:000308509500007 PM 22763059 ER PT J AU Bot, AGJ Mulders, MAM Fostvedt, S Ring, D AF Bot, Arjan G. J. Mulders, Marjolein A. M. Fostvedt, Sigrid Ring, David TI Determinants of Grip Strength in Healthy Subjects Compared to That in Patients Recovering From a Distal Radius Fracture SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Anxiety; depression; distal radius fracture; grip strength; pain ID CATASTROPHIZING SCALE; UNSTABLE FRACTURES; INTERNAL-FIXATION; MUSCLE STRENGTH; PINCH STRENGTH; OPEN REDUCTION; NORMATIVE DATA; CHRONIC PAIN; BODY-MASS; DEPRESSION AB Purpose Grip strength is influenced primarily by body mass index, sex, and age. It is also partly voluntary and correlates with symptoms of depression. This study examined whether psychological factors influence grip more in the setting of injury than in healthy volunteers. Methods Grip strength was evaluated in one hundred subjects, 50 healthy individuals and 50 patients 6 weeks after a nonsurgically treated fracture of the distal radius. Grip strength was measured as the mean of 3 attempts, and patients completed questionnaires for arm-specific disability (Disabilities of the Arm, Shoulder, and Hand), depression, pain anxiety, catastrophic thinking, and negative thoughts in response to pain. Results The mean grip strength in the injured group was 55% of the uninjured side. Pain anxiety accounted for 9% of the variability in grip strength in injured wrists. Among healthy patients, sex was the only correlate of dominant-side grip strength, and body mass index accounted for 8% of the variation in the grip strength of the nondominant side divided by the dominant side. Conclusions The majority of the variation in grip strength remains unaccounted for, but physical factors correlate best with grip strength and percent grip strength of the nondominant side divided by the dominant side in healthy patients, and psychological factors correlate best with absolute grip in patients recovering from distal radius fractures. Clinical relevance The influences on grip strength are complex, but the differences among recovering and healthy patients demonstrate a role for nonphysical factors in grip strength during recovery. (J Hand Surg 2012;37A:1874-1880. (C) 2012 Published by Elsevier Inc. on behalf of the American Society for Surgery of the Hand.) C1 [Ring, David] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey Ctr, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org FU Stichting Anna Fonds; VSB-fonds; Prins Bernhard Cultuurfonds; Banning-de Jong fonds FX Support provided by Stichting Anna Fonds (A.G.J.B., M.A.M.M.), VSB-fonds (A.G.J.B.), Prins Bernhard Cultuurfonds (A.G.J.B.), Banning-de Jong fonds (A.G.J.B.). NR 31 TC 10 Z9 10 U1 0 U2 9 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD SEP PY 2012 VL 37A IS 9 BP 1874 EP 1880 DI 10.1016/j.jhsa.2012.04.032 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 002CV UT WOS:000308509500017 PM 22749477 ER PT J AU Fiorella, D Hirsch, JA Woo, HH Rasmussen, PA Hussain, MS Hui, FK Frei, D Meyers, PM Jabbour, P Gonzalez, LF Mocco, J Turk, A Turner, RD Arthur, AS Gupta, R Cloft, HJ AF Fiorella, David Hirsch, Joshua A. Woo, Henry H. Rasmussen, Peter A. Hussain, Muhammad Shazam Hui, Ferdinand K. Frei, Donald Meyers, Phil M. Jabbour, Pascal Gonzalez, L. Fernando Mocco, J. Turk, Aquilla Turner, Raymond D. Arthur, Adam S. Gupta, Rishi Cloft, Harry J. TI Should neurointerventional fellowship training be suspended indefinitely? SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Editorial Material ID ACUTE ISCHEMIC-STROKE; UNRUPTURED CEREBRAL ANEURYSMS; UNITED-STATES; ENDOVASCULAR EMBOLECTOMY; VOLUME; INTRAARTERIAL; INTERVENTION; MORTALITY; THERAPY C1 [Fiorella, David] SUNY Stony Brook, Hlth Sci Ctr 080, Med Ctr, Dept Neurosurg,Cerebrovasc Ctr, Stony Brook, NY 11794 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Neuroendovasc Program, Boston, MA 02114 USA. [Rasmussen, Peter A.; Hussain, Muhammad Shazam; Hui, Ferdinand K.] Cleveland Clin, Cerebrovasc Ctr, Cleveland, OH 44106 USA. [Frei, Donald] Swedish Med Ctr, Radiol Imaging Associates, Dept Intervent Neuroradiol, Denver, CO USA. [Meyers, Phil M.] Columbia Univ, Coll Phys & Surg, Dept Radiol, NYC, New York, NY USA. [Meyers, Phil M.] Columbia Univ, Coll Phys & Surg, Dept Neurol Surg, NYC, New York, NY USA. [Jabbour, Pascal; Gonzalez, L. Fernando] Thomas Jefferson Univ Hosp, Dept Neurosurg, Philadelphia, PA 19107 USA. [Mocco, J.] Vanderbilt Univ, Dept Neurosurg, Nashville, TN USA. [Turk, Aquilla] Med Univ S Carolina, Dept Radiol, Cerebrovasc Ctr, Charleston, SC 29425 USA. [Turner, Raymond D.] Med Univ S Carolina, Dept Neurosci, Cerebrovasc Ctr, Charleston, SC 29425 USA. [Arthur, Adam S.] Semmes Murphey Neurol & Spine Inst, Dept Neurosurg, Memphis, TN USA. [Gupta, Rishi] Grady Mem Hosp Atlanta, Marcus Stroke & Neurosci Ctr, Dept Neurol, Atlanta, GA USA. [Cloft, Harry J.] Mayo Clin, Dept Radiol, Rochester, MN USA. RP Fiorella, D (reprint author), SUNY Stony Brook, Hlth Sci Ctr 080, Med Ctr, Dept Neurosurg,Cerebrovasc Ctr, Stony Brook, NY 11794 USA. EM david.fiorella@sbumed.org OI Arthur, Adam/0000-0002-1536-1613 NR 17 TC 28 Z9 28 U1 2 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD SEP PY 2012 VL 4 IS 5 DI 10.1136/neurintsurg-2012-010471 PG 4 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 005GL UT WOS:000308738800011 PM 22933732 ER PT J AU Gupta, AC Yoo, AJ Stone, J Barr, JC Brook, A Tutton, S Ortiz, O Hirsch, AE Larvie, M Frey, ME Jayaraman, MV Hirsch, JA AF Gupta, Amar C. Yoo, Albert J. Stone, Jeffrey Barr, John C. Brook, Allan Tutton, Sean Ortiz, Orlando Hirsch, Ariel E. Larvie, Mykol Frey, Michael E. Jayaraman, Mahesh V. Hirsch, Joshua A. TI Percutaneous sacroplasty SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Review ID SACRAL INSUFFICIENCY FRACTURES; CT-GUIDED SACROPLASTY; INTERVENTIONAL PROCEDURES; FLUOROSCOPIC GUIDANCE; BONE; PAIN; VERTEBROPLASTY; CEMENTOPLASTY; AUGMENTATION; COMPRESSION AB The recognition of sacral insufficiency fractures continues to be poor, and diagnosis is often delayed resulting in significant morbidity. Percutaneous sacroplasty is an image guided procedure that is safe and potentially effective for treating the pain and disability related to these fractures. Several cohort studies reviewed here report successful outcomes using this procedure, with patients experiencing nearly full pain relief immediately and longitudinally. As with the well proven results from percutaneous vertebral augmentation within the thoracic and lumbar spine, sacroplasty reduces the cost associated with bed rest and physical therapy and allows patients to return to activities of daily living sooner than with conservative therapy. C1 [Gupta, Amar C.; Yoo, Albert J.; Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Intervent Neuroradiol & Endovasc Neurosurg, Boston, MA 02114 USA. [Stone, Jeffrey] Mayo Clin Florida, Dept Radiol, Jacksonville, FL USA. [Barr, John C.] Scrripps Mem Hosp, La Jolla, CA USA. [Brook, Allan] Montefiore Med Ctr, Dept Radiol, Bronx, NY 10467 USA. [Tutton, Sean] Med Coll Wisconsin, Froedtert Mem Lutheran Hosp, Dept Intervent & Diagnost Radiol, Milwaukee, WI 53226 USA. [Ortiz, Orlando] Winthrop Univ Hosp, Dept Radiol, Mineola, NY 11501 USA. [Hirsch, Ariel E.] Boston Univ, Med Ctr, Dept Radiat Oncol, Boston, MA USA. [Larvie, Mykol] Massachusetts Gen Hosp, Dept Neuroradiol, Boston, MA 02114 USA. [Frey, Michael E.] Virginia Commonwealth Univ, Dept Phys Med & Rehabil, Richmond, VA USA. [Frey, Michael E.] Adv Pain Management & Spine Specialists, Ft Myers, FL USA. [Jayaraman, Mahesh V.] Brown Univ, Rhode Isl Hosp, Dept Diagnost Imaging, Providence, RI 02903 USA. [Jayaraman, Mahesh V.] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA. RP Hirsch, JA (reprint author), Massachusetts Gen Hosp, Dept Intervent & Diagnost Neuroradiol, Gray 241,55 Fruit St, Boston, MA 02114 USA. EM jahirsch@partners.org FU Benvenue Medical FX JS: restricted research grant (Benvenue Medical). AB: CareFusion consultant. ST: consultant for Benvenue Medical. OO: speakers bureau, Orthovita. MF: consultant for Boston Scientific. JH: CareFusion consultant. NR 63 TC 8 Z9 9 U1 0 U2 6 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD SEP PY 2012 VL 4 IS 5 DI 10.1136/neurintsurg-2011-010136 PG 5 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 005GL UT WOS:000308738800026 PM 22003050 ER PT J AU Jayaraman, MV Meyers, PM Derdeyn, CP Fraser, JF Hirsch, JA Hussain, MS Blackham, KA Eskey, CJ Jensen, ME Moran, CJ Prestigiacomo, CJ Rasmussen, PA McDougall, CG AF Jayaraman, Mahesh V. Meyers, Philip M. Derdeyn, Colin P. Fraser, Justin F. Hirsch, Joshua A. Hussain, M. Shazam Blackham, Kristine A. Eskey, Clifford J. Jensen, Mary E. Moran, Christopher J. Prestigiacomo, Charles Joseph Rasmussen, Peter A. McDougall, Cameron G. TI Reporting standards for angiographic evaluation and endovascular treatment of cerebral arteriovenous malformations SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Article ID N-BUTYL CYANOACRYLATE; MARTIN GRADE-IV; PREOPERATIVE EMBOLIZATION; TECHNICAL ASPECTS; AVM EMBOLIZATION; NATURAL-HISTORY; BRAIN; HEMORRHAGE; COMPLICATIONS; ONYX AB These guidelines were developed by consensus of a multidisciplinary panel of specialists interested in the evaluation and treatment of patients with arteriovenous malformations (AVMs) of the CNS. The reporting criteria described will serve as a template for trial design and for clinical investigators who wish to report on endovascular therapy of cerebral AVMs. Direct comparison of various treatment paradigms is important to standardization of care, maximization of good treatment outcomes, assessment of new methods and technologies. C1 [Jayaraman, Mahesh V.] Brown Univ, Alpert Med Sch, Dept Diagnost Imaging, Providence, RI USA. [Jayaraman, Mahesh V.] Brown Univ, Alpert Med Sch, Dept Neurosurg, Providence, RI 02912 USA. [Meyers, Philip M.] Columbia Univ, Dept Radiol & Neurol Surg, New York, NY USA. [Derdeyn, Colin P.; Moran, Christopher J.] Washington Univ, Dept Neuroradiol, St Louis, MO USA. [Fraser, Justin F.] Univ Kentucky, Dept Neurol Surg, Louisville, KY USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Intervent & Diagnost Neuroradiol, Boston, MA 02114 USA. [Hussain, M. Shazam] Cleveland Clin, Cerebrovasc Ctr, Cleveland, OH 44106 USA. [Blackham, Kristine A.] Case Western Reserve Univ, Dept Radiol, Univ Hosp, Cleveland, OH 44106 USA. [Eskey, Clifford J.] Dartmouth Hitchcock Med Ctr, Dept Radiol Neurol & Neurosurg, Lebanon, NH 03766 USA. [Jensen, Mary E.] Univ Virginia, Dept Radiol & Neurol Surg, Charlottesville, VA USA. [Prestigiacomo, Charles