FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Offner, H Vandenbark, AA AF Offner, Halina Vandenbark, Arthur A. TI RTL therapy for multiple sclerosis Phase 1 clinical study SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Meeting Abstract CT 2nd International Conference on Advances in Clinical Neuroimmunology CY MAY 31-JUN 01, 2010 CL Gdansk, POLAND C1 [Offner, Halina; Vandenbark, Arthur A.] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD MAY PY 2010 VL 222 IS 1-2 BP 2 EP 3 PG 2 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 603WR UT WOS:000278239300004 ER PT J AU Ditman, T Kuperberg, GR AF Ditman, Tali Kuperberg, Gina R. TI Building coherence: A framework for exploring the breakdown of links across clause boundaries in schizophrenia SO JOURNAL OF NEUROLINGUISTICS LA English DT Article DE Schizophrenia; Discourse; ERP; fMRI; Language; Inferences; N400; Pragmatics; Right hemisphere; semantics; Reference; Sentences ID WORKING-MEMORY CAPACITY; FORMAL THOUGHT-DISORDER; 2 CEREBRAL HEMISPHERES; COMMUNICATION DISTURBANCES; NARRATIVE COMPREHENSION; LANGUAGE COMPREHENSION; TEXT COMPREHENSION; CONTEXTUAL INSENSITIVITY; INDIVIDUAL-DIFFERENCES; COGNITIVE IMPAIRMENTS AB Clinically, patients with schizophrenia show prominent abnormalities at the discourse level, with production characterized by tangential and illogical relationships between ideas and unclear references. Despite these clinical manifestations, Most Studies of language in schizophrenia have focused on semantic relationships between single words and the build-LIP of meaning within single-Clause sentences. The present paper discusses the few studies that have gone beyond clause boundaries to fully understand language impairments in schizophrenia. We also give an overview of a relevant literature that considers the neurocognitive mechanisms by which coherence links are established across clauses in healthy adults, providing a framework that may guide future research in this area. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Ditman, Tali; Kuperberg, Gina R.] Tufts Univ, Dept Psychol, Medford, MA 02155 USA. [Ditman, Tali; Kuperberg, Gina R.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. [Ditman, Tali; Kuperberg, Gina R.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Ditman, T (reprint author), Tufts Univ, Dept Psychol, Psychol Bldg,490 Boston Ave, Medford, MA 02155 USA. EM tditman@nmr.mgh.harvard.edu; kuperber@nmr.mgh.harvard.edu FU NIDA NIH HHS [R90 DA023427]; NIMH NIH HHS [R01 MH071635, R01 MH071635-05] NR 138 TC 14 Z9 15 U1 0 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0911-6044 J9 J NEUROLINGUIST JI J. Neurolinguist. PD MAY PY 2010 VL 23 IS 3 SI SI BP 254 EP 269 DI 10.1016/j.jneuroling.2009.03.003 PG 16 WC Linguistics; Neurosciences; Psychology, Experimental SC Linguistics; Neurosciences & Neurology; Psychology GA 569AC UT WOS:000275567200007 PM 20383285 ER PT J AU Nelson, PT Kukull, WA Frosch, MP AF Nelson, Peter T. Kukull, Walter A. Frosch, Matthew P. TI Thinking Outside the Box: Alzheimer-Type Neuropathology That Does Not Map Directly Onto Current Consensus Recommendations SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE Alzheimer disease; Braak; Consortium to Establish a Registry for Alzheimer Disease; Neuropathology; Neurofibrillary tangles; Plaques ID BRAINNET EUROPE CONSORTIUM; LEWY BODIES; NEUROFIBRILLARY TANGLES; DISEASE; DEMENTIA; DIAGNOSIS; PLAQUES; CRITERIA; PATHOLOGY; AUTOPSY AB The brains of many cognitively impaired patients fall into neuropathologic diagnostic categories that cannot be defined explicitly by guidelines of the National Institute on Aging and Reagan Institute. Here, 2 specific case categories are considered: i) "tangle-intensive" patients with the highest density of neurofibrillary tangles (as graded by the Braak staging system) but only moderate density of neuritic amyloid plaques (as graded by the Consortium to Establish a Registry for Alzheimer's Disease); and ii) "plaque-intensive" patients with intermediate severity neurofibrillary tangles and high density of neuritic amyloid plaques. To understand these technically unclassifiable cases better, we analyzed 1,677 cases with antemortem diagnoses of dementia from the National Alzheimer's Coordinating Center Registry; this registry includes both clinical and pathologic data from the National Institute on Aging-funded Alzheimer Disease Center. To evaluate the diagnostic tendencies of Alzheimer Disease Center neuropathologists, we assessed how the plaque-intensive and tangle-intensive cases were diagnosed. Tangle-intensive cases were more likely to be designated "high-likelihood" that the dementia was due to Alzheimer disease, whereas plaque-intensive cases were typically designated as "intermediate likelihood." Only the Braak Stage VI tangle-intensive cases had lower final Mini-Mental State Examination scores than the plaque-intensive cases (p < 0.02). We conclude that more explicit diagnostic categories and a better understanding of the pathology in earlier phases of the disease may be helpful for guiding neuropathologists in the diagnosis of Alzheimer disease. C1 [Nelson, Peter T.] Univ Kentucky, Dept Pathol, Div Neuropathol, Med Ctr, Lexington, KY 40536 USA. Univ Kentucky, Sanders Brown Ctr Aging, Lexington, KY 40536 USA. [Kukull, Walter A.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Frosch, Matthew P.] Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Nelson, PT (reprint author), Univ Kentucky, Dept Pathol, Div Neuropathol, Med Ctr, Rm 311,Sanders Brown Bldg,800 S Limestone, Lexington, KY 40536 USA. EM pnels2@email.uky.edu OI Kukull, Walter/0000-0001-8761-9014 FU National Institutes of Health [R01 NS061933, K08 NS050110, P30 AG028383, P50 AG005134, U01 AG016976]; Alzheimer's Association [NIRG (89917)] FX This study was supported by Grant Nos. R01 NS061933, K08 NS050110, P30 AG028383, P50 AG005134, and U01 AG016976 from the National Institutes of Health and Grant No. NIRG (89917) from Alzheimer's Association. NR 22 TC 23 Z9 23 U1 0 U2 1 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 MAY PY 2010 VL 69 IS 5 BP 449 EP 454 DI 10.1097/NEN.0b013e3181d8db07 PG 6 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 594WV UT WOS:000277571500003 PM 20418781 ER PT J AU Camelo-Piragua, S Jansen, M Ganguly, A Kim, JC Cosper, A Dias-Santagata, D Iafrate, J Nutt, C Louis, D AF Camelo-Piragua, Sandra Jansen, Michael Ganguly, Aniruddha Kim, J. ChulMin Cosper, Arjola Dias-Santagata, Dora Iafrate, John Nutt, Catherine Louis, David TI A Useful Panel to Differentiate Astrocytoma From Astrocytosis SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 86th Annual Meeting of the American-Association-of-Neuropathologists CY JUN 10-13, 2010 CL Philadelphia, PA SP Amer Assoc Neuropathologists C1 [Camelo-Piragua, Sandra; Ganguly, Aniruddha; Cosper, Arjola; Dias-Santagata, Dora; Iafrate, John; Louis, David] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Jansen, Michael; Kim, J. ChulMin; Nutt, Catherine] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2010 VL 69 IS 5 MA 5 BP 522 EP 522 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 594WV UT WOS:000277571500014 ER PT J AU Ramkissoon, S Maire, C Ligon, K AF Ramkissoon, Shakti Maire, Cecile Ligon, Keith TI Directed Pten Loss in Olig2+Stem Cells Results in Massive Myelination and Neurodegeneration in the Absence of Neoplasia SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 86th Annual Meeting of the American-Association-of-Neuropathologists CY JUN 10-13, 2010 CL Philadelphia, PA SP Amer Assoc Neuropathologists C1 [Ramkissoon, Shakti] Brigham & Womens Hosp, Div Neuropathol, Boston, MA 02115 USA. [Maire, Cecile] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA USA. [Ligon, Keith] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2010 VL 69 IS 5 MA 77 BP 541 EP 541 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 594WV UT WOS:000277571500086 ER PT J AU Mckee, A Gavett, B Stern, R Nowinski, C Cantu, R Sullivan, C Perl, D Hedley-Whyte, ET Daneshvar, D Kowall, N Budson, A AF Mckee, Ann Gavett, Brandon Stern, Robert Nowinski, Christopher Cantu, Robert Sullivan, Chris Perl, Daniel Hedley-Whyte, E. Tessa Daneshvar, Daniel Kowall, Neil Budson, Andrew TI TDP-43 Proteinopathy in Chronic Traumatic Encephalopathy SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 86th Annual Meeting of the American-Association-of-Neuropathologists CY JUN 10-13, 2010 CL Philadelphia, PA SP Amer Assoc Neuropathologists C1 [Mckee, Ann] Boston Univ, Sch Med, Bedford VAMC, Boston, MA 02215 USA. [Sullivan, Chris] GRECC, Bedford VAMC, Bedford, MA USA. [Perl, Daniel] Mt Sinai Sch Med, New York, NY USA. [Hedley-Whyte, E. Tessa] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. RI Kowall, Neil/G-6364-2012 OI Kowall, Neil/0000-0002-6624-0213 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2010 VL 69 IS 5 MA 120 BP 552 EP 552 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 594WV UT WOS:000277571500129 ER PT J AU Jansen, M Mohapatra, G Keohane, C Louis, D AF Jansen, Michael Mohapatra, Gayatry Keohane, Catherine Louis, David TI Frequent Gain at Chromosome 1q Occurs in Atypical Meningioma but is a Poor Predictor of Likelihood of Recurrence SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 86th Annual Meeting of the American-Association-of-Neuropathologists CY JUN 10-13, 2010 CL Philadelphia, PA SP Amer Assoc Neuropathologists C1 [Jansen, Michael; Mohapatra, Gayatry] Massachusetts Gen Hosp, Pathol Serv, Boston, MA 02114 USA. [Keohane, Catherine] Cork Univ Hosp, Cork, Ireland. [Louis, David] Massachusetts Gen Hosp, Pathol Serv, Boston, MA 02114 USA. [Louis, David] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2010 VL 69 IS 5 MA 146 BP 559 EP 559 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 594WV UT WOS:000277571500154 ER PT J AU Snuderl, M Kirkpatrick, N Walsh, E Chung, E Kamoun, W Peterson, T Duda, D Fukumura, D Carmeliet, P Xu, L Jain, R AF Snuderl, Matija Kirkpatrick, Nathaniel Walsh, Elisa Chung, Euiheon Kamoun, Walid Peterson, Teresa Duda, Dan Fukumura, Dai Carmeliet, Peter Xu, Lei Jain, Rakesh TI Inhibition of Placental Growth Factor (P1GF) Leads to Regression of Medulloblastoma SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 86th Annual Meeting of the American-Association-of-Neuropathologists CY JUN 10-13, 2010 CL Philadelphia, PA SP Amer Assoc Neuropathologists C1 [Snuderl, Matija] Massachusetts Gen Hosp, Pathol Serv, Boston, MA 02114 USA. [Kirkpatrick, Nathaniel; Walsh, Elisa; Chung, Euiheon; Kamoun, Walid; Peterson, Teresa; Duda, Dan; Fukumura, Dai; Xu, Lei; Jain, Rakesh] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Carmeliet, Peter] Katholieke Univ Leuven, Dept Transgene Technol & Gene Therapy, Louvain, Belgium. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2010 VL 69 IS 5 MA 159 BP 562 EP 562 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 594WV UT WOS:000277571500167 ER PT J AU Chen, ZQ Kujawa, SG Sewell, WF AF Chen, Zhiqiang Kujawa, Sharon G. Sewell, William F. TI Functional Roles of High-Affinity Glutamate Transporters in Cochlear Afferent Synaptic Transmission in the Mouse SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID AMINO-ACID TRANSPORTERS; INNER HAIR CELL; GUINEA-PIG COCHLEA; ASPARTATE TRANSPORTER; MAMMALIAN COCHLEA; RAT; EXPRESSION; SYNAPSES; GLAST; L-TRANS-PYRROLIDINE-2,4-DICARBOXYLATE AB Chen Z, Kujawa SG, Sewell WF. Functional roles of highaffinity glutamate transporters in cochlear afferent synaptic transmission in the mouse. J Neurophysiol 103: 2581-2586, 2010. First published March 10, 2010; doi: 10.1152/jn.00018.2010. In the cochlea, afferent transmission between inner hair cells and auditory neurons is mediated by glutamate receptors. Glutamate transporters located near the synapse and in spiral ganglion neurons are thought to maintain low synaptic levels of glutamate. We analyzed three glutamate transporter blockers for their ability to alter the effects of glutamate, exogenously applied to the synapse via perfusion of the scala tympani of the mouse, and compared that action to their ability to alter the effects of intense acoustic stimulation. Threo-beta-benzyloxyaspartate (TBOA) is a broad-spectrum glutamate transporter antagonist, affecting all three transporters [glutamate/aspartate transporter (GLAST), glutamate transporter-1 (GLT1), and excitatory amino acid carrier 1 (EAAC1)]. L-serine-O-sulfate (SOS) blocks both GLAST and EAAC1 without effect on GLT1. Dihydrokainate (DHK) is selective for GLT1. Infusion of glutamate (10 mu M for 220 min), TBOA (200 mu M for 220 min), or SOS (100 mu M for 180 min) alone did not alter auditory neural thresholds. When infused together with glutamate, TBOA and SOS produced significant neural threshold shifts, leaving otoacoustic emissions intact. In addition, both TBOA and SOS exacerbated noise-induced hearing loss by producing larger neural threshold shifts and delaying recovery. DHK did not alter glutamate- or noise-induced hearing loss. The evidence points to a major role for GLAST, both in protecting the synapse from exposure to excess extracellular glutamate and in attenuating hearing loss due to acoustic overstimulation. C1 [Chen, Zhiqiang; Kujawa, Sharon G.; Sewell, William F.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Kujawa, Sharon G.] Massachusetts Eye & Ear Infirm, Dept Audiol, Boston, MA 02114 USA. [Sewell, William F.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. [Chen, Zhiqiang; Kujawa, Sharon G.; Sewell, William F.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Sewell, WF (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM wfs@epl.meei.harvard.edu FU National Institute of Deafness and Other Communication Disorders [DC-19097, DC-8577] FX This work was supported by National Institute of Deafness and Other Communication Disorders Grant DC-19097 to W. F. Sewell and DC-8577 to S. G. Kujawa. NR 27 TC 9 Z9 10 U1 2 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 MAY PY 2010 VL 103 IS 5 BP 2581 EP 2586 DI 10.1152/jn.00018.2010 PG 6 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 594UN UT WOS:000277564500023 PM 20220082 ER PT J AU Slee, SJ Higgs, MH Fairhall, AL Spain, WJ AF Slee, Sean J. Higgs, Matthew H. Fairhall, Adrienne L. Spain, William J. TI Tonotopic Tuning in a Sound Localization Circuit SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID INTERAURAL TIME DIFFERENCE; IMPROVES COINCIDENCE DETECTION; SUPERIOR OLIVARY NUCLEUS; STEM AUDITORY NUCLEI; BRAIN-STEM; COCHLEAR NUCLEUS; SYNAPTIC TRANSMISSION; CENTRAL NEURONS; LAMINARIS; CHICKEN AB Slee SJ, Higgs MH, Fairhall AL, Spain WJ. Tonotopic tuning in a sound localization circuit. J Neurophysiol 103: 2857-2875, 2010. First published March 10, 2010; doi: 10.1152/jn.00678.2009. Nucleus laminaris (NL) neurons encode interaural time difference (ITD), the cue used to localize low-frequency sounds. A physiologically based model of NL input suggests that ITD information is contained in narrow frequency bands around harmonics of the sound frequency. This suggested a theory, which predicts that, for each tone frequency, there is an optimal time course for synaptic inputs to NL that will elicit the largest modulation of NL firing rate as a function of ITD. The theory also suggested that neurons in different tonotopic regions of NL require specialized tuning to take advantage of the input gradient. Tonotopic tuning in NL was investigated in brain slices by separating the nucleus into three regions based on its anatomical tonotopic map. Patch-clamp recordings in each region were used to measure both the synaptic and the intrinsic electrical properties. The data revealed a tonotopic gradient of synaptic time course that closely matched the theoretical predictions. We also found postsynaptic band-pass filtering. Analysis of the combined synaptic and postsynaptic filters revealed a frequency-dependent gradient of gain for the transformation of tone amplitude to NL firing rate modulation. Models constructed from the experimental data for each tonotopic region demonstrate that the tonotopic tuning measured in NL can improve ITD encoding across sound frequencies. C1 [Slee, Sean J.; Higgs, Matthew H.; Fairhall, Adrienne L.; Spain, William J.] Univ Washington, Dept Physiol & Biophys, Seattle, WA 98195 USA. [Spain, William J.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Spain, William J.] VA Puget Sound Hlth Care Syst, Neurol Sect, Seattle, WA USA. RP Spain, WJ (reprint author), Neurol 127,1660 S Columbian Way, Seattle, WA 98108 USA. EM spain@u.washington.edu FU Veterans Administration; National Institutes of Health; Burroughs-Welcome Careers at the Scientific Interface award; Sloan Research Fellowship FX This work was supported by a Veterans Administration Merit Review to W. J. Spain, a National Institutes of Health training grant to S. J. Slee, and a Burroughs-Welcome Careers at the Scientific Interface award and Sloan Research Fellowship to A. L. Fairhall. NR 49 TC 17 Z9 17 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAY PY 2010 VL 103 IS 5 BP 2857 EP 2875 DI 10.1152/jn.00678.2009 PG 19 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 594UN UT WOS:000277564500048 PM 20220079 ER PT J AU de Kemp, RA Epstein, FH Catana, C Tsui, BMW Ritman, EL AF de Kemp, Robert A. Epstein, Frederick H. Catana, Ciprian Tsui, Benjamin M. W. Ritman, Erik L. TI Small-Animal Molecular Imaging Methods SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE PET; SPECT; MRI; CT ID ULTRA-HIGH-RESOLUTION; RAY COMPUTED-TOMOGRAPHY; DISPLACEMENT-ENCODED MRI; PINHOLE GATED SPECT; MAGNETIC-RESONANCE; MYOCARDIAL-INFARCTION; SYNCHROTRON-RADIATION; EMISSION-TOMOGRAPHY; MURINE MYOCARDIUM; SIMULTANEOUS PET AB The ability to trace or identify specific molecules within a specific anatomic location provides insight into metabolic pathways, tissue components, and tracing of solute transport mechanisms. With the increasing use of small animals for research, such imaging must have sufficiently high spatial resolution to allow anatomic localization as well as sufficient specificity and sensitivity to provide an accurate description of the molecular distribution and concentration. Methods: Imaging methods based on electromagnetic radiation, such as PET, SPECT, MRI, and CT, are increasingly applicable because of recent advances in novel scanner hardware and image reconstruction software and the availability of novel molecules that have enhanced sensitivity in these methodologies. Results: Small-animal PET has been advanced by the development of detector arrays that provide higher resolution and positron-emitting elements that allow new molecular tracers to be labeled. Micro-MRI has been improved in terms of spatial resolution and sensitivity through increased magnet field strength and the development of special-purpose coils and associated scan protocols. Of particular interest is the associated ability to image local mechanical function and solute transport processes, which can be directly related to the molecular information. This ability is further strengthened by the synergistic integration of PET with MRI. Micro-SPECT has been improved through the use of coded aperture imaging approaches as well as image reconstruction algorithms that can better deal with the photon-limited scan data. The limited spatial resolution can be partially overcome by integrating SPECT with CT. Micro-CT by itself provides exquisite spatial resolution of anatomy, but recent developments in high-spatial-resolution photon counting and spectrally sensitive imaging arrays, combined with x-ray optical devices, hold promise for actual molecular identification by virtue of the chemical bond lengths of molecules, especially biopolymers. Conclusion: Given the increasing use of small animals for evaluating new clinical imaging techniques and providing more insight into pathophysiologic phenomena as well as the availability of improved detection systems, scanning protocols, and associated software, the sensitivity and specificity of molecular imaging are increasing. C1 [Ritman, Erik L.] Mayo Clin, Coll Med, Dept Physiol & Biomed Engn, Rochester, MN 55905 USA. [de Kemp, Robert A.] Univ Ottawa, Inst Heart, Ottawa, ON, Canada. [Epstein, Frederick H.] Univ Virginia, Charlottesville, VA USA. [Catana, Ciprian] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Catana, Ciprian] Harvard Univ, Sch Med, Boston, MA USA. [Tsui, Benjamin M. W.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. RP Ritman, EL (reprint author), Mayo Clin, Coll Med, Dept Physiol & Biomed Engn, 200 1st St SW, Rochester, MN 55905 USA. EM elran@mayo.edu FU National Institutes of Health [R01-EB01558, U24-CA092871, R01-EB000305] FX This work was supported in part by National Institutes of Health grants R01-EB01558, U24-CA092871, and R01-EB000305. NR 97 TC 54 Z9 55 U1 2 U2 16 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 MAY PY 2010 VL 51 SU 1 BP 18S EP 32S DI 10.2967/jnumed.109.068148 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 592XG UT WOS:000277414600003 PM 20457793 ER PT J AU Libby, P DiCarli, M Weissleder, R AF Libby, Peter DiCarli, Marcelo Weissleder, Ralph TI The Vascular Biology of Atherosclerosis and Imaging Targets SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE vascular; atherosclerosis; vascular biology; segmental arterial stenosis ID OXIDATION-SPECIFIC ANTIBODIES; POSITRON-EMISSION-TOMOGRAPHY; DENSITY-LIPOPROTEIN RECEPTOR; ACUTE CORONARY SYNDROMES; PLAQUE VULNERABILITY; IN-VIVO; APOLIPOPROTEIN-E; ARTERY-DISEASE; CELL-DEATH; INFLAMMATION AB The growing worldwide health challenge of atherosclerosis, together with advances in imaging technologies, have stimulated considerable interest in novel approaches to gauging this disease. The last several decades have witnessed a burgeoning in understanding of the molecular pathways involved in atherogenesis, lesion progression, and the mechanisms underlying the complications of human atherosclerotic plagues. The imaging of atherosclerosis is reaching beyond anatomy to encompass assessment of aspects of plague biology related to the pathogenesis and complication of the disease. The harnessing of these biologic insights promises to provide a plethora of new targets for molecular imaging of atherosclerosis. The goals for the years to come must include translation of the experimental work to visualization of these appealing biologic targets in humans. C1 [Libby, Peter; DiCarli, Marcelo; Weissleder, Ralph] Harvard Univ, Sch Med, Donald W Reynolds Cardiovasc Clin Res Ctr, Boston, MA 02115 USA. [Libby, Peter; DiCarli, Marcelo] Brigham & Womens Hosp, Dept Radiol, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. [Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. RP Libby, P (reprint author), Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp,Div Cardiovasc Med, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM plibby@rics.bwh.harvard.edu FU National Institutes of Health; American Heart Association FX We thank our many colleagues affiliated with the Donald W. Reynolds Clinical Cardiovascular Research Center at Harvard Medical School who contributed to our efforts to develop molecular imaging of atherosclerosis. We also acknowledge the National Institutes of Health and the American Heart Association for their support. NR 51 TC 64 Z9 68 U1 1 U2 14 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 MAY PY 2010 VL 51 SU 1 BP 33S EP 37S DI 10.2967/jnumed.109.069633 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 592XG UT WOS:000277414600004 PM 20395349 ER PT J AU O'Donnell, M McVeigh, ER Strauss, HW Tanaka, A Bouma, BE Tearney, GJ Guttman, MA Garcias, EV AF O'Donnell, Matthew McVeigh, Elliot R. Strauss, H. William Tanaka, Atsushi Bouma, Brett E. Tearney, Guillermo J. Guttman, Michael A. Garcias, Ernest V. TI Multimodality Cardiovascular Molecular Imaging Technology SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE molecular imaging; cardiovascular; multidisciplinary approach ID OPTICAL COHERENCE TOMOGRAPHY; ACUTE MYOCARDIAL-INFARCTION; ACUTE CORONARY SYNDROME; MESENCHYMAL STEM-CELLS; MONOCYTE CHEMOATTRACTANT PROTEIN-1; STABLE ANGINA-PECTORIS; ATHEROSCLEROTIC PLAQUES; VULNERABLE PLAQUE; LESION MORPHOLOGY; PROGNOSTIC VALUE AB Cardiovascular molecular imaging is a new discipline that integrates scientific advances in both functional imaging and molecular probes to improve our understanding of the molecular basis of the cardiovascular system. These advances are driven by in vivo imaging of molecular processes in animals, usually small animals, and are rapidly moving toward clinical applications. Molecular imaging has the potential to revolutionize the diagnosis and treatment of cardiovascular disease. The 2 key components of all molecular imaging systems are the molecular contrast agents and the imaging system providing spatial and temporal localization of these agents within the body. They must deliver images with the appropriate sensitivity and specificity to drive clinical applications. As work in molecular contrast agents matures and highly sensitive and specific probes are developed, these systems will provide the imaging technologies required for translation into clinical tools. This is the promise of molecular medicine. C1 [McVeigh, Elliot R.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. [O'Donnell, Matthew] Univ Washington, Seattle, WA 98195 USA. [Strauss, H. William] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Tanaka, Atsushi] Harvard Univ, Sch Med, Boston, MA USA. [Bouma, Brett E.; Tearney, Guillermo J.] Harvard MIT Hlth Sci & Technol, Cambridge, MA USA. [Bouma, Brett E.; Tearney, Guillermo J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Guttman, Michael A.] Surgivision Inc, Baltimore, MD USA. [Garcias, Ernest V.] Emory Univ, Atlanta, GA 30322 USA. RP McVeigh, ER (reprint author), Johns Hopkins Univ, Sch Med, 720 Rutland Ave,720 Ross Bldg, Baltimore, MD 21205 USA. EM emcveigh@jhu.edu FU National Heart Lung and Blood Institute, NIH, DHHS FX Dr. E.R. McVeigh thanks Joni Taylor, Kathy Lucas, Shawn Kozlov, and Timothy Hunt for animal care and support. Much of the development of rtMRI interventional procedures was a collaboration with the following investigators: Robert Lederman, Keith Horvath, Cenghizhan Ozturk, Parag V. Karmarkar, Amish N. Raval, Venkatesh K. Raman, Alexander J. Dick, Ranil DeSilva, Peter Kellman, and Ming Li. This work was supported in part through the Intramural Research Program of the National Heart Lung and Blood Institute, NIH, DHHS. NR 66 TC 9 Z9 9 U1 0 U2 2 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 MAY PY 2010 VL 51 SU 1 BP 38S EP 50S DI 10.2967/jnumed.109.068155 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 592XG UT WOS:000277414600005 PM 20457794 ER PT J AU Dixon, JA Spinale, FG AF Dixon, Jennifer A. Spinale, Francis G. TI Pathophysiology of Myocardial Injury and Remodeling: Implications for Molecular Imaging SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE basic cardiology; technical cardiology; clinical cardiology; MRI; cardiac MRI; infarct expansion; myocardial remodeling ID CARDIOVASCULAR MAGNETIC-RESONANCE; MESENCHYMAL STEM-CELLS; COLLAGEN DEPOSITION; INFARCTION; TRANSPLANTATION; INHIBITION; METABOLISM; MODEL; RAT AB Despite advances in reperfusion therapy, acute coronary syndromes can still result in myocardial injury and subsequent myocardial infarction (MI). Molecular, cellular, and interstitial events antecedent to the acute MI culminate in deleterious changes in the size, shape, and function of the left ventricle (LV), collectively termed LV remodeling. Three distinct anatomic and physiologic LV regions can be described after MI: the infarct, border zone, and remote regions. Given the complexity of post-MI remodeling, imaging modalities must be equally diverse to elucidate this process. The focus of this review will first be on cardiovascular MRI of the anatomic and pathophysiologic LV regions of greatest interest with regard to the natural history of the post-MI remodeling process. This review will then examine imaging modalities that provide translational and molecular insight into burgeoning treatment fields for the attenuation of post-MI remodeling, such as cardiac restraint devices and stem cell therapy. C1 Med Univ S Carolina, Div Cardiothorac Surg, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Spinale, FG (reprint author), Strom Thurmond Res Ctr, 114 Doughty St,Suite 625, Charleston, SC 29425 USA. EM wilburnm@musc.edu FU NHLBI NIH HHS [R01 HL059165-12, R01 HL059165] NR 38 TC 4 Z9 5 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2010 VL 51 SU 1 BP 102S EP 106S DI 10.2967/jnumed.109.068213 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 592XG UT WOS:000277414600010 PM 20395340 ER PT J AU Kramer, CM Sinusas, AJ Sosnovik, DE French, BA Bengel, FM AF Kramer, Christopher M. Sinusas, Albert J. Sosnovik, David E. French, Brent A. Bengel, Frank M. TI Multimodality Imaging of Myocardial Injury and Remodeling SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE MRI; PET; SPECT; myocardial infarction; noninvasive imaging; remodeling ID MATRIX-METALLOPROTEINASE ACTIVITY; LATE GADOLINIUM ENHANCEMENT; HEART-FAILURE PATIENTS; SYMPATHETIC INNERVATION; IN-VIVO; CONTRACTILE DYSFUNCTION; CONTRAST AGENT; INFARCTED MYOCARDIUM; VENTRICULAR-FUNCTION; VIABLE MYOCARDIUM AB Advances in cardiovascular molecular imaging have come at a rapid pace over the last several years. Multiple approaches have been taken to better understand the structural, molecular, and cellular events that underlie the progression from myocardial injury to myocardial infarction (MI) and, ultimately, to congestive heart failure. Multimodality molecular imaging including SPECT, PET, cardiac MRI, and optical approaches is offering new insights into the pathophysiology of MI and left ventricular remodeling in small-animal models. Targets that are being probed include, among others, angiotensin receptors, matrix metalloproteinases, integrins, apoptosis, macrophages, and sympathetic innervation. It is only a matter of time before these advances are applied in the clinical setting to improve post-MI prognostication and identify appropriate therapies in patients to prevent the onset of congestive heart failure. C1 [Kramer, Christopher M.; French, Brent A.] Univ Virginia, Dept Med, Charlottesville, VA USA. [Kramer, Christopher M.; French, Brent A.] Univ Virginia, Dept Radiol, Charlottesville, VA USA. [Kramer, Christopher M.; French, Brent A.] Univ Virginia, Dept Biomed Engn, Charlottesville, VA USA. [Kramer, Christopher M.; French, Brent A.] Univ Virginia, Cardiovasc Imaging Ctr, Charlottesville, VA USA. [Sinusas, Albert J.] Yale Univ, Sch Med, Dept Med, Div Cardiovasc, New Haven, CT 06510 USA. [Sosnovik, David E.] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. [Bengel, Frank M.] Johns Hopkins Sch Med, Dept Radiol, Div Nucl Med, Baltimore, MD USA. RP Kramer, CM (reprint author), Univ Virginia Hlth Syst, Dept Med, 1215 Lee St,Box 800170, Charlottesville, VA 22908 USA. EM ckramer@virginia.edu FU [AHA 0855409E]; [R01 HL078650]; [R01 HL065662]; [R01 HL093038]; [K08 HL079984]; [R01 HL058582] FX This work was supported in part by grants AHA 0855409E, R01 HL078650, R01 HL065662, R01 HL093038, K08 HL079984, and R01 HL058582. NR 88 TC 33 Z9 33 U1 0 U2 3 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 MAY PY 2010 VL 51 SU 1 BP 107S EP 121S DI 10.2967/jnumed.109.068221 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 592XG UT WOS:000277414600011 PM 20395347 ER PT J AU Balakrishnan, A Stearns, AT Ashley, SW Tavakkolizadeh, A Rhoads, DB AF Balakrishnan, Anita Stearns, Adam T. Ashley, Stanley W. Tavakkolizadeh, Ali Rhoads, David B. TI Restricted Feeding Phase Shifts Clock Gene and Sodium Glucose Cotransporter 1 (SGLT1) Expression in Rats SO JOURNAL OF NUTRITION LA English DT Article ID MESSENGER-RNA EXPRESSION; PERIPHERAL-TISSUES; SUPRACHIASMATIC NUCLEUS; CIRCADIAN EXPRESSION; DIURNAL RHYTHMICITY; SMALL-INTESTINE; LIVER; TRANSPORTERS; HEART; MICE AB The intestine exhibits striking diurnal rhythmicity in glucose uptake, mediated by the sodium glucose cotransporter (SGLT1); however, regulatory pathways for these rhythms remain incompletely characterized. We hypothesized that SGLT1 rhythmicity is linked to the circadian clock. To investigate this, we examined rhythmicity of SOH and individual clock genes in rats that consumed food ad libitum (AL). We further compared phase shifts of Sglt1 and clock genes in a second group of rats following restricted feeding to either the dark (DF) or light (LF) phase. Rats fed during the DF were pair-fed to rats fed during the LF. Jejunal mucosa was harvested across the diurnal period to generate expression profiles of Sglt1 and clock genes Clock, Bmal1 (brain-muscle Arnt-like 1), ReverbA/B, Per (Period) 1/2, and Cry (Cryptochrome) 1/2. All clock genes were rhythmic in AL rats (P < 0.05). Sglt1 also exhibited diurnal rhythmicity, with peak expression preceding nutrient arrival (P < 0.05). Light-restricted feeding shifted the expression rhythms of Sglt1 and most clock genes (Bmal1, ReverbA and B, Per1, Per2, and Cry1) compared with dark-restricted feeding (P < 0.05). The Sglt1 rhythm shifted in parallel with rhythms of Per1 and ReverbB. These effects of restricted feeding highlight luminal nutrients as a key Zeitgeber in the intestine, capable of simultaneously shifting the phases of transporter and clock gene expression, and suggest a role for clock genes in regulating Sglt1 and therefore glucose uptake. Understanding the regulatory cues governing rhythms in intestinal function may allow new therapeutic options for conditions of dysregulated absorption such as diabetes and obesity. J. Nutr. 140: 908-914, 2010. C1 [Balakrishnan, Anita; Stearns, Adam T.; Ashley, Stanley W.; Tavakkolizadeh, Ali] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Balakrishnan, Anita; Stearns, Adam T.; Ashley, Stanley W.; Tavakkolizadeh, Ali] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Balakrishnan, Anita] Univ Liverpool, Div Gastroenterol, Sch Clin Sci, Liverpool L69 3GE, Merseyside, England. [Stearns, Adam T.] Univ Oxford, Dept Physiol Anat & Genet, Oxford OX1 2JD, England. [Rhoads, David B.] MassGen Hosp Children, Pediat Endocrine Unit, Boston, MA 02114 USA. [Rhoads, David B.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Balakrishnan, A (reprint author), Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. EM anita.balakrishnan@doctors.org; rhoads@helix.mgh.harvard.edu OI Stearns, Adam/0000-0003-4327-7360 FU NIH [5 R01 DK047326]; ADA [7-05-RA-121]; Harvard Clinical Nutrition Research Center [P30-DK040561]; Nutricia Research Foundation; Berkeley Fellowship FX Supported by the NIH grant 5 R01 DK047326 (S.W.A.), ADA grant 7-05-RA-121 IDEA.), the Harvard Clinical Nutrition Research Center grant (A.T.) P30-DK040561, the Nutricia Research Foundation (A.B.), and the Berkeley Fellowship (A.T.S.). NR 35 TC 12 Z9 13 U1 0 U2 5 PU AMER SOC NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD MAY PY 2010 VL 140 IS 5 BP 908 EP 914 DI 10.3945/jn.109.116749 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 589CI UT WOS:000277121800005 PM 20200113 ER PT J AU Katsnelson, A Flick, WG Susarla, S Tartakovsky, JV Miloro, M AF Katsnelson, Alexander Flick, William G. Susarla, Seenu Tartakovsky, Julia V. Miloro, Michael TI Use of Panoramic X-Ray to Determine Position of Impacted Maxillary Canines SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID RADIOGRAPHIC LOCALIZATION AB Purpose: To evaluate the position of impacted maxillary canines in the alveolus using panoramic radiographs. Materials and Methods: The present study was a retrospective chart review of 102 patients with 130 impacted maxillary canines from the University of Illinois at Chicago College of Dentistry and private practice. Of the 130 impacted maxillary canines, 59 were impacted buccally and 71 were impacted palatally. The inclination of the impacted maxillary canines to a horizontal line from the mesiobuccal cusps of the maxillary molars was measured. We used these measurements to predict the position of the tooth and correlate this prediction with the actual approach used during surgery. Results: The mean angulation of the buccally impacted maxillary canines was 75.1 degrees +/- 18.2 degrees (range, 8 degrees to 111 degrees). The mean angulation of the palatally impacted maxillary canines was 51.3 degrees +/- 15.3 degrees (range, 12 degrees to 91 degrees). The mean difference between the angulation of the impacted maxillary canines as measured on the panoramic radiographs was statistically significant (P < .001). From a receiver-operator characteristic curve and using a logistic regression model, impactions greater than 65 degrees were 26.6 times more likely to be buccally impacted maxillary canines (P < .001). Conclusions: Panoramic radiographs are useful for predicting the location of impacted maxillary canines and the subsequent surgical approach required for exposure and orthodontic appliance attachment when computed tomography is unavailable or unnecessary otherwise. The use of panoramic radiographs for determing impacted maxillary canine position has a high sensitivity and specificity, with angulations greater than 65 degrees associated with buccal impactions. (C) 2010 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved. J Oral Maxillofac Surg 68:996-1000, 2010 C1 [Flick, William G.; Miloro, Michael] Univ Illinois, Coll Dent, Dept Oral & Maxillofacial Surg, Chicago, IL 60611 USA. [Katsnelson, Alexander; Susarla, Seenu] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Tartakovsky, Julia V.] Harvard Univ, Cambridge, MA 02138 USA. RP Miloro, M (reprint author), Univ Illinois, Coll Dent, Dept Oral & Maxillofacial Surg, 801 S Paulina St,MC 835, Chicago, IL 60611 USA. EM mmiloro@uic.edu OI Susarla, Srinivas/0000-0003-0155-8260 NR 15 TC 6 Z9 7 U1 0 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 MAY PY 2010 VL 68 IS 5 BP 996 EP 1000 DI 10.1016/j.joms.2009.09.022 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 592RR UT WOS:000277397700008 PM 20138419 ER PT J AU Alcorn, SR Balboni, MJ Prigerson, HG Reynolds, A Phelps, AC Wright, AA Block, SD Peteet, JR Kachnic, LA Balboni, TA AF Alcorn, Sara R. Balboni, Michael J. Prigerson, Holly G. Reynolds, Amy Phelps, Andrea C. Wright, Alexi A. Block, Susan D. Peteet, John R. Kachnic, Lisa A. Balboni, Tracy A. TI "If God Wanted Me Yesterday, I Wouldn't Be Here Today": Religious and Spiritual Themes in Patients' Experiences of Advanced Cancer SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID QUALITY-OF-LIFE; NEAR-DEATH; CARE; END; ASSOCIATIONS; ILLNESS; NEEDS AB Background: This study sought to inductively derive core themes of religion and/or spirituality (R/S) active in patients' experiences of advanced cancer to inform the development of spiritual care interventions in the terminally ill cancer setting. Methods: This is a multisite, cross-sectional, mixed-methods study of randomly-selected patients with advanced cancer (n = 68). Scripted interviews assessed the role of R/S and R/S concerns encountered in the advanced cancer experience. Qualitative and quantitative data were analyzed. Theme extraction was performed with interdisciplinary input (sociology of religion, medicine, theology), utilizing grounded theory. Spearman correlations determined the degree of association between R/S themes. Predictors of R/S concerns were assessed using linear regression and analysis of variance. Results: Most participants (n = 53, 78%) stated that R/S had been important to the cancer experience. In descriptions of how R/S was related to the cancer experience, five primary R/S themes emerged: coping, practices, beliefs, transformation, and community. Most interviews (75%) contained two or more R/S themes, with 45% mentioning three or more R/S themes. Multiple significant subtheme interrelationships were noted between the primary R/S themes. Most participants (85%) identified 1 or more R/S concerns, with types of R/S concerns spanning the five R/S themes. Younger, more religious, and more spiritual patients identified R/S concerns more frequently (beta = -0.11, p < 0.001; beta = 0.83, p = 0.03; and beta = 0.89, p = 0.04, respectively). Conclusions: R/S plays a variety of important and inter-related roles for most advanced cancer patients. Future research is needed to determine how spiritual care can incorporate these five themes and address R/S concerns. C1 [Alcorn, Sara R.; Balboni, Michael J.; Prigerson, Holly G.; Phelps, Andrea C.; Wright, Alexi A.; Block, Susan D.; Peteet, John R.; Balboni, Tracy A.] Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, Boston, MA 01225 USA. [Alcorn, Sara R.; Balboni, Tracy A.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 01225 USA. [Balboni, Michael J.; Prigerson, Holly G.; Phelps, Andrea C.; Wright, Alexi A.; Block, Susan D.; Peteet, John R.; Balboni, Tracy A.] Dana Farber Canc Inst, Dept Psychooncol & Palliat Care, Boston, MA 01225 USA. [Wright, Alexi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 01225 USA. [Prigerson, Holly G.; Block, Susan D.; Peteet, John R.] Harvard Univ, Sch Med, Ctr Palliat Care, Boston, MA USA. [Balboni, Michael J.] Boston Univ, Dept Pract Theol, Boston, MA 02215 USA. [Reynolds, Amy] Princeton Univ, Dept Sociol, Princeton, NJ 08544 USA. [Kachnic, Lisa A.] Boston Med Ctr, Dept Radiat Oncol, Boston, MA USA. RP Balboni, TA (reprint author), Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, 44 Binney St, Boston, MA 01225 USA. EM tbalboni@lroc.harvard.edu FU American Society of Clinical Oncology FX This research was supported in part by an American Society of Clinical Oncology Young Investigator Award to Dr. Tracy Balboni. NR 27 TC 68 Z9 70 U1 1 U2 10 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD MAY PY 2010 VL 13 IS 5 BP 581 EP 588 DI 10.1089/jpm.2009.0343 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 600GQ UT WOS:000277973800016 PM 20408763 ER PT J AU Katavetin, P Cheunsuchon, P Swearingen, B Hedley-Whyte, ET Misra, M Levitsky, LL AF Katavetin, Paravee Cheunsuchon, Pornsuk Swearingen, Brooke Hedley-Whyte, E. Tessa Misra, Madhusmita Levitsky, Lynne L. TI Review: Pituitary Adenomas in Children and Adolescents SO JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM LA English DT Review DE pituitary adenoma; prolactinoma; somatotropinoma; Cushing disease; children; adolescents ID TRANSSPHENOIDAL SURGERY; CUSHINGS-DISEASE; CHILDHOOD; SERIES AB Clinical manifestations and outcomes of pituitary adenomas in children are not clearly defined. We retrospectively reviewed cases of pituitary adenomas in children 0-18 years treated at MassGeneral Hospital for Children over 15 years. Thirty-five patients were identified. Age at presentation was 7-18 years. Seventeen had prolactinomas, 3 had somatotropinomas, and 15 had Cushing disease. Thirteen prolactinoma patients were female and most commonly presented with oligomenorrhea (10/13) and galactorrhea (7/13). Nine were successfully treated medically. Two somatotropinoma patients presented with visual disturbances; the third was an incidental finding. Two were cured by transsphenoidal surgery (TSS). Thirteen Cushing disease patients were initially cured by TSS; six recurred after 3-6 years. Patients with or without recurrence did not differ for age, tumor-size and hormone levels. The high recurrence rate of Cushing disease in our series (46%) compared with adults treated surgically at this institution (7%) emphasizes the need for long-term follow-up. C1 [Katavetin, Paravee; Misra, Madhusmita; Levitsky, Lynne L.] MassGeneral Hosp Children, Pediat Endocrine Unit, Boston, MA USA. [Katavetin, Paravee; Misra, Madhusmita; Levitsky, Lynne L.] Harvard Univ, Sch Med, Boston, MA USA. [Cheunsuchon, Pornsuk; Hedley-Whyte, E. Tessa] Massachusetts Gen Hosp, Dept Pathol Neuropathol, Boston, MA 02114 USA. [Swearingen, Brooke] Massachusetts Gen Hosp, Div Neurosurg, Boston, MA 02114 USA. RP Levitsky, LL (reprint author), MassGeneral Hosp Children, Pediat Endocrine Unit, Boston, MA USA. EM llevitsky@partners.org RI Cheunsuchon, Pornsuk/O-7915-2015 OI Cheunsuchon, Pornsuk/0000-0001-8851-3553 NR 16 TC 4 Z9 5 U1 0 U2 1 PU WALTER DE GRUYTER GMBH PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 0334-018X EI 2191-0251 J9 J PEDIATR ENDOCR MET JI J. Pediatr. Endocrinol. Metab. PD MAY PY 2010 VL 23 IS 5 BP 427 EP 431 DI 10.1515/jpem.2010.072 PG 5 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 620OV UT WOS:000279510100002 PM 20662340 ER PT J AU Wong, K Levitsky, LL Misra, M AF Wong, Kara Levitsky, Lynne L. Misra, Madhusmita TI Predictors and Growth Consequences of Central Hypothyroidism in Pediatric Patients Receiving Recombinant Human Growth Hormone SO JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM LA English DT Article DE hypothyroidism; growth hormone; MRI; pituitary; growth hormone deficiency ID GH REPLACEMENT THERAPY; CHILDREN; DEFICIENCY; THYROXINE; GIRLS; AXIS AB Objective: Although recombinant human growth hormone (rhGH) can unmask central hypothyroidism, few studies have investigated prevalence, predictors and growth consequences of evolving hypothyroidism in children receiving rhGH based on therapeutic indication. We hypothesized that children with GH deficiency (GHD) and greatest severity of GHD would be most likely to develop central hypothyroidism and decreased growth velocity (GV). Design: Retrospective chart review Patients: Children currently receiving rhGH with data available for at least 24 months after rhGH initiation (n=119). Indications included GHD, Prader-Willi syndrome, Turner syndrome, and idiopathic short stature (ISS) and SGA (n=60, 20, 19 and 20 respectively). Methods: We categorized patients as those hypothyroid at baseline (HYPO-B; n=13), those who developed hypothyroidism over 24-months of rhGH (HYPO-24; n=16), and those never hypothyroid (NO-HYPO; n=90). Groups did not differ for age or gender. Results: Central hypothyroidism developed in 25% of GHD patients. For all patients on rhGH, baseline IGF-1 (p=0.007), IGFBP-3 (p=0.006) and peak GH (p=0.02) differed between groups. HYPO-24 had lower baseline IGF-1, IGFBP-3 and peak GH than NO-HYPO, but did not differ from HYPO-B. Peak GH was <7 ng/ml in 100% of HYPO-24, 77% HYPO-B, and 71% NO-HYPO (p=0.01). GV SDS decreased between the first and second years in HYPO-24 in HYPO-24 compared with NO-HYPO. Conclusion: Evolution of central hypothyroidism is more likely in patients receiving rhGH for GHD than other indications, becomes more likely with greater severity of GHD and is associated with a reduction in GV SDS. C1 [Wong, Kara; Levitsky, Lynne L.; Misra, Madhusmita] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Levitsky, Lynne L.; Misra, Madhusmita] MassGen Hosp Children, Pediat Endocrine Unit, Boston, MA USA. [Misra, Madhusmita] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. RP Misra, M (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM mmisra@partners.org NR 15 TC 1 Z9 3 U1 0 U2 2 PU WALTER DE GRUYTER GMBH PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 0334-018X EI 2191-0251 J9 J PEDIATR ENDOCR MET JI J. Pediatr. Endocrinol. Metab. PD MAY PY 2010 VL 23 IS 5 BP 451 EP 461 DI 10.1515/jpem.2010.076 PG 11 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 620OV UT WOS:000279510100006 PM 20662344 ER PT J AU Demidenko, A Jakobiec, FA Hanna, E Walton, DS AF Demidenko, Alexander Jakobiec, Frederick A. Hanna, Eissa Walton, David S. TI Congenital Pupillary-Iris-Lens Membrane With Goniodysgenesis: Histopathologic Findings in an Enucleated Eye SO JOURNAL OF PEDIATRIC OPHTHALMOLOGY & STRABISMUS LA English DT Article ID IDIOPATHIC TRACTIONAL CORECTOPIA AB A 10-year-old boy with clinically confirmed congenital pupillary-iris-lens membrane with goniodysgenesis underwent light microscopic examination of the enucleated eye. The anterior segment changes consisted of the absence of the iridial pupillary sphincter muscle and dilator muscle processes. Endothelialization and descemetization of the anterior chamber angle and the anterior surface of the iris covered the original eccentric pupillary opening (occlusio pupillae), but grew around the fibrotic edges of the surgically created, patent pseudopupil, probably secondary responses to surgery. The anterior chamber findings in this case establish a localized syndrome that includes absence of the pupillary sphincter and dilator muscle processes. Incomplete development of the iris may be partly attributable to an abnormality of stromal development and inductions by the anterior neuroectodermal layer, together with anomalies of the pupillo-iridial vasculature. [J Pediatr Ophthalmol Strabismus 2010;47:178-182.] C1 [Demidenko, Alexander; Jakobiec, Frederick A.; Hanna, Eissa] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Walton, David S.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Jakobiec, FA (reprint author), Room 321,243 Charles St, Boston, MA 02114 USA. NR 13 TC 0 Z9 0 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0191-3913 J9 J PEDIAT OPHTH STRAB JI J. Pediatr. Ophthalmol. Strabismus. PD MAY-JUN PY 2010 VL 47 IS 3 BP 178 EP 182 DI 10.3928/01913913-20100305-09 PG 5 WC Ophthalmology; Pediatrics SC Ophthalmology; Pediatrics GA 598TZ UT WOS:000277862900011 PM 20507003 ER PT J AU McKlveen, JM Wilson, JM Rubin, RT Rhodes, ME AF McKlveen, Jessica M. Wilson, Jared M. Rubin, Robert T. Rhodes, Michael E. TI Sexually diergic, dose-dependent hypothalamic-pituitary-adrenal axis responses to nicotine in a dynamic in vitro perfusion system SO JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS LA English DT Article DE ACTH; AVP; Cholinergic; CORT; CRH; Hormones; HPA Axis; Methods; Nicotine; Rat ID CORTICOTROPIN-RELEASING HORMONE; ESTROUS-CYCLE INFLUENCES; HPA AXIS; ARGININE-VASOPRESSIN; FEMALE RATS; CHOLINERGIC STIMULATION; PARAVENTRICULAR NUCLEUS; ANTERIOR-PITUITARY; STRESS-RESPONSE; SEX-DIFFERENCES AB Introduction: The hypothalamic-pituitary-adrenal cortical (HPA) axis modulates physiological responses to stress. We previously reported sexually diergic, dose-dependent HPA responses in vivo following nicotine administration: Male rats had greater arginine vasopressin (AVP) responses than females, and female rats had greater adrenocorticotropic hormone (ACTH) and corticosterone (CORT) responses than males. The goal of the present study was to further investigate sexually diergic, dose-dependent HPA responses following nicotine addition to an in vitro model of the HPA axis, so that hormone output could be determined at each level of the axis. Methods: Hypothalami, pituitaries, and adrenal glands were harvested from male and female rats. One-half hypothalamus, one-half pituitary, and one adrenal gland were placed individually into three jacketed tissue baths connected by tubing and perfused in series with physiological medium. Sampling ports between tissue baths were used to collect buffer before and after addition of various doses of nicotine, for measurement of AVP and corticotropin-releasing hormone (CRH) from the hypothalamus bath, ACTH from the pituitary bath, and CORT from the adrenal bath. Hormones were measured by highly specific immunoassays. Results: Stable temperatures, flow rates, pH, and hormone baselines were achieved in the in vitro system. Consistent with our in vivo and earlier in vitro studies, nicotine added to the hypothalamus tissue bath significantly increased HPA responses in a sex- and dose-dependent manner: Males had greater AVP responses than did females, and females had greater CRH responses than did males. Sexually diergic ACTH and CORT responses were less apparent and were higher in females. Discussion: Our in vitro system accurately models in vivo HPA responses to nicotine in both sexes and thus represents a reliable method for investigating the effects of nicotine on components of the HPA axis. These studies may be pertinent to understanding the biological differences to nicotine between men and women smokers. (C) 2010 Elsevier Inc. All rights reserved. C1 [McKlveen, Jessica M.; Wilson, Jared M.; Rhodes, Michael E.] St Vincent Coll, Dept Biol, Latrobe, PA 15650 USA. [Rubin, Robert T.] VA Greater Los Angeles Healthcare Syst, Dept Psychiat, Los Angeles, CA 90073 USA. RP Rhodes, ME (reprint author), St Vincent Coll, Dept Biol, 300 Fraser Purchase Rd, Latrobe, PA 15650 USA. EM michael.rhodes@email.stvincent.edu FU NIH [MH28380-28]; Saint Vincent College FX The technical assistance of Anna N. Taylor, Ph.D. and Delia L Tio, for their contributions to the AVP, ACTH and CORT assays, is gratefully acknowledged. This work was supported by NIH grant MH28380-28 to RTR and a Saint Vincent College Faculty Research Grant to MER. NR 58 TC 4 Z9 4 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1056-8719 J9 J PHARMACOL TOX MET JI J. Pharmacol. Toxicol. Methods PD MAY-JUN PY 2010 VL 61 IS 3 BP 311 EP 318 DI 10.1016/j.vascn.2010.01.009 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 660FE UT WOS:000282624700011 PM 20117222 ER PT J AU Sponheim, SR Jung, RE Seidman, LJ Mesholam-Gately, RI Manoach, DS O'Leary, DS Ho, BC Andreasen, NC Lauriello, J Schulz, SC AF Sponheim, S. R. Jung, R. E. Seidman, L. J. Mesholam-Gately, R. I. Manoach, D. S. O'Leary, D. S. Ho, B. C. Andreasen, N. C. Lauriello, J. Schulz, S. C. TI Cognitive deficits in recent-onset and chronic schizophrenia SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article; Proceedings Paper CT 14th Biennial Winter Workshop on Schizophrenia and Bipolar Disorders CY FEB 01-02, 2008 CL Montreux, SWITZERLAND DE Schizophrenia; Cognition; Recent-onset; Chronic disease; Psychosis ID 10-YEAR FOLLOW-UP; 1ST-EPISODE SCHIZOPHRENIA; 1ST EPISODE; NEUROCOGNITIVE FUNCTION; LIFE-SPAN; PSYCHOSIS; DECLINE; AGE; PERFORMANCE; HALOPERIDOL AB Although cognitive dysfunction is a primary characteristic of schizophrenia, only recently have investigations begun to pinpoint when the dysfunction develops in the individual afflicted by the disorder. Research to date provides evidence for significant cognitive impairments prior to disorder onset. Less is known about the course of cognitive dysfunction from onset to the chronic phase of schizophrenia. Although longitudinal studies are optimal for assessing stability of cognitive deficits, practice effects often confound assessments, and large and representative subject samples have not been followed over long periods of time. We report results of a cross-sectional study of cognitive deficits early and late in the course of schizophrenia carried out at four different geographic locations to increase sample size and generalizability of findings. We examined a broad set of cognitive functions in 41 recent-onset schizophrenia patients and 106 chronic schizophrenia patients. The study included separate groups of 43 matched controls for the recent-onset sample and 105 matched controls for the chronic schizophrenia sample in order to evaluate the effects of cohort (i.e., age) and diagnosis (i.e., schizophrenia) on cognitive functions. All measures of cognitive function showed effects of diagnosis; however, select time-based measures of problem solving and fine motor dexterity exhibited interactions of diagnosis and cohort indicating that these deficits may progress beyond what is expected with normal aging. Also, worse recall of material in episodic memory was associated with greater length of illness. Nevertheless, findings indicate that nearly all cognitive deficits are comparably impaired across recent-onset and chronic schizophrenia. Published by Elsevier Ltd. C1 [Sponheim, S. R.] VA Med Ctr, Minneapolis, MN 55417 USA. [Sponheim, S. R.; Schulz, S. C.] Dept Psychiat, Minneapolis, MN 55454 USA. [Jung, R. E.] Mind Res Network, Albuquerque, NM 87106 USA. [Jung, R. E.; Lauriello, J.] Univ New Mexico, Dept Psychol, Albuquerque, NM 87131 USA. [O'Leary, D. S.; Ho, B. C.; Andreasen, N. C.] UI Hosp & Clin, Dept Psychiat, Iowa City, IA 52242 USA. [Seidman, L. J.; Mesholam-Gately, R. I.; Manoach, D. S.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Seidman, L. J.; Mesholam-Gately, R. I.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Seidman, L. J.; Manoach, D. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Sponheim, SR (reprint author), 116B VA Med Ctr,1 Vet Dr, Minneapolis, MN 55417 USA. EM sponh001@umn.edu RI Ho, Beng-Choon/D-6959-2011 OI Ho, Beng-Choon/0000-0003-3976-1555 FU NIMH NIH HHS [R01 MH040856, K23 MH068380] NR 50 TC 41 Z9 42 U1 5 U2 17 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 MAY PY 2010 VL 44 IS 7 BP 421 EP 428 DI 10.1016/j.jpsychires.2009.09.010 PG 8 WC Psychiatry SC Psychiatry GA 603XA UT WOS:000278240200002 PM 19878956 ER PT J AU Zhang, XY Xiu, MH Chen, DC Zhu, FY Wu, GY Haile, CN Lu, L Kosten, TA Kosten, TR AF Zhang, Xiang Yang Xiu, Mei Hong Chen, Da Chun Zhu, Feng Yan Wu, Gui Ying Haile, Colin N. Lu, Lin Kosten, Therese A. Kosten, Thomas R. TI Increased S100B serum levels in schizophrenic patients with tardive dyskinesia: Association with dyskinetic movements SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Tardive dyskinesia; Schizophrenia; S100B; Antipsychotic treatment ID S-100B PROTEIN; ANTIPSYCHOTICS; CLOZAPINE; SYMPTOMS; BRAIN; BLOOD AB Several studies show that calcium-binding protein S100B is increased in schizophrenia and may be involved in the pathogenesis of tardive dyskinesia (TD). We therefore compared serum S100B levels in normal controls (n = 60), schizophrenic patients with (n = 32) and without TD (n = 50). Assessments included the abnormal involuntary movement scale (AIMS) and the positive and negative syndrome scale (PANSS). Serum S100B levels were measured by enzyme-linked immunosorbent assay (ELISA). The results indicated that patients with TD had higher serum S100B levels than normals and those without TD. Serum S100B levels were positively correlated with AIMS scores in patients with TD. These data suggest that increased S100B levels may be related to neuro-degeneration, associated with TO pathophysiology. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Zhang, Xiang Yang; Wu, Gui Ying; Haile, Colin N.; Kosten, Therese A.; Kosten, Thomas R.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Zhang, Xiang Yang; Xiu, Mei Hong; Chen, Da Chun; Zhu, Feng Yan] Beijing HuiLongGuan Hosp, Ctr Biol Psychiat, Beijing, Peoples R China. [Lu, Lin] Peking Univ, Natl Inst Drug Dependence, Beijing 100871, Peoples R China. RP Zhang, XY (reprint author), VA Med Ctr, Res Bldg 109,Room 130,2002 Holcombe Blvd, Houston, TX 77030 USA. EM xyzhang@bcm.edu; kosten@bcm.edu OI Haile, Colin/0000-0001-8293-7291 FU Beijing Municipal Natural Science Foundation [7072035]; Stanley Medical Research Institute [03T-459, 05T-726]; Department of Veterans Affairs; VISN 16; Mental Illness Research, Education and Clinical Center (MIRECC); United States National Institute of Health [K05-DA0454, P50-DA18827, U01-MH79639] FX The authors would like to thank Drs. Yun Long Tan, Wu Fang Zhang, Zhi Ren Wang, Bao Hua Zhang, and Gui Gang Yang for all of their hard work and significant contributions toward the study.; This study was funded by the Beijing Municipal Natural Science Foundation (ID: 7072035), the Stanley Medical Research Institute (03T-459 and 05T-726), and the Department of Veterans Affairs, VISN 16, Mental Illness Research, Education and Clinical Center (MIRECC), United States National Institute of Health K05-DA0454, P50-DA18827 and U01-MH79639. NR 33 TC 10 Z9 11 U1 0 U2 0 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 MAY PY 2010 VL 44 IS 7 BP 429 EP 433 DI 10.1016/j.jpsychires.2009.10.012 PG 5 WC Psychiatry SC Psychiatry GA 603XA UT WOS:000278240200003 PM 19932492 ER PT J AU Buccheri, R Trygstad, L Buffum, MD Gerlock, AA AF Buccheri, Robin Trygstad, Louise Buffum, Martha D. Gerlock, April A. TI Developing an Evidence-Based Practice for Psychiatric Nursing SO JOURNAL OF PSYCHOSOCIAL NURSING AND MENTAL HEALTH SERVICES LA English DT Editorial Material ID BEHAVIORAL-MANAGEMENT; HALLUCINATIONS C1 [Buccheri, Robin; Trygstad, Louise] Univ San Francisco, Sch Nursing, San Francisco, CA 94117 USA. [Buffum, Martha D.] VA Med Ctr, San Francisco, CA USA. [Gerlock, April A.] Univ Washington, Sch Nursing, Seattle, WA 98195 USA. [Gerlock, April A.