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. [Kraft, Peter; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. [Sun, Qi; Hunter, David J.; Qi, Lu; Hu, Frank] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [van Dam, Rob M.] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117548, Singapore. [Chines, Peter S.; Bonnycastle, Lori L.; Collins, Francis S.] NHGRI, US Natl Inst Hlth, Bethesda, MD 20892 USA. [Holmen, Oddgeir L.; Platou, Carl G. P.; Hveem, Kristian] Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, Nord Trondelag Hlth Study HUNT Res Ctr, Levanger, Norway. [Lawrence, Robert] Univ Western Australia, Ctr Genet Epidemiol & Biostat, Nedlands, WA 6009, Australia. [Perry, John R. B.; Wood, Andrew R.; Frayling, Timothy M.] Univ Exeter, Peninsula Med Sch, Inst Biomed & Clin Sci, Exeter, Devon, England. [Platou, Carl G. P.] Nord Trondelag Hlth Trust, Levanger Hosp, Dept Internal Med, Levanger, Norway. [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. [Atalay, Mustafa; Lakka, Timo A.] Univ Eastern Finland, Inst Biomed, Kuopio, Finland. [Benediktsson, Rafn; Thorsteinsdottir, Unnur; Stefansson, Kari] Univ Iceland, Fac Med, Reykjavik, Iceland. [Benediktsson, Rafn; Hreidarsson, Astradur B.; Sigurdsson, Gunnar] Landspitali Univ Hosp, Dept Endocrinol & Metab, Reykjavik, Iceland. [Charpentier, Guillaume] Corbeil Essonnes Hosp, Endocrinol Diabetol Unit, Corbeil Essonnes, France. [Doney, Alex S. F.; Palmer, Colin N. A.; Morris, Andrew D.] Univ Dundee, Ninewells Hosp, Biomed Res Inst, Diabet Res Ctr, Dundee, Scotland. [Doney, Alex S. F.; Palmer, Colin N. A.; Morris, Andrew D.] Univ Dundee, Ninewells Hosp, Biomed Res Inst, Pharmacogen Ctr, Dundee, Scotland. [Emilsson, Valur; Sigurdsson, Gunnar] Iceland Heart Assoc, Kopavogur, Iceland. [Forsen, Tom; Eriksson, Johan G.] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland. [Forsen, Tom] Vaasa Hlth Care Ctr, Vaasa, Finland. [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. [Wheeler, Eleanor; Kanoni, Stavroula; Stirrups, Kathleen; Edkins, Sarah; Deloukas, Panos; Barroso, Ines] Wellcome Trust Sanger Inst, Cambridge, England. [Montasser, May E.; O'Connell, Jeffrey R.; Shuldiner, Alan R.] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA. [Maegi, Reedik; Perola, Markus; Esko, Tonu; Metspalu, Andres] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia. [Strawbridge, Rona J.; Sennblad, Bengt; Folkersen, Lasse; Hamsten, Anders] Karolinska Inst, Dept Med Solna, Atherosclerosis Res Unit, Stockholm, Sweden. [Strawbridge, Rona J.; Folkersen, Lasse; Hamsten, Anders] Karolinska Univ Hosp, Ctr Mol Med, Stockholm, Sweden. [Rehnberg, Emil; Gustafsson, Stefan; Fall, Tove; Magnusson, Patrik K. E.; Pedersen, Nancy L.; Ingelsson, Erik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Rasmussen-Torvik, Laura J.] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. [Yengo, Loic; Lecoeur, Cecile; Froguel, Philippe; Bouatia-Naji, Nabila] Univ Lille Nord France, Lille, France. [Yengo, Loic; Lecoeur, Cecile; Froguel, Philippe; Bouatia-Naji, Nabila] Inst Pasteur, CNRS, UMR 8199, F-59019 Lille, France. [Shungin, Dmitry; Varga, Tibor V.; Franks, Paul W.] Lund Univ, Dept Clin Sci, Skane Univ Hosp Malmo, Genet & Mol Epidemiol Unit, Malmo, Sweden. [Shungin, Dmitry; Franks, Paul W.] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden. [Shungin, Dmitry] Umea Univ, Dept Odontol, Umea, Sweden. [Sanna, Serena; Sidore, Carlo; Antonella, Mulas; Cucca, Francesco] CNR, Ist Ric Genet & Biomed, Monserrato, Italy. [Sidore, Carlo; Cucca, Francesco] Univ Sassari, Dipartimento Sci Biomed, I-07100 Sassari, Italy. [Johnson, Paul C. D.; Ford, Ian] Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland. [Jukema, J. Wouter; Trompet, Stella] Durrer Ctr Cardiogenet Res, ICIN, Utrecht, Netherlands. [Jukema, J. Wouter; Trompet, Stella] Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands. [Johnson, Toby; Munroe, Patricia B.; Caulfield, Mark] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, Dept Clin Pharmacol, London, England. [Johnson, Toby; Munroe, Patricia B.; Caulfield, Mark] Queen Mary Univ London, Barts & London Sch Med & Dent, Genome Ctr, London, England. [Verweij, Niek; van der Harst, Pim] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands. [Thorleifsson, Gudmar; Kong, Augustine; Stefansson, Kari] deCODE Genet, Rekjavik, Iceland. [Hottenga, Jouke-Jan; Willemsen, Gonneke; de Geus, Eco J. C.; Boomsma, Dorret I.] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands. [Hottenga, Jouke-Jan; Willemsen, Gonneke; de Geus, Eco J. C.; Boomsma, Dorret I.] EMGO Inst, Amsterdam, Netherlands. [Shah, Sonia] UCL, Univ Coll London Genet Inst UGI, London, England. [Smith, Albert V.; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland. [Smith, Albert V.; Gudnason, Vilmundur; Stefansson, Kari] Univ Iceland, Fac Med, Reykjavik, Iceland. [Gieger, Christian; Mueller-Nurasyid, Martina] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Genet Epidemiol, Neuherberg, Germany. [Salo, Perttu; Perola, Markus; Antti, Jula] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. [Perola, Markus; Kaprio, Jaakko; Ripatti, Samuli] Univ Helsinki, Inst Mol Med, Finland FIMM, Helsinki, Finland. [Timpson, Nicholas J.; Evans, David M.; Smith, George Davey] Univ Bristol, Sch Social & Community Med, MRC Council Ctr Causal Anal Translat Epidemiol CA, Bristol, Avon, England. [Wu, Ying; Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Andrews, Jeanette S.] Wake Forest Sch Med, Div Publ Hlth Sci, Dept Biostat Sci, Winston Salem, NC USA. [Hui, Jennie; James, Alan L.; Beilby, John P.] Sir Charles Gairdner Hosp, Busselton Populat Med Res Inst, Nedlands, WA 6009, Australia. [Hui, Jennie] Univ Western Australia, Sch Populat Hlth, Nedlands, WA 6009, Australia. [Hui, Jennie; Beilby, John P.] Univ Western Australia, Sch Pathol & Lab Med, Nedlands, WA 6009, Australia. [Hui, Jennie; Beilby, John P.] PathW Lab Med WA, Nedlands, WA, Australia. [Bielak, Lawrence F.; Zhao, Wei; Peyser, Patricia A.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Navarro, Pau; Vitart, Veronique; Hayward, Caroline; Campbell, Susan; Hastie, Nicholas D.; Wright, Alan F.] Univ Edinburgh, Western Gen Hosp, Med Res Council Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland. [Isaacs, Aaron; Rivadeneira, Fernando; Uitterlinden, Andre G.; Oostra, Ben A.; van Duijn, Cornelia M.] CMSB, Leiden, Netherlands. [Isaacs, Aaron; Willems, Sara M.; Oostra, Ben A.; van Duijn, Cornelia M.] Erasmus Univ, Med Ctr, Dept Epidemiol, Genet Epidemiol Unit, Rotterdam, Netherlands. [Esko, Tonu; Mihailov, Evelin; Metspalu, Andres] Univ Tartu, Inst Mol & Cell Biol, EE-50090 Tartu, Estonia. [Fraser, Ross M.; Bolton, Jennifer L.; Fowkes, Gerard R.; Wild, Sarah H.; Rudan, Igor; Campbell, Harry; Wilson, James F.; Price, Jackie F.] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland. [Voight, Benjamin F.] Broad Inst Harvard & MIT, Boston, MA USA. [Voight, Benjamin F.] Univ Penn, Perelman Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA. [Raychaudhuri, Soumya] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [Raychaudhuri, Soumya] Brigham & Womens Hosp, Div Rheumatol, Boston, MA 02115 USA. [Chen, Han; Liu, Ching-Ti; Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Rybin, Denis] Boston Univ, Data Coordinating Ctr, Boston, MA 02215 USA. [Beckmann, Jacques S.] Univ Lausanne, Dept Med Genet, Lausanne, Switzerland. [Beckmann, Jacques S.] Univ Lausanne Hosp, CHUV, Serv Med Genet, Lausanne, Switzerland. [Chines, Peter S.; Bonnycastle, Lori L.; Collins, Francis S.] NHGRI, Genome Technol Branch, US Natl Inst Hlth NIH, Bethesda, MD 20892 USA. [Song, Kijoung; Waterworth, Dawn M.] GlaxoSmithKline, Genet, Upper Merion, PA USA. [Tanaka, Toshiko; Ferrucci, Luigi] NIA, Clin Res Branch, NIH, Baltimore, MD 21224 USA. [Goel, Anuj; Pramstaller, Peter P.; Watkins, Hugh; Farrall, Martin] Univ Oxford, Dept Cardiovasc Med, Oxford, England. [Hicks, Andrew A.] Univ Lubeck, European Acad Bozen Bolzano EURAC, Ctr Biomed, Bolzano, Italy. [An, Ping; Province, Michael A.; Borecki, Ingrid B.] Washington Univ, Sch Med, Div Stat Genom, St Louis, MO USA. [Mueller-Nurasyid, Martina] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany. [Mueller-Nurasyid, Martina] Univ Munich, Univ Hosp Grosshadern, Dept Med 1, Munich, Germany. [Franco-Cereceda, Anders] Karolinska Inst, Dept Mol Med & Surg, Cardiothorac Surg Unit, Stockholm, Sweden. [Marullo, Letizia] Univ Ferrara, Genet Sect, Dept Evolutionary Biol, I-44100 Ferrara, Italy. [Jansen, Hanneke] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands. [Oldehinkel, Albertine J.] Univ Groningen, Univ Med Ctr Groningen, Interdisciplinary Ctr Pathol Emot, Groningen, Netherlands. [Pankow, James S.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [North, Kari E.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA. [North, Kari E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Hallmans, Goeran] Umea Univ Hosp, Dept Publ Hlth & Clin Med, Sect Nutr Res, S-90185 Umea, Sweden. [Oksa, Heikki; Saaristo, Timo E.] Pirkanmaa Hosp Dist, Tampere, Finland. [Nagaraja, Ramaiah] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. [Bakker, Stephan J. L.] Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, Groningen, Netherlands. [Kumari, Meena; Kivimaki, Mika; Hingorani, Aroon; Langenberg, Claudia] UCL, Dept Epidemiol & Publ Hlth, London, England. [Gigante, Bruna; de Faire, Ulf] Karolinska Inst, Inst Environm Med, Div Cardiovasc Epidemiol, Stockholm, Sweden. [Herder, Christian] Univ Dusseldorf, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Clin Diabetol, D-40225 Dusseldorf, Germany. [Mangino, Massimo; Small, Kerrin; Spector, Tim D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England. [Miljkovic, Iva] Univ Pittsburgh, Ctr Aging & Populat Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Liu, Yongmei] Wake Forest Sch Med, Div Publ Hlth Sci, Dept Epidemiol & Prevent, Winston Salem, NC USA. [Atalay, Mustafa; Lakka, Timo A.] Univ Eastern Finland, Inst Biomed, Kuopio, Finland. [Kiess, Wieland; Stumvoll, Michael; Toenjes, Anke; Koerner, Antje] Univ Leipzig, Integrated Res & Treatment Ctr IFB Adipos Dis, Leipzig, Germany. [Kiess, Wieland; Koerner, Antje] Univ Leipzig, Dept Womens & Child Hlth, Pediat Res Ctr, Leipzig, Germany. [James, Alan L.] Univ Western Australia, Sch Med & Pharmacol, Nedlands, WA 6009, Australia. [Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands. [Rivadeneira, Fernando; Uitterlinden, Andre G.; Oostra, Ben A.; van Duijn, Cornelia M.] Genom Initiat NGI, Netherlands Consortium Hlth Ageing NCHAH, Leiden, Netherlands. [Rivadeneira, Fernando; Uitterlinden, Andre G.; Hofman, Albert; van Duijn, Cornelia M.] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands. [Palmer, Colin N. A.; Doney, Alex S. F.; Morris, Andrew D.] Univ Dundee, Med Res Inst, Dundee, Scotland. [Smit, Johannes H.; Penninx, Brenda W.] Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, Amsterdam, Netherlands. [Polasek, Ozren; Zemunik, Tatijana] Univ Split, Fac Med, Split, Croatia. [Hercberg, Serge] Univ Paris 13, INRA, INSERM, U557,U1125, Bobigny, France. [Dimitriou, Maria; Dedoussis, George V.] Harokopio Univ, Dept Nutr & Dietet, Athens, Greece. [Kovacs, Peter] Univ Leipzig, Interdisciplinary Ctr Clin Res, Leipzig, Germany. [Lindstrom, Jaana; Tuomilehto, Jaakko] Natl Inst Hlth & Welf, Diabet Prevent Unit, Helsinki, Finland. [Bandinelli, Stefania] Azienda Sanit Firenze, Dept Geriatr, Florence, Italy. [Basart, Hanneke V.; Hovingh, G. Kees] Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands. [Rathmann, Wolfgang] Univ Dusseldorf, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Biometr & Epidemiol, D-40225 Dusseldorf, Germany. [Grallert, Harald; Illig, Thomas] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Neuherberg, Germany. [Maerz, Winfried] Synlab Acad, Mannheim, Germany. [Maerz, Winfried; Kleber, Marcus E.] Heidelberg Univ, Med Fac Mannheim, Mannheim Inst Publ Hlth Social & Prevent Med, D-6800 Mannheim, Germany. [Kleber, Marcus E.] Ludwigshafen Risk & Cardiovasc Hlth LURIC Study, Freiburg, Germany. [Boehm, Bernhard O.] Univ Hosp, Dept Med, Div Endocrinol & Diabet, Ulm, Germany. [Peters, Annette] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany. [Pramstaller, Peter P.] Gen Cent Hosp, Dept Neurol, Bolzano, Italy. [Pramstaller, Peter P.; Toenjes, Anke] Univ Lubeck, Dept Neurol, Lubeck, Germany. [Stumvoll, Michael] Univ Leipzig, Dept Med, Leipzig, Germany. [Bergman, Richard N.] Cedars Sinai Med Ctr, Diabet & Obes Res Inst, Los Angeles, CA 90048 USA. [Tuomilehto, Jaakko] S Ostrobothnia Cent Hosp, Seinajoki, Finland. [Tuomilehto, Jaakko] Hosp Univ La Paz, Red RECAVA La Red Temat Invest Cooperat Enfermeda, Madrid, Spain. [Tuomilehto, Jaakko] Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria. [Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA. [Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Vollenweider, Peter] Univ Lausanne Hosp, Dept Internal Med, Lausanne, Switzerland. [Uusitupa, Matti] Univ Eastern Finland, Dept Publ Hlth & Clin Nutr, Kuopio, Finland. [Uusitupa, Matti] Kuopio Univ Hosp, Res Unit, SF-70210 Kuopio, Finland. [Kyvik, Kirsten O.] Odense Patient Data Explorat Network OPEN, Odense, Denmark. [Kyvik, Kirsten O.] Inst Reg Hlth Serv Res, Odense, Denmark. [Kaprio, Jaakko] Univ Helsinki, Dept Publ Hlth, Hjelt Inst, Helsinki, Finland. [Kaprio, Jaakko] Natl Inst Hlth & Welf, Dept Mental Hlth & Subst Abuse Serv, Helsinki, Finland. [Meneton, Pierre] Ctr Rech Cordeliers, INSTERM U872, Paris, France. [Lind, Lars] Uppsala Univ, Dept Med Sci, Uppsala, Sweden. [Shuldiner, Alan R.] Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Baltimore, MD 21218 USA. [Kuusisto, Johanna; Laakso, Markku] Univ Eastern Finland, Dept Med, Kuopio, Finland. [Bornstein, Stefan R.; Schwarz, Peter E. H.] Univ Dresden, Med Fac Carl Gustav Carus, Dept Med 3, Dresden, Germany. [Lakka, Timo A.; Rauramaa, Rainer] Kuopio Res Inst Exercise Med, Kuopio, Finland. [Rauramaa, Rainer] Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, SF-70210 Kuopio, Finland. [Adair, Linda S.] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA. [Illig, Thomas] Hannover Med Sch, Hannover Unified Biobank, D-3000 Hannover, Germany. [Hamsten, Anders] Karolinska Univ Hosp, Dept Cardiol, Stockholm, Sweden. [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. [Dupuis, Josee] NHLBI, Framingham Heart Study, Framingham, MA USA. [Sattar, Naveed] Univ Glasgow, Inst Cardiovasc & Med Sci, British Heart Fdn BHF Bldg, Glasgow, Lanark, Scotland. [Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. [Ripatti, Samuli] Natl Inst Hlth & Welf, Publ Hlth Genom Unit, Helsinki, Finland. [Ripatti, Samuli] Wellcome Trust Sanger Inst, Hinxton, England. [Salomaa, Veikko] Natl Inst Hlth & Welf, Unit Chron Dis Epidemiol & Prevent, Helsinki, Finland. [Balkau, Beverley] INSERM, Ctr Rech Epidemiol & Sante Populat CESP, Ctr Res Epidemiol & Publ Hlth, Epidemiol Diabet Obes & Chron Kidney Dis Lifecour, Villejuif, France. [Balkau, Beverley] Univ Paris 11, UMRS 1018, Villejuif, France. [Froguel, Philippe] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Sch Publ Hlth, Dept Genom Common Dis, London, England. [Pouta, Anneli] Univ Oulu, Dept Clin Sci Obstet & Gynecol, Oulu, Finland. [Pouta, Anneli; Jarvelin, Marjo-Riitta] Natl Inst Hlth & Welf, Dept Lifecourse & Serv, Oulu, Finland. [Jarvelin, Marjo-Riitta] Univ Oulu, Bioctr Oulu, Oulu, Finland. [Jarvelin, Marjo-Riitta] Univ London Imperial Coll Sci Technol & Med, Fac Med, MRC Hlth Protect Agcy HPA,Ctr Environm & Hlth, Dept Epidemiol & Biostat,Sch Publ Hlth, London, England. [Jarvelin, Marjo-Riitta] Univ Oulu, Inst Hlth Sci, Oulu, Finland. [Bouatia-Naji, Nabila] INSERM, U970, Paris Cardiovasc Res Ctr PARCC, Paris, France. [McCarthy, Mark I.] Churchill Hosp, Oxford Natl Inst Hlth Res NIHR, Biomed Res Ctr, Oxford OX3 7LJ, England. [Franks, Paul W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Florez, Jose C.] Massachusetts Gen Hosp, Diabet Unit, Diabet Res Ctr, Boston, MA 02114 USA. [Florez, Jose C.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Barroso, Ines] Addenbrookes Hosp, Inst Metab Sci, NIHR Cambridge Biomed Res Ctr, Cambridge, England. [Barroso, Ines] Univ Cambridge, Addenbrookes Hosp, Metab Res Labs, Inst Metab Sci, Cambridge CB2 2QQ, England. RP Florez, JC (reprint author), Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. EM jcflorez@partners.org; claudia.langenberg@mrc-epid.cam.ac.uk; erik.ingelsson@ki.se; inga@well.ox.ac.uk; ib1@sanger.ac.uk RI Smith, Albert/K-5150-2015; Kyvik, Kirsten /K-5680-2016; Study, GoDARTS/K-9448-2016; mangino, massimo/F-5134-2011; Hayward, Caroline/M-8818-2016; BOUATIA-NAJI, NABILA/D-5863-2013; Schwarz, Peter/B-5127-2013; Fox, Laura /C-6249-2016; Verweij, Niek/A-4499-2017; Davey Smith, George/A-7407-2013; Magnusson, Patrik/C-4458-2017; Yengo, Loic/D-2692-2017; Hicks, Andrew/E-9518-2017; Johnson, Paul/O-9695-2014; Korner, Antje/B-3988-2015; Boehm, Bernhard/F-8750-2015; Bakker, Stephan/J-4023-2015; Gudnason, Vilmundur/K-6885-2015; Ripatti, Samuli/H-9446-2014; Wilson, James F/A-5704-2009; Polasek, Ozren/B-6002-2011; de Geus, Eco/M-9318-2015; Rivadeneira, Fernando/O-5385-2015; Prokopenko, Inga/H-3241-2014; Peters, Annette/A-6117-2011; Grallert, Harald/B-3424-2013; Beckmann, Jacques S /A-9772-2008; Evans, David/H-6325-2013; Colaus, PsyColaus/K-6607-2013; Lagou, Vasiliki/N-8451-2013; Pramstaller, Peter/C-2357-2008; Strawbridge, Rona/H-5422-2012; Rudan, Igor/I-1467-2012; Gigante, Bruna/I-9252-2012; Palmer, Colin/C-7053-2008; Fraser, Ross/J-9519-2012; Deloukas, Panos/B-2922-2013; Fall, Tove/O-7226-2014; OI Smith, Albert/0000-0003-1942-5845; Kyvik, Kirsten /0000-0003-2981-0245; mangino, massimo/0000-0002-2167-7470; Hayward, Caroline/0000-0002-9405-9550; Schwarz, Peter/0000-0001-6317-7880; Davey Smith, George/0000-0002-1407-8314; Yengo, Loic/0000-0002-4272-9305; Hicks, Andrew/0000-0001-6320-0411; Pankow, James/0000-0001-7076-483X; Bergmann, Sven/0000-0002-6785-9034; Wheeler, Eleanor/0000-0002-8616-6444; Kleber, Marcus/0000-0003-0663-7275; Verweij, Niek/0000-0002-4303-7685; Forouhi, Nita/0000-0002-5041-248X; Jarvelin, Marjo-Riitta/0000-0002-2149-0630; Chen, Han/0000-0002-9510-4923; Navarro, Pau/0000-0001-5576-8584; Watkins, Hugh/0000-0002-5287-9016; Small, Kerrin/0000-0003-4566-0005; Varga, Tibor/0000-0002-2383-699X; Evans, David/0000-0003-0663-4621; Kaprio, Jaakko/0000-0002-3716-2455; Timpson, Nicholas/0000-0002-7141-9189; Lakka, Timo/0000-0002-9199-2871; Dupuis, Josee/0000-0003-2871-3603; Folkersen, Lasse/0000-0003-0708-9530; Gieger, Christian/0000-0001-6986-9554; Franks, Paul/0000-0002-0520-7604; St Pourcain, Beate/0000-0002-4680-3517; Kumari, Meena/0000-0001-9716-1035; Miljkovic, Iva/0000-0002-3155-9777; Rybin, Denis/0000-0002-3657-4829; sanna, serena/0000-0002-3768-1749; Kivimaki, Mika/0000-0002-4699-5627; Monsalve, Beatriz Elena/0000-0002-5994-866X; Esko, Tonu/0000-0003-1982-6569; Johnson, Paul/0000-0001-6663-7520; Korner, Antje/0000-0001-6001-0356; Bakker, Stephan/0000-0003-3356-6791; Gudnason, Vilmundur/0000-0001-5696-0084; Ripatti, Samuli/0000-0002-0504-1202; Wilson, James F/0000-0001-5751-9178; Polasek, Ozren/0000-0002-5765-1862; de Geus, Eco/0000-0001-6022-2666; Rivadeneira, Fernando/0000-0001-9435-9441; Prokopenko, Inga/0000-0003-1624-7457; Beckmann, Jacques S /0000-0002-9741-1900; Strawbridge, Rona/0000-0001-8506-3585; Rudan, Igor/0000-0001-6993-6884; Palmer, Colin/0000-0002-6415-6560; Fraser, Ross/0000-0003-0488-2592; Deloukas, Panos/0000-0001-9251-070X; Shungin, Dmitry/0000-0001-7900-5856; Mulas, Antonella/0000-0002-6856-1483; Bouatia-Naji, Nabila/0000-0001-5424-2134; Johnson, Toby/0000-0002-5998-3270; Sidore, Carlo/0000-0001-7504-7477; Magi, Reedik/0000-0002-2964-6011 FU National Institutes of Health [N01-AG-1-2100]; National Institute on Aging Intramural Research Program; Hjartavernd (the Icelandic Heart Association); Althingi (the Icelandic Parliament) FX The AGES-Reykjavik study was supported by a contract from the National Institutes of Health (N01-AG-1-2100), National Institute on Aging Intramural Research Program, Hjartavernd (the Icelandic Heart Association) and the Althingi (the Icelandic Parliament). NR 98 TC 248 Z9 253 U1 5 U2 69 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 991 EP + DI 10.1038/ng.2385 PG 18 WC Genetics & Heredity SC Genetics & Heredity GA 001WP UT WOS:000308491200010 PM 22885924 ER PT J AU Falk, MJ Zhang, Q Nakamaru-Ogiso, E Kannabiran, C Fonseca-Kelly, Z Chakarova, C Audo, I Mackay, DS Zeitz, C Borman, AD Staniszewska, M Shukla, R Palavalli, L Mohand-Said, S Waseem, NH Jalali, S Perin, JC Place, E Ostrovsky, J Xiao, R Bhattacharya, SS Consugar, M Webster, AR Sahel, JA Moore, AT Berson, EL Liu, Q Gai, XW Pierce, EA AF Falk, Marni J. Zhang, Qi Nakamaru-Ogiso, Eiko Kannabiran, Chitra Fonseca-Kelly, Zoe Chakarova, Christina Audo, Isabelle Mackay, Donna S. Zeitz, Christina Borman, Arundhati Dev Staniszewska, Magdalena Shukla, Rachna Palavalli, Lakshmi Mohand-Said, Saddek Waseem, Naushin H. Jalali, Subhadra Perin, Juan C. Place, Emily Ostrovsky, Julian Xiao, Rui Bhattacharya, Shomi S. Consugar, Mark Webster, Andrew R. Sahel, Jose-Alain Moore, Anthony T. Berson, Eliot L. Liu, Qin Gai, Xiaowu Pierce, Eric A. TI NMNAT1 mutations cause Leber congenital amaurosis SO NATURE GENETICS LA English DT Article ID GENE-THERAPY; WALLERIAN DEGENERATION; SUBCELLULAR COMPARTMENTATION; RETINITIS-PIGMENTOSA; PROTEIN; DISEASE; WLD(S); IDENTIFICATION; NICOTINAMIDE; DYSTROPHIES AB Leber congenital amaurosis (LCA) is an infantile-onset form of inherited retinal degeneration characterized by severe vision loss(1,2). Two-thirds of LCA cases are caused by mutations in 17 known disease-associated genes(3) (Retinal Information Network (RetNet)). Using exome sequencing we identified a homozygous missense mutation (c.25G> A, p.Val9Met) in NMNAT1 that is likely to be disease causing in two siblings of a consanguineous Pakistani kindred affected by LCA. This mutation segregated with disease in the kindred, including in three other children with LCA. NMNAT1 resides in the previously identified LCA9 locus and encodes the nuclear isoform of nicotinamide mononucleotide adenylyltransferase, a rate-limiting enzyme in nicotinamide adenine dinucleotide (NAD(+)) biosynthesis(4,5). Functional studies showed that the p.Val9Met alteration decreased NMNAT1 enzyme activity. Sequencing NMNAT1 in 284 unrelated families with LCA identified 14 rare mutations in 13 additional affected individuals. These results are the first to link an NMNAT isoform to disease in humans and indicate that NMNAT1 mutations cause LCA. C1 [Zhang, Qi; Fonseca-Kelly, Zoe; Staniszewska, Magdalena; Place, Emily; Consugar, Mark; Berson, Eliot L.; Liu, Qin; Pierce, Eric A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat,Dept Opht, Boston, MA 02114 USA. [Falk, Marni J.; Place, Emily; Ostrovsky, Julian] Childrens Hosp Philadelphia, Div Human Genet, Dept Pediat, Philadelphia, PA 19104 USA. [Nakamaru-Ogiso, Eiko] Univ Penn, Perelman Sch Med, Dept Biochem & Biophys, Philadelphia, PA 19104 USA. [Falk, Marni J.] Childrens Hosp Philadelphia, Dept Pediat, Div Child Dev & Metab Dis, Philadelphia, PA 19104 USA. [Zhang, Qi; Fonseca-Kelly, Zoe; Staniszewska, Magdalena; Place, Emily; Consugar, Mark; Liu, Qin; Pierce, Eric A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Ocular Genom Inst, Boston, MA USA. [Kannabiran, Chitra; Shukla, Rachna; Palavalli, Lakshmi; Jalali, Subhadra] LVPEI, Kallam Anji Reddy Mol Genet Lab, Hyderabad, Andhra Pradesh, India. [Chakarova, Christina; Mackay, Donna S.; Borman, Arundhati Dev; Waseem, Naushin H.; Bhattacharya, Shomi S.; Webster, Andrew R.; Moore, Anthony T.] UCL, Inst Ophthalmol, London, England. [Audo, Isabelle; Zeitz, Christina; Mohand-Said, Saddek; Sahel, Jose-Alain] INSERM, U968, Paris, France. [Audo, Isabelle; Zeitz, Christina; Mohand-Said, Saddek; Sahel, Jose-Alain] Univ Paris 06, Unite Mixte Rech UMR S 968, Inst Vis, Paris, France. [Audo, Isabelle; Zeitz, Christina; Mohand-Said, Saddek; Sahel, Jose-Alain] CNRS, UMR 7210, Paris, France. [Audo, Isabelle; Mohand-Said, Saddek; Sahel, Jose-Alain] Ctr Hosp Natl Ophtalmol Quinze Vingts, INSERM, DHOS, Ctr Invest Clin 503, Paris, France. [Borman, Arundhati Dev; Webster, Andrew R.; Moore, Anthony T.] Moorfields Eye Hosp, London, England. [Jalali, Subhadra] LVPEI, Srimati Kanuri Santhamma Ctr Vitreoretinal Dis, Hyderabad, Andhra Pradesh, India. [Perin, Juan C.] Childrens Hosp Philadelphia, Ctr Biomed Informat, Philadelphia, PA 19104 USA. [Xiao, Rui] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Bhattacharya, Shomi S.] Ctr Andaluz Biol Mol & Med Regenerat CABIMER, Seville, Spain. [Sahel, Jose-Alain] Fdn Ophtalmol Adolphe Rothschild, Paris, France. [Sahel, Jose-Alain] Acad Sci Inst France, Paris, France. [Moore, Anthony T.] Great Ormond St Hosp Sick Children, London WC1N 3JH, England. [Gai, Xiaowu] Loyola Univ, Chicago Hlth Sci Div, Dept Mol Pharmacol & Therapeut, Maywood, IL 60153 USA. [Gai, Xiaowu] Loyola Univ, Chicago Hlth Sci Div, Ctr Biomed Informat, Maywood, IL 60153 USA. RP Pierce, EA (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat,Dept Opht, Boston, MA 02114 USA. EM eric_pierce@meei.harvard.edu RI Chakarova, Christina/C-9479-2013; Waseem, Naushin/C-9573-2013; Falk, Marni/K-1997-2014; Staniszewska, Monika/B-1939-2015; Zeitz, Christina/F-2757-2017; Sahel, Jose-Alain/F-3172-2017; OI Fonseca-Kelly, Zoe/0000-0002-3960-7796; Kannabiran, Chitra/0000-0001-8435-0320; Mackay, Donna/0000-0002-2499-1203; Pierce, Eric/0000-0002-2354-4102 FU US National Institutes of Health [RO1-EY12910, R03-DK082446, R01-GM097409, P30HD026979, P30EY014104]; Foundation Fighting Blindness USA; Rosanne Silbermann Foundation; Penn Genome Frontiers Institute; Loyola University Stritch School of Medicine; Division of Child Development and Metabolic Disease at the Children's Hospital of Philadelphia; Clinical and Translational Research Center at the Children's Hospital of Philadelphia [UL1-RR-024134]; Department of Biotechnology, the Government of India; Champalimaud Foundation, Portugal; Hyderabad Eye Research Foundation; Council for Scientific and Industrial Research; Foundation Voir et Entendre, Ville de Paris and Region Ille de France; RP Fighting Blindness (UK); Fight For Sight (UK); Moorfields Eye Hospital National Institute of Health Research (NIHR) British Research Council (BRC) for Ophthalmology; Special Trustees of Moorfields Eye Hospital; Penn Genome Frontiers Institute under Pennsylvania Department of Health FX This work was supported by grants from the US National Institutes of Health (RO1-EY12910 (E.A.P.), R03-DK082446 (M.J.F.), R01-GM097409 (E.N.-O.), P30HD026979 (M.J.F. and R. X.) and P30EY014104 (Massachusetts Eye and Ear Infirmary core support)); the Foundation Fighting Blindness USA (I.A., A.D.B., E.L.B., S.S.B., Q.L., A.T.M., D.S.M., E.A.P., J.-A.S., S.M.-S. and A.R.W.); the Rosanne Silbermann Foundation (E.A.P.); the Penn Genome Frontiers Institute (E.A.P. and X.G.); the Institutional Fund to the Center for Biomedical Informatics by the Loyola University Stritch School of Medicine (X.G.); the Foerderer Award for Excellence from the Children's Hospital of Philadelphia (M.J.F. and X.G.); the Angelina Foundation Fund from the Division of Child Development and Metabolic Disease at the Children's Hospital of Philadelphia (M.J.F.); the Clinical and Translational Research Center at the Children's Hospital of Philadelphia (UL1-RR-024134) (M.J.F. and E.A.P.); the Department of Biotechnology, the Government of India and the Champalimaud Foundation, Portugal (C.K.); the Hyderabad Eye Research Foundation (C.K.); a senior research fellowship from the Council for Scientific and Industrial Research (R.S.); the Foundation Voir et Entendre, Ville de Paris and Region Ille de France (C.Z.); RP Fighting Blindness (UK)(A.R.W.); Fight For Sight (UK) (A.D. B., S.S.B., A.T.M., D.S. M. and A.R.W.); Moorfields Eye Hospital National Institute of Health Research (NIHR) British Research Council (BRC) for Ophthalmology (A.D.B., S.S.B., A.T.M., D.S.M. and A.R.W.); and the Special Trustees of Moorfields Eye Hospital (A.D.B., S.S. B., A.T.M., D.S. M. and A.R.W.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding organizations or the National Institutes of Health. This project is funded, in part, by the Penn Genome Frontiers Institute under a grant with the Pennsylvania Department of Health, which disclaims responsibility for any analyses, interpretations or conclusions. NR 41 TC 62 Z9 64 U1 0 U2 17 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD SEP PY 2012 VL 44 IS 9 BP 1040 EP + DI 10.1038/ng.2361 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 001WP UT WOS:000308491200017 PM 22842227 ER PT J AU Feng, JX Liu, T Qin, B Zhang, Y Liu, XS AF Feng, Jianxing Liu, Tao Qin, Bo Zhang, Yong Liu, Xiaole Shirley TI Identifying ChIP-seq enrichment using MACS SO NATURE PROTOCOLS LA English DT Article ID TRANSCRIPTION FACTOR-BINDING; HUMAN GENOME; CHROMATIN-IMMUNOPRECIPITATION; SITES; IDENTIFICATION; TECHNOLOGY; ALIGNMENT; SOFTWARE; BROWSER; LOCI AB Model-based analysis of ChIP-seq (MACS) is a computational algorithm that identifies genome-wide locations of transcription/chromatin factor binding or histone modification from ChIP-seq data. MACS consists of four steps: removing redundant reads, adjusting read position, calculating peak enrichment and estimating the empirical false discovery rate (FDR). In this protocol, we provide a detailed demonstration of how to install MACS and how to use it to analyze three common types of ChIP-seq data sets with different characteristics: the sequence-specific transcription factor FoxA1, the histone modification mark H3K4me3 with sharp enrichment and the H3K36me3 mark with broad enrichment. We also explain how to interpret and visualize the results of MACS analyses. The algorithm requires similar to 3 GB of RAM and 1.5 h of computing time to analyze a ChIP-seq data set containing 30 million reads, an estimate that increases with sequence coverage. MACS is open source and is available from http://liulab.dfci.harvard.edu/MACS/. C1 [Feng, Jianxing; Qin, Bo; Zhang, Yong] Tongji Univ, Sch Life Sci & Technol, Dept Bioinformat, Shanghai 200092, Peoples R China. [Liu, Tao; Liu, Xiaole Shirley] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Zhang, Y (reprint author), Tongji Univ, Sch Life Sci & Technol, Dept Bioinformat, Shanghai 200092, Peoples R China. EM yzhang@tongji.edu.cn; xsliu@jimmy.harvard.edu RI Zhang, Yong/B-4838-2011; Liu, Tao/G-3585-2010; OI Zhang, Yong/0000-0001-6316-2734; Liu, Tao/0000-0002-8818-8313; Liu, Tao/0000-0003-0446-9001 FU National Natural Science Foundation of China [31028011, 31071114]; National Basic Research Program of China (973 Program) [2010CB944904, 2011CB965104]; US National Institutes of Health [HG4069]; Excellent Young Teachers Program of Tongji University [2010KJ041] FX This project was supported by the National Natural Science Foundation of China (31028011 and 31071114); the National Basic Research Program of China (973 Program: 2010CB944904 and 2011CB965104); US National Institutes of Health grant HG4069; and the Excellent Young Teachers Program of Tongji University (2010KJ041). NR 42 TC 183 Z9 185 U1 5 U2 53 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 EI 1750-2799 J9 NAT PROTOC JI Nat. Protoc. PD SEP PY 2012 VL 7 IS 9 BP 1728 EP 1740 DI 10.1038/nprot.2012.101 PG 13 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 002IW UT WOS:000308526300013 PM 22936215 ER PT J AU Karst, AM Drapkin, R AF Karst, Alison M. Drapkin, Ronny TI Primary culture and immortalization of human fallopian tube secretory epithelial cells SO NATURE PROTOCOLS LA English DT Article ID SEROUS OVARIAN CARCINOGENESIS; CANCER; CARCINOMA; SUSCEPTIBILITY; PATHOGENESIS; RETROVIRUS; ORIGIN; MODEL; RISK AB Primary human fallopian tube secretory epithelial cell (FTSEC) cultures are useful for studying normal fallopian tube epithelial biology, as well as for developing models of fallopian tube disease, such as cancer. Because of the limited ability of primary human FTSECs to proliferate in vitro, it is necessary to immortalize them in order to establish a cell line that is suitable for long-term culture and large-scale in vitro experimentation. This protocol describes the isolation of FTSECs from human fallopian tube tissue, conditions for primary FTSEC culture and techniques for establishing immortal FTSEC lines. The entire process, from primary cell isolation to establishment of an immortal cell line, may take up to 2 months. Once established, immortal FTSECs can typically be maintained for at least 30 passages. C1 [Karst, Alison M.; Drapkin, Ronny] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Drapkin, Ronny] Brigham & Womens Hosp, Dept Pathol, Div Womens & Perinatal Pathol, Boston, MA 02115 USA. RP Drapkin, R (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM ronny_drapkin@dfci.harvard.edu RI Drapkin, Ronny/E-9944-2016 OI Drapkin, Ronny/0000-0002-6912-6977 FU Canadian Institutes of Health Research Fellowship; Kaleidoscope of Hope Young Investigator Research Grant; US National Institutes of Health [P50 CA105009]; Ovarian Cancer Research Fund; Robert and Debra First Fund; Randi and Joel Cutler Ovarian Cancer Research Fund; Mary Kay Foundation; Sandy Rollman Ovarian Cancer Foundation; Susan Smith Center for Women's Cancers at the Dana-Farber Cancer Institute FX Special thanks to the faculty and staff of the Brigham and Women's Hospital Department of Pathology for allocation of tissues. This work was supported by a Canadian Institutes of Health Research Fellowship (A.M.K.), a Kaleidoscope of Hope Young Investigator Research Grant (A.M.K.), US National Institutes of Health grant no. P50 CA105009 (SPORE), the Ovarian Cancer Research Fund (R.D.), the Robert and Debra First Fund (R.D.), the Randi and Joel Cutler Ovarian Cancer Research Fund (R.D.), the Mary Kay Foundation (R.D.), the Sandy Rollman Ovarian Cancer Foundation (R.D.) and the Susan Smith Center for Women's Cancers at the Dana-Farber Cancer Institute (R.D.). NR 28 TC 24 Z9 24 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PD SEP PY 2012 VL 7 IS 9 BP 1755 EP 1764 DI 10.1038/nprot.2012.097 PG 10 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 002IW UT WOS:000308526300015 PM 22936217 ER PT J AU Block, K Gorin, Y AF Block, Karen Gorin, Yves TI Aiding and abetting roles of NOX oxidases in cellular transformation SO NATURE REVIEWS CANCER LA English DT Review ID GENERATING NADPH OXIDASE; ADENINE-DINUCLEOTIDE PHOSPHATE; EPIDERMAL-GROWTH-FACTOR; PROSTATE-CANCER CELLS; SMOOTH-MUSCLE-CELLS; MEDIATED TYROSINE PHOSPHORYLATION; ACTIVATE SUPEROXIDE GENERATION; TUMOR-SUPPRESSOR PROTEIN; NON-HODGKIN-LYMPHOMA; REACTIVE OXYGEN AB NADPH oxidases of the NADPH oxidase (NOX) family are dedicated reactive oxygen species-generating enzymes that broadly and specifically regulate redox-sensitive signalling pathways that are involved in cancer development and progression. They act at specific cellular membranes and microdomains through the activation of oncogenes and the inactivation of tumour suppressor proteins. In this Review, we discuss primary targets and redox-linked signalling systems that are influenced by NOX-derived ROS, and the biological role of NOX oxidases in the aetiology of cancer. C1 [Block, Karen] S Texas Vet Hlth Care Syst, Audie L Murphy Mem Hosp Div, Dept Med MC 7882, San Antonio, TX 78229 USA. [Block, Karen; Gorin, Yves] Univ Texas Hlth Sci Ctr San Antonio, Dept Med MC 7882, San Antonio, TX 78229 USA. RP Block, K (reprint author), S Texas Vet Hlth Care Syst, Audie L Murphy Mem Hosp Div, Dept Med MC 7882, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM block@uthscsa.edu OI Gorin, Yves/0000-0003-4048-6925 FU Veterans Administration Career Development Award, NIH [R01 NCI CA131272] FX The authors acknowledge H. E. Abboud, R. A. Clark and R. Li for critical reading of the Review and F. Wauquier for unconditional assistance. Supported by Veterans Administration Career Development Award, NIH R01 NCI CA131272 (K.B.). NR 187 TC 84 Z9 87 U1 1 U2 21 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD SEP PY 2012 VL 12 IS 9 BP 627 EP 637 DI 10.1038/nrc3339 PG 11 WC Oncology SC Oncology GA 998OI UT WOS:000308249400015 PM 22918415 ER PT J AU Silverman, JM Schmeidler, J Beeri, MS Rosendorff, C Sano, M Grossman, HT Carrion-Baralt, JR Bespalova, IN West, R Haroutunian, V AF Silverman, Jeremy M. Schmeidler, James Beeri, Michal S. Rosendorff, Clive Sano, Mary Grossman, Hillel T. Carrion-Baralt, Jose R. Bespalova, Irina N. West, Rebecca Haroutunian, Vahram TI C-reactive protein and familial risk for dementia A phenotype for successful cognitive aging SO NEUROLOGY LA English DT Article ID MINI-MENTAL-STATE; OLDEST-OLD; ALZHEIMER-DISEASE; INFLAMMATORY MARKERS; METABOLIC SYNDROME; HISTORY METHOD; AGE; POPULATION; DECLINE; PLASMA AB Objectives: Identifying phenotypes for successful cognitive aging, intact cognition into late-old age (>age 75), can help identify genes and neurobiological systems that may lead to interventions against and prevention of late-life cognitive impairment. The association of C-reactive protein (CRP) with cognitive impairment and dementia, observed primarily in young-elderly samples, appears diminished or reversed in late-old age (75+ years). A family history study determined if high CRP levels in late-old aged cognitively intact probands are associated with a reduced risk of dementia in their first-degree family members, suggesting a familial successful cognitive aging phenotype. Methods: The primary sample was 1,329 parents and siblings of 277 cognitively intact male veteran probands at least 75 years old. The replication sample was 202 relatives of 51 cognitively intact community-ascertained probands at least 85 years old. Relatives were assessed for dementia by proband informant interview. Their hazard ratio (HR) for dementia as a function of the proband's log-transformed CRP was calculated using the proportional hazards model. Results: Covarying for key demographics, higher CRP in probands was strongly associated with lower risk of dementia in relatives (HR = 0.55 [95% confidence interval (CI) 0.41, 0.74], p < 0.02). The replication sample relationship was in the same direction, stronger in magnitude, and also significant (HR = 0.15 [95% CI 0.06, 0.37], p < 0.0001). Conclusions: Relatives of successful cognitive aging individuals with high levels of CRP are relatively likely to remain free of dementia. High CRP in successful cognitive aging individuals may constitute a phenotype for familial-and thus possibly genetic-successful cognitive aging. Neurology (R) 2012;79:1116-1123 C1 [Silverman, Jeremy M.; Schmeidler, James; Beeri, Michal S.; Sano, Mary; Grossman, Hillel T.; Bespalova, Irina N.; West, Rebecca; Haroutunian, Vahram] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Silverman, Jeremy M.; Beeri, Michal S.; Sano, Mary; Haroutunian, Vahram] Mt Sinai Sch Med, Friedman Brain Inst, New York, NY USA. [Rosendorff, Clive] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Silverman, Jeremy M.; Beeri, Michal S.; Rosendorff, Clive; Sano, Mary; Grossman, Hillel T.; Haroutunian, Vahram] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. [Carrion-Baralt, Jose R.] Univ Puerto Rico, Grad Sch Publ Hlth, Gerontol Program, San Juan, PR 00936 USA. RP Silverman, JM (reprint author), Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. EM jeremy.silverman@mssm.edu FU National Institute of Aging [P01-AG02219, K01-AG023515, K01-AG025203, P50-AG05138]; United States Department of Veterans Affairs; Berkman Charitable Trust; Alzheimer's Association FX National Institute of Aging grants: P01-AG02219, K01-AG023515, K01-AG025203, P50-AG05138; United States Department of Veterans Affairs; Berkman Charitable Trust; and Alzheimer's Association. NR 40 TC 10 Z9 10 U1 2 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 11 BP 1116 EP 1123 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 005JE UT WOS:000308745900029 PM 22895578 ER PT J AU Brashear, A Cook, JF Hill, DF Amponsah, A Snively, BM Light, L Boggs, N Suerken, CK Stacy, M Ozelius, L Sweadner, KJ McCall, WV AF Brashear, Allison Cook, Jared F. Hill, Deborah F. Amponsah, Alethea Snively, Beverly M. Light, Laney Boggs, Niki Suerken, Cynthia K. Stacy, Mark Ozelius, Laurie Sweadner, Kathleen J. McCall, W. Vaughn TI Psychiatric disorders in rapid-onset dystonia-parkinsonism SO NEUROLOGY LA English DT Article ID MUTATION CARRIERS; SCALE; RELIABILITY; DEPRESSION AB Objective: Rapid-onset dystonia-parkinsonism (RDP) is caused by a variety of missense mutations in the ATP1A3 gene. Psychiatric comorbidity has been reported, although systematic examination of psychiatric disease in individuals with RDP is lacking. This study examines psychiatric morbidity for 23 patients with RDP in 10 families with family member control subjects and in 3 unrelated patients with RDP, totaling 56 individuals. Methods: Twenty-nine ATP1A3 mutation-positive individuals were examined; 26 exhibited motor symptoms (motor manifesting carrier [MMC]) and 3 did not (nonmotor manifesting carriers [NMC]). Twenty-seven ATP1A3 mutation-negative participants (noncarriers [NC]) were included. Rates of psychiatric illness for patients with RDP and related asymptomatic gene mutation carriers were compared with those for related nonmutation carriers. Outcome measures included the Unified Parkinson's Disease Rating Scale, Burke-Fahn-Marsden Dystonia Rating Scale, Instrumental Activities of Daily Living, Composite International Diagnostic Interview, Structured Clinical Interview for DSM-IV, Hamilton Depression Scale, Hamilton Anxiety Scale, and Yale-Brown Obsessive-Compulsive Scale. Results: NMC participants did not report any history of psychiatric disorder. Findings in MMC and NC groups included anxiety (MMC 48%, NC 41%), mood (MMC 50%, NC 22%), psychotic (MMC 19%, NC 0%), and substance abuse/dependence (MMC 38%, NC 27%). Conclusions: ATP1A3 mutations cause a wide spectrum of motor and nonmotor features. Psychotic symptoms tended to emerge before or concurrent with motor symptom onset, suggesting that this could be another expression of the ATP1A3 gene mutation. Neurology (R) 2012;79:1168-1173 C1 [Brashear, Allison; Cook, Jared F.; Hill, Deborah F.; Amponsah, Alethea] Wake Forest Baptist Hlth, Wake Forest Sch Med, Dept Neurol, Winston Salem, NC USA. [Snively, Beverly M.; Light, Laney; Suerken, Cynthia K.] Wake Forest Baptist Hlth, Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC USA. [Boggs, Niki; McCall, W. Vaughn] Wake Forest Baptist Hlth, Wake Forest Sch Med, Dept Psychiat & Behav Med, Winston Salem, NC USA. [Stacy, Mark] Duke Univ, Sch Med, Duke Hlth, Dept Neurol, Durham, NC USA. [Ozelius, Laurie] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA. [Sweadner, Kathleen J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Brashear, A (reprint author), Wake Forest Baptist Hlth, Wake Forest Sch Med, Dept Neurol, Winston Salem, NC USA. EM abrashea@wakehealth.edu RI Brashear, Allison/G-3853-2015 FU NINDS [5R01-NS058949-04]; Ceregene; IMPAX; Neuraltus; Novartis; Schering-Plough; Parkinson Study Group; Bachmann-Strauss Dystonia; Parkinson Foundation; Dystonia Medical Research Foundation; NIMH; Cephalon; Sealy FX Supported by the NINDS (grant 5R01-NS058949-04 to A.B.).; A. Brashear has salary support from NINDS (this project); performs research for Allergan, Merz USA, and Ipsen; and consults for Allergan, Merz USA and Ipsen. Her conflict of interest is being managed by Wake Forest University School of Medicine. J. Cook, D. Hill, A. Amponsah, B. Snively, L. Light, N. Boggs, and C. Suerken receive salary support from NINDS 5R01-NS058949-04. M. Stacy has received a grant/research support from Ceregene, IMPAX, Neuraltus, Novartis, Schering-Plough, and Parkinson Study Group; has acted as a consultant for Allergan, Biogen, GE, Novartis, Osmotica, TEVA, and Synosia; has received honoraria from Allergan, Boeringher-Ingelheim, Novartis, and TEVA; and is also on the Safety Monitoring Board for Biogen and Neurologix. His conflict of interest is being managed by Duke University. He is a consultant on this project. L. Ozelius receives salary support from the NIH [NS046340, NS058949, NS037409, RR026123] and has received previous grant support from the Bachmann-Strauss Dystonia and Parkinson Foundation and The Dystonia Medical Research Foundation. She is a current member of the scientific advisory boards of the National Spasmodic Dysphonia Association and the Benign Essential Blepharospasm Research Foundation and a past member of the scientific advisory boards of the Bachmann-Strauss Dystonia and Parkinson Foundation and The Dystonia Medical Research Foundation. Dr. Ozelius receives royalty payments from Athena Diagnostics related to a patent. Athena has supported one Grand Rounds given by Dr. Ozelius. K. Sweadner has salary support from NINDS (R01 NS050696 [PI] and R01 NS058949 [co-investigator]) and the DoD (PR100747) and has received research support from the Bachmann-Strauss Dystonia and Parkinson Foundation. W. McCall's research has been supported by NIMH, Cephalon, and Sealy. He has been on the speaker's bureau for Merck and Sepracor and is a scientific advisor for Sepracor, Sealy, and Merck. His conflict of interest is being managed by Wake Forest University School of Medicine. Go to Neurology.org for full disclosures. NR 21 TC 25 Z9 26 U1 0 U2 6 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 11 BP 1168 EP 1173 DI 10.1212/WNL.0b013e3182698d6c PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 005JE UT WOS:000308745900036 PM 22933743 ER PT J AU Ginat, DT Martuza, RL AF Ginat, Daniel T. Martuza, Robert L. TI Postoperative imaging of vestibular schwannomas SO NEUROSURGICAL FOCUS LA English DT Article DE vestibular schwannoma; magnetic resonance imaging; computed tomography; postoperative imaging ID HEARING-PRESERVATION SURGERY; SURGICAL-MANAGEMENT; ACOUSTIC NEUROMA; COMPLICATIONS; RADIOSURGERY; SIGNAL; TUMOR AB Symptomatic vestibular schwannomas can be treated with resection (translabyrinthine, retrosigmoid [suboccipital], or middle cranial fossa approaches) or stereotactic radiosurgery. When appropriate, auditory brainstem stimulators can also be implanted in patients with current or impending hearing loss due to bilateral vestibular schwannomas. Imaging plays a prominent role in determining management following these procedures. In this article, the expected postoperative imaging appearances are depicted. The radiological features of complications are also reviewed, including recurrent tumor, fat graft necrosis, CSF leakage, infection, hydrocephalus, cerebral infarction, venous sinus thrombosis, hemorrhage, and temporal lobe and cerebellar contusions. (http://thejns.org/doi/abs/10.3171/2012.6.FOCUS12150) C1 [Ginat, Daniel T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Martuza, Robert L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. RP Ginat, DT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM ginatd01@gmail.com NR 26 TC 5 Z9 5 U1 0 U2 2 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 1092-0684 J9 NEUROSURG FOCUS JI Neurosurg. Focus PD SEP PY 2012 VL 33 IS 3 DI 10.3171/2012.6.FOCUS12150 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 003HD UT WOS:000308599400019 PM 22937852 ER PT J AU Jones, D AF Jones, Dorothy TI Realizing the IOM Future of Nursing Research Within Clinical Practice SO NURSING RESEARCH LA English DT Editorial Material C1 [Jones, Dorothy] Boston Coll, Chestnut Hill, MA 02167 USA. [Jones, Dorothy] Massachusetts Gen Hosp, YL Munn Ctr Nursing Res, Boston, MA 02114 USA. RP Jones, D (reprint author), Boston Coll, Chestnut Hill, MA 02167 USA. EM djones9@partners.org NR 1 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-6562 J9 NURS RES JI Nurs. Res. PD SEP-OCT PY 2012 VL 61 IS 5 BP 315 EP 315 DI 10.1097/NNR.0b013e31826e1666 PG 1 WC Nursing SC Nursing GA 003HK UT WOS:000308600400001 PM 22935767 ER PT J AU Tessema, M Yingling, CM Thomas, CL Klinge, DM Bernauer, AM Liu, Y Dacic, S Siegfried, JM Dahlberg, SE Schiller, JH Belinsky, SA AF Tessema, M. Yingling, C. M. Thomas, C. L. Klinge, D. M. Bernauer, A. M. Liu, Y. Dacic, S. Siegfried, J. M. Dahlberg, S. E. Schiller, J. H. Belinsky, S. A. TI SULF2 methylation is prognostic for lung cancer survival and increases sensitivity to topoisomerase-I inhibitors via induction of ISG15 SO ONCOGENE LA English DT Article DE NSCLC; camptothecin; SULF-2; topotecan ID HEPARAN-SULFATE; ORAL TOPOTECAN; PHASE-II; HEPATOCELLULAR-CARCINOMA; PROMOTER METHYLATION; PROTEASOME PATHWAY; ANTITUMOR-ACTIVITY; EXPRESSION; GROWTH; CELLS AB The heparan sulfate 6-O-endosulfatase (SULF2) promotes growth and metastasis of solid tumors. We recently identified that cytosine methylation of the SULF2 promoter is associated with better survival of resected lung adenocarcinoma patients, and now also demonstrates a marginal improvement in survival of advanced non-small cell lung cancer (NSCLC) patients receiving standard chemotherapy (hazard ratio = 0.63, P = 0.07). Subsequent studies focused on investigating the effect of methylation on SULF2 expression and its genome-wide impact. The genes and pathways modulated by epigenetic inactivation of SULF2 and the effects on sensitivity to chemotherapy were characterized in vitro and in vivo. Silencing SULF2 through small interfering RNA or methylation primarily increased expression of interferon-inducible genes including ISG15, a marker for increased sensitivity to topoisomerase-1 inhibitors such as camptothecin (CPT). NSCLC cell lines with methylated SULF2 (SULF2M) express 60-fold higher ISG15 compared with SULF2 unmethylated (SULF2U) NSCLC cell lines and normal human bronchial epithelial cells. In vitro, SULF2M and high ISG15 (ISG15H)-expressing NSCLC cell lines were 134-fold more sensitive to CPT than SULF2U and low ISG15 (ISG15L)-expressing cell lines. Topotecan, a soluble analog of CPT and FDA-approved anticancer drug, dramatically arrested the growth of SULF2M-ISG15H, but not SULF2U-ISG15L lung tumors in nude mice (P<0.002). Similarly, high ISG15 expression that is comparable to the topotecan (TPT)-sensitive NSCLC cell lines was found in tumors from 25% of NSCLC patients compared with normal lung, indicating a potential to identify and target the most sensitive NSCLC subpopulation for personalized TPT therapy. Oncogene (2012) 31, 4107-4116; doi: 10.1038/onc.2011.577; published online 12 December 2011 C1 [Tessema, M.; Yingling, C. M.; Thomas, C. L.; Klinge, D. M.; Bernauer, A. M.; Liu, Y.; Belinsky, S. A.] LRRI, Lovelace Resp Res Inst, Lung Canc Program, Albuquerque, NM 87108 USA. [Dacic, S.] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA. [Siegfried, J. M.] Univ Pittsburgh, Dept Pharmacol, Pittsburgh, PA 15261 USA. [Dahlberg, S. E.] Dana Farber Canc Inst, Dept Biostat & Comput Biol, Boston, MA 02115 USA. [Schiller, J. H.] Univ Texas SW, Dept Internal Med, Dallas, TX USA. RP Belinsky, SA (reprint author), LRRI, Lovelace Resp Res Inst, Lung Canc Program, 2425 Ridgecrest Dr SE, Albuquerque, NM 87108 USA. EM sbelinsk@LRRI.org FU NIH [R01 ES008801, CA089551, P50 CA090440] FX This study was supported by NIH grants R01 ES008801 and CA089551 to SAB, and P50 CA090440 to JMS. NR 34 TC 16 Z9 17 U1 2 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 37 BP 4107 EP 4116 DI 10.1038/onc.2011.577 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 004NR UT WOS:000308688900003 PM 22158045 ER PT J AU Chang, EW Kobler, JB Yun, SH AF Chang, Ernest W. Kobler, James B. Yun, Seok H. TI Subnanometer optical coherence tomographic vibrography SO OPTICS LETTERS LA English DT Article ID PHASE MICROSCOPY; MOTION; ELASTOGRAPHY AB The ability to quantify and visualize submicrometer-scale oscillatory motions of objects in three dimensions has a wide range of application in acoustics, materials sciences, and medical imaging. Here we demonstrate that volumetric snapshots of rapid periodic motion can be captured using optical coherence tomography (OCT) with subnanometer-scale motion sensitivity and microsecond-scale temporal resolution. This technique, termed OCT vibrography, was applied to generate time-resolved volumetric vibrographs of a miniature drum driven acoustically at several kilohertz. (c) 2012 Optical Society of America C1 [Chang, Ernest W.; Yun, Seok H.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Chang, Ernest W.; Yun, Seok H.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Chang, Ernest W.] Boston Univ, Dept Biomed Engn, Boston, MA 02115 USA. [Kobler, James B.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. RP Yun, SH (reprint author), Harvard Univ, Sch Med, 40 Blossom St, Boston, MA 02114 USA. EM syun@hms.harvard.edu FU National Institutes of Health [P41EB015903, U54CA143837] FX We thank J. J. Rosowski and J. T. Cheng for discussion. This work was funded by the National Institutes of Health (P41EB015903, U54CA143837). NR 16 TC 15 Z9 15 U1 0 U2 7 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD SEP 1 PY 2012 VL 37 IS 17 BP 3678 EP 3680 PG 3 WC Optics SC Optics GA 003GD UT WOS:000308595300068 PM 22940988 ER PT J AU Luskin, KL Cutler, CS Sonis, ST Peterson, DE Treister, NS AF Luskin, K. L. Cutler, C. S. Sonis, S. T. Peterson, D. E. Treister, N. S. TI mTOR inhibitor-associated stomatitis following hematopoietic cell transplantation SO ORAL DISEASES LA English DT Meeting Abstract C1 [Luskin, K. L.] Univ Connecticut, Ctr Hlth, Sch Dent Med SDM, Farmington, CT USA. [Cutler, C. S.; Sonis, S. T.; Treister, N. S.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Peterson, D. E.] Univ Connecticut, Ctr Hlth, Dept Oral Hlth & Diagnost Sci, Farmington, CT 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 1354-523X J9 ORAL DIS JI Oral Dis. PD SEP PY 2012 VL 18 SU 1 SI SI BP 20 EP 20 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 004YX UT WOS:000308718600090 ER PT J AU Palmason, S Stock, S Woo, SB Treister, NS AF Palmason, S. Stock, S. Woo, S. B. Treister, N. S. TI Topical clonazepam solution for the treatment of burning mouth syndrome SO ORAL DISEASES LA English DT Meeting Abstract C1 [Palmason, S.; Woo, S. B.; Treister, N. S.] Brigham & Womens Hosp, Div Oral Med & Dent, Boston, MA 02115 USA. [Palmason, S.; Woo, S. B.; Treister, N. S.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Stock, S.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, 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 1354-523X J9 ORAL DIS JI Oral Dis. PD SEP PY 2012 VL 18 SU 1 SI SI BP 30 EP 30 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 004YX UT WOS:000308718600136 ER PT J AU Villa, A Stock, S Lerman, MA Woo, SB Sonis, ST Treister, NS AF Villa, A. Stock, S. Lerman, M. A. Woo, S. B. Sonis, S. T. Treister, N. S. TI Oral medicine referrals at a hospital-based practice in the United States SO ORAL DISEASES LA English DT Meeting Abstract C1 [Villa, A.; Lerman, M. A.; Woo, S. B.; Sonis, S. T.; Treister, N. S.] Brigham & Womens Hosp, Div Oral Med & Dent, Boston, MA 02115 USA. [Villa, A.; Lerman, M. A.; Woo, S. B.; Sonis, S. T.; Treister, N. S.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Stock, S.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, 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 1354-523X J9 ORAL DIS JI Oral Dis. PD SEP PY 2012 VL 18 SU 1 SI SI BP 31 EP 31 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 004YX UT WOS:000308718600139 ER PT J AU Permaul, P Hoffman, E Fu, CX Sheehan, W Baxi, S Gaffin, J Lane, J Bailey, A King, E Chapman, M Gold, D Phipatanakul, W AF Permaul, Perdita Hoffman, Elaine Fu, Chunxia Sheehan, William Baxi, Sachin Gaffin, Jonathan Lane, Jeffrey Bailey, Ann King, Eva Chapman, Martin Gold, Diane Phipatanakul, Wanda TI Allergens in urban schools and homes of children with asthma SO PEDIATRIC ALLERGY AND IMMUNOLOGY LA English DT Article DE asthma; Can f 1; Fel d 1; indoor allergens; inner city; mouse; Mus m 1; school; SICAS; urban ID INNER-CITY CHILDREN; ION-CHARGING DEVICE; MOUSE ALLERGEN; INDOOR ALLERGENS; ENVIRONMENTAL INTERVENTION; AIRBORNE ALLERGENS; DUST-MITE; EXPOSURE; CAT; DESIGN AB To cite this article: Permaul P, Hoffman E, Fu C, Sheehan W, Baxi S, Gaffin J, Lane J, Bailey A, King E, Chapman M, Gold D, Phipatanakul W. Allergens in urban schools and homes of children with asthma. Pediatr Allergy Immunol 2012: 23: 543549. Abstract Background: Most studies of indoor allergens have focused on the home environment. However, schools may be an important site of allergen exposure for children with asthma. We compared school allergen exposure to home exposure in a cohort of children with asthma. Correlations between settled dust and airborne allergen levels in classrooms were examined. Methods: Settled dust and airborne samples from 12 inner-city schools were analyzed for indoor allergens using multiplex array technology (MARIA). School samples were linked to students with asthma enrolled in the School Inner-City Asthma Study (SICAS). Settled dust samples from students bedrooms were analyzed similarly. Results: From schools, 229 settled dust and 197 airborne samples were obtained. From homes, 118 settled dust samples were obtained. Linear mixed regression models of log-transformed variables showed significantly higher settled dust levels of mouse, cat and dog allergens in schools than homes (545% higher for Mus m 1, estimated absolute difference 0.55 mu g/g, p < 0.0001; 198% higher for Fel d 1, estimated absolute difference 0.13 mu g/g, p = 0.0033; and 144% higher for Can f 1, estimated absolute difference 0.05 mu g/g, p = 0.0008). Airborne and settled dust Mus m 1 levels in classrooms were moderately correlated (r = 0.48; p < 0.0001). There were undetectable to very low levels of cockroach and dust mite allergens in both homes and schools. Conclusion: Mouse allergen levels in schools were substantial. In general, cat and dog allergen levels were low, but detectable, and were higher in schools. Aerosolization of mouse allergen in classrooms may be a significant exposure for students. Further studies are needed to evaluate the effect of indoor allergen exposure in schools on asthma morbidity in students with asthma. C1 [Sheehan, William; Baxi, Sachin; Phipatanakul, Wanda] Childrens Hosp, Div Immunol, Dept Med, Boston, MA 02115 USA. [Permaul, Perdita] Massachusetts Gen Hosp, Dept Pediat, Div Pediat Pulm Allergy & Immunol, Boston, MA 02114 USA. [Permaul, Perdita; Sheehan, William; Baxi, Sachin; Gaffin, Jonathan; Gold, Diane; Phipatanakul, Wanda] Harvard Univ, Sch Med, Boston, MA USA. [Hoffman, Elaine] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Fu, Chunxia; Bailey, Ann; Gold, Diane; Phipatanakul, Wanda] Brigham & Womens Hosp, Channing Lab, Div Resp Epidemiol, Boston, MA 02115 USA. [Gaffin, Jonathan] Childrens Hosp, Dept Med, Div Pulm & Resp Dis, Boston, MA 02115 USA. [Lane, Jeffrey] Sch Facil Management, Boston, MA USA. [King, Eva; Chapman, Martin] Indoor Biotechnol Inc, Charlottesville, VA USA. RP Phipatanakul, W (reprint author), Childrens Hosp, Div Immunol, Dept Med, 300 Longwood Ave, Boston, MA 02115 USA. EM wanda.phipatanakul@childrens.harvard.edu FU Harvard Catalyst/The Harvard Clinical and Translational Science Center (NIH) [UL1 RR 025758]; Harvard University FX This work was conducted with the support from Harvard Catalyst/The Harvard Clinical and Translational Science Center (NIH Award #UL1 RR 025758) and financial contributions from Harvard University and its affiliated academic healthcare centers. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic healthcare centers, the National Center for Research Resources, or the National Institutes of Health. NR 38 TC 34 Z9 35 U1 3 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0905-6157 EI 1399-3038 J9 PEDIAT ALLERG IMM-UK JI Pediatr. Allergy Immunol. PD SEP PY 2012 VL 23 IS 6 BP 543 EP 549 DI 10.1111/j.1399-3038.2012.01327.x PG 7 WC Allergy; Immunology; Pediatrics SC Allergy; Immunology; Pediatrics GA 995VK UT WOS:000308041800008 PM 22672325 ER PT J AU Typpo, KV Tcharmtchi, MH Thomas, EJ Kelly, PA Castillo, LD Singh, H AF Typpo, Katri V. Tcharmtchi, M. Hossein Thomas, Eric J. Kelly, P. Adam Castillo, Leticia D. Singh, Hardeep TI Impact of resident duty hour limits on safety in the intensive care unit: A national survey of pediatric and neonatal intensivists SO PEDIATRIC CRITICAL CARE MEDICINE LA English DT Article DE graduate medical education; intensive care; medical errors; patient safety; pediatrics; resident duty-hours ID EXTENDED WORK SHIFTS; ACCREDITATION-COUNCIL; ATTENDING PHYSICIANS; MEDICAL ERRORS; PATIENT SAFETY; EDUCATION; INTERNS; FACULTY; RISK; PRODUCTIVITY AB Objective: Resident duty-hour regulations potentially shift the workload from resident to attending physicians. We sought to understand how current or future regulatory changes might impact safety in academic pediatric and neonatal intensive care units. Design: Web-based survey. Setting: U.S. academic pediatric and neonatal intensive care units. Subjects: Attending pediatric and neonatal intensivists. Interventions: We evaluated perceptions on four intensive care unit safety-related risk measures potentially affected by current duty-hour regulations: 1) attending physician and resident fatigue; 2) attending physician workload; 3) errors (self-reported rates by attending physicians or perceived resident error rates); and 4) safety culture. We also evaluated perceptions of how these risks would change with further duty-hour restrictions. Measurements and Main Results: We administered our survey between February and April 2010 to 688 eligible physicians, of whom 360 (52.3%) responded. Most believed that resident error rates were unchanged or worse (91.9%) and safety culture was unchanged or worse (84.4%) with current duty-hour regulations. Of respondents, 61.9% believed their own work-hours providing direct patient care increased and 55.8% believed they were more fatigued while providing direct patient care. Most (85.3%) perceived no increase in their own error rates currently, but in the scenario of further reduction in resident duty-hours, over half (53.3%) believed that safety culture would worsen and a significant proportion (40.3%) believed that their own error rates would increase. Conclusions: Pediatric intensivists do not perceive improved patient safety from current resident duty-hour restrictions. Policies to further restrict resident duty-hours should consider unintended consequences of worsening certain aspects of intensive care unit safety. (Pediatr Crit Care Med 2012; 13:578-582) C1 [Typpo, Katri V.; Singh, Hardeep] Baylor Coll Med, Houston VA HSR&D Ctr Excellence, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. [Typpo, Katri V.] Univ Arizona, Hlth Sci Ctr, Dept Pediat, Sect Crit Care Med, Tucson, AZ 85721 USA. [Typpo, Katri V.] Univ Arizona, Dept Pediat, Sect Crit Care Med, Steele Childrens Res Ctr, Tucson, AZ 85721 USA. [Tcharmtchi, M. Hossein] Baylor Coll Med, Dept Pediat, Sect Crit Care Med, Houston, TX 77030 USA. [Thomas, Eric J.] Univ Texas Houston, Mem Herman Ctr Healthcare Qual & Safety, Houston, TX USA. [Thomas, Eric J.] Univ Texas Med Sch Houston, Dept Med, Div Gen Med, Houston, TX USA. [Kelly, P. Adam] Tulane Univ, Sch Med, Dept Med, New Orleans, LA 70112 USA. [Castillo, Leticia D.] Univ Texas Dallas, Dept Pediat, Sect Pediat Crit Care Med, Dallas, TX 75230 USA. RP Typpo, KV (reprint author), Baylor Coll Med, Houston VA HSR&D Ctr Excellence, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. EM ktyppo@email.arizona.edu FU National Institutes of Health K23 career development award [K23CA125585]; Houston VA HSR&D Center of Excellence [HFP90[hyphen]020]; Eunice Kennedy Shriver National Institute of Child Health and Human Development, Improving the Safety and Quality of Pediatric Health Care [1K24HD053771] FX This work was partially supported by a National Institutes of Health K23 career development award (K23CA125585) and in part by the Houston VA HSR&D Center of Excellence (HFP90[hyphen]020) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Improving the Safety and Quality of Pediatric Health Care (1K24HD053771). NR 36 TC 9 Z9 9 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1529-7535 J9 PEDIATR CRIT CARE ME JI Pediatr. Crit. Care Med. PD SEP PY 2012 VL 13 IS 5 BP 578 EP 582 DI 10.1097/PCC.0b013e318241785c PG 5 WC Critical Care Medicine; Pediatrics SC General & Internal Medicine; Pediatrics GA 002NB UT WOS:000308537800022 PM 22614570 ER PT J AU Heit, YI Lancerotto, L Mesteri, I Ackermann, M Navarrete, MF Nguyen, CT Mukundan, S Konerding, MA Del Vecchio, DA Orgill, DP AF Heit, Yvonne I. Lancerotto, Luca Mesteri, Ildiko Ackermann, Maximilian Navarrete, Maria F. Nguyen, Collin T. Mukundan, Srinivasan, Jr. Konerding, Moritz A. Del Vecchio, Daniel A. Orgill, Dennis P. TI External Volume Expansion Increases Subcutaneous Thickness, Cell Proliferation, and Vascular Remodeling in a Murine Model SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID AUTOLOGOUS FAT TRANSPLANTATION; VACUUM-ASSISTED CLOSURE; BREAST RECONSTRUCTION; ADIPOSE-TISSUE; PRE-EXPANSION; AUGMENTATION; LYMPHEDEMA; WOUNDS AB Background: Fat grafting is a powerful tool for soft-tissue reconstruction; however, the science behind recipient bed preparation has not been thoroughly explored. External volume expansion using suction before fat grafting has been used clinically to improve reliability and consistency of graft survival. The authors developed a murine model to investigate the underlying mechanism of external volume expansion. Methods: The authors created an external volume expansion device using a soft-silicone dome connected to a vacuum source (25 mmHg) to treat the dorsum of mice, and the response was compared with treatment with an occlusive dressing. Treated areas were monitored with magnetic resonance imaging. Remodeling of microvasculature was studied with corrosion casting on day 7. Effects on tissue thickness, number of adipocytes, cell proliferation, and blood vessel density were analyzed at 28 days. Results: Macroscopic analysis showed tissue swelling at sites treated with the external volume expansion device by 21 days, without skin damage. On day 28, external volume expansion increased the thickness of the subcutaneous fat layer twofold, consistent with magnetic resonance imaging observations. The proliferation rate in the subcutaneous layer of expansion-treated areas increased twofold, with a net 2.2-fold increase in number of adipocytes in columns; remodeling of the vessels network occurred, with reorientation and increase of vessel diameters shown by corrosion casting and 1.9-fold augmentation of vessels density. Conclusions: External volume expansion applied to mouse integument induces highly proliferative and vascularized subcutaneous tissue. Recipient-site preparation using external volume expansion devices may be a promising tool to enhance cell and tissue engraftment. (Plast. Reconstr. Surg. 130: 541, 2012.) C1 [Orgill, Dennis P.] Brigham & Womens Hosp, Div Plast Surg, Tissue Engn & Wound Healing Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Magdeburg, Dept Plast Aesthet & Hand Surg, Magdeburg, Germany. Univ Padua, Inst Plast Surg, Padua, Italy. Univ Vienna, Clin Inst Pathol, Vienna, Austria. Johannes Gutenberg Univ Mainz, Univ Med Ctr, Inst Funct & Clin Anat, Mainz, Germany. Pontificia Univ Catolica Chile, Dept Surg, Santiago, Chile. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Back Bay Plast Surg, Cambridge, MA 02138 USA. RP Orgill, DP (reprint author), Brigham & Womens Hosp, Div Plast Surg, Tissue Engn & Wound Healing Lab, 75 Francis St, Boston, MA 02115 USA. EM dorgill@partners.org RI Lancerotto, Luca/A-5745-2013; OI Lancerotto, Luca/0000-0002-2908-678X; Orgill, Dennis/0000-0002-8279-7310 NR 26 TC 27 Z9 28 U1 0 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD SEP PY 2012 VL 130 IS 3 BP 541 EP 547 DI 10.1097/PRS.0b013e31825dc04d PG 7 WC Surgery SC Surgery GA 001KB UT WOS:000308458300040 PM 22929239 ER PT J AU Kachadourian, LK Homish, GG Quigley, BM Leonard, KE AF Kachadourian, Lorig K. Homish, Gregory G. Quigley, Brian M. Leonard, Kenneth E. TI Alcohol Expectancies, Alcohol Use, and Hostility as Longitudinal Predictors of Alcohol-Related Aggression SO PSYCHOLOGY OF ADDICTIVE BEHAVIORS LA English DT Article DE alcohol expectancies; alcohol use; violence and aggression; couples ID HUMAN PHYSICAL AGGRESSION; DISPOSITIONAL AGGRESSIVITY; DRINKING PATTERNS; TRAIT ANGER; MEN; CONSUMPTION; MARRIAGE; OTHERS; WOMEN; SELF AB The direct and interactive effects of alcohol expectancies for aggression, dispositional hostility, and heavy alcohol consumption on alcohol-related physical aggression were examined across the first four years of marriage in a sample of 634 newlywed couples. For husbands, alcohol aggression expectancies predicted increases in alcohol-related aggression; across husbands and wives, however, aggression expectancies were not found to interact with hostility or alcohol consumption to predict physical aggression. Consistent with previous research, hostility and alcohol consumption interacted with each other to predict alcohol-related aggression. Specifically, for both husbands and wives high in dispositional hostility, heavy alcohol consumption was positively associated with the occurrence of alcohol-related aggression; for those low in dispositional hostility, however, there was no association between alcohol consumption and alcohol-related aggression. Findings are contrasted with previous longitudinal research on alcohol aggression expectancies and physical aggression in married couples. The article discusses the extent to which findings may vary depending on whether expectancies are assessed in relation to alcohol's effect on one's own behavior versus alcohol's effect on others' behavior. C1 [Kachadourian, Lorig K.; Homish, Gregory G.; Quigley, Brian M.] SUNY Buffalo, Res Inst Addict, Buffalo, NY 14260 USA. [Homish, Gregory G.] SUNY Buffalo, Sch Publ Hlth & Hlth Profess, Dept Community Hlth & Hlth Behav, Buffalo, NY 14260 USA. [Leonard, Kenneth E.] SUNY Buffalo, Sch Med, Dept Psychiat, Buffalo, NY 14260 USA. RP Kachadourian, LK (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, 150 S Huntington Ave, Boston, MA 02130 USA. EM lorig.kachadourian@va.gov FU NIAAA NIH HHS [R37 AA009922, R37-AA009922] NR 48 TC 14 Z9 14 U1 3 U2 15 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0893-164X J9 PSYCHOL ADDICT BEHAV JI Psychol. Addict. Behav. PD SEP PY 2012 VL 26 IS 3 BP 414 EP 422 DI 10.1037/a0025842 PG 9 WC Substance Abuse; Psychology, Multidisciplinary SC Substance Abuse; Psychology GA 005XZ UT WOS:000308784700005 PM 22004128 ER PT J AU Morissette, SB Gulliver, SB Kamholz, BW Spiegel, DA Tiffany, ST Barlow, DH AF Morissette, Sandra B. Gulliver, Suzy Bird Kamholz, Barbara W. Spiegel, David A. Tiffany, Stephen T. Barlow, David H. TI Transdermal Nicotine During Cue Reactivity in Adult Smokers With and Without Anxiety Disorders SO PSYCHOLOGY OF ADDICTIVE BEHAVIORS LA English DT Article DE nicotine; smoking; cue reactivity; anxiety disorders ID POSTTRAUMATIC-STRESS-DISORDER; CURRENT CIGARETTE-SMOKING; WITHDRAWAL SYMPTOMS; PSYCHIATRIC-DISORDERS; REPLACEMENT THERAPY; TOBACCO DEPENDENCE; UNITED-STATES; CESSATION; ABSTINENCE; QUESTIONNAIRE AB Transdermal nicotine almost doubles tobacco cessation rates; however, little is known about what happens to smokers during the quit process when they are wearing the nicotine patch and are confronted with high-risk smoking triggers. This is particularly important for smokers with psychological disorders who disproportionately represent today's smokers and have more trouble quitting. Using a mixed between- and within-subjects design, smokers with anxiety disorders (n = 61) and smokers without any current Axis I disorders (n = 38) received transdermal nicotine (21 mg) or a placebo patch over two assessment days separated by 48 hr. Urge to smoke was evaluated during a 5-hr patch absorption period (reflecting general smoking deprivation) and during imaginal exposure to theoretically high-risk triggers containing smoking cues, anxiety cues, both, or neutral cues. No differences were observed between smokers with and without anxiety disorders. Significant Patch X Time and Patch X Cue Content interactions were found. Both patch conditions experienced an increase in urge during the deprivation period, but postabsorption urge was significantly higher in the placebo condition, suggesting that transdermal nicotine attenuated the degree to which urge to smoke increased over time. During the cue reactivity trials, when participants received the nicotine patch, they experienced significantly lower urge in response to both smoking-only and neutral cues, but not when anxiety cues were present (alone or in combination with smoking cues). These data suggest that transdermal nicotine alleviates urge only under certain circumstances and that adjunctive interventions are likely necessary to address smoking urges in response to spikes in distress among smokers trying to quit. C1 [Morissette, Sandra B.; Gulliver, Suzy Bird; Kamholz, Barbara W.] Boston Healthcare Syst, Vet Affairs, Boston, MA USA. [Morissette, Sandra B.; Gulliver, Suzy Bird; Kamholz, Barbara W.; Spiegel, David A.; Barlow, David H.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Spiegel, David A.; Barlow, David H.] Boston Univ, Ctr Anxiety & Related Disorders, Boston, MA 02215 USA. [Tiffany, Stephen T.] SUNY Buffalo, Dept Psychol, Buffalo, NY 14260 USA. RP Morissette, SB (reprint author), Vet Affairs VISN 17 Ctr Excellence Res Returning, 4800 Mem Dr,151C, Waco, TX 76711 USA. EM Sandra.Morissette@va.gov FU NIDA NIH HHS [K23 DA016376, DA016376] NR 54 TC 2 Z9 2 U1 1 U2 3 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0893-164X J9 PSYCHOL ADDICT BEHAV JI Psychol. Addict. Behav. PD SEP PY 2012 VL 26 IS 3 BP 507 EP 518 DI 10.1037/a0028828 PG 12 WC Substance Abuse; Psychology, Multidisciplinary SC Substance Abuse; Psychology GA 005XZ UT WOS:000308784700016 PM 22686966 ER PT J AU Ginat, DT Singh, AD Moonis, G AF Ginat, Daniel T. Singh, Arun D. Moonis, Gul TI MULTIMODALITY IMAGING OF HYDROGEL SCLERAL BUCKLES SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article DE scleral buckle; MRI; CT; complications; hydrogel ID LONG-TERM COMPLICATIONS; RETINAL REATTACHMENT SURGERY; FRAGMENTATION; EXOPLANT; EXPLANTS; REMOVAL; IMPLANT; DETACHMENT; EXTRUSION; SILICONE AB Background: Hydrogel scleral buckles were used for treating retinal detachment in the 1980s and early 1990s. However, these devices have a propensity to degrade over time and cause several long-term complications, including hydration and overexpansion, fragmentation, extrusion, intrusion, and intraocular erosion, and the potential to mimic mass lesions. Methods: The imaging features of hydrogel scleral buckles and their complications are reviewed in this article. Results: Radiographic imaging plays an important role in managing patients with complications of hydrogel buckles. Hydrated buckles display attenuation intermediate between fluid and soft tissue on computed tomography, demonstrate approximately fluid signal on magnetic resonance imaging, and are anechoic on ultrasonography. Linear margins and peripheral dystrophic calcification are characteristic. Conclusion: The constellation of imaging features helps distinguish expanded hydrogel buckles from other orbital diseases. Imaging also serves to precisely localize hydrogel scleral buckle components requiring removal. C1 [Ginat, Daniel T.