Joseph] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Neurol Surg, Newark, NJ 07103 USA. [Rasmussen, Peter A.] Cleveland Clin, Dept Neurosurg, Cleveland, OH 44106 USA. [McDougall, Cameron G.] Barrow Neurol Inst, Dept Neurosurg, Phoenix, AZ 85013 USA. RP Jayaraman, MV (reprint author), Brown Univ, Alpert Med Sch, Dept Diagnost Imaging, 593 Eddy St,Room 377, Providence, RI USA. EM mjayaraman@lifespan.org OI Derdeyn, Colin/0000-0002-5932-2683 NR 62 TC 4 Z9 4 U1 1 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD SEP PY 2012 VL 4 IS 5 DI 10.1136/neurintsurg-2011-010173 PG 6 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 005GL UT WOS:000308738800015 PM 22131440 ER PT J AU Abramovitch, A Dar, R Hermesh, H Schweiger, A AF Abramovitch, Amitai Dar, Reuven Hermesh, Haggai Schweiger, Avraham TI Comparative neuropsychology of adult obsessive-compulsive disorder and attention deficit/hyperactivity disorder: Implications for a novel executive overload model of OCD SO JOURNAL OF NEUROPSYCHOLOGY LA English DT Review ID DEFICIT HYPERACTIVITY DISORDER; CEREBRAL-BLOOD-FLOW; NEUROPSYCHIATRIC INTERVIEW MINI; GLUCOSE METABOLIC-RATE; BEHAVIORAL-INHIBITION; NONVERBAL MEMORY; RESPONSE-INHIBITION; FUNCTIONAL CONNECTIVITY; SYMPTOM PROVOCATION; CLINICAL-VARIABLES AB Research implicates frontostriatal pathophysiology in both attention deficit/hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). Nevertheless, ADHD is characterized with frontostriatal hypoactivity and OCD with hyperactivity. Furthermore, both disorders seem to lie on opposite ends of a clinical impulsive-compulsive continuum. While never having directly been compared, and despite these differences, OCD and ADHD appear to share similar neuropsychological impairments especially in executive functions. This study aimed at comparing adults with OCD and adults with ADHD on neuropsychological measures and behavioural impulsivity and OC measures. Thirty OCD, 30 ADHD, and 30 matched healthy control (HC) participants were administered a comprehensive neuropsychological battery and completed several questionnaires. The groups were compared on all neuropsychological and clinical measures and correlations between neuropsychological and clinical symptoms were computed. The ADHD and OCD groups performed more poorly than HC on all neuropsychological domains and most domain subtests. The ADHD group reported significantly higher impulsivity than the OCD group. OCD patients did not differ from HC on behavioural impulsivity. A unique dissociation was found between impulsivity and response inhibition where both clinical groups showed similar response inhibition deficit, but differed significantly on impulsivity. Moreover, a negative association between OC symptoms and response inhibition and a bias in self-perception of impulsivity was found only in the OCD group. We propose an executive overload model of OCD that views neuropsychological impairments in OCD as an epiphenomenon, according to which continuous attempts to control automatic processes are associated with obsessive thoughts overflow that causes an overload on the executive system. C1 [Abramovitch, Amitai] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Abramovitch, Amitai] Harvard Univ, Sch Med, Boston, MA USA. [Abramovitch, Amitai; Dar, Reuven] Tel Aviv Univ, Dept Psychol, Tel Aviv, Israel. [Hermesh, Haggai] Rabin Med Ctr, Geha Mental Hlth Ctr, Outpatient Dept, Petah Tiquva, Israel. [Hermesh, Haggai] Rabin Med Ctr, Geha Mental Hlth Ctr, Anxiety Disorders & Behav Therapy Unit, Petah Tiquva, Israel. [Hermesh, Haggai] Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel. [Schweiger, Avraham] Acad Coll Tel Aviv, Dept Behav Sci, Tel Aviv, Israel. RP Abramovitch, A (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 185 Cambridge St,Suite 2000, Boston, MA 02114 USA. EM aabramovitch@partners.org RI Abramovitch, Amitai/I-3333-2012 OI Abramovitch, Amitai/0000-0001-9640-0970 NR 126 TC 39 Z9 40 U1 6 U2 32 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1748-6645 EI 1748-6653 J9 J NEUROPSYCHOL JI J. Neuropsychol. PD SEP PY 2012 VL 6 BP 161 EP 191 DI 10.1111/j.1748-6653.2011.02021.x PN 2 PG 31 WC Psychology; Psychology, Experimental SC Psychology GA 000ZN UT WOS:000308429700002 PM 22257360 ER PT J AU Wortzel, HS Arciniegas, DB Anderson, CA Vanderploeg, RD Brenner, LA AF Wortzel, Hal S. Arciniegas, David B. Anderson, C. Alan Vanderploeg, Rodney D. Brenner, Lisa A. TI A Phase I Study of Low-Pressure Hyperbaric Oxygen Therapy for Blast-Induced Post-Concussion Syndrome and Post-Traumatic Stress Disorder: A Neuropsychiatric Perspective SO JOURNAL OF NEUROTRAUMA LA English DT Letter ID TRAUMATIC BRAIN-INJURY; METAANALYSIS; ANTIDEPRESSANT; DEPRESSION; VETERANS; IMPACT C1 [Wortzel, Hal S.; Brenner, Lisa A.] Denver Vet Affairs Med Ctr, VISN MIRECC 19, VA Rocky Mt Network, Mental Illness Res Educ & Clin Ctr, Denver, CO 80220 USA. [Arciniegas, David B.; Anderson, C. Alan; Brenner, Lisa A.] Univ Colorado, Sch Med, Dept Psychiat, Denver, CO 80262 USA. [Wortzel, Hal S.; Arciniegas, David B.] Univ Colorado, Sch Med, Dept Neurol, Denver, CO USA. [Anderson, C. Alan] Denver Vet Affairs Med Ctr, Neurol Serv, Denver, CO 80220 USA. [Vanderploeg, Rodney D.] James A Haley Vet Hosp, Tampa, FL 33612 USA. RP Wortzel, HS (reprint author), Denver Vet Affairs Med Ctr, VISN MIRECC 19, VA Rocky Mt Network, Mental Illness Res Educ & Clin Ctr, 1055 Clermont St, Denver, CO 80220 USA. EM hal.wortzel@ucdenver.edu NR 24 TC 1 Z9 1 U1 1 U2 9 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 SEP PY 2012 VL 29 IS 14 BP 2421 EP 2424 DI 10.1089/neu.2012.2426 PG 4 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 004SM UT WOS:000308701400006 PM 22519979 ER PT J AU Chen, Y Rice, W Gu, ZZ Li, J Huang, JM Brenner, MB Van Hoek, A Xiong, JP Gundersen, GG Norman, JC Hsu, VW Fenton, RA Brown, D Lu, HAJ AF Chen, Ying Rice, William Gu, Zhizhan Li, Jian Huang, Jianmin Brenner, Michael B. Van Hoek, Alfred Xiong, Jianping Gundersen, Gregg G. Norman, Jim C. Hsu, Victor W. Fenton, Robert A. Brown, Dennis Lu, Hua A. Jenny TI Aquaporin 2 Promotes Cell Migration and Epithelial Morphogenesis SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID NEPHROGENIC DIABETES-INSIPIDUS; URINARY CONCENTRATING DEFECT; RENAL COLLECTING DUCT; ARG-GLY-ASP; MICE LACKING; PLASMA-MEMBRANE; WATER CHANNEL; RAT-KIDNEY; BRANCHING MORPHOGENESIS; ENDOCYTIC TRANSPORT AB The aquaporin 2 (AQP2) water channel, expressed in kidney collecting ducts, contributes critically to water homeostasis in mammals. Animals lacking or having significantly reduced levels of AQP2, however, have not only urinary concentrating abnormalities but also renal tubular defects that lead to neonatal mortality from renal failure. Here, we show that AQP2 is not only a water channel but also an integrin-binding membrane protein that promotes cell migration and epithelial morphogenesis. AQP2 expression modulates the trafficking and internalization of integrin beta 1, facilitating its turnover at focal adhesions. In vitro, disturbing the interaction between AQP2 and integrin beta 1 by mutating the RGD motif led to reduced endocytosis, retention of integrin beta 1 at the cell surface, and defective cell migration and tubulogenesis. Similarly, in vivo, AQP2-null mice exhibited significant retention of integrin beta 1 at the basolateral membrane and had tubular abnormalities. In summary, these data suggest that the water channel AQP2 interacts with integrins to promote renal epithelial cell migration, contributing to the structural and functional integrity of the mammalian kidney. C1 [Chen, Ying; Rice, William; Huang, Jianmin; Van Hoek, Alfred; Xiong, Jianping; Brown, Dennis; Lu, Hua A. Jenny] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol,Program Membrane Biol,Simches Res C, Boston, MA 02114 USA. [Chen, Ying; Rice, William; Huang, Jianmin; Van Hoek, Alfred; Xiong, Jianping; Brown, Dennis; Lu, Hua A. Jenny] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Nephrol,Dept Med,Simches Res Ctr, Boston, MA 02114 USA. [Gu, Zhizhan; Li, Jian; Brenner, Michael B.; Hsu, Victor W.] Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Gu, Zhizhan; Li, Jian; Brenner, Michael B.; Hsu, Victor W.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. [Gundersen, Gregg G.] Columbia Univ, Dept Pathol & Cell Biol, New York, NY USA. [Norman, Jim C.] Beatson Inst Canc Res, Integrin Cell Biol Lab, Glasgow G61 1BD, Lanark, Scotland. [Fenton, Robert A.] Aarhus Univ, Dept Anat, Water & Salt Res Ctr, Aarhus, Denmark. RP Lu, HAJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol,Program Membrane Biol,Simches Res C, 185 Cambridge St, Boston, MA 02114 USA. EM halu@partners.org OI NORMAN, Jim/0000-0002-0098-3014 FU NIH KO8 grant [DK075940]; Gottschalk research grant from the American Society of Nephrology (ASN); NIH [DK38452, NIH 5T32 DK007540-24]; Boston Area Diabetes and Endocrinology Research Center [NIH DK-57521]; Center for the Study of Inflammatory Bowel Disease [NIH DK-43351] FX H.J.L. is supported by an NIH KO8 grant (DK075940) and a Gottschalk research grant from the American Society of Nephrology (ASN). D.B. is supported by a NIH grant (DK38452). W.R. is supported by a NIH training grant (NIH 5T32 DK007540-24). The Microscopy Core Facility of the Program in Membrane Biology receives additional support from the Boston Area Diabetes and Endocrinology Research Center (NIH DK-57521) and from the Center for the Study of Inflammatory Bowel Disease (NIH DK-43351). NR 64 TC 23 Z9 23 U1 0 U2 5 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2012 VL 23 IS 9 BP 1506 EP 1517 DI 10.1681/ASN.2012010079 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 005UM UT WOS:000308775600012 PM 22859853 ER PT J AU Chan, KE Warren, HS Thadhani, RI Steele, DJR Hymes, JL Maddux, FW Hakim, RM AF Chan, Kevin E. Warren, H. Shaw Thadhani, Ravi I. Steele, David J. R. Hymes, Jeffrey L. Maddux, Franklin W. Hakim, Raymond M. TI Prevalence and Outcomes of Antimicrobial Treatment for Staphylococcus aureus Bacteremia in Outpatients with ESRD SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID BLOOD-STREAM INFECTIONS; METHICILLIN-RESISTANT; UNITED-STATES; VANCOMYCIN; HEMODIALYSIS; ENDOCARDITIS; MULTICENTER; CEFAZOLIN; MORTALITY; TRENDS AB Staphylococcus bacteremia is a common and life-threatening medical emergency, but it is treatable with appropriate antibiotic therapy. To identify opportunities that may reduce morbidity and mortality associated with S. aureus, we analyzed data from 293,094 chronic hemodialysis outpatients to characterize practices of antibiotic selection. In the study population, the overall rate of bacteremia was 15.4 per 100 outpatient-years; the incidence rate for methicillin-sensitive (MSSA) was 2.1 per 100 outpatient-years, and the incidence rate for methicillin-resistant (MRSA) S. aureus was 1.9 per 100 outpatient-years. One week after the collection of the index blood culture, 56.1% of outpatients with MSSA bacteremia were receiving vancomycin, and 16.7% of outpatients with MSSA were receiving cefazolin. Among MSSA-bacteremic patients who did not die or get hospitalized 1 week after blood culture collection, use of cefazolin was associated with a 38% lower risk for hospitalization or death compared with vancomycin (adjusted HR=0.62, 95% CI=0.46-0.84). In conclusion, vancomycin is commonly used to treat MSSA bacteremia in outpatients receiving chronic dialysis, but there may be more risk of treatment failure than observed among those individuals who receive a beta-lactam antibiotic such as cefazolin. C1 [Chan, Kevin E.; Hymes, Jeffrey L.; Maddux, Franklin W.; Hakim, Raymond M.] Fresenius Med Care N Amer, Div Clin Res, Waltham, MA 02451 USA. [Warren, H. Shaw] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Chan, Kevin E.; Thadhani, Ravi I.; Steele, David J. R.] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. RP Chan, KE (reprint author), Fresenius Med Care N Amer, Div Clin Res, 920 Winter St, Waltham, MA 02451 USA. EM kevin.chan@fmc-na.com NR 31 TC 22 Z9 24 U1 0 U2 4 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 SEP PY 2012 VL 23 IS 9 BP 1551 EP 1559 DI 10.1681/ASN.2012010050 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 005UM UT WOS:000308775600016 PM 22904350 ER PT J AU Burstein, HJ AF Burstein, Harold J. TI Pathway-Based Oncology Care: Time for More Transparency SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Editorial Material C1 [Burstein, Harold J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Burstein, Harold J.] Dana Farber Canc Inst, Boston, MA USA. [Burstein, Harold J.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Burstein, HJ (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 1 TC 1 Z9 1 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 SEP PY 2012 VL 10 IS 9 BP 1043 EP 1044 PG 2 WC Oncology SC Oncology GA 002YO UT WOS:000308575200001 PM 22956802 ER PT J AU Mohler, JL Armstrong, AJ Bahnson, RR Boston, B Busby, JE D'Amico, AV Eastham, JA Enke, CA Farrington, T Higano, CS Horwitz, EM Kantoff, PW Kawachi, MH Kuettel, M Lee, RJ MacVicar, GR Malcolm, AW Miller, D Plimack, ER Pow-Sang, JM Roach, M Rohren, E Rosenfeld, S Srinivas, S Strope, SA Tward, J Twardowski, P Walsh, PC Ho, M Shead, DA AF Mohler, James L. Armstrong, Andrew J. Bahnson, Robert R. Boston, Barry Busby, J. Erik D'Amico, Anthony Victor Eastham, James A. Enke, Charles A. Farrington, Thomas Higano, Celestia S. Horwitz, Eric Mark Kantoff, Philip W. Kawachi, Mark H. Kuettel, Michael Lee, Richard J. MacVicar, Gary R. Malcolm, Arnold W. Miller, David Plimack, Elizabeth R. Pow-Sang, Julio M. Roach, Mack, III Rohren, Eric Rosenfeld, Stan Srinivas, Sandy Strope, Seth A. Tward, Jonathan Twardowski, Przemyslaw Walsh, Patrick C. Ho, Maria Shead, Dorothy A. TI Prostate Cancer, Version 3.2012 Featured Updates to the NCCN Guidelines SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID DOSE-RATE BRACHYTHERAPY; EXTERNAL-BEAM RADIOTHERAPY; RADIATION-THERAPY; ABIRATERONE ACETATE; FOLLOW-UP; ANDROGEN DEPRIVATION; RANDOMIZED PROSTATE; TRIAL; MORTALITY; RISK AB The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prostate Cancer provide multidisciplinary recommendations for the clinical management of patients with prostate cancer. These NCCN Guidelines Insights highlight notable recent updates. Abiraterone acetate is a first-in-class hormonal agent that represents a new standard of care for patients with metastatic castration-recurrent prostate cancer who have previously received docetaxel (category 1 recommendation). Abiraterone acetate also received category 2B recommendations in the prechemotherapy setting for asymptomatic patients or symptomatic patients who are not candidates for docetaxel. The NCCN Prostate Cancer Panel also added new indications for existing agents, including the option of sipuleucel-T as second-line therapy. In addition, brachytherapy in combination with external beam radiation therapy with or without androgen deprivation therapy is now an alternative for patients with high-risk localized tumors or locally advanced disease. (JNCCN 2012;10:1081-1187) C1 [Mohler, James L.; Kuettel, Michael] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Bahnson, Robert R.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Bahnson, Robert R.] Ohio State Univ, Solove Res Inst, Columbus, OH 43210 USA. [Boston, Barry] Univ Tennessee, Inst Canc, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Busby, J. Erik] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [D'Amico, Anthony Victor] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Eastham, James A.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Enke, Charles A.] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. [Higano, Celestia S.] Univ Washington, Seattle Canc Care Alliance, Seattle, WA 98195 USA. [Horwitz, Eric Mark; Plimack, Elizabeth R.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Kawachi, Mark H.; Twardowski, Przemyslaw] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Lee, Richard J.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [MacVicar, Gary R.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Malcolm, Arnold W.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Miller, David] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Pow-Sang, Julio M.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Roach, Mack, III] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Rohren, Eric] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Rosenfeld, Stan] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Srinivas, Sandy] Stanford Canc Inst, Stanford, CA USA. [Strope, Seth A.] Washington Univ, Sch Med, Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO 63130 USA. [Tward, Jonathan] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Walsh, Patrick C.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. RP Mohler, JL (reprint author), Roswell Pk Canc Inst, Buffalo, NY 14263 USA. OI Strope, Seth/0000-0002-5176-1550 NR 34 TC 135 Z9 144 U1 0 U2 10 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 SEP PY 2012 VL 10 IS 9 BP 1081 EP 1087 PG 7 WC Oncology SC Oncology GA 002YO UT WOS:000308575200006 PM 22956807 ER PT J AU Coccia, PF Altman, J Bhatia, S Borinstein, SC Flynn, J George, S Goldsby, R Hayashi, R Huang, MS Johnson, RH Beaupin, LK Link, MP Oeffinger, KC Orr, KM Pappo, AS Reed, D Spraker, HL Thomas, DA von Mehren, M Wechsler, DS Whelan, KF Zebrack, BJ AF Coccia, Peter F. Altman, Jessica Bhatia, Smita Borinstein, Scott C. Flynn, Joseph George, Suzanne Goldsby, Robert Hayashi, Robert Huang, Mary S. Johnson, Rebecca H. Beaupin, Lynda Kwon Link, Michael P. Oeffinger, Kevin C. Orr, Kathleen M. Pappo, Alberto S. Reed, Damon Spraker, Holly L. Thomas, Deborah A. von Mehren, Margaret Wechsler, Daniel S. Whelan, Kimberly F. Zebrack, Bradley J. TI Adolescent and Young Adult Oncology SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID CHILDHOOD-CANCER-SURVIVOR; LONG-TERM SURVIVORS; ACUTE LYMPHOBLASTIC-LEUKEMIA; COLLABORATIVE BRITISH COHORT; CHRONIC HEALTH CONDITIONS; NON-HODGKINS-LYMPHOMA; TESTICULAR-CANCER; BREAST-CANCER; FOLLOW-UP; FERTILITY PRESERVATION AB Cancer is the leading cause of death among the adolescent and young adult (AYA) population, excluding homicide, suicide, or unintentional injury. AYA patients should be managed by a multidisciplinary team of health care professionals who are well-versed in the specific developmental issues relevant to this patient population. The recommendations for age-appropriate care outlined in these NCCN Guidelines include psychosocial assessment, a discussion of infertility risks associated with treatment and options for fertility preservation, genetic and familial risk assessment for all patients after diagnosis, screening and monitoring of late effects in AYA cancer survivors after successful completion of therapy, and palliative care and end-of-life considerations for patients for whom curative therapy fails. (JNCCN 2012;10:1112-1150) C1 [Coccia, Peter F.] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. [Altman, Jessica] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Borinstein, Scott C.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Flynn, Joseph] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Goldsby, Robert] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Hayashi, Robert] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Hayashi, Robert] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Huang, Mary S.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Johnson, Rebecca H.] Seattle Canc Care Alliance, Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Beaupin, Lynda Kwon] Roswell Pk Canc Inst, Buffalo, NY USA. [Link, Michael P.] Stanford Inst Canc, Stanford, CA USA. [Oeffinger, Kevin C.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Orr, Kathleen M.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Pappo, Alberto S.] Univ Tennessee, Inst Canc, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Reed, Damon] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Spraker, Holly L.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Thomas, Deborah A.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [von Mehren, Margaret] Fox Chase Canc Ctr, Philadelphia, PA USA. [Wechsler, Daniel S.] Duke Canc Inst, Durham, NC USA. [Whelan, Kimberly F.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Zebrack, Bradley J.