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Buccheri, R (reprint author), Univ San Francisco, Sch Nursing, San Francisco, CA 94117 USA. NR 11 TC 3 Z9 3 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0279-3695 J9 J PSYCHOSOC NURS MEN JI J. Psychosoc. Nurs. Ment. Health Serv. PD MAY PY 2010 VL 48 IS 5 BP 3 EP 5 DI 10.3928/02793695-20100331-01 PG 3 WC Nursing SC Nursing GA 595BU UT WOS:000277586500001 PM 20645442 ER PT J AU Gerlock, AA Buccheri, R Buffum, MD Trygstad, L Dowling, GA AF Gerlock, April A. Buccheri, Robin Buffum, Martha D. Trygstad, Louise Dowling, Glenna A. TI Responding to Command Hallucinations to Harm The Unpleasant Voices Scale and Harm Command Safety Protocol SO JOURNAL OF PSYCHOSOCIAL NURSING AND MENTAL HEALTH SERVICES LA English DT Article ID AUDITORY HALLUCINATIONS; BEHAVIORAL-MANAGEMENT; SCHIZOPHRENIA; DANGEROUSNESS AB Command hallucinations are relatively common in voice hearers and are taken seriously because of the potential threat to self and others. Many variables mediate the relationship between hearing commands and acting on them. This article describes the implementation of the Harm Command Safety Protocol and the Unpleasant Voices Scale to respond to command hallucinations to harm in the context of the dissemination of a multisite, evidence-based behavioral management course for patients with auditory hallucinations. C1 [Gerlock, April A.] VA Puget Sound Hlth Care Syst, Amer Lake Div, Tacoma, WA 98493 USA. [Gerlock, April A.] Univ Washington, Sch Nursing, Seattle, WA 98195 USA. [Trygstad, Louise] Univ San Francisco, Sch Nursing, San Francisco, CA 94117 USA. [Dowling, Glenna A.] Univ Calif San Francisco, Dept Physiol Nursing, San Francisco, CA 94143 USA. RP Gerlock, AA (reprint author), VA Puget Sound Hlth Care Syst, Amer Lake Div, 5000 Vet Dr, Tacoma, WA 98493 USA. EM April.Gerlock@va.gov NR 25 TC 5 Z9 5 U1 2 U2 6 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0279-3695 J9 J PSYCHOSOC NURS MEN JI J. Psychosoc. Nurs. Ment. Health Serv. PD MAY PY 2010 VL 48 IS 5 BP 26 EP 33 DI 10.3928/02793695-20100304-03 PG 8 WC Nursing SC Nursing GA 595BU UT WOS:000277586500008 PM 20349886 ER PT J AU Goldstein, DP AF Goldstein, Donald P. TI Gestational Trophoblastic Neoplasia: Where We Came From, Where We Stand Today, Where We Are Heading Keynote Address SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article; Proceedings Paper CT 15th World Congress on Gestational Trophoblastic Diseases CY NOV 12-15, 2009 CL Kochi, INDIA SP Int Soc Study Trophoblast Dis DE gestational trophoblastic neoplasms; International Society for the Study of Trophoblastic Disease; Donald P. Goldstein ID HUMAN CHORIONIC-GONADOTROPIN; COMPLETE MOLAR PREGNANCY; GYNECOLOGIC-ONCOLOGY-GROUP; FREE BETA-SUBUNIT; HYDATIDIFORM MOLE; ACTINOMYCIN-D; PROPHYLACTIC CHEMOTHERAPY; ORAL-CONTRACEPTIVES; RELIABLE MARKER; FOLINIC ACID C1 [Goldstein, Donald P.] Brigham & Womens Hosp, Div Gynecol Oncol, New England Trophoblast Dis Ctr, Dana Farber Canc Inst, Boston, MA 02115 USA. [Goldstein, Donald P.] Harvard Univ, Sch Med, Boston, MA USA. RP Goldstein, DP (reprint author), Brigham & Womens Hosp, Div Gynecol Oncol, New England Trophoblast Dis Ctr, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. EM dgoldstein@partners.org NR 70 TC 1 Z9 1 U1 0 U2 1 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 J9 J REPROD MED JI J. Reprod. Med. PD MAY-JUN PY 2010 VL 55 IS 5-6 BP 184 EP 193 PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 610CT UT WOS:000278708400003 PM 20626173 ER PT J AU Elias, KM Goldstein, DP Berkowitz, RS AF Elias, Kevin M. Goldstein, Donald P. Berkowitz, Ross S. TI Complete Hydatidiform Mole in Women Older than Age 50 SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article; Proceedings Paper CT 15th World Congress on Gestational Trophoblastic Diseases CY NOV 12-15, 2009 CL Kochi, INDIA SP Int Soc Study Trophoblast Dis DE complete hydatidiform mole; gestational trophoblastic disease ID GESTATIONAL TROPHOBLASTIC DISEASE; EPIDEMIOLOGY; EVACUATION; PREGNANCY AB OBJECTIVE: To describe the presentation, clinical course and outcomes of women aged 50 or older who present with a new diagnosis of complete hydatidiform mole. STUDY DESIGN: All cases of complete hydatidiform mole diagnosed at the New England Trophoblastic Disease Center from June 1970 to April 2009 were reviewed. Twenty-two patients met the study criteria. RESULTS: The mean age in the patient population was 52, gravidity 5.8, parity 3.7 and gestational age 10.4 weeks. The majority of patients (68.4%) reported regular menses immediately prior to the index pregnancy. The most common presenting symptoms were vaginal bleeding (81.0%), stigmata of pregnancy (47.6%) and nausea or vomiting (28.6%). We were unable to delineate characteristics that would distinguish those patients who developed gestational trophoblastic neoplasia (GTN) following dilation and curettage from those who did not. In contrast, 60% of the 15 patients initially treated with dilation and curettage developed GTN, while there were no cases of GTN among the 7 patients receiving primary hysterectomy. CONCLUSION: The risk of developing GTN in this age group appears to correspond to the choice of initial surgical therapy rather than hCG level or demographic factors. Hysterectomy should be considered as the initial treatment of choice. (J Reprod Med 2010;55:208-212) C1 [Elias, Kevin M.] Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Boston, MA 02115 USA. Trophoblast Tumor Registry, New England Trophoblast Dis Ctr, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Elias, KM (reprint author), Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, 75 Francis St, Boston, MA 02115 USA. EM kelias1@partners.org OI Elias, Kevin/0000-0003-1502-5553 NR 19 TC 12 Z9 12 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 J9 J REPROD MED JI J. Reprod. Med. PD MAY-JUN PY 2010 VL 55 IS 5-6 BP 208 EP 212 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 610CT UT WOS:000278708400006 PM 20626176 ER PT J AU Fulop, V Szigetvari, I Szepesi, J Vegh, G Batorfi, J Nagymanyoki, Z Torok, M Berkowitz, RS AF Fulop, Vilmos Szigetvari, Ivan Szepesi, Janos Vegh, Gyoergy Batorfi, Jozsef Nagymanyoki, Zoltan Torok, Miklos Berkowitz, Ross S. TI 30 Years' Experience in the Treatment of Low-Risk Gestational Trophoblastic Neoplasia in Hungary SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article; Proceedings Paper CT 15th World Congress on Gestational Trophoblastic Diseases CY NOV 12-15, 2009 CL Kochi, INDIA SP Int Soc Study Trophoblast Dis DE anatomical stages; chemotherapy; low risk gestational trophoblastic neoplasia; prognostic score ID CHORIOCARCINOMA; DISEASE; MANAGEMENT; THERAPY; TUMORS; WOMEN AB OBJECTIVE: To review the clinical experience in the treatment of patients with low-risk gestational trophoblastic neoplasia (GTN) over the past 30 years in a national trophoblastic disease center. STUDY DESIGN: Between January 1, 1977, and December 31, 2007, 302 patients with low-risk GTN were treated. The patients were directed to our institution from all parts of Hungary. The patients were 14 to 53 years of age with an average age of 28.3 years. Methotrexate (MTX)/folinic acid or actinomycin-D (Act-D) primary chemotherapy was selected based upon the patient's stage and prognostic score of GTN. RESULTS: Among 218 low-risk patients, 210 (96.3%) achieved remission as a result of MTX therapy. In 8 patients (3.7%), MTX-Act-D-cyclophosphamide (MAC) combination chemotherapy was needed to achieve complete remission, in some cases assisted by operation. Among 84 patients, 81 (96.4%) achieved remission as a result of Act-D therapy. In 3 cases (3.6%) complete remission was achieved by MAC combination chemotherapy. We detected metastases in 22.8% (69/302) of our low-risk patients. Chemotherapy, surgical intervention or other supplementary treatments resulted in 100% remission in cases of low-risk nonmetastatic and metastatic disease. CONCLUSION: Our data indicate that MTX/folinic acid or Act-D should be the primary treatment in patients with nonmetastatic or metastatic low-risk GTN. Importantly, patients with resistance to single-agent chemotherapy regularly achieve complete remission with MAC combination chemotherapy. Results show that patient care under the direction of experienced clinicians serves to optimize the opportunity for cure and minimize morbidity. (J Reprod Med 2010;55:253-257) C1 [Fulop, Vilmos] State Hlth Ctr, Dept Obstet & Gynecol, H-1062 Budapest, Hungary. Harvard Univ, Brigham & Womens Hosp, New England Trophoblast Dis Ctr,Div Gynecol Oncol, Dana Farber Canc Inst,Sch Med, Boston, MA 02115 USA. RP Fulop, V (reprint author), State Hlth Ctr, Dept Obstet & Gynecol, 111 Podmaniczky St, H-1062 Budapest, Hungary. EM fulopvilmos@freemail.hu NR 14 TC 6 Z9 6 U1 0 U2 3 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 J9 J REPROD MED JI J. Reprod. Med. PD MAY-JUN PY 2010 VL 55 IS 5-6 BP 253 EP 257 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 610CT UT WOS:000278708400012 PM 20626182 ER PT J AU Nagymanyoki, Z Kindelberger, D Clark, R Rodriguez, N Fulop, V Berkowitz, RS AF Nagymanyoki, Zoltan Kindelberger, David Clark, Rachel Rodriguez, Noah Fulop, Vilmos Berkowitz, Ross S. TI Age Related Cellular Immune Response Against Complete Molar Pregnancy SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article; Proceedings Paper CT 15th World Congress on Gestational Trophoblastic Diseases CY NOV 12-15, 2009 CL Kochi, INDIA SP Int Soc Study Trophoblast Dis DE gestational trophoblastic disease; immune response; immunosenescence; maternal age ID NATURAL-KILLER-CELLS; REGULATORY T-CELLS; HYDATIDIFORM MOLES; GRANZYME-B; NK CELLS; ACTIVATION AB OBJECTIVE: Advanced maternal age may result in a weaker immune response against complete molar pregnancy, therefore increasing the risk of gestational trophoblastic neoplasia due to ineffective elimination of the trophoblastic cells after evacuation. The present study was undertaken to investigate the cellular immune response against complete molar pregnancy at the implantation site in younger and older patients. STUDY DESIGN: Immunolocalization of CD8, granzyme B (GrB), FoxP3 and CD56 was performed on histologic tissue sections prepared from 18 patients aged <= 40 years and 10 patients aged > 40 years to characterize effector (GrB+CD8+) cytotoxic T cells, GrB positive and negative natural killer cells (CD56) and regulatory T cells (FoxP3+) at the implantation site in complete molar pregnancies. RESULTS: The number of the different immune cell types did not show significant differences in the implantation sites of complete molar pregnancies between the 2 age groups or between persistent and nonpersistent cases. CONCLUSION: Immunosenescence of the natural killer and T cells most likely does not play a role in the increased incidence of gestational trophoblastic neoplasm in older patients with complete moles. (J Reprod Med 2010;55:261-266) C1 [Berkowitz, Ross S.] Harvard Univ, Sch Med, Dept Obstet & Gynecol,Brigham & Womens Hosp, Div Gynecol Oncol,Dana Farber Canc Inst, Boston, MA 02117 USA. Trophoblast Tumor Registry, New England Trophoblast Dis Ctr, Div Gynecol Oncol, Lab Gynecol Oncol, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Womens & Perinatal Pathol,Dept Pathol, Boston, MA 02117 USA. State Hlth Ctr, Dept Obstet & Gynecol, Budapest, Hungary. Semmelweis Univ, Dept Obstet & Gynecol 2, Budapest, Hungary. RP Berkowitz, RS (reprint author), Harvard Univ, Sch Med, Dept Obstet & Gynecol,Brigham & Womens Hosp, Div Gynecol Oncol,Dana Farber Canc Inst, 75 Francis St, Boston, MA 02117 USA. EM rberkowitz@partners.org NR 28 TC 0 Z9 0 U1 1 U2 2 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 J9 J REPROD MED JI J. Reprod. Med. PD MAY-JUN PY 2010 VL 55 IS 5-6 BP 261 EP 266 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 610CT UT WOS:000278708400014 PM 20626184 ER PT J AU Hirsh, JM Boyle, DJ Collier, DH Oxenfeld, AJ Caplan, L AF Hirsh, Joel M. Boyle, Dennis J. Collier, David H. Oxenfeld, Abbey J. Caplan, Liron TI Health Literacy Predicts the Discrepancy Between Patient and Provider Global Assessments of Rheumatoid Arthritis Activity at a Public Urban Rheumatology Clinic SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE RHEUMATOID ARTHRITIS; LITERACY; PATIENT OUTCOME ASSESSMENT; EDUCATION STATUS ID DISEASE-ACTIVITY; OLDER-ADULTS; ASSESSMENT QUESTIONNAIRE; PHYSICIAN; CARE; ASSOCIATION; DISPARITIES; PERCEPTION; SCORES; SCALE AB Objective. Numerous studies report that significant discordance exists between patient and provider [physician] measures of rheumatoid arthritis (RA). We examined whether health literacy explains this discordance. Methods. We recruited English-speaking adult patients with RA for this cross-sectional study. Subjects completed 2 versions of patient global assessments of disease activity (PTGA), using standard terminology from the Multi-Dimensional Health Assessment Questionnaire (MDHAQ) and the 28-joint count Disease Activity Score 28 (DAS28). The provider global assessment (MDGA) was also obtained. The discrepancy between PTGA and MDGA was calculated as the absolute difference between these assessments. We used validated instruments l:Short Test of Functional Health Literacy in Adults (S-TOFHLA) and Rapid Estimate of Adult Literacy in Medicine (REALM)] and linear regression to determine whether health literacy predicts disease measure discrepancy. Results. The study included 110 subjects. Limited health literacy was a common finding by both the REALM and S-TOFHLA. PTGA and MDGA showed fair to good correlation (r = 0.66-0.68), although both versions of the PTGA were significantly higher than MDGA by the t-test (p < 0.001). The S-TOFHLA and REALM both were associated with the absolute difference between the MDGA and PTGA by linear regression, and results remained statistically significant in multivariate analysis. Conclusion. Health literacy was independently associated with the extent of discrepancy between PTGA and MDGA in English-speaking patients with RA at an urban clinic. This finding should influence our interpretation of disease measures. (First Release March 15 2010; J Rheumatol 2010;37:961-6; doi:10.3899/jrheum.090964) C1 [Hirsh, Joel M.; Oxenfeld, Abbey J.] Denver Hlth Med Ctr, Dept Med, Div Rheumatol, Denver, CO 80204 USA. [Collier, David H.; Caplan, Liron] Univ Colorado, Dept Med, Denver Sch Med, Div Rheumatol, Denver, CO USA. [Caplan, Liron] Denver VA Med Ctr, Dept Med, Denver, CO USA. RP Hirsh, JM (reprint author), Denver Hlth Med Ctr, Dept Med, Div Rheumatol, 777 Bannock St,Mail Code 4000, Denver, CO 80204 USA. EM joel.hirshMD@dhha.org FU Denver Health Department of Medicine; VA Health Service Research and Development Career Development Award [07-221] FX Supported by the Denver Health Department of Medicine. Dr. Caplan is supported by a VA Health Service Research and Development Career Development Award (07-221). The views expressed in this article are those Of the authors and do not necessarily reflect the position or policy of the US Department of Veterans Affairs. NR 44 TC 19 Z9 20 U1 1 U2 1 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X EI 1499-2752 J9 J RHEUMATOL JI J. Rheumatol. PD MAY PY 2010 VL 37 IS 5 BP 961 EP 966 DI 10.3899/jrheum.090964 PG 6 WC Rheumatology SC Rheumatology GA 596PH UT WOS:000277696700015 PM 20231210 ER PT J AU Maserejian, N Gerstenberger, E Connor, M Shifren, J Braunstein, G Parish, S Rosen, R AF Maserejian, Nancy Gerstenberger, Eric Connor, Megan Shifren, Jan Braunstein, Glenn Parish, Sharon Rosen, Raymond TI BASELINE CHARACTERISTICS OF PREMENOPAUSAL WOMEN WITH HYPOACTIVE SEXUAL DESIRE DISORDER ENROLLED IN THE HSDD REGISTRY FOR WOMEN SO JOURNAL OF SEXUAL MEDICINE LA English DT Meeting Abstract C1 [Maserejian, Nancy; Gerstenberger, Eric; Connor, Megan; Rosen, Raymond] New England Res Inst Inc, Watertown, MA USA. [Shifren, Jan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Braunstein, Glenn] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Parish, Sharon] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Parish, Sharon] Montefiore Med Ctr, Bronx, NY 10467 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1743-6095 J9 J SEX MED JI J. Sex. Med. PD MAY PY 2010 VL 7 SU 3 BP 120 EP 120 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 592EG UT WOS:000277358100011 ER PT J AU Smith, KB Blair, KL Pukall, CF AF Smith, Kelly B. Blair, Karen L. Pukall, Caroline F. TI CHRONIC VULVAR AND PELVIC PAIN EXPERIENCES AMONG HETEROSEXUAL, LESBIAN, AND BISEXUAL WOMEN SO JOURNAL OF SEXUAL MEDICINE LA English DT Meeting Abstract C1 [Smith, Kelly B.; Blair, Karen L.; Pukall, Caroline F.] Queens Univ, Kingston, ON, Canada. [Smith, Kelly B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1743-6095 J9 J SEX MED JI J. Sex. Med. PD MAY PY 2010 VL 7 SU 3 BP 139 EP 139 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 592EG UT WOS:000277358100065 ER PT J AU Smith, KB Pukall, CF Chamberlain, S AF Smith, Kelly B. Pukall, Caroline F. Chamberlain, Susan TI NEW INVESTIGATOR AWARD: PSYCHOLOGY SEXUAL AND RELATIONSHIP SATISFACTION AND VESTIBULAR PAIN SENSITIVITY AMONG WOMEN WITH PROVOKED VESTIBULODYNIA SO JOURNAL OF SEXUAL MEDICINE LA English DT Meeting Abstract C1 [Smith, Kelly B.; Pukall, Caroline F.; Chamberlain, Susan] Queens Univ, Kingston, ON, Canada. [Smith, Kelly B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1743-6095 J9 J SEX MED JI J. Sex. Med. PD MAY PY 2010 VL 7 SU 3 BP 145 EP 145 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 592EG UT WOS:000277358100081 ER PT J AU Wang, Y Zhang, YG Mao, K Zhang, XS Wang, Z Zheng, GQ Li, G Wood, KB AF Wang, Yan Zhang, YongGang Mao, Keya Zhang, XueSong Wang, Zheng Zheng, GuoQuan Li, Gang Wood, Kirkham B. TI Transpedicular Bivertebrae Wedge Osteotomy and Discectomy in Lumbar Spine for Severe Ankylosing Spondylitis SO JOURNAL OF SPINAL DISORDERS & TECHNIQUES LA English DT Article DE ankylosing spondylitis; kyphosis; osteotomy; discectomy ID KYPHOTIC DEFORMITY AB Study Design: A prospective study was performed in 8 patients with severe ankylosing spondylitis. Objectives: To observe the feasibility, reliability, and complications of a method of transpedicular bivertebrae wedge osteotomy and discectomy to manage the sagittal plane deformity in ankylosing spondylitis with chin-brow vertical angles beyond 90 degrees. Summary of Background Data: In ankylosing spondylitis, the correction of sagittal plane deformity can be achieved by lengthening the anterior elements, shortening the posterior elements, or a combination of the 2. Neither Smith-Petersen osteotomy, nor pedicle subtraction osteotomy in 1 segment can achieve adequate correction for cases of severe ankylosing spondylitis kyphosis. Methods: From January 2003 to May 2007, 8 patients (3 males and 5 females) with severe ankylosing spondylitis in our institution underwent a single stage transpedicular bivertebrae wedge osteotomy and discectomy. The operation technique includes resection of the posterior elements of 2 adjacent vertebrae, resection of the inferior-posterior aspect of proximal vertebra, and the superior-posterior aspect of the distal vertebra, followed by posterior instrumentation with pedicle screws and spinal fusion. Preoperative and postoperative height, chin-brow vertical angle, sagittal balance, and sagittal Cobb angle of the vertebral osteotomy segment were documented. Intraoperative, postoperative, and general complications were registered. Results: The mean follow-up was 18.7 +/- 6.1 months (range: 14 to 54 mo). The mean duration of surgery was 236 minutes (range: 198 to 310 min), and the average volume of intraoperative blood loss was 2200 mL (range: 1600 to 3860 mL). The patients' height increased from 120.5 +/- 12.0 cm to 159.6 +/- 12.4 cm (P = 0.000). The mean chin-brow vertical angle was improved from 102.8 +/- 9.7 to 19.3 +/- 13.9 degrees (P = 0.000). The spinal sagittal Cobb angle of the vertebral osteotomy segment was corrected from kyphosis 38.6 +/- 16.5 degrees to lordosis 26.6 +/- 10.1 degrees (P = 0.000). One patient with the involvement of the cervical spine suffered an extension spinal fracture at C5/6 as the operating table was extended. Translation at the osteotomy site occurred in 1 patient during the correction. Fusion of the osteotomy was achieved in all patients, and no loosening or breakage of pedicle screws was found. Conclusions: In cases of severe ankylosing spondylitis kyphosis with chin-brow vertical angles beyond 90 degrees, a single stage transpedicular bivertebrae wedge osteotomy and discectomy is an effective corrected method of correction. C1 [Wang, Yan; Zhang, YongGang; Mao, Keya; Zhang, XueSong; Wang, Zheng; Zheng, GuoQuan] Chinese Peoples Liberat Army Gen Hosp, Dept Orthopaed, Beijing 100853, Peoples R China. [Li, Gang; Wood, Kirkham B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA USA. RP Wang, Y (reprint author), Chinese Peoples Liberat Army Gen Hosp, Dept Orthopaed, Fuxing Rd, Beijing 100853, Peoples R China. EM 301wangyan@sina.com NR 10 TC 21 Z9 30 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1536-0652 J9 J SPINAL DISORD TECH JI J. Spinal Disord. Tech. PD MAY PY 2010 VL 23 IS 3 BP 186 EP 191 DI 10.1097/BSD.0b013e3181a5abde PG 6 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 622LS UT WOS:000279665900007 PM 20072030 ER PT J AU Chiu, D Peterson, L Elkind, MSV Rosand, J Gerber, LM Silverstein, MD AF Chiu, David Peterson, Leif Elkind, Mitchell S. V. Rosand, Jonathan Gerber, Linda M. Silverstein, Marc D. CA Glycine Antagonist Neuroprotection TI Comparison of Outcomes after Intracerebral Hemorrhage and Ischemic Stroke SO JOURNAL OF STROKE & CEREBROVASCULAR DISEASES LA English DT Article DE Stroke; intracerebral hemorrhage; outcomes; prognosis ID INPATIENT REHABILITATION; PROGNOSTIC VALUE; GAIN-AMERICA; PREDICTION; TRIAL; SCALE; HEMATOMAS; PRESSURE; RECOVERY; BLOOD AB Background: intracerebral hemorrhage (ICH) is associated with a greater average initial stroke severity, higher mortality, and poorer long-term neurologic outcomes than ischemic stroke. The purpose of this study was to determine whether the poorer prognosis of ICH is independent of initial stroke severity. Methods: We analyzed data from the Glycine Antagonist in Neuroprotection (GAIN) Americas trial, in which 1604 non-obtunded patients with acute stroke were treated within 6 hours of symptom onset irrespective of hemorrhagic (N = 237) versus ischemic (N = 1367) subtype. Multiple logistic regression analysis was performed to evaluate predictors of mortality and neurologic outcome (modified Rankin scale [mRS] score of 0-1 v 2-6 at 3 months) adjusting for baseline National Institutes of Health Stroke Scale score, stroke risk factors, clinical and demographic characteristics, and gavestinel treatment group. Multiple linear regression techniques were used to assess the impact of various predictors on the full mRS score at 3 months. Results: ICH significantly increased the odds of a poor neurologic outcome (odds ratio 1.94, 95% confidence interval 1.23-3.06) and was independently associated with a mean 0.25-point increase in the 3-month mRS score (P = .04). ICH had no effect on mortality compared with ischemic stroke (odds ratio 1.01, 95% confidence interval .68-1.49) after adjusting for initial stroke severity (National Institutes of Health Stroke Scale score) and other baseline characteristics. Conclusions: Among conscious stroke patients, ICH is an independent predictor of poor neurologic outcome, nearly doubling the odds of long-term disability. However, ICH is not associated with higher mortality compared with ischemic stroke after adjusting for initial stroke severity and other baseline characteristics. C1 [Chiu, David; Peterson, Leif; Silverstein, Marc D.] Methodist Neurol Inst, New York, NY USA. [Gerber, Linda M.] Weill Cornell Med Coll, Dept Publ Hlth, New York, NY USA. [Peterson, Leif] Columbia Univ, Coll Phys & Surg, New York, NY USA. [Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Chiu, D (reprint author), Weill Cornell Med Coll, Methodist Neurol Inst, 6560 Fannin,Suite 802, Houston, TX USA. EM dchiu@tmhs.org OI Peterson, Leif/0000-0002-1187-0883 NR 30 TC 15 Z9 17 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1052-3057 J9 J STROKE CEREBROVASC JI J. Stroke Cerebrovasc. Dis. PD MAY-JUN PY 2010 VL 19 IS 3 BP 225 EP 229 DI 10.1016/j.jstrokecerebrovasdis.2009.06.002 PG 5 WC Neurosciences; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 596DK UT WOS:000277664200009 PM 20434051 ER PT J AU Rost, NS Rahman, R Sonni, S Kanakis, A Butler, C Massasa, E Cloonan, L Gilson, A Delgado, P Chang, YC Biffi, A Jimenez-Conde, J Besanger, A Silva, G Smith, EE Rosand, J Furie, KL AF Rost, Natalia S. Rahman, Rosanna Sonni, Shruti Kanakis, Allison Butler, Christi Massasa, Efi Cloonan, Lisa Gilson, Aaron Delgado, Pilar Chang, Yuchiao Biffi, Alessandro Jimenez-Conde, Jordi Besanger, Angela Silva, Gisele Smith, Eric E. Rosand, Jonathan Furie, Karen L. TI Determinants of White Matter Hyperintensity Volume in Patients with Acute Ischemic Stroke SO JOURNAL OF STROKE & CEREBROVASCULAR DISEASES LA English DT Article DE White matter hyperintensity; leukoaraiosis; ischemic stroke; cerebral infarct; risk factors; magnetic resonance imaging ID SMALL-VESSEL DISEASE; CEREBRAL AMYLOID ANGIOPATHY; TOTAL HOMOCYSTEINE LEVELS; CARDIOVASCULAR HEALTH; ROTTERDAM-SCAN; NORTHERN MANHATTAN; ELDERLY PERSONS; RISK PROFILE; LESIONS; LEUKOARAIOSIS AB Background: White matter hyperintensity (WMH) is a common radiographic finding in the aging population and a potent risk factor for symptomatic cerebrovascular disease. It is unclear whether WMH represents a single or multiple biological processes. We sought to investigate the extent and determinants of WMH in patients with acute ischemic stroke (AIS). Methods: We retrospectively analyzed a prospectively enrolled hospital-based cohort of patients with AIS. WMH volume (WMHV) was measured using a previously published method with high interrater reliability based on a semiautomated image analysis program. Results: WMHV was measured in 523 consecutive patients with stroke (mean age 65.2 years, median WMHV 8.2 cm(3)). In univariate linear regression analyses, individuals who were older, had elevated homocysteine (HCY) level or systolic blood pressure, or history of hypertension (all P < .0001), decreased glomerular filtration rate (P < .0002), atrial fibrillation (P < .0008), or coronary artery disease (P < .03) had significantly greater WMHV. After multivariable adjustment, only age (P < .0001) and HCY levels greater than 9 mu mol/L (P < .003) remained independently associated with WMHV. Conclusions: In patients with AIS, risk factors for WMH severity do not appear to overlap with those previously reported for population-based cohorts. Only age and higher HCY levels were independently associated with more severe WMH in patients with stroke. This suggests that some of the processes underlying WMH burden accumulation in patients with stroke may differ from those in the general population and are not simply mediated by traditional vascular risk factors. C1 [Rost, Natalia S.; Rahman, Rosanna; Biffi, Alessandro; Jimenez-Conde, Jordi; Rosand, Jonathan] Massachusetts Gen Hosp, J Philip Kistler Stroke Res Ctr, Ctr Human Genet Res, Boston, MA 02114 USA. [Rost, Natalia S.; Rahman, Rosanna; Sonni, Shruti; Kanakis, Allison; Butler, Christi; Massasa, Efi; Cloonan, Lisa; Gilson, Aaron; Delgado, Pilar; Biffi, Alessandro; Jimenez-Conde, Jordi; Besanger, Angela; Silva, Gisele; Rosand, Jonathan; Furie, Karen L.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Chang, Yuchiao] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Rost, Natalia S.; Rahman, Rosanna; Biffi, Alessandro; Jimenez-Conde, Jordi; Rosand, Jonathan] MIT, Program Med & Populat Genet, Broad Inst, Boston, MA USA. [Smith, Eric E.] Univ Calgary, Dept Clin Neurosci, Calgary, AB, Canada. RP Rost, NS (reprint author), Massachusetts Gen Hosp, J Philip Kistler Stroke Res Ctr, Ctr Human Genet Res, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM nrost@partners.org RI JIMENEZ-CONDE, JORDI/C-1941-2012; Smith, Eric/C-5443-2012 OI Smith, Eric/0000-0003-3956-1668 FU Bugher Foundation-American Stroke Association; National Institutes of Neurological Disorders and Stroke [R01 NS04217]; Deane Institute for Integrative Study of Atrial Fibrillation and Stroke FX Supported by Bugher Foundation-American Stroke Association; National Institutes of Neurological Disorders and Stroke (R01 NS04217); and the Deane Institute for Integrative Study of Atrial Fibrillation and Stroke. NR 38 TC 27 Z9 29 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1052-3057 J9 J STROKE CEREBROVASC JI J. Stroke Cerebrovasc. Dis. PD MAY-JUN PY 2010 VL 19 IS 3 BP 230 EP 235 DI 10.1016/j.jstrokecerebrovasdis.2009.05.007 PG 6 WC Neurosciences; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 596DK UT WOS:000277664200010 PM 20434052 ER PT J AU Kelly, JF Stout, RL Tonigan, JS Magill, M Pagano, ME AF Kelly, John F. Stout, Robert L. Tonigan, J. Scott Magill, Molly Pagano, Maria E. TI Negative Affect, Relapse, and Alcoholics Anonymous (AA): Does AA Work by Reducing Anger? SO JOURNAL OF STUDIES ON ALCOHOL AND DRUGS LA English DT Article ID DRINKING OUTCOMES; PROJECT MATCH; SELF-HELP; MECHANISMS; MEDIATION; HISTORY; MODEL AB Objective: Anger and other indices of negative affect have been implicated in a stress-induced pathway to relapse. The Alcoholics Anonymous (AA) literature states that reduction of anger is critical to recovery, yet this proposed mechanism has rarely been investigated. Using lagged, controlled hierarchical linear modeling analyses, this study investigated whether AA attendance mobilized changes in anger and whether such changes explained AA-related benefit. Method: Alcohol-dependent adults (N = 1,706) receiving treatment as part of a clinical trial were assessed at intake and at 3, 6, 9, 12, and 15 months. Results: Findings revealed substantially elevated levels of anger compared with the general population (98th percentile) that decreased over 15-month follow-up but remained high (89th percentile). AA attendance was associated with better drinking outcomes, and higher levels of anger were associated with heavier drinking. However, AA attendance was unrelated to changes in anger. Conclusions: Although support was not found for anger as a mediator, there was strong convergence between AA's explicit emphasis on anger and the present findings: Anger appears to be a serious, enduring problem related to relapse and heavy alcohol consumption. Methodological factors may have contributed to the lack of association between AA and anger, but results suggest that AA attendance alone may be insufficient to alleviate the suffering and alcohol-related risks specifically associated with anger. (J. Stud. Alcohol Drugs, 71, 434-444, 2010) C1 [Kelly, John F.] Massachusetts Gen Hosp, Dept Psychiat, Ctr Addict Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Kelly, JF (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Ctr Addict Med, 60 Staniford St,Suite 120, Boston, MA 02114 USA. EM jkelly11@partners.org FU National Institute on Alcohol Abuse and Alcoholism [R21AA016762, K01AA015137-04] FX This research was supported by National Institute on Alcohol Abuse and Alcoholism grants R21AA016762 (John F. Kelly, principal investigator) and K01AA015137-04 (Maria E. Pagano, principal investigator). NR 55 TC 16 Z9 16 U1 3 U2 10 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 J9 J STUD ALCOHOL DRUGS JI J. Stud. Alcohol Drugs PD MAY PY 2010 VL 71 IS 3 BP 434 EP 444 PG 11 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA 590EM UT WOS:000277207200015 PM 20409438 ER PT J AU Chertoff, M Lichtenhan, J Willis, M AF Chertoff, Mark Lichtenhan, Jeffery Willis, Marie TI Click- and chirp-evoked human compound action potentials SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID BRAIN-STEM RESPONSES; COCHLEAR TRAVELING-WAVE; LATENCIES; STIMULI AB In the experiments reported here, the amplitude and the latency of human compound action potentials (CAPs) evoked from a chirp stimulus are compared to those evoked from a traditional click stimulus. The chirp stimulus was created with a frequency sweep to compensate for basilar membrane traveling wave delay using the O-Chirp equations from Fobel and Dau [(2004). J. Acoust. Soc. Am. 116, 2213-2222] derived from otoacoustic emission data. Human cochlear traveling wave delay estimates were obtained from derived compound band action potentials provided by Eggermont [(1979). J. Acoust. Soc. Am. 65, 463-470]. CAPs were recorded from an electrode placed on the tympanic membrane (TM), and the acoustic signals were monitored with a probe tube microphone attached to the TM electrode. Results showed that the amplitude and latency of chirp-evoked N1 of the CAP differed from click-evoked CAPs in several regards. For the chirp-evoked CAP, the N1 amplitude was significantly larger than the click-evoked N1s. The latency-intensity function was significantly shallower for chirp-evoked CAPs as compared to click-evoked CAPs. This suggests that auditory nerve fibers respond with more unison to a chirp stimulus than to a click stimulus. (C) 2010 Acoustical Society of America. [DOI: 10.1121/1.3372756] C1 [Chertoff, Mark; Willis, Marie] Univ Kansas, Med Ctr, Dept Speech & Hearing, Kansas City, KS 66160 USA. [Lichtenhan, Jeffery] Massachusetts Eye & Ear Infirm, Eaton Peaboy Lab Auditory Physiol, Boston, MA 02114 USA. RP Chertoff, M (reprint author), Univ Kansas, Med Ctr, Dept Speech & Hearing, Kansas City, KS 66160 USA. EM mchertof@kumc.edu FU NIDCD [F32 DC010112]; National Institutes of Health FX We thank Christopher A. Shera for several helpful discussions on this research. J. T. L. was supported by grants from the University of Kansas Medical Center Biomedical Research Training Program and Grant No. F32 DC010112 from the NIDCD, National Institutes of Health. NR 21 TC 10 Z9 10 U1 0 U2 1 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD MAY PY 2010 VL 127 IS 5 BP 2992 EP 2996 DI 10.1121/1.3372756 PG 5 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 595NG UT WOS:000277617300038 PM 21117748 ER PT J AU Stepp, CE Hillman, RE Heaton, JT AF Stepp, Cara E. Hillman, Robert E. Heaton, James T. TI A virtual trajectory model predicts differences in vocal fold kinematics in individuals with vocal hyperfunction SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID NONORGANIC HABITUAL DYSPHONIA; MUSCLE TENSION DYSPHONIA; VOICE DISORDERS; BIOMECHANICAL MODEL; SPEECH PRODUCTION; MOVEMENTS; NODULES; ABDUCTION/ADDUCTION; ADDUCTION; VIBRATION AB A simple, one degree of freedom virtual trajectory model of vocal fold kinematics was developed to investigate whether kinematic features of vocal fold movement confirm increased muscle stiffness. Model simulations verified that increases in stiffness were associated with changes in kinematic parameters, suggesting that increases in gesture rate would affect kinematic features to a lesser degree in vocal hyperfunction patients given the increased levels of muscle tension they typically employ to phonate. This hypothesis was tested experimentally in individuals with muscle tension dysphonia (MTD; N = 10) and vocal nodules (N = 10) relative to controls with healthy normal voice (N = 10) who were examined with trans-nasal endoscopy during a simple vocal fold abductory-adductory task. Kinematic measures in MTD patients were less affected by increased gesture rate, consistent with the hypothesis that these individuals have elevated typical laryngeal muscle tension. Group comparisons of the difference between medium and fast gesture rates (Mann-Whitney, one-tailed) showed statistically significant differences between the control and MTD individuals on the two kinematic features examined (p < 0.05). Results in nodules participants were mixed and are discussed independently. The findings support the potential use of vocal fold kinematics as an objective clinical assay of vocal hyperfunction. (C) 2010 Acoustical Society of America. [DOI: 10.1121/1.3365257] C1 [Stepp, Cara E.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Hillman, Robert E.; Heaton, James T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hillman, Robert E.; Heaton, James T.] Harvard Univ, Sch Med, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. RP Stepp, CE (reprint author), Univ Washington, Dept Comp Sci & Engn, Seattle, WA 98195 USA. EM cstepp@alum.mit.edu FU National Institute on Deafness and other Communication Disorders [5T32DC000038-17] FX This work was supported in part by Grant No. 5T32DC000038-17 from the National Institute on Deafness and other Communication Disorders. The authors thank Maia Braden, Tara Stadelman-Cohen, Marie Jette, and Drs. Matthew Lutch and James Burns for their assistance in participant recruitment and their technical expertise in performing endoscopy on many of the participants of this study. Many thanks also to Drs. Neville Hogan, Joseph Perkell, Steve Massaquoi, Robert Howe, and Serge Roy for their thoughtful comments on portions of this work. Special thanks to Dr. James Kobler for the use of his custom angle-marking software, and to Ashley Schuler for technical assistance. NR 50 TC 8 Z9 8 U1 0 U2 8 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD MAY PY 2010 VL 127 IS 5 BP 3166 EP 3176 DI 10.1121/1.3365257 PG 11 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 595NG UT WOS:000277617300055 PM 21117765 ER PT J AU Konrad-Martin, D James, KE Gordon, JS Reavis, KM Phillips, DS Bratt, GW Fausti, SA AF Konrad-Martin, Dawn James, Kenneth E. Gordon, Jane S. Reavis, Kelly M. Phillips, David S. Bratt, Gene W. Fausti, Stephen A. TI Evaluation of Audiometric Threshold Shift Criteria for Ototoxicity Monitoring SO JOURNAL OF THE AMERICAN ACADEMY OF AUDIOLOGY LA English DT Article DE Audiologic monitoring/testing; distortion-product otoacoustic emissions; hearing loss; high-frequency audiometry; ototoxicity monitoring; tinnitus; veteran ID HIGH-FREQUENCY AUDIOMETRY; PURE-TONE THRESHOLDS; CIS-DIAMMINEDICHLOROPLATINUM; HEARING-LOSS; AMINOGLYCOSIDE OTOTOXICITY; CISPLATIN OTOTOXICITY; OTOACOUSTIC EMISSIONS; SENNHEISER HDA-200; DOSE CISPLATIN; RISK-FACTORS AB Background: There is disagreement about ototoxicity monitoring methods. Controversy exists about what audiometric threshold shift criteria should be used, which frequencies should be tested, and with what step size. An evaluation of the test performance achieved using various criteria and methods for ototoxicity monitoring may help resolve these issues. Purpose: (1) Evaluate test performance achieved using various significant threshold shift (STS) definitions for ototoxicity monitoring in a predominately veteran population; and (2) determine whether testing in 1/6- or 1/3-octave steps improves test performance compared to 1/2-octave steps. Research Design: A prospective, observational study design was used in which STSs were evaluated at frequencies within an octave of each subject's high-frequency hearing limit at two time points, an early monitoring test and the final monitoring test. Study Sample: Data were analyzed from 78 ears of 41 patients receiving cisplatin and from 53 ears of 28 hospitalized patients receiving nonototoxic antibiotics. Cisplatin-treated subjects received a cumulative dosage >= 350 mg by the final monitoring test. Testing schedule, age, and pre-exposure hearing characteristics were similar between the subject groups. Data Collection and Analysis: Threshold shifts relative to baseline were examined to determine whether they met criteria based on magnitudes of positive STS (shifts of >= 5, 10, 15, or 20 dB) and numbers of frequencies affected (shifts at >= 1, 2, or 3 adjacent frequencies) for data collected using approximately 16-, 1/3-, or 1/2-octave steps. Thresholds were confirmed during monitoring sessions in which shifts were identified. Test performance was evaluated with receiver operating characteristic (ROC) curves developed using a surrogate "gold standard"; true positive (TP) rates were derived from the cisplatin-exposed group and false positive (FP) rates from the nonexposed, control group. Best STS definitions were identified that achieved the greatest areas under ROC curves or resulted in the highest TP rates for a fixed FP rate near 5%, chosen to minimize the number of patients incorrectly diagnosed with ototoxic hearing loss. Results: At the early monitoring test, average threshold shifts differed only slightly across groups. Test-frequency step size did not affect performance, and changes at one or more frequencies yielded the best test performance. At the final monitoring test, average threshold shifts were +10.5 dB for the cisplatin group, compared with -0.2 dB for the control group. Compared with the 1/2-octave step size used clinically, use of smaller frequency steps improved test performance for threshold shifts at >= 2 or >= 3 adjacent frequencies. Best overall test performance was achieved using a criterion cutoff of >= 10 dB threshold shift at >= 2 adjacent frequencies tested in 1/6-octave steps. Best test performance for the 1/2-octave step size was achieved for shifts >= 15 dB at one or more frequencies. Conclusions: An ototoxicity monitoring protocol that uses an individualized, one-octave range of frequencies tested in 1/6-octave steps is quick to administer and has an acceptable FP rate. Similar test performance can be achieved using 1/3-octave test frequencies, which further reduces monitoring test time. C1 [Konrad-Martin, Dawn; James, Kenneth E.; Gordon, Jane S.; Reavis, Kelly M.; Phillips, David S.; Fausti, Stephen A.] Oregon Hlth & Sci Univ, Sch Med, Portland VA Med Ctr, VA RR&D Natl Ctr Rehabil Auditory Res, Nashville, TN USA. [Konrad-Martin, Dawn; Fausti, Stephen A.] Oregon Hlth & Sci Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Nashville, TN USA. [Bratt, Gene W.] Oregon Hlth & Sci Univ, Sch Med, Dept Publ Hlth & Prevent Med, Nashville, TN USA. [Bratt, Gene W.] Tennessee Valley Healthcare Syst, Dept Vet Affairs, Audiol Serv, Nashville, TN USA. [Bratt, Gene W.] Tennessee Valley Healthcare Syst, Dept Vet Affairs, Speech Pathol Serv, Nashville, TN USA. [James, Kenneth E.; Phillips, David S.] Vanderbilt Univ, Dept Hearing & Speech Sci, Nashville, TN USA. RP Konrad-Martin, D (reprint author), 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM dawn.martin@va.gov OI Reavis, Kelly/0000-0002-4906-1010 FU United States Department of Veterans Affairs (VA), Veterans Health Administration, Office of Research and Development Rehabilitation Research and Development (RRD) Service [C4447K, C4183R, C2346R] FX Work supported by the United States Department of Veterans Affairs (VA), Veterans Health Administration, Office of Research and Development Rehabilitation Research and Development (RR&D) Service grants C4447K, C4183R, and C2346R. The authors appreciate significant contributions to this work by Douglas Noffsinger, Oregon Health and Science University; Amy Britt, Jennifer Dillard, Mia Rosenfeld, Kirsti Raleigh, Dawn Bradley, VA Tennessee Valley Health Care System; Stephanie Girvan, Karen Sugiura, VA Greater Los Angeles Health Care System; and Daniel McDermott, Carolyn Landsverk, VA RR&D National Center for Rehabilitative Auditory Research. Portions of this paper were presented at the 2007 American Auditory Society Meeting in Scottsdale, AZ, and the 2007 American Speech-Language-Hearing Association Convention in Boston, MA. NR 47 TC 8 Z9 8 U1 2 U2 10 PU AMER ACAD AUDIOLOGY PI RESTON PA 11730 PLAZA DR, STE 300, RESTON, VA 20190 USA SN 1050-0545 J9 J AM ACAD AUDIOL JI J. Am. Acad. Audiol. PD MAY PY 2010 VL 21 IS 5 BP 301 EP 314 DI 10.3766/jaaa.21.5.3 PG 14 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA 615MH UT WOS:000279138900003 PM 20569665 ER PT J AU Stebbins, WG Garibyan, L Sober, AJ AF Stebbins, William G. Garibyan, Lilit Sober, Arthur J. TI Sentinel lymph node biopsy and melanoma: 2010 update Part I SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE melanoma; sentinel lymph node biopsy ID POLYMERASE-CHAIN-REACTION; PRIMARY CUTANEOUS MELANOMA; EARLY-STAGE MELANOMA; AMERICAN JOINT COMMITTEE; MALIGNANT-MELANOMA; CLINICAL-RELEVANCE; PROGNOSTIC-SIGNIFICANCE; PATHOLOGICAL ANALYSIS; METASTATIC MELANOMA; COST-EFFECTIVENESS AB Sentinel lymph node biopsy for melanoma was introduced in the early 1990s as a minimally invasive method of identifying and pathologically staging regional lymph node basins in patients with clinical stage I/II melanoma. Numerous large trials have demonstrated that sentinel lymph node evaluation has utility in improving accuracy of prognostication and for risk stratifying patients into appropriate groups for clinical trials. However, there remains a great deal of controversy regarding the therapeutic role of removal of the remainder of locoregional lymph nodes should metastatic cells be identified in the sentinel node. This CME article will outline a brief history of the sentinel node concept before reviewing updates in surgical technique, histopathologic evaluation of nodal tissue, and cost effectiveness of sentinel node biopsy. (J Am Acad Dermatol 2010;62:723-34.) Learning objectives: After completing this learning activity, participants should be able to describe the concept of sentinel lymph node biopsy, to discuss the risks and benefits associated with this procedure, and to summarize the role of sentinel lymph node biopsy in management of patients with melanoma. C1 [Stebbins, William G.; Garibyan, Lilit; Sober, Arthur J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Stebbins, WG (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol, 55 Fruit St,Bartlett Hall 616, Boston, MA 02114 USA. EM bstebbins@gmail.com NR 89 TC 21 Z9 22 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 MAY PY 2010 VL 62 IS 5 SI SI BP 723 EP 734 DI 10.1016/j.jaad.2009.11.695 PG 12 WC Dermatology SC Dermatology GA 589YM UT WOS:000277190100001 PM 20398810 ER PT J AU Stebbins, WG Garibyan, L Sober, AJ AF Stebbins, William G. Garibyan, Lilit Sober, Arthur J. TI Sentinel lymph node biopsy and melanoma: 2010 update Part II SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE melanoma; Multicenter Selective Lymphadenectomy Trial; sentinel lymph node biopsy ID CUTANEOUS MALIGNANT-MELANOMA; AMERICAN JOINT COMMITTEE; THICK GREATER-THAN-OR-EQUAL-TO-4-MM MELANOMA; SELECTIVE LYMPHADENECTOMY TRIAL; IN-TRANSIT METASTASES; EARLY-STAGE MELANOMA; COMPLETION LYMPHADENECTOMY; RANDOMIZED-TRIAL; REGIONAL NODES; MITOTIC RATE AB This article will discuss the evidence for and against the therapeutic efficacy of early removal of potentially affected lymph nodes, morbidity associated with sentinel lymph node biopsy and completion lymphadenectomy, current guidelines regarding patient selection for sentinel lymph node biopsy, and the remaining questions that ongoing clinical trials are attempting to answer. The Sunbelt Melanoma Trial and the Multicenter Selective Lymphadenectomy Trials I and II will be discussed in detail. (J Am Acad Dermatol 2010;62:737-48.) Learning objectives: At the completion of this learning activity, participants should be able to discuss the data regarding early surgical removal of lymph nodes and its effect on the overall survival of melanoma patients, be able to discuss the potential benefits and morbidity associated with complete lymph node dissection, and to summarize the ongoing trials aimed at addressing the question of therapeutic value of early surgical treatment of regional lymph nodes that may contain micrometastases. C1 [Stebbins, William G.; Garibyan, Lilit; Sober, Arthur J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA 02114 USA. RP Stebbins, WG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, 55 Fruit St,Bartlett Hall 616, Boston, MA 02114 USA. EM bstebbins@gmail.com NR 69 TC 15 Z9 16 U1 0 U2 1 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 MAY PY 2010 VL 62 IS 5 SI SI BP 737 EP 748 DI 10.1016/j.jaad.2009.11.696 PG 12 WC Dermatology SC Dermatology GA 589YM UT WOS:000277190100002 PM 20398811 ER PT J AU Strickland, PAO Hudson, SV Piasecki, A Hahn, K Cohen, D Orzano, AJ Parchman, ML Crabtree, BF AF Strickland, Pamela A. Ohman Hudson, Shawna V. Piasecki, Alicja Hahn, Karissa Cohen, Deborah Orzano, A. John Parchman, Michael L. Crabtree, Benjamin F. TI Features of the Chronic Care Model (CCM) Associated with Behavioral Counseling and Diabetes Care in Community Primary Care SO JOURNAL OF THE AMERICAN BOARD OF FAMILY MEDICINE LA English DT Article DE Primary Health Care; Chronic Disease; Diabetes; Chronic Care Model ID QUALITY IMPROVEMENT; HEALTH-CARE; CHRONIC ILLNESS; DIETARY INTERVENTION; RANDOMIZED-TRIAL; SELF-MANAGEMENT; FAMILY MEDICINE; CHRONIC DISEASE; OBESE-PATIENTS; RISK-FACTORS AB Background: The Chronic Care Model (CCM) was developed to improve chronic disease care, but it may also inform delivery of other types of preventive care. Using hierarchical analyses of service delivery to patients, we explored associations of CCM implementation with diabetes care and counseling for diet or weight loss and physical activity in community-based primary care offices. Methods: Secondary analysis focused on baseline data from 25 practices (with an average of 4 physicians per practice) participating in an intervention trial targeting improved colorectal cancer screening rates. This intervention made no reference to the CCM. CCM implementation was measured through staff and clinical management surveys and was associated with patient care indicators (chart audits and patient questionnaires). Results: Overall, practices had low levels of CCM implementation. However, higher levels of CCM implementation were associated with better diabetes assessment and treatment of patients (P = .009 and .015, respectively), particularly among practices open to "innovation." Physical activity counseling for obese and, particularly, overweight patients was strongly associated with CCM implementation (P = .0017), particularly among practices open to "innovation"; however, this association did not hold for overweight and obese patients with diabetes. Conclusions: Very modest levels of CCM implementation in unsupported primary care practices are associated with improved care for patients with diabetes and higher rates of behavioral counseling. Incremental incorporation of CCM components is an option, especially for community practices with stretched resources and with cultures of "innovativeness." (J Am Board Fam Med 2010;23:295-305.) C1 [Strickland, Pamela A. Ohman] Univ Med & Dent New Jersey, Sch Publ Hlth, Dept Biostat, Piscataway, NJ 08854 USA. [Crabtree, Benjamin F.] Univ Med & Dent New Jersey, Sch Publ Hlth, Dept Epidemiol, Piscataway, NJ 08854 USA. [Strickland, Pamela A. Ohman; Hudson, Shawna V.; Piasecki, Alicja; Hahn, Karissa; Cohen, Deborah; Crabtree, Benjamin F.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Family Med, New Brunswick, NJ USA. [Strickland, Pamela A. Ohman; Hudson, Shawna V.; Crabtree, Benjamin F.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Canc Inst New Jersey, New Brunswick, NJ USA. [Orzano, A. John] Dept Family Med, Concord, NH USA. [Crabtree, Benjamin F.] Ctr Res Family Practice & Primary Care, Cleveland, OH USA. [Parchman, Michael L.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Strickland, PAO (reprint author), Univ Med & Dent New Jersey, Sch Publ Hlth, Dept Biostat, 683 Hoes Lane W,Room 218,POB 9, Piscataway, NJ 08854 USA. EM ohmanpa@umdnj.edu OI Parchman, Michael/0000-0001-7129-2889 FU National Cancer Institute [R01 CA11287]; American Academy of Family Physicians' Research Center; Cancer Institute of New Jersey's Primary Care Research shared resource FX Research was supported by the National Cancer Institute (R01 CA11287), an American Academy of Family Physicians' Research Center grant, and the Cancer Institute of New Jersey's Primary Care Research shared resource. NR 59 TC 19 Z9 19 U1 2 U2 16 PU AMER BOARD FAMILY MEDICINE PI LEXINGTON PA 2228 YOUNG DR, LEXINGTON, KY 40505 USA SN 1557-2625 J9 J AM BOARD FAM MED JI J. Am. Board Fam. Med. PD MAY-JUN PY 2010 VL 23 IS 3 BP 295 EP 305 DI 10.3122/jabfm.2010.03.090141 PG 11 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 592OZ UT WOS:000277390200004 PM 20453175 ER PT J AU Thrall, JH AF Thrall, James H. TI Working Together for the ACR SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Thrall, JH (reprint author), Massachusetts Gen Hosp, Dept Radiol, 32 Fruit St,Room 216, Boston, MA 02114 USA. EM jthrall@partners.org 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 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD MAY PY 2010 VL 7 IS 5 BP 319 EP 320 DI 10.1016/j.jacr.2010.03.020 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V23SO UT WOS:000208362700001 PM 20439068 ER PT J AU Tan, J Saini, S Datar, SM AF Tan, John Saini, Sanjay Datar, Srikant M. TI Leadership Effort in Professional Radiology Associations SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Leadership committees; professional associations; cooperation; research and development AB Professional associations advocate for their members' interests; provide forums for education, training, and certification; and support domain-specific research and development efforts. The purpose of this study was to determine the amount of resources devoted to the leadership committees of professional radiology associations in the United States. Internet research was conducted to identify general, subspecialty, and special interest radiology associations, followed by a survey that focused on the number of committees and the average number of members per committee for each association. Established or published benchmarks were used to calculate committee-related annual expenditures from the survey data. Two hundred forty full-time equivalents, or nearly $100 million, are devoted to leadership activities within radiology associations each year. This is equivalent to approximately 1% of the professional income in radiology. These resources have enabled individual radiologists and societies to cooperate on important initiatives. More research should be conducted on other specialties or industries to provide comparable data on the optimal investment in the leadership effort. C1 [Tan, John; Saini, Sanjay] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Tan, John; Saini, Sanjay] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Datar, Srikant M.] Harvard Univ, Harvard Business Sch, Boston, MA 02115 USA. RP Saini, S (reprint author), Harvard Univ, Sch Med, Dept Radiol, 32 Fruit St, Boston, MA 02114 USA. EM ssaini@partners.org NR 8 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 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD MAY PY 2010 VL 7 IS 5 BP 346 EP 350 DI 10.1016/j.jacr.2009.12.016 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V23SO UT WOS:000208362700010 PM 20439077 ER PT J AU Semla, TP Ouslander, JG AF Semla, Todd P. Ouslander, Joseph G. TI The American Geriatrics Society Transitions to New Leadership SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Editorial Material C1 [Semla, Todd P.] US Dept Vet Affairs, Chicago, IL USA. [Semla, Todd P.] Northwestern Univ, Dept Med, Chicago, IL 60611 USA. [Semla, Todd P.] Northwestern Univ, Dept Psychiat & Behav Sci, Chicago, IL 60611 USA. [Ouslander, Joseph G.] Florida Atlantic Univ, Geriatr Programs, Charles E Schmidt Coll Biomed Sci, Boca Raton, FL 33431 USA. RP Semla, TP (reprint author), US Dept Vet Affairs, Chicago, IL USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAY PY 2010 VL 58 IS 5 BP 820 EP 821 DI 10.1111/j.1532-5415.2010.02846.x PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 592XE UT WOS:000277414400003 PM 20722818 ER PT J AU Martin, JL Fiorentino, L Jouldjian, S Josephson, KR Alessi, CA AF Martin, Jennifer L. Fiorentino, Lavinia Jouldjian, Stella Josephson, Karen R. Alessi, Cathy A. TI Sleep Quality in Residents of Assisted Living Facilities: Effect on Quality of Life, Functional Status, and Depression SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE sleep; assisted living facilities; depression; quality of life; functional status ID FORM HEALTH SURVEY; OLDER-ADULTS; OSTEOPOROTIC FRACTURES; COGNITIVE IMPAIRMENT; DAYTIME SLEEPINESS; NURSING FACILITY; SELF-REPORT; COMORBIDITY; PEOPLE; WOMEN AB OBJECTIVES To describe sleep patterns in older adults living in assisted living facilities (ALFs) and to explore the relationship between sleep disturbance and quality of life, functional status, and depression over 6 months of follow-up. DESIGN Prospective, observational cohort study. SETTING Eighteen ALFs in the Los Angeles area. PARTICIPANTS One hundred twenty-one ALF residents aged 65 and older (mean age 85.3, 86% female, 88% non-Hispanic white). MEASUREMENTS Data were collected at baseline and 3 and 6 months after enrollment. Data collected were demographics, physical and cognitive functioning, depression, quality of life, comorbidities, medications, and subjective (i.e., questionnaires) and objective (i.e., 3 days and nights of wrist actigraphy) measures of sleep. RESULTS Sixty-five percent of participants reported clinically significant sleep disturbance on the Pittsburgh Sleep Quality Index, and objective wrist actigraphy confirmed poor sleep quality. In regression analyses including sleep variables and other predictors, more self-reported sleep disturbance at baseline was associated with worse health-related quality of life (Medical Outcomes Study 12-item Short Form Survey Mental Component Summary score) and worse depressive symptoms five-item Geriatric Depression Scale at follow-up. Worse nighttime sleep (according to actigraphy) at baseline was associated with worse activities of daily living functioning and more depressive symptoms at follow-up. CONCLUSIONS Sleep disturbance is common in older ALF residents, and poor sleep is associated with declining functional status and quality of life and greater depression over 6 months of follow-up. Studies are needed to determine whether improving sleep in ALF residents will result in improvements in these outcomes. Well-established treatments should be adapted for use in ALFs and systematically evaluated in future research. C1 Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Cousins Ctr Psychoneuroimmunol, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Martin, JL (reprint author), VAGLAHS GRECC 11E, 16111 Plummer St, North Hills, CA 91343 USA. EM Jennifer.martin@va.gov FU Sepracor Inc., Marlborough, Massachusetts; National Institutes of Health (NIH), National Institute on Aging [K23 AG028452]; National Institute of Mental Health [T32 MH 019925-11]; University of California at Los Angeles (UCLA) Academic Senate Council on Research; Veterans Affairs (VA) Greater Los Angeles Healthcare System, Geriatric Research, Education and Clinical Center; VA Health Services Research and Development [IIR 04-321-2]; UCLA Cousins Center for Psychoneuroimmunology FX The authors thank the participating facilities, the residents who took part in the study, and the research staff who made this study possible. In particular, we wish to thank Terry Vandenberg, MA, and Rebecca Saia, who served as project coordinators for this study.; Conflicts of Interest: Funding for this project was provided to Dr. Alessi from Sepracor Inc., Marlborough, Massachusetts. The authors have no other potential conflicts of interest to disclose. This study was supported by National Institutes of Health (NIH), National Institute on Aging Grant K23 AG028452 and National Institute of Mental Health Grant T32 MH 019925-11; the University of California at Los Angeles (UCLA) Academic Senate Council on Research; the Veterans Affairs (VA) Greater Los Angeles Healthcare System, Geriatric Research, Education and Clinical Center; VA Health Services Research and Development (IIR 04-321-2); and the UCLA Cousins Center for Psychoneuroimmunology.; Author Contributions: Dr. Martin: study design, analysis and interpretation of data, and preparation of the manuscript. Dr. Fiorentino, Ms. Jouldjian, and Ms. Josephson: analysis and interpretation of data and preparation of the manuscript. Dr. Alessi: study concept and design, analysis and interpretation of data, and preparation of the manuscript.; Sponsor's Role: The study sponsors had no input into the design, implementation, analysis, or interpretation of this study. NR 47 TC 17 Z9 17 U1 4 U2 15 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAY PY 2010 VL 58 IS 5 BP 829 EP 836 DI 10.1111/j.1532-5415.2010.02815.x PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 592XE UT WOS:000277414400005 PM 20722819 ER PT J AU Burgio, KL Johnson, TM Goode, PS Markland, AD Richter, HE Roth, DL Sawyer, P Allman, RM AF Burgio, Kathryn L. Johnson, Theodore M., II Goode, Patricia S. Markland, Alayne D. Richter, Holly E. Roth, David L. Sawyer, Patricia Allman, Richard M. TI Prevalence and Correlates of Nocturia in Community-Dwelling Older Adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE nocturia; urination; epidemiology; prevalence; risk factors ID URINARY-TRACT SYMPTOMS; DANISH POPULATION; BACH SURVEY; RISK-FACTOR; WOMEN; SLEEP; MEN; ASSOCIATION; FINLAND; DISEASE AB OBJECTIVES To determine the prevalence and correlates of nocturia in community-dwelling older adults. DESIGN Planned secondary analysis of cross-sectional data from the University of Alabama at Birmingham Study of Aging population-based survey. SETTING Participants' homes. PARTICIPANTS One thousand older adults (aged 65-106) recruited from Medicare beneficiary lists between 1999 and 2001. The sample was selected to include 25% each African-American women, African-American men, white women, and white men. MEASUREMENTS In-person interviews included sociodemographic information, medical history, Mini-Mental State Examination (MMSE) score, and measurement of body mass index (BMI). Nocturia was defined in the main analyses as rising two or more times per night to void. RESULTS Nocturia was more common in men than women (63.2% vs 53.8%, odds ratio (OR)=1.48, 95% confidence interval (CI)=1.15-1.91, P=.003) and more common in African Americans than whites (66.3% vs 50.9%, OR=1.89, 95% CI=1.46-2.45, P <.001). In multiple backward elimination regression analysis in men, nocturia was significantly associated with African-American race (OR=1.54) and BMI (OR=1.22 per 5 kg/m2). Higher MMSE score was protective (OR=0.96). In women, nocturia was associated with older age (OR=1.21 per 5 years), African-American race (OR=1.64), history of any urine leakage (OR=2.17), swelling in feet and legs (OR=1.67), and hypertension (OR=1.62). Higher education was protective (OR=0.92). CONCLUSION Nocturia in community-dwelling older adults is a common symptom associated with male sex, African-American race, and some medical conditions. Given the significant morbidity associated with nocturia, any evaluation of lower urinary tract symptoms should include assessment for the presence of nocturia. C1 [Burgio, Kathryn L.; Johnson, Theodore M., II; Goode, Patricia S.; Markland, Alayne D.; Roth, David L.; Allman, Richard M.] Birmingham Atlanta Geriatr Res Educ & Clin Ctr, Dept Vet Affairs, Birmingham, AL USA. [Burgio, Kathryn L.; Goode, Patricia S.; Markland, Alayne D.; Sawyer, Patricia; Allman, Richard M.] Univ Alabama, Sch Med, Dept Med, Birmingham, AL USA. [Richter, Holly E.] Univ Alabama, Sch Med, Dept Surg, Birmingham, AL USA. [Burgio, Kathryn L.; Goode, Patricia S.; Markland, Alayne D.; Richter, Holly E.; Roth, David L.; Sawyer, Patricia; Allman, Richard M.] Univ Alabama, Ctr Aging, Sch Publ Hlth, Birmingham, AL USA. [Roth, David L.] Univ Alabama, Dept Biostat, Sch Publ Hlth, Birmingham, AL USA. [Johnson, Theodore M., II; Roth, David L.] Emory Univ, Sch Med, Dept Med, Atlanta, GA USA. RP Burgio, KL (reprint author), Birmingham VA Med Ctr, GRECC 11G,700 S 19th St, Birmingham, AL 35294 USA. EM kburgio@uab.edu OI Markland, Alayne/0000-0002-6567-6744 FU National Institute on Aging; Birmingham/Atlanta Geriatric Research, Education and Clinical Center, Department of Veterans Affairs, Birmingham, Alabama FX Conflict of Interest: Because the present manuscript describes an epidemiological study, we do not believe that any of the financial relationships listed here represent a conflict of interest.; This project was funded by grants from the National Institute on Aging, including the Resource Center on Minority Aging Research and the Birmingham/Atlanta Geriatric Research, Education and Clinical Center, Department of Veterans Affairs, Birmingham, Alabama.; Kathryn L. Burgio: Pfizer (consultant and co-investigator on a behavioral trial, research grant), Astellas (Pelvic Floor Advisory Board), Johnson & Johnson (consultant). Theodore M. Johnson: Johnson & Johnson (consultant), Pfizer (consultant, research grant), Ferring (consultant), Astellas (adviser to a mentee with an investigator-initiated grant). Patricia S. Goode: Pfizer (research grant). Holly E. Richter: Astellas (research grant), Pfizer (research grant).; Author Contributions: All individuals who contributed significantly are listed as authors. All authors approved the final version for submission. Kathryn L. Burgio, Theodore M. Johnson, Patricia S. Goode, and Alayne D. Markland: conception and design, analysis and interpretation of data, drafting article. Holly E. Richter and David L. Roth: Conception and design, analysis and interpretation of data, critical revision. Patricia Sawyer and Richard M. Allman: Acquisition of data, analysis and interpretation of data, critical revision.; Sponsor's Role: The sponsor was not involved in the design, methods, subject recruitment, data collection, data analysis, or preparation of the manuscript. NR 35 TC 33 Z9 36 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAY PY 2010 VL 58 IS 5 BP 861 EP 866 DI 10.1111/j.1532-5415.2010.02822.