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Singh, Arun D.] Cleveland Clin Fdn, Dept Ophthalmol, Cleveland, OH 44195 USA. [Moonis, Gul] Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02114 USA. RP Ginat, DT (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM ginatd01@gmail.com NR 20 TC 6 Z9 7 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD SEP PY 2012 VL 32 IS 8 BP 1449 EP 1452 DI 10.1097/IAE.0b013e318261a76e PG 4 WC Ophthalmology SC Ophthalmology GA 004HN UT WOS:000308672300003 PM 22791178 ER PT J AU Fawzi, AA Pappuru, RR Sarraf, D Le, PP McCannel, CA Sobrin, L Goldstein, DA Honowitz, S Walsh, AC Sadda, SR Jampol, LM Eliott, D AF Fawzi, Amani A. Pappuru, Rajeev R. Sarraf, David Le, Philip Phuc McCannel, Colin A. Sobrin, Lucia Goldstein, Debra A. Honowitz, Scott Walsh, Alex C. Sadda, Srinivas R. Jampol, Lee M. Eliott, Dean TI ACUTE MACULAR NEURORETINOPATHY Long-Term Insights Revealed by Multimodal Imaging SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; VISUALIZATION; FUNDUS; REFLECTANCE; MACULOPATHY; OCT AB Purpose: To report the structural and functional changes in acute macular neuroretinopathy (AMN) and their long-term evolution. Multimodal retinal imaging was acquired, including Fourier domain optical coherence tomography (OCT), infrared (IR) reflectance, and near IR autofluorescence (NIA). Methods: In this retrospective observational case series, detailed clinical history and multimodal imaging are reported in eight patients with AMN. Manual segmentation of the Fourier domain OCT volume scans was done in one patient with the largest AMN lesion to yield retinal sublayer topographic maps. Results: Two patients were seen within the first 1 to 2 days of symptoms, and both showed outer nuclear and outer plexiform layer hyperreflectivity. Both patients developed enlargement of the lesion over the first week on IR reflectance imaging with a corresponding lateral extension of the outer retinal disruption on Fourier domain OCT. Thinning of the outer nuclear layer persisted in all patients with lesions > 100 mu m width, and in one patient this thinning worsened over the course of follow-up, as noted on the sublayer maps. This structural abnormality correlated with long-term functional deficits, persisting up to 14 months after the initial episode. Infrared reflectance highlights the lesion best, and abnormalities on near IR autofluorescence may be present. Conclusion: Acutemacular neuroretinopathy acutely affects the outer nuclear and plexiform layers manifesting as OCT hyperreflectivity. The hallmark long-term changes are outer nuclear thinning on Fourier domain OCT and a fading dark lesion on IR reflectance imaging. These changes correspond to focal disruption of the outer segment/retinal pigment epithelium junction on OCT, and not the inner segment/outer segment junction, as previously reported. Optical coherence tomography and near IR autofluorescence abnormalities suggest previously unrecognized melanin and retinal pigment epithelium derangements in this condition. RETINA 32:1500-1513, 2012 C1 [Fawzi, Amani A.; Jampol, Lee M.] Northwestern Univ, Dept Ophthalmol, Feinberg Sch Med, Chicago, IL 60611 USA. [Fawzi, Amani A.; Pappuru, Rajeev R.; Le, Philip Phuc; Honowitz, Scott; Walsh, Alex C.; Sadda, Srinivas R.] Univ So Calif, Dept Ophthalmol, Keck Sch Med, Doheny Eye Inst, Los Angeles, CA 90089 USA. [Sarraf, David; McCannel, Colin A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Ophthalmol, Jules Stein Eye Inst, Los Angeles, CA 90095 USA. [Sobrin, Lucia; Eliott, Dean] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. [Goldstein, Debra A.] Univ Illinois, Dept Ophthalmol & Visual Sci, Chicago, IL USA. RP Fawzi, AA (reprint author), Northwestern Univ, Dept Ophthalmol, Feinberg Sch Med, 645 N Michigan Ave,Suite 440, Chicago, IL 60611 USA. EM afawzimd@gmail.com OI McCannel, Colin/0000-0003-0774-6414; fawzi, amani/0000-0002-9568-3558 FU Research to Prevent Blindness, New York, Northwestern University; Research to Prevent Blindness, Inc, NYC (Northwestern University) FX Supported in part by an unrestricted grant from Research to Prevent Blindness, New York, Northwestern University (D.A.G.), an unrestricted grant from Research to Prevent Blindness, Inc, NYC (Northwestern University, L.M.J.), and a grant from Kevin Hitzeman and Mary Dempsey (L.M.J.). NR 29 TC 43 Z9 45 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD SEP PY 2012 VL 32 IS 8 BP 1500 EP 1513 DI 10.1097/IAE.0b013e318263d0c3 PG 14 WC Ophthalmology SC Ophthalmology GA 004HN UT WOS:000308672300010 PM 22846801 ER PT J AU Hayward, CPM Moffat, KA Plumhoff, E Timleck, M Hoffman, S Spitzer, E Van Cott, EM Meijer, P AF Hayward, Catherine P. M. Moffat, Karen A. Plumhoff, Elizabeth Timleck, Marnie Hoffman, Suzanne Spitzer, Ernie Van Cott, Elizabeth M. Meijer, Piet TI External Quality Assessment of Platelet Disorder Investigations: Results of International Surveys on Diagnostic Tests for Dense Granule Deficiency and Platelet Aggregometry Interpretation SO SEMINARS IN THROMBOSIS AND HEMOSTASIS LA English DT Article DE platelet disorders; dense granule deficiency; light transmission platelet aggregometry; electron microscopy; external quality assurance ID LIGHT TRANSMISSION AGGREGOMETRY; BLEEDING DISORDERS; ASSURANCE; LABORATORIES; HEMOSTASIS; GUIDELINES; RELEASE; SAMPLES AB The quality of platelet aggregation and dense granule deficiency testing is important for diagnosing platelet function disorders. After a successful pilot exercise on diagnosing platelet dense granule deficiency by electron microscopy (EM), the North American Specialized Coagulation Laboratory Association (NASCOLA) has launched regular external quality assurance (EQA) for dense granule EM, as well as for the interpretation of platelet aggregation findings. EQA records were analyzed to assess performance. For EM EQA, between 2009 and 2011, there was excellent performance in distinguishing normal from dense granule-deficient samples and good (>70%) agreement on classifying most electron dense structures in platelets. For aggregation EQA, some normal variants were misclassified and overall case interpretations were more acceptable for rare disorders than for common findings. NASCOLA experiences with these EQAs indicate that there is a need to improve the quality of platelet disorder evaluations. For aggregometry interpretations, deficits in performance could be addressed by translating guideline recommendations into practice. C1 [Hayward, Catherine P. M.; Timleck, Marnie] McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON L8S 4K1, Canada. [Hayward, Catherine P. M.; Moffat, Karen A.; Spitzer, Ernie] Special Coagulat Lab, Hamilton Reg Lab Med Program, Hamilton, ON, Canada. [Moffat, Karen A.] McMaster Univ, Dept Med, Hamilton, ON L8S 4K1, Canada. [Plumhoff, Elizabeth] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Hoffman, Suzanne] Univ Wisconsin Hosp & Clin, UWHC Special Coagulat Lab, Madison, WI 53792 USA. [Van Cott, Elizabeth M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. [Meijer, Piet] ECAT Fdn, Leiden, Netherlands. RP Hayward, CPM (reprint author), McMaster Univ, Dept Pathol & Mol Med, 2N29A,1280 Main St W, Hamilton, ON L8S 4K1, Canada. EM haywrdc@mcmaster.ca OI Hayward, Catherine/0000-0002-2843-0817 FU NASCOLA; Heart and Stroke Career Investigator Award FX This work was supported by NASCOLA and a Heart and Stroke Career Investigator Award (C.P.M.H.). We thank members of NASCOLA and ECAT Foundation for their participation in these EQA exercises. NR 28 TC 10 Z9 10 U1 1 U2 2 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0094-6176 J9 SEMIN THROMB HEMOST JI Semin. Thromb. Hemost. PD SEP PY 2012 VL 38 IS 6 BP 622 EP 631 DI 10.1055/s-0032-1319767 PG 10 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 000QH UT WOS:000308401300010 PM 22718255 ER PT J AU Srinivasan, P Westover, MB Bianchi, MT AF Srinivasan, Preethi Westover, M. Brandon Bianchi, Matt T. TI Propagation of Uncertainty in Bayesian Diagnostic Test Interpretation SO SOUTHERN MEDICAL JOURNAL LA English DT Article DE Bayes; decision; sensitivity; specificity; statistics ID CLINICAL DECISION-MAKING; LIKELIHOOD RATIOS; PROBABILITY; DISEASE; UTILITY AB Objectives: Bayesian interpretation of diagnostic test results usually involves point estimates of the pretest probability and the likelihood ratio corresponding to the test result; however, it may be more appropriate in clinical situations to consider instead a range of possible values to express uncertainty in the estimates of these parameters. We thus sought to demonstrate how uncertainty in sensitivity, specificity, and disease pretest probability can be accommodated in Bayesian interpretation of diagnostic testing. Methods: We investigated three questions: How does uncertainty in the likelihood ratio propagate to the posttest probability range, assuming a point estimate of pretest probability? How does uncertainty in the sensitivity and specificity of a test affect uncertainty in the likelihood ratio? How does uncertainty propagate when present in both the pretest probability and the likelihood ratio? Results: Propagation of likelihood ratio uncertainty depends on the pretest probability and is more prominent for unexpected test results. Uncertainty in sensitivity and specificity propagates into the calculation of likelihood ratio prominently as these parameters approach 100%; even modest errors of +/- 10% caused dramatic propagation. Combining errors of +/- 20% in the pretest probability and in the likelihood ratio exhibited modest propagation to posttest probability, suggesting a realistic target range for clinical estimations. Conclusions: The results provide a framework for incorporating ranges of uncertainty into Bayesian reasoning. Although point estimates simplify the implementation of Bayesian reasoning, it is important to recognize the implications of error propagation when ranges are considered in this multistep process. C1 [Bianchi, Matt T.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Northeastern Univ, Bioinformat Dept, Boston, MA 02115 USA. RP Bianchi, MT (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St,Wang 720, Boston, MA 02114 USA. EM mtbianchi@partners.org FU Department of Neurology, Massachusetts General Hospital; Clinical Investigator Training Program: Harvard/Massachusetts Institute of Technology Health Sciences and Technology-Beth Israel Deaconess Medical Center; Pfizer, Inc.; Merck Co. FX M. T. B. received funding from the Department of Neurology, Massachusetts General Hospital, and the Clinical Investigator Training Program: Harvard/Massachusetts Institute of Technology Health Sciences and Technology-Beth Israel Deaconess Medical Center, in collaboration with Pfizer, Inc. and Merck & Co. The other authors have no financial relationships to disclose and no conflicts of interest to report. NR 21 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0038-4348 J9 SOUTH MED J JI South.Med.J. PD SEP PY 2012 VL 105 IS 9 BP 452 EP 459 DI 10.1097/SMJ.0b013e3182621a2c PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 004GM UT WOS:000308669000002 PM 22948322 ER PT J AU LaVela, SL Burns, SP Goldstein, B Miskevics, S Smith, B Weaver, FM AF LaVela, S. L. Burns, S. P. Goldstein, B. Miskevics, S. Smith, B. Weaver, F. M. TI Dysfunctional sleep in persons with spinal cord injuries and disorders SO SPINAL CORD LA English DT Article DE sleep dysfunction; spinal cord injury; prevalence; health behaviors; comorbidities ID APNEA-HYPOPNEA; DURATION; POPULATION; PREVALENCE; QUALITY; WEIGHT AB Study design: Cross-sectional survey of veterans with spinal cord injuries and disorders (SCI/D). Objectives: To describe sleep dysfunction (independent of sleep apnea) in persons with traumatic and non-traumatic SCI/D, and to examine characteristics and health outcomes independently associated with sleep dysfunction unrelated to sleep apnea. Setting: Seven Veterans Affairs SCI care facilities in the United States. Methods: Mailed cross-sectional survey with follow-up calls completed by end of 2008. Bivariate analyses to compare measures outcomes in persons with SCI/D who were dysfunctional sleepers vs those who were not. Multivariate logistic regression used to identify variables independently associated with dysfunctional sleep in veterans with SCI/D. Results: Overall, 49% of the sample had sleep dysfunction unrelated to sleep apnea. In this subgroup, bivariate analyses showed that a greater proportion of dysfunctional sleepers than non-dysfunctional sleepers were current smokers, had problems with drinking alcohol, hypertension, asthma, chronic obstructive pulmonary disease (COPD) and problematic weight gain. Variables independently associated with higher odds of dysfunctional sleep included white race, being a current smoker, problems with drinking alcohol, asthma, COPD and problematic weight gain. Conclusion: Consistent with epidemiological evidence for the general population, we found significant associations of sleep dysfunction with weight gain, smoking, alcohol misuse and select chronic conditions (COPD, asthma). Sustained sleep dysfunction may contribute to health deterioration and mortality, highlighting the need to address the high prevalence of sleep dysfunction (independent of sleep apnea) in persons with SCI/D. In particular, efforts aimed at modifying problematic weight gain, alcohol misuse and smoking are warranted in this cohort to improve sleep. Spinal Cord (2012) 50, 682-685; doi:10.1038/sc.2012.31; published online 17 April 2012 C1 [LaVela, S. L.; Smith, B.; Weaver, F. M.] Hines VA Hosp, Ctr Management Complex Chron Care, Hines, IL 60141 USA. [LaVela, S. L.] Northwestern Univ, Feinberg Sch Med, Inst Healthcare Studies, Chicago, IL 60611 USA. [Burns, S. P.; Goldstein, B.] Spinal Cord Injury Qual Enhancement Improvement I, VA Puget Sound, Seattle, WA USA. [Smith, B.; Weaver, F. M.] Loyola Univ, Stritch Sch Med, Program Hlth Serv Res, Maywood, IL 60153 USA. RP LaVela, SL (reprint author), Hines VA Hosp, Ctr Management Complex Chron Care, 5000 S 5th Ave,151-H, Hines, IL 60141 USA. EM Sherri.LaVela@va.gov FU Office of Research and Development, Health Services Research and Development Service of the Department of Veterans Affairs FX This material is based on work supported by the Office of Research and Development, Health Services Research and Development Service of the Department of Veterans Affairs. This paper reflects only the authors' opinions and does not necessarily reflect the official position of the Department of Veterans Affairs. NR 25 TC 6 Z9 6 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1362-4393 J9 SPINAL CORD JI Spinal Cord PD SEP PY 2012 VL 50 IS 9 BP 682 EP 685 DI 10.1038/sc.2012.31 PG 4 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 004UC UT WOS:000308705600007 PM 22508535 ER PT J AU Bao, Q Zhao, Y Niess, H Conrad, C Schwarz, B Jauch, KW Huss, R Nelson, PJ Bruns, CJ AF Bao, Qi Zhao, Yue Niess, Hanno Conrad, Claudius Schwarz, Bettina Jauch, Karl-Walter Huss, Ralf Nelson, Peter J. Bruns, Christiane J. TI Mesenchymal Stem Cell-Based Tumor-Targeted Gene Therapy in Gastrointestinal Cancer SO STEM CELLS AND DEVELOPMENT LA English DT Review ID VERSUS-HOST-DISEASE; STROMAL CELLS; IN-VITRO; HEPATOCELLULAR-CARCINOMA; CHEMOKINE RECEPTORS; SUICIDE GENE; TRANSGENE EXPRESSION; POTENTIAL PRECURSORS; PANCREATIC-CARCINOMA; ANTITUMOR-ACTIVITY AB Mesenchymal stem (or stromal) cells (MSCs) are nonhematopoietic progenitor cells that can be obtained from bone marrow aspirates or adipose tissue, expanded and genetically modified in vitro, and then used for cancer therapeutic strategies in vivo. Here, we review available data regarding the application of MSC-based tumor-targeted therapy in gastrointestinal cancer, provide an overview of the general history of MSC-based gene therapy in cancer research, and discuss potential problems associated with the utility of MSC-based therapy such as biosafety, immunoprivilege, transfection methods, and distribution in the host. C1 [Bao, Qi; Zhao, Yue; Niess, Hanno; Schwarz, Bettina; Jauch, Karl-Walter; Bruns, Christiane J.] Univ Munich, Dept Surg, D-81377 Munich, Germany. [Bao, Qi] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Plast & Reconstruct Surg, Hangzhou 310003, Zhejiang, Peoples R China. [Conrad, Claudius] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Conrad, Claudius] Harvard Stem Cell Inst, Boston, MA USA. [Huss, Ralf] Apceth GmbH & Co KG, Munich, Germany. [Nelson, Peter J.] Univ Munich, Med Klin & Poliklin 4, Nephrol Zentrum, D-81377 Munich, Germany. [Nelson, Peter J.] Univ Munich, Arbeitsgrp Klin Biochem, D-81377 Munich, Germany. RP Bruns, CJ (reprint author), Univ Munich, Dept Surg, Marchioninistr 15, D-81377 Munich, Germany. EM christiane.bruns@med.uni-muenchen.de NR 85 TC 25 Z9 26 U1 3 U2 27 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1547-3287 J9 STEM CELLS DEV JI Stem Cells Dev. PD SEP 1 PY 2012 VL 21 IS 13 BP 2355 EP 2363 DI 10.1089/scd.2012.0060 PG 9 WC Cell & Tissue Engineering; Hematology; Medicine, Research & Experimental; Transplantation SC Cell Biology; Hematology; Research & Experimental Medicine; Transplantation GA 998UC UT WOS:000308264900003 PM 22530882 ER PT J AU Li, YQ Liu, BL Gu, XS Kochanek, AR Fukudome, EY Liu, ZC Zhao, T Chong, W Zhao, YL Zhang, DN Libermann, TA Alain, HB AF Li, Yongqing Liu, Baoling Gu, Xuesong Kochanek, Ashley R. Fukudome, Eugene Y. Liu, Zhengcai Zhao, Ting Chong, Wei Zhao, Yili Zhang, Dainan Libermann, Towia A. Alain, Hasan B. TI Creating a "pro-survival" phenotype through epigenetic modulation SO SURGERY LA English DT Article; Proceedings Paper CT 7th Annual Academic Surgical Congress CY FEB 14-16, 2012 CL Las Vegas, NV SP Assoc Acad Surg (AAS), Soc Univ Surg (SUS) ID HUMORAL INNATE IMMUNITY; LONG PENTRAXIN PTX3; NF-KAPPA-B; LUNG INJURY; SEPSIS; EXPRESSION; PROTEIN; RECOGNITION; INHIBITION; MANAGEMENT AB Background. We demonstrated recently that treatment with suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibiton improved survival in a rodent model of lipopolysaccharide (LPS)-induced endotoxic shock. The precise mechanisms, however; have not been well-defined. The aim of this study was to investigate the impact of SAHA treatment on gene expression profiles at an early stage of shock. Methods. Male C57BL/6f mice were treated with or without SAHA (50 mg/kg, IP), followed by a lethal dose of LPS (20 mg/kg, IP) and a second dose of SAHA. Lungs of the animals (LPS and SAHA+LPS groups; n = 3 per group) were harvested 3 hours post-LPS insult. Sham mice (no LPS and no SAHA) served as controls. RNA was isolated from the tissues and gene expression was analyzed using Affymatrix microarray (23,000 genes). A lower confidence bound of fold change was determined for comparison of LPS versus SAHA + LPS, and genes with a lower confidence bound of > 2 were considered to be differentially expressed. Reverse transcriptase polymerase chain reaction, Western blotting, and tissue staining were performed to verify the key changes. Network graphs were used to determine gene interaction and biologic relevance. Results. The expression of many genes known to be involved in septic pathophysiology changed after the LPS insult. Interestingly, a number of genes not implicated previously in the septic response were also altered. SAHA treatment attenuated expression of several key genes involved in inflammation. It also decreased neutrophil infiltration in lungs and histologic evidence of acute lung injury. Further analysis confirmed genes engaged in the cellular and humoral arms of the innate immune system were specifically inhibited by SAHA. Gene network analysis identified numerous molecules for the potential development of targeted therapies. Conclusion. Administration of SA HA in a rodent model of LPS shock rapidly modulates gene transcription, with an attenuation of inflammatory mediators derived from both arms (cellular and humoral) of the innate immune system. This may be a novel mechanism responsible for the survival advantage seen with SAHA treatment. (Surgery 2012;152:455-64.) C1 [Li, Yongqing; Liu, Baoling; Kochanek, Ashley R.; Fukudome, Eugene Y.; Liu, Zhengcai; Zhao, Ting; Chong, Wei; Zhao, Yili; Alain, Hasan B.] Massachusetts Gen Hosp, Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. [Gu, Xuesong; Libermann, Towia A.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Genom & Prote Core, Boston, MA 02215 USA. [Liu, Zhengcai] Fourth Mil Med Univ, Dept Hepatobiliary Surg, Xijing Hosp, Xian 710032, Peoples R China. [Chong, Wei] China Med Univ, Emergency Dept, Hosp 1, Shenyang, Peoples R China. [Zhang, Dainan] Xinxiang Med Univ, Affiliated Hosp 1, Xinxiang, Peoples R China. RP Alain, HB (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM hbalam@partners.org OI Libermann, Towia/0000-0002-4006-8179 FU NIGMS NIH HHS [R01 GM084127] NR 31 TC 9 Z9 9 U1 0 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD SEP PY 2012 VL 152 IS 3 BP 455 EP 464 DI 10.1016/j.surg.2012.06.036 PG 10 WC Surgery SC Surgery GA 003PJ UT WOS:000308623500021 PM 22938904 ER PT J AU Cogdill, AP Frederick, DT Cooper, ZA Garber, HR Ferrone, CR Fiedler, A Rosenberg, L Thayer, SP Warshaw, AL Wargo, JA AF Cogdill, Alexandria P. Frederick, Dennie T. Cooper, Zachary A. Garber, Haven R. Ferrone, Cristina R. Fiedler, Amy Rosenberg, Laura Thayer, Sarah P. Warshaw, Andrew L. Wargo, Jennifer A. TI Targeting the MAGE A3 antigen in pancreatic cancer SO SURGERY LA English DT Article ID SECRETING TUMOR VACCINE; ADOPTIVE CELL TRANSFER; IMMUNE ACTIVATION; EXPRESSION; IMMUNOTHERAPY; MELANOMA; REGRESSION; EPITOPES; THERAPY; FAMILY AB Pancreatic cancer is the fourth-leading cause of death in the United States and one of the most aggressive known malignancies. New and innovative advances in treatment are desperately needed. One promising area of investigational treatment for pancreatic cancer involves the use of immunotherapy. The development of immunotherapy for pancreatic cancer has been hampered by difficulty in, generating tumor-reactive lymphocytes from resected specimens and by a lack of appropriate target antigens expressed on tumor cells. Innovative strategies have been developed with the use of peripheral blood lymphocytes that are genetically engineered to express T-cell receptors targeting common tumor antigens, including cancer-testis antigens, such as the MAGE-A3 antigen. Cancer-testis antigens pose excellent targets for immunotherapy because they are expressed in cancer and in the testis, an immune-privileged, site, but have limited expression in normal tissue. An additional advantage in targeting cancer-testis antigens for immunotherapy is that their expression can be selectively up-regulated in tumor cells via epigenetic regulation with chromatin remodeling agents. Current interest in targeting cancer-testis antigens in Pancreatic cancer is well-founded because cancer-testis antigens have been shown to be expressed in, pancreatic cancer as potential targets for therapy. In our studies, we validated the expression pattern of cancer-testis antigens in resected specimens of pancreatic cancer and tested the hypothesis that treatment of pancreatic cancer cells with chromatin remodeling agents would render them more sensitive to antigen-specific T lymphocytes. We focused predominately on the MAGE-A3 antigen because it is highly expressed in pancreatic cancer, and several immunotherapeutic strategies are in clinical trials targeting this specific antigen. The results of these studies have important translational implications and provide the rationale for combined treatment with chromatin remodeling agents and immunotherapeutic approaches for pancreatic cancer (Surgery 2012;152:S13-8.) C1 [Cogdill, Alexandria P.; Frederick, Dennie T.; Cooper, Zachary A.; Garber, Haven R.; Ferrone, Cristina R.; Fiedler, Amy; Rosenberg, Laura; Thayer, Sarah P.; Warshaw, Andrew L.; Wargo, Jennifer A.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Wargo, JA (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St, Boston, MA 02114 USA. EM jwargo@partners.org RI Rosenberg, Laura/C-9145-2014; OI Rosenberg, Laura/0000-0002-1852-3075; Garber, Haven/0000-0002-8221-2167; Cogdill, Alexandria/0000-0001-8917-9462; Cooper, Zachary/0000-0003-1059-0940 FU intramural funds from the Massachusetts General Hospital; Andrew L. Warshaw, MD, Institute for Pancreatic Cancer Research FX Supported by intramural funds from the Massachusetts General Hospital, and the Andrew L. Warshaw, MD, Institute for Pancreatic Cancer Research. NR 26 TC 9 Z9 9 U1 0 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD SEP PY 2012 VL 152 IS 3 SU 1 BP S13 EP S18 DI 10.1016/j.surg.2012.05.031 PG 6 WC Surgery SC Surgery GA 003PK UT WOS:000308623600003 PM 22770803 ER PT J AU Fernandez-del Castillo, C Sarr, MG AF Fernandez-del Castillo, Carlos Sarr, Michael G. TI Andrew L. Warshaw, MD: Modern pioneer of pancreatic surgery SO SURGERY LA English DT Biographical-Item C1 [Fernandez-del Castillo, Carlos; Sarr, Michael G.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Fernandez-del Castillo, C (reprint author), Massachusetts Gen Hosp, Dept Surg, CR15 Parkman St,ACC 460, Boston, MA 02114 USA. EM cfernandez@partners.org NR 1 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD SEP PY 2012 VL 152 IS 3 SU 1 BP S1 EP S3 DI 10.1016/j.surg.2012.05.032 PG 3 WC Surgery SC Surgery GA 003PK UT WOS:000308623600001 PM 22906889 ER PT J AU Fernandez-del Castillo, C Morales-Oyarvide, V McGrath, D Wargo, JA Ferrone, CR Thayer, SP Lillemoe, KD Warshaw, AL AF Fernandez-del Castillo, Carlos Morales-Oyarvide, Vicente McGrath, Deborah Wargo, Jennifer A. Ferrone, Cristina R. Thayer, Sarah P. Lillemoe, Keith D. Warshaw, Andrew L. TI Evolution of the Whipple procedure at the Massachusetts General Hospital SO SURGERY LA English DT Article ID PANCREATIC RESECTION; PANCREATICODUODENECTOMY; COMPLICATIONS; EXPERIENCE; MANAGEMENT; SURGERY; VOLUME AB Background. Since Allen O. Whipple published his seminal paper in 1935, the procedure that bears his name has been performed widely throughout the world and is now a common operation in major medical centers. The goal of this study was to investigate the evolution of pancreatoduodenectomy at the Massachusetts General Hospital (MGH). Methods. We sought to identify all pancreatoduodenectomies performed at the MGH since 1935. Cases were obtained from a computerized database, hospital medical records, and the MGH historical archive. Demographics, diagnosis, intraoperative variables and short-term surgical outcomes were recorded. Results. The first pancreatoduodenectomy at the MGH was carried out in 1941; since then, 2,050 Whipple procedures have been performed. Pancreatic ductal adenocarcinoma was the most frequent indication (36%). Pylorus preservation has been the most important variation in technique, accounting for 45% of Whipple procedures in the 1980s; observation of frequent delayed gastric emptying after this procedure led to decline in its use. Pancreatic fistula was the most frequent complication (13 %). Operative blood replacement and reoperation rates have decreased markedly over time; the most frequent indication for reoperation was intra-abdominal bleeding. Mortality has decreased from 45% to 0.8%, with sepsis and hypovolemic shock being the most frequent causes of death. Mean duration of hospital stay has decreased from > 30 to 9.5 days, along with an increasing readmission rate (currently 19%). Conclusion. The Whipple procedure in the 21st century is a well- established operation. Improvements in operative technique and perioperative care have contributed in making it a safe operation that continues evolving. (Surgery 2012;152:S56-63.) C1 [Fernandez-del Castillo, Carlos; Morales-Oyarvide, Vicente; McGrath, Deborah; Wargo, Jennifer A.; Ferrone, Cristina R.; Thayer, Sarah P.; Lillemoe, Keith D.; Warshaw, Andrew L.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Fernandez-del Castillo, C (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Parkman St,WAC 460, Boston, MA 02114 USA. EM cfernandez@partners.org FU NCI NIH HHS [P01 CA117969] NR 24 TC 31 Z9 31 U1 1 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD SEP PY 2012 VL 152 IS 3 SU 1 BP S56 EP S63 DI 10.1016/j.surg.2012.05.022 PG 8 WC Surgery SC Surgery GA 003PK UT WOS:000308623600008 PM 22770961 ER PT J AU Ferrone, CR Pieretti-Vanmarcke, R Bloom, JP Zheng, H Szymonifka, J Wargo, JA Thayer, SP Lauwers, GY Deshpande, V Mino-Kenudson, M Fernandez-del Castillo, C Lillemoe, KD Warshaw, AL AF Ferrone, Cristina R. Pieretti-Vanmarcke, Rafael Bloom, Jordan P. Zheng, Hui Szymonifka, Jackye Wargo, Jennifer A. Thayer, Sarah P. Lauwers, Gregory Y. Deshpande, Vikram Mino-Kenudson, Mari Fernandez-del Castillo, Carlos Lillemoe, Keith D. Warshaw, Andrew L. TI Pancreatic ductal adenocarcinoma: Long-term survival does not equal cure SO SURGERY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; MESENCHYMAL TRANSITION; ADJUVANT CHEMOTHERAPY; 5-YEAR SURVIVORS; CANCER; RESECTION; GEMCITABINE; MANAGEMENT; CELLS AB Background. Pancreatic ductal adenocarcinoma represents 90% of pancreatic cancers and is an important cause of cancer death in the United States. Operative resection remains as the only treatment providing prolonged survival, but even after a curative resection, 5-year survival rates are low. Our aim was to identify the prognostic factors for long-term survival after resection of pancreatic ductal adenocarcinoma related to patients, treatments, and tumor biology. Methods. Retrospective review identified 959 patients who underwent resection of their pancreatic adenocarcinoma between February 1985 and December 2010, of whom 499 were resected before November 2006 and represent the cohort we describe in this study. Patient, tumor; and treatment-related variables were assessed for their associations with 5- and 10-year overall survival. Results. Of the 499 patients, 49% were female and median age was 65 years. The majority of patients had stage fib disease (60%). Actual 5-year survival after resection of pancreatic adenocarcinoma was 19% (95/499), and actual 10-year survival was 10% (33/329). Significant clinicopathologic factors predicting 5- and 10-year survival were negative margins and negative nodal status. Interestingly, 41% (39/95) of long-term survivors had positive nodes and 24% (23/95) had positive margins. Conclusion. Pancreatic ductal adenocarcinoma demonstrates a very heterogeneous biology, but patients with negative resection margins and node negative cancers are more likely to survive 5 years after resection. However; our series demonstrates that the biology of the cancer rather than simple pathologic factors determine a patient's prognosis. (Surgery 2012;152:S43-9.) C1 [Ferrone, Cristina R.; Pieretti-Vanmarcke, Rafael; Bloom, Jordan P.; Wargo, Jennifer A.; Thayer, Sarah P.; Fernandez-del Castillo, Carlos; Lillemoe, Keith D.; Warshaw, Andrew L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. [Zheng, Hui; Szymonifka, Jackye] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Stat, Boston, MA 02114 USA. [Lauwers, Gregory Y.; Deshpande, Vikram; Mino-Kenudson, Mari] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Ferrone, CR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, 15 Parkman St,WAC 460, Boston, MA 02114 USA. EM cferrone@partners.org FU NCI NIH HHS [P01 CA117969, P50 CA127003] NR 25 TC 54 Z9 56 U1 1 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD SEP PY 2012 VL 152 IS 3 SU 1 BP S43 EP S49 DI 10.1016/j.surg.2012.05.020 PG 7 WC Surgery SC Surgery GA 003PK UT WOS:000308623600006 PM 22763261 ER PT J AU Rosow, DE Liss, AS Strobel, O Fritz, S Bausch, D Valsangkar, NP Alsina, J Kulemann, B Park, JK Yamaguchi, J LaFemina, J Thayer, SP AF Rosow, David E. Liss, Andrew S. Strobel, Oliver Fritz, Stefan Bausch, Dirk Valsangkar, Nakul P. Alsina, Janivette Kulemann, Birte Park, Joo Kyung Yamaguchi, Junpei LaFemina, Jennifer Thayer, Sarah P. TI Sonic Hedgehog in pancreatic cancer: From bench to bedside, then back to the bench SO SURGERY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; STEM-CELLS; SIGNALING PATHWAYS; EPITHELIAL-CELLS; MOUSE MODEL; EXPRESSION; REGENERATION; INHIBITION; THERAPY; DISEASE C1 [Rosow, David E.; Liss, Andrew S.; Strobel, Oliver; Fritz, Stefan; Bausch, Dirk; Valsangkar, Nakul P.; Alsina, Janivette; Kulemann, Birte; Park, Joo Kyung; Yamaguchi, Junpei; LaFemina, Jennifer; Thayer, Sarah P.] Massachusetts Gen Hosp, Dept Surg, Pancreat Biol Lab, Boston, MA 02114 USA. RP Thayer, SP (reprint author), 15 Parkman St,WACC 460, Boston, MA 02114 USA. EM sthayer@partners.org RI YAMAGUCHI, Junpei/E-4440-2015 FU NCI NIH HHS [P01 CA117969, P50 CA127003]; NIDDK NIH HHS [K08 DK071329] NR 70 TC 8 Z9 9 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD SEP PY 2012 VL 152 IS 3 SU 1 BP S19 EP S32 DI 10.1016/j.surg.2012.05.030 PG 14 WC Surgery SC Surgery GA 003PK UT WOS:000308623600004 PM 22770959 ER PT J AU Valsangkar, NP Morales-Oyarvide, V Thayer, SP Ferrone, CR Wargo, JA Warshaw, AL Fernandez-del Castillo, C AF Valsangkar, Nakul P. Morales-Oyarvide, Vicente Thayer, Sarah P. Ferrone, Cristina R. Wargo, Jennifer A. Warshaw, Andrew L. Fernandez-del Castillo, Carlos TI 851 resected cystic tumors of the pancreas: A 33-year experience at the Massachusetts General Hospital SO SURGERY LA English DT Article ID PAPILLARY-MUCINOUS NEOPLASMS; 10-YEAR EXPERIENCE; SINGLE INSTITUTION; LESIONS; MANAGEMENT; FLUID; PREVALENCE AB Background. The objective of this study was to identify trends in the diagnosis and treatment of cystic neoplasms of the pancreas using a retrospective review of patients from a surgical database at an academic referral center during a 33-year period. Methods. Patient characteristics, including demographics, pathology, and survival, were analyzed over 5 time periods between 1978 and 2011. Results. A total of 851 consecutive patients underwent resection for a cystic neoplasm of the pancreas during a 33-year period. Sixty-five percent of patients were female, and mean age was 60 years. The most common pathologic diagnoses were intraductal papillary mucinous neoplasm (38%), mucinous cystic neoplasm (23%), serous cystadenoma (16%), and cystic neuroendocrine neoplasm (7%). There was a stepwise increase in the number of resections across time periods (67 between 1978 and 1989; 376 between 2005 and 2011), with a parallel increase in the proportion of incidentally discovered lesions (22% to 50%). Diagnosis of intraductal papillary mucinous neoplasm was very uncommon in the first 2 time periods (before the first recognition of intraductal papillary mucinous neoplasm as a distinct entity) but predominated in the last 2 (41% and 49%), and cystic neuroendocrine neoplasms, which constituted 3% of the cystic neoplasms in the first time-period, now comprise more than 8% of pancreatic cystic neoplasms. The proportion of malignant neoplasms decreased over time (41% between 1978 and 1989; 12% between 2005 and 2011), reflecting probably the earlier diagnosis and treatment of premalignant neoplasms. Although operative mortality was minimal (4/849, 0.5%), the postoperative complication rate was 38%. Overall 5-year survival for all mucinous lesions was 87%. Conclusion. Cystic neoplasms of the pancreas are being diagnosed and treated with increasing frequency. At present, most are incidentally discovered intraductal papillary mucinous neoplasms. (Surgery 2012;152:S4-12.) C1 [Valsangkar, Nakul P.; Morales-Oyarvide, Vicente; Thayer, Sarah P.; Ferrone, Cristina R.; Wargo, Jennifer A.; Warshaw, Andrew L.; Fernandez-del Castillo, Carlos] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Fernandez-del Castillo, C (reprint author), 15 Parkman St,WAC 460, Boston, MA 02114 USA. EM cfernandez@partners.org FU NCI NIH HHS [P01 CA117969] NR 25 TC 76 Z9 82 U1 0 U2 8 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD SEP PY 2012 VL 152 IS 3 SU 1 BP S4 EP S12 DI 10.1016/j.surg.2012.05.033 PG 9 WC Surgery SC Surgery GA 003PK UT WOS:000308623600002 PM 22770958 ER PT J AU Li, Q Samir, AE AF Li, Qian Samir, Anthony E. TI Echinococcal Cysts of the Liver and Spleen Complex Hepatic and Splenic Cystic Lesions SO ULTRASOUND QUARTERLY LA English DT Editorial Material C1 [Li, Qian; Samir, Anthony E.] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Samir, AE (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, 55 Fruit St, Boston, MA 02114 USA. EM asamir@partners.org OI Samir, Anthony/0000-0002-7801-8724 NR 5 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-8771 J9 ULTRASOUND Q JI Ultrasound Q. PD SEP PY 2012 VL 28 IS 3 BP 205 EP 207 DI 10.1097/RUQ.0b013e318262cd49 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 000FS UT WOS:000308372500010 PM 22902848 ER PT J AU Coursey, CA Casalino, DD Remer, EM Arellano, RS Bishoff, JT Dighe, M Fulgham, P Goldfarb, S Israel, GM Lazarus, E Leyendecker, JR Majd, M Nikolaidis, P Papanicolaou, N Prasad, S Ramchandani, P Sheth, S Vikram, R AF Coursey, Courtney A. Casalino, David D. Remer, Erick M. Arellano, Ronald S. Bishoff, Jay T. Dighe, Manjiri Fulgham, Pat Goldfarb, Stanley Israel, Gary M. Lazarus, Elizabeth Leyendecker, John R. Majd, Massoud Nikolaidis, Paul Papanicolaou, Nicholas Prasad, Srinivasa Ramchandani, Parvati Sheth, Sheila Vikram, Raghunandan TI ACR Appropriateness Criteria (R) Acute Onset Flank Pain-Suspicion of Stone Disease SO ULTRASOUND QUARTERLY LA English DT Article DE Appropriateness Criteria; computed tomography; ultrasound; nephroureterolithiasis; comparative studies ID UNENHANCED HELICAL CT; ACUTE URETERAL OBSTRUCTION; DOSE COMPUTED-TOMOGRAPHY; INTRAVENOUS UROGRAPHY; EXCRETORY UROGRAPHY; URINARY-TRACT; MR UROGRAPHY; DIAGNOSTIC PERFORMANCE; RENAL OBSTRUCTION; ACUTE URETEROLITHIASIS AB Low dose (<3 mSv) noncontrast CT (NCCT) is the imaging study of choice for accurate evaluation of patients with acute onset of flank pain and suspicion of stone disease (sensitivity 97%, specificity 95%). NCCT can reliably characterize the location and size of an offending ureteral calculus, identify complications, and diagnose alternative etiologies of abdominal pain such as appendicitis. By comparison, the sensitivity of radiographs (59%) and ultrasound (24-57%) for the detection of renal and ureteral calculi is relatively poor. Ultrasound can accurately diagnose pelvicaliectasis and ureterectasis, but it may take several hours for these findings to develop. In the pregnant patient, however, ultrasound is a first line test as it does not expose the fetus to ionizing radiation. MR is an accurate test for the diagnosis of pelvicaliectasis and ureterectasis, but is less sensitive than CT for the diagnosis of renal and ureteral calculi. For patients with known stone disease whose stones are visible on radiographs, radiographs are a good tool for post-treatment follow-up. The American College of Radiology Appropriateness Criteria (R) are evidence-based guidelines for specific clinical conditions that are reviewed every two years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. C1 [Coursey, Courtney A.] Emory Univ Hosp, Dept Radiol, Atlanta, GA 30322 USA. [Casalino, David D.; Nikolaidis, Paul] Northwestern Univ, Chicago, IL 60611 USA. [Remer, Erick M.] Cleveland Clin, Cleveland, OH 44106 USA. [Arellano, Ronald S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bishoff, Jay T.] Amer Urol Assoc, Intermt Urol Inst, Murray, UT USA. [Dighe, Manjiri] Univ Washington, Med Ctr, Seattle, WA 98195 USA. [Fulgham, Pat] Presbyterian Med Ctr, Amer Urol Assoc, Dallas, TX USA. [Goldfarb, Stanley] Univ Penn, Sch Med, Amer Soc Nephrol, Philadelphia, PA 19104 USA. [Israel, Gary M.] Yale Univ, Sch Med, New Haven, CT USA. [Lazarus, Elizabeth] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA. [Leyendecker, John R.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. [Majd, Massoud] Childrens Natl Med Ctr, Soc Nucl Med, Washington, DC 20010 USA. [Papanicolaou, Nicholas; Ramchandani, Parvati] Hosp Univ Penn, Philadelphia, PA 19104 USA. [Prasad, Srinivasa; Vikram, Raghunandan] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Sheth, Sheila] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. RP Coursey, CA (reprint author), Emory Univ Hosp, Dept Radiol, 1364 Clifton Rd NE, Atlanta, GA 30322 USA. EM cc766@columbia.edu NR 70 TC 44 Z9 44 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-8771 J9 ULTRASOUND Q JI Ultrasound Q. PD SEP PY 2012 VL 28 IS 3 BP 227 EP 233 DI 10.1097/RUQ.0b013e3182625974 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 000FS UT WOS:000308372500016 PM 22902840 ER PT J AU Ollendorf, DA Blackmore, CC Lee, JM AF Ollendorf, Daniel A. Blackmore, C. Craig Lee, Janie M. TI Toward Evidence-based Decisions in Diagnostic Radiology: A Research and Rating Process for Multiple Decision-makers SO ACADEMIC RADIOLOGY LA English DT Article DE Comparative effectiveness research; evidence-based medicine; diagnostic imaging ID CORONARY-ANGIOGRAPHY; COMPUTED-TOMOGRAPHY; CT COLONOGRAPHY; HEALTH-CARE; PERFORMANCE; SERVICES; DISEASE; TRENDS AB The use of diagnostic imaging tests and the development of evidence-based guidelines, reviews, and other materials have both undergone substantial growth in recent years. However, the proliferation of evidence-based information has not translated into the universal deployment of medical and coverage policy for diagnostic imaging that is similarly evidence-based. One possible reason is the failure of those institutions generating evidence-based information to format findings in an accessible manner for all relevant stakeholders. The Institute for Clinical and Economic Review has developed a simple and transparent method for rating evidence that is accessible to clinicians, patients, payers, and other policy makers. The authors describe this process in relation to three imaging-based examples (computed tomographic colonography, coronary computed tomographic angiography, and positron emission tomography for dementia neuropathology). The issues raised, controversies considered, and use of the ratings in setting policy are discussed in relation to each example. C1 [Ollendorf, Daniel A.] Massachusetts Gen Hosp, Inst Clin & Econ Review, Boston, MA 02114 USA. [Lee, Janie M.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Lee, Janie M.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Blackmore, C. Craig] Virginia Mason Med Ctr, Ctr Hlth Serv Res, Seattle, WA 98101 USA. [Blackmore, C. Craig] Virginia Mason Med Ctr, Dept Radiol, Seattle, WA 98101 USA. RP Ollendorf, DA (reprint author), Massachusetts Gen Hosp, Inst Clin & Econ Review, 101 Merrimac St,10th Floor, Boston, MA 02114 USA. EM dollendorf@icer-review.org FU National Institutes of Health (Bethesda, MD) [K07 CA128816] FX From the Institute for Clinical and Economic Review (D.A.O.) and the Institute for Technology Assessment and Department of Radiology (J.M.L.), Massachusetts General Hospital, 101 Merrimac Street, 10th Floor, Boston, MA 02114; and the Center for Health Services Research and Department of Radiology, Virginia Mason Medical Center, Seattle, WA 98101 (C.C.B.). Received January 27, 2012; accepted April 3, 2012. Dr Lee's participation was supported in part by grant K07 CA128816 from the National Institutes of Health (Bethesda, MD). Address correspondence to: D.A.O. e-mail: dollendorf@icer-review.org NR 32 TC 5 Z9 5 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD SEP PY 2012 VL 19 IS 9 BP 1049 EP 1054 DI 10.1016/j.acra.2012.04.009 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 993MR UT WOS:000307864300002 PM 22727624 ER PT J AU Blashill, AJ Gordon, JR Safren, SA AF Blashill, Aaron J. Gordon, Janna R. Safren, Steven A. TI Appearance Concerns and Psychological Distress Among HIV-Infected Individuals with Injection Drug Use Histories: Prospective Analyses SO AIDS PATIENT CARE AND STDS LA English DT Article ID QUALITY-OF-LIFE; BODY-IMAGE; HAART ADHERENCE; ADIPOSE-TISSUE; WEIGHT-LOSS; MEN; LIPODYSTROPHY; DEPRESSION; VALIDATION; IMPACT AB Morphologic alterations in body composition are common among HIV-infected individuals, and these changes are associated with increased appearance concerns. Previous cross-sectional data indicate that appearance concerns among HIV-infected individuals are related to increased levels of psychological distress. However, to date, no known prospective data have been published on these relationships. The purpose of the current study was to address the temporal prediction of appearance concerns on depression and anxiety severity. Data were culled from a prospective, randomized controlled trial of cognitive behavioral therapy for depression and medication adherence in individuals with a history of injection drug use (IDU). Participants were 89 HIV-infected individuals who were randomized to either a cognitive behavioral therapy or treatment as usual condition. Linear mixed-level modeling revealed elevated levels of appearance concerns were prospectively related to increased depression and anxiety, as rated by both clinician-administered and self-report measures. Appearance concerns among depressed, IDU, HIV-infected individuals are associated with changes in psychological distress. Psychosocial interventions should consider the role of appearance as it relates to psychological functioning. C1 [Blashill, Aaron J.; Gordon, Janna R.; Safren, Steven A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Blashill, Aaron J.; Safren, Steven A.] MGH Harvard Med, Dept Psychiat, Boston, MA USA. RP Blashill, AJ (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM ablashill@partners.org FU National Institutes of Health [R01 DA018603, K24 MH094214]; Harvard University Center for AIDS Research/National Institutes of Health [5P30 AI060354-08] FX Funding from this project came from the National Institutes of Health (R01 DA018603 to S.A.S). Some investigator time was supported by the National Institutes of Health (K24 MH094214 to S.A.S.) and the Harvard University Center for AIDS Research/National Institutes of Health (5P30 AI060354-08 to A.J.B.). NR 28 TC 6 Z9 6 U1 1 U2 6 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD SEP PY 2012 VL 26 IS 9 BP 557 EP 561 DI 10.1089/apc.2012.0122 PG 5 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 998GR UT WOS:000308226000008 PM 22792882 ER PT J AU Williams, EC Lapham, GT Hawkins, EJ Rubinsky, AD Morales, LS Young, BA Bradley, KA AF Williams, Emily C. Lapham, Gwen T. Hawkins, Eric J. Rubinsky, Anna D. Morales, Leo S. Young, Bessie A. Bradley, Katharine A. TI Variation in Documented Care for Unhealthy Alcohol Consumption Across Race/Ethnicity in the Department of Veterans Affairs Healthcare System SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Race; Ethnicity; Alcohol; Alcohol Misuse; Healthcare Disparities ID BEHAVIORAL-COUNSELING INTERVENTIONS; ETHNIC DISPARITIES; AUDIT-C; PREVENTIVE-SERVICES; SCREENING-TEST; UNITED-STATES; USE DISORDERS; SUBSTANCE USE; MISUSE; RISK AB Background The VA Healthcare System has made progress implementing evidence-based care for unhealthy alcohol use, but whether there are differences in care across race/ethnicity is unclear. We describe alcohol-related care for 3 racial/ethnic groups among VA outpatients with unhealthy alcohol use. Methods This cross-sectional study utilized secondary quality improvement data collected for the VA Office of Quality and Performance (July 2006 to June 2007) to identify a sample of 9,194 black (n=1,436), Hispanic (n=500), and white (n=7,258) VA outpatients who screened positive for unhealthy alcohol use (AUDIT-C score=4 men; =3 women). Alcohol-related care was defined as medical record documentation of brief intervention (advice or feedback) and/or referral (discussion of or scheduled). Logistic regression models estimated the prevalence of alcohol-related care among black, Hispanic, and white patients after adjustment for sociodemographic characteristics, alcohol use severity, other substance use, and mental health comorbidity. Results Among all eligible patients, 2,903 (32%) had documented alcohol-related care. Adjusted prevalences were 35.3% (95% CI 30.0 to 40.5) for black, 27.3% (95% CI 21.1 to 33.5) for Hispanic, and 28.9% (95% CI 25.5 to 32.3) for white patients. Differences in documented alcohol-related care between all racial/ethnic groups were significant (p-values all<0.05). Conclusions Among VA patients with unhealthy alcohol use, black patients had the highest, and Hispanic the lowest, prevalence of documented alcohol-related care. Future research should evaluate contextual and system-, provider-, or patient-level factors that may attenuate racial/ethnic differences in documented alcohol-related care, as well as whether differences in documented care are associated with differences in outcomes. C1 [Williams, Emily C.; Lapham, Gwen T.; Hawkins, Eric J.; Rubinsky, Anna D.; Bradley, Katharine A.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98101 USA. [Williams, Emily C.; Lapham, Gwen T.; Hawkins, Eric J.; Rubinsky, Anna D.; Young, Bessie A.; Bradley, Katharine A.] Vet Affairs VA Puget Sound Hlth Care Syst, NW Ctr Excellence Hlth Serv Res & Dev, Seattle, WA USA. [Williams, Emily C.; Lapham, Gwen T.; Hawkins, Eric J.; Bradley, Katharine A.] VA Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA 98101 USA. [Williams, Emily C.; Lapham, Gwen T.; Rubinsky, Anna D.; Morales, Leo S.; Young, Bessie A.; Bradley, Katharine A.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Hawkins, Eric J.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Young, Bessie A.] VA Puget Sound Hlth Care Syst, Hosp & Specialty Med Serv, Seattle, WA 98101 USA. [Young, Bessie A.] VA Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA 98101 USA. [Young, Bessie A.; Bradley, Katharine A.] Univ Washington, Dept Med, Seattle, WA USA. [Bradley, Katharine A.] Res Inst, Grp Hlth, Seattle, WA USA. RP Williams, EC (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM emily.williams3@va.gov FU VA Substance Use Disorders Quality Enhancement Research Initiative (SUD QuERI); VA's Northwest Center of Excellence for Health Services Research Development FX The authors gratefully acknowledge India J. Ornelas, PhD, MPH, and David Grembowski, PhD, MA, for critical review of the conceptual framework presented, as well as Stacey Rittmueller, MPH, and Rachel M. Thomas, MPH, for help with manuscript preparation and revision. This study was supported by the VA Substance Use Disorders Quality Enhancement Research Initiative (SUD QuERI) and the VA's Northwest Center of Excellence for Health Services Research & Development. Data for this study came from the VA Office of Quality and Performance. NR 55 TC 15 Z9 15 U1 2 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD SEP PY 2012 VL 36 IS 9 BP 1614 EP 1622 DI 10.1111/j.1530-0277.2012.01761.x PG 9 WC Substance Abuse SC Substance Abuse GA 001BQ UT WOS:000308435200018 PM 22404130 ER PT J AU Koushik, A Spiegelman, D Albanes, D Anderson, KE Bernstein, L van den Brandt, PA Bergkvist, L English, DR Freudenheim, JL Fuchs, CS Genkinger, JM Giles, GG Goldbohm, RA Horn-Ross, PL Mannisto, S McCullough, ML Millen, AE Miller, AB Robien, K Rohan, TE Schatzkin, A Shikany, JM Stolzenberg-Solomon, RZ Willett, WC Wolk, A Ziegler, RG Smith-Warner, SA AF Koushik, Anita Spiegelman, Donna Albanes, Demetrius Anderson, Kristin E. Bernstein, Leslie van den Brandt, Piet A. Bergkvist, Leif English, Dallas R. Freudenheim, Jo L. Fuchs, Charles S. Genkinger, Jeanine M. Giles, Graham G. Goldbohm, R. Alexandra Horn-Ross, Pamela L. Mannisto, Satu McCullough, Marjorie L. Millen, Amy E. Miller, Anthony B. Robien, Kim Rohan, Thomas E. Schatzkin, Arthur Shikany, James M. Stolzenberg-Solomon, Rachael Z. Willett, Walter C. Wolk, Alicja Ziegler, Regina G. Smith-Warner, Stephanie A. TI Intake of Fruits and Vegetables and Risk of Pancreatic Cancer in a Pooled Analysis of 14 Cohort Studies SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Review DE diet; fruit; pancreatic neoplasms; prospective studies; vegetables ID FOOD-FREQUENCY QUESTIONNAIRE; PAST MEDICAL HISTORY; UNITED-STATES; ALCOHOL-CONSUMPTION; REGRESSION-MODELS; MEASUREMENT-ERROR; GLYCEMIC INDEX; LIFE-STYLE; EXOCRINE PANCREAS; DIETARY PATTERNS AB Fruit and vegetable intake may protect against pancreatic cancer, since fruits and vegetables are rich in potentially cancer-preventive nutrients. Most case-control studies have found inverse associations between fruit and vegetable intake and pancreatic cancer risk, although bias due to reporting error cannot be ruled out. In most prospective studies, inverse associations have been weaker and imprecise because of small numbers of cases. The authors examined fruit and vegetable intake in relation to pancreatic cancer risk in a pooled analysis of 14 prospective studies from North America, Europe, and Australia (study periods between 1980 and 2005). Relative risks and 2-sided 95 confidence intervals were estimated separately for the 14 studies using the Cox proportional hazards model and were then pooled using a random-effects model. Of 862,584 men and women followed for 720 years, 2,212 developed pancreatic cancer. The pooled multivariate relative risks of pancreatic cancer per 100-g/day increase in intake were 1.01 (95 confidence interval (CI): 0.99, 1.03) for total fruits and vegetables, 1.01 (95 CI: 0.99, 1.03) for total fruits, and 1.02 (95 CI: 0.99, 1.06) for total vegetables. Associations were similar for men and women separately and across studies. These results suggest that fruit and vegetable intake during adulthood is not associated with a reduced pancreatic cancer risk. C1 [Koushik, Anita] Univ Montreal, Hosp Res Ctr CRCHUM, Montreal, PQ H2W 1V1, Canada. [Koushik, Anita] Univ Montreal, Dept Social & Prevent Med, Fac Med, Montreal, PQ H2W 1V1, Canada. [Spiegelman, Donna; Willett, Walter C.; Smith-Warner, Stephanie A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Spiegelman, Donna] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Spiegelman, Donna; Willett, Walter C.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Spiegelman, Donna; Willett, Walter C.] Harvard Univ, Sch Med, Boston, MA USA. [Albanes, Demetrius; Schatzkin, Arthur; Stolzenberg-Solomon, Rachael Z.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Anderson, Kristin E.; Robien, Kim] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Anderson, Kristin E.; Robien, Kim] Univ Minnesota, Mason Canc Ctr, Minneapolis, MN USA. [Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Div Canc Etiol, Dept Populat Sci, Duarte, CA 91010 USA. [van den Brandt, Piet A.] Maastricht Univ Med Ctr, Dept Epidemiol, GROW Sch Oncol & Dev Biol, Maastricht, Netherlands. [Bergkvist, Leif] Cent Hosp Vasteras, Dept Surg, Vasteras, Sweden. [Bergkvist, Leif] Cent Hosp Vasteras, Clin Res Ctr, Vasteras, Sweden. [English, Dallas R.; Giles, Graham G.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Australia. [English, Dallas R.; Giles, Graham G.] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia. [Freudenheim, Jo L.; Millen, Amy E.] SUNY Buffalo, Dept Social & Prevent Med, Sch Publ Hlth & Hlth Profess, Buffalo, NY 14260 USA. [Fuchs, Charles S.] Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. [Genkinger, Jeanine M.] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY USA. [Goldbohm, R. Alexandra] TNO Qual Life, Dept Prevent & Hlth Care, Leiden, Netherlands. [Horn-Ross, Pamela L.] Canc Prevent Inst Calif, Fremont, CA USA. [Mannisto, Satu] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. [McCullough, Marjorie L.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Miller, Anthony B.] Univ Toronto, Div Epidemiol, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. [Rohan, Thomas E.] Yeshiva Univ, Dept Epidemiol & Populat Hlth, Albert Einstein Coll Med, Bronx, NY USA. [Ziegler, Regina G.] NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Shikany, James M.] Univ Alabama Birmingham, Sch Med, Div Prevent Med, Birmingham, AL USA. [Willett, Walter C.; Smith-Warner, Stephanie A.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Wolk, Alicja] Karolinska Inst, Natl Inst Environm Med, Stockholm, Sweden. RP Koushik, A (reprint author), Univ Montreal, Hosp Res Ctr CRCHUM, 3875 St Urbain St,3rd Floor, Montreal, PQ H2W 1V1, Canada. EM anita.koushik@umontreal.ca RI Albanes, Demetrius/B-9749-2015; OI Mannisto, Satu/0000-0002-8668-3046; Robien, Kim/0000-0002-2120-2280; Giles, Graham/0000-0003-4946-9099; English, Dallas/0000-0001-7828-8188 FU US National Cancer Institute [P01 CA55075]; Canadian Institutes of Health Research FX This work was supported by grant P01 CA55075 from the US National Cancer Institute. Dr. Anita Koushik currently holds a New Investigator Award from the Canadian Institutes of Health Research. NR 81 TC 20 Z9 20 U1 0 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD SEP 1 PY 2012 VL 176 IS 5 BP 373 EP 386 DI 10.1093/aje/kws027 PG 14 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 998GX UT WOS:000308226600002 PM 22875754 ER PT J AU Nelson, CC Li, Y Sorensen, G Berkman, LF AF Nelson, Candace C. Li, Yi Sorensen, Glorian Berkman, Lisa F. TI Assessing the Relationship Between Work-Family Conflict and Smoking SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID TOBACCO USE; SOCIAL DISPARITIES; HEALTH; SPILLOVER; MODEL; ENVIRONMENT; CESSATION; DRINKING; ROLES; INTERFACE AB Objectives. We examined the relationship between smoking and work-family conflict among a sample of New England long-term-care facility workers. Methods. To collect data, we conducted in-person, structured interviews with workers in 4 extended-care facilities. Results. There was a strong association between smoking likelihood and work-family conflict. Workers who experienced both stress at home from work issues (i.e., work-to-home conflict) and stress at work from personal issues (i.e., home-to-work conflict) had 3.1 times higher odds of smoking than those who did not experience these types of conflict. Workers who experienced home-to-work conflict had an odds of 2.3 compared with those who did not experience this type of conflict, and workers who experienced work-to-home conflict had an odds of 1.6 compared with workers who did not experience this type of conflict. Conclusions. The results of this study indicate that there is a robust relationship between work-family conflict and smoking, but that this relationship is dependent upon the total amount of conflict experienced and the direction of the conflict. (Am J Public Health. 2012;102:1767-1772. doi:10.2105/AJPH.2011.300413) C1 [Berkman, Lisa F.] Harvard Ctr Populat & Dev Studies, Cambridge, MA 02138 USA. [Nelson, Candace C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Li, Yi] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA. [Sorensen, Glorian] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. RP Berkman, LF (reprint author), Harvard Ctr Populat & Dev Studies, 9 Bow St, Cambridge, MA 02138 USA. EM lberkman@hsph.harvard.edu FU National Institutes of Health; Center for Disease Control and Prevention (Eunice Kennedy Shriver National Institute of Child Health and Human Development) [U01HD051217, U01HD051218, U01HD051256, U01HD051276]; Center for Disease Control and Prevention (National Institute on Aging) [U01AG027669]; Center for Disease Control and Prevention (Office of Behavioral and Science Sciences Research); Center for Disease Control and Prevention (National Institute for Occupational Safety and Health) [U01OH008788, U01HD059773]; William T. Grant Foundation; Alfred P. Sloan Foundation; Administration for Children and Families FX This research was conducted as part of the Work, Family and Health Network (http://www.WorkFamilyHealthNetwork.org), which is funded by a cooperative agreement through the National Institutes of Health and the Centers for Disease Control and Prevention: Eunice Kennedy Shriver National Institute of Child Health and Human Development (grants U01HD051217, U01HD051218, U01HD051256, U01HD051276); National Institute on Aging (grant U01AG027669); Office of Behavioral and Science Sciences Research, and National Institute for Occupational Safety and Health (grant U01OH008788, U01HD059773). Grants from the William T. Grant Foundation, Alfred P. Sloan Foundation, and the Administration for Children and Families provided additional funding. NR 36 TC 7 Z9 7 U1 4 U2 25 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD SEP PY 2012 VL 102 IS 9 BP 1767 EP 1772 DI 10.2105/AJPH.2011.300413 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 994EJ UT WOS:000307913400023 PM 22720765 ER PT J AU Rodriguez, HP Chen, J Owusu-Edusei, K Suh, A Bekemeier, B AF Rodriguez, Hector P. Chen, Jie Owusu-Edusei, Kwame Suh, Allen Bekemeier, Betty TI Local Public Health Systems and the Incidence of Sexually Transmitted Diseases SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID US LATINO ADULTS; UNITED-STATES; RACIAL/ETHNIC DISPARITIES; INSURANCE-COVERAGE; CARE ACCESS; PARTNERSHIPS; RATES; INFECTIONS; BEHAVIORS; CHLAMYDIA AB Objectives. We examined the associations of local public health system organization and local health department resources with county-level sexually transmitted disease (STD) incidence rates in large US health jurisdictions. Methods. We linked annual county STD incidence data (2005-2008) to local health department director responses (n = 211) to the 2006 wave of the National Longitudinal Study of Local Public Health Systems, the 2005 national Local Health Department Profile Survey, and the Area Resource File. We used nested mixed effects regression models to assess the relative contribution of local public health system organization, local health department financial and resource factors, and sociodemographic factors known to be associated with STD incidence to county-level (n = 307) STD incidence. Results. Jurisdictions with local governing boards had significantly lower county-level STD incidence. Local public health systems with comprehensive services where local health departments shoulder much of the effort had higher county-level STD rates than did conventional systems. Conclusions. More integration of system partners in local public health system activities, through governance and interorganizational arrangements, may reduce the incidence and burden of STDs. (Am J Public Health. 2012;102: 1773-1781. doi:10.2105/AJPH.2011.300497) C1 [Rodriguez, Hector P.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA 90095 USA. [Chen, Jie] CUNY Coll Staten Isl, Dept Polit Sci Econ & Philosophy, Staten Isl, NY USA. [Owusu-Edusei, Kwame] Ctr Dis Control & Prevent, Natl Ctr HIV AIDS Viral Hepatitis STD & TB Preven, Atlanta, GA USA. [Suh, Allen] Vet Affairs Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. [Bekemeier, Betty] Univ Washington, Sch Nursing, Div Psychosocial & Community Hlth, Seattle, WA 98195 USA. RP Rodriguez, HP (reprint author), Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Hlth Policy & Management, 650 Charles E Young Dr S, Los Angeles, CA 90095 USA. EM hrod@ucla.edu FU Center for Public Health Systems and Services Research at the University of Kentucky; Robert Wood Johnson Foundation FX The Center for Public Health Systems and Services Research at the University of Kentucky and the Robert Wood Johnson Foundation funded this research project. NR 64 TC 5 Z9 5 U1 3 U2 10 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD SEP PY 2012 VL 102 IS 9 BP 1773 EP 1781 DI 10.2105/AJPH.2011.300497 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 994EJ UT WOS:000307913400024 PM 22813090 ER PT J AU Moran, CJ Kolman, OK Russell, GJ Brown, IS Mino-Kenudson, M AF Moran, Christopher J. Kolman, Olga K. Russell, Gary J. Brown, Ian S. Mino-Kenudson, Mari TI Neutrophilic Infiltration in Gluten-sensitive Enteropathy Is Neither Uncommon Nor Insignificant Assessment of Duodenal Biopsies From 267 Pediatric and Adult Patients SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE celiac disease; gluten-sensitive enteropathy; neutrophil; lymphocytic gastritis ID INTRAEPITHELIAL LYMPHOCYTE-COUNT; HELICOBACTER-PYLORI INFECTION; CELIAC-DISEASE; RECTAL MUCOSA; GASTROINTESTINAL SYMPTOMS; MORPHOMETRIC-ANALYSIS; VILLOUS ARCHITECTURE; INTESTINAL-MUCOSA; TIME-COURSE; SMALL-BOWEL AB The histologic findings of celiac disease, that is, gluten-sensitive enteropathy (GSE), are dominated by increased intraepithelial lymphocytes, villous blunting, lymphoplasmacytic infiltration of lamina propria, and crypt hyperplasia. To date, neutrophils have not been thought to constitute a significant cell type in GSE, and their presence often invokes consideration of alternative diagnoses. Thus, we sought to determine the prevalence and severity of neutrophilic infiltration in duodenal biopsies from patients with GSE. The degree of neutrophilic infiltration and features characteristic of GSE were assessed in duodenal biopsies from 267 clinically confirmed GSE patients (116 adults and 151 children). These specimens were graded by the disease activity score (DAS) and the neutrophilic activity score (NAS). Gastric antral biopsies obtained from 195 patients were also evaluated for lymphocytic gastritis. NAS was correlated with DAS and other clinicopathologic features. We found that 56% of pediatric and 28% of adult GSE patients had significant duodenal neutrophilia. NAS was higher in children than in adults (2.3 vs. 1.2, P < 0.001). Multivariate regression showed that DAS, eosinophilic infiltration, and foveolar metaplasia correlated positively, and age correlated negatively with NAS. Lymphocytic gastritis was seen in 21.5% of the gastric biopsies. The presence of lymphocytic gastritis correlated positively with NAS and DAS, and in the pediatric population it correlated negatively with age. Significant duodenal neutrophilia is often found in patients with celiac disease, especially in the pediatric population, and is associated with more active disease. Thus, the findings of duodenal neutrophilia in biopsies, otherwise consistent with GSE, should not preclude the diagnosis of GSE. C1 [Kolman, Olga K.; Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Moran, Christopher J.; Russell, Gary J.] Mass Gen Hosp Children, Dept Pediat, Boston, MA USA. [Moran, Christopher J.; Russell, Gary J.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Mino-Kenudson, Mari] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Brown, Ian S.] Sullivan Nicolaides Pathol, Taringa, Qld, Australia. RP Mino-Kenudson, M (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren 122, Boston, MA 02114 USA. EM mminokenudson@partners.org RI Brown, Ian/R-7763-2016 OI Brown, Ian/0000-0001-6329-2547 NR 47 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD SEP PY 2012 VL 36 IS 9 BP 1339 EP 1345 DI 10.1097/PAS.0b013e318254f413 PG 7 WC Pathology; Surgery SC Pathology; Surgery GA 998CF UT WOS:000308214100006 PM 22531172 ER PT J AU Stineman, MG Xie, DW Streim, JE Pan, Q Kurichi, JE Henry-Sanchez, JT Zhang, Z Saliba, D AF Stineman, Margaret G. Xie, Dawei Streim, Joel E. Pan, Qiang Kurichi, Jibby E. Henry-Sanchez, John T. Zhang, Zi Saliba, Debra TI Home Accessibility, Living Circumstances, Stage of Activity Limitation, and Nursing Home Use SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Activities of daily living; Nursing homes; Rehabilitation ID DWELLING OLDER-ADULTS; FUNCTIONAL STATUS; CHRONIC DISEASE; INDEPENDENCE; COMMUNITY; HEALTH; ADMISSION; RISK; INSTITUTIONALIZATION; INTERVENTION AB Stineman MG, Xie D, Streim JE, Pan Q, Kurichi JE, Henry-Sanchez JT, Zhang Z, Saliba D. Home accessibility, living circumstances, stage of activity limitation, and nursing home use. Arch Phys Med Rehabil 2012;93: 1609-16. Objective: To explore the influence of physical home and social environments and disability patterns on nursing home (NH) use. Design: Longitudinal cohort study. Self- or proxy-reported perception of home environmental barriers accessibility, 5 stages expressing the severity and pattern of activities of daily living (ADLs) limitations, and other characteristics at baseline were applied to predict NH use within 2 years or prior to death through logistic regression. Setting: General community. Participants: Population-based, community-dwelling individuals (N=7836; >= 70y) from the Second Longitudinal Study of Aging interviewed in 1994 with 2-year follow-up that was prospectively collected. Interventions: Not applicable. Main Outcome Measure: NH use within 2 years. Results: Perceptions of home environmental barriers and living alone were both associated with approximately 40% increased odds of NH use after adjustment for other factors. Compared with those with no limitations at ADL stage 0, the odds of NH use peaked for those with severe limitations at ADL stage III (odds ratio [OR]=3.12; 95% confidence interval [CI] 2.20-4.41), then declined sharply for those with total limitations at ADL stage IV (OR=.96; 95% CI,.33-2.81). Sensitivity analyses for missing NH use showed similar results. Conclusions: Accessibility of home environment, living circumstance, and ADL stage represent potentially modifiable targets for rehabilitation interventions for decreasing NH use in the aging U.S. population. C1 [Stineman, Margaret G.; Xie, Dawei; Kurichi, Jibby E.; Zhang, Zi] Univ Penn, Dept Biostat & Epidemiol, Ctr Clin Epidemiol & Biostat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Stineman, Margaret G.; Henry-Sanchez, John T.] Univ Penn, Dept Phys Med & Rehabil, Perelman Sch Med, Philadelphia, PA 19104 USA. [Streim, Joel E.] Univ Penn, Geriatr Psychiat Sect, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Streim, Joel E.] Philadelphia VA Med Ctr, VISN Mental Illness Res Educ & Clin Ctr MIRECC 4, Philadelphia, PA USA. [Saliba, Debra] Greater Los Angeles Vet Affairs Geriatr Res Educ, Los Angeles, CA USA. Univ Calif Los Angeles, JH Bonin Ctr Gerontol Res, Los Angeles, CA USA. [Saliba, Debra] RAND Hlth, Santa Monica, CA USA. RP Stineman, MG (reprint author), Univ Penn, Dept Biostat & Epidemiol, Ctr Clin Epidemiol & Biostat, Perelman Sch Med, 904 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM mstinema@exchange.upenn.edu FU National Institutes of Health [AG032420-01A1]; National Institute of Child Health and Human Development National Center for Medical Rehabilitation Research [T32-HD-007425] FX Supported by the National Institutes of Health (grant no. AG032420-01A1) and by a postdoctoral fellowship (no. T32-HD-007425) awarded to the University of Pennsylvania from the National Institute of Child Health and Human Development National Center for Medical Rehabilitation Research. NR 37 TC 8 Z9 8 U1 5 U2 13 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD SEP PY 2012 VL 93 IS 9 BP 1609 EP 1616 DI 10.1016/j.apmr.2012.03.027 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 001IL UT WOS:000308453800014 PM 22484216 ER PT J AU Seifarth, H Schlett, CL Nakano, M Otsuka, F Karolyi, M Liew, G Maurovich-Horvat, P Alkadhi, H Virmani, R Hoffmann, U AF Seifarth, Harald Schlett, Christopher L. Nakano, Masataka Otsuka, Fumiyuki Karolyi, Mihaly Liew, Gary Maurovich-Horvat, Pal Alkadhi, Hatem Virmani, Renu Hoffmann, Udo TI Histopathological correlates of the napkin-ring sign plaque in coronary CT angiography SO ATHEROSCLEROSIS LA English DT Article DE Coronary CT angiography; Vulnerable plaque; Atherosclerosis; Angiogenesis; Calcification ID MULTIDETECTOR COMPUTED-TOMOGRAPHY; OPTICAL COHERENCE TOMOGRAPHY; AMERICAN-HEART-ASSOCIATION; DUAL-SOURCE CT; ATHEROSCLEROTIC PLAQUE; NONINVASIVE ASSESSMENT; VASCULAR-LESIONS; ARTERY PLAQUES; IN-VIVO; CULPRIT AB Objective: The purpose of this study was to identify histologic characteristics of advanced coronary atherosclerotic plaques that are related with the detection of the napkin-ring sign (NRS) in coronary CT angiography (CCTA). Methods: CCTA was performed in 7 human donor hearts. Histological slicing and stainings were performed in 1 mm increments of each major coronary artery. Histology was co-registered with the CT-data and classified according to the modified AHA classification. Results: Advanced plaques (types IV-VI) were present in 139 (23%) of 611 cross sections. Of these 33 (24%) demonstrated an NRS in CCTA. NRS plaques were associated with greater non-core plaque area (median 10.2 vs. 6.4 mm(2), p < 0.01) and larger vessel area (median 17.1 vs. 13.0 mm(2), p < 0.01). The area of the necrotic/lipid core was larger in plaques with NRS (median 1.1 vs. 0.5 mm(2), p = 0.05). Angiogenesis tended to be more frequent in plaques with NRS (48% vs. 30%) whereas micro-calcifications tended to be more frequent in plaques without NRS (27% vs. 46%) (p = 0.06 and 0.07 respectively). In a multivariate analysis, necrotic/lipid core area (OR = 1.9), non-core plaque area (OR = 1.6), and total vessel area (OR = 0.9) independently predicted the appearance of the NRS in coronary CT angiography. Conclusion: Delineation of NRS in CCTA is independently linked to the size of the necrotic/lipid core, the size of the non-core plaque and to the vessel area as measured in histology of advanced coronary atherosclerotic plaques. (c) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Seifarth, Harald; Schlett, Christopher L.; Karolyi, Mihaly; Liew, Gary; Maurovich-Horvat, Pal; Alkadhi, Hatem; Hoffmann, Udo] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Seifarth, Harald; Schlett, Christopher L.; Karolyi, Mihaly; Liew, Gary; Maurovich-Horvat, Pal; Alkadhi, Hatem; Hoffmann, Udo] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Seifarth, Harald] Univ Munster, Dept Clin Radiol, Munster, Germany. [Nakano, Masataka; Otsuka, Fumiyuki; Virmani, Renu] CV Path Inst Inc, Gaithersburg, MD USA. RP Hoffmann, U (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, 165 Cambridge St, Boston, MA 02114 USA. EM uhoffmann@partners.org OI Maurovich-Horvat, Pal/0000-0003-0885-736X FU GE Healthcare, Milwaukee, Wisconsin; Deutsche Forschungsgemeinschaft [DFG Se 2029/1-1] FX This study was supported by an unrestricted grant from GE Healthcare, Milwaukee, Wisconsin.; Dr. Seifarth was supported by a grant from Deutsche Forschungsgemeinschaft (DFG Se 2029/1-1). NR 30 TC 17 Z9 17 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD SEP PY 2012 VL 224 IS 1 BP 90 EP 96 DI 10.1016/j.atherosclerosis.2012.06.021 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 996IK UT WOS:000308078000014 PM 22771191 ER PT J AU Lee, Y Shin, H Vassy, JL Kim, JT Cho, SI Kang, SM Choi, SH Kim, KW Park, KS Jang, HC Lim, S AF Lee, Yenna Shin, Hayley Vassy, Jason L. Kim, Jin Taek Cho, Sung Il Kang, Seon Mee Choi, Sung Hee Kim, Ki Woong Park, Kyong Soo Jang, Hak Chul Lim, Soo TI Comparison of regional body composition and its relation with cardiometabolic risk between BMI-matched young and old subjects SO ATHEROSCLEROSIS LA English DT Article DE Regional body composition; Cardiometabolic marker; Dual-energy X-ray absorptiometry; Computed tomography ID CORONARY-HEART-DISEASE; BINDING-PROTEIN 4; X-RAY ABSORPTIOMETRY; METABOLIC SYNDROME; ADIPOSE-TISSUE; CARDIOVASCULAR-DISEASE; VISCERAL FAT; ABDOMINAL ADIPOSITY; INSULIN-RESISTANCE; ADIPONECTIN LEVELS AB Objective: Difference in regional body composition between young and old people may be related with differential cardiometabolic risks. We investigated regional body composition in BMI-matched young and old subjects to compare its relation with cardiometabolic risk. Methods: We recruited 1:3 gender- and BMI-matched 86 young subjects (mean age 27.3 +/- 2.9 years) and 258 older subjects (75.6 +/- 8.2 years) from a community. Abdominal visceral (VAT) and subcutaneous adipose tissue (SAT) and muscle area at mid-thigh level were evaluated by computed tomography. Fat depots in the gynoid area and lower extremity were measured by dual energy X-ray absorptiometry. Adiponectin, retinol binding protein-4 (RBP-4), and C-reactive protein (CRP) concentrations, pulse wave velocity (PWV) and ankle-brachial index (ABI) were measured for cardiometabolic risk. Results: VAT was greater in older subjects while SAT was almost the same, resulting in twice higher VAT/SAT ratio in older men and women (1.03 +/- 0.37 and 0.57 +/- 0.18) than younger counterparts (0.55 +/- 0.24 and 0.23 +/- 0.23) (both P < 0.01). Fat mass in the gynoid area and lower extremity was smaller in older subjects than younger subjects. The VAT correlated with adiponectin level negatively and RBP-4 level positively while gynoid fat correlated with them in opposite direction. The CRP levels negatively correlated with mid-thigh muscle in older subjects. Older subjects had higher PWV and lower ABI compared to BMI-matched younger counterparts. Conclusion: In conclusion, older adults in this cohort had increased visceral fat and decreased gynoid and lower extremity fat, along with less muscle mass. These findings may help explain the worse cardiometabolic profiles in the elderly who have the same BMI as the young. Crown Copyright (c) 2012 Published by Elsevier Ireland Ltd. All rights reserved. C1 [Lee, Yenna; Kang, Seon Mee; Choi, Sung Hee; Kim, Ki Woong; Park, Kyong Soo; Jang, Hak Chul; Lim, Soo] Seoul Natl Univ, Coll Med, Seoul, South Korea. [Shin, Hayley] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Vassy, Jason L.] Harvard Univ, Sch Med, Boston, MA USA. [Vassy, Jason L.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Kim, Jin Taek] Eulji Gen Hosp, Dept Internal Med, Seoul, South Korea. [Cho, Sung Il] Seoul Natl Univ, Grad Sch Publ Hlth, Seoul, South Korea. [Kim, Ki Woong] Seoul Natl Univ, Bundang Hosp, Seoul, South Korea. [Lee, Yenna; Kang, Seon Mee; Choi, Sung Hee; Jang, Hak Chul; Lim, Soo] Seoul Natl Univ, Bundang Hosp, Songnam, South Korea. RP Lim, S (reprint author), Seoul Natl Univ, Bundang Hosp, Dept Internal Med, Songnam 463707, South Korea. EM limsoo@snu.ac.kr RI Choi, Sung-hee/J-5689-2012; Jang, Hak Chul/D-9637-2012; Park, Kyong Soo/C-2265-2008; OI Park, Kyong Soo/0000-0003-3597-342X; CHOI, SUNG HEE/0000-0003-0740-8116 FU National Research Foundation grant; Korea government [2006-2005410]; Seoul National University Bundang Hospital [11-2008-029]; Seoul National University Research & Development Business Foundation, Republic of Korea [800-20100050] FX The work was funded by the National Research Foundation grant funded by the Korea government (2006-2005410), Seoul National University Bundang Hospital (11-2008-029) and Seoul National University Research & Development Business Foundation, Republic of Korea (800-20100050). NR 34 TC 10 Z9 10 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD SEP PY 2012 VL 224 IS 1 BP 258 EP 265 DI 10.1016/j.atherosclerosis.2012.07.013 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 996IK UT WOS:000308078000041 PM 22832005 ER PT J AU Tuomela, J Sandholm, J Karihtala, P Ilvesaro, J Vuopala, KS Kauppila, JH Kauppila, S Chen, DQ Pressey, C Harkonen, P Harris, KW Graves, D Auvinen, PK Soini, Y Jukkola-Vuorinen, A Selander, KS AF Tuomela, Johanna Sandholm, Jouko Karihtala, Peeter Ilvesaro, Joanna Vuopala, Katri S. Kauppila, Joonas H. Kauppila, Saila Chen, Dongquan Pressey, Christine Harkonen, Pirkko Harris, Kevin W. Graves, David Auvinen, Paivi K. Soini, Ylermi Jukkola-Vuorinen, Arja Selander, Katri S. TI Low TLR9 expression defines an aggressive subtype of triple-negative breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Toll-like receptor-9; Triple negative; Hypoxia; Invasion; Breast cancer ID TOLL-LIKE RECEPTOR-9; HELICOBACTER-PYLORI; CELLULAR INVASION; PROSTATE-CANCER; POOR-PROGNOSIS; IN-VITRO; HYPOXIA; TUMORS; CELLS; CARCINOMA AB Toll-like receptor-9 (TLR9) is a DNA receptor widely expressed in cancers. Although synthetic TLR9 ligands induce cancer cell invasion in vitro, the role of TLR9 in cancer pathophysiology is unclear. We discovered that low tumor TLR9 expression is associated with significantly shortened disease-specific survival in patients with triple negative but not with ER+ breast cancers. A likely mechanism of this clinical finding involves differential responses to hypoxia. Our pre-clinical studies indicate that while TLR9 expression is hypoxia-regulated, low TLR9 expression has different effects on triple negative and ER+ breast cancer invasion in hypoxia. Hypoxia-induced invasion is augmented by TLR9 siRNA in triple negative, but not in ER+ breast cancer cells. This is possibly due to differential TLR9-regulated TIMP-3 expression, which remains detectable in ER+ cells but disappears from triple-negative TLR9 siRNA cells in hypoxia. Our results demonstrate a novel role for this innate immunity receptor in cancer biology and suggest that TLR9 expression may be a novel marker for triple-negative breast cancer patients who are at a high risk of relapse. Furthermore, these results suggest that interventions or events, which induce hypoxia or down-regulate TLR9 expression in triple-negative breast cancer cells may actually induce their spread. C1 [Tuomela, Johanna; Sandholm, Jouko; Ilvesaro, Joanna; Chen, Dongquan; Pressey, Christine; Harris, Kevin W.; Selander, Katri S.] Univ Alabama Birmingham, Dept Med, Div Hematol Oncol, Birmingham, AL 35294 USA. [Tuomela, Johanna; Sandholm, Jouko; Ilvesaro, Joanna; Chen, Dongquan; Pressey, Christine; Harris, Kevin W.; Graves, David; Selander, Katri S.