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. RP Coccia, PF (reprint author), Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. NR 182 TC 68 Z9 68 U1 3 U2 27 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 SEP PY 2012 VL 10 IS 9 BP 1112 EP 1150 PG 39 WC Oncology SC Oncology GA 002YO UT WOS:000308575200009 PM 22956810 ER PT J AU Bosworth, CR Levin, G Robinson-Cohen, C Hoofnagle, AN Ruzinski, J Young, B Schwartz, SM Himmelfarb, J Kestenbaum, B de Boer, IH AF Bosworth, Cortney R. Levin, Gregory Robinson-Cohen, Cassianne Hoofnagle, Andrew N. Ruzinski, John Young, Bessie Schwartz, Stephen M. Himmelfarb, Jonathan Kestenbaum, Bryan de Boer, Ian H. TI The serum 24,25-dihydroxyvitamin D concentration, a marker of vitamin D catabolism, is reduced in chronic kidney disease SO KIDNEY INTERNATIONAL LA English DT Article DE chronic kidney disease; mineral metabolism; vitamin D ID CHRONIC-RENAL-FAILURE; D METABOLISM; BIOLOGICAL ACTIVITY; MINERAL METABOLISM; EXPRESSION; RAT; 1,25-DIHYDROXYCHOLECALCIFEROL; 1,25-DIHYDROXYVITAMIN-D; 25-HYDROXYVITAMIN-D3; DYSREGULATION AB Chronic kidney disease is characterized, in part, as a state of decreased production of 1,25-dihydroxyvitamin D (1,25(OH)(2)D); however, this paradigm overlooks the role of vitamin D catabolism. We developed a mass spectrometric assay to quantify serum concentration of 24,25-dihydroxyvitamin D (24,25(OH)(2)D), the first metabolic product of 25-hydroxyvitamin D (25(OH)D) by CYP24A1, and determined its clinical correlates and associated outcomes among 278 participants with chronic kidney disease in the Seattle Kidney Study. For eGFRs of 60 or more, 45-59, 30-44, 15-29, and under 15 ml/min per 1.73m(2), the mean serum 24,25(OH)(2)D concentrations significantly trended lower from 3.6, 3.2, 2.6, 2.6, to 1.7 ng/ml, respectively. Non-Hispanic black race, diabetes, albuminuria, and lower serum bicarbonate were also independently and significantly associated with lower 24,25(OH)(2)D concentrations. The 24,25(OH)(2)D concentration was more strongly correlated with that of parathyroid hormone than was 25(OH)D or 1,25(OH)(2)D. A 24,25(OH)(2)D concentration below the median was associated with increased risk of mortality in unadjusted analysis, but this was attenuated with adjustment for potential confounding variables. Thus, chronic kidney disease is a state of stagnant vitamin D metabolism characterized by decreases in both 1,25(OH)(2)D production and vitamin D catabolism. C1 [Bosworth, Cortney R.; Ruzinski, John; Young, Bessie; Himmelfarb, Jonathan; Kestenbaum, Bryan; de Boer, Ian H.] Univ Washington, Div Nephrol, Dept Med, Seattle, WA 98104 USA. [Bosworth, Cortney R.; Ruzinski, John; Young, Bessie; Himmelfarb, Jonathan; Kestenbaum, Bryan; de Boer, Ian H.] Univ Washington, Kidney Res Inst, Seattle, WA 98104 USA. [Levin, Gregory] Univ Washington, Dept Biostat, Seattle, WA 98104 USA. [de Boer, Ian H.] Univ Washington, Dept Epidemiol, Div Nephrol, Seattle, WA 98104 USA. [Hoofnagle, Andrew N.] Univ Washington, Dept Lab Med, Seattle, WA 98104 USA. [Young, Bessie] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP de Boer, IH (reprint author), Univ Washington, Div Nephrol, Dept Med, Box 359606,325 9th Ave, Seattle, WA 98104 USA. EM deboer@u.washington.edu OI Robinson-Cohen, Cassianne/0000-0003-4783-7046; Schwartz, Stephen/0000-0001-7499-8502 FU Abbott Laboratories; Amgen; National Institutes of Health [R01HL096875, R01HL070938, R01DK087726]; Northwest Kidney Center Foundation; NIH grant [R01DK079745]; Veterans Affairs Puget Sound Health Care System FX IHdB has received research funding from Abbott Laboratories. BK has received research funding from Amgen. JH has consulting and advisory roles for Ardea Biosciences, Cytopheryx, and Thrasos Innovation.; This work was supported by the National Institutes of Health (R01HL096875, R01HL070938, and R01DK087726) and an unrestricted grant from the Northwest Kidney Center Foundation. BY was supported by NIH grant R01DK079745 and the Veterans Affairs Puget Sound Health Care System. We would like to thank study coordinators Noah Citron and Georgia Galvin, and study manager Ernie Ayers for their contributions to the study. NR 42 TC 50 Z9 50 U1 1 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 EI 1523-1755 J9 KIDNEY INT JI Kidney Int. PD SEP PY 2012 VL 82 IS 6 BP 693 EP 700 DI 10.1038/ki.2012.193 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 004FF UT WOS:000308665200012 PM 22648296 ER PT J AU Baernighausen, T Chaiyachati, K Chimbindi, N Haberer, J Newell, ML AF Baernighausen, Till Chaiyachati, Krisda Chimbindi, Natsayi Haberer, Jessica Newell, Marie-Louise TI Antiretroviral therapy requires life-long adherence reply SO LANCET INFECTIOUS DISEASES LA English DT Letter ID SUB-SAHARAN AFRICA; INTERVENTIONS C1 [Baernighausen, Till] Harvard Univ, Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA 02115 USA. [Baernighausen, Till; Chimbindi, Natsayi; Newell, Marie-Louise] Univ KwaZulu Natal, Africa Ctr Hlth & Populat Studies, Mtubatuba, South Africa. [Chaiyachati, Krisda] Yale Univ, Sch Med, New Haven, CT USA. [Haberer, Jessica] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Newell, Marie-Louise] UCL, Ctr Paediat Epidemiol & Biostat, Inst Child Hlth, London, England. RP Baernighausen, T (reprint author), Harvard Univ, Sch Publ Hlth, Dept Global Hlth & Populat, 665 Huntington Ave, Boston, MA 02115 USA. EM tbaernig@hsph.harvard.edu NR 5 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1473-3099 EI 1474-4457 J9 LANCET INFECT DIS JI Lancet Infect. Dis. PD SEP PY 2012 VL 12 IS 9 BP 662 EP 662 DI 10.1016/S1473-3099(12)70202-5 PG 1 WC Infectious Diseases SC Infectious Diseases GA 994FM UT WOS:000307916300017 ER PT J AU Pol, S Ghalib, RH Rustgi, VK Martorell, C Everson, GT Tatum, HA Hezode, C Lim, JK Bronowicki, JP Abrams, GA Brau, N Morris, DW Thuluvath, PJ Reindollar, RW Yin, PD Diva, U Hindes, R McPhee, F Hernandez, D Wind-Rotolo, M Hughes, EA Schnittman, S AF Pol, Stanislas Ghalib, Reem H. Rustgi, Vinod K. Martorell, Claudia Everson, Greg T. Tatum, Harvey A. Hezode, Christophe Lim, Joseph K. Bronowicki, Jean-Pierre Abrams, Gary A. Braeu, Norbert Morris, David W. Thuluvath, Paul J. Reindollar, Robert W. Yin, Philip D. Diva, Ulysses Hindes, Robert McPhee, Fiona Hernandez, Dennis Wind-Rotolo, Megan Hughes, Eric A. Schnittman, Steven TI Daclatasvir for previously untreated chronic hepatitis C genotype-1 infection: a randomised, parallel-group, double-blind, placebo-controlled, dose-finding, phase 2a trial SO LANCET INFECTIOUS DISEASES LA English DT Article ID SUSTAINED VIROLOGICAL RESPONSE; REPLICATION COMPLEX INHIBITOR; 1B-INFECTED NULL RESPONDERS; VIRUS-INFECTION; NS5A INHIBITOR; PEGINTERFERON ALPHA-2A; COMBINATION THERAPY; PROTEASE INHIBITOR; IN-VITRO; BMS-790052 AB Background Several direct-acting antivirals for chronic hepatitis C virus (HCV) infection are available, but they are limited by tolerability and dosing schedules. Once-daily daclatasvir, a potent NS5A replication complex inhibitor, was generally well tolerated in phase 1 studies. We assessed daclatasvir in combination with pegylated interferon (peginterferon) and ribavirin for chronic HCV. Methods In this double-blind, parallel-group, dose-finding, phase 2a study, treatment-naive patients with HCV genotype-1 infection (without cirrhosis) from 14 centres in the USA and France were randomly assigned (1:1:1:1) to receive peginterferon alfa-2a (180 mu g per week) and ribavirin (1000-1200 mg daily) plus placebo or 3 mg, 10 mg, or 60 mg of daclatasvir taken once daily, for 48 weeks. The primary efficacy endpoint was undetectable HCV RNA at 4 weeks and 12 weeks after start of treatment (extended rapid virological response, eRVR). Analysis was of all participants who received one dose of study drug. We used descriptive analyses to compare results. This study is registered with ClinicalTrials.gov, number NCT00874770. Findings 48 patients were randomly assigned (12 per group); all received at least one dose of study drug. 15 patients discontinued treatment before week 48. Five of 12 patients (42%, 80% CI 22-64%) who received 3 mg daclatasvir achieved eRVR, compared with ten of 12 (83%, 61-96%) who received 10 mg daclatasvir, nine of 12 (75%, 53-90%) who received 60 mg daclatasvir, and one of 12 (8%, 1-29%) who received placebo. Adverse events and discontinuations as a result of adverse events occurred with similar frequency across groups. Interpretation Daclatasvir seems to be a potent NS5A replication complex inhibitor that increases the antiviral potency of peginterferon and ribavirin. Our findings support the further development of regimens containing 60 mg daclatasvir for the treatment of chronic genotype-1 HCV infection. C1 [Pol, Stanislas] Hop Cochin, F-75679 Paris 14, France. [Ghalib, Reem H.] Texas Clin Res Inst, Arlington, TX USA. [Rustgi, Vinod K.] Metropolitan Res, Fairfax, VA USA. [Martorell, Claudia] Res Inst, Springfield, MA USA. [Everson, Greg T.] Univ Colorado Denver, Aurora, CO USA. [Tatum, Harvey A.] Opt Hlth Res, Tulsa, OK USA. [Hezode, Christophe] Hop Henri Mondor, F-94010 Creteil, France. [Lim, Joseph K.] Yale Univ, Sch Med, New Haven, CT USA. [Bronowicki, Jean-Pierre] Univ Lorraine, INSERM 954, Ctr Hosp Univ Nancy, Vandoeuvre Les Nancy, France. [Abrams, Gary A.] Alabama Liver & Digest Specialists, Montgomery, AL USA. [Braeu, Norbert] James J Peters VA Med Ctr, Bronx, NY USA. [Morris, David W.] Healthcare Res Consultants, Tulsa, OK USA. [Thuluvath, Paul J.] St Johns Mercy Med Ctr, Baltimore, MD USA. [Reindollar, Robert W.] Carolinas Ctr Liver Dis, Statesville, NC USA. [Yin, Philip D.; Diva, Ulysses; McPhee, Fiona; Hernandez, Dennis; Schnittman, Steven] Bristol Myers Squibb Co, Res & Dev, Wallingford, CT 06492 USA. [Hindes, Robert] Gilead Sci Inc, Foster City, CA 94404 USA. [Wind-Rotolo, Megan; Hughes, Eric A.] Bristol Myers Squibb Co, Res & Dev, Princeton, NJ USA. RP Pol, S (reprint author), Hop Cochin, 27 Rue Faubourg St Jacques, F-75679 Paris 14, France. EM stanislas.pol@cch.aphp.fr FU Bristol-Myers Squibb; Gilead; Merck/Schering-Plough; Roche; Abbott; Boehringer Ingelheim; GlaxoSmithKline; Novartis; Tibotec; Achillion; Debio; Genentech; Inhibitex; Pharmasset; Vertex; Zymogenetics (Bristol-Myers Squibb); Globe Immune; Roche/Genentech; Merck; Janssen FX SP has received research grants from Bristol-Myers Squibb, Gilead, Merck/Schering-Plough, and Roche; and consulting or lecture fees from Abbott, Bristol-Myers Squibb, Boehringer Ingelheim, Gilead, GlaxoSmithKline, Merck/Schering-Plough, Novartis, Roche, and Tibotec. RHG has received research grants from Abbott, Achillion, Boehringer Ingelheim, Bristol-Myers Squibb, Debio, Genentech, Gilead, Inhibitex, Pharmasset, Tibotec, Vertex, and Zymogenetics (Bristol-Myers Squibb). VKR received research grants from Bristol-Myers Squibb for this study. CM has received research grants from Abbott, Bristol-Myers Squibb, Gilead, and Novartis; and lecture fees from Abbott, Bristol-Myers Squibb, and Gilead. GTE received a research grant from Bristol-Myers Squibb (administered by the University of Colorado Denver) for this study; and has served on advisory boards for Bristol-Myers Squibb. JKL has received research grants from Bristol-Myers Squibb, Gilead, Globe Immune, Roche/Genentech, Tibotec, and Vertex; and consulting fees from Bristol-Myers Squibb, Gilead, Merck, and Vertex. J-PB has received consulting fees from Bristol-Myers Squibb, Merck, Boehringer Ingelheim, Novartis, Roche, Gilead, and Janssen. PIT received research grants