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 592XE UT WOS:000277414400009 PM 20406317 ER PT J AU Yaffe, K Lindquist, K Vittinghoff, E Barnes, D Simonsick, EM Newman, A Satterfield, S Rosano, C Rubin, SM Ayonayon, HN Harris, T AF Yaffe, Kristine Lindquist, Karla Vittinghoff, Eric Barnes, Deborah Simonsick, Eleanor M. Newman, Anne Satterfield, Suzanne Rosano, Caterina Rubin, Susan M. Ayonayon, Hilsa N. Harris, Tamara CA Hlth Aging & Body Compsition Study TI The Effect of Maintaining Cognition on Risk of Disability and Death SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE cognition; cognitive maintenance; mortality; disability ID INDIVIDUAL-DIFFERENCES; OLDER-ADULTS; DECLINE; IMPAIRMENT; AGE; DEMENTIA; TRAJECTORIES; PERFORMANCE; MORTALITY; RATS AB OBJECTIVES To determine whether long-term maintenance of cognition is associated with health advantages such as lower mortality or incident disability in older adults. DESIGN Longitudinal cohort study. SETTING Community clinics at two sites. PARTICIPANTS Two thousand seven hundred thirty-three adults with a mean age of 74 at baseline and 80 at follow-up. MEASUREMENTS Cognitive function was assessed using the Modified Mini-Mental State Examination (3MS), a test of global cognition, at least two times. Three cognitive groups were defined based on 4-year participant-specific slopes (maintainers, slopes of >= 0; minor decliners, slopes < 0 but no more than 1 standard deviation (SD) below the mean; major decliners, slopes > 1 SD below the mean). Whether the cognitive groups differed in mortality and incident disability during the subsequent 3 years was determined. RESULTS Nine hundred eighty-four (36%) participants were maintainers, 1,314 (48%) were minor decliners, and 435 (16%) were major decliners. Maintainers had lower mortality (7% vs 14%, hazard ratio (HR)=0.48, 95% confidence interval (CI)=0.36-0.63) and incident disability (22% vs 29%, HR=0.74, 95% CI=0.62-0.89) than minor decliners. After adjustment for age, race, sex, education, apolipoprotein E epsilon 4, depression, body mass index, stroke, hypertension, and diabetes mellitus, these differences remained. As expected, major decliners had greater mortality (20%) and incident disability (40%) than minor decliners. CONCLUSION A substantial proportion of older adults maintain cognitive function in their eighth and ninth decades of life. These older adults demonstrate lower risk of death and functional decline than those with minor cognitive decline, supporting the concept of "successful" cognitive aging. C1 [Yaffe, Kristine; Barnes, Deborah] Univ Calif San Francisco, Dept Psychiat, Sch Med, San Francisco, CA 94121 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, Sch Med, San Francisco, CA 94121 USA. [Yaffe, Kristine; Vittinghoff, Eric; Rubin, Susan M.; Ayonayon, Hilsa N.] Univ Calif San Francisco, Dept Epidemiol & Biostat, Sch Med, San Francisco, CA 94121 USA. [Lindquist, Karla] Univ Calif San Francisco, Dept Med, Sch Med, San Francisco, CA 94121 USA. [Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. [Simonsick, Eleanor M.] NIA, Intramural Res Program, Baltimore, MD 21224 USA. [Newman, Anne; Rosano, Caterina] Univ Pittsburgh, Dept Med, Div Geriatr Med, Pittsburgh, PA USA. [Satterfield, Suzanne] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. [Harris, Tamara] NIA, Dept Epidemiol, Demog & Biometry Program, Bethesda, MD 20892 USA. RP Yaffe, K (reprint author), Univ Calif San Francisco, Dept Psychiat, Sch Med, Box 181,4150 Clement St, San Francisco, CA 94121 USA. EM kristine.yaffe@ucsf.edu RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU National Institutes of Health, National Institute on Aging; [AG-6-2101]; [AG-6-2103]; [AG-6-2106]; [AG021918]; [AG031155] FX Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper.; Funded by Grants AG-6-2101, AG-6-2103, AG-6-2106, and AG021918. This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute on Aging. Dr. Yaffe was supported in part by AG031155 and an anonymous foundation.; Author Contributions: Study concept and design: KY, KL, EV, DB. Acquisition of subjects and data: ES, AN, SS, SR, HA, TH. Analysis and interpretation of data: KY, KL, EV, DB, ES, AN, SS, CR, SR, HA, TH. Preparation of manuscript: KY, KL, EV, DB, ES, AN, SS, CR, SR, HA, TH).; Sponsor's Role: The National Institute on Aging played a role in overseeing study performance and data collection. NR 24 TC 33 Z9 33 U1 1 U2 5 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAY PY 2010 VL 58 IS 5 BP 889 EP 894 DI 10.1111/j.1532-5415.2010.02818.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 592XE UT WOS:000277414400013 PM 20406308 ER PT J AU Norton, MC Smith, KR Ostbye, T Tschanz, JT Corcoran, C Schwartz, S Piercy, KW Rabins, PV Steffens, DC Skoog, I Breitner, JCS Welsh-Bohmer, KA AF Norton, Maria C. Smith, Ken R. Ostbye, Truls Tschanz, JoAnn T. Corcoran, Chris Schwartz, Sarah Piercy, Kathleen W. Rabins, Peter V. Steffens, David C. Skoog, Ingmar Breitner, John C. S. Welsh-Bohmer, Kathleen A. CA Cache Cty Investigators TI Greater Risk of Dementia When Spouse Has Dementia? The Cache County Study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE dementia; caregiving; stress ID COGNITIVE DECLINE; PHYSICAL HEALTH; CAREGIVERS; STRESS; QUESTIONNAIRE; METAANALYSIS; PREVALENCE; DEPRESSION; IMPACT AB OBJECTIVES To examine the effects of caring for a spouse with dementia on the caregiver's risk for incident dementia. DESIGN Population-based study of incident dementia in spouses of persons with dementia. SETTING Rural county in northern Utah. PARTICIPANTS Two thousand four hundred forty-two subjects (1,221 married couples) aged 65 and older. MEASUREMENTS Incident dementia was diagnosed in 255 subjects, with onset defined as age when subject met Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised, criteria for dementia. Cox proportional hazards regression tested the effect of time-dependent exposure to dementia in one's spouse, adjusted for potential confounders. RESULTS A subject whose spouse experienced incident dementia onset had a six times greater risk for incident dementia as subjects whose spouses were dementia free (hazard rate ratio (HRR)=6.0, 95% confidence interval (CI)=2.2-16.2, P <.001). In sex-specific analyses, husbands had higher risks (HRR=11.9, 95% CI=1.7-85.5, P=.01) than wives (HRR=3.7, 95% CI=1.2-11.6, P=.03). CONCLUSION The chronic and often severe stress associated with dementia caregiving may exert substantial risk for the development of dementia in spouse caregivers. Additional (not mutually exclusive) explanations for findings are discussed. C1 [Norton, Maria C.; Piercy, Kathleen W.] Univ Utah, Dept Family Consumer & Human Dev, Salt Lake City, UT USA. [Norton, Maria C.; Tschanz, JoAnn T.] Univ Utah, Dept Psychol, Salt Lake City, UT USA. [Norton, Maria C.; Tschanz, JoAnn T.; Corcoran, Chris; Schwartz, Sarah; Piercy, Kathleen W.] Univ Utah, Ctr Epidemiol Studies, Salt Lake City, UT USA. [Smith, Ken R.] Univ Utah, Dept Family & Consumer Studies, Salt Lake City, UT USA. [Smith, Ken R.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [Ostbye, Truls] Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27710 USA. [Ostbye, Truls; Welsh-Bohmer, Kathleen A.] Duke Univ, Med Ctr, Joseph & Kathleen Bryan Alzheimers Dis Res Ctr, Durham, NC 27710 USA. [Ostbye, Truls] Duke NUS Grad Med Sch, Singapore, Singapore. [Corcoran, Chris; Schwartz, Sarah] Utah State Univ, Dept Math & Stat, Logan, UT 84322 USA. [Rabins, Peter V.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Steffens, David C.] Univ Gothenburg, Dept Psychiat & Behav Sci, Gothenburg, Sweden. [Skoog, Ingmar] Univ Gothenburg, Inst Neurosci & Physiol, Sect Psychiat & Neurochem, Unit Neuropsychiat Epidemiol, Gothenburg, Sweden. [Breitner, John C. S.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Breitner, John C. S.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Norton, MC (reprint author), Utah State Univ, Cache Cty Memory Study, 4440 Old Main Hill, Logan, UT 84322 USA. EM maria.norton@usu.edu RI Corcoran, Chris/F-2155-2010; piercy, kathleen/F-4808-2010; Tschanz, JoAnn/E-5986-2010; Norton, Maria/E-6994-2013; Schwartz, Sarah/E-2050-2016 OI Schwartz, Sarah/0000-0001-9980-7493 FU National Institutes of Health [AG-031272, AG-011380, AG-021136] FX Dr. Welsh-Bohmer and Dr. Breitner developed the neuropsychological testing and clinical assessment procedures. Dr. Tschanz provided training and oversight of all field staff and reviewed all individual neuropsychological test results to render professional diagnoses. The board-certified or board-eligible geriatric psychiatrists or neurologists who examined the study members included Drs. Steinberg, Breitner, Steffens, Lyketsos, Gagliardi, Raj, Christopher, and Green. Dr. Williams also examined several subjects and provided expert neurologic consultation. Dr. Townsend conducted autopsy examinations. Ms. Leslie coordinated the autopsy enrollment program. Diagnosticians at the expert consensus conferences included Drs. Breitner, Burke, Lyketsos, Plassman, Steffens, Steinberg, Toohill, Tschanz, and Welsh-Bohmer. We acknowledge the additional contributions of the following individuals whose activities have helped to ensure the success of the project: Cara Brewer, BA, Tony Calvert, BSC, Carol Leslie, MS, Georgiann Sanborn, MS, Michelle McCart, Heidi Wengreen, PhD, RD, James Wyatt, and Peter P. Zandi, PhD, MPH, Roxane Pfister, MS, Nancy Sassano, PhD.; Conflict of Interest: None of the authors has any financial or personal conflicts of interest, or relationships and affiliations relevant to the subject of this manuscript. This work was supported by National Institutes of Health Grants AG-031272, AG-011380, and AG-021136.; Author Contributions: Dr. Norton had full access to all the data and takes responsibility for data integrity and accuracy of the data analysis. Dr. Norton and Dr. Tschanz: obtaining funding; conception and design; acquisition, analysis, and interpretation of data; preparation of manuscript. Dr. Smith, Dr. circle divide stbye, and Dr. Corcoran: conception and design, analysis and interpretation of data, preparation of manuscript. Ms. Schwartz: data file creation and statistical analysis, preparation of manuscript. Dr. Piercy, Dr. Rabins, Dr. Skoog: conception and design, preparation of manuscript. Dr. Steffens: conception and design, acquisition of data, preparation of manuscript. Dr. Breitner and Dr. Welsh-Bohmer: obtaining funding, acquisition of the data, preparation of manuscript.; Sponsor's Role: Provision of funding to support data collection, analysis, interpretation, and manuscript preparation. NR 30 TC 32 Z9 32 U1 0 U2 11 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAY PY 2010 VL 58 IS 5 BP 895 EP 900 DI 10.1111/j.1532-5415.2010.02806.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 592XE UT WOS:000277414400014 PM 20722820 ER PT J AU Dzierzewski, JM Williams, JM Roditi, D Marsiske, M Mccoy, K McNamara, J Dautovich, N Robinson, ME McCrae, CS AF Dzierzewski, Joseph M. Williams, Jacob M. Roditi, Daniela Marsiske, Michael McCoy, Karin McNamara, Joseph Dautovich, Natalie Robinson, Michael E. McCrae, Christina S. TI Daily Variations in Objective Nighttime Sleep and Subjective Morning Pain in Older Adults with Insomnia: Evidence of Covariation over Time SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE sleep; pain; older adults; multilevel modeling; daily associations ID MINI-MENTAL-STATE; DEPRESSION; HEALTH; METAANALYSIS; COMPLAINTS; INTENSITY; THERAPY; TRIALS AB OBJECTIVES To examine the relationship between objectively measured nocturnal sleep and subjective report of morning pain in older adults with insomnia; to examine not only the difference between persons in the association between sleep and pain (mean level over 14 days), but also the within-person, day-to-day association. DESIGN Cross-sectional. SETTING North-central Florida. PARTICIPANTS Fifty community-dwelling older adults (mean age +/- standard deviation 69.1 +/- 7.0, range 60-90) with insomnia. MEASUREMENTS Daily home-based assessment using nightly actigraphic measurement of sleep and daily self-report of pain over 14 consecutive days. RESULTS Between persons, average sleep over 14 days was not associated with average levels of rated pain, but after a night in which an older adult with insomnia experienced above-average total sleep time he or she subsequently reported below-average pain ratings. The model explained approximately 24% of the within-person and 8% of the between-person variance in pain ratings. CONCLUSIONS Sleep and pain show day-to-day associations (i.e., covary over time) in older adults with insomnia. Such associations may suggest that common physiological systems underlie the experience of insomnia and pain. Future research should examine the crossover effects of sleep treatment on pain and of pain treatment on sleep. C1 [Dzierzewski, Joseph M.; Williams, Jacob M.; Roditi, Daniela; Marsiske, Michael; Robinson, Michael E.; McCrae, Christina S.] Univ Florida, Dept Clin & Hlth Psychol, Gainesville, FL 32610 USA. [McNamara, Joseph] Univ Florida, Dept Psychiat, Gainesville, FL 32610 USA. [Dautovich, Natalie] Univ Florida, Dept Psychol, Gainesville, FL 32610 USA. [McCoy, Karin] Univ Texas Hlth Sci Ctr San Antonio, Psychol Serv, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [McCoy, Karin] Univ Texas Hlth Sci Ctr San Antonio, Dept Neurosurg, San Antonio, TX 78229 USA. RP McCrae, CS (reprint author), Univ Florida, Dept Clin & Hlth Psychol, POB 100165 HSC,101 S Newell Dr, Gainesville, FL 32610 USA. EM csmccrae@phhp.ufl.edu OI Marsiske, Michael/0000-0001-5973-2116; McCrae, Christina/0000-0003-4313-6867 FU National Institutes of Health, National Institute on Aging [AG0244591]; National Institute on Aging [F31-AG-032802, T32-AG-020499] FX Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper.; This study was supported by the National Institutes of Health, National Institute on Aging (AG0244591; McCrae-PI). Joseph M. Dzierzewski was supported by an Institutional Training Grant (T32-AG-020499) awarded to the University of Florida and by an Individual Training Grant (F31-AG-032802), both awarded by the National Institute on Aging.; Author Contributions: Joseph M. Dzierzewski: conceptualization, acquisition of subjects and data, analysis and interpretation of data, and preparation of manuscript. Jacob M. Williams and Daniela Roditi: conceptualization, interpretation of data, and preparation of manuscript. Michael Marsiske: study design, acquisition of subjects, critical review and feedback, and interpretation of data. Karin McCoy: study design, critical review and feedback. Joseph McNamara and Natalie Dautovich: acquisition of subjects and data, critical review and feedback. Michael E. Robinson: interpretation of data, critical review and feedback. Christina S. McCrae: study design, acquisition of subjects and data, interpretation of data, critical review and feedback.; Sponsor's Role: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute on Aging or the National Institutes of Health, nor was either funding institution responsible for the design, methods, subject recruitment, data collection, analysis, or preparation of manuscript. NR 30 TC 12 Z9 12 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAY PY 2010 VL 58 IS 5 BP 925 EP 930 DI 10.1111/j.1532-5415.2010.02803.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 592XE UT WOS:000277414400019 PM 20406316 ER PT J AU Shah, F Burack, O Boockvar, KS AF Shah, Faraaz Burack, Orah Boockvar, Kenneth S. TI Perceived Barriers to Communication Between Hospital and Nursing Home at Time of Patient Transfer SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Article DE Communication barriers; nursing homes; hospitals; patient transfer ID TRANSITIONAL CARE; SAFETY CULTURE; QUALITY; RESIDENTS; EMERGENCY; OUTCOMES AB Objectives: To identify perceived barriers to communication between hospital and nursing home at the time of patient transfer and examine associations between perceived barriers and hospital and nursing home characteristics. Design: Mailed survey. Setting: Medicare- or Medicaid-certified nursing homes in New York State. Participants: Nursing home administrators, with input from other nursing home staff. Measurements: Respondents rated the importance as a barrier to hospital-nursing home communication of (1) hospital providers' attitude, time, effort, training, payment, and familiarity with nursing home patients; (2) unplanned and off-hours transfers; (3) HIPAA privacy regulations; and (4) lost or failed information transmission. Associations were determined between barriers and the following organizational characteristics: (1) hospital-nursing home affiliations, pharmacy or laboratory agreements, cross-site staff visits, and cross-site physician care; (2) hospital size, teaching status, and frequency of geriatrics specialty care; (3) nursing home size, location, type, staffing, and Medicare quality indicators; and (4) hospital-to-nursing home communication, consistency of hospital care with health care goals, and communication quality improvement efforts. Results: Of 647 questionnaires sent, 229 were returned (35.4%). The most frequently reported perceived barriers to communication were sudden or unplanned transfers (44.4%), transfers that occur at night or on the weekend (41.4%), and hospital providers' lack of effort (51.0%), lack of familiarity with patients (45.0%), and lack of time (43.5%). Increased hospital size, teaching hospitals, and urban nursing home location were associated with greater perceived importance of these barriers, and cross-site staff visits and hospital provision of laboratory and pharmacy services to the nursing home were associated with lower perceived importance of these barriers. Conclusions: Hospital and nursing home characteristics and interorganizational relationships were associated with nursing home administrators' perceptions of barriers to hospital-nursing home communication. These findings may inform design and targeting of interventions to improve intersite communication processes. (J Am Med Dir Assoc 2010; 11: 239-245) C1 [Boockvar, Kenneth S.] James J Peters VA Med Ctr, Bronx, NY 10468 USA. [Shah, Faraaz] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Burack, Orah; Boockvar, Kenneth S.] Jewish Home Lifecare, New York, NY USA. [Boockvar, Kenneth S.] Mt Sinai Sch Med, New York, NY USA. RP Boockvar, KS (reprint author), James J Peters VA Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM kenneth.boockvar@mssm.edu OI Boockvar, Kenneth/0000-0003-1165-5558 FU Mount Sinai School of Medicine; Pfizer/Foundation for Health in Aging; New York State Department of Health; VA Health Services Research and Development Service FX Financial support was provided by a Mount Sinai School of Medicine Summer Research Fellowship (F.S.), a Pfizer/Foundation for Health in Aging Junior Faculty Scholarship for Research on Health Outcomes in Geriatrics (K.S.B.), and the New York State Department of Health. K.S.B. is currently a Research Career Development Awardee from the VA Health Services Research and Development Service. NR 21 TC 13 Z9 13 U1 2 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 MAY PY 2010 VL 11 IS 4 BP 239 EP 245 DI 10.1016/j.jamda.2009.08.006 PG 7 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 600ZX UT WOS:000278028800004 PM 20439042 ER PT J AU Almendral, JL Shick, V Rosendorff, C Atlas, SA AF Almendral, Jesus L. Shick, Vladislav Rosendorff, Clive Atlas, Steven A. TI Association between transforming growth factor-beta(1) and left ventricular mass and diameter in hypertensive patients SO JOURNAL OF THE AMERICAN SOCIETY OF HYPERTENSION LA English DT Article DE Echocardiography; growth factors; left ventricular hypertrophy; renin-angiotensin-aldosterone system ID FACTOR-BETA; ANGIOTENSIN-II; BLOOD-PRESSURE; CARDIAC FIBROSIS; HYPERTROPHY; EXPRESSION; HEART; TGF-BETA-1; CARDIOMYOCYTES; MECHANISMS AB Angiotensin II influences development of left ventricular hypertrophy (LVH) by stimulating cardiomyocyte hypertrophy, fibroblast proliferation, and collagen synthesis. Because pro-fibrotic actions of angiotensin may be mediated by increased production of transforming growth factor-beta(1) (TGF-beta(1)), we assessed whether serum TGF-beta(1) levels might reflect involvement in LVH development. We analyzed relationships between left ventricular mass and levels of renin, aldosterone, and TGF-beta(1) in 67 hypertensive subjects (mean age 64 +/- 11.3 years) with electrocardiographic evidence of LVH. Levels were obtained after a 2-week washout of antihypertensive medications; two-dimensional echocardiography was subsequently performed. Linear regression analysis showed a correlation between TGF-beta(1) and LV mass (r = 0.36, P = .002). This was apparently explained by the correlation between TGF-beta(1), and left ventricular diastolic internal diameter (r = 0.42, P < .001), because no correlation between TGF-beta(1) levels and LV wall thickness was found. In multivariate analysis, the correlation between TGF-beta(1) and internal diameter remained significant (r = 0.39, P = .0014). There were no racial differences in levels of TGF-beta(1), or left ventricular geometry, and no correlations between age, blood pressure, renin, aldosterone, and left ventricular mass or dimensions. These findings indicate that serum TGF-beta(1) levels are related to left ventricular structure in hypertensive subjects, suggesting its possible involvement in the process of hypertensive left ventricular remodeling. J Am Soc Hypertens 2010;4(3):135-141. Published by Elsevier Inc on behalf of American Society of Hypertension. C1 James J Peters Dept Vet Affairs Med Ctr, Bronx, NY USA. Mt Sinai Sch Med, New York, NY USA. RP Atlas, SA (reprint author), James J Peters VA Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Steven.Atlas@va.gov FU Sankyo Pharma, Inc.; Department of Veterans Affairs FX Supported by a grant from Sankyo Pharma, Inc., and by general research support from the Department of Veterans Affairs. NR 30 TC 12 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1933-1711 J9 J AM SOC HYPERTENS JI J. Am. Soc. Hypertens. PD MAY-JUN PY 2010 VL 4 IS 3 BP 135 EP 141 DI 10.1016/j.jash.2010.02.007 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 602CG UT WOS:000278115200005 PM 20470998 ER PT J AU Burstein, HJ AF Burstein, Harold J. TI Re-engineering the Cooperative Groups 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 0 TC 0 Z9 0 U1 0 U2 0 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD MAY PY 2010 VL 8 IS 5 BP 505 EP 505 PG 1 WC Oncology SC Oncology GA 615ZO UT WOS:000279177500001 PM 20495080 ER PT J AU Tuttle, RM Ball, DW Byrd, D Daniels, GH Dilawari, RA Doherty, GM Duh, QY Ehya, H Farrar, WB Haddad, RI Kandeel, F Kloos, RT Kopp, P Lamonica, DM Loree, TR Lydiatt, WM McCaffrey, J Olson, JA Parks, L Ridge, JA Shah, JP Sherman, SI Sturgeon, C Waguespack, SG Wang, TN Wirth, LJ AF Tuttle, R. Michael Ball, Douglas W. Byrd, David Daniels, Gilbert H. Dilawari, Raza A. Doherty, Gerard M. Duh, Quan-Yang Ehya, Hormoz Farrar, William B. Haddad, Robert I. Kandeel, Fouad Kloos, Richard T. Kopp, Peter Lamonica, Dominick M. Loree, Thom R. Lydiatt, William M. McCaffrey, Judith Olson, John A., Jr. Parks, Lee Ridge, John A. Shah, Jatin P. Sherman, Steven I. Sturgeon, Cord Waguespack, Steven G. Wang, Thomas N. Wirth, Lori J. CA NCCN Medullary Carcinoma TI Medullary Carcinoma Clinical Practice Guidelines in Oncology (TM) SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review DE NCCN Clinical Practice Guidelines; thyroid gland; cancer; malignancy; tumor; medullary thyroid cancer; thyroidectomy; external beam irradiation; radiation therapy ID NEOPLASIA TYPE 2A; DIFFERENTIATED THYROID-CANCER; RET PROTOONCOGENE MUTATIONS; SERUM CALCITONIN; ROUTINE MEASUREMENT; PROGNOSTIC-FACTORS; PROPHYLACTIC THYROIDECTOMY; CARCINOEMBRYONIC-ANTIGEN; MANAGEMENT GUIDELINES; MULTIVARIATE-ANALYSIS C1 [Tuttle, R. Michael] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Byrd, David] Univ Washington, Seattle, WA 98195 USA. [Daniels, Gilbert H.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Dilawari, Raza A.] Univ Tennessee, Inst Canc, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Doherty, Gerard M.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Farrar, William B.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Haddad, Robert I.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Kopp, Peter] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Lamonica, Dominick M.] Roswell Pk Canc Inst, Roswell, GA USA. [Lydiatt, William M.] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. [McCaffrey, Judith] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Olson, John A., Jr.] Duke Comprehens Canc Ctr, Durham, NC USA. [Parks, Lee] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Shah, Jatin P.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Sherman, Steven I.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Wang, Thomas N.] Univ Alabama Birmingham, Birmingham, AL USA. RP Tuttle, RM (reprint author), Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 85 TC 25 Z9 27 U1 0 U2 0 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD MAY PY 2010 VL 8 IS 5 BP 512 EP 530 PG 19 WC Oncology SC Oncology GA 615ZO UT WOS:000279177500003 PM 20495082 ER PT J AU Hartman, ML Esposito, JM Yeap, BY Sugarbaker, DJ AF Hartman, Mor-Li Esposito, John Matthew Yeap, Beow Yong Sugarbaker, David John TI Combined treatment with cisplatin and sirolimus to enhance cell death in human mesothelioma SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID MALIGNANT-PLEURAL-MESOTHELIOMA; INDUCED APOPTOSIS; MAMMALIAN TARGET; PHASE-III; CANCER; RAPAMYCIN; THERAPY; INVITRO; AKT; CHEMOSENSITIVITY AB Objective: Although platinum-based chemotherapy is widely used in malignant pleural mesothelioma, its modest therapeutic effect warrants identification of enhancing agents. As with many cancers, the phosphatidylinositol 3-kinase/Akt pathway is often activated in malignant pleural mesothelioma and has been implicated in the tumor's aggressiveness. Sirolimus is a well-established inhibitor of the mammalian target of rapamycin. We sought to determine whether combination treatment with sirolimus and cisplatin would enhance cell death in malignant pleural mesothelioma. Methods: Human malignant pleural mesothelioma cell lines were incubated with sirolimus or cisplatin alone or in combination and assayed for cell viability. To characterize phosphorylation status after treatment, Akt and downstream proteins of mammalian target of rapamycin pathway, p70 S6 kinase and 4E-BP1, were analyzed by Western blot. Effect of combination treatment was also analyzed with extreme drug resistance assay in 12 human malignant pleural mesothelioma tumors with varying resistance to cisplatin. Results: Individual malignant pleural mesothelioma cell lines exhibited a range of sensitivities to each drug without correlation with subtype. Sirolimus and cisplatin significantly (P = .029) increased cell death versus either drug alone in 4 cell lines. Combined treatment caused dephosphorylation of Akt, 4E-BP1, and p70 S6 kinase. Cell proliferation was significantly decreased in tumors subjected to sirolimus and cisplatin versus cisplatin or sirolimus alone. Conclusions: Sirolimus appears to enhance the cytotoxicity of cisplatin in malignant pleural mesothelioma cell lines through the mammalian target of rapamycin pathway. These results provide a basis for the clinical evaluation of combined sirolimus and cisplatin chemotherapy in malignant pleural mesothelioma. (J Thorac Cardiovasc Surg 2010; 139: 1233-40) C1 [Hartman, Mor-Li; Esposito, John Matthew; Sugarbaker, David John] Harvard Univ, Brigham & Womens Hosp, Sch Med, Novel Therapeut Lab,Div Thorac Surg, Boston, MA 02115 USA. [Yeap, Beow Yong] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hematol Oncol Unit,Dept Med, Boston, MA 02115 USA. RP Sugarbaker, DJ (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Novel Therapeut Lab,Div Thorac Surg, 75 Francis St, Boston, MA 02115 USA. EM dsugarbaker@partners.org FU International Mesothelioma Program, Brigham; Women's Hospital, Boston, Mass FX Supported by the International Mesothelioma Program, Brigham and Women's Hospital, Boston, Mass. NR 25 TC 16 Z9 16 U1 2 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD MAY PY 2010 VL 139 IS 5 BP 1233 EP 1240 DI 10.1016/j.jtcvs.2009.06.027 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 586VZ UT WOS:000276944300020 PM 19853261 ER PT J AU Nehra, D Vagefi, PA Chang, H Louissaint, A Mino-Kenudson, M Ryan, DP AF Nehra, Deepika Vagefi, Parsia A. Chang, Henry Louissaint, Abner Mino-Kenudson, Mari Ryan, Daniel P. TI Clear cell sugar tumor of the lung masquerading as tuberculosis in a pediatric patient SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article C1 [Nehra, Deepika; Vagefi, Parsia A.; Chang, Henry; Ryan, Daniel P.] Massachusetts Gen Hosp, Div Pediat Surg, Boston, MA 02114 USA. [Louissaint, Abner; Mino-Kenudson, Mari] Massachusetts Gen Hosp, Div Pathol, Boston, MA 02114 USA. RP Ryan, DP (reprint author), Massachusetts Gen Hosp, Div Pediat Surg, 55 Fruit St,WRN 1121, Boston, MA 02114 USA. EM dryan@partners.org NR 5 TC 3 Z9 4 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD MAY PY 2010 VL 139 IS 5 BP E108 EP E109 DI 10.1016/j.jtcvs.2009.03.037 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 586VZ UT WOS:000276944300057 PM 19660379 ER PT J AU Abbott, GF AF Abbott, Gerald F. TI Dr Jud Gurney 1954-2010 IN MEMORIAM SO JOURNAL OF THORACIC IMAGING LA English DT Biographical-Item C1 Massachusetts Gen Hosp, Dept Imaging, Boston, MA 02114 USA. RP Abbott, GF (reprint author), Massachusetts Gen Hosp, Dept Imaging, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0883-5993 J9 J THORAC IMAG JI J. Thorac. Imaging PD MAY PY 2010 VL 25 IS 2 BP 98 EP 99 DI 10.1097/RTI.0b013e3181e0f8eb PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 603HO UT WOS:000278199600006 PM 20463529 ER PT J AU Iafrate, J Kwak, E Bang, Y Solomon, B Shaw, A Camidge, DR Ou, SH Maki, R Salgia, R Clark, J AF Iafrate, J. Kwak, E. Bang, Y. Solomon, B. Shaw, A. Camidge, D. R. Ou, S. H. Maki, R. Salgia, R. Clark, J. TI TARGETING ALK-REARRANGED NON-SMALL CELL LUNG CARCINOMA SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Iafrate, J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. [Kwak, E.; Shaw, A.; Clark, J.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Bang, Y.] Seoul Natl Univ Hosp, Seoul 110744, South Korea. [Solomon, B.] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Camidge, D. R.] Univ Colorado, Hlth Sci Ctr, Denver, CO 80202 USA. [Ou, S. H.] UC Irvine, Ctr Med, Chao Family Comprehens Canc Ctr, Orange, CA USA. [Maki, R.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Salgia, R.] Univ Chicago, Chicago, IL 60637 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD MAY PY 2010 VL 5 IS 5 SU 1 BP S20 EP S20 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 590QU UT WOS:000277242900031 ER PT J AU Alam, HB Hashmi, S Frankelstein, RA Shuja, F Fukudome, EY Li, YQ Liu, BL deMoya, M Velmahos, GC AF Alam, Hasan B. Hashmi, Sahar Frankelstein, Robert A. Shuja, Fahad Fukudome, Eugene Y. Li, Yongqing Liu, Baoling deMoya, Marc Velmahos, George C. TI Alterations in Gene Expression After Induction of Profound Hypothermia for the Treatment of Lethal Hemorrhage SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article; Proceedings Paper CT 68th Annual Meeting of the American-Association-for-the-Surgery-of-Trauma (AAST) CY OCT 01-03, 2009 CL Pittsburgh, PA SP Amer Assoc Surg Trauma (AAST) DE Hypothermia; Hemorrhage; Liver; Transcription; Survival; Resuscitation; Preservation; Cell survival; Apoptosis; Metabolism; Genes; Proteins ID MILD THERAPEUTIC HYPOTHERMIA; SWINE MODEL; MODERATE HYPOTHERMIA; CARDIAC-ARREST; CARDIOPULMONARY BYPASS; HEME OXYGENASE-1; OXIDATIVE STRESS; FAMILY PROTEINS; BRAIN-INJURY; APOPTOSIS AB Introduction: We have previously demonstrated that induction of profound hypothermia improves long-term survival in animal models of complex injuries/lethal hemorrhage. However, the precise mechanisms have not been well defined. The aim of this high-throughput study was to investigate the impact of profound hypothermia on gene expression profiles. Methods: Wistar-Kyoto rats underwent 40% blood volume arterial hemorrhage over 10 minutes and were randomized into two groups based on core body temperatures (n = 7 per group): hypothermia (H, 15 degrees C) and normothermia (N, 37 degrees C). Hypothermia was induced by infusing cold isotonic solution using a cardiopulmonary bypass (CPB) setup. After reaching target body temperature, low-flow state (CPB flow rate of 20 mL . kg(-1) . min(-1)) was maintained for 60 minutes. Hypothermic rats were rewarmed to baseline temperature, and all rats were resuscitated on CPB and monitored for 3 hours. The N group underwent identical CPB management. Sham rats (no hemorrhage and no instrumentation) were used as controls. Blood samples were collected serially, and hepatic tissues were harvested after 3 hours. Affymatrix Rat Gene 1.0 ST Array (27,342 genes, >700,000 probes) was used to determine gene expression profiles (n = 3 per group), which were further analyzed using GeneSpring (Agilent Technologies, Santa Clara, CA) and GenePattern (Broad Institute, Cambridge, MA) programs. Data were further queried using network analysis tools including Gene Ontology, and Ingenuity Pathway Analysis (Ingenuity Systems). Key findings were verified using real-time polymerase chain reaction and Western blots. Results: Induction of hypothermia significantly (p < 0.05) decreased the magnitude of lactic acidosis and increased the survival rates (100% vs. 0% in normothermia group). Five hundred seventy-one of 23,000 genes had altered expression in response to the induction of hypothermia: 382 were up-regulated and 187 were down-regulated. Twelve key pathways were specifically modulated by hypothermia. Interleukin-6, interleukin-10, p38 mitogen-activated protein kinase (MAPK), nuclear factor kappa-light-chain-enhancer of activated B cells, glucocorticoids, and other signaling pathways involved with acute phase reactants were up-regulated. Multiple metabolic pathways were down-regulated. The largest change was in the peroxisome proliferator-activated receptor gamma gene that codes for a transcriptional coactivator, which in turn controls mitochondrial biogenesis, glycerolipid, and other metabolic pathways in the liver. Apoptotic cell death cascades were activated in response to blood loss (H and N groups), but multiple specific anti-apoptotic genes (baculoviral Inhibitor of apoptosis protein repeat-containing 3, BCL3L1, NFKB2) displayed an increased expression specifically in the hypothermia treated animals, suggesting an overall pro-survival phenotype. Conclusions: Profound hypothermia increases survival in a rodent model of hemorrhagic shock. In addition to decreasing tissue oxygen consumption, induction of hypothermia directly alters the expression profiles of key genes, with an overall up-regulation of pro-survival pathways and a down-regulation of metabolic pathways. C1 [Alam, Hasan B.; Hashmi, Sahar; Frankelstein, Robert A.; Shuja, Fahad; Fukudome, Eugene Y.; Li, Yongqing; Liu, Baoling; deMoya, Marc; Velmahos, George C.] Harvard Univ, Sch Med, Div Trauma Emergency Surg & Surg Crit Care, Massachusetts Gen Hosp,Dept Surg, Boston, MA 02114 USA. RP Alam, HB (reprint author), Harvard Univ, Sch Med, Div Trauma Emergency Surg & Surg Crit Care, Massachusetts Gen Hosp,Dept Surg, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM hbalam@partners.org NR 56 TC 15 Z9 16 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0022-5282 EI 1529-8809 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD MAY PY 2010 VL 68 IS 5 BP 1084 EP 1098 DI 10.1097/TA.0b013e3181d76bd1 PG 15 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 595MQ UT WOS:000277615200012 PM 20453763 ER PT J AU Cannuscio, CC Weiss, EE Asch, DA AF Cannuscio, Carolyn C. Weiss, Eve E. Asch, David A. TI The Contribution of Urban Foodways to Health Disparities SO JOURNAL OF URBAN HEALTH-BULLETIN OF THE NEW YORK ACADEMY OF MEDICINE LA English DT Article DE Food environment; Foodways; Food deserts; Nutrition; Health disparities; Violence; Segregation; Alcohol; Mental health; Youth; Corner stores; Fast food; Economic exclusion ID NEIGHBORHOOD ALCOHOL ENVIRONMENT; PHYSICAL-ACTIVITY; VEGETABLE CONSUMPTION; BUILT ENVIRONMENT; RETAIL ACCESS; OBESITY; DESERTS; FRUIT; ASSOCIATIONS; STORES AB How do urban food environments produce health disparities? The literature currently emphasizes the etiologic relevance of urban food deserts and their nutritional shortcomings. This paper instead examines the health relevance of foodways-the social dynamics surrounding the production, purchase, and consumption of food. We report on data from 32 photo-elicitation interviews conducted with adult residents of Philadelphia, examining distinct foodways and health concerns that play out in the most commonly discussed retail establishments: corner stores, "Stop and Go's" (delis that also sell beer), and Chinese takeout restaurants. Corner store visits, described as a routinized element of children's school day, were implicated in early life patterning of unsound nutritional choices. Stop and Go's were described as a health threat because of their alcohol sales and tacit promotion of public drunkenness, coupled with accessibility to youth. Stop and Go's and Chinese takeouts both were perceived as generators of violence in part because of on-site sales of alcohol, drug paraphernalia, and illicit drugs. Chinese takeouts also were described as symbolic reminders of African Americans' economic exclusion and as places infused with race/ethnic tension and hostile merchant-customer interactions. Instead of viewing the food environment simply as a source of calories and nutrients, participants discussed the complex social dynamics that play out therein, raising a range of important considerations for (especially disadvantaged) urban residents' safety, physical well-being, and mental health. C1 [Cannuscio, Carolyn C.] Univ Penn, Sch Med, Sect Publ Hlth, Dept Family Med & Community Hlth, Philadelphia, PA 19104 USA. [Cannuscio, Carolyn C.; Asch, David A.] Univ Penn, Sch Med, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Cannuscio, Carolyn C.; Weiss, Eve E.] Univ Penn, Sch Med, Ctr Publ Hlth Initiat, Philadelphia, PA 19104 USA. [Asch, David A.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Asch, David A.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Asch, David A.] Univ Penn, Wharton Sch, Hlth Care Management Dept, Philadelphia, PA 19104 USA. RP Cannuscio, CC (reprint author), Univ Penn, Sch Med, Sect Publ Hlth, Dept Family Med & Community Hlth, Philadelphia, PA 19104 USA. EM carolyncannu@gmail.com OI Asch, David/0000-0002-7970-286X FU Robert Wood Johnson Foundation FX This project was supported by a grant from the Robert Wood Johnson Foundation Health & Society Scholars Program at the University of Pennsylvania. We thank the project's participants and the following staff photographers and research assistants: Nora Becker, Elias Friedman, Hannah Fruchtman, Rachel X. Han, Michelle Holshue, Jeremy Kaplan, Amina Massey, Jeannette Schroeder, Liz Sullivan, Aaron Walker, Ahmed Whitt, and Janet Weiner. We also thank the reviewers for their insightful comments. NR 63 TC 38 Z9 38 U1 3 U2 46 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1099-3460 J9 J URBAN HEALTH JI J. Urban Health PD MAY PY 2010 VL 87 IS 3 BP 381 EP 393 DI 10.1007/s11524-010-9441-9 PG 13 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 596WK UT WOS:000277716000004 PM 20354910 ER PT J AU Reisner, SL Mimiaga, MJ Johnson, CV Bland, S Case, P Safren, SA Mayer, KH AF Reisner, Sari L. Mimiaga, Matthew J. Johnson, Carey V. Bland, Sean Case, Patricia Safren, Steven A. Mayer, Kenneth H. TI What Makes a Respondent-Driven Sampling "Seed" Productive? Example of Finding At-Risk Massachusetts Men Who Have Sex with Men SO JOURNAL OF URBAN HEALTH-BULLETIN OF THE NEW YORK ACADEMY OF MEDICINE LA English DT Article DE MSM; Respondent-driven sampling; Methods; HIV ID HIV BEHAVIORAL SURVEILLANCE; PARTNER NOTIFICATION; HIDDEN POPULATIONS; CAGE QUESTIONNAIRE; UNITED-STATES; DRUG-USERS; PREVENTION; INTERNET; ATTITUDES; MSM AB Several recent studies have sought to elaborate upon the applicability and validity of respondent-driven sampling (RDS) to find hard-to-reach samples in general and men who have sex with men (MSM) in particular. Few published studies have elucidated the characteristics associated with initial RDS participants ("seeds") who successfully recruited others into a study. A total of 74 original seeds were analyzed from four Massachusetts studies conducted between 2006 and 2008 that used RDS to reach high-risk MSM. Seeds were considered "generative" if they recruited two or more subsequent participants and "non-generative" if they recruited zero or one participant. Overall, 34% of seeds were generative. In separate multivariable logistic regression models controlling for age, race, health insurance, HIV status, and the study for which the seed was enrolled, unprotected anal sex in the past 12 months [adjusted odds ratio (AOR) = 6.68; 95% confidence interval (95% CI) = 1.27-35.12; p = 0.03], cocaine use during sex at least monthly during the past 12 months (AOR = 8.81; 95% CI = 1.68-46.27; p = 0.01), and meeting sex partners at social gatherings (AOR = 7.42; 95% CI = 1.58-34.76; p = 0.01) and public cruising areas (AOR = 4.92; 95% CI = 1.27-19.01; p = 0.02) were each significantly associated with increased odds of being a generative seed. These findings have methodological and practical implications for the recruitment of MSM via RDS. Finding ways to identify RDS seeds that are consistently generative may facilitate collecting a sample that is closer to reflecting the MSM who live in all of the communities in a given location or study sample. C1 [Reisner, Sari L.; Mimiaga, Matthew J.; Johnson, Carey V.; Bland, Sean; Case, Patricia; Safren, Steven A.; Mayer, Kenneth H.] Fenway Hlth, Fenway Inst, Boston, MA USA. [Reisner, Sari L.; Mimiaga, Matthew J.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Mimiaga, Matthew J.; Safren, Steven A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Case, Patricia] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Mayer, Kenneth H.] Miriam Hosp, Brown Med Sch, Providence, RI 02906 USA. RP Mimiaga, MJ (reprint author), 1340 Boylston St,8th Floor, Boston, MA 02215 USA. EM mmimiaga@fenwayhealth.org FU National Institute on Drug Abuse (NIDA) [R03DA023393] FX The investigator and staff time on this project was supported in part by grant number R03DA023393 from the National Institute on Drug Abuse (NIDA) (PI: M. Mimiaga). The content is solely the responsibility of the authors and does not necessarily represent the official views of NIDA or the National Institutes of Health. NR 49 TC 11 Z9 11 U1 2 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1099-3460 J9 J URBAN HEALTH JI J. Urban Health PD MAY PY 2010 VL 87 IS 3 BP 467 EP 479 DI 10.1007/s11524-010-9439-3 PG 13 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 596WK UT WOS:000277716000011 PM 20354911 ER PT J AU Hoffman, KE Nguyen, PL Ng, AK D'Amico, AV AF Hoffman, Karen E. Nguyen, Paul L. Ng, Andrea K. D'Amico, Anthony V. TI Prostate Cancer Screening in Men 75 Years Old or Older: An Assessment of Self-Reported Health Status and Life Expectancy SO JOURNAL OF UROLOGY LA English DT Article DE prostatic neoplasms; prostate-specific antigen; early detection of cancer; aged; aged; 80 and over ID RATED HEALTH; MORTALITY; SURVIVAL; TRIAL AB Purpose: Opinions vary regarding the appropriate age at which to stop prostate specific antigen screening. Some groups recommend screening men with a greater than 10-year life expectancy while the United States Preventive Services Task Force recommends against screening men 75 years old or older. In this study we evaluated the influence of health status and life expectancy on prostate specific antigen screening in older men in the United States before the 2008 United States Preventive Services Task Force guidelines. Materials and Methods: The study cohort comprised 718 men age 75 years or older without a history of prostate cancer who responded to the 2005 National Health Interview Survey, representing an estimated 4.47 million noninstitutionalized men in the United States. Life expectancy was estimated from age and self-reported health status. Results: Overall 19% of the men were 85 years old or older and 27% reported fair or poor health. In the previous 2 years 52% had a prostate specific antigen screening test. After adjustment for age, race, education and physician access, men with fair or poor health were less likely to receive prostate specific antigen screening than those with excellent or very good health (adjusted OR 0.51, 95% CI 0.33-0.80, p = 0.003). Overall 42% of the men predicted to live less than 5 years and 65% of those predicted to live more than 10 years reported having recent prostate specific antigen screening. Conclusions: Before the United States Preventive Services Task Force recommendation, health status and life expectancy were used to select older men for prostate specific antigen screening. However, many men expected to live less than 5 years were screened. A strict age cutoff of 75 years reduces over screening but also prohibits screening in healthy older men with a long life expectancy who may benefit from screening. C1 [Hoffman, Karen E.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. [Nguyen, Paul L.; Ng, Andrea K.; D'Amico, Anthony V.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 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 14 Z9 15 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 MAY PY 2010 VL 183 IS 5 BP 1798 EP 1802 DI 10.1016/j.juro.2010.01.002 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 584JJ UT WOS:000276747600044 PM 20299039 ER PT J AU Bergman, J Gore, JL Singer, JS Anger, JT Litwin, MS AF Bergman, Jonathan Gore, John L. Singer, Jennifer S. Anger, Jennifer T. Litwin, Mark S. TI Readability of Health Related Quality of Life Instruments in Urology SO JOURNAL OF UROLOGY LA English DT Article DE urology; reading; comprehension; quality of life; questionnaires ID BENIGN PROSTATIC HYPERPLASIA; URINARY-INCONTINENCE; QUESTIONNAIRE; INFORMATION; VALIDATION; INTERNET; DISEASES; IMPACT; CANCER; MEN AB Purpose: The average American adult reads at a fifth to eighth-grade level, with wide variability, presenting challenges for the assessment of self-reported health related quality of life. We identified the health related quality of life instruments used in patients with urological diseases and evaluated their readability. Materials and Methods: We focused on the most burdensome urological diseases, based on total expenditures in the United States. We then identified disease specific instruments by systematically searching PubMed (R), the Cochrane Database of Systematic Reviews, Googlel (TM), Google Scholar (TM), the Patient Reported Outcome and Quality of Life Instruments Database (Mapi Research Institute, Lyon, France) and Yahoo!(R) for health related quality of life studies in patients with these urological conditions. Where disease specific instruments were lacking, we noted the general health related quality of life measures most commonly used. For each instrument, we calculated the median Flesch-Kincaid grade level, the proportion of questionnaire items below an eighth-grade reading level, the mean Flesch Reading Ease, and the mean number of words per sentence and characters per word, all of which are validated measures of readability. Results: The average +/-SD of the median Flesh-Kincaid reading levels was 6.5 +/- 2.1 (range 1.0 to 12.0). Of the 76 instruments 61 (80%) were at or below an eighth-grade reading level. The mean reading ease was greater than 30 for each of the 76 questionnaires and greater than 60 for 66 (87%). Urinary tract infection, the costliest urological disease, has only 1 disease specific health related quality of life measure. Urolithiasis, the second costliest, has none. Conclusions: The reading level of health related quality of life questionnaires in urology is appropriate for the reading ability of most adults in the United States. However, the most burdensome urological diseases lack disease specific health related quality of life instruments. C1 [Bergman, Jonathan; Gore, John L.; Singer, Jennifer S.; Anger, Jennifer T.; Litwin, Mark S.] Univ Calif Los Angeles, Dept Urol, Los Angeles, CA 90095 USA. [Litwin, Mark S.] Univ Calif Los Angeles, Dept Hlth Serv, Los Angeles, CA 90095 USA. [Litwin, Mark S.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. [Gore, John L.] Univ Calif Los Angeles, Robert Wood Johnson Clin Scholars Program, Los Angeles, CA 90095 USA. [Gore, John L.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Bergman, J (reprint author), Univ Calif Los Angeles, Dept Urol, Box 951738, Los Angeles, CA 90095 USA. EM jbergman@mednet.ucla.edu OI Gore, John/0000-0002-2847-5062 NR 21 TC 15 Z9 15 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAY PY 2010 VL 183 IS 5 BP 1977 EP 1981 DI 10.1016/j.juro.2009.12.107 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 584JJ UT WOS:000276747600131 PM 20303519 ER PT J AU Kasirajan, K Kwolek, CJ Gupta, N Fairman, RM AF Kasirajan, Karthik Kwolek, Christopher J. Gupta, Naren Fairman, Ronald M. TI Incidence of and outcomes after misaligned deployment of the Talent Thoracic Stent Graft System SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID ENDOVASCULAR REPAIR; AORTIC DISSECTION; PLACEMENT; ANEURYSM AB Objective: Various types of device-specific adverse events can occur during deployment of thoracic stent grafts due to the high flow rate and severe aortic angulation that is often encountered in the thoracic aorta. This study assessed the incidence, etiology, and overall effect of misaligned deployment of the Talent Thoracic Stent Graft (TSG) System. Techniques to predict and avoid this complication are discussed. Methods: Data collection included pivotal-trial follow-up, direct surveys of centers inside and outside the United States and principal investigators, a targeted literature search, and review of complaint files. Misaligned deployment was considered to occur when the proximal covered or uncovered stent apices of a thoracic stent graft folded back on itself and remained nonparallel to the wall of the aorta after deployment had been completed. Results: Of about 20,305 deployments to date of the Talent TSG, 24 misaligned deployments were identified for an incidence of 0.1%. Nineteen (79%) events occurred during treatment of degenerative aneurysms or penetrating ulcers, four (17%) during treatment of dissections, and the underlying pathology could not be determined for one patient. The misalignment was noted at the proximal end of the stent graft in 15 patients (63%), and the other 9 events (37%) occurred at the graft overlap junction. Two events were treated intraoperatively, with a second overlapping device placed in one patient and a snare used to reposition the proximal stent in another. Adverse clinical events occurred in three patients and included a persistent type I endoleak, continued false lumen perfusion in a patient with dissection, and delayed retrograde type A dissection in a patient undergoing total arch repair. No intraoperative contrast extravasation or computed tomography evidence of perforation was noted. There were no perioperative deaths or cerebrovascular events, with one report of paraplegia among the 24 patients in this series. Conclusion: Misaligned deployment is an unusual phenomenon that tends to occur in the context of certain well-defined anatomic conditions in the thoracic aorta. To date, most of these events have not led to significant adverse sequelae. However, careful patient selection, periprocedural imaging, and case planning can help to identify anatomies in which misaligned opening is likely to occur, allowing physicians to avoid this complication. (J Vase Surg 2010;51:1096-102.) C1 [Kasirajan, Karthik] Emory Univ, Sch Med, Dept Surg, Atlanta, GA 30322 USA. [Kwolek, Christopher J.] Hosp Univ Penn, Philadelphia, PA 19104 USA. [Fairman, Ronald M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kasirajan, K (reprint author), Emory Univ, Sch Med, Dept Surg, 1365 A Clifton Rd NE, Atlanta, GA 30322 USA. EM karthik.kasirajan@emoryhealthcare.org FU Medtronic; W. L. Gore and Associates; Cook; Bolton; Aptus; Abbott FX Competition of interest: Dr Kasirajan receives research support from Medtronic and W. L. Gore and Associates. Dr Kwolak receives research support from Medtronic, Cook, W.L. Gore and Associates, and Bolton. Dr Fairman is a consultant to Medtronic and receives research support from Medtronic, Cook, Aptus, Boston Scientific, and Abbott. NR 14 TC 7 Z9 7 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD MAY PY 2010 VL 51 IS 5 BP 1096 EP 1101 DI 10.1016/j.jvs.2009.11.071 PG 6 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 590HL UT WOS:000277216000003 PM 20299179 ER PT J AU Narak, J Cox, NR Sanchez, CE Sena-Esteves, M Martin, DR AF Narak, Jill Cox, Nancy R. Sanchez, Carlos E. Sena-Esteves, Miguel Martin, Douglas R. TI DISTRIBUTION OF ADENO-ASSOCIATED VIRUS VECTOR SEROTYPES 1, 9, AND 10 IN THE NORMAL FELINE BRAIN SO JOURNAL OF VETERINARY INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Narak, Jill] Univ Tennessee, Knoxville, TN USA. [Cox, Nancy R.; Martin, Douglas R.] Auburn Univ, Auburn, AL 36849 USA. [Sanchez, Carlos E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sena-Esteves, Miguel] Univ Massachusetts, Worcester, MA 01605 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0891-6640 J9 J VET INTERN MED JI J. Vet. Intern. Med. PD MAY-JUN PY 2010 VL 24 IS 3 MA 233 BP 742 EP 742 PG 1 WC Veterinary Sciences SC Veterinary Sciences GA 592XZ UT WOS:000277416600267 ER PT J AU Morales, HD Abramowitz, L Gertz, J Sowa, J Vogel, A Robert, J AF Morales, Heidi D. Abramowitz, Lara Gertz, Jacqueline Sowa, Jessica Vogel, Ashley Robert, Jacques TI Innate Immune Responses and Permissiveness to Ranavirus Infection of Peritoneal Leukocytes in the Frog Xenopus laevis SO JOURNAL OF VIROLOGY LA English DT Article ID MONOCLONAL-ANTIBODIES; MOLECULAR CHARACTERIZATION; MURINE MACROPHAGES; AMPHIBIAN XENOPUS; MORTALITY EVENTS; NK CELLS; IN-VITRO; VIRUS; EXPRESSION; IDENTIFICATION AB Ranaviruses such as frog virus 3 ([FV3] family Iridoviridae) are increasingly prevalent pathogens that infect reptiles, amphibians, and fish worldwide. Whereas studies in the frog Xenopus laevis have revealed the critical involvement of CD8 T-cell and antibody responses in host resistance to FV3, little is known about the role played by innate immunity to infection with this virus. We have investigated the occurrence, composition, activation status, and permissiveness to infection of peritoneal leukocytes (PLs) in Xenopus adults during FV3 infection by microscopy, flow cytometry, and reverse transcription-PCR. The total number of PLs and the relative fraction of activated mononucleated macrophage-like cells significantly increase as early as 1 day postinfection (dpi), followed by NK cells at 3 dpi, before the peak of the T-cell response at 6 dpi. FV3 infection also induces a rapid upregulation of proinflammatory genes including arginase 1, interleukin-1 beta, and tumor necrosis factor alpha. Although PLs are susceptible to FV3 infection, as evidenced by apoptotic cells, active FV3 transcription, and the detection of viral particles by electron microscopy, the infection is weaker (fewer infectious particles), more transitory, and involves a smaller fraction (less than 1%) of PLs than the kidney, the main site of infection. However, viral DNA remains detectable in PLs for at least 3 weeks postinfection, past the point of viral clearance observed in the kidneys. This suggests that although PLs are actively involved in anti-FV3 immune responses, some of these cells can be permissive and harbor quiescent, asymptomatic FV3. C1 [Gertz, Jacqueline; Sowa, Jessica; Vogel, Ashley; Robert, Jacques] Univ Rochester, Med Ctr, Dept Microbiol & Immunol, Rochester, NY 14642 USA. [Morales, Heidi D.] Harvard Univ, Sch Med, Dept Neurobiol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Abramowitz, Lara] Univ Penn, Med Ctr, Dept Genet, Philadelphia, PA 19104 USA. RP Robert, J (reprint author), Univ Rochester, Med Ctr, Dept Microbiol & Immunol, Rochester, NY 14642 USA. EM Jacques_Robert@urmc.rochester.edu FU NIH [T32-AI-07285, AI-059830-1]; NSF [MCB-0136536] FX This research was supported by grants T32-AI-07285 (H. D. M.) and R24-AI-059830-1 from the NIH and grant MCB-0136536 from the NSF. NR 48 TC 42 Z9 42 U1 0 U2 21 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2010 VL 84 IS 10 BP 4912 EP 4922 DI 10.1128/JVI.02486-09 PG 11 WC Virology SC Virology GA 591QW UT WOS:000277318600005 PM 20200236 ER PT J AU Isakova, T Gutierrez, OM Wolf, M AF Isakova, Tamara Gutierrez, Orlando M. Wolf, Myles TI Proposed controlled trials of phosphate reduction in CKD: which whey should we go? Reply SO KIDNEY INTERNATIONAL LA English DT Letter C1 [Gutierrez, Orlando M.; Wolf, Myles] Univ Miami, Miller Sch Med, Div Nephrol & Hypertens, Dept Med, Miami, FL 33136 USA. [Isakova, Tamara] Harvard Univ, Sch Med, Dept Med, Renal Unit,Massachusetts Gen Hosp, Boston, MA USA. RP Wolf, M (reprint author), Univ Miami, Miller Sch Med, Div Nephrol & Hypertens, Dept Med, 1120 NW 14th St, Miami, FL 33136 USA. EM mwolf2@med.miami.edu NR 3 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAY PY 2010 VL 77 IS 10 BP 930 EP 930 DI 10.1038/ki.2010.53 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589RF UT WOS:000277169800017 ER PT J AU Lum, G AF Lum, Gifford TI Artefactually Low Hemoglobin A(1C) in a Patient with Hemolytic Anemia SO LABMEDICINE LA English DT Article DE diabetes; HbA(1C); falsely low HbA(1C); shortened red cell survival; hemolytic anemia ID GLYCATED HEMOGLOBIN; DIABETES-MELLITUS; DIAGNOSIS; AUTOANTIBODIES AB Hemoglobin A(1C) (HbA(1C)) is widely used for the monitoring and management of diabetes mellitus. Shortened red cell survival may result in artefactually low HbA(1C) values. In patients with hemoglobin variants or chemically-modified derivatives of hemoglobin, falsely decreased or increased HbA(1C) results may be found depending on the particular assay method. Although in most such cases, HbA(1C) can be reported if the appropriate methodology is selected. In diabetic patients with shortened red cell survival and in a small number of patients with certain hemoglobin variants, alternate approaches such as frequent glucose measurements and/or self glucose monitoring and fructosamine should be used to assess glycemic control. In diabetic patients with these conditions, HbA(1C) as the preferred diagnostic test for diabetes is not valid. C1 VA Boston Healthcare Syst, Pathol & Lab Med Serv, Boston, MA USA. RP Lum, G (reprint author), VA Boston Healthcare Syst, Pathol & Lab Med Serv, Boston, MA USA. EM gifford.lum@med.va.gov NR 13 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0007-5027 J9 LABMEDICINE JI Labmedicine PD MAY PY 2010 VL 41 IS 5 BP 267 EP 270 DI 10.1309/LME5Q0LRZ0W40HJR PG 4 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 587HJ UT WOS:000276980800003 ER PT J AU Ashley, EA Butte, AJ Wheeler, MT Chen, R Klein, TE Dewey, FE Dudley, JT Ormond, KE Pavlovic, A Morgan, AA Pushkarev, D Neff, NF Hudgins, L Gong, L Hodges, LM Berlin, DS Thorn, CF Sangkuhl, K Hebert, JM Woon, M Sagreiya, H Whaley, R Knowles, JW Chou, MF Thakuria, JV Rosenbaum, AM Zaranek, AW Church, GM Greely, HT Quake, SR Altman, RB AF Ashley, Euan A. Butte, Atul J. Wheeler, Matthew T. Chen, Rong Klein, Teri E. Dewey, Frederick E. Dudley, Joel T. Ormond, Kelly E. Pavlovic, Aleksandra Morgan, Alexander A. Pushkarev, Dmitry Neff, Norma F. Hudgins, Louanne Gong, Li Hodges, Laura M. Berlin, Dorit S. Thorn, Caroline F. Sangkuhl, Katrin Hebert, Joan M. Woon, Mark Sagreiya, Hersh Whaley, Ryan Knowles, Joshua W. Chou, Michael F. Thakuria, Joseph V. Rosenbaum, Abraham M. Zaranek, Alexander Wait Church, George M. Greely, Henry T. Quake, Stephen R. Altman, Russ B. TI Clinical assessment incorporating a personal genome SO LANCET LA English DT Article ID RIGHT-VENTRICULAR DYSPLASIA/CARDIOMYOPATHY; HYPERTROPHIC CARDIOMYOPATHY; PRAVASTATIN PHARMACOKINETICS; HEREDITARY HEMOCHROMATOSIS; WIDE ASSOCIATION; GENE; MUTATIONS; POLYMORPHISMS; DISEASE; THERAPY AB Background The cost of genomic information has fallen steeply, but the clinical translation of genetic risk estimates remains unclear. We aimed to undertake an integrated analysis of a complete human genome in a clinical context. Methods We assessed a patient with a family history of vascular disease and early sudden death. Clinical assessment included analysis of this patient's full genome sequence, risk prediction for coronary artery disease, screening for causes of sudden cardiac death, and genetic counselling. Genetic analysis included the development of novel methods for the integration of whole genome and clinical risk. Disease and risk analysis focused on prediction of genetic risk of variants associated with mendelian disease, recognised drug responses, and pathogenicity for novel variants. We queried disease-specific mutation databases and pharmacogenomics databases to identify genes and mutations with known associations with disease and drug response. We estimated post-test probabilities of disease by applying likelihood ratios derived from integration of multiple common variants to age-appropriate and sex-appropriate pretest probabilities. We also accounted for gene-environment interactions and conditionally dependent risks. Findings Analysis of 2.6 million single nucleotide polymorphisms and 752 copy number variations showed increased genetic risk for myocardial infarction, type 2 diabetes, and some cancers. We discovered rare variants in three genes that are clinically associated with sudden cardiac death-TMEM43, DSP, and MYBPC3. A variant in LPA was consistent with a family history of coronary artery disease. The patient had a heterozygous null mutation in CYP2C19 suggesting probable clopidogrel resistance, several variants associated with a positive response to lipid-lowering therapy, and variants in CYP4F2 and VKORC1 that suggest he might have a low initial dosing requirement for warfarin. Many variants of uncertain importance were reported. Interpretation Although challenges remain, our results suggest that whole-genome sequencing can yield useful and clinically relevant information for individual patients. C1 [Ashley, Euan A.; Wheeler, Matthew T.; Dewey, Frederick E.; Pavlovic, Aleksandra; Knowles, Joshua W.] Stanford Univ, Sch Med, Div Cardiovasc Med, Ctr Inherited Cardiovasc Dis, Stanford, CA 94305 USA. [Altman, Russ B.] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA. [Pushkarev, Dmitry; Neff, Norma F.; Quake, Stephen R.; Altman, Russ B.] Stanford Univ, Sch Med, Dept Bioengn, Stanford, CA 94305 USA. [Hudgins, Louanne] Stanford Univ, Sch Med, Div Med Genet, Stanford, CA 94305 USA. [Butte, Atul J.; Chen, Rong; Dudley, Joel T.; Morgan, Alexander A.] Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA. [Pushkarev, Dmitry; Neff, Norma F.; Quake, Stephen R.] Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94305 USA. [Klein, Teri E.; Ormond, Kelly E.; Gong, Li; Hodges, Laura M.; Berlin, Dorit S.; Thorn, Caroline F.; Sangkuhl, Katrin; Hebert, Joan M.; Woon, Mark; Sagreiya, Hersh; Whaley, Ryan; Altman, Russ B.] Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA. [Greely, Henry T.] Stanford Univ, Sch Law, Ctr Law & Biosci, Stanford, CA 94305 USA. [Thakuria, Joseph V.] Massachusetts Gen Hosp, Div Clin & Biochem Genet, Boston, MA 02114 USA. [Chou, Michael F.; Thakuria, Joseph V.; Rosenbaum, Abraham M.; Zaranek, Alexander Wait; Church, George M.] Harvard Univ, Dept Genet, Boston, MA 02115 USA. RP Ashley, EA (reprint author), Falk Cardiovasc Res Bldg,300 Pasteur Dr, Stanford, CA 94305 USA. EM euan@stanford.edu RI Dudley, Joel/E-9283-2010; Sincan, Murat /A-3794-2010; Osborne, Nicholas/N-4915-2015 OI Osborne, Nicholas/0000-0002-6700-2284 FU National Institute of General Medical Sciences; National Heart, Lung And Blood Institute; National Human Genome Research Institute; Howard Hughes Medical Institute; National Library of Medicine, Lucile Packard Foundation for Children's Health; Hewlett Packard Foundation; Breetwor Family Foundation FX Funding National Institute of General Medical Sciences; National Heart, Lung And Blood Institute; National Human Genome Research Institute; Howard Hughes Medical Institute; National Library of Medicine, Lucile Packard Foundation for Children's Health; Hewlett Packard Foundation; Breetwor Family Foundation. NR 54 TC 378 Z9 387 U1 19 U2 151 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD MAY 1 PY 2010 VL 375 IS 9725 BP 1525 EP 1535 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 596AH UT WOS:000277655100025 PM 20435227 ER PT J AU Aggarwal, SP Zinman, L Simpson, E McKinley, J Jackson, KE Pinto, H Kaufman, P Conwit, RA Schoenfeld, D Shefner, J Cudkowicz, M AF Aggarwal, Swati P. Zinman, Lorne Simpson, Elizabeth McKinley, Jane Jackson, Katherine E. Pinto, Hanika Kaufman, Petra Conwit, Robin A. Schoenfeld, David Shefner, Jeremy Cudkowicz, Merit CA NE Canadian Amyotrophic Lateral Sc TI Safety and efficacy of lithium in combination with riluzole for treatment of amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled trial SO LANCET NEUROLOGY LA English DT Article ID FUNCTIONAL RATING-SCALE; CELLS IN-VITRO; REPORT QIDS-SR; DEPRESSIVE SYMPTOMATOLOGY; NEURONAL DIFFERENTIATION; PSYCHOMETRIC EVALUATION; QUICK INVENTORY; MOUSE MODEL; ALSFRS-R; AUTOPHAGY AB Background In a pilot study, lithium treatment slowed progression of amyotrophic lateral sclerosis (ALS). We aimed to confirm or disprove these findings by assessing the safety and efficacy of lithium in combination with riluzole in patients with ALS. Methods We did a double-blind, placebo-controlled trial with a time-to-event design. Between January and June, 2009, patients with ALS who were taking a stable dose of riluzole for at least 30 days were randomly assigned (1:1) by a centralised computer to receive either lithium or placebo. Patients, caregivers, investigators, and all site study staff with the exception of site pharmacists were masked to treatment assignment. The primary endpoint was the time to an event, defined as a decrease of at least six points on the revised ALS functional rating scale score or death. Interim analyses were planned for when 84 patients had been allocated treatment, 6 months later or after 55 events, and after 100 events. Analysis was by intention to treat. The stopping boundary for futility at the first interim analysis was a p value of at least 0.68. We used a log-rank test to compare the distributions of the time to an event between the lithium and placebo groups. This trial is registered with ClinicalTrials.gov, NCT00818389. Findings At the first interim analysis, 22 of 40 patients in the lithium group had an event compared with 20 of 44 patients in the placebo group (log rank p=0.51). The hazard ratio of reaching the primary endpoint was 1.13 (95% CI 0.61-2.07). The study was stopped at the first interim analysis because criterion for futility was met (p=0.78). The difference in mean decline in the ALS functional rating scale score between the lithium group and the placebo group was 0.15 (95% CI -0.43 to 0.73, p=0.61). There were no major safety concerns. Falls (p=0.04) and back pain (p=0.05) were more common in the lithium group than in the placebo group. Interpretation We found no evidence that lithium in combination with riluzole slows progression of ALS more than riluzole alone. The time-to-event endpoint and use of prespecified interim analyses enabled a clear result to be obtained rapidly. This design should be considered for future trials testing the therapeutic efficacy of drugs that are easily accessible to people with ALS. C1 [Aggarwal, Swati P.; Simpson, Elizabeth; Jackson, Katherine E.; Cudkowicz, Merit] Massachusetts Gen Hosp, Neurol Clin Trials Unit, Charlestown, MA 02129 USA. [Schoenfeld, David] Massachusetts Gen Hosp, Dept Biostat, Charlestown, MA 02129 USA. [Zinman, Lorne; McKinley, Jane; Pinto, Hanika] Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. [Kaufman, Petra; Conwit, Robin A.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA. [Shefner, Jeremy] SUNY Upstate Med Univ, Syracuse, NY USA. RP Aggarwal, SP (reprint author), Massachusetts Gen Hosp, Neurol Clin Trials Unit, Bldg 149,13th St, Charlestown, MA 02129 USA. EM spaggarwal@partners.org FU University of Rochester central pharmacy; National Institute of Neurological Disorders and Stroke, USA; ALS Association, USA; ALS Society of Canada, Canada FX We thank Claudia Moy and Louise Ritz of the National Institute of Neurological Disorders and Stroke, Lucie Bruijn of the ALS Association, and Denise Figlewicz of the ALS Society of Canada. We thank the members of the data and safety monitoring board for their guidance, medical monitors Carl Leventhal and James Russell, cardiologist Judy Hung, and drug monitor Francine Vriesendorp, and the patients and carers for their commitment and time. We also thank Apotex for providing the lithium and matching placebo at a discounted rate and the University of Rochester central pharmacy for their support. Granting agencies in the USA (the National Institute of Neurological Disorders and Stroke and the ALS Association) and Canada (the ALS Society of Canada) provided funds outside of the normal grant cycle after peer review from the ALS Association while awaiting NIH peer review. PK worked on this trial whilst at Columbia University; her contribution to the trial was not related to the National Institutes of Neurological Disorders and Stroke. NR 23 TC 102 Z9 104 U1 2 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1474-4422 J9 LANCET NEUROL JI Lancet Neurol. PD MAY PY 2010 VL 9 IS 5 BP 481 EP 488 DI 10.1016/S1474-4422(10)70068-5 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 592MY UT WOS:000277384600012 PM 20363190 ER PT J AU Saylor, PJ Fogerty, AE AF Saylor, Philip J. Fogerty, Annemarie E. TI Prostate-cancer-associated hypercoagulability: do we need to worry about androgen deprivation? SO LANCET ONCOLOGY LA English DT Editorial Material ID CARDIOVASCULAR-DISEASE; THERAPY; THROMBOEMBOLISM; THROMBOSIS C1 [Saylor, Philip J.; Fogerty, Annemarie E.] Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Boston, MA 02114 USA. RP Saylor, PJ (reprint author), Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Lawrence House,55 Fruit St, Boston, MA 02114 USA. EM psaylor@partners.org NR 13 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 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD MAY PY 2010 VL 11 IS 5 BP 406 EP 407 DI 10.1016/S1470-2045(10)20063-2 PG 2 WC Oncology SC Oncology GA 607DL UT WOS:000278478800005 PM 20395175 ER PT J AU Stone, ME AF Stone, Martha E. TI Jr. Swedenborg, Mesmer, and the Mind/Body Connection: The Roots of Complementary Medicine. SO LIBRARY JOURNAL LA English DT Book Review C1 [Stone, Martha E.] Massachusetts Gen Hosp Lib, Boston, MA 02114 USA. RP Stone, ME (reprint author), Massachusetts Gen Hosp Lib, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU REED BUSINESS INFORMATION PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010 USA SN 0363-0277 J9 LIBR J JI Libr. J. PD MAY 1 PY 2010 VL 135 IS 8 BP 87 EP 88 PG 2 WC Information Science & Library Science SC Information Science & Library Science GA 591OY UT WOS:000277312100167 ER PT J AU Sonnenberg, A Naugler, WE AF Sonnenberg, Amnon Naugler, Willscott E. TI Models of influence in chronic liver disease SO LIVER INTERNATIONAL LA English DT Article DE autoimmune hepatitis; Child A and Child C cirrhosis; decision analysis; hepatitis C virus infection; Markov chain; stochastic modelling ID CHRONIC HEPATITIS-C; HEPATOCELLULAR-CARCINOMA; COST-EFFECTIVENESS; CIRRHOSIS; MANAGEMENT; RIBAVIRIN AB Background & Aims: Liver disease is often characterized by an intricate network of multiple, simultaneously interacting factors with organ-specific, as well as systemic effects. The aim of the present study is to introduce a new mathematical model on how to weigh a variety of factors contributing to chronic liver disease by the relevance of their influence on the overall disease processes. Methods: Liver disease is modelled as the interaction of multiple internal and external factors. Each factor can potentially interact with any of the other factors in the model. The strength of interactions is expressed as per cent. The sum of all interactions contributing to each individual factor adds up to 100%. This model corresponds mathematically to a transposed Markov matrix. The analysis uses the two examples of hepatitis C virus (HCV) and autoimmune hepatitis (AIH). Results: Impaired liver function is the most influential factor and increases in relevance as the degree of hepatic fibrosis increases. The relative importance of treating the primary disease process (HCV or AIH) diminishes as fibrosis develops. Similarly, psychosocial factors become less important with disease progression. Liver transplant is most important for Child's C cirrhosis. It is relatively influential for the early phase of AIH but not HCV, reflecting the fact that some cases of non-cirrhotic AIH can progress rapidly to acute liver failure. Conclusion: In a disease process characterized by a large array of multiple interacting factors, the decision tool of a transposed Markov chain helps to sort the contributing factors by the magnitude of their influence. C1 Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr P3 GI, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 18 TC 3 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1478-3223 J9 LIVER INT JI Liver Int. PD MAY PY 2010 VL 30 IS 5 BP 718 EP 724 DI 10.1111/j.1478-3231.2009.02196.x PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 581DU UT WOS:000276502500010 PM 20040051 ER PT J AU Yeh, ED AF Yeh, Eren D. TI Breast Magnetic Resonance Imaging: Current Clinical Indications SO MAGNETIC RESONANCE IMAGING CLINICS OF NORTH AMERICA LA English DT Article DE Breast; Magnetic resonance; Indications; Breast cancer ID EXTENSIVE INTRADUCTAL COMPONENT; INVASIVE LOBULAR CARCINOMA; NEOADJUVANT CHEMOTHERAPY; IMPLANT RUPTURE; PREOPERATIVE CHEMOTHERAPY; MAMMOGRAPHIC FINDINGS; HODGKINS LYMPHOMA; RESIDUAL DISEASE; MR MAMMOGRAPHY; HIGH-RISK AB Breast magnetic resonance (MR) is highly sensitive in the detection of invasive breast malignancies. As technology improves, as interpretations and reporting by radiologists become standardized through the development of guidelines by expert consortiums, and as scientific investigation continues, the indications and uses of breast MR as an adjunct to mammography continue to evolve. This article discusses the current clinical indications for breast MR including screening for breast cancer, diagnostic indications for breast MR, and MR guidance for interventional procedures. C1 Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Div Breast Imaging,Dept Radiol,Med Sch, Boston, MA 02115 USA. RP Yeh, ED (reprint author), Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Div Breast Imaging,Dept Radiol,Med Sch, 75 Francis St,RA Bldg 014, Boston, MA 02115 USA. EM eyeh@partners.org NR 57 TC 9 Z9 9 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1064-9689 J9 MAGN RESON IMAGING C JI Magn. Reson. Imaging Clin. N. Am. PD MAY PY 2010 VL 18 IS 2 BP 155 EP + DI 10.1016/j.mric.2010.02.009 PG 16 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 615FE UT WOS:000279118200002 PM 20494303 ER PT J AU Zarkin, GA Bray, JW Aldridge, A Mills, M Cisler, RA Couper, D Mckay, JR O'Malley, S AF Zarkin, Gary A. Bray, Jeremy W. Aldridge, Arnie Mills, Michael Cisler, Ron A. Couper, David McKay, James R. O'Malley, Stephanie TI The Effect of Alcohol Treatment on Social Costs of Alcohol Dependence Results From the COMBINE Study SO MEDICAL CARE LA English DT Article DE alcohol treatment; social costs; cost offsets ID HEALTH-CARE UTILIZATION; UNITED-STATES; ABUSE; TRIAL AB Background: The COMBINE (combined pharmacotherapies and behavioral intervention) clinical trial recently evaluated the efficacy of pharmacotherapies, behavioral therapies, and their combinations for the treatment of alcohol dependence. Previously, the cost and cost-effectiveness of COMBINE have been studied. Policy makers, patients, and nonalcohol-dependent individuals may be concerned not only with alcohol treatment costs but also with the effect of alcohol interventions on broader social costs and outcomes. Objectives: To estimate the sum of treatment costs plus the costs of health care utilization, arrests, and motor vehicle accidents for the 9 treatments in COMBINE 3 years postrandomization. Research Design: A cost study based on a randomized controlled clinical trial. Subjects: The study involved 786 participants 3 years postrandomization. Results: Multivariate results show no significant differences in mean costs between any of the treatment arms as compared with medical management (MM) + placebo for the 3-year postrandomization sample. The median costs of MM + acamprosate, MM + naltrexone, MM + acamprosate + naltrexone, and MM + acamprosate + combined behavioral intervention were significantly lower than the median cost for MM + placebo. Conclusions: The results show that social cost savings are generated relative to MM + placebo by 3 years postrandomization, and the magnitude of these cost savings is greater than the costs of the COMBINE treatment received 3 years prior. Our study suggests that several alcohol treatments may indeed lead to reduced median social costs associated with health care, arrests, and motor vehicle accidents. C1 [Zarkin, Gary A.; Bray, Jeremy W.; Aldridge, Arnie; Mills, Michael] RTI Int, Res Triangle Pk, NC 27709 USA. [Cisler, Ron A.] Univ Wisconsin, Sch Med & Publ Hlth, Ctr Urban Populat Hlth, Milwaukee, WI 53201 USA. [Cisler, Ron A.] Aurora Hlth Care Inc, Milwaukee, WI USA. [Couper, David] Univ N Carolina, Chapel Hill, NC USA. [McKay, James R.] Univ Penn, Philadelphia, PA 19104 USA. [McKay, James R.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [O'Malley, Stephanie] Yale Univ, New Haven, CT USA. RP Zarkin, GA (reprint author), RTI Int, 3040 Cornwallis Rd,POB 12194, Res Triangle Pk, NC 27709 USA. EM gaz@rti.org FU NIAAA [1-R01-AA12788, K05014715] FX Supported by NIAAA grant 1-R01-AA12788 and K05014715. NR 21 TC 15 Z9 15 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD MAY PY 2010 VL 48 IS 5 BP 396 EP 401 DI 10.1097/MLR.0b013e3181d68859 PG 6 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 591YW UT WOS:000277342500002 PM 20393362 ER PT J AU Srinivas, SK Epstein, AJ Nicholson, S Herrin, J Asch, DA AF Srinivas, Sindhu K. Epstein, Andrew J. Nicholson, Sean Herrin, Jeph Asch, David A. TI Improvements in US Maternal Obstetrical Outcomes From 1992 to 2006 SO MEDICAL CARE LA English DT Article DE obstetrics; maternal outcomes; trends; complications after delivery ID PRIMARY CESAREAN DELIVERY; IDENTIFY INDICATIONS; UNITED-STATES; TRENDS; RISK; RATES; EPISIOTOMY; HEMORRHAGE AB Background: Over 4 million women give birth annually in the United States, making delivery one of the most common reasons for hospital care. Objective: We examined 15-year trends in risk-adjusted maternal complications following childbirth. Research Design: We examined maternal obstetrical outcomes from 1992-2006 among women undergoing cesarean delivery (CD) and vaginal delivery (VD). A composite measure of major maternal complications including infection, hemorrhage, laceration, and other major operative and thrombotic complications was evaluated. Subjects: Population-based sample of over 6 million women from Florida and New York hospital discharge data. Measures: Obstetric procedures and maternal complications post-delivery. Results: During the 15-year time period, the CD rate decreased from 24.7% in 1992 to 23% in 1996 and increased to 34.7% in 2006. The risk-adjusted rate of any major complication declined from 14.7% in 1992 to 10.7% in 2006 for all deliveries; from 14.4% to 11.6% for VD; and from 15.7% to 8.5% for CD. During 1992 to 2006, the average number of comorbidities increased from 0.65 to 0.93 for patients overall, from 0.43 to 0.58 for VD patients, and 1.34 to 1.59 for CD patients. Conclusion: As evidenced by New York and Florida, the US has seen large reductions in major maternal complications over the past 15 years. Concurrently, the average number of comorbidities increased. These results reflect substantial improvements in maternal delivery outcomes. C1 [Srinivas, Sindhu K.] Univ Penn, Dept OB GYN, Philadelphia, PA 19104 USA. [Srinivas, Sindhu K.; Epstein, Andrew J.; Nicholson, Sean; Asch, David A.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Epstein, Andrew J.; Herrin, Jeph] Yale Univ, New Haven, CT USA. [Nicholson, Sean] Cornell Univ, New York, NY 10021 USA. [Asch, David A.] Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Srinivas, SK (reprint author), Univ Penn, Dept OB GYN, 421 Curie Blvd,BRB 2-3 1353, Philadelphia, PA 19104 USA. EM ssrinivas@obgyn.upenn.edu OI Asch, David/0000-0002-7970-286X FU Stemmler Fund of the National Board of Medical Examiners FX Supported by the Stemmler Fund of the National Board of Medical Examiners. This research has been performed independent of the funding source. NR 26 TC 26 Z9 26 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD MAY PY 2010 VL 48 IS 5 BP 487 EP 493 DI 10.1097/MLR.0b013e3181d68840 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 591YW UT WOS:000277342500015 PM 20393363 ER PT J AU Sox, HC Helfand, M Grimshaw, J Dickersin, K Tovey, D Knottnerus, JA Tugwell, P AF Sox, Harold C. Helfand, Mark Grimshaw, Jeremy Dickersin, Kay Tovey, David Knottnerus, J. Andre Tugwell, Peter TI Comparative Effectiveness Research: Challenges for Medical Journals SO MEDICAL DECISION MAKING LA English DT Editorial Material C1 [Helfand, Mark] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97239 USA. [Sox, Harold C.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dartmouth Inst, Hanover, NH 03756 USA. [Helfand, Mark] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97239 USA. [Grimshaw, Jeremy] Ottawa Hosp Res Inst, Clin Epidemiol Program, Ottawa, ON, Canada. [Dickersin, Kay] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Tovey, David] Cochrane Lib, London, England. [Knottnerus, J. Andre] Univ Maastricht, Dept Gen Practice, Maastricht, Netherlands. [Tugwell, Peter] Univ Ottawa, Dept Med, Ottawa, ON, Canada. [Tugwell, Peter] Univ Ottawa, Dept Epidemiol & Community Med, Ottawa, ON, Canada. RP Helfand, M (reprint author), Oregon Hlth & Sci Univ, Portland VA Med Ctr, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM helfand@ohsu.edu RI Grimshaw, Jeremy/D-8726-2013; Knottnerus, Andre/F-4866-2013; Knottnerus, Johannes/A-3829-2009 NR 7 TC 3 Z9 3 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD MAY-JUN PY 2010 VL 30 IS 3 BP 301 EP 303 DI 10.1177/0272989X10370815 PG 3 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 599EH UT WOS:000277892800004 PM 20424174 ER PT J AU Stollenwerk, B Stock, S Siebert, U Lauterbach, KW Holle, R AF Stollenwerk, Bjoern Stock, Stephanie Siebert, Uwe Lauterbach, Karl W. Holle, Rolf TI Uncertainty Assessment of Input Parameters for Economic Evaluation: Gauss's Error Propagation, an Alternative to Established Methods SO MEDICAL DECISION MAKING LA English DT Article DE decision-analytic modeling; health economic evaluation; error propagation law; uncertainty assessment ID PROBABILISTIC SENSITIVITY-ANALYSIS; COST-EFFECTIVENESS AB In decision modeling for health economic evaluation, bootstrapping and the Cholesky decomposition method are frequently used to assess parameter uncertainty and to support probabilistic sensitivity analysis. An alternative, Gauss's error propagation law, is rarely known but may be useful in some settings. Bootstrapping, the Cholesky decomposition method, and the error propagation law were compared regarding standard deviation estimates of a hypothetic parameter, which was derived from a regression model fitted to simulated data. Furthermore, to demonstrate its value, the error propagation law was applied to German administrative claims data. All 3 methods yielded almost identical estimates of the standard deviation of the target parameter. The error propagation law was much faster than the other 2 alternatives. Furthermore, it succeeded the claims data example, a case in which the established methods failed. In conclusion, the error propagation law is a useful extension of parameter uncertainty assessment. C1 [Stollenwerk, Bjoern; Holle, Rolf] Helmholtz Zentrum Munchen GmbH, Inst Hlth Econ & Hlth Care Management, D-85764 Neuherberg, Germany. [Stollenwerk, Bjoern; Siebert, Uwe] UMIT Univ Hlth Sci Med Informat & Technol, Dept Publ Hlth Med Decis Making & Hlth Technol As, Hall In Tirol, Austria. [Stollenwerk, Bjoern; Stock, Stephanie; Lauterbach, Karl W.] Univ Cologne, Inst Hlth Econ & Clin Epidemiol, Cologne, Germany. [Siebert, Uwe] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Siebert, Uwe] Harvard Univ, Sch Med, Inst Technol Assessment, Boston, MA 02115 USA. [Siebert, Uwe; Lauterbach, Karl W.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Ctr Hlth Decis Sci, Boston, MA 02115 USA. RP Stollenwerk, B (reprint author), Helmholtz Zentrum Munchen GmbH, Inst Hlth Econ & Hlth Care Management, Ingolstadter Landstr 1, D-85764 Neuherberg, Germany. EM bjoern.stollenwerk@helmholtz-muenchen.de RI Stollenwerk, Bjorn/G-5408-2013; Holle, Rolf/D-9333-2013 OI Holle, Rolf/0000-0001-5395-2695 NR 23 TC 11 Z9 11 U1 2 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD MAY-JUN PY 2010 VL 30 IS 3 BP 304 EP 313 DI 10.1177/0272989X09347015 PG 10 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 599EH UT WOS:000277892800005 PM 19815659 ER PT J AU Marconi, VC Kradin, R Marty, FM Hospenthal, DR Kotton, CN AF Marconi, Vincent C. Kradin, Richard Marty, Francisco M. Hospenthal, Duane R. Kotton, Camille N. TI Disseminated dermatophytosis in a patient with hereditary hemochromatosis and hepatic cirrhosis: case report and review of the literature SO MEDICAL MYCOLOGY LA English DT Review DE Dermatophytosis; Trichophyton; tinea; invasive; disseminated ID TRICHOPHYTON-RUBRUM INFECTION; DEEP DERMATOPHYTOSIS; MICROSPORUM-CANIS; IMMUNOCOMPROMISED PATIENT; IMMUNOSUPPRESSED PATIENTS; RESEMBLING BLASTOMYCOSIS; PSEUDOMYCETOMA; GRANULOMA; SKIN; ABSCESSES AB The most common presentation of dermatophytosis is as a superficial infection characterized by a rash (tinea). In very rare cases, this infection can become invasive, involve deeper dermal structures, and even disseminate. We present a case of biopsy-proven, disseminated dermatophytosis caused by Trichophyton rubrum in a patient with advanced cirrhosis. In addition, we provide a review of the literature. C1 [Marconi, Vincent C.; Kotton, Camille N.] Massachusetts Gen Hosp, Div Infect Dis, Transplant Infect Dis & Compromised Host Serv, Boston, MA 02114 USA. [Kradin, Richard] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Marconi, Vincent C.; Hospenthal, Duane R.] San Antonio Mil Med Ctr, Infect Dis Serv, San Antonio, TX USA. [Marconi, Vincent C.; Kradin, Richard; Marty, Francisco M.; Kotton, Camille N.] Harvard Univ, Sch Med, Boston, MA USA. [Marconi, Vincent C.; Marty, Francisco M.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. RP Kotton, CN (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Transplant Infect Dis & Compromised Host Serv, Cox 512,55 Fruit St, Boston, MA 02114 USA. EM ckotton@partners.org RI Marconi, Vincent/N-3210-2014 OI Marconi, Vincent/0000-0001-8409-4689 FU NIAID [T32 AI07387-14, K08 AI001701] FX For a period of the preparation of this case, the authors received salary support by NIAID grant T32 AI07387-14 to V.M. and NIAID grant K08 AI001701 to C.N.K. NR 49 TC 21 Z9 21 U1 0 U2 5 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1369-3786 J9 MED MYCOL JI Med. Mycol. PD MAY PY 2010 VL 48 IS 3 BP 518 EP 527 DI 10.3109/13693780903213512 PG 10 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA 579IV UT WOS:000276363900012 PM 20092423 ER PT J AU Nierenberg, NE Thompson, GR Lewis, JS Hogan, BK Patterson, TF AF Nierenberg, Natalie E. Thompson, George R., III Lewis, James S., II Hogan, Brian K. Patterson, Thomas F. TI Voriconazole use and pharmacokinetics in combination with interferon-gamma for refractory cryptococcal meningitis in a patient receiving low-dose ritonavir SO MEDICAL MYCOLOGY LA English DT Article DE cryptococcus; voriconazole; salvage; therapeutic drug monitoring ID FUNGAL-INFECTIONS; ANTIFUNGAL CHEMOTHERAPY; ADVERSE EVENTS; SAFETY; POSACONAZOLE; NEOFORMANS; EFFICACY AB We present a case of relapsing cryptococcal meningitis unresponsive to standard therapy. Voriconazole induction, including the utilization of voriconazole therapeutic drug monitoring in both serum and CSF, with transition to voriconazole plus interferon-gamma (IFN-gamma) was successfully used in a patient receiving antiretroviral therapy with abacavir/lamivudine and lopinavir/ritonavir. Initial voriconazole levels at standard doses of 4 mg/kg twice daily intravenously were low when co-administered with lopinavir/ritonavir but increased to recommended therapeutic levels with an increase of the voriconazole dose to 7 mg/kg twice daily. This case highlights the utility of voriconazole therapeutic drug monitoring when prescribed concurrently with a ritonavir boosted protease inhibitor and the potential role of combination therapy with IFN-gamma for refractory cryptococcal meningitis. C1 [Nierenberg, Natalie E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Internal Med, Div Gen Med, San Antonio, TX 78229 USA. [Thompson, George R., III; Lewis, James S., II; Patterson, Thomas F.] Univ Texas Hlth Sci Ctr San Antonio, Div Infect Dis, San Antonio, TX 78229 USA. [Lewis, James S., II] Univ Texas Hlth Sci Ctr San Antonio, Pharm Serv Univ Hlth Syst, San Antonio, TX 78229 USA. [Hogan, Brian K.] Brooke Army Med Ctr, San Antonio, TX USA. [Thompson, George R., III; Patterson, Thomas F.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Nierenberg, NE (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Internal Med, Div Gen Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM nierenberg@uthscsa.edu FU Basilea; Merck; Pfizer; Schering-Plough FX Declaration of interest: G. R. T. has served as a consultant for Basilea. T. F. P. has received research support from Basilea, Merck, Pfizer, and Schering-Plough and has received honoraria or served as a consultant for Basilea, Merck, and Pfizer. All other authors have no potential conflicts to disclose. NR 19 TC 10 Z9 11 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1369-3786 J9 MED MYCOL JI Med. Mycol. PD MAY PY 2010 VL 48 IS 3 BP 532 EP 536 DI 10.3109/13693780903325282 PG 5 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA 579IV UT WOS:000276363900014 PM 19835489 ER PT J AU Westbrook, SD Wiederhold, NP Vallor, AC Kotara, S Bernardo, S Lee, SA Kirkpatrick, WR Toro, JJ Freytes, C Patterson, TF Redding, SW AF Westbrook, Steven D. Wiederhold, Nathan P. Vallor, Ana C. Kotara, Susann Bernardo, Stella Lee, Samuel A. Kirkpatrick, William R. Toro, Juan J. Freytes, Cesaro Patterson, Thomas F. Redding, Spencer W. TI Loss of in vitro resistance in Candida glabrata following discontinuation of fluconazole prophylaxis in a hematopoietic stem cell transplantation patient SO MEDICAL MYCOLOGY LA English DT Article DE hematopoietic stem cell transplantation; Candida glabrata; fluconazole resistance ID CHROMOGENIC AGAR; ALBICANS; PCR AB We report a case of fluconazole-resistant oropharyngeal colonization caused by a strain of Candida glabrata that rapidly regained susceptibility once prophylaxis with this agent was discontinued and echinocandin therapy was initiated. Isolates collected before and after discontinuation of fluconazole were confirmed to be isogenic by RAPD analysis. Transcription analysis demonstrated constitutive expression of genes encoding efflux pumps in the isolate recovered on fluconazole prophylaxis and transient expression in those isolates collected after fluconazole was discontinued. C1 [Westbrook, Steven D.; Redding, Spencer W.] Univ Texas Hlth Sci Ctr San Antonio, Dept Dent Diagnost Sci, San Antonio, TX 78229 USA. [Wiederhold, Nathan P.; Vallor, Ana C.; Kotara, Susann; Bernardo, Stella; Lee, Samuel A.; Kirkpatrick, William R.; Toro, Juan J.; Freytes, Cesaro; Patterson, Thomas F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Westbrook, Steven D.; Vallor, Ana C.; Bernardo, Stella; Lee, Samuel A.; Kirkpatrick, William R.; Toro, Juan J.; Freytes, Cesaro; Patterson, Thomas F.; Redding, Spencer W.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Wiederhold, Nathan P.] Univ Texas Austin, Coll Pharm, Div Pharmacotherapy, Austin, TX 78712 USA. RP Westbrook, SD (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Dent Diagnost Sci, 7703 Floyd Curl Dr,Mail Code 7919, San Antonio, TX 78229 USA. EM westbrooks@uthscsa.edu OI Wiederhold, Nathan/0000-0002-2225-5122 FU National Institute of Dental and Craniofacial Research [DE-18096]; Pfizer; Schering-Plough; CyDex Pharmaceuticals; Merck; Nektar Therapeutics FX This work was supported in part by Public Health Service Grant DE-18096 from the National Institute of Dental and Craniofacial Research. The authors gratefully acknowledge Jon Maust and Marcos Olivo for their technical assistance with yeast identification and isolation.; Conflict of interest: SDW, ACV, SK, SB, SAL, WRK, JJT, COF: None to declare. N.P.W. has received research support from Pfizer, Schering-Plough, and CyDex Pharmaceuticals. T. F. P. has received research support from Merck, Pfizer, Schering-Plough, and Nektar Therapeutics, has served on the speakers bureau for Merck and Pfizer, and as a consultant for Basilea, Merck, Nektar, Pfizer, and NR 9 TC 2 Z9 2 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1369-3786 J9 MED MYCOL JI Med. Mycol. PD MAY PY 2010 VL 48 IS 3 BP 557 EP U24 DI 10.3109/13693780903213504 PG 4 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA 579IV UT WOS:000276363900018 PM 20370365 ER PT J AU Bednarz, B Athar, B Xu, XG AF Bednarz, Bryan Athar, Basit Xu, X. George TI A comparative study on the risk of second primary cancers in out-of-field organs associated with radiotherapy of localized prostate carcinoma using Monte Carlo-based accelerator and patient models SO MEDICAL PHYSICS LA English DT Article DE biomedical equipment; cancer; dosimetry; linear accelerators; Monte Carlo methods; phantoms; radiation therapy; risk management ID FATAL SECONDARY MALIGNANCIES; PROTON THERAPY; RADICAL PROSTATECTOMY; CALCULATED RISK; RECTAL-CANCER; RADIATION; IMRT; IMPACT; IRRADIATION; PARAMETERS AB Methods: Monte Carlo simulations were performed using a detailed medical linear accelerator model and an anatomically realistic adult male whole-body phantom. A four-field box treatment, a four-field box treatment plus a six-field boost, and a seven-field IMRT treatment were simulated. Using BEIR VII risk models, the age-dependent lifetime attributable risks to various organs outside the primary beam with a known predilection for cancer were calculated using organ-averaged equivalent doses. Results: The four-field box treatment had the lowest treatment-related second primary cancer risks to organs outside the primary beam ranging from 7.3x10(-9) to 2.54x10(-5)%/MU depending on the patients age at exposure and second primary cancer site. The risks to organs outside the primary beam from the four-field box and six-field boost and the seven-field IMRT were nearly equivalent. The risks from the four-field box and six-field boost ranged from 1.39x10(-8) to 1.80x10(-5)%/MU, and from the seven-field IMRT ranged from 1.60x10(-9) to 1.35x10(-5)%/MU. The second cancer risks in all organs considered from each plan were below the baseline risks. Conclusions: The treatment-related second cancer risks in organs outside the primary beam due to 3D-CRT and IMRT is small. New risk assessment techniques need to be investigated to address the concern of radiation-induced second cancers from prostate treatments, particularly focusing on risks to organs inside the primary beam. C1 [Bednarz, Bryan] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02108 USA. Harvard Univ, Sch Med, Boston, MA 02108 USA. Rensselaer Polytech Inst, Dept Mech Aerosp & Nucl Engn, Troy, NY 12180 USA. RP Bednarz, B (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02108 USA. EM bbednarz@partners.org FU NCI [R01CA116743]; NIH/NCI [CO6-CA059267] FX This project was funded in part by a NCI grant (Grant No. R01CA116743) and NIH/NCI grant (Grant No. CO6-CA059267). The authors would like to thank Dr. Harald Paganetti for providing assistance with this manuscript. NR 36 TC 24 Z9 24 U1 1 U2 4 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 MAY PY 2010 VL 37 IS 5 BP 1987 EP 1994 DI 10.1118/1.3367012 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 590QT UT WOS:000277242800006 PM 20527532 ER PT J AU Otten, MHC Kreshak, J Rifat, SF AF Otten, Matthew H. C. Kreshak, Jennifer Rifat, Sami F. TI Ribbing Disease, a Rare Disease Presenting as Shin Pain; a Case Review SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-College-Sports-Medicine/Inaugural World Congress on Exercise is Medicine CY JUN 05, 2010 CL Baltimore, MD SP Amer Coll Sports Med C1 [Otten, Matthew H. C.; Rifat, Sami F.] Beaumont Hosp Sports Med, Royal Oak, MI USA. [Kreshak, Jennifer] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Otten, Matthew H. C.; Rifat, Sami F.] Beaumont Hosp Sports Med, Troy, MI USA. EM otten02@yahoo.com NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2010 VL 42 IS 5 SU 1 MA 1237 BP 204 EP 204 PG 1 WC Sport Sciences SC Sport Sciences GA 759FO UT WOS:000290226300552 ER PT J AU Emmons, RR Cirnigliaro, CM Kirshblum, SC Galea, MD Spungen, AM Bauman, WA AF Emmons, Racine R. Cirnigliaro, Christopher M. Kirshblum, Steven C. Galea, Marinella D. Spungen, Ann M. Bauman, William A. TI Abdominal Adiposity and Insulin Level Influence Lipoprotein Particle Size and Concentration in Spinal Cord Injury SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-College-Sports-Medicine/Inaugural World Congress on Exercise is Medicine CY JUN 05, 2010 CL Baltimore, MD SP Amer Coll Sports Med C1 [Emmons, Racine R.; Cirnigliaro, Christopher M.; Galea, Marinella D.; Spungen, Ann M.; Bauman, William A.] James J Peters VA Med Ctr, Bronx, NY USA. [Kirshblum, Steven C.] Kessler Inst Rehabil, W Orange, NJ USA. EM racine.emmons@va.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2010 VL 42 IS 5 SU 1 MA 2168 BP 532 EP 532 PG 1 WC Sport Sciences SC Sport Sciences GA 759FO UT WOS:000290226301821 ER PT J AU Mahalingam, M Nguyen, LP Richards, JE Muzikansky, A Hoang, MP AF Mahalingam, Meera Nguyen, Lisa P. Richards, Joanna E. Muzikansky, Alona Hoang, Mai P. TI The diagnostic utility of immunohistochemistry in distinguishing primary skin adnexal carcinomas from metastatic adenocarcinoma to skin: an immunohistochemical reappraisal using cytokeratin 15, nestin, p63, D2-40, and calretinin SO MODERN PATHOLOGY LA English DT Article DE cytokeratin 15; nestin; p63; D2-40; adnexal neoplasm; cutaneous metastasis ID FOLLICLE STEM-CELLS; HUMAN HAIR FOLLICLE; CUTANEOUS METASTASES; EXPRESSION; NEOPLASMS; MARKER; TUMORS; PODOPLANIN; CANCER AB Often the distinction of primary adnexal carcinoma from metastatic adenocarcinoma to skin from breast, lung, and other sites can be a diagnostic dilemma. Current markers purportedly of utility as diagnostic adjuncts include p63 and D2-40; however, their expression has been demonstrated in 11-22% and 5% of metastatic cutaneous metastases, respectively. Both cytokeratin (CK) 15 and nestin have been reported as follicular stem cell markers. We performed CK15 and nestin, as well as previously reported stains (such as p63, D2-40, and calretinin) on 113 cases (59 primary adnexal carcinomas and 54 cutaneous metastases). Expressions of p63, CK15, nestin, D2-40, and calretinin were observed in 91, 40, 37, 44, and 14% of primary adnexal carcinoma, respectively, and in 8, 2, 8, 4, and 10% of cutaneous metastases, respectively. p63 appeared to be the most sensitive marker (with a sensitivity of 91%) in detecting primary adnexal carcinomas. CK15 appeared to be the most specific marker with a specificity of 98%. Using chi(2) analysis, statistically significant P-values (<0.05) were observed for p63, CK15, nestin, and D2-40 in the distinction of primary adnexal carcinoma versus cutaneous metastases. In logistic regression and stepwise selection for predicting a primary adnexal carcinoma, statistical significance was observed for p63, CK15, and D2-40 (P-values: <0.001, 0.0275, and 0.0298, respectively) but not for nestin (P-value = 0.4573). Our study indicates that diagnostic sensitivity and specificity are significantly improved using a selected panel of immunohistochemical markers, including p63, CK15, and D2-40. Positive staining with all three markers argues in favor of a primary cutaneous adnexal neoplasm. Modern Pathology (2010) 23, 713-719; doi: 10.1038/modpathol.2010.46; published online 26 February 2010 C1 [Hoang, Mai P.] Massachusetts Gen Hosp, Dermatopathol Unit, Dept Pathol, Boston, MA 02114 USA. [Mahalingam, Meera; Nguyen, Lisa P.; Richards, Joanna E.] Boston Univ, Sch Med, Dept Dermatol, Dermatopathol Sect, Boston, MA 02118 USA. [Muzikansky, Alona] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Hoang, Mai P.] Harvard Univ, Sch Med, Boston, MA USA. RP Hoang, MP (reprint author), Massachusetts Gen Hosp, Dermatopathol Unit, Dept Pathol, 55 Fruit St,Warren 820, Boston, MA 02114 USA. EM mhoang@partners.org OI Mahalingam, Meera/0000-0002-2800-9985 NR 34 TC 38 Z9 38 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD MAY PY 2010 VL 23 IS 5 BP 713 EP 719 DI 10.1038/modpathol.2010.46 PG 7 WC Pathology SC Pathology GA 590UE UT WOS:000277252900010 PM 20190734 ER PT J AU Smith, BL AF Smith, Barbara L. TI Clinical applications of breast pathology: management of in situ breast carcinomas and sentinel node biopsy issues SO MODERN PATHOLOGY LA English DT Article DE sentinel node biopsy; breast cancer; ductal carcinoma in situ ID QUALITY-OF-LIFE; LYMPH-NODE; AXILLARY DISSECTION; CANCER PATIENTS; MORBIDITY; LYMPHADENECTOMY; ARM; MICROMETASTASES; SURGERY; EDEMA AB The purpose of this article is to review the current clinical management of in situ breast carcinomas, including how specific aspects of a pathology report are used in clinical decision-making, and to discuss the current role of sentinel node biopsy in management of invasive breast carcinomas and ductal carcinoma in situ of the breast. Modern Pathology (2010) 23, S33-S35; doi:10.1038/modpathol.2010.53 C1 Massachusetts Gen Hosp, Gillette Ctr Womens Cancers, Boston, MA 02114 USA. RP Smith, BL (reprint author), Massachusetts Gen Hosp, Gillette Ctr Womens Cancers, Yawkey 9A,55 Fruit St, Boston, MA 02114 USA. EM blsmith1@partners.org NR 32 TC 4 Z9 4 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD MAY PY 2010 VL 23 SU 2 BP S33 EP S35 DI 10.1038/modpathol.2010.53 PG 3 WC Pathology SC Pathology GA 590SR UT WOS:000277248500005 PM 20436500 ER PT J AU Levitt, JM Yamashita, H Jian, WG Lerner, SP Sonpavde, G AF Levitt, Jonathan M. Yamashita, Hideyuki Jian, Weiguo Lerner, Seth P. Sonpavde, Guru TI Dasatinib Is Preclinically Active against Src-Overexpressing Human Transitional Cell Carcinoma of the Urothelium with Activated Src Signaling SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID FAMILY KINASE INHIBITOR; OVARIAN-CANCER CELLS; NUDE-MOUSE MODEL; TYROSINE KINASE; ADENOCARCINOMA CELLS; PROSTATE-CANCER; BLADDER-CANCER; CYCLE ARREST; EXPRESSION; APOPTOSIS AB Dasatinib is an orally administered multitargeted kinase inhibitor that targets Src family tyrosine kinases, Abl, c-Kit, and PDGFR. A preclinical study was conducted to evaluate dasatinib alone or combined with cisplatin for human transitional cell carcinoma (TCC). Expression of Src in a human TCC tissue microarray was evaluated by immunohistochemistry. The activity of dasatinib and/or cisplatin was evaluated in six human TCC cell lines. Western blot was done to assess Src and phosphorylated-Src (p-Src) expression. The activity of dasatinib alone and in combination with cisplatin was determined in murine subcutaneous xenografts. Sixty-two percent to 75% of human TCC expressed Src. Dasatinib displayed significant antiproliferative activity at nanomolar concentrations against two human TCC cell lines (RT4 and Hu456) that exhibited high Src and p-Src expression and were cisplatin-resistant. RT4 cells were the most sensitive and displayed the highest level of Src pathway activation (p-Src/Src ratio). Dasatinib downregulated p-Src in either sensitive or resistant cells. TCC cells that were sensitive to cisplatin (5637 and TCC-SUP) were highly resistant to dasatinib and exhibited low Src expression. Dasatinib showed antitumor activity in RT4 murine xenografts, and the combination of dasatinib and cisplatin was significantly more active than placebo. Combination dasatinib plus cisplatin significantly inhibited proliferation and promoted apoptosis in vivo. In conclusion, dasatinib displayed significant preclinical antitumor activity against Src-overexpressing human TCC with active Src signaling and was highly active in combination with cisplatin in vivo. Further clinical development might be warranted in selected human subjects. Mol Cancer Ther; 9(5); 1128-35. (C) 2010 AACR. C1 [Levitt, Jonathan M.; Yamashita, Hideyuki; Jian, Weiguo; Lerner, Seth P.; Sonpavde, Guru] Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA. [Levitt, Jonathan M.] Baylor Coll Med, Dept Immunol, Houston, TX 77030 USA. [Sonpavde, Guru] Baylor Coll Med, Dept Med, Sect Med Oncol, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Sonpavde, G (reprint author), 501 Med Ctr Blvd, Webster, TX 77598 USA. EM gurus@bcm.edu FU Bristol-Myers Squibb FX G. Sonpavde and S. P. Lerner: research funding, Bristol-Myers Squibb. No other potential conflicts of interest were disclosed. NR 34 TC 17 Z9 17 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD MAY PY 2010 VL 9 IS 5 BP 1128 EP 1135 DI 10.1158/1535-7163.MCT-10-0096 PG 8 WC Oncology SC Oncology GA 607GQ UT WOS:000278487500007 PM 20406945 ER PT J AU Zhang, Y Askenazi, M Jiang, JR Luckey, CJ Griffin, JD Marto, JA AF Zhang, Yi Askenazi, Manor Jiang, Jingrui Luckey, C. John Griffin, James D. Marto, Jarrod A. TI A Robust Error Model for iTRAQ Quantification Reveals Divergent Signaling between Oncogenic FLT3 Mutants in Acute Myeloid Leukemia SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article; Proceedings Paper CT 9th International Symposium on Mass Spectrometry in the Health and Life Sciences CY AUG 23-27, 2009 CL San Francisco, CA ID MULTIPLEXED PROTEIN QUANTITATION; TYROSINE-PHOSPHATASE SHP-1; HYBRID MASS-SPECTROMETER; LIQUID-CHROMATOGRAPHY; NEGATIVE REGULATION; VARIANCE FUNCTION; NOISE MODEL; ION-TRAP; BCR-ABL; KINASE AB The FLT3 receptor tyrosine kinase plays an important role in normal hematopoietic development and leukemogenesis. Point mutations within the activation loop and inframe tandem duplications of the juxtamembrane domain represent the most frequent molecular abnormalities observed in acute myeloid leukemia. Interestingly these gain-of-function mutations correlate with different clinical outcomes, suggesting that signals from constitutive FLT3 mutants activate different downstream targets. In principle, mass spectrometry offers a powerful means to quantify protein phosphorylation and identify signaling events associated with constitutively active kinases or other oncogenic events. However, regulation of individual phosphorylation sites presents a challenging case for proteomics studies whereby quantification is based on individual peptides rather than an average across different peptides derived from the same protein. Here we describe a robust experimental framework and associated error model for iTRAQ-based quantification on an Orbitrap mass spectrometer that relates variance of peptide ratios to mass spectral peak height and provides for assignment of p value, q value, and confidence interval to every peptide identification, all based on routine measurements, obviating the need for detailed characterization of individual ion peaks. Moreover, we demonstrate that our model is stable over time and can be applied in a manner directly analogous to ubiquitously used external mass calibration routines. Application of our error model to quantitative proteomics data for FLT3 signaling provides evidence that phosphorylation of tyrosine phosphatase SHP1 abrogates the transformative potential, but not overall kinase activity, of FLT3-D835Y in acute myeloid leukemia. Molecular & Cellular Proteomics 9: 780-790, 2010. C1 [Zhang, Yi; Askenazi, Manor; Marto, Jarrod A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Jiang, Jingrui; Griffin, James D.] Harvard Univ, Sch Med, Dept Med Oncol, Boston, MA 02115 USA. [Zhang, Yi; Askenazi, Manor; Marto, Jarrod A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Blais Prote Ctr, Boston, MA 02115 USA. [Askenazi, Manor; Marto, Jarrod A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Luckey, C. John] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Askenazi, Manor] Hebrew Univ Jerusalem, Dept Biol Chem, IL-919004 Jerusalem, Israel. RP Marto, JA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St,Smith 1158A, Boston, MA 02115 USA. EM jarrod_marto@dfci.harvard.edu FU NHGRI NIH HHS [P50 HG004233, P50HG004233] NR 59 TC 39 Z9 39 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD MAY PY 2010 VL 9 IS 5 BP 780 EP 790 DI 10.1074/mcp.M900452-MCP200 PG 11 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 618ZX UT WOS:000279396700004 PM 20019052 ER PT J AU Argetsinger, LS Stuckey, JA Robertson, SA Koleva, RI Cline, JM Marto, JA Myers, MG Carter-Su, C AF Argetsinger, Lawrence S. Stuckey, Jeanne A. Robertson, Scott A. Koleva, Rositsa I. Cline, Joel M. Marto, Jarrod A. Myers, Martin G., Jr. Carter-Su, Christin TI Tyrosines 868, 966, and 972 in the Kinase Domain of JAK2 Are Autophosphorylated and Required for Maximal JAK2 Kinase Activity SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID GROWTH-HORMONE RECEPTOR; PHOSPHORYLATION SITES; SIGNAL-TRANSDUCTION; PROTEIN-KINASES; LEPTIN RECEPTOR; MEK/ERK PATHWAY; ACTIVATION; IDENTIFICATION; SH2-B-BETA; FAMILY AB Janus kinase 2 (JAK2) is activated by a majority of cytokine family receptors including receptors for GH, leptin, and erythropoietin. To identify novel JAK2-regulatory and/or -binding sites, we set out to identify autophosphorylation sites in the kinase domain of JAK2. Two-dimensional phosphopeptide mapping of in vitro autophosphorylated JAK2 identified tyrosines 868, 966, and 972 as sites of autophosphorylation. Phosphorylated tyrosines 868 and 972 were also identified by mass spectrometry analysis of JAK2 activated by an erythropoietin-bound chimeric erythropoietin receptor/leptin receptor. Phosphospecific antibodies suggest that the phosphorylation of all three tyrosines increases in response to GH. Compared with wild-type JAK2, which is constitutively active when overexpressed, JAK2 lacking tyrosine 868, 966, or 972 has substantially reduced activity. Coexpression with GH receptor and protein tyrosine phosphatase1B allowed us to investigate GH-dependent activation of these mutated JAK2s in human embryonic kidney 293T cells. All three mutated JAK2s are activated by GH, although to a lesser extent than wild-type JAK2. The three mutated JAK2s also mediate GH activation of signal transducer and activator of transcription 3 (Stat3), signal transducer and activator of transcription 5b (Stat5b) and ERK1, but at reduced levels. Coexpression with Src-homology 2B1 beta (SH2B1 beta), like coexpression with GH-bound GH receptor, partially restores the activity of all three JAK2 mutants. Based on these results and the crystal structure of the JAK2 kinase domain, we hypothesize that small changes in the conformation of the regions of JAK2 surrounding tyrosines 868, 966, and 972 due to e. g. phosphorylation, binding to a ligand-bound cytokine receptor, and/or binding to Src-homology 2B1, may be essential for JAK2 to assume a maximally active conformation. (Molecular Endocrinology 24: 1062-1076, 2010) C1 [Argetsinger, Lawrence S.; Robertson, Scott A.; Cline, Joel M.; Myers, Martin G., Jr.; Carter-Su, Christin] Univ Michigan, Sch Med, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA. [Stuckey, Jeanne A.] Univ Michigan, Sch Med, Dept Biol Chem, Ann Arbor, MI 48109 USA. Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA. [Robertson, Scott A.; Myers, Martin G., Jr.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA. [Koleva, Rositsa I.; Marto, Jarrod A.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Carter-Su, C (reprint author), Univ Michigan, Sch Med, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA. EM cartersu@umich.edu FU National Institutes of Health (NIH) [DK34171]; Michigan Economic Development Corporation; University of Michigan Center for Structural Biology; NIH [DK56731]; American Diabetes Association; American Heart Association; Michigan Diabetes Research and Training Center [P60-DK20572]; University of Michigan Multipurpose Arthritis Center [P60-AR20557]; University of Michigan Comprehensive Cancer Center [NIH P30 CA46592] FX This work was supported by National Institutes of Health (NIH) Grant DK34171 (to C.C.-S.), the Michigan Economic Development Corporation for the Michigan Life Sciences Corridor Initiative (to J.A.S.), the University of Michigan Center for Structural Biology (to J.A.S.), and NIH DK56731 (to M. G. M.). S. R. was supported by predoctoral fellowships from the American Diabetes Association and the American Heart Association. Oligonucleotides were synthesized by the Biomedical Research Core Facility at the University of Michigan with support from the Michigan Diabetes Research and Training Center (P60-DK20572), the University of Michigan Multipurpose Arthritis Center (P60-AR20557), and the University of Michigan Comprehensive Cancer Center (NIH P30 CA46592). Synthesis of Stat5 peptide and cDNA sequencing were supported by the Peptide and Proteomics Core and Cellular and Molecular Biology Core, respectively, of the Michigan Diabetes Research and Training Center (P60-DK20572). NR 55 TC 12 Z9 13 U1 1 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD MAY PY 2010 VL 24 IS 5 BP 1062 EP 1076 DI 10.1210/me.2009-0355 PG 15 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 588LH UT WOS:000277071100016 PM 20304997 ER PT J AU Jackson, PL Xu, X Wilson, L Weathington, NM Clancy, JP Blalock, JE Gaggar, A AF Jackson, Patricia L. Xu, Xin Wilson, Landon Weathington, Nathaniel M. Clancy, John Paul Blalock, James Edwin Gaggar, Amit TI Human Neutrophil Elastase-Mediated Cleavage Sites of MMP-9 and TIMP-1: Implications to Cystic Fibrosis Proteolytic Dysfunction SO MOLECULAR MEDICINE LA English DT Article ID MATRIX METALLOPROTEINASES; TISSUE INHIBITOR; ACTIVATION; LUNG; MATRIX-METALLOPROTEINASE-9; INFLAMMATION; GELATINASE; EXPRESSION; MULTIPLE; DISEASE AB Cystic fibrosis (CF) is a lethal genetic disorder characterized by airway remodeling and inflammation, leading to premature death. Recent evidence suggests the importance of protease activity in CF pathogenesis. One prominent protease, matrix metalloprotease (MMP)-9, demonstrates increased activity in CF individuals undergoing acute pulmonary exacerbation. This is thought to be mediated by both direct MMP-9 activation and the degradation of its natural inhibitor, tissue inhibitor of metalloprotease-1 (TIMP-1). To examine if this relationship exists in nonexacerbating CF individuals, we examined protease activity in sputum from these individuals compared with nondisease controls. We demonstrated increased gelatinolytic activity in CF sputum. These samples had elevated human neutrophil elastase (HNE) levels which correlated with an increased MMP-9/TIMP-1 ratio. To determine if HNE could discretely cleave and activate MMP-9, these enzymes were coincubated and two specific cleavage sites, between Valine(38) and Alanine(39), and between Alanine(39) and glutamic acid(40) were observed. These sites corresponded with appropriate molecular weight for the activated MMP-9 isoform in CF sputum. Using N-terminal sequencing of cleavage fragments obtained with TIMP-1 incubation with HNE, we confirmed the TIMP-1 cleavage site for HNE is at Valine(69)-Cysteine(70). We also show for the first time that human neutrophils were capable of degrading TIMP-1 ex vivo and that a 16 kDa TIMP-1 fragment was identified in CF sputum, consistent with the expected cleavage of TIMP-1 by HNE. These results demonstrate increased MMP-9 activity in stable CF lung disease, and the presence of specific protease products in CF sputum highlights that HNE-mediated activity plays a role in this dysregulation. (C) 2010 The Feinstein Institute for Medical Research, www.feinsteininstitute.org C1 [Jackson, Patricia L.; Xu, Xin; Weathington, Nathaniel M.; Blalock, James Edwin; Gaggar, Amit] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. [Jackson, Patricia L.; Xu, Xin; Blalock, James Edwin; Gaggar, Amit] Univ Alabama, Dept Physiol & Biophys, Birmingham, AL 35294 USA. [Wilson, Landon] Univ Alabama, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Clancy, John Paul] Univ Alabama, Dept Pediat, Birmingham, AL 35294 USA. [Clancy, John Paul; Blalock, James Edwin; Gaggar, Amit] Univ Alabama, Gregory Fleming James Cyst Fibrosis Ctr, Birmingham, AL 35294 USA. [Gaggar, Amit] Birmingham VA Med Ctr, Birmingham, AL USA. RP Gaggar, A (reprint author), 1918 Univ Blvd,MCLM 898, Birmingham, AL 35294 USA. EM plj@uab.edu; agaggar@uab.edu OI Blalock, J. Edwin/0000-0001-5303-8123 FU UAB Comprehensive Cancer Center [P30 CA13148]; NHLBI; NIDDK; [S10 RR16849] FX The authors would like to thank Marion Kirk for his efforts in sequencing TIMP-1 fragments. We also would like to thank Uros Djekic for his contribution to this manuscript. We would like to thank cessing of proteomics samples were provided by NCRR Shared Instrumentation grant S10 RR16849 (HK). Funds for the operation of the Mass Spectrometry Shared Facility came in part from the UAB Comprehensive Cancer Center Core Support Grant (P30 CA13148).; This project was supported in part by grants from the NHLBI and NIDDK. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. NR 32 TC 35 Z9 37 U1 1 U2 8 PU FEINSTEIN INST MED RES PI MANHASSET PA 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1076-1551 J9 MOL MED JI Mol. Med. PD MAY-JUN PY 2010 VL 16 IS 5-6 BP 159 EP 166 DI 10.2119/molmed.2009.00109 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 593VF UT WOS:000277489000002 PM 20111696 ER PT J AU Meng, YR Mauceri, HJ Khodarev, NN Darga, TE Pitroda, SP Beckett, MA Kufe, DW Weichselbaum, RR AF Meng, Yuru Mauceri, Helena J. Khodarev, Nikolai N. Darga, Thomas E. Pitroda, Sean P. Beckett, Michael A. Kufe, Donald W. Weichselbaum, Ralph R. TI Ad.Egr-TNF and Local Ionizing Radiation Suppress Metastases by Interferon-beta-Dependent Activation of Antigen-specific CD8(+) T Cells SO MOLECULAR THERAPY LA English DT Article ID NECROSIS-FACTOR-ALPHA; INNATE IMMUNE-RESPONSE; TRANSCRIPTIONAL ACTIVATION; DENDRITIC CELLS; BREAST-CANCER; I INTERFERONS; GAMMA GENE; KAPPA-B; PHASE-I; TUMOR AB Ad.Egr-TNF is a radioinducible adenovector currently in phase 3 trials for inoperable pancreatic cancer. The combination of Ad.Egr-TNF and ionizing radiation (IR) contributes to local tumor control through the production of tumor necrosis factor-alpha (TNF alpha) in the tumor microenvironment. Moreover, clinical and preclinical studies with Ad.Egr-TNF/IR have suggested that this local approach suppresses the growth of distant metastatic disease; however, the mechanisms responsible for this effect remain unclear. These studies have been performed in wild-type (WT) and TNFR1,2(-/-) mice to assess the role of TNF alpha-induced signaling in the suppression of draining lymph node (DLN) metastases. The results demonstrate that production of TNF alpha in the tumor microenvironment induces expression of interferon (IFN beta). In turn, IFN beta stimulates the production of chemokines that recruit CD8(+) T cells to the tumor. The results further demonstrate that activation of tumor antigen-specific CD8(+) CTLs contributes to local antitumor activity and suppression of DLN metastases. These findings support a model in which treatment of tumors with Ad.Egr-TNF and IR is mediated by local and distant immune-mediated antitumor effects that suppress the development of metastases. C1 [Weichselbaum, Ralph R.] Univ Chicago, Dept Radiat & Cellular Oncol, Duchossois Ctr Adv Med, Chicago, IL 60637 USA. [Kufe, Donald W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Weichselbaum, RR (reprint author), Univ Chicago, Dept Radiat & Cellular Oncol, Duchossois Ctr Adv Med, 5758 S Maryland Ave,MC 9006, Chicago, IL 60637 USA. EM rrw@radonc.uchicago.edu FU NCI [RO-1 CA111423, P50 CA090386]; Center for Radiation Therapy; Ludwig Foundation FX This work was funded in part by grant RO-1 CA111423 from the NCI (RRW), Prostate Cancer Spore P50 CA090386, The Center for Radiation Therapy, The Ludwig Foundation, and a generous gift from the Foglia Family. R.R.W. and D.W.K. have stock in and are consultants to GenVec. NR 44 TC 7 Z9 7 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2010 VL 18 IS 5 BP 912 EP 920 DI 10.1038/mt.2010.18 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 595HR UT WOS:000277601800010 PM 20197756 ER PT J AU Kim, SS Ye, CT Kumar, P Chiu, I Subramanya, S Wu, HQ Shankar, P Manjunath, N AF Kim, Sang-Soo Ye, Chunting Kumar, Priti Chiu, Isaac Subramanya, Sandesh Wu, Haoquan Shankar, Premlata Manjunath, N. TI Targeted Delivery of siRNA to Macrophages for Anti-inflammatory Treatment SO MOLECULAR THERAPY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; NITRIC-OXIDE SYNTHASE; SMALL INTERFERING RNA; NECROSIS-FACTOR-ALPHA; NEURODEGENERATIVE DISEASE; CYTOKINE TRANSCRIPTS; SYNTHETIC SIRNAS; BRAIN; MICE; INFLAMMATION AB Inflammation mediated by tumor necrosis factor-alpha (TNF-alpha) and the associated neuronal apoptosis characterizes a number of neurologic disorders. Macrophages and microglial cells are believed to be the major source of TNF-alpha in the central nervous system (CNS). Here, we show that suppression of TNF-alpha by targeted delivery of small interfering RNA (siRNA) to macrophage/microglial cells dramatically reduces lipopolysaccharide (LPS)-induced neuroinflammation and neuronal apoptosis in vivo. Because macrophage/microglia express the nicotinic acetylcholine receptor (AchR) on their surface, we used a short AchR-binding peptide derived from the rabies virus glycoprotein (RVG) as a targeting ligand. This peptide was fused to nona-D-arginine residues (RVG-9dR) to enable siRNA binding. RVG-9dR was able to deliver siRNA to induce gene silencing in macro-phages and microglia cells from wild type, but not AchR-deficient mice, confirming targeting specificity. Treatment with anti-TNF-alpha siRNA complexed to RVG-9dR achieved efficient silencing of LPS-induced TNF-alpha production by primary macrophages and microglia cells in vitro. Moreover, intravenous injection with RVG-9dR-complexed siRNA in mice reduced the LPS-induced TNF-alpha levels in blood as well as in the brain, leading to a significant reduction in neuronal apoptosis. These results demonstrate that RVG-9dR provides a tool for siRNA delivery to macrophages and microglia and that suppression of TNF-alpha can potentially be used to suppress neuroinflammation in vivo. C1 [Kim, Sang-Soo; Ye, Chunting; Subramanya, Sandesh; Wu, Haoquan; Shankar, Premlata; Manjunath, N.] Texas Tech Univ Hlth Sci Ctr, Ctr Excellence Infect Dis, Paul L Foster Sch Med, El Paso, TX 79905 USA. [Kumar, Priti] Yale Univ, Sch Med, Dept Internal Med, Infect Dis Sect, New Haven, CT 06510 USA. [Chiu, Isaac] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA USA. RP Manjunath, N (reprint author), Texas Tech Univ Hlth Sci Ctr, Ctr Excellence Infect Dis, Paul L Foster Sch Med, 5001 El Paso Dr, El Paso, TX 79905 USA. EM manjunath.swamy@ttuhsc.edu RI Kumar, Priti/C-5699-2009 FU NIH [AI075419]; Korean Government (MOEHRD) [KRF-2006-352-D00070] FX This work was supported by NIH grant AI075419 to N.M. S.