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Karihtala, Peeter; Jukkola-Vuorinen, Arja] Oulu Univ Hosp, Dept Radiotherapy & Oncol, Oulu, Finland. [Vuopala, Katri S.] Lapland Cent Hosp, Dept Pathol, Rovaniemi, Finland. [Kauppila, Joonas H.; Kauppila, Saila] Oulu Univ Hosp, Dept Pathol, Oulu, Finland. [Kauppila, Joonas H.] Oulu Univ Hosp, Dept Surg, Oulu, Finland. [Kauppila, Joonas H.] Univ Oulu, Dept Anat & Cell Biol, Oulu, Finland. [Harkonen, Pirkko] Univ Turku, Dept Cell Biol & Anat, Turku, Finland. [Harris, Kevin W.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Graves, David] Univ Alabama Birmingham, Dept Chem, Birmingham, AL 35294 USA. [Auvinen, Paivi K.] Kuopio Univ Hosp, Canc Ctr Eastern Finland, Dept Oncol, SF-70210 Kuopio, Finland. [Soini, Ylermi] Univ Eastern Finland, Dept Pathol & Forens Med, Kuopio, Finland. RP Selander, KS (reprint author), Univ Alabama Birmingham, Dept Med, Div Hematol Oncol, SHEL 514,1825 Univ Blvd, Birmingham, AL 35294 USA. EM Katri.Selander@ccc.uab.edu RI Kauppila, Joonas/P-1363-2015; OI Kauppila, Joonas/0000-0001-6740-3726; Tuomela, Johanna/0000-0003-4390-4563 FU Lapland Cultural Foundation; Northern Finnish Duodecim Foundation; Finnish Medical Foundation; Oulu University Scholarship Foundation; Cancer Foundation of Northern Finland; Elsa U. Pardee Foundation; Department of Defense FX This work was funded by grants from the Lapland Cultural Foundation (K. S. V., A.J-V., K.S.S.), Northern Finnish Duodecim Foundation (A.J-V), the Finnish Medical Foundation (P.K.), Oulu University Scholarship Foundation (J.H.K.), Cancer Foundation of Northern Finland (J.H.K.), Elsa U. Pardee Foundation (K.S.S) and Department of Defense (K.S.S., D.G.). NR 41 TC 17 Z9 18 U1 3 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD SEP PY 2012 VL 135 IS 2 BP 481 EP 493 DI 10.1007/s10549-012-2181-7 PG 13 WC Oncology SC Oncology GA 996QU UT WOS:000308108700014 PM 22847512 ER PT J AU Jaff, MR Bates, M Sullivan, T Popma, J Gao, XY Zaugg, M Verta, P AF Jaff, Michael R. Bates, Mark Sullivan, Timothy Popma, Jeffrey Gao, Xingyu Zaugg, Margo Verta, Patrick CA HERCULES Investigators TI Significant reduction in systolic blood pressure following renal artery stenting in patients with uncontrolled hypertension: Results from the HERCULES trial SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE renal artery stenosis; renovascular hypertension; stents ID BALLOON ANGIOPLASTY; STENOSIS; REVASCULARIZATION; THERAPY AB Background: Atherosclerotic renal artery stenosis (ARAS) causes hypertension (HTN) and threatens renal function (RF). The HERCULES Trial is a prospective, multicenter trial of renal stenting in patients with uncontrolled HTN and ARAS evaluating the safety and effectiveness of the RX Herculink Elite Renal Stent System (Abbott Vascular, Santa Clara, CA). Methods: A total of 202 patients (241 total lesions; 78 bilateral lesions) were enrolled between August 2007 and October 2009. The primary endpoint was 9-month binary restenosis determined by duplex ultrasound and/or angiography. Secondary endpoints included changes in blood pressure, antihypertensive medications, and RF between baseline and 9 months. Brain natriuretic peptide (BNP) was measured at baseline, 24 hr and 30 days postprocedure. Results: Mean systolic blood pressure (SBP) at baseline was 162 mm Hg. Nearly 70% of patients were receiving three or more antihypertensive medications (mean 3.4 medications per patient). Baseline serum creatinine was 1.2 +/- 0.4 and 61.5% of subjects had estimated glomerular filtration <60. The restenosis rate was 10.5% at 9 months. The study device, procedure, and clinical success rates were 96.0, 99.2, and 98.0%, respectively. Freedom from major adverse events was 94.8%. At 9 months, the mean SBP significantly decreased (mean 145, paired t test P < 0.0001) after stenting with no change in medications. There was no correlation between SBP reduction and baseline BNP or BNP reduction. Conclusions: HERCULES demonstrates clinically and statistically significant SBP reduction in patients with uncontrolled HTN, low in-stent restenosis, and complication rates. This study highlights that when appropriate patients are selected for renal artery stenting, impressive reductions in blood pressure may be anticipated. Although the magnitude of absolute reduction in SBP was related to baseline SBP, elevated baseline BNP levels were not predictive of reduction in SBP. Further studies for predictors of clinical response following percutaneous renal revascularization are needed. (c) 2012 Wiley Periodicals, Inc. C1 [Jaff, Michael R.] Massachusetts Gen Hosp, Vasc Ctr, Boston, MA 02114 USA. [Bates, Mark] W Virginia Univ, Sch Med, Dept Surg, Charleston Div, Charleston, WV 25304 USA. [Sullivan, Timothy] Abbott NW Hosp, Minneapolis Heart Inst, Minneapolis, MN 55407 USA. [Popma, Jeffrey] Beth Israel Deaconess Med Ctr, Dept Cardiol, Boston, MA 02215 USA. [Gao, Xingyu; Zaugg, Margo; Verta, Patrick] Abbott Vasc, Santa Clara, CA USA. RP Jaff, MR (reprint author), 55 Fruit St, Boston, MA 02114 USA. EM mjaff@partners.org FU Abbott Vascular FX Michael R. Jaff: Non-compensated advisor: Abbott Vascular; Cordis Corporation; Covidien/eV3; Medtronic Vascular Board Member, VIVA Physicians, a 501 c 3 not-for-profit education and research organization (www.vivapvd.com); Mark Bates, MD: Founder, Inventor and Shareholder: Nexeon MedSystems Shareholder, Inventor and Board Member: CeloNova Bio-Sciences; Timothy Sullivan, MD: Research grants, Abbott Vascular; Jeffrey Popma, MD: Research grants, Abbott Vascular; Xingyu Gao, MS: Full-time employee of Abbott Vascular and a shareholder of Abbott Laboratories; Margo Zaugg, RN, BSN: Full-time employee of Abbott Vascular and a shareholder of Abbott Laboratories; Patrick Verta, MS: Full-time employee of Abbott Vascular and a shareholder of Abbott Laboratories. NR 21 TC 33 Z9 35 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD SEP 1 PY 2012 VL 80 IS 3 BP 343 EP 350 DI 10.1002/ccd.24449 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 996JH UT WOS:000308080500003 PM 22511402 ER PT J AU Rodriguez, AE Rodriguez-Granillo, AM Antoniucci, D Mieres, J Fernandez-Pereira, C Rodriguez-Granillo, GA Santaera, O Rubilar, B Palacios, IF Serruys, PW AF Rodriguez, Alfredo E. Rodriguez-Granillo, Alfredo M. Antoniucci, David Mieres, Juan Fernandez-Pereira, Carlos Rodriguez-Granillo, Gaston A. Santaera, Omar Rubilar, Bibiana Palacios, Igor F. Serruys, Patrick W. CA ORAR III Investigators TI Randomized comparison of cost-saving and effectiveness of oral rapamycin plus bare-metal stents with drug-eluting stents: Three-year outcome from the randomized oral rapamycin in Argentina (ORAR) III trial SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE restenosis; percutaneous coronary interventions; drug delivery; thrombosis; complications ID CORONARY-ARTERY-DISEASE; FOLLOW-UP; RESTENOSIS PREVENTION; OFF-LABEL; SIROLIMUS; IMPLANTATION; LESIONS; REGISTRY; REVASCULARIZATION; THROMBOSIS AB Objectives: The Oral Rapamycin in ARgentina (ORAR) III trial is a randomized study comparing a strategy of oral rapamycin (OR) plus bare-metal stent (BMS) versus a strategy of drug-eluting stents (DES) in patients with de novo coronary lesions. The purpose of this study was to assess the 3 years cost-effectiveness outcome of each strategy. Background: OR after BMS has been associated with reduction of target vessel revascularization (TVR) although its value in long-term efficacy in comparison with DES is unknown. Methods: In three hospitals in Buenos Aires, Argentina, 200 patients were randomized to OR plus BMS (n = 100) or DES (n = 100). Primary objectives were costs and effectiveness. Cost analysis included in-hospital and follow-up costs. Safety was defined as the composite of death, myocardial infarction (MI), and stroke. Efficacy was defined as TVR. Results: Baseline characteristics between groups were similar. The 3-year follow-up rate was 99%. Cardiac mortality was 2% and 5% in OR group and DES group, respectively (P = 0.44). The composite of death, MI and stroke rate was 11% in OR group and 20% in DES group (P = 0.078). TVR rate was 14.5% in OR group and 17.6% in DES group (P = 0.50), respectively. Three year cumulative costs were significantly lower in the OR arm as compared to the DES arm (P = 0.0001) and DES strategy did not result cost-effective according to the non-inferiority test. Conclusions: At 3 years follow-up, there were no differences in effectiveness between the two strategies, and DES strategy was not more cost-effective as compared to OR plus BMS. (c) 2011 Wiley Periodicals, Inc. C1 [Rodriguez, Alfredo E.; Mieres, Juan; Fernandez-Pereira, Carlos; Rodriguez-Granillo, Gaston A.; Rubilar, Bibiana] Sanatorio Otamendi, Cardiac Unit, Buenos Aires, DF, Argentina. [Rodriguez, Alfredo E.; Rodriguez-Granillo, Alfredo M.] CECI, Buenos Aires, DF, Argentina. [Antoniucci, David] Careggi Hosp, Florence, Italy. [Santaera, Omar] Clin IMA, Cardiac Unit, Buenos Aires, DF, Argentina. [Palacios, Igor F.] Argentina Soc Cardiac Intervent CACI, Buenos Aires, DF, Argentina. [Palacios, Igor F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Serruys, Patrick W.] Cardialysis, Rotterdam, Netherlands. RP Rodriguez, AE (reprint author), Callao 1441 4B, RA-1112 Buenos Aires, DF, Argentina. EM arodriguez@centroceci.com.ar NR 31 TC 7 Z9 7 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD SEP 1 PY 2012 VL 80 IS 3 BP 385 EP 394 DI 10.1002/ccd.23352 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 996JH UT WOS:000308080500011 PM 22109997 ER PT J AU Bashore, TM Balter, S Barac, A Byrne, JG Cavendish, JJ Chambers, CE Hermiller, JB Kinlay, S Landzberg, JS Laskey, WK McKay, CR Miller, JM Moliterno, DJ Moore, JWM Oliver-McNeil, SM Popma, JJ Tommaso, CL AF Bashore, Thomas M. Balter, Stephen Barac, Ana Byrne, John G. Cavendish, Jeffrey J. Chambers, Charles E. Hermiller, James Bernard, Jr. Kinlay, Scott Landzberg, Joel S. Laskey, Warren K. McKay, Charles R. Miller, Julie M. Moliterno, David J. Moore, John W. M. Oliver-McNeil, Sandra M. Popma, Jeffrey J. Tommaso, Carl L. TI 2012 American college of cardiology foundation/society for cardiovascular angiography and interventions expert consensus document on cardiac catheterization laboratory standards update: American college of cardiology foundation task force on expert consensus documents society of thoracic surgeons society for vascular medicine SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE ACCF expert consensus document; catheter-based coronary interventions; quality assurance; registries C1 [Bashore, Thomas M.] Duke Univ, Med Ctr, Durham, NC 27706 USA. [Balter, Stephen] Columbia Univ, Med Ctr, New York, NY 10027 USA. [Barac, Ana] Washington Hosp Ctr, Cardiac Rehabil Program, Washington, DC 20010 USA. [Byrne, John G.] Vanderbilt Univ Sch Med, Dept Cardiac Surg, Nashville, TN USA. [Cavendish, Jeffrey J.] Kaiser Permanente, San Diego, CA USA. [Chambers, Charles E.] Milton S Hershey Med Ctr, Hershey, PA USA. [Hermiller, James Bernard, Jr.] St Vincent Hosp, St Vincent Med Grp, Worcester, MA 01604 USA. [Kinlay, Scott] VA Boston Healthcare Syst, Boston, MA USA. [Landzberg, Joel S.] UMDNJ, New Brunswick, NJ USA. [McKay, Charles R.] Harbor UCLA Med Ctr, Torrance, CA USA. [Oliver-McNeil, Sandra M.] William Beaumont Hosp, Beaumont, TX USA. [Miller, Julie M.] Johns Hopkins, Baltimore, MD 21218 USA. [Moliterno, David J.] Univ Kentucky, Lexington, KY 40506 USA. [Moore, John W. M.] Univ Calif San Diego, San Diego, CA 92103 USA. [Popma, Jeffrey J.] Beth Israel Deaconess Med Ctr, Boston, MA USA. [Tommaso, Carl L.] Skokie Hosp, Cardiac Catheterizat Lab, Evanston, IL USA. RP Bashore, TM (reprint author), Duke Univ, Med Ctr, Durham, NC 27706 USA. NR 1 TC 5 Z9 5 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD SEP 1 PY 2012 VL 80 IS 3 BP E37 EP E49 DI 10.1002/ccd.24466 PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 996JH UT WOS:000308080500001 PM 22570114 ER PT J AU deFilippi, C Seliger, SL Kelley, W Duh, SH Hise, M Christenson, RH Wolf, M Gaggin, H Januzzi, J AF deFilippi, Christopher Seliger, Stephen L. Kelley, Walter Duh, Show-Hong Hise, Michael Christenson, Robert H. Wolf, Myles Gaggin, Hanna Januzzi, James TI Interpreting Cardiac Troponin Results from High-Sensitivity Assays in Chronic Kidney Disease without Acute Coronary Syndrome SO CLINICAL CHEMISTRY LA English DT Article ID LEFT-VENTRICULAR HYPERTROPHY; STAGE RENAL-DISEASE; CARDIOVASCULAR-DISEASE; SERUM CREATININE; T ASSAY; COMPUTED-TOMOGRAPHY; HEART-FAILURE; CYSTATIN-C; ASSOCIATION; CKD AB BACKGROUND: Quantification and comparison of high-sensitivity (hs) cardiac troponin I (cTnI) and cTnT concentrations in chronic kidney disease (CKD) have not been reported. We examined the associations between hs cTnI and cTnT, cardiovascular disease, and renal function in outpatients with stable CKD. METHODS: Outpatients (n = 148; 16.9% with prior myocardial infarction or coronary revascularization) with an estimated glomerular filtration rate (eGFR) of <60 mL . min(-1). (1.73 m(2))(-1) had serum cTnI (99th percentile of a healthy population = 9.0 ng/L), and cTnT (99th percentile = 14 ng/L) measured with hs assays. Left ventricular ejection fraction (LVEF) and mass were assessed by echocardiography, and coronary artery calcification (CAC) was determined by computed tomography. Renal function was estimated by eGFR and urine albumin/creatinine ratio (UACR). RESULTS: The median (interquartile range) concentrations of cTnI and cTnT were 6.3 (3.4-14.4) ng/L and 17.0 (11.2-31.4) ng/L, respectively; 38 A) and 68% of patients had a cTnI and cTnT above the 99th percentile, respectively. The median CAC score was 80.8 (0.7-308.6), LV mass index was 85 (73-99) g/m(2), and LVEF was 58% (57%-61%). The prevalences of prior coronary disease events, CAC score, and LV mass index were higher with increasing concentrations from both hs cardiac troponin assays (P < 0.05 for all). After adjustment for demographics and risk factors, neither cardiac troponin assay was associated with CAC, but both remained associated with LV mass index as well as eGFR and UACR. CONCLUSIONS: Increased hs cTnI and cTnT concentrations are common in outpatients with stable CKD and are influenced by both underlying cardiac and renal disease. (C) 2012 American Association for Clinical Chemistry C1 [deFilippi, Christopher] Univ Maryland, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21201 USA. [Kelley, Walter; Duh, Show-Hong; Christenson, Robert H.] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA. [Wolf, Myles] Univ Miami, Dept Med, Miami, FL USA. [Gaggin, Hanna; Januzzi, James] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. RP deFilippi, C (reprint author), Univ Maryland, Sch Med, Dept Med, Div Cardiol, G3K63,22 S Greene St, Baltimore, MD 21201 USA. EM cdefilip@medicine.umaryland.edu FU Roche Diagnostics Corporation; Siemens Healthcare Diagnostics; Critical Diagnostics; Thermo Fisher FX Roche Diagnostics Corporation, Siemens Healthcare Diagnostics, Critical Diagnostics, and Thermo Fisher; C. deFilippi, Dade Behring (now Siemens Healthcare Diagnostics). NR 29 TC 42 Z9 44 U1 1 U2 3 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD SEP PY 2012 VL 58 IS 9 BP 1342 EP 1351 DI 10.1373/clinchem.2012.185322 PG 10 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 002WR UT WOS:000308570100013 PM 22791885 ER PT J AU Johansen, KL Zhang, R Huang, YJ Patzer, RE Kutner, NC AF Johansen, Kirsten L. Zhang, Rebecca Huang, Yijian Patzer, Rachel E. Kutner, Nancy C. TI Association of Race and Insurance Type with Delayed Assessment for Kidney Transplantation among Patients Initiating Dialysis in the United States SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CADAVERIC RENAL-TRANSPLANTATION; RACIAL-DIFFERENCES; DISPARITIES; ACCESS; PREFERENCES; RATES AB Background and objectives The extent to which racial and socioeconomic disparities in access to kidney transplantation are related to not being assessed for transplant suitability before or shortly after the time of initiation of dialysis is not known. The aims of this study were to determine whether there were disparities based on race, ethnicity, or type of insurance in delayed assessment for transplantation and whether delayed assessment was associated with lower likelihood of waitlisting and kidney transplantation. Design, setting, participants, & measurements This retrospective cohort study used data from the US Renal Data System and included 426,489 adult patients beginning dialysis in the United States between January 1, 2005 and September 30, 2009 without prior kidney transplant. Results Overall, 12.5% of patients had reportedly not been assessed for transplantation. Patients without private insurance were more likely to be reported as not assessed (multivariable adjusted odds ratio=1.33, 95% confidence interval=1.28-1.40 for Medicaid), with a pronounced racial disparity but no ethnic disparity among patients aged 18 to <35 years (odds ratio=1.27, 95% confidence interval=1.13-1.43; P<0.001 for interaction with age). Not being assessed for transplant around the time of dialysis initiation was associated with lower likelihood of waitlisting in multivariable analysis (hazard ratio=0.59, 95% confidence interval=0.57-0.62 in the first year) and transplantation (hazard ratio=0.46, 95% confidence interval=0.41-0.51 in the first year), especially within the first 2 years. Conclusions Racial and insurance-related disparities in transplant assessment potentially delay transplantation, particularly among younger patients. Clin J Am Soc Nephrol 7: 1490-1497, 2012. doi: 10.2215/CJN.13151211 C1 [Johansen, Kirsten L.] San Francisco VA Med Ctr, Nephrol Sect, San Francisco, CA 94121 USA. [Johansen, Kirsten L.; Zhang, Rebecca; Huang, Yijian; Kutner, Nancy C.] Emory Univ, US Renal Data Syst Rehabil Qual Life Special Stud, Atlanta, GA 30322 USA. [Johansen, Kirsten L.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Patzer, Rachel E.] Emory Univ, Sch Med, Dept Surg, Div Transplantat, Atlanta, GA 30322 USA. RP Johansen, KL (reprint author), San Francisco VA Med Ctr, Nephrol Sect, 111J,4150 Clement St, San Francisco, CA 94121 USA. EM kirsten.johansen@ucsf.edu FU National Institutes of Health Contract [HHSN267200715004C]; NIH Administrative Database Contract [N01-DK-7-5004] FX Sources of support were National Institutes of Health Contract HHSN267200715004C and NIH Administrative Database Contract N01-DK-7-5004. NR 16 TC 31 Z9 31 U1 0 U2 2 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD SEP PY 2012 VL 7 IS 9 BP 1490 EP 1497 DI 10.2215/CJN.13151211 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 002DG UT WOS:000308510600016 PM 22837273 ER PT J AU Scagliotti, GV Novello, S Schiller, JH Hirsh, V Sequist, LV Soria, JC von Pawel, J Schwartz, B Von Roemeling, R Sandler, AB AF Scagliotti, Giorgio V. Novello, Silvia Schiller, Joan H. Hirsh, Vera Sequist, Lecia V. Soria, Jean-Charles von Pawel, Joachim Schwartz, Brian Von Roemeling, Reinhard Sandler, Alan B. TI Rationale and Design of MARQUEE: A Phase III, Randomized, Double-Blind Study of Tivantinib Plus Erlotinib Versus Placebo Plus Erlotinib in Previously Treated Patients With Locally Advanced or Metastatic, Nonsquamous, Non-Small-Cell Lung Cancer SO CLINICAL LUNG CANCER LA English DT Editorial Material DE Epidermal growth factor receptor; Hepatocyte growth factor receptor; MET; Tyrosine kinase inhibitors ID MET; AMPLIFICATION; RESISTANCE; GEFITINIB; EXPRESSION; MUTATIONS; GROWTH; TUMORS AB We present the rationale and design for MARQUEE, a phase III, randomized, double-blind, placebo-controlled study of ARQ 197 plus erlotinib versus placebo plus erlotinib in previously treated subjects with locally advanced or metastatic, nonsquamous, non-small-cell lung cancer (NSCLC). The design of MARQUEE is based on preclinical data, the current understanding of the role of cellular N-methyl-N'-nitroso-guanidine human osteosarcoma (MNNG HOS) transforming gene (MET) in NSCLC, and clinical data from a randomized phase II study. The available evidence suggests that dual inhibition of MET and the epidermal growth factor receptor (EGFR) may overcome resistance to EGFR inhibitors. In the phase II study, the combination of tivantinib plus erlotinib significantly improved progression-free survival (PFS) and overall survival (OS) compared with placebo plus erlotinib in the subset of patients with nonsquamous histology, a population enriched for MET overexpression. The primary endpoint in MARQUEE is OS. Secondary and exploratory objectives include determination of PFS, OS in molecular subgroups (defined by EGFR and KRAS mutation status, amplification or overexpression of MET, and serum hepatocyte growth factor), and safety. All patients will be tested for biomarkers, and the results will provide a wealth of information on the role of tivantinib in treating nonsquamous NSCLC. C1 [Scagliotti, Giorgio V.] Univ Turin, San Luigi Hosp, Dept Clin & Biol Sci, I-10043 Turin, Italy. [Schiller, Joan H.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Hirsh, Vera] McGill Univ, Royal Victoria Hosp, Montreal, PQ H3A 1A1, Canada. [Sequist, Lecia V.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Sequist, Lecia V.] Harvard Univ, Sch Med, Boston, MA USA. [Soria, Jean-Charles] Inst Gustave Roussy, Paris, France. [Soria, Jean-Charles] Univ Paris, F-75252 Paris, France. [von Pawel, Joachim] Asklepios Klinikum Gauting, Munich, Germany. [Schwartz, Brian] ArQule Inc, Woburn, MA USA. [Von Roemeling, Reinhard] Daiichi Sankyo Inc, Parsippany, NJ USA. [Sandler, Alan B.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Scagliotti, GV (reprint author), Univ Turin, San Luigi Hosp, Dept Clin & Biol Sci, Reg Gonzole 10, I-10043 Turin, Italy. EM giorgio.scagliotti@unito.it NR 19 TC 74 Z9 81 U1 0 U2 2 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1525-7304 J9 CLIN LUNG CANCER JI Clin. Lung Cancer PD SEP PY 2012 VL 13 IS 5 BP 391 EP 395 DI 10.1016/j.cllc.2012.01.003 PG 5 WC Oncology SC Oncology GA 998OX UT WOS:000308251200012 PM 22440336 ER PT J AU Preffer, FI AF Preffer, Frederic I. TI Hematopoietic stem cell transplantation therapy and flow cytometry: A long-standing productive and useful relationship SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Preffer, FI (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 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 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD SEP PY 2012 VL 82B IS 5 BP 265 EP 265 DI 10.1002/cyto.b.21037 PG 1 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 001MU UT WOS:000308465600001 ER PT J AU Spitzer, TR Dey, BR Chen, YB Attar, E Ballen, KK AF Spitzer, Thomas R. Dey, Bimalangshu R. Chen, Yi-Bin Attar, Eyal Ballen, Karen K. TI The Expanding Frontier of Hematopoietic Cell Transplantation SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Review ID ACUTE MYELOID-LEUKEMIA; PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; FLOW-CYTOMETRY; CHEMOTHERAPY; GUIDELINES; DIAGNOSIS C1 [Spitzer, Thomas R.; Dey, Bimalangshu R.; Chen, Yi-Bin; Attar, Eyal; Ballen, Karen K.] Massachusetts Gen Hosp, Dept Med, Bone Marrow Transplant Unit, Boston, MA 02114 USA. RP Spitzer, TR (reprint author), Massachusetts Gen Hosp, Dept Med, Bone Marrow Transplant Unit, Boston, MA 02114 USA. EM tspitzer@partners.org NR 18 TC 10 Z9 11 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD SEP PY 2012 VL 82B IS 5 BP 271 EP 279 DI 10.1002/cyto.b.21036 PG 9 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 001MU UT WOS:000308465600004 PM 22865649 ER PT J AU Kelliher, AS Delelys, ME Dillon, LJ Preffer, FI AF Kelliher, Abigail S. Delelys, Michelle E. Dillon, Laura J. Preffer, Frederic I. TI COMPARISON OF BD (TM) STEM CELL ENUMERATION KIT (BD-SCE) WITH CURRENT LABORATORY ISHAGE PROTOCOL STEM CELL ENUMERATION ASSAY SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Meeting Abstract CT 27th Annual Meeting of the International-Clinical-Cytometry-Society CY OCT 05-09, 2012 CL New Orleans, LA SP Int Clin Cytometry Soc C1 [Kelliher, Abigail S.; Delelys, Michelle E.; Dillon, Laura J.; Preffer, Frederic I.] Massachusetts Gen Hosp, 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 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD SEP PY 2012 VL 82B IS 5 MA P20 BP 333 EP 333 PG 1 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 001MU UT WOS:000308465600031 ER PT J AU Cadena, J Sreeramoju, P Nair, S Henao-Martinez, A Jorgensen, J Patterson, JE AF Cadena, Jose Sreeramoju, Pranavi Nair, Shalini Henao-Martinez, Andres Jorgensen, James Patterson, Jan E. TI Clindamycin-resistant methicillin-resistant Staphylococcus aureus: epidemiologic and molecular characteristics and associated clinical factors SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Article DE Methicillin-resistant Staphylococcus aureus; Clindamycin resistance; Epidemiology; Skin and soft tissue infection; Adults ID SOFT-TISSUE INFECTIONS; EMERGENCY-DEPARTMENT; USA-300 CLONE; UNITED-STATES; SKIN; CARE; SURVEILLANCE; CHILDREN; DISEASE; USA300 AB In this prospective, observational study of 618 consecutive adult patients with skin and soft tissue infections (SSTI) caused by methicillin-resistant Staphylococcus aureus (MRSA), the clinical characteristics, molecular epidemiology, and outcome of patients with clindamycin-resistant MRSA (n = 64) and clindamycin-susceptible MRSA (n = 554) were compared (including factors predictive of clindamycin-resistant MRSA SSTI). Patients with clindamycin-resistant MRSA were more likely to have had antibiotic exposure within 3 months (37.5% versus 17%, P < 0.01), surgery (25% versus 8%, P < 0.01), MRSA infection/colonization within 12 months (23% versus 7%, P < 0.01), or intravascular catheters (5% versus 0.5%, P = 0.02). On multivariate analysis, previous surgery (adjusted odds ratio [AOR] 2.97; 95% confidence interval [C] 1.5-6.0), history of MRSA (AOR 3.4:95% CI 1.7-7.1), and exposure to clindamycin (AOR 8.5:95% CI 2.3-32) and to macrolides (AOR 7.2, 95% CI 1.6-31.8) were independently associated with presence of clindamycin-resistant MRSA. Clinical resolution was similar between groups (77% versus 68%; P = 0.26). Clindamycin-resistant MRSA was less often USA-300 (82% versus 98%, P = 0.004). Clindamycin resistance did not affect MRSA-SSTI clinical outcomes. Published by Elsevier Inc. C1 [Cadena, Jose; Patterson, Jan E.] S Texas Vet Healthcare Syst, San Antonio, TX 78229 USA. [Cadena, Jose; Nair, Shalini; Henao-Martinez, Andres; Patterson, Jan E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Cadena, Jose; Patterson, Jan E.] Univ Texas Hlth Sci Ctr San Antonio, Div Infect Dis, San Antonio, TX 78229 USA. [Jorgensen, James; Patterson, Jan E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Sreeramoju, Pranavi] Univ Texas SW Med Ctr Dallas, Div Infect Dis, Dept Med, Dallas, TX 75390 USA. RP Cadena, J (reprint author), S Texas Vet Healthcare Syst, San Antonio, TX 78229 USA. EM cadenazuluag@uthscsa.edu RI Henao-Martinez, Andres/E-1488-2012 OI Henao-Martinez, Andres/0000-0001-7363-8652 FU BD diagnostics; bioMerieux; Pfizer; Merck; Schering Plough; Basilea/Astellas FX James Jorgensen, PhD, has served on the advisory boards of BD Diagnostics and RibX Pharmaceuticals, and has received research support from BD diagnostics, bioMerieux, and Pfizer. Dr. Patterson's spouse has been on the advisory boards for Pfizer and Basilea, and has received research support from Merck, Schering Plough, Pfizer, and Basilea/Astellas. Other authors did not report any conflicts of interest. NR 34 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0732-8893 J9 DIAGN MICR INFEC DIS JI Diagn. Microbiol. Infect. Dis. PD SEP PY 2012 VL 74 IS 1 BP 16 EP 21 DI 10.1016/j.diagmicrobio.2012.05.010 PG 6 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 996TE UT WOS:000308116900004 PM 22795962 ER PT J AU Banks, WA AF Banks, William A. TI Brain Meets Body: The Blood-Brain Barrier as an Endocrine Interface SO ENDOCRINOLOGY LA English DT Review ID SLEEP-INDUCING PEPTIDE; NECROSIS-FACTOR-ALPHA; APOLIPOPROTEIN-E GENOTYPE; ENDOTHELIAL-CELLS; CEREBROSPINAL-FLUID; INTRACEREBROVENTRICULAR INJECTION; ALZHEIMERS-DISEASE; P-GLYCOPROTEIN; DELTA-SLEEP; LEPTIN RESISTANCE AB The blood-brain barrier (BBB) separates the central nervous system (CNS) from the peripheral tissues. However, this does not prevent hormones from entering the brain, but shifts the main control of entry to the BBB. In general, steroid hormones cross the BBB by transmembrane diffusion, a nonsaturable process resulting in brain levels that reflect blood levels, whereas thyroid hormones and many peptides and regulatory proteins cross using transporters, a saturable process resulting in brain levels that reflect blood levels and transporter characteristics. Protein binding, brain-to-blood transport, and pharmacokinetics modulate BBB penetration. Some hormones have the opposite effect within the CNS than they do in the periphery, suggesting that these hormones cross the BBB to act as their own counterregulators. The cells making up the BBB are also endocrine like, both responding to circulating substances and secreting substances into the circulation and CNS. By dividing a hormone's receptors into central and peripheral pools, the former of which may not be part of the hormone's negative feed back loop, the BBB fosters the development of variable hormone resistance syndromes, as exemplified by evidence that altered insulin action in the CNS can contribute to Alzheimer's disease. In summary, the BBB acts as a regulatory interface in an endocrine-like, humoral-based communication between the CNS and peripheral tissues. (Endocrinology 153: 4111-4119, 2012) C1 [Banks, William A.] Univ Washington, Sch Med, Vet Affairs Puget Sound Hlth Care Syst, GRECC, Seattle, WA 98195 USA. [Banks, William A.] Univ Washington, Sch Med, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. RP Banks, WA (reprint author), 1660 S Columbian Way, Seattle, WA 98108 USA. EM wabanks1@uw.edu FU National Institutes of Health [RO1 DK083485, R01 AG029839, R01 NS051134]; Veterans Affairs Merit Review FX This work was supported by National Institutes of Health grants RO1 DK083485, R01 AG029839, R01 NS051134, and Veterans Affairs Merit Review. NR 131 TC 31 Z9 31 U1 7 U2 26 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 2012 VL 153 IS 9 BP 4111 EP 4119 DI 10.1210/en.2012-1435 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 997VH UT WOS:000308194900002 PM 22778219 ER PT J AU Thibert, RL Pfeifer, HH Larson, AM Raby, AR Reynolds, AA Morgan, AK Thiele, EA AF Thibert, Ronald L. Pfeifer, Heidi H. Larson, Anna M. Raby, Annabel R. Reynolds, Ashley A. Morgan, Amy K. Thiele, Elizabeth A. TI Low glycemic index treatment for seizures in Angelman syndrome SO EPILEPSIA LA English DT Article DE Angelman syndrome; Epilepsy; Low glycemic index treatment; Ketogenic diet; Refractory epilepsy ID KETOGENIC DIET; EPILEPSY; QUESTIONNAIRE; DIAGNOSIS; CRITERIA; EFFICACY; SAFETY AB Purpose: The low glycemic index treatment (LGIT) is a high fat, limited carbohydrate diet used in the treatment of epilepsy. The purpose of this study was to assess the efficacy and tolerability of the LGIT for the treatment of refractory seizures in pediatric patients with Angelman syndrome. Methods: A pediatric Angelman syndrome cohort with refractory epilepsy was treated with the LGIT and followed prospectively over 4 months. Parents recorded a daily seizure log for a minimum of 1 month prior to the start of treatment as well as throughout the LGIT trial. Electroencephalography (EEG) and neuropsychological assessments (Scales of Independent Behavior-Revised and the Vineland Adaptive Behavior Scales-2nd Edition were obtained for each subject at both baseline and 4-month follow-up time points. Clinical evaluations of subjects were completed by a neurologist and dietitian at the time of enrollment, as well as following both the first and fourth months of dietary therapy. At each time point, blood for laboratory chemistries was drawn and anthropometric measures were obtained. Key Findings: Six children (mean age 3.3 years, range 1.14.8) with genetically confirmed Angelman syndrome initiated the LGIT, and completed the trial with no significant adverse events. Cohort averages for indices of seizure severity were as follows: age of 1.6 years at seizure onset, 3 lifetime antiepileptic drugs tried (range 16), and baseline seizure frequency of 10.1 events/week (range: 0.430.9). All subjects had a decrease in seizure frequency on the LGIT, with five of six exhibiting >80% seizure frequency reduction. All posttrial EEG studies showed improvement and three of four children with epileptiform activity on his or her baseline EEG had no discharges present on follow-up EEG. Developmental gains were noted by parents in all cases, although few of these neurocognitive gains were statistically significant on neuropsychological assessment. Significance: This is the first prospective study assessing the LGIT for epilepsy. Our results indicate that this dietary therapy is highly effective in treating Angelman syndromerelated seizures. The diet was well tolerated by subjects as evidenced by five of six subjects remaining on the LGIT after completion of the trial. Beyond the prospective trial window, all five subjects who remained on the diet had >90% seizure reduction after 1 year of LGIT therapy. Despite the small sample size in this prospective study, the results indicate a potentially higher degree of efficacy of the LGIT for the Angelman syndrome population than that observed in the general epilepsy population. Although this study is too small to make definitive recommendations, these results suggest that the LGIT is a promising treatment option for Angelman syndromerelated epilepsy. C1 [Thiele, Elizabeth A.] Massachusetts Gen Hosp, Pediat Epilepsy Program, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Angelman Syndrome Clin, Boston, MA 02114 USA. RP Thiele, EA (reprint author), Massachusetts Gen Hosp, Pediat Epilepsy Program, Dept Neurol, 175 Cambridge St,Suite 340, Boston, MA 02114 USA. EM ethiele@partners.org FU ASF FX This study was supported by the ASF. NR 18 TC 12 Z9 15 U1 3 U2 7 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 IS 9 BP 1498 EP 1502 DI 10.1111/j.1528-1167.2012.03537.x PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 001EJ UT WOS:000308442900005 PM 22779920 ER PT J AU Tritos, NA Hamrahian, AH King, D Greenspan, SL Cook, DM Jonsson, PJ Wajnrajch, MP Koltowska-Haggstrom, M Biller, BMK AF Tritos, Nicholas A. Hamrahian, Amir H. King, Donna Greenspan, Susan L. Cook, David M. Jonsson, Peter J. Wajnrajch, Michael P. Koltowska-Haggstrom, Maria Biller, Beverly M. K. TI A longer interval without GH replacement and female gender are associated with lower bone mineral density in adults with childhood-onset GH deficiency: a KIMS database analysis SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article ID GROWTH-HORMONE GH; YOUNG-ADULTS; FACTOR-I; SKELETAL INTEGRITY; THYROID-HORMONE; MULTICENTER; THERAPY; 2-YEAR; STANDARDIZATION; ACQUISITION AB Objective: Childhood-onset GH deficiency (COGHD) is associated with low bone mineral density (BMD). Adults with persistent COGHD may be at risk for insufficient bone accrual or bone loss during adulthood. The purpose of this study was to identify BMD predictors and to characterize the effects of GH replacement on BMD in COGHD adults with persistent GHD. Design: Retrospective analysis of the KIMS database. Methods: Variables predicting standardized BMD (sBMD) were identified. The effect of GH replacement (3 years) on BMD was examined. Results: Three hundred and fourteen COGHD adults (148 women, 166 men; 62 non-naive, 178 semi-naive, and 74 true naive, depending on length and timing of previous GH replacement), who had BMD measured in lumbar spine (LS) and femoral neck (FN) at study entry. In semi-naive subjects, a longer gap in GH replacement between childhood and adulthood was predictive of lower sBMD in the FN (r=-0.18, P=0.038). TSH deficiency predicted lower sBMD in the LS (r=-0.16, P=0.052). In true naive patients, a longer gap between onset of pituitary disease and study entry (r=-0.35, P=0.012), and female gender (r=-0.27, P=0.043) independently predicted lower sBMD in the FN. There were no differences in BMD increases between non-naive, semi-naive, and true naive subjects on GH replacement. Conclusions: In semi-naive subjects a longer interval off GH replacement was associated with lower sBMD in the FN. Among true naive patients, a longer gap between the onset of pituitary disease and GH replacement, and female gender predicted lower sBMD in the FN. C1 [Tritos, Nicholas A.; Biller, Beverly M. K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Tritos, Nicholas A.; Biller, Beverly M. K.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Hamrahian, Amir H.; Koltowska-Haggstrom, Maria] Cleveland Clin, Dept Endocrinol Diabet & Metab, Cleveland, OH 44106 USA. [Greenspan, Susan L.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Cook, David M.] Oregon Hlth & Sci Univ, Dept Endocrinol, Portland, OR 97201 USA. [King, Donna; Jonsson, Peter J.; Koltowska-Haggstrom, Maria] Pfizer Inc, SE-19190 Sollenuna, Sweden. [Wajnrajch, Michael P.] Pfizer Inc, New York, NY USA. RP Tritos, NA (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Zero Emerson Pl,Suite 112, Boston, MA 02114 USA. EM ntritos@partners.org OI Wajnrajch, Michael/0000-0002-8211-9237 FU Pfizer, Inc.; Novartis; Ipsen; Eli Lilly; Warner Chilcott; Tarsa; Pfizer; Novo-Nordisk; Serono FX Drs N A Tritos, A H Hamrahian, S L Greenspan, D M Cook, and B M K Biller were not compensated for their contributions to this manuscript. N A Tritos has been a recipient of research funding and lecture fees from Pfizer, Inc.; spouse is an employee of Pfizer, Inc. A H Hamrahian has been a recipient of lecture fees from Novartis, Ipsen, and Pfizer and has served as a consultant to Ipsen and Pfizer, Inc. S L Greenspan has been a recipient of research funding from Eli Lilly, Warner Chilcott, Tarsa and has consulted and served on an advisory board for Amgen and Merck. D King, M P Wajnrajch, P J Jonsson and M Koltowska-Haggstrom are full-time employees of Pfizer, Inc. BM K Biller has been a recipient of research funding from Pfizer, Eli Lilly, Novo-Nordisk and Serono and has served on an advisory board and received consulting fees from Pfizer and Novo-Nordisk. NR 33 TC 8 Z9 8 U1 0 U2 3 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0804-4643 EI 1479-683X J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD SEP PY 2012 VL 167 IS 3 BP 343 EP 351 DI 10.1530/EJE-12-0070 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 001KJ UT WOS:000308459200006 PM 22711759 ER PT J AU Seal, KH Abadjian, L McCamish, N Shi, Y Tarasovsky, G Weingardt, K AF Seal, Karen H. Abadjian, Linda McCamish, Nicole Shi, Ying Tarasovsky, Gary Weingardt, Kenneth TI A randomized controlled trial of telephone motivational interviewing to enhance mental health treatment engagement in Iraq and Afghanistan veterans SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE War veterans; Treatment engagement; Trial; Posttraumatic stress disorder; Motivational interviewing ID POSTTRAUMATIC-STRESS-DISORDER; REFERRAL-CARE MANAGEMENT; SUBSTANCE USE DISORDERS; WAR VETERANS; INTERVENTION; SOLDIERS; PTSD; DEPRESSION; ATTITUDES; SERVICES AB Objective: To test the efficacy of telephone-administered motivational interviewing (MI) to enhance treatment engagement in Iraq and Afghanistan veterans with mental health (MH) problems. Method: Between April 23, 2008, and February 25, 2011, 73 Iraq and Afghanistan veterans who screened positive for >= 1 MH problem(s) on telephone-administered psychometric assessment, but were not engaged in treatment, were randomized to either personalized referral for MH services and four sessions of telephone MI or standard referral and four neutral telephone check-in sessions (control) at baseline, 2, 4 and 8 weeks. Blinded assessment occurred at 8 and 16 Results: In intent-to-treat analyses, 62% assigned to telephone MI engaged in MH treatment compared to 26% of controls [relative risk (RR)=2.41, 95% confidence interval (CI)=1.33-4.37, P=.004], which represented a large effect size (Cohen's h=0.74). Participants in the MI group also demonstrated significantly greater retention in MH treatment than controls [MI mean visits (S.D.)=1.68 (2.73) and control mean visits (S.D.)=0.38 (0.81), incidence rate ratio (IRR)=4.36, 95% CI=1.96-9.68, P<.001], as well as significant reductions in stigma and marijuana use at 8 weeks (P<.05). Conclusions: Telephone MI enhances MH treatment engagement in Iraq and Afghanistan veterans with MH problems. Published by Elsevier Inc. C1 [Seal, Karen H.] Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Med, San Francisco, CA 94121 USA. [Weingardt, Kenneth] Palo Alto VA Hlth Care Syst, Palo Alto, CA USA. [Weingardt, Kenneth] Stanford Univ, Sch Med, Stanford, CA 94305 USA. RP Seal, KH (reprint author), Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Med, 4150 Clement St,Box 111A-1, San Francisco, CA 94121 USA. EM Karen.Seal@va.gov FU Department of Veterans Affairs (VA), Clinical Sciences Research and Development [MN078889-01]; VA Health Services Research and Development (HSR&D) Research Enhancement Award Program at the San Francisco VA Medical Center FX This work was funded by a grant from the Department of Veterans Affairs (VA), Clinical Sciences Research and Development (award no. MN078889-01) and by the VA Health Services Research and Development (HSR&D) Research Enhancement Award Program at the San Francisco VA Medical Center. NR 42 TC 21 Z9 21 U1 0 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD SEP-OCT PY 2012 VL 34 IS 5 BP 450 EP 459 DI 10.1016/j.genhosppsych.2012.04.007 PG 10 WC Psychiatry SC Psychiatry GA 002DP UT WOS:000308511500002 PM 22632925 ER PT J AU Zivin, K Campbell, DG Lanto, AB Chaney, EF Bolkan, C Bonner, LM Miller, EM Valenstein, M Waltz, TJ Rubenstein, LV AF Zivin, Kara Campbell, Duncan G. Lanto, Andrew B. Chaney, Edmund F. Bolkan, Cory Bonner, Laura M. Miller, Erin M. Valenstein, Marcia Waltz, Thomas J. Rubenstein, Lisa V. TI Relationships between mood and employment over time among depressed VA primary care patients SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Employment; Veterans; Depression ID MENTAL-HEALTH; PSYCHIATRIC-DISORDERS; WORK PRODUCTIVITY; UNEMPLOYMENT; UNDEREMPLOYMENT; VETERANS; IMPACT; POPULATION; ADJUSTMENT; INSURANCE AB Objective: Associations between depression, productivity and work loss have been reported, yet few studies have examined relationships between longitudinal depression status and employment continuity. We assessed these relationships among Veterans of conventional working ages. Methods: We used longitudinal survey data from Veterans receiving primary care in 1 of 10 Veterans Health Administration primary care practices in five states. Our sample included 516 participants with nine-item Patient Health Questionnaire (PHQ-9) scores indicating probable major depression (PHQ-9 >= 10) at baseline and who completed either the 7-month follow-up survey or follow-up surveys at both 7 and 18 months postbaseline. We examined relationships between depression persistence and employment status using multinomial logistic regression models. Results: Although general employment rates remained stable (21%-23%), improved depression status was associated with an increased likelihood of becoming employed over 7 months among those who were both depressed and nonemployed at baseline. Improvements in depression status starting at 7 months and continuing through 18 months were associated with remaining employed over the 18-month period, relative to those who were depressed throughout the same time frame. Conclusions: Given the pressing need to prevent socioeconomic deterioration in the increasing population of conventional working-aged Operation Enduring Freedom and Operation Iraqi Freedom Veterans, further attention to the depression/employment relationship is urgently needed. Published by Elsevier Inc. C1 [Zivin, Kara; Miller, Erin M.; Valenstein, Marcia] Vet Affairs Ann Arbor, Natl Serious Mental Illness Treatment Resource &, HSR&D, Ann Arbor, MI USA. [Zivin, Kara; Miller, Erin M.; Valenstein, Marcia] Univ Michigan, Sch Med, Dept Psychiat, Ann Arbor, MI 48109 USA. [Campbell, Duncan G.] Univ Montana, Dept Psychol, Missoula, MT 59812 USA. [Lanto, Andrew B.] Vet Affairs Greater Los Angeles, HSR&D, Los Angeles, CA USA. [Chaney, Edmund F.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Chaney, Edmund F.] Univ Washington, Sch Publ Hlth & Community Med, Dept Hlth Serv, Seattle, WA 98195 USA. [Bonner, Laura M.] VA Puget Sound, HSR&D, Washington, DC USA. [Bolkan, Cory] Washington State Univ, Dept Human Dev, Vancouver, WA USA. [Waltz, Thomas J.] Little Rock Dept Vet Affairs, HSR&D, Little Rock, AR USA. [Waltz, Thomas J.] Univ Arkansas Med Sci, Dept Psychiat, Little Rock, AR 72205 USA. [Rubenstein, Lisa V.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. RP Zivin, K (reprint author), Vet Affairs Ann Arbor, Natl Serious Mental Illness Treatment Resource &, HSR&D, Ann Arbor, MI USA. EM kzivin@umich.edu OI Waltz, Thomas/0000-0001-7976-430X FU Department of Veterans Affairs (VA) Health Services Research and Development (HSRD) Service; VA Quality Enhancement Research Initiative (QUERI) [MHI 99-375, MNT 01-027, MHQ 10-06, RRP 12-175]; Department of Veterans Affairs [CD2 07-206-1] FX This project was funded by the Department of Veterans Affairs (VA) Health Services Research and Development (HSR&D) Service and the VA Quality Enhancement Research Initiative (QUERI) (Project nos. MHI 99-375, MNT 01-027, MHQ 10-06, RRP 12-175) and Department of Veterans Affairs CD2 07-206-1 and IIR #10-176-3. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. NR 41 TC 8 Z9 8 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD SEP-OCT PY 2012 VL 34 IS 5 BP 468 EP 477 DI 10.1016/j.genhosppsych.2012.05.008 PG 10 WC Psychiatry SC Psychiatry GA 002DP UT WOS:000308511500004 PM 22771108 ER PT J AU Ganzini, L Mansoor, D Socherman, R Duckart, J AF Ganzini, Linda Mansoor, David Socherman, Robert Duckart, Jonathan TI Delirium and decisional incapacity in veterans with schizophrenia and medical illness SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Delirium; Schizophrenia; Decision-making capacity; Veterans ID CONSULTATION; MANAGEMENT; CARE; ILL AB Objective: The objective was to examine the characteristics of Veterans with schizophrenia admitted for nonpsychiatric hospitalizations. Method: We conducted a review of the electronic medical record and data warehouse downloads of Veterans with schizophrenia admitted to nonpsychiatric services of a large, academic Veterans Affairs hospital between 2004 and 2009 on whom psychiatry was consulted. Results: Seventy-four veterans were admitted 89 times. Their mean age was 62 years. Among these veterans, the most common reasons for nonpsychiatric admission were infection, cardiac disease or altered mental status. Thirty-three percent of consultations were for patients who required intensive care. Consultation was requested most frequently for assessing psychotropic medication, decision-making capacity or altered mental status, or for assistance with behavioral problems. Thirty-seven percent of patients were diagnosed with delirium, and 42% lacked decision-making capacity, mostly secondary to delirium. Twenty-seven percent of patients died during the study period. Conclusion: In an aging cohort of Veterans with schizophrenia, a substantial proportion of patients developed delirium, lost decision-making capacity and required intensive care during nonpsychiatric hospital admission. Published by Elsevier Inc. C1 [Ganzini, Linda; Mansoor, David; Socherman, Robert; Duckart, Jonathan] Portland VA Med Ctr, Div Mental Hlth, Portland, OR 97207 USA. [Ganzini, Linda; Mansoor, David; Socherman, Robert] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97239 USA. RP Ganzini, L (reprint author), Portland VA Med Ctr, Div Mental Hlth, POB 1034, Portland, OR 97207 USA. EM Linda.Ganzini@va.gov NR 13 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 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD SEP-OCT PY 2012 VL 34 IS 5 BP 506 EP 509 DI 10.1016/j.genhosppsych.2012.04.003 PG 4 WC Psychiatry SC Psychiatry GA 002DP UT WOS:000308511500008 PM 22632926 ER PT J AU Pompili, M Innamorati, M Serafini, G Gonda, X Campi, S Rapinesi, C Giordano, G Montebovi, F Palermo, M Giupponi, G Tatarelli, R Biondi, M Amore, M Sher, L Rihmer, Z Girardi, P AF Pompili, Maurizio Innamorati, Marco Serafini, Gianluca Gonda, Xenia Campi, Sandra Rapinesi, Chiara Giordano, Gloria Montebovi, Franco Palermo, Mario Giupponi, Giancarlo Tatarelli, Roberto Biondi, Massimo Amore, Mario Sher, Leo Rihmer, Zoltan Girardi, Paolo TI How does subjective experience of pain relate to psychopathology among psychiatric patients? SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Anxiety disorder; Depressive disorder; Pain severity; Psychopathology ID INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; PRIMARY-CARE; DEPRESSIVE SYMPTOMS; ANXIETY DISORDERS; PHYSICAL SYMPTOMS; SOMATIC SYMPTOMS; DSM-IV; GENDER; MINI; SOMATIZATION AB Objective: The study aimed to investigate to what extent general psychopathology is associated with subjective experience of pain in psychiatric outpatients without comorbidity with severe physical diagnosis and whether there are any differences in the experience of pain between genders or diagnoses. Method: Participants were 575 consecutive outpatients affected by mood disorder or anxiety disorder. Patients completed the West Haven-Yale Multidimensional Pain Inventory (WHYMPI) and the Symptom Checklist 90-Revised. Results: Women had higher mean scores on the Global Severity Index (1.52 +/- 0.76 vs. 1.33 +/- 0.79), higher perception of negative responses from others (1.84 +/- 1.59 vs. 1.46 +/- 1.35) and higher perception of pain severity (3.31 +/- 1.73 vs. 2.88 +/- 1.63) than men. They also reported higher mean scores on the WHYMPI's General Activity (2.14 +/- 0.98 vs. 1.93 +/- 0.95) and Household Chores (3.64 +/- 1.75 vs. 2.27 +/- 1.58) and lower mean scores on the Outdoor Work (1.24 +/- 1.26 vs. 1.87 +/- 1.51) dimension than men. Higher pain severity, more negative responses from others and higher household chores are predictors of higher psychopathology, while the general level of activity may be considered as a protective factor. Conclusions: Pain and its subjective experience play a central role in psychiatric disorders, and it is a great burden for patients and caregivers. Clinicians should pay more attention to recognize and adequately treat painful symptoms in patients with anxiety and depressive disorder. (C) 2012 Elsevier Inc. All rights reserved. C1 [Pompili, Maurizio; Innamorati, Marco; Serafini, Gianluca; Campi, Sandra; Rapinesi, Chiara; Giordano, Gloria; Montebovi, Franco; Palermo, Mario; Tatarelli, Roberto; Girardi, Paolo] Univ Roma La Sapienza, St Andrea Hosp, Suicide Prevent Ctr, Dept Neurosci Mental Hlth & Sensory Organs, I-00189 Rome, Italy. [Pompili, Maurizio] Harvard Univ, McLean Hosp, Sch Med, Belmont, MA USA. [Gonda, Xenia] Semmelweis Univ, Kutvolgyi Clin Ctr, Dept Clin & Theoret Mental Hlth, H-1125 Budapest, Hungary. [Campi, Sandra; Biondi, Massimo; Rihmer, Zoltan] Univ Roma La Sapienza, Dept Psychiat & Psychol Med, I-00189 Rome, Italy. [Giupponi, Giancarlo] Dept Psychiat, Bolzano, Italy. [Sher, Leo] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Sher, Leo] James J Peters Vet Adm Med Ctr, Dept Psychiat, New York, NY USA. [Amore, Mario] Univ Parma, Dept Neurosci, Div Psychiat, I-43100 Parma, Italy. RP Pompili, M (reprint author), Univ Roma La Sapienza, St Andrea Hosp, Dept Psychiat, 1035-1039 Via Grottarossa, I-00189 Rome, Italy. EM maurizio.pompili@uniroma1.it RI Innamorati, Marco/H-8877-2013; Giupponi, Giancarlo/J-9824-2016; OI Innamorati, Marco/0000-0003-1389-2290; Giupponi, Giancarlo/0000-0001-6430-0000; biondi, massimo/0000-0001-8777-5498; Pompili, Maurizio/0000-0003-1886-4977; Tatarelli, Roberto/0000-0003-4396-2632 NR 52 TC 6 Z9 6 U1 3 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD SEP-OCT PY 2012 VL 34 IS 5 BP 534 EP 540 DI 10.1016/j.genhosppsych.2012.03.022 PG 7 WC Psychiatry SC Psychiatry GA 002DP UT WOS:000308511500013 PM 22595339 ER PT J AU Ting, SA Sullivan, AF Boudreaux, ED Miller, I Camargo, CA AF Ting, Sarah A. Sullivan, Ashley F. Boudreaux, Edwin D. Miller, Ivan Camargo, Carlos A., Jr. TI Trends in US emergency department visits for attempted suicide and self-inflicted injury, 1993-2008 SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Suicide; Emergency departments; Public health ID PREVALENCE; INTERVENTION; ADOLESCENTS; REPETITION; IDEATION; HARM AB Objective: The objective was to describe the epidemiology of emergency department (ED) visits for attempted suicide and self-inflicted injury over a 16-year period. Method: Data were obtained from the National Hospital Ambulatory Medical Care Survey including all visits for attempted suicide and self-inflicted injury (E950-E959) during 1993-2008. Results: Over the 16-year period, there was an average of 420,000 annual ED visits for attempted suicide and self-inflicted injury [1.50 (95% confidence interval, 1.33-1.67) visits per 1000 US population], and the average annual number for these ED visits more than doubled from 244,000 in 1993-1996 to 538,000 in 2005-2008. During the same time frame, ED visits for these injuries per 1000 US population almost doubled for males (0.84 to 1.62), females (1.04 to 1.96), whites (0.94 to 1.82) and blacks (1.14 to 2.10). Visits were most common among ages 15-19, and the number of visits coded as urgent/emergent decreased from 0.95 in 1993-1996 to 0.70 in 2005-2008. Conclusions: ED visit volume for attempted suicide and self-inflicted injury has increased over the past two decades in all major demographic groups. Awareness of these longitudinal trends may assist efforts to increase research on suicide prevention. In addition, this information may be used to inform current suicide and self-injury related ED interventions and treatment programs. (c) 2012 Elsevier Inc. All rights reserved. C1 [Ting, Sarah A.; Sullivan, Ashley F.; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Boudreaux, Edwin D.] Univ Massachusetts, Sch Med, Dept Emergency Med, Worcester, MA USA. [Boudreaux, Edwin D.] Univ Massachusetts, Sch Med, Dept Psychiat, Worcester, MA 01655 USA. [Boudreaux, Edwin D.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA 01655 USA. [Miller, Ivan] Butler Hosp, Providence, RI 02906 USA. RP Ting, SA (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. EM sting@partners.org OI Boudreaux, Edwin/0000-0002-3223-6371 FU National Institute of Mental Health [U01MH088278] FX This project was supported by Award Number U01MH088278 from the National Institute of Mental Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health or the National Institutes of Health. NR 33 TC 60 Z9 62 U1 0 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD SEP-OCT PY 2012 VL 34 IS 5 BP 557 EP 565 DI 10.1016/j.genhosppsych.2012.03.020 PG 9 WC Psychiatry SC Psychiatry GA 002DP UT WOS:000308511500017 PM 22554432 ER PT J AU del Carmen, MG Micha, J Small, L Street, DG Londhe, A McGowan, T AF del Carmen, Marcela G. Micha, John Small, Laurie Street, Daron G. Londhe, Anil McGowan, Tracy TI A phase II clinical trial of pegylated liposomal doxorubicin and carboplatin plus bevacizumab in patients with platinum-sensitive recurrent ovarian, fallopian tube, or primary peritoneal cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Pegylated liposomal doxorubicin; Carboplatin; Bevacizumab; Ovarian cancer; Fallopian tube cancer; Primary peritoneal cancer ID GYNECOLOGIC-ONCOLOGY-GROUP; EPITHELIAL OVARIAN; 1ST-LINE TREATMENT; STAGE-III; PACLITAXEL; CHEMOTHERAPY; CARCINOMA; CYCLOPHOSPHAMIDE; CALIFORNIA; CISPLATIN AB Objective. To assess the safety and efficacy of pegylated liposomal doxorubicin (PLD), carboplatin, plus bevacizumab in patients with ovarian, fallopian tube, or primary peritoneal cancer. Methods. Patients with platinum-sensitive, recurrent disease received PLD 30 mg/m(2) and carboplatin area under the curve (AUC) 5 on Day 1 plus bevacizumab 10 mg/kg on Days 1 and 15 of every 28-day cycle, for a maximum of 10 cycles. The primary endpoint was objective response rate (ORR) [complete + partial response]: additional endpoints were safety, duration of response, progression-free survival (PFS), and time to progression (TTP). Results. Of the 54 patients enrolled, 15(27.8%) completed the study treatment as planned. Intent-to-treat (all enrolled patients) ORR was 72.2% (95% Cl: 58.4, 83.5). Median duration of response was 11.9 months (95% Cl: 9.3, not estimable) and median TTP was 13.9 months (95% Cl: 11.4, 16.0). PFS was virtually the same as TTP. Three (5.6%) patients discontinued therapy due to disease progression, and another 3 (5.6%) patients discontinued therapy due to serious adverse events (Grade 4 thrombocytopenia, Grade 3 small/large intestinal obstruction/small intestinal perforation, and Grade 3 abdominal abscess). Fifty (92.6%) patients had >= 1 adverse event of interest, most commonly neutropenia (42.6%), hypertension (37.0%), stomatitis (37.0%), proteinuria (37.0%), and palmar-plantar erythrodysesthesia (27.8%). No appreciable decreases in left-ventricular ejection fraction were observed. Conclusion. Most patients responded to PLD, carboplatin, and bevacizumab combination therapy. The safety profile was consistent with the known toxicities of these agents. These findings present a potential treatment option for women with ovarian, fallopian tube, or primary peritoneal cancer. (C) 2012 Elsevier Inc. All rights reserved. C1 [McGowan, Tracy] Janssen Serv LLC, Horsham, PA 19044 USA. [del Carmen, Marcela G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol, Boston, MA USA. [Micha, John] Gynecol Oncol Associates, Newport Beach, CA USA. [Small, Laurie] Maine Med Ctr, Scarborough, ME USA. [Street, Daron G.] Canc Care Associates, Tulsa, OK USA. [Londhe, Anil] Janssen Res & Dev LLC, Horsham, PA USA. RP McGowan, T (reprint author), Janssen Serv LLC, 800 Ridgeview Dr, Horsham, PA 19044 USA. EM tmcgowan@its.jnj.com FU Janssen Services, LLC, Horsham, PA, USA; JJ; Genentech FX This study was supported by Janssen Services, LLC, Horsham, PA, USA.; Dr. Micha owns stock in Johnson & Johnson OM, of which Janssen is a subsidiary, Bristol Myers Squibb, and Roche and has received research funding from J&J and Genentech for projects. Drs. McGowan and Londhe are employees of J&J and own stock in J&J. The remaining authors have nothing to disclose. NR 24 TC 17 Z9 17 U1 0 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD SEP PY 2012 VL 126 IS 3 BP 369 EP 374 DI 10.1016/j.ygyno.2012.05.028 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 986DU UT WOS:000307322000010 PM 22659190 ER PT J AU Smith, AL Krivak, TC Scott, EM Rauh-Hain, JA Sukumvanich, P Olawaiye, AB Richard, SD AF Smith, Ashlee L. Krivak, Thomas C. Scott, Eirwen M. Rauh-Hain, Jose Alejandro Sukumvanich, Paniti Olawaiye, Alexander B. Richard, Scott D. TI Dual-console robotic surgery compared to laparoscopic surgery with respect to surgical outcomes in a gynecologic oncology fellowship program SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Dual-console robotic surgery; Laparoscopic surgery; Gynecologic oncology; Fellowship training program ID ENDOMETRIAL CANCER; ASSISTED HYSTERECTOMY; RADICAL HYSTERECTOMY; LEARNING-CURVE; LAPAROTOMY; LYMPHADENECTOMY; COST AB Objective. Minimally invasive surgical techniques decrease surgical morbidity and recovery time. Studies demonstrate similar surgical outcomes comparing robotic to laparoscopic surgery. These studies have not accounted for the incorporation of fellow education. With the dual-console da Vinci Si Surgical System, a two surgeon approach could be performed. We sought to compare surgical outcomes at a gynecologic oncology fellowship program of traditional laparoscopic to robotic,surgeries using the dual-console system. Methods. We identified patients who underwent laparoscopic or robotic surgery performed by a gynecologic oncologist from November 2009-November 2010. Robotic surgeries were conducted using the dual-console, utilizing a two surgeon approach. Surgeries involved a staff physician with a gynecologic oncology fellow. Statistical analysis was performed using student t-test and chi-squared analysis. Results. A total of 222 cases were identified. Cases were analyzed in groups: all cases identified, all cancer cases, and endometrial cancer cases only. When analyzing all cases, no statistical difference was noted in total operating room time (172 vs. 175 min; p = 0.6), pelvic lymph nodes removed (10.1 vs. 9.6; p = 0.69), para-aortic lymph nodes dissected (3.7. vs. 3.8; p=0.91), or length of stay (1.5 vs. 1.3 days; p = 0.3). There was a significant difference in total surgical time (131 vs.110 min; p<0.0001) and EBL (157 vs.94 ml; p<0.0001), favoring robotic surgery. When analyzing all cancer cases, the advantage in total surgical time for robotic surgery was lost. Complications were similar between cohorts. Conclusion. Incorporating fellow education into robotic surgery does not adversely affect outcomes when compared to traditional laparoscopic surgery. (C) 2012 Elsevier Inc. All rights reserved. C1 [Smith, Ashlee L.] Magee Womens Hosp UPMC, Dept Gynecol Oncol, Div Gynecol Oncol, Pittsburgh, PA 15213 USA. [Rauh-Hain, Jose Alejandro] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol Vincent Obstet & Gynecol, Boston, MA USA. RP Smith, AL (reprint author), Magee Womens Hosp UPMC, Dept Gynecol Oncol, Div Gynecol Oncol, 300 Halket St, Pittsburgh, PA 15213 USA. EM smitha11@upmc.edu NR 22 TC 15 Z9 16 U1 2 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD SEP PY 2012 VL 126 IS 3 BP 432 EP 436 DI 10.1016/j.ygyno.2012.05.017 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 986DU UT WOS:000307322000022 PM 22613352 ER PT J AU del Carmen, MG Birrer, M Schorge, JO AF del Carmen, Marcela G. Birrer, Michael Schorge, John O. TI Clear cell carcinoma of the ovary: A review of the literature SO GYNECOLOGIC ONCOLOGY LA English DT Review DE Clear cell; Ovarian; Cancer; Surgery ID GRADE SEROUS CARCINOMA; PACLITAXEL PLUS CARBOPLATIN; WHOLE ABDOMINAL RADIOTHERAPY; PLATINUM-BASED CHEMOTHERAPY; GYNECOLOGIC-ONCOLOGY-GROUP; FERTILITY-SPARING SURGERY; DISTINCT-HISTOLOGIC-TYPE; CANCER INTERGROUP TRIAL; PHASE-III TRIAL; EPITHELIAL OVARIAN AB Objective. Different histologic types of epithelial ovarian cancer may represent different diseases with unique clinical and molecular characteristics. Clear cell carcinoma (CCC) of the ovary has been reported as having a worse prognosis than high grade serous epithelial ovarian cancer (EOC). This article critically reviews the literature pertinent to the pathology, pathogenesis, diagnosis, management, and outcome of patients with ovarian CCC. Methods. MEDLINE was searched for all research articles published in English between January 01, 1977 and January 30, 2012 which reported on patients diagnosed with ovarian CCC. Given the rarity of this tumor, studies were not limited by design or number of reported patients. Results. Ovarian CCC tumors represent 5-25% of ovarian cancers. Its histologic diagnosis can be challenging, resulting often times in misclassification of these tumors. Ovarian CCC tends to present at earlier stages and has been associated with endometriosis, ARID1A and PIK3CA mutations. When compared to stage-matched controls, patients with early-stage ovarian CCCs may have a better prognosis than patients with high-grade serous tumors. For those with advanced stage disease, high-grade serous histology confers a better prognosis than ovarian CCC. Patients with Stage IC-IV have a relatively poor prognosis and efforts should center in discovery of more effective treatment strategies. Conclusions. Ovarian CCC is a biologically distinct entity, different from high-grade serous EOC. Future studies should explore the role of targeted therapies in the management of ovarian CCC. (c) 2012 Elsevier Inc. All rights reserved. C1 [del Carmen, Marcela G.; Schorge, John O.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol,Vincent Obstet & Gynecol, Boston, MA 02114 USA. [Birrer, Michael] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Med Oncol, Boston, MA 02114 USA. RP del Carmen, MG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol,Vincent Obstet & Gynecol, 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. EM mdelcarmen@partners.org NR 136 TC 60 Z9 60 U1 1 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD SEP PY 2012 VL 126 IS 3 BP 481 EP 490 DI 10.1016/j.ygyno.2012.04.021 PG 10 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 986DU UT WOS:000307322000030 PM 22525820 ER PT J AU Santaniello, S Sherman, DL Thakor, NV Eskandar, EN Sarma, SV AF Santaniello, Sabato Sherman, David L. Thakor, Nitish V. Eskandar, Emad N. Sarma, Sridevi V. TI Optimal Control-Based Bayesian Detection of Clinical and Behavioral State Transitions SO IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING LA English DT Article DE Bayesian estimation; neural systems; optimal control; quickest detection (QD) ID PRINCIPAL COMPONENT ANALYSIS; EPILEPTIC SEIZURE DETECTION; ARTIFICIAL NEURAL-NETWORKS; QUICKEST DETECTION; EEG RECORDINGS; SCALP EEG; TIME; MODEL; ONSET; CLASSIFICATION AB Accurately detecting hidden clinical or behavioral states from sequential measurements is an emerging topic in neuroscience and medicine, which may dramatically impact neural prosthetics, brain-computer interface and drug delivery. For example, early detection of an epileptic seizure from sequential electroencephalographic (EEG) measurements would allow timely administration of anticonvulsant drugs or neurostimulation, thus reducing physical impairment and risks of overtreatment. We develop a Bayesian paradigm for state transition detection that combines optimal control and Markov processes. We define a hidden Markov model of the state evolution and develop a detection policy that minimizes a loss function of both probability of false positives and accuracy (i.e., lag between estimated and actual transition time). Our strategy automatically adapts to each newly acquired measurement based on the state evolution model and the relative loss for false positives and accuracy, thus resulting in a time varying threshold policy. The paradigm was used in two applications: 1) detection of movement onset (behavioral state) from subthalamic single unit recordings in Parkinson's disease patients performing a motor task; 2) early detection of an approaching seizure (clinical state) from multichannel intracranial EEG recordings in rodents treated with pentylenetetrazol chemoconvulsant. Our paradigm performs significantly better than chance and improves over widely used detection algorithms. C1 [Santaniello, Sabato; Sherman, David L.; Thakor, Nitish V.; Sarma, Sridevi V.] Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21218 USA. [Eskandar, Emad N.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Santaniello, S (reprint author), Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21218 USA. EM ssantan5@jhu.edu; sherman@jhu.edu; nthakor@jhu.edu; ssarma2@jhu.edu RI Thakor, Nitish/G-9110-2015; OI Thakor, Nitish/0000-0002-9981-9395; Santaniello, Sabato/0000-0002-2133-9471 FU US National Science Foundation [1055560]; Burroughs Wellcome Fund CASI Award [1007274] FX The work of S. V. Sarma was supported by the US National Science Foundation Career Award 1055560 and the Burroughs Wellcome Fund CASI Award 1007274. Date of publication August 08, 2012; date of current version September 07, 2012. NR 62 TC 8 Z9 8 U1 0 U2 10 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1534-4320 EI 1558-0210 J9 IEEE T NEUR SYS REH JI IEEE Trans. Neural Syst. Rehabil. Eng. PD SEP PY 2012 VL 20 IS 5 BP 708 EP 719 DI 10.1109/TNSRE.2012.2210246 PG 12 WC Engineering, Biomedical; Rehabilitation SC Engineering; Rehabilitation GA 001LQ UT WOS:000308462600010 PM 22893447 ER PT J AU Kaser, DJ Kinsler, EL Mackenzie, TA Hanissian, P Strohbehn, K Whiteside, JL AF Kaser, Daniel J. Kinsler, Erron L. Mackenzie, Todd A. Hanissian, Paul Strohbehn, Kris Whiteside, James L. TI Anatomic and functional outcomes of sacrocolpopexy with or without posterior colporrhaphy SO INTERNATIONAL UROGYNECOLOGY JOURNAL LA English DT Article; Proceedings Paper CT 30th Annual Scientific Meeting of the American-Urogynecologic-Society CY SEP 24-26, 2009 CL Hollywood, FL SP Amer Urogynecol Soc, Hitchcock Fdn, Dartmouth-Hitchcock Med Ctr DE Bowel function; Colporrhaphy; Pelvic Organ Prolapse Quantification (POP-Q); Posterior repair; Rectocele; Sacrocolpopexy ID ABDOMINAL SACROCOLPOPEXY; URINARY-INCONTINENCE; SEXUAL FUNCTION; WOMEN; QUESTIONNAIRE; COMPARTMENT; RECTOCELE; PROLAPSE AB The optimal surgery for combined apical and posterior vaginal prolapse is not well defined. Our objective was to examine the anatomic and functional outcomes following sacrocolpopexy (SCP) with or without posterior colporrhaphy (PC). We retrospectively evaluated 258 women who underwent abdominal (n = 62) or laparoscopic (n = 196) SCP with or without PC. Preoperative anatomic support and standardized bowel symptoms were compared to 6-week and 1-year postoperative values, using Student's t test and Wilcoxon rank sum test, respectively. Six-week follow-up data were available for 235 of 258 (91.1 %) women, while 125 of 258 (48.4 %) women had 1-year anatomic and functional outcomes recorded. While the SCP + PC group had worse posterior descent and bowel function preoperatively, there were no significant differences in postoperative anatomic support or symptoms. Long-term pelvic floor function was similar, as measured by three validated instruments. Reduction in the proportion of women with splinting was greater in the SCP + PC group. SCP with or without PC is associated with improved posterior support and decreased obstructive and irritative bowel symptoms at 1 year in women with apical and posterior prolapse. C1 [Kaser, Daniel J.] Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Brigham & Womens Hosp,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Kinsler, Erron L.; Mackenzie, Todd A.; Hanissian, Paul; Strohbehn, Kris; Whiteside, James L.] Dartmouth Hitchcock Med Ctr, Dept Obstet & Gynecol, Div Female Pelv Med & Reconstruct Surg, Dartmouth Med Sch, Lebanon, NH 03756 USA. RP Kaser, DJ (reprint author), Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Brigham & Womens Hosp,Massachusetts Gen Hosp, 75 Francis St,ASB 3, Boston, MA 02115 USA. EM dkaser@partners.org NR 15 TC 5 Z9 5 U1 0 U2 3 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0937-3462 J9 INT UROGYNECOL J JI Int. Urogynecol. J. PD SEP PY 2012 VL 23 IS 9 BP 1215 EP 1220 DI 10.1007/s00192-012-1695-1 PG 6 WC Obstetrics & Gynecology; Urology & Nephrology SC Obstetrics & Gynecology; Urology & Nephrology GA 991MN UT WOS:000307705500013 PM 22426873 ER PT J AU Elkhawad, M Rudd, JHF Sarov-Blat, L Cai, GQ Wells, R Davies, LC Collier, DJ Marber, MS Choudhury, RP Fayad, ZA Tawakol, A Gleeson, FV Lepore, JJ Davis, B Willette, RN Wilkinson, IB Sprecher, DL Cheriyan, J AF Elkhawad, Maysoon Rudd, James H. F. Sarov-Blat, Lea Cai, Gengqian Wells, Richard Davies, L. Ceri Collier, David J. Marber, Michael S. Choudhury, Robin P. Fayad, Zahi A. Tawakol, Ahmed Gleeson, Fergus V. Lepore, John J. Davis, Bill Willette, Robert N. Wilkinson, Ian B. Sprecher, Dennis L. Cheriyan, Joseph TI Effects of p38 Mitogen-Activated Protein Kinase Inhibition on Vascular and Systemic Inflammation in Patients With Atherosclerosis SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE atherosclerosis; biomarkers; imaging; inflammation; p38 mitogen-activated protein kinase inhibition; randomized controlled trial ID POSITRON-EMISSION-TOMOGRAPHY; C-REACTIVE PROTEIN; PLAQUE INFLAMMATION; CARDIOVASCULAR-DISEASE; REDUCES INFLAMMATION; DENSITY-LIPOPROTEIN; GLUCOSE-TRANSPORT; F-18-FDG PET; MACROPHAGES; CELLS AB OBJECTIVES This study sought to determine the effects of a p38 mitogen-activated protein kinase inhibitor, losmapimod, on vascular inflammation, by F-18-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography imaging. BACKGROUND The p38 mitogen-activated protein kinase cascade plays an important role in the initiation and progression of inflammatory diseases, including atherosclerosis. METHODS Patients with atherosclerosis on stable statin therapy (n = 99) were randomized to receive losmapimod 7.5 mg once daily (lower dose [LD]), twice daily (higher dose [HD]) or placebo for 84 days. Vascular inflammation was assessed by FDG positron emission tomography/computed tomography imaging of the carotid arteries and aorta; analyses focused on the index vessel (the artery with the highest average maximum tissue-to-background ratio [TBR] at baseline). Serum inflammatory biomarkers and FDG uptake in visceral and subcutaneous fat were also measured. RESULTS The primary endpoint, change from baseline in average TBR across all segments in the index vessel, was not significantly different between HD and placebo (Delta TBR: -0.04 [95% confidence interval [CI]: -0.14 to +0.06], p = 0.452) or LD and placebo (Delta TBR: -0.02 [95% CI: -0.11 to +0.06], p = 0.579). However, there was a statistically significant reduction in average TBR in active segments (TBR >= 1.6) (HD vs. placebo:Delta TBR: -0.10 [95% CI: -0.19 to -0.02], p = 0.0125; LD vs. placebo:Delta TBR: -0.10 [95% CI: -0.18 to -0.02], p = 0.0194). The probability of a segment being active was also significantly reduced for HD when compared with placebo (OR: 0.57 [95% CI: 0.41 to 0.81], p = 0.002). Within the HD group, reductions were observed in placebo-corrected inflammatory biomarkers including high-sensitivity C-reactive protein (% reduction: -28% [95% CI: -46 to -5], p = 0.023) as well as FDG uptake in visceral fat (Delta SUV: -0.05 [95% CI: -0.09 to -0.01], p = 0.018), but not subcutaneous fat. CONCLUSIONS Despite nonsignificant changes for the primary endpoint of average vessel TBR, HD losmapimod reduced vascular inflammation in the most inflamed regions, concurrent with a reduction in inflammatory biomarkers and FDG uptake in visceral fat. These results suggest a systemic anti-inflammatory effect. (A Study to Evaluate the Effects of 3 Months Dosing With GW856553, as Assessed FDG-PET/CT Imaging; NCT00633022) (J Am Coll Cardiol Img 2012;5:911-22) (C) 2012 by the American College of Cardiology Foundation C1 [Sarov-Blat, Lea; Cai, Gengqian; Lepore, John J.; Willette, Robert N.; Sprecher, Dennis L.] GlaxoSmithKline, Metab Pathways & Cardiovasc Therapy Area Unit, King Of Prussia, PA 19406 USA. [Elkhawad, Maysoon; Wells, Richard; Wilkinson, Ian B.; Cheriyan, Joseph] Univ Cambridge, Clin Pharmacol Unit, Cambridge, England. [Elkhawad, Maysoon; Rudd, James H. F.] Univ Cambridge, Div Cardiovasc Med, Cambridge, England. [Davies, L. Ceri; Collier, David J.] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, Ctr Clin Pharmacol, London, England. [Marber, Michael S.] Kings Coll London, London WC2R 2LS, England. [Choudhury, Robin P.; Gleeson, Fergus V.] Univ Oxford, Oxford, England. [Fayad, Zahi A.] Mt Sinai Med Ctr, New York, NY 10029 USA. [Tawakol, Ahmed] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tawakol, Ahmed] Harvard Univ, Sch Med, Boston, MA USA. [Davis, Bill; Cheriyan, Joseph] GlaxoSmithKline Clin Unit, Cambridge, England. [Cheriyan, Joseph] Natl Hlth Serv Fdn Trust, Cambridge Univ Hosp, Cambridge, England. RP Sprecher, DL (reprint author), GlaxoSmithKline, Metab Pathways & Cardiovasc Therapy Area Unit, 709 Swedeland Rd,UW2421, King Of Prussia, PA 19406 USA. EM dennis.l.sprecher@gsk.com RI Cheriyan, Joseph/B-2596-2009; OI Cheriyan, Joseph/0000-0001-6921-1592; Davies, Ceri/0000-0001-7239-2996; Rudd, James/0000-0003-2243-3117 FU GlaxoSmithKline; National Institute for Health Research (NIHR) Cambridge Comprehensive Biomedical Research Centre; Raymond and Beverly Sackler Foundation; NIHR Cardiovascular Biomedical Research Unit, Bart's; London School of Medicine and Dentistry; NIHR Comprehensive Biomedical Research Centre; Guy's and St Thomas's National Health Service Foundation Trust; British Heart Foundation Centre, King's College, London; NIHR Oxford Comprehensive Biomedical Research Centre; British Heart Foundation Centre for Research Excellence, Oxford; AstraZeneca; AstraZeneca and Roche; Bristol-Myers Squibb Merck Co. Inc.; VBL Therapeutics; Philips; Siemens; Novartis; National Institute of Health; Bristol-Myers Squibb; Merck Co. Inc.; Genentech/Roche; British Heart Foundation FX This study was funded by GlaxoSmithKline. Ms. Elkhawad, and Drs. Rudd, Wilkinson, and Cheriyan, as well as the Cambridge University Hospitals PET/CT Unit, have received funding support from National Institute for Health Research (NIHR) Cambridge Comprehensive Biomedical Research Centre. Ms. Elkhawad has received funding support from the Raymond and Beverly Sackler Foundation. Drs. Rudd and Wilkinson are consultants for GlaxoSmithKline. Drs. Sarov-Blat, Cai, Lepore, Davis, Willette, and Sprecher are employees of and own stock in GlaxoSmithKline. Mr. Wells has reported that he has no relationships relevant to the contents of this paper to disclose. Drs. Davies and Collier have received funding from NIHR Cardiovascular Biomedical Research Unit, Bart's and the London School of Medicine and Dentistry. Dr. Collier has received a research grant from GlaxoSmithKline for this study. Dr. Marber has received funding from the NIHR Comprehensive Biomedical Research Centre, Guy's and St Thomas's National Health Service Foundation Trust in partnership with the British Heart Foundation Centre, King's College, London. He has received a research grant from and is a consultant for GlaxoSmithKline for this compound. Drs. Choudhury and Gleeson have received funding from the NIHR Oxford Comprehensive Biomedical Research Centre. Dr. Choudhury is a Wellcome Trust Senior Research fellow and is supported by the British Heart Foundation Centre for Research Excellence, Oxford. He has received a research grant for this study and is on the advisory board of AstraZeneca and Roche. Dr. Fayad has received research grants from GlaxoSmithKline, AstraZeneca, Roche, Bristol-Myers Squibb Merck & Co. Inc., VBL Therapeutics, Philips, Siemens, Novartis, and the National Institute of Health. Dr. Tawakol has received research grants from Bristol-Myers Squibb, GlaxoSmithKline, Merck & Co. Inc., Genentech/Roche, VBL Therapeutics, Siemens, Novartis, and the National Institute of Health. He consults for Bristol-Myers Squibb, GlaxoSmithKline, Merck & Co. Inc., Novartis, and Roche. Dr. Wilkinson has received funding support from the British Heart Foundation as a funded post holder; he has also received educational grants from GlaxoSmithKline for current clinical trials. Dr. Cheriyan is employed by Cambridge University Hospitals National Health Service Foundation Trust and is obligated to spend 50% of his time on GlaxoSmithKline clinical trial research, representing a significant relationship; however, he receives no other benefits or compensations from GlaxoSmithKline. Ms. Elkhawad and Dr. Rudd contributed equally to this paper. H. William Strauss, MD, served as Guest Editor for this paper. NR 35 TC 57 Z9 59 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD SEP PY 2012 VL 5 IS 9 BP 911 EP 922 DI 10.1016/j.jcmg.2012.02.016 PG 12 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 003DX UT WOS:000308589500009 PM 22974804 ER PT J AU Fleg, JL Stone, GW Fayad, ZA Granada, JF Hatsukami, TS Kolodgie, FD Ohayon, J Pettigrew, R Sabatine, MS Tearney, GJ Waxman, S Domanski, MJ Srinivas, PR Narula, J AF Fleg, Jerome L. Stone, Gregg W. Fayad, Zahi A. Granada, Juan F. Hatsukami, Thomas S. Kolodgie, Frank D. Ohayon, Jacques Pettigrew, Roderic Sabatine, Marc S. Tearney, Guillermo J. Waxman, Sergio Domanski, Michael J. Srinivas, Pothur R. Narula, Jagat TI Detection of High-Risk Atherosclerotic Plaque Report of the NHLBI Working Group on Current Status and Future Directions SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE cardiovascular event; high-risk plaque; imaging; prognosis; vulnerable plaque ID CORONARY-ARTERY-DISEASE; OPTICAL COHERENCE TOMOGRAPHY; INFRARED SPECTROSCOPY SYSTEM; POSITRON-EMISSION-TOMOGRAPHY; RADIOFREQUENCY DATA-ANALYSIS; C-REACTIVE PROTEIN; INTRAVASCULAR ULTRASOUND; VULNERABLE PLAQUE; CAROTID PLAQUE; MYOCARDIAL-INFARCTION AB The leading cause of major morbidity and mortality in most countries around the world is atherosclerotic cardiovascular disease, most commonly caused by thrombotic occlusion of a high-risk coronary plaque resulting in myocardial infarction or cardiac death, or embolization from a high-risk carotid plaque resulting in stroke. The lesions prone to result in such clinical events are termed vulnerable or high-risk plaques, and their identification may lead to the development of pharmacological and mechanical intervention strategies to prevent such events. Autopsy studies from patients dying of acute myocardial infarction or sudden death have shown that such events typically arise from specific types of atherosclerotic plaques, most commonly the thin-cap fibroatheroma. However, the search in human beings for vulnerable plaques before their becoming symptomatic has been elusive. Recently, the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study demonstrated that coronary plaques that are likely to cause future cardiac events, regardless of angiographic severity, are characterized by large plaque burden and small lumen area and/or are thin-cap fibroatheromas verified by radiofrequency intravascular ultrasound imaging. This study opened the door to identifying additional invasive and noninvasive imaging modalities that may improve detection of high-risk atherosclerotic lesions and patients. Beyond classic risk factors, novel biomarkers and genetic profiling may identify those patients in whom noninvasive imaging for vulnerable plaque screening, followed by invasive imaging for risk confirmation is warranted, and in whom future pharmacological and/or device-based focal or regional therapies may be applied to improve long-term prognosis. (J Am Coll Cardiol Img 2012;5:941-55) (C) 2012 by the American College of Cardiology Foundation C1 [Fleg, Jerome L.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA. [Stone, Gregg W.; Granada, Juan F.] Columbia Univ, Med Ctr, New York, NY USA. [Stone, Gregg W.; Granada, Juan F.] Cardiovasc Res Fdn, New York, NY USA. [Fayad, Zahi A.; Domanski, Michael J.; Narula, Jagat] Mt Sinai Sch Med, New York, NY USA. [Hatsukami, Thomas S.] Univ Washington, Seattle, WA 98195 USA. [Kolodgie, Frank D.] Cardiovasc Pathol Inst, Gaithersburg, MD USA. [Ohayon, Jacques; Pettigrew, Roderic] NIDDKD, Bethesda, MD 20892 USA. [Sabatine, Marc S.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Sabatine, Marc S.; Tearney, Guillermo J.] Harvard Univ, Sch Med, Boston, MA USA. [Tearney, Guillermo J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Waxman, Sergio] Lahey Clin Fdn, Boston, MA USA. RP Fleg, JL (reprint author), NHLBI, Div Cardiovasc Sci, 6701 Rockledge Dr,Room 8150, Bethesda, MD 20892 USA. EM flegj@nhlbi.nih.gov; narula@mountsinai.org FU Brigham and Women's Hospital from Abbott Laboratories; Amgen; AstraZeneca; BRAHMS; Bristol-Myers Squibb/Sanofi-Aventis Joint Venture; Critical Diagnostics; Daiichi-Sankyo; Merck; Roche Diagnostics; Takeda; Nanosphere; Terumo Corporation FX Dr. Stone has been a consultant to InfraReDx, Boston Scientific, Abbott Vascular, Medtronic, and Volcano. Dr. Sabatine has received research grant support (>$25,000) through Brigham and Women's Hospital from Abbott Laboratories, Amgen, AstraZeneca, BRAHMS, Bristol-Myers Squibb/Sanofi-Aventis Joint Venture, Critical Diagnostics, Daiichi-Sankyo, Merck, Roche Diagnostics, and Takeda; has served on the scientific advisory board (<$10,000) for Bristol-Myers Squibb/Sanofi-Aventis Joint Venture, GlaxoSmithKline, Merck, and Pfizer; and (>$10,000) Sanofi-Aventis; and has received research support (>$25,000) from Nanosphere. Dr. Tearney has been a consultant to Samsung and Merck; has performed sponsored research for Terumo Corporation; and has the right to receive royalties from Terumo Corporation and MIT. Dr. Narula serves on the advisory boards of GE, Philips, and Siemens Healthcare. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. H. William Strauss, MD, served as Guest Editor for this paper. NR 78 TC 71 Z9 76 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD SEP PY 2012 VL 5 IS 9 BP 941 EP 955 DI 10.1016/j.jcmg.2012.07.007 PG 15 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 003DX UT WOS:000308589500013 PM 22974808 ER PT J AU Cliffe, ST Bloch, DB Suryani, S Kamsteeg, EJ Avery, DT Palendira, U Church, JA Wainstein, BK Trizzino, A Lefranc, G Akatcherian, C Megarbane, A Gilissen, C Moshous, D Reichenbach, J Misbah, S Salzer, U Abinun, M Ong, PY Stepensky, P Ruga, E Ziegler, JB Wong, M Tangye, SG Lindeman, R Buckley, MF Roscioli, T AF Cliffe, Simon T. Bloch, Donald B. Suryani, Santi Kamsteeg, Erik-Jan Avery, Danielle T. Palendira, Umaimainthan Church, Joseph A. Wainstein, Brynn K. Trizzino, Antonino Lefranc, Gerard Akatcherian, Carlo Megarbane, Andre Gilissen, Christian Moshous, Despina Reichenbach, Janine Misbah, Siraj Salzer, Uli Abinun, Mario Ong, Peck Y. Stepensky, Polina Ruga, Ezia Ziegler, John B. Wong, Melanie Tangye, Stuart G. Lindeman, Robert Buckley, Michael F. Roscioli, Tony TI Clinical, molecular, and cellular immunologic findings in patients with SP110-associated veno-occlusive disease with immunodeficiency syndrome SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Veno-occlusive disease with immunodeficiency; hypogammaglobulinemia; SP110; B-cell development ID MEMORY B-CELLS; IMPAIRED HUMORAL IMMUNITY; DIFFERENTIAL EXPRESSION; NUCLEAR-BODY; SECRETING CELLS; GENUS MUS; RECEPTOR; GENERATION; EVOLUTION; CLUSTER AB Background: Mutations in the SP110 gene result in infantile onset of the autosomal recessive primary immunodeficiency disease veno-occlusive disease with immunodeficiency syndrome (VODI), which is characterized by hypogammaglobulinemia, T-cell dysfunction, and a high frequency of hepatic veno-occlusive disease. Objectives: We sought to further characterize the clinical features, B-lineage cellular immunologic findings, and molecular pathogenesis of this disorder in 9 patients with new diagnoses, including 4 novel mutations from families of Italian, Hispanic, and Arabic ethnic origin. Methods: Methods used include clinical review; Sanger DNA sequencing of the SP110 gene; determination of transfected mutant protein function by using immunofluorescent studies in Hep-2 cells; quantitation of B-cell subsets by means of flow cytometry; assessments of B-cell function after stimulation with CD40 ligand, IL-21, or both; and differential gene expression array studies of EBV-transformed B cells. Results: We confirm the major diagnostic criteria and the clinical utility of SP110 mutation testing for the diagnosis of VODI. Analysis of 4 new alleles confirms that VODI is caused by reduced functional SP110 protein levels. Detailed B-cell immunophenotyping demonstrated that Sp110 deficiency compromises the ability of human B cells to respond to T cell-dependent stimuli and differentiate into immunoglobulin-secreting cells in vitro. Expression microarray studies have identified pathways involved in B-lymphocyte differentiation and macrophage function. Conclusion: These studies show that a range of mutations in SP110 that cause decreased SP110 protein levels and impaired late B-cell differentiation cause VODI and that the condition is not restricted to the Lebanese population. (J Allergy Clin Immunol 2012;130:735-42.) C1 [Cliffe, Simon T.; Lindeman, Robert; Buckley, Michael F.; Roscioli, Tony] Prince Wales Hosp, Dept Haematol & Genet, Sydney, NSW 2031, Australia. [Bloch, Donald B.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [Bloch, Donald B.] Harvard Univ, Sch Med, Boston, MA USA. [Suryani, Santi; Avery, Danielle T.; Palendira, Umaimainthan; Tangye, Stuart G.] Univ New S Wales, Program Immunol, Garvan Inst Med Res, Sydney, NSW, Australia. [Suryani, Santi; Avery, Danielle T.; Palendira, Umaimainthan] Univ New S Wales, St Vincents Clin Sch, Sydney, NSW, Australia. [Kamsteeg, Erik-Jan; Gilissen, Christian] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands. [Church, Joseph A.; Ong, Peck Y.] Childrens Hosp Los Angeles, Div Clin Immunol & Allergy, Los Angeles, CA USA. [Wainstein, Brynn K.; Ziegler, John B.] Sydney Childrens Hosp, Dept Immunol & Infect Dis, Sydney, NSW, Australia. [Trizzino, Antonino] Osped Bambini G Di Cristina, ARNAS Civico, Palermo, Italy. [Lefranc, Gerard] Univ Montpellier 2, Montpellier, France. [Lefranc, Gerard] CNRS, Inst Human Genet, UPR 1142, Montpellier, France. [Akatcherian, Carlo] St Joseph Univ, Hosp Hotel Dieu France, Dept Pediat, Beirut, Lebanon. [Megarbane, Andre] St Joseph Univ, Fac Med, Med Genet Unit, Beirut, Lebanon. [Moshous, Despina] Univ Paris 05, Fac Med Rene Descartes, IFR94, Paris, France. [Moshous, Despina] Hop Necker Enfants Malad, AP HP, Unite Immunol & Hematol Pediat, Paris, France. [Reichenbach, Janine] Univ Childrens Hosp Zurich, Div Immunol Haematol BMT, Zurich, Switzerland. [Reichenbach, Janine] Univ Childrens Hosp Zurich, Childrens Res Ctr, Zurich, Switzerland. [Reichenbach, Janine] Univ Zurich, Zurich Ctr Integrat Human Physiol ZIHP, CH-8006 Zurich, Switzerland. [Misbah, Siraj] John Radcliffe Hosp, Oxford Ctr Clin Immunol, Dept Clin Immunol, Oxford, England. [Salzer, Uli] Univ Med Ctr Freiburg, Ctr Chron Immunodeficiency CCI, Freiburg, Germany. [Salzer, Uli] Univ Freiburg, Freiburg, Germany. [Abinun, Mario] Newcastle Gen Hosp, Dept Paediat Immunol, Newcastle, England. [Stepensky, Polina] Hadassah Univ Hosp, IL-91120 Jerusalem, Israel. [Ruga, Ezia] Univ Padua, Dept Pediat, Padua, Italy. [Wong, Melanie] Childrens Hosp, Dept Allergy Immunol & Infect Dis, Westmead, NSW, Australia. [Roscioli, Tony] Sydney Childrens Hosp, Sch Women & Childrens Hlth, Sydney, NSW, Australia. RP Buckley, MF (reprint author), Prince Wales Hosp, Dept Haematol & Genet, Barker St, Sydney, NSW 2031, Australia. EM michael.buckley@sesiahs.health.nsw.gov.au RI Tangye, Stuart/H-4023-2014; Kamsteeg, E.J./L-4421-2015; Gilissen, Christian/E-5246-2012; Moshous, Despina/B-7507-2017 OI Gilissen, Christian/0000-0003-1693-9699; FU Massachusetts General Hospital; Research Council of the Saint Joseph University, Beirut; Robert A Good/Jeffrey Modell Fellowship in Transplantation and Immunodeficiency; Gebert Ruf Stiftung, Program Rare Diseases-New Approaches [GRS-046/10]; NHMRC [427620]; EU Science Directorate [PIIF-GA-2008-221048]; Australian NHMRC postdoctoral research fellowship; Jeffrey Modell Foundation; Chronic Granulomatous Disorder Research Trust; Gebert Ruf Stiftung; European Union Directorate of Science FX Infrastructure support was provided by the Department of Haematology and Genetics, South Eastern Area Laboratory Services, Sydney, and the Department of Human Genetics, Radboud University, Nijmegen Medical Centre. D. B. B. is supported by a grant from the Massachusetts General Hospital. C. A. and A. M. were supported in part by the Research Council of the Saint Joseph University, Beirut. D. M. was supported by the Robert A Good/Jeffrey Modell Fellowship in Transplantation and Immunodeficiency. J.R. was supported by the Gebert Ruf Stiftung, Program Rare Diseases-New Approaches, grant no. GRS-046/10. S. G. T. is an NHMRC Senior Research Fellow with research funding provided by NHMRC Program Grant no. 427620. M. F. B. is the recipient of a Marie Curie Fellowship (PIIF-GA-2008-221048) from the EU Science Directorate. T. R. is supported by an Australian NHMRC postdoctoral research fellowship.; D. Moshous has received research support from the Jeffrey Modell Foundation. J. Reichenbach has received research support from the Chronic Granulomatous Disorder Research Trust and Gebert Ruf Stiftung. M. F. Buckley has received research support from the European Union Directorate of Science. The rest of the authors declare they have no relevant conflicts of interest. NR 32 TC 13 Z9 13 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD SEP PY 2012 VL 130 IS 3 BP 735 EP + DI 10.1016/j.jaci.2012.02.054 PG 14 WC Allergy; Immunology SC Allergy; Immunology GA 001LZ UT WOS:000308463500024 PM 22621957 ER PT J AU Orange, JS Ballow, M Stiehm, ER Ballas, ZK Chinen, J De La Morena, M Kumararatne, D Harville, TO Hesterberg, P Koleilat, M McGhee, S Perez, EE Raasch, J Scherzer, R Schroeder, H Seroogy, C Huissoon, A Sorensen, RU Katial, R AF Orange, Jordan S. Ballow, Mark Stiehm, E. Richard Ballas, Zuhair K. Chinen, Javier De La Morena, Maite Kumararatne, Dinakantha Harville, Terry O. Hesterberg, Paul Koleilat, Majed McGhee, Sean Perez, Elena E. Raasch, Jason Scherzer, Rebecca Schroeder, Harry Seroogy, Christine Huissoon, Aarnoud Sorensen, Ricardo U. Katial, Rohit TI Use and interpretation of diagnostic vaccination in primary immunodeficiency: A working group report of the Basic and Clinical Immunology Interest Section of the American Academy of Allergy, Asthma & Immunology SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Vaccines; primary immunodeficiency; diagnosis; guideline; antigen challenge; neoantigen; antibody deficiency; common variable immunodeficiency; specific antibody deficiency ID PNEUMOCOCCAL CONJUGATE VACCINE; INFLUENZAE TYPE-B; COMMON VARIABLE IMMUNODEFICIENCY; ADENOSINE-DEAMINASE DEFICIENCY; RANDOMIZED CONTROLLED-TRIAL; POLYSACCHARIDE ANTIBODY-RESPONSE; STREPTOCOCCUS-PNEUMONIAE VACCINE; RESPIRATORY-TRACT INFECTIONS; BONE-MARROW TRANSPLANTATION; 22Q11.2 DELETION SYNDROME AB A major diagnostic intervention in the consideration of many patients suspected to have primary immunodeficiency diseases (PIDDs) is the application and interpretation of vaccination. Specifically, the antibody response to antigenic challenge with vaccines can provide substantive insight into the status of human immune function. There are numerous vaccines that are commonly used in healthy individuals, as well as others that are available for specialized applications. Both can potentially be used to facilitate consideration of PIDD. However, the application of vaccines and interpretation of antibody responses in this context are complex. These rely on consideration of numerous existing specific studies, interpolation of data from healthy populations, current diagnostic guidelines, and expert subspecialist practice. This document represents an attempt of a working group of the American Academy of Allergy, Asthma & Immunology to provide further guidance and synthesis in this use of vaccination for diagnostic purposes in consideration of PIDD, as well as to identify key areas for further research. (J Allergy Clin Immunol 2012; 130: S1-24.) C1 [Orange, Jordan S.; Chinen, Javier] Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA. [Ballow, Mark] SUNY Buffalo, Women & Childrens Hosp Buffalo, Sch Med & Biomed Sci, Buffalo, NY 14260 USA. [Stiehm, E. Richard; McGhee, Sean] Univ Calif Los Angeles, David Geffen Sch Med, Mattel Childrens Hosp, Los Angeles, CA 90095 USA. [Ballas, Zuhair K.] Univ Iowa, Coll Med, Iowa City, IA USA. [De La Morena, Maite] Univ Texas SW Med Ctr Dallas, Childrens Med Ctr, Dallas, TX 75390 USA. [Kumararatne, Dinakantha] Addenbrookes Hosp, Dept Clin Biochem & Immunol, Cambridge, England. [Harville, Terry O.] Univ Arkansas Med Sci, Dept Pathol, Little Rock, AR 72205 USA. [Harville, Terry O.] Univ Arkansas Med Sci, Lab Serv & Pediat, Little Rock, AR 72205 USA. [Hesterberg, Paul] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Koleilat, Majed] Deaconess Clin, Evansville, IN USA. [Perez, Elena E.] Univ S Florida, All Childrens Hosp, Coll Med, St Petersburg, FL 33701 USA. [Raasch, Jason] Midwest Immunol Clin, Plymouth, Devon, England. [Scherzer, Rebecca] Ohio State Univ, Nationwide Childrens Hosp, Columbus, OH 43210 USA. [Schroeder, Harry] Univ Alabama Birmingham, Sch Med, Birmingham, AL USA. [Seroogy, Christine] Univ Wisconsin, Madison, WI 53706 USA. [Huissoon, Aarnoud] Birmingham Heartlands Hosp, Birmingham, W Midlands, England. [Sorensen, Ricardo U.] Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA USA. [Katial, Rohit] Natl Jewish Hlth, Denver, CO USA. [Katial, Rohit] Univ Colorado, Sch Med, Denver, CO USA. RP Orange, JS (reprint author), Texas Childrens Hosp, Baylor Coll Med, 1102 Bates St,Suite 330, Houston, TX 77030 USA. EM orange@bcm.edu RI Scherzer, Rebecca/E-4034-2011; OI orange, jordan/0000-0001-7117-7725 FU Baxter Bioscience; Grifols; Octapharma USA; CSL Behring; IBT Reference Laboratories; Cangene; Baxter; ACAAI; UpToDate; Talecris; VA; National Institutes of Health (NIH); Jeffrey Modell Foundation; NIHR, UK; Viropharma FX J S. Orange has received consultancy fees from Baxter Bioscience, Grifols, Octapharma USA, CSL Behring, IBT Reference Laboratories, and Cangene; has received lecture fees from Baxter Bioscience; and receives royalties from UpToDate. M. Ballow has received consulting fees from Baxter, CSL Behring, Grifols; has received fees for participation in review activities from Green Cross DSMB; has received legal fees to review a case; has received lecture fees from Baxter, CSL Behring, and the ACAAI; and has received payment for manuscript preparation from Baxter. E.R. Stiehm has received consultancy fees from UpToDate; is employed by Vela; has provided expert witness testimony on the topic of vaccine adverse effects; has received an unrestricted donation to Dr. Roger Kobayashi Allergy and Immunology Associates of Omaha for travel expenses; and has received travel expenses from the US Immune Deficiency Foundation and March of Dimes. Z.K. Ballas has received research support from Talecris, VA, and the National Institutes of Health (NIH); receives royalties from UpToDate; and has served as a member of the AAAAI Board of Directors. M. De La Morena has received research support from the Jeffrey Modell Foundation. D. Kumararatne has received research support from NIHR, UK; has received consultancy fees from Viropharma; has received lecture payments from Baxter; and has received travel funds from CSL Behring. S. McGhee has received lecture fees from Baxter. E.E. Perez has received consultancy fees from Baxter and CSL Behring; is employed by the University of South Florida; and has received payment for the development of educational presentations from Baxter. J. Raasch has received lecture fees from Baxter and CSL Behring and has received payment for the development of educational presentations from Baxter. H. Schroeder has received research support from the NIAID, NABI Pharmaceuticals, and Green Cross Pharmaceuticals; has received lecture fees from the AAAAI and NABI Pharmaceuticals; and has received royalties from Elsevier as the editor of Clinical Immunology: Principles and Practices. C. Seroogy has received consultancy fees from UpToDate; is employed by the University of Wisconsin; and has received research support from Midwest Athletes Against Childhood Cancer and the NIH. A. Huissoon has served on the Advisory Boards for Biotest, Shire, Swedish Orphan Biovitrum, and Meda; has received lecture fees from GlaxoSmithKline; holds shares in GlaxoSmithKline; has received travel expenses from CSL Behring; and has organized meetings that have been funded by The Binding Site, Ltd. The rest of the authors have declared that they have no relevant conflicts of interest. NR 167 TC 92 Z9 93 U1 0 U2 10 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD SEP PY 2012 VL 130 IS 3 SU S BP S1 EP S24 DI 10.1016/j.jaci.2012.07.002 PG 24 WC Allergy; Immunology SC Allergy; Immunology GA 001MH UT WOS:000308464300001 PM 22935624 ER PT J AU Tanpowpong, P Broder-Fingert, S Katz, AJ Camargo, CA AF Tanpowpong, Pornthep Broder-Fingert, Sarabeth Katz, Aubrey J. Camargo, Carlos A., Jr. TI Predictors of duodenal bulb biopsy performance in the evaluation of coeliac disease in children SO JOURNAL OF CLINICAL PATHOLOGY LA English DT Review ID PATCHY VILLOUS ATROPHY; VARIABILITY; DIAGNOSIS; HISTOPATHOLOGY; PATHOLOGISTS; MULTICENTER; PREVALENCE; MORTALITY; LESIONS; GLUTEN AB Aims Studies on the role of duodenal bulb biopsy (DBB) in coeliac disease (CD) evaluation have increased in recent years; growing evidence suggests that the disease can present solely in the duodenal bulb. Moreover, recent CD guidelines recommend obtaining a DBB. The study aim was to examine DBB performance in children undergoing CD evaluation and to identify independent predictors of DBB performance. Methods The authors performed a structured chart review of children aged <18 years who underwent CD evaluation between 2000 and 2010 at a large teaching hospital. The authors collected data including demographics, serology, endoscopy and histopathological findings. Predictors of DBB performance (obtained vs not obtained) were determined using multivariable logistic regression. Results Among 616 children who underwent endoscopy, DBB was performed in 103 children (17%, 95% CI 14% to 20%) with an increasing trend in the more recent years (2008-2010, 25%; 2004-2007, 16%; and 2000-2003, 5%, p<0.001). Three independent predictors of DBB performance were older age at endoscopy (OR 1.05 per year of age), gross gastric antral abnormalities (OR 2.81) and gross duodenal abnormalities (OR 5.55). Regarding the DBB histological findings, patchiness of CD was found in 15%. Positive Marsh III biopsy presented solely on the DBB in 6/103 (6%, 95% CI 2% to 12%) children. Conclusions The authors found a significant increase in DBB performance over time, but the overall performance remains suboptimal. Improving education on obtaining a DBB for CD evaluation is crucial, especially among those children in whom DBB is more likely to be omitted. C1 [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02114 USA. [Tanpowpong, Pornthep; Broder-Fingert, Sarabeth; Katz, Aubrey J.] Harvard Univ, Massachusetts Gen Hosp Children, Sch Med, Dept Pediat, Boston, MA 02114 USA. RP Camargo, CA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM ccamargo@partners.org OI Broder-Fingert, Sarabeth/0000-0002-0932-4461 NR 23 TC 2 Z9 4 U1 0 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0021-9746 J9 J CLIN PATHOL JI J. Clin. Pathol. PD SEP PY 2012 VL 65 IS 9 BP 791 EP 794 DI 10.1136/jclinpath-2012-200874 PG 4 WC Pathology SC Pathology GA 000YC UT WOS:000308426000003 PM 22718844 ER PT J AU Farnan, JM Burger, A Boonayasai, RT Leykum, L Harrison, R Machulsky, J Parekh, V Sharpe, BA Schleyer, AM Arora, VM AF Farnan, Jeanne M. Burger, Alfred Boonayasai, Romsai T. Leykum, Luci Harrison, Rebecca Machulsky, Julie Parekh, Vikas Sharpe, Bradley A. Schleyer, Anneliese M. Arora, Vineet M. CA SGIM Housestaff Oversight Subcomm TI Survey of overnight academic hospitalist supervision of trainees SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID SAFETY AB In 2003, Accreditation Council for Graduate Medical Education (ACGME) announced the first in a series of guidelines related to the residency training. The most recent recommendations include explicit recommendations regarding the provision of on-site clinical supervision for trainees of internal medicine. To meet these standards, many internal medicine residency programs turned to hospitalist programs to fill that need. However, much is unknown about the current relationships between hospitalist and residency programs, specifically with regard to supervisory roles and supervision policies. We aimed to describe how academic hospitalists currently supervise housestaff during the on-call, or overnight, period and hospitalist program leader their perceptions of how these new policies would impact trainee-hospitalist interactions. Journal of Hospital Medicine 2012;(C) 2012 Society of Hospital Medicine C1 [Farnan, Jeanne M.] Univ Chicago, Dept Med, Sect Hosp Med, Chicago, IL 60637 USA. [Burger, Alfred] Albert Einstein Coll Med, Dept Med, Gen Internal Med Sect, Beth Israel Med Ctr, New York, NY USA. [Boonayasai, Romsai T.] Johns Hopkins Univ, Sch Med, Dept Med, Gen Internal Med Sect, Baltimore, MD 21205 USA. [Leykum, Luci] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Harrison, Rebecca] Oregon Hlth & Sci Univ, Dept Med, Div Hosp Med, Portland, OR 97201 USA. [Machulsky, Julie] Soc Gen Internal Med, Alexandria, VA USA. [Parekh, Vikas] Univ Michigan, Sch Med, Dept Med, Div Gen Med, Ann Arbor, MI 48104 USA. [Sharpe, Bradley A.] Univ Calif San Francisco, Dept Med, Div Hosp Med, San Francisco, CA USA. [Schleyer, Anneliese M.] Univ Washington, Dept Med, Div Gen Internal Med, Seattle, WA USA. [Arora, Vineet M.] Gen Internal Med Sect, Dept Med, New Haven, CT USA. RP Farnan, JM (reprint author), Univ Chicago, Dept Med, Sect Hosp Med, 5841 S Maryland Ave,MC 2007,AMB W216, Chicago, IL 60637 USA. EM jfarnan@medicine.bsd.uchicago.edu OI Arora, Vineet/0000-0002-4745-7599 FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service [REA 05-129, CDA 07-022] FX The research reported here was supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service (REA 05-129, CDA 07-022). 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. NR 8 TC 8 Z9 8 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1553-5592 EI 1553-5606 J9 J HOSP MED JI J. Hosp. Med. PD SEP PY 2012 VL 7 IS 7 BP 521 EP 523 DI 10.1002/jhm.1961 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 000YQ UT WOS:000308427400002 PM 22956452 ER PT J AU Englander, H Kansagara, D AF Englander, Honora Kansagara, Devan TI Planning and designing the care transitions innovation (C-Train) for uninsured and Medicaid patients SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID CONTROLLED-TRIAL; HOSPITALIZATION; INTERVENTION; QUALITY AB BACKGROUND: Uninsured and Medicaid patients are particularly vulnerable as they transition from hospital to home. Transitional care improvement programs require time and capital, incentives for which may be unclear for those lacking a third-party payor. This article describes our experience developing a hospital-funded transitional care program for uninsured and Medicaid patients. METHODS: We performed an inpatient needs assessment, convened multi-stakeholder work groups, and engaged institutional change-agents to inform program development and a business case. RESULTS: We mapped needs to specific program elements, including a transitional care nurse, pharmacy consult and provision of medications for uninsured patients, medical home linkages including community payment for medical homes, and monthly quality improvement meetings. A business case was informed by local needs and utilization data, and compelled the hospital to invest in up-front resources for this population. DISCUSSION: We are studying our program's impact on 30-day readmission and emergency department rates through a clustered, randomized controlled trial. Lessons from our experience may be useful to others aiming to improve care for socioeconomically disadvantaged patients. Journal of Hospital Medicine 2012; (C) 2012 Society of Hospital Medicine C1 [Englander, Honora; Kansagara, Devan] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97239 USA. [Kansagara, Devan] Portland VA Med Ctr, Portland, OR USA. RP Englander, H (reprint author), Oregon Hlth & Sci Univ, Dept Med, Mail Code BTE 119,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM englandh@ohsu.edu NR 16 TC 11 Z9 11 U1 2 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1553-5592 J9 J HOSP MED JI J. Hosp. Med. PD SEP PY 2012 VL 7 IS 7 BP 524 EP 529 DI 10.1002/jhm.1926 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 000YQ UT WOS:000308427400003 PM 22411913 ER PT J AU Ganguli, I Pierce, C Sharpe, B Hansra, N Hollander, H AF Ganguli, Ishani Pierce, Cason Sharpe, Bradley Hansra, Nina Hollander, Harry TI The hand that feeds you SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID CAPNOCYTOPHAGA-CANIMORSUS INFECTIONS; PURPURA FULMINANS; DOG-BITE; GANGRENE C1 [Hollander, Harry] Univ Calif San Francisco, Div Infect Dis, San Francisco, CA 94143 USA. [Ganguli, Ishani] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Pierce, Cason] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Sharpe, Bradley] Univ Calif San Francisco, Div Hosp Med, San Francisco, CA 94143 USA. [Hansra, Nina] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. RP Hollander, H (reprint author), Univ Calif San Francisco, Div Infect Dis, Box 0119, San Francisco, CA 94143 USA. EM harry.hollander@ucsf.edu NR 8 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1553-5592 J9 J HOSP MED JI J. Hosp. Med. PD SEP PY 2012 VL 7 IS 7 BP 590 EP 594 DI 10.1002/jhm.1939 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 000YQ UT WOS:000308427400013 PM 22532484 ER PT J AU Goldfarb, E Fromson, JA Gorrindo, T Birnbaum, RJ AF Goldfarb, Elizabeth Fromson, John A. Gorrindo, Tristan Birnbaum, Robert J. TI Enhancing informed consent best practices: gaining patient, family and provider perspectives using reverse simulation SO JOURNAL OF MEDICAL ETHICS LA English DT Article ID DECISION-MAKING; CENTERED CARE; INFORMATION; SCHIZOPHRENIA; RECOMMENDATIONS; MEDICATIONS; PREFERENCES; QUALITY; DOCTORS; WANT AB Background Obtaining informed consent in the clinical setting is an important yet challenging aspect of providing safe and collaborative care to patients. While the medical profession has defined best practices for obtaining informed consent, it is unclear whether these standards meet the expressed needs of patients, their families as well as healthcare providers. The authors sought to address this gap by comparing the responses of these three groups with a standardised informed consent paradigm. Methods Piloting a web-based 'reverse' simulation paradigm, participants viewed a video showing a standardised doctor engaging in an informed consent discussion. The scenario depicted a simulated patient with psychotic symptoms who is prescribed an atypical antipsychotic medication. 107 participants accessed the simulation online and completed a web-based debriefing survey. Results Survey responses from patients, family members and healthcare providers indicated disparities in information retention, perception of the doctor's performance and priorities for required elements of the consent process. Conclusions To enhance existing informed consent best practices, steps should be taken to improve patient retention of critical information. Adverse events should be described in the short-term and long-term along with preventative measures, and alternative psychosocial and pharmacological treatment options should be reviewed. Information about treatment should include when the medication takes therapeutic effect and how to safely maintain the treatment. The reverse simulation design is a model that can discern gaps in clinical practice, which can be used to improve patient care. C1 [Fromson, John A.] Massachusetts Gen Hosp, Div Postgrad Med Educ, Dept Psychiat, Boston, MA 02114 USA. [Fromson, John A.; Gorrindo, Tristan; Birnbaum, Robert J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Fromson, JA (reprint author), Massachusetts Gen Hosp, Div Postgrad Med Educ, Dept Psychiat, 1 Bowdoin Sq,7 th Fl, Boston, MA 02114 USA. EM jfromson@partners.org NR 35 TC 2 Z9 3 U1 1 U2 3 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0306-6800 J9 J MED ETHICS JI J. Med. Ethics PD SEP PY 2012 VL 38 IS 9 BP 546 EP 551 DI 10.1136/medethics-2011-100206 PG 6 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 999YV UT WOS:000308352900009 PM 22522147 ER PT J AU Dziurzynski, K Blas-Boria, D Suki, D Cahill, DP Prabhu, SS Puduvalli, V Levine, N AF Dziurzynski, Kristine Blas-Boria, David Suki, Dima Cahill, Daniel P. Prabhu, Sujit S. Puduvalli, Vinay Levine, Nicholas TI Butterfly glioblastomas: a retrospective review and qualitative assessment of outcomes SO JOURNAL OF NEURO-ONCOLOGY LA English DT Review DE Butterfly gliomblastoma; Butterfly glioma; Bifrontal glioma; Biftrontal glioblastoma; Bihemispheric glioma; Corpus callosum glioblastoma ID CORPUS-CALLOSUM; GLIOMA AB To address a paucity of literature and treatment guidelines regarding the management of butterfly glioblastomas, we performed a ten year retrospective analysis of data from twenty-three consecutive patients treated for this disease at a single institution. Clinical characteristics and outcomes were assessed. Median age was 59 years; 52 % were female; median preoperative Karnofsky performance score (KPS) was 80. Twelve patients underwent biopsy and eleven underwent surgical decompression. The median tumor volume for the biopsy group was 60.6 cm(3) and for the surgically decompressed group 40.5 cm(3). In the biopsy group, five patients received adjuvant therapy but one died prior to its completion; two died prior to the initiation of adjuvant therapy and five were lost to follow up. In the surgical decompression group, seven patients received adjuvant therapy, one died prior to the initiation of adjuvant therapy, two were treated with palliative measures only, and one was lost to follow up. Kaplan-Meier estimates of overall median post surgical-survival of the whole group was 180 days, the biopsy group 48 days, and the surgically decompressed group 265 days (p = 0.14). Our results show that there was a higher median survival in the surgically decompressed group; but a direct correlation could not be established, and that the median KPS did not improve in either group after treatment. A larger multicenter review is required to quantitatively assess the factors, including tumor biomarkers that are associated with patient outcome. C1 [Dziurzynski, Kristine; Suki, Dima; Prabhu, Sujit S.; Levine, Nicholas] Univ Texas MD Anderson Canc Ctr, Dept Neurosurg, Houston, TX 77030 USA. [Puduvalli, Vinay] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. [Blas-Boria, David] Univ Puerto Rico, Dept Internal Med, Neurol Sect, San Juan, PR 00936 USA. [Cahill, Daniel P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA USA. RP Dziurzynski, K (reprint author), Wheaton Franciscan All St, 3805-B Spring St,Suite 320, Racine, WI 53405 USA. EM krdziurzynski@gmail.com RI Puduvalli, Vinay/A-2411-2016; OI Cahill, Daniel/0000-0003-2552-6546 FU NCI NIH HHS [K24 CA160777] NR 15 TC 8 Z9 8 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD SEP PY 2012 VL 109 IS 3 BP 555 EP 563 DI 10.1007/s11060-012-0926-0 PG 9 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 001DZ UT WOS:000308441700013 PM 22806339 ER PT J AU Blaney, SM Kocak, M Gajjar, A Chintagumpala, M Merchant, T Kieran, M Pollack, IF Gururangan, S Geyer, R Phillips, P McLendon, RE Packer, R Goldman, S Banerjee, A Heideman, R Boyett, JM Kun, L AF Blaney, Susan M. Kocak, Mehmet Gajjar, Amar Chintagumpala, Murali Merchant, Thomas Kieran, Mark Pollack, Ian F. Gururangan, Sri Geyer, Russ Phillips, Peter McLendon, Roger E. Packer, Roger Goldman, Stewart Banerjee, Anu Heideman, Richard Boyett, James M. Kun, Larry TI Pilot study of systemic and intrathecal mafosfamide followed by conformal radiation for infants with intracranial central nervous system tumors: a pediatric brain tumor consortium study (PBTC-001) SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Mafosfamide; Intrathecal; Infant brain tumor; Embryonal CNS tumor; Conformal radiation therapy ID EARLY-CHILDHOOD MEDULLOBLASTOMA; THAN 3 YEARS; POSTOPERATIVE CHEMOTHERAPY; YOUNG-CHILDREN; DEFERRED RADIOTHERAPY; CYCLOPHOSPHAMIDE; IRRADIATION; SURVIVAL; AGE AB A pilot study to investigate the feasibility of the addition of intrathecal (IT) mafosfamide to a regimen of concomitant multi-agent systemic chemotherapy followed by conformal radiation therapy (RT) for children < 3 years with newly diagnosed embryonal CNS tumors was performed. Ninety-three newly diagnosed infants and children (< 3 years) with embryonal CNS tumors were enrolled. Twenty weeks of systemic multi-agent chemotherapy commenced within 35 days of surgery. Patients without CSF flow obstruction (n = 71) received IT mafosfamide (14 mg) with chemotherapy. Localized (M-0) patients with SD or better subsequently received RT followed by 20 additional weeks of chemotherapy. Second look surgery was encouraged prior to RT if there was an incomplete surgical resection at diagnosis. 71 evaluable patients with normal CSF flow received IT Mafosfamide with systemic chemotherapy; patients with M + disease were removed from protocol therapy at 20 weeks and those with PD at the time of progression. One and 5-year progression free survival (PFS) and overall survival (OS) for the cohort of 71 evaluable patients were 52 +/- A 6.5 % and 33 +/- A 13 %, and 67 +/- A 6.2 % and 51 +/- A 11 %, respectively. The 1-year Progression Free Survival (PFS) for M0 patients with medulloblastoma (MB, n = 20), supratentorial primitive neuroectodermal tumor (PNET, n = 9), and atypical teratoid rhabdoid tumor (ATRT, n = 12) was 80 +/- A 7 %, 67 +/- A 15 % and 27 +/- A 13 % and 5-year PFS was 65 +/- A 19 %, 37 +/- A 29 %, and 0 +/- A 0 %, respectively. The addition of IT mafosfamide to systemic chemotherapy in infants with embryonal CNS tumors was feasible. The PFS for M0 patients appears comparable to or better than most prior historical comparisons and was excellent for those receiving conformal radiotherapy. C1 [Blaney, Susan M.; Chintagumpala, Murali] Baylor Coll Med, Texas Childrens Canc Ctr, Houston, TX 77030 USA. [Kocak, Mehmet; Gajjar, Amar; Merchant, Thomas; Heideman, Richard; Boyett, James M.; Kun, Larry] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. [Kieran, Mark] Dana Farber Canc Inst, Boston, MA 02115 USA. [Pollack, Ian F.] Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA. [Gururangan, Sri; McLendon, Roger E.] Duke Univ, Med Ctr, Durham, NC 27710 USA. [Geyer, Russ] Childrens Hosp & Med Ctr, Seattle, WA 98105 USA. [Phillips, Peter] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Packer, Roger] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Goldman, Stewart] Childrens Mem Hosp, Chicago, IL 60614 USA. [Banerjee, Anu] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Kocak, Mehmet] Univ Tennessee, Hlth Sci Ctr, Memphis, TN 38105 USA. [Kieran, Mark] Childrens Hosp, Boston, MA 02115 USA. RP Kocak, M (reprint author), St Jude Childrens Res Hosp, 332 N Lauderdale St, Memphis, TN 38105 USA. EM smblaney@txch.org; mehmet.kocak@stjude.org OI Kocak, Mehmet/0000-0002-3386-1734; Kieran, Mark/0000-0003-2184-7692 FU NIH, Bethesda, MD [CA-98-007, U01 CA81457]; Asta Medica, Frankfurt, Germany; American Lebanese Syrian Associated Charities, Memphis, TN FX This work was supported in part by NIH CA-98-007 & NIH U01 CA81457, Bethesda, MD; Asta Medica, Frankfurt, Germany; and the American Lebanese Syrian Associated Charities, Memphis, TN. NR 18 TC 7 Z9 9 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD SEP PY 2012 VL 109 IS 3 BP 565 EP 571 DI 10.1007/s11060-012-0929-x PG 7 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 001DZ UT WOS:000308441700014 PM 22790443 ER PT J AU Rodriguez, FJ Ligon, AH Horkayne-Szakaly, I Rushing, EJ Ligon, KL Vena, N Garcia, DI Cameron, JD Eberhart, CG AF Rodriguez, Fausto J. Ligon, Azra H. Horkayne-Szakaly, Iren Rushing, Elisabeth J. Ligon, Keith L. Vena, Natalie Garcia, Denise I. Cameron, J. Douglas Eberhart, Charles G. TI BRAF Duplications and MAPK Pathway Activation Are Frequent in Gliomas of the Optic Nerve Proper SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE BRAF; Fluorescence in situ hybridization; Glioma; MAPK; Neurofibromatosis; Optic nerve; Pilocytic astrocytoma ID ONCOGENE-INDUCED SENESCENCE; LOW-GRADE ASTROCYTOMAS; PILOCYTIC ASTROCYTOMAS; NEUROFIBROMATOSIS TYPE-1; FUSION GENE; 7Q34; MUTATIONS; SIGNATURE; GENOTYPE; DEFINES AB Optic pathway gliomas represent a specific subtype of astrocytoma with unique clinicopathologic and biologic properties, but studies of tumors in the optic nerve proper have been hampered by limited tissue availability. We analyzed optic nerve gliomas of 59 patients (median age, 9 years; range, 3 months-66 years; 33 female, 26 male) using formalin-fixed paraffin-embedded material in tissue microarrays. Seven patients had the clinical diagnosis of neurofibromatosis type 1 (NF1). Fluorescence in situ hybridization studies were performed for BRAF, PTEN, CDKN2A (p16), and NF1. Immunohistochemistry was performed for glial fibrillary acidic protein, phospho-ERK, and mutant IDH1(R132H) protein. The BRAF duplication was present in 11 (73%) of 15 evaluable tumors, including 1 NF1 patient (1 of 4 tested; 25%). The single tumor lacking BRAF duplication or NF1 association had histologic features of a ganglioglioma. Conversely, heterozygous PTEN deletions were present in 2 (8%) of 25 evaluable cases, one of which was BRAF duplicated and the other was NF1 associated. CDKN2A and NF1 deletions were absent in all tumors tested. Phospho-ERK immunoreactivity was present in 55 (96%) of 57 tumors and was mostly strong and diffuse (80%). Only 1 case of 53 expressed IDH1(R132H). Thus, optic nerve gliomas demonstrated molecular alterations typical of pilocytic astrocytomas, including the universal presence of either BRAF duplication or NF1 association and common mitogen-activated protein kinase pathway activation but very rare mutant IDH1 expression. C1 [Rodriguez, Fausto J.; Eberhart, Charles G.] Johns Hopkins Univ Hosp, Dept Pathol, Baltimore, MD 21287 USA. [Ligon, Azra H.; Ligon, Keith L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Ligon, Keith L.] Childrens Hosp, Boston, MA 02115 USA. [Ligon, Azra H.; Ligon, Keith L.; Vena, Natalie; Garcia, Denise I.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ligon, Azra H.; Ligon, Keith L.; Vena, Natalie; Garcia, Denise I.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Ligon, Azra H.; Ligon, Keith L.] Harvard Univ, Sch Med, Boston, MA USA. [Horkayne-Szakaly, Iren] Joint Pathol Ctr, Silver Spring, MD USA. [Rushing, Elisabeth J.] Univ Zurich Hosp, Inst Neuropathol, CH-8091 Zurich, Switzerland. [Cameron, J. Douglas] Univ Minnesota, Dept Ophthalmol, Minneapolis, MN 55455 USA. [Cameron, J. Douglas] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. RP Rodriguez, FJ (reprint author), Johns Hopkins Univ, Dept Pathol, Div Neuropathol, 720 Rutland Ave,Ross Bldg 558, Baltimore, MD 21205 USA. EM frodrig4@jhmi.edu OI Ligon, Keith/0000-0002-7733-600X FU Children's Cancer Foundation; Childhood Brain Tumor Foundation; DFCI Pediatric Low-Grade Astrocytoma Foundation; NCI [P01CA142536]; Research to Prevent Blindness of the University of Minnesota FX This work was funded in part by the Children's Cancer Foundation and contributors to the Pilocytic/Pilomyxoid Astrocytoma Fund, including Lauren's First and Goal (Charles G. Eberhart), the Childhood Brain Tumor Foundation (Fausto J. Rodriguez), the DFCI Pediatric Low-Grade Astrocytoma Foundation (Keith L. Ligon, Azra H. Ligon), NCI P01CA142536, and an unrestricted grant from Research to Prevent Blindness to the Department of Ophthalmology of the University of Minnesota (J. Douglas Cameron). NR 35 TC 22 Z9 22 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD SEP PY 2012 VL 71 IS 9 BP 789 EP 794 DI 10.1097/NEN.0b013e3182656ef8 PG 6 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 001FK UT WOS:000308445700003 PM 22892521 ER PT J AU Kellermayer, R Mir, SAV Nagy-Szakal, D Cox, SB Dowd, SE Kaplan, JL Sun, Y Reddy, S Bronsky, J Winter, HS AF Kellermayer, Richard Mir, Sabina A. V. Nagy-Szakal, Dorottya Cox, Stephen B. Dowd, Scot E. Kaplan, Jess L. Sun, Yan Reddy, Sahna Bronsky, Jiri Winter, Harland S. TI Microbiota Separation and C-reactive Protein Elevation in Treatment-naive Pediatric Granulomatous Crohn Disease SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article DE Crohn disease; fungi; granuloma; inflammatory bowel disease; microbiota ID INFLAMMATORY-BOWEL-DISEASE; EPITHELIOID GRANULOMAS; ULCERATIVE-COLITIS; MUCOSAL FLORA; COLONIZATION; EPIDEMIOLOGY; PREVALENCE; DIVERSITY; FREQUENCY; CHILDREN AB Objectives: In patients with inflammatory bowel diseases (IBDs), the presence of noncaseating mucosal granuloma is sufficient for diagnosing Crohn disease (CD) and may represent a specific immune response or microbial-host interaction. The cause of granulomas in CD is unknown and their association with the intestinal microbiota has not been addressed with high-throughput methodologies. Methods: The mucosal microbiota from 3 different pediatric centers was studied with 454 pyrosequencing of the bacterial 16S rRNA gene and the fungal small subunit (SSU) ribosomal region in transverse colonic biopsy specimens from 26 controls and 15 treatment-naive pediatric CD cases. Mycobacterium avium subspecies paratuberculosis (MAP) was tested with real-time polymerase chain reaction. The correlation of granulomatous inflammation with C-reactive protein was expanded to 86 treatment-naive CD cases. Results: The CD microbiota separated from controls by distance-based redundancy analysis (P = 0.035). Mucosal granulomata found in any portion of the intestinal tract associated with an augmented colonic bacterial microbiota divergence (P = 0.013). The granuloma-based microbiota separation persisted even when research center bias was eliminated (P = 0.04). Decreased Roseburia and Ruminococcus in granulomatous CD were important in this separation; however, principal coordinates analysis did not reveal partitioning of the groups. CRP levels >1 mg/dL predicted the presence of mucosal granulomata (odds ratio 28 [6-134.32]; 73% sensitivity, 91% specificity). Conclusions: Granulomatous CD associates with microbiota separation and C-reactive protein elevation in treatment-naive children; however, overall dysbiosis in pediatric CD appears rather limited. Geographical/center bias should be accounted for in future multicenter microbiota studies. C1 [Kellermayer, Richard; Mir, Sabina A. V.; Nagy-Szakal, Dorottya; Reddy, Sahna] Texas Childrens Hosp, ARS, USDA, Dept Pediat,Baylor Coll Med,Childrens Nutr Res Ct, Houston, TX 77030 USA. [Cox, Stephen B.; Sun, Yan] Res & Testing Lab, Lubbock, TX USA. [Dowd, Scot E.] Mol Res MR DNA, Shallowater, TX USA. [Kaplan, Jess L.; Winter, Harland S.] MassGen Hosp Children, Dept Pediat, Boston, MA USA. [Bronsky, Jiri] Charles Univ Prague, Fac Med 2, Dept Pediat, Prague, Czech Republic. [Bronsky, Jiri] Univ Hosp Motol, Prague, Czech Republic. RP Kellermayer, R (reprint author), Baylor Coll Med, Sect Pediat Gastroenterol Hepatol & Nutr, 6621 Fannin St,CC1010-00, Houston, TX 77030 USA. EM kellerma@bcm.edu FU Broad Medical Research Program; Broad Foundation [IBD-0252]; Child Health Research Career Development Agency of the Baylor College of Medicine [5K12 HD041648]; Public Health Service [DK56338]; Texas Medical Center Digestive Diseases Center; Baylor biorepository; Pediatric IBD Foundation FX R.K. was supported in part by the Broad Medical Research Program, the Broad Foundation (IBD-0252), the Child Health Research Career Development Agency of the Baylor College of Medicine (NIH # 5K12 HD041648), and Public Health Service grant DK56338, funding the Texas Medical Center Digestive Diseases Center, which supported the Baylor biorepository as well. The biorepository of MassGeneral Hospital was supported by the Pediatric IBD Foundation, and H.W. was supported in part by philanthropic support from Martin Schlaff. The other authors report no conflicts of interest. NR 46 TC 12 Z9 12 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD SEP PY 2012 VL 55 IS 3 BP 243 EP 250 DI 10.1097/MPG.0b013e3182617c16 PG 8 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 998YS UT WOS:000308276900004 PM 22699834 ER PT J AU Tanpowpong, P Broder-Fingert, S Katz, AJ Camargo, CA AF Tanpowpong, Pornthep Broder-Fingert, Sarabeth Katz, Aubrey J. Camargo, Carlos A., Jr. TI Predictors of Gluten Avoidance and Implementation of a Gluten-Free Diet in Children and Adolescents without Confirmed Celiac Disease SO JOURNAL OF PEDIATRICS LA English DT Article ID IRRITABLE-BOWEL-SYNDROME; QUALITY-OF-LIFE; AT-RISK GROUPS; LACTOSE-INTOLERANCE; UNITED-STATES; PREVALENCE; DIAGNOSIS; AUTISM; BLIND; INDIVIDUALS AB Objectives To determine independent predictors of gluten avoidance and of a physician's decision to initiate a gluten-free diet (GFD) in children and adolescents without confirmed celiac disease. Study design We performed a structured medical record review of 579 patients aged 1-19 years presenting for evaluation of celiac disease between January 2000 and December 2010 at a large Boston teaching hospital. We collected data including demographic information, medical history, serology, small intestinal biopsy, history of gluten avoidance, and the postworkup recommendation of implementation of a GFD. Predictors of gluten-related issues were identified by multivariate logistic regression. Results Among 579 children without a previous diagnosis of celiac disease (mean age, 8.7 years), 43 (7.4%) had ever avoided gluten. Independent predictors of gluten avoidance were irritability or poor temper (OR, 3.2), diarrhea (OR, 2.5), weight issues (OR, 0.4), pervasive developmental disorder (OR, 5.3), and family history of celiac disease (OR, 2.2). Among 143 children without confirmed celiac disease who underwent diagnostic evaluation, several predictive factors were associated with a physician-recommended/parent-initiated GFD: irritability (OR, 6.4), diarrhea (OR, 3.4), pervasive developmental disorder (OR, 7.9), and positive serology before the referral (OR, 4.3). Conclusion Gluten avoidance among children and adolescents without a previous diagnosis of celiac disease is relatively common. The identified predictors suggest that gluten avoidance is associated with nonspecific behavioral and gastrointestinal complaints and perhaps with the perceived dietary responses in another family member thought to have celiac disease. (J Pediatr 2012;161:471-5). C1 [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Dept Emergency Med, Sch Med, Boston, MA 02114 USA. [Tanpowpong, Pornthep; Broder-Fingert, Sarabeth; Katz, Aubrey J.] Harvard Univ, Massachusetts Gen Hosp, Div Pediat Gastroenterol & Nutr, Sch Med, Boston, MA 02114 USA. RP Camargo, CA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Emergency Med, Sch Med, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM ccamargo@partners.org OI Broder-Fingert, Sarabeth/0000-0002-0932-4461 NR 29 TC 11 Z9 11 U1 0 U2 21 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 J9 J PEDIATR-US JI J. Pediatr. PD SEP PY 2012 VL 161 IS 3 BP 471 EP 475 DI 10.1016/j.jpeds.2012.02.049 PG 5 WC Pediatrics SC Pediatrics GA 997CL UT WOS:000308141700023 PM 22484356 ER PT J AU Frangos, JE Duncan, LM Piris, A Nazarian, RM Mihm, MC Hoang, MP Gleason, B Flotte, TJ Byers, HR Barnhill, RL Kimball, AB AF Frangos, Jason E. Duncan, Lyn M. Piris, Adriano Nazarian, Rosalynn M. Mihm, Martin C., Jr. Hoang, Mai P. Gleason, Briana Flotte, Thomas J. Byers, Hugh R. Barnhill, Raymond L. Kimball, Alexa B. TI Increased diagnosis of thin superficial spreading melanomas: A 20-year study SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE dermatopathology; diagnostic drift; dysplastic nevi; epidemiology; melanoma; melanoma epidemic ID MALIGNANT-MELANOMA; DYSPLASTIC NEVI; INCREASED SURVEILLANCE; CUTANEOUS MELANOMA; UNITED-STATES; EPIDEMIC; TRENDS; LESIONS; PRECURSOR; CRITERIA AB Background: Diagnostic practice by dermatopathologists evaluating pigmented lesions may have evolved over time. Objectives: We sought to investigate diagnostic drift among a group of dermatopathologists asked to re-evaluate cases initially diagnosed 20 years ago. Methods: Twenty nine cases of dysplastic nevi with severe atypia and 11 cases of thin radial growth-phase melanoma from 1988 through 1990 were retrieved from the pathology files of the Massachusetts General Hospital. All dermatopathologists who had rendered an original diagnosis for any of the 40 slides and the current faculty in the Massachusetts General Hospital Dermatopathology Unit were invited to evaluate the slide set in 2008 through 2009. Results: The mean number of melanoma diagnoses by the 9 study participants was 18, an increase from the original 11 melanoma diagnoses. A majority agreed with the original diagnosis of melanoma in all 11 cases. In contrast, a majority of current raters diagnosed melanoma in 4 of the 29 cases originally reported as dysplastic nevus with severe atypia. Interrater agreement over time was excellent (kappa 0.88) and fair (kappa 0.47) for cases originally diagnosed as melanoma and severely atypical dysplastic nevus, respectively. Limitations: The unbalanced composition of the slide set, lack of access to clinical or demographic information, access to only one diagnostic slide, and imposed dichotomous categorization of tumors were limitations. Conclusions: A selected cohort of dermatopathologists demonstrated a general trend toward the reclassification of prior nonmalignant diagnoses of severely atypical dysplastic nevi as malignant but did not tend to revise prior diagnoses of cutaneous melanoma as benign. (J Am Acad Dermatol 2012;67:387-94.) C1 [Frangos, Jason E.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Frangos, Jason E.; Kimball, Alexa B.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Duncan, Lyn M.; Piris, Adriano; Nazarian, Rosalynn M.; Hoang, Mai P.] Massachusetts Gen Hosp, Dermatopathol Unit, Pathol Serv, Boston, MA 02114 USA. [Mihm, Martin C., Jr.] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. [Gleason, Briana] Diagnost Pathol Med Grp, Sacramento, CA USA. [Flotte, Thomas J.] Mayo Clin, Div Anat Pathol, Rochester, MN USA. [Byers, Hugh R.] Western Dermatopathol, San Luis Obispo, CA USA. [Barnhill, Raymond L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol, Los Angeles, CA 90095 USA. [Barnhill, Raymond L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Lab Med, Los Angeles, CA 90095 USA. RP Frangos, JE (reprint author), Massachusetts Gen Hosp, Dept Dermatol, 55 Fruit St,Bartlett Hall,6th Floor, Boston, MA 02114 USA. EM pigmentedlesionstudy@gmail.com OI Nazarian, Rosalynn/0000-0003-4003-7193 FU Dermatopathology Unit and Department of Dermatology, Massachusetts General Hospital, Boston, MA FX Supported by departmental research funds from the Dermatopathology Unit and Department of Dermatology, Massachusetts General Hospital, Boston, MA. NR 43 TC 20 Z9 20 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD SEP PY 2012 VL 67 IS 3 BP 387 EP 394 DI 10.1016/j.jaad.2011.10.026 PG 8 WC Dermatology SC Dermatology GA 993AK UT WOS:000307824000021 PM 22153791 ER PT J AU Bae, YSC Van Voorhees, AS Hsu, S Korman, NJ Lebwohl, MG Young, M Bebo, B Kimball, AB AF Bae, Yoon-Soo Cindy Van Voorhees, Abby S. Hsu, Sylvia Korman, Neil J. Lebwohl, Mark G. Young, Melody Bebo, Bruce, Jr. Kimball, Alexa Boer CA Natl Psoriasis Fdn TI Review of treatment options for psoriasis in pregnant or lactating women: From the Medical Board of the National Psoriasis Foundation SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Review DE consensus; female; lactation; pregnancy; psoriasis; treatment; women ID LOW-DOSE METHOTREXATE; NECROSIS-FACTOR ANTAGONISTS; BREAST-MILK; CROHNS-DISEASE; SYSTEMIC ABSORPTION; TOPICAL TACROLIMUS; ANTENATAL CORTICOSTEROIDS; PERCUTANEOUS-ABSORPTION; PHOTOCHEMOTHERAPY PUVA; TRANSPLANT RECIPIENTS AB Background: Treating psoriasis in pregnant and lactating women presents a special challenge. For ethical reasons, prospective randomized control trials have not been conducted in this patient population although these patients do encounter new-onset psoriasis in addition to flares and may require treatment throughout their pregnancies. Objective: Our aim was to arrive at consensus recommendations on treatment options for psoriasis in pregnant and lactating women. Methods: The literature was reviewed regarding all psoriasis therapies in pregnant and lactating women. Results: Topical therapies including emollients and low-to moderate-potency topical steroids are first-line therapy for patients with limited psoriasis who are pregnant or breast-feeding. The consensus was that second-line treatment for pregnant women is narrowband ultraviolet B phototherapy or broadband ultraviolet B, if narrowband ultraviolet B is not available. Lastly, tumor necrosis factor-alpha inhibitors including adalimumab, etanercept, and infliximab may be used with caution as may cyclosporine and systemic steroids (in second and third trimesters). Some specific strategies may be used to minimize risk and exposure. Limitations: There are few evidence-based studies on treating psoriasis in pregnant and lactating women. Conclusions: Because there will always be a question of ethical concerns placing pregnant and lactating women in prospective clinical trials, investigation of both conventional and biologic agents are unlikely to ever be performed. Some of these medications used to treat psoriasis are known abortifacients, mutagens, or teratogens and must be clearly avoided but others can be used with relative confidence in select patients with appropriate counseling of risks and benefits. (J Am Acad Dermatol 2012;67:459-77.) C1 [Van Voorhees, Abby S.] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. [Bae, Yoon-Soo Cindy; Kimball, Alexa Boer] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Hsu, Sylvia] Baylor Coll Med, Dept Dermatol, Houston, TX 77030 USA. [Korman, Neil J.] Case Western Reserve Univ, Univ Hosp Cleveland, Dept Dermatol, Cleveland, OH 44106 USA. [Korman, Neil J.] Case Western Reserve Univ, Univ Hosp Cleveland, Murdough Family Ctr Psoriasis, Cleveland, OH 44106 USA. [Lebwohl, Mark G.] NYU, Dept Dermatol, Mt Sinai Sch Med, New York, NY 10016 USA. [Young, Melody] Modern Dermatol, Dallas, TX USA. [Bebo, Bruce, Jr.] Natl Psoriasis Fdn, Portland, OR USA. RP Van Voorhees, AS (reprint author), Univ Penn, Dept Dermatol, 2M44,3600 Spruce St, Philadelphia, PA 19104 USA. EM abby.vanvoorhees@uphs.upenn.edu FU Abbott; Astellas; Celgene; Pfizer; Centocor; Amgen; Wyeth; Genentech; Stiefel; Galderma; Warner Chilcott; Photomedix FX Dr Van Voorhees has served as a consultant/speaker/advisor for Amgen, Abbott, Biogen, Centocor, Genentech, Incyte, Warner Chilcott, Connetics, VGX, and Xtrac. She has been an investigator for Amgen, Astellas, Genentech, Warner Chilcott, Roche, Bristol Myers Squibb, and IDEC. She has served on a drug safety monitoring board for Synta. She also is a stockholder and owns stock options in Merck. Dr Hsu has been a consultant for Abbott, Amgen, Biogen Idec, Centocor, and Genentech. She has been a clinical investigator for Amgen and Centocor. Dr Korman has served on the Advisory Board and was an investigator and speaker for Abbott and Astellas, receiving grants and honoraria; served on the Advisory Board and was an investigator for Celgene and Pfizer, receiving grants and honoraria; was an investigator for Amgen, receiving grants; and was an investigator and speaker for Centocor, receiving grants and honoraria, as well as residency/fellowship program funding. Dr Lebwohl has been a consultant for Abbott, Amgen, Astellas, Centocor, Genentech, UCB Pharma, Stiefel, Triax, Pharmaderm, Medicis, Novartis, and Warner Chilcott. He has been a speaker for Abbott, Amgen, Astellas, Centocor, and Genentech. Ms Young has been a consultant or speaker for Abbott, Amgen, Astellas, Biogen Idec, Centocor, and Genentech. Dr Bebo is employed by the National Psoriasis Foundation, which receives unrestricted financial support from Abbott, Centocor, Amgen, Wyeth, Genentech, Astellas, Stiefel, Galderma, Warner Chilcott, and Photomedix. Dr Kimball is an investigator and consultant for Abbott, Amgen, and Centocor. Dr Bae has no conflicts of interest to declare. NR 91 TC 30 Z9 31 U1 1 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD SEP PY 2012 VL 67 IS 3 BP 459 EP 477 DI 10.1016/j.jaad.2011.07.039 PG 19 WC Dermatology SC Dermatology GA 993AK UT WOS:000307824000031 PM 22018758 ER PT J AU Saliba, D Jones, M Streim, J Ouslander, J Berlowitz, D Buchanan, J AF Saliba, Debra Jones, Malia Streim, Joel Ouslander, Joseph Berlowitz, Dan Buchanan, Joan TI Overview of Significant Changes in the Minimum Data Set for Nursing Homes Version 3.0 SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Article DE Nursing home; assessment; pain; mood; preferences; Minimum Data Set 3.0; pressure ulcers; delirium; behavior; falls; continence ID CONFUSION ASSESSMENT METHOD; PAIN INTENSITY; COGNITIVE IMPAIRMENT; DEPRESSIVE SYMPTOMS; RESIDENTS; CARE; DELIRIUM; RECOGNITION; PERFORMANCE; OUTCOMES AB The Minimum Data Set (MDS) is a standardized assessment that is completed on all residents admitted to Medicare certified nursing homes in the US. It is also completed on all residents admitted to Veteran Health Administration Community Living Centers. Its content addresses multiple domains of resident health and function and is intended to facilitate better recognition of each resident's needs. A new version of the MDS, MDS 3.0, was implemented in October, 2010. This article highlights significant clinical changes found in the MDS 3.0, including new structured resident interviews to assess mood, preferences, pain and cognition; inclusion of the Confusion Assessment Method to screen for delirium; revised psychosis and behavior items; revised balance and falls sections; revised bladder and bowel assessment items; revised pressure ulcer assessment items; revisions to the nutrition items; items reporting on resident expectations for return to the community; and changes to race/ethnicity item and language report. These changes aim to improve the clinical utility of these assessment items. Published by Elsevier Inc. on behalf of the American Medical Directors Association, Inc. C1 [Saliba, Debra] UCLA JH Borun Ctr Gerontol Res, Los Angeles, CA 90095 USA. [Saliba, Debra] RAND Corp, Greater Los Angeles VA GRECC, Santa Monica, CA USA. [Jones, Malia] RAND Corp, UCLA Sch Publ Hlth, Dept Community Hlth Sci, Santa Monica, CA USA. [Streim, Joel] Univ Penn, Perelman Sch Med, Geriatr Psychiat Sect, Philadelphia, PA 19104 USA. [Ouslander, Joseph] Florida Atlantic Univ, Charles E Schmidt Coll Med, Geriatr Programs, Boca Raton, FL 33431 USA. [Berlowitz, Dan] Bedford VA Hosp, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Berlowitz, Dan] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Berlowitz, Dan] Boston Univ, Sch Med, Boston, MA 02118 USA. [Buchanan, Joan] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Saliba, Debra] RAND Corp, HSR&D Ctr Excellence, Santa Monica, CA USA. [Streim, Joel] Philadelphia VA Med Ctr, VISN Mental Illness Res Educ & Clin Ctr 4, Philadelphia, PA USA. [Ouslander, Joseph] Florida Atlantic Univ, Christine E Lynn Coll Nursing, Boca Raton, FL 33431 USA. RP Saliba, D (reprint author), UCLA JH Borun Ctr Gerontol Res, 10945 Le Conte Ave,Suite 2339, Los Angeles, CA 90095 USA. EM saliba@rand.org OI Jones, Malia/0000-0002-8198-0826 FU U.S. Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development (HSRD) Service [SDR 03-217]; Centers for Medicare & Medicaid Services; UCLA/JH Borun Center FX Parts of this work were funded by the U.S. Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development (HSR&D) Service (Project SDR 03-217), the Centers for Medicare & Medicaid Services, and the UCLA/JH Borun Center. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the U.S. Department of Veterans Affairs or the Centers for Medicare and Medicaid Services. NR 43 TC 37 Z9 38 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-8610 EI 1538-9375 J9 J AM MED DIR ASSOC JI J. Am. Med. Dir. Assoc. PD SEP PY 2012 VL 13 IS 7 BP 595 EP 601 DI 10.1016/j.jamda.2012.06.001 PG 7 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 002IX UT WOS:000308526400006 PM 22784698 ER PT J AU Saliba, D Buchanan, J Edelen, MO Streim, J Ouslander, J Berlowitz, D Chodosh, J AF Saliba, Debra Buchanan, Joan Edelen, Maria Orlando Streim, Joel Ouslander, Joseph Berlowitz, Dan Chodosh, Joshua TI MDS 3.0: Brief Interview for Mental Status SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Article DE Cognition; nursing home; assessment; Minimum Data Set; screening; interview; procedural memory ID NURSING-HOME RESIDENTS; MINIMUM DATA SET; CONFUSION ASSESSMENT METHOD; INTENSIVE-CARE-UNIT; COGNITIVE IMPAIRMENT; DEMENTIA; VALIDITY; RECOGNITION; DELIRIUM; 3MS AB Objectives: To test the feasibility and validity of the Brief Interview for Mental Status (BIMS) as a performance-based cognitive screener that could be easily completed by nursing home staff. The current study examines the performance of the BIMS as part of the national testing of the Minimum Data Set 3.0 (MDS 3.0) for Nursing Homes. Methods: The BIMS was tested as part of the national MDS 3.0 evaluation study among 3822 residents scheduled for MDS 2.0 assessments. Residents were from 71 community nursing homes (NHs) in eight states. Residents were randomly included in a feasibility sample (n = 3258) and a validation sample (n = 418). Cognition was assessed with three instruments: the Brief Interview for Mental Status (BIMS), the MDS 2.0 Cognitive Performance Scale (CPS), and the Modified Mini-Mental State Examination (3MS). Trained research nurses administered the 3MS and BIMS to all subjects in the validation study. The CPS score was determined based on the MDS 2.0 completed by nursing home staff who had undergone additional training on cognitive testing. Standard cutoff scores on the 100-point 3MS were used as the gold standard for any cognitive impairment (<78) and for severe impairment (<48). Staff impressions were obtained from anonymous surveys. Results: The BIMS was attempted and completed in 90% of the 3258 residents in the feasiblity sample. BIMS scores covered the full instrument range (0-15). In the validation sample, correlation with the criterion measure (3MS) was higher for BIMS (0.906, P<.0001) than for CPS (-0.739, P<.0001); P<.01 for difference. For identifying any impairment, a BIMS score of 12 had sensitivity = 0.83 and specificity = 0.91; for severe impairment, a BIMS score of 7 had sensitivity = 0.83 and specificity = 0.92. The area under the receiver operator characteristics curve, a measure of test accuracy, was higher for BIMS than for CPS for identifying any impairment (AUC = 0.930 and 0.824, respectively) and for identifying severe impairment (AUC = 0.960 and 0.857, respectively). Eighty-eight percent of survey respondents reported that the BIMS provided new insight into residents' cognitive abilities. The average time for completing the BIMS was 3.2 minutes. Discussion: The BIMS, a short performance-based cognitive screener expressly designed to facilitate cognitive screening in MDS assessments, was completed in the majority of NH residents scheduled for MDS assessments in a large sample of NHs, demonstrating its feasibility. Compared with MDS 2.0 observational items, the BIMS performance-based assessment approach was more highly correlated with a criterion cognitive screening test and demonstrated greater accuracy. The majority of surveyed staff reported improved assessments with the new approach. Published by Elsevier Inc. on behalf of the American Medical Directors Association, Inc. C1 [Saliba, Debra] UCLA Jewish Home Borun Ctr Gerontol Res, Los Angeles, CA USA. [Saliba, Debra] RAND Corp, Greater Los Angeles VA GRECC, Santa Monica, CA USA. [Saliba, Debra] RAND Corp, HSR&D Ctr Excellence, Santa Monica, CA USA. [Buchanan, Joan] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Edelen, Maria Orlando] RAND Corp, Boston, MA USA. [Streim, Joel] Philadelphia Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr, Vet Integrated Serv Network 4, Philadelphia, PA USA. [Streim, Joel] Univ Penn, Dept Psychiat, Geriatr Psychiat Sect, Philadelphia, PA 19104 USA. [Ouslander, Joseph] Florida Atlantic Univ, Charles E Schmidt Coll Med, Boca Raton, FL 33431 USA. [Ouslander, Joseph] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Berlowitz, Dan] Bedford VA Hosp, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Berlowitz, Dan] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Chodosh, Joshua] UCLA Dept Med, Greater Los Angeles VA GRECC, Los Angeles, CA USA. [Chodosh, Joshua] UCLA Dept Med, HSR&D Ctr Excellence, Los Angeles, CA USA. RP Saliba, D (reprint author), UCLA Borun Ctr Gerontol Res, 10945 Le Conte Ave,Suite 2339, Los Angeles, CA 90095 USA. EM saliba@rand.org OI Chodosh, Joshua/0000-0001-7784-4306 FU U.S. Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development (HSRD) Service [SDR 03-217]; Centers for Medicare & Medicaid Services; UCLA/JH Borun Center FX This work was funded by the U.S. Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development (HSR&D) Service (Project SDR 03-217), the Centers for Medicare & Medicaid Services, and the UCLA/JH Borun Center. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the U.S. Department of Veterans Affairs or the Centers for Medicare and Medicaid Services. NR 30 TC 36 Z9 36 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-8610 EI 1538-9375 J9 J AM MED DIR ASSOC JI J. Am. Med. Dir. Assoc. PD SEP PY 2012 VL 13 IS 7 BP 611 EP 617 DI 10.1016/j.jamda.2012.06.004 PG 7 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 002IX UT WOS:000308526400008 PM 22796362 ER PT J AU Saliba, D DiFilippo, S Edelen, MO Kroenke, K Buchanan, J Streim, J AF Saliba, Debra DiFilippo, Suzanne Edelen, Maria Orlando Kroenke, Kurt Buchanan, Joan Streim, Joel TI Testing the PHQ-9 Interview and Observational Versions (PHQ-9 OV) for MDS 3.0 SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Article DE Mood; nursing home; assessment; Minimum Data Set; depression; observation; interview; PHQ-9 ID NURSING-HOME RESIDENTS; QUALITY-OF-LIFE; LONG-TERM-CARE; PATIENT HEALTH QUESTIONNAIRE; SEROTONIN REUPTAKE INHIBITORS; OLDER-ADULTS; MYOCARDIAL-INFARCTION; DEPRESSIVE SYMPTOMS; ELDERLY-PATIENTS; PRIME-MD AB Objectives: To test the feasibility and validity of the Patient Health Questionnaire-9 item interview (PHQ-9) and the newly developed Patient Health Questionnaire Observational Version (PHQ-9 OV) for screening for mood disorder in nursing home populations. Methods: The PHQ-9 was tested as part of the national Minimum Data Set 3.0 (MDS 3.0) evaluation study among 3822 residents scheduled for MDS 2.0 assessments. Residents from 71 community nursing homes (NHs) in eight states were randomly included in a feasibility sample (n = 3258) and a validation sample (n = 418). Each resident's ability to communicate determined whether the PHQ-9 interview or the PHQ-9 OV was initially attempted. In the validation sample, trained research nurses administered the instruments. For residents in the validation sample without severe cognitive impairment (3 MS >= 30) agreement between PHQ-9 and the modified Schedule for Affective Disorders and Schizophrenia (m-SADS) was measured with weighted kappas (kappa). For residents with severe cognitive impairment (3MS < 30), agreement between PHQ-9 interview or PHQ-9 OV and the Cornell Scale for Depression in Dementia (Cornell Scale) was measured using correlation coefficients. Staff impressions were obtained from an anonymous survey mailed to all MDS assessors. Results: The PHQ-9 was completed in 86% of the 3258 residents in the feasibility sample. In the validation sample, the agreement between PHQ-9 and m-SADS was very good (weighted kappa = 0.69, 95% CI = 0.61-0.76), whereas agreement between MDS 2.0 and m-SADS was poor (weighted kappa = 0.15, 95% CI = 0.06-0.25). Likewise, in residents with severe cognitive impairment, PHQ correlations with the criterion standard Cornell Scale were superior to the MDS 2.0 for both the PHQ-9 (0.63 vs 0.34) and the PHQ-9 OV (0.84 vs 0.28). Eighty-six percent of survey respondents reported that the PHQ-9 provided new insight into residents' mood. The average time for completing the PHQ-9 interview was 4 minutes. Discussion: Compared with the MDS 2.0 observational items, the PHQ-9 interview had greater agreement with criterion standard diagnostic assessments. For residents who could not complete the interview, the PHQ-9 OV also had greater agreement with a criterion measure for depression than did the MDS 2.0 observational items. Moreover, the majority of NH residents were able to complete the PHQ-9, and most surveyed staff reported improved assessments with the new approach. Published by Elsevier Inc. on behalf of the American Medical Directors Association, Inc. C1 [Saliba, Debra] UCLA Jewish Home Borun Ctr Gerontol Res, Los Angeles, CA USA. [Saliba, Debra] RAND Corp, Greater Los Angeles VA GRECC, Santa Monica, CA USA. [Saliba, Debra] RAND Corp, HSR&D Ctr Excellence, Santa Monica, CA USA. [DiFilippo, Suzanne] Philadelphia Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr, Vet Integrated Serv Network 4, Philadelphia, PA USA. [DiFilippo, Suzanne] Univ Penn, Dept Psychiat, Geriatr Psychiat Sect, Philadelphia, PA 19104 USA. [Edelen, Maria Orlando] RAND Corp, Boston, MA USA. [Kroenke, Kurt] Richard Roudebush VA Med Ctr, Ctr Implementing Evidence Based Practice, Indianapolis, IN USA. [Buchanan, Joan] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Streim, Joel] Univ Penn, Perelman Sch Med, Geriatr Psychiat Sect, Philadelphia, PA 19104 USA. [Streim, Joel] Philadelphia VA Med Ctr, VISN Mental Illness Res Educ & Clin Ctr 4, Philadelphia, PA USA. RP Saliba, D (reprint author), UCLA Borun Ctr Gerontol Res, 10945 Le Conte Ave,Suite 2339, Los Angeles, CA 90095 USA. EM saliba@rand.org FU U.S. Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development (HSRD) Service [SDR 03-217]; Centers for Medicare & Medicaid Services; UCLA/JH Borun Center FX This work was funded by the U.S. Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development (HSR&D) Service (Project SDR 03-217), the Centers for Medicare & Medicaid Services and the UCLA/JH Borun Center. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the U. S. Department of Veterans Affairs or the Centers for Medicare and Medicaid Services. NR 91 TC 32 Z9 32 U1 4 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-8610 EI 1538-9375 J9 J AM MED DIR ASSOC JI J. Am. Med. Dir. Assoc. PD SEP PY 2012 VL 13 IS 7 BP 618 EP 625 DI 10.1016/j.jamda.2012.06.003 PG 8 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 002IX UT WOS:000308526400009 PM 22796361 ER PT J AU Tena-Nelson, R Santos, K Weingast, E Amrhein, S Ouslander, J Boockvar, K AF Tena-Nelson, Roxanne Santos, Kathryn Weingast, Elizabeth Amrhein, Scott Ouslander, Joseph Boockvar, Kenneth TI Reducing Potentially Preventable Hospital Transfers: Results from a Thirty Nursing Home Collaborative SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Article DE Nursing homes; hospitalization; quality improvement ID RESIDENTS; INFECTION; ILLNESS AB Background: Nursing home (NH) residents experience frequent hospital transfers, some potentially avoidable. The objective of this report is to describe a replication of the Interventions to Reduce Acute Care Transfers program among member facilities of a New York City area NH provider association (INTERACT NY) and estimate its effect on hospital transfers. Methods: INTERACT is a program that provides tools and strategies to assist NH staff in early identification, communication, and documentation of changes in resident status. Funding was obtained from a New York State health workforce training grant to conduct 13 INTERACT education and training sessions in 2010-2011. INTERACT NY session topics included the implementation process; use of its simple standardized communication tools, advance care planning tools, care paths, and change in condition support tools; quality review of hospital transfers; exercises for refining clinical skills; teamwork; and lessons learned. Sessions engaged NH executives, department heads, front-line nursing staff and their labor union, and staff from NHs' partner hospitals. Pre-/post-INTERACT NY hospitalization rates per 1000-resident days were compared using paired t-tests, stratified by level of facility engagement with the program and by baseline hospitalization rates. Results: All 100% of participating NHs were non-profit or public. Those with complete evaluation data had 377 beds on average. There were a total of 333 attendees of the program (mean 25.6 per session; mean 11.1 per facility over the course of the program; range 1e44 per facility). The most common attendees in order of frequency were (1) nurse administrators, (2) unit-based nurses, (3) medical directors and attending physicians, (4) nursing home administrators, (5) certified nursing assistants, and (6) case managers and social workers. Sixteen nursing homes implemented at least one INTERACT tool. Overall, there was a nonsignificant 10.6% reduction in hospital admissions from 4.07 to 3.64 per 1000 resident-days from pre-to post-INTERACT NY (P=.332). Among nursing homes with high engagement there was a nonsignificant 14.3% reduction in hospital admissions from 4.19 to 3.59 per 1000 resident-days (P=0.213). Finally, among nursing homes in the highest tertile of baseline (pre-INTERACT NY) hospital admission rate, there was a nonsignificant 27.2% reduction in hospital admissions from 7.32 to 5.33 per 1000 resident-days (P=.102). Planning and implementation lessons from INTERACT NY leaders and participants are reported. Conclusions: INTERACT NY, a novel collaborative training program, resulted in good uptake of the INTERACT tools and processes among its member nursing homes. Changes in hospitalization rates associated with INTERACT NY were similar to those observed in previous implementations of INTERACT. The program addresses a growing interest in reducing potentially preventable hospital admissions among nursing home residents and providing alternatives to hospital care through standardized approaches to communication, early identification of clinical issues, decision-support, and support for partnerships between acute and post-acute care providers. Copyright (C) 2012 - American Medical Directors Association, Inc. C1 [Weingast, Elizabeth; Boockvar, Kenneth] Jewish Home Lifecare, New York, NY 10025 USA. [Tena-Nelson, Roxanne; Santos, Kathryn; Amrhein, Scott] Continuing Care Leadership Coalit, New York, NY 10019 USA. [Ouslander, Joseph] Florida Atlantic Univ, Boca Raton, FL 33431 USA. [Boockvar, Kenneth] Mt Sinai Sch Med, New York, NY USA. [Boockvar, Kenneth] James J Peters VA Med Ctr, Bronx, NY USA. RP Boockvar, K (reprint author), Jewish Home Lifecare, 120 W 106th St, New York, NY 10025 USA. EM tena-nelson@gnyha.org; kenneth.boockvar@mssm.edu OI Boockvar, Kenneth/0000-0003-1165-5558 FU New York State Workforce Training grant; Greenwall Foundation FX This project was supported by a New York State Workforce Training grant. One author was supported by the Greenwall Foundation. NR 10 TC 21 Z9 21 U1 0 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-8610 J9 J AM MED DIR ASSOC JI J. Am. Med. Dir. Assoc. PD SEP PY 2012 VL 13 IS 7 BP 651 EP 656 DI 10.1016/j.jamda.2012.06.011 PG 6 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 002IX UT WOS:000308526400015 PM 22835484 ER PT J AU Bamberg, F Marcus, RP Schlett, CL Schoepf, UJ Johnson, TR Nance, JW Hoffmann, U Reiser, MF Nikolaou, K AF Bamberg, Fabian Marcus, Roy P. Schlett, Christopher L. Schoepf, U. Joseph Johnson, Thorsten R. Nance, John W. Hoffmann, Udo Reiser, Maximilian F. Nikolaou, Konstantin TI Imaging Evaluation of Acute Chest Pain Systematic Review of Evidence Base and Cost-effectiveness SO JOURNAL OF THORACIC IMAGING LA English DT Article DE cardiac computed tomography; magnetic resonance imaging; myocardial perfusion imaging; cost-effectiveness; evidence-based medicine; acute chest pain ID ACUTE CORONARY SYNDROMES; 64-SLICE COMPUTED-TOMOGRAPHY; CARDIAC MAGNETIC-RESONANCE; ASSOCIATION TASK-FORCE; EMERGENCY-DEPARTMENT PATIENTS; RANDOMIZED CONTROLLED-TRIAL; MYOCARDIAL-INFARCTION; ARTERY-DISEASE; AMERICAN-COLLEGE; LOW-RISK AB Given the often inconclusive initial evaluation of patients presenting with acute chest pain in the Emergency Department, advanced imaging techniques have been evaluated in the quest for improving the current standard of care. In this article, we systematically compare and evaluate the available evidence and cost-effectiveness of radionucleotide myocardial perfusion imaging, cardiac computed tomography angiography, and cardiac magnetic resonance imaging using data from PubMed and EMBASE through January 2012. The obtained data were summarized and categorized according to the reached level of evidence and its impact on the decision-making process. C1 [Bamberg, Fabian; Marcus, Roy P.; Johnson, Thorsten R.; Reiser, Maximilian F.; Nikolaou, Konstantin] Univ Munich, Inst Clin Radiol, Klinikum Grosshadern, D-81377 Munich, Germany. [Schlett, Christopher L.; Hoffmann, Udo] Harvard Univ, Sch Med, Dept Radiol,Cardiac MR PET CT Program, Massachusetts Gen Hosp,Div Cardiol, Boston, MA 02115 USA. [Schoepf, U. Joseph] Med Univ S Carolina, Dept Radiol & Radiol Sci, Charleston, SC 29425 USA. [Nance, John W.] Johns Hopkins Univ, Dept Radiol, Baltimore, MD USA. RP Bamberg, F (reprint author), Univ Munich, Inst Clin Radiol, Marchioninistr 15, D-81377 Munich, Germany. EM fbamberg@post.harvard.edu OI Nikolaou, Konstantin/0000-0003-2668-7325 NR 59 TC 7 Z9 7 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0883-5993 EI 1536-0237 J9 J THORAC IMAG JI J. Thorac. Imaging PD SEP PY 2012 VL 27 IS 5 BP 289 EP 295 DI 10.1097/RTI.0b013e3182628053 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 998EK UT WOS:000308219900012 PM 22914122 ER PT J AU Hoang, T Dahlberg, SE Sandler, AB Brahmer, JR Schiller, JH Johnson, DH AF Tien Hoang Dahlberg, Suzanne E. Sandler, Alan B. Brahmer, Julie R. Schiller, Joan H. Johnson, David H. TI Prognostic Models to Predict Survival in Non-Small-Cell Lung Cancer Patients Treated with First-Line Paclitaxel and Carboplatin with or without Bevacizumab SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Prognostic models; Nomograms; Non-small-cell lung cancer; Chemotherapy; Bevacizumab ID COOPERATIVE-ONCOLOGY-GROUP; ENDOTHELIAL GROWTH-FACTOR; CHEMOTHERAPY REGIMENS; MUTATIONS; TISSUES; LDH-5; TRIAL; GENE AB Background: To determine prognostic factors and build a model to predict 1-year overall survival (OS) and 6-month progression-free survival (PFS) in advanced non-small-cell lung cancer (NSCLC) patients treated with first-line paclitaxel and carboplatin with or without bevacizumab. Materials and Methods: We analyzed 26 pretreatment clinical variables in 850 NSCLC patients treated in the randomized Eastern Cooperative Oncology Group 4599 study. Univariate and multivariate analyses were performed to identify prognostic factors. Cox regression with 50% randomly sampled data was used to build nomograms with a prognostic score assigned to each factor. The model was validated with the remaining 50% of data. Results: Eleven poor factors for OS (hazard ratio) were as follows: skin metastasis (4.49), body mass index less than 18.5 (2.09), increased serum lactate dehydrogenase (1.74), adrenal metastasis (1.52), performance status greater than 0 (1.45), low serum albumin (1.45), men (1.39), bone metastasis (1.39), large cell/not otherwise specified histology (1.29), mediastinal nodal metastasis (1.23), and treatment without bevacizumab (1.18). Seven poor factors for PFS were as follows: skin metastasis (3.13), treatment without bevacizumab (1.52), bone metastasis (1.41), liver metastasis (1.40), low serum albumin (1.39), performance status greater than 0 (1.21), and mediastinal nodal metastasis (1.14). Based on these factors, we built and validated two nomograms predicting 1-year OS and 6-month PFS. Conclusion: Using our proposed models, the probability of survival with first-line paclitaxel and carboplatin with or without bevacizumab in nonsquamous NSCLC patients can be estimated. These prognostic models provide a tool for research design and clinical decision making, such as patient stratification and therapy selection. C1 [Tien Hoang] Univ Wisconsin, Dept Med, Madison, WI USA. [Dahlberg, Suzanne E.] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. [Sandler, Alan B.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Brahmer, Julie R.] Johns Hopkins Univ, Baltimore, MD USA. [Schiller, Joan H.; Johnson, David H.] Univ Texas SW Med Ctr Dallas, Dept Med, Dallas, TX 75390 USA. RP Hoang, T (reprint author), Wisconsin Inst Med Res, 1111 Highland Ave,Room 3131, Madison, WI 53705 USA. EM txh@medicine.wisc.edu FU Public Health Service from the National Cancer Institute, the National Institutes of Health [CA23318, CA66636, CA21115, CA21076, CA49957, CA16116]; Department of Health and Human Services FX Supported, in part, by Public Health Service grants CA23318, CA66636, CA21115, CA21076, CA49957, and CA16116 and from the National Cancer Institute, the National Institutes of Health, and the Department of Health and Human Services. NR 21 TC 16 Z9 16 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2012 VL 7 IS 9 BP 1361 EP 1368 DI 10.1097/JTO.0b013e318260e106 PG 8 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 996GQ UT WOS:000308073300012 PM 22843087 ER PT J AU Sauna, ZE Ameri, A Kim, B Yanover, C Viel, KR Rajalingam, R Cole, SA Howard, TE AF Sauna, Z. E. Ameri, A. Kim, B. Yanover, C. Viel, K. R. Rajalingam, R. Cole, S. A. Howard, T. E. TI Observations regarding the immunogenicity of BDD-rFVIII derived from a mechanistic personalized medicine perspective SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Letter ID RECOMBINANT FACTOR-VIII; HEMOPHILIA-A; INHIBITORS; PROTEIN C1 [Howard, T. E.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Pathol & Lab Med, Los Angeles, CA 90073 USA. [Sauna, Z. E.] US FDA, Lab Hemostasis, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Ameri, A.] Georgia Hlth Sci Univ, Div Hematol & Oncol, Dept Pediat, Augusta, GA USA. [Kim, B.] Univ Calif San Francisco, Dept Med, Div Hematol & Oncol, San Francisco, CA USA. [Yanover, C.] Fred Hutchinson Canc Res Ctr, Program Computat Biol, Seattle, WA 98104 USA. [Viel, K. R.] Histonis Inc, Atlanta, GA USA. [Rajalingam, R.] Univ Calif Los Angeles, Dept Pathol & Lab Med, David Geen Sch Med, Immunogenet Ctr, Los Angeles, CA USA. [Cole, S. A.] Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA. [Howard, T. E.] Univ So Calif, Keck Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90033 USA. [Howard, T. E.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA. RP Howard, TE (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Dept Pathol & Lab Med, Bldg 500,Room 1258, Los Angeles, CA 90073 USA. EM tom.howard@va.gov RI Yanover, Chen/A-3754-2012 OI Yanover, Chen/0000-0003-3663-4286 FU NHLBI NIH HHS [1RC2-HL101851, HL-71130, HL-72533] NR 17 TC 6 Z9 6 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1538-7933 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD SEP PY 2012 VL 10 IS 9 BP 1961 EP 1965 DI 10.1111/j.1538-7836.2012.04830.x PG 5 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 999FI UT WOS:000308294400032 PM 22734827 ER PT J AU Habito, CMR Wicky, S Kalva, SP AF Habito, Cicero Matthew R. Wicky, Stephan Kalva, Sanjeeva P. TI Garland Vein: Sequela of Left Innominate Occlusion SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Editorial Material C1 [Habito, Cicero Matthew R.; Wicky, Stephan; Kalva, Sanjeeva P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Habito, CMR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM habito.cicero@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD SEP PY 2012 VL 23 IS 9 BP 1223 EP 1223 DI 10.1016/j.jvir.2012.06.013 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 002FZ UT WOS:000308518800016 PM 22841899 ER PT J AU Harshman, LC Xie, WL Bjarnason, GA Knox, JJ MacKenzie, M Wood, L Srinivas, S Vaishampayan, UN Tan, MH Rha, SY Donskov, F Agarwal, N Kollmannsberger, C North, S Rini, BI Heng, DYC Choueiri, TK AF Harshman, Lauren C. Xie, Wanling Bjarnason, Georg A. Knox, Jennifer J. MacKenzie, Mary Wood, Lori Srinivas, Sandy Vaishampayan, Ulka N. Tan, Min-Han Rha, Sun-Young Donskov, Frede Agarwal, Neeraj Kollmannsberger, Christian North, Scott Rini, Brian I. Heng, Daniel Y. C. Choueiri, Toni K. TI Conditional survival of patients with metastatic renal-cell carcinoma treated with VEGF-targeted therapy: a population-based study SO LANCET ONCOLOGY LA English DT Article ID PHASE-III TRIAL; INTERFERON-ALPHA; BREAST-CANCER; DENMARK; LUNG AB Background The advent of targeted therapies in the past 7 years has extended median survival for metastatic renal-cell carcinoma. This improvement in clinical outcome has created a need for new, more accurate prognostic measures. We assessed the use of conditional survival-a measure that accounts for elapsed time since treatment initiation-for prognostication in patients with metastatic renal-cell carcinoma treated with first-line VEGF-targeted therapies. Methods We obtained data for patients with metastatic renal-cell carcinoma who were treated with a first-line VEGF-targeted therapy between April 7, 2003, and Oct 12, 2010, from our large multi-institutional International mRCC Database Consortium (centres in Canada, the USA, Singapore, Denmark, and South Korea). All histologies, performance statuses, and prognostic risk groups were included. The primary outcome was 2-year conditional survival, defined as the probability of surviving an additional 2 years from a given timepoint since the start of targeted therapy. Secondary analyses included 1-year and 3-year conditional survival, along with stratification of patients by Heng prognostic risk criteria and Karnofsky performance score, and conditional survival based on length of time on therapy. We used the Kaplan-Meier method and a landmark analysis to calculate conditional survival. Findings In the 1673 patients analysed, median follow-up for alive patients was 20.1 months (IQR 9.0-34.4). We recorded an increase in the 2-year conditional survival probability from 44% (95% CI 41-47) at 0 months to 51% (46-55) at 18 months since beginning targeted therapy. When stratified by the Heng prognostic risk criteria defined at therapy initiation, 2-year conditional survival changed little in the favourable and intermediate groups, but in the poor-risk group, 2-year conditional survival improved from 11% (8-15) at 0 months to 33% (18-48) after 18 months. When conditioned on time on targeted therapy from 0 months to 18 months, 2-year conditional survival improved from 44% (41-47) to 68% (60-75) in the overall population and from 74% (68-79) to 90% (77-96) in the favourable group, 49% (45-53) to 57% (45-67) in the intermediate group, and 11% (8-15) to 73% (43-89) in the poor risk group. Interpretation Conditional survival is a clinically useful prediction measure that adjusts prognosis of patients with metastatic renal-cell carcinoma on the basis of survival since treatment initiation or therapy duration. Conditional survival might be especially relevant to adjust prognosis for poor-risk patients. C1 [Harshman, Lauren C.; Srinivas, Sandy] Stanford Univ, Stanford Canc Inst, Sch Med, Stanford, CA 94305 USA. [Choueiri, Toni K.] Brigham & Womens Hosp, Dana Farber Canc Inst, Kidney Canc Ctr, Boston, MA 02215 USA. [Xie, Wanling; Choueiri, Toni K.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Bjarnason, Georg A.] Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. [Knox, Jennifer J.] Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada. [MacKenzie, Mary] London Hlth Sci Ctr, London, ON, Canada. [Wood, Lori] Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada. [Vaishampayan, Ulka N.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. [Tan, Min-Han] Natl Canc Ctr, Dept Med Oncol, Singapore, Singapore. [Tan, Min-Han] Inst Bioengn & Nanotechnol, Singapore, Singapore. [Rha, Sun-Young] Yonsei Univ, Coll Med, Yonsei Canc Ctr, Seoul, South Korea. [Donskov, Frede] Aarhus Univ Hosp, Dept Oncol, DK-8000 Aarhus, Denmark. [Agarwal, Neeraj] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [Kollmannsberger, Christian] British Columbia Canc Agcy, Vancouver Canc Ctr, Vancouver, BC V5Z 4E6, Canada. [North, Scott] Univ Alberta, Cross Canc Ctr, Edmonton, AB, Canada. [Rini, Brian I.] Cleveland Clin Fdn, Taussig Canc Inst, Cleveland, OH 44195 USA. [Heng, Daniel Y. C.] Univ Calgary, Tom Baker Canc Ctr, Calgary, AB, Canada. RP Choueiri, TK (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Kidney Canc Ctr, 450 Brookline Ave,DANA 1230, Boston, MA 02215 USA. EM toni_choueiri@dfci.harvard.edu OI Bjarnason, Georg Arnold/0000-0001-6903-5357; Donskov, Frede/0000-0002-8449-863X FU Trust Family Fund for Kidney Cancer Research; Bristol-Myers Squibb; Novartis; Genentech; Pfizer; GlaxoSmithKline; Bayer Korea FX The Trust Family Fund for Kidney Cancer Research.; LCH has a consultant or advisory role at Novartis and Pfizer and has received research funding from Bristol-Myers Squibb, Novartis, and Genentech. GAB has a consultant or advisory role at and has received honoraria and research funding from Pfizer. JJK has a consultant or advisory role at Aveo and and has received research funding from Pfizer. MM has a consultant or advisory role at and has received research funding from Novartis and Pfizer. LW has a consultant or advisory role at Pfizer and Novartis and has received research funding from Pfizer, Novartis, and GlaxoSmithKline. SS has a consultant or advisory role at Pfizer, Novartis, and Genentech. UNV has received honoraria and research funding from Pfizer, Novartis, and GlaxoSmithKline. S-YR has a consultant or advisory role at Novartis, Pfizer, and GlaxoSmithKline, and has received research funding from Novartis and Bayer Korea. FD has received research funding from Novartis. CK has a consultant or advisory role at and has received honoraria and research funding from Pfizer, Novartis, and GlaxoSmithKline. SN has a consultant or advisory role at Pfizer, Novartis, Bayer, and GlaxoSmithKline. BIR has a consultant or advisory role at Pfizer, GlaxoSmithKline, Aveo, and Bayer/Onyx, and has received research funding from GlaxoSmithKline and Pfizer. DYCH has a consultant or advisory role at Pfizer, Novartis, and Bayer/Onyx. TKC has received research funding from Pfizer and has a consultant or advisory role at Aveo, Pfizer, Novartis, GlaxoSmithKline, Genentech, and Bayer/Onyx. WX, M-HT, and NA declare that they have no conflicts of interest. NR 25 TC 49 Z9 49 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD SEP PY 2012 VL 13 IS 9 BP 927 EP 935 DI 10.1016/S1470-2045(12)70285-1 PG 9 WC Oncology SC Oncology GA 000XZ UT WOS:000308425600020 PM 22877847 ER PT J AU Schiff, D Taylor, JW Flanagan, E O'Neill, BP Siegal, T Omuro, A Baehring, J Gonzalez-Aguilar, A Chamberlain, M Nishikawa, R AF Schiff, D. Taylor, J. W. Flanagan, E. O'Neill, B. P. Siegal, T. Omuro, A. Baehring, J. Gonzalez-Aguilar, A. Chamberlain, M. Nishikawa, R. TI PRESENTATION, DIAGNOSTICS AND TREATMENT OF PRIMARY LEPTOMENINGEAL LYMPHOMA: AN INTERNATIONAL PRIMARY CNS LYMPHOMA COLLABORATIVE GROUP SERIES SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 10th Congress of the European-Association-of-NeuroOncology CY SEP 06-09, 2012 CL Marseille, FRANCE SP European Assoc NeuroOncol C1 [Schiff, D.] Univ Virginia, Charlottesville, VA USA. [Taylor, J. W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Flanagan, E.; O'Neill, B. P.] Mayo Clin, Rochester, MN USA. [Siegal, T.] Hadassah Hebrew Univ, Med Ctr, Jerusalem, Israel. [Omuro, A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Baehring, J.] Yale Univ, New Haven, CT USA. [Gonzalez-Aguilar, A.] La Pitie Salpetriere, Paris, France. [Chamberlain, M.] Univ Washington, Seattle, WA 98195 USA. [Nishikawa, R.] Saitama Med Univ, Saitama, Japan. OI Omuro, Antonio/0000-0003-4299-3664 NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD SEP PY 2012 VL 14 SU 3 BP 9 EP 9 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 002PW UT WOS:000308545600034 ER PT J AU Peereboom, DM Sloan, AE Supko, JG Ye, X Rich, JN Prados, MD Ahluwalia, M Grossman, SA AF Peereboom, D. M. Sloan, A. E. Supko, J. G. Ye, X. Rich, J. N. Prados, M. D. Ahluwalia, M. Grossman, S. A. TI ABTC 0906: A PHASE II AND PHARMACODYNAMIC TRIAL OF RO4929097 FOR PATIENTS WITH RECURRENT/PROGRESSIVE GLIOBLASTOMA SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 10th Congress of the European-Association-of-NeuroOncology CY SEP 06-09, 2012 CL Marseille, FRANCE SP European Assoc NeuroOncol C1 [Peereboom, D. M.; Rich, J. N.; Ahluwalia, M.] Cleveland Clin, Cleveland, OH 44106 USA. [Sloan, A. E.] Case Comprehens Canc Ctr, Cleveland, OH USA. [Supko, J. G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ye, X.; Grossman, S. A.] Johns Hopkins Univ, Baltimore, MD USA. [Prados, M. D.] Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD SEP PY 2012 VL 14 SU 3 BP 40 EP 40 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 002PW UT WOS:000308545600146 ER PT J AU Coron, E Neunlist, M Pieretti, A Mahe, M Auksorius, E Tearney, G Goldstein, A AF Coron, E. Neunlist, M. Pieretti, A. Mahe, M. Auksorius, E. Tearney, G. Goldstein, A. TI Full-Field Optical Coherence Microscopy (FFOCM) is a novel technique for imaging enteric ganglia in the gastrointestinal tract SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Meeting Abstract C1 [Coron, E.] Univ Hosp Nantes, Inst Digest Dis, Nantes, France. [Neunlist, M.] Univ Hosp Hotel Dieu, Univ Nantes Inst, Nantes, France. [Pieretti, A.; Goldstein, A.] Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA 02114 USA. [Mahe, M.] Univ Hosp, Inst Digest Dis, Nantes, France. [Auksorius, E.; Tearney, G.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 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 1350-1925 J9 NEUROGASTROENT MOTIL JI Neurogastroenterol. Motil. PD SEP PY 2012 VL 24 SU 2 BP 37 EP 37 PG 1 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA 001BS UT WOS:000308435400115 ER PT J AU Goebel-Stengel, M Stengel, A Lambrecht, N Sachs, G AF Goebel-Stengel, M. Stengel, A. Lambrecht, N. Sachs, G. TI Selective gene expression by rat small and large bowel epithelia SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Meeting Abstract C1 [Goebel-Stengel, M.] Martin Luther Krankenhaus Berlin, Innere Med Abt, Berlin, Germany. [Stengel, A.] Charite, Innere Med Abt, Berlin, Germany. [Lambrecht, N.] VA Long Beach, Long Beach, CA USA. [Sachs, G.] VA Greater Los Angeles, Los Angeles, CA USA. [Sachs, G.] Univ Calif Los Angeles, Membrane Biol Lab, Los Angeles, CA 90024 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 1350-1925 J9 NEUROGASTROENT MOTIL JI Neurogastroenterol. Motil. PD SEP PY 2012 VL 24 SU 2 BP 153 EP 153 PG 1 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA 001BS UT WOS:000308435400500 ER PT J AU Ward, NL Pieretti, A Dowd, SE Cox, SB Goldstein, AM AF Ward, N. L. Pieretti, A. Dowd, S. E. Cox, S. B. Goldstein, A. M. TI Intestinal aganglionosis is associated with early and sustained disruption of the colonic microbiome SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Article DE enteric nervous system; enterocolitis; Hirschsprung's disease; microbiome ID DISEASE-ASSOCIATED ENTEROCOLITIS; INFLAMMATORY BOWEL DISEASES; RIBOSOMAL-RNA GENE; HIRSCHSPRUNGS-DISEASE; BACTERIAL DIVERSITY; GUT MICROBIOTA; MURINE MODEL; MICE; COMMUNITIES; ECOLOGY AB Background Congenital aganglionosis (Hirschsprungs disease) results in colonic dysmotility and a risk for Hirschsprungs-associated enterocolitis (HAEC), whose cause is unknown. We hypothesized that aganglionosis leads to microbiome changes that may contribute to HAEC risk. Methods Colon and fecal samples were collected from endothelin receptor B-null (Ednrb-/-) mice, an established model of colorectal aganglionosis, at postnatal day 7 (P7), P20, and P24. We determined microbiome composition by 16S ribosomal RNA gene pyrosequencing and fecal metabolite profile by nuclear magnetic resonance spectroscopy. Key Results Wild-type (WT) mice exhibited increasing species diversity with age, with mutant mice possessing even greater diversity. WT and mutant microbiomes, both fecal and colonic, significantly segregated by principal coordinates analysis based on species composition at all ages examined. Importantly, mutant mice contained more Bacteroidetes and less Firmicutes than WT, with additional genus- and species-level differences observed. Notably, mutant P7 colon was dominated by coagulase-negative Staphylococcus species, which were rare in WT. Mutant fecal metabolite profiles also differed, particularly in the abundance of formate, a short-chain fatty acid product of microbial fermentation. Conclusions & Inferences Colorectal aganglionosis is associated with early and sustained disruption of the normal colonic and fecal microbiome, supporting the enteric nervous system as a determinant of microbiome composition. Furthermore, the differences observed suggest a potential contributory role for the microbiome in the etiology of HAEC. These findings provide a basis for further studies to determine the causative role of specific bacterial communities in HAEC and the potential to restore the normal microbiome in Hirschsprungs disease. C1 [Pieretti, A.; Goldstein, A. M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA 02114 USA. [Ward, N. L.] Univ Wyoming, Dept Mol Biol, Laramie, WY 82071 USA. [Ward, N. L.] Univ Wyoming, Dept Bot, Laramie, WY 82071 USA. [Dowd, S. E.; Cox, S. B.] Res & Testing Lab, Lubbock, TX USA. RP Goldstein, AM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat Surg, 55 Fruit St,Warren 1153, Boston, MA 02114 USA. EM agoldstein@partners.org FU United States National Science Foundation [EPS-0447681] FX This research was supported by the United States National Science Foundation (EPS-0447681). NR 66 TC 16 Z9 16 U1 3 U2 24 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1350-1925 EI 1365-2982 J9 NEUROGASTROENT MOTIL JI Neurogastroenterol. Motil. PD SEP PY 2012 VL 24 IS 9 BP 874 EP + DI 10.1111/j.1365-2982.2012.01937.x PG 12 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA 996LK UT WOS:000308089000016 PM 22626027 ER PT J AU Wang, L Magen, I Yuan, PQ Subramaniam, SR Richter, F Chesselet, MF Tache, Y AF Wang, L. Magen, I. Yuan, P. -Q. Subramaniam, S. R. Richter, F. Chesselet, M. -F Tache, Y. TI Mice overexpressing wild-type human alpha-synuclein display alterations in colonic myenteric ganglia and defecation SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Article DE colon; defecation; gastric emptying; mice; myenteric neurons; peripheral choline acetyltransferase; a-synuclein ID CORTICOTROPIN-RELEASING-FACTOR; ENTERIC DOPAMINERGIC-NEURONS; PARKINSONS-DISEASE; NERVOUS-SYSTEM; CHOLINE-ACETYLTRANSFERASE; MOTOR FUNCTION; FACTOR CRF; MOUSE; RATS; DYSFUNCTION AB Background Prevalent non-motor symptoms of Parkinsons disease (PD) include gastrointestinal motor impairments and advanced stage PD displays pathological aggregates of a-synuclein in colonic enteric neurons. We previously showed that 12 months old mice overexpressing human wild type (WT) a-synuclein under the Thy1 promoter (Thy1-aSyn) displayed colonic motor dysfunction. We investigated functional gut alterations at earlier ages and histological correlates. Methods Defecation, gastric emptying (GE), and immunostaining for a-synuclein, peripheral choline acetyltransferase (pChAT), tyrosine hydroxylase (TH), neuronal nitric oxide synthase (nNOS), and vasoactive intestinal peptide (VIP) in distal colon myenteric plexuses were assessed in male Thy1-aSyn compared to littermate WT mice. Key Results Thy1-aSyn mice aged 2.53 or 78 months old had 81% and 55% reduction in fecal pellet output, respectively, in the first 15 min of exposure to a novel environment. The reduction remained significant in the older group for 2-h, and subsequent refeeding resulted also in a 60% and 69% reduction of defecation in the first hour, respectively. Thy1-aSyn mice (810 months) displayed increased a-synuclein in the myenteric plexuses with abundant varicose terminals surrounding pChAT-immunoreactive (ir) neurons, and only a few, nNOS-ir neurons. There were no conspicuous changes in pChAT- and nNOS-ir neurons, or TH- and VIP-ir nerve fibers. Thy1-aSyn mice aged 418 months had normal GE. Conclusions & Inferences The occurrence of over-production of pre-synaptic a-synuclein in colonic myenteric ganglia several months before the loss of striatal dopamine may provide an anatomical basis for interference with cholinergic neuronal activation, causing an early impairment in defecation to stimuli. C1 [Wang, L.; Yuan, P. -Q.; Tache, Y.] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Dept Med,CURE Digest Dis Res Ctr, Los Angeles, CA 90095 USA. [Wang, L.; Yuan, P. -Q.; Tache, Y.] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Dept Med,Ctr Neurobiol Stress, Los Angeles, CA 90095 USA. [Wang, L.; Yuan, P. -Q.; Tache, Y.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Magen, I.; Subramaniam, S. R.; Richter, F.; Chesselet, M. -F] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. RP Wang, L (reprint author), 11301 Wilshire Blvd,Bldg 115, Los Angeles, CA 90073 USA. EM lixinw@ucla.edu RI Richter, Franziska/N-8009-2014 OI Richter, Franziska/0000-0003-0803-4398 FU Michael Fox Foundation; Morris K. Udall Parkinson's Disease Research Center of Excellence at UCLA [P50NS38367]; Center grant NIHDDK [41301, RO1 DK 57238]; VA Career Scientist Award FX The authors thank Dr. G. Ohning (CURE: Digestive Diseases Research Center, Bldg 115, VA Greater Los Angeles Health Care System, Los Angeles) for the generous supply of the VIP antibody CURE ab 7913 and Dr. Hiroshi Kimura (Molecular Neuroscience Research Center, Shiga University of Medical Science, Otsu, Japan) for the generous donation of pChAT antibody, Mrs. Honghui Liang for her technical support, and Ms. Eugenia Hu for her review of the manuscript. This work was supported by the (Target validation grant, Michael Fox Foundation), the Morris K. Udall Parkinson's Disease Research Center of Excellence at UCLA (P50NS38367), Center grant NIHDDK 41301 (Animal Core), RO1 DK 57238 and a VA Career Scientist Award. NR 55 TC 19 Z9 20 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1350-1925 J9 NEUROGASTROENT MOTIL JI Neurogastroenterol. Motil. PD SEP PY 2012 VL 24 IS 9 BP e425 EP e436 DI 10.1111/j.1365-2982.2012.01974.x PG 12 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA 996LK UT WOS:000308089000003 PM 22779732 ER PT J AU Castillo-Martinez, L Colin-Ramirez, E Orea-Tejeda, A Islas, DGG Garcia, WDR Diaz, CS Rodriguez, AEG Duran, MV Davies, CK AF Castillo-Martinez, Lilia Colin-Ramirez, Eloisa Orea-Tejeda, Arturo Gonzalez Islas, Dulce Gabriela Rodriguez Garcia, Wendy Daniella Santillan Diaz, Cira Gutierrez Rodriguez, Ana Elizabeth Vazquez Duran, Marisela Davies, Candace Keirns TI Cachexia assessed by bioimpedance vector analysis as a prognostic indicator in chronic stable heart failure patients SO NUTRITION LA English DT Article DE Cachexia; Heart failure; Bioelectrical impedance vector analysis ID BIOELECTRICAL-IMPEDANCE ANALYSIS; CLINICAL-PRACTICE; BODY; MASS; DISEASE; AGE AB Background: This study explored whether the cachectic state assessed by bioimpedance vector analysis provides additional prognostic information about mortality from all causes. Methods: We included 519 consecutive patients with stable chronic heart failure (mean age 62.5 +/- 16.4 y; 286 males). Cachexia was identified in those subjects who fell outside the right lower quadrant of the reference curve of 95% on the resistance/reactance graph [bioelectrical impedance vectorial analysis (BIVA)-cachexia]. Clinical, anthropometric, and biochemical data were also evaluated. Results: Patients with BIVA-cachexia (n = 196,37.8%) were older and had significantly lower ejection fraction, handgrip strength, serum albumin, total cholesterol, and triglycerides. The frequency of patients with body mass index < 20, decreased muscle strength, hypoalbuminemia, anemia, anorexia, New York Heart Association functional classes III/IV and edema, as well as creatinine levels, resistance/height, and impedance index was significantly higher in the cachexia group. During 29 +/- 11 mo of follow-up, 39 (19.9%) patients with BIVA-cachexia and 38 (11.7%) patients without BIVA-cachexia (P < 0.0001) died. Conclusions: The cachectic state is an independent risk factor for mortality in chronic heart failure patients. BIVA could represent a valuable tool to assess presence of cachexia as changes in body cell mass in heart failure patients because provide information additional to weight loss. (C) 2012 Elsevier Inc. All rights reserved. C1 [Castillo-Martinez, Lilia; Colin-Ramirez, Eloisa; Orea-Tejeda, Arturo; Gonzalez Islas, Dulce Gabriela; Rodriguez Garcia, Wendy Daniella; Santillan Diaz, Cira; Gutierrez Rodriguez, Ana Elizabeth; Vazquez Duran, Marisela] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Cardiol, Heart Failure Clin, Del Valle, Benito Juarez C, Mexico. [Davies, Candace Keirns] Massachussets Gen Hosp, Boston, MA USA. RP Orea-Tejeda, A (reprint author), Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Cardiol, Heart Failure Clin, Del Valle, Benito Juarez C, Mexico. EM oreatart@gmail.com RI Castillo-Martinez, Lilia/H-3750-2013 NR 27 TC 12 Z9 13 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0899-9007 EI 1873-1244 J9 NUTRITION JI Nutrition PD SEP PY 2012 VL 28 IS 9 BP 886 EP 891 DI 10.1016/j.nut.2011.11.024 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 994DQ UT WOS:000307911500011 PM 22480798 ER PT J AU Colin-Ramirez, E Castillo-Martinez, L Orea-Tejeda, A Vazquez-Duran, M Rodriguez, AE Keirns-Davis, C AF Colin-Ramirez, Eloisa Castillo-Martinez, Lilia Orea-Tejeda, Arturo Vazquez-Duran, Marisela Rodriguez, Ana E. Keirns-Davis, Candace TI Bioelectrical impedance phase angle as a prognostic marker in chronic heart failure SO NUTRITION LA English DT Article DE Phase angle; Heart failure; Bioelectrical impedance; Prognosis; Body composition ID NUTRITIONAL-STATUS; CLINICAL-PRACTICE; BODY-COMPOSITION; HEMODIALYSIS-PATIENTS; VECTOR ANALYSIS; LUNG-CANCER; MORTALITY; PREDICTOR; INDICATOR; DISEASE AB Objective: The main purpose of the present study was to assess the prognostic value of the bioelectrical phase angle (PA) in patients with heart failure independently of other parameters of a poor prognosis. Methods: This retrospective study included 389 patients with heart failure. Anthropometric, body composition, clinical, biochemical, and echocardiographic data were collected from all patients. The quartiles were obtained for the PA, and patients were classified according to the quartiles into four groups. The endpoint was all-cause mortality. A Cox proportional hazards regression analysis was performed to estimate the adjusted relative risks, and 95% confidence intervals were obtained for the potential predictors of death. Results: Patients below the lowest quartile of PA (<4.2 degrees) had decreased mean body mass index, handgrip strength, and hemoglobin values and a larger proportion of patients in New York Heart Association functional class III and renal failure. The Kaplan-Meier survival analysis among PA groups showed a better survival for patients above the highest quartile of PA (>= 5.7 degrees), and survival decreased as the PA decreased. The Cox regression analysis found that a PA <4.2 was an independent predictor of mortality (relative risk 3.08, 95% confidence interval 1.06-8.99), adjusting for age, hemoglobin levels, and diabetes, compared with a PA >= 5.7. Conclusion: In this study population, a smaller PA was associated with malnutrition markers such as decreased body mass index, handgrip strength, and hemoglobin values and with a poor New York Heart Association functional class and renal failure. Adjusting for age, hemoglobin levels, and diabetes, a PA <4.2 was found to be an independent predictor of all-cause mortality in chronic heart failure. (C) 2012 Elsevier Inc. All rights reserved. C1 [Colin-Ramirez, Eloisa; Castillo-Martinez, Lilia; Orea-Tejeda, Arturo; Vazquez-Duran, Marisela; Rodriguez, Ana E.] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Cardiol, Heart Failure Clin, Mexico City, DF, Mexico. [Keirns-Davis, Candace] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Castillo-Martinez, L (reprint author), Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Cardiol, Heart Failure Clin, Mexico City, DF, Mexico. EM caml1225@yahoo.com RI Castillo-Martinez, Lilia/H-3750-2013 NR 30 TC 16 Z9 18 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0899-9007 J9 NUTRITION JI Nutrition PD SEP PY 2012 VL 28 IS 9 BP 901 EP 905 DI 10.1016/j.nut.2011.11.033 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 994DQ UT WOS:000307911500014 PM 22465907 ER PT J AU Seixas, NS Neitzel, R Stover, B Sheppard, L Feeney, P Mills, D Kujawa, S AF Seixas, Noah S. Neitzel, Rick Stover, Bert Sheppard, Lianne Feeney, Patrick Mills, David Kujawa, Sharon TI 10-Year prospective study of noise exposure and hearing damage among construction workers SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID OTOACOUSTIC EMISSIONS; INDUSTRY; HEALTH; SURVEILLANCE; PROTECTION AB Objectives To characterise the effects of noise exposure, including intermittent and peaky exposure, on hearing damage as assessed by standard pure-tone thresholds and otoacoustic emissions, a longitudinal study was conducted on newly hired construction apprentices and controls over a 10-year period. Methods Among the 456 subjects recruited at baseline, 316 had at least two (mean 4.6) examinations and were included in this analysis. Annual examinations included hearing threshold levels (HTLs) for air conducted pure tones and distortion product otoacoustic emission (DPOAE) amplitudes. Task-based occupational noise exposure levels and recreational exposures were estimated. Linear mixed models were fit for HTLs and DPOAEs at 3, 4 and 6 kHz in relation to time since baseline and average noise level since baseline, while controlling for hearing level at baseline and other risk factors. Results Estimated L-EQ noise exposures were 87 +/- 3.6 dBA among the construction workers. Linear mixed modelling demonstrated significant exposure-related elevations in HTL of about 2-3 dB over a projected 10-year period at 3, 4 or 6 kHz for a 10 dB increase in exposure. The DPOAE models (using L1=40) predicted about 1 dB decrease in emission amplitude over 10 years for a 10 dB increase in exposure. Conclusions The study provides evidence of noise-induced damage at an average exposure level around the 85 dBA level. The predicted change in HTLs was somewhat higher than would be predicted by standard hearing loss models, after accounting for hearing loss at baseline. Limited evidence for an enhanced effect of high peak component noise was observed, and DPOAEs, although similarly affected, showed no advantage over standard hearing threshold evaluation in detecting effects of noise on the ear and hearing. C1 [Seixas, Noah S.; Stover, Bert] Univ Washington, Sch Publ Hlth, Dept Environm & Occupat Hlth Sci, Seattle, WA 98115 USA. [Neitzel, Rick] Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA. [Sheppard, Lianne] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA. [Feeney, Patrick] VA Natl Ctr Rehabil Auditory Res, Portland, OR USA. [Mills, David] Univ Washington, Bloedel Hearing Res Ctr, Seattle, WA 98195 USA. [Kujawa, Sharon] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Kujawa, Sharon] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Seixas, NS (reprint author), Univ Washington, Sch Publ Hlth, Dept Environm & Occupat Hlth Sci, 4225 Roosevelt Way NE, Seattle, WA 98115 USA. EM nseixas@uw.edu RI Neitzel, Richard/P-7733-2015 OI Neitzel, Richard/0000-0001-5500-2589 FU US CDC (NIOSH) [5R01 OH003912] FX This work was supported by US CDC (NIOSH), grant number 5R01 OH003912. NR 37 TC 21 Z9 21 U1 1 U2 29 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1351-0711 EI 1470-7926 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD SEP PY 2012 VL 69 IS 9 BP 643 EP 650 DI 10.1136/oemed-2011-100578 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 997UJ UT WOS:000308191900006 PM 22693267 ER PT J AU Jensen, KB Kosek, E Wicksell, R Kemani, M Olsson, G Merle, JV Kadetoff, D Ingvar, M AF Jensen, Karin B. Kosek, Eva Wicksell, Rikard Kemani, Mike Olsson, Gunnar Merle, Julia V. Kadetoff, Diana Ingvar, Martin TI Cognitive Behavioral Therapy increases pain-evoked activation of the prefrontal cortex in patients with fibromyalgia (vol 153, pg 1495, 2012) SO PAIN LA English DT Correction C1 [Jensen, Karin B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. [Jensen, Karin B.] Athinoula A Martinos Ctr Biomed Imaging, Boston, MA USA. [Kosek, Eva; Wicksell, Rikard; Kemani, Mike; Kadetoff, Diana; Ingvar, Martin] Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden. [Kosek, Eva; Kadetoff, Diana; Ingvar, Martin] Karolinska Inst, Osher Ctr Integrat Med, Stockholm, Sweden. [Wicksell, Rikard; Kemani, Mike; Olsson, Gunnar] Karolinska Univ Hosp, Behav Med Pain Treatment Serv, Stockholm, Sweden. [Olsson, Gunnar] Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden. [Merle, Julia V.] Charite, Dept Child & Adolescent Psychiat, D-13353 Berlin, Germany. RP Jensen, KB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Psychiat Neuroimaging Bldg,120 2nd Ave, Charlestown, MA 02129 USA. EM karinj@nmr.mgh.harvard.edu NR 1 TC 0 Z9 0 U1 2 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD SEP PY 2012 VL 153 IS 9 BP 1981 EP 1981 DI 10.1016/j.pain.2012.07.004 PG 1 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 985VV UT WOS:000307299500034 ER PT J AU Price, M Gros, DF McCauley, JL Gros, KS Ruggiero, KJ AF Price, Matthew Gros, Daniel F. McCauley, Jenna L. Gros, Kirstin Stauffacher Ruggiero, Kenneth J. TI Nonuse and Dropout Attrition for a Web-Based Mental Health Intervention Delivered in a Post-Disaster Context SO PSYCHIATRY-INTERPERSONAL AND BIOLOGICAL PROCESSES LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; 2004 FLORIDA HURRICANES; INTERNET INTERVENTIONS; TERRORIST ATTACKS; RANDOMIZED-TRIAL; CLINICAL-TRIALS; NEW-YORK; DEPRESSION; DISASTER; ADULTS AB Web-based mental health interventions are an excellent means to provide low cost, easily accessible care to disaster-affected populations shortly after exposure to an event. However, the extent that individuals will access and use such interventions is largely unknown. We examined predictors of nonuse and dropout attrition for a web-based mental health intervention in 1,249 randomly selected adults in two Texas counties-Galveston and Chambers-that were hardest hit by Hurricane Ike in 2008. Participants completed a structured telephone interview to assess demographics, impact of disaster exposure, history of traumatic events, mental health symptoms, and service utilization. Following the interview, participants were oriented and invited to access a web-based intervention and then contacted four months later to evaluate their use of the website and mental health functioning. Separate logistic and Poisson regressions were used to determine baseline predictors of nonuse attrition, predictors of dropout attrition, and predictors of completing intervention modules. Results suggested that the strongest buffer against nonuse attrition and dropout attrition was having considered seeking formal mental health treatment. Results of this study inform the development and dissemination of web-based interventions in future disaster affected areas. C1 [Price, Matthew] Med Univ S Carolina, Natl Crime Victims Res & Treatment Ctr, Charleston, SC 29425 USA. [Price, Matthew; Gros, Daniel F.; Gros, Kirstin Stauffacher; Ruggiero, Kenneth J.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Price, M (reprint author), Med Univ S Carolina, Natl Crime Victims Res & Treatment Ctr, 67 President St,2 S MSC 861, Charleston, SC 29425 USA. EM prima@musc.edu FU National Institute of Mental Health [R34 MH77149]; NIMH [R01 MH081056]; [T32 MH018869]; [P60 MH082598] FX This study is supported by National Institute of Mental Health Grant R34 MH77149 (PI: Ruggiero). Dr. Price is supported by T32 MH018869. Dr. Ruggiero is also supported by P60 MH082598 (PI: Norris); and Drs. Ruggiero, McCauley, and K. S. Gros are supported by NIMH Grant R01 MH081056 (PI: Ruggiero). NR 57 TC 15 Z9 16 U1 2 U2 7 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0033-2747 J9 PSYCHIATRY JI Psychiatry-Interpers. Biol. Process. PD FAL PY 2012 VL 75 IS 3 BP 267 EP 284 PG 18 WC Psychiatry SC Psychiatry GA 001GO UT WOS:000308448800007 PM 22913502 ER PT J AU Wiener, L Oppenheim, D Breyer, J Battles, H Zadeh, S Patenaude, AF AF Wiener, Lori Oppenheim, Daniel Breyer, Joanna Battles, Haven Zadeh, Sima Patenaude, Andrea Farkas TI A worldview of the professional experiences and training needs of pediatric psycho-oncologists SO PSYCHO-ONCOLOGY LA English DT Article DE pediatrics; psycho-oncology; childhood cancer; training; professional rewards; clinical challenges ID BURNOUT; STRESS AB Background Thirty years after the origin of the field of psycho-oncology, limited data exist about the work practices of professionals providing psychosocial care to children with cancer and their families. Method A survey was designed to assess training, work environment, theoretical orientation, services provided, subspecialty areas or areas of special interest, satisfactions, challenges, and continuing education needs of pediatric psycho-oncologists. Members of national and international psycho-oncology organizations were invited to participate in the web-based survey. Results Seven hundred eighty-six professionals from 63 countries responded. The sample consisted mostly of psychologists (41%), physicians (20%), and social workers (14%). Approximately half of the participants worked in a designated psycho-oncology unit. Psychologists and social workers provided the majority of psychosocial services. Individual sessions with parents were most common (42%), followed by sessions with children (41%), survivors (36%), families (31%), and siblings (25%). Therapies provided include cognitive behavioral therapy (50%), relaxation (43%), psychodynamic psychotherapy (27%), play therapy (26%), and imagery (23%). Two-thirds reported having appropriate supervision, 37% were conducting research, and only half felt their salary was appropriate. Differences in therapeutic modalities were found by country. Clinicians desire training on clinical interventions, improving communication with medical staff, research, and ethics. Conclusions An international cohort of clinicians providing pediatric psycho-oncology services perform a wide variety of tasks, use a range of therapeutic approaches, and report considerable work satisfaction. Problem areas include professional inter-relations, inadequate supervision, and need for additional specialized training. Opportunity exists for global collaboration in pediatric psycho-oncology research and practices to enhance clinical effectiveness and reduce professional isolation. Copyright (c) 2012 John Wiley & Sons, Ltd. C1 [Wiener, Lori; Battles, Haven; Zadeh, Sima] NCI, Behav Sci Core, Psychosocial Support & Res Program, Pediat Oncol Branch,Ctr Canc Res, Bethesda, MD 20892 USA. [Breyer, Joanna; Patenaude, Andrea Farkas] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. [Breyer, Joanna; Patenaude, Andrea Farkas] Childrens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Breyer, Joanna; Patenaude, Andrea Farkas] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Oppenheim, Daniel] Inst Sensorial Dev Children Visual Impairment IDE, Paris, France. RP Wiener, L (reprint author), NCI, Behav Sci Core, Psychosocial Support & Res Program, Pediat Oncol Branch,Ctr Canc Res, 10 Ctr Dr, Bethesda, MD 20892 USA. EM wienerl@mail.nih.gov FU NIH, National Cancer Institute, Center for Cancer Research FX The authors would like to acknowledge the support of several individuals who helped make this work possible. Elliot Graham (IPOS) and Martha Grootenhuis (SIOP) were instrumental in the distribution of the survey information. At NCI, we would like to thank Caroline Crum, Nia Billings, and Lauren Latella who assisted with the coding of the qualitative data. We also appreciate the insights provided to us by the Pediatric SIG Members at both IPOS and APOS. This work is supported in part by the Intramural Research Programs of the NIH, National Cancer Institute, Center for Cancer Research. NR 19 TC 5 Z9 5 U1 2 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD SEP PY 2012 VL 21 IS 9 BP 944 EP 953 DI 10.1002/pon.3064 PG 10 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 999GY UT WOS:000308299000006 PM 22461180 ER PT J AU Manschreck, TC Merrill, AM Jabbar, G Chun, J DeLisi, LE AF Manschreck, T. C. Merrill, A. M. Jabbar, G. Chun, J. DeLisi, L. E. TI Frequency of normative word associations in the speech of individuals at familial high-risk for schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Familial high-risk; Language; Normative word associations; Schizotypy; Formal thought disorder ID COMMUNICATION DISTURBANCES; 1ST-DEGREE RELATIVES; UTTERANCES; SCHIZOTYPY; INTERVIEW; LANGUAGE; DISORDER; THOUGHT AB The intrusion of associations into speech in schizophrenia disrupts coherence and comprehensibility, a feature of formal thought disorder referred to as loosened associations. We have previously proposed that loosened associations may result from hyperactivity in semantic association networks, leading to an increased frequency of associated words appearing in speech. Using Computed Associations in Sequential Text (CAST) software to quantify the frequency of such associations in speech, we have reported more frequent normative associations in language samples from patients with schizophrenia and in individuals with schizotypal characteristics. The present study further examined this deviance in schizophrenia by studying normative associations in those who share genes with an individual with schizophrenia, (i.e. first-degree relatives of probands with schizophrenia; HR) but who do not have an illness. Familial high-risk participants (n=22), and controls (n=24) provided verbal responses to cards from the Thematic Apperception Test. CAST analysis revealed that HR used more associated words in their speech compared to controls. Furthermore, the frequency of normative word associations was positively correlated with dimensional and total scores of schizotypy derived from ratings of the structured interview for schizotypy, which confirms past research showing a relationship between schizotypy and hyperassociations. Our results suggest that some language disturbances in schizophrenia likely arise from an underlying psychopathological mechanism, hyperactivity of semantic associations. (C) 2012 Elsevier B. V. All rights reserved. C1 [Manschreck, T. C.; Merrill, A. M.; Chun, J.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Harvard Commonwealth Res Ctr,Lab Clin & Expt Psyc, Fall River, MA 02720 USA. [Manschreck, T. C.; Jabbar, G.; DeLisi, L. E.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Manschreck, T. C.; DeLisi, L. E.] VA Boston Healthcare Syst, Brockton, MA 02301 USA. RP Manschreck, TC (reprint author), Lab Clin & Expt Psychopathol, 49 Hillside St, Fall River, MA 02706 USA. EM theo.manschreck@state.ma.us FU National Institute of Mental Health [MHR21-083205] FX This study was funded in part by a grant awarded to Dr. DeLisi from the National Institute of Mental Health (MHR21-083205). NR 25 TC 7 Z9 7 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD SEP PY 2012 VL 140 IS 1-3 BP 99 EP 103 DI 10.1016/j.schres.2012.06.034 PG 5 WC Psychiatry SC Psychiatry GA 996FK UT WOS:000308070000018 PM 22819779 ER PT J AU Bartzokis, G Lu, PH Raven, EP Amar, CP Detore, NR Couvrette, AJ Mintz, J Ventura, J Casaus, LR Luo, JS Subotnik, KL Nuechterlein, KH AF Bartzokis, George Lu, Po H. Raven, Erika P. Amar, Chetan P. Detore, Nicole R. Couvrette, Alexander J. Mintz, Jim Ventura, Joseph Casaus, Laurie R. Luo, John S. Subotnik, Kenneth L. Nuechterlein, Keith H. TI Impact on intracortical myelination trajectory of long acting injection versus oral risperidone in first-episode schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Antipsychotic; Medication; Dopamine; Second generation; Atypical; Myelin; White matter; Gray matter; Oligodendrocyte; Development; Aging ID WHITE-MATTER; SCHIZOAFFECTIVE DISORDER; PREFRONTAL CORTEX; ATYPICAL ANTIPSYCHOTICS; DIFFERENTIAL IMPACT; TREATMENT RESPONSE; NEURONAL DENSITY; BIPOLAR DISORDER; MOOD DISORDERS; 1ST EPISODE AB Context: Imaging and post-mortem studies suggest that frontal lobe intracortical myelination is dysregulated in schizophrenia (SZ). Prior MRI studies suggested that early in the treatment of SZ, antipsychotic medications initially increase frontal lobe intracortical myelin (ICM) volume, which subsequently declines prematurely in chronic stages of the disease. Insofar as the trajectory of ICM decline in chronic SZ is due to medication non-adherence or pharmacokinetics, it may be modifiable by long acting injection (LAI) formulations. Objectives: Assess the effect of risperidone formulation on the ICM trajectory during a six-month randomized trial of LAI (RLAI) versus oral (RisO) in first-episode SZ subjects. Design: Two groups of SZ subjects (RLAI, N=9; and RisO, N=13) matched on pre-randomization oral medication exposure were prospectively examined at baseline and 6 months later, along with 12 healthy controls (HCs). Frontal lobe ICM volume was assessed using inversion recovery (IR) and proton density (PD) MRI images. Medication adherence was tracked. Main outcome measure: ICM volume change scores were adjusted for the change in the HCs. Results: ICM volume increased significantly (p=.005) in RLAI and non-significantly (p=.39) in the RisO groups compared with that of the healthy controls. A differential between-group treatment effect was at a trend level (p=.093). SZ subjects receiving RLAI had better medication adherence and more ICM increases (chi-square p<.05). Conclusions: The results suggest that RLAI may promote ICM development in first-episode SZ patients. Better adherence and/or pharmacokinetics provided by LAI may modify the ICM trajectory. In vivo MRI myelination measures can help clarify pharmacotherapeutic mechanisms of action. (C) 2012 Elsevier B. V. All rights reserved. C1 [Bartzokis, George; Raven, Erika P.; Amar, Chetan P.; Detore, Nicole R.; Couvrette, Alexander J.; Ventura, Joseph; Casaus, Laurie R.; Luo, John S.; Subotnik, Kenneth L.; Nuechterlein, Keith H.] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Bartzokis, George] Univ Calif Los Angeles, David Geffen Sch Med, Div Brain Mapping, Dept Neurol,Lab Neuroimaging, Los Angeles, CA 90095 USA. [Bartzokis, George; Raven, Erika P.; Amar, Chetan P.; Couvrette, Alexander J.] Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. [Mintz, Jim] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. [Nuechterlein, Keith H.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. RP Bartzokis, G (reprint author), 300 UCLA Med Plaza,Suite 2200, Los Angeles, CA 90095 USA. EM gbar@ucla.edu RI Bartzokis, George/K-2409-2013 FU NIH [MH 0266029, AG027342, MH51928, MH6357, MH037705, P50 MH066286]; Ortho-McNeil Janssen Scientific Affairs, LLC.; Department of Veterans Affairs; Janssen Pharmaceutical Inc. FX Funding for this study was supported in part by NIH grants (MH 0266029; AG027342; MH51928; MH6357; MH037705; P50 MH066286), and by two investigator-initiated grants from Ortho-McNeil Janssen Scientific Affairs, LLC., and the Department of Veterans Affairs. The NIH, Janssen Pharmaceutical Inc., and the Department of Veterans Affairs had no further role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.; George Bartzokis and Keith Nuechterlein have received funding from Janssen Pharmaceutical Inc. George Bartzokis has consulted for Janssen Pharmaceutical Inc. All other authors declare that they have no conflicts of interest. NR 78 TC 17 Z9 17 U1 3 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD SEP PY 2012 VL 140 IS 1-3 BP 122 EP 128 DI 10.1016/j.schres.2012.06.036 PG 7 WC Psychiatry SC Psychiatry GA 996FK UT WOS:000308070000022 PM 22809684 ER PT J AU Wang, JJ Fan, XD Liu, DT Yi, ZH Freudenreich, O Goff, D Henderson, DC AF Wang, Jijun Fan, Xiaoduo Liu, Dengtang Yi, Zhenghui Freudenreich, Oliver Goff, Donald Henderson, David C. TI Both physical activity and food intake are associated with metabolic risks in patients with schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Letter ID INFLAMMATION; GLUCOSE C1 [Fan, Xiaoduo; Freudenreich, Oliver; Henderson, David C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Schizophrenia Program, Cambridge, MA 02138 USA. [Wang, Jijun; Liu, Dengtang; Yi, Zhenghui] Shanghai Jiao Tong Univ, Sch Med, Shanghai Mental Hlth Ctr, Shanghai 200030, Peoples R China. [Goff, Donald] NYU, Nathan Kline Psychiat Res Inst, New York, NY 10003 USA. RP Fan, XD (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Schizophrenia Program, Cambridge, MA 02138 USA. EM xfan@partners.org NR 9 TC 4 Z9 4 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD SEP PY 2012 VL 140 IS 1-3 BP 260 EP 261 DI 10.1016/j.schres.2012.05.008 PG 2 WC Psychiatry SC Psychiatry GA 996FK UT WOS:000308070000042 PM 22682987 ER PT J AU Ruiter, B Shreffler, WG AF Ruiter, Bert Shreffler, Wayne G. TI Innate immunostimulatory properties of allergens and their relevance to food allergy SO SEMINARS IN IMMUNOPATHOLOGY LA English DT Review DE Food allergy; Innate; Th2; Food; Respiratory; Allergen; Parasite; Helminth ID HOUSE-DUST MITE; HUMAN DENDRITIC CELLS; ALTERNATIVELY ACTIVATED MACROPHAGES; PATTERN-RECOGNITION RECEPTORS; THYMIC STROMAL LYMPHOPOIETIN; ANTIGEN-PRESENTING CELLS; SIMULATED GASTRIC FLUID; HELPER TYPE-2 RESPONSE; TH2 IMMUNE-RESPONSES; NONINTEGRIN DC-SIGN AB Food allergy is an increasingly prevalent disease of immune dysregulation directed to a small subset of proteins. Shared structural and functional features of allergens, such as glycosylation, lipid-binding and protease activity may provide insight into the mechanisms involved in the induction of primary Th2 immune responses. We review the literature of innate Th2-type immune activation as a context for better understanding the properties of allergens that contribute to the induction of Th2-biased immune responses in at least a subset of individuals. Th2-priming signals have been largely identified in the context of parasite immunity and wound healing. Some of the features of parasite antigens and the innate immune responses to them are now understood to play a role in allergic inflammation as well. These include both exogenous and endogenous activators of innate immunity and subsequent release of key cytokine mediators such as thymic stromal lymphopoietin (TSLP), interleukin (IL)-25 and IL-33. Moreover, numerous innate immune cells including epithelium, dendritic cells, basophils, innate lymphoid cells and others all interact to shape the adaptive Th2 immune response. Progress toward understanding Th2-inducing innate immune signals more completely may lead to novel strategies for primary prevention and therapy of respiratory and food allergies. C1 [Ruiter, Bert; Shreffler, Wayne G.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. [Shreffler, Wayne G.] Massachusetts Gen Hosp, Food Allergy Ctr, Boston, MA 02114 USA. [Ruiter, Bert; Shreffler, Wayne G.] Harvard Univ, Sch Med, Boston, MA USA. RP Ruiter, B (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Bldg 149,13th St,Room 8-312, Charlestown, MA 02129 USA. EM bruiter@partners.org FU NIAID NIH HHS [U19 AI095261]; NIDDK NIH HHS [P30 DK040561] NR 150 TC 16 Z9 17 U1 3 U2 24 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1863-2297 J9 SEMIN IMMUNOPATHOL JI Semin. Immunopathol. PD SEP PY 2012 VL 34 IS 5 BP 617 EP 632 DI 10.1007/s00281-012-0334-8 PG 16 WC Immunology; Pathology SC Immunology; Pathology GA 002PP UT WOS:000308544600002 PM 22886110 ER PT J AU DeLelys, ME Ochoa, G Cserti-Gazdewich, CM Vietz, CM Preffer, FI Dzik, W AF DeLelys, M. E. Ochoa, G. Cserti-Gazdewich, C. M. Vietz, C. M. Preffer, F. I. Dzik, W. TI Relationship Between ABH Genotype and A Antigen Expression on Platelets SO TRANSFUSION LA English DT Meeting Abstract CT AABB Annual Meeting and CTTXPO CY OCT 06-09, 2012 CL Boston, MA SP AABB, CTTXPO C1 [Dzik, W.] Massachusetts Gen Hosp, Blood Transfus Serv, Boston, MA 02114 USA. [DeLelys, M. E.; Preffer, F. I.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Cserti-Gazdewich, C. M.] Univ Hlth Network, Toronto, ON, Canada. [Cserti-Gazdewich, C. M.] Toronto Gen Hosp, Toronto, ON, Canada. [Ochoa, G.; Vietz, C. M.] Genotyping Lab, Boston, MA USA. EM mdelelys@partners.org 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 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2012 VL 52 SU 3 SI SI BP 16A EP 16A PG 1 WC Hematology SC Hematology GA 000PH UT WOS:000308398600016 ER PT J AU Meyer, E Dzik, W AF Meyer, E. Dzik, W. TI Computerized Blood Utilization Review Educates Transfusing Clinician SO TRANSFUSION LA English DT Meeting Abstract CT AABB Annual Meeting and CTTXPO CY OCT 06-09, 2012 CL Boston, MA SP AABB, CTTXPO C1 [Meyer, E.; Dzik, W.] Massachusetts Gen Hosp, Blood Transfus Serv, Boston, MA 02114 USA. EM ekgmeyer@gmail.com 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 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2012 VL 52 SU 3 SI SI BP 122A EP 122A PG 1 WC Hematology SC Hematology GA 000PH UT WOS:000308398600284 ER PT J AU Pena, J Saidman, S Dzik, W Makar, R AF Pena, J. Saidman, S. Dzik, W. Makar, R. TI Anti-HLA Alloantibodies in Platelet Refractory Patients Cannot be Overwhelmed by Dilution in Massive Transfusion SO TRANSFUSION LA English DT Meeting Abstract CT AABB Annual Meeting and CTTXPO CY OCT 06-09, 2012 CL Boston, MA SP AABB, CTTXPO C1 [Pena, J.; Saidman, S.; Dzik, W.; Makar, R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM rpena1@partners.org 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 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2012 VL 52 SU 3 SI SI BP 129A EP 129A PG 1 WC Hematology SC Hematology GA 000PH UT WOS:000308398600303 ER PT J AU Tsukamoto, H Zhu, NL Asahina, K Machida, K AF Tsukamoto, H. Zhu, N-L. Asahina, K. Machida, K. TI DLK1 IN ALCOHOLIC LIVER FIBROSIS, REGENERATION, AND CANCER SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 16th World Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY SEP 09-12, 2012 CL Sapporo, JAPAN SP Int Soc Biomed Res Alcoholism (ISBRA), Japanese Med Soc Alcohol & Drug Studies (JMSAS), Sci Council Japan C1 Univ So Calif, So Calif Res Ctr ALPD & Cirrhosis, Los Angeles, CA USA. Greater Los Angeles VA Healthcare Syst, Los Angeles, CA 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD SEP PY 2012 VL 36 SU 2 SI SI BP 21A EP 21A PG 1 WC Substance Abuse SC Substance Abuse GA 000OS UT WOS:000308396700037 ER PT J AU Chen, S Charness, ME AF Chen, S. Charness, M. E. TI ALCOHOL DISRUPTION OF AXON OUTGROWTH AND SIGNALING SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 16th World Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY SEP 09-12, 2012 CL Sapporo, JAPAN SP Int Soc Biomed Res Alcoholism (ISBRA), Japanese Med Soc Alcohol & Drug Studies (JMSAS), Sci Council Japan C1 Harvard Univ, VA Boston Healthcare Syst, Sch Med, W Roxbury, MA 02132 USA. Harvard Univ, Dept Neurol, Sch Med, W Roxbury, MA 02132 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD SEP PY 2012 VL 36 SU 2 SI SI BP 63A EP 63A PG 1 WC Substance Abuse SC Substance Abuse GA 000OS UT WOS:000308396700202 ER PT J AU Chen, S Charness, ME AF Chen, S. Charness, M. E. TI ALCOHOL DISRUPTION OF NEURAL CIRCUITS DEVELOPMENT AND SIGNALING SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 16th World Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY SEP 09-12, 2012 CL Sapporo, JAPAN SP Int Soc Biomed Res Alcoholism (ISBRA), Japanese Med Soc Alcohol & Drug Studies (JMSAS), Sci Council Japan C1 Harvard Univ, Sch Med, VA Boston Healthcare Syst, W Roxbury, MA 02132 USA. Harvard Univ, Sch Med, Dept Neurol, W Roxbury, MA 02132 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD SEP PY 2012 VL 36 SU 2 SI SI BP 109A EP 109A PG 1 WC Substance Abuse SC Substance Abuse GA 000OS UT WOS:000308396700377 ER PT J AU Mendez, MF Lee, AS Joshi, A Shapira, JS AF Mendez, Mario F. Lee, Albert S. Joshi, Aditi Shapira, Jill S. TI Nonamnestic Presentations of Early-Onset Alzheimer's Disease SO AMERICAN JOURNAL OF ALZHEIMERS DISEASE AND OTHER DEMENTIAS LA English DT Article DE Alzheimer's disease; early-onset; aphasia; posterior cortical atrophy; apraxia ID POSTERIOR CORTICAL ATROPHY; CLINICAL CHARACTERISTICS; PROGRESSIVE APHASIA; GREY-MATTER; DEMENTIA; AGE; DIAGNOSIS; FEATURES; BATTERY; ASSOCIATION AB Early-onset Alzheimer's disease (EOAD) beginning before the age of 65 may differ from late-onset AD (LOAD) in clinical course and frequency of nonamnestic presentations. In a 10-year retrospective review, 125 patients with EOAD, diagnosed clinically and verified by functional neuroimaging, were compared with 56 patients with LOAD and further classified depending on predominant cognitive difficulty on presentation. Eighty (64%) of the patients with EOAD had a nonamnestic presentation, compared with only 7 (12.5%) of the patients with LOAD. Compared with LOAD, the patients with EOAD had a shorter duration with lower Mini-Mental State Examination scores. The neuroimaging reports among the patients with EOAD showed more hippocampal atrophy with an amnestic presentation, more left parietal changes with impaired language presentations, and more right parietal and occipital changes with impaired visuospatial presentations. These findings indicate that EOAD differs from LOAD in a more aggressive course and in having predominantly nonamnestic presentations that vary in neuropathological location. C1 [Mendez, Mario F.; Joshi, Aditi; Shapira, Jill S.] Univ Calif Los Angeles, Dept Neurol, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Mendez, Mario F.] VA Greater Los Angeles Healthcare Ctr, Neurobehav Unit 691 116AF, Neurol Sect, Los Angeles, CA 90073 USA. [Mendez, Mario F.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Mendez, Mario F.] Univ Calif Los Angeles, Mary S Easton Ctr Alzheimers Dis Res, Los Angeles, CA USA. [Lee, Albert S.] Western Univ Hlth Sci, Pomona, CA USA. RP Mendez, MF (reprint author), VA Greater Los Angeles Healthcare Ctr, Neurobehav Unit 691 116AF, Neurol Sect, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM mmendez@ucla.edu FU VA Merit Review; Alzheimer's Disease Research Center [NIA P50 AG-16570]; [R01AG034499-03] FX The authors disclosed receipt of the following financial support for the research, authorship and/or publication of this article: grant #R01AG034499-03 and a VA Merit Review (A. Joshi, A. Lee, M. F. Mendez) and Alzheimer's Disease Research Center Grant NIA P50 AG-16570 (M.F. Mendez). NR 44 TC 25 Z9 25 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1533-3175 J9 AM J ALZHEIMERS DIS JI Am. J. Alzheimers Dis. Other Dement. PD SEP PY 2012 VL 27 IS 6 BP 413 EP 420 DI 10.1177/1533317512454711 PG 8 WC Geriatrics & Gerontology; Clinical Neurology SC Geriatrics & Gerontology; Neurosciences & Neurology GA 995PA UT WOS:000308021300007 PM 22871906 ER PT J AU Salloway, S Mintzer, J Cummings, JL Geldmacher, D Sun, YJ Yardley, J Mackell, J AF Salloway, Stephen Mintzer, Jacobo Cummings, Jeffrey L. Geldmacher, David Sun, Yijun Yardley, Jane Mackell, Joan TI Subgroup Analysis of US and Non-US Patients in a Global Study of High-Dose Donepezil (23 mg) in Moderate and Severe Alzheimer's Disease SO AMERICAN JOURNAL OF ALZHEIMERS DISEASE AND OTHER DEMENTIAS LA English DT Article DE Alzheimer's disease; donepezil; efficacy; tolerability; clinical trial; United States ID MILD COGNITIVE IMPAIRMENT; APOLIPOPROTEIN-E EPSILON-4; DOUBLE-BLIND; DECLINE; TOLERABILITY; EDUCATION; EFFICACY; 24-WEEK; SAFETY; RATES AB To better understand responses in the large number of US-based patients included in a global trial of donepezil 23 mg/d versus 10 mg/d for moderate-to-severe Alzheimer's disease (AD), post hoc exploratory analyses were performed to assess the efficacy and safety in US and non-US (rest of the world [RoW]) patient subgroups. In both subgroups, donepezil 23 mg/d was associated with significantly greater cognitive benefits than donepezil 10 mg/d. Significant global function benefits of donepezil 23 mg/d over 10 mg/d were also observed in the US subgroup only. Compared with RoW patients, US patients had relatively more severe AD, had been treated with donepezil 10 mg/d for longer periods prior to the start of the study, and a higher proportion took concomitant memantine. In both subgroups, donepezil had acceptable tolerability; overall incidence of treatment-emergent adverse events was higher in patients receiving donepezil 23 mg/d compared with donepezil 10 mg/d. C1 [Salloway, Stephen] Brown Alpert Med Sch, Providence, RI 02906 USA. [Mintzer, Jacobo] Med Univ S Carolina, Alzheimers Res Program, Charleston, SC 29425 USA. [Mintzer, Jacobo] Med Univ S Carolina, Clin Program, Charleston, SC 29425 USA. [Mintzer, Jacobo] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Cummings, Jeffrey L.] Cleveland Clin, Lou Ruvo Ctr Brain Hlth, Las Vegas, NV USA. [Geldmacher, David] Univ Alabama Birmingham, Div Memory Disorders & Behav Neurol, Birmingham, AL USA. [Sun, Yijun] Eisai Inc, Dept Biometr, Woodcliff Lake, NJ USA. [Yardley, Jane] Eisai Ltd, Neurosci Prod Creat Unit, European Knowledge Ctr, Hatfield, Herts, England. [Mackell, Joan] Pfizer Inc, New York, NY USA. RP Salloway, S (reprint author), Brown Alpert Med Sch, 345 Blackstone Blvd, Providence, RI 02906 USA. EM ssalloway@butler.org FU Eisai Inc.; Pfizer Inc.; Pfizer; Eisai FX The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Stephen Salloway has received consultation fees from the Eisai Inc. Jacobo Mintzer has no relevant conflicts of interest to disclose. Jeffrey L. Cummings has provided consultation to Eisai Inc. David Geldmacher has received both research support related to the conduct of the reported study and consulting honoraria in relation to donepezil from Eisai Inc. Yijun Sun is a ex-employee of Eisai Inc. Jane Yardley is a current employee of Eisai Ltd. Joan Mackell is a current employee of Pfizer Inc and holds stock in Pfizer Inc.; The authors disclosed receipt of the following financial support for the research, authorship and/or publication of this article: The described analyses derive from a phase 3 clinical study (ClinicalTrials.gov identifier: NCT00478205) is sponsored by Eisai Inc. Editorial support in the development of this manuscript was provided by Richard Daniel, PhD, of PAREXEL, and was funded by Eisai Inc. and Pfizer Inc. Jacobo Mintzer has received grant research support from Pfizer and Eisai, but not for the specific activities reported in this study. NR 19 TC 6 Z9 6 U1 0 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1533-3175 J9 AM J ALZHEIMERS DIS JI Am. J. Alzheimers Dis. Other Dement. PD SEP PY 2012 VL 27 IS 6 BP 421 EP 432 DI 10.1177/1533317512454708 PG 12 WC Geriatrics & Gerontology; Clinical Neurology SC Geriatrics & Gerontology; Neurosciences & Neurology GA 995PA UT WOS:000308021300008 PM 22930699 ER PT J AU Baron, JM Mermel, CH Lewandrowski, KB Dighe, AS AF Baron, Jason M. Mermel, Craig H. Lewandrowski, Kent B. Dighe, Anand S. TI Detection of Preanalytic Laboratory Testing Errors Using a Statistically Guided Protocol SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE Machine learning; Decision tree; Preanalytic error; Glucose; Informatics; Line draw ID SYSTEM; VALIDATION; BLOOD; INFORMATION; REGRESSION; MEDICINE AB Preanalytic laboratory testing errors are often difficult to identify. We demonstrate how laboratories can integrate statistical models with clinical judgment to develop protocols for preanalytic error detection. Specifically, we developed a protocol to identify spuriously elevated glucose values resulting from improper "line draws" or related phlebotomy errors. Using a decision tree-generating algorithm and an annotated set of training data, we generated decision trees to classify critically elevated glucose results as "real" or "spurious" based on available laboratory parameters. Decision trees revealed that a 30-day patient-specific average glucose concentration lower than 186.3 mg/dL (10.3 mmol/L), a current glucose concentration higher than 663 mg/dL (37 mmol/L), and an anion gap lower than 16.5 mEy/L (16.5 mmol/L) suggested a spurious result. We then used the results from the decision tree analysis to inform the implementation of a clinical protocol that significantly improved the laboratory's identification of spurious results. Similar approaches may be useful in developing protocols to identify other errors or to assist in clinical interpretation of results. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Dighe, AS (reprint author), Bigelow Bldg,Room 510A,55 Fruit St, Boston, MA 02114 USA. EM asdighe@partners.org NR 23 TC 4 Z9 4 U1 0 U2 6 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD SEP PY 2012 VL 138 IS 3 BP 406 EP 413 DI 10.1309/AJCPQIRIB3CT1EJV PG 8 WC Pathology SC Pathology GA 998SD UT WOS:000308259800014 PM 22912358 ER PT J AU Kovach, AE DeLelys, ME Kelliher, AS Preffer, FI Sohani, AR Stowell, CP AF Kovach, Alexandra E. DeLelys, Michelle E. Kelliher, Abigail S. Preffer, Frederic I. Sohani, Aliyah R. Stowell, Christopher P. TI Criteria for Cost-Effective Flow Cytometric Analysis on Cerebrospinal Fluid Specimens SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Meeting Abstract CT 47th Annual Meeting of the Academy-of-Clinical-Laboratory-Physicians-and-Scientists (ACLPS)/Conference on Lab Medicine CY MAY 31-JUN 02, 2012 CL Milwaukee, WI SP Acad Clin Lab Phys & Scientists (ACLPS) C1 [Kovach, Alexandra E.; DeLelys, Michelle E.; Kelliher, Abigail S.; Preffer, Frederic I.; Sohani, Aliyah R.; Stowell, Christopher P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD SEP PY 2012 VL 138 IS 3 MA 23 BP 462 EP 462 PG 1 WC Pathology SC Pathology GA 998SD UT WOS:000308259800034 ER PT J AU Herskovits, AZ Ivinson, AJ Scherzer, CR Hyman, BT Lindeman, N AF Herskovits, A. Zara Ivinson, Adrian J. Scherzer, Clemens R. Hyman, Bradley T. Lindeman, Neal TI CSF and Blood Biomarkers for Alzheimer's Disease SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Meeting Abstract CT 47th Annual Meeting of the Academy-of-Clinical-Laboratory-Physicians-and-Scientists (ACLPS)/Conference on Lab Medicine CY MAY 31-JUN 02, 2012 CL Milwaukee, WI SP Acad Clin Lab Phys & Scientists (ACLPS) C1 [Herskovits, A. Zara] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Ivinson, Adrian J.] Harvard Univ, Sch Med, Harvard NeuroDiscovery Ctr, Boston, MA USA. [Scherzer, Clemens R.] Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. [Hyman, Bradley T.] Massachusetts Gen Hosp, Dept Neurol, MassGeneral Inst Neurodegenerat Dis, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD SEP PY 2012 VL 138 IS 3 MA 60 BP 469 EP 469 PG 1 WC Pathology SC Pathology GA 998SD UT WOS:000308259800055 ER PT J AU Giardino, AA Shinagare, AB Shinagare, SA Dewar, R Weckstein, D Mauch, P Ramaiya, NH Freedman, AS AF Giardino, Angela A. Shinagare, Atul B. Shinagare, Shweta A. Dewar, Rajan Weckstein, Doug Mauch, Peter Ramaiya, Nikhil H. Freedman, Arnold S. TI Primary bone lymphoma involving bilateral tibia SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Editorial Material ID SINGLE-INSTITUTION C1 [Giardino, Angela A.; Shinagare, Atul B.; Ramaiya, Nikhil H.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02215 USA. [Giardino, Angela A.; Shinagare, Atul B.; Ramaiya, Nikhil H.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Shinagare, Shweta A.; Dewar, Rajan] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Pathol, Boston, MA 02215 USA. [Weckstein, Doug; Freedman, Arnold S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Mauch, Peter] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. RP Shinagare, AB (reprint author), Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA. EM ashinagare@partners.org NR 10 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD SEP PY 2012 VL 87 IS 9 BP 924 EP 925 DI 10.1002/ajh.23245 PG 2 WC Hematology SC Hematology GA 993FY UT WOS:000307843300016 PM 22641233 ER PT J AU Ruiz-Arguelles, GJ Gomez-Almaguer, D Steensma, DP AF Ruiz-Argueelles, Guillermo J. Gomez-Almaguer, David Steensma, David P. TI Outdated dogma? Busulfan, seizure prophylaxis, and stem cell allografting SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Letter ID HIGH-DOSE BUSULFAN C1 [Ruiz-Argueelles, Guillermo J.] Clin Ruiz, Ctr Hematol & Med Interna, Puebla 72530, Pue, Mexico. [Steensma, David P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Steensma, David P.] Harvard Univ, Sch Med, Boston, MA USA. RP Ruiz-Arguelles, GJ (reprint author), Clin Ruiz, Ctr Hematol & Med Interna, 8B Sur 3710, Puebla 72530, Pue, Mexico. EM gruiz1@clinicaruiz.com OI Steensma, David/0000-0001-5130-9284 NR 9 TC 5 Z9 5 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD SEP PY 2012 VL 87 IS 9 BP 941 EP 941 DI 10.1002/ajh.23270 PG 1 WC Hematology SC Hematology GA 993FY UT WOS:000307843300024 PM 22674687 ER PT J AU Ault, KA Heine, RP Riley, LE AF Ault, Kevin A. Heine, R. Phillips Riley, Laura E. TI Programmatic and research priorities for improving influenza immunization of pregnant women SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE infants; influenza; maternal immunization; pregnancy; vaccination AB Despite evidence regarding the benefits of influenza immunization during pregnancy for both the pregnant woman and her infant, as well as reassuring safety data, influenza vaccination rates in pregnancy have lagged. The 2009 influenza pandemic was accompanied by increased maternal vaccination rates. In this article, we review programmatic and research priorities with regard to overcoming barriers to influenza immunization of pregnant women. C1 [Ault, Kevin A.] Emory Univ, Sch Med, Dept Gynecol & Obstet, Atlanta, GA USA. [Ault, Kevin A.] Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA USA. [Ault, Kevin A.] Emory Univ, Rollins Sch Publ Hlth, Hubert Dept Global Hlth, Atlanta, GA 30322 USA. [Heine, R. Phillips] Duke Univ, Sch Med, Dept Obstet & Gynecol, Durham, NC USA. [Heine, R. Phillips] Duke Univ, Sch Med, Dept Pediat, Durham, NC USA. [Riley, Laura E.