from Bristol-Myers Squibb for this study. RWR has received research grants from Abbott, Bristol-Myers Squibb, Merck, Novartis, Pharmasset, and Tibotec; and lecture fees from Merck and Vertex. PDY, UD, FM, DH, MW-R, EAH, and SS are employees of Bristol-Myers Squibb. HAT, CH, GAA, NB, DWM, and RH declare that they have no conflicts of interest. NR 30 TC 104 Z9 107 U1 0 U2 11 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1473-3099 EI 1474-4457 J9 LANCET INFECT DIS JI Lancet Infect. Dis. PD SEP PY 2012 VL 12 IS 9 BP 671 EP 677 DI 10.1016/S1473-3099(12)70138-X PG 7 WC Infectious Diseases SC Infectious Diseases GA 994FM UT WOS:000307916300022 PM 22714001 ER PT J AU Kirchhausen, T AF Kirchhausen, Tom TI Bending membranes SO NATURE CELL BIOLOGY LA English DT Editorial Material ID CURVATURE; MECHANISMS; PROTEINS; COMPONENTS AB It is widely assumed that peripheral membrane proteins induce intracellular membrane curvature by the asymmetric insertion of a protein segment into the lipid bilayer, or by imposing shape by adhesion of a curved protein domain to the membrane surface. Two papers now provide convincing evidence challenging these views. The first shows that specific assembly of a clathrin protein scaffold, coupled to the membrane, seems to be the most prevalent mechanism for bending a lipid bilayer in a cell. The second reports that membrane crowding, driven by protein-protein interactions, can also drive membrane bending, even in the absence of any protein insertion into the bilayer. C1 [Kirchhausen, Tom] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Kirchhausen, Tom] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. RP Kirchhausen, T (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. EM kirchhausen@crystal.harvard.edu FU NIGMS NIH HHS [R01 GM075252] NR 15 TC 33 Z9 33 U1 2 U2 40 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD SEP PY 2012 VL 14 IS 9 BP 906 EP 908 DI 10.1038/ncb2570 PG 4 WC Cell Biology SC Cell Biology GA 004GJ UT WOS:000308668600006 PM 22945258 ER PT J AU Morris, AP Voight, BF Teslovich, TM Ferreira, T Segre, AV Steinthorsdottir, V Strawbridge, RJ Khan, H Grallert, H Mahajan, A Prokopenko, I Kang, HM Dina, C Esko, T Fraser, RM Kanoni, S Kumar, A Lagou, V Langenberg, C Luan, JA Lindgren, CM Muller-Nurasyid, M Pechlivanis, S Rayner, NW Scott, LJ Wiltshire, S Yengo, L Kinnunen, L Rossin, EJ Raychaudhuri, S Johnson, AD Dimas, AS Loos, RJF Vedantam, S Chen, H Florez, JC Fox, C Liu, CT Rybin, D Couper, DJ Kao, WHL Li, M Cornelis, MC Kraft, P Sun, Q van Dam, RM Stringham, HM Chines, PS Fischer, K Fontanillas, P Holmen, OL Hunt, SE Jackson, AU Kong, A Lawrence, R Meyer, J Perry, JRB Platou, CGP Potter, S Rehnberg, E Robertson, N Sivapalaratnam, S Stancakova, A Stirrups, K Thorleifsson, G Tikkanen, E Wood, AR Almgren, P Atalay, M Benediktsson, R Bonnycastle, LL Burtt, N Carey, J Charpentier, G Crenshaw, AT Doney, ASF Dorkhan, M Edkins, S Emilsson, V Eury, E Forsen, T Gertow, K Gigante, B Grant, GB Groves, CJ Guiducci, C Herder, C Hreidarsson, AB Hui, JN James, A Jonsson, A Rathmann, W Klopp, N Kravic, J Krjutskov, K Langford, C Leander, K Lindholm, E Lobbens, S Mannisto, S Mirza, G Muhleisen, TW Musk, B Parkin, M Rallidis, L Saramies, J Sennblad, B Shah, S Sigurdsson, G Silveira, A Steinbach, G Thorand, B Trakalo, J Veglia, F Wennauer, R Winckler, W Zabaneh, D Campbell, H van Duijn, C Uitterlinden, AG Hofman, A Sijbrands, E Abecasis, GR Owen, KR Zeggini, E Trip, MD Forouhi, NG Syvanen, AC Eriksson, JG Peltonen, L Nothen, MM Balkau, B Palmer, CNA Lyssenko, V Tuomi, T Isomaa, B Hunter, DJ Qi, L Shuldiner, AR Roden, M Barroso, I Wilsgaard, T Beilby, J Hovingh, K Price, JF Wilson, JF Rauramaa, R Lakka, TA Lind, L Dedoussis, G Njolstad, I Pedersen, NL Khaw, KT Wareham, NJ Keinanen-Kiukaanniemi, SM Saaristo, TE Korpi-Hyovalti, E Saltevo, J Laakso, M Kuusisto, J Metspalu, A Collins, FS Mohlke, KL Bergman, RN Tuomilehto, J Boehm, BO Gieger, C Hveem, K Cauchi, S Froguel, P Baldassarre, D Tremoli, E Humphries, SE Saleheen, D Danesh, J Ingelsson, E Ripatti, S Salomaa, V Erbel, R Jockel, KH Moebus, S Peters, A Illig, T de Faire, U Hamsten, A Morris, AD Donnelly, PJ Frayling, TM Hattersley, AT Boerwinkle, E Melander, O Kathiresan, S Nilsson, PM Deloukas, P Thorsteinsdottir, U Groop, LC Stefansson, K Hu, F Pankow, JS Dupuis, J Meigs, JB Altshuler, D Boehnke, M McCarthy, MI AF Morris, Andrew P. Voight, Benjamin F. Teslovich, Tanya M. Ferreira, Teresa Segre, Ayellet V. Steinthorsdottir, Valgerdur Strawbridge, Rona J. Khan, Hassan Grallert, Harald Mahajan, Anubha Prokopenko, Inga Kang, Hyun Min Dina, Christian Esko, Tonu Fraser, Ross M. Kanoni, Stavroula Kumar, Ashish Lagou, Vasiliki Langenberg, Claudia Luan, Jian'an Lindgren, Cecilia M. Mueller-Nurasyid, Martina Pechlivanis, Sonali Rayner, N. William Scott, Laura J. Wiltshire, Steven Yengo, Loic Kinnunen, Leena Rossin, Elizabeth J. Raychaudhuri, Soumya Johnson, Andrew D. Dimas, Antigone S. Loos, Ruth J. F. Vedantam, Sailaja Chen, Han Florez, Jose C. Fox, Caroline Liu, Ching-Ti Rybin, Denis Couper, David J. Kao, Wen Hong L. Li, Man Cornelis, Marilyn C. Kraft, Peter Sun, Qi van Dam, Rob M. Stringham, Heather M. Chines, Peter S. Fischer, Krista Fontanillas, Pierre Holmen, Oddgeir L. Hunt, Sarah E. Jackson, Anne U. Kong, Augustine Lawrence, Robert Meyer, Julia Perry, John R. B. Platou, Carl G. P. Potter, Simon Rehnberg, Emil Robertson, Neil Sivapalaratnam, Suthesh Stancakova, Alena Stirrups, Kathleen Thorleifsson, Gudmar Tikkanen, Emmi Wood, Andrew R. Almgren, Peter Atalay, Mustafa Benediktsson, Rafn Bonnycastle, Lori L. Burtt, Noel Carey, Jason Charpentier, Guillaume Crenshaw, Andrew T. Doney, Alex S. F. Dorkhan, Mozhgan Edkins, Sarah Emilsson, Valur Eury, Elodie Forsen, Tom Gertow, Karl Gigante, Bruna Grant, George B. Groves, Christopher J. Guiducci, Candace Herder, Christian Hreidarsson, Astradur B. Hui, Jennie James, Alan Jonsson, Anna Rathmann, Wolfgang Klopp, Norman Kravic, Jasmina Krjutskov, Kaarel Langford, Cordelia Leander, Karin Lindholm, Eero Lobbens, Stephane Mannisto, Satu Mirza, Ghazala Muehleisen, Thomas W. Musk, Bill Parkin, Melissa Rallidis, Loukianos Saramies, Jouko Sennblad, Bengt Shah, Sonia Sigurdsson, Gunnar Silveira, Angela Steinbach, Gerald Thorand, Barbara Trakalo, Joseph Veglia, Fabrizio Wennauer, Roman Winckler, Wendy Zabaneh, Delilah Campbell, Harry van Duijn, Cornelia Uitterlinden, Andre G. Hofman, Albert Sijbrands, Eric Abecasis, Goncalo R. Owen, Katharine R. Zeggini, Eleftheria Trip, Mieke D. Forouhi, Nita G. Syvanen, Ann-Christine Eriksson, Johan G. Peltonen, Leena Noethen, Markus M. Balkau, Beverley Palmer, Colin N. A. Lyssenko, Valeriya Tuomi, Tiinamaija Isomaa, Bo Hunter, David J. Qi, Lu Shuldiner, Alan R. Roden, Michael Barroso, Ines Wilsgaard, Tom Beilby, John Hovingh, Kees Price, Jackie F. Wilson, James F. Rauramaa, Rainer Lakka, Timo A. Lind, Lars Dedoussis, George Njolstad, Inger Pedersen, Nancy L. Khaw, Kay-Tee Wareham, Nicholas J. Keinanen-Kiukaanniemi, Sirkka M. Saaristo, Timo E. Korpi-Hyovalti, Eeva Saltevo, Juha Laakso, Markku Kuusisto, Johanna Metspalu, Andres Collins, Francis S. Mohlke, Karen L. Bergman, Richard N. Tuomilehto, Jaakko Boehm, Bernhard O. Gieger, Christian Hveem, Kristian Cauchi, Stephane Froguel, Philippe Baldassarre, Damiano Tremoli, Elena Humphries, Steve E. Saleheen, Danish Danesh, John Ingelsson, Erik Ripatti, Samuli Salomaa, Veikko Erbel, Raimund Joeckel, Karl-Heinz Moebus, Susanne Peters, Annette Illig, Thomas de Faire, Ulf Hamsten, Anders Morris, Andrew D. Donnelly, Peter J. Frayling, Timothy M. Hattersley, Andrew T. Boerwinkle, Eric Melander, Olle Kathiresan, Sekar Nilsson, Peter M. Deloukas, Panos Thorsteinsdottir, Unnur Groop, Leif C. Stefansson, Kari Hu, Frank Pankow, James S. Dupuis, Josee Meigs, James B. Altshuler, David Boehnke, Michael McCarthy, Mark I. CA Wellcome Trust Case Control Meta-Anal Glucose Insulin-Related Genetic Invest ANthropometric Asian Genetic Epidemiology S Asian Type 2 Diabet SAT2D DIAbet Genetics Replication TI Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; INSULIN-RESISTANCE; COMMON VARIANTS; METAANALYSIS; RISK; EXPRESSION; SNPS; MAP; INDIVIDUALS AB To extend understanding of the genetic architecture and molecular basis of type 2 diabetes (T2D), we conducted a meta-analysis of genetic variants on the Metabochip, including 34,840 cases and 114,981 controls, overwhelmingly of European descent. We identified ten previously unreported T2D susceptibility loci, including two showing sex-differentiated association. Genomewide analyses of these data are consistent with a long tail of additional common variant loci explaining much of the variation in susceptibility to T2D. Exploration of the enlarged set of susceptibility loci implicates several processes, including CREBBP-related transcription, adipocytokine signaling and cell cycle regulation, in diabetes pathogenesis. C1 [Morris, Andrew P.; Ferreira, Teresa; Mahajan, Anubha; Prokopenko, Inga; Kumar, Ashish; Lagou, Vasiliki; Lindgren, Cecilia M.; Rayner, N. William; Wiltshire, Steven; Dimas, Antigone S.; Perry, John R. B.; Robertson, Neil; Mirza, Ghazala; Trakalo, Joseph; Donnelly, Peter J.; McCarthy, Mark I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Voight, Benjamin F.; Segre, Ayellet V.; Rossin, Elizabeth J.; Raychaudhuri, Soumya; Fontanillas, Pierre; Burtt, Noel; Carey, Jason; Crenshaw, Andrew T.; Grant, George B.; Guiducci, Candace; Parkin, Melissa; Winckler, Wendy; Kathiresan, Sekar; Altshuler, David] Broad Inst Harvard & Massachusetts Inst Technol M, Cambridge, MA USA. [Voight, Benjamin F.] Univ Penn, Perelman Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA. [Teslovich, Tanya M.; Kang, Hyun Min; Scott, Laura J.; Stringham, Heather M.; Jackson, Anne U.; Abecasis, Goncalo R.; Boehnke, Michael] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Segre, Ayellet V.; Rossin, Elizabeth J.; Florez, Jose C.; Kathiresan, Sekar; Altshuler, David] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Segre, Ayellet V.; Florez, Jose C.; Meigs, James B.; Altshuler, David] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Steinthorsdottir, Valgerdur; Kong, Augustine; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Stefansson, Kari] deCODE Genet, Reykjavik, Iceland. [Strawbridge, Rona J.; Gertow, Karl; Sennblad, Bengt; Silveira, Angela; Hamsten, Anders] Karolinska Inst, Dept Med Solna, Atherosclerosis Res Unit, Stockholm, Sweden. [Strawbridge, Rona J.; Gertow, Karl; Sennblad, Bengt; Silveira, Angela; Hamsten, Anders] Karolinska Univ Hosp Solna, Ctr Mol Med, Stockholm, Sweden. [Khan, Hassan; Khaw, Kay-Tee; Saleheen, Danish; Danesh, John] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England. [Grallert, Harald; Klopp, Norman; Illig, Thomas] Helmholtz Zentrum Muenchen, Res Unit Mol Epidemiol, Neuherberg, Germany. [Prokopenko, Inga; Rayner, N. William; Robertson, Neil; Groves, Christopher J.; Owen, Katharine R.; McCarthy, Mark I.