-S.K. was supported by the Korea Research Foundation Grant funded by the Korean Government (MOEHRD) (KRF-2006-352-D00070). S.-S. Kim performed research, analyzed data, and wrote the paper. C.Y. performed research, P.K. performed research, I.C. performed research, S. S. performed research, H. W. performed research, P. S. designed research, and N.M. designed research and wrote the paper. NR 35 TC 86 Z9 88 U1 1 U2 19 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2010 VL 18 IS 5 BP 993 EP 1001 DI 10.1038/mt.2010.27 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 595HR UT WOS:000277601800020 PM 20216529 ER PT J AU Kwiatkowski, N Jelluma, N Filippakopoulos, P Soundararajan, M Manak, MS Kwon, M Choi, HG Sim, T Deveraux, QL Rottmann, S Pellman, D Shah, JV Kops, GJPL Knapp, S Gray, NS AF Kwiatkowski, Nicholas Jelluma, Nannette Filippakopoulos, Panagis Soundararajan, Meera Manak, Michael S. Kwon, Mijung Choi, Hwan Geun Sim, Taebo Deveraux, Quinn L. Rottmann, Sabine Pellman, David Shah, Jagesh V. Kops, Geert J. P. L. Knapp, Stefan Gray, Nathanael S. TI Small-molecule kinase inhibitors provide insight into Mps1 cell cycle function SO NATURE CHEMICAL BIOLOGY LA English DT Article ID SPINDLE-ASSEMBLY CHECKPOINT; POLE BODY DUPLICATION; RECEPTOR TYROSINE KINASE; GROWTH IN-VIVO; MITOTIC CHECKPOINT; CENTROSOME DUPLICATION; KINETOCHORE LOCALIZATION; CHROMOSOMAL INSTABILITY; EXTRA CENTROSOMES; PROTEIN-KINASE AB Mps1, a dual-specificity kinase, is required for the proper functioning of the spindle assembly checkpoint and for the maintenance of chromosomal stability. As Mps1 function has been implicated in numerous phases of the cell cycle, the development of a potent, selective small-molecule inhibitor of Mps1 should facilitate dissection of Mps1-related biology. We describe the cellular effects and Mps1 cocrystal structures of new, selective small-molecule inhibitors of Mps1. Consistent with RNAi studies, chemical inhibition of Mps1 leads to defects in Mad1 and Mad2 establishment at unattached kinetochores, decreased Aurora B kinase activity, premature mitotic exit and gross aneuploidy, without any evidence of centrosome duplication defects. However, in U2OS cells having extra centrosomes (an abnormality found in some cancers), Mps1 inhibition increases the frequency of multipolar mitoses. Lastly, Mps1 inhibitor treatment resulted in a decrease in cancer cell viability. C1 [Kwiatkowski, Nicholas; Choi, Hwan Geun; Sim, Taebo; Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Kwiatkowski, Nicholas; Choi, Hwan Geun; Sim, Taebo; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Jelluma, Nannette; Kops, Geert J. P. L.] Univ Med Ctr Utrecht, Dept Physiol Chem, Utrecht, Netherlands. [Jelluma, Nannette; Kops, Geert J. P. L.] Univ Med Ctr Utrecht, Canc Genom Ctr, Utrecht, Netherlands. [Filippakopoulos, Panagis; Soundararajan, Meera; Knapp, Stefan] Univ Oxford, Struct Genom Consortium, Oxford, England. [Filippakopoulos, Panagis; Soundararajan, Meera; Knapp, Stefan] Univ Oxford, Dept Clin Pharmacol, Oxford, England. [Manak, Michael S.; Shah, Jagesh V.] Brigham & Womens Hosp, Div Renal, Harvard Inst Med, Boston, MA 02115 USA. [Kwon, Mijung; Pellman, David] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Deveraux, Quinn L.; Rottmann, Sabine] Novartis Res Fdn, Genom Inst, San Diego, CA USA. RP Gray, NS (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. EM nathanael_gray@dfci.harvard.edu OI Kops, Geert/0000-0003-3555-5295; Filippakopoulos, Panagis/0000-0002-1515-1317; Knapp, Stefan/0000-0001-5995-6494 FU Canadian Institutes for Health Research; Canadian Foundation for Innovation, Genome Canada; Knut and Alice Wallenberg Foundation; Ontario Innovation Trust; Ontario Ministry for Research and Innovation, Merck Co., Inc.; Novartis Research Foundation; Swedish Agency for Innovation Systems; Swedish Foundation for Strategic Research; Wellcome Trust FX We thank R. King ( Harvard Medical School), B. Vogelstein ( Howard Hughes Medical Institute and Johns Hopkins Medical Institutions) and E. Nigg ( Max Planck Institute of Biochemistry, Munich) for reagents and R. King, T. Mitchison, A. Abrieu, U. Eggert, C. Walsh, F. Sigoillot and E. Chung for helpful discussions. We also thank Ambit Biosciences and Invitrogen Corporation for technical support in the initial compound screening and enzymatic activity assays, respectively, as well as the Nikon Imaging Facility ( Harvard Medical School) and the Dana-Farber Flow Cytometry Lab for technical help and instrument use. The Structural Genomics Consortium is a registered charity (number 1097737) that receives funds from the Canadian Institutes for Health Research, the Canadian Foundation for Innovation, Genome Canada through the Ontario Genomics Institute, GlaxoSmithKline, Karolinska Institutet, the Knut and Alice Wallenberg Foundation, the Ontario Innovation Trust, the Ontario Ministry for Research and Innovation, Merck & Co., Inc., the Novartis Research Foundation, the Swedish Agency for Innovation Systems, the Swedish Foundation for Strategic Research and the Wellcome Trust. NR 50 TC 116 Z9 117 U1 0 U2 18 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1552-4450 J9 NAT CHEM BIOL JI Nat. Chem. Biol. PD MAY PY 2010 VL 6 IS 5 BP 359 EP 368 DI 10.1038/nchembio.345 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 585KC UT WOS:000276823200015 PM 20383151 ER PT J AU Furberg, H Kim, Y Dackor, J Boerwinkle, E Franceschini, N Ardissino, D Bernardinelli, L Mannucci, PM Mauri, F Merlini, PA Absher, D Assimes, TL Fortmann, SP Iribarren, C Knowles, JW Quertermous, T Ferrucci, L Tanaka, T Bis, JC Furberg, CD Haritunians, T McKnight, B Psaty, BM Taylor, KD Thacker, EL Almgren, P Groop, L Ladenvall, C Boehnke, M Jackson, AU Mohlke, KL Stringham, HM Tuomilehto, J Benjamin, EJ Hwang, SJ Levy, D Preis, SR Vasan, RS Duan, J Gejman, PV Levinson, DF Sanders, AR Shi, JX Lips, EH Mckay, JD Agudo, A Barzan, L Bencko, V Benhamou, S Castellsague, X Canova, C Conway, DI Fabianova, E Foretova, L Janout, V Healy, CM Holcatova, I Kjaerheim, K Lagiou, P Lissowska, J Lowry, R Macfarlane, TV Mates, D Richiardi, L Rudnai, P Szeszenia-Dabrowska, N Zaridze, D Znaor, A Lathrop, M Brennan, P Bandinelli, S Frayling, TM Guralnik, JM Milaneschi, Y Perry, JRB Altshuler, D Elosua, R Kathiresan, S Lucas, G Melander, O O'Donnell, CJ Salomaa, V Schwartz, SM Voight, BF Penninx, BW Smit, JH Vogelzangs, N Boomsma, DI de Geus, EJC Vink, JM Willemsen, G Chanock, SJ Gu, FY Hankinson, SE Hunter, DJ Hofman, A Tiemeier, H Uitterlinden, AG van Duijn, CM Walter, S Chasman, DI Everett, BM Pare, G Ridker, PM Li, MD Maes, HH Audrain-McGovern, J Posthuma, D Thornton, LM Lerman, C Kaprio, J Rose, JE Ioannidis, JPA Kraft, P Lin, DY Sullivan, PF AF Furberg, Helena Kim, YunJung Dackor, Jennifer Boerwinkle, Eric Franceschini, Nora Ardissino, Diego Bernardinelli, Luisa Mannucci, Pier M. Mauri, Francesco Merlini, Piera A. Absher, Devin Assimes, Themistocles L. Fortmann, Stephen P. Iribarren, Carlos Knowles, Joshua W. Quertermous, Thomas Ferrucci, Luigi Tanaka, Toshiko Bis, Joshua C. Furberg, Curt D. Haritunians, Talin McKnight, Barbara Psaty, Bruce M. Taylor, Kent D. Thacker, Evan L. Almgren, Peter Groop, Leif Ladenvall, Claes Boehnke, Michael Jackson, Anne U. Mohlke, Karen L. Stringham, Heather M. Tuomilehto, Jaakko Benjamin, Emelia J. Hwang, Shih-Jen Levy, Daniel Preis, Sarah Rosner Vasan, Ramachandran S. Duan, Jubao Gejman, Pablo V. Levinson, Douglas F. Sanders, Alan R. Shi, Jianxin Lips, Esther H. Mckay, James D. Agudo, Antonio Barzan, Luigi Bencko, Vladimir Benhamou, Simone Castellsague, Xavier Canova, Cristina Conway, David I. Fabianova, Eleonora Foretova, Lenka Janout, Vladimir Healy, Claire M. Holcatova, Ivana Kjaerheim, Kristina Lagiou, Pagona Lissowska, Jolanta Lowry, Ray Macfarlane, Tatiana V. Mates, Dana Richiardi, Lorenzo Rudnai, Peter Szeszenia-Dabrowska, Neonilia Zaridze, David Znaor, Ariana Lathrop, Mark Brennan, Paul Bandinelli, Stefania Frayling, Timothy M. Guralnik, Jack M. Milaneschi, Yuri Perry, John R. B. Altshuler, David Elosua, Roberto Kathiresan, Sek Lucas, Gavin Melander, Olle O'Donnell, Christopher J. Salomaa, Veikko Schwartz, Stephen M. Voight, Benjamin F. Penninx, Brenda W. Smit, Johannes H. Vogelzangs, Nicole Boomsma, Dorret I. de Geus, Eco J. C. Vink, Jacqueline M. Willemsen, Gonneke Chanock, Stephen J. Gu, Fangyi Hankinson, Susan E. Hunter, David J. Hofman, Albert Tiemeier, Henning Uitterlinden, Andre G. van Duijn, Cornelia M. Walter, Stefan Chasman, Daniel I. Everett, Brendan M. Pare, Guillaume Ridker, Paul M. Li, Ming D. Maes, Hermine H. Audrain-McGovern, Janet Posthuma, Danielle Thornton, Laura M. Lerman, Caryn Kaprio, Jaakko Rose, Jed E. Ioannidis, John P. A. Kraft, Peter Lin, Dan-Yu Sullivan, Patrick F. TI Genome-wide meta-analyses identify multiple loci associated with smoking behavior SO NATURE GENETICS LA English DT Article ID NICOTINE DEPENDENCE; ENVIRONMENTAL-FACTORS; IMPUTATION; GENES; VARIANTS; DISEASES; SETS AB Consistent but indirect evidence has implicated genetic factors in smoking behavior1,2. We report meta-analyses of several smoking phenotypes within cohorts of the Tobacco and Genetics Consortium (n = 74,053). We also partnered with the European Network of Genetic and Genomic Epidemiology (ENGAGE) and Oxford-GlaxoSmithKline (Ox-GSK) consortia to follow up the 15 most significant regions (n > 140,000). We identified three loci associated with number of cigarettes smoked per day. The strongest association was a synonymous 15q25 SNP in the nicotinic receptor gene CHRNA3 (rs1051730[A], b = 1.03, standard error (s.e.) = 0.053, beta = 2.8 x 10(-73)). Two 10q25 SNPs (rs1329650[G], b = 0.367, s. e. = 0.059, beta = 5.7 x 10(-10); and rs1028936[A], b = 0.446, s. e. = 0.074, beta = 1.3 x 10(-9)) and one 9q13 SNP in EGLN2 (rs3733829[G], b = 0.333, s. e. = 0.058, P = 1.0 x 10(-8)) also exceeded genome-wide significance for cigarettes per day. For smoking initiation, eight SNPs exceeded genome-wide significance, with the strongest association at a nonsynonymous SNP in BDNF on chromosome 11 (rs6265[C], odds ratio (OR) = 1.06, 95% confidence interval (Cl) 1.04-1.08, P = 1.8 x 10(-8)). One SNP located near DBH on chromosome 9 (rs3025343[G], OR = 1.12, 95% Cl 1.08-1.18, P = 3.6 x 10(-8)) was significantly associated with smoking cessation. C1 [Furberg, Helena; Kim, YunJung; Dackor, Jennifer; Mohlke, Karen L.; Ioannidis, John P. A.; Sullivan, Patrick F.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27515 USA. [Furberg, Helena; Mohlke, Karen L.; Ioannidis, John P. A.; Sullivan, Patrick F.] Univ N Carolina, Univ N Carolina Lineberger Comprehens Canc Ct, Chapel Hill, NC USA. [Boerwinkle, Eric; Lin, Dan-Yu] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX USA. [Boerwinkle, Eric; Lin, Dan-Yu] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX USA. [Franceschini, Nora] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Ardissino, Diego] Univ Parma, Azienda Osped, Div Cardiol, I-43100 Parma, Italy. [Bernardinelli, Luisa] Univ Cambridge, Stat Lab, Ctr Math Sci, Cambridge CB2 1SB, England. [Bernardinelli, Luisa] Univ Pavia, Dept Appl Hlth Sci, I-27100 Pavia, Italy. [Mannucci, Pier M.] Univ Milan, Dept Internal Med & Med Specialties, Fondaz Ist Ricovero & Cura Carattere Sci, Osped Maggiore, Milan, Italy. [Mauri, Francesco; Merlini, Piera A.] Azienda Osped Niguarda Ca Granda, Dept Cardiol, Milan, Italy. [Absher, Devin; Ioannidis, John P. A.; Lin, Dan-Yu] HudsonAlpha Inst Biotechnol, Huntsville, AL USA. [Assimes, Themistocles L.; Knowles, Joshua W.; Quertermous, Thomas] Stanford Univ, Stanford, CA 94305 USA. [Fortmann, Stephen P.] Stanford Univ, Stanford Prevent Res Ctr, Stanford, CA 94305 USA. [Iribarren, Carlos] Kaiser Permanente No Calif Div Res, Oakland, CA USA. [Tanaka, Toshiko] NIA, Medstart Res Inst, Baltimore, MD 21224 USA. [Bis, Joshua C.; McKnight, Barbara; Psaty, Bruce M.; Thacker, Evan L.; Schwartz, Stephen M.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Bis, Joshua C.; Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Furberg, Curt D.] Wake Forest Univ Hlth Sci, Div Publ Hlth Sci, Winston Salem, NC USA. [Haritunians, Talin; Taylor, Kent D.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [McKnight, Barbara] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Epidemiol & Hlth Serv, Seattle, WA 98195 USA. [Psaty, Bruce M.] Grp Hlth Res Inst, Seattle, WA USA. [Thacker, Evan L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Almgren, Peter; Groop, Leif; Ladenvall, Claes] Lund Univ, Diabet & Endocrinol Unit, Dept Clin Sci, Malmo, Sweden. [Boehnke, Michael; Jackson, Anne U.; Stringham, Heather M.] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA. [Tuomilehto, Jaakko; Kaprio, Jaakko] Univ Helsinki, Dept Publ Hlth, Hjelt Inst, Helsinki, Finland. [Tuomilehto, Jaakko] Natl Inst Hlth & Welf, Diabet Prevent Unit, Helsinki, Finland. [Tuomilehto, Jaakko] Finland S Ostrobothnia Cent Hosp, Seinajoki, Finland. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA. [Hwang, Shih-Jen; Preis, Sarah Rosner] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Levy, Daniel; Vasan, Ramachandran S.] Boston Univ, Sect Prevent Med, Dept Med, Sch Med, Boston, MA 02118 USA. [Levy, Daniel; Vasan, Ramachandran S.] Boston Univ, Cardiol Sect, Dept Med, Sch Med, Boston, MA 02118 USA. [Duan, Jubao; Gejman, Pablo V.; Sanders, Alan R.] NorthShore Univ, Ctr Psychiat Genet, HealthSyst Res Inst, Evanston, IL USA. [Levinson, Douglas F.] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Shi, Jianxin] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Lips, Esther H.; Mckay, James D.; Brennan, Paul] IARC, Lyon, France. [Agudo, Antonio; Castellsague, Xavier] Inst Catala Oncol, Barcelona, Spain. [Barzan, Luigi] Gen Hosp, Pordenone, Italy. [Bencko, Vladimir; Holcatova, Ivana] Charles Univ Prague, Fac Med 1, Inst Hyg & Epidemiol, Prague, Czech Republic. [Benhamou, Simone] INSERM, U794, Paris, France. [Benhamou, Simone] Inst Gustave Roussy, Villejuif, France. [Canova, Cristina] Univ Padua, Dept Environm Med & Publ Hlth, Padua, Italy. [Conway, David I.] Univ Glasgow, Sch Dent, Fac Med, Glasgow, Lanark, Scotland. [Fabianova, Eleonora] Specialized Inst Hyg & Epidemiol, Banska Bystrica, Slovakia. [Foretova, Lenka] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic. [Janout, Vladimir] Palacky Univ, CR-77147 Olomouc, Czech Republic. [Healy, Claire M.] Trinity Coll Dublin, Sch Dent Sci, Dublin, Ireland. [Kjaerheim, Kristina] Canc Registry Norway, Oslo, Norway. [Lagiou, Pagona] Univ Athens, Sch Med, GR-11527 Athens, Greece. [Lissowska, Jolanta] Maria Sklodowska Curie Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland. [Lissowska, Jolanta] Inst Oncol, Warsaw, Poland. [Lowry, Ray] Univ Newcastle, Sch Dent, Newcastle Upon Tyne, Tyne & Wear, England. [Macfarlane, Tatiana V.] Univ Aberdeen, Sch Med, Aberdeen AB9 2ZD, Scotland. [Mates, Dana] Inst Publ Hlth, Bucharest, Romania. [Richiardi, Lorenzo] Univ Turin, Ctr Expt Res & Med Studies, Turin, Italy. [Rudnai, Peter] Natl Inst Environm Hlth, Budapest, Hungary. [Szeszenia-Dabrowska, Neonilia] Inst Occupat Med, Dept Epidemiol, Lodz, Poland. [Zaridze, David] Inst Carcinogenesis Canc Res Ctr, Moscow, Russia. [Znaor, Ariana] Croatian Natl Canc Registry, Zagreb, Croatia. [Lathrop, Mark] Inst Genom Comissariat Energie Atom, Ctr Natl Genotypage, Evry, France. [Lathrop, Mark] Fondat Jean Dausset Ctr Etud Polymorphisme Humain, Paris, France. [Bandinelli, Stefania] Azienda Sanitaria Firenze, Geriatr Unit, Florence, Italy. [Frayling, Timothy M.; Perry, John R. B.] Univ Exeter, Peninsula Med Sch, Genet Complex Traits, Exeter, Devon, England. [Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD USA. [Milaneschi, Yuri] Tuscany Hlth Reg Agcy, Florence, Italy. [Altshuler, David; Kathiresan, Sek] Broad Inst Harvard, Cambridge, MA USA. [Altshuler, David; Kathiresan, Sek] MIT, Cambridge, MA 02139 USA. [Altshuler, David] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Altshuler, David] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. [Altshuler, David; Kathiresan, Sek] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Altshuler, David] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Elosua, Roberto; Lucas, Gavin] Inst Municipal Invest Med, E-08003 Barcelona, Spain. [Melander, Olle] Lund Univ, Malmo Univ Hosp, Dept Clin Sci Hypertens & Cardiovasc Dis, Malmo, Sweden. [O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Salomaa, Veikko; Kaprio, Jaakko] Natl Inst Hlth & Welf THL, Helsinki, Finland. [Voight, Benjamin F.] Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Penninx, Brenda W.; Smit, Johannes H.; Vogelzangs, Nicole] Vrije Univ VU, EMGO Inst, Med Ctr, Amsterdam, Netherlands. [Penninx, Brenda W.; Smit, Johannes H.; Vogelzangs, Nicole] Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, Amsterdam, Netherlands. [Boomsma, Dorret I.; de Geus, Eco J. C.; Vink, Jacqueline M.; Willemsen, Gonneke] Vrije Univ Amsterdam, Amsterdam, Netherlands. [Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Gu, Fangyi; Hunter, David J.; Kraft, Peter] Harvard Univ, Dept Epidemiol, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. [Hankinson, Susan E.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [Hofman, Albert; Tiemeier, Henning; Uitterlinden, Andre G.; van Duijn, Cornelia M.; Walter, Stefan] Erasmus MC, Member Netherlands Consortium Healthy Aging, Dept Epidemiol, Rotterdam, Netherlands. [Tiemeier, Henning] Erasmus MC, Dept Child & Adolescent Psychiat, Rotterdam, Netherlands. [Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [van Duijn, Cornelia M.] Erasmus MC, Ctr Med Syst Biol, Rotterdam, Netherlands. [Walter, Stefan] Erasmus MC, Dept Publ Hlth, Rotterdam, Netherlands. [Chasman, Daniel I.; Everett, Brendan M.; Pare, Guillaume; Ridker, Paul M.] Harvard Univ, Brigham & Womens Hosp, Dept Med, Div Prevent Med,Sch Med, Boston, MA 02115 USA. [Everett, Brendan M.; Ridker, Paul M.] Harvard Univ, Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med,Sch Med, Boston, MA 02115 USA. [Li, Ming D.] Univ Virginia, Dept Psychiat & Neurobehav Sci, Charlottesville, VA USA. [Maes, Hermine H.] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA. [Maes, Hermine H.] Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA USA. [Audrain-McGovern, Janet; Lerman, Caryn] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Posthuma, Danielle] Vrije Univ Amsterdam, Dept Funct Gen, Amsterdam, Netherlands. [Posthuma, Danielle] Vrije Univ Amsterdam, Med Ctr Amsterdam, Dept Med Genom, Amsterdam, Netherlands. [Thornton, Laura M.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [Lerman, Caryn] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Kaprio, Jaakko] Univ Helsinki, Inst Mol Med, Helsinki, Finland. [Rose, Jed E.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA. [Ioannidis, John P. A.] Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece. Tufts Univ, Sch Med, Tufts Clin & Translat Sci Inst, Boston, MA 02111 USA. Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Ctr Genet Epidemiol & Modeling, Boston, MA USA. Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. RP Furberg, H (reprint author), Univ N Carolina, Dept Genet, Chapel Hill, NC 27515 USA. EM helena_furberg@med.unc.edu; pfsulliv@med.unc.edu RI de Geus, Eco/M-9318-2015; Benhamou, Simone/K-6554-2015; Castellsague, Xavier/N-5795-2014; Kaprio, Jaakko/A-1820-2008; Hernandez, Tonia/J-9335-2012; Zaridze, David/K-5605-2013; Mannucci, Pier/C-3102-2014; Gu, Fangyi/I-5957-2014; Janout, Vladimir/M-5133-2014; ****, ****/F-3368-2011; Voight, Benjamin/F-1775-2011; Ioannidis, John/G-9836-2011; Vink, Jacqueline/A-7648-2012; Lucas, Gavin/D-4346-2012; Altshuler, David/A-4476-2009; Szeszenia-Dabrowska, Neonila/F-7190-2010; OI de Geus, Eco/0000-0001-6022-2666; Castellsague, Xavier/0000-0002-0802-3595; ELOSUA, ROBERTO/0000-0001-8235-0095; Agudo, Antonio/0000-0001-9900-5677; Thacker, Evan/0000-0002-3813-0885; mates, dana/0000-0002-6219-9807; Lissowska, Jolanta/0000-0003-2695-5799; Ramachandran, Vasan/0000-0001-7357-5970; Macfarlane, Tatiana/0000-0002-9392-0812; Altshuler, David/0000-0002-7250-4107; richiardi, lorenzo/0000-0003-0316-9402; Tiemeier, Henning/0000-0002-4395-1397; Benjamin, Emelia/0000-0003-4076-2336; Kjaerheim, Kristina/0000-0003-0691-3735; Healy, Claire M/0000-0001-7940-4611; Kaprio, Jaakko/0000-0002-3716-2455 FU University of North Carolina Lineberger Comprehensive Cancer Center University; US National Cancer Institute [K07 CA118412]; Netherlands Scientific Organization [NWO 480-05-003] FX This work was funded by the University of North Carolina Lineberger Comprehensive Cancer Center University Cancer Research Fund Award and by US National Cancer Institute K07 CA118412 to H. F. Statistical analyses were carried out on the Genetic Cluster Computer (see URLs), which is supported by the Netherlands Scientific Organization (NWO 480-05-003). Acknowledgments for studies included in TAG are listed in the Supplementary Note. NR 41 TC 346 Z9 346 U1 9 U2 60 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 MAY PY 2010 VL 42 IS 5 BP 441 EP U134 DI 10.1038/ng.571 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 589UK UT WOS:000277179500017 ER PT J AU Gonzalez, SF Lukacs-Kornek, V Kuligowski, MP Pitcher, LA Degn, SE Kim, YA Cloninger, MJ Martinez-Pomares, L Gordon, S Turley, SJ Carroll, MC AF Gonzalez, Santiago F. Lukacs-Kornek, Veronika Kuligowski, Michael P. Pitcher, Lisa A. Degn, Soren E. Kim, Young-A Cloninger, Mary J. Martinez-Pomares, Luisa Gordon, Siamon Turley, Shannon J. Carroll, Michael C. TI Capture of influenza by medullary dendritic cells via SIGN-R1 is essential for humoral immunity in draining lymph nodes SO NATURE IMMUNOLOGY LA English DT Article ID ZONE B-CELLS; SUBCAPSULAR SINUS MACROPHAGES; MANNOSE-BINDING LECTIN; SPLENIC MARGINAL ZONE; IN-VIVO DEPLETION; CD8(+) T-CELLS; GERMINAL-CENTERS; CAPSULAR POLYSACCHARIDE; STAPHYLOCOCCUS-AUREUS; ANTIGEN PRESENTATION AB A major pathway for B cell acquisition of lymph-borne particulate antigens relies on antigen capture by subcapsular sinus macrophages of the lymph node. Here we tested whether this mechanism is also important for humoral immunity to inactivated influenza virus. By multiple approaches, including multiphoton intravital imaging, we found that antigen capture by sinus-lining macrophages was important for limiting the systemic spread of virus but not for the generation of influenza-specific humoral immunity. Instead, we found that dendritic cells residing in the lymph node medulla use the lectin receptor SIGN-R1 to capture lymph-borne influenza virus and promote humoral immunity. Thus, our results have important implications for the generation of durable humoral immunity to viral pathogens through vaccination. C1 [Gonzalez, Santiago F.; Kuligowski, Michael P.; Pitcher, Lisa A.; Degn, Soren E.; Kim, Young-A; Carroll, Michael C.] Harvard Univ, Childrens Hosp, Immune Dis Inst, Sch Med,Dept Pediat, Boston, MA 02115 USA. [Gonzalez, Santiago F.; Kuligowski, Michael P.; Pitcher, Lisa A.; Degn, Soren E.; Kim, Young-A; Carroll, Michael C.] Harvard Univ, Childrens Hosp, Program Cellular & Mol Med, Sch Med,Dept Pediat, Boston, MA 02115 USA. [Gonzalez, Santiago F.; Kuligowski, Michael P.; Pitcher, Lisa A.; Degn, Soren E.; Kim, Young-A; Carroll, Michael C.] Harvard Univ, Childrens Hosp, Immune Dis Inst, Sch Med,Dept Pathol, Boston, MA 02115 USA. [Gonzalez, Santiago F.; Kuligowski, Michael P.; Pitcher, Lisa A.; Degn, Soren E.; Kim, Young-A; Carroll, Michael C.] Harvard Univ, Childrens Hosp, Program Cellular & Mol Med, Sch Med,Dept Pathol, Boston, MA 02115 USA. [Lukacs-Kornek, Veronika; Turley, Shannon J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS,Dept Pathol, Boston, MA 02115 USA. [Cloninger, Mary J.] Montana State Univ, Dept Chem & Biochem, Bozeman, MT 59717 USA. [Degn, Soren E.] Aarhus Univ, Dept Med Microbiol & Immunol, Aarhus, Denmark. [Martinez-Pomares, Luisa] Univ Nottingham, Sch Mol Med Sci, Nottingham NG7 2RD, England. [Gordon, Siamon] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England. RP Carroll, MC (reprint author), Harvard Univ, Childrens Hosp, Immune Dis Inst, Sch Med,Dept Pediat, Boston, MA 02115 USA. EM shannon_turley@dfci.harvard.edu; carroll@idi.harvard.edu OI Martinez-Pomares, Luisa/0000-0002-2331-127X; Degn, Soren/0000-0001-5409-045X FU US National Institutes of Health [5 R01 AI039246, 1 P01 AI078897, 5 R01 AI067706, RO1 GM62444, RO1 DK074500]; European Union [220044] FX We thank J. Nolting (Dana Farber Cancer Institute) for hemagglutinin- T cell antigen receptor- transgenic mice; M. Nussenzweig (Rockefeller University) for CD11c- eYFP mice; R. Steinman (Rockefeller University) for the anti- SIGN- R1 hybridoma; K. Rajewsky (Harvard Medical School) for B1.8 mice; W. Gerhard (Wistar Institute) for the anti- hemagglutinin hybridoma; A. Garcia- Sastre (Mount Sinai School of Medicine) for influenza A/PR/8; J. Jensenius (Aarhus University) and S. Thiel (Aarhus University) for anti- MBL and technical advice; T. Mempel for the use of microscopy facilities and technical assistance; and H. Leung, E. Marino, M. Ericsson, H. Kim and A. Gillmore for technical assistance. Supported by the US National Institutes of Health (5 R01 AI039246, 1 P01 AI078897 and 5 R01 AI067706 to M.C.C., RO1 GM62444 to M.J.C. and RO1 DK074500 to S.J.T.) and the Seventh Framework Programme of the European Union (Marie Curie International Outgoing Fellowship 220044 to S.F.G.). NR 54 TC 101 Z9 102 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD MAY PY 2010 VL 11 IS 5 BP 427 EP U90 DI 10.1038/ni.1856 PG 9 WC Immunology SC Immunology GA 585TN UT WOS:000276852200012 PM 20305659 ER PT J AU Clair, C Cornuz, J AF Clair, Carole Cornuz, Jacques TI DIABETES Risk of diabetes mellitus: should smokers quit smoking? SO NATURE REVIEWS ENDOCRINOLOGY LA English DT Editorial Material ID TYPE-2; PREVALENCE; COHORT; WEIGHT; WOMEN C1 [Clair, Carole] Massachusetts Gen Hosp, Dept Med, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. [Clair, Carole] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Cornuz, Jacques] Univ Lausanne Hosp, Dept Ambulatory Care & Community Med, CH-1011 Lausanne, Switzerland. RP Clair, C (reprint author), Massachusetts Gen Hosp, Dept Med, Tobacco Res & Treatment Ctr, 9th Floor,50 Staniford St, Boston, MA 02114 USA. EM cclair@partners.org RI Clair, Carole/D-9786-2014 OI Clair, Carole/0000-0001-5281-0943 NR 9 TC 3 Z9 3 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5029 J9 NAT REV ENDOCRINOL JI Nat. Rev. Endocrinol. PD MAY PY 2010 VL 6 IS 5 BP 250 EP 251 DI 10.1038/nrendo.2010.45 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 587FX UT WOS:000276976500005 PM 20414317 ER PT J AU Peleg, AY Hogan, DA Mylonakis, E AF Peleg, Anton Y. Hogan, Deborah A. Mylonakis, Eleftherios TI Medically important bacterial-fungal interactions SO NATURE REVIEWS MICROBIOLOGY LA English DT Review ID VENTILATOR-ASSOCIATED PNEUMONIA; INTENSIVE-CARE UNITS; CANDIDA-ALBICANS; PSEUDOMONAS-AERUGINOSA; STAPHYLOCOCCUS-AUREUS; ACINETOBACTER-BAUMANNII; ESCHERICHIA-COLI; BIOFILM FORMATION; CYSTIC-FIBROSIS; CAENORHABDITIS-ELEGANS AB Whether it is in the setting of disease or in a healthy state, the human body contains a diverse range of microorganisms, including bacteria and fungi. The interactions between these taxonomically diverse microorganisms are highly dynamic and dependent on a multitude of microorganism and host factors. Human disease can develop from an imbalance between commensal bacteria and fungi or from invasion of particular host niches by opportunistic bacterial and fungal pathogens. This Review describes the clinical and molecular characteristics of bacterial-fungal interactions that are relevant to human disease. C1 [Peleg, Anton Y.; Mylonakis, Eleftherios] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Peleg, Anton Y.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Peleg, Anton Y.; Mylonakis, Eleftherios] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Hogan, Deborah A.] Dartmouth Med Sch, Dept Microbiol & Immunol, Hanover, NH 03755 USA. RP Peleg, AY (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM apeleg@bidmc.harvard.edu; Deborah.A.Hogan@Dartmouth.edu; emylonakis@partners.org OI Hogan, Deborah A./0000-0002-6366-2971; Peleg, Anton/0000-0002-2296-2126 FU Massachusetts General Hospital ECOR FX A.Y.P. is funded by a Massachusetts General Hospital ECOR Fund for Medical Discovery Award. NR 95 TC 132 Z9 137 U1 6 U2 67 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1740-1526 J9 NAT REV MICROBIOL JI Nat. Rev. Microbiol. PD MAY PY 2010 VL 8 IS 5 BP 340 EP 349 DI 10.1038/nrmicro2313 PG 10 WC Microbiology SC Microbiology GA 584XT UT WOS:000276788300011 PM 20348933 ER PT J AU Kraut, JA Madias, NE AF Kraut, Jeffrey A. Madias, Nicolaos E. TI Metabolic acidosis: pathophysiology, diagnosis and management SO NATURE REVIEWS NEPHROLOGY LA English DT Review ID RENAL TUBULAR-ACIDOSIS; SERUM ANION GAP; CHRONIC KIDNEY-DISEASE; 5-OXOPROLINE PYROGLUTAMIC ACID; HYPOVOLEMIC CIRCULATORY SHOCK; CRITICALLY-ILL PATIENTS; LACTIC-ACIDOSIS; SODIUM-BICARBONATE; DIABETIC-KETOACIDOSIS; POTASSIUM BICARBONATE AB Metabolic acidosis is characterized by a primary reduction in serum bicarbonate (HCO3-) concentration, a secondary decrease in the arterial partial pressure of carbon dioxide (PaCO2) of similar to 1 mmHg for every 1 mmol/l fall in serum HCO3- concentration, and a reduction in blood pH. Acute forms (lasting minutes to several days) and chronic forms (lasting weeks to years) of the disorder can occur, for which the underlying cause/s and resulting adverse effects may differ. Acute forms of metabolic acidosis most frequently result from the overproduction of organic acids such as ketoacids or lactic acid; by contrast, chronic metabolic acidosis often reflects bicarbonate wasting and/or impaired renal acidification. The calculation of the serum anion gap, calculated as [Na+]-([HCO3 ]+[Cl ]), aids diagnosis by classifying the disorders into categories of normal (hyperchloremic) anion gap or elevated anion gap. These categories can overlap, however. Adverse effects of acute metabolic acidosis primarily include decreased cardiac output, arterial dilatation with hypotension, altered oxygen delivery, decreased ATP production, predisposition to arrhythmias, and impairment of the immune response. The main adverse effects of chronic metabolic acidosis are increased muscle degradation and abnormal bone metabolism. Using base to treat acute metabolic acidosis is controversial because of a lack of definitive benefit and because of potential complications. By contrast, the administration of base for the treatment of chronic metabolic acidosis is associated with improved cellular function and few complications. C1 [Madias, Nicolaos E.] St Elizabeths Med Ctr, Dept Med, Div Nephrol, Brighton, MA 02135 USA. [Kraut, Jeffrey A.] Vet Adm Greater Los Angeles VHAGLA Healthcare Sys, Div Nephrol, Los Angeles, CA 90073 USA. RP Madias, NE (reprint author), St Elizabeths Med Ctr, Dept Med, Div Nephrol, 736 Cambridge St, Brighton, MA 02135 USA. EM nicolaos.madias@caritaschristi.org FU Veterans Administration FX J. A. Kraut's work is supported in part by research funds from the Veterans Administration. C. P. Vega, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the MedscapeCME-accredited continuing medical education activity associated with this article. NR 124 TC 73 Z9 78 U1 8 U2 87 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5061 EI 1759-507X J9 NAT REV NEPHROL JI Nat. Rev. Nephrol. PD MAY PY 2010 VL 6 IS 5 BP 274 EP 285 DI 10.1038/nrneph.2010.33 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 589NZ UT WOS:000277158400009 PM 20308999 ER PT J AU Gerstner, ER Chen, PJ Wen, PY Jain, RK Batchelor, TT Sorensen, G AF Gerstner, Elizabeth R. Chen, Poe-Jou Wen, Patrick Y. Jain, Rakesh K. Batchelor, Tracy T. Sorensen, Gregory TI Infiltrative patterns of glioblastoma spread detected via diffusion MRI after treatment with cediranib SO NEURO-ONCOLOGY LA English DT Article DE ADC; antiangiogenic therapy; diffusion MRI; glioma; infiltration ID EARLY SURROGATE MARKER; HIGH-GRADE GLIOMA; BRAIN-TUMORS; THERAPEUTIC-EFFICACY; RESPONSE CRITERIA; IN-VIVO; BIOMARKER; SURVIVAL; MAP; ANGIOGENESIS AB To evaluate the role of apparent diffusion coefficient (ADC) imaging in assessing tumor cell infiltration after treatment with the antivascular endothelial growth factor (anti-VEGF) agent, cediranib, we prospectively analyzed diffusion MRI scans from 30 patients participating in a Phase II trial of cediranib for recurrent glioblastoma. A patient-specific threshold was selected below which ADC values were determined to be abnormally low and suggestive of tumor. We determined the percent of low ADC in the FLAIR hyperintensity surrounding the enhancing tumor and then visualized the location of these low ADC voxels. The percent volume of the FLAIR hyperintensity comprised by low ADC increased significantly from baseline (2.3%) to day 28 (2.9%), day 56 (5.0%), and day 112 (6.3%) of treatment with cediranib suggesting increasing infiltrative tumor in some patients. Visualization of the location of the low ADC voxels suggested regions of tumor growth that were not visible on contrast-enhanced MRI. ADC maps can be used to suggest regions of infiltrative tumor cells with anti-VEGF therapy and should be validated in future studies. C1 [Gerstner, Elizabeth R.; Batchelor, Tracy T.] Massachusetts Gen Hosp, Dept Neurol, Ctr Canc, Boston, MA 02114 USA. [Jain, Rakesh K.; Batchelor, Tracy T.] Massachusetts Gen Hosp, Dept Radiat Oncol, Ctr Canc, Boston, MA 02114 USA. [Sorensen, Gregory] Massachusetts Gen Hosp, Dept Radiol, Ctr Canc, Boston, MA 02114 USA. [Gerstner, Elizabeth R.; Batchelor, Tracy T.] Massachusetts Gen Hosp, Ctr Canc, Div Hematol & Oncol, Boston, MA 02114 USA. [Wen, Patrick Y.] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. [Chen, Poe-Jou] MIT, Dept Nucl Sci & Engn, Cambridge, MA 02139 USA. RP Gerstner, ER (reprint author), Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol, Yawkey 9E,55 Fruit St, Boston, MA 02114 USA. EM egerstner@partners.org FU National Institutes of Health, National Center for Research Resources [R01CA129371-01, M01-RR-01066] FX This work was supported by R01CA129371-01 (Batchelor) and M01-RR-01066, National Institutes of Health, National Center for Research Resources, General Clinical Research Centers Program. NR 24 TC 72 Z9 73 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 MAY PY 2010 VL 12 IS 5 BP 466 EP 472 DI 10.1093/neuonc/nop051 PG 7 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 586VU UT WOS:000276943300006 PM 20406897 ER PT J AU Kloetzer, L Chey, WD McCallum, RW Koch, KL Wo, JM Sitrin, M Katz, LA Lackner, JM Parkman, HP Wilding, GE Semler, JR Hasler, WL Kuo, B AF Kloetzer, L. Chey, W. D. McCallum, R. W. Koch, K. L. Wo, J. M. Sitrin, M. Katz, L. A. Lackner, J. M. Parkman, H. P. Wilding, G. E. Semler, J. R. Hasler, W. L. Kuo, B. TI Motility of the antroduodenum in healthy and gastroparetics characterized by wireless motility capsule SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Article DE ambulatory capsule; gastroparesis; manometry ID DUODENOJEJUNAL MANOMETRY; HEIDELBERG CAPSULE; CLINICAL-PRACTICE; SYMPTOMS; HUMANS; SCINTIGRAPHY; PHYSIOLOGY; ENDOSCOPY; DIAGNOSIS; DISEASE AB Background The wireless motility capsule (WMC) measures intraluminal pH and pressure, and records transit time and contractile activity throughout the gastrointestinal tract. Our hypothesis is that WMC can differentiate antroduodenal pressure profiles between healthy people and patients with upper gut motility dysfunctions. This study aims to analyze differences in the phasic pressure profiles of the stomach and small intestine in healthy and gastroparetic subjects. Methods Data from 71 healthy and 42 gastroparetic subjects were analyzed. The number of contractions (Ct), area under the pressure curve and motility index (MI = Ln (Ct *sum amplitudes +1)) were analyzed for 60 min before gastric emptying of the capsule (GET), (gastric window) and after GET (small bowel window) and results between groups were compared with the Wilcoxon rank sum test. Key Results Significant differences were observed between healthy and gastroparetic subjects for Ct and MI (P < 0.05). Median values of the motility parameters in gastric window were Ct = 72, MI = 11.83 for healthy and Ct = 47, MI = 11.12 for gastroparetics. In the small bowel, median values were Ct = 144.5, MI = 12.78 for healthy and Ct = 93, MI = 12.12 for gastroparetics. Diabetic subjects with gastroparesis showed significantly lower Ct and MI compared with healthy subjects in both gastric and small bowel windows while idiopathic gastroparetic subjects did not show significant differences. Conclusions & Inferences The WMC is able to differentiate between healthy and gastroparetic subjects based on gastric and small bowel motility profiles. C1 [Kloetzer, L.; Kuo, B.] Harvard Univ, Gastroenterol Unit, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Chey, W. D.; Hasler, W. L.] Univ Michigan, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA. [McCallum, R. W.] Univ Kansas, Med Ctr, Ctr Gastrointestinal Nerve & Muscle Funct & GI Mo, Kansas City, KS 66103 USA. [Koch, K. L.] Wake Forest Univ, Baptist Med Ctr, Winston Salem, NC 27109 USA. [Wo, J. M.] Univ Louisville, Div Gastroenterol Hepatol, Louisville, KY 40292 USA. [Sitrin, M.] SUNY Buffalo, Div Gastroenterol Hepatol & Nutr, Dept Med, Western New York VA Med Ctr, Buffalo, NY 14260 USA. [Katz, L. A.] SUNY Buffalo, Sch Med, Dept Med, Buffalo, NY 14260 USA. [Lackner, J. M.] SUNY Buffalo, Sch Med, Behav Med Clin,Dept Med, Div Gastroenterol Hepatol & Nutr, Buffalo, NY 14260 USA. [Parkman, H. P.] Temple Univ, Sch Med, Dept Med, Gastroenterol Sect, Philadelphia, PA 19122 USA. [Wilding, G. E.] SUNY Buffalo, Dept Biostat, Buffalo, NY 14260 USA. [Semler, J. R.] Smart Pill Corp, Buffalo, NY USA. RP Kuo, B (reprint author), Harvard Univ, Gastroenterol Unit, Massachusetts Gen Hosp, Sch Med, Blake 4,55 Fruit St, Boston, MA 02114 USA. EM bkuo@partners.org FU Smart Pill Corporation FX This study was sponsored by The Smart Pill Corporation. Drs Kuo, McCallum, Sitrin, Lackner, Chey, Hasler and Parkman serve as speakers, consultants or advisory board members for The Corporation, and have received research funding from The Smart Pill Corporation. Dr Katz is an advisory board member for The Smart Pill Corporation. Dr Wilding serves as a consultant to The Smart Pill Corporation. Dr Semler is an employee of The Smart Pill Corporation and owns stock in The Smart Pill Corporation. NR 32 TC 36 Z9 37 U1 2 U2 10 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1350-1925 J9 NEUROGASTROENT MOTIL JI Neurogastroenterol. Motil. PD MAY PY 2010 VL 22 IS 5 BP 527 EP + DI 10.1111/j.1365-2982.2010.01468.x PG 8 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA 579WE UT WOS:000276406700009 PM 20122128 ER PT J AU Schwartz, DL Mitchell, AD Lahna, DL Luber, HS Huckans, MS Mitchell, SH Hoffman, WF AF Schwartz, Daniel L. Mitchell, Alex D. Lahna, David L. Luber, Hannah S. Huckans, Marilyn S. Mitchell, Suzanne H. Hoffman, William F. TI Global and local morphometric differences in recently abstinent methamphetamine-dependent individuals SO NEUROIMAGE LA English DT Article ID VOXEL-BASED MORPHOMETRY; DELAY DISCOUNTING TASK; DECISION-MAKING; OXIDATIVE STRESS; STRUCTURAL ABNORMALITIES; MICROGLIAL ACTIVATION; INTERTEMPORAL CHOICE; CIGARETTE-SMOKING; AMYGDALA VOLUME; IMPULSE CONTROL AB Methamphetamine (MA) is associated with behavioral and cognitive deficits that may be related to macrostructural abnormalities. Quantitative anatomical comparisons between controls and methamphetamine-dependent individuals have produced conflicting results. We examined local and global differences in brain structure in 61 abstinent methamphetamine-dependent individuals and 44 controls with voxel-based morphometry and tissue segmentation. We related regional differences in gray matter density and whole brain segmentation volumes to performance on a behavioral measure of impulsivity and group membership using multiple linear regression. Within the MA group, we related cortical and subcortical gray matter density to length of abstinence. Controls had greater density relative to MA in bilateral insula and left middle frontal gyros. Impulsivity was higher in the MA group and, within all subjects, impulsivity was positively correlated with gray matter density in posterior cingulate cortex and ventral striatum and negatively correlated in left superior frontal gyrus. Length of abstinence from MA was associated with greater amygdalar density. Earlier age of first use of MA (in subjects who initiated use before age 2D was associated with smaller intracranial volume. The findings are consistent with multiple possible mechanisms including neuroadaptations due to addictive behavior, neuroinflammation as well as dopaminergic and serotonergic neurotoxicity. (C) 2010 Elsevier Inc. All rights reserved. C1 [Schwartz, Daniel L.; Mitchell, Alex D.; Lahna, David L.; Luber, Hannah S.; Huckans, Marilyn S.; Hoffman, William F.] Portland VA Med Ctr, Res Serv, Portland, OR USA. [Mitchell, Alex D.; Huckans, Marilyn S.; Hoffman, William F.] Portland VA Med Ctr, Mental Hlth & Clin Neurosci Div, Portland, OR USA. [Schwartz, Daniel L.; Lahna, David L.; Luber, Hannah S.; Huckans, Marilyn S.; Mitchell, Suzanne H.; Hoffman, William F.] Portland VA Med Ctr, Methamphetamine Abuse Res Ctr, Portland, OR USA. [Schwartz, Daniel L.; Lahna, David L.; Luber, Hannah S.; Huckans, Marilyn S.; Mitchell, Suzanne H.; Hoffman, William F.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Mitchell, Suzanne H.; Hoffman, William F.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. RP Schwartz, DL (reprint author), Portland VA Med Ctr, Res Serv, Portland, OR USA. EM schwartd@ohsu.edu OI Mitchell, Suzanne/0000-0002-0225-7200 FU Department of Veterans Affairs Merit Review Program; Stanley Medical Research Institute; Department of Veterans Affairs Career Development Program; NM [P50DA018165, DA015543] FX Supported by the Department of Veterans Affairs Merit Review Program (WFH), Stanley Medical Research Institute and Department of Veterans Affairs Career Development Program (MSH), NM grants P50DA018165 (WFH, SHM, BHM), and DA015543 (SHM). NR 74 TC 58 Z9 63 U1 3 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD MAY 1 PY 2010 VL 50 IS 4 BP 1392 EP 1401 DI 10.1016/j.neuroimage.2010.01.056 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 574VY UT WOS:000276023500006 PM 20096794 ER PT J AU Rubin, EB Bernat, JL AF Rubin, Emily B. Bernat, James L. TI Consent Issues in Neurology SO NEUROLOGIC CLINICS LA English DT Article DE Informed consent; Valid consent; Shared decision making; Emergency exception; tPA; Surrogate; Do-not-resuscitate; Carotid endarterectomy ID ACUTE ISCHEMIC-STROKE; SYMPTOMATIC CAROTID STENOSIS; INVASIVE MEDICAL PROCEDURES; SHARED DECISION-MAKING; INFORMED-CONSENT; CARDIOPULMONARY RESUSCITATION; PLASMINOGEN-ACTIVATOR; ENDARTERECTOMY; RISKS; THROMBOLYSIS AB The requirement that doctors obtain valid consent from patients before providing medical treatment has long been ingrained in both legal doctrine and medical ethics. We summarize the foundations of the informed consent doctrine and discuss the recent evolution in thinking about consent and medical decision making. We show how consent has evolved from physicians merely providing patients information to shared decision making between patients and physicians. We then address three specific examples of situations common in neurological practice that pose challenges in obtaining valid consent: the administration of intravenous tPA following ischemic stroke, consideration of carotid endarterectomy for carotid artery stenosis, and implementation of do-not-resuscitate orders. C1 [Rubin, Emily B.] Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. [Rubin, Emily B.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Bernat, James L.] Dartmouth Med Sch, Hanover, NH 03755 USA. [Bernat, James L.] Dartmouth Hitchcock Med Ctr, Dept Neurol, Lebanon, NH 03756 USA. RP Rubin, EB (reprint author), Massachusetts Gen Hosp, Dept Internal Med, 55 Fruit St, Boston, MA 02114 USA. EM emmyrubin@gmail.com NR 38 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 0733-8619 J9 NEUROL CLIN JI Neurol. Clin. PD MAY PY 2010 VL 28 IS 2 BP 459 EP + DI 10.1016/j.nc1.2009.11.007 PG 16 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 581RU UT WOS:000276542800010 PM 20202504 ER PT J AU Koenigsberg, HW Fan, J Ochsner, KN Liu, X Guise, K Pizzarello, S Dorantes, C Tecuta, L Guerreri, S Goodman, M New, A Flory, J Siever, LJ AF Koenigsberg, Harold W. Fan, Jin Ochsner, Kevin N. Liu, Xun Guise, Kevin Pizzarello, Scott Dorantes, Christine Tecuta, Lucia Guerreri, Stephanie Goodman, Marianne New, Antonia Flory, Janine Siever, Larry J. TI Neural correlates of using distancing to regulate emotional responses to social situations SO NEUROPSYCHOLOGIA LA English DT Article DE Emotion; Cognitive reappraisal; Social cognitive neuroscience; Emotional distancing; Emotion regulation; fMRI ID EVENT-RELATED FMRI; BORDERLINE PERSONALITY-DISORDER; ANTERIOR CINGULATE CORTEX; PREFRONTAL CORTEX; NEGATIVE AFFECT; VOLUNTARY SUPPRESSION; ATTENTIONAL CONTROL; SELF; BRAIN; ACTIVATION AB Cognitive reappraisal is a commonly used and highly adaptive strategy for emotion regulation that has been studied in healthy volunteers. Most studies to date have focused on forms of reappraisal that involve reinterpreting the meaning of stimuli and have intermixed social and non-social emotional stimuli. Here we examined the neural correlates of the regulation of negative emotion elicited by social situations using a less studied form of reappraisal known as distancing. Whole brain fMRI data were obtained as participants viewed aversive and neutral social scenes with instructions to either simply look at and respond naturally to the images or to downregulate their emotional responses by distancing. Three key findings were obtained accompanied with the reduced aversive response behaviorally. First, across both instruction types, aversive social images activated the amygdala. Second, across both image types, distancing activated the precuneus and posterior cingulate cortex (PCC), intraparietal sulci (IPS), and middle/superior temporal gyrus (M/STG). Third, when distancing one's self from aversive images, activity increased in dorsal anterior cingulate (dACC), medial prefrontal cortex (mPFC), lateral prefrontal cortex, precuneus and PCC, IPS, and M/STG, meanwhile, and decreased in the amygdala. These findings demonstrate that distancing from aversive social cues modulates amygdala activity via engagement of networks implicated in social perception, perspective-taking, and attentional allocation. Published by Elsevier Ltd. C1 [Koenigsberg, Harold W.] James J Peters VA Med Ctr, Mt Sinai Sch Med, Bronx, NY 10468 USA. [Koenigsberg, Harold W.; Fan, Jin; Liu, Xun; Guise, Kevin; Dorantes, Christine; Tecuta, Lucia; Guerreri, Stephanie; Goodman, Marianne; New, Antonia; Flory, Janine; Siever, Larry J.] Mt Sinai Sch Med, New York, NY USA. [Ochsner, Kevin N.] Columbia Univ, Dept Psychol, New York, NY 10027 USA. [Pizzarello, Scott] Univ Florida, Tallahassee, FL USA. RP Koenigsberg, HW (reprint author), James J Peters VA Med Ctr, Mt Sinai Sch Med, 130 W Kingsbridge Rd,116A, Bronx, NY 10468 USA. EM HWarrenK@nyc.rr.com RI Fan, Jin/A-6716-2009; Liu, Xun/C-2400-2009; OI Fan, Jin/0000-0001-9630-8330; Liu, Xun/0000-0003-1366-8926; TECUTA, LUCIA/0000-0002-7984-3064 FU National Institute of Mental Health [RO1 MH077813, MH076137]; National Center for Research Resources, National Institutes of Health [5MO1 RR00071] FX Completion of this work was supported in part by grants from the National Institute of Mental Health (RO1 MH077813, PI: H.W.K.; MH076137, PI: K.N.O.) and from the National Center for Research Resources, National Institutes of Health for the Mount Sinai General Clinical Research Center (5MO1 RR00071). NR 67 TC 68 Z9 69 U1 6 U2 25 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD MAY PY 2010 VL 48 IS 6 BP 1813 EP 1822 DI 10.1016/j.neuropsychologia.2010.03.002 PG 10 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 604FE UT WOS:000278261900033 PM 20226799 ER PT J AU McClure, MM Harvey, PD Goodman, M Triebwasser, J New, A Koenigsberg, HW Sprung, LJ Flory, JD Siever, LJ AF McClure, Margaret M. Harvey, Philip D. Goodman, Marianne Triebwasser, Joseph New, Antonia Koenigsberg, Harold W. Sprung, Larry J. Flory, Janine D. Siever, Larry J. TI Pergolide Treatment of Cognitive Deficits Associated with Schizotypal Personality Disorder: Continued Evidence of the Importance of the Dopamine System in the Schizophrenia Spectrum SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE schizotypal personality; schizotypy; schizophrenia spectrum; cognition; pergolide; dopamine ID VISUOSPATIAL WORKING-MEMORY; PREFRONTAL CORTEX; PARKINSONS-DISEASE; NEUROPSYCHOLOGICAL PERFORMANCE; RECEPTOR STIMULATION; AGED MONKEYS; FOLLOW-UP; TASK; DYSFUNCTION; IMPAIRMENT AB Cognitive deficits observed in schizophrenia are also frequently found in individuals with other schizophrenia spectrum disorders, such as schizotypal personality disorder (SPD). Dopamine appears to be a particularly important modulator of cognitive processes such as those impaired in schizophrenia spectrum disorders. In a double-blind, placebo-controlled clinical trial, we administered pergolide, a dopamine agonist targeting D(1) and D(2) receptors, to 25 participants with SPD and assessed the effect of pergolide treatment, as compared with placebo, on neuropsychological performance. We found that the pergolide group showed improvements in visual-spatial working memory, executive functioning, and verbal learning and memory. These results suggest that dopamine agonists may provide benefit for the cognitive abnormalities of schizophrenia spectrum disorders. Neuropsychopharmacology (2010) 35, 1356-1362; doi: 10.1038/npp.2010.5; published online 3 February 2010 C1 [McClure, Margaret M.] Mt Sinai Sch Med, VA VISN MIRECC 3, Bronx, NY 10468 USA. [Harvey, Philip D.] Emory Univ, Sch Med, Atlanta, GA USA. [Goodman, Marianne; Triebwasser, Joseph; Koenigsberg, Harold W.; Flory, Janine D.; Siever, Larry J.] James J Peters VA Med Ctr, Bronx, NY USA. [Flory, Janine D.] Queens Coll, Queens, NY USA. RP McClure, MM (reprint author), Mt Sinai Sch Med, VA VISN MIRECC 3, 130 W Kingsbridge Rd,00MH, Bronx, NY 10468 USA. EM Margaret.McNamara@mssm.edu FU Veterans Affairs [7609-028]; Veterans Affairs VISN3 Mental Illness Research, Education, and Clinical Center; National Center for Research Resources (NCRR), National Institutes of Health (NIH) [MO1-RR-00071] FX This work was supported by a Veterans Affairs Merit Review Grant (7609-028) to Dr Larry J Siever and by the Veterans Affairs VISN3 Mental Illness Research, Education, and Clinical Center. This work was also supported in part by Grant Number MO1-RR-00071 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of NCRR or NIH. NR 60 TC 27 Z9 27 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD MAY PY 2010 VL 35 IS 6 BP 1356 EP 1362 DI 10.1038/npp.2010.5 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 586KJ UT WOS:000276906500012 PM 20130535 ER PT J AU Agarwalla, PK Dunn, GP Laws, ER AF Agarwalla, Pankaj K. Dunn, Gavin P. Laws, Edward R. TI An historical context of modern principles in the management of intracranial injury from projectiles SO NEUROSURGICAL FOCUS LA English DT Article DE military; traumatic brain injury; neurosurgical history; projectile injury ID PENETRATING CRANIOCEREBRAL INJURIES; GUNSHOT WOUNDS; BONE FRAGMENTS; MISSILE WOUNDS; HEAD WOUNDS; FOLLOW-UP; BRAIN; VIETNAM; WAR; NEUROSURGERY AB The contemporary management of projectile head injuries owes much to the lessons neurosurgeons have distilled from their experiences in war. Through early investigation and an increasingly detailed account of wartime clinical experience, neurosurgeons-including the field's early giants-began to gain a greater understanding not only of intracranial missile pathophysiology but also of appropriate management. In this paper, the authors trace the development of the principles of managing intracranial projectile injury from the Crimean War in the 19th century through the Vietnam War to provide a context that frames a summary of today's core management principles. (DOI: 10.3171/2010.2.FOCUS1038) C1 [Laws, Edward R.] Harvard Univ, Sch Med, Dept Neurosurg, Brigham & Womens Hosp, Boston, MA 02115 USA. [Agarwalla, Pankaj K.; Dunn, Gavin P.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Laws, ER (reprint author), Harvard Univ, Sch Med, Dept Neurosurg, Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM elaws@partners.org NR 80 TC 5 Z9 5 U1 0 U2 0 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 MAY PY 2010 VL 28 IS 5 AR E23 DI 10.3171/2010.2.FOCUS1038 PG 13 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 589ZU UT WOS:000277193600023 PM 20568940 ER PT J AU Santos, CF Kurhanewicz, J Tabatabai, ZL Simko, JP Keshari, KR Gbegnon, A DeLos Santos, R Federman, S Shinohara, K Carroll, PR Haqq, CM Swanson, MG AF Santos, Carissa F. Kurhanewicz, John Tabatabai, Z. Laura Simko, Jeffry P. Keshari, Kayvan R. Gbegnon, Akpene DeLos Santos, Romelyn Federman, Scot Shinohara, Katsuto Carroll, Peter R. Haqq, Christopher M. Swanson, Mark G. TI Metabolic, pathologic, and genetic analysis of prostate tissues: quantitative evaluation of histopathologic and mRNA integrity after HR-MAS spectroscopy SO NMR IN BIOMEDICINE LA English DT Article DE cDNA microarray; gene expression; high resolution magic angle spinning (HR-MAS) spectroscopy; prostate cancer; radical prostatectomy; RNA integrity number (RIN); significance analysis of microarrays (SAM); transrectal ultrasound (TRUS) guided biopsy ID POLYMERASE CHAIN-REACTION; MAGNETIC-RESONANCE SPECTROSCOPY; SPINNING H-1-NMR SPECTROSCOPY; EXPRESSION ANALYSIS; PROTON NMR; RADICAL PROSTATECTOMY; CANCER TISSUE; FATTY-ACIDS; IN-VIVO; RESOLUTION AB The impact of high-resolution magic angle spinning (HR-MAS) spectroscopy on the histopathologic and mRNA integrity of human prostate tissues was evaluated. Forty prostate tissues were harvested at transrectal ultrasound (TRUS) guided biopsy (n = 20) or radical prostatectomy surgery (n = 20), snap-frozen on dry ice, and stored at 80 C until use. Twenty-one samples (n = 11 biopsy, n = 10 surgical) underwent HR-MAS spectroscopy prior to histopathologic and cDNA microarray analysis, while 19 control samples (n = 9 biopsy, n = 10 surgical) underwent only histopathologic and microarray analysis. Frozen tissues were sectioned at 14-mu m intervals and placed on individual histopathology slides. Every 8th slide was stained with hematoxylin and eosin (H&E) and used to target areas of predominantly epithelial tissue on the remaining slides for mRNA integrity and cDNA microarray analysis. Histopathologic integrity was graded from 1 (best) to 5 (worst) by two 'blinded' pathologists. Histopathologic integrity scores were not significantly different for post-surgical tissues (HR-MAS vs controls); however, one pathologist's scores were significantly lower for biopsy tissues following HR-MAS while the other pathologist's scores were not. mRNA integrity assays were performed using an Agilent 2100 Bioanalyzer and the electrophoretic traces were scored with an RNA integrity number (RIN) from 1 (degraded) to 10 (intact). RIN scores were not significantly different for surgical tissues, but were significantly lower for biopsy tissues following HR-MAS spectroscopy. The isolated mRNA then underwent two rounds of amplification, conversion to cDNA, coupling to Cy3 and Cy5 dyes, microarray hybridization, imaging, and analysis. Significance analysis of microarrays (SAM) identified no significantly over- or under-expressed genes, including 14 housekeeping genes, between HR-MAS and control samples of surgical and biopsy tissues (5% false discovery rate). This study demonstrates that histopathologic and genetic microarray analysis can be successfully performed on prostate surgical and biopsy tissues following HR-MAS analysis; however, biopsy tissues are more fragile than surgical tissues. Copyright (C) 2009 John Wiley & Sons, Ltd. C1 [Santos, Carissa F.; Kurhanewicz, John; Keshari, Kayvan R.; Gbegnon, Akpene; DeLos Santos, Romelyn; Swanson, Mark G.] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94158 USA. [Tabatabai, Z. Laura; Simko, Jeffry P.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94158 USA. [Federman, Scot] Univ Calif San Francisco, Dept Med, San Francisco, CA 94158 USA. [Shinohara, Katsuto; Carroll, Peter R.; Haqq, Christopher M.] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94158 USA. [Tabatabai, Z. Laura] San Francisco Vet Adm Med Ctr, San Francisco, CA USA. [Haqq, Christopher M.] Cougar Biotechnol, Los Angeles, CA USA. RP Kurhanewicz, J (reprint author), Univ Calif San Francisco, Dept Radiol, Byers Hall,Box 2520,1700 4th St,Room 203E, San Francisco, CA 94158 USA. EM john.kurhanewicz@radiology.ucsf.edu FU National Institutes of Health [K01 CA096618, R01 CA/02751, R01 CA101042]; American Cancer Society [RSG-05-241-01-CCE]; University of California Discovery [ITL-B1004-10148] FX Contract/grant sponsor: National Institutes of Health; contract/grant number: K01 CA096618, R01 CA/02751, R01 CA101042.; Contract/grant sponsor: American Cancer Society; contract/grant number: RSG-05-241-01-CCE.; Contract/grant sponsor: University of California Discovery Grant; contract/ grant number: ITL-B1004-10148. NR 55 TC 17 Z9 17 U1 0 U2 4 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0952-3480 J9 NMR BIOMED JI NMR Biomed. PD MAY PY 2010 VL 23 IS 4 BP 391 EP 398 DI 10.1002/nbm.1474 PG 8 WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA 594HA UT WOS:000277525800008 PM 20033906 ER PT J AU Scarcelli, G Yun, SH AF Scarcelli, G. Yun, S. H. TI Remote imaging of incoherent processes with second-order light correlation SO NUOVO CIMENTO DELLA SOCIETA ITALIANA DI FISICA B-BASIC TOPICS IN PHYSICS LA English DT Article; Proceedings Paper CT 95th National Congress of IL Nuovo Climento B of the Italian-Physical-Society CY SEP 28-OCT 03, 2009 CL ITALY SP Italian Phys Soc ID PARAMETRIC DOWN-CONVERSION; QUANTUM; OPTICS AB We show that second-order light correlation properties can be retrieved in the presence of fluorescent or scattering samples. Hence, we analyze the possibility of extending entangled ghost imaging to the case of fluorescent and scattering samples and present a microscopy protocol that takes advantage of temporal, spatial and spectral correlation of entangled states for imaging retrieval. C1 [Scarcelli, G.] Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusets Gen Hosp, Wellman Ctr PhotoMed, Boston, MA 02114 USA. RP Scarcelli, G (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA. EM gscarcelli@partners.org OI scarcelli, giuliano/0000-0002-1736-077X NR 25 TC 0 Z9 0 U1 0 U2 3 PU SOC ITALIANA FISICA PI BOLOGNA PA VIA SARAGOZZA, 12, I-40123 BOLOGNA, ITALY SN 1594-9982 J9 NUOVO CIM B JI Nouvo Cimento Soc. Ital. Fis. B-Basic Top. Phys. PD MAY-JUN PY 2010 VL 125 IS 5-6 SI SI BP 741 EP 748 DI 10.1393/ncb/i2010-10846-x PG 8 WC Physics, Multidisciplinary SC Physics GA 649PU UT WOS:000281785600027 ER PT J AU Yamamoto, Y Gesta, S Lee, KY Tran, TT Saadatirad, P Kahn, CR AF Yamamoto, Yuji Gesta, Stephane Lee, Kevin Y. Tran, Thien T. Saadatirad, Parshin Kahn, C. Ronald TI Adipose Depots Possess Unique Developmental Gene Signatures SO OBESITY LA English DT Article ID HUMAN PREADIPOCYTES; DIFFERENTIATION; FAT; TISSUE; ADIPOGENESIS; ORIGIN; OBESITY; CELLS AB We have previously demonstrated that subcutaneous and intra-abdominal adipose tissue show different patterns of expression for developmental genes (Shox2, En1, Tbx15 Hoxa5, Hoxc8, and Hoxc9), and that the expression level of Tbx15 and Hoxa5 in humans correlated with the level of obesity and fat distribution. To further explore the role of these developmental genes in adipose tissue, we have characterized their expression in different adipose depots in mice, and studied their regulation in obesity and by fasting. Developmental and adipogenic gene expression was compared in two subcutaneous and three intra-abdominal white adipose tissue (WAT) depots as well as brown adipose tissue (BAT) from lean or obese mice in a fed or fasting state. Each of these six adipose depots display a unique pattern of developmental gene expression, whereas expression of adipogenic transcription factors PPAR gamma 2 C/EBP alpha, beta, and delta showed constant expression levels in all depots. Expression levels of developmental genes were similar in obese (ob/ob and high-fat diet (HFD)) and lean mice in most depots. Fasting systematically decreased expression of Hoxc8, PPAR gamma 2, and increased C/EBP delta in both lean and ob/ob mice, but produced only variable changes in the expression of other developmental and adipogenic genes. These data indicate that each fat depot has a unique developmental gene expression signature, which is largely independent of nutritional state. This finding further supports a fundamental role of developmental genes in fat distribution and the development and/or function of specific adipose tissue depots. C1 [Yamamoto, Yuji; Gesta, Stephane; Lee, Kevin Y.; Tran, Thien T.; Saadatirad, Parshin; Kahn, C. Ronald] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Kahn, CR (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. EM c.ronald.kahn@joslin.harvard.edu FU Diabetes Genome Anatomy Project (DGAP) [DK60837]; NIH [DK82659, DK34834]; Mary K. Iacocca FX This work was supported by the Diabetes Genome Anatomy Project (DGAP) (DK60837) and NIH grant DK82659, the NIH-funded Joslin Diabetes and Endocrinology Center grant DK34834, and the Mary K. Iacocca Professorship fund. NR 21 TC 61 Z9 61 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD MAY PY 2010 VL 18 IS 5 BP 872 EP 878 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 590OA UT WOS:000277234800005 PM 20111017 ER PT J AU Tadros, TM Massaro, JM Rosito, GA Hoffmann, U Vasan, RS Larson, MG Keaney, JF Lipinska, I Meigs, JB Kathiresan, S O'Donnell, CJ Fox, CS Benjamin, EJ AF Tadros, Thomas M. Massaro, Joseph M. Rosito, Guido A. Hoffmann, Udo Vasan, Ramachandran S. Larson, Martin G. Keaney, John F., Jr. Lipinska, Izabella Meigs, James B. Kathiresan, Sekar O'Donnell, Christopher J. Fox, Caroline S. Benjamin, Emelia J. TI Pericardial Fat Volume Correlates With Inflammatory Markers: The Framingham Heart Study SO OBESITY LA English DT Article ID EPICARDIAL ADIPOSE-TISSUE; CORONARY-ARTERY-DISEASE; C-REACTIVE PROTEIN; METABOLIC SYNDROME; INSULIN-RESISTANCE; RISK-FACTORS; CARDIOVASCULAR-DISEASE; MAJOR DETERMINANT; OXIDATIVE STRESS; VISCERAL FAT AB The objective of this study was to determine whether systemic inflammatory and oxidative stress marker concentrations correlate with pericardial and intrathoracic fat volumes. Participants of the Framingham Offspring Study (n = 1,175, 53% women, mean age 59 +/- 9 years) had pericardial and intrathoracic fat volumes assessed by multidetector computed tomography (MDCT) scans, and provided fasting blood and urine samples to measure concentrations of 14 inflammatory markers: C-reactive protein (CRP), interleukin-6, monocyte chemoattractant protein-1 (MCP-1), CD40 ligand, fibrinogen, intracellular adhesion molecule-1, lipoprotein-associated phospholipase A 2 activity and mass, myeloperoxidase, osteoprotegerin, P-selectin, tumor necrosis factor-a, tumor necrosis factor receptor-2, and urinary isoprostanes. Multivariable linear regression models were used to determine the association of log-transformed inflammatory marker concentrations with fat volumes, using fat volume as the dependent variable. Due to smaller sample sizes, models were rerun after adding urinary isoprostanes (n = 961) and tumor necrosis factor-a (n = 813) to the marker panel. Upon backward elimination, four of the biomarkers correlated positively with each fat depot: CRP (P < 0.0001 for each fat depot), interleukin-6 (P < 0.05 for each fat depot), MCP-1 (P < 0.01 for each fat depot), and urinary isoprostanes (P < 0.01 for pericardial fat; P < 0.001 for intrathoracic fat). Even after adjusting for BMI, waist circumference (WC), and abdominal visceral fat, CRP (P = 0.0001) and urinary isoprostanes (P = 0.02) demonstrated significant positive associations with intrathoracic fat, but not with pericardial fat. Multiple markers of inflammation and oxidative stress correlated with pericardial and intrathoracic fat volumes, extending the known association between regional adiposity and inflammation and oxidative stress. C1 [Tadros, Thomas M.; Massaro, Joseph M.; Vasan, Ramachandran S.; Larson, Martin G.; O'Donnell, Christopher J.; Fox, Caroline S.; Benjamin, Emelia J.] NHLBI, Framingham Heart Study, Boston, MA USA. [Tadros, Thomas M.; Benjamin, Emelia J.] Boston Univ, Sch Med, Div Cardiol, Boston Univ Med Ctr, Boston, MA 02118 USA. [Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Rosito, Guido A.; Hoffmann, Udo] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Div Cardiol, Boston, MA 02118 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Div Prevent Med, Boston, MA 02118 USA. [Larson, Martin G.] Boston Univ, Dept Math, Boston, MA 02118 USA. [Keaney, John F., Jr.; Lipinska, Izabella] Univ Massachusetts, Sch Med, Div Cardiol, Worcester, MA USA. [Meigs, James B.; Benjamin, Emelia J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02115 USA. [Kathiresan, Sekar; O'Donnell, Christopher J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02115 USA. [Fox, Caroline S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Diabet Endocrinol & Metab, Boston, MA 02115 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA. RP Benjamin, EJ (reprint author), NHLBI, Framingham Heart Study, Boston, MA USA. EM emelia@bu.edu OI Massaro, Joseph/0000-0002-2682-4812; Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU National Heart, Lung, and Blood Institute [N01-HC-25195]; National Institute of Health, National Center for Research Resources [RO1-HL076784, RO1-HL064753, R01-AG028321]; General Clinical Research Centers [M01-RR-01066]; American Diabetes Association; National Institute of Health/National Heart, Lung, and Blood Institute [2K24HL04334]; NIDDK [K24 DK080140] FX Lipoprotein-associated phospholipase A2 activity was measured by GlaxoSmithKline and lipoprotein-associated phospholipase A2 mass was measured by diaDexus without cost to the Framingham Heart Study. This study was funded by the National Heart, Lung, and Blood Institute's Framingham Heart Study N01-HC-25195 and by RO1-HL076784, RO1-HL064753, and R01-AG028321 (E.J.B), National Institute of Health, National Center for Research Resources, General Clinical Research Centers Program (grant number M01-RR-01066), and by a Career Development Award from the American Diabetes Association (J.B.M.). R. S. V. is partially supported by 2K24HL04334 (National Institute of Health/National Heart, Lung, and Blood Institute). J.B.M. was supported by NIDDK K24 DK080140. NR 39 TC 39 Z9 40 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD MAY PY 2010 VL 18 IS 5 BP 1039 EP 1045 DI 10.1038/oby.2009.343 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 590OA UT WOS:000277234800031 PM 19875999 ER PT J AU Livhits, M Mercado, C Yermilov, I Parikh, JA Dutson, E Mehran, A Ko, CY Gibbons, MM AF Livhits, Masha Mercado, Cheryl Yermilov, Irina Parikh, Janak A. Dutson, Erik Mehran, Amir Ko, Clifford Y. Gibbons, Melinda Maggard TI Exercise Following Bariatric Surgery: Systematic Review SO OBESITY SURGERY LA English DT Review DE Bariatric surgery; Weight loss; Exercise ID PHYSICAL-ACTIVITY QUESTIONNAIRE; GASTRIC BYPASS-SURGERY; WEIGHT-LOSS; CONTROLLED-TRIAL; OBESITY; OVERWEIGHT; BMI; MEN; ASSOCIATION; RELIABILITY AB The contribution of physical activity on the degree of weight loss following bariatric surgery is unclear. To determine impact of exercise on postoperative weight loss. Medline search (1988-2009) was completed using MeSH terms including bariatric procedures and a spectrum of patient factors with potential relationship to weight loss outcomes. Of the 934 screened articles, 14 reported on exercise and weight loss outcomes. The most commonly used instruments to measure activity level were the Baecke Physical Activity Questionnaire, the International Physical Activity Questionnaire, and a variety of self-made questionnaires. The definition of an active patient varied but generally required a minimum of 30 min of exercise at least 3 days per week. Thirteen articles reported on exercise and degree of postoperative weight loss (n = 4,108 patients). Eleven articles found a positive association of exercise on postoperative weight loss, and two did not. Meta-analysis of three studies revealed a significant increase in 1-year postoperative weight loss (mean difference = 4.2% total body mass index (BMI) loss, 95% confidence interval (CI; 0.26-8.11)) for patients who exercise postoperatively. Exercise following bariatric surgery appears to be associated with a greater weight loss of over 4% of BMI. While a causal relationship cannot be established with observational data, this finding supports the continued efforts to encourage and support patients' involvement in post-surgery exercise. Further research is necessary to determine the recommended activity guidelines for this patient population. C1 [Livhits, Masha; Yermilov, Irina; Parikh, Janak A.; Ko, Clifford Y.; Gibbons, Melinda Maggard] VA Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA 90073 USA. [Gibbons, Melinda Maggard] Olive View UCLA, Dept Surg, Sylmar, CA 91342 USA. [Livhits, Masha; Mercado, Cheryl; Yermilov, Irina; Parikh, Janak A.; Dutson, Erik; Mehran, Amir; Ko, Clifford Y.; Gibbons, Melinda Maggard] Univ Calif Los Angeles, Dept Surg, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Livhits, M (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Surg, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM mlivhits@mednet.ucla.edu FU VA Department of Surgery, Robert Wood Johnson Physician Faculty FX We would like to acknowledge the generous contribution of Paul G. Shekelle to the design of our project and critical review of the analysis. The VA Department of Surgery provided support for Dr. Livhits and Dr. Maggard. Dr. Maggard's time was supported in part by a grant from the Robert Wood Johnson Physician Faculty Scholars program.; VA Department of Surgery, Robert Wood Johnson Physician Faculty Scholars program NR 33 TC 63 Z9 65 U1 6 U2 14 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0960-8923 J9 OBES SURG JI Obes. Surg. PD MAY PY 2010 VL 20 IS 5 BP 657 EP 665 DI 10.1007/s11695-010-0096-0 PG 9 WC Surgery SC Surgery GA 580SR UT WOS:000276470700018 PM 20180039 ER PT J AU Wylie, BJ D'Alton, ME AF Wylie, Blair J. D'Alton, Mary E. TI Fetomaternal Hemorrhage SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID FETAL INTRAVASCULAR TRANSFUSION; RED-CELL ALLOIMMUNIZATION; BLOOD-VOLUME RESTORATION; FLOW-CYTOMETRIC METHOD; INTRAUTERINE TRANSFUSION; MATERNAL HEMORRHAGE; PLACENTAL PATHOLOGY; NONIMMUNE HYDROPS; POST PARTUM; PREGNANCY AB Fetomaternal hemorrhage refers to the entry of fetal blood into the maternal circulation before or during delivery. Antenatal fetomaternal hemorrhage is a pathological condition with a wide spectrum of clinical variation. Secondary to the resultant anemia, fetomaternal hemorrhage may have devastating consequences for the fetus such as neurologic injury, stillbirth, or neonatal death. Presentation is frequently without an evident precipitating factor. Recognition may become apparent only after injury has occurred, if at all. The most common antenatal presentation is decreased fetal activity and a heightened index of suspicion is warranted in cases of persistent maternal perception of decreased fetal movements. The diagnostic standard, the Kleihauer-Betke screen, has several limitations. Management remains challenging. When detected antenatally, cordocentesis with intrauterine transfusion may be attempted to correct the anemia; however, repeat intrauterine transfusion or delivery may be necessitated to correct ongoing bleeding. Although the occurrence of large antenatal fetomaternal hemorrhage is fortunately rare, this entity likely remains underreported and underrecognized. A national registry should be created to advance our learning across institutions by reviewing the clinical presentations of fetomaternal hemorrhage, the variety of fetal heart rate tracings observed, the management strategies undertaken, and the outcomes achieved. (Obstet Gynecol 2010;115:1039-51) C1 [Wylie, Blair J.] Massachusetts Gen Hosp, Div Maternal Fetal Med, Dept Obstet & Gynecol, Boston, MA 02114 USA. Columbia Univ, Div Maternal Fetal Med, Dept Obstet & Gynecol, Med Ctr, New York, NY USA. RP Wylie, BJ (reprint author), Massachusetts Gen Hosp, Div Maternal Fetal Med, Dept Obstet & Gynecol, 55 Fruit St,Founders 4, Boston, MA 02114 USA. EM bwylie@partners.org NR 86 TC 41 Z9 45 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD MAY PY 2010 VL 115 IS 5 BP 1039 EP 1051 DI 10.1097/AOG.0b013e3181da7929 PG 13 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 589WV UT WOS:000277185800024 PM 20410781 ER PT J AU Kaimal, AJ Smith, CC Laros, RK Caughey, AB Cheng, YW AF Kaimal, Anjali J. Smith, Catherine C. Laros, Russell K., Jr. Caughey, Aaron B. Cheng, Yvonne W. TI Cost-Effectiveness of Private Umbilical Cord Blood Banking Reply SO OBSTETRICS AND GYNECOLOGY LA English DT Letter ID TRANSPLANTATION C1 [Kaimal, Anjali J.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Div Maternal Fetal Med, Boston, MA 02114 USA. RP Kaimal, AJ (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, Div Maternal Fetal Med, Boston, MA 02114 USA. NR 6 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD MAY PY 2010 VL 115 IS 5 BP 1090 EP 1091 DI 10.1097/AOG.0b013e3181d68fbb PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 589WV UT WOS:000277185800032 ER PT J AU Kilbridge, KL AF Kilbridge, Kerry L. TI Quality-Adjusted Life-Years, Comparative Effectiveness in Cancer Care, and Measuring Outcomes in the Underserved SO ONCOLOGY-NEW YORK LA English DT Article ID HEALTH-STATE PREFERENCES; PAPER STANDARD GAMBLE; OF-LIFE; PROSTATE-CANCER; CLASSIFICATION-SYSTEM; CLINICAL-TRIALS; UTILITY; THERAPY; QUESTIONNAIRE; METHODOLOGY AB Recently, the American Recovery and Reinvestment Act (ARRA) set aside $1.1 billion for comparative effectiveness research (CER) to investigate what healthcare strategies and interventions offer the greatest benefits to individual patients and the population as a whole. The Institute of Medicine has identified CER in cancer care as a high priority research focus for ARRA funding. The ability to measure quality of life will be central to CER in oncology because survival and disease-free survival do not adequately capture outcomes important to policy makers, physicians, and patients. There are two ways to measure quality of life: descriptive health status and patient preference weights (utilities). However, only patient preference weights can be incorporated into the economic analysis of medical resources and be used in the calculation of quality-adjusted life-years (QALYs). Some of the advantages and limitations inherent in measuring quality of life with descriptive health status and patient preference weights are discussed. Both types of measurements face health literacy barriers to their application in underserved populations, an important concern for CER in all medical fields. C1 [Kilbridge, Kerry L.] Massachusetts Gen Hosp, Gen Internal Med Unit, Boston, MA 02114 USA. [Kilbridge, Kerry L.] Massachusetts Gen Hosp, Dept Hematol & Oncol, Boston, MA 02114 USA. [Kilbridge, Kerry L.] Harvard Univ, Sch Med, Boston, MA USA. RP Kilbridge, KL (reprint author), Massachusetts Gen Hosp, Gen Internal Med Unit, Boston, MA 02114 USA. NR 40 TC 4 Z9 4 U1 1 U2 2 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 MAY PY 2010 VL 24 IS 6 BP 530 EP 536 PG 7 WC Oncology SC Oncology GA 800BH UT WOS:000293331500011 PM 20568594 ER PT J AU Woods, RL Giorgi, RG Berson, EL Peli, E AF Woods, Russell L. Giorgi, Robert G. Berson, Eliot L. Peli, Eli TI Extended wearing trial of Trifield lens device for 'tunnel vision' SO OPHTHALMIC AND PHYSIOLOGICAL OPTICS LA English DT Article DE choroideremia; low vision rehabilitation; mobility; retinitis pigmentosa; Trifield glasses; tunnel vision ID SALISBURY EYE EVALUATION; VISUAL-FIELD EXPANSION; RETINITIS-PIGMENTOSA; MOBILITY PERFORMANCE; AMORPHIC LENSES; RISK-FACTORS; WALKING; FALLS; RELIABILITY; REHABILITATION AB Severe visual field constriction (tunnel vision) impairs the ability to navigate and walk safely. We evaluated Trifield glasses as a mobility rehabilitation device for tunnel vision in an extended wearing trial. Twelve patients with tunnel vision (5-22 degrees wide) due to retinitis pigmentosa or choroideremia participated in the 5-visit wearing trial. To expand the horizontal visual field, one spectacle lens was fitted with two apex-to-apex prisms that vertically bisected the pupil on primary gaze. This provides visual field expansion at the expense of visual confusion (two objects with the same visual direction). Patients were asked to wear these spectacles as much as possible for the duration of the wearing trial (median 8, range 6-60 weeks). Clinical success (continued wear, indicating perceived overall benefit), visual field expansion, perceived direction and perceived visual ability were measured. Of 12 patients, nine chose to continue wearing the Trifield glasses at the end of the wearing trial. Of those nine patients, at long-term follow-up (35-78 weeks), three reported still wearing the Trifield glasses. Visual field expansion (median 18, range 9-38 degrees) was demonstrated for all patients. No patient demonstrated adaptation to the change in visual direction produced by the Trifield glasses (prisms). For reported difficulty with obstacles, some differences between successful and non-successful wearers were found. Trifield glasses provided reported benefits in obstacle avoidance to 7 of the 12 patients completing the wearing trial. Crowded environments were particularly difficult for most wearers. Possible reasons for long-term discontinuation and lack of adaptation to perceived direction are discussed. C1 [Woods, Russell L.; Giorgi, Robert G.; Peli, Eli] Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. [Berson, Eliot L.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Berman Gund Lab Study Retinal Degenerat, Boston, MA USA. RP Woods, RL (reprint author), Harvard Univ, Sch Med, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM russell.woods@schepens.harvard.edu RI Woods, Russell/O-2600-2015 OI Woods, Russell/0000-0002-7193-1211 FU NIH [EY12890]; Foundation Fighting Blindness (ELB) FX Supported in part by a grant from the Joint SERI-MEEI Clinical Research Center, by NIH grant #EY12890 (EP), and by the Foundation Fighting Blindness (ELB). Dan Stringer and Jenn Segawa helped with data collection. Bob Goldstein developed the software for measurement of the perceived direction. Karen Keeney (Chadwick Optical, White River Junction, VT) was instrumental in the development of techniques to make the Trifield glasses. NR 61 TC 8 Z9 8 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0275-5408 EI 1475-1313 J9 OPHTHAL PHYSL OPT JI Ophthalmic Physiol. Opt. PD MAY PY 2010 VL 30 IS 3 BP 240 EP 252 DI 10.1111/j.1475-1313.2010.00718.x PG 13 WC Ophthalmology SC Ophthalmology GA 580QX UT WOS:000276465500003 PM 20444130 ER PT J AU Borodic, GE AF Borodic, Gary E. TI Orbicularis Oculi Myo-osseous Fixation: A New Treatment for Benign Essential Blepharospasm and Blepharospasm Associated With Diffuse Facial Dystonia (Meige Syndrome) SO OPHTHALMIC SURGERY LASERS & IMAGING LA English DT Article ID DEEP BRAIN-STIMULATION; BOTULINUM TOXIN THERAPY; BLINK REFLEX; FOLLOW-UP; NERVE; DOXORUBICIN; MODULATION; MYECTOMY; SURGERY; MUSCLE AB BACKGROUND AND OBJECTIVE: This article describes a novel surgical procedure, myo-osseous fixation, as an adjunct therapy for patients with reduced or poor response to repeated botulinum toxin injections for essential blepharospasm and Meige syndrome. PATIENTS AND METHODS: The small-incision, rapidly healing, rapidly performed technique uses self-drilling titanium screws tightly engaged with a compression wrench. The screws fixate the periorbital orbicularis oculi muscle to bone, creating mechanical resistance to outer portions of the orbicularis muscle involved in debilitating involuntary contractions. RESULTS: Eleven of the treated 12 patients experienced immediate improvement in function. Each responding patient noted enhanced effect of subsequent botulinum toxin injections at previously ineffective doses. The benefit was substantial and sustained for 6 months in 9 of 12 patients. Decreased brow depression during forced closure, forced frown, and brow elevation at rest was apparent in all patients postoperatively. Although the brow elevation effect was reduced after 6 months, reduced brow depression during forced closure still was easily demonstrated in most patients. Complications included a nodular bump over the brow, more commonly found when large titanium screws were used, transient headache, and easily removed dislodged screw. CONCLUSION: Initial data suggest that this procedure appears safe, well tolerated, and useful in the treatment of patients with essential blepharospasm and Meige syndrome responding poorly to botulinum toxin therapy. C1 [Borodic, Gary E.] Harvard Univ, Sch Med, Boston, MA USA. [Borodic, Gary E.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Borodic, GE (reprint author), Massachusetts Eye & Ear Infirm, 1261 Furnace Brook Pkwy, Quincy, MA 02169 USA. NR 33 TC 0 Z9 0 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1542-8877 J9 OPHTHAL SURG LAS IM JI Ophthalmic Surg. Lasers Imaging PD MAY-JUN PY 2010 VL 41 IS 3 BP 360 EP 369 DI 10.3928/15428877-20100430-11 PG 10 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 598YS UT WOS:000277876700011 PM 20507022 ER PT J AU Aiello, LP Edwards, AR Beck, RW Bressler, NM Davis, MD Ferris, F Glassman, AR Ip, MS Miller, KM AF Aiello, Lloyd Paul Edwards, Allison R. Beck, Roy W. Bressler, Neil M. Davis, Matthew D. Ferris, Frederick Glassman, Adam R. Ip, Michael S. Miller, Kellee M. CA Diabet Retinopathy Clinical Res TI Factors Associated with Improvement and Worsening of Visual Acuity 2 Years after Focal/Grid Photocoagulation for Diabetic Macular Edema SO OPHTHALMOLOGY LA English DT Article ID INTRAVITREAL TRIAMCINOLONE; RETINOPATHY; TRIAL; PROGRESSION AB Purpose: To identify factors associated with the visual acuity outcome after focal/grid photocoagulation for diabetic macular edema (DME) among eyes randomized to the focal/grid photocoagulation treatment group within the Diabetic Retinopathy Clinical Research Network (DRCR.net) trial comparing triamcinolone with focal/grid laser. Design: Multicenter, randomized, clinical trial. Participants: Three hundred thirty eyes with DME assigned to the focal/grid photocoagulation group, visual acuity 20/40 to 20/320, and optical coherence tomography (OCT) central subfield thickness >= 250 microns. Methods: Eyes were treated with a protocol-defined photocoagulation technique, which was repeated at 4-month intervals for persistent or recurrent edema. Separate logistic regression models were used to evaluate the associations of demographic, clinical, OCT, and fundus photographic variables with visual acuity improvement or worsening of >= 10 letters from baseline to 2 years. The association of the initial visual acuity outcome after treatment with the subsequent visual acuity course also was evaluated. Main Outcome Measures: Visual acuity measured with the electronic Early Treatment Diabetic Retinopathy Study method. Results: Worse baseline visual acuity was the only factor found to be associated with more frequent visual acuity improvement (P<0.001), and both greater baseline OCT-measured retinal volume (P = 0.001) and better baseline visual acuity (P = 0.009) were found to be associated with more frequent visual acuity worsening. Visual acuity outcomes were similar in eyes with and without prior macular or panretinal photocoagulation. The initial visual acuity outcome at 4 months was not generally predictive of the subsequent course. Many eyes that worsened >= 10 letters from baseline to 4 months subsequently improved, and many eyes that initially improved, subsequently worsened. Conclusions: At this time, focal/grid photocoagulation remains the standard management for DME and these results do not alter this paradigm. C1 [Ferris, Frederick] NEI, NIH, Bethesda, MD 20892 USA. [Ip, Michael S.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. [Bressler, Neil M.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA. [Edwards, Allison R.; Beck, Roy W.; Glassman, Adam R.; Miller, Kellee M.] Jaeb Ctr Hlth Res, Tampa, FL 33647 USA. [Aiello, Lloyd Paul] Harvard Univ, Sch Med, Dept Ophthalmol, Cambridge, MA 02138 USA. [Aiello, Lloyd Paul] Harvard Univ, Sch Med, Joslin Diabet Ctr, Cambridge, MA 02138 USA. RP Edwards, AR (reprint author), Jaeb Ctr Hlth Res, 15310 Amberly Dr,Suite 350, Tampa, FL 33647 USA. EM drcrstat1@jaeb.org FU Allergan; National Eye Institute; National Institute of Diabetes and Digestive and Kidney Diseases; National Institutes of Health; U.S. Department of Health and Human Services [EY14231, EY14269, EY14229] FX Dr. Michael S. Ip receives consultant fees for QLT, Sirion Therapeutics, Heidelberg Engineering. He also receives financial support from Allergan. However, we do not believe that any of these constitutes a financial conflict of interest for this manuscript.; Supported through a cooperative agreement from the National Eye Institute and the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, U.S. Department of Health and Human Services EY14231, EY14269, EY14229. NR 14 TC 37 Z9 38 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 EI 1549-4713 J9 OPHTHALMOLOGY JI Ophthalmology PD MAY PY 2010 VL 117 IS 5 BP 946 EP 953 DI 10.1016/j.ophtha.2009.10.002 PG 8 WC Ophthalmology SC Ophthalmology GA 590XM UT WOS:000277261800015 PM 20122739 ER PT J AU Martin, K Rossi, V Ferrucci, S Pian, D AF Martin, Krista Rossi, Victoria Ferrucci, Steven Pian, Debi TI Retinal astrocytic hamartoma SO OPTOMETRY-JOURNAL OF THE AMERICAN OPTOMETRIC ASSOCIATION LA English DT Article DE Astrocytic hamartoma; Astrocytoma; Phakomatoses; Tuberous sclerosis ID OPTICAL COHERENCE TOMOGRAPHY; TUBEROUS SCLEROSIS; SIMULATING RETINOBLASTOMA; NEUROFIBROMATOSIS TYPE-1; SPONTANEOUS REGRESSION; NEUROIMAGING FINDINGS; PIGMENT EPITHELIUM; TUMORS; PHAKOMATOSIS; HYPERPLASIA AB BACKGROUND: Retinal astrocytic hamartomas are glial tumors of the retinal nerve fiber layer that arise from retinal astrocytes. Classically they appear as a cream-white, well-circumscribed, elevated lesion that may present as multiple or solitary sites. A lesion is commonly seen with a multilobulated, "mulberry" appearance, but can also appear flat and semitranslucent. It is most frequently associated with tuberous sclerosis (TS) but may also be found rarely in patients with neurofibromatosis. Although the finding may point toward a systemic association, it can also be found incidentally on retinal examination as an isolated presentation. CASE REPORTS: Two cases of solitary retinal astrocytic hamartomas without systemic complications discovered at routine examination are presented. Both patients were found to have a raised, multilobulated retinal lesion consistent with the appearance of a retinal astrocytic hamartoma. In both cases, the patients had no personal or family history of seizures or any signs of unusual dermatologic lesions. B-scan ultrasonography, fluorescein angiography, and magnetic resonance imaging (MRI) were performed as necessary. CONCLUSION: A retinal astrocytic hamartoma is typically associated with TS but can also present as a spontaneous, idiopathic lesion. Prompt referral to rule out TS or other systemic associations, particularly in young children, is important. Neuroimaging, along with other diagnostic tests, may ensure the proper management and rule out need for further evaluation. Spontaneous lesions without systemic association can initially be monitored closely to rule out possible progression. Once stability has been established, annual follow-up with a primary care eye practitioner is appropriate. Optometry 2010;81:221-233 C1 [Martin, Krista] Vet Affairs Greater Los Angeles Healthcare Syst, Santa Maria Vet Affairs Community Based Outpatien, Santa Maria, CA USA. [Rossi, Victoria; Ferrucci, Steven] Vet Affairs Greater Los Angeles Healthcare Syst, Sepulveda Vet Affairs Ambulatory Care Ctr Nursing, Sepulveda, CA USA. [Ferrucci, Steven] So Calif Coll Optometry, Fullerton, CA USA. [Pian, Debi] SUNY Coll Optometry, New York, NY 10010 USA. RP Ferrucci, S (reprint author), Sepulveda VA Ambulatory Care Ctr, Dept Optometry, 16111 Plummer St,112E, Sepulveda, CA 91343 USA. EM steven.ferrucci@va.gov NR 48 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 1529-1839 J9 OPTOMETRY JI Optometry PD MAY PY 2010 VL 81 IS 5 BP 221 EP 233 DI 10.1016/j.optm.2009.12.009 PG 13 WC Ophthalmology SC Ophthalmology GA 800MD UT WOS:000293364100003 PM 20435268 ER PT J AU Yumori, JW Ilsen, P Bright, DC AF Yumori, Jasmine W. Ilsen, Pauline Bright, David C. TI Conjunctival plasmacytoma SO OPTOMETRY-JOURNAL OF THE AMERICAN OPTOMETRIC ASSOCIATION LA English DT Article DE Plasmacytoma; Solitary extramedullary plasmacytoma; Multiple myeloma; Conjunctival tumor; Excisional biopsy ID HEPATITIS-C VIRUS; EXTRAMEDULLARY PLASMACYTOMA; SOLITARY PLASMACYTOMA; MULTIPLE-MYELOMA; LYMPHOMA; TUMORS; HEAD; NECK; MANIFESTATIONS; INFECTION AB BACKGROUND: Plasmacytomas are plasma cell tumors that may be a primary or secondary tumor focus, the latter of which are associated with multiple myeloma. We present a rare case of a solitary extramedullary plasmacytoma involving the conjunctiva. CASE REPORT: A 33-year-old white man presented with the initial complaint of redness in both eyes, more in his right than left eye. A vascularized conjunctival lesion was noted in his right eye. The patient underwent excisional biopsy, which found a conjunctival plasmacytoma. CONCLUSION: Although plasmacytomas of the eye and orbit are rare, it is important to be familiar with these tumors that may be associated with multiple myeloma. Definitive diagnosis is made by biopsy and histopathologic examination of the tissue. Plasmacytomas may be treated with external beam radiation, local excision, or radiotherapy after surgical excision. Long-term follow-up, including periodic systemic evaluation, is required to establish that orbital involvement is not an early manifestation of multiple myeloma. Optometry 2010;81:234-239 C1 [Yumori, Jasmine W.; Ilsen, Pauline; Bright, David C.] W Los Angeles Vet Affairs Hlth Ctr, Los Angeles, CA USA. [Yumori, Jasmine W.] Western Univ Hlth Sci, Pomona, CA USA. [Ilsen, Pauline; Bright, David C.] So Calif Coll Optometry, Fullerton, CA USA. RP Yumori, JW (reprint author), 309 E 2nd St, Pomona, CA 91766 USA. EM jyumori@westernu.edu NR 43 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1529-1839 J9 OPTOMETRY JI Optometry PD MAY PY 2010 VL 81 IS 5 BP 234 EP 239 DI 10.1016/j.optm.2009.11.006 PG 6 WC Ophthalmology SC Ophthalmology GA 800MD UT WOS:000293364100004 PM 20435269 ER PT J AU Glynn, SM AF Glynn, Shirley M. TI The Psychosocial Characteristics and Needs of Patients Presenting with Orofacial Injury SO ORAL AND MAXILLOFACIAL SURGERY CLINICS OF NORTH AMERICA LA English DT Article DE Sociodemographic; Socioeconomic; Orofacial injury; Trauma ID POSTTRAUMATIC-STRESS-DISORDER; RANDOMIZED CONTROLLED-TRIAL; FACIAL INJURY; MANDIBULAR FRACTURES; MAXILLOFACIAL INJURY; SCREENING INSTRUMENT; UNITED-STATES; TRAUMA CENTER; HEALTH-CARE; PREVALENCE AB Individuals with orofacial injury presenting to urban trauma centers in the United States tend to be disproportionately socioeconomically disadvantaged, young, adult, ethnic minority men. Most injuries are assaultive in origin, suggesting poor impulse control and maladaptive social behaviors. Compared with matched control populations, patients with orofacial injuries are more likely to report higher levels of substance use behaviors and to manifest greater levels of hostility, anxiety, and depression. Although they have significantly greater current and lifetime need for mental health service and social service, actual use of social services is low. The underlying psychosocial characteristics of many patients with orofacial injury, along with unmet service needs, render them vulnerable for posttrauma psychological sequelae and may compromise functional outcomes and recovery. C1 [Glynn, Shirley M.] VA Greater Los Angeles Healthcare Syst W Los Ange, Res Serv, Los Angeles, CA 90073 USA. [Glynn, Shirley M.] Univ Calif Los Angeles, Semel Inst, Los Angeles, CA USA. RP Glynn, SM (reprint author), VA Greater Los Angeles Healthcare Syst, Res Serv, B151J,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM sglynn@ucla.edu FU National Institutes of Health/National Institute of Dental and Craniofacial Research [P50/DE-10598] FX This work was supported by Grant Number P50/DE-10598 from the National Institutes of Health/National Institute of Dental and Craniofacial Research. NR 31 TC 2 Z9 2 U1 2 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 1042-3699 J9 ORAL MAXIL SURG CLIN JI Oral Maxillofac. Surg. Clin. N. Am. PD MAY PY 2010 VL 22 IS 2 BP 209 EP + DI 10.1016/j.coms.2010.01.003 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 864TV UT WOS:000298263900002 PM 20403551 ER PT J AU Glynn, SM Shetty, V AF Glynn, Shirley M. Shetty, Vivek TI The Long-Term Psychological Sequelae of Orofacial Injury SO ORAL AND MAXILLOFACIAL SURGERY CLINICS OF NORTH AMERICA LA English DT Article DE Facial injury; Chronic sequela; Psychosocial; Screening ID POSTTRAUMATIC-STRESS-DISORDER; RISK-FACTORS; ASSAULT VICTIMS; FACIAL INJURY; TRAUMA CENTER; DEPRESSION; PTSD; INTERVENTIONS; PREVENTION; SAMPLE AB Significant subsets of patients who experience orofacial injury are at risk for developing adverse psychological sequelae such as posttraumatic stress disorder and depression. If undetected and untreated, the psychopathology can become recalcitrant and burden the social and vocational functioning of the patients and greatly diminish their quality of life. The hospital encounter and follow-up care visits provide the oral and maxillofacial surgeon with opportunities to screen for emerging psychological problems. Several screening instruments are available to assist the surgeon in identifying individuals who are at risk for subsequent mental health problems. Facilitated referrals to mental health services can be a practical approach for improving comprehensive medical care for vulnerable individuals and for reducing the potential morbidity of these covert, but disabling, sequelae. C1 [Glynn, Shirley M.] Univ Calif Los Angeles, Semel Inst, Los Angeles, CA USA. [Shetty, Vivek] 23009 UCLA Sch Dent, Sect Oral & Maxillofacial Surg, Los Angeles, CA 90095 USA. [Glynn, Shirley M.] VA Greater Angeles Healthcare Syst W Los Angeles, Res Serv, Los Angeles, CA 90073 USA. RP Glynn, SM (reprint author), VA Greater Los Angeles Healthcare Syst, Res Serv, B151J,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM sglynn@ucla.edu FU National Institutes of Health/NIDCR [P50/DE-10598] FX This work was supported by grant number P50/DE-10598 from the National Institutes of Health/NIDCR. NR 40 TC 4 Z9 4 U1 3 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 1042-3699 J9 ORAL MAXIL SURG CLIN JI Oral Maxillofac. Surg. Clin. N. Am. PD MAY PY 2010 VL 22 IS 2 BP 217 EP + DI 10.1016/j.coms.2010.01.008 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 864TV UT WOS:000298263900003 PM 20403552 ER PT J AU Halpern, LR AF Halpern, Leslie R. TI Orofacial Injuries as Markers for Intimate Partner Violence SO ORAL AND MAXILLOFACIAL SURGERY CLINICS OF NORTH AMERICA LA English DT Article DE Intimate partner violence (IPV); Maxillofacial injuries; Head; Neck and facial injuries; Diagnostic protocol ID MOTOR-VEHICLE ACCIDENTS; DOMESTIC VIOLENCE; EMERGENCY-DEPARTMENT; BATTERED WOMEN; MAXILLOFACIAL FRACTURES; FACIAL INJURIES; HEAD-INJURY; TRAUMA; ASSAULT; ETIOLOGY AB Health care professionals have increasingly recognized that intimate partner violence (IPV) is a highly prevalent public health problem with devastating effects on individuals, families, and communities. However, there are no obvious clinical characteristics of IPV. Interventions may prevent future IPV-related injuries, but they cannot be initiated until the diagnosis is made. Because of the frequency of IPV-related orofacial injuries, oral and maxillofacial surgeons (OMSs) may be the first and only health care providers to see these patients. Therefore, OMSs are in a pivotal position to diagnosis IPV-related injuries and expedite referral for interventional therapy. This article presents data that support the use of orofacial injuries as a prime predictor variable in identifying victims of IPV and provides: (1) an overview of the epidemiology of IPV-related orofacial injuries; (2) a discussion of the role of head, neck, and facial injuries as markers of IPV, and their role as a diagnostic tool to facilitate the early diagnosis and referral for management of IPV; (3) a list of the advantages and limitations of using orofacial injuries as indicators of IPV; and (4) future directions to improve efforts to educate OMSs in identifying patients who are at high risk for an IPV-related injury. C1 Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Halpern, LR (reprint author), Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 55 Fruit St,Warren Bldg,Suite 1201, Boston, MA 02114 USA. EM Lhalpern1@partners.org NR 72 TC 5 Z9 6 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 1042-3699 J9 ORAL MAXIL SURG CLIN JI Oral Maxillofac. Surg. Clin. N. Am. PD MAY PY 2010 VL 22 IS 2 BP 239 EP + DI 10.1016/j.coms.2010.01.009 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 864TV UT WOS:000298263900006 PM 20403555 ER PT J AU Gironda, MW Lui, A AF Gironda, Melanie W. Lui, Anna TI Social Support and Resource Needs as Mediators of Recovery After Facial Injury SO ORAL AND MAXILLOFACIAL SURGERY CLINICS OF NORTH AMERICA LA English DT Article DE Social support; Social network; Measures; Resource; Facial injury ID SPINAL-CORD-INJURY; QUALITY-OF-LIFE; MULTIDIMENSIONAL SCALE; STRESS RESISTANCE; BREAST-CANCER; HEALTH; IMPACT; ADOLESCENTS; DEPRESSION; COMMUNITY AB Although many trauma centers provide excellent surgical care, little attention is paid to psychosocial needs and problems of posttrauma adaptation. Social support and resource needs have been identified as significant mediators of recovery after injuries. This article presents an overview of various social and material resources instrumental to psychological adjustment and recovery. It also discusses the ways in which complex social networks can be both beneficial and damaging toward the recovery process and the implications for clinical care of patients with orofacial injury. Finally, appropriate social support resource measuring tools that may be used in clinical settings are presented. C1 [Gironda, Melanie W.] Univ Calif Los Angeles, Div Publ Hlth & Community Dent, UCLA Sch Dent, Los Angeles, CA 90095 USA. [Gironda, Melanie W.] Univ Calif Los Angeles, Sch Publ Affairs, Dept Social Welf, Los Angeles, CA 90095 USA. [Lui, Anna] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Psychiat, Los Angeles, CA 90073 USA. RP Gironda, MW (reprint author), Univ Calif Los Angeles, Div Publ Hlth & Community Dent, UCLA Sch Dent, Box 951668,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM mgironda@ucla.edu NR 81 TC 3 Z9 3 U1 2 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 1042-3699 J9 ORAL MAXIL SURG CLIN JI Oral Maxillofac. Surg. Clin. N. Am. PD MAY PY 2010 VL 22 IS 2 BP 251 EP + DI 10.1016/j.coms.2010.01.006 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 864TV UT WOS:000298263900008 PM 20403557 ER PT J AU Rosengren, BE Nilsson, JA Ohlsson, C Mellstrom, D Lorentzon, M Ljunggren, O Ribom, E Mallmin, H Stefanick, ML Lapidus, JA Leung, PC Barrett-Connor, E Orwoll, E Karlsson, MK AF Rosengren, B. E. Nilsson, J. A. Ohlsson, C. Mellstrom, D. Lorentzon, M. Ljunggren, O. Ribom, E. Mallmin, H. Stefanick, M. L. Lapidus, J. A. Leung, P. C. Barrett-Connor, E. Orwoll, E. Karlsson, M. K. CA MrOs Study Grp TI EPIDEMIOLOGY OF FALLS AMONG 11009 ELDERLY MEN - THE MR OS STUDY SO OSTEOPOROSIS INTERNATIONAL LA English DT Meeting Abstract CT IOF World Congress on Osteoporosis/10th European Congress on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis CY MAY 05-08, 2010 CL Florence, ITALY C1 [Rosengren, B. E.; Nilsson, J. A.; Karlsson, M. K.] Lund Univ, Clin & Mol Osteoporosis Res Unit, Dept Orthoped Surg, Malmo, Sweden. [Rosengren, B. E.; Nilsson, J. A.; Karlsson, M. K.] Lund Univ, Dept Clin Sci, Malmo Univ Hosp, Malmo, Sweden. [Ohlsson, C.; Mellstrom, D.; Lorentzon, M.] Univ Gothenburg, Ctr Bone Res, Dept Internal Med & Geriatr, Sahlgrenska Acad, Gothenburg, Sweden. [Ljunggren, O.] Uppsala Univ, Ctr Metab Bone Dis, Dept Med Sci, Uppsala, Sweden. [Ribom, E.; Mallmin, H.] Uppsala Univ, Dept Orthoped Surg, Dept Surg Sci, Uppsala, Sweden. [Stefanick, M. L.] Stanford Univ, Stanford Prevent Res Ctr, Dept Med, Palo Alto, CA 94304 USA. [Lapidus, J. A.; Orwoll, E.] Oregon Hlth & Sci Univ, Bone & Mineral Res Unit, Portland, OR USA. [Lapidus, J. A.] Portland VA Med Ctr, Portland, OR USA. [Barrett-Connor, E.] Univ Calif San Diego, Dept Family & Prevent Med, San Diego, CA 92103 USA. [Leung, P. C.] Chinese Univ Hong Kong, Inst Chinese Med, Hong Kong, Hong Kong, Peoples R China. RI Rosengren, Bjorn/F-8345-2011 NR 0 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD MAY PY 2010 VL 21 SU 1 BP 7 EP 8 DI 10.1007/s00198-010-1246-x PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 591KN UT WOS:000277299400015 ER PT J AU Kenan, Y Kochba, E Shahar, M Gadasi, H Levin, G Foldes, AJ Ish-Shalom, S Matsumoto, T Lindsay, R Christiansen, C Neer, R AF Kenan, Y. Kochba, E. Shahar, M. Gadasi, H. Levin, G. Foldes, A. J. Ish-Shalom, S. Matsumoto, T. Lindsay, R. Christiansen, C. Neer, R. TI COMPARISON OF TRANSDERMAL AND SUBCUTANEOUS TERIPARATIDE EFFECTS ON MARKERS OF BONE TURNOVER AND SAFETY IN POSTMENOPAUSAL WOMEN SO OSTEOPOROSIS INTERNATIONAL LA English DT Meeting Abstract CT IOF World Congress on Osteoporosis/10th European Congress on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis CY MAY 05-08, 2010 CL Florence, ITALY C1 [Kenan, Y.; Kochba, E.; Shahar, M.; Gadasi, H.; Levin, G.] TransPharma Med Ltd, Lod, Israel. [Foldes, A. J.] Hadassah Hebrew Univ, Med Ctr, Jerusalem, Israel. [Ish-Shalom, S.] Rambam Hlth Care Ctr, Metabol Bone Dis Unit, Haifa, Israel. [Matsumoto, T.] Univ Tokushima, Grad Sch Med Sci, Dept Med & Bioregulatory Sci, Tokushima 770, Japan. [Lindsay, R.] Helen Hayes Hosp, W Haverstraw, NY USA. [Neer, R.] Massachusetts Gen Hosp, Boston, MA USA. [Christiansen, C.] Nord Biosci, Herlev, Denmark. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD MAY PY 2010 VL 21 SU 1 BP 178 EP 178 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 591KN UT WOS:000277299400384 ER PT J AU Shin, JJ Randolph, GW Rauch, SD AF Shin, Jennifer J. Randolph, Gregory W. Rauch, Steven D. TI Evidence-based medicine in otolaryngology, part 1: The multiple faces of evidence-based medicine SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; EVIDENCE-BASED GUIDELINES; USERS GUIDES; CLINICAL EXPERTISE; CONTROLLED-TRIAL; DECISION-MAKING; COMMON-SENSE; OUTCOMES; IMPLEMENTATION; CARE AB Evidence-based medicine, with its capacity to improve patient outcomes, has grown prominent throughout the medical field. Otolaryngology is at a crucial stage in the expansion of evidence-based medicine, with its impact seen in many arenas. As the evidence continues to shape our field, we hope to serve our otolaryngology community through this invited series, which is dedicated to the exposition of evidence-based medicine and its applications. This first installment examines evidence-based medicine itself and its multiple interpretations, including a purist view, a population-based view, and a view centered on the individual. Strengths and weaknesses of each are discussed, as well the potential for unification and evolution of these concepts. We also place evidence-based medicine in the context of the mindset of traditional medicine and anticipate future developments. (C) 2010 American Academy of Otolaryngology-Head and Neck Surgery Foundation. All rights reserved. C1 [Shin, Jennifer J.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Div Otolaryngol, Boston, MA 02114 USA. [Shin, Jennifer J.] Los Angeles Med Ctr, Div Head & Neck Surg, So Calif Permanente Med Grp, Los Angeles, CA USA. RP Shin, JJ (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Div Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM jennifer_shin@meei.harvard.edu RI Shin, Jennifer/A-3169-2016 NR 71 TC 11 Z9 11 U1 0 U2 6 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 EI 1097-6817 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD MAY PY 2010 VL 142 IS 5 BP 637 EP 646 DI 10.1016/j.otohns.2010.01.018 PG 10 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 591LT UT WOS:000277302800001 PM 20416448 ER PT J AU Dohadwala, M Wang, GY Heinrich, E Luo, J Lau, O Shih, H Munaim, Q Lee, G Hong, LS Lai, C Abemayor, E Fishbein, MC Elashoff, DA Dubinett, SM John, MAS AF Dohadwala, Mariam Wang, Guanyu Heinrich, Eileen Luo, Jie Lau, Ontario Shih, Hubert Munaim, Qahera Lee, Gina Hong, Longsheng Lai, Chi Abemayor, Elliot Fishbein, Michael C. Elashoff, David A. Dubinett, Steven M. John, Maie A. St. TI The role of ZEB1 in the inflammation-induced promotion of EMT in HNSCC SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Otolaryngology-Head-and-Neck-Surgery-Foundation CY OCT 04-07, 2009 CL San Diego, CA SP Amer Acad Otolaryngol Head & Neck Surg Fdn ID GROWTH-FACTOR RECEPTOR; CELL CARCINOMA LINES; E-CADHERIN; EXPRESSION; CANCER; CYCLOOXYGENASE-2; HEAD; DIFFERENTIATION; PHENOTYPE; SNAIL AB OBJECTIVES: To determine the role of ZEB1 in the inflammation-induced promotion of the epithelial-mesenchymal transition (EMT) in head and neck squamous cell carcinoma (HNSCC). STUDY DESIGN: A molecular biology study. Real-time quantitative reverse-transcriptase polymerase chain reaction (RT-PCR), Western blot analysis, and immunohistochemical staining of human HNSCC tissue sections were used to determine how inflammation affects the transcriptional repressor, ZEB1. SETTING: An academic hospital laboratory. SUBJECTS AND METHODS: Relative ZEB1 RNA levels were determined by RT-PCR, and protein expression was evaluated in situ by immunohistochemical staining of human HNSCC tissue sections. RESULTS: IL-1 beta-treated HNSCC cell lines demonstrated a significant decrease in E-cadherin mRNA and an increase in the mRNA expression of the transcriptional repressor ZEB1. IL-1 beta exposure led to enhanced ZEB1 binding at the chromatin level, as determined by chromatin immunoprecipitation assays (ChIP). An inverse relationship between ZEB1 and E-cadherin was demonstrated in situ by immunohistochemical staining of human HNSCC tissue sections. CONCLUSIONS: Our recent investigations indicate that inflammatory mediators are potent regulators of EMT in HNSCC. This is the first report indicating the role of ZEB1 in the inflammation-induced promotion of EMT in HNSCC. This newly defined pathway for transcriptional regulation of E-cadherin in HNSCC has important implications for targeted chemoprevention and therapy. (C) 2010 American Academy of Otolaryngology Head and Neck Surgery Foundation. All rights reserved. C1 [Lau, Ontario; Shih, Hubert; Munaim, Qahera; Abemayor, Elliot; John, Maie A. St.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Div Head & Neck Surg, Los Angeles, CA 90095 USA. [Dohadwala, Mariam; Wang, Guanyu; Heinrich, Eileen; Luo, Jie; Lee, Gina; Dubinett, Steven M.] Univ Calif Los Angeles, David Geffen Sch Med, Lung Canc Res Program, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. [Dohadwala, Mariam; Wang, Guanyu; Heinrich, Eileen; Luo, Jie; Lee, Gina; Dubinett, Steven M.] Univ Calif Los Angeles, David Geffen Sch Med, Div Pulm & Crit Care Med, Dept Med, Los Angeles, CA 90095 USA. [Heinrich, Eileen; Hong, Longsheng; Lai, Chi; Fishbein, Michael C.; Dubinett, Steven M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Abemayor, Elliot; Dubinett, Steven M.; John, Maie A. St.] Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. [Elashoff, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biostat, Los Angeles, CA 90095 USA. [Dohadwala, Mariam; Lee, Gina; Dubinett, Steven M.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP John, MAS (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Div Head & Neck Surg, 37-131 CHS,10833 Conte Ave, Los Angeles, CA 90095 USA. EM mstjohn@mednet.ucla.edu FU NCI NIH HHS [R01 CA111851] NR 18 TC 21 Z9 22 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD MAY PY 2010 VL 142 IS 5 BP 753 EP 759 DI 10.1016/j.otohns.2010.01.034 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 591LT UT WOS:000277302800021 PM 20416468 ER PT J AU Merchant, FM Heist, EK Nandigam, KV Mulligan, LJ Blendea, D Riedl, L McCarty, D Orencole, M Picard, MH Ruskin, JN Singh, JP AF Merchant, Faisal M. Heist, E. Kevin Nandigam, K. Veena Mulligan, Lawrence J. Blendea, Dan Riedl, Lindsay McCarty, David Orencole, Mary Picard, Michael H. Ruskin, Jeremy N. Singh, Jagmeet P. TI Interlead Distance and Left Ventricular Lead Electrical Delay Predict Reverse Remodeling During Cardiac Resynchronization Therapy SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article DE cardiac resynchronization therapy; left ventricle lead electrical delay; interlead distance; reverse remodeling; heart failure ID HEART-FAILURE; ECHOCARDIOGRAPHIC EVALUATION; ISCHEMIC CARDIOMYOPATHY; SITE; DYSSYNCHRONY; MORTALITY AB Methods: We studied 61 consecutive patients undergoing CRT for standard clinical indications. All patients underwent intraprocedural measurement of LVLED. Interlead distances in the horizontal (HD), vertical (VD), and direct (DD) dimensions were measured from postprocedure chest radiographs (CXR). Remodeling indices [percent change in left ventricle (LV) ejection fraction, end-diastolic, end-systolic dimensions] were assessed by transthoracic echocardiogram. Results: There was a positive correlation between corrected LVLED and HD on lateral CXR (r = 0.361, P = 0.004) and a negative correlation between LVLED and VD on posteroanterior (PA) CXR (r = -0.281, P = 0.028). To account for this inverse relationship, we developed a composite anatomic distance (defined as: lateral HD-PA VD), which correlated most closely with LVLED (r = 0.404, P = 0.001). Follow-up was available for 48 patients. At a mean of 4.1 +/- 3.2 months, patients with optimal values for both corrected LVLED (>= 75%) and composite anatomic distance (>= 15 cm) demonstrated greater reverse LV remodeling than patients with either one or neither of these optimized values. Conclusions: We identified a significant correlation between LV-right ventricular interlead distance and LVLED; additionally, both parameters act synergistically in predicting LV anatomic reverse remodeling. Efforts to optimize both interlead distance and electrical delay may improve CRT outcomes. (PACE 2010; 575-582). C1 [Singh, Jagmeet P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv,Heart Ctr,Cardiol Div, Boston, MA 02114 USA. [Mulligan, Lawrence J.] Medtronic Inc, Minneapolis, MN USA. RP Singh, JP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv,Heart Ctr,Cardiol Div, GRB 109,55 Fruit St, Boston, MA 02114 USA. EM jsingh@partners.org OI Picard, Michael/0000-0002-9264-3243 FU Medtronic Inc; St. Jude Medical; Sorin/ELA; Biotronik; Boston Scientific FX Part of this study was funded by an unrestricted research grant from Medtronic Inc.; Faisal M. Merchant MD, None; E. KevinHeist, MD, PhD: Lecture Honorarium, Consulting and Research Grants from St. Jude Medical, Medtronic, Sorin/ELA, Biotronik, and Boston Scientific; K. Veena Nandigam, MD, None; Lawrence J. Mulligan, Salary support from Medtronic; Dan Blendea, MD, None; David McCarty, MD, None; Mary Orencole, NP, MS, Lecture honorarium from Boston Scientific; Michael H. Picard, MD, None; Jeremy N. Ruskin, MD, Lecture Honorarium and Consultant to Medtronic; Jagmeet P. Singh, MD, PhD, Research grants, Consulting and Lecture Honorarium from Biotronik, Boston Scientific, St. Jude Medical, and Medtronic. NR 24 TC 25 Z9 25 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD MAY PY 2010 VL 33 IS 5 BP 575 EP 582 DI 10.1111/j.1540-8159.2009.02624.x PG 8 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA 587RQ UT WOS:000277010500011 PM 20070543 ER PT J AU Campbell, CM Witmer, K Simango, M Carteret, A Loggia, ML Campbell, JN Haythornthwaite, JA Edwards, RR AF Campbell, Claudia M. Witmer, Kenny Simango, Mpepera Carteret, Alene Loggia, Marco L. Campbell, James N. Haythornthwaite, Jennifer A. Edwards, Robert R. TI Catastrophizing delays the analgesic effect of distraction SO PAIN LA English DT Article DE Experimental pain; Behavioral analgesia; Distraction; Catastrophizing; Capsaicin ID IMMERSIVE VIRTUAL-REALITY; COLD-PRESSOR PAIN; SEX-DIFFERENCES; THERMAL PAIN; COGNITIVE MODULATION; ATTENTION; RESPONSES; PERCEPTION; FMRI; CAPSAICIN AB Behavioral analgesic techniques such as distraction reduce pain in both clinical and experimental settings. Individuals differ in the magnitude of distraction-induced analgesia, and additional study is needed to identify the factors that influence the pain relieving effects of distraction. Catastrophizing, a set of negative emotional and cognitive processes, is widely recognized to be associated with increased reports of pain. We sought to evaluate the relationship between catastrophizing and distraction analgesia. Healthy participants completed three sessions in a randomized order. In one session (Pain Alone), pain was induced by topical application of a 10% capsaicin cream and simultaneous administration of a tonic heat stimulus. In another session (Pain + Distraction), identical capsaicin + heat application procedures were followed, but subjects played video games that required a high level of attention. During both sessions, verbal ratings of pain were obtained and participants rated their degree of catastrophizing. During the other session (Distraction Alone) subjects played the video games in the absence of any pain stimulus. Pain was rated significantly lower during the distraction session compared to the "Pain Alone" session. In addition, high catastrophizers rated pain significantly higher regardless of whether the subjects were distracted. Catastrophizing did not influence the overall degree of distraction analgesia; however, early in the session high catastrophizers had little distraction analgesia, though later in the session low and high catastrophizers rated pain similarly. These results suggest that both distraction and catastrophizing have substantial effects on experimental pain in normal subjects and these variables interact as a function of time. (C) 2009 International Association for the Study of Pain. Published by Elsevier B. V. All rights reserved. C1 [Campbell, Claudia M.; Witmer, Kenny; Simango, Mpepera; Haythornthwaite, Jennifer A.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA. [Carteret, Alene; Campbell, James N.] Johns Hopkins Univ, Sch Med, Dept Neurosurg, Baltimore, MD 21287 USA. [Loggia, Marco L.; Edwards, Robert R.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, Cambridge, MA 02138 USA. [Loggia, Marco L.] Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat, Cambridge, MA 02138 USA. RP Campbell, CM (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, 600 N Wolfe St,Meyer 1-108, Baltimore, MD 21287 USA. EM ccampb41@son.jhmi.edu FU NIH [AT 001433, F32 NS063624] FX This work was supported by NIH Grants AT 001433 and F32 NS063624. NR 52 TC 20 Z9 22 U1 2 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD MAY PY 2010 VL 149 IS 2 BP 202 EP 207 DI 10.1016/j.pain.2009.11.012 PG 6 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 587HK UT WOS:000276980900009 PM 20188470 ER PT J AU Manchikanti, L Pampati, V Boswell, MV Smith, HS Hirsch, JA AF Manchikanti, Laxmaiah Pampati, Vidyasagar Boswell, Mark V. Smith, Howard S. Hirsch, Joshua A. TI Analysis of the Growth of Epidural Injections and Costs in the Medicare Population: A Comparative Evaluation of 1997, 2002, and 2006 Data SO PAIN PHYSICIAN LA English DT Review DE Epidural injections; interventional techniques; interventional pain management; chronic pain; ambulatory surgery center (ASC); hospital outpatient department (HOPD) ID LOW-BACK-PAIN; EVIDENCE-BASED MEDICINE; CLINICAL-PRACTICE GUIDELINE; FACET JOINT INTERVENTIONS; CHRONIC WIDESPREAD PAIN; LUMBAR SURGERY SYNDROME; MANAGING CHRONIC PAIN; 5-YEAR FOLLOW-UP; SYSTEMATIC REVIEWS; PRIMARY-CARE AB Background: Interventional techniques for the treatment of spinal techniques are commonly used and are increasing exponentially. Epidural injections and facet joint interventions are the 2 most commonly utilized procedures in interventional pain management. The current literature regarding the effectiveness of epidural injections is sparse with highly variable outcomes based on the technique, outcome measures, patient selection, and methodology. Multiple reports have illustrated the exponential growth of lumbosacral injections with significant geographic variations in the administration of epidural injections in Medicare patients. However, an analysis of the growth of epidural injections and costs in the Medicare population has not been performed with recent data and has not been looked at from an interventional pain management perspective. Study Design: Analysis of epidural injection growth and costs in Medicare's population 1997, 2002, and 2006. Objectives: The primary purpose of this study was to evaluate the use of all types of epidural injections (i.e. caudal, interlaminar, and transforaminal in lumbar, cervical and thoracic regions), and other epidural procedures, including epidural adhesiolysis. In addition, the purpose was to identify trends in the number of procedures, reimbursement, specialty involvement, fluoroscopy use, and indications from 1997 to 2006. Methods: The Centers for Medicare and Medicaid Services (CMS) 5% national sample carrier claim record data from 1997, 2002, and 2006 was utilized. Outcomes Assessment: Outcome measures included characteristics receiving epidural injections, epidural injections by specialty, reimbursement characteristics, and other variables. Results: Epidural injections increased significantly in Medicare to 2006. Patients receiving epidurals increased by 106.3%; visits increased 102.7%. Medicare beneficiaries' place of service, type of beneficiaries from 1997 per 100,000 population Hospital outpatient department (HOPD) payments increased significantly; ASC average payments decreased; overall payments increased. The increase in procedures performed by general physicians outpaced that of interventional pain management (IPM) physicians. Limitations: Study limitations include no Medicare Advantage patients; potential documentation, coding, and billing errors. Conclusions: Epidural injections grew significantly. This growth appears to coincide with chronic low back pain growth and other treatments for low back pain. Since many procedures are performed without fluoroscopy, continued growth and inappropriate provision of services might reduce access. C1 [Manchikanti, Laxmaiah; Pampati, Vidyasagar] Pain Management Ctr Paducah, Paducah, KY USA. [Boswell, Mark V.] Texas Tech Univ, Hlth Sci Ctr, Int Pain Ctr, Lubbock, TX 79430 USA. [Smith, Howard S.] Albany Med Coll, Dept Anesthesiol, Albany, NY 12208 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com NR 81 TC 108 Z9 109 U1 0 U2 4 PU AM SOC INTERVENTIONAL PAIN PHYSICIANS PI PADUCAH PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA SN 1533-3159 J9 PAIN PHYSICIAN JI Pain Physician PD MAY-JUN PY 2010 VL 13 IS 3 BP 199 EP 212 PG 14 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA 609SN UT WOS:000278677500001 PM 20495584 ER PT J AU Deer, TR Smith, HS Cousins, M Doleys, DM Levy, RM Rathmell, JP Staats, PS Wallace, M Webster, LR AF Deer, Timothy R. Smith, Howard S. Cousins, Michael Doleys, Daniel M. Levy, Robert M. Rathmell, James P. Staats, Peter S. Wallace, Mark Webster, Lynn R. TI Consensus Guidelines for the Selection and Implantation of Patients With Noncancer Pain for Intrathecal Drug Delivery SO PAIN PHYSICIAN LA English DT Article DE Chronic pain; noncancer pain; opioids; intrathecal drug delivery systems; guidelines; consensus guidelines ID LOW-BACK-PAIN; CHRONIC SPINAL PAIN; CHRONIC NONMALIGNANT PAIN; EVIDENCE-BASED MEDICINE; INTRASPINAL INFUSION THERAPY; ANESTHESIOLOGISTS TASK-FORCE; FACET JOINT INTERVENTIONS; LUMBAR SURGERY SYNDROME; TERM OPIOID THERAPY; NEUROPATHIC PAIN AB Intrathecal therapy offers an invasive alternative for the long-term management of select patients with intractable pain associated with various disease states, including those of noncancer origin. It is commonly accepted that proper patient selection is essential to optimizing treatment outcomes, yet the practice of candidate selection for device implantation varies widely. A multifaceted approach-with consideration of preexisting medical comorbidities; psychological status; associated social, technical, and economic issues; and response to intrathecal trialing-enables practitioners to fully evaluate the appropriateness of implanting a patient with an intrathecal drug delivery system. Yet, to date no standard set of guidelines have been developed to aid practitioners in navigating this evaluation process. Using experience- and knowledge-based expert opinion to systematically evaluate the available evidence, this article provides consensus guidelines aimed at optimizing the selection of patients with noncancer pain for intrathecal therapy. In conclusion, complete assessment of a patient's physical, psychological, and social characteristics, can guide practitioners in determining the appropriateness of initiating intrathecal therapy. These consensus guidelines are intended to assist with weighing this risk/benefit ratio of intrathecal therapy, thereby minimizing the potential for treatment failure, unacceptable adverse effects, and excess mortality. C1 [Deer, Timothy R.] Ctr Pain Relief Inc, Charleston, WV 25301 USA. [Smith, Howard S.] Albany Med Coll, Albany, NY 12208 USA. [Cousins, Michael] Royal N Shore Hosp, St Leonards, NSW 2065, Australia. [Doleys, Daniel M.] Pain & Rehabil Inst, Birmingham, AL USA. [Levy, Robert M.