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Ault, KA (reprint author), Emory Univ, Sch Med, Dept Gynecol & Obstet, Atlanta, GA USA. NR 11 TC 3 Z9 3 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 2012 VL 207 IS 3 SU S BP S75 EP S77 DI 10.1016/j.ajog.2012.06.078 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 997SC UT WOS:000308185400014 PM 22920064 ER PT J AU Read, JS Riley, L AF Read, Jennifer S. Riley, Laura TI Progress in overcoming barriers to influenza immunization of pregnant women SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material C1 [Read, Jennifer S.] Natl Vaccine Program Off, Off Secretary, Off Assistant Secretary Hlth, Dept Hlth & Human Serv, Washington, DC USA. [Riley, Laura] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Read, JS (reprint author), Natl Vaccine Program Off, Off Secretary, Off Assistant Secretary Hlth, Dept Hlth & Human Serv, Washington, DC USA. NR 21 TC 6 Z9 6 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 2012 VL 207 IS 3 SU S BP S1 EP S2 DI 10.1016/j.ajog.2012.06.067 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 997SC UT WOS:000308185400001 PM 22920052 ER PT J AU Silva, PS Cavallerano, JD Sun, JK Noble, J Aiello, LM Aiello, LP AF Silva, Paolo S. Cavallerano, Jerry D. Sun, Jennifer K. Noble, Jason Aiello, Lloyd M. Aiello, Lloyd Paul TI Nonmydriatic Ultrawide Field Retinal Imaging Compared With Dilated Standard 7-Field 35-mm Photography and Retinal Specialist Examination for Evaluation of Diabetic Retinopathy SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID DIGITAL PHOTOGRAPHY; FUNDUS PHOTOGRAPHY; SCREENING APPROACH; COMPLICATIONS; CAMERA; FILM; SEVERITY; OPHTHALMOSCOPY; MELLITUS; SYSTEM AB PURPOSE: To compare nonmydriatic stereoscopic Optotmap ultrawide field images with dilated stereoscopic Early Treatment Diabetic Retinopathy Study 7-standard field 35-mm color 30-degree fundus photographs (ETDRS photography) and clinical examination for determining diabetic retinopathy (DR) and diabetic macular edema (DME) severity. DESIGN: Single-site, prospective, comparative, instrument validation study. METHODS: One hundred three diabetic patients (206 eyes) representing the full spectrum of DR severity underwent nonmydriatic ultrawide field 100-degree and 200-degree imaging, dilated ETDRS photography, and dilated fundus examination by a retina specialist. Two independent readers graded images to determine DR and DME severity. A third masked retina specialist adjudicated discrepancies. RESULTS: Based on ETDRS photography (n = 200), the results were as follows: no DR (n = 25 eyes [12.5%]), mild nonproliferative DR (NPDR; 47 [23.5%]), moderate NPDR (61 [30.5%]), severe NPDR (11 [5.5%]), very so ere NPDR (3 [1.5%]), and proliferative DR (52 [2.5%]). One (0.5%) eye was ungradable and 6 eyes did not complete ETDRS photography. No DME was found in 114 eyes (57.0%), DME was found in 28 eyes (14.0%), and clinically significant DME was found in 47 eyes (23.5%), an I 11 (5.5%) eyes were ungradable. Exact DR severity agreement between ultrawide field 100-degree imaging and ETDRS photography occurred in 84%, with agreement within 1 level in 91% (K-w = 0.85; K = 0.79). Nonmydriatic ultrawide field images exactly matched clinical examination results for DR in 70% and were within 1 level in 93 % (K-w = 0.71; K = 0.61). Nonmydriatic ultrawide field imaging acquisition time was less than half that of dilated ETDRS photography (P < .0001). CONCLUSIONS: Nonmydriatic ultrawide field images compare favorably with dilated ETDRS photography and dilated fundus examination in determining DR and DME severity; however, they are acquired more rapidly. If confirmed in broader diabetic populations, nonmydriatic ultrawide field imaging may prove to be beneficial in DR evaluation in research and clinical settings. (Am J Ophthalmol 2012;154:549-559. (C) 2012 by Elsevier Inc. All rights reserved.) C1 [Silva, Paolo S.; Cavallerano, Jerry D.; Sun, Jennifer K.; Noble, Jason; Aiello, Lloyd M.; Aiello, Lloyd Paul] Harvard Univ, Sch Med, Beetham Eye Inst, Joslin Diabet Ctr, Boston, MA 02215 USA. [Silva, Paolo S.; Cavallerano, Jerry D.; Sun, Jennifer K.; Noble, Jason; Aiello, Lloyd M.; Aiello, Lloyd Paul] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02215 USA. RP Silva, PS (reprint author), Harvard Univ, Sch Med, Beetham Eye Inst, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM paoloantonio.silva@joslin.harvard.edu FU Optos, plc, Dunfermline, United Kingdom; Massachusetts Lions' Eye Research Fund, Inc (Commonwealth of Massachusetts, USA) FX ALL AUTHORS HAVE COMPLETED AND SUBMITTED THE ICMJE FORM FOR DISCLOSURE OF POTENTIAL CONFLICTS OF interest and none were reported. Publication of this article was supported by grant funding provided to the Joslin Diabetes Center by Optos, plc, Dunfermline, United Kingdom, and the Massachusetts Lions' Eye Research Fund, Inc (Commonwealth of Massachusetts, USA). Involved in Design of study (P.S.S., J.D.C., J.K.S., J.N., L.M.A., L.P.A.); Conduct of study (P.S.S., J.D.C., J.K.S., J.N., L.M.A., L.P.A.); Collection and management of data (P.S.S., J.D.C., J.K.S., J.N.); Analysis and interpretation of data (P.S.S., J.D.C., J.K.S., J.N., L.M.A., L.P.A.); and Preparation and review of manuscript (P.S.S., J.D.C., J.K.S., J.N., L.M.A., L.P.A.). Prospective approval was obtained from the Joslin Diabetes Center Institutional Review Board before the study commenced, and the study was in compliance with the Health Insurance Portability and Accountability Act of 1996. The principles of the Declaration of Helsinki were followed. All subjects provided written informed consent before participation in the study. NR 34 TC 36 Z9 41 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 EI 1879-1891 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD SEP PY 2012 VL 154 IS 3 BP 549 EP 559 DI 10.1016/j.ajo.2012.03.019 PG 11 WC Ophthalmology SC Ophthalmology GA 996SR UT WOS:000308115600020 PM 22626617 ER PT J AU Levy, DE Riis, J Sonnenberg, LM Barraclough, SJ Thorndike, AN AF Levy, Douglas E. Riis, Jason Sonnenberg, Lillian M. Barraclough, Susan J. Thorndike, Anne N. TI Food Choices of Minority and Low-Income Employees A Cafeteria Intervention SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID SUGAR-SWEETENED BEVERAGES; NEW-YORK-CITY; US ADULTS; UNITED-STATES; WEIGHT-GAIN; RESTAURANTS; OBESITY; INFORMATION; HEALTH; TRENDS AB Background: Effective strategies are needed to address obesity, particularly among minority and low-income individuals. Purpose: To test whether a two-phase point-of-purchase intervention improved food choices across racial, socioeconomic (job type) groups. Design: A 9-month longitudinal study from 2009 to 2010 assessing person-level changes in purchases of healthy and unhealthy foods following sequentially introduced interventions. Data were analyzed in 2011. Setting/participants: Participants were 4642 employees of a large hospital in Boston MA who were regular cafeteria patrons. Interventions: The first intervention was a traffic light-style color-coded labeling system encouraging patrons to purchase healthy items (labeled green) and avoid unhealthy items (labeled red). The second intervention manipulated "choice architecture" by physically rearranging certain cafeteria items, making green-labeled items more accessible and red-labeled items less accessible. Main outcome measures: Proportion of green- (or red-) labeled items purchased by an employee. Subanalyses tracked beverage purchases, including calories and price per beverage. Results: Employees self-identified as white (73%); black (10%); Latino (7%); and Asian (10%). Compared to white employees, Latino and black employees purchased a higher percentage of red items at baseline (18%, 28%, and 33%, respectively, p<0.001) and a lower percentage of green (48%, 38%, and 33%, p<0.001). Labeling decreased all employees' red item purchases (-11.2%, 95% CI=-13.6%, -8.9%) and increased green purchases (6.6%, 95% CI=5.2%, 7.9%). Red beverage purchases decreased most(-23.8%, 95% CI=-28.1%, -19.6%). The choice architecture intervention further decreased red purchases after the labeling. Intervention effects were similar across all race/ethnicity and job types (p>0.05 for interaction between race or job type and intervention). Mean calories per beverage decreased similarly over the study period for all racial groups and job types, with no increase in per-beverage spending. Conclusions: Despite baseline differences in healthy food purchases, a simple color-coded labeling and choice architecture intervention improved food and beverage choices among employees from all racial and socioeconomic backgrounds. (Am J Prev Med 2012;43(3):240-248) (c) 2012 American Journal of Preventive Medicine C1 [Levy, Douglas E.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Levy, Douglas E.; Sonnenberg, Lillian M.; Thorndike, Anne N.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Sonnenberg, Lillian M.; Barraclough, Susan J.] Massachusetts Gen Hosp, Dept Nutr & Food Serv, Boston, MA 02114 USA. [Levy, Douglas E.; Sonnenberg, Lillian M.; Thorndike, Anne N.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Riis, Jason] Harvard Univ, Sch Business, Boston, MA 02163 USA. RP Levy, DE (reprint author), Massachusetts Gen Hosp, Mongan Inst Hlth Policy, 50 Staniford St, Boston, MA 02114 USA. EM dlevy3@partners.org FU Harvard Clinical and Translational Science Center [1 UL1 RR025758-03]; National Center for Research Resources; National Heart Lung and Blood Institute [1 K23HL93221] FX The project described was supported by Grant Number 1 UL1 RR025758-03, Harvard Clinical and Translational Science Center, from the National Center for Research Resources. Dr. Thorndike is supported by the grant 1 K23HL93221 from the National Heart Lung and Blood Institute. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, and approval of the paper. The authors acknowledge the assistance of Ms. Emily Gelsomin, RD, LDN, in defining and applying the color-coded labeling criteria to the thousands of items in the cafeteria. NR 45 TC 31 Z9 31 U1 6 U2 45 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD SEP PY 2012 VL 43 IS 3 BP 240 EP 248 DI 10.1016/j.amepre.2012.05.004 PG 9 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 993TK UT WOS:000307882300002 PM 22898116 ER PT J AU Sweet, RA Seltman, H Emanuel, JE Lopez, OL Becker, JT Bis, JC Weamer, EA DeMichele-Sweet, MAA Kuller, LH AF Sweet, Robert A. Seltman, Howard Emanuel, James E. Lopez, Oscar L. Becker, James T. Bis, Joshua C. Weamer, Elise A. DeMichele-Sweet, Mary Ann A. Kuller, Lewis H. TI Effect of Alzheimer's Disease Risk Genes on Trajectories of Cognitive Function in the Cardiovascular Health Study SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID GENOME-WIDE ASSOCIATION; COMPLEMENT RECEPTOR 1; IDENTIFIES VARIANTS; SYNAPSE LOSS; FLIP-FLOP; DECLINE; BINDING; EPIDEMIOLOGY; METAANALYSIS; BIOMARKERS AB Objective: The trajectory of cognitive decline in patients with late-onset Alzheimer's disease varies widely. Genetic variations in CLU, PICALM, and CR1 are associated with Alzheimer's disease, but it is unknown whether they exert their effects by altering cognitive trajectory in elderly individuals at risk for the disease. Method: The authors developed a Bayesian model to fit cognitive trajectories in a cohort of elderly subjects and test for genetic effects. They first validated the model's ability to detect the previously established effects of APOE epsilon 4 alleles on age at cognitive decline and of psychosis on the rate of cognitive decline in 802 subjects from the Cardiovascular Health Cognition Study who did not have dementia at study entry and developed incident dementia during follow-up. The authors then evaluated the effects of CLU, PICALM, and CR1 on age and rate of decline in 1,831 subjects who did not have dementia at study entry and then did or did not develop incident dementia by study's end. Results: The model generated robust fits to the observed cognitive trajectory data, and validation analysis supported the model's utility. CLU and CR1 were associated with more rapid cognitive decline. PICALM was associated with an earlier age at midpoint of cognitive decline. Associations remained after accounting for the effects of APOE and demographic factors. Conclusions: Evaluation of cognitive trajectories provides a powerful approach to dissecting genetic effects on the processes leading to cognitive deterioration and Alzheimer's disease. C1 [Sweet, Robert A.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Neurol, Pittsburgh, PA USA. Carnegie Mellon Univ, Dept Stat, Pittsburgh, PA 15213 USA. Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr 4, Pittsburgh, PA USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA USA. RP Sweet, RA (reprint author), Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA. EM sweetra@upmc.edu OI Seltman, Howard/0000-0002-7543-3578; Becker, James/0000-0003-4425-4726 FU National Institute on Aging (NIA) [AG05133, AG027224, AG20098]; National Heart, Lung, and Blood Institute [N0-1-HC-85239, N01-HC-85079, N01-HC-85080, N01-HC-85081, N01-HC-85082, N01-HC-85083, N01-HC-85084, N01-HC-85085, N01-HC-85086, N01-HC-35129, N01-HC-15103, N01-HC-55222, N01-HC-75150, N01-HC-45133, U01 HL080295, HL087251]; NIA [AG15928] FX Supported in part by National Institute on Aging (NIA) grants AG05133, AG027224, and AG20098. The research reported in this article was also supported by National Heart, Lung, and Blood Institute contracts N0-1-HC-85239, N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01-HC-15103, N01-HC-55222, N01-HC-75150, and N01-HC-45133 and grants U01 HL080295 and HL087251, with additional contributions from the National Institute of Neurological Disorders and Stroke and from NIA grant AG15928. A full list of Cardiovascular Health Study principal investigators and institutions can be found at http://www.chs-nhlbi.org/pi.htm. NR 38 TC 30 Z9 31 U1 1 U2 7 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD SEP PY 2012 VL 169 IS 9 BP 954 EP 962 DI 10.1176/appi.ajp.2012.11121815 PG 9 WC Psychiatry SC Psychiatry GA 998ZE UT WOS:000308278100012 PM 22952074 ER PT J AU Levinson, DF Shi, JX Wang, K Oh, S Riley, B Pulver, AE Wildenauer, DB Laurent, C Mowry, BJ Gejman, PV Owen, MJ Kendler, KS Nestadt, G Schwab, SG Mallet, J Nertney, D Sanders, AR Williams, NM Wormley, B Lasseter, VK Albus, M Godard-Bauche, S Alexander, M Duan, JB O'Donovan, MC Walsh, D O'Neill, A Papadimitriou, GN Dikeos, D Maier, W Lerer, B Campion, D Cohen, D Jay, M Fanous, A Eichhammer, P Silverman, JM Norton, N Zhang, N Hakonarson, H Gao, C Citri, A Hansen, M Ripke, S Dudbridge, F Holmans, PA AF Levinson, Douglas F. Shi, Jianxin Wang, Kai Oh, Sang Riley, Brien Pulver, Ann E. Wildenauer, Dieter B. Laurent, Claudine Mowry, Bryan J. Gejman, Pablo V. Owen, Michael J. Kendler, Kenneth S. Nestadt, Gerald Schwab, Sibylle G. Mallet, Jacques Nertney, Deborah Sanders, Alan R. Williams, Nigel M. Wormley, Brandon Lasseter, Virginia K. Albus, Margot Godard-Bauche, Stephanie Alexander, Madeline Duan, Jubao O'Donovan, Michael C. Walsh, Dermot O'Neill, Anthony Papadimitriou, George N. Dikeos, Dimitris Maier, Wolfgang Lerer, Bernard Campion, Dominique Cohen, David Jay, Maurice Fanous, Ayman Eichhammer, Peter Silverman, Jeremy M. Norton, Nadine Zhang, Nancy Hakonarson, Hakon Gao, Cynthia Citri, Ami Hansen, Mark Ripke, Stephan Dudbridge, Frank Holmans, Peter A. CA Schizophrenia Psychiat GWAS Consor TI Genome-Wide Association Study of Multiplex Schizophrenia Pedigrees SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID SUSCEPTIBILITY LOCI; MULTICENTER LINKAGE; COMMON VARIANTS; FAMILIES; GENES; SCAN; DELETIONS; SAMPLE; RISK; 6Q AB Objective: The authors used a genome-wide association study (GWAS) of multiply affected families to investigate the association of schizophrenia to common single-nucleotide polymorphisms (SNPs) and rare copy number variants (CNVs). Method: The family sample included 2,461 individuals from 631 pedigrees (581 in the primary European-ancestry analyses). Association was tested for single SNPs and genetic pathways. Polygenic scores based on family study results were used to predict case-control status in the Schizophrenia Psychiatric GWAS Consortium (PGC) data set, and consistency of direction of effect with the family study was determined for top SNPs in the PGC GWAS analysis. Within-family segregation was examined for schizophrenia-associated rare CNVs. Results: No genome-wide significant associations were observed for single SNPs or for pathways. PGC case and control subjects had significantly different genome-wide polygenic scores (computed by weighting their genotypes by log-odds ratios from the family study) (best p=10(-17), explaining 0.4% of the variance). Family study and PGC analyses had consistent directions for 37 of the 58 independent best PGC SNPs (p=0.024). The overall frequency of CNVs in regions with reported associations with schizophrenia (chromosomes 1q21.1, 15q13.3, 16p11.2, and 22q11.2 and the neurexin-1 gene [NRXN1]) was similar to previous case-cortrol studies. NRXN1 deletions and 16p11.2 duplications (both of which were transmitted from parents) and 22q11.2 deletions (de novo in four cases) did not segregate with schizophrenia in families. Conclusions: Mary common SNPs are likely to contribute to schizophrenia risk, with substantial overlap in genetic risk factors between multiply affected families and cases in large case-control studies. Our findings are consistent with a role for specific CNVs in disease pathogenesis, but the partial segregation of some CNVs with schizophrenia suggests that researcher; should exercise caution in using them for predictive genetic testing until their effects in diverse populations have been fully studied. C1 [Levinson, Douglas F.] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. Univ So Calif, Dept Psychiat, Los Angeles, CA USA. Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA 23284 USA. Virginia Commonwealth Univ, Dept Human Genet, Richmond, VA 23284 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA. Univ Western Australia, Dept Psychiat, Perth, WA 6009, Australia. NorthShore Univ, Healthcare Res Inst, Evanston, IL USA. Univ Queensland, Inst Brain, Brisbane, Qld, Australia. Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA. Queensland Ctr Mental Hlth Res, Brisbane, Qld, Australia. Univ Paris 06, Dept Child & Adolescent Psychiat, Fac Med, Paris, France. Univ Erlangen Nurnberg, Dept Psychiat & Psychotherapy, D-91054 Erlangen, Germany. Hop La Pitie Salpetriere, ICM Inst, Paris, France. State Mental Hosp, Haar, Germany. Hop La Pitie Salpetriere, INSERM, Paris, France. Univ Bonn, Dept Psychiat, Bonn, Germany. Univ Athens, Sch Med, Dept Psychiat, GR-11527 Athens, Greece. Queens Univ, Belfast, Antrim, North Ireland. Hlth Res Board, Dublin, Ireland. Hadassah Hebrew Univ Med Ctr, Dept Psychiat, Jerusalem, Israel. Inst Hosp Univ Rech Biomed, INSERM, U614, Rouen, France. Ctr Hosp St Etienne Rouvray, Dept Res, Rouen, France. Washington VA Med Ctr, Mental Hlth Serv Line, Washington, DC USA. Georgetown Univ, Sch Med, Dept Psychiat, Washington, DC USA. Univ Regensburg, Dept Psychiat, Regensburg, Germany. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. Illumina Inc, La Jolla, CA USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Univ Penn, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA USA. Univ London London Sch Hyg & Trop Med, Dept Stat Genet & Epidemiol, London WC1E 7HT, England. Cardiff Univ, MRC Ctr Neuropsychiat Genet & Genom, Dept Psychol Med & Neurol, Sch Med, Cardiff, S Glam, Wales. Cardiff Univ, Neurosci & Mental Hlth Res Inst, Cardiff, S Glam, Wales. RP Levinson, DF (reprint author), Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. EM dflev@stanford.edu RI Hansen, Thomas/O-5965-2014; Holmans, Peter/F-4518-2015; OI Hansen, Thomas/0000-0001-6703-7762; Holmans, Peter/0000-0003-0870-9412; O'Donovan, Michael/0000-0001-7073-2379; O'Neill, Francis Anthony/0000-0002-7531-7657 FU AstraZeneca; Bristol-Myers Squibb; Eli Lilly; Janssen-Cilag; Lundbeck; Merck; Pfizer; Sanofi-Aventis; Schering; Bohringer; Janssen; Sanofi; Server; Wyeth; Lilly; Boehringer; Bristol; Genesis Pharma; GlaxoSmithKline; UniPharma; NIMH [R01MH062276, R01MH068922, R01MH068921, R01MH068881] FX Dr. O'Donovan's institution received an honorarium from Lilly with respect to a presentation he gave at a satellite meeting of the Japanese Schizophrenia Society. Dr. Hansen works for Illumina, Inc. Dr. Mallet is founder and part owner of Newvectys, Inc. (Paris). Dr. Maier has received research grants from, is a member of the advisory boards of, or receives speaking fees from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen-Cilag, Lundbeck, Merck, Pfizer, Sanofi-Aventis, Schering, and Bohringer. Dr. Papadimitriou has been on speakers or advisory boards for or has received travel expenses, honoraria, or consultancy fees for participation in research and in clinical expert groups from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen, Lundbeck, Pfizer, Sanofi, Server, and Wyeth; he has also received unrestricted grants from AstraZeneca, Janssen, and Lilly for the Department of Psychiatry of Egirition Hospital (Athens University), of which he is the chairman. Dr. Dikeos has been on speakers or advisory boards for or has received honoraria or travel expenses from AstraZeneca, Boehringer, Bristol, Eli Lilly, Genesis Pharma, GlaxoSmithKline, Janssen, Lundbeck, Sanofi, UniPharma, and Wyeth; he has also received consultancy fees for participation in research for Eli Lilly and for participation in clinical expert groups for Bristol Myers Squibb and unrestricted grants from Lilly and AstraZeneca for the Sleep Research Unit of Eginition Hospital (Athens University), of which he is director. Dr. Jay and Ms. Lasseter are deceased and had no competing interests during this study. The remaining authors report no financial relatioaships with commercial interests.; Supported by NIMH grant R01MH062276 (to Drs. Levinson, Laurent, Owen, and Wildenauer), grant R01MH068922 (to Dr. Gejman), grant R01MH068921 (to Dr. Pulver) and grant R01MH068881 (to Dr. Riley). Data from the Molecular Genetics of Schizophrenia data set are available from the NIMH Center for Genetic Studies (http://nimhgenetics.org) and dbGAP (http://www.ncbi.nlm.nih.gov/gap); they were collected under funding by collaborative NIMH grants to NorthShore University HealthSystem, Evanston, Ill. (MH59571; Pablo V. Gejman, M.D., collaboration coordinator and principal investigator; and Alan R. Sanders, M.D.); Stanford University, Palo Alto, Calif. (MH61675; Douglas F. Levinson, M.D., principal investigator); Louisiana State University, New Orleans (MH67257; Nancy G. Buccola, A.P.R.N., B.C., principal investigator); University of Queensland, Brisbane, Queensland, Australia (MH59588; Bryan J. Mowry, M.D., principal investigator); University of Colorado, Denver (MH59565; Robert Freedman, M.D., principal investigator; and Ann Olincy, M.D.); Emory University School of Medicine, Atlanta (MH59587; Farooq Amin, M.D., principal investigator); University of Iowa, Iowa City (MH59566; Donald W. Black, M.D., principal investigator; and Raymond R. Crowe, M.D.); Mount Sinai School of Medicine, New York (MH59586; Jeremy M. Silverman, Ph.D., principal investigator); University of California, San Francisco (MH60870; William F. Byerley, M.D., principal investigator); and Washington University, St. Louis (MH60879; C. Robert Cloninger, M.D., principal investigator). NR 37 TC 33 Z9 33 U1 3 U2 27 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD SEP PY 2012 VL 169 IS 9 BP 963 EP 973 DI 10.1176/appl.ajp.2012.11091423 PG 11 WC Psychiatry SC Psychiatry GA 998ZE UT WOS:000308278100013 PM 22885689 ER PT J AU Morris, MI Daly, JS Blumberg, E Kumar, D Sester, M Schluger, N Kim, SH Schwartz, BS Ison, MG Humar, A Singh, N Michaels, M Orlowski, JP Delmonico, F Pruett, T John, GT Kotton, CN AF Morris, M. I. Daly, J. S. Blumberg, E. Kumar, D. Sester, M. Schluger, N. Kim, S. -H. Schwartz, B. S. Ison, M. G. Humar, A. Singh, N. Michaels, M. Orlowski, J. P. Delmonico, F. Pruett, T. John, G. T. Kotton, C. N. TI Diagnosis and Management of Tuberculosis in Transplant Donors: A Donor-Derived Infections Consensus Conference Report SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Donor-derived; interferon-gamma release assay; solid-organ transplant; TB screening; tuberculosis ID GAMMA RELEASE ASSAYS; ACID AMPLIFICATION TESTS; MYCOBACTERIUM-TUBERCULOSIS; ACTIVE TUBERCULOSIS; UNITED-STATES; LUNG TRANSPLANTATION; DISEASE TRANSMISSION; RISK-FACTORS; HEAD-INJURY; RECIPIENTS AB Mycobacterium tuberculosis is a ubiquitous organism that infects one-third of the world's population. In previous decades, access to organ transplantation was restricted to academic medical centers in more developed, low tuberculosis (TB) incidence countries. Globalization, changing immigration patterns, and the expansion of sophisticated medical procedures to medium and high TB incidence countries have made tuberculosis an increasingly important posttransplant infectious disease. Tuberculosis is now one of the most common bacterial causes of solid-organ transplant donor-derived infection reported in transplant recipients in the United States. Recognition of latent or undiagnosed active TB in the potential organ donor is critical to prevent emergence of disease in the recipient posttransplant. Donor-derived tuberculosis after transplantation is associated with significant morbidity and mortality, which can best be prevented through careful screening and targeted treatment. To address this growing challenge and provide recommendations, an expert international working group was assembled including specialists in transplant infectious diseases, transplant surgery, organ procurement and TB epidemiology, diagnostics and management. This working group reviewed the currently available data to formulate consensus recommendations for screening and management of TB in organ donors. C1 [Morris, M. I.] Univ Miami, Miller Sch Med, Div Infect Dis, Miami, FL 33136 USA. [Daly, J. S.] Univ Massachusetts, Sch Med, Div Infect Dis & Immunol, Worcester, MA USA. [Blumberg, E.] Univ Penn, Div Infect Dis, Perelman Sch Med, Philadelphia, PA 19104 USA. [Kumar, D.; Humar, A.] Univ Alberta, Transplant Infect Dis & Alberta Inst Transplant S, Edmonton, AB, Canada. [Sester, M.] Univ Saarland, Dept Transplant & Infect Immunol, Inst Virol, D-6650 Homburg, Germany. [Schluger, N.] Columbia Univ, Med Ctr, Div Pulm Allergy & Crit Care Med, New York, NY USA. [Kim, S. -H.] Univ Ulsan, Coll Med, Dept Infect Dis, Asan Med Ctr, Seoul, South Korea. [Schwartz, B. S.] Univ Calif San Francisco, Sch Med, Div Infect Dis, San Francisco, CA USA. [Ison, M. G.] Northwestern Univ, Feinberg Sch Med, Div Infect Dis, Chicago, IL 60611 USA. [Ison, M. G.] Northwestern Univ, Feinberg Sch Med, Div Organ Transplantat, Chicago, IL 60611 USA. [Singh, N.] VA Pittsburgh Healthcare Syst, Div Infect Dis, Pittsburgh, PA USA. [Singh, N.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Michaels, M.] Childrens Hosp Pittsburgh, Div Infect Dis, Pittsburgh, PA 15213 USA. [Orlowski, J. P.] LifeShare Oklahoma, Oklahoma City, OK USA. [Delmonico, F.] Massachusetts Gen Hosp, New England Organ Bank, Boston, MA 02114 USA. [Pruett, T.] Univ Minnesota, Sch Med, Dept Surg, Minneapolis, MN 55455 USA. [John, G. T.] Royal Brisbane & Womens Hosp, Dept Renal Med, Brisbane, Qld, Australia. [Kotton, C. N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA USA. RP Morris, MI (reprint author), Univ Miami, Miller Sch Med, Div Infect Dis, Miami, FL 33136 USA. EM mmorris2@med.miami.edu OI Sester, Martina/0000-0001-5482-0002 FU American Society of Transplantation; Canadian Society of Transplantation; Transplantation Society; Cellestis Inc. FX Funding for the Donor-Derived Infections Consensus Conference on Mycobacterium tuberculosis was provided by the American Society of Transplantation, the Canadian Society of Transplantation and The Transplantation Society.; D.K. and A. H. have received research funding from Cellestis Inc. All other authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation. NR 43 TC 34 Z9 35 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD SEP PY 2012 VL 12 IS 9 BP 2288 EP 2300 DI 10.1111/j.1600-6143.2012.04205.x PG 13 WC Surgery; Transplantation SC Surgery; Transplantation GA 994QC UT WOS:000307945000008 PM 22883346 ER PT J AU Aoyama, A Klarin, D Yamada, Y Boskovic, S Nadazdin, O Kawai, K Schoenfeld, D Madsen, JC Cosimi, AB Benichou, G Kawai, T AF Aoyama, A. Klarin, D. Yamada, Y. Boskovic, S. Nadazdin, O. Kawai, K. Schoenfeld, D. Madsen, J. C. Cosimi, A. B. Benichou, G. Kawai, T. TI Low-Dose IL-2 for In Vivo Expansion of CD4(+) and CD8(+) Regulatory T Cells in Nonhuman Primates SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Immunotherapy; interleukin-2; nonhuman primates; T-regulatory cells ID INTERLEUKIN-2 THERAPY; HIV-INFECTION; TOLERANCE; DISEASES AB IL-2 is a known potent T cell growth factor that amplifies lymphocyte responses in vivo. This capacity has led to the use of high-dose IL-2 to enhance T cell immunity in patients with AIDS or cancer. However, more recent studies have indicated that IL-2 is also critical for the development and peripheral expansion of regulatory T cells (Tregs). In the current study, low-dose IL-2 (1 million IU/m2 BSA/day) was administered to expand Tregs in vivo in naive nonhuman primates. Our study demonstrated that low-dose IL-2 therapy significantly expanded peripheral blood CD4+ and CD8+ Tregs in vivo with limited expansion of non-Treg cells. These expanded Tregs are mainly CD45RA- Foxp3 high activated Tregs and demonstrated potent immunosuppressive function in vitro. The results of this preclinical study can serve as a basis to develop Treg immunotherapy, which has significant therapeutic potential in organ/cellular transplantation. C1 [Aoyama, A.; Klarin, D.; Yamada, Y.; Boskovic, S.; Nadazdin, O.; Kawai, K.; Madsen, J. C.; Cosimi, A. B.; Benichou, G.; Kawai, T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplant Ctr, Boston, MA 02115 USA. [Schoenfeld, D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Biostat, Boston, MA USA. RP Kawai, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplant Ctr, Boston, MA 02115 USA. EM tkawai@partners.org FU NIH-NIAID [ROIA137692]; NIH/NIAID [5R01 AI50987-03]; NIH [R00000000008108]; [5U19DK080652-02 NHL-BI]; [POI-HL18646] FX This study was supported in part by 5U19DK080652-02 NHL-BI, POI-HL18646, NIH-NIAID, ROIA137692 and NIH/NIAID 5R01 AI50987-03 and NIH R00000000008108. NR 19 TC 8 Z9 9 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD SEP PY 2012 VL 12 IS 9 BP 2532 EP 2537 DI 10.1111/j.1600-6143.2012.04133.x PG 6 WC Surgery; Transplantation SC Surgery; Transplantation GA 994QC UT WOS:000307945000033 PM 22682297 ER PT J AU Scemama, PH Hull, JW AF Scemama, Pascal H. Hull, Jeffrey W. TI Developing Leaders in Anesthesiology A Practical Framework SO ANESTHESIOLOGY LA English DT Article ID MEMBER EXCHANGE; CREATIVE PERFORMANCE; PERSONAL GROWTH; INTELLIGENCE; DISTANCE; IMPACT C1 [Scemama, Pascal H.; Hull, Jeffrey W.] Harvard Univ, Massachusetts Gen Hosp, Dept Anesthesiol Crit Care & Pain Med, Sch Med, Boston, MA 02114 USA. RP Scemama, PH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Anesthesiol Crit Care & Pain Med, Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM pscemamadegialluly@partners.org NR 32 TC 3 Z9 3 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 2012 VL 117 IS 3 BP 651 EP 656 DI 10.1097/ALN.0b013e3182632358 PG 6 WC Anesthesiology SC Anesthesiology GA 994QZ UT WOS:000307947700026 PM 22790960 ER PT J AU Bian, SX Kuban, DA Levy, LB Oh, J Castle, KO Pugh, TJ Choi, S McGuire, SE Nguyen, QN Frank, SJ Nguyen, PL Lee, AK Hoffman, KE AF Bian, S. X. Kuban, D. A. Levy, L. B. Oh, J. Castle, K. O. Pugh, T. J. Choi, S. McGuire, S. E. Nguyen, Q. N. Frank, S. J. Nguyen, P. L. Lee, A. K. Hoffman, K. E. TI Addition of short-term androgen deprivation therapy to dose-escalated radiation therapy improves failure-free survival for select men with intermediate-risk prostate cancer SO ANNALS OF ONCOLOGY LA English DT Article DE androgen deprivation therapy; comorbidity; prostate cancer; radiotherapy ID RANDOMIZED CONTROLLED-TRIAL; RADIOTHERAPY; SUPPRESSION; DISEASE AB Dose-escalated (DE) radiation therapy (RT) and androgen deprivation therapy (ADT) improve prostate cancer outcomes over standard-dose RT. The benefit of adding ADT to DE-RT for men with intermediate-risk prostate cancer (IR-PrCa) is uncertain. We identified 636 men treated for IR-PrCa with DE-RT (> 75Gy). The adult comorbidity evaluation-27 index classifed comorbidity. Kaplan-Meier and log-rank tests compared failure-free survival (FFS) with and without ADT. Forty-five percent received DE-RT and 55% DE-RT with ADT (median 6 months). On Cox proportional hazard regression that adjusted for comorbidity and tumor characteristics, ADT improved FFS (adjusted hazard ratio 0.36; P = 0.004). Recursive partitioning analysis of men without ADT classified Gleason 4 + 3 = 7 or >= 50% positive cores as unfavorable disease. The addition of ADT to DE-RT improved 5-year FFS for men with unfavorable disease (81.6% versus 92.9%; P = 0.009) but did not improve FFS for men with favorable disease (96.3% versus 97.4%; P = 0.874). When stratified by comorbidity, ADT improved FFS for men with unfavorable disease and no or mild comorbidity (P = 0.006) but did not improve FFS for men with unfavorable disease and moderate or severe comorbidity (P = 0.380). The addition of ADT to DE-RT improves FFS for men with unfavorable IR-PrCa, especially those with no or minimal comorbidity. C1 [Bian, S. X.; Kuban, D. A.; Levy, L. B.; Castle, K. O.; Pugh, T. J.; Choi, S.; McGuire, S. E.; Nguyen, Q. N.; Frank, S. J.; Lee, A. K.; Hoffman, K. E.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. [Bian, S. X.] Baylor Coll Med, Houston, TX 77030 USA. [Oh, J.] Univ Texas MD Anderson Canc Ctr, Dept Internal Med, Houston, TX 77030 USA. [Nguyen, P. L.] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA USA. RP Hoffman, KE (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, 1515 Holcombe Blvd,Unit 1202, Houston, TX 77030 USA. EM khoffman1@mdanderson.org NR 23 TC 10 Z9 10 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD SEP PY 2012 VL 23 IS 9 BP 2346 EP 2352 DI 10.1093/annonc/mds001 PG 7 WC Oncology SC Oncology GA 995NU UT WOS:000308017000021 PM 22357249 ER PT J AU Sher, DJ Thotakura, V Balboni, TA Norris, CM Haddad, RI Posner, MR Lorch, J Goguen, LA Annino, DJ Tishler, RB AF Sher, D. J. Thotakura, V. Balboni, T. A. Norris, C. M. Haddad, R. I. Posner, M. R. Lorch, J. Goguen, L. A. Annino, D. J. Tishler, R. B. TI Treatment of oropharyngeal squamous cell carcinoma with IMRT: patterns of failure after concurrent chemoradiotherapy and sequential therapy SO ANNALS OF ONCOLOGY LA English DT Article DE combined modality therapy; head and neck cancer; human papillomavirus; IMRT; oropharynx cancer; sequential therapy ID INTENSITY-MODULATED RADIOTHERAPY; LOCOREGIONALLY ADVANCED HEAD; NECK-CANCER; RECURRENCE; CISPLATIN; INDUCTION; DOCETAXEL AB The optimal management of oropharyngeal squamous cell carcinoma (OPSCC) is controversial. Modern radiotherapy typically employs intensity-modulated radiation therapy (IMRT), and herein, we report the Dana-Farber Cancer Institute (DFCI) experience with IMRT-based treatment of OPSCC. Retrospective study of all patients treated at DFCI for OPSCC with definitive or adjuvant IMRT between 8/04 and 8/09. The primary end point was overall survival (OS); secondary end points were locoregional control (LRC) and freedom from distant metastases (FFDM). Propensity score matching was used to create concurrent chemoradiotherapy (CCRT) and sequential therapy (ST) cohorts equally balanced for patient and disease characteristics. One hundred and sixty-three patients were included with 75% presenting with stage IV disease. Fifty-six patients (34%) were treated with ST. The three-year actuarial OS, LRC, and FFDM rates for the entire cohort/ST subset were 86%/89%, 86%/87%, and 88%/93%, respectively. There were no differences in OS, LRC, or FFDM between CCRT and ST in the propensity-matched cohort. IMRT was associated with excellent OS, LRC, and FFDM. Although the results following ST were superb, there was no obvious benefit to ST after adjustment for selection bias. We recommend that ST be reserved for medically fit patients with a high risk of distant metastases. C1 [Sher, D. J.; Balboni, T. A.; Tishler, R. B.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Thotakura, V.; Haddad, R. I.; Lorch, J.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Thotakura, V.; Haddad, R. I.; Lorch, J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Norris, C. M.; Goguen, L. A.; Annino, D. J.] Brigham & Womens Hosp, Div Otolaryngol, Dept Surg, Boston, MA 02115 USA. [Posner, M. R.] Mt Sinai Sch Med, Tisch Canc Inst, Dept Med Oncol, New York, NY USA. RP Sher, DJ (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. EM dsher@lroc.harvard.edu NR 19 TC 14 Z9 15 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD SEP PY 2012 VL 23 IS 9 BP 2391 EP 2398 DI 10.1093/annonc/mdr609 PG 8 WC Oncology SC Oncology GA 995NU UT WOS:000308017000028 PM 22425872 ER PT J AU Markman, B Tabernero, J Krop, I Shapiro, GI Siu, L Chen, LC Mita, M Cuero, MM Stutvoet, S Birle, D Anak, O Hackl, W Baselga, J AF Markman, B. Tabernero, J. Krop, I. Shapiro, G. I. Siu, L. Chen, L. C. Mita, M. Cuero, M. Melendez Stutvoet, S. Birle, D. Anak, Oe. Hackl, W. Baselga, J. TI Phase I safety, pharmacokinetic, and pharmacodynamic study of the oral phosphatidylinositol-3-kinase and mTOR inhibitor BGT226 in patients with advanced solid tumors SO ANNALS OF ONCOLOGY LA English DT Article DE anticancer agent; BGT226; dual inhibitor; mTOR catalytic inhibitor; PI3K pathway; solid tumors ID ANTITUMOR-ACTIVITY; DOSE-ESCALATION; PI3K PATHWAY; CANCER-CELLS; RESISTANCE; NVP-BEZ235; MUTATIONS; 3-KINASE; TARGET; TRIALS AB This phase I dose-escalation study investigated the maximum tolerated dose (MTD), safety, pharmacokinetics, pharmacodynamics (PDs), and preliminary antitumor activity of BGT226, a potent, oral dual phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin inhibitor. Fifty-seven patients with advanced solid tumors received BGT226 2.5-125 mg/day three times weekly (TIW). Dose escalation was guided by an adaptive Bayesian logistic regression model with overdose control. Assessments included response per RECIST, [18F]-fluorodeoxyglucose uptake, and phosphorylated-S6 in skin and paired tumor samples. Three patients (125 mg cohort) had dose-limiting toxic effects (grade 3 nausea/vomiting, diarrhea). BGT226-related adverse events included nausea (68%), diarrhea (61%), vomiting (49%), and fatigue (19%). BGT226 demonstrated rapid absorption, variable systemic exposure, and a median half-life of 6-9 h. Seventeen patients (30%) had stable disease (SD) as best response. Nine patients had SD for >= 16 weeks. Thirty patients (53%) achieved stable metabolic disease as assessed by [18F]-fluorodeoxyglucose-positron emission tomography; however, no correlation between metabolic response and tumor shrinkage according to computed tomography was observed. PD changes suggested PI3K pathway inhibition but were inconsistent. The MTD of BGT226 was 125 mg/day TIW, and the clinically recommended dose was 100 mg/day TIW. Limited preliminary antitumor activity and inconsistent target inhibition were observed, potentially due to low systemic exposure. C1 [Markman, B.; Tabernero, J.; Baselga, J.] Univ Autonoma Barcelona, Dept Med Oncol, Vall Hebron Univ Hosp, E-08193 Barcelona, Spain. [Krop, I.; Shapiro, G. I.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Siu, L.] Princess Margaret Hosp, Dept Med Oncol & Hematol, Toronto, ON M4X 1K9, Canada. [Chen, L. C.] NCI, Las Vegas, NV USA. [Mita, M.] Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA. [Cuero, M. Melendez; Stutvoet, S.; Anak, Oe.; Hackl, W.] Novartis Pharma AG, Oncol Translat Med, Basel, Switzerland. [Birle, D.] Novartis Inst Biomed Res, Cambridge, MA USA. RP Baselga, J (reprint author), Massachusetts Gen Hosp, Ctr Canc, Div Hematol & Oncol, 55 Fruit St,Lawrence House 108, Boston, MA 02114 USA. EM jbaselga@partners.org FU European Society of Medical Oncology (ESMO); Novartis Pharmaceuticals Corporation; Novartis Pharma AG FX We thank the following investigators, Steven Isakoff (Massachussets General Hospital, Boston, USA), Sunil Sharma (Nevada Cancer Institute, Las Vegas, USA), Christophe LeTourneau (Princess Margaret Hospital, Toronto, Canada), and contributors Beatrix Staffler, Humphrey Gardner, Nina Huseinovic, Nassim Sleiman, Mikael Sacco, Hartmut Zehender, and Stefan de Buck (Novartis Pharma AG), whose efforts were essential toward the completion of this work. We would also like to thank the European Society of Medical Oncology (ESMO) for awarding BM with an ESMO fellowship grant that contributed to his involvement in this trial. The authors would also like to acknowledge Dina Marenstein, PhD, of Chameleon Communications International, who provided medical writing services with funding from Novartis Pharmaceuticals Corporation.; MMC, SS, DS, OA, and WH are employees of Novartis Pharma AG, the developer of BGT226 and the study sponsor. IK receives clinical trial funding from Novartis Pharma AG. JB has received consulting honoraria from Novartis. BM, JT, GIS, LS, LCC, and MM have no conflict of interest to declare. NR 20 TC 58 Z9 58 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD SEP PY 2012 VL 23 IS 9 BP 2399 EP 2408 DI 10.1093/annonc/mds011 PG 10 WC Oncology SC Oncology GA 995NU UT WOS:000308017000029 PM 22357447 ER PT J AU Bonvalot, S Raut, CP Pollock, RE Rutkowski, P Strauss, DC Hayes, AJ Van Coevorden, F Fiore, M Stoeckle, E Hohenberger, P Gronchi, A AF Bonvalot, Syvie Raut, Chandrajit P. Pollock, Raphael E. Rutkowski, Piotr Strauss, Dirk C. Hayes, Andrew J. Van Coevorden, Frits Fiore, Marco Stoeckle, Eberhard Hohenberger, Peter Gronchi, Alessandro TI Technical Considerations in Surgery for Retroperitoneal Sarcomas: Position Paper from E-Surge, a Master Class in Sarcoma Surgery, and EORTC-STBSG SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID SOFT-TISSUE SARCOMA; SINGLE INSTITUTION; EXPERIENCE; MANAGEMENT; RECURRENCE; MORBIDITY; RESECTION; SURVIVAL; GRADE AB Surgery is the principal treatment for retroperitoneal sarcoma. These tumors typically involve or abut multiple organs and therefore require multivisceral resections. Despite the complexity of such operations, a standardized approach has not been described. As a result, referral centers often see patients who have undergone suboptimal surgery, with gross disease left behind. This is one of the causes of the dismal prognosis of this disease. These consensus statements came out from E-Surge, an educational symposium with live sarcoma surgery, performed by European and North American expert sarcoma surgeons illustrating an optimal technique to an international audience, held in 2010 and 2011. The content was then shared among members of the local subcommittee of European Organization for Research and Treatment of Cancer (EORTC)-Soft Tissue and Bone Sarcoma Group (STBSG). An attempt to describe a reproducible and standardized approach to these tumors is illustrated. A detailed description of the different procedures according to the variety of different presentations is made. The approach described herein should be used as the reference standard in clinical practice and serve to perform quality check of local treatment in future trials. C1 [Bonvalot, Syvie] Inst Gustave Roussy, Dept Surg, Villejuif, France. [Raut, Chandrajit P.] Brigham & Womens Hosp, Dept Surg, Ctr Sarcoma & Bone Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Raut, Chandrajit P.] Harvard Univ, Sch Med, Boston, MA USA. [Pollock, Raphael E.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Div Surg, Houston, TX 77030 USA. [Rutkowski, Piotr] Maria Sklodowska Curie Mem Canc Ctr, Dept Soft Tissue Bone Sarcoma & Melanoma, Warsaw, Poland. [Rutkowski, Piotr] Inst Oncol, Warsaw, Poland. [Strauss, Dirk C.; Hayes, Andrew J.] Royal Marsden Hosp, Sarcoma Unit, London SW3 6JJ, England. [Van Coevorden, Frits] Netherlands Canc Inst, Dept Surg Oncol, Amsterdam, Netherlands. [Fiore, Marco; Gronchi, Alessandro] Fdn IRCCS Ist Nazl Tumori, Dept Surg, Milan, Italy. [Stoeckle, Eberhard] Inst Bergonie, Dept Surg, Bordeaux, France. [Hohenberger, Peter] Univ Heidelberg, Div Surg Oncol & Thorac Surg, Med Fac Mannheim, D-6800 Mannheim, Germany. RP Bonvalot, S (reprint author), Inst Gustave Roussy, Dept Surg, Villejuif, France. EM sylvie.bonvalot@igr.fr; alessandro.gronchi@istitutotumori.mi.it RI Fiore, Marco/M-6587-2016; OI Fiore, Marco/0000-0001-8220-424X; Gronchi, Alessandro/0000-0002-4703-3534; Rutkowski, Piotr/0000-0002-8920-5429 NR 27 TC 55 Z9 58 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD SEP PY 2012 VL 19 IS 9 BP 2981 EP 2991 DI 10.1245/s10434-012-2342-2 PG 11 WC Oncology; Surgery SC Oncology; Surgery GA 000AC UT WOS:000308357100029 PM 22476756 ER PT J AU Yeh, DD Velmahos, GC AF Yeh, Daniel Dante Velmahos, George C. TI Vital signs are unreliable SO ANZ JOURNAL OF SURGERY LA English DT Article ID SYSTOLIC BLOOD-PRESSURE; LEVEL FACILITIES IMPACT; IMPROVE TRAUMA TRIAGE; 110 MM HG; RELATIVE BRADYCARDIA; MAJOR TRAUMA; SHOCK INDEX; REDEFINING HYPOTENSION; INJURED PATIENTS; DIRECT TRANSPORT C1 [Yeh, Daniel Dante; Velmahos, George C.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Yeh, DD (reprint author), Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 36 TC 0 Z9 0 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1445-1433 J9 ANZ J SURG JI ANZ J. Surg. PD SEP PY 2012 VL 82 IS 9 BP 574 EP 576 DI 10.1111/j.1445-2197.2012.06171.x PG 3 WC Surgery SC Surgery GA 999RB UT WOS:000308330800003 PM 23106073 ER PT J AU Winickoff, JP Joseph, A AF Winickoff, Jonathan P. Joseph, Anne TI Toward a Population Free of Tobacco Smoke Exposure Testing of Children in the Pediatric Setting SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Editorial Material ID HOUSEHOLDS; CESSATION C1 [Winickoff, Jonathan P.] Massachusetts Gen Hosp, Ctr Child& Adolescent Hlth Res & Policy, Boston, MA 02114 USA. [Winickoff, Jonathan P.] Massachusetts Gen Hosp, Div Gen Med, Tobacco Res & Treatment Ctr,setts Gen, Boston, MA 02114 USA. [Winickoff, Jonathan P.] Amer Acad Pediat, Julius B Richmond Ctr Excellence, Elk Grove Village, IL USA. [Joseph, Anne] Univ Minnesota, Dept Med, St Paul, MN 55108 USA. [Joseph, Anne] Univ Minnesota, Masonic Canc Ctr, St Paul, MN 55108 USA. RP Winickoff, JP (reprint author), MGH Ctr Child & Adolescent Hlth Res & Policy, 100 Cambridge St,Ste 1542A, Boston, MA 02114 USA. EM jwinickoff@partners.org NR 15 TC 1 Z9 1 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD SEP PY 2012 VL 166 IS 9 BP 871 EP 872 DI 10.1001/archpediatrics.2012.297 PG 2 WC Pediatrics SC Pediatrics GA 998FG UT WOS:000308222200016 PM 22566516 ER PT J AU Schumacher, HR Chen, LX Mandell, BF AF Schumacher, H. Ralph Chen, Lan X. Mandell, Brian F. TI The time has come to incorporate more teaching and formalized assessment of skills in synovial fluid analysis into rheumatology training programs SO ARTHRITIS CARE & RESEARCH LA English DT Editorial Material ID ARTHRITIS CLASSIFICATION CRITERIA; AMERICAN-COLLEGE; CRYSTAL IDENTIFICATION; QUALITY-CONTROL; REPRODUCIBILITY; LABORATORIES; LEAGUE C1 [Schumacher, H. Ralph] Univ Penn, Philadelphia, PA 19104 USA. [Schumacher, H. Ralph] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Chen, Lan X.] Penn Presbyterian Med Ctr, Philadelphia, PA USA. [Mandell, Brian F.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. RP Mandell, BF (reprint author), Cleveland Clin, A50,9500 Euclid Ave, Cleveland, OH 44195 USA. EM mandelb@ccf.org NR 18 TC 5 Z9 5 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2151-464X EI 2151-4658 J9 ARTHRIT CARE RES JI Arthritis Care Res. PD SEP PY 2012 VL 64 IS 9 BP 1271 EP 1273 DI 10.1002/acr.21714 PG 3 WC Rheumatology SC Rheumatology GA 995ST UT WOS:000308033800001 PM 22555864 ER PT J AU White, DK Keysor, JJ Neogi, T Felson, DT LaValley, M Gross, KD Niu, JB Nevitt, M Lewis, CE Torner, J Fredman, L AF White, Daniel K. Keysor, Julie J. Neogi, Tuhina Felson, David T. LaValley, Michael Gross, K. Doug Niu, Jingbo Nevitt, Michael Lewis, Cora E. Torner, Jim Fredman, Lisa TI When it hurts, a positive attitude may help: association of positive affect with daily walking in knee osteoarthritis. Results from a multicenter longitudinal cohort study SO ARTHRITIS CARE & RESEARCH LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; PHYSICAL-ACTIVITY; OLDER-ADULTS; DEPRESSIVE SYMPTOMS; SELF-AFFIRMATION; PAIN; HEALTHY; ARTHRITIS; RECOVERY; ACCELEROMETER AB Objective While depressive symptoms and knee pain are independently known to impede daily walking in older adults, it is unknown whether positive affect promotes daily walking. This study investigated this association among adults with knee osteoarthritis (OA) and examined whether knee pain modified this association. Methods This study is a cross-sectional analysis of the Multicenter Osteoarthritis Study. We included 1,018 participants (mean +/- SD age 63.1 +/- 7.8 years, 60% women) who had radiographic knee OA and had worn a StepWatch monitor to record their number of steps per day. High and low positive affect and depressive symptoms were based on the Center for Epidemiologic Studies Depression Scale. Knee pain was categorized as present in respondents who reported pain on most days at both a clinic visit and a telephone screening. Results Compared to respondents with low positive affect (27% of all respondents), those with high positive affect (63%) walked a similar number of steps per day, while those with depressive symptoms (10%) walked less (adjusted beta -32.6 [95% confidence interval (95% CI) -458.9, 393.8] and -579.1 [95% CI -1,274.9, 116.7], respectively). There was a statistically significant interaction of positive affect by knee pain (P = 0.0045). Among the respondents with knee pain (39%), those with high positive affect walked significantly more steps per day (adjusted beta 711.0 [95% CI 55.1, 1,366.9]) than those with low positive affect. Conclusion High positive affect was associated with more daily walking among adults with painful knee OA. Positive affect may be an important psychological factor to consider for promoting physical activity among people with painful knee OA. C1 [White, Daniel K.; Keysor, Julie J.; Neogi, Tuhina; Felson, David T.; LaValley, Michael; Gross, K. Doug; Niu, Jingbo; Fredman, Lisa] Boston Univ, Boston, MA 02215 USA. [Gross, K. Doug] Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. [Nevitt, Michael] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Lewis, Cora E.] Univ Alabama Birmingham, Birmingham, AL USA. [Torner, Jim] Univ Iowa, Iowa City, IA USA. RP White, DK (reprint author), 635 Commonwealth Ave,5th Floor, Boston, MA 02115 USA. EM dwtbn@bu.edu FU NIH [AG-18820, AG-18832, AG-18947, AG-19069, AR-007598, AR-47885, R01-AG-18037, R01-AG-028144, R01-AG-028556, R21-AT-002959]; National Institute of Arthritis and Musculoskeletal and Skin Diseases [K23-AR-055127]; American College of Rheumatology/Research and Education Foundation; Arthritis Foundation Arthritis Investigator Award; Boston Claude D. Pepper Older Americans Independence Center [P30-AG-031679]; Foundation for Physical Therapy; Association of Rheumatology Health Professionals; American Physical Therapy Association FX Supported by the NIH (grants AG-18820, AG-18832, AG-18947, AG-19069, AR-007598, AR-47885, R01-AG-18037, R01-AG-028144, R01-AG-028556, and R21-AT-002959), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant K23-AR-055127), an American College of Rheumatology/Research and Education Foundation Rheumatology Investigator Award (White), an Arthritis Foundation Arthritis Investigator Award (Neogi), the Boston Claude D. Pepper Older Americans Independence Center (grant P30-AG-031679), and a Geriatric Research Grant from the Foundation for Physical Therapy.; Dr. Keysor has received consultant fees, speaking fees, and/or honoraria (less than $10,000 each) from the Association of Rheumatology Health Professionals and the American Physical Therapy Association. NR 52 TC 15 Z9 16 U1 1 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2151-464X J9 ARTHRIT CARE RES JI Arthritis Care Res. PD SEP PY 2012 VL 64 IS 9 BP 1312 EP 1319 DI 10.1002/acr.21694 PG 8 WC Rheumatology SC Rheumatology GA 995ST UT WOS:000308033800007 PM 22504854 ER PT J AU Piper, SL Kim, HT AF Piper, Samantha L. Kim, Hubert T. TI Thermal Stress Potentiates Bupivacaine Chondrotoxicity SO ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY LA English DT Article ID GLENOHUMERAL FLUID TEMPERATURE; BOVINE ARTICULAR CHONDROCYTES; SHOULDER ARTHROSCOPY; IN-VITRO; 0.5-PERCENT BUPIVACAINE; RADIOFREQUENCY ENERGY; RAPID CHONDROLYSIS; PAIN PUMP; CARTILAGE; CAPSULORRHAPHY AB Purpose: The primary objective of this study was to determine whether thermal stress potentiates the chondrotoxic effect of bupivacaine, resulting in decreased articular chondrocyte viability compared with exposure to bupivacaine alone. Methods: Bovine articular cartilage explants and cultured chondrocytes were treated with a range of thermal exposures (10 to 20 minutes at 37 degrees C to 65 degrees C) to create time/temperature viability curves and to determine threshold conditions for cell death. A second set of experiments was performed to determine whether subthreshold thermal stress potentiates bupivacaine toxicity. Explants were exposed to 37 degrees C or 55 degrees C for 10 or 20 minutes, and cultured chondrocytes were exposed to 37 degrees C or 45 degrees C for 10 or 20 minutes. Thirty minutes later, the explants and chondrocytes were treated with either 0.9% normal saline solution or 0.5% bupivacaine for 30 minutes. Chondrocyte viability was quantified 24 hours after treatment. Results: There was a temperature-and time-dependent decrease in chondrocyte viability above the thermo-toxicity threshold in both intact cartilage explants and cultured chondrocytes (55 degrees C and 45 degrees C, respectively; P < .05). Chondrocyte viability in cartilage explants was significantly lower after treatment with thermal stress for 10 or 20 minutes followed by bupivacaine for 30 minutes compared with treatment with bupivacaine at 37 degrees C (bupivacaine and 55 degrees C for 10 minutes, 0.09% +/- 0%; bupivacaine and 55 degrees C for 20 minutes, 0.08% +/- 0%; bupivacaine and 37 degrees C for 10 minutes, 37.4% +/- 1.2% [P < .001]; and bupivacaine and 37 degrees C for 20 minutes, 47.1% +/- 0.8% [P < .001]). A similar trend was seen in cultured chondrocytes, although it was not statistically significant (P > .05). Conclusions: Thermal stress potentiates the chondrotoxic effects of bupivacaine in intact cartilage, leading to decreased chondrocyte viability compared with exposure to bupivacaine alone. Clinical Relevance: Intra-articular injection of bupivacaine after arthroscopic procedures during which cartilage is exposed to elevated temperatures, such as with prolonged use of radiofrequency probes, may increase the risk of chondrocyte toxicity. C1 [Piper, Samantha L.; Kim, Hubert T.] Univ Calif San Francisco, Dept Orthopaed Surg, San Francisco, CA 94143 USA. [Kim, Hubert T.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Kim, HT (reprint author), Univ Calif San Francisco, Dept Orthopaed Surg, 500 Parnassus Ave,MUW 320, San Francisco, CA 94143 USA. EM KimH@orthosurg.ucsf.edu FU Orthopaedic Research and Education Foundation (OREF)/DePuy Resident Research Project Grant FX The authors report the following source of funding in relation to this article: Orthopaedic Research and Education Foundation (OREF)/DePuy Resident Research Project Grant. NR 38 TC 4 Z9 4 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 0749-8063 J9 ARTHROSCOPY JI Arthroscopy PD SEP PY 2012 VL 28 IS 9 BP 1246 EP U296 DI 10.1016/j.arthro.2012.02.012 PG 10 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 996DW UT WOS:000308065500012 PM 22579775 ER PT J AU Chen, CY Paw, BH AF Chen, Caiyong Paw, Barry H. TI Cellular and mitochondrial iron homeostasis in vertebrates SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Review DE Iron; Transferrin; Non-transferrin bound iron; Mitochondrion; Mitoferrin ID TRANSFERRIN RECEPTOR 2; GELATINASE-ASSOCIATED LIPOCALIN; HUMAN ERYTHROID PRECURSORS; SULFUR CLUSTER BIOGENESIS; HEREDITARY HEMOCHROMATOSIS PROTEIN; BINDING CASSETTE TRANSPORTER; ISCHEMIA-REPERFUSION INJURY; SINGLE CALCIUM CHANNELS; METAL-ION TRANSPORTER; SIDEROBLASTIC ANEMIA AB Iron plays an essential role in cellular metabolism and biological processes. However, due to its intrinsic redox activity, free iron is a potentially toxic molecule in cellular biochemistry. Thus, organisms have developed sophisticated ways to import, sequester, and utilize iron. The transferrin cycle is a well-studied iron uptake pathway that is important for most vertebrate cells. Circulating iron can also be imported into cells by mechanisms that are independent of transferrin. Once imported into erythroid cells, iron is predominantly consumed by the mitochondria for the biosynthesis of heme and iron sulfur clusters. This review focuses on canonical transferrin-mediated and the newly discovered, non-transferrin mediated iron uptake pathways, as well as, mitochondrial iron homeostasis in higher eukaryotes. This article is part of a Special Issue entitled: Cell Biology of Metals. (C) 2012 Elsevier BM. All rights reserved. C1 [Paw, Barry H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Hematol Div, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp Boston, Sch Med, Dept Med,Hematol Oncol Div, Boston, MA 02115 USA. Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Pediat Oncol, Boston, MA 02115 USA. RP Paw, BH (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Hematol Div, Boston, MA 02115 USA. EM bpaw@rics.bwh.harvard.edu FU Cooley's Anemia Foundation; March of Dimes Foundation; National Institutes of Health [R01 DK070838, P01 HL032262] FX This work was supported by grants from the Cooley's Anemia Foundation (C.C.), March of Dimes Foundation (B.H.P.), and the National Institutes of Health Grants R01 DK070838 and P01 HL032262 (B.H.P.). NR 147 TC 37 Z9 38 U1 1 U2 28 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD SEP PY 2012 VL 1823 IS 9 SI SI BP 1459 EP 1467 DI 10.1016/j.bbamcr.2012.01.003 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 994GE UT WOS:000307918100008 PM 22285816 ER PT J AU Nelissen, K Jarraya, B Arsenault, JT Rosen, BR Wald, LL Mandeville, JB Marota, JJ Vanduffel, W AF Nelissen, Koen Jarraya, Bechir Arsenault, John T. Rosen, Bruce R. Wald, Lawrence L. Mandeville, Joseph B. Marota, John J. Vanduffel, Wim TI Neural Correlates of the Formation and Retention of Cocaine-Induced Stimulus-Reward Associations SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Cocaine; conditioning; fMRI; macaque; orbitofrontal; reward ID INCENTIVE-SENSITIZATION THEORY; PRIMATE ORBITOFRONTAL CORTEX; PREFRONTAL CORTEX; VISUAL-CORTEX; BASOLATERAL AMYGDALA; ADDICTIVE BEHAVIOR; NUCLEUS-ACCUMBENS; DRUG-ADDICTION; CUE; RESPONSES AB Background: Cocaine can elicit drug-seeking behavior for drug-predicting stimuli, even after a single stimulus-cocaine pairing. Although orbitofrontal cortex is thought to be important during encoding and maintenance of stimulus-reward value, we still lack a comprehensive model of the neural circuitry underlying this cognitive process. Methods: We studied the conditioned effects of cocaine with monkey functional magnetic resonance imaging and classical conditioning by pairing a visual shape (conditioning stimulus [CS+]) with a noncontingent cocaine infusion; a control stimulus was never paired. We correlated the behavioral preference of the monkey for the CS+, as measured offline, with the activity induced by the CS+ relative to the control stimulus as function of time. Results: We observed that during formation of stimulus-cocaine associations strong CS+-induced functional magnetic resonance imaging activations emerged in frontal cortex that correlated significantly with behavioral CS+ preference. Afterward, CS+ preference correlated only with activity in early visual cortex. Control experiments suggest that these findings cannot be explained by increased familiarity for the CS+. Conclusions: Our findings suggest a complex interaction between frontal and occipital cortex during cocaine conditioning. Frontal cortex is important for establishing novel representations of stimulus valence when cocaine is used as reinforcer, whereas early visual cortex is involved in retaining these cocaine-stimulus associations. C1 [Nelissen, Koen; Arsenault, John T.; Vanduffel, Wim] Katholieke Univ Leuven, Lab Neuroen Psychofysiol, Sch Med, B-3000 Louvain, Belgium. [Jarraya, Bechir] CEA Saclay Ctr, Neurospin, IFR49, Inserm Avenir Bettencourt Schueller Lab, Gif Sur Yvette, France. [Nelissen, Koen; Jarraya, Bechir; Arsenault, John T.; Rosen, Bruce R.; Wald, Lawrence L.; Mandeville, Joseph B.; Marota, John J.; Vanduffel, Wim] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Nelissen, Koen; Jarraya, Bechir; Arsenault, John T.; Rosen, Bruce R.; Wald, Lawrence L.; Mandeville, Joseph B.; Marota, John J.; Vanduffel, Wim] Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. [Marota, John J.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Nelissen, K (reprint author), Katholieke Univ Leuven, Lab Neuroen Psychofysiol, Sch Med, O&N 2 Campus Gasthuisberg,Herestr 49,Bus 1021, B-3000 Louvain, Belgium. EM koen.nelissen@med.kuleuven.be RI Wald, Lawrence/D-4151-2009; OI Jarraya, Bechir/0000-0003-0878-763X FU National Center for Biomedical Imaging and Bioengineering [R01EB001782, R03EB008134]; National Center for Drug Abuse [R21DA021773, R01DA016187]; National Institute of Neurological Disorders and Stroke [R21NS064432]; National Science Foundation in the United States [0745436]; Programme Financing [PFV/10/008]; Geconcerteerde Onderzoeks Actie [10/19]; Fonds Wetenschappelijk Onderzoek-Vlaanderen [G062208N10, G083111N10, G071912N]; Hercules Foundation in Belgium; Fondation Bettencourt Schueller; Fondation pour la Recherche Medicale, Association pour la recherche sur la stimulation cerebrale; Fondation Planiol in France; Fonds Wetenschappelijk Onderzoek Vlaanderen FX This work was supported by the National Center for Biomedical Imaging and Bioengineering (R01EB001782, R03EB008134), the National Center for Drug Abuse (R21DA021773, R01DA016187), the National Institute of Neurological Disorders and Stroke (R21NS064432), and the National Science Foundation (0745436) in the United States; Programme Financing PFV/10/008, Geconcerteerde Onderzoeks Actie 10/19, Fonds Wetenschappelijk Onderzoek-Vlaanderen grants G062208N10, G083111N10, and G071912N, and Hercules Foundation in Belgium; and the Fondation Bettencourt Schueller, The Fondation pour la Recherche Medicale, Association pour la recherche sur la stimulation cerebrale, and the Fondation Planiol in France. We thank Drs. H. Deng, L. Ekstrom, R. Farivar, T. Benner, M. Gunjan, and M. Foley, Mr. T. Van Kerkoerle, Mrs. A. Coeman, C. Fransen, M. Nderlita, and C. Van Eupen for technical assistance; and Drs. H. Peuskens, S. Raiguel, and M. Vandenbulcke for comments on the manuscript. A poster with preliminary data was presented at the Society for Neuroscience; November 3-7, 2007; San Diego, California. KN is a postdoctoral fellow of the Fonds Wetenschappelijk Onderzoek Vlaanderen. NR 58 TC 6 Z9 6 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD SEP 1 PY 2012 VL 72 IS 5 BP 422 EP 428 DI 10.1016/j.biopsych.2012.02.021 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 985ZD UT WOS:000307308100013 PM 22440616 ER PT J AU Cutler, C AF Cutler, Corey TI Transplantation for MDS in the Elderly: More Evidence, or More Bias? SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Editorial Material ID STEM-CELL TRANSPLANTATION; MYELODYSPLASTIC SYNDROME; UNRELATED DONORS C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. RP Cutler, C (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM Corey_Cutler@dfci.harvard.edu NR 7 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD SEP PY 2012 VL 18 IS 9 BP 1320 EP 1321 DI 10.1016/j.bbmt.2012.06.009 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 996VF UT WOS:000308122200003 PM 22750646 ER PT J AU Ballen, KK Woolfrey, AE Zhu, XC Ahn, KW Wirk, B Arora, M George, B Savani, BN Bolwell, B Porter, DL Copelan, E Hale, G Schouten, HC Lewis, I Cahn, JY Halter, J Cortes, J Kalaycio, ME Antin, J Aljurf, MD Carabasi, MH Hamadani, M McCarthy, P Pavletic, S Gupta, V Deeg, HJ Maziarz, RT Horowitz, MM Saber, W AF Ballen, Karen K. Woolfrey, Ann E. Zhu, Xiaochun Ahn, Kwang Woo Wirk, Baldeep Arora, Mukta George, Biju Savani, Bipin N. Bolwell, Brian Porter, David L. Copelan, Ed Hale, Gregory Schouten, Harry C. Lewis, Ian Cahn, Jean Yves Halter, Joerg Cortes, Jorge Kalaycio, Matt E. Antin, Joseph Aljurf, Mahmoud D. Carabasi, Matthew H. Hamadani, Mehdi McCarthy, Philip Pavletic, Steven Gupta, Vikas Deeg, H. Joachim Maziarz, Richard T. Horowitz, Mary M. Saber, Wael TI Allogeneic Hematopoietic Cell Transplantation for Advanced Polycythemia Vera and Essential Thrombocythemia SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Transplantation; PV; ET ID ACUTE MYELOID-LEUKEMIA; MYELODYSPLASTIC SYNDROMES; PRIMARY MYELOFIBROSIS; CURATIVE THERAPY; RISK-FACTORS; FOLLOW-UP; HYDROXYUREA; MUTATION; JAK2; CRITERIA AB Allogeneic hematopoietic cell transplantation (HCT) is curative for selected patients with advanced essential thrombocythemia (ET) or polycythemia vera (PV). From 1990 to 2007, 75 patients with ET (median age 49 years) and 42 patients with PV (median age 53 years) underwent transplantations at the Fred Hutchinson Cancer Research Center (FHCRC; n = 43) or at other Center for International Blood and Marrow Transplant Research (CIBMTR) centers (n = 74). Thirty-eight percent of the patients had splenomegaly and 28% had a prior splen ectomy. Most patients (69% for ET and 67% for PV) received a myeloablative (MA) conditioning regimen. Cumulative incidence of neutrophil engraftment at 28 days was 88% for ET patients and 90% for PV patients. Acute graft-versus-host disease (aGVHD) grades II to IV occurred in 57% and 50% of ET and PV patients, respectively. The 1-year treatment-related mortality (TRM) was 27% for ET and 22% for PV. The 5-year cumulative incidence of relapse was 13% for ET and 30% for PV. Five-year survival/progression-free survival (PFS) was 55%/47% and 71%/48% for ETand PV, respectively. Patients without splenomegaly had faster neutrophil and platelet engraftment, but there were no differences in TRM, survival, or PFS. Presence of myelofibrosis (MF) did not affect engraftment or TRM. Over 45% of the patients who undergo transplantations for ET and PV experience long-term PFS. Biol Blood Marrow Tramp/ant 18: 1446-1454 (2012) (C) 2012 American Society for Blood and Marrow Transplantation C1 [Ballen, Karen K.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02214 USA. [Woolfrey, Ann E.; Deeg, H. Joachim] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Zhu, Xiaochun; Horowitz, Mary M.; Saber, Wael] Med Coll Wisconsin, Dept Med, CIBMTR, Milwaukee, WI 53226 USA. [Ahn, Kwang Woo] Med Coll Wisconsin, Div Biostat, Milwaukee, WI 53226 USA. [Wirk, Baldeep] Univ Florida, Shands Healthcare, Dept Hematol Oncol, Gainesville, FL USA. [Arora, Mukta] Univ Minnesota, Med Ctr, Dept Hematol Oncol & Transplant, Minneapolis, MN 55455 USA. [George, Biju] Christian Med Coll & Hosp, Dept Hematol, Vellore 632004, Tamil Nadu, India. [Savani, Bipin N.] Vanderbilt Univ, Med Ctr, Brentwood, TN USA. [Bolwell, Brian; Copelan, Ed; Kalaycio, Matt E.] Cleveland Clin, Dept Bone Marrow Transplant, Cleveland, OH 44106 USA. [Porter, David L.] Univ Penn, Med Ctr, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Hale, Gregory] Univ S Florida, All Childrens Hosp, Dept Pediat Hematol Oncol BMT, St Petersburg, FL 33701 USA. [Schouten, Harry C.] Acad Ziekenhuis, Maastricht, Netherlands. [Lewis, Ian] Royal Adelaide Hosp, S Australia Pathol, Haematol & Bone Marrow Transplant Unit, Adelaide, SA 5000, Australia. [Cahn, Jean Yves] CHU Grenoble, Hop A Michallon, Dept Hematol, F-38043 Grenoble, France. [Halter, Joerg] Univ Basel Hosp, Dept Internal Med, CH-4031 Basel, Switzerland. [Cortes, Jorge] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Antin, Joseph] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Aljurf, Mahmoud D.] King Faisal Specialist Hosp & Res Ctr, Dept Oncol, Riyadh 11211, Saudi Arabia. [Carabasi, Matthew H.] Thomas Jefferson Univ Hosp, Dept Med Oncol, Philadelphia, PA 19107 USA. [Hamadani, Mehdi] W Virginia Univ Hosp Inc, Dept Hematol Oncol, Morgantown, WV USA. [McCarthy, Philip] Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA. [Pavletic, Steven] NCI, Graft Vs Host & Autoimmun Unit, NIH, Bethesda, MD 20892 USA. [Gupta, Vikas] Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada. [Maziarz, Richard T.] Oregon Hlth & Sci Univ, Ctr Hematol Malignancies, Portland, OR 97201 USA. RP Ballen, KK (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, 0 Emerson,Suite 118, Boston, MA 02214 USA. EM kballen@partners.org RI Cahn, Jean-Yves/M-6493-2014; OI Hamadani, Mehdi/0000-0001-5372-510X FU Public Health Service Grant/Cooperative Agreement from the National Cancer Institute (NCI) [U24-CA76518]; National Heart, Lung, and Blood Institute (NIMBI); National Institute of Allergy and Infectious Diseases (NRID); NIMBI [5U01HL069294]; NCI; Health Resources and Services Administration (HRSA/DHHS) [HHSH234200637015C]; Office of Naval Research [N00014-06-1-0704, N00014-08-1-0058]; Allos, Inc.; Amgen, Inc.; Angioblast FX The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA76518 from the National Cancer Institute (NCI), the National Heart, Lung, and Blood Institute (NIMBI), and the National Institute of Allergy and Infectious Diseases (NRID); a Grant/Cooperative Agreement 5U01HL069294 from NIMBI and NCI; a contract HHSH234200637015C with Health Resources and Services Administration (HRSA/DHHS); two Grants N00014-06-1-0704 and N00014-08-1-0058 from the Office of Naval Research; and grants from Allos, Inc.; Amgen, Inc.; Angioblast; anonymous donation to the Medical College of Wisconsin; Ariad; Be the Match Foundation; Blue Cross and Blue Shield Association; Buchanan Family Foundation; CaridianBCT; Celgene Corporation; CellGenix, GmbH; Children's Leukemia Research Association; Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; Genzyme Corporation; GlaxSmithKline; Kiadis Pharma; The Leukemia & Lymphoma Society; The Medical College of Wisconsin; Millennium Pharmaceuticals, Inc.; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; RemedyMD; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; Swedish Orphan Biovitrum; Tarix Pharmaceuticals; Teva Neuroscience, Inc.; THERAKOS, Inc.; and Wellpoint, Inc. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, or any other agency of the U.S. Government. NR 35 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD SEP PY 2012 VL 18 IS 9 BP 1446 EP 1454 DI 10.1016/j.bbmt.2012.03.009 PG 9 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 996VF UT WOS:000308122200018 PM 22449610 ER PT J AU Kubiak, DW Koo, S Hammond, SP Armand, P Baden, LR Antin, JH Marty, FM AF Kubiak, David W. Koo, Sophia Hammond, Sarah P. Armand, Philippe Baden, Lindsey R. Antin, Joseph H. Marty, Francisco M. TI Safety of Posaconazole and Sirolimus Coadministration in Allogeneic Hematopoietic Stem Cell Transplants SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Posaconazole; Sirolimus; Tacrolimus; Drug interactions; Coadministration ID VERSUS-HOST-DISEASE; DRUG-INTERACTIONS; PROPHYLAXIS; METHOTREXATE; TACROLIMUS; RAPAMYCIN; ANTIFUNGALS; DONOR AB Sirolimus is used in allogeneic hematopoietic stem cell transplants (HSCTs) for prevention and treatment of graft-versus-host disease (GVHD). Posaconazole is used in this population for invasive fungal disease (IFD) prophylaxis and treatment. As posaconazole strongly inhibits CYP3A4, concurrent administration of sirolimus, a CYP3A4 substrate, and posaconazole has been reported to increase sirolimus drug exposure substantially. Coadministration of posaconazole and sirolimus is contraindicated by the manufacturer of posaconazole. We identified 15 patients who underwent HSCTs at our institution receiving a steady-state dose of sirolimus who subsequently started posaconazole therapy from January 2006 to March 2009. We recorded baseline characteristics, drug administration details, and potential adverse effects related to either drug. All patients underwent HSCTs for treatment of hematologic malignancy. All patients were initially prescribed sirolimus for GVHD prophylaxis and continued therapy after developing GVHD. Twelve patients (80%) received posaconazole for IFD prophylaxis in the setting of GVHD and 3 (20%) for IFD treatment. Patients received sirolimus and posaconazole concurrently for a median of 78 days (interquartile range [IQR] 25-177; range, 6-503). The median daily dose of sirolimus (2 mg/day) before initiation of posaconazole was reduced 50% to a median daily dose of I mg/day at steady state. Six patients experienced sirolimus trough levels greater than 12 ng/mL during coadministration, but only I patient experienced an adverse event potentially associated with sirolimus exposure during the first month of coadministration. This patient's sirolimus dose was empirically reduced by only 30% on posaconazole initiation. Concurrent sirolimus and posaconazole use seems to be well tolerated with a 33% to 50% empiric sirolimus dose reduction and close monitoring of serum sirolimus trough levels at the time of posaconazole initiation. Biol Blood Marrow Transplant IS: 1462-1465 (2012) (C) 2012 American Society for Blood and Marrow Transplantation C1 [Kubiak, David W.; Koo, Sophia; Hammond, Sarah P.; Baden, Lindsey R.; Marty, Francisco M.