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. [Dina, Christian] INSERM, UMR 1087, Nantes, France. [Dina, Christian] CNRS, UMR 6291, Nantes, France. [Dina, Christian] Univ Nantes, Dept Biol Med & Hlth, Nantes, France. [Esko, Tonu; Fischer, Krista; Krjutskov, Kaarel; Metspalu, Andres] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia. [Esko, Tonu; Metspalu, Andres] Univ Tartu, Inst Mol & Cell Biol, EE-50090 Tartu, Estonia. [Fraser, Ross M.; Campbell, Harry; Price, Jackie F.; Wilson, James F.] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland. [Kanoni, Stavroula; Hunt, Sarah E.; Potter, Simon; Stirrups, Kathleen; Edkins, Sarah; Langford, Cordelia; Zeggini, Eleftheria; Barroso, Ines; Ripatti, Samuli; Deloukas, Panos] Wellcome Trust Sanger Inst, Cambridge, England. [Langenberg, Claudia; Luan, Jian'an; Loos, Ruth J. F.; Forouhi, Nita G.; Wareham, Nicholas J.] Addenbrookes Hosp, Inst Metab Sci, Med Res Council MRC Epidemiol Unit, Cambridge, England. [Mueller-Nurasyid, Martina] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany. [Mueller-Nurasyid, Martina; Meyer, Julia; Gieger, Christian] Helmholtz Zentrum Muenchen, Inst Genet Epidemiol, Neuherberg, Germany. [Mueller-Nurasyid, Martina] Univ Munich, Univ Hosp Grosshadern, Dept Med 1, Munich, Germany. [Pechlivanis, Sonali; Joeckel, Karl-Heinz; Moebus, Susanne] Univ Duisburg Essen, Univ Hosp Essen, Inst Med Informat Biometry & Epidemiol, Essen, Germany. [Yengo, Loic; Eury, Elodie; Lobbens, Stephane; Cauchi, Stephane; Froguel, Philippe] Inst Pasteur, CNRS, UMR 8199, Inst Biol, F-59019 Lille, France. [Yengo, Loic; Eury, Elodie; Lobbens, Stephane; Cauchi, Stephane; Froguel, Philippe] Univ Lille 2, Inst Pasteur, Lille, France. [Yengo, Loic] Univ Lille 1, Model Data Anal & Learning MODAL Team, Inst Natl Rech Informat & Automat INRIA Lille Nor, Math Lab,CNRS,UMR 8524, Lille, France. [Kinnunen, Leena; Tuomilehto, Jaakko] Natl Inst Hlth & Welf, Diabet Prevent Unit, Helsinki, Finland. [Rossin, Elizabeth J.] Harvard Univ, Hlth Sci & Technol MD Program, Boston, MA 02115 USA. [Rossin, Elizabeth J.] MIT, Boston, MA USA. [Rossin, Elizabeth J.] Harvard Univ, Harvard Biol & Biomed Sci Program, Boston, MA 02115 USA. [Raychaudhuri, Soumya] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. [Raychaudhuri, Soumya] Partners Ctr Personalized Genom Med, Boston, MA USA. [Johnson, Andrew D.; Fox, Caroline; Dupuis, Josee] NHLBI, Framingham Heart Study, Framingham, MA USA. [Dimas, Antigone S.] Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland. [Dimas, Antigone S.] Biomed Sci Res Ctr Al Fleming, Vari, Greece. [Loos, Ruth J. F.] Mt Sinai Sch Med, Charles R Bronfman Inst Personalized Med, New York, NY USA. [Loos, Ruth J. F.] Mt Sinai Sch Med, Child Hlth & Dev Inst, New York, NY USA. [Loos, Ruth J. F.] Mt Sinai Sch Med, Dept Prevent Med, New York, NY USA. [Vedantam, Sailaja; Florez, Jose C.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Vedantam, Sailaja] Childrens Hosp, Div Genet & Endocrinol, Boston, MA 02115 USA. [Chen, Han; Liu, Ching-Ti; Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Florez, Jose C.] Massachusetts Gen Hosp, Diabet Unit, Diabet Res Ctr, Boston, MA 02114 USA. [Fox, Caroline] Brigham & Womens Hosp, Div Endocrinol & Metab, Boston, MA 02115 USA. [Rybin, Denis] Boston Univ, Data Coordinating Ctr, Boston, MA 02215 USA. [Couper, David J.] Univ N Carolina, Dept Biostat, Collaborat Studies Coordinating Ctr, Chapel Hill, NC USA. [Kao, Wen Hong L.; Li, Man] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Cornelis, Marilyn C.; Kraft, Peter; Sun, Qi; van Dam, Rob M.; Hunter, David J.; Qi, Lu; Hu, Frank] Harvard Univ, Sch Publ Hlth, Dept Nutr & Epidemiol, Boston, MA 02115 USA. 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[Rehnberg, Emil; Pedersen, Nancy L.; Ingelsson, Erik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Sivapalaratnam, Suthesh; Trip, Mieke D.; Hovingh, Kees] Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands. [Stancakova, Alena; Laakso, Markku; Kuusisto, Johanna] Univ Eastern Finland, Dept Med, Kuopio, Finland. [Stancakova, Alena; Laakso, Markku; Kuusisto, Johanna] Kuopio Univ Hosp, SF-70210 Kuopio, Finland. [Tikkanen, Emmi; Ripatti, Samuli] Inst Mol Med Finland FIMM, Helsinki, Finland. [Tikkanen, Emmi; Mannisto, Satu; Eriksson, Johan G.; Ripatti, Samuli; Salomaa, Veikko] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. [Almgren, Peter; Dorkhan, Mozhgan; Jonsson, Anna; Kravic, Jasmina; Lindholm, Eero; Lyssenko, Valeriya; Melander, Olle; Nilsson, Peter M.; Groop, Leif C.] Lund Univ, Scania Univ Hosp, Ctr Diabet, Dept Clin Sci Malmo, Malmo, Sweden. 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[Gigante, Bruna; Leander, Karin; de Faire, Ulf] Karolinska Inst, Inst Environm Med, Div Cardiovasc Epidemiol, S-10401 Stockholm, Sweden. [Herder, Christian; Roden, Michael] Univ Dusseldorf, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Clin Diabetol, D-40225 Dusseldorf, Germany. [Hui, Jennie; James, Alan; Musk, Bill; Beilby, John] Sir Charles Gairdner Hosp, Busselton Populat Med Res Inst, Nedlands, WA 6009, Australia. [Hui, Jennie; Beilby, John] Queen Elizabeth II Med Ctr, PathW Lab Med Western Australia, Nedlands, WA, Australia. [Hui, Jennie; Beilby, John] Univ Western Australia, Sch Pathol & Lab Med, Nedlands, WA 6009, Australia. [Hui, Jennie; Musk, Bill] Univ Western Australia, Sch Populat Hlth, Nedlands, WA 6009, Australia. [James, Alan] Queen Elizabeth II Med Ctr, W Australian Sleep Disorders Res Inst, Dept Pulm Physiol & Sleep Med, Nedlands, WA, Australia. [James, Alan; Musk, Bill] Univ Western Australia, Sch Med & Pharmacol, Nedlands, WA 6009, Australia. [Rathmann, Wolfgang] Univ Dusseldorf, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Biometr & Epidemiol, D-40225 Dusseldorf, Germany. [Muehleisen, Thomas W.; Noethen, Markus M.] Univ Bonn, Inst Human Genet, Bonn, Germany. [Muehleisen, Thomas W.; Noethen, Markus M.] Univ Bonn, Life & Brain Ctr, Dept Genom, Bonn, Germany. [Rallidis, Loukianos] Univ Gen Hosp Attikon, Dept Cardiol, Athens, Greece. [Saramies, Jouko] S Karelia Cent Hosp, Lappeenranta, Finland. [Shah, Sonia; Zabaneh, Delilah] UCL, Genet Inst, Dept Genet Evolut & Environm, London, England. [Steinbach, Gerald; Wennauer, Roman] Univ Ulm, Dept Clin Chem, Ulm, Germany. [Steinbach, Gerald; Wennauer, Roman] Univ Ulm, Cent Lab, Ulm, Germany. [Thorand, Barbara; Peters, Annette] Helmholtz Zentrum Muenchen, Inst Epidemiol 2, Neuherberg, Germany. [Veglia, Fabrizio; Baldassarre, Damiano; Tremoli, Elena] IRCCS, Ctr Cardiol Monzino, Milan, Italy. [Campbell, Harry; Wilson, James F.] Univ Edinburgh, Western Gen Hosp, MRC Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland. [van Duijn, Cornelia; Uitterlinden, Andre G.; Hofman, Albert] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands. [van Duijn, Cornelia; Uitterlinden, Andre G.] Netherlands Consortium Hlth Ageing, Netherland Genom Initiat, Rotterdam, Netherlands. [van Duijn, Cornelia; Uitterlinden, Andre G.] Ctr Med Syst Biol, Rotterdam, Netherlands. [Uitterlinden, Andre G.; Sijbrands, Eric] Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands. [Owen, Katharine R.; McCarthy, Mark I.] Churchill Hosp, Oxford Natl Inst Hlth Res, Biomed Res Ctr, Oxford OX3 7LJ, England. [Syvanen, Ann-Christine] Uppsala Univ, Dept Med Sci, Uppsala, Sweden. [Eriksson, Johan G.] Univ Helsinki, Gen Hosp, Unit Gen Practice, Helsinki, Finland. [Eriksson, Johan G.; Tuomi, Tiinamaija; Isomaa, Bo] Folkhalsan Res Ctr, Helsinki, Finland. [Balkau, Beverley] INSERM CESP U1018, Villejuif, France. [Balkau, Beverley] Univ Paris 11, UMRS 1018, Villejuif, France. [Tuomi, Tiinamaija] Univ Helsinki, Helsinki Univ Hosp, Dept Med, Helsinki, Finland. [Isomaa, Bo] Dept Social Serv & Hlth Care, Pietarsaari, Finland. [Shuldiner, Alan R.] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA. [Shuldiner, Alan R.] Baltimore Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Baltimore, MD USA. [Shuldiner, Alan R.] Univ Maryland, Sch Med, Program Personalized & Genom Med, Baltimore, MD 21201 USA. [Roden, Michael] Univ Dusseldorf, Dept Med Metab Dis, D-40225 Dusseldorf, Germany. [Barroso, Ines] Univ Cambridge, Addenbrookes Hosp, Metab Res Labs, Inst Metab Sci, Cambridge CB2 2QQ, England. [Barroso, Ines] Addenbrookes Hosp, Inst Metab Sci, Cambridge Biomed Res Ctr, NIHR, Cambridge, England. [Wilsgaard, Tom; Njolstad, Inger] Univ Tromso, Fac Hlth Sci, Dept Community Med, Tromso, Norway. [Rauramaa, Rainer; Lakka, Timo A.] Kuopio Res Inst Exercise Med, Kuopio, Finland. [Rauramaa, Rainer] Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, SF-70210 Kuopio, Finland. [Lind, Lars] Uppsala Univ, Akad Sjukhuset, Dept Med Sci, Uppsala, Sweden. [Dedoussis, George] Harokopio Univ, Dept Dietet Nutr, Athens, Greece. [Keinanen-Kiukaanniemi, Sirkka M.] Univ Oulu, Inst Hlth Sci, Fac Med, Oulu, Finland. [Keinanen-Kiukaanniemi, Sirkka M.] Oulu Univ Hosp, Unit Gen Practice, Oulu, Finland. [Saaristo, Timo E.] Finnish Diabet Assoc, Tampere, Finland. [Saaristo, Timo E.] Pirkanmaa Hosp Dist, Tampere, Finland. [Korpi-Hyovalti, Eeva; Tuomilehto, Jaakko] S Ostrobothnia Cent Hosp, Dept Internal Med, Seinajoki, Finland. [Saltevo, Juha] Cent Finland Cent Hosp, Dept Med, Jyvaskyla, Finland. [Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Bergman, Richard N.] Cedars Sinai Med Ctr, Diabet & Obes Res Inst, Los Angeles, CA 90048 USA. [Tuomilehto, Jaakko] Hosp Univ La Paz, Red RECAVA Grp RD06 0014 0015, Madrid, Spain. [Tuomilehto, Jaakko] Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria. [Boehm, Bernhard O.] Univ Med Ctr Ulm, Dept Internal Med, Div Endocrinol & Diabet, Ulm, Germany. [Froguel, Philippe] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, London, England. [Baldassarre, Damiano; Tremoli, Elena] Univ Milan, Dept Pharmacol Sci, Milan, Italy. [Humphries, Steve E.] UCL, Inst Cardiovasc Sci, London, England. [Saleheen, Danish] Ctr Noncommunicable Dis Pakistan, Karachi, Pakistan. [Erbel, Raimund] Univ Duisburg Essen, Univ Hosp Essen, W German Heart Ctr, Clin Cardiol, Essen, Germany. [Illig, Thomas] Hannover Med Sch, Hannover Unified Biobank, D-3000 Hannover, Germany. [Donnelly, Peter J.] Univ Oxford, Dept Stat, Oxford OX1 3TG, England. [Hattersley, Andrew T.] Univ Exeter, Peninsula Med Sch, Inst Biomed & Clin Sci, Exeter, Devon, England. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX USA. [Boerwinkle, Eric] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Pankow, James S.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Altshuler, David] Harvard Univ, Sch Med, Dept Mol Biol, Boston, MA USA. RP Morris, AP (reprint author), Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. EM amorris@well.ox.ac.uk; boehnke@umich.edu; mark.mccarthy@drl.ox.ac.uk RI Boehm, Bernhard/F-8750-2015; Krjutskov, Kaarel/H-8401-2015; Ripatti, Samuli/H-9446-2014; Wilson, James F/A-5704-2009; Prokopenko, Inga/H-3241-2014; Thorand, Barbara/B-5349-2014; Peters, Annette/A-6117-2011; Veglia, Fabrizio/K-1958-2016; kinnunen, leena/B-7059-2012; Study, GoDARTS/K-9448-2016; Leander, Karin/C-7261-2017; Yengo, Loic/D-2692-2017; Baldassarre, Damiano/J-3295-2016; Gigante, Bruna/I-9252-2012; Palmer, Colin/C-7053-2008; Dina, Christian/D-3535-2015; Fraser, Ross/J-9519-2012; Deloukas, Panos/B-2922-2013; Grallert, Harald/B-3424-2013; Khan, Hassan/D-6267-2013; Abecasis, Goncalo/B-7840-2010; Johnson, Andrew/G-6520-2013; Altshuler, David/A-4476-2009; Lagou, Vasiliki/N-8451-2013; van Dam, Rob/F-9674-2010; Strawbridge, Rona/H-5422-2012; OI Esko, Tonu/0000-0003-1982-6569; Zeggini, Eleftheria/0000-0003-4238-659X; Mannisto, Satu/0000-0002-8668-3046; Lakka, Timo/0000-0002-9199-2871; Dupuis, Josee/0000-0003-2871-3603; Humphries, Stephen E/0000-0002-8221-6547; Gieger, Christian/0000-0001-6986-9554; Rybin, Denis/0000-0002-3657-4829; Kumar, Ashish/0000-0002-7075-5930; Sijbrands, Eric/0000-0001-8857-7389; TREMOLI, ELENA/0000-0002-0929-6106; Hunt, Sarah/0000-0002-8350-1235; Abecasis, Goncalo/0000-0003-1509-1825; Krjutskov, Kaarel/0000-0003-1297-1464; Ripatti, Samuli/0000-0002-0504-1202; Wilson, James F/0000-0001-5751-9178; Prokopenko, Inga/0000-0003-1624-7457; Thorand, Barbara/0000-0002-8416-6440; Veglia, Fabrizio/0000-0002-9378-8874; kinnunen, leena/0000-0001-8739-4812; Leander, Karin/0000-0002-1404-9222; Yengo, Loic/0000-0002-4272-9305; Baldassarre, Damiano/0000-0002-2766-8882; Palmer, Colin/0000-0002-6415-6560; Dina, Christian/0000-0002-7722-7348; Fraser, Ross/0000-0003-0488-2592; Deloukas, Panos/0000-0001-9251-070X; Altshuler, David/0000-0002-7250-4107; van Dam, Rob/0000-0002-7354-8734; Strawbridge, Rona/0000-0001-8506-3585; Forouhi, Nita/0000-0002-5041-248X; Chen, Han/0000-0002-9510-4923; Nothen, Markus/0000-0002-8770-2464; Tuomi, Tiinamaija/0000-0002-8306-6202; Eriksson, Johan/0000-0002-2516-2060; Pankow, James/0000-0001-7076-483X; Hattersley, Andrew/0000-0001-5620-473X FU Academy of Finland [77299, 102318, 110413, 118065, 123885, 124243, 129680, 129293, 129494, 136895, 139635, 141005, 213506, 251217]; Agence Nationale de la Recherche (France); American Diabetes Association [7-08-MN-OK]; Association Francaise des Diabetiques; Association de Langue Francaise pour l'Etude du Diabete et des Maladies Metaboliques (France); Association Diabete Risque Vasculaire (France); British Diabetic Association (BDA) Research (UK); British Heart Foundation [RG/98002, RG2008/08]; Cancer Research UK; Central Norway Health Authority; Central Finland Hospital District; Center for Inherited Disease Research (CIDR) (USA); Chief Scientist Office, Scotland [CZB/4/672]; City of Kuopio (Finland); City of Leutkirch (Germany); Department of Health (UK); Deutsche Forschungsgemeinschaft [ER1 55/6-2]; Diabetes UK; Doris Duke Charitable Foundation (USA); Estonian government [SF0180142s0]; European Commission: ENGAGE [HEALTH-F4-2007-201413]; EXGENESIS [LSHM-CT-2004-005272, 245536, QLG1-CT-2002-00896, 2004310]; European Commission (Marie Curie: FP7-PEOPLE-IEF); European Regional Development Fund; Faculty of Medicine at the Norwegian University of Science and Technology; Finnish Diabetes Association; Finnish Diabetes Research Foundation; Finnish Foundation for Cardiovascular Research; Finnish Heart Association; Folkhalsan Research Foundation (Finland); Food Standards Agency (UK); Foundation for Life and Health in Finland; Federal Ministry of Education and Research (BMBF) (Germany); Federal Ministry of Health (Germany); General Secretary of Research and Technology (Greece); German Center for Diabetes Research (DZD); German Research Council [GRK 1041]; Great Wine Estates of the Margaret River region of Western Australia; Groupe d'Etude des Maladies Metaboliques et Systemiques (France); Harvard Medical School (USA); Heinz Nixdorf Foundation (Germany); Helmholtz Zentrum Munchen-Research Center for Environment and Health (Germany); Helsinki University Central Hospital Research Foundation (Finland); IngaBritt and Arne Lundberg's Research Foundation (Sweden) [359]; Ministry of Health (Ricerca Corrente) (Italy); Karolinska Institutet (Sweden); Knut and Alice Wallenberg Foundation (Sweden) [KAW 2009.0243]; Kuopio University Hospital (Finland); Municipal Heath Care Center and Hospital, Jakobstad, Finland; Ministry of Social Affairs and Health (Finland); Ministry of Education and Culture (Finland) [627]; Ministry of Innovation, Science, Research and Technology of North Rhine-Westphalia (Germany); Medical Research Council (UK) [G0000649, G0601261]; MRC-GSK pilot programme grant (UK); Munich Center of Health Sciences (MC Health) (Germany); National Genome Research Network (NGFN) (Germany); National Heart, Lung, and Blood Institute (NHLBI) [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL087641, R01HL59367, R01HL086694, N01HC25195, N02HL64278]; National Human Genome Research Institute (NHGRI) [U01HG004402, N01HG65403]; US National Institutes of Health (USA) [HHSN268200625226C, UL1RR025005, U01HG004399, 1R21NS064908, 1Z01HG000024, AG028555, AG08724, AG04563, AG10175, AG08861, CA055075]; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [DK062370, DK058845, DK072193, DK078616, DK080140, DK073490]; Narpes Health Care Foundation (Finland); National Health Screening Service of Norway; National Institute of Health Research (UK); National Institute for Health and Welfare (Finland); Nord-Trondelag County Council (Norway); Nordic Center of Excellence in Disease Genetics; Norwegian Institute of Public Health; Norwegian Research Council; Novo Nordisk Fonden (Denmark); Ollqvist Foundation (Sweden); Oxford NIHR Biomedical Research Centre (UK); Paavo Nurmi Foundation (Finland); Paivikki and Sakari Sohlberg Foundation (Finland); Perklen Foundation (Sweden); Pfizer; Pirkanmaa Hospital District (Finland); Programme National de Recherche sur le Diabete (France); Programme Hospitalier de Recherche Clinique (French Ministry of Health); Region of Nord-Pas-de-Calais (Contrat de Projets Etat-Region) (France); Research into Ageing (UK); Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center; Royal Swedish Academy of Sciences; Sarstedt AG Co. (Germany); Signe and Ane Gyllenberg Foundation (Sweden); Slottery Machine Association (Finland); Social Insurance Institution of Finland [4/26/2010]; South OstroBothnia Hospital District (Finland); State of Baden-Wurttemberg, Germany; Stockholm County Council [560183, 562183]; Stroke Association (UK); Swedish Research Council [8691, 09533, 2009-1039, Dnr 521-2010-3490, Dnr 521-2007-4037, Dnr 521-2008-2974, Dnr 825-2010-5983, Dnr 349-2008-6589]; Swedish Cultural Foundation in Finland; Swedish Diabetes Foundation; Swedish Heart-Lung Foundation; Swedish Foundation for Strategic Research; Swedish Society of Medicine; Swedish Research Council; Swedish Research Council for Infrastructures; Sigrid Juselius Foundation (Finland); Torsten and Ragnar Sderberg Foundation (Sweden) [MT33/09]; University Hospital Essen (Germany); University of Tromso (Norway); Uppsala University (Sweden); Uppsala University Hospital (Sweden); Wellcome Trust [GR072960, 076113, 077016, 081682, 083948, 083270, 084711, 086596, 090367, 090532, 098051] FX Funding for this study was provided by the Academy of Finland (77299, 102318, 110413, 118065, 123885, 124243, 129680, 129293, 129494, 136895, 139635, 141005, 213506 and 251217); Agence Nationale de la Recherche (France); the American Diabetes Association (7-08-MN-OK); Association Francaise des Diabetiques; Association de Langue Francaise pour l'Etude du Diabete et des Maladies Metaboliques (France); Association Diabete Risque Vasculaire (France); British Diabetic Association (BDA) Research (UK); the British Heart Foundation (RG/98002 and RG2008/08); Cancer Research UK; the Central Norway Health Authority; the Central Finland Hospital District; the Center for Inherited Disease Research (CIDR) (USA); the Chief Scientist Office, Scotland (CZB/4/672); the City of Kuopio (Finland); the City of Leutkirch (Germany); the Department of Health (UK); Deutsche Forschungsgemeinschaft (ER1 55/6-2); Diabetes UK; the Doris Duke Charitable Foundation (USA); the Estonian government (SF0180142s0); the European Commission: ENGAGE (HEALTH-F4-2007-201413), EXGENESIS (LSHM-CT-2004-005272), 245536, QLG1-CT-2002-00896 and 2004310; the European Commission (Marie Curie: FP7-PEOPLE-2010-IEF); the European Regional Development Fund; the Faculty of Medicine at the Norwegian University of Science and Technology; the Finnish Diabetes Association; the Finnish Diabetes Research Foundation; the Finnish Foundation for Cardiovascular Research; the Finnish Heart Association; the Finnish Medical Society; the Folkhalsan Research Foundation (Finland); the Food Standards Agency (UK); the Foundation for Life and Health in Finland; the Federal Ministry of Education and Research (BMBF) (Germany); the Federal Ministry of Health (Germany); the General Secretary of Research and Technology (Greece); the German Center for Diabetes Research (DZD); the German Research Council (GRK 1041); the Great Wine Estates of the Margaret River region of Western Australia; Groupe d'Etude des Maladies Metaboliques et Systemiques (France); Harvard Medical School (USA); the Heinz Nixdorf Foundation (Germany); Helmholtz Zentrum Munchen-Research Center for Environment and Health (Germany); the Helsinki University Central Hospital Research Foundation (Finland); IngaBritt and Arne Lundberg's Research Foundation (Sweden) (grant 359); the Ministry of Health (Ricerca Corrente) (Italy); Karolinska Institutet (Sweden); the Knut and Alice Wallenberg Foundation (Sweden) (KAW 2009.; 0243); Kuopio University Hospital (Finland); the Municipal Heath Care Center and Hospital, Jakobstad, Finland; the Ministry of Social Affairs and Health (Finland); the Ministry of Education and Culture (Finland) (627; 2004-2011); the Ministry of Innovation, Science, Research and Technology of North Rhine-Westphalia (Germany); the Medical Research Council (UK) (G0000649 and G0601261); an MRC-GSK pilot programme grant (UK); the Munich Center of Health Sciences (MC Health) (Germany); the National