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Rathmell, James P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Staats, Peter S.] Metzger Pain Management, Shrewsbury, NJ USA. [Wallace, Mark] Univ Calif San Diego, San Diego, CA 92103 USA. [Webster, Lynn R.] Lifetree Clin Res & Pain Clin, Salt Lake City, UT USA. RP Deer, TR (reprint author), Ctr Pain Relief Inc, 400 Court St,Suite 302, Charleston, WV 25301 USA. EM DocTDeer@aol.com FU Inset Technologies Inc; Medtronic; Abbott; Advanced Bionic; Ameritox; Ariya; AstraZeneca; Boehringer Ingelheim; cervelo; CoMentis; Durect; Elan; Elite; Forest; GlaxoSmithKline; Jazz Pharmaceuticals, Inc; King Pharmaceuticals; Merck Co, Inc; Nektar; NeurogesX; Pain Therapeutics, Inc; Purdue; QRxPharma; Respironics; Takeda Pharmaceutical North America; TorreyPines; Wyeth; Zars FX The faculty has reported the following financial relationships with relevant commercial interests: Dr. Deer: Consultant-Codman, Elan, Inset Technologies Inc. Dr. Doleys: Promotional speakers bureau-Medtronic. Dr. Levy: Codman, Medtronic, St. Jude Medical. Dr. Rauck: Grant/research support-Inset Technologies Inc, Medtronic; Consultant-Codman, Elan, Inset Technologies Inc, Medtronic; Promotional speakers bureau-Elan. Dr. Staats: Consultant-ElectroCore; Scientific advisor-ElectroCore; Stock shareholder-ElectroCore: Employee/officer/board member-ElectroCore. Dr. Wallace: Grant/research support-Medtronic; Scientific advisor-Elan. Dr. Webster: Consultant-Ameritox, Boston Scientific, Cephalon, Corona Productions, Elan, King Pharmaceuticals, MediCom Worldwide, Medtronic, Medscape; Research/grant support-Abbott, Advanced Bionic, Ameritox, Ariya, AstraZeneca, Boehringer Ingelheim, cervelo, CoMentis, Durect, Elan, Elite, Forest, GlaxoSmithKline, Jazz Pharmaceuticals, Inc, King Pharmaceuticals, Medtronic, Merck & Co, Inc, Nektar, NeurogesX, Pain Therapeutics, Inc, Purdue, QRxPharma, Respironics, Takeda Pharmaceutical North America, TorreyPines, Wyeth, Zars; Scientific advisor-Ameritox, King Pharmaceuticals, Nektar, Nervo, Neuromed, Purdue, QRxPharma. Dr. Cousins, Dr. Rathmell, and Dr. Smith disclosed no relevant financial relationships with any commercial interests NR 205 TC 45 Z9 46 U1 0 U2 5 PU AM SOC INTERVENTIONAL PAIN PHYSICIANS PI PADUCAH PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA SN 1533-3159 J9 PAIN PHYSICIAN JI Pain Physician PD MAY-JUN PY 2010 VL 13 IS 3 BP E175 EP E213 PG 39 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA 857KP UT WOS:000297717700002 PM 20495597 ER PT J AU Manchikanti, L Datta, S Derby, R Wolfer, LR Benyamin, RM Hirsch, JA AF Manchikanti, Laxmaiah Datta, Sukdeb Derby, Richard Wolfer, Lee R. Benyamin, Ramsin M. Hirsch, Joshua A. TI A Critical Review of the American Pain Society Clinical Practice Guidelines for Interventional Techniques: Part 1. Diagnostic Interventions SO PAIN PHYSICIAN LA English DT Review DE Guidelines; evidence-based medicine; comparative effectiveness research; systematic reviews; American Pain Society; interventional pain management; interventional techniques; low back pain; diagnostic interventions; lumbar facet joint nerve blocks; lumbar provocation discography; sacroiliac joint nerve blocks ID LOW-BACK-PAIN; EVIDENCE-BASED MEDICINE; FACET JOINT PAIN; CHRONIC NONCANCER PAIN; MEDIAL BRANCH BLOCKS; CHRONIC SPINAL PAIN; LUMBAR ZYGAPOPHYSIAL JOINTS; LOCAL-ANESTHETIC BLOCKS; SERVICES-TASK-FORCE; PREVIOUSLY ASYMPTOMATIC SUBJECTS AB Background: Clinical guidelines are defined as systematically developed statements to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances. The clinical guideline industry has been erupting even faster than innovation in health care, constantly adding unhealthy perspectives with broad and complex mandates to health care interventions. Clinical guidelines are based on evidence-based medicine (EBM) and comparative effectiveness research (CER). Multiple issues related to the development of clinical guidelines are based on conflicts of interest, controversies, and limitations of the guideline process. Recently, the American Pain Society (APS) developed and published multiple guidelines in managing low back pain resulting in multiple publications. However, these guidelines have been questioned regarding their development process, their implementation, and their impact on various specialties. Objectives: To reassess the APS guidelines evidence synthesis for low back pain diagnostic interventions using the same methodology utilized by the APS authors. The interventions examined were diagnostic techniques for managing low back pain of facet joint origin, discogenic origin, and sacroiliac joint origin. Methods: A literature search by two authors was carried out utilizing appropriate databases from 1966 through July 2008. Methodologic quality assessment was also performed by at least 2 authors utilizing the same criteria applied in APS guidelines. The guideline reassessment process included the evaluation of individual studies and systematic reviews and the translation into practice recommendations. Results: Our reassessment of Chou et al's evaluation, utilizing Chou et al's criteria, showed good evidence for lumbar facet joint nerve blocks, fair evidence for lumbar provocation discography, and fair to poor evidence for sacroiliac joint blocks to diagnose sacroiliac joint pain. The reassessment illustrates that Chou et al have utilized multiple studies inappropriately and have excluded appropriate studies. Also, Chou et al failed to eliminate their bias in their study evaluations. Conclusion: The reassessment, using appropriate methodology and including high quality studies, shows evidence that differs from published APS guidelines. C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA. [Datta, Sukdeb] Vanderbilt Univ, Med Ctr, Dept Anesthesiol, Nashville, TN USA. [Derby, Richard; Wolfer, Lee R.] Spinal Diagnost & Treatment Ctr, Daly City, CA USA. [Benyamin, Ramsin M.] Millennium Pain Ctr, Bloomington, IL USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA. [Datta, Sukdeb] Vanderbilt Univ, Intervent Pain Program, Nashville, TN USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com FU Sucampo Pharmaceuticals FX Dr. Hirsch is a consultant for Cardinal Healthcare. He is a minor shareholder in Medtronic and Cardinal Healthcare. He serves on the Steering Committee for KAVIAR trial (volunteer position), and on the Data and Safety Monitoring Board (DSMB): CEEP trial (volunteer position). Dr. Datta receives research support from Sucampo Pharmaceuticals and an honorarium from Smith and Nephew. Dr. Derby has stock options with Laurimed and Medtronics. NR 304 TC 104 Z9 106 U1 1 U2 9 PU AM SOC INTERVENTIONAL PAIN PHYSICIANS PI PADUCAH PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA SN 1533-3159 J9 PAIN PHYSICIAN JI Pain Physician PD MAY-JUN PY 2010 VL 13 IS 3 BP E141 EP E174 PG 34 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA 857KP UT WOS:000297717700001 PM 20495596 ER PT J AU Lau, MK Davila, JA Shaib, YH AF Lau, Melvin K. Davila, Jessica A. Shaib, Yasser H. TI Incidence and Survival of Pancreatic Head and Body and Tail Cancers A Population-Based Study in the United States SO PANCREAS LA English DT Article DE pancreas; cancer; head; body; tail; incidence; survival; United States ID ADENOCARCINOMA; EPIDEMIOLOGY; TRENDS AB Objectives: Cancer of the body/tail of the pancreas is frequently separated from pancreatic head tumors. No studies have examined whether the demographics, disease characteristics, and patient survival with pancreatic body/tail cancers are different from pancreatic head tumors. Methods: We used the Surveillance, Epidemiology, and End Results (SEER) registry to identify 43,946 cases of pancreatic cancer. The yearly incidence and survival rates were calculated. Cox proportional hazards model examined temporal trends in survival. Results: The incidence rate for pancreatic head cancer has remained at 5.6% per 100,000, whereas the rate for pancreatic body/tail cancers has increased by 46% between 1973 and 2002. The 3-year survival rate has increased slightly for both groups. The Cox proportional hazards model analysis confirms this improvement. The 3-year survival rate for local-stage pancreatic body/tail cancer is 20.0% compared with 9% for local-stage pancreatic head cancer. Conclusions: This study indicates that the incidence of pancreatic head cancer has remained stable, whereas the incidence of pancreatic body/tail cancers is rising. Despite higher survival rates among patients with pancreatic head cancer compared with those with pancreatic body/tail cancers in several variables, patients with local-stage pancreatic body/tail cancers had higher survival rates compared with local-stage pancreatic head cancer. C1 Dept Vet Affairs Med Ctr, Gastroenterol Sect, Houston, TX USA. Dept Vet Affairs Med Ctr, Sect Hlth Serv Res, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. RP Shaib, YH (reprint author), Michael E Debakey VA Med Ctr 111D, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM yshaib@bcm.tmc.edu NR 9 TC 35 Z9 36 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD MAY PY 2010 VL 39 IS 4 BP 458 EP 462 DI 10.1097/MPA.0b013e3181bd6489 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 587IP UT WOS:000276984800006 PM 19924019 ER PT J AU Sahani, D Kambadakone, A AF Sahani, Dushyant Kambadakone, Avinash TI The Radiological Exposure of Pancreatic Perfusion Computed Tomography Reply SO PANCREAS LA English DT Letter C1 [Sahani, Dushyant; Kambadakone, Avinash] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Sahani, D (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. EM dsahani@partners.org NR 5 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD MAY PY 2010 VL 39 IS 4 BP 541 EP 543 DI 10.1097/MPA.0b013e3181c15f8f PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 587IP UT WOS:000276984800019 ER PT J AU Stavitsky, K Saurman, JL McNamara, P Cronin-Golomb, A AF Stavitsky, K. Saurman, J. L. McNamara, P. Cronin-Golomb, A. TI Sleep in Parkinson's disease: A comparison of actigraphy and subjective measures SO PARKINSONISM & RELATED DISORDERS LA English DT Article DE Parkinson's disease; Sleep; Actigraphy; Subjective sleep ratings ID EXCESSIVE DAYTIME SLEEPINESS; DISTURBANCES; SCALE; INSOMNIA; TIME AB Sleep disturbances are common in Parkinson's disease (PD). Actigraphy has emerged as an alternative to polysomnography to measure sleep, raising the question of its ability to capture sleep quality in PD patients. Our aim was to compare self-report data with actigraphic data. Thirty non-demented individuals with PD and 14 normal control participants (NC) were included. Sleep was measured using 24-h wrist actigraphy over a seven day period, during which time participants kept a sleep diary. Subjective sleep and arousal questionnaires included the Parkinson's Disease Sleep Scale and Epworth Sleepiness Scale. Patients with PD presented with more sleep problems than NC. In NC, none of the actigraphic sleep variables were related to any of the self-report measures of sleep. In PD, scores on subjective sleep measures correlated with actigraphy-derived estimates of sleep quality. Our results suggest that actigraphy is an appropriate method of measuring sleep quality in PD. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Stavitsky, K.; Saurman, J. L.; Cronin-Golomb, A.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [McNamara, P.] Boston Univ, Dept Neurol, Sch Med, Boston, MA 02215 USA. [McNamara, P.] Boston VA Healthcare Syst, Dept Neurol, Boston, MA USA. RP Cronin-Golomb, A (reprint author), Boston Univ, Dept Psychol, 648 Beacon St,2nd Floor, Boston, MA 02215 USA. EM alicecg@bu.edu FU Ruth L. Kirschstein National Research Service [1F31NS061555-01]; Clara Mayo Foundation; Department of Psychology, Boston University; NINDS [R01 NS050446-01A2]; NIMH [1R21MH076916-01A2] FX This study was supported by a Ruth L. Kirschstein National Research Service Award (1F31NS061555-01) and a Clara Mayo Foundation fellowship from the Department of Psychology, Boston University, to K.S.; by NINDS grant R01 NS050446-01A2 to A.C-G; and by NIMH federal grant 1R21MH076916-01A2 to P.M. The authors would like to thank Denyse Turpin, R.N., MPH, Cathi Thomas, R.N., M.S., and Marie Saint-Hilaire, M.D., for their assistance in subject recruitment, and Chase Ansok, Erica Appleman, Sophie Blease, Eric Griffith, Patricia Johnson, and Barrett Phillips for their assistance with testing participants and scoring data. NR 26 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1353-8020 J9 PARKINSONISM RELAT D JI Parkinsonism Relat. Disord. PD MAY PY 2010 VL 16 IS 4 BP 280 EP 283 DI 10.1016/j.parkreldis.2010.02.001 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 599BB UT WOS:000277883900010 PM 20202887 ER PT J AU Ginde, AA Santillan, AA Clark, S Camargo, CA AF Ginde, Adit A. Santillan, Alfredo A. Clark, Sunday Camargo, Carlos A., Jr. TI Body mass index and acute asthma severity among children presenting to the emergency department SO PEDIATRIC ALLERGY AND IMMUNOLOGY LA English DT Article DE acute asthma; adolescent; body mass index; child; obesity; emergency medicine ID ADULT-ONSET ASTHMA; CHILDHOOD ASTHMA; HOSPITAL ADMISSION; PROSPECTIVE COHORT; NONOBESE CHILDREN; OVERWEIGHT STATUS; INCIDENT ASTHMA; BIRTH-WEIGHT; OBESITY; SYMPTOMS AB To determine the prevalence of obesity among children presenting to the emergency department (ED) with acute asthma, and to examine the relationship between body mass index (BMI) and acute asthma severity in the ED setting. We analyzed data from a multicenter prospective cohort study during 1997-1998; 44 ED in 17 US states and two Canadian provinces enrolled 672 patients, age 5-17, with acute asthma. BMI and Pulmonary Index were collected in the ED. We defined overweight and obesity using age, sex, and race-specific BMI values from national and international databases. The prevalence of obesity was significantly higher among ED patients with acute asthma as compared with children from the general population (23% vs. 9-15%; p < 0.001). Obese children with acute asthma did not differ from their non-obese counterparts, by demographic factors or chronic asthma severity (all p > 0.2). Initial Pulmonary Index was the same across underweight, intermediate, and obese groups (3.7 +/- 2.4, 3.8 +/- 2.2, 3.7 +/- 2.3; p = 0.70). Admission status also did not vary across groups (22%, 22% and 23%; p = 0.98). Stratifying the analysis by age group and sex did not change these results. The prevalence of obesity among children presenting to the ED with acute asthma was significantly higher compared with children from the general population. BMI was not associated with markers of chronic and acute asthma severity. The results of this study support a positive association between obesity and asthma, and suggest that asthma exacerbations among obese children are very similar to those experienced by other children. C1 [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med,EMNet Coordinating Ctr, Boston, MA 02114 USA. [Ginde, Adit A.] Univ Colorado, Denver Sch Med, Dept Emergency Med, Aurora, CO USA. [Clark, Sunday] Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA USA. RP Camargo, CA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med,EMNet Coordinating Ctr, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM ccamargo@partners.org RI Siry, Bonnie/D-7189-2017 FU National Institutes of Health (Bethesda, MD) [HL-84401]; GlaxoSmithKline (Research Triangle Park, NC) FX Dr. Camargo is supported by grant HL-84401 from the National Institutes of Health (Bethesda, MD). This project was supported by an unrestricted grant from GlaxoSmithKline (Research Triangle Park, NC). NR 54 TC 15 Z9 16 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0905-6157 J9 PEDIAT ALLERG IMM-UK JI Pediatr. Allergy Immunol. PD MAY PY 2010 VL 21 IS 3 BP 480 EP 488 DI 10.1111/j.1399-3038.2009.00911.x PG 9 WC Allergy; Immunology; Pediatrics SC Allergy; Immunology; Pediatrics GA 588OX UT WOS:000277082900004 PM 19548965 ER PT J AU Debelenko, LV Perez-Atayde, AR Dubois, SG Grier, HE Pai, SY Shamberger, RC Kozakewich, HPW AF Debelenko, Larisa V. Perez-Atayde, Antonio R. Dubois, Steven G. Grier, Holcombe E. Pai, Sung-Yun Shamberger, Robert C. Kozakewich, Harry P. W. TI p53(+)/mdm2(-) Atypical Lipomatous Tumor/Well-Differentiated Liposarcoma in Young Children: An Early Expression of Li-Fraumeni Syndrome SO PEDIATRIC AND DEVELOPMENTAL PATHOLOGY LA English DT Article DE Li-Fraumeni; liposarcoma; mdm2; p53 ID GERMLINE TP53 MUTATIONS; CANCER FAMILY SYNDROME; SOFT-TISSUE SARCOMAS; MDM2 AMPLIFICATION; RING CHROMOSOMES; P53 MUTATION; TUMORS; LIPOBLASTOMA; GENE; HETEROZYGOSITY AB The spectrum of lipomatous tumors differs in the adult and pediatric populations, with liposarcoma being rare in children. Nearly 10% of individuals with Li-Fraumeni syndrome develop sarcomas in the first 2 decades of life; however, the frequency of sarcoma types and subtypes in this syndrome is unknown. Two atypical lipomatous tumors/well-differentiated liposarcomas (ALT/WDLS) were identified in the pathology files of our institution in young children from "classical" Li-Fraumeni and Li-Fraumeni variant kindreds with a known germline TP53 mutation (Y220C) in one of the families. The patients were 5 and 6 years of age and the ALT/WDLSs were the first expression of the syndrome. The tumors had a high degree of cellular atypia and differed from sporadic ALT/WDLS by strong nuclear immunoreactivity for p53 and absent mdm2 expression. This is the first report of 2 ALT/WDLSs presenting in children before 10 years of age, both in association with Li-Fraumeni syndrome/variant. ALT/WDLS in a young child should raise the possibility of a cancer predisposition syndrome and, in this setting, the p53(+)/mdm2(-) immunophenotype might be characteristic. Recognition of this lesion and its association is important for early diagnosis and subsequent tumor surveillance in the proband and affected family members. C1 [Debelenko, Larisa V.; Perez-Atayde, Antonio R.; Kozakewich, Harry P. W.] Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. [Dubois, Steven G.; Grier, Holcombe E.; Pai, Sung-Yun] St Jude Childrens Res Hosp, Dept Surg Hematol Oncol, Memphis, TN 38105 USA. [Dubois, Steven G.; Grier, Holcombe E.; Pai, Sung-Yun] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Shamberger, Robert C.] Childrens Hosp, Dept Surg, Boston, MA 02115 USA. RP Debelenko, LV (reprint author), St Jude Childrens Res Hosp, Dept Pathol, 262 Danny Thomas Pl, Memphis, TN 38105 USA. EM larisa.debelenko@stjude.org NR 43 TC 3 Z9 3 U1 0 U2 1 PU ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 1093-5266 J9 PEDIATR DEVEL PATHOL JI Pediatr. Dev. Pathol. PD MAY-JUN PY 2010 VL 13 IS 3 BP 218 EP 224 DI 10.2350/09-08-0694-OA.1 PG 7 WC Pathology; Pediatrics SC Pathology; Pediatrics GA 633KG UT WOS:000280500400007 PM 20028212 ER PT J AU O'Brien, MM Lacayo, NJ Lum, BL Kshirsagar, S Buck, S Ravindranath, Y Bernstein, M Weinstein, H Chang, MN Arceci, RJ Sikic, BI Dahl, GV AF O'Brien, Maureen M. Lacayo, Norman J. Lum, Bert L. Kshirsagar, Smita Buck, Steven Ravindranath, Yaddanapudi Bernstein, Mark Weinstein, Howard Chang, Myron N. Arceci, Robert J. Sikic, Branimir I. Dahl, Gary V. TI Phase I Study of Valspodar (PSC-833) With Mitoxantrone and Etoposide in Refractory and Relapsed Pediatric Acute Leukemia: A Report From the Children's Oncology Group SO PEDIATRIC BLOOD & CANCER LA English DT Article DE leukemia; MDR1; multidrug resistance; P-glycoprotein; PSC-833; valspodar ID ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; P-GLYCOPROTEIN EXPRESSION; MULTIDRUG-RESISTANCE; GEMTUZUMAB OZOGAMICIN; TRIHYDROCHLORIDE LY335979; CYCLOSPORINE-A; COMBINATION; TRIAL; PHARMACODYNAMICS AB Background. Valspodar, a non-immunosuppressive analog of cylosporine, is a potent P-glycoprotein (MDR1) inhibitor. As MDR1-mediated efflux of chemotherapeutic agents from leukemic blasts may contribute to drug resistance, a phase 1 study of valspodar combined with mitoxantrone and etoposide in pediatric patients with relapsed or refractory leukemias was performed. Procedure. Patients received a valspodar-loading dose (2 mg/kg) followed by a 5-day continuous valspodar infusion (8, 10, 12.5, or 15 mg/kg/day) combined with lower than standard closes of mitoxantrone and etoposide. The valspodar dose was escalated using a standard 3 + 3 phase I design. Results. Twenty-one patients were evaluable for toxicity and 20 for response. The maximum tolerated close (MTD) of valspodar was 12.5 mg/kg/day, combined with 50% dose-reduced mitoxantrone and etoposide. The clearance of mitoxantrone and etoposide was decreased by 64% and 60%, respectively, when combined with valspodar. Dose-limiting toxicities included stomatitis, ataxia, and bone marrow aplasia. Three of 11 patients with acute lymphoblastic leukemia (ALL) had complete responses while no patient with acute myeloid leukemia (AML) had an objective response. In vitro studies demonstrated P-glycoprotein expression on the blasts of 5 of 14 patients, although only 1 had inhibition of rhodamine efflux by valspodar. Conclusions. While this regimen was tolerable, responses in this heavily pretreated population were limited to a subset of patients with ALL. Pediatr Blood Cancer 2010;54:694-702. (c) 2010 Wiley-Liss, Inc. C1 [O'Brien, Maureen M.; Lacayo, Norman J.; Dahl, Gary V.] Stanford Univ, Sch Med, Dept Pediat, Div Hematol Oncol, Palo Alto, CA 94304 USA. [Lum, Bert L.; Sikic, Branimir I.] Stanford Univ, Sch Med, Dept Med, Div Oncol, Palo Alto, CA 94304 USA. [Lum, Bert L.; Kshirsagar, Smita; Sikic, Branimir I.] Stanford Univ, Sch Med, Div Clin Pharmacol, Palo Alto, CA 94304 USA. [Buck, Steven; Ravindranath, Yaddanapudi] Childrens Hosp Michigan, Detroit, MI 48201 USA. [Bernstein, Mark] IWK Hlth Ctr, Halifax, NS, Canada. [Weinstein, Howard] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chang, Myron N.] Ctr Data, Childrens Oncol Grp, Gainesville, FL USA. [Arceci, Robert J.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. RP Dahl, GV (reprint author), Stanford Univ, Sch Med, Div Pediat Hematol Oncol, 1000 Welch Rd,Suite 100, Palo Alto, CA 94304 USA. EM gary.dahl@stanford.edu FU NIH [R01 52168, M01 RR 00070, U10 CA98543, U10 CA98413] FX This study was supported in part by NIH grants: R01 52168 (BIS.), M01 RR 00070 (General Clinical Research Center, Stanford University School of Medicine; N.J.L.-Clinical Associate Physician Award), U10 CA98543 (COG Chair's Grant) and U10 CA98413 (COG Statistics and Data Center Grant). A complete listing of grant support for research conducted by the Children's Cancer Group and Pediatric Oncology Group before initiation of the COG grant in 2003 is available online at "hop://www.childrensoncologyuoup.org/admin/grantinfo.htm." The work was in part supported by an endowment to Robert J. Arceci for the King Fand Chair in Pediatric Oncology. NR 34 TC 16 Z9 16 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD MAY PY 2010 VL 54 IS 5 BP 694 EP 702 DI 10.1002/pbc.22366 PG 9 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 573SR UT WOS:000275935700009 PM 20209646 ER PT J AU Jalmsell, L Kreicbergs, U Onelov, E Steineck, G Henter, JI AF Jalmsell, Li Kreicbergs, Ulrika Onelov, Erik Steineck, Gunnar Henter, Jan-Inge TI Anxiety is Contagious-Symptoms of Anxiety in the Terminally Ill Child Affect Long-Term Psychological Well-Being in Bereaved Parents SO PEDIATRIC BLOOD & CANCER LA English DT Article DE bereavement; child; end-of-life; pediatric; symptoms ID NATIONWIDE FOLLOW-UP; CANCER; DEATH; LIFE; CARE; OUTCOMES; HOME; END AB Background. We studied the relation between unrelieved symptoms in terminally ill children and the psychological well-being in the bereaved parents 4-9 years after their loss. Procedure. We contacted parents in Sweden who had lost a child to a malignancy 1992-1997. The parents were asked to assess symptoms affecting their child's well-being during his or her last month of life, and their own current psychological well-being. Results. Altogether 449/561 (80%) eligible parents supplied information on 19 specific symptoms that may occur in children with a malignancy and how each of these symptoms had affected their child's well-being during his or her last month of life (not applicable, none, low, moderate, or severe). These results were linked to questions concerning the parents' self-assessed mental health. Parents whose children were affected by anxiety reported depression (RR 2.0 [1.3-3.0]), anxiety, (RR 1.6 [1.1-2.4]), decreased psychological well-being (RR 1.6 [1.2-2.0]) and decreased quality of life (RR 1.5 [1.2-1.8]) more frequently than parents of children without these symptoms. Parents of children who were affected by disturbed sleep also had increased risk to develop these symptoms; RR 2.0 [1.4-2.9] for depression, 1.8 [1.3-2.5] for anxiety, 1.5 [1.2-1.8] for decreased psychological well-being, and 1.5 [1.3-1.9] for decreased quality of life. Conclusions. Bereaved parents whose children were affected by anxiety or disturbed sleep due to anxiety or pain had an increased risk of long-term psychological morbidity. Reducing psychological complications in seriously ill children may also improve the psychological well-being in bereaved parents. Pediatr Blood Cancer 2010;54:751-757. (c) 2010 Wiley-Liss, Inc. C1 [Jalmsell, Li; Kreicbergs, Ulrika; Henter, Jan-Inge] Karolinska Inst, Karolinska Univ Hosp, Dept Womens & Childrens Hlth, Childhood Canc Res Unit, SE-17176 Stockholm, Sweden. [Kreicbergs, Ulrika] Phyllis F Cantor Ctr, Dana Farber Canc Inst, Boston, MA USA. [Onelov, Erik; Steineck, Gunnar] Karolinska Inst, Karolinska Univ Hosp, Dept Pathol & Oncol, Div Clin Canc Epidemiol, SE-17176 Stockholm, Sweden. [Steineck, Gunnar] Dept Sahlgrenska Acad, Div Clin Canc Epidemiol, Gothenburg, Sweden. RP Kreicbergs, U (reprint author), Karolinska Inst, Karolinska Univ Hosp, Dept Womens & Childrens Hlth, Childhood Canc Res Unit, SE-17176 Stockholm, Sweden. EM ulrika.kreicbergs@ki.se OI Steineck, Gunnar/0000-0002-0787-3969 FU Swedish Children's Cancer Foundation; Swedish Research Council; Stockholm County Council; Capio's Research Foundation; Marta and Gunnar V Philipson Foundation FX This study was supported by grants from the Swedish Children's Cancer Foundation, the Swedish Research Council, the Stockholm County Council, Capio's Research Foundation, and the Marta and Gunnar V Philipson Foundation. The funding sources had no involvement in any part of the study. NR 19 TC 14 Z9 15 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD MAY PY 2010 VL 54 IS 5 BP 751 EP 757 DI 10.1002/pbc.22418 PG 7 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 573SR UT WOS:000275935700018 PM 20135696 ER PT J AU Lara-Corrales, I Arbuckle, A Zarinehbaf, S Pope, E AF Lara-Corrales, Irene Arbuckle, Alan Zarinehbaf, Sanaz Pope, Elena TI Principles of Wound Care in Patients with Epidermolysis Bullosa SO PEDIATRIC DERMATOLOGY LA English DT Review ID AMNIOTIC MEMBRANE; GROWTH-FACTOR; SKIN WOUNDS; MANAGEMENT; ULCERS; INFLAMMATION AB Epidermolysis bullosa comprises a series of hereditary skin fragility disorders characterized by blister formation in response to minor friction or trauma. Acute and chronic wounds are part of the daily life of many epidermolysis bullosa patients. To offer proper care, health care providers need to understand the wound healing process, recognize the different types of wounds these patients may present, and be able to select among a wide variety of wound care products to optimize healing. C1 [Lara-Corrales, Irene; Zarinehbaf, Sanaz; Pope, Elena] Hosp Sick Children, Dept Dermatol, Toronto, ON M5G 1X8, Canada. [Arbuckle, Alan] Denver VA Med Ctr, Dept Dermatol, Denver, CO USA. RP Pope, E (reprint author), Hosp Sick Children, Dept Dermatol, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. EM elena.pope@sickkids.ca NR 49 TC 10 Z9 11 U1 1 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0736-8046 J9 PEDIATR DERMATOL JI Pediatr. Dermatol. PD MAY-JUN PY 2010 VL 27 IS 3 BP 229 EP 237 DI 10.1111/j.1525-1470.2010.01086.x PG 9 WC Dermatology; Pediatrics SC Dermatology; Pediatrics GA 601DB UT WOS:000278037100003 PM 20403117 ER PT J AU Tollefsen, WW Chapman, J Frakes, M Gallagher, M Shear, M Thomas, SH AF Tollefsen, William W. Chapman, Jacob Frakes, Michael Gallagher, Michael Shear, Melissa Thomas, Stephen H. TI Endotracheal Tube Cuff Pressures in Pediatric Patients Intubated Before Aeromedical Transport SO PEDIATRIC EMERGENCY CARE LA English DT Article DE endotracheal cuff pressure; emergency medical service; airway; aeromedical transport ID BLOOD-FLOW AB Objectives: Prolonged endotracheal tube cuff pressures (ETTCPs) greater than 30 cm H(2)O can cause complications. With increasing utilization of cuffed endotracheal tubes (ETTs) in pediatric patients comes the risk of overinflation. We evaluated the incidence of elevated ETTCP in pediatric patients intubated with cuffed ETTs, transported by a critical-care transport service and attempted to identify whether elevated ETTCP was associated with factors such as patient demographics, diagnostic category, and intubator credentials. Methods: In this prospective study, assessment of ETTCP was made upon transport crew arrival at the bedside. The study focused on a consecutive sample of pediatric patients undergoing transport with cuffed ETTs placed before transport team arrival. All patients had cuff pressures assessed by the same cuff manometry device. Pressures found to be greater than 30 cm H(2)O were corrected immediately. Results: Forty-one percent of cases met the a priori defined cutoff for elevated ETTCP of 30 cm H(2)O; 30% of those elevated cuff pressures were twice that cutoff (>60 cm H(2)O). There were no associations between high ETTCP and any of the following independent variables: demographics, physician versus nonphysician intubator, and intubation location (ie, scene vs emergency department vs intensive care unit). Conclusions: A significant number of pediatric patients transported by a critical-care transport service had elevated ETTCP. Furthermore, there was no clear risk factor for elevated cuff pressures. This is further evidence that cuff pressures should be measured in all patients. Further research should focus on the effect of educational intervention and on the possible clinical results of elevated ETTCPs. C1 [Chapman, Jacob; Shear, Melissa] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Frakes, Michael; Gallagher, Michael; Thomas, Stephen H.] Boston MedFlight, Boston, MA USA. [Thomas, Stephen H.] Univ Oklahoma, Sch Community Med, Dept Emergency Med, Tulsa, OK USA. [Tollefsen, William W.] Massachusetts Gen Hosp, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Tollefsen, WW (reprint author), Massachusetts Gen Hosp, Brigham & Womens Hosp, 75 Francis St,Neville House 236A, Boston, MA 02115 USA. EM wtollefsen@partners.org NR 11 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0749-5161 J9 PEDIATR EMERG CARE JI Pediatr. Emerg. Care PD MAY PY 2010 VL 26 IS 5 BP 361 EP 363 DI 10.1097/PEC.0b013e3181db224d PG 3 WC Emergency Medicine; Pediatrics SC Emergency Medicine; Pediatrics GA 598JI UT WOS:000277831800006 PM 20404779 ER PT J AU Pieretti, RV Goldstein, AM Pieretti-Vanmarcke, R AF Pieretti, Rafael V. Goldstein, Allan M. Pieretti-Vanmarcke, Rafael TI Late complications of newborn circumcision: a common and avoidable problem SO PEDIATRIC SURGERY INTERNATIONAL LA English DT Article DE Circumcision; Complications; Newborn ID NEONATAL CIRCUMCISION; AMPUTATION; PENIS; RISKS; CLAMP AB The purpose of this paper is to study the types of operative and post-operative late complications resulting from newborn circumcisions and to make recommendations to prevent them. After obtaining IRB approval, a retrospective review of the late complications resulting from newborn circumcisions treated at the MassGeneral Hospital for Children from January 2003 to December 2007 was undertaken. The source used was the consultation notes and operative reports of affected patients. Additionally, cases seen in the outpatient Pediatric Urology Clinic from April 2007 to April 2008 were reviewed. A total of 8,967 children were operated during the study period, of which 424 (4.7%) were for complications resulting from previous neonatal circumcision. Penile adhesions, skin bridges, meatal stenosis, redundant foreskin (incomplete circumcision with uncircumcised appearance), recurrent phimosis, buried penis and penile rotation were the most frequent complications. At the outpatient clinic of the Section of Pediatric Urology, 127 boys with concerns following newborn circumcision were evaluated, representing 7.4% of the total volume of cases seen in this clinic. Our results indicate the need to undertake a collaborative study to define the incidence of complications following newborn circumcisions, which should be performed by practitioners with adequate training in the technique of their choice and its post-operative care. C1 [Pieretti, Rafael V.] Massachusetts Gen Hosp, Sect Pediat Urol, Boston, MA 02114 USA. [Goldstein, Allan M.] Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA 02114 USA. [Pieretti-Vanmarcke, Rafael] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Pieretti, RV (reprint author), Massachusetts Gen Hosp, Sect Pediat Urol, Boston, MA 02114 USA. EM rpieretti@gmail.com NR 21 TC 25 Z9 25 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0179-0358 J9 PEDIATR SURG INT JI Pediatr. Surg. Int. PD MAY PY 2010 VL 26 IS 5 BP 515 EP 518 DI 10.1007/s00383-010-2566-9 PG 4 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 586EM UT WOS:000276885300011 PM 20155423 ER PT J AU Berkey, CS Willett, WC Frazier, AL Rosner, B Tamimi, RM Rockett, HRH Colditz, GA AF Berkey, Catherine S. Willett, Walter C. Frazier, A. Lindsay Rosner, Bernard Tamimi, Rulla M. Rockett, Helaine R. H. Colditz, Graham A. TI Prospective Study of Adolescent Alcohol Consumption and Risk of Benign Breast Disease in Young Women SO PEDIATRICS LA English DT Article DE teens; BBD; alcohol; drinking; BMI; breast cancer; beer; wine; liquor; longitudinal ID BODY-MASS INDEX; CANCER RISK; PREMENOPAUSAL WOMEN; EARLY-LIFE; COHORT; HEALTH; CHILDHOOD; DENSITY; FATNESS; WEIGHT AB OBJECTIVE: To investigate prospectively, using alcoholic beverage consumption data collected in real time, the association between adolescent drinking and risk of biopsy-confirmed benign breast disease (BBD) in young women. PARTICIPANTS AND METHODS: The Growing Up Today Study is a prospective cohort study of US girls, aged 9 to 15 years at baseline, with annual questionnaires from 1996 through 2001, followed by questionnaires in 2003, 2005, and 2007. On the 2003 survey, the participants (then aged 16-23 years) provided information about their alcoholic beverage consumption in the previous year. On the 2005 and 2007 surveys, a total of 6899 women (aged 18-27 years) reported whether a health care provider had ever diagnosed them with BBD (n = 147 cases) and whether it was confirmed by biopsy (n = 67 cases); 6752 women reported never being diagnosed with BBD. RESULTS: Adjusted for age and BMI, quantity of alcohol consumed was associated with increased risk of biopsy-confirmed BBD (odds ratio: 1.50 per drink per day [95% confidence interval: 1.19-1.90]). Girls who typically drank 6 or 7 days/week were at higher risk (odds ratio: 5.50 [95% confidence interval: 1.23-24.53]) compared with those who never drank or who drank less than once per week. CONCLUSIONS: Higher amounts consumed, and more frequent consumption, of alcoholic beverages in adolescence may increase the occurrence of BBD in young women. Advising teenagers to avoid alcoholic beverages, along with smoking and sun exposure, may reduce cancer incidence in adulthood. Pediatrics 2010; 125: e1081-e1087 C1 [Berkey, Catherine S.; Rosner, Bernard; Tamimi, Rulla M.; Rockett, Helaine R. H.] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. [Berkey, Catherine S.; Rosner, Bernard; Tamimi, Rulla M.; Rockett, Helaine R. 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. [Frazier, A. Lindsay] Dana Farber Canc Inst, Boston, MA 02115 USA. [Colditz, Graham A.] Washington Univ, Sch Med, Alvin J Siteman Canc Ctr, St Louis, MO USA. RP Berkey, CS (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. EM catherine.berkey@channing.harvard.edu RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU Breast Cancer Research Foundation (BCRF); National Institutes of Health (NIH) [DK46834]; Breast Cancer Research Foundation (New York, NY) FX Funded by the Breast Cancer Research Foundation (BCRF) and the National Institutes of Health (NIH).; This study was funded by grant DK46834 from the National Institutes of Health (Bethesda, MD) for initiation of the cohort and collection/management of the data during years of follow-up, and by a grant from the Breast Cancer Research Foundation (New York, NY) for design, conduct, and analysis for the manuscript. Neither sponsor was involved in the preparation, review, or approval of the manuscript. NR 33 TC 26 Z9 26 U1 1 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 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD MAY PY 2010 VL 125 IS 5 BP E1081 EP E1087 DI 10.1542/peds.2009-2347 PG 7 WC Pediatrics SC Pediatrics GA 590NI UT WOS:000277232800040 PM 20385629 ER PT J AU Pompili, M Tatarelli, R Girardi, P Tondo, L Baldessarini, RJ AF Pompili, Maurizio Tatarelli, Roberto Girardi, Paolo Tondo, Leonardo Baldessarini, Ross J. TI Suicide risk during anticonvulsant treatment SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE anticonvulsants; epilepsy; depression; suicide ID ANTIEPILEPTIC DRUGS; DISORDER PATIENTS; EPILEPSY; PSYCHOPATHOLOGY AB Recent research findings suggest possible increases in risk of suicidal behaviors among patients treated with anticonvulsants. The available evidence appears to support such a risk more clearly for patients diagnosed with epilepsy rather than with primary psychiatric disorders. However, the studies involved are limited by providing associational findings that may be confounded by several uncontrolled variables. Such limitations should be considered in future research on adverse effects of anticonvulsants and other centrally acting drugs. For now, however, clinical prudence calls for routine, ongoing assessment of mood and suicidal thoughts among neurological or psychiatric patients, whether or not treated with particular drugs. Copyright (C) 2010 John Wiley & Sons, Ltd. C1 [Pompili, Maurizio; Tatarelli, Roberto; Girardi, Paolo] Univ Roma La Sapienza, Dept Neurosci Mental Hlth & Sensory Funct, Suicide Prevent Ctr St Andrea Hosp, Rome, Italy. [Pompili, Maurizio; Tondo, Leonardo; Baldessarini, Ross J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Pompili, Maurizio; Tondo, Leonardo; Baldessarini, Ross J.] Massachusetts Gen Hosp, Int Consortium Psychot & Bipolar Disorders Res, McLean Div, Boston, MA 02114 USA. [Tondo, Leonardo] Lucio Bini Mood Disorder Ctr, Cagliari, Sardinia, Italy. RP Pompili, M (reprint author), Univ Roma La Sapienza, Dept Neurosci Mental Hlth & Sensory Funct, Suicide Prevent Ctr St Andrea Hosp, Rome, Italy. EM maurizio.pompili@uniroma1.it OI Tatarelli, Roberto/0000-0003-4396-2632; Pompili, Maurizio/0000-0003-1886-4977 FU Bruce J. Anderson Foundation; McLean Private Donors Psychopharmacology Research Fund FX Supported in part by a grant from the Bruce J. Anderson Foundation and the McLean Private Donors Psychopharmacology Research Fund (RIB). NR 18 TC 4 Z9 5 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD MAY PY 2010 VL 19 IS 5 BP 525 EP 528 DI 10.1002/pds.1936 PG 4 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 600LM UT WOS:000277987600013 PM 20437459 ER PT J AU Mauer, J Chaurasia, B Plum, L Quast, T Hampel, B Bluher, M Kolanus, W Kahn, CR Bruning, JC AF Mauer, Jan Chaurasia, Bhagirath Plum, Leona Quast, Thomas Hampel, Brigitte Blueher, Matthias Kolanus, Waldemar Kahn, C. Ronald Bruening, Jens C. TI Myeloid Cell-Restricted Insulin Receptor Deficiency Protects Against Obesity-Induced Inflammation and Systemic Insulin Resistance SO PLOS GENETICS LA English DT Article ID TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; ADIPOSE-TISSUE; FACTOR-ALPHA; WEIGHT-LOSS; IKK-BETA; METABOLIC SYNDROME; INDUCED APOPTOSIS; CRITICALLY-ILL; MICE AB A major component of obesity-related insulin resistance is the establishment of a chronic inflammatory state with invasion of white adipose tissue by mononuclear cells. This results in the release of pro-inflammatory cytokines, which in turn leads to insulin resistance in target tissues such as skeletal muscle and liver. To determine the role of insulin action in macrophages and monocytes in obesity-associated insulin resistance, we conditionally inactivated the insulin receptor (IR) gene in myeloid lineage cells in mice (IR(Delta myel)-mice). While these animals exhibit unaltered glucose metabolism on a normal diet, they are protected from the development of obesity-associated insulin resistance upon high fat feeding. Euglycemic, hyperinsulinemic clamp studies demonstrate that this results from decreased basal hepatic glucose production and from increased insulin-stimulated glucose disposal in skeletal muscle. Furthermore, IR(Delta myel)-mice exhibit decreased concentrations of circulating tumor necrosis factor (TNF) alpha and thus reduced c-Jun N-terminal kinase (JNK) activity in skeletal muscle upon high fat feeding, reflecting a dramatic reduction of the chronic and systemic low-grade inflammatory state associated with obesity. This is paralleled by a reduced accumulation of macrophages in white adipose tissue due to a pronounced impairment of matrix metalloproteinase (MMP) 9 expression and activity in these cells. These data indicate that insulin action in myeloid cells plays an unexpected, critical role in the regulation of macrophage invasion into white adipose tissue and in the development of obesity-associated insulin resistance. C1 [Mauer, Jan; Chaurasia, Bhagirath; Plum, Leona; Hampel, Brigitte; Bruening, Jens C.] Univ Cologne, Inst Genet, Dept Mouse Genet & Metab, D-5000 Cologne, Germany. [Plum, Leona; Bruening, Jens C.] CMMC, Cologne, Germany. [Quast, Thomas; Kolanus, Waldemar] Life & Med Sci Inst LIMES, Mol Immune & Cell Biol Unit, Bonn, Germany. [Blueher, Matthias] Univ Leipzig, Dept Med, Leipzig, Germany. [Kahn, C. Ronald] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Bruening, Jens C.] Univ Hosp Cologne, Dept Internal Med 2, Cologne, Germany. [Bruening, Jens C.] Max Planck Inst Biol Ageing, Cologne, Germany. RP Mauer, J (reprint author), Univ Cologne, Inst Genet, Dept Mouse Genet & Metab, Weyertal 121, D-5000 Cologne, Germany. EM jens.bruening@uni-koeln.de FU ZMMK [SFB 670]; NIH [DK31036] FX This work was supported by grants from ZMMK, SFB 670 (to JCB) and NIH DK31036 (CRK). The funders had no role in study design, data colletion and analysis, decision to publish, or preparation of the manuscript. NR 60 TC 40 Z9 41 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD MAY PY 2010 VL 6 IS 5 AR e1000938 DI 10.1371/journal.pgen.1000938 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 608BU UT WOS:000278557300008 PM 20463885 ER PT J AU Yang, J Liu, XQ Zhao, Y Adamian, M Pawlyk, B Sun, X McMillan, DR Liberman, MC Li, TS AF Yang, Jun Liu, Xiaoqing Zhao, Yun Adamian, Michael Pawlyk, Basil Sun, Xun McMillan, D. Randy Liberman, M. Charles Li, Tiansen TI Ablation of Whirlin Long Isoform Disrupts the USH2 Protein Complex and Causes Vision and Hearing Loss SO PLOS GENETICS LA English DT Article ID HAIR-CELL STEREOCILIA; ANKLE-LINK COMPLEX; SYNDROME TYPE IIA; RETINITIS-PIGMENTOSA; PHOTORECEPTOR CELLS; RETINAL PHOTORECEPTORS; CILIARY ROOTLET; DOMAIN PROTEIN; MYOSIN-XVA; GENE AB Mutations in whirlin cause either Usher syndrome type II (USH2), a deafness-blindness disorder, or nonsyndromic deafness. The molecular basis for the variable disease expression is unknown. We show here that only the whirlin long isoform, distinct from a short isoform by virtue of having two N-terminal PDZ domains, is expressed in the retina. Both long and short isoforms are expressed in the inner ear. The N-terminal PDZ domains of the long whirlin isoform mediates the formation of a multi-protein complex that includes usherin and VLGR1, both of which are also implicated in USH2. We localized this USH2 protein complex to the periciliary membrane complex (PMC) in mouse photoreceptors that appears analogous to the frog periciliary ridge complex. The latter is proposed to play a role in photoreceptor protein trafficking through the connecting cilium. Mice carrying a targeted disruption near the N-terminus of whirlin manifest retinal and inner ear defects, reproducing the clinical features of human USH2 disease. This is in contrast to mice with mutations affecting the C-terminal portion of whirlin in which the phenotype is restricted to the inner ear. In mice lacking any one of the USH2 proteins, the normal localization of all USH2 proteins is disrupted, and there is evidence of protein destabilization. Taken together, our findings provide new insights into the pathogenic mechanism of Usher syndrome. First, the three USH2 proteins exist as an obligatory functional complex in vivo, and loss of one USH2 protein is functionally close to loss of all three. Second, defects in the three USH2 proteins share a common pathogenic process, i.e., disruption of the PMC. Third, whirlin mutations that ablate the N-terminal PDZ domains lead to Usher syndrome, but non-syndromic hearing loss will result if they are spared. C1 [Yang, Jun; Liu, Xiaoqing; Zhao, Yun; Adamian, Michael; Pawlyk, Basil; Sun, Xun; Li, Tiansen] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA USA. [McMillan, D. Randy] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA. [Liberman, M. Charles] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Liberman, M. Charles] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Yang, J (reprint author), Univ Utah, Dept Neurobiol & Anat, Dept Ophthalmol & Visual Sci, Salt Lake City, UT 84112 USA. EM jun.yang@hsc.utah.edu; tiansen.li@nih.gov FU National Institutes of Health [R01 EY10309, R01 DC00188, P30 DC05209, P30 EY014104]; Foundation Fighting Blindness; Knights Templar Eye Foundation; Fight for Sight FX This work was supported by National Institutes of Health grants R01 EY10309, R01 DC00188, and P30 DC05209; the Foundation Fighting Blindness; the Knights Templar Eye Foundation; Fight for Sight; and NIH Core Grant for Vision Research P30 EY014104. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 44 TC 48 Z9 48 U1 1 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD MAY PY 2010 VL 6 IS 5 AR e1000955 DI 10.1371/journal.pgen.1000955 PG 17 WC Genetics & Heredity SC Genetics & Heredity GA 608BU UT WOS:000278557300025 PM 20502675 ER PT J AU Zhong, H Beaulaurier, J Lum, PY Molony, C Yang, X MacNeil, DJ Weingarth, DT Zhang, B Greenawalt, D Dobrin, R Hao, K Woo, S Fabre-Suver, C Qian, S Tota, MR Keller, MP Kendziorski, CM Yandell, BS Castro, V Attie, AD Kaplan, LM Schadt, EE AF Zhong, Hua Beaulaurier, John Lum, Pek Yee Molony, Cliona Yang, Xia MacNeil, Douglas J. Weingarth, Drew T. Zhang, Bin Greenawalt, Danielle Dobrin, Radu Hao, Ke Woo, Sangsoon Fabre-Suver, Christine Qian, Su Tota, Michael R. Keller, Mark P. Kendziorski, Christina M. Yandell, Brian S. Castro, Victor Attie, Alan D. Kaplan, Lee M. Schadt, Eric E. TI Liver and Adipose Expression Associated SNPs Are Enriched for Association to Type 2 Diabetes SO PLOS GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; QUANTITATIVE TRAIT LOCI; GENE-EXPRESSION; MALIC ENZYME; MACULAR DEGENERATION; SUSCEPTIBILITY LOCI; PANCREATIC-ISLETS; FATTY-ACIDS; NETWORKS; DISEASE AB Genome-wide association studies (GWAS) have demonstrated the ability to identify the strongest causal common variants in complex human diseases. However, to date, the massive data generated from GWAS have not been maximally explored to identify true associations that fail to meet the stringent level of association required to achieve genome-wide significance. Genetics of gene expression (GGE) studies have shown promise towards identifying DNA variations associated with disease and providing a path to functionally characterize findings from GWAS. Here, we present the first empiric study to systematically characterize the set of single nucleotide polymorphisms associated with expression (eSNPs) in liver, subcutaneous fat, and omental fat tissues, demonstrating these eSNPs are significantly more enriched for SNPs that associate with type 2 diabetes (T2D) in three large-scale GWAS than a matched set of randomly selected SNPs. This enrichment for T2D association increases as we restrict to eSNPs that correspond to genes comprising gene networks constructed from adipose gene expression data isolated from a mouse population segregating a T2D phenotype. Finally, by restricting to eSNPs corresponding to genes comprising an adipose subnetwork strongly predicted as causal for T2D, we dramatically increased the enrichment for SNPs associated with T2D and were able to identify a functionally related set of diabetes susceptibility genes. We identified and validated malic enzyme 1 (Me1) as a key regulator of this T2D subnetwork in mouse and provided support for the association of this gene to T2D in humans. This integration of eSNPs and networks provides a novel approach to identify disease susceptibility networks rather than the single SNPs or genes traditionally identified through GWAS, thereby extracting additional value from the wealth of data currently being generated by GWAS. C1 [Zhong, Hua; Beaulaurier, John; Lum, Pek Yee; Molony, Cliona; Yang, Xia; Zhang, Bin; Greenawalt, Danielle; Dobrin, Radu; Hao, Ke; Fabre-Suver, Christine] Rosetta Inpharmat, Dept Genet, Seattle, WA USA. [MacNeil, Douglas J.; Weingarth, Drew T.; Qian, Su; Tota, Michael R.] Merck & Co Inc, Dept Metab Disorders, Rahway, NJ USA. [Woo, Sangsoon] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Keller, Mark P.; Attie, Alan D.] Univ Wisconsin, Dept Biochem, Madison, WI 53705 USA. [Kendziorski, Christina M.] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI USA. [Yandell, Brian S.] Univ Wisconsin, Dept Stat, Madison, WI 53706 USA. [Castro, Victor; Kaplan, Lee M.] Massachusetts Gen Hosp, Weight Ctr, Boston, MA 02114 USA. [Kaplan, Lee M.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Schadt, Eric E.] Sage Bionetworks, Dept Integrat & Syst Biol, Seattle, WA USA. [Schadt, Eric E.] Pacific Biosci, Menlo Pk, CA USA. RP Zhong, H (reprint author), Rosetta Inpharmat, Dept Genet, Seattle, WA USA. EM eschadt@pacificbiosciences.com OI Suver, Christine/0000-0002-2986-385X; Dobrin, Radu/0000-0002-3336-0091 FU Merck FX This study was funded in part by Merck, which employed several of the authors responsible for study design, data collection and analysis, decision to publish, and preparation of the manuscript. NR 62 TC 89 Z9 91 U1 3 U2 14 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD MAY PY 2010 VL 6 IS 5 AR e1000932 DI 10.1371/journal.pgen.1000932 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 608BU UT WOS:000278557300002 PM 20463879 ER PT J AU Harley, AE Devine, CM Beard, B Stoddard, AM Hunt, MK Sorensen, G AF Harley, Amy E. Devine, Carol M. Beard, Binta Stoddard, Anne M. Hunt, Mary K. Sorensen, Glorian TI Multiple Health Behavior Changes in a Cancer Prevention Intervention for Construction Workers, 2001-2003 SO PREVENTING CHRONIC DISEASE LA English DT Article AB Introduction Few multiple behavior change interventions have addressed tobacco use in conjunction with fruit and vegetable consumption, particularly among high-risk blue-collar workers. Tools for Health, a cancer prevention intervention for construction laborers, was effective in achieving behavior change for smoking cessation and fruit and vegetable consumption separately. This study examines whether addressing smoking and fruit and vegetable consumption was successful in achieving positive change for both behaviors. We also explored possible explanations for the relationship between behavior changes in these 2 behavioral domains. Methods We retrospectively analyzed data from a randomized controlled trial testing a smoking cessation and fruit and vegetable consumption intervention for construction workers. We used survey data from 300 intervention participants to answer our primary research question: Did participants who reported being smokers at baseline successfully quit smoking and increase their fruit and vegetable consumption by the end of the intervention? We used qualitative data from 16 small group discussions to help interpret these results. Results Tools for Health participants achieved substantial levels of smoking cessation and increased their fruit and vegetable consumption, concurrently, during the course of the intervention. Conclusion This study provides evidence that pairing smoking cessation with increasing fruit and vegetable consumption can be successful in a multiple behavior change intervention designed for high-risk blue-collar workers. Further, our findings provide potential directions for examining why this pairing might be complementary. C1 [Devine, Carol M.] Cornell Univ, Ithaca, NY USA. [Beard, Binta] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Stoddard, Anne M.] New England Res Inst, Watertown, MA 02172 USA. [Hunt, Mary K.; Sorensen, Glorian] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sorensen, Glorian] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Harley, AE (reprint author), Univ Wisconsin, Ctr Urban Populat Hlth, 1020 N 12th St,Ste 4180, Milwaukee, WI 53233 USA. EM harley@uwm.edu FU National Institutes of Health [5 P01 CA75308]; Dana-Farber Cancer Institute, Liberty Mutual, National Grid; Patterson Fellowship Fund FX We thank Melissa Lemke for her assistance in completing this manuscript. This research was supported by the National Institutes of Health (Grant 5 P01 CA75308) and the Dana-Farber Cancer Institute, Liberty Mutual, National Grid, and the Patterson Fellowship Fund. NR 30 TC 16 Z9 16 U1 0 U2 8 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1545-1151 J9 PREV CHRONIC DIS JI Prev. Chronic Dis. PD MAY PY 2010 VL 7 IS 3 AR A55 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA V20SB UT WOS:000208158600010 PM 20394694 ER PT J AU Askenazi, M Li, SJ Singh, S Marto, JA AF Askenazi, Manor Li, Shaojuan Singh, Saurav Marto, Jarrod A. TI Pathway Palette: A rich internet application for peptide-, protein- and network-oriented analysis of MS data SO PROTEOMICS LA English DT Article DE Bioinformatics; Mass Spectrometry proteomics; Network analysis; Protein-protein interaction; Quantitative proteomics; Rich internet application ID GENE ONTOLOGY; PROTEOMICS; GENOMES AB Recent improvements in proteomic technologies have collectively yielded data sets that far exceed the capabilities of typical low-throughput interpretation strategies. Unfortunately, tools designed to leverage the "peptide-centric" content of MS-based proteomics lag the current rate of data production. Here, we describe Pathway Palette (http://blaispathways.dfci.harvard.edu), a freely accessible internet application that enables researchers to easily transition from peptides to biological pathways, while simultaneously retaining the qualitative and quantitative aspects of the underlying MS data. C1 [Askenazi, Manor; Li, Shaojuan; Singh, Saurav; Marto, Jarrod A.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Askenazi, Manor; Li, Shaojuan; Singh, Saurav; Marto, Jarrod A.] Dana Farber Canc Inst, Blais Prote Ctr, Boston, MA 02115 USA. [Askenazi, Manor; Marto, Jarrod A.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Askenazi, Manor] Hebrew Univ Jerusalem, Dept Biol Chem, Jerusalem, Israel. RP Marto, JA (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St,Smith 1158A, Boston, MA 02115 USA. EM jarrod_marto@dfci.harvard.edu FU Dana-Farber Cancer Institute; National Human Genome Research Institute [P50HG004233] FX The authors thank Eric Smith for preparation of figures, and also members of the Marto Lab for valuable discussions and testing of Pathway Palette. This work was supported by the Dana-Farber Cancer Institute and the National Human Genome Research Institute (P50HG004233). NR 23 TC 13 Z9 13 U1 0 U2 2 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1615-9853 J9 PROTEOMICS JI Proteomics PD MAY PY 2010 VL 10 IS 9 BP 1880 EP 1885 DI 10.1002/pmic.200900723 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 597BO UT WOS:000277730900013 PM 20198642 ER PT J AU Espinola-Nadurille, M Huicochea, IV Raviola, G Ramirez-Bermudez, J Kutcher, S AF Espinola-Nadurille, Mariana Huicochea, Ingrid Vargas Raviola, Giuseppe Ramirez-Bermudez, Jesus Kutcher, Stan TI Child and Adolescent Mental Health Services in Mexico SO PSYCHIATRIC SERVICES LA English DT Editorial Material AB This column provides an overview of child and adolescent mental health services in Mexico, where prevalence rates of mental disorders among young people are up to twice as high as U. S. and Canadian rates. The mental health care system in Mexico is underdeveloped and underfunded, and for the approximately 40% of the population with no insurance, access to and quality of care are particularly poor. This column offers policy recommendations aimed at better meeting the needs of this vulnerable population. (Psychiatric Services 61:443-445, 2010) C1 [Espinola-Nadurille, Mariana; Ramirez-Bermudez, Jesus] Inst Nacl Neurol & Neurocirugia Mexico, Unidad Neuropsiquiatria, Mexico City, DF, Mexico. [Huicochea, Ingrid Vargas] Univ Nacl Autonoma Mexico, Dept Psiquiatria & Salud Mental, Mexico City 04510, DF, Mexico. [Raviola, Giuseppe] Massachusetts Gen Hosp, Div Psychiat & Med, Boston, MA 02114 USA. [Kutcher, Stan] Dalhousie Univ, Dept Psychiat, Halifax, NS, Canada. RP Kutcher, S (reprint author), IWK Hlth Ctr, 5850-5980 Univ Ave,POB 9700, Halifax, NS B3K 6R8, Canada. EM stan.kutcher@dal.ca NR 11 TC 3 Z9 3 U1 1 U2 1 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 MAY PY 2010 VL 61 IS 5 BP 443 EP 445 PG 3 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 590SX UT WOS:000277249200003 PM 20439361 ER PT J AU Miller, AL Dassori, A Lopez, L Castillo, DA Gonzalez, JM Boone, C Milam, C Bond, GR Velligan, DI AF Miller, Alexander L. Dassori, Albana Lopez, Linda Castillo, Desiree A. Gonzalez, Jodi M. Boone, Charles Milam, Camis Bond, Gary R. Velligan, Dawn I. TI Tools for Mental Health Agencies to Evaluate Research Protocols SO PSYCHIATRIC SERVICES LA English DT Editorial Material AB Research involving community mental health center clients, resources, or both can affect clinical care, administrative processes, and costs. To help agencies identify and quantify these effects, a stakeholder group examined and discussed a range of protocols and then developed questionnaires and rating scales for agency use. The purpose of these materials is to make explicit the risks, costs, and benefits of a research protocol so an agency can make informed decisions about protocol approval and implementation. The goal of this work was to promote the conduct of appropriate research in community mental health settings while reducing risks to the agency and its clientele. (Psychiatric Services 61:446-448, 2010) C1 [Miller, Alexander L.; Dassori, Albana; Castillo, Desiree A.; Gonzalez, Jodi M.; Velligan, Dawn I.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Dassori, Albana] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Lopez, Linda; Boone, Charles; Milam, Camis] Ctr Hlth Care Serv, San Antonio, TX USA. [Bond, Gary R.] Dartmouth Med Sch, Dept Psychiat, Lebanon, NH USA. RP Miller, AL (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM millera@uthscsa.edu FU NIMH NIH HHS [5R24-MH72830] NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD MAY PY 2010 VL 61 IS 5 BP 446 EP 448 PG 3 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 590SX UT WOS:000277249200004 PM 20439362 ER PT J AU Kilbourne, AM Goodrich, D Miklowitz, DJ Austin, K Post, EP Bauer, MS AF Kilbourne, Amy M. Goodrich, David Miklowitz, David J. Austin, Karen Post, Edward P. Bauer, Mark S. TI Characteristics of Patients With Bipolar Disorder Managed in VA Primary Care or Specialty Mental Health Care Settings SO PSYCHIATRIC SERVICES LA English DT Article ID COMORBIDITY SURVEY REPLICATION; CARDIOVASCULAR-DISEASE; US POPULATION; UNITED-STATES; MEDICAL-CARE; PREVALENCE; QUALITY; ADULTS; RISK; SCHIZOPHRENIA AB Objectives: This study compared the clinical characteristics, use of guideline-concordant pharmacotherapy, and outcomes of patients diagnosed as having bipolar disorder who were exclusively seen in Department of Veteran Affairs (VA) primary care settings with those of patients with bipolar disorder who received any VA mental health services. Methods: Data from the 1999 Large Health Survey of Veterans were linked to VA data from the National Psychosis Registry to identify patients diagnosed as having bipolar disorder (N=14,643). Multivariable analyses adjusting for sociodemographic characteristics and clinical and severity factors determined whether exclusive primary care use versus any mental health care use was associated with poor clinical and services outcomes. Results: Overall, 7.6% used primary care services exclusively. Compared with persons who used specialty care services, those who used primary care exclusively were more likely to be diagnosed as having cardiovascular disease (odds ratio [OR]=1.26, p<.05) or hypertension (OR=1.31, p<.01), less likely to receive guideline-concordant pharmacotherapy (OR=.18, p<.001), more likely to have an inpatient medical visit (OR=1.36, p<.01), and less likely to have an inpatient psychiatric visit (OR=.36, p<.001). Persons who received only primary care were more likely to have worse physical health and better mental health, as measured by the 36-Item Short-Form Health Survey. Conclusions: Patients with bipolar disorder treated in primary care settings were more likely than those who received some care in a mental health specialty setting to have comorbid general medical disorders. Optimal care settings for patients with bipolar disorder may require strategies that address gaps in general medical as well as psychiatric care. (Psychiatric Services 61:500-507, 2010) C1 [Kilbourne, Amy M.; Goodrich, David; Austin, Karen; Post, Edward P.] Hlth Serv Res & Dev Ctr Excellence, Serious Mental Illness Treatment Res & Evaluat Ct, Dept Vet Affairs Ann Arbor, Ann Arbor, MI 48105 USA. [Kilbourne, Amy M.] Univ Michigan, Sch Med, Dept Psychiat, Ann Arbor, MI USA. [Post, Edward P.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA. [Miklowitz, David J.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Bauer, Mark S.] VA Boston Healthcare Syst, Boston, MA USA. [Bauer, Mark S.