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Koo, Sophia; Hammond, Sarah P.; Armand, Philippe; Baden, Lindsey R.; Antin, Joseph H.; Marty, Francisco M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Koo, Sophia; Hammond, Sarah P.; Armand, Philippe; Baden, Lindsey R.; Antin, Joseph H.; Marty, Francisco M.] Harvard Univ, Sch Med, Boston, MA USA. [Kubiak, David W.] Brigham & Womens Hosp, Dept Pharm, Boston, MA 02115 USA. [Armand, Philippe; Antin, Joseph H.] Brigham & Womens Hosp, Div Med Oncol, Boston, MA 02115 USA. RP Kubiak, DW (reprint author), Brigham & Womens Hosp, Div Infect Dis, 75 Francis St,PBB A4, Boston, MA 02115 USA. EM dwkubiak@partners.org OI Koo, Sophia/0000-0002-4973-7439 FU Jock and Bunny Adams Research and Education Endowment FX Sarah P. Hammond has received research support from Merck & Co. Joseph H. Antin is supported by the Jock and Bunny Adams Research and Education Endowment. All other authors have no relevant financial disclosures. NR 16 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD SEP PY 2012 VL 18 IS 9 BP 1462 EP 1465 DI 10.1016/j.bbmt.2012.04.015 PG 4 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 996VF UT WOS:000308122200020 PM 22564264 ER PT J AU Poon, SH Sim, K Sum, MY Kuswanto, CN Baldessarini, RJ AF Poon, Shi Hui Sim, Kang Sum, Min Yi Kuswanto, Carissa Nadia Baldessarini, Ross J. TI Evidence-based options for treatment-resistant adult bipolar disorder patients SO BIPOLAR DISORDERS LA English DT Review DE bipolar disorder; depression; mania; polytherapy; treatment resistance ID TRANSCRANIAL MAGNETIC STIMULATION; REFRACTORY AFFECTIVE-DISORDERS; MAJOR DEPRESSIVE DISORDER; PLACEBO-CONTROLLED TRIAL; BONE-MINERAL DENSITY; DOUBLE-BLIND; I-DISORDER; MOOD DISORDERS; ANTIDEPRESSANT EFFICACY; FUNCTIONAL IMPAIRMENT AB Poon SH, Sim K, Sum MY, Kuswanto CN, Baldessarini RJ. Evidence-based options for treatment-resistant adult bipolar disorder patients. Bipolar Disord 2012: 14: 573584. (c) 2012 The Authors. Journal compilation (c) 2012 John Wiley & Sons A/S. Objectives: Many patients diagnosed with bipolar disorder (BD) respond incompletely or unsatisfactorily to available treatments. Given the potentially devastating nature of this prevalent disorder, there is a pressing need to improve clinical care of such patients. Methods: We performed a literature review of the research findings related to treatment-resistant BD reported through February 2012. Results: Therapeutic trials for treatment-resistant bipolar mania are uncommon, and provide few promising leads other than the use of clozapine. Far more pressing challenges are the depressive-dysthymic-dysphoric-mixed phases of BD and long-term prophylaxis. Therapeutic trials for treatment-resistant bipolar depression have assessed anticonvulsants, modern antipsychotics, glutamate [N-methyl-D-aspartate (NMDA)] antagonists, dopamine agonists, calcium-channel blockers, and thyroid hormones, as well as behavioral therapy, sleep deprivation, light therapy, electroconvulsive therapy (ECT), transcranial magnetic stimulation, and deep brain stimulationall of which are promising but limited in effectiveness. Several innovative pharmacological treatments (an anticholinesterase, a glutamine antagonist, a calcium-channel blocker, triiodothyronine, olanzapine and topiramate), ECT, and cognitive-behavior therapy have some support for long-term treatment of resistant BD patients, but most of trials of these treatments have been methodologically limited. Conclusions: Most studies identified were small, involved supplementation of typically complex ongoing treatments, varied in controls, randomization, and blinding, usually involved brief follow-up, and lacked replication. Clearer criteria for defining and predicting treatment resistance in BD are needed, as well as improved trial design with better controls, assessment of specific clinical subgroups, and longer follow-up. C1 [Poon, Shi Hui; Sim, Kang] Inst Mental Hlth, Dept Gen Psychiat, Singapore 539747, Singapore. [Sim, Kang; Sum, Min Yi; Kuswanto, Carissa Nadia] Inst Mental Hlth, Div Res, Singapore 539747, Singapore. [Baldessarini, Ross J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Baldessarini, Ross J.] Massachusetts Gen Hosp, McLean Div, Int Consortium Bipolar Disorder Res, Boston, MA 02114 USA. RP Sim, K (reprint author), Inst Mental Hlth, Dept Gen Psychiat, 10 Buangkok View, Singapore 539747, Singapore. EM kang_sim@imh.com.sg FU Bruce J. Anderson Foundation; McLean Private Donors Bipolar Disorder Research Fund FX This study was supported, in part, by a grant from the Bruce J. Anderson Foundation and by the McLean Private Donors Bipolar Disorder Research Fund (RJB). NR 96 TC 19 Z9 20 U1 7 U2 20 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD SEP PY 2012 VL 14 IS 6 BP 573 EP 584 DI 10.1111/j.1399-5618.2012.01042.x PG 12 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 999CN UT WOS:000308286800001 PM 22938165 ER PT J AU Fleming, AJ Hukin, J Rassekh, R Fryer, C Kim, J Stemmer-Rachamimov, A Birks, DK Huang, A Yip, S Dunham, C AF Fleming, Adam J. Hukin, Juliette Rassekh, Rod Fryer, Christopher Kim, James Stemmer-Rachamimov, Anat Birks, Diane K. Huang, Annie Yip, Stephen Dunham, Christopher TI Atypical Teratoid Rhabdoid Tumors (ATRTs): The British Columbia's Children's Hospital's Experience, 1986-2006 SO BRAIN PATHOLOGY LA English DT Article DE atypical teratoid rhabdoid tumor (ATRT); claudin-6; epigenetics; INI-1; methylation specific PCR (MSP); MGMT ID CENTRAL-NERVOUS-SYSTEM; TERATOID/RHABDOID TUMORS; IMMUNOHISTOCHEMICAL ANALYSIS; PROMOTER HYPERMETHYLATION; MISMATCH REPAIR; INI1; CHILDHOOD; INI1/SMARCB1; INACTIVATION; EXPRESSION AB As atypical teratoid rhabdoid tumors (ATRTs) may mimic small round blue cell tumors (SRBCT), we reexamined our ATRT experience focusing upon INI-1 immunohistochemistry (IHC). All high-grade pediatric brain tumors occurring from 19862006 at our institution underwent INI-1 IHC. Clinicopathologic data from each INI-1 immunonegative case were reviewed. Additional genetic, epigenetic and IHC analyses (including interrogation of INI-1 and CLDN6) were performed on a subset of the INI-1 immunonegative cases. Twelve INI-1 IHC negative tumors were identified retrospectively, of which only two previously carried the diagnosis of ATRT. Overall, the clinicopathologic and genetic data supported the assertion that all 12 cases represented ATRT. Unexpectedly, three long-term survivors (4.2, 7.0 and 8.5 years) were identified. As hypothesized, teratoid and rhabdoid histologic features were relatively infrequent despite gross total resections in some cases. Methylation specific polymer chain reaction (PCR) (MSP) revealed a uniform methylation pattern across all cases and gene promoters tested (ie, MGMT, HIC1, MLH3 and RASSF1); notably, all cases demonstrated unmethylated MGMT promoters. Our data demonstate that a primitive non-rhabdoid histophenotype is common among ATRTs and highlights the diagnostic importance of INI-1 IHC. Epigenetically, the MGMT promoter is usually unmethylated in ATRT, suggesting that potential temozolomide-based chemotherapy may be of limited efficacy. C1 [Dunham, Christopher] Univ British Columbia, British Columbia Childrens Hosp, Childrens & Womens Hlth Ctr British Columbia, Div Anat Pathol, Vancouver, BC, Canada. [Fleming, Adam J.; Hukin, Juliette; Rassekh, Rod; Fryer, Christopher] British Columbia Childrens Hosp, Div Hematol Oncol & Bone Marrow Transplantat, Vancouver, BC V6H 3V4, Canada. [Hukin, Juliette] British Columbia Childrens Hosp, Div Neurol, Vancouver, BC V6H 3V4, Canada. [Kim, James; Stemmer-Rachamimov, Anat] Massachusetts Gen Hosp, Div Neuropathol, Mol Neuro Oncol Lab, Boston, MA 02114 USA. [Birks, Diane K.] Childrens Hosp, Dept Neurosurg, Aurora, CO USA. [Huang, Annie] Univ Toronto, Hosp Sick Children, Dept Lab Med & Pathobiol, Sonia & Arthur Labatt Brain Tumor Res Ctr,Div Hem, Toronto, ON M5G 1X8, Canada. [Yip, Stephen] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. RP Dunham, C (reprint author), Univ British Columbia, British Columbia Childrens Hosp, Childrens & Womens Hlth Ctr British Columbia, Div Anat Pathol, 4500 Oak St,Room L218,Shaughnessy Bldg, Vancouver, BC, Canada. EM cdunham@cw.bc.ca RI rassekh, shahrad/G-5301-2010; OI rassekh, shahrad/0000-0001-8005-2641; Dunham, Christopher/0000-0002-6244-0584; Fleming, Adam/0000-0002-7194-3220 NR 44 TC 11 Z9 11 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD SEP PY 2012 VL 22 IS 5 BP 625 EP 635 DI 10.1111/j.1750-3639.2011.00561.x PG 11 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 994NC UT WOS:000307936500005 PM 22188464 ER PT J AU Sanoff, HK Carpenter, WR Freburger, J Li, L Chen, K Zullig, LL Goldberg, RM Schymura, MJ Schrag, D AF Sanoff, Hanna K. Carpenter, William R. Freburger, Janet Li, Ling Chen, Kun Zullig, Leah L. Goldberg, Richard M. Schymura, Maria J. Schrag, Deborah TI Comparison of adverse events during 5-fluorouracil versus 5-fluorouracil/oxaliplatin adjuvant chemotherapy for stage III colon cancer A Population-Based Analysis SO CANCER LA English DT Article DE colon cancer; adjuvant chemotherapy; toxicity; elderly; oxaliplatin ID SEER-MEDICARE DATA; POOLED ANALYSIS; COMORBIDITY INDEX; COLORECTAL-CANCER; CLINICAL-TRIALS; FLUOROURACIL; OXALIPLATIN; PARTICIPATION; DISPARITIES; LEUCOVORIN AB BACKGROUND: In clinical trials, combined 5-fluorouracil (5FU) plus oxaliplatin improves the survival of patients who have resected, stage III colon cancer with manageable toxicity. However, the tolerability of this in the general population of patients with colon cancer is uncertain. METHODS: Adverse outcomes were compared in patients with stage III colon cancer who received either 5FU or 5FU/oxaliplatin within 120 days of undergoing resection versus a control group of patients with stage II colon cancer who did not receive chemotherapy in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database and in data from the New York State Cancer Registry linked to Medicare and Medicaid. Hospitalizations, emergency room (ER) visits, and outpatient adverse events (AEs) were measured in claims from 30 days to 9 months after patients underwent resection. Multiple logistic regression was used to calculate adjusted odds ratios of events by treatment. Propensity score matching was used to minimize selection bias. RESULTS: Adverse outcomes were more frequent for chemotherapy recipients. AE rates were higher in patients who received 5FU/oxaliplatin (81%) compared with patients who received 5FU alone (72%), in the SEER-Medicare data. The effect of oxaliplatin on AEs was greater in older patients: The odds ratio was 2.10 (95% confidence interval, 1.53-2.87) for patients aged =75 years versus 1.75 (95% confidence interval, 1.39-2.21) for patients aged <75 years. ER use was high in Medicaid patients (83% of those who received chemotherapy), but neither ER use nor hospitalization was increased by oxaliplatin. The 60-day mortality rate was 1% to 3% for patients who received 5FU alone and 1% to 2% for patients who received combined 5FU/oxaliplatin. CONCLUSIONS: The incremental harms of adjuvant chemotherapy with 5FU/oxaliplatin versus 5FU alone were modest in patients with stage III colon cancer who were insured by Medicare and Medicaid. The additional harms in patients aged =75 years largely were restricted to outpatient events and did not extend to an increased rate of hospitalization or early death. Cancer 2012. (c) 2012 American Cancer Society C1 [Schrag, Deborah] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Schymura, Maria J.] New York State Dept Hlth, New York State Canc Registry, Albany, NY 12237 USA. [Sanoff, Hanna K.] Univ Virginia, Dept Med, Div Hematol & Oncol, Charlottesville, VA USA. [Carpenter, William R.; Freburger, Janet; Zullig, Leah L.; Goldberg, Richard M.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Hlth Policy & Management, Chapel Hill, NC USA. RP Schrag, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM deb_schrag@dfci.harvard.edu RI Carpenter, William/E-5125-2013; Goldberg , Richard/M-1311-2013 FU Agency for Healthcare Research and Quality; US Department of Health and Human Services through the "Developing Evidence to Inform Decisions About Effectiveness" program [HSA290-2005-0016-I-TO7-WA1, 36-BWH-1, HHSA290-2005-0040-I-TO4-WA1, 36-UNC]; NCI [R01CA131847]; Centers for Disease Control and Prevention through the Association of Schools of Public Health [S3888]; National Cancer Institute [1 R25 CA11633901] FX This project was supported by the Agency for Healthcare Research and Quality and the US Department of Health and Human Services through the "Developing Evidence to Inform Decisions About Effectiveness" program (contract HSA290-2005-0016-I-TO7-WA1, 36-BWH-1; HHSA290-2005-0040-I-TO4-WA1, 36-UNC); by grant R01CA131847 from the NCI (D. Schrag, principal investigator); by grant S3888 from the Centers for Disease Control and Prevention through the Association of Schools of Public Health (M. J. Schymura, principal investigator); and by 1 R25 CA11633901 from the National Cancer Institute (L. Zullig). NR 23 TC 16 Z9 16 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD SEP 1 PY 2012 VL 118 IS 17 BP 4309 EP 4320 DI 10.1002/cncr.27422 PG 12 WC Oncology SC Oncology GA 993GN UT WOS:000307845200029 PM 22294436 ER PT J AU Volandes, AE Levin, TT Slovin, S Carvajal, RD O'Reilly, EM Keohan, ML Theodoulou, M Dickler, M Gerecitano, JF Morris, M Epstein, AS Naka-Blackstone, A Walker-Corkery, ES Chang, YC Noy, A AF Volandes, Angelo E. Levin, Tomer T. Slovin, Susan Carvajal, Richard D. O'Reilly, Eileen M. Keohan, Mary Louise Theodoulou, Maria Dickler, Maura Gerecitano, John F. Morris, Michael Epstein, Andrew S. Naka-Blackstone, Anastazia Walker-Corkery, Elizabeth S. Chang, Yuchiao Noy, Ariela TI Augmenting advance care planning in poor prognosis cancer with a video decision aid A Preintervention-Postintervention Study SO CANCER LA English DT Article DE decision-making; video decision aids; end-of-life decision-making; advanced cancer; advance care planning; code status; resuscitation; preferences ID RANDOMIZED CONTROLLED-TRIAL; HEALTH-CARE; DISCUSSIONS; PHYSICIANS; DIRECTIVES; DEMENTIA AB BACKGROUND: The authors tested whether an educational video on the goals of care in advanced cancer (life-prolonging care, basic care, or comfort care) helped patients understand these goals and had an impact on their preferences for resuscitation. METHODS: A survey of 80 patients with advanced cancer was conducted before and after they viewed an educational video. The outcomes of interest included changes in goals of care preference and knowledge and consistency of preferences with code status. RESULTS: Before viewing the video, 10 patients (13%) preferred life-prolonging care, 24 patients (30%) preferred basic care, 29 patients (36%) preferred comfort care, and 17 patients (21%) were unsure. Preferences did not change after the video, when 9 patients (11%) chose life-prolonging care, 28 patients (35%) chose basic care, 29 patients (36%) chose comfort care, and, 14 patients (18%) were unsure (P = .28). Compared with baseline, after the video presentation, more patients did not want cardiopulmonary resuscitation (CPR) (71% vs 62%; P = .03) or ventilation (80% vs 67%; P = .008). Knowledge about goals of care and likelihood of resuscitation increased after the video (P < .001). Of the patients who did not want CPR or ventilation after the video augmentation, only 4 patients (5%) had a documented do-not-resuscitate order in their medical record (kappa statistic, -0.01; 95% confidence interval, -0.06 to 0.04). Acceptability of the video was high. CONCLUSIONS: Patients with advanced cancer did not change care preferences after viewing the video, but fewer wanted CPR or ventilation. Documented code status was inconsistent with patient preferences. Patients were more knowledgeable after the video, reported that the video was acceptable, and said they would recommend it to others. The current results indicated that this type of video may enable patients to visualize goals of care, enriching patient understanding of worsening health states and better informing decision making. Cancer 2012. (c) 2012 American Cancer Society. C1 [Volandes, Angelo E.; Walker-Corkery, Elizabeth S.; Chang, Yuchiao] Massachusetts Gen Hosp, Gen Med Unit, Dept Med, Boston, MA 02114 USA. [Volandes, Angelo E.; Walker-Corkery, Elizabeth S.; Chang, Yuchiao] Harvard Univ, Sch Med, Boston, MA USA. [Levin, Tomer T.; Naka-Blackstone, Anastazia] Mem Sloan Kettering Comprehens Canc Ctr, Dept Psychiat, New York, NY USA. [Levin, Tomer T.; Naka-Blackstone, Anastazia] Weill Cornell Med Coll, Dept Psychiat, New York, NY USA. [Slovin, Susan; Carvajal, Richard D.; O'Reilly, Eileen M.; Keohan, Mary Louise; Theodoulou, Maria; Dickler, Maura; Gerecitano, John F.; Morris, Michael; Epstein, Andrew S.; Noy, Ariela] Mem Sloan Kettering Comprehens Canc Ctr, Dept Med, New York, NY USA. [Slovin, Susan; Carvajal, Richard D.; O'Reilly, Eileen M.; Keohan, Mary Louise; Theodoulou, Maria; Dickler, Maura; Gerecitano, John F.; Morris, Michael; Epstein, Andrew S.; Noy, Ariela] Weill Cornell Med Coll, Deparment Med, New York, NY USA. RP Volandes, AE (reprint author), Massachusetts Gen Hosp, Gen Med Unit, Dept Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM avolandes@partners.org RI Levin, Tomer/D-2997-2016 OI Levin, Tomer/0000-0001-5054-5103 FU National Cancer Institute [R21CA139121]; Agency for Healthcare Research and Quality [K08HS018780] FX The project described was supported by award R21CA139121 from the National Cancer Institute. Dr. Volandes also was supported by grant K08HS018780 from the Agency for Healthcare Research and Quality. NR 21 TC 26 Z9 26 U1 3 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD SEP 1 PY 2012 VL 118 IS 17 BP 4331 EP 4338 DI 10.1002/cncr.27423 PG 8 WC Oncology SC Oncology GA 993GN UT WOS:000307845200031 PM 22252775 ER PT J AU Platzer, B Dehlink, E Turley, SJ Fiebiger, E AF Platzer, Barbara Dehlink, Eleonora Turley, Shannon J. Fiebiger, Edda TI How to connect an IgE-driven response with CTL activity? SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE AllergoOncology; Dendritic cells; Antigen presentation; Fc receptors; Fc epsilon RI; CD23 ID FC-EPSILON-RI; CELLS IN-VIVO; DENDRITIC CELLS; ANTIGEN PRESENTATION; CROSS-PRESENTATION; IMMUNE-COMPLEXES; RECEPTOR-I; EXPRESSION; INDUCTION; ALLERGY AB One of the goals of cell-based immune therapy in cancer is the induction of tumor-specific cytotoxic T-lymphocyte (CTL) responses. To achieve this objective, the ability of dendritic cells (DC) to cross-present tumor antigens can be exploited. One of the most efficient pathways for the induction of CTLs by cross-presentation is mediated by immunoglobulins of the IgG class, which are used by DCs to sample antigen in the form of immune complexes via Fc-gamma receptors. Could DCs use an IgE-mediated cross-presentation mechanism in a comparable manner to induce CTLs? We here discuss the potential of two human IgE Fc receptors, Fc epsilon RI and Fc epsilon RII, to serve as antigen uptake receptors for IgE-mediated cross-presentation. We conclude that the existence of an IgE-mediated cross-presentation pathway would provide a direct link between IgE-driven immune responses and CTL activity. C1 [Platzer, Barbara; Fiebiger, Edda] Childrens Hosp, Div Gastroenterol & Nutr, Boston, MA 02115 USA. [Platzer, Barbara; Fiebiger, Edda] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Dehlink, Eleonora] Med Univ Vienna, Dept Pediat & Adolescent Med, Div Pediat Pulmonol Allergol & Endocrinol, A-1090 Vienna, Austria. [Turley, Shannon J.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Turley, Shannon J.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. RP Fiebiger, E (reprint author), Childrens Hosp, Div Gastroenterol & Nutr, 300 Longwood Ave,Enders 630, Boston, MA 02115 USA. EM edda.fiebiger@childrens.harvard.edu FU National Institutes of Health [AI075037]; American Cancer Society FX We apologize to colleagues whose work was not cited in this manuscript due to space limitations. This work is supported by the National Institutes of Health grant AI075037 (to E. F.) and the American Cancer Society Research Scholar Award (to S.J.T). NR 38 TC 7 Z9 7 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD SEP PY 2012 VL 61 IS 9 BP 1521 EP 1525 DI 10.1007/s00262-011-1127-y PG 5 WC Oncology; Immunology SC Oncology; Immunology GA 995BK UT WOS:000307981300017 PM 22042251 ER PT J AU Thiagarajah, JR Verkman, AS AF Thiagarajah, J. R. Verkman, A. S. TI CFTR Inhibitors for Treating Diarrheal Disease SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID FLUID SECRETION; POTENT AB Secretory diarrhea remains a major health challenge worldwide. Excessive fluid secretion in the intestine caused by enterotoxins results in activation of luminal Cl- channels on enterocytes. The cystic fibrosis transmembrane conductance regulator (CFTR) protein is the major cyclic adenosine monophosphate (cAMP)-regulated Cl- channel activated in cholera as well as in diarrheas caused by other bacterial enterotoxins. Small-molecule screens have yielded CFTR inhibitors with half-maximal inhibitory concentration (IC50) values as low as 4 nmol/l. The data from proof-of-concept studies in animal models support the development of CFTR inhibitors for antidiarrheal therapy. C1 [Thiagarajah, J. R.; Verkman, A. S.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Thiagarajah, J. R.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Verkman, A. S.] Univ Calif San Francisco, Dept Physiol, San Francisco, CA USA. RP Verkman, AS (reprint author), Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. EM Alan.Verkman@ucsf.edu FU NIDDK NIH HHS [P30 DK072517] NR 5 TC 25 Z9 29 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD SEP PY 2012 VL 92 IS 3 BP 287 EP 290 DI 10.1038/clpt.2012.114 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 994PU UT WOS:000307944100009 PM 22850599 ER PT J AU Seifirad, S Keshavarz, A Taslimi, S Aran, S Abbasi, H Ghaffari, A AF Seifirad, Soroush Keshavarz, Amirhossein Taslimi, Shervin Aran, Shima Abbasi, Hamidreza Ghaffari, Alireza TI Effect of pirfenidone on pulmonary fibrosis due to paraquat poisoning in rats SO CLINICAL TOXICOLOGY LA English DT Article DE Drug therapy; Pirfenidone; Paraquat; Pulmonary fibrosis ID CHRONIC CYCLOSPORINE NEPHROTOXICITY; BLEOMYCIN HAMSTER MODEL; LUNG EPITHELIAL-CELLS; IN-VITRO; TRANSCRIPTIONAL LEVEL; LIPID-PEROXIDATION; GENE-EXPRESSION; APOPTOSIS; ACTIVATION; TOXICITY AB Background. This study investigated the effectiveness of pirfenidone compared with antioxidants, in the prevention of pulmonary fibrosis and increasing the survival in acutely paraquat poisoned rats. Methods. Five groups of ten rats were included in this study. Three groups were poisoned with intraperitoneal injection of 15 mg/kg paraquat. Among these poisoned groups, one group was treated with vitamin C (500 mg/kg, intraperitoneal), vitamin E (200 mg/kg, intraperitoneal) and N-acetylcysteine (250 mg/kg, intravenous); two others were treated with either normal saline or pirfenidone (200 mg/kg, intravenous); two groups were not poisoned and received normal saline or pirfenidone (200 mg/kg, intravenous). All injections except paraquat were repeated in four consecutive days. On the 15th day of study a semi-quantitative determination of lung fibrosis was done using Ashcroft staging criteria on the lung sections. Results. Pirfenidone decreased paraquat induced lung fibrosis (p < 0.001) while antioxidants did not decrease the lung fibrosis (p = 0.413). Life expectancy decreased in paraquat + normal saline (11 days, 95% CI 7.94-14.05) and paraquat + antioxidant (11 days, 95% CI 7.77-14.23) groups. The increase in the survival of rats in paraquat/pirfenidone group was insignificant (13.4 days, 95% CI 11.13-15.67). Conclusion. This study showed that pirfenidone is able to decrease pulmonary fibrosis following paraquat poisoning in a rat model. C1 [Seifirad, Soroush] Univ Tehran Med Sci, Endocrinol & Metab Res Ctr, Shariati Hosp, Tehran 1411413137, Iran. [Seifirad, Soroush; Keshavarz, Amirhossein; Taslimi, Shervin; Abbasi, Hamidreza] Univ Tehran Med Sci, Pulm & Crit Care Res Ctr, Tehran 1411413137, Iran. [Aran, Shima] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. [Ghaffari, Alireza] Tabriz Univ Med Sci, Dept Internal Med, Tabriz, Iran. RP Seifirad, S (reprint author), Univ Tehran Med Sci, Endocrinol & Metab Res Ctr, Shariati Hosp, N Kargar St, Tehran 1411413137, Iran. EM sseifirad@gmail.com OI Seifirad, Soroush/0000-0003-2598-1899 NR 40 TC 12 Z9 17 U1 1 U2 11 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 1556-3650 J9 CLIN TOXICOL JI Clin. Toxicol. PD SEP PY 2012 VL 50 IS 8 BP 754 EP 758 DI 10.3109/15563650.2012.718783 PG 5 WC Toxicology SC Toxicology GA 995GP UT WOS:000307996400006 PM 22924653 ER PT J AU Cooke, CR Kennedy, EH Wiitala, WL Almenoff, PL Sales, AE Iwashyna, TJ AF Cooke, Colin R. Kennedy, Edward H. Wiitala, Wyndy L. Almenoff, Peter L. Sales, Anne E. Iwashyna, Theodore J. TI Despite variation in volume, Veterans Affairs hospitals show consistent outcomes among patients with non-postoperative mechanical ventilation SO CRITICAL CARE MEDICINE LA English DT Article DE critical care; delivery of health care; health services research; intensive care units/organization and administration; respiratory insufficiency; risk adjustment ID UNIT RISK ADJUSTMENT; HEALTH-CARE-SYSTEM; QUALITY-OF-CARE; INTENSIVE-CARE; LONGITUDINAL DATA; PROPENSITY SCORE; MORTALITY; TRANSFORMATION; ORGANIZATION; REGRESSION AB Objective: To assess the relationship between volume of non-operative mechanically ventilated patients receiving care in a specific Veterans Health Administration hospital and their mortality. Design: Retrospective cohort study. Setting: One-hundred nineteen Veterans Health Administration medical centers. Patients: We identified 5,131 hospitalizations involving mechanically ventilated patients in an intensive care unit during 2009, who did not receive surgery. Interventions: None. Measurements and Main Results: We extracted demographic and clinical data from the VA Inpatient Evaluation Center. For each hospital, we defined volume as the total number of nonsurgical admissions receiving mechanical ventilation in an intensive care unit during 2009. We examined the hospital contribution to 30-day mortality using multilevel logistic regression models with a random intercept for each hospital. We quantified the extent of interhospital variation in 30-day mortality using the intraclass correlation coefficient and median odds ratio. We used generalized estimating equations to examine the relationship between volume and 30-day mortality and risk-adjusted all models using a patient-level prognostic score derived from clinical data representing the risk of death conditional on treatment at a high-volume hospital. Mean age for the sample was 65 (so 11) yrs, 97% were men, and 60% were white. The median VA hospital cared for 40 (interquartile range 19-62) mechanically ventilated patients in 2009. Crude 30-day mortality for these patients was 36.9%. After reliability and risk adjustment to the median patient, adjusted hospital-level mortality varied from 33.5% to 40.6%. The intraclass correlation coefficient for the hospital-level variation was 0.6% (95% confidence interval 0.1, 3.4%), with a median odds ratio of 1.15 (95% confidence interval 1.06, 1.38). The relationship between hospital volume of mechanically ventilated and 30-day mortality was not statistically significant: each 50-patient increase in volume was associated with a nonsignificant 2% decrease in the odds of death within 30 days (odds ratio 0.98, 95% confidence interval 0.87-1.10). Conclusions: Veterans Health Administration hospitals caring for lower volumes of mechanically ventilated patients do not have worse mortality. Mechanisms underlying this finding are unclear, but, if elucidated, may offer other integrated health systems ways to overcome the disadvantages of small-volume centers in achieving good outcomes. (Crit Care Med 2012; 40:2569-2575) C1 Univ Michigan, Ctr Healthcare Outcomes & Policy, Ann Arbor, MI 48109 USA. [Kennedy, Edward H.; Wiitala, Wyndy L.; Sales, Anne E.; Iwashyna, Theodore J.] Ann Arbor VA Hlth Serv Res & Dev Ctr Excellence, VA Ctr Clin Management Res, Ann Arbor, MI USA. [Almenoff, Peter L.] Univ Kansas, Div Pulm Crit Care Med, Kansas City, KS USA. [Almenoff, Peter L.; Sales, Anne E.] US Dept Vet Affairs, Vet Hlth Adm, Off Informat & Analyt, Washington, DC USA. Univ Michigan, Dept Med, Div Pulm & Crit Care Med, Ann Arbor, MI 48109 USA. EM cookecr@umich.edu OI Sales, Anne/0000-0001-9360-3334; Iwashyna, Theodore/0000-0002-4226-9310; Cooke, Colin/0000-0001-9713-5371 FU U.S. Department of Veterans Affairs Health Services Research & Development Services [IIR 11-109] FX Supported, in part, by U.S. Department of Veterans Affairs Health Services Research & Development Services IIR 11-109 (TJI). NR 44 TC 19 Z9 19 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD SEP PY 2012 VL 40 IS 9 BP 2569 EP 2575 DI 10.1097/CCM.0b013e3182591eee PG 7 WC Critical Care Medicine SC General & Internal Medicine GA 992RP UT WOS:000307797700004 PM 22732289 ER PT J AU Hart, JL Kohn, R Halpern, SD AF Hart, Joanna L. Kohn, Rachel Halpern, Scott D. TI Perceptions of organ donation after circulatory determination of death among critical care physicians and nurses: A national survey SO CRITICAL CARE MEDICINE LA English DT Article DE conflict of interest; health personnel; organ transplantation; practice guidelines as topic; terminal care; tissue and organ procurement ID CARDIAC DEATH; UNITED-STATES; ATTITUDES; DONORS AB Objective: We sought to identify factors related to critical care physicians' and nurses' willingness to help manage potential donors after circulatory determination of death, and to elicit opinions on the presence of role conflict in donors after circulatory determination of death and its impact on end-of-life care. Design and Setting: Randomized trial administered by Web or post of four donors after circulatory determination of death vignettes. Response rates were 31.0% and 44.3%, respectively. Subjects: Two thousand two hundred and six academic intensive care unit physicians and 988 intensive care unit nurses in the United States. Measurements and Main Results: Majorities of intensive care unit physicians (72.5%; 95% confidence interval 69.2-75.9) and nurses (74.3%; 95% confidence interval 70.2-78.5) believed they should help manage potential donors after circulatory determination of death. 14.7% (95% confidence interval 12.0-17.4) of physicians and 14.3% (95% confidence interval 11.0-17.6) of nurses believed that management of donors after circulatory determination of death would create professional role conflicts. 33.8% (95% confidence interval 30.0-37.4) of physicians and 55.1% (95% confidence interval 50.3-59.7) of nurses believed that preserving opportunities for donors after circulatory determination of death could improve end-of-life care. More favorable views of donors after circulatory determination of death were provided by clinicians randomly assigned to vignettes depicting donors with previously denoted preferences for organ donation; similar effects were not introduced by vignettes in which surrogates actively initiated donation discussions. Conclusions: These findings suggest that critical care physicians and nurses are generally supportive of managing donors after circulatory determination of death, particularly when patients were registered organ donors. However, minorities of clinicians harbor concerns regarding conflicts of interest, and many are uncertain of the practice's impact on end-of-life care. (Crit Care Med 2012; 40:2595-2600) C1 [Hart, Joanna L.; Halpern, Scott D.] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Hart, Joanna L.; Halpern, Scott D.] Univ Penn, Perelman Sch Med, FIELDS Program, Philadelphia, PA 19104 USA. [Halpern, Scott D.] Univ Penn, Perelman Sch Med, Ctr Hlth Incent & Behav Econ, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Halpern, Scott D.] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Kohn, Rachel] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Hart, JL (reprint author), Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA. EM shalpern@exchange.upenn.edu FU Greenwall Foundation Faculty Scholar Award in Bioethics FX Supported, in part, by Greenwall Foundation Faculty Scholar Award in Bioethics (SDH). NR 27 TC 11 Z9 11 U1 3 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD SEP PY 2012 VL 40 IS 9 BP 2595 EP 2600 DI 10.1097/CCM.0b013e3182590098 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA 992RP UT WOS:000307797700008 PM 22732286 ER PT J AU Soto, GJ Frank, AJ Christiani, DC Gong, MN AF Soto, Graciela J. Frank, Angela J. Christiani, David C. Gong, Michelle Ng TI Body mass index and acute kidney injury in the acute respiratory distress syndrome SO CRITICAL CARE MEDICINE LA English DT Article DE acute kidney injury; acute respiratory distress syndrome; body mass index; mortality; obesity ID ACUTE-RENAL-FAILURE; ACUTE LUNG INJURY; CRITICALLY-ILL PATIENTS; INTENSIVE-CARE-UNIT; MECHANICALLY VENTILATED PATIENTS; HOSPITALIZED-PATIENTS; INTERLEUKIN-18 LEVELS; CONSENSUS CONFERENCE; INSULIN-RESISTANCE; METABOLIC SYNDROME AB Objectives: Obesity is increasingly encountered in intensive care units but the relationship between obesity and acute kidney injury is unclear. We aimed to evaluate whether body mass index was associated with acute kidney injury in the acute respiratory distress syndrome and to examine the association between acute kidney injury and mortality in patients with and without obesity. Design: Retrospective study. Setting: Massachusetts General Hospital and Beth Israel Deaconess Medical Center. Patients: Seven hundred fifty-one patients with acute respiratory distress syndrome. Interventions: None. Measurements and Main Results: Acute kidney injury was defined as meeting the "Risk" category according to modified Risk, Injury, Failure, Loss, End-stage criteria based on creatinine and glomerular filtration rate because urine output was only available on the day of intensive care unit admission. Body mass index was calculated from height and weight at intensive care unit admission. The prevalence of acute kidney injury increased significantly with increasing weight (p = .01). The odds of acute kidney injury were twice in obese and severely obese patients compared to patients with normal body mass index, after adjusting for predictors of acute kidney injury (age, diabetes, Acute Physiology and Chronic Health Evaluation III, aspiration, vasopressor use, and thrombocytopenia [platelets <= 80,000/mm(3)]). After adjusting for the same predictors, body mass index was significantly associated with acute kidney injury (odds ratio(adj) 1.20 per 5 kg/m(2) increase in body mass index, 95% confidence interval 1.07-1.33). On multivariate analysis, acute kidney injury was associated with increased acute respiratory distress syndrome mortality (odds ratioad, 2.76, 95% confidence interval 1.72-4.42) whereas body mass index was associated with decreased mortality (odds ratio(adj) 0.81 per 5 kg/m(2) increase in body mass index, 95% confidence interval 0.71-0.93) after adjusting for mortality predictors. Conclusions: In acute respiratory distress syndrome patients, obesity is associated with increased development of acute kidney injury, which is not completely explained by severity of illness or shock. Although increased body mass index is associated with decreased mortality, acute kidney injury remained associated with higher mortality even after adjusting for body mass index. (Crit Care Med 2012; 40:2601-2608) C1 [Soto, Graciela J.; Gong, Michelle Ng] Montefiore Med Ctr, Dept Med, Jay B Langner Crit Care Serv, Div Crit Care Med, Bronx, NY 10467 USA. [Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm & Occupat Med & Epidemiol Program, Boston, MA 02115 USA. [Frank, Angela J.; Christiani, David C.] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Gong, Michelle Ng] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. RP Soto, GJ (reprint author), Montefiore Med Ctr, Dept Med, Jay B Langner Crit Care Serv, Div Crit Care Med, 111 E 210th St, Bronx, NY 10467 USA. EM gsoto@montefiore.org FU National Heart, Lung, and Blood Institute (Massachusetts General Hospital, Boston, MA) [R01 HL 84060, R01 HL 86667, R01 HL 60710]; National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) [UL1 RR025750, KL2 RR025749, TL1 RR025748]; NIH roadmap for Medical Research FX Supported, in part, by research grants R01 HL 84060, R01 HL 86667, and R01 HL 60710 from the National Heart, Lung, and Blood Institute (Massachusetts General Hospital, Boston, MA); and by the Clinical and Translational Science Awards Grant UL1 RR025750, KL2 RR025749, and TL1 RR025748 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessary represent The official view of the NCRR or NIH (Albert Einstein College of Medicine, Bronx, NY). NR 51 TC 25 Z9 26 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD SEP PY 2012 VL 40 IS 9 BP 2601 EP 2608 DI 10.1097/CCM.0b013e3182591ed9 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 992RP UT WOS:000307797700009 PM 22732288 ER PT J AU Yager, PH Cummings, BM Whalen, MJ Noviski, N AF Yager, Phoebe H. Cummings, Brian M. Whalen, Michael J. Noviski, Natan TI Nighttime telecommunication between remote staff intensivists and bedside personnel in a pediatric intensive care unit: A retrospective study SO CRITICAL CARE MEDICINE LA English DT Article DE communication; critical care; pediatrics; pediatric intensive care unit; staffing models; telemedicine ID ECONOMIC OUTCOMES; TELEMEDICINE; PARADIGM AB Objective: To investigate the hypothesis that nighttime telemedicine can help staff intensivists remotely manage patients in a pediatric intensive care unit, preserve continuity of care, communicate with the bedside team, and provide reassurance to families in a unit where fellows provide nighttime, onsite care, with supervision by staff intensivists available by pager. Design: A retrospective review. Setting: A pediatric intensive care unit in an academic, tertiary medical center with telemedicine capability, including a mobile telemedicine cart in the pediatric intensive care unit and a home-based unit for each pediatric staff intensivist. Patients: Critically ill pediatric patients between 0 and 19 yrs, who were admitted to the pediatric intensive care unit between May 2010 and July 2011 and were managed via telemedicine. Interventions: Consecutive intake forms completed by staff intensivists following each telemedicine encounter were reviewed. Main Results: Fifty-six consecutive intake forms were evaluated for the study period. Connectivity was established in 95% of attempts. Audio and video qualities were excellent 94% and 85% of the time, respectively. The median call duration was 15 mins. The pediatric critical care fellow was present for 100% of calls, nurses 68%, and parents 66%. Reasons for initiating the call were "patient assessment" (98%), "team meeting" (25%), and/or parent update (40%). "Patient assessment," "communication with multidisciplinary care team," and "communication with a patient's family" were the outcomes most often cited that would not have been possible via telephone. A change in medical management was noted following 32% of encounters. Conclusions: This study demonstrates that nighttime telecommunication linking staff intensivists on home-call with pediatric intensive care unit bedside care providers, patients, and their families is technologically feasible and may enhance team communication, provide reassurance to families, and impact patient management. (Crit Care Med 2012; 40:2700-2703) C1 [Yager, Phoebe H.; Cummings, Brian M.; Whalen, Michael J.; Noviski, Natan] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. RP Yager, PH (reprint author), Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. EM nnoviski@partners.org FU Department of Pediatrics, Massachusetts General Hospital FX Departmental funding is provided by the Department of Pediatrics, Massachusetts General Hospital. NR 19 TC 11 Z9 11 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD SEP PY 2012 VL 40 IS 9 BP 2700 EP 2703 DI 10.1097/CCM.0b013e3182591dab PG 4 WC Critical Care Medicine SC General & Internal Medicine GA 992RP UT WOS:000307797700022 PM 22732287 ER PT J AU Singla, A Kumar, G Bardia, A AF Singla, Abhishek Kumar, Gautam Bardia, Aditya TI Personalizing cardiovascular disease prevention among breast cancer survivors SO CURRENT OPINION IN CARDIOLOGY LA English DT Review DE aspirin; breast cancer; cardiovascular risk; personalized medicine; prevention ID ANGIOTENSIN RECEPTOR BLOCKERS; RANDOMIZED CONTROLLED-TRIALS; ADJUVANT ENDOCRINE THERAPY; PRACTICE GUIDELINE UPDATE; CONGESTIVE-HEART-FAILURE; CAUSE-SPECIFIC MORTALITY; CARDIAC RISK-FACTORS; LONG-TERM SURVIVORS; PHYSICAL-ACTIVITY; POSTMENOPAUSAL WOMEN AB Purpose of review With the advancement of breast cancer therapies, most women diagnosed with breast cancer in the United States are now expected to survive their disease, and management of competing comorbidities, particularly cardiovascular disease (CVD), is crucial. Recent findings Recent studies have suggested that CVD is the most common cause of death for women diagnosed with ductal carcinoma in situ or stage I disease and for women aged more than 80 years with stage II disease. Various breast cancer therapies, including targeted therapies, can accentuate CVD risk; referrals for cardiology opinion are not uncommon at the time at which treatment options are under consideration. The use of less cardiotoxic alternatives, such as liposomal doxorubicin, and intensity-modulated radiation therapy should be considered when appropriate. Doppler myocardial imaging and cardiac MRI might allow early recognition of cardiotoxicity. Summary It is important to weigh both the risk of CVD and that of breast cancer recurrence in a breast cancer survivor. Certain interventions for the primary prevention of CVD, including diet, physical activity, smoking cessation and aspirin, can reduce breast cancer risk as well. The management of CVD risk factors is of increasing importance in the management of breast cancer survivors. C1 [Bardia, Aditya] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. [Singla, Abhishek] Creighton Univ, Dept Med, Omaha, NE 68178 USA. [Kumar, Gautam] Emory Univ, Div Cardiol, Atlanta, GA 30322 USA. RP Bardia, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Profess Off,Bldg 214,10N Grove St, Boston, MA 02114 USA. EM Bardia.Aditya@mgh.harvard.edu NR 136 TC 5 Z9 5 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0268-4705 J9 CURR OPIN CARDIOL JI Curr. Opin. Cardiol. PD SEP PY 2012 VL 27 IS 5 BP 515 EP 524 DI 10.1097/HCO.0b013e3283570040 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 991EM UT WOS:000307684300008 PM 22874128 ER PT J AU Paski, SC Dominitz, JA AF Paski, Shirley C. Dominitz, Jason A. TI Endoscopic solutions to challenging enteral feeding problems SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Review DE enteral feeding; feeding tube; gastrostomy; jejunostomy ID GASTROSTOMY TUBE PLACEMENT; DOUBLE-BALLOON ENTEROSCOPY; Y GASTRIC BYPASS; JEJUNOSTOMY PLACEMENT; ACCESS; COMPLICATIONS; INSERTION; CHILDREN; STOMACH; PREVENT AB Purpose of review Enteral nutrition support is often required in patients who are unable to meet their own nutritional requirements. Endoscopists play a key role in the placement of enteral feeding catheters. This review focuses on the recently published solutions to common problems encountered during endoscopic placement of enteral feeding devices. Recent findings Case reports and case series describe solutions for overcoming common problems encountered during the placement of enteral feeding devices. Transnasal techniques can simplify nasojejunal tube placement, whereas deep enteroscopy techniques provide more reliable jejunostomy placement. Endoscopic ultrasound can help when transillumination is not possible or in the setting of postsurgical anatomy like Roux-en-Y. Laparoscopic-assisted procedures are useful when endoscopic techniques have failed in adults or in select high-risk pediatric patients. The American Society for Gastrointestinal Endoscopy and the American Gastroenterology Association both published comprehensive guidelines that outline the indications, contraindications, technical aspects of feeding catheter placement, and complications. Summary Advances in endoscopic techniques, including deep enteroscopy, endoscopic ultrasound, ultra-slim transnasal endoscopes and laparoscopic-assisted procedures, have enabled endoscopists to successfully place enteral feeding tubes in patients who previously required open procedures. C1 VA Puget Sound Healthcare Syst, Seattle, WA USA. Univ Washington, Sch Med, Dept Med, Div Gastroenterol, Seattle, WA 98195 USA. RP Paski, SC (reprint author), VAPSHCS S111GI, 1660 S Columbian Way, Seattle, WA 98108 USA. EM shirley.paski@va.gov OI Dominitz, Jason/0000-0002-8070-7086 FU American Society for Gastrointestinal Endoscopy Endoscopic Research Career Development Award (JAD); VA Puget Sound Healthcare System, Department of Veterans Affairs FX Grant Support: American Society for Gastrointestinal Endoscopy Endoscopic Research Career Development Award (JAD).; This material is based upon work supported by the VA Puget Sound Healthcare System, Department of Veterans Affairs. 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. NR 32 TC 3 Z9 4 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0267-1379 EI 1531-7056 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD SEP PY 2012 VL 28 IS 5 BP 427 EP 431 DI 10.1097/MOG.0b013e328355ecc9 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 991DI UT WOS:000307681300003 PM 22885942 ER PT J AU Warshaw, AL Lillemoe, KD Fernandez-del Castillo, C AF Warshaw, Andrew L. Lillemoe, Keith D. Fernandez-del Castillo, Carlos TI Pancreatic surgery for adenocarcinoma SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Review DE pancreatectomy; pancreatic cancer; pancreatic surgery ID EXPANDABLE METAL STENTS; CELIAC AXIS RESECTION; DISTAL PANCREATECTOMY; CANCER SURGERY; NEOADJUVANT THERAPY; ARTERIAL RESECTION; OUTCOMES; PANCREATICODUODENECTOMY; METAANALYSIS; SURVIVAL AB Purpose of review Pancreatic resection remains among the most formidable and complex of abdominal surgical operations. Nonetheless, recent observations have continued to provide incremental improvement in both our evidence for treatment regimens and the technology, resulting in better outcomes. Recent findings Neoadjuvant regimens appear to have promise, at least in local control and perhaps in long-term survival. More extensive operations focusing on perineural invasion along with minimally invasive laparoscopic and robotic techniques are attracting increasing attention. The effectiveness of major vascular resection remains controversial. Concentration of patients in centers of expertise has contributed to improved outcomes. Summary Improved management of pancreatic resections for cancer with more extensive and less-invasive surgical techniques has increased the number of patients who are candidates for effective surgical treatment. C1 [Warshaw, Andrew L.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Warshaw, AL (reprint author), Massachusetts Gen Hosp, Dept Surg, Bulfinch 370,55 Fruit St, Boston, MA 02114 USA. EM awarshaw@partners.org NR 56 TC 10 Z9 11 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD SEP PY 2012 VL 28 IS 5 BP 488 EP 493 DI 10.1097/MOG.0b013e3283567f2c PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 991DI UT WOS:000307681300011 PM 22782020 ER PT J AU Jacobson, CA Freedman, AS AF Jacobson, Caron A. Freedman, Arnold S. TI Early stage follicular lymphoma, current management and controversies SO CURRENT OPINION IN ONCOLOGY LA English DT Review DE chemoimmunotherapy; follicular lymphoma; minimal residual disease; observation; radiation therapy ID NON-HODGKINS-LYMPHOMA; TERM-FOLLOW-UP; LOW-GRADE; STANFORD-UNIVERSITY; RADIATION-THERAPY; RADIOTHERAPY; CLASSIFICATION; CHEMOTHERAPY; SURVIVAL; TRIAL AB Purpose of review In this article, we focus on the epidemiology, outcomes, and treatment options of early stage follicular lymphoma. Recent findings Radiation therapy has been the predominant treatment for patients with early stage follicular lymphoma for decades. It is associated with a 10-year progression-free survival of 45-60%, thought to represent cures in this otherwise incurable disease with conventional modalities. Limiting the radiation field and dose does not diminish outcomes. On the contrary, the addition of chemotherapy does not benefit this patient population as a whole. The use of polymerase chain reaction for Bcl-2 gene rearrangements to detect molecular disease, however, may identify patients with early occult disseminated disease, who are at risk for relapse and would benefit from the addition of systemic therapy. For patients in whom radiation would be too toxic or prefer to not have radiation, observation is a reasonable alternative and a proportion of patients observed do not require therapy for a number of years. Despite the potential cures achieved by radiation therapy, a minority of patients in the United States receive such therapy; the majority are instead observed or treated with chemoimmunotherapy. Summary Patients with early stage follicular lymphoma enjoy excellent outcomes following definitive radiation therapy, many of whom may even be cured. The addition of other therapies has not enhanced cure rates but identifying patients at greatest risk for disease relapse may change this paradigm. Despite the proven success of radiation, the majority of early stage follicular lymphoma patients in the United States do not receive radiation. C1 [Jacobson, Caron A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Hematol Malignancies,Div Med Oncol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Jacobson, CA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Hematol Malignancies,Div Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM cajacobson@partners.org NR 27 TC 6 Z9 6 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8746 J9 CURR OPIN ONCOL JI Curr. Opin. Oncol. PD SEP PY 2012 VL 24 IS 5 BP 475 EP 479 DI 10.1097/CCO.0b013e328356898b PG 5 WC Oncology SC Oncology GA 991DK UT WOS:000307681500003 PM 22820411 ER PT J AU Wang, P Moore, A AF Wang, Ping Moore, Anna TI Molecular Imaging of Stem Cell Transplantation for Neurodegenerative Diseases SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review DE Molecular imaging; stem cells; neurodegenerative diseases ID MARROW STROMAL CELLS; SPINAL-CORD-INJURY; IN-VIVO TRACKING; NEURAL PROGENITOR CELLS; POSITRON-EMISSION-TOMOGRAPHY; MAGNETIC-RESONANCE TRACKING; FOCAL CEREBRAL-ISCHEMIA; FETAL STRIATAL TRANSPLANTATION; PARKINSONS-DISEASE; HUNTINGTONS-DISEASE AB Cell replacement therapy with stem cells holds tremendous therapeutic potential for treating neurodegenerative diseases. Over the last decade, molecular imaging techniques have proven to be of great value in tracking transplanted cells and assessing the therapeutic efficacy. This current review summarizes the role and capabilities of different molecular imaging modalities including optical imaging, nuclear imaging and magnetic resonance imaging in the field of stem cell therapy for neurodegenerative disorders. We discuss current challenges and perspectives of these techniques and encompass updated information such as theranostic imaging and optogenetics in stem cell-based treatment of neurodegenerative diseases. C1 [Wang, Ping; Moore, Anna] Harvard Univ, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Massachusetts Gen Hosp, Mol Imaging Lab,Med Sch,Dept Radiol, Charlestown, MA 02129 USA. RP Moore, A (reprint author), Harvard Univ, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Massachusetts Gen Hosp, Mol Imaging Lab,Med Sch,Dept Radiol, Bldg 75,13th St, Charlestown, MA 02129 USA. EM amoore@helix.mgh.harvard.edu OI Wang, Ping/0000-0001-6712-8939 NR 186 TC 3 Z9 3 U1 1 U2 37 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PD SEP PY 2012 VL 18 IS 28 BP 4426 EP 4440 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 993QF UT WOS:000307873900011 PM 22788952 ER PT J AU Kulkarni, RN Mizrachi, EB Ocana, AG Stewart, AF AF Kulkarni, Rohit N. Mizrachi, Ernesto-Bernal Ocana, Adolfo Garcia Stewart, Andrew F. TI Human beta-cell Proliferation and Intracellular Signaling: Driving in the Dark Without a Road Map SO DIABETES LA English DT Article ID KINASE C-ZETA; INSULIN-RESISTANCE; CYCLIN D2; MAMMALIAN TARGET; IN-VIVO; TRANSCRIPTION FACTOR; DIABETES-MELLITUS; GLUCOSE-TOLERANCE; GROWTH-FACTOR; SECRETORY DEFECT AB A major goal in diabetes research is to find ways to enhance the mass and function of insulin secreting beta-cells in the endocrine pancreas to prevent and/or delay the onset or even reverse overt diabetes. In this Perspectives in Diabetes article, we highlight the contrast between the relatively large body of information that is available in regard to signaling pathways, proteins, and mechanisms that together provide a road map for efforts to regenerate beta-cells in rodents versus the scant information in human beta-cells. To reverse the state of ignorance regarding human beta-cell signaling, we suggest a series of questions for consideration by the scientific community to construct a human beta-cell proliferation road map. The hope is that the knowledge from the new studies will allow the community to move faster towards developing therapeutic approaches to enhance human beta-cell mass in the long-term goal of preventing and/or curing type 1 and type 2 diabetes. Diabetes 61:2205-2213, 2012 C1 [Kulkarni, Rohit N.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Kulkarni, Rohit N.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Mizrachi, Ernesto-Bernal] Univ Michigan, Div Metab Endocrinol & Diabet, Ann Arbor, MI 48109 USA. [Ocana, Adolfo Garcia; Stewart, Andrew F.] Univ Pittsburgh, Sch Med, Div Endocrinol, Pittsburgh, PA USA. RP Kulkarni, RN (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. EM rohit.kulkarni@joslin.harvard.edu; stewarta@pitt.edu FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)/National Institutes of Health (NIH) [R01-DK-67536, R21-RR-24905]; Juvenile Diabetes Research Foundation (JDRF) [17-2011-644]; NIDDK/NIH [R01-DK-73716, R01-DK-84236, R01-DK-77096, R01-DK-67351]; JDRF [46-2010-758, 1-2008-39, 34-2008-630]; American Diabetes Association (ADA) [7-06-CD-02]; ADA [1-10-BS-59]; NIDDK; Beta Cell Biology Consortium through NIH [U01-DK-089538, R01-DK-55023] FX This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)/National Institutes of Health (NIH) grants R01-DK-67536 and R21-RR-24905 and Juvenile Diabetes Research Foundation (JDRF) Grant 17-2011-644 (to R.N.K.), NIDDK/NIH grants R01-DK-73716 and R01-DK-84236, JDRF Grant 46-2010-758, and Career Development Award 7-06-CD-02 from the American Diabetes Association (ADA) (to E.-B.M.), NIDDK/NIH grants R01-DK-77096 and R01-DK-67351 and Research Award 1-10-BS-59 from the ADA (to A.G.O.), NIDDK and the Beta Cell Biology Consortium through NIH grants U01-DK-089538 and R01-DK-55023, and JDRF grants 1-2008-39 and 34-2008-630 (to A.F.S.). NR 93 TC 87 Z9 88 U1 1 U2 12 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 2012 VL 61 IS 9 BP 2205 EP 2213 DI 10.2337/db12-0018 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 998PY UT WOS:000308254100002 PM 22751699 ER PT J AU Ussar, S Bezy, O Bluher, M Kahn, CR AF Ussar, Siegfried Bezy, Olivier Blueher, Matthias Kahn, C. Ronald TI Glypican-4 Enhances Insulin Signaling via Interaction With the Insulin Receptor and Serves as a Novel Adipokine SO DIABETES LA English DT Article ID PHOSPHOLIPASE-D; ADIPOCYTE DIFFERENTIATION; METABOLIC SYNDROME; C/EBP-BETA; PRECURSOR CELLS; ADIPOSE-TISSUE; OBESITY; GLUCOSE; FAT; PHOSPHORYLATION AB Obesity, especially visceral obesity, is associated with insulin resistance and metabolic syndrome. We previously identified the cell surface proteoglycan glypican-4 as differentially expressed in subcutaneous versus visceral white fat depots. Here we show that glypican-4 is released from cells and adipose tissue explants of mice, and that circulating glypican-4 levels correlate with BMI and insulin sensitivity in humans. Furthermore, glypican-4 interacts with the insulin receptor, enhances insulin receptor signaling, and enhances adipocyte differentiation. Conversely, depletion of glypican-4 results in reduced activation of the insulin receptor and prevents adipocyte differentiation in vitro by inhibiting insulin-mediated C/EBP beta phosphorylation. These functions of glypican-4 are independent of its glycosylphosphatidylinositol membrane anchorage, as a nonmembrane-bound mutant of glypican-4 phenocopies the effects of native glypican-4 overexpression. In summary, glypican-4 is a novel circulating insulin sensitizing adipose-derived factor that, unlike other insulin sensitizers, acts directly on the insulin receptor to enhance signaling. Diabetes 61:2289-2298, 2012 C1 [Ussar, Siegfried; Bezy, Olivier; Kahn, C. Ronald] Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02215 USA. [Ussar, Siegfried; Bezy, Olivier; Kahn, C. Ronald] Harvard Univ, Sch Med, Boston, MA USA. [Blueher, Matthias] Univ Leipzig, Dept Med, Leipzig, Germany. RP Kahn, CR (reprint author), Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02215 USA. EM c.ronald.kahn@joslin.harvard.edu OI Ussar, Siegfried/0000-0001-7575-0920 FU National Institutes of Health [DK31036, DK82654]; Joslin DERC core laboratories [DK36836]; Mary K. Iacocca Professorship; Human Frontier Science Program; Deutsche Forschungsgemeinschaft [KFO 152, BL 833/1-1] FX The work was supported by National Institutes of Health grants DK31036 and DK82654, the Joslin DERC core laboratories (DK36836), the Mary K. Iacocca Professorship and the Human Frontier Science Program, and the Deutsche Forschungsgemeinschaft, KFO 152 (project BL 833/1-1). NR 32 TC 17 Z9 19 U1 1 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 2012 VL 61 IS 9 BP 2289 EP 2298 DI 10.2337/db11-1395 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 998PY UT WOS:000308254100016 PM 22751693 ER PT J AU Musen, G Jacobson, AM Bolo, NR Simonson, DC Shenton, ME McCartney, RL Flores, VL Hoogenboom, WS AF Musen, Gail Jacobson, Alan M. Bolo, Nicolas R. Simonson, Donald C. Shenton, Martha E. McCartney, Richard L. Flores, Veronica L. Hoogenboom, Wouter S. TI Resting-State Brain Functional Connectivity Is Altered in Type 2 Diabetes SO DIABETES LA English DT Article ID INSULIN-RESISTANCE; ADULTS AB Type 2 diabetes mellitus (T2DM) is a risk factor for Alzheimer disease (AD). Populations at risk for AD show altered brain activity in the default mode network (DMN) before cognitive dysfunction. We evaluated this brain pattern in T2DM patients. We compared T2DM patients (n = 10, age = 56 +/- 2.2 years, fasting plasma glucose [FPG] = 8.4 +/- 1.3 mmol/L, HbA(1c) = 7.5 +/- 0.54%) with nondiabetic age-matched control subjects (n = 11, age = 54 +/- 1.8 years, FPG = 4.8 +/- 0.2 mmol/L) using resting-state functional magnetic resonance imaging to evaluate functional connectivity strength among DMN regions. We also evaluated hippocampal volume, cognition, and insulin sensitivity by homeostasis model assessment of insulin resistance (HOMA-IR). Control subjects showed stronger correlations versus T2DM patients in the DMN between the seed (posterior cingulate) and bilateral middle temporal gyrus (beta = 0.67 vs. 0.43), the right inferior and left medial frontal gyri (beta = 0.75 vs. 0.54), and the left thalamus (beta = 0.59 vs. 0.37), respectively, with no group differences in cognition or hippocampal size. In T2DM patients, HOMA-IR was inversely correlated with functional connectivity in the right inferior frontal gyrus and precuneus. T2DM patients showed reduced functional connectivity in the DMN compared with control subjects, which was associated with insulin resistance in selected brain regions, but there were no group effects of brain structure or cognition. Diabetes 61:2375-2379, 2012 C1 [Musen, Gail; Jacobson, Alan M.; McCartney, Richard L.; Flores, Veronica L.; Hoogenboom, Wouter S.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Musen, Gail; Jacobson, Alan M.; Bolo, Nicolas R.; Shenton, Martha E.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Jacobson, Alan M.] Winthrop Univ Hosp, Mineola, NY 11501 USA. [Bolo, Nicolas R.] Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA. [Bolo, Nicolas R.] McLean Hosp, Brain Imaging Ctr, Belmont, MA 02178 USA. [Simonson, Donald C.] Brigham & Womens Hosp, Dept Med, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. [Simonson, Donald C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Shenton, Martha E.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Shenton, Martha E.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Shenton, Martha E.] Brigham & Womens Hosp, Dept Psychiat & Behav Sci Imaging, Boston, MA 02115 USA. [Shenton, Martha E.; Hoogenboom, Wouter S.] Brigham & Womens Hosp, Psychiat Neuroimaging Lab, Boston, MA 02115 USA. [Shenton, Martha E.] Harvard Univ, Sch Med, Neurosci Lab, Clin Neurosci Div,VA Boston Healthcare Syst, Brockton, MA 02401 USA. RP Musen, G (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM gail.musen@joslin.harvard.edu FU National Institutes of Health [5R01-AG-034165-A2, P30-DK-36836]; Herbert Graetz Fund FX This study was supported in part by National Institutes of Health grants 5R01-AG-034165-A2 (G.M.) and P30-DK-36836 (to the Joslin Diabetes and Endocrinology Research Center) and by the Herbert Graetz Fund. NR 25 TC 81 Z9 95 U1 2 U2 14 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 2012 VL 61 IS 9 BP 2375 EP 2379 DI 10.2337/db11-1669 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 998PY UT WOS:000308254100025 PM 22664957 ER PT J AU Thameem, F Puppala, S Schneider, J Bhandari, B Arya, R Arar, NH Vasylyeva, TL Farook, VS Fowler, S Almasy, L Blangero, J Duggirala, R Abboud, HE AF Thameem, Farook Puppala, Sobha Schneider, Jennifer Bhandari, Basant Arya, Rector Arar, Nedal H. Vasylyeva, Tetyana L. Farook, Vidya S. Fowler, Sharon Almasy, Laura Blangero, John Duggirala, Ravindranath Abboud, Hanna E. TI The Gly(972)Arrg Variant of Human IRS1 Gene Is Associated with Variation in Glomerular Filtration Rate Likely Through Impaired Insulin Receptor Signaling SO DIABETES LA English DT Article ID DEPENDENT DIABETES-MELLITUS; AMINO-ACID POLYMORPHISM; CHRONIC KIDNEY-DISEASE; WIDE LINKAGE SCANS; SERUM CREATININE; MEXICAN-AMERICANS; SUBSTRATE-1 GENE; RENAL-FUNCTION; MEASURED GENOTYPE; G972R VARIANT AB The objective of this study is to identify and characterize the genetic variants related to the glomerular filtration rate (GFR) linkage on 2q37. Of the positional candidate genes, we selected IRS1 and resequenced its 2-kb promoter region and exons for sequence variants in 32 subjects. A total of 11 single nucleotide polymorphisms (SNPs) were identified. To comprehensively cover the 59-kb-long intron-1, eight additional tagging SNPs were selected from the HapMap. All the 19 SNPs were genotyped by TaqMan Assay in the entire data set (N = 670; 39 families). Association analyses between the SNPs and GFR and type 2 diabetes-related traits were performed using the measured genotype approach. Of the SNPs examined for association, only the Gly(972) Arg variant of IRS1 exhibited a significant association with GFR (P = 0.0006) and serum triglycerides levels (P = 0.003), after accounting for trait-specific covariate effects. Carriers of Arg972 had significantly decreased GFR values. Gly(972)Arg contributed to 26% of the linkage signal on 2q. Expression of IRS1 mutant Arg972 in human mesangial cells significantly reduced the insulin-stimulated phosphorylation of IRS1 and Akt kinase. Taken together, the data provide the first evidence that genetic variation in IRS1 may influence variation in GFR probably through impaired insulin receptor signaling. Diabetes 61:2385-2393,2012 C1 [Thameem, Farook; Bhandari, Basant; Arar, Nedal H.; Vasylyeva, Tetyana L.; Abboud, Hanna E.] Univ Texas Hlth Sci Ctr San Antonio, Div Nephrol, San Antonio, TX 78229 USA. [Puppala, Sobha; Schneider, Jennifer; Farook, Vidya S.; Almasy, Laura; Blangero, John; Duggirala, Ravindranath] Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA. [Arya, Rector] Univ Texas Hlth Sci Ctr San Antonio, Dept Pediat, San Antonio, TX 78229 USA. [Arar, Nedal H.; Abboud, Hanna E.] S Texas Vet Healthcare Syst, San Antonio, TX USA. [Fowler, Sharon] Univ Texas Hlth Sci Ctr San Antonio, Div Clin Epidemiol, Dept Med, San Antonio, TX 78229 USA. RP Thameem, F (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Div Nephrol, San Antonio, TX 78229 USA. EM thameem@uthscsa.edu RI Abu Laban , Dr. Nidal /E-5809-2011 FU American Heart Association [0855175F]; American Society of Nephrology; Satellite Healthcare; Diabetes Action Research and Education Foundation; National Institute of Diabetes and Digestive and Kidney Diseases [DK-42273, DK-47482, DK-53889]; VA-Merit Review; National Center for Research Resources [RR025767, KL2 RR025766] FX This study was supported by a grant-in-aid award (0855175F) (F.T.) from the American Heart Association, the Carl W. Gottschalk Research Scholar Award from the American Society of Nephrology (F.T.), the Norman S. Coplon Award from Satellite Healthcare (F.T.), and the Diabetes Action Research and Education Foundation (F.T.). This work was also supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (DK-42273, DK-47482, and DK-53889 [to R.D.]) and VA-Merit Review and the National Center for Research Resources Contracts UL1 RR025767 and KL2 RR025766 for the Institute for Integration of Medicine and Science. NR 52 TC 18 Z9 19 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 2012 VL 61 IS 9 BP 2385 EP 2393 DI 10.2337/db11-1078 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 998PY UT WOS:000308254100027 PM 22617042 ER PT J AU Hong, ES Khang, AR Yoon, JW Kang, SM Choi, SH Park, KS Jang, HC Shin, H Walford, GA Lim, S AF Hong, E. S. Khang, A. R. Yoon, J. W. Kang, S. M. Choi, S. H. Park, K. S. Jang, H. C. Shin, H. Walford, G. A. Lim, S. TI Comparison between sitagliptin as add-on therapy to insulin and insulin dose-increase therapy in uncontrolled Korean type 2 diabetes: CSI study SO DIABETES OBESITY & METABOLISM LA English DT Article DE ss-cell function; hypoglycaemia; insulin; sitagliptin; weight gain ID DIPEPTIDYL PEPTIDASE-4 INHIBITOR; BETA-CELL FUNCTION; RANDOMIZED CONTROLLED-TRIAL; TWICE-DAILY EXENATIDE; GLYCEMIC CONTROL; BASAL INSULIN; GLUCOSE-TOLERANCE; TREATED PATIENTS; NON-INFERIORITY; DOUBLE-BLIND AB Aim: Individuals requiring insulin therapy for type 2 diabetes often require escalation of their regimen to achieve glycaemic control. Optimal management strategies for uncontrolled type 2 diabetes would improve glycaemic control without hypoglycaemia and weight gain. This study compared the efficacy and tolerability of adding sitagliptin, an oral dipeptidyl peptidase-4 inhibitor, and an up to 20% increase in insulin dose in patients with uncontrolled type 2 diabetes on insulin therapy. Methods: We conducted a 24-week, randomized, active-competitor, parallel-group study in subjects with uncontrolled type 2 diabetes [haemoglobin A1c (HbA1c) = 7.5-11%] currently using insulin therapy. Subjects were randomly assigned to either the sitagliptin adding (100 mg daily, n = 70) or an insulin-increasing arm (>= 10% at week 12 and >= 10% at week 24, n = 70) while continuing other medications. Results: Average baseline HbA1c was 9.2% in both groups. HbA1c decreased more at 24 weeks in the sitagliptin adding than the insulin-increasing arm (-0.6 +/- 0.1% vs. -0.2 +/- 0.1%, p < 0.01). Insulin was increased by 25% at 24 weeks in the insulin-increasing group. Hypoglycaemic events were less common and less severe in sitagliptin adding arm than insulin-increasing arm (7.0 vs. 14.3 events per patient-year, p < 0.05). Weight was stable in the sitagliptin adding subjects (68.6 +/- 11.6 vs. 68.1 +/- 11.4 kg) but increased in the insulin-increasing subjects (66.2 +/- 10.6 vs. 67.4 +/- 9.7 kg, p < 0.05). Other adverse events occurred at similar rates in both arms. Conclusions: Compared to a 25% increase in insulin dose, adding sitagliptin to an insulin-based regimen was more effective at lowering HbA1c and associated with less hypoglycaemia and weight gain over 24 weeks. Clinical trial number: NCT01100125. C1 [Hong, E. S.; Kang, S. M.; Choi, S. H.; Jang, H. C.; Lim, S.] Seoul Natl Univ, Bundang Hosp, Dept Internal Med, Songnam 463707, Gyeonggi Do, South Korea. [Hong, E. S.; Khang, A. R.; Yoon, J. W.; Kang, S. M.; Choi, S. H.; Park, K. S.; Jang, H. C.; Lim, S.] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 151, South Korea. [Shin, H.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Walford, G. A.] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. [Walford, G. A.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Lim, S (reprint author), Seoul Natl Univ, Bundang Hosp, Dept Internal Med, 300 Gumi Dong Bundang Gu, Songnam 463707, Gyeonggi Do, South Korea. EM limsoo@snu.ac.kr RI Park, Kyong Soo/C-2265-2008 OI Park, Kyong Soo/0000-0003-3597-342X FU National Research Foundation; Korea government [2006-2005410]; Seoul National University Bundang Hospital [02-2008-036] FX This study was supported by the National Research Foundation grant funded by the Korea government (2006-2005410) and a research grant (02-2008-036) from the Seoul National University Bundang Hospital. Statistical analyses were aided by consultation with the Medical Research Collaborating Center of Seoul National University Bundang Hospital (Soyeon Ahn, PhD). NR 49 TC 32 Z9 34 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1462-8902 J9 DIABETES OBES METAB JI Diabetes Obes. Metab. PD SEP PY 2012 VL 14 IS 9 BP 795 EP 802 DI 10.1111/j.1463-1326.2012.01600.x PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 979HJ UT WOS:000306807800004 PM 22443183 ER PT J AU Sihag, S Wright, CD Wain, JC Gaissert, HA Lanuti, M Allan, JS Mathisen, DJ Morse, CR AF Sihag, Smita Wright, Cameron D. Wain, John C. Gaissert, Henning A. Lanuti, Michael Allan, James S. Mathisen, Douglas J. Morse, Christopher R. TI Comparison of perioperative outcomes following open versus minimally invasive Ivor Lewis oesophagectomy at a single, high-volume centre SO EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY LA English DT Article DE Oesophagectomy; Minimally invasive; Outcomes; Oesophageal cancer ID PULMONARY COMPLICATIONS; TRANSTHORACIC ESOPHAGECTOMY; CANCER; MORTALITY; PREDICTION; MORBIDITY; TRIAL; RISK AB With the increasing popularity of minimally invasive oesophageal resections, equivalence, if not superiority, to open techniques must be demonstrated. Here we compare our open and minimally invasive Ivor Lewis oesophagectomy (MIE) experience. A prospective database of all oesophagectomies performed at Massachusetts General Hospital in Boston, MA between November 2007 and January 2011 was analysed. A total of 38 MIE and 76 open Ivor Lewis (OIE) oesophagectomies were performed for oesophageal carcinoma. Sixty-day surgical, oncological and postoperative outcomes were examined between the two groups. Groups had similar demographics in terms of age, gender, tumour histology, clinical stage, preoperative comorbidities and neoadjuvant therapy. No difference was found with respect to adequacy of oncological resections. The median number of lymph nodes retrieved (OIE: 21, inter-quartile range (IQR): (16, 27) versus MIE: 19, IQR: (15, 28)), resection margins (OIE: 6.6% positive versus MIE: no positive margins) and 60-day mortality (OIE: 2.6% versus MIE: no deaths) were comparable. However, rates of pulmonary complications were significantly lower in the MIE group (OIE: 43.4 versus MIE: 2.6%, P < 0.001). Additionally, the median length of ICU and hospital stay, intraoperative blood loss and amount of intravenous fluids infused intraoperatively were also significantly decreased with MIE, while median operative times and the requirement for intraoperative blood transfusion were not significantly different between the two groups. Multivariate logistic regression analysis identified MIE as the only variable associated with a significant reduction in the rate of pulmonary complications in our study, while pre-existing pulmonary comborbidity was associated with an increased risk of pulmonary complications. Open and MIE appear equivalent with regard to early oncological outcomes. A minimally invasive approach, however, appears to lead to a significant reduction in the rate of postoperative pulmonary complications. Length of ICU and hospital stay, as well as intraoperative blood loss and intravenous fluid requirements are also reduced in the setting of MIE. Long-term survival data will need to be followed closely. A large, multi-centred, randomized, controlled trial is warranted to confirm these results. C1 [Sihag, Smita; Wright, Cameron D.; Wain, John C.; Gaissert, Henning A.; Lanuti, Michael; Allan, James S.; Mathisen, Douglas J.; Morse, Christopher R.] Massachusetts Gen Hosp, Dept Thorac Surg, Boston, MA 02114 USA. RP Morse, CR (reprint author), Massachusetts Gen Hosp, Dept Thorac Surg, 55 Fruit St,Blake 1570, Boston, MA 02114 USA. EM crmorse@partners.org FU Thoracic Surgery Foundation for Research and Education Research Fellowship FX This study was supported by a Thoracic Surgery Foundation for Research and Education Research Fellowship (SS). NR 27 TC 29 Z9 39 U1 1 U2 11 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1010-7940 J9 EUR J CARDIO-THORAC JI Eur. J. Cardio-Thorac. Surg. PD SEP PY 2012 VL 42 IS 3 BP 430 EP 437 DI 10.1093/ejcts/ezs031 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 992NP UT WOS:000307784500010 PM 22345284 ER PT J AU Sinclair, SJ Siefert, CJ Slavin-Mulford, JM Stein, MB Renna, M Blais, MA AF Sinclair, Samuel Justin Siefert, Caleb J. Slavin-Mulford, Jenelle M. Stein, Michelle B. Renna, Megan Blais, Mark A. TI Psychometric Evaluation and Normative Data for the Depression, Anxiety, and Stress Scales-21 (DASS-21) in a Nonclinical Sample of U.S. Adults SO EVALUATION & THE HEALTH PROFESSIONS LA English DT Article DE depression; anxiety; stress; DASS-21; psychometric ID OUTCOMES; VALIDATION; STATES; SENSE AB Health care professionals are coming under increased pressure to empirically monitor patient outcomes across settings as a means of improving clinical practice. Within the psychiatric and primary care communities, many have begun utilizing brief psychometric measures of psychological functioning to accomplish these goals. The purpose of this study was to evaluate the psychometric properties and clinical utility of the Depression, Anxiety, and Stress Scales-21-item version (DASS-21), and contribute normative data to facilitate interpretation using a sample of U.S. adults (N = 503). Item-scale convergence was generally supported, although assumptions of item-scale divergence were not met. Only 86%, 50%, and 43% of Depression, Anxiety, and Stress items, respectively, correlated significantly greater with their hypothesized scales than other scales. Internal consistency reliability was acceptable for all scales and comparable to existing research (alpha s = .91, .80, and .84 for Depression, Anxiety, and Stress, respectively). Scale-level correlations were greater than what has been reported elsewhere (range of rs = .68 to .73), and principal components analysis supported the extraction of only one component accounting for 47% of the item-level variance. However, confirmatory factor analysis (CFA) favored a three-factor structure when compared to a one-factor model. The implications for the health care professions are discussed. C1 [Sinclair, Samuel Justin; Slavin-Mulford, Jenelle M.; Stein, Michelle B.; Renna, Megan; Blais, Mark A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sinclair, Samuel Justin] Harvard Univ, Sch Med, Psychol Evaluat & Res Lab PEaRL, Boston, MA USA. [Siefert, Caleb J.] Univ Michigan, Deerborn, MI USA. RP Sinclair, SJ (reprint author), Massachusetts Gen Hosp, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM JSincl@Post.Harvard.Edu NR 27 TC 36 Z9 36 U1 20 U2 67 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0163-2787 J9 EVAL HEALTH PROF JI Eval. Health Prof. PD SEP PY 2012 VL 35 IS 3 BP 259 EP 279 DI 10.1177/0163278711424282 PG 21 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 984FL UT WOS:000307175400001 PM 22008979 ER PT J AU Lionetto, L Negro, A Palmisani, S Gentile, G Del Fiore, MR Mercieri, M Simmaco, M Smith, T Al-Kaisy, A Arcioni, R Martelletti, P AF Lionetto, Luana Negro, Andrea Palmisani, Stefano Gentile, Giovanna Del Fiore, Maria Rosaria Mercieri, Marco Simmaco, Maurizio Smith, Thomas Al-Kaisy, Adnan Arcioni, Roberto Martelletti, Paolo TI Emerging treatment for chronic migraine and refractory chronic migraine SO EXPERT OPINION ON EMERGING DRUGS LA English DT Review DE antiepileptic drugs; chronic migraine; neuromodulation; onabotulinumtoxinA; refractory chronic migraine ID TOXIN TYPE-A; CHRONIC DAILY HEADACHE; TENSION-TYPE HEADACHE; PLACEBO-CONTROLLED PHASE; OCCIPITAL NERVE-STIMULATION; PREEMPT CLINICAL-PROGRAM; QUALITY-OF-LIFE; BOTULINUM-TOXIN; DOUBLE-BLIND; PROPHYLACTIC TREATMENT AB Introduction: Chronic migraine (CM), the suffering of 15 or more headache days with at least 8 of these migraine days, afflicts 1.3% - 5.1% of the global population. CM is the most common disorder faced by experts in tertiary headache centers. When resistant to conventional medical treatment and prophylactic medication this condition is known as refractory chronic migraine (RCM). RCM is one of the greatest challenges in headache medicine. Areas covered: State-of-the-art and future medical treatments of chronic migraine include: OnabotulinumtoxinA, antiepileptic drugs (Levetiracetam, Magnesium valproate hydrate, Lacosamide, BGG-492), 5-HT agonists (Lasmiditan, NXN-188, novel delivery systems of Sumatriptan, a well-established drug treatment for acute migraine), CGRP receptor antagonists (BMS-927711), ML-1 agonists (Ramelteon), orexin receptor antagonist (MK-6096), plant-derived compound (LLL-2011) and other multitarget drugs such as Tezampanel, Tonabersat, intranasal carbon dioxide and BOL-148. The role for neuromodulation, the application of targeted electrical stimulation, will be examined. Expert opinion: Medication overuse headache (MOH) is now recognized to be a major factor in many cases of both chronic and refractory chronic migraine. MOH must be addressed prior to evaluating the effectiveness of new preventative and prophylactic treatment approaches. Innovative new drugs and electrical neuromodulation are promising CM treatments. Future studies must carefully screen patients and acquire data that can lead to personalized, tailored treatment strategies. C1 [Lionetto, Luana; Negro, Andrea; Gentile, Giovanna; Del Fiore, Maria Rosaria; Mercieri, Marco; Simmaco, Maurizio; Arcioni, Roberto; Martelletti, Paolo] Univ Roma La Sapienza, I-00189 Rome, Italy. [Negro, Andrea; Martelletti, Paolo] St Andrea Hosp, Dept Clin & Mol Med, Reg Referral Headache Ctr, I-00189 Rome, Italy. [Lionetto, Luana; Gentile, Giovanna; Simmaco, Maurizio] St Andrea Hosp, Adv Mol Diagnost Unit, NESMOS Dept, Rome, Italy. [Palmisani, Stefano; Smith, Thomas; Al-Kaisy, Adnan] Guys & St Thomas NHS Trust, Pain Management & Neuromodulat Ctr, London, England. [Del Fiore, Maria Rosaria; Mercieri, Marco; Arcioni, Roberto] St Andrea Hosp, Dept Med & Surg Sci & Translat Med, Pain Therapy Unit, Rome, Italy. [Negro, Andrea] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp,Stroke & Neurovasc Reg Lab, Boston, MA 02115 USA. RP Martelletti, P (reprint author), Univ Roma La Sapienza, Via Grottarossa 1035-1039, I-00189 Rome, Italy. EM paolo.martelletti@uniroma1.it RI Lionetto, Luana/J-3632-2016; gentile, giovanna/M-3565-2016; OI Lionetto, Luana/0000-0002-5272-6642; gentile, giovanna/0000-0001-8667-3094; Mercieri, Marco/0000-0003-4321-6525 FU Allergan; A.C.R.A.F. Angelini FX Paolo Martelletti has received grants from Allergan and A.C.R.A.F. Angelini. NR 104 TC 34 Z9 34 U1 1 U2 18 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1472-8214 J9 EXPERT OPIN EMERG DR JI Expert Opin Emerg. Drugs PD SEP PY 2012 VL 17 IS 3 BP 393 EP 406 DI 10.1517/14728214.2012.709846 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 995HJ UT WOS:000307998500010 PM 22862686 ER PT J AU Lopez, MM Fuertes-Alvarez, S Shah, K Marques, MM Marin, MC AF Lopez, M. M. Fuertes-Alvarez, S. Shah, K. Marques, M. M. Marin, M. C. TI Generation and study of a bimodal lentiviral vectors for the transcriptional analysis of the TP73 gene SO FEBS JOURNAL LA English DT Meeting Abstract CT 22nd IUBMB Congress/37th FEBS Congress CY SEP 04-09, 2012 CL Seville, SPAIN SP IUBMB, FEBS C1 [Lopez, M. M.; Fuertes-Alvarez, S.; Marin, M. C.] Univ Leon, Inst Biomed IBIOMED, E-24071 Leon, Spain. [Lopez, M. M.; Fuertes-Alvarez, S.; Marin, M. C.] Univ Leon, Dept Mol Biol, E-24071 Leon, Spain. [Shah, K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol & Neurol, Boston, MA USA. [Marques, M. M.] Univ Leon, INDEGSAL, E-24071 Leon, Spain. RI Marin Vieira, Maria del Carmen/B-8108-2015; Marques , Margarita/I-1260-2015 OI Marin Vieira, Maria del Carmen/0000-0002-7149-287X; Marques , Margarita/0000-0003-2818-035X 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 1742-464X J9 FEBS J JI FEBS J. PD SEP PY 2012 VL 279 SU 1 SI SI BP 549 EP 549 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 996XR UT WOS:000308128602788 ER PT J AU Janiszewska, M Suva, ML Riggi, N Houtkooper, RH Auwerx, J Clement-Schatlo, V Radovanovic, I Rheinbay, E Provero, P Stamenkovic, I AF Janiszewska, Michalina Suva, Mario L. Riggi, Nicolo Houtkooper, Riekelt H. Auwerx, Johan Clement-Schatlo, Virginie Radovanovic, Ivan Rheinbay, Esther Provero, Paolo Stamenkovic, Ivan TI Imp2 controls oxidative phosphorylation and is crucial for preserving glioblastoma cancer stem cells SO GENES & DEVELOPMENT LA English DT Article DE Imp2; cancer stem cells; OXPHOS; glioblastoma; respiratory complex; mitochondria ID RNA-BINDING PROTEINS; GENOME-WIDE ASSOCIATION; TUMOR-INITIATING CELLS; COMPLEX-I; HEPATOCELLULAR-CARCINOMA; SUBUNIT COMPOSITION; GLIOMA-CELLS; GROWTH; MITOCHONDRIAL; EXPRESSION AB Growth of numerous cancer types is believed to be driven by a subpopulation of poorly differentiated cells, often referred to as cancer stem cells (CSCs), that have the capacity for self-renewal, tumor initiation, and generation of nontumorigenic progeny. Despite their potentially key role in tumor establishment and maintenance, the energy requirements of these cells and the mechanisms that regulate their energy production are unknown. Here, we show that the oncofetal insulin-like growth factor 2 mRNA-binding protein 2 (IMP2, IGF2BP2) regulates oxidative phosphorylation (OXPHOS) in primary glioblastoma (GBM) sphere cultures (gliomaspheres), an established in vitro model for CSC expansion. We demonstrate that IMP2 binds several mRNAs that encode mitochondrial respiratory chain complex subunits and that it interacts with complex I (NADH: ubiquinone oxidoreductase) proteins. Depletion of IMP2 in gliomaspheres decreases their oxygen consumption rate and both complex I and complex IV activity that results in impaired clonogenicity in vitro and tumorigenicity in vivo. Importantly, inhibition of OXPHOS but not of glycolysis abolishes GBM cell clonogenicity. Our observations suggest that gliomaspheres depend on OXPHOS for their energy production and survival and that IMP2 expression provides a key mechanism to ensure OXPHOS maintenance by delivering respiratory chain subunit-encoding mRNAs to mitochondria and contributing to complex I and complex IV assembly. C1 [Janiszewska, Michalina; Stamenkovic, Ivan] Univ Lausanne, CHUV, Dept Labs, CH-1011 Lausanne, Switzerland. [Suva, Mario L.; Riggi, Nicolo; Rheinbay, Esther] Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs,Dept Pathol, Boston, MA 02114 USA. [Houtkooper, Riekelt H.; Auwerx, Johan] Ecole Polytech Fed Lausanne, NCEM, Lab Integrat & Syst Physiol, CH-1015 Lausanne, Switzerland. [Houtkooper, Riekelt H.] Univ Amsterdam, Acad Med Ctr, Lab Genet Metab Dis, NL-1105 AZ Amsterdam, Netherlands. [Clement-Schatlo, Virginie; Radovanovic, Ivan] Univ Hosp Geneva, Dept Clin Neurosci, CH-1211 Geneva, Switzerland. [Provero, Paolo] Univ Turin, Dept Genet Biol & Biochem, I-10126 Turin, Italy. [Rheinbay, Esther] Boston Univ, Bioinformat Program, Boston, MA 02215 USA. RP Stamenkovic, I (reprint author), Univ Lausanne, CHUV, Dept Labs, CH-1011 Lausanne, Switzerland. EM ivan.stamenkovic@chuv.ch RI Houtkooper, Riekelt/E-1602-2011 OI Houtkooper, Riekelt/0000-0001-9961-0842 FU Swiss National Foundation (FNRS) grant [310030_130350]; NCCR Molecular Oncology; MEDIC Foundation grant; Oncosuisse grant [BIL-KFS-02590-02-2010]; Italian Association for Cancer Research (AIRC); Rubicon fellowship from the Netherlands Organization for Scientific Research (NWO); Ecole Polytechnique Federale de Lausanne, Swiss National Science Foundation, NIH [DK59820]; Velux Stiftung; European Research Council Ideas program (Sirtuins) [ERC-2008-AdG23118] FX We thank Keith Harshman (Genomic Technologies Facility, Faculty of Biology and Medicine, University of Lausanne) for performing the microarray experiments, and Manfredo Quadroni (Protein Analysis Facility, Faculty of Biology and Medicine, University of Lausanne) for the mass spectrometry analysis. We also thank Whitney Quong, Claudio De Vito, Karine Baumer, Benoit Lhermitte, and Carlo Fusco for technical assistance and discussions, and Sylviane Trepey, Jean-Christophe Stehle, and Janine Holbeck for immunohistochemistry. This work was supported by Swiss National Foundation (FNRS) grant 310030_130350, NCCR Molecular Oncology, a MEDIC Foundation grant to I.S., and Oncosuisse grant BIL-KFS-02590-02-2010 to M.S. P.P. acknowledges funding from the Italian Association for Cancer Research (AIRC). R.H.H. was supported by a Rubicon fellowship from the Netherlands Organization for Scientific Research (NWO). The work in the Auwerx laboratory was supported by grants of the Ecole Polytechnique Federale de Lausanne, Swiss National Science Foundation, NIH (DK59820), the Velux Stiftung, and the European Research Council Ideas program (Sirtuins; ERC-2008-AdG23118). We thank all the members of the Auwerx laboratory for inspiring discussions. NR 63 TC 67 Z9 67 U1 0 U2 11 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD SEP 1 PY 2012 VL 26 IS 17 BP 1926 EP 1944 DI 10.1101/gad.188292.112 PG 19 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 000NA UT WOS:000308391800005 PM 22899010 ER PT J AU Landt, SG Marinov, GK Kundaje, A Kheradpour, P Pauli, F Batzoglou, S Bernstein, BE Bickel, P Brown, JB Cayting, P Chen, YW DeSalvo, G Epstein, C Fisher-Aylor, KI Euskirchen, G Gerstein, M Gertz, J Hartemink, AJ Hoffman, MM Iyer, VR Jung, YL Karmakar, S Kellis, M Kharchenko, PV Li, QH Liu, T Liu, XS Ma, LJ Milosavljevic, A Myers, RM Park, PJ Pazin, MJ Perry, MD Raha, D Reddy, TE Rozowsky, J Shoresh, N Sidow, A Slattery, M Stamatoyannopoulos, JA Tolstorukov, MY White, KP Xi, S Farnham, PJ Lieb, JD Wold, BJ Snyder, M AF Landt, Stephen G. Marinov, Georgi K. Kundaje, Anshul Kheradpour, Pouya Pauli, Florencia Batzoglou, Serafim Bernstein, Bradley E. Bickel, Peter Brown, James B. Cayting, Philip Chen, Yiwen DeSalvo, Gilberto Epstein, Charles Fisher-Aylor, Katherine I. Euskirchen, Ghia Gerstein, Mark Gertz, Jason Hartemink, Alexander J. Hoffman, Michael M. Iyer, Vishwanath R. Jung, Youngsook L. Karmakar, Subhradip Kellis, Manolis Kharchenko, Peter V. Li, Qunhua Liu, Tao Liu, X. Shirley Ma, Lijia Milosavljevic, Aleksandar Myers, Richard M. Park, Peter J. Pazin, Michael J. Perry, Marc D. Raha, Debasish Reddy, Timothy E. Rozowsky, Joel Shoresh, Noam Sidow, Arend Slattery, Matthew Stamatoyannopoulos, John A. Tolstorukov, Michael Y. White, Kevin P. Xi, Simon Farnham, Peggy J. Lieb, Jason D. Wold, Barbara J. Snyder, Michael TI ChIP-seq guidelines and practices of the ENCODE and modENCODE consortia SO GENOME RESEARCH LA English DT Article ID TRANSCRIPTION FACTOR-BINDING; GENOME-WIDE ANALYSIS; CHROMATIN IMMUNOPRECIPITATION; DNA ASSOCIATION; PROTEIN; IDENTIFICATION; ELEMENTS; SITES; METHYLATIONS; MACROPHAGE AB Chromatin immunoprecipitation (ChIP) followed by high-throughput DNA sequencing (ChIP-seq) has become a valuable and widely used approach for mapping the genomic location of transcription-factor binding and histone modifications in living cells. Despite its widespread use, there are considerable differences in how these experiments are conducted, how the results are scored and evaluated for quality, and how the data and metadata are archived for public use. These practices affect the quality and utility of any global ChIP experiment. Through our experience in performing CHIP-seq experiments, the ENCODE and modENCODE consortia have developed a set of working standards and guidelines for ChIP experiments that are updated routinely. The current guidelines address antibody validation, experimental replication, sequencing depth, data and metadata reporting, and data quality assessment. We discuss how ChIP quality, assessed in these ways, affects different uses of chip-seq data. All data sets used in the analysis have been deposited for public viewing and downloading at the ENCODE (http:/ / encodeproject.org/ENCODE/) and modENCODE (http:/ /www.modencode. org/) portals. C1 [Farnham, Peggy J.] Univ So Calif, Dept Biochem & Mol Biol, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90089 USA. [Lieb, Jason D.] Univ N Carolina, Dept Biol, Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA. [Lieb, Jason D.