Genome Research Network (NGFN) (Germany); the National Heart, Lung, and Blood Institute (NHLBI) (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL087641, R01HL59367, R01HL086694, N01HC25195 and N02HL64278); the National Human Genome Research Institute (NHGRI) (U01HG004402 and N01HG65403); the US National Institutes of Health (USA) (HHSN268200625226C, UL1RR025005, U01HG004399, 1R21NS064908, 1Z01HG000024, AG028555, AG08724, AG04563, AG10175, AG08861 and CA055075); the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (DK062370, DK058845, DK072193, DK078616, DK080140 and DK073490); the Narpes Health Care Foundation (Finland); the National Health Screening Service of Norway; the National Institute of Health Research (UK); the National Institute for Health and Welfare (Finland); the Nord-Trondelag County Council (Norway); the Nordic Center of Excellence in Disease Genetics; the Norwegian Institute of Public Health; the Norwegian Research Council; Novo Nordisk Fonden (Denmark); the Ollqvist Foundation (Sweden); the Oxford NIHR Biomedical Research Centre (UK); the Paavo Nurmi Foundation (Finland); the Paivikki and Sakari Sohlberg Foundation (Finland); the Perklen Foundation (Sweden); Pfizer; the Pirkanmaa Hospital District (Finland); Programme National de Recherche sur le Diabete (France); Programme Hospitalier de Recherche Clinique (French Ministry of Health); the Region of Nord-Pas-de-Calais (Contrat de Projets Etat-Region) (France); Research into Ageing (UK); the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center; the Royal Swedish Academy of Sciences; Sarstedt AG & Co. (Germany); the Signe and Ane Gyllenberg Foundation (Sweden); the Slottery Machine Association (Finland); the Social Insurance Institution of Finland (4/26/2010); the South OstroBothnia Hospital District (Finland); the State of Baden-Wurttemberg, Germany; the Stockholm County Council (560183 and 562183); Stroke Association (UK); the Swedish Research Council (8691, 09533, 2009-1039, Dnr 521-2010-3490, Dnr 521-2007-4037, Dnr 521-2008-2974, Dnr 825-2010-5983 and Dnr 349-2008-6589); the Swedish Cultural Foundation in Finland; the Swedish Diabetes Foundation; the Swedish Heart-Lung Foundation; the Swedish Foundation for Strategic Research; the Swedish Society of Medicine; the Swedish Research Council; the Swedish Research Council for Infrastructures; The Sigrid Juselius Foundation (Finland); the Torsten and Ragnar Sderberg Foundation (Sweden) (MT33/09); University Hospital Essen (Germany); University of Tromso (Norway); Uppsala University (Sweden); Uppsala University Hospital (Sweden); and the Wellcome Trust (GR072960, 076113, 077016, 081682, 083948, 083270, 084711, 086596, 090367, 090532 and 098051). NR 55 TC 626 Z9 633 U1 12 U2 140 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD SEP PY 2012 VL 44 IS 9 BP 981 EP + DI 10.1038/ng.2383 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 001WP UT WOS:000308491200009 PM 22885922 ER PT J AU Scott, RA Lagou, V Welch, RP Wheeler, E Montasser, ME Luan, JA Magi, R Strawbridge, RJ Rehnberg, E Gustafsson, S Kanoni, S Rasmussen-Torvik, LJ Yengo, L Lecoeur, C Shungin, D Sanna, S Sidore, C Johnson, PCD Jukema, JW Johnson, T Mahajan, A Verweij, N Thorleifsson, G Hottenga, JJ Shah, S Smith, AV Sennblad, B Gieger, C Salo, P Perola, M Timpson, NJ Evans, DM St Pourcain, B Wu, Y Andrews, JS Hui, JN Bielak, LF Zhao, W Horikoshi, M Navarro, P Isaacs, A O'Connell, JR Stirrups, K Vitart, V Hayward, C Esko, T Mihailov, E Fraser, RM Fall, T Voight, BF Raychaudhuri, S Chen, H Lindgren, CM Morris, AP Rayner, NW Robertson, N Rybin, D Liu, CT Beckmann, JS Willems, SM Chines, PS Jackson, AU Kang, HM Stringham, HM Song, KJ Tanaka, T Peden, JF Goel, A Hicks, AA An, P Muller-Nurasyid, M Franco-Cereceda, A Folkersen, L Marullo, L Jansen, H Oldehinkel, AJ Bruinenberg, M Pankow, JS Kari, EN Forouhi, NG Loos, RJF Edkins, S Varga, TV Hallmans, G Oksa, H Antonella, M Nagaraja, R Trompet, S Ford, I Bakker, SJL Kong, A Kumari, M Gigante, B Herder, C Munroe, PB Caulfield, M Antti, J Mangino, M Small, K Miljkovic, I Liu, YM Atalay, M Kiess, W James, AL Rivadeneira, F Uitterlinden, AG Palmer, CNA Doney, ASF Willemsen, G Smit, JH Campbell, S Polasek, O Bonnycastle, LL Hercberg, S Dimitriou, M Bolton, JL Fowkes, GR Kovacs, P Lindstrom, J Zemunik, T Bandinelli, S Wild, SH Basart, HV Rathmann, W Grallert, H Maerz, W Kleber, ME Boehm, BO Peters, A Pramstaller, PP Province, MA Borecki, IB Hastie, ND Rudan, I Campbell, H Watkins, H Farrall, M Stumvoll, M Ferrucci, L Waterworth, DM Bergman, RN Collins, FS Tuomilehto, J Watanabe, RM de Geus, EJC Penninx, BW Hofman, A Oostra, BA Psaty, BM Vollenweider, P Wilson, JF Wright, AF Hovingh, GK Metspalu, A Uusitupa, M Magnusson, PKE Kyvik, KO Kaprio, J Price, JF Dedoussis, GV Deloukas, P Meneton, P Lind, L Boehnke, M Shuldiner, AR van Duijn, CM Morris, AD Toenjes, A Peyser, PA Beilby, JP Korner, A Kuusisto, J Laakso, M Bornstein, SR Schwarz, PEH Lakka, TA Rauramaa, R Adair, LS Smith, GD Spector, TD Illig, T de Faire, U Hamsten, A Gudnason, V Kivimaki, M Hingorani, A Keinanen-Kiukaanniemi, SM Saaristo, TE Boomsma, DI Stefansson, K van der Harst, P Dupuis, J Pedersen, NL Sattar, N Harris, TB Cucca, F Ripatti, S Salomaa, V Mohlke, KL Balkau, B Froguel, P Pouta, A Jarvelin, MR Wareham, NJ Bouatia-Naji, N McCarthy, MI Franks, PW Meigs, JB Teslovich, TM Florez, JC Langenberg, C Ingelsson, E Prokopenko, I Barroso, I AF Scott, Robert A. Lagou, Vasiliki Welch, Ryan P. Wheeler, Eleanor Montasser, May E. Luan, Jian'an Maegi, Reedik Strawbridge, Rona J. Rehnberg, Emil Gustafsson, Stefan Kanoni, Stavroula Rasmussen-Torvik, Laura J. Yengo, Loic Lecoeur, Cecile Shungin, Dmitry Sanna, Serena Sidore, Carlo Johnson, Paul C. D. Jukema, J. Wouter Johnson, Toby Mahajan, Anubha Verweij, Niek Thorleifsson, Gudmar Hottenga, Jouke-Jan Shah, Sonia Smith, Albert V. Sennblad, Bengt Gieger, Christian Salo, Perttu Perola, Markus Timpson, Nicholas J. Evans, David M. St Pourcain, Beate Wu, Ying Andrews, Jeanette S. Hui, Jennie Bielak, Lawrence F. Zhao, Wei Horikoshi, Momoko Navarro, Pau Isaacs, Aaron O'Connell, Jeffrey R. Stirrups, Kathleen Vitart, Veronique Hayward, Caroline Esko, Tonu Mihailov, Evelin Fraser, Ross M. Fall, Tove Voight, Benjamin F. Raychaudhuri, Soumya Chen, Han Lindgren, Cecilia M. Morris, Andrew P. Rayner, Nigel W. Robertson, Neil Rybin, Denis Liu, Ching-Ti Beckmann, Jacques S. Willems, Sara M. Chines, Peter S. Jackson, Anne U. Kang, Hyun Min Stringham, Heather M. Song, Kijoung Tanaka, Toshiko Peden, John F. Goel, Anuj Hicks, Andrew A. An, Ping Mueller-Nurasyid, Martina Franco-Cereceda, Anders Folkersen, Lasse Marullo, Letizia Jansen, Hanneke Oldehinkel, Albertine J. Bruinenberg, Marcel Pankow, James S. North, Kari E. Forouhi, Nita G. Loos, Ruth J. F. Edkins, Sarah Varga, Tibor V. Hallmans, Goeran Oksa, Heikki Antonella, Mulas Nagaraja, Ramaiah Trompet, Stella Ford, Ian Bakker, Stephan J. L. Kong, Augustine Kumari, Meena Gigante, Bruna Herder, Christian Munroe, Patricia B. Caulfield, Mark Antti, Jula Mangino, Massimo Small, Kerrin Miljkovic, Iva Liu, Yongmei Atalay, Mustafa Kiess, Wieland James, Alan L. Rivadeneira, Fernando Uitterlinden, Andre G. Palmer, Colin N. A. Doney, Alex S. F. Willemsen, Gonneke Smit, Johannes H. Campbell, Susan Polasek, Ozren Bonnycastle, Lori L. Hercberg, Serge Dimitriou, Maria Bolton, Jennifer L. Fowkes, Gerard R. Kovacs, Peter Lindstrom, Jaana Zemunik, Tatijana Bandinelli, Stefania Wild, Sarah H. Basart, Hanneke V. Rathmann, Wolfgang Grallert, Harald Maerz, Winfried Kleber, Marcus E. Boehm, Bernhard O. Peters, Annette Pramstaller, Peter P. Province, Michael A. Borecki, Ingrid B. Hastie, Nicholas D. Rudan, Igor Campbell, Harry Watkins, Hugh Farrall, Martin Stumvoll, Michael Ferrucci, Luigi Waterworth, Dawn M. Bergman, Richard N. Collins, Francis S. Tuomilehto, Jaakko Watanabe, Richard M. de Geus, Eco J. C. Penninx, Brenda W. Hofman, Albert Oostra, Ben A. Psaty, Bruce M. Vollenweider, Peter Wilson, James F. Wright, Alan F. Hovingh, G. Kees Metspalu, Andres Uusitupa, Matti Magnusson, Patrik K. E. Kyvik, Kirsten O. Kaprio, Jaakko Price, Jackie F. Dedoussis, George V. Deloukas, Panos Meneton, Pierre Lind, Lars Boehnke, Michael Shuldiner, Alan R. van Duijn, Cornelia M. Morris, Andrew D. Toenjes, Anke Peyser, Patricia A. Beilby, John P. Koerner, Antje Kuusisto, Johanna Laakso, Markku Bornstein, Stefan R. Schwarz, Peter E. H. Lakka, Timo A. Rauramaa, Rainer Adair, Linda S. Smith, George Davey Spector, Tim D. Illig, Thomas de Faire, Ulf Hamsten, Anders Gudnason, Vilmundur Kivimaki, Mika Hingorani, Aroon Keinanen-Kiukaanniemi, Sirkka M. Saaristo, Timo E. Boomsma, Dorret I. Stefansson, Kari van der Harst, Pim Dupuis, Josee Pedersen, Nancy L. Sattar, Naveed Harris, Tamara B. Cucca, Francesco Ripatti, Samuli Salomaa, Veikko Mohlke, Karen L. Balkau, Beverley Froguel, Philippe Pouta, Anneli Jarvelin, Marjo-Riitta Wareham, Nicholas J. Bouatia-Naji, Nabila McCarthy, Mark I. Franks, Paul W. Meigs, James B. Teslovich, Tanya M. Florez, Jose C. Langenberg, Claudia Ingelsson, Erik Prokopenko, Inga Barroso, Ines CA DIAbet Genetics Replication TI Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; BODY-MASS INDEX; KLOTHO GENE POLYMORPHISMS; BINDING-PROTEIN-ALPHA; INSULIN-RESISTANCE; GLUCOSE-METABOLISM; SUSCEPTIBILITY LOCI; KAPPA-B; CARDIOVASCULAR-DISEASE; SKELETAL-MUSCLE AB Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control. C1 [Meigs, James B.; Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Scott, Robert A.; Luan, Jian'an; Forouhi, Nita G.; Loos, Ruth J. F.; Wareham, Nicholas J.; Langenberg, Claudia] Addenbrookes Hosp, Inst Metab Sci, Med Res Council MRC Epidemiol Unit, Cambridge, England. [Lagou, Vasiliki; Maegi, Reedik; Mahajan, Anubha; Horikoshi, Momoko; Lindgren, Cecilia M.; Morris, Andrew P.; Rayner, Nigel W.; Robertson, Neil; Peden, John F.; Goel, Anuj; Marullo, Letizia; Watkins, Hugh; Farrall, Martin; McCarthy, Mark I.; Prokopenko, Inga] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Lagou, Vasiliki; Horikoshi, Momoko; Rayner, Nigel W.; Robertson, Neil; McCarthy, Mark I.; Prokopenko, Inga] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. [Welch, Ryan P.] Univ Michigan, Sch Med, Bioinformat Grad Program, Ann Arbor, MI USA. [Welch, Ryan P.; Sidore, Carlo; Jackson, Anne U.; Kang, Hyun Min; Stringham, Heather M.; Boehnke, Michael; Teslovich, Tanya M.] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Welch, Ryan P.; Sidore, Carlo; Jackson, Anne U.; Kang, Hyun Min; Stringham, Heather M.; Boehnke, Michael; Teslovich, Tanya M.] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. 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