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Kilbourne, AM (reprint author), Hlth Serv Res & Dev Ctr Excellence, Serious Mental Illness Treatment Res & Evaluat Ct, Dept Vet Affairs Ann Arbor, 2215 Fuller Rd, Ann Arbor, MI 48105 USA. EM amykilbo@umich.edu FU NIMH NIH HHS [R01 MH79994, R34 MH74509] NR 39 TC 15 Z9 15 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 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD MAY PY 2010 VL 61 IS 5 BP 500 EP 507 PG 8 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 590SX UT WOS:000277249200015 PM 20439372 ER PT J AU Rodriguez, KL Bayliss, N Alexander, SC Jeffreys, AS Olsen, MK Pollak, KI Kennifer, SL Tulsky, JA Arnold, RM AF Rodriguez, Keri L. Bayliss, Nichole Alexander, Stewart C. Jeffreys, Amy S. Olsen, Maren K. Pollak, Kathryn I. Kennifer, Sarah L. Tulsky, James A. Arnold, Robert M. TI How oncologists and their patients with advanced cancer communicate about health-related quality of life SO PSYCHO-ONCOLOGY LA English DT Article DE cancer; communication; oncology; patient provider relationship; qualitative research; quality of life ID CELL LUNG-CANCER; PHYSICIAN COMMUNICATION; CARE; CHEMOTHERAPY; DEFINITION; AGREEMENT; OUTCOMES; SCORES; TRIAL AB Objective: To describe the content and frequency of communication about health-related quality of life (HRQOL) during outpatient encounters between oncologists and their patients with advanced cancer. Methods: We coded for HRQOL talk in a subset of audio-recorded conversations (each previously found to contain prognostic talk by the oncologist) from the Study of Communication in Oncologist-Patient Encounters Trial, a randomized controlled trial conducted from 2003 to 2008 in two large US academic medical centers and one Veterans Affairs Medical Center. Results: Seventy-three encounters involved 70 patients and 37 oncologists. Patients were more likely to be female (53%), White (86%), married (78%), and possessing some college education (62%). Most oncologists were male (78%) and White (78%). Mean ages were 59 years for patients and 44 years for oncologists. Every encounter included some talk about HRQOL and HRQOL discussions made up, on average, 25% of the visit time. HRQOL segments described symptoms (50%), general HRQOL (27%), and the following concerns: physical (27%), functional (22%), psychological (9%), social (7%), spiritual (1%), and other (28%). Topics included treatment (56%), disease (14%), and testing (3%), and conversations focused on past (44%), present (68%), and future HRQOL (59%). Conclusions: HRQOL discussions between oncologists and patients are common, but the emphasis is often on treatment (e.g. side effects) and symptoms (e.g. pain) even in patients with advanced disease. Given the often intense emotional experience of patients with advanced cancer, oncologists may need to pay more attention to psychological, social, and spiritual HRQOL concerns. Copyright (C) 2009 John Wiley & Sons, Ltd. C1 [Rodriguez, Keri L.; Bayliss, Nichole] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15206 USA. [Rodriguez, Keri L.; Arnold, Robert M.] Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med, Pittsburgh, PA USA. [Rodriguez, Keri L.] VA Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA 15206 USA. [Alexander, Stewart C.; Jeffreys, Amy S.; Olsen, Maren K.; Tulsky, James A.] Durham VA Med Ctr, Hlth Serv Res & Dev, Durham, NC USA. [Alexander, Stewart C.; Tulsky, James A.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Alexander, Stewart C.; Kennifer, Sarah L.; Tulsky, James A.] Duke Univ, Med Ctr, Ctr Palliat Care, Durham, NC 27710 USA. [Olsen, Maren K.] Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC 27710 USA. [Pollak, Kathryn I.] Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27710 USA. [Pollak, Kathryn I.] Duke Univ, Med Ctr, Duke Comprehens Canc Ctr, Duke Canc Prevent Detect & Control Res Program, Durham, NC 27710 USA. [Tulsky, James A.] Duke Univ, Med Ctr, Ctr Aging & Human Dev, Durham, NC 27710 USA. [Arnold, Robert M.] Univ Pittsburgh, Sect Palliat Care & Med Eth, Pittsburgh, PA USA. [Arnold, Robert M.] Univ Pittsburgh, Inst Enhance Palliat Care, Pittsburgh, PA USA. RP Rodriguez, KL (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, 7180 Highland Dr,Bldg 2,Rm 4083E,151 CH, Pittsburgh, PA 15206 USA. EM Keri.rodriguez@va.gov FU VA HSRD Merit Review [MRP 04-410]; National Cancer Institute [3R01 CA-100387-03S1, R01 CA-100387] FX Dr Rodriguez is supported by a VA HSR&D Merit Review Entry Program Award (MRP 04-410) and a Minority Supplement Award from the National Cancer Institute (3R01 CA-100387-03S1). This work was supported in part by a grant awarded to Dr Tulsky by the National Cancer Institute (R01 CA-100387). 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. All manuscript authors declare that there are no conflicts of interest (i.e. financial and personal relationships between themselves and others that might bias their work). NR 38 TC 25 Z9 25 U1 1 U2 7 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD MAY PY 2010 VL 19 IS 5 BP 490 EP 499 DI 10.1002/pon.1579 PG 10 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 591ZP UT WOS:000277344400005 PM 19449348 ER PT J AU Gordon, AJ Haas, GL Luther, JF Hilton, MT Goldstein, G AF Gordon, Adam J. Haas, Gretchen L. Luther, James F. Hilton, Michael T. Goldstein, Gerald TI Personal, Medical, and Healthcare Utilization Among Homeless Veterans Served by Metropolitan and Nonmetropolitan Veteran Facilities SO PSYCHOLOGICAL SERVICES LA English DT Article DE homelessness; rural health; veterans; health services research ID URBAN HOMELESS; MENTAL-ILLNESS; MOBILE CLINICS; HOUSED POOR; ADULTS; SERVICES; PROGRAM; USERS AB This study assessed differences in personal, medical, and health care utilization characteristics of homeless veterans living in metropolitan versus nonmetropolitan environments. Data were obtained from a Veterans Health Administration (VHA) network sample of homeless veterans. Chi-square tests were used to assess differences in demographics, military history, living situation, medical history, employment status, and health care utilization. Moderator analyses determined whether predictors of health care utilization varied by metropolitan status. Of 3,595 respondents, 60% were residing in metropolitan areas. Age, sex, and marital status were similar between metropolitan and nonmetropolitan homeless. Metropolitan homeless were less likely to receive public financial support or to be employed, to have at least one medical problem, one psychiatric problem, or current alcohol dependency, but more likely to be homeless longer. Of the 52% of the sample who used VHA care in the last 6 months, 53% were metropolitan versus 49% nonmetropolitan (p = .01). Metropolitan status predicted at least one VHA visit within the prior 6 months (OR: 1.3, CI: 1.1, 1.6). Significant differences occur in the personal, medical, and health care utilization characteristics of homeless veterans in metropolitan versus nonmetropolitan areas. C1 [Gordon, Adam J.; Haas, Gretchen L.; Luther, James F.; Goldstein, Gerald] VA Pittsburgh Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA 15206 USA. [Gordon, Adam J.; Haas, Gretchen L.; Hilton, Michael T.; Goldstein, Gerald] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. [Luther, James F.] Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA 15260 USA. RP Gordon, AJ (reprint author), VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr 4, Mailcode 151-C-H,7180 Highland Dr, Pittsburgh, PA 15206 USA. EM adam.gordon@va.gov FU NIMH NIH HHS [R25 MH054318, R25 MH054318-16] NR 23 TC 10 Z9 10 U1 0 U2 1 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1541-1559 J9 PSYCHOL SERV JI Psychol. Serv. PD MAY PY 2010 VL 7 IS 2 BP 65 EP 74 DI 10.1037/a0018479 PG 10 WC Psychology, Clinical SC Psychology GA 789QF UT WOS:000292529700002 PM 21152352 ER PT J AU Lysaker, PH Glynn, SM Wilkniss, SM Silverstein, SM AF Lysaker, Paul H. Glynn, Shirley M. Wilkniss, Sandra M. Silverstein, Steven M. TI Psychotherapy and Recovery From Schizophrenia: A Review of Potential Applications and Need for Future Study SO PSYCHOLOGICAL SERVICES LA English DT Review DE schizophrenia; recovery; psychotherapy; metacognition; self ID BORDERLINE PERSONALITY-DISORDER; COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; SEVERE MENTAL-ILLNESS; SPECTRUM DISORDERS; INDIVIDUAL PSYCHOTHERAPY; FOLLOW-UP; 1ST-EPISODE PSYCHOSIS; INTERNALIZED STIGMA; SELF-EXPERIENCE AB Recovery from schizophrenia has been conceptualized to involve not only symptom remission of symptoms and achievement of psychosocial milestones but also subjective changes in how persons appraise their lives and the extent to which they experience themselves as meaningful agents in the world. In this article we review the potential of individual psychotherapy to address these more subjective aspects of recovery. Literature on the effectiveness of psychotherapy for persons with schizophrenia is discussed, and two different paths by which psychotherapy might modify self-experience are described. First, we detail how psychotherapy could be conceptualized and tailored to help persons with schizophrenia to construct richer and fuller narrative accounts of their lives, including their strengths, challenges, losses, and hopes. Second, we explore how psychotherapy could target the capacity for metacognition or thinking about thinking, assisting persons with psychosis to become able to think about themselves and others in a generally more complex and flexible manner. The needs for future research are discussed along with a commentary on how current evidence- and skill-based treatments may contain key elements that could be considered psychotherapeutic. C1 [Lysaker, Paul H.] Richard L Roudebush Vet Affairs Med Ctr, Indianapolis, IN 46202 USA. [Lysaker, Paul H.] Indiana Univ Sch Med, Indianapolis, IN USA. [Glynn, Shirley M.] Univ Calif Los Angeles, Ctr Med, Los Angeles, CA 90024 USA. [Glynn, Shirley M.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Wilkniss, Sandra M.] Thresholds Inst, Chicago, IL USA. [Silverstein, Steven M.] Univ Med & Dent New Jersey, Univ Behav HealthCare, Piscataway, NJ 08854 USA. [Silverstein, Steven M.] Robert Wood Johnson Med Sch, Piscataway, NJ USA. RP Lysaker, PH (reprint author), Roudebush VA Med Ctr 116H, 1481 W 10th St, Indianapolis, IN 46202 USA. EM plysaker@iupui.Ed OI Lysaker, Paul/0000-0002-6617-9387 FU NIMH NIH HHS [R34 MH082161, R34 MH082161-03] NR 123 TC 73 Z9 74 U1 5 U2 17 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1541-1559 J9 PSYCHOL SERV JI Psychol. Serv. PD MAY PY 2010 VL 7 IS 2 BP 75 EP 91 DI 10.1037/a0019115 PG 17 WC Psychology, Clinical SC Psychology GA 789QF UT WOS:000292529700003 PM 20526422 ER PT J AU Bauer, AM Fielke, K Brayley, J Araya, M Alem, A Frankel, BL Fricchione, GL AF Bauer, Amy M. Fielke, Ken Brayley, John Araya, Mesfin Alem, Atalay Frankel, Bernard L. Fricchione, Gregory L. TI Tackling the Global Mental Health Challenge: A Psychosomatic Medicine/Consultation-Liaison Psychiatry Perspective SO PSYCHOSOMATICS LA English DT Article ID PRIMARY-CARE-PHYSICIANS; RANDOMIZED CONTROLLED-TRIAL; CONSULTATION-LIAISON; MAJOR DEPRESSION; MEDICAL-CARE; DISORDERS; SCHIZOPHRENIA; PRACTITIONERS; MANAGEMENT; MORTALITY AB Background: Consultation-liaison (C-L) psychiatry, informed by principles of psychosomatic medicine, is well-positioned to address the global impact of mental disorders through primary care C-L models. Objective/Method: The authors review the international burden of mental disorders, highlighting medical comorbidity, undertreatment, and the rationale for enhancing primary-care management. Results: C-L psychiatry fosters the skills required for global mental health work. The authors describe successful C-L models developed in a low-income country (Ethiopia) and an under-resourced region of a high-income country (Australia). Conclusion: C-L psychiatrists have the potential to marshal their unique skill-set to reduce the global burden of mental disorders. (Psychosomatics 2010; 51: 185-193) C1 [Bauer, Amy M.] Cambridge Hlth Alliance, Dept Psychiat, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Country Mental Hlth S Australia, Adelaide, SA, Australia. Off Publ Advocate, Collinswood, SA, Australia. Univ Addis Ababa, Dept Psychiat, Addis Ababa, Ethiopia. Amanuel Hosp, Addis Ababa, Ethiopia. Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. Massachusetts Gen Hosp, Dept Psychiat, Int Psychiat Div, Boston, MA 02114 USA. RP Bauer, AM (reprint author), Cambridge Hlth Alliance, Dept Psychiat, 1493 Cambridge St, Cambridge, MA 02139 USA. EM abauer@challiance.org NR 67 TC 6 Z9 7 U1 1 U2 5 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAY-JUN PY 2010 VL 51 IS 3 BP 185 EP 193 PG 9 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 598MH UT WOS:000277840900001 PM 20484715 ER PT J AU Ku, BS Scott, KC Kertesz, SG Pitts, SR AF Ku, Bon S. Scott, Kevin C. Kertesz, Stefan G. Pitts, Stephen R. TI Factors Associated with Use of Urban Emergency Departments by the US Homeless Population SO PUBLIC HEALTH REPORTS LA English DT Article ID HEALTH-CARE UTILIZATION; NEW-YORK-CITY; FREQUENT USERS; SERVICE USE; CASE-MANAGEMENT; LOS-ANGELES; ADULTS; PROGRAM; COHORT; COSTS AB Objective. Homeless individuals frequently use emergency departments (EDs), but previous studies have investigated local rather than national ED utilization rates. This study sought to characterize homeless people who visited urban EDs across the U.S. Methods. We analyzed the ED subset of the National Hospital Ambulatory Medical Care Survey (NHAMCS-ED), a nationally representative probability survey of ED visits, using methods appropriate for complex survey samples to compare demographic and clinical characteristics of visits by homeless vs. non-homeless people for survey years 2005 and 2006. Results. Homeless individuals from all age groups made 550,000 ED visits annually (95% confidence interval [Cl] 419,000, 682,000), or 72 visits per 100 homeless people in the U.S. per year. Homeless people were older than others who used EDs (mean age of homeless people = 44 years compared with 36 years for others). ED visits by homeless people were independently associated with male gender, Medicaid coverage and lack of insurance, and Western geographic region. Additionally, homeless ED visitors were more likely to have arrived by ambulance, to be seen by a resident or intern, and to be diagnosed with either a psychiatric or substance abuse problem. Compared with others, ED visits by homeless people were four times more likely to occur within three days of a prior ED evaluation, and more than twice as likely to occur within a week of hospitalization. Conclusions. Homeless people who seek care in urban EDs come by ambulance, lack medical insurance, and have psychiatric and substance abuse diagnoses more often than non-homeless people. The high incidence of repeat ED visits and frequent hospital use identifies a pressing need for policy remedies. C1 [Ku, Bon S.] Thomas Jefferson Univ, Dept Emergency Med, Philadelphia, PA 19107 USA. [Scott, Kevin C.] Thomas Jefferson Univ, Dept Family & Community Med, Philadelphia, PA 19107 USA. [Kertesz, Stefan G.] Birmingham VA Med Ctr, Ctr Surg Med Acute Care Res & Transit, Birmingham, AL USA. [Kertesz, Stefan G.] Univ Alabama, Sch Med, Birmingham, AL USA. [Pitts, Stephen R.] Emory Univ, Sch Med, Dept Emergency Med, Atlanta, GA USA. RP Ku, BS (reprint author), Thomas Jefferson Univ, Dept Emergency Med, 1020 Sansom St,239 Thompson Bldg, Philadelphia, PA 19107 USA. EM bon.ku@jefferson.edu NR 44 TC 37 Z9 37 U1 2 U2 13 PU ASSOC SCHOOLS PUBLIC HEALTH PI WASHINGTON PA 1101 15TH ST NW, STE 910, WASHINGTON, DC 20005 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD MAY-JUN PY 2010 VL 125 IS 3 BP 398 EP 405 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 581WD UT WOS:000276555100008 PM 20433034 ER PT J AU Abujudeh, HH Kaewlai, R Asfaw, BA Thrall, JH AF Abujudeh, Hani H. Kaewlai, Rathachai Asfaw, Benjamin A. Thrall, James H. TI Quality Initiatives Key Performance Indicators for Measuring and Improving Radiology Department Performance SO RADIOGRAPHICS LA English DT Article ID CARE AB Key performance indicators (KPIs) are financial and nonfinancial measures that are used to define and evaluate the success of an organization. KPIs differ, depending on the nature of the organization and the organizational strategy; they are devised to help evaluate the progress of an organization toward achieving its long-term goals and fulfilling its vision. In healthcare organizations, performance assessment is especially critical for the development of best practices that can lead to improved outcomes in patient care, and KPIs have been incorporated into many healthcare management systems. In the future, radiology-specific KPIs such as those in use at the authors' institution may help provide a framework for measuring performance in radiology practice. (C) RSNA, .2010 radiographics.rsna.org C1 [Abujudeh, Hani H.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Abujudeh, HH (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,FND 220, Boston, MA 02114 USA. EM habujudeh@partners.org FU Bracco Group FX From the Department of Radiology, Massachusetts General Hospital and Harvard Medical School, 55 Fruit St, FND-220, Boston, MA 02114. Received October 12, 2009; revision requested November 13 and received January 5, 2010; accepted January 5. H. H. A. and R. K. received research funding from Bracco Group; H. H. A. is a consultant with RCG HealthCare; J.H.T. is a board member of Mobile Aspects, a medical advisor to Genelux, and a stockholder in General Electric and Microsoft; all other authors have no financial relationships to disclose. Address correspondence to H. H. A. (e-mail: habujudeh@partners.org). NR 23 TC 22 Z9 23 U1 0 U2 4 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 MAY PY 2010 VL 30 IS 3 BP 571 EP 580 DI 10.1148/rg.303095761 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 598HN UT WOS:000277826100001 PM 20219841 ER PT J AU Cai, WL Yoshida, H Zalis, ME Nappi, JJ Harris, GJ AF Cai, Wenli Yoshida, Hiroyuki Zalis, Michael E. Naeppi, Janne Johannes Harris, Gordon J. TI Informatics in Radiology Electronic Cleansing for Noncathartic CT Colonography: A Structure-Analysis Scheme SO RADIOGRAPHICS LA English DT Article ID COMPUTED TOMOGRAPHIC COLONOGRAPHY; RENAL CYST PSEUDOENHANCEMENT; ORAL SODIUM-PHOSPHATE; EXTRACT COLON LUMEN; VIRTUAL COLONOSCOPY; CATHARTIC PREPARATION; COLORECTAL-CANCER; SEGMENTATION; POLYPS; IMAGES AB Computed tomographic (CT) colonography performed after tagging of fecal matter but without a cathartic agent, or noncathartic CT colonography (also known as laxative-free CT colonography), is regarded as a promising next-generation technique for reducing or eliminating the discomfort associated with cathartic bowel preparation, which is the major barrier to undergoing colon cancer screening. Electronic cleansing is an emerging technique for the removal of tagged fecal materials from CT colonographic images. Three major electronic cleansing artifacts-soft-tissue degradation, pseudo-soft-tissue structures, and incomplete cleansing-severely impair the quality of electronically cleansed noncathartic CT colonographic images and limit the diagnostic utility of this modality. A structure-analysis electronic cleansing scheme was developed that makes use of local morphologic information to identify submerged colonic soft-tissue structures while removing the tagged material. Combined with other cutting-edge image processing techniques, including local roughness analysis, mosaic decomposition, and level set segmentation, structure-analysis cleansing helps eliminate the aforementioned artifacts, providing diagnostic-quality cleansed CT colonographic images for the detection of colon cancer. Noncathartic CT colonography with the application of structure-analysis cleansing is expected to help promote CT colonography as a patient-friendly method of colorectal cancer screening. (C) RSNA, 2010 .radiographics.rsna.org C1 [Cai, Wenli] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Cai, WL (reprint author), Massachusetts Gen Hosp, Dept Radiol, 25 New Chardon St,400C, Boston, MA 02114 USA. EM Cai.Wenli@mgh.harvard.edu FU Prevent Cancer Foundation; GE Healthcare FX From the Department of Radiology, Massachusetts General Hospital and Harvard Medical School, 25 New Chardon St, 400C, Boston, MA 02114. Received July 27, 2009; revision requested November 19 and received December 15; accepted December 22. Supported by a Prevent Cancer Foundation research grant. H.Y. is a patent holder with Hologic and Median Technologies, M.E.Z. received a research grant from GE Healthcare, G.J.H. is on the Medical Advisory Board with Fovia; all other authors have no financial relationships to disclose. Address correspondence to W. C. (e-mail: Cai.Wenli@mgh.harvard.edu). NR 42 TC 9 Z9 9 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 MAY PY 2010 VL 30 IS 3 BP 585 EP 602 DI 10.1148/rg.303095154 PG 18 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 598HN UT WOS:000277826100003 PM 20219839 ER PT J AU Kambadakone, AR Eisner, BH Catalano, OA Sahani, DV AF Kambadakone, Avinash R. Eisner, Brian H. Catalano, Onofrio Antonio Sahani, Dushyant V. TI New and Evolving Concepts in the Imaging and Management of Urolithiasis: Urologists' Perspective SO RADIOGRAPHICS LA English DT Article ID SHOCK-WAVE LITHOTRIPSY; UNENHANCED HELICAL CT; ACUTE FLANK PAIN; SPIRAL COMPUTERIZED-TOMOGRAPHY; TUBE CURRENT MODULATION; URINARY STONE DISEASE; DUAL-ENERGY CT; RADIATION-DOSE REDUCTION; KIDNEY-STONES; MULTIDETECTOR CT AB Urolithiasis is a universal problem that has become increasingly prevalent in the United States and has a high rate of recurrence. Imaging of urolithiasis has evolved over the years due to technologic advances and a better understanding of the disease process. Computed tomography (CT) has been the investigation of choice for the evaluation of urinary stone disease. The emergence of multidetector CT and the recent introduction of dual-energy CT have further reinforced the superiority of this modality over other imaging techniques in the management of urolithiasis. Multidetector CT is not limited to simply helping make an accurate diagnosis in patients with stone disease; it is also useful in the assessment of stone burden, composition, and fragility, findings that are helpful in determining appropriate treatment strategies. In addition, multidetector CT is a valuable tool in the follow-up of patients after urologic intervention or institution of medical therapy. Familiarity with recent technologic developments will help radiologists meet the growing expectations of urologists in this setting. In addition, radiologists should be aware of the radiation risks inherent in the imaging of patients with urolithiasis and take appropriate measures to minimize this risk and optimize image quality. (C) RSNA, 2010 .radiographics.rsna.org C1 [Kambadakone, Avinash R.; Catalano, Onofrio Antonio; Sahani, Dushyant V.] Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. [Eisner, Brian H.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. RP Sahani, DV (reprint author), Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, 55 Fruit St,White 270, Boston, MA 02114 USA. EM dsahani@partners.org FU GE Healthcare FX From the Division of Abdominal Imaging and Interventional Radiology (A. R. K., O.A.C., D. V. S.) and Department of Urology (B. H. E.), Massachusetts General Hospital, 55 Fruit St, White 270, Boston, MA 02114. Recipient of a Certificate of Merit award for an education exhibit at the 2008 RSNA Annual Meeting. Received July 10, 2009; revision requested August 27 and received October 20; accepted November 17. For this CME activity, the authors (A. R. K., O.A.C.), editors, and reviewers have no relevant relationships to disclose. B. H. E. is a consultant for the Ravine Group and PercSys and a speaker for Boston Scientific; D. V. S. has received research grant support from GE Healthcare. Address correspondence to DV.S. (e-mail: dsahani@partners.org). NR 115 TC 49 Z9 50 U1 0 U2 2 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 MAY PY 2010 VL 30 IS 3 BP 603 EP 623 DI 10.1148/rg.303095146 PG 21 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 598HN UT WOS:000277826100004 PM 20462984 ER PT J AU Mahmood, U AF Mahmood, Umar TI Science to Practice: Can a Targeted Nanoparticle Be Used to Image Autoimmune Nephritis? SO RADIOLOGY LA English DT Editorial Material AB Serkova et al (1) have developed a targeted magnetic resonance (MR) imaging agent that depicts activated complement deposition in an animal model of nephritis. C1 Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mahmood, U (reprint author), Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, 55 Fruit St,White 427, Boston, MA 02114 USA. EM umahmood@mgh.harvard.edu NR 6 TC 1 Z9 1 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAY PY 2010 VL 255 IS 2 BP 309 EP 310 DI 10.1148/radiol.100186 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 587FU UT WOS:000276976200001 PM 20413745 ER PT J AU Ahmed, HM DiPiro, PJ Devlin, PM Nguyen, ML Bellon, JR AF Ahmed, Haitham M. DiPiro, Pamela J. Devlin, Phillip M. Nguyen, My-Linh Bellon, Jennifer R. TI Mammographic Appearance Following Accelerated Partial Breast Irradiation by Using MammoSite Brachytherapy SO RADIOLOGY LA English DT Article ID INITIAL CLINICAL-EXPERIENCE; RADIATION-THERAPY SYSTEM; CONSERVING SURGERY; CONSENSUS STATEMENT; TREATMENT EFFICACY; PROGNOSTIC-FACTORS; AMERICAN SOCIETY; FAT NECROSIS; TUMOR BED; CANCER AB Purpose: To describe a single institution's experience with mammographic appearance in low-risk patients with early stage breast cancer who have received accelerated partial breast irradiation (APBI) by using MammoSite balloon brachytherapy. Materials and Methods: This study was approved by an institutional review board and was conducted under strict adherence to the Privacy Rule of HIPAA. This was a retrospective review of patients who underwent MammoSite brachytherapy from October 2003 to March 2007. Informed consent for participation in the research project was waived by the institutional review board. Posttherapy mammograms were categorized as showing mild, moderate, or severe distortion and were correlated with patient complaints and complications. Results: Twenty-two women were included in the study, and 93 mammograms were obtained during a median follow-up period of 46 months (range, 22-58 months). Median age was 61 years (range, 47-81 years). One patient developed severe distortion after APBI, while two patients developed only mild distortion throughout follow-up. Eleven (79%) of 14 patients developed moderate distortion, with a median peak in distortion occurring at 21 months. Four (18%) patients developed fat necrosis, two (9%) developed seromas, and two (9%) developed both fat necrosis and seromas. None of the patients required biopsy, and none had an ipsilateral breast recurrence. One patient died of metastatic disease with no evidence of local recurrence. Conclusion: Patients treated with MammoSite APBI developed peak distortion 21 months following therapy, which may be sooner than distortion following conventional whole breast radiation. (C) RSNA, 2010 C1 [Ahmed, Haitham M.; Devlin, Phillip M.; Nguyen, My-Linh; Bellon, Jennifer R.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [DiPiro, Pamela J.] Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. [DiPiro, Pamela J.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Devlin, Phillip M.; Bellon, Jennifer R.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. RP Ahmed, HM (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. EM haitham.m.ahmed@gmail.com NR 41 TC 3 Z9 3 U1 0 U2 0 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 MAY PY 2010 VL 255 IS 2 BP 362 EP 368 DI 10.1148/radiol.10091625 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 587FU UT WOS:000276976200007 PM 20332376 ER PT J AU Almandoz, JED Kelly, HR Schaefer, PW Lev, MH Gonzalez, RG Romero, JM AF Almandoz, Josser E. Delgado Kelly, Hillary R. Schaefer, Pamela W. Lev, Michael H. Gonzalez, R. Gilberto Romero, Javier M. TI Prevalence of Traumatic Dural Venous Sinus Thrombosis in High-Risk Acute Blunt Head Trauma Patients Evaluated with Multidetector CT Venography SO RADIOLOGY LA English DT Article ID COMPUTED TOMOGRAPHIC ANGIOGRAPHY; SUPERIOR SAGITTAL SINUS; NONINVASIVE SCREENING-TEST; DEPRESSED SKULL FRACTURE; CEREBROVASCULAR INJURIES; DIAGNOSIS; CHILD; OBSTRUCTION; ACCURACY AB Purpose: To determine the prevalence of trauma-related dural venous sinus thrombosis (DVST) in high-risk patients with blunt head trauma who are examined with multidetector computed tomographic (CT) venography. Materials and Methods: With institutional review board approval, HIPAA compliance, and waived informed consent, the authors retrospectively studied the findings in 195 consecutive patients who presented to the emergency department with acute blunt head trauma and were examined with multidetector CT venography because they were considered to be at high risk for DVST owing to the presence of a fracture near a dural venous sinus or jugular bulb or a high index of clinical suspicion. Nonenhanced CT images and CT venograms were reviewed for the presence of skull fractures, intracranial hemorrhage, and traumatic DVST. Magnetic resonance and nonenhanced CT images subsequently obtained in patients with traumatic DVST were assessed for hemorrhagic venous infarctions. Statistical analyses were performed by using Student t and Pearson chi(2) tests. Results: Multidetector CT venography depicted thrombosis of 98 dural sinuses or jugular bulbs in 57 (40.7%) of the 140 patients with skull fractures extending to a dural sinus or jugular bulb. Fifty-four (55%) of the 98 sinuses or bulbs had occlusive thrombosis. DVST was seen in only those patients with skull fractures extending to a dural sinus or jugular bulb. Among the skull fractures extending to the transverse sinus, sigmoid sinus, or jugular bulb, those of the petrous temporal bone had a higher risk (50%, 36 of 72 fractures) of traumatic DVST than did those of the occipital bone (34% risk [ 32 of 93 fractures]) (P = .044). However, among the skull fractures extending to the superior sagittal sinus, those of the occipital bone had a higher risk (67% [ eight of 12 fractures]) of traumatic DVST than did those of the parietal (39% risk [ 11 of 28 fractures]) and frontal (24% risk [ four of 17 fractures]) bones (P = .065). Four (7%) patients with traumatic DVST had associated hemorrhagic venous infarctions, all secondary to occlusive DVST. Conclusion: In patients with blunt head trauma, multidetector CT venographic evaluation should be performed only if there is a fracture extending to a dural venous sinus or jugular bulb. (C) RSNA, 2010 C1 [Almandoz, Josser E. Delgado; Kelly, Hillary R.; Schaefer, Pamela W.; Lev, Michael H.; Gonzalez, R. Gilberto; Romero, Javier M.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp,Div Neuroradiol, Boston, MA 02115 USA. RP Almandoz, JED (reprint author), Washington Univ, Sch Med, Div Neuroradiol, Mallinckrodt Inst Radiol, 510 S Kingshighway Blvd,Campus Box 8131, St Louis, MO 63110 USA. EM delgadoj@mir.wustl.edu NR 52 TC 24 Z9 24 U1 0 U2 4 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAY PY 2010 VL 255 IS 2 BP 570 EP 577 DI 10.1148/radiol.10091565 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 587FU UT WOS:000276976200031 ER PT J AU Barnes, TA Gale, DD Kacmarek, RM Kageler, WV AF Barnes, Thomas A. Gale, David D. Kacmarek, Robert M. Kageler, Woody V. TI Competencies Needed by Graduate Respiratory Therapists in 2015 and Beyond SO RESPIRATORY CARE LA English DT Article DE respiratory care; respiratory therapist; manpower; education; training; competency; licensure; credentialing; accreditation; credentials; specialty; protocols ID MECHANICAL VENTILATION; CONTROLLED-TRIAL; PROTOCOL; CARE; ICU AB The American Association for Respiratory Care has established a task force to identify potential new roles and responsibilities of respiratory therapists (RTs) in 2015 and beyond. The first task force conference confirmed that the healthcare system in the United States is on the verge of dramatic change, driven by the need to decrease costs and improve quality. Use of evidence-based protocols that follow a nationally accepted standard of practice, and application of biomedical innovation continue to be important competency areas for RTs. The goal of the second task force conference was to identify specific competencies needed to assure safe and effective execution of RT roles and responsibilities in the future. The education needed by the workforce to assume the new responsibilities emerging as the healthcare system changes starts with a close look at the competencies that will be needed by graduate RTs upon entry into practice. Future specialty practice areas for experienced RTs are identified without defining specific competencies. We present the findings of the task force on the competencies needed by graduate RTs upon entry into practice in 2015. C1 [Barnes, Thomas A.] Northeastern Univ, Dept Hlth Sci, Bouve Coll Hlth Sci, Boston, MA 02115 USA. [Gale, David D.] Eastern Kentucky Univ, Coll Hlth Sci, Richmond, KY 40475 USA. [Kacmarek, Robert M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Resp Care Serv, Boston, MA USA. [Kageler, Woody V.] Tarrant Cty Coll, Dept Hlth Sci, Ft Worth, TX USA. RP Barnes, TA (reprint author), Northeastern Univ, Dept Hlth Sci, Bouve Coll Hlth Sci, 360 Huntington Ave, Boston, MA 02115 USA. EM t.barnes@neu.edu NR 29 TC 24 Z9 27 U1 0 U2 0 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESP CARE JI Respir. Care PD MAY PY 2010 VL 55 IS 5 BP 601 EP 616 PG 16 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 599TK UT WOS:000277936100011 PM 20420732 ER PT J AU Hoo, GWS AF Hoo, Guy W. Soo TI Chronic Obstructive Pulmonary Disease in the Veterans Affairs Hospitals: Haven't We Seen This Before? SO RESPIRATORY CARE LA English DT Editorial Material ID COPD; DIAGNOSIS; SPIROMETRY; BURDEN; PREVALENCE; TRIAL C1 [Hoo, Guy W. Soo] W Los Angeles Vet Affairs Healthcare Ctr, Pulm & Crit Care Sect, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Hoo, Guy W. Soo] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Hoo, GWS (reprint author), W Los Angeles Vet Affairs Healthcare Ctr, Pulm & Crit Care Sect, Vet Affairs Greater Los Angeles Healthcare Syst, 111Q,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM guy.soohoo@va.gov NR 29 TC 0 Z9 0 U1 0 U2 0 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESP CARE JI Respir. Care PD MAY PY 2010 VL 55 IS 5 BP 643 EP 645 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 599TK UT WOS:000277936100018 ER PT J AU Villarruel, AM Zhou, Y Gallegos, EC Ronis, DL AF Villarruel, Antonia M. Zhou, Yan Gallegos, Esther C. Ronis, David L. TI Examining long-term effects of Cuidate-a sexual risk reduction program in Mexican youth SO REVISTA PANAMERICANA DE SALUD PUBLICA-PAN AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article DE Adolescent behavior; sexual behavior; adolescent health; risk reduction behavior; follow-up studies; intervention studies; randomized controlled trial; Mexico ID RANDOMIZED CONTROLLED-TRIAL; SOCIAL-DESIRABILITY-SCALE; HIV PREVENTION PROGRAM; LATINO YOUTH; INTERVENTION; ADOLESCENTS; BEHAVIORS AB Objectives. To examine the effectiveness of a safer sex program (Cuidate) on sexual behavior, use of condoms, and use of other contraceptives among Mexican youth 48 months after the intervention. Methods. A total of 708 or 85% of those who participated in the original randomized control study (n = 829) were assessed in the 48-month follow-up. Each participant completed a questionnaire on sexual behavior. Results. Findings indicated that adolescents who participated in the Cuidate program were more likely to be older at first sex (odds ratio [OR], 1.27; 95% confidence interval [CI], 0.41-2.12; P < 0.05) and to use condoms at first sex (OR, 1.75; 95% CI, 1.14-2.69; P < 0.05) or some other type of contraception at first sex (OR, 1.53; 95% CI, 1.00-2.33; P < 0.05) than those in the control group. Effects of the intervention on consistent condom use, condom use at last sex, and number of sexual partners were not significant. Gender did not moderate any intervention effects. Social desirability moderated the effect of the intervention on age at first sex. Conclusions. Results demonstrate the efficacy of Cuidate among Mexican adolescents. Future research, policy, and practice efforts should be directed at sustaining safe sex practices across adolescents' developmental and relationship trajectory. C1 [Villarruel, Antonia M.; Ronis, David L.] Univ Michigan, Sch Nursing, Ann Arbor, MI 48103 USA. [Zhou, Yan] US FDA, Div Biometr 2, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Gallegos, Esther C.] Univ Autonoma Nuevo Leon, Escuela Enfermeria, Monterrey, NL, Mexico. [Ronis, David L.] US Dept Vet Affairs, Ann Arbor, MI USA. RP Villarruel, AM (reprint author), Univ Michigan, Sch Nursing, 400 North Ingalls, Ann Arbor, MI 48103 USA. EM avillarr@umich.edu FU NINR NIH HHS [R01 NR008059, NR04855] NR 23 TC 13 Z9 13 U1 0 U2 8 PU PAN AMER HEALTH ORGANIZATION PI WASHINGTON PA 525 23RD ST NW, WASHINGTON, DC 20037 USA SN 1020-4989 J9 REV PANAM SALUD PUBL JI Rev. Panam. Salud Publica PD MAY PY 2010 VL 27 IS 5 BP 345 EP 351 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 620UT UT WOS:000279526700004 PM 20602068 ER PT J AU Medalia, A Thysen, J AF Medalia, Alice Thysen, Julie TI A comparison of insight into clinical symptoms versus insight into neuro-cognitive symptoms in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Insight; Neuro-cognition; Schizophrenia; Awareness; Cognition ID PSYCHOTIC-PATIENTS; PERFORMANCE; IMPAIRMENT; AWARENESS; DEFICITS; SCALE; METAANALYSIS; UNAWARENESS; INTERVIEW; ILLNESS AB Background: Schizophrenia is associated with neuropsychological deficits that have been linked to poor functional outcome. To address this problem, pharmacologic and behavioral treatments are being developed for cognitive impairments, but they will not be well utilized if people with schizophrenia do not perceive a need for treatment. Aims: This study compared whether people with schizophrenia have a similar degree of insight into neuro-cognitive symptoms as clinical symptoms, and whether neuro-cognitive and clinical symptoms are similarly related to degree of insight into these two aspects of the illness. Method: Seventy-one patients with schizophrenia were administered measures of clinical and neuro-cognitive status as well as clinician rated measures of insight into clinical and neuro-cognitive symptoms. Results: Patients had significantly less insight into their neuro-cognitive symptoms than their clinical symptoms. On average, patients had good insight into clinical symptoms and partial insight into neuro-cognitive symptoms. Neuropsychological variables were related to insight into clinical symptoms, but not insight into neuro-cognition. Clinical variables were not significantly related to either type of insight. Conclusions: Insight is not a unitary concept and the differences between awareness of neuro-cognition and awareness of clinical symptoms suggest that they have to be addressed separately in treatment. Specific education about cognitive symptoms may be necessary to improve awareness of this aspect of the schizophrenia. (C) 2009 Elsevier B.V. All rights reserved. C1 [Medalia, Alice] Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. [Thysen, Julie] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Thysen, Julie] James J Peter VA Med Ctr, Bronx, NY USA. RP Medalia, A (reprint author), 180 Ft Washington Ave,HP234, New York, NY 10032 USA. EM am2938@columbia.edu FU Eli Lilly, PI [F1D-US-X267] FX This research was supported by an Eli Lilly Investigator Initiated Trial, Grant # F1D-US-X267, PI: Alice Medalia, PhD. Eli Lilly 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. NR 35 TC 28 Z9 29 U1 2 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY PY 2010 VL 118 IS 1-3 BP 134 EP 139 DI 10.1016/j.schres.2009.09.027 PG 6 WC Psychiatry SC Psychiatry GA 603NE UT WOS:000278214500021 PM 19840898 ER PT J AU Fan, XD Liu, EY Freudenreich, O Park, JH Liu, DT Wang, JJ Yi, ZH Goff, D Henderson, DC AF Fan, Xiaoduo Liu, Emily Y. Freudenreich, Oliver Park, Ju Hyung Liu, Dengtang Wang, Jijun Yi, Zhenghui Goff, Donald Henderson, David C. TI Higher white blood cell counts are associated with an increased risk for metabolic syndrome and more severe psychopathology in non-diabetic patients with schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE White blood cell count; Inflammation; Metabolic syndrome; Schizophrenia ID C-REACTIVE PROTEIN; LEUKOCYTE COUNT; GLUCOSE-METABOLISM; NEGATIVE SYMPTOMS; DOUBLE-BLIND; CSF LEVELS; INFLAMMATION; ATHEROSCLEROSIS; INTERLEUKIN-2; RISPERIDONE AB Background: Unequivocal evidence has emerged linking inflammation to the risk of metabolic problems. Previous research also has suggested a relationship between inflammation and schizophrenia. The present study examined whether white blood cell count (WBC), a marker of systemic inflammation, is associated with metabolic syndrome and psychiatric symptoms in non-diabetic patients with schizophrenia. Methods: Outpatients 19 to 75 years old diagnosed with schizophrenia or schizoaffective disorder participated in a multi-center, cross-sectional study. Vital signs and anthropometric measures were obtained. Fasting blood samples were collected to determine levels of glucose, lipids and WBC. Psychiatric symptoms were assessed using the Brief Psychiatric Rating Scale (BPRS). Results: In the sample of 199 patients, multiple logistic regression showed that WBC (log transformed) strongly predicted the condition of metabolic syndrome after potential confounding variables including age, gender, race, age of illness onset, family history of diabetes, smoking status and antipsychotic agent used were taken into consideration (odds ratio 47.2, 95% Cl 3.4-658.7, p = 0.004). On the other hand, significant correlations were found between WBC (log transformed) and BPRS-total score (r = 0.18, p = 0.014), negative symptom score (r = 0.15, p = 0.039) as well as anxious depression factor score (r = 0.21, p = 0.004) after potential confounding variables were taken into consideration. Conclusion: This study suggested that WBC, a simple, readily available and inexpensive measure, may potentially be a useful marker to predict an increased risk for metabolic syndrome and more severe psychiatric symptoms in non-diabetic patients with schizophrenia. (C) 2010 Elsevier B.V. All rights reserved. C1 [Fan, Xiaoduo; Freudenreich, Oliver; Park, Ju Hyung; Goff, Donald; Henderson, David C.] Massachusetts Gen Hosp, Dept Psychiat, Schizophrenia Program, Boston, MA 02114 USA. [Fan, Xiaoduo; Freudenreich, Oliver; Goff, Donald; Henderson, David C.] Harvard Univ, Sch Med, Boston, MA USA. [Liu, Emily Y.] Partners Community Healthcare Inc, Haverhill, MA USA. [Liu, Dengtang; Wang, Jijun; Yi, Zhenghui] Shanghai Mental Hlth Ctr, Shanghai, Peoples R China. RP Fan, XD (reprint author), Freedom Trail Clin, 25 Staniford St, Boston, MA 02114 USA. EM xfan@partners.org FU Eli Lilly and Company; Eli Lilly; AstraZeneca; Bristol-Myer-Squibb; Janssen; Pfizer; Cephalon; Organon; Xytis; Wyeth; Forest Labs; Indevus; Schering Plough; Novartis; Takeda; Solvay; COVANCE FX The original study was sponsored by Eli Lilly and Company. Eli Lilly was responsible for the collection of the data. However, Eli Lilly was not involved in analyzing or interpreting the data, or deciding to submit the paper for publication.; Dr. Fan has received research support or honoraria from Eli Lilly, AstraZeneca, Bristol-Myer-Squibb, Janssen, and Pfizer. Dr. Freudenreich has received research support or honoraria from AstraZeneca, Bristol-Myer-Squibb, Janssen, Eli Lilly, Cephalon and Pfizer. Dr. Goff has received research support or honoraria from Organon, Xytis, Wyeth, Forest Labs, Eli Lilly, Pfizer, Indevus, Schering Plough, AstraZeneca, Janssen and Bristol-Myer-Squibb, Novartis and Cephalon. Dr. Henderson has received research support or honoraria from Takeda, Bristol-Myers Squibb, Pfizer, AstraZeneca, Eli Lilly, Solvay, Janssen and COVANCE. Drs. E Liu, D Liu, Wang, Vi and Ms. Park report no disclosures. NR 51 TC 29 Z9 29 U1 2 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY PY 2010 VL 118 IS 1-3 BP 211 EP 217 DI 10.1016/j.schres.2010.02.1028 PG 7 WC Psychiatry SC Psychiatry GA 603NE UT WOS:000278214500031 PM 20189773 ER PT J AU Delos Santos, RB Gmurczyk, A Obhrai, JS Watnick, SG AF Delos Santos, Rowena B. Gmurczyk, Aleksandra Obhrai, Jagdeep S. Watnick, Suzanne G. TI Cardiac Evaluation Prior to Kidney Transplantation SO SEMINARS IN DIALYSIS LA English DT Article ID CORONARY-ARTERY-DISEASE; RENAL REPLACEMENT THERAPY; ISCHEMIC-HEART-DISEASE; STRESS ECHOCARDIOGRAPHY; RISK SCORE; CANDIDATES; FAILURE; ANGIOGRAPHY; RECIPIENTS; DIALYSIS AB Kidney transplantation is the treatment of choice for most patients with stage 5 chronic kidney disease and end-stage renal disease (ESRD), offering improved quality of life and overall survival rates. However, the limited supply of available organs makes this a scarce resource. Cardiovascular complications continue to be the leading cause of mortality in the kidney transplant population, accounting for over 30% of deaths with a functioning allograft. Thus, preoperative cardiac risk assessment is critical to optimize patient selection and outcomes. Currently there is no consensus for cardiovascular evaluation in the chronic kidney disease and ESRD population prior to kidney transplantation; the recommendations of the American Society of Nephrology and American Society of Transplantation differ from those of the American Heart Association and the American College of Cardiology. Previously developed risk scores have also been used to risk stratify this population. In this review, we discuss two cases that illustrate the difficulties of interpreting the prognostic value of current testing strategies. We also discuss the importance of different tests for cardiovascular evaluation as well as previous nonkidney transplant specific risk scores used in the pre-kidney transplant population. C1 [Watnick, Suzanne G.] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Div Nephrol & Hypertens, Dept Internal Med, Portland, OR 97239 USA. [Gmurczyk, Aleksandra] Northwestern Univ, Div Nephrol Hypertens, Dept Internal Med, Chicago, IL 60611 USA. [Obhrai, Jagdeep S.] Oregon Hlth & Sci Univ, Transplant Med Sect, Div Nephrol & Hypertens, Dept Internal Med, Portland, OR 97239 USA. RP Watnick, SG (reprint author), Oregon Hlth & Sci Univ, Portland VA Med Ctr, Div Nephrol & Hypertens, Dept Internal Med, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM watnicks@ohsu.edu FU NIH/NIDDK [T32 DK067864] FX This work was supported by NIH/NIDDK grant T32 DK067864. NR 28 TC 2 Z9 3 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0894-0959 J9 SEMIN DIALYSIS JI Semin. Dial. PD MAY-JUN PY 2010 VL 23 IS 3 BP 324 EP 328 DI 10.1111/j.1525-139X.2010.00725.x PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 614TI UT WOS:000279082300016 PM 20636926 ER PT J AU Epstein, MD Bhargava, P Medverd, JR AF Epstein, Matthew D. Bhargava, Puneet Medverd, Jonathan R. TI A 48-year-old man with chronic right shoulder pain and weakness after a fall SO SKELETAL RADIOLOGY LA English DT Editorial Material C1 [Bhargava, Puneet; Medverd, Jonathan R.] Univ Washington, Dept Radiol, Seattle, WA 98108 USA. [Bhargava, Puneet; Medverd, Jonathan R.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Epstein, Matthew D.] Univ Washington, Dept Radiol, Seattle, WA 98195 USA. RP Bhargava, P (reprint author), Univ Washington, Dept Radiol, 1660 S Columbian Way,S-114 Radiol,Mail Stop 35828, Seattle, WA 98108 USA. EM mde1@u.washington.edu; bhargp@u.washington.edu; jmed@u.washington.edu RI Bhargava, Puneet /F-1330-2011; OI Bhargava, Puneet/0000-0002-3849-9666 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD MAY PY 2010 VL 39 IS 5 BP 489 EP 490 DI 10.1007/s00256-009-0846-z PG 2 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 573IZ UT WOS:000275907900010 ER PT J AU Teodorescu, MC Szklo-Coxe, M AF Teodorescu, Mihai C. Szklo-Coxe, Mariana TI Sleep Well to Stay Safe: Ready for Primetime? SO SLEEP LA English DT Editorial Material ID OCCUPATIONAL INJURIES; WORKERS C1 [Teodorescu, Mihai C.] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI USA. [Szklo-Coxe, Mariana] Old Dominion Univ, Coll Hlth Sci, Sch Community & Environm Hlth, Norfolk, VA USA. [Szklo-Coxe, Mariana] Eastern Virginia Med Sch, Dept Internal Med, Div Sleep Med, Norfolk, VA 23501 USA. [Teodorescu, Mihai C.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. RP Teodorescu, MC (reprint author), William S Middleton Mem Vet Adm Med Ctr, 2500 Overlook Terrace,B5056, Madison, WI 53705 USA. EM mct@medicine.wisc.edu NR 15 TC 0 Z9 0 U1 0 U2 1 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD MAY 1 PY 2010 VL 33 IS 5 BP 577 EP 578 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 590NC UT WOS:000277232200003 PM 20469798 ER PT J AU Frisbie, JH AF Frisbie, J. H. TI Correction of orthostatic hypotension by respiratory effort SO SPINAL CORD LA English DT Article DE blood pressure; breathing; spinal cord injury; tetraplegia AB Study design: Case report. Objective: To describe a role for breathing in maintenance for blood pressure in a tetraplegic man. Setting: Veterans Administration Hospital, USA. Methods/Results: A 60-year-old man, tetraplegic for 14 years, was successfully treated for orthostatic hypotension (OH) by raising the head of his bed in the mornings before transfer to his wheelchair. To test the role of breathing in the compensation for OH, we monitored the nasal airflow with a thermistor clipped onto a naris and pulse pressure was measured with a transducer held against a supraorbital artery with an elastic band. On raising the head of the bed to 301 the pulse pressure fell and breathing effort increased. Within 1 min, however, pulse pressure rose to baseline levels whereas increased breathing effort continued. On transfer to his wheelchair OH was avoided and medication was unnecessary. Conclusion: For the tetraplegic subject the partial raising of the head of the bed for a period of time to be determined individually will recruit increased breathing effort and venous return to the chest, preventing OH on transfer to an upright position in a wheelchair. Spinal Cord (2010) 48, 434-435; doi:10.1038/sc.2009.148; published online 24 November 2009 C1 [Frisbie, J. H.] Harvard Univ, Sch Med, Dept Med, VA Boston Healthcare Syst,Res Serv, Boston, MA USA. RP Frisbie, JH (reprint author), VA Boston Healthcare Syst, Dept Med, Res Serv, 832 Woodland Dr, W Roxbury 55115, MA USA. EM jfrisbie@comcast.net FU VA Boston Healthcare System, Boston, MA, USA FX This paper is the result of a study supported with the resources and the use of facilities at the VA Boston Healthcare System, Boston, MA, USA. NR 5 TC 1 Z9 1 U1 0 U2 0 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 MAY PY 2010 VL 48 IS 5 BP 434 EP 435 DI 10.1038/sc.2009.148 PG 2 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 592DP UT WOS:000277355900015 PM 19935753 ER PT J AU Suri, P Hunter, DJ Jouve, C Hartigan, C Limke, J Pena, E Swaim, B Li, L Rainville, J AF Suri, Pradeep Hunter, David J. Jouve, Cristin Hartigan, Carol Limke, Janet Pena, Enrique Swaim, Bryan Li, Ling Rainville, James TI Inciting events associated with lumbar disc herniation SO SPINE JOURNAL LA English DT Article DE Herniation; Intervertebral disc displacement; Etiology; Trigger; Event; Activities of daily living; Exercise ID LOW-BACK-PAIN; PHYSICAL-ACTIVITIES; SCIATIC PAIN; DEGENERATION; COMPLAINTS; EXERCISE; STRENGTH; TRIAL; MEN AB BACKGROUND CONTEXT: No prior study has investigated the frequency of patient-identified inciting events in lumbar disc herniation (LDH) or their clinical significance. PURPOSE: To examine the clinical frequency of patient-identified inciting events in LDH, and to identify associations between the presence of inciting events and the severity of the clinical presentation. STUDY DESIGN/SETTING: Cross-sectional analysis of data from a cohort study with prospective recruitment, with retrospective data collection on inciting events. The setting was a hospital-based specialty spine clinic. PATIENT SAMPLE: One hundred fifty-four adults with lumbosacral radicular pain and LDH confirmed by magnetic resonance imaging. OUTCOME MEASURES: Self-report measures of disability measured by the Oswestry Disability Index (ODI), the visual analog scale (VAS) for leg pain, and the VAS for back pain. METHODS: Dependent variables included the presence of a patient-identified inciting event, which were categorized as spontaneous onset, nonlifting physical activity, heavy lifting (>35 lbs), light lifting (<35 lbs), nonexertional occurrence, or physical trauma. We examined the association of an inciting event, or a lifting-related event, with each outcome, first using univariate analyses, and second using multivariate modeling, accounting for important adjustment variables. RESULTS: Sixty-two percent of LDH did not have a specific patient-identified event associated with onset of symptoms. Nonlifting activities were the most common inciting event, comprising 26% of all LDH. Heavy lifting (6.5%), light lifting (2%), nonexertional occurrences (2%), and physical trauma (1.3%) accounted for relatively small proportions of all LDH. Patient-identified inciting events were not significantly associated with a more severe clinical presentation in crude analyses. Spontaneous LDH was significantly associated with higher baseline ODI scores in multivariate analysis, although the magnitude of this effect was small. There were no significant associations (p <=.05) between the presence of a lifting-associated event and the outcomes of ODI, VAS leg pain, or VAS back pain. CONCLUSIONS: The majority of LDH occurred without specific inciting events. A history of an inciting event was not significantly associated with a more severe clinical presentation. There was no significant association between the occurrence of a lifting-related event and the severity of the clinical presentation. This information may be useful in the counseling of patients recovering from acute LDH. (c) 2010 Published by Elsevier Inc. C1 [Suri, Pradeep; Hunter, David J.; Swaim, Bryan; Li, Ling] New England Baptist Hosp, Div Res, Boston, MA 02120 USA. [Suri, Pradeep; Jouve, Cristin; Hartigan, Carol; Limke, Janet; Rainville, James] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA 02114 USA. [Suri, Pradeep] Spaulding Rehabil Hosp, Boston, MA 02114 USA. [Suri, Pradeep] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Jouve, Cristin; Hartigan, Carol; Limke, Janet; Pena, Enrique; Rainville, James] New England Baptist Hosp, Spine Ctr, Boston, MA 02120 USA. RP Suri, P (reprint author), New England Baptist Hosp, Div Res, 125 Parker Hill Ave, Boston, MA 02130 USA. EM psuri@caregroup.harvard.edu RI Hunter, David/A-4622-2010 OI Hunter, David/0000-0003-3197-752X FU National Institutes of Health [K12 HD 01097]; AF; ACR; New England Baptist Hospital Research; DonJoy FX PS (research support, National Institutes of Health K12 HD 01097; grants, New England Baptist Hospital Research Funding Award); DJH (royalties, DonJoy; consulting, NicOx; board of directors, OARS!: scientific advisory board. Smith and Nephew: research support, chief of research; grants. NIH, AF, ACR).; Dr Suri is funded by the Rehabilitation Medicine Scientist Training Program and the National Institutes of Health (K12 HD 01097). NR 25 TC 5 Z9 5 U1 2 U2 3 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 MAY PY 2010 VL 10 IS 5 BP 388 EP 395 DI 10.1016/j.spinee.2010.02.003 PG 8 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 601DW UT WOS:000278039300006 PM 20347617 ER PT J AU Iwai, M Stetler, RA Xing, J Hu, XM Gao, YQ Zhang, WT Chen, J Cao, GD AF Iwai, Masanori Stetler, R. Anne Xing, Juan Hu, Xiaoming Gao, Yanqin Zhang, Wenting Chen, Jun Cao, Guodong TI Enhanced Oligodendrogenesis and Recovery of Neurological Function by Erythropoietin After Neonatal Hypoxic/Ischemic Brain Injury SO STROKE LA English DT Article DE erythropoietin; neonatal hypoxia/ischemia; neurogenesis; oligodendrogenesis; white matter injury ID HYPOXIA-ISCHEMIA; IN-VITRO; OLIGODENDROCYTES; RAT; HYPOXIA/ISCHEMIA; PROLIFERATION; NEUROGENESIS; PROGENITORS; REPLACEMENT; THERAPY AB Background and Purpose-Neuronal replacement has recently gained attention as a potential therapeutic target under ischemic conditions. However, the oligodendrogenic infrastructure is equally critical for restoration of brain function and is also sensitive to ischemic injury. Erythropoietin (EPO) is a neuroprotective molecule that stimulates neuronal replacement after neonatal hypoxia/ischemia (H/I) when delivered soon after the onset of reperfusion. Because EPO can improve recovery of neurological function in the absence of tissue protection, we hypothesize that EPO may improve neurological function via enhancement of white matter recovery after H/I. Thus, we sought to determine the effects of delayed administration of EPO on white matter injury and recovery of neurological function after neonatal H/I. Methods-EPO (1000 U/kg) was injected intraperitoneally at multiple time points beginning 48 hours after H/I in postnatal day 7 rats. The effects of EPO on oligodendrogenesis, white matter injury, and neurogenesis were evaluated using bromodeoxyuridine incorporation and cell-specific immunohistochemistry. Neurological function was assessed by sensorimotor behavioral tests. Results-Delayed administration of EPO was incapable of reducing brain volume loss but significantly increased oligodendrogenesis and maturation of oligodendrocytes and attenuated white matter injury after H/I. These effects occurred concurrently with enhanced neurogenesis. Delayed EPO treatment improved behavioral neurological outcomes 14 days after H/I injury. Conclusions-Our study demonstrates that delayed administration of EPO promotes oligodendrogenesis and attenuates white matter injury concurrently with increased neurogenesis. These effects likely contribute to the observed improvement in neurological functional outcomes. (Stroke. 2010;41:1032-1037.) C1 [Iwai, Masanori; Stetler, R. Anne; Xing, Juan; Hu, Xiaoming; Chen, Jun; Cao, Guodong] Univ Pittsburgh, Dept Neurol, Sch Med, Pittsburgh, PA 15260 USA. [Iwai, Masanori; Stetler, R. Anne; Chen, Jun; Cao, Guodong] Vet Affairs Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Stetler, R. Anne; Gao, Yanqin; Zhang, Wenting; Chen, Jun; Cao, Guodong] Fudan Univ, State Key Lab Med Neurobiol, Shanghai 200433, Peoples R China. RP Cao, GD (reprint author), Univ Pittsburgh, Dept Neurol, Sch Med, BST S505,3500 Terrace St, Pittsburgh, PA 15260 USA. EM caog@upmc.edu RI Gao, Yanqin/I-6790-2016 OI Gao, Yanqin/0000-0002-4915-9819 FU National Institutes of Health/NINDS [NS43802, NS45048, NS36736, NS56118, NS053473]; VA Merit Review; AHA Scientist Development [06300064N] FX This project was supported by National Institutes of Health/NINDS grants NS43802, NS45048, NS36736, NS56118 (J.C.), and NS053473 (G. C.), VA Merit Review grants (J.C. and G. C.), and AHA Scientist Development grant 06300064N (G. C.). NR 18 TC 85 Z9 93 U1 1 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 MAY PY 2010 VL 41 IS 5 BP 1032 EP 1037 DI 10.1161/STROKEAHA.109.570325 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 588IY UT WOS:000277064300034 PM 20360553 ER PT J AU Reeves, MJ Vaidya, RS Fonarow, GC Liang, L Smith, EE Matulonis, R Olson, DM Schwamm, LH AF Reeves, Mathew J. Vaidya, Robert S. Fonarow, Gregg C. Liang, Li Smith, Eric E. Matulonis, Robert Olson, DaiWai M. Schwamm, Lee H. CA Get Guidelines Steering Comm Hosp TI Quality of Care and Outcomes in Patients With Diabetes Hospitalized With Ischemic Stroke Findings From Get With the Guidelines-Stroke SO STROKE LA English DT Article DE diabetes; ischemic stroke; quality of care; registries ID INTRACEREBRAL HEMORRHAGE; GLUCOSE LEVEL; PREVALENCE; MORTALITY; MELLITUS; ATTACK; RISK; ASSOCIATION; POPULATION; PREVENTION AB Background and Purpose-Diabetes is a common comorbid disease in stroke patients and has a strong influence on stroke-related outcomes, including stroke recurrence. We sought to examine the quality of care and in-hospital outcomes in patients with diabetes in the Get With the Guidelines-Stroke (GWTG-Stroke) program. Methods-Data were obtained from 415 926 ischemic stroke patients from 1070 United States hospitals that participated in GWTG-Stroke between 2003 and 2008. We analyzed the relationships between diabetes and quality of care, in-hospital mortality, and discharge home using multivariable logistic regression. Results-There were 130 817 (31%) ischemic stroke patients with diabetes. Quality of care received by patients with and without diabetes was similar except for intravenous recombinant tissue plasminogen activator (rt-PA) and cholesterol treatment. Fifty-four percent of patients with diabetes who arrived within 2 hours of onset received rt-PA compared to 60.8% of patients without diabetes (adjusted odds ratio [aOR], 0.83; 95% CI, 0.79-0.88). Almost 80% of patients with diabetes were discharged on cholesterol treatment compared to 71% of patients without diabetes (aOR, 1.40; 95% CI, 1.37-1.44). Diabetes patients were less likely to be discharged home (aOR, 0.80; 95% CI, 0.78-0.81) and had a higher risk of in-hospital death (aOR, 1.12; 95% CI, 1.08-1.15). Conclusions-Quality of care among patients with and without diabetes was similar except for rt-PA and cholesterol treatment. Diabetes was associated with worse stroke-related outcomes. Greater quality-improvement efforts to increase the use of rt-PA and other secondary prevention treatments in patients with diabetes are warranted. (Stroke. 2010;41:e409-e417.) C1 [Reeves, Mathew J.; Vaidya, Robert S.; Matulonis, Robert] Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA USA. [Liang, Li; Olson, DaiWai M.] Duke Clin Res Ctr, Durham, NC USA. [Smith, Eric E.] Univ Calgary, Dept Clin Neurosci, Calgary, AB, Canada. [Schwamm, Lee H.] Massachusetts Gen Hosp, Div Neurol, Boston, MA 02114 USA. RP Reeves, MJ (reprint author), Michigan State Univ, Dept Epidemiol, B601 W Fee Hall, E Lansing, MI 48824 USA. EM reevesm@msu.edu RI Smith, Eric/C-5443-2012; OI Smith, Eric/0000-0003-3956-1668; Schwamm, Lee/0000-0003-0592-9145 FU American Heart Association; American Stroke Association; Pfizer (New York, NY); Merck-Schering Plough Partnership (North Wales, PA); Michigan Stroke Registry; National Institutes of Health [NINDS R01 NS062028]; Canadian Stroke Network; Heart and Stroke Foundation of Canada; Canadian Institute for Health Research FX The Get With the Guidelines Program (GWTG) is funded by the American Heart Association and the American Stroke Association. The program is also supported in part by unrestricted educational grants to the American Heart Association by Pfizer (New York, NY) and the Merck-Schering Plough Partnership (North Wales, PA), who did not participate in the design, analysis, or manuscript preparation, and did not require