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Landt, Stephen G.; Cayting, Philip; Euskirchen, Ghia; Sidow, Arend; Snyder, Michael] Stanford Univ, Dept Genet, Stanford, CA 94305 USA. [Marinov, Georgi K.; DeSalvo, Gilberto; Fisher-Aylor, Katherine I.; Wold, Barbara J.] CALTECH, Div Biol, Pasadena, CA 92116 USA. [Kundaje, Anshul; Batzoglou, Serafim] Stanford Univ, Dept Comp Sci, Stanford, CA 94305 USA. [Kheradpour, Pouya; Kellis, Manolis] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Pauli, Florencia; Gertz, Jason; Myers, Richard M.; Reddy, Timothy E.] HudsonAlpha Inst Biotechnol, Huntsville, AL 35806 USA. [Bernstein, Bradley E.; Epstein, Charles; Shoresh, Noam] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Bickel, Peter; Brown, James B.] Univ Calif Berkeley, Dept Stat, Berkeley, CA 94720 USA. [Chen, Yiwen; Liu, Tao; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Gerstein, Mark; Rozowsky, Joel] Yale Univ, Computat Biol & Bioinformat Program, New Haven, CT 06511 USA. [Hartemink, Alexander J.] Duke Univ, Dept Comp Sci, Durham, NC 27708 USA. [Hartemink, Alexander J.] Duke Univ, Ctr Syst Biol, Durham, NC 27708 USA. [Hoffman, Michael M.; Stamatoyannopoulos, John A.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Iyer, Vishwanath R.; Kharchenko, Peter V.] Univ Texas Austin, Inst Cellular & Mol Biol, Sect Mol Genet & Microbiol, Ctr Syst & Synthet Biol, Austin, TX 78701 USA. [Jung, Youngsook L.; Park, Peter J.; Tolstorukov, Michael Y.] Harvard Univ, Ctr Biomed Informat, Sch Med, Boston, MA 02115 USA. [Jung, Youngsook L.; Park, Peter J.; Tolstorukov, Michael Y.] Brigham & Womens Hosp, Div Genet, Dept Med, Boston, MA 02115 USA. [Karmakar, Subhradip; Ma, Lijia; Slattery, Matthew; White, Kevin P.] Univ Chicago, Inst Genom & Syst Biol, Chicago, IL 60637 USA. [Li, Qunhua] Penn State Univ, Dept Stat, University Pk, PA 16802 USA. [Milosavljevic, Aleksandar] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Pazin, Michael J.] NHGRI, NIH, Rockville, MD 20852 USA. [Perry, Marc D.] Ontario Inst Canc Res, Toronto, ON MSG 0A3, Canada. [Raha, Debasish] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06511 USA. [Sidow, Arend] Stanford Univ, Dept Pathol, Stanford, CA 94305 USA. [Stamatoyannopoulos, John A.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Xi, Simon] Univ Massachusetts, Sch Med, Worcester, MA 01655 USA. RP Farnham, PJ (reprint author), Univ So Calif, Dept Biochem & Mol Biol, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90089 USA. EM pfarnham@usc.edu; jlieb@bio.unc.edu; woldb@caltech.edu; mpsnyder@stanford.edu RI Hoffman, Michael/I-1924-2012; Liu, Tao/G-3585-2010; Brown, James/H-2971-2015; OI Farnham, Peggy/0000-0003-4469-7914; Rozowsky, Joel/0000-0002-3565-0762; Pazin, Michael/0000-0002-7561-3640; Hoffman, Michael/0000-0002-4517-1562; Liu, Tao/0000-0002-8818-8313; Liu, Tao/0000-0003-0446-9001; Marinov, Georgi/0000-0003-1822-7273 FU NHGRI NIH HHS [K99 HG006698] NR 51 TC 391 Z9 393 U1 5 U2 63 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD SEP PY 2012 VL 22 IS 9 SI SI BP 1813 EP 1831 DI 10.1101/gr.136184.111 PG 19 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 998XD UT WOS:000308272800021 PM 22955991 ER PT J AU Sauna, ZE Ameri, A Kim, B Yanover, C Viel, KR Rajalingam, R Cole, SA Howard, TE AF Sauna, Z. E. Ameri, A. Kim, B. Yanover, C. Viel, K. R. Rajalingam, R. Cole, S. A. Howard, T. E. TI A view of the Aledort-Iorio Debate concerning the immunogenicity of B-Domain-deleted and full-length recombinant FVIII products from a mechanistic personalized medicine perspective SO HAEMOPHILIA LA English DT Meeting Abstract C1 [Sauna, Z. E.] US FDA, Lab Hemostasis, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Ameri, A.] Georgia Hlth Sci Univ, Div Hematol & Oncol, Dept Pediat, Augusta, GA USA. [Kim, B.; Howard, T. E.] Univ Calif San Francisco, Dept Med, Div Hematol & Oncol, San Francisco, CA USA. [Kim, B.] Univ Calif Los Angeles, David Geffen Sch Med, Div Hematol & Oncol, Dept Med, Los Angeles, CA 90095 USA. [Yanover, C.] Fred Hutchinson Canc Res Ctr, Program Computat Biol, Seattle, WA 98104 USA. [Viel, K. R.] Histonis Inc, Atlanta, GA USA. [Rajalingam, R.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, UCLA Immunogenet Ctr, Los Angeles, CA 90095 USA. [Cole, S. A.] Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA. [Howard, T. E.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Pathol & Lab Med, Los Angeles, CA USA. [Howard, T. E.] Univ So Calif, Keck Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90033 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 1351-8216 J9 HAEMOPHILIA JI Haemophilia PD SEP PY 2012 VL 18 IS 5 BP 830 EP 830 PG 1 WC Hematology SC Hematology GA 993ZT UT WOS:000307900700054 ER PT J AU Cordasco, KM Homeier, DC Franco, I Wang, PC Sarkisian, CA AF Cordasco, Kristina M. Homeier, Diana C. Franco, Idalid Wang, Pin-Chieh Sarkisian, Catherine A. TI Health literacy screening of geriatric monolingual Spanish-speaking patients using single-item literacy screening questions and education SO HEALTH EDUCATION JOURNAL LA English DT Article DE aged; educational achievement; health literacy; Latinos; receiving-operator characteristic curve ID IDENTIFY PATIENTS AB Objective: We describe the performance of Single Item Literacy Screener (SILS) questions, and educational attainment, as screening for inadequate health literacy (IHL) in older monolingual Spanish speakers. Design: We used a cross-sectional design, interviewing participants once at the time of their arrival for a clinic appointment. Setting: We conducted this study in primary care and geriatrics clinics in an urban US safety-net hospital. Method: We conducted in-person interviews with older monolingual Spanish-speaking diabetes patients, comparing responses to three SILS questions, and education, to shortened Test of Functional Health Literacy in Adults (sTOFHLA) scores. We calculated sensitivities, specificities and areas under the receiving-operator characteristic (AUROC) curve. Results: We interviewed 160 patients -134 (84%) had IHL by sTOFHLA scores. The best performing SILS question, 'How confident are you filling out medical forms by yourself?' had an AUROC curve of 0.82 (95% CI 0.75-0.89). Using this question's most stringent cut-off, sensitivity was 0.93 (95% CI 0.89-0.97); specificity was 0.27 (95% CI 0.20-0.34). The other two SILS questions had AUROC curves less than 0.50. The educational achievement AUROC curve was 0.88 (95% CI 0.78-0.97); using an education cut-off of six years or less had a specificity to 0.81 (95% CI 0.75-0.87) and sensitivity of 0.83 (95% CI 0.77-0.89). Conclusion: Clinicians and investigators considering using single items as screeners for IHL in older US monolingual Spanish speakers should either use the ` confidence with forms' SILS, being aware of its specificity limitations, or a single question assessing educational achievement. C1 [Cordasco, Kristina M.; Franco, Idalid; Sarkisian, Catherine A.] RAND Corp, Santa Monica, CA 90407 USA. [Cordasco, Kristina M.; Sarkisian, Catherine A.] VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA. [Cordasco, Kristina M.; Wang, Pin-Chieh; Sarkisian, Catherine A.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA USA. [Homeier, Diana C.] Univ So Calif, Dept Family Med, Los Angeles, CA 90089 USA. RP Cordasco, KM (reprint author), RAND Corp, 1776 Main St,POB 2138, Santa Monica, CA 90407 USA. EM kcordasc@rand.org FU NINR NIH HHS [R21 NR011309-02, R21 NR011309-01, R21 NR011309] NR 13 TC 4 Z9 4 U1 0 U2 3 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0017-8969 EI 1748-8176 J9 HEALTH EDUC J JI Health Educ. J. PD SEP PY 2012 VL 71 IS 5 BP 597 EP 605 DI 10.1177/0017896911411764 PG 9 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA 995CK UT WOS:000307984400007 PM 23788818 ER PT J AU Nevzorova, YA Bangen, JM Hu, W Haas, U Weiskirchen, R Gassler, N Huss, S Tacke, F Sicinski, P Trautwein, C Liedtke, C AF Nevzorova, Yulia A. Bangen, Joerg-Martin Hu, Wei Haas, Ute Weiskirchen, Ralf Gassler, Nikolaus Huss, Sebastian Tacke, Frank Sicinski, Piotr Trautwein, Christian Liedtke, Christian TI Cyclin E1 controls proliferation of hepatic stellate cells and is essential for liver fibrogenesis in mice SO HEPATOLOGY LA English DT Article ID FIBROSIS; MECHANISMS; ENDOREPLICATION; EXPRESSION; E2; MOUSE AB Liver fibrogenesis is associated with the transition of quiescent hepatocytes and hepatic stellate cells (HSCs) into the cell cycle. Exit from quiescence is controlled by E-type cyclins (cyclin E1 [CcnE1] and cyclin E2 [CcnE2]). Thus, the aim of the current study was to investigate the contribution of E-type cyclins for liver fibrosis in man and mice. Expression of CcnE1, but not of its homolog, CcnE2, was induced in fibrotic and cirrhotic livers from human patients with different etiologies and in murine wild-type (WT) livers after periodical administration of the profibrotic toxin, CCl4. To further evaluate the potential function of E-type cyclins for liver fibrogenesis, we repetitively treated constitutive CcnE1-/- and CcnE2-/- knock-out mice with CCl4 to induce liver fibrosis. Interestingly, CcnE1-/- mice were protected against CCl4-mediated liver fibrogenesis, as evidenced by reduced collagen type I a1 expression and the lack of septum formation. In contrast, CcnE2-/- mice showed accelerated fibrogenesis after CCl4 treatment. We isolated primary HSCs from WT, CcnE1-/-, and CcnE2-/- mice and analyzed their activation, proliferation, and survival in vitro. CcnE1 expression in WT HSCs was maximal when they started to proliferate, but decreased after the cells transdifferentiated into myofibroblasts. CcnE1-/- HSCs showed dramatically impaired survival, cell-cycle arrest, and strongly reduced expression of alpha smooth muscle actin, indicating deficient HSC activation. In contrast, CcnE2-deficient HSCs expressed an elevated level of CcnE1 and showed enhanced cell-cycle activity and proliferation, compared to WT cells. Conclusions: CcnE1 and CcnE2 have antagonistic roles in liver fibrosis. CcnE1 is indispensable for the activation, proliferation, and survival of HSCs and thus promotes the synthesis of extracellular matrix and liver fibrogenesis. (HEPATOLOGY 2012;56:11401149) C1 [Nevzorova, Yulia A.; Bangen, Joerg-Martin; Hu, Wei; Haas, Ute; Tacke, Frank; Trautwein, Christian; Liedtke, Christian] Rhein Westfal TH Aachen, Dept Med 3, Univ Hosp, D-52074 Aachen, Germany. [Weiskirchen, Ralf] Rhein Westfal TH Aachen, Inst Clin Chem & Pathobiochem, Univ Hosp, D-52074 Aachen, Germany. [Gassler, Nikolaus] Rhein Westfal TH Aachen, Inst Pathol, Univ Hosp, D-52074 Aachen, Germany. [Huss, Sebastian] Univ Hosp Bonn, Inst Pathol, Bonn, Germany. [Sicinski, Piotr] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Genet, Boston, MA 02115 USA. RP Liedtke, C (reprint author), Rhein Westfal TH Aachen, Dept Med 3, Univ Hosp Aachen, Pauwelsstr 30, D-52074 Aachen, Germany. EM cliedtke@ukaachen.de FU Deutsche Forschungsgemeinschaft (DFG) [SFB TRR57, R01 CA108950] FX This work was supported by the Deutsche Forschungsgemeinschaft (DFG), SFB TRR57, project P04 (to C. L. and C. T) and grant R01 CA108950 (to P.S.). NR 24 TC 15 Z9 15 U1 1 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD SEP PY 2012 VL 56 IS 3 BP 1140 EP 1149 DI 10.1002/hep.25736 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 995WX UT WOS:000308046700037 PM 22454377 ER PT J AU Hartmann, AS Czaja, J Rief, W Hilbert, A AF Hartmann, Andrea Sabrina Czaja, Julia Rief, Winfried Hilbert, Anja TI Psychosocial risk factors of loss of control eating in primary school children: A retrospective case-control study SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article DE etiology; eating disorder psychopathology; LOC eating; risk factors; children; Oxford Risk Factor Interview; case-control design ID OVERWEIGHT CHILDREN; PROTECTIVE FACTORS; ADOLESCENT GIRLS; OBESE YOUNGSTERS; WEIGHT-GAIN; DISORDER; ONSET; BEHAVIORS; PSYCHOPATHOLOGY; PREVALENCE AB Objective: To provide a comprehensive investigation of the retrospective correlates of loss of control (LOC) over eating in children close to the onset of their first LOC eating episodes. Method: A community-based, case-control design was used to compare matched groups of 60 children with and without LOC eating. Retrospective correlates were assessed using a child-adapted version of the Oxford Risk Factor Interview. Results: Children with LOC eating revealed greater levels of exposure to parental problems, (e.g., underinvolvement, arguments, and depression of family members) and dieting-related risk factors than children without LOC eating. Predictors of LOC eating were risk correlates parental underinvolvement, and critical comments by the family and the critical life event change of school. Discussion: Results underline the influence of parental behavior and the impact of dieting behavior on the development of non-normative eating in middle childhood. (c) 2012 by Wiley Periodicals, Inc. (Int J Eat Disord 2012; 45:751758) C1 [Hartmann, Andrea Sabrina] Massachusetts Gen Hosp, Dept Psychiat, OCD & Related Disorders Program, Boston, MA 02114 USA. [Hartmann, Andrea Sabrina] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Czaja, Julia] Univ Lubeck, Dept Psychosomat Med & Psychotherapy, Lubeck, Germany. [Rief, Winfried] Univ Marburg, Dept Psychol, D-3550 Marburg, Germany. [Hilbert, Anja] Univ Hosp Leipzig, Dept Med Psychol & Med Sociol, Leipzig, Germany. RP Hartmann, AS (reprint author), Massachusetts Gen Hosp, Dept Psychiat, OCD & Related Disorders Program, Simches Res Bldg,185 Cambridge St,Suite 2200, Boston, MA 02114 USA. EM ahartmann1@partners.org FU German Research Foundation [HI 1111/1-1, HI 1111/1-2]; German Ministry of Education and Research [01GP0491] FX Supported by HI 1111/1-1, 2 from The German Research Foundation and by 01GP0491 from The German Ministry of Education and Research. NR 44 TC 13 Z9 13 U1 3 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD SEP PY 2012 VL 45 IS 6 BP 751 EP 758 DI 10.1002/eat.22018 PG 8 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 986LC UT WOS:000307342100004 PM 22431297 ER PT J AU Wethington, SL Cibula, D Duska, LR Garrett, L Kim, CH Chi, DS Sonoda, Y Abu-Rustum, NR AF Wethington, Stephanie L. Cibula, David Duska, Linda R. Garrett, Leslie Kim, Christine H. Chi, Dennis S. Sonoda, Yukio Abu-Rustum, Nadeem R. TI An International Series on Abdominal Radical Trachelectomy 101 Patients and 28 Pregnancies SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Article DE Trachelectomy; Cervical cancer; Fertility preservation ID STAGE CERVICAL-CANCER; PATHOLOGICAL OUTCOMES; HYSTERECTOMY; CARCINOMA; LYMPHADENECTOMY AB Objectives: Abdominal radical trachelectomy (ART) is a type C resection (uterine vessels ligated at origin from the hypogastric vessels). Questions arise as to whether fertility is maintained after ART, particularly when uterine vessels are sacrificed. We report an international series on ART to describe fertility and oncologic outcomes. Methods: Databases at 3 institutions were queried to identify patients planned for ART from 1999 to 2011. Clinical and demographic data were gathered. Results: One hundred one patients underwent ART. Mean age was 31 years (range, 19-43 years). Histologic classifications were adenocarcinoma (n = 54), squamous cell carcinoma (n = 40), adenosquamous carcinoma (n = 6), and clear cell carcinoma (n = 1). Twenty patients (20%) required conversion to hysterectomy (10 margins and 10 nodes). Eight patients underwent completion hysterectomy owing to the following: positive margins on final pathology (n = 3), patient's choice (n = 4), or recurrence (n = 1). Postoperatively, 20 patients (20%) received adjuvant chemotherapy and/or radiation (4 final pathology margins and 16 nodes). Four patients (4%) had recurrence and lived 22 to 35 months after diagnosis. Of the 70 women who had neither hysterectomy nor adjuvant therapy, 38 (54%) attempted pregnancy and 28 (74%) achieved pregnancy. Thirty-one pregnancies resulted in 16 (52%) third trimester deliveries. Six patients are currently pregnant with outcomes pending. Conclusions: These data demonstrate that ART preserves fertility and maintains excellent oncologic outcomes. Most women (74%) attempting pregnancy after ART are able to achieve pregnancy and deliver in the third trimester (52%). Preservation of the uterine vasculature is not necessary for fertility; obstetrical outcomes are similar to those of the historical vaginal radical trachelectomy cohorts. C1 [Wethington, Stephanie L.; Kim, Christine H.; Chi, Dennis S.; Sonoda, Yukio; Abu-Rustum, Nadeem R.] Mem Sloan Kettering Canc Ctr, Div Gynecol, Dept Surg, New York, NY 10065 USA. [Cibula, David] Charles Univ Prague, Fac Med 1, Dept Obstet & Gynecol, Gynecol Oncol Ctr,Gen Univ Hosp, Prague, Czech Republic. [Duska, Linda R.] Univ Virginia Hlth Syst, Thornton Gynecol Oncol Serv, Dept Obstet & Gynecol, Charlottesville, VA USA. [Garrett, Leslie] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol, Boston, MA USA. [Chi, Dennis S.; Sonoda, Yukio; Abu-Rustum, Nadeem R.] Weill Cornell Med Coll, Dept Obstet & Gynecol, New York, NY USA. RP Abu-Rustum, NR (reprint author), Mem Sloan Kettering Canc Ctr, Div Gynecol, Dept Surg, 1275 York Ave,Box 225, New York, NY 10065 USA. EM gynbreast@mskcc.org OI Kim, Christine/0000-0002-0715-1413; Cibula, David/0000-0001-6387-9356 NR 25 TC 40 Z9 41 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1048-891X J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD SEP PY 2012 VL 22 IS 7 BP 1251 EP 1257 DI 10.1097/IGC.0b013e318263eee2 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 998DE UT WOS:000308216600026 PM 22914213 ER PT J AU McBride, SM Ali, NN Margalit, DN Chan, AW AF McBride, Sean M. Ali, Nawal N. Margalit, Danielle N. Chan, Annie W. TI Active Tobacco Smoking and Distant Metastasis in Patients With Oropharyngeal Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 54th Annual Meeting of the American-Society-for-Radiology-Oncology (ASTRO) CY 2011 CL Miami, FL SP Amer Soc Radiol Oncol (ASTRO) DE Cigarette; Distant metastasis; HPV; Human papillomavirus; Oropharyngeal carcinoma; Radiation; Smoking; Tobacco ID SQUAMOUS-CELL CARCINOMA; HUMAN-PAPILLOMAVIRUS; SURVIVAL; HEAD; EXPERIENCE AB Purpose: Distant metastasis is the site of first relapse in approximately one-third of patients with locally advanced oropharyngeal carcinoma, irrespective of human papillomavirus status. Yet the risk factors associated with distant metastasis are not well characterized. We sought to characterize the relationship between smoking status and distant metastasis. Methods and Materials: We evaluated the association between tobacco smoking status and distant metastasis in a retrospective cohort study of 132 patients who underwent definitive radiation therapy and chemotherapy for Stage III-IVA/B oropharyngeal cancer. Information on tobacco smoking was prospectively collected by patient questionnaires and physician notes at the time of diagnosis. Thirty-three percent of the patients were nonsmokers, 51% were former smokers, 16% were active smokers. The cumulative lifetime tobacco smoking in pack-years was 20 (range, 0-150). Results: With a median follow-up time of 52 months, the overall rate of distant metastasis at 4 years was 8%. Distant metastasis was the most common first site of relapse, occurring in 56% of the patients with recurrences. Active smokers had higher rates of distant metastasis than non-active smokers (including never-and former smokers; 31% vs. 4%, p < 0.001) and former smokers (31% vs. 3%, p < 0.001). There was no statistically significant difference in the risk of distant metastasis for patients with lifetime cumulative pack-years >20 and <= 20 (10% vs. 4%, p = 0.19). In univariate analysis, active smoking (p = 0.0004) and N category (p = 0.009) were predictive of increased risk of distant metastasis. In multivariate analysis, active smoking was the most significant predictive factor for increased risk of distant metastasis (hazard ratio, 12.7, p < 0.0001). Conclusions: This study identified a strong association between active smoking and distant metastasis in patients with oropharyngeal cancer. (C) 2012 Elsevier Inc. C1 [McBride, Sean M.; Ali, Nawal N.; Margalit, Danielle N.; Chan, Annie W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. [McBride, Sean M.; Margalit, Danielle N.] Harvard Radiat Oncol Program, Boston, MA USA. RP Chan, AW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, 55 Fruit St,Cox 337, Boston, MA 02114 USA. EM awchan@partners.org NR 20 TC 8 Z9 9 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD SEP 1 PY 2012 VL 84 IS 1 BP 183 EP 188 DI 10.1016/j.ijrobp.2011.11.044 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 996CO UT WOS:000308061900053 PM 22330993 ER PT J AU Henderson, TO Rajaraman, P Stovall, M Constine, LS Olive, A Smith, SA Mertens, A Meadows, A Neglia, JP Hammond, S Whitton, J Inskip, PD Robison, LL Diller, L AF Henderson, Tara O. Rajaraman, Preetha Stovall, Marilyn Constine, Louis S. Olive, Aliza Smith, Susan A. Mertens, Ann Meadows, Anna Neglia, Joseph P. Hammond, Sue Whitton, John Inskip, Peter D. Robison, Leslie L. Diller, Lisa TI Risk Factors Associated With Secondary Sarcomas in Childhood Cancer Survivors: A Report From the Childhood Cancer Survivor Study SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Childhood cancer survivors; Secondary sarcomas; Radiation late effects ID 2ND MALIGNANT NEOPLASMS; SOFT-TISSUE SARCOMA; BREAST-CANCER; 5-YEAR SURVIVORS; LATE MORTALITY; BONE SARCOMAS; SOLID TUMORS; RADIATION; CHEMOTHERAPY; RADIOTHERAPY AB Purpose: Childhood cancer survivors have an increased risk of secondary sarcomas. To better identify those at risk, the relationship between therapeutic dose of chemotherapy and radiation and secondary sarcoma should be quantified. Methods and Materials: We conducted a nested case-control study of secondary sarcomas (105 cases, 422 matched controls) in a cohort of 14,372 childhood cancer survivors. Radiation dose at the second malignant neoplasm (SMN) site and use of chemotherapy were estimated from detailed review of medical records. Odds ratios (ORs) and 95% confidence intervals were estimated by conditional logistic regression. Excess odds ratio (EOR) was modeled as a function of radiation dose, chemotherapy, and host factors. Results: Sarcomas occurred a median of 11.8 years (range, 5.3-31.3 years) from original diagnosis. Any exposure to radiation was associated with increased risk of secondary sarcoma (OR = 4.1, 95% CI = 1.8-9.5). A dose-response relation was observed, with elevated risks at doses between 10 and 29.9 Gy (OR = 15.6, 95% CI = 4.5-53.9), 30-49.9 Gy (OR = 16.0, 95% CI 3.8-67.8) and >50 Gy (OR = 114.1, 95% CI 13.5-964.8). Anthracycline exposure was associated with sarcoma risk (OR = 3.5, 95% CI = 1.6-7.7) adjusting for radiation dose, other chemotherapy, and primary cancer. Adjusting for treatment, survivors with a first diagnosis of Hodgkin lymphoma (OR = 10.7, 95% CI = 3.1-37.4) or primary sarcoma (OR = 8.4, 95% CI = 3.2-22.3) were more likely to develop a sarcoma. Conclusions: Of the risk factors evaluated, radiation exposure was the most important for secondary sarcoma development in childhood cancer survivors; anthracycline chemotherapy exposure was also associated with increased risk. (C) 2012 Elsevier Inc. C1 [Henderson, Tara O.] Univ Chicago, Dept Pediat, Chicago, IL 60637 USA. [Rajaraman, Preetha; Inskip, Peter D.] NCI, Bethesda, MD 20892 USA. [Stovall, Marilyn; Smith, Susan A.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Constine, Louis S.] Univ Rochester, Rochester, NY USA. [Olive, Aliza] Drexel Univ, Philadelphia, PA 19104 USA. [Mertens, Ann] Emory Univ, Atlanta, GA 30322 USA. [Meadows, Anna] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Neglia, Joseph P.] Univ Minnesota, Minneapolis, MN USA. [Hammond, Sue] Nationwide Childrens Hosp, Columbus, OH USA. [Whitton, John] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Robison, Leslie L.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. [Diller, Lisa] Childrens Hosp, Dana Farber Canc Inst, Ctr Canc, Boston, MA 02115 USA. RP Henderson, TO (reprint author), Univ Chicago, Dept Pediat, 5841 S Maryland Ave,MC 4060, Chicago, IL 60637 USA. EM thenderson@peds.bsd.uchicago.edu FU National Cancer Institute (NCI) [U24 CA55727, K07CA134935]; NIH; American Lebanese-Syrian Associated Charities FX The Childhood Cancer Survivor Study is a collaborative, multi-institutional study funded by the National Cancer Institute (NCI, grant # U24 CA55727; L. L. Robison, Principal Investigator). Additional support was provided by the Intramural Research Program of the NIH and NCI, and the American Lebanese-Syrian Associated Charities. The primary investigator, Dr. Henderson, received support from the NCI (grant #K07CA134935, Health Beliefs and Behaviors: Cohort Studies in Childhood Cancer Survivors). NR 20 TC 36 Z9 36 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD SEP 1 PY 2012 VL 84 IS 1 BP 224 EP 230 DI 10.1016/j.ijrobp.2011.11.022 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 996CO UT WOS:000308061900059 PM 22795729 ER PT J AU Wakatsuki, M Magpayo, N Kawamura, H Held, KD AF Wakatsuki, Masaru Magpayo, Nicole Kawamura, Hidemasa Held, Kathryn D. TI Differential Bystander Signaling Between Radioresistant Chondrosarcoma Cells and Fibroblasts After X-Ray, Proton, Iron Ion and Carbon Ion Exposures SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID MEDIATED INTERCELLULAR COMMUNICATION; IRRADIATED-CELLS; CARCINOMA-CELLS; GLIOMA-CELLS; LOW-LET; RADIATION; RESPONSES; RADIOTHERAPY AB Purpose: Chondrosarcoma is well known as a radioresistant tumor, but the mechanisms underlying that resistance are still unclear. The bystander effect is well documented in the field of radiation biology. We investigated the bystander response induced by X-rays, protons, carbon ions, and iron ions in chondrosarcoma cells using a transwell insert co-culture system that precludes physical contact between targeted and bystander cells. Methods and Materials: Human chondrosarcoma cells were irradiated with 0.1-, 0.5-, 1-, and 2-Gy X-rays, protons, carbon ions or iron ions using a transwell insert co-culture system. Formation of micronuclei and p53 binding protein 1 staining in bystander and irradiated cells were analyzed and bystander signaling between mixed cultures of chondrosarcoma cells, and normal human skin fibroblasts was investigated. Results: In this study, we show that the fraction of cells with DNA damages in irradiated chondrosarcoma cells showed dose-dependent increases with all beams. However, the fraction of cells with DNA damages in all bystander chondrosarcoma cells did not show any change from the levels in control cells. In the bystander signaling between mixed cultures of chondrosarcoma cells and fibroblasts, the amount of micronucleus formation in all bystander chondrosarcoma cells co-cultured with irradiated fibroblasts were the same as the levels for control cells. However, all bystander fibroblasts co-cultured with irradiated chondrosarcoma cells showed significant increases in the fraction of micronucleated cells compared to the rate of control cells. Conclusions: We conclude that chondrosarcoma cells in the transwell insert co-culture system could release bystander stimulations but could not develop bystander responses. (C) 2012 Elsevier Inc. C1 [Wakatsuki, Masaru] Natl Inst Radiol Sci, Res Ctr Charged Particle Therapy, Inage Ku, Chiba 2638555, Japan. [Wakatsuki, Masaru; Magpayo, Nicole; Kawamura, Hidemasa; Held, Kathryn D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. RP Wakatsuki, M (reprint author), Natl Inst Radiol Sci, Res Ctr Charged Particle Therapy, Inage Ku, 4-9-1 Anagawa, Chiba 2638555, Japan. EM wa@mbe.nifty.com FU National Aeronautics and Space Administration (NASA) [NNX07AE40G] FX Supported in part by National Aeronautics and Space Administration (NASA) grant # NNX07AE40G. NR 20 TC 7 Z9 7 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD SEP 1 PY 2012 VL 84 IS 1 BP E103 EP E108 DI 10.1016/j.ijrobp.2012.02.052 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 996CO UT WOS:000308061900015 PM 22537542 ER PT J AU Neauport, A Rodgers, RF Simon, NM Birmes, PJ Schmitt, L Bui, E AF Neauport, Audrey Rodgers, Rachel F. Simon, Naomi M. Birmes, Philippe J. Schmitt, Laurent Bui, Eric TI Effects of a psychiatric label on medical residents' attitudes SO INTERNATIONAL JOURNAL OF SOCIAL PSYCHIATRY LA English DT Article DE labeling; medical residents; psychiatric stigma; vignette ID MENTAL-ILLNESS; SCHIZOPHRENIA; BELIEFS; PEOPLE AB Background: Few data are available on the effects of a psychiatric label on medical residents' attitudes towards an individual. Aims: To investigate the effect of a psychiatric label on the attitudes of medical residents towards an individual. Methods: Medical residents were randomly assigned to one of two vignettes describing the same apparently healthy person, differing only in the presence of a psychiatric label for one of them. Participants (N = 322) reported their attitudes towards the described individual and their willingness to treat this person. Results: Residents allocated to the psychiatric-diagnostic label group reported being less at ease with becoming the individual's nextdoor neighbour, working in the same place, sharing a house, having him look after their children, having a member of their family date him, having their finances run by the individual, less willing to become friends with the described individual and more uneasy having to examine him the next time he visits the emergency room. Conclusion: Implementing effective programmes to combat stigma in the curriculum of medical residents appears to be needed. C1 [Bui, Eric] CHU Toulouse, Lab Stress Traumat, EA4560, F-31059 Toulouse, France. [Rodgers, Rachel F.] Univ Toulouse, Ctr Etud & Rech Psychopathol, F-31059 Toulouse, France. [Simon, Naomi M.; Bui, Eric] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Bui, E (reprint author), CHU Toulouse, Lab Stress Traumat, EA4560, 170 Ave Casselardit, F-31059 Toulouse, France. EM bui.e@chu-toulouse.fr RI Bui, Eric/J-8347-2015 OI Bui, Eric/0000-0002-1413-6473 NR 9 TC 2 Z9 2 U1 0 U2 3 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0020-7640 J9 INT J SOC PSYCHIATR JI Int. J. Soc. Psychiatr. PD SEP PY 2012 VL 58 IS 5 BP 485 EP 487 DI 10.1177/0020764011408652 PG 3 WC Psychiatry SC Psychiatry GA 995CT UT WOS:000307985500005 PM 21712301 ER PT J AU Volk, JE Liu, A Vittinghoff, E Irvin, R Kroboth, E Krakower, D Mimiaga, MJ Mayer, KH Sullivan, PS Buchbinder, SP AF Volk, Jonathan E. Liu, Albert Vittinghoff, Eric Irvin, Risha Kroboth, Elizabeth Krakower, Douglas Mimiaga, Matthew J. Mayer, Kenneth H. Sullivan, Patrick S. Buchbinder, Susan P. TI Sexual Frequency and Planning Among At-Risk Men Who Have Sex With Men in the United States: Implications for Event-Based Intermittent Pre-Exposure Prophylaxis SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE intermittent pre-exposure prophylaxis; pre-exposure prophylaxis; event-based dosing; men-who-have-sex-with-men; HIV; sexual frequency; sexual planning ID HIV-INFECTION; POSTEXPOSURE PROPHYLAXIS; EMTRICITABINE; TENOFOVIR AB Intermittent dosing of pre-exposure prophylaxis (iPrEP) has potential to decrease costs, improve adherence, and minimize toxicity. Practical event-based dosing of iPrEP requires men who have sex with men (MSM) to be sexually active on fewer than 3 days each week and plan for sexual activity. MSM who may be most suitable for event-based dosing were older, more educated, more frequently used sexual networking websites, and more often reported that their last sexual encounter was not with a committed partner. A substantial proportion of these MSM endorse high-risk sexual activity, and event-based iPrEP may best target this population. C1 [Volk, Jonathan E.; Liu, Albert; Irvin, Risha; Kroboth, Elizabeth; Buchbinder, Susan P.] HIV Res Sect, Dept Publ Hlth, San Francisco, CA USA. [Volk, Jonathan E.] Univ Calif San Francisco, Div Infect Dis, San Francisco, CA 94143 USA. [Volk, Jonathan E.] Univ Calif San Francisco, Ctr AIDS Prevent Studies, San Francisco, CA 94143 USA. [Liu, Albert] Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA. [Vittinghoff, Eric; Buchbinder, Susan P.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Krakower, Douglas; Mayer, Kenneth H.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Infect Dis, Boston, MA 02215 USA. [Mimiaga, Matthew J.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Mimiaga, Matthew J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Mimiaga, Matthew J.; Mayer, Kenneth H.] Fenway Hlth, Fenway Inst, Boston, MA USA. [Sullivan, Patrick S.] Emory Univ, Dept Epidemiol, Rollings Sch Publ Hlth, Atlanta, GA 30322 USA. RP Volk, JE (reprint author), 25 Van Ness Ave,Suite 500, San Francisco, CA 94102 USA. EM jonathan.volk@ucsf.edu OI Sullivan, Patrick/0000-0002-7728-0587 FU National Institutes of Health [R01-AI083060]; Emory Center for AIDS Research [P30 AI0050409]; National Institutes of Mental Health of the US Public Health Service [MH-19105-23]; Harvard T32 post-doctoral HIV Clinical Research Fellowship [NIAID AI007433]; Gilead Sciences FX Supported by National Institutes of Health grant R01-AI083060 and the Emory Center for AIDS Research (P30 AI0050409). Dr J.V. received support from the Traineeship in AIDS Prevention Studies T32 post-doctoral fellowship (MH-19105-23) from the National Institutes of Mental Health of the US Public Health Service and Dr D.K. received support from the Harvard T32 post-doctoral HIV Clinical Research Fellowship (NIAID AI007433).; D.K. has conducted research with project support from Gilead Sciences. All other authors have no funding or conflicts of interest to disclose. NR 17 TC 11 Z9 11 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD SEP 1 PY 2012 VL 61 IS 1 BP 112 EP 115 DI 10.1097/QAI.0b013e31825bd87d PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 999YO UT WOS:000308352000022 PM 22592590 ER PT J AU Suzuki, T Campbell, J Kim, Y Swoboda, JG Mylonakis, E Walker, S Gilmore, MS AF Suzuki, Takashi Campbell, Jennifer Kim, Younghoon Swoboda, Jonathan G. Mylonakis, Eleftherios Walker, Suzanne Gilmore, Michael S. TI Wall teichoic acid protects Staphylococcus aureus from inhibition by Congo red and other dyes SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article DE bacteria; antibiotics; S; aureus ID LIPOTEICHOIC ACID; ASPERGILLUS-NIGER; SACCHAROMYCES-CEREVISIAE; CAENORHABDITIS-ELEGANS; NASAL COLONIZATION; CALCOFLUOR WHITE; BIOSYNTHESIS; GENE; VIRULENCE; PATHWAY AB Polyanionic polymers, including lipoteichoic acid and wall teichoic acid, are important determinants of the charged character of the staphylococcal cell wall. This study was designed to investigate the extent to which teichoic acid contributes to protection from anionic azo dyes and to identify barriers to drug penetration for development of new antibiotics for multidrug-resistant Staphylococcus aureus infection. We studied antimicrobial activity of azo dyes against S. aureus strains with or without inhibition of teichoic acid in vitro and in vivo. We observed that inhibition of wall teichoic acid expression resulted in an approximate to 1000-fold increase in susceptibility to azo dyes such as Congo red, reducing its MIC from 1024 to 4 mg/L. Sensitization occurred when the first step in the wall teichoic acid pathway, catalysed by TarO, was inhibited either by mutation or by chemical inhibition. In contrast, genetic blockade of lipoteichoic acid biosynthesis did not confer Congo red susceptibility. Based on this finding, combination therapy was tested using the highly synergistic combination of Congo red plus tunicamycin at sub-MIC concentrations (to inhibit wall teichoic acid biosynthesis). The combination rescued Caenorhabditis elegans from a lethal challenge of S. aureus. Our studies show that wall teichoic acid confers protection to S. aureus from anionic azo dyes and related compounds, and its inhibition raises the prospect of development of new combination therapies based on this inhibition. C1 [Suzuki, Takashi; Gilmore, Michael S.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. [Campbell, Jennifer; Swoboda, Jonathan G.; Walker, Suzanne; Gilmore, Michael S.] Harvard Univ, Sch Med, Dept Microbiol & Immunol, Boston, MA 02115 USA. [Kim, Younghoon] Chonbuk Natl Univ, Dept Anim Sci, Jeonju 561756, South Korea. [Mylonakis, Eleftherios] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Gilmore, MS (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM michael_gilmore@meei.harvard.edu FU Harvard-wide project [AI083214]; PHHS [EY017381, EY08289, GM078477, F3178727, F32AI084316]; Uehara Memorial Foundation; Japanese Eye Bank Society FX This work was supported by Harvard-wide project AI083214 and by PHHS grants EY017381 and EY08289 to M. S. G., GM078477 to S. W., F3178727 to J. G. S., F32AI084316 to J. C. and by the Uehara Memorial Foundation and the Japanese Eye Bank Society to T. S. NR 51 TC 9 Z9 9 U1 0 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD SEP PY 2012 VL 67 IS 9 BP 2143 EP 2151 DI 10.1093/jac/dks184 PG 9 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 993CN UT WOS:000307832800012 PM 22615298 ER PT J AU Fazeli, PK Bredella, MA Freedman, L Thomas, BJ Breggia, A Meenaghan, E Rosen, CJ Klibanski, A AF Fazeli, Pouneh K. Bredella, Miriam A. Freedman, Lauren Thomas, Bijoy J. Breggia, Anne Meenaghan, Erinne Rosen, Clifford J. Klibanski, Anne TI Marrow fat and preadipocyte factor-1 levels decrease with recovery in women with anorexia nervosa SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE MARROW ADIPOSITY; ANOREXIA NERVOSA; PREF-1; BONE MINERAL DENSITY; ADIPOSE DEPOTS ID BONE-MARROW; WEIGHT-GAIN; STEM-CELLS; REDISTRIBUTION; OSTEOPOROSIS; POPULATIONS; TURNOVER; TISSUE AB Women with anorexia nervosa (AN) have elevated marrow fat mass despite low visceral and subcutaneous fat depots, which is inversely associated with bone mineral density (BMD). Whether marrow fat mass remains persistently elevated or decreases with recovery from AN is currently unknown. In this study, we investigated changes in marrow fat in women who have recovered from AN (AN-R). We also studied the relationship between preadipocyte factor (Pref)-1a member of the EGF-like family of proteins and regulator of adipocyte and osteoblast differentiationand fat depots and BMD in AN-R compared with women with AN and healthy controls (HC). We studied 29 women: 14 with active or recovered AN (30.7?+?2.2 years [mean?+/-?SEM]) and 15 normal-weight controls (27.8?+/-?1.2 years). We measured marrow adipose tissue (MAT) of the L4 vertebra and femur by 1H-magnetic resonance spectroscopy; BMD of the spine, hip, and total body by DXA; and serum Pref-1 and leptin levels. We found that MAT of the L4 vertebra was significantly lower in AN-R compared with AN (p?=?0.03) and was comparable to levels in HC. Pref-1 levels were also significantly lower in AN-R compared with AN (p?=?0.02) and comparable to levels in healthy controls. Although Pref-1 was positively associated with MAT of the L4 vertebra in AN (R?=?0.94; p?=?0.002), we found that it was inversely associated with MAT of the L4 vertebra in HC (R?=?-0.71; p?=?0.004). Therefore, we have shown that MAT and Pref-1 levels decrease with recovery from AN. Our data suggest that Pref-1 may have differential effects in states of nutritional deprivation compared with nutritional sufficiency. (c) 2012 American Society for Bone and Mineral Research. C1 [Fazeli, Pouneh K.; Freedman, Lauren; Meenaghan, Erinne; Klibanski, Anne] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Fazeli, Pouneh K.; Bredella, Miriam A.; Freedman, Lauren; Thomas, Bijoy J.; Meenaghan, Erinne; Klibanski, Anne] Harvard Univ, Sch Med, Boston, MA USA. [Bredella, Miriam A.; Thomas, Bijoy J.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Breggia, Anne; Rosen, Clifford J.] Maine Med Ctr, Res Inst, Scarborough, ME USA. RP Fazeli, PK (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B, Boston, MA 02114 USA. EM pkfazeli@partners.org FU NIH [UL1 RR025758, R24 DK084970]; Harvard Clinical and Translational Science Center; National Center for Research Resources; KL2 Medical Research Investigator Training (MeRIT) program of Harvard Catalyst FX We would like to that the nurses and bionutritionists of the MGH Clinical Research Center for their expert care. The project described was supported by NIH grant numbers UL1 RR025758, Harvard Clinical and Translational Science Center, the National Center for Research Resources, the KL2 Medical Research Investigator Training (MeRIT) program of Harvard Catalyst and NIH grant R24 DK084970. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. NR 24 TC 30 Z9 31 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2012 VL 27 IS 9 BP 1864 EP 1871 DI 10.1002/jbmr.1640 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 993VV UT WOS:000307889000003 PM 22508185 ER PT J AU Park, ER Kirchhoff, AC Zallen, JP Weissman, JS Pajolek, H Mertens, AC Armstrong, GT Robison, LL Donelan, K Recklitis, CJ Diller, LR Kuhlthau, KA AF Park, Elyse R. Kirchhoff, Anne C. Zallen, Jennifer P. Weissman, Joel S. Pajolek, Hannah Mertens, Ann C. Armstrong, Gregory T. Robison, Leslie L. Donelan, Karen Recklitis, Christopher J. Diller, Lisa R. Kuhlthau, Karen A. TI Childhood Cancer Survivor Study participants' perceptions and knowledge of health insurance coverage: implications for the Affordable Care Act SO JOURNAL OF CANCER SURVIVORSHIP-RESEARCH AND PRACTICE LA English DT Article DE Childhood cancer; Childhood Cancer Survivor Study; Health insurance; Affordable Care Act ID LONG-TERM SURVIVORS; ADULT SURVIVORS; 5-YEAR SURVIVORS; COHORT; INTERVENTION; INTERVIEWS; NEOPLASMS; DISEASE AB Childhood cancer survivors face long-term health consequences, and comprehensive health insurance is critical. However, childhood cancer survivors may face barriers in accessing medical services due to being uninsured or underinsured. Little is known about the quality of survivors' health insurance coverage, and improving health insurance within the context of changes mandated by the 2010 Affordable Care Act requires understanding survivors' coverage. The current study explored adult childhood cancer survivors' quality of health insurance coverage. From 9/09 to 2/10, we conducted in-depth, semistructured qualitative interviews with 39 adult participants from the Childhood Cancer Survivor Study, a cohort of 5-year survivors of cancers diagnosed before age 21. Interviews were recorded and transcribed; content analyses were conducted by two coders (kappa = 0.88) using NVivo 8. Most insured survivors reported satisfaction with the quality of their coverage; however, they expressed low expectations. Almost half reported annual out-of-pocket costs exceeding $2,000, yet most felt fortunate to simply have coverage. One third of insured survivors had difficulty obtaining coverage, and many had difficulties understanding how to utilize it. Most uninsured survivors minimized their need for care. Worry about future health care costs seemed inevitable among insured and uninsured survivors. Almost all participants lacked knowledge about existing health insurance-related laws. Insured survivors had low coverage expectations, and uninsured survivors avoided care. Childhood cancer survivors will likely benefit from assistance in how to access and utilize the new health care reform provisions (e.g., Medicaid expansion, expansion of parents' insurance, and mandatory primary care coverage). C1 [Park, Elyse R.; Zallen, Jennifer P.; Weissman, Joel S.; Pajolek, Hannah; Donelan, Karen; Kuhlthau, Karen A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kirchhoff, Anne C.] Univ Utah, Dept Pediat, Huntsman Canc Inst, Salt Lake City, UT USA. [Mertens, Ann C.] Emory Sch Publ Hlth, Dept Pediat, Atlanta, GA USA. [Armstrong, Gregory T.; Robison, Leslie L.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. [Recklitis, Christopher J.; Diller, Lisa R.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Park, ER (reprint author), Massachusetts Gen Hosp, 50 Staniford St,Suite 901, Boston, MA 02114 USA. EM epark@partners.org FU Lance Armstrong Foundation; National Cancer Institute [U24 CA 55727] FX We want to acknowledge the Lance Armstrong Foundation and the National Cancer Institute (U24 CA 55727) for supporting this work. We want to thank Drs. Howard Weinstein and Mary Huang in the Center for Pediatric Hematology and Oncology at the Massachusetts General Hospital Cancer Center for their assistance in identifying pilot participants. Finally, we would like to thank Aaron McDonald, Melanie Jackson, and Blair Benavides at the Childhood Cancer Survivor Study for their work on data collection and study coordination. NR 32 TC 18 Z9 18 U1 0 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1932-2259 J9 J CANCER SURVIV JI J. Cancer Surviv.-Res. Pract. PD SEP PY 2012 VL 6 IS 3 BP 251 EP 259 DI 10.1007/s11764-012-0225-y PG 9 WC Oncology; Social Sciences, Biomedical SC Oncology; Biomedical Social Sciences GA 999PB UT WOS:000308325200002 PM 22592507 ER PT J AU Ananthakrishnan, AN AF Ananthakrishnan, Ashwin N. TI Causality in administrative datasets Reply SO JOURNAL OF CROHNS & COLITIS LA English DT Letter ID INFLAMMATORY-BOWEL-DISEASE; HOSPITAL VOLUME; MORTALITY; IMPACT C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. EM aananthakrishnan@partners.org NR 5 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1873-9946 J9 J CROHNS COLITIS JI J. Crohns Colitis PD SEP PY 2012 VL 6 IS 8 BP 868 EP 868 DI 10.1016/j.crohns.2012.04.012 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 994HF UT WOS:000307920800008 ER PT J AU Ioannou, GN AF Ioannou, George N. TI Beyond obesity: Is cholesterol-induced liver injury the cause of non-alcoholic steatohepatitis? SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Editorial Material ID DIETARY-CHOLESTEROL; MICE; INFLAMMATION; STEATOSIS; FIBROSIS AB See article in J. Gastroenterol. Hepatol. 2012; 27: 15201527. C1 [Ioannou, George N.] Vet Affairs Puget Sound Hlth Care Syst, Div Gastroenterol, Seattle, WA 98108 USA. [Ioannou, George N.] Univ Washington, Seattle, WA 98195 USA. RP Ioannou, GN (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Div Gastroenterol, S-111-GI,1660 S Columbian Way, Seattle, WA 98108 USA. EM georgei@medicine.washington.edu FU NIDDK NIH HHS [P30 DK017047] NR 11 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0815-9319 J9 J GASTROEN HEPATOL JI J. Gastroenterol. Hepatol. PD SEP PY 2012 VL 27 IS 9 BP 1412 EP 1414 DI 10.1111/j.1440-1746.2012.07196.x PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 994WN UT WOS:000307965100002 PM 22908868 ER PT J AU Verma, A White, M Vathipadiekal, V Tripathi, S Mbianda, J Ieong, M Qi, L Taubenberger, JK Takahashi, K Jensenius, JC Thiel, S Hartshorn, KL AF Verma, Anamika White, Mitchell Vathipadiekal, Vinod Tripathi, Shweta Mbianda, Julvet Ieong, Micheal Qi, Li Taubenberger, Jeffery K. Takahashi, Kazue Jensenius, Jens C. Thiel, Steffen Hartshorn, Kevan L. TI Human H-Ficolin Inhibits Replication of Seasonal and Pandemic Influenza A Viruses SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SURFACTANT PROTEIN-D; PATTERN-RECOGNITION MOLECULES; INNATE IMMUNE PROTEINS; MANNAN-BINDING LECTIN; ANTIINFLUENZA ACTIVITIES; COMPLEMENT ACTIVATION; ANTIVIRAL ACTIVITY; PENTRAXIN PTX3; HAKATA ANTIGEN; ACETYL GROUPS AB The collectins have been shown to have a role in host defense against influenza A virus (IAV) and other significant viral pathogens (e. g., HIV). The ficolins are a related group of innate immune proteins that are present at relatively high concentrations in serum, but also in respiratory secretions; however, there has been little study of the role of ficolins in viral infection. In this study, we demonstrate that purified recombinant human H-ficolin and H-ficolin in human serum and bronchoalveolar lavage fluid bind to IAV and inhibit viral infectivity and hemagglutination activity in vitro. Removal of ficolins from human serum or bronchoalveolar lavage fluid reduces their antiviral activity. Inhibition of IAV did not involve the calcium-dependent lectin activity of H-ficolin. We demonstrate that H-ficolin is sialylated and that removal of sialic acid abrogates IAV inhibition, while addition of the neuraminidase inhibitor oseltamivir potentiates neutralization, hemagglutinin inhibition, and viral aggregation caused by H-ficolin. Pandemic and mouse-adapted strains of IAV are generally not inhibited by the collectins surfactant protein D or mannose binding lectin because of a paucity of glycan attachments on the hemagglutinin of these strains. In contrast, H-ficolin inhibited both the mouse-adapted PR-8 H1N1 strain and a pandemic H1N1 strain from 2009. H-ficolin also fixed complement to a surface coated with IAV. These findings suggest that H-ficolin contributes to host defense against IAV. The Journal of Immunology, 2012, 189: 2478-2487. C1 [Verma, Anamika; White, Mitchell; Tripathi, Shweta; Mbianda, Julvet; Ieong, Micheal; Hartshorn, Kevan L.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Vathipadiekal, Vinod] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA. [Qi, Li; Taubenberger, Jeffery K.] NIAID, Bethesda, MD 20892 USA. [Takahashi, Kazue] Massachusetts Gen Hosp, Dept Pediat, Program Dev Immunol, Boston, MA 02114 USA. [Jensenius, Jens C.; Thiel, Steffen] Aarhus Univ, Dept Biomed, DK-8000 Aarhus, Denmark. RP Hartshorn, KL (reprint author), Boston Univ, Sch Med, Dept Med, Room 414,650 Albany St, Boston, MA 02118 USA. EM khartsho@bu.edu OI Hartshorn, Kevan/0000-0002-7196-7433; Vathipadiekal, Vinod/0000-0002-8181-6890 FU National Institutes of Health [AI-83222, HL069031]; National Institutes of Health; Novo Nordisk Foundation FX This work was supported by National Institutes of Health Grants AI-83222 and HL069031 (to K. L. H.), National Institutes of Health intramural funds (to J.K.T.), and the Novo Nordisk Foundation (to S. Thiel). NR 39 TC 29 Z9 30 U1 0 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 2012 VL 189 IS 5 BP 2478 EP 2487 DI 10.4049/jimmunol.1103786 PG 10 WC Immunology SC Immunology GA 996JZ UT WOS:000308083600048 PM 22851708 ER PT J AU Vasir, B Zarwan, C Ahmad, R Crawford, KD Rajabi, H Matsuoka, KI Rosenblatt, J Wu, ZK Mills, H Kufe, D Avigan, D AF Vasir, Baldev Zarwan, Corrine Ahmad, Rehan Crawford, Keith D. Rajabi, Hassan Matsuoka, Ken-Ichi Rosenblatt, Jacalyn Wu, Zekui Mills, Heidi Kufe, Donald Avigan, David TI Induction of Antitumor Immunity Ex Vivo Using Dendritic Cells Transduced With Fowl Pox Vector Expressing MUC1, CEA, and a Triad of Costimulatory Molecules (rF-PANVAC) SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE cancer vaccines; immunotherapy; dendritic cells; rF-PANVAC; regulatory T cells ID REGULATORY T-CELLS; CARCINOEMBRYONIC ANTIGEN CEA; CHEMOKINE RECEPTOR EXPRESSION; ADVANCED PROSTATE-CANCER; RECOMBINANT VACCINIA; TRANSGENIC MICE; HELPER-CELLS; PHASE-I; VIRUS; STAT3 AB The fowl pox vector expressing the tumor-associated antigens, mucin-1 and carcinoembryonic antigen in the context of costimulatory molecules (rF-PANVAC) has shown promise as a tumor vaccine. However, vaccine-mediated expansion of suppressor T-cell populations may blunt clinical efficacy. We characterized the cellular immune response induced by ex vivo dendritic cells (DCs) transduced with (rF)-PANVAC. Consistent with the functional characteristics of potent antigen-presenting cells, rF-PANVAC-DCs demonstrated strong expression of mucin-1 and carcinoembryonic antigen and costimulatory molecules, CD80, CD86, and CD83; decreased levels of phosphorylated STAT3, and increased levels of Tyk2, Janus kinase 2, and STAT1. rF-PAN-VAC-DCs stimulated expansion of tumor antigen-specific T cells with potent cytolytic capacity. However, rF-PANVAC-transduced DCs also induced the concurrent expansion of FOXP3 expressing CD4 (+) CD25 (+) high regulatory T cells (Tregs) that inhibited T-cell activation. Moreover, Tregs expressed high levels of Th2 cytokines [interleukin (IL)-10, IL-4, IL-5, and IL-13] together with phosphorylated STAT3 and STAT6. In contrast, the vaccine-expanded Treg population expressed high levels of Th1 cytokines IL-2 and interferon-gamma and the proinflammatory receptor-related orphan receptor gamma t (ROR gamma t) and IL-17A suggesting that these cells may share effector functions with conventional T(H)17 T cells. These data suggest that Tregs expanded by rF-PANVAC-DCs, exhibit immunosuppressive properties potentially mediated by Th2 cytokines, but simultaneous expression of Th1 and Th17-associated factors suggests a high degree of plasticity. C1 [Avigan, David] Beth Israel Deaconess Med Ctr, Hematol Malignancy Bone Marrow Transplant Program, Boston, MA 02115 USA. [Vasir, Baldev; Ahmad, Rehan; Rajabi, Hassan; Matsuoka, Ken-Ichi; Wu, Zekui; Kufe, Donald] Dana Farber Canc Inst, Boston, MA 02115 USA. [Crawford, Keith D.] Brigham & Womens Hosp, Ctr Mol Orthopaed, Boston, MA 02115 USA. RP Avigan, D (reprint author), Beth Israel Deaconess Med Ctr, Hematol Malignancy Bone Marrow Transplant Program, 330 Brookline Ave,KS-121, Boston, MA 02115 USA. EM davigan@bidmc.harvard.edu FU Dana-Farber/Harvard Cancer Center Ovarian Cancer Specialized Program of Research Excellence (SPORE) [P50CA105009-04] FX Supported by Dana-Farber/Harvard Cancer Center Ovarian Cancer Specialized Program of Research Excellence (SPORE) Grant P50CA105009-04. NR 59 TC 4 Z9 4 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD SEP PY 2012 VL 35 IS 7 BP 555 EP 569 DI 10.1097/CJI.0b013e31826a73de PG 15 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 997AG UT WOS:000308135700004 PM 22892452 ER PT J AU Roullet, JB Merkens, LS Pappu, AS Jacobs, MD Winter, R Connor, WE Steiner, RD AF Roullet, Jean-Baptiste Merkens, Louise S. Pappu, Anuradha S. Jacobs, Megan D. Winter, Rolf Connor, William E. Steiner, Robert D. TI No evidence for mevalonate shunting in moderately affected children with Smith-Lemli-Opitz syndrome SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Article ID CHOLESTEROL-SYNTHESIS; DIETARY-CHOLESTEROL; LIPOPROTEIN CHOLESTEROL; REDUCTASE GENE; PLASMA; URINARY; ACID; 7-DEHYDROCHOLESTEROL; MUTATIONS; BIOSYNTHESIS AB Smith-Lemli-Opitz syndrome (SLOS) is caused by a genetic deficiency in 7-dehydrocholesterol (7-DHC) reductase (EC 1.3.1.21), the last enzyme of the cholesterol synthetic pathway. In SLOS, plasma cholesterol concentration is reduced and immediate precursor concentration (7-DHC) is elevated. Surprisingly, total sterol synthesis is reduced but HMG-CoA reductase activity, a rate-limiting enzyme in cholesterol synthesis is unaltered as judged by normal urinary excretion of mevalonic acid (MVA) (Pappu et al. J Lipid Res 43:1661-1669, 2002). These findings raise the possibility of increased diversion of MVA into the MVA shunt pathway away from sterol synthesis, by activation of the shunt pathway enzymes. To test this hypothesis, we measured the urinary excretion of 3-methylglutaconic acid (U-3MGC), a by-product of the shunt pathway, in 19 mildly to moderately severely affected SLOS subjects (ten males, nine females) receiving either a cholesterol-free or a high cholesterol diet, and in 20 age- and sex-matched controls. U-3MGC was similar in SLOS and controls, and was unaffected by dietary cholesterol intake. Further, no change in U-3MGC was observed in a subset of SLOS subjects (n = 9) receiving simvastatin. In contrast, U-MVA was reduced by cholesterol supplementation (54%, p < 0.05) and by simvastatin (50%, p < 0.04). There was no correlation between U-3MGC and either plasma sterol concentrations, urinary isoprenoids, or the subjects' clinical severity score. However U-3MGC was inversely correlated with age (p < 0.04) and body weight (p < 0.02), and higher in females than in males (65%, p < 0.025). The data show that DHCR7 deficiency does not result in 3MGC accumulation in SLOS and suggest that the MVA shunt pathway is not activated in patients with the condition. C1 [Roullet, Jean-Baptiste] Oregon Hlth & Sci Univ, Dept Pediat, CDRC P, Div Res, Portland, OR 97239 USA. [Pappu, Anuradha S.] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97239 USA. [Winter, Rolf] Portland VA Med Ctr, Antimalarial Drug Discovery Lab, Portland, OR USA. [Connor, William E.] Oregon Hlth & Sci Univ, Dept Med, Div Endocrinol Diabet & Clin Nutr, Portland, OR 97239 USA. [Steiner, Robert D.] Oregon Hlth & Sci Univ, Doernbecher Childrens Hosp, Oregon Clin & Translat Res Inst, Dept Pediat,Child Dev & Rehabil Ctr, Portland, OR 97239 USA. [Steiner, Robert D.] Oregon Hlth & Sci Univ, Doernbecher Childrens Hosp, Oregon Clin & Translat Res Inst, Dept Mol & Med Genet,Child Dev & Rehabil Ctr, Portland, OR 97239 USA. RP Roullet, JB (reprint author), Oregon Hlth & Sci Univ, Dept Pediat, CDRC P, Div Res, 707 SW Gaines St, Portland, OR 97239 USA. EM roulletj@ohsu.edu OI Steiner, Robert/0000-0003-4177-4590 FU NIH [R01 HL073980]; Oregon Clinical and Translational Research Institute (OCTRI) from National Center for Research Resources (NCRR), National Institutes of Health (NIH) [UL1 RR024140]; NIH Roadmap for Medical Research FX This work was supported by a grant from NIH (R01 HL073980). This publication was made possible with support from the Oregon Clinical and Translational Research Institute (OCTRI), grant number UL1 RR024140 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. The authors confirm independence from the sponsors; the content of the article has not been influenced by the sponsors. NR 36 TC 8 Z9 8 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PD SEP PY 2012 VL 35 IS 5 BP 859 EP 869 DI 10.1007/s10545-012-9453-6 PG 11 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 998NO UT WOS:000308247000013 PM 22391996 ER PT J AU Kothari, CL Rhodes, KV Wiley, JA Fink, J Overholt, S Dichter, ME Marcus, SC Cerulli, C AF Kothari, Catherine L. Rhodes, Karin V. Wiley, James A. Fink, Jeffrey Overholt, Scott Dichter, Melissa E. Marcus, Steven C. Cerulli, Catherine TI Protection Orders Protect Against Assault and Injury: A Longitudinal Study of Police-Involved Women Victims of Intimate Partner Violence SO JOURNAL OF INTERPERSONAL VIOLENCE LA English DT Article DE battered women; legal intervention; domestic violence ID DOMESTIC VIOLENCE; HELP-SEEKING; ABUSE; SYSTEM; STATES AB The objective of this study was to measure the efficacy of protection orders (POs) in reducing assault and injury-related outcomes using a matched comparison group and tracking outcomes over time. This study was a retrospective review of police, emergency department, family court, and prosecutor administrative records for a cohort of police-involved female IPV victims; all events over a 4-year study period were abstracted. Victims who obtained POs were compared with a propensity-score-based match group without POs over three time periods: Before, During, and After the issuance of a PO. Having a PO in place was associated with significantly more calls to police for nonassaultive incidents and more police charging requests that were of multiple-count and felony-level. Comparing outcomes, PO victims had police incident rates that were more than double the matched group prior to the PO but dropped to the level of the matched group during and after the order. ED visits dropped over time for both groups. This study confirmed the protective effect of POs, which are associated with reduced police incidents and emergency department visits both during and after the order and reduced police incidents compared with a matched comparison group. C1 [Kothari, Catherine L.] Michigan State Univ, Kalamazoo Ctr Med Studies, Kalamazoo, MI 49008 USA. [Rhodes, Karin V.] Univ Penn, Sch Med, Dept Emergency Med, Div Emergency Care Policy Res, Philadelphia, PA 19104 USA. [Wiley, James A.] San Francisco State Univ, Hlth Dispar Program, San Francisco, CA 94132 USA. [Fink, Jeffrey] Kalamazoo Cty, Kalamazoo, MI USA. [Overholt, Scott] State Michigan, Judicial Circuit Court 9, Kalamazoo, MI USA. [Dichter, Melissa E.; Marcus, Steven C.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Marcus, Steven C.] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19104 USA. [Cerulli, Catherine] Univ Rochester, Med Ctr, Sch Med & Dent, Dept Psychiat, Rochester, NY 14642 USA. RP Kothari, CL (reprint author), Michigan State Univ, Kalamazoo Ctr Med Studies, 1000 Oakland Dr, Kalamazoo, MI 49008 USA. EM kothari@kcms.msu.edu OI Kothari, Catherine/0000-0001-8072-8920 FU NIMH NIH HHS [K01 MH075965, K23MH64572, K11MH75965] NR 43 TC 9 Z9 9 U1 0 U2 18 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0886-2605 J9 J INTERPERS VIOLENCE JI J. Interpers. Violence PD SEP PY 2012 VL 27 IS 14 BP 2845 EP 2868 DI 10.1177/0886260512438284 PG 24 WC Criminology & Penology; Family Studies; Psychology, Applied SC Criminology & Penology; Family Studies; Psychology GA 995RZ UT WOS:000308031300006 PM 22491224 ER PT J AU Chien, KR Yi, BA Xu, HS Mummery, CL AF Chien, Kenneth R. Yi, B. Alexander Xu, Huansheng Mummery, Christine L. TI Cardiomyocyte reprogramming and the new age of cellular alchemy SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Editorial Material ID TRANSCRIPTION FACTOR GATA-4; PLURIPOTENT STEM-CELLS; TROPONIN-I GENE; CARDIAC FIBROBLASTS; FUNCTIONAL CARDIOMYOCYTES; EXPRESSION; HEART; VIVO; PHENOTYPE; LINEAGES C1 [Chien, Kenneth R.; Yi, B. Alexander; Xu, Huansheng] Harvard Univ, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Chien, Kenneth R.; Yi, B. Alexander; Xu, Huansheng] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Mummery, Christine L.] Leiden Univ, Med Ctr, Dept Anat & Embryol, NL-2333 ZC Leiden, Netherlands. RP Chien, KR (reprint author), Harvard Univ, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, 7 Divin Ave, Cambridge, MA 02138 USA. EM kchien@harvard.edu; C.L.mummery@umnc.nl FU NHLBI NIH HHS [U01 HL100408] NR 28 TC 5 Z9 5 U1 0 U2 3 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD SEP PY 2012 VL 53 IS 3 BP 311 EP 313 DI 10.1016/j.yjmcc.2012.06.010 PG 3 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 993LO UT WOS:000307861400001 PM 22749824 ER PT J AU Sham, CW Chan, AM Kwong, JMK Caprioli, J Nusinowitz, S Chen, B Lee, JG Gandhi, NM Francisco, LM Sharpe, AH Chen, L Braun, J Gordon, LK AF Sham, Caroline W. Chan, Ann M. Kwong, Jacky M. K. Caprioli, Joseph Nusinowitz, Steven Chen, Bryan Lee, Janice G. Gandhi, Nishant M. Francisco, Loise M. Sharpe, Arlene H. Chen, Ling Braun, Jonathan Gordon, Lynn K. TI Neuronal Programmed Cell Death-1 Ligand Expression Regulates Retinal Ganglion Cell Number in Neonatal and Adult Mice SO JOURNAL OF NEURO-OPHTHALMOLOGY LA English DT Article ID NERVE GROWTH-FACTOR; MOUSE RETINA; VERTEBRATE RETINA; IN-VIVO; RECEPTOR; PD-1; RESPONSES; SURVIVAL; DIFFERENTIATION; AP-2-ALPHA AB Objectives: During mouse retina maturation, the final number of retinal ganglion cells (RGCs) is determined by highly regulated programmed cell death. Previous studies demonstrated that the immunoregulatory receptor programmed cell death-1 (PD-1) promotes developmental RGC death. To identify the functional signaling partner(s) for PD-1, we identified retinal expression of PD-1 ligands and examined the effect of PD-1 ligand expression on RGC number. We also explored the hypothesis that PD-1 signaling promotes the development of functional visual circuitry. Methods: Characterization of retinal and brain programmed cell death-1 ligand 1 (PD-L1) expression were examined by immunofluorescence on tissue sections. The contribution of PD-ligands, PD-L1, and programmed cell death-1 ligand 2 (PD-L2) to RGC number was examined in PD-ligand knockout mice lacking 1 or both ligands. Retinal architecture was assessed by spectral-domain optical coherence tomography, and retinal function was analyzed by electroretinography in wild-type and PD-L1/L2 double-deficient mice. Results: PD-L1 expression is found throughout the neonatal retina and persists in adult RGCs, bipolar interneurons, and Muller glia. In the absence of both PD-ligands, there is a significant numerical increase in RGCs (34% at postnatal day 2 [P2] and 18% in adult), as compared to wild type, and PD-ligands have redundant function in this process. Despite the increased RGC number, adult PD-L1/L2 double-knockout mice have normal retinal architecture and outer retina function. Conclusion: This study demonstrates that PD-L1 and PD-L2 together impact the final number of RGCs in adult mice and supports a novel role for active promotion of neuronal cell death through PD- 1 receptor-ligand engagement. C1 [Chan, Ann M.; Kwong, Jacky M. K.; Caprioli, Joseph; Nusinowitz, Steven; Chen, Bryan; Lee, Janice G.; Gandhi, Nishant M.; Gordon, Lynn K.] Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, Dept Ophthalmol, Los Angeles, CA 90095 USA. [Sham, Caroline W.; Braun, Jonathan] Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Francisco, Loise M.; Sharpe, Arlene H.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Francisco, Loise M.; Sharpe, Arlene H.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Chen, Ling] Fudan Univ, Shanghai Med Sch, Eye & ENT Hosp, Dept Ophthalmol, Shanghai 200433, Peoples R China. [Gordon, Lynn K.] Greater Los Angeles Vet Affairs Healthcare Syst, Ophthalmol Sect, Los Angeles, CA USA. RP Gordon, LK (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, Dept Ophthalmol, 100 Stein Plaza, Los Angeles, CA 90095 USA. EM lgordon@mednet.ucla.edu OI Caprioli, Joseph/0000-0002-2383-7263 FU UCLA Medical Scientist Training Program NIH [T32 GM08042]; National Institutes of Health/National Institute of Allergy and Infectious Diseases Grant [RO1 AI021256]; JSEI Vision Science Training Grant NIH/NEI [T32 EY007026, P01AI56299]; Pujiang Talent Foundation [10PJ1401900]; National Science Foundation of China [81000381] FX This work was supported by the UCLA Medical Scientist Training Program NIH T32 GM08042 (CWS), National Institutes of Health/National Institute of Allergy and Infectious Diseases Grant RO1 AI021256 (CWS), JSEI Vision Science Training Grant NIH/NEI T32 EY007026 (CWS), P01AI56299 (AHS), Pujiang Talent Foundation 10PJ1401900 (LC), and National Science Foundation of China 81000381 (LC). NR 44 TC 1 Z9 2 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1070-8022 J9 J NEURO-OPHTHALMOL JI J. Neuro-Ophthal. PD SEP PY 2012 VL 32 IS 3 BP 227 EP 237 DI 10.1097/WNO.0b013e3182589589 PG 11 WC Clinical Neurology; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 997SY UT WOS:000308187800010 PM 22635166 ER PT J AU Paganoni, S Zhang, M Zarate, AQ Jaffa, M Yu, H Cudkowicz, ME Wills, AM AF Paganoni, Sabrina Zhang, May Zarate, Alejandro Quiroz Jaffa, Matthew Yu, Hong Cudkowicz, Merit E. Wills, Anne-Marie TI Uric acid levels predict survival in men with amyotrophic lateral sclerosis SO JOURNAL OF NEUROLOGY LA English DT Article DE Uric acid; Urate; Amyotrophic lateral sclerosis; Predictor; Survival ID PARKINSON-DISEASE; OXIDATIVE STRESS; PLASMA URATE; SERUM; RISK; PROGRESSION; DIAGNOSIS; TRIAL; GOUT; ALS AB Elevated uric acid levels have recently been found to be associated with slower disease progression in Parkinson's disease, Huntington's disease, multiple system atrophy, and mild cognitive impairment. The aim of this study is to determine whether serum uric acid levels predict survival in amyotrophic lateral sclerosis (ALS). A total of 251 people with ALS enrolled in two multicenter clinical trials were included in our analysis. The main outcome measure was survival time, which was calculated as time to death, tracheostomy, or permanent assistive ventilation, with any event considered a survival endpoint. Cox proportional hazards models were used to estimate the hazard ratio (HR) of reaching a survival endpoint according to baseline uric acid levels after adjusting for markers of disease severity (FVC, total ALSFRS-R score, time since symptom onset, diagnostic delay, BMI, bulbar vs. spinal onset, age, and riluzole use). There was a dose-dependent survival advantage in men, but not women, with higher baseline uric acid levels (logrank test: p = 0.018 for men, p = 0.81 for women). There was a 39% reduction in risk of death during the study for men with each 1 mg/dl increase in uric acid levels (adjusted HR: 0.61, 95% CI 0.39-0.96, p = 0.03). This is the first study to demonstrate that serum uric acid is associated with prolonged survival in ALS, after adjusting for markers of disease severity. Similar to previous reports in Parkinson's disease, this association was seen in male subjects only. C1 [Paganoni, Sabrina; Zhang, May; Jaffa, Matthew; Yu, Hong; Cudkowicz, Merit E.; Wills, Anne-Marie] Harvard Univ, Neurol Clin Trials Unit, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA. [Zarate, Alejandro Quiroz] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Wills, AM (reprint author), Harvard Univ, Neurol Clin Trials Unit, Massachusetts Gen Hosp, Sch Med, Bldg 149,149 13th St,2nd Floor,Room 2274, Charlestown, MA 02129 USA. EM awills@partners.org FU Muscular Dystrophy Association; Digiovanni ALS research fund FX We would like to thank Patrick Sluss, Ph.D., and the Clinical Laboratory Research Core at Massachusetts General Hospital for performing the biochemical analyses and for their excellent technical support. We thank David Schoenfeld, Ph.D. and Alberto Ascherio, M.D., Dr. P.H. for helpful discussions about data analysis and interpretation. We thank Swati Aggarwal, M.D. for helping with study design. We would also like to thank the Massachusetts General Hospital Neurology Clinical Trials Unit and the members of the Northeast ALS Consortium (NEALS) for allowing access to the blood samples and clinical data that were used in this study. Finally, we thank patients and their families for participating in these clinical trials and for contributing to clinical research. Drs. Wills and Paganoni had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. The study was supported by the Muscular Dystrophy Association and the Digiovanni ALS research fund. NR 23 TC 34 Z9 37 U1 2 U2 7 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0340-5354 J9 J NEUROL JI J. Neurol. PD SEP PY 2012 VL 259 IS 9 BP 1923 EP 1928 DI 10.1007/s00415-012-6440-7 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 999PT UT WOS:000308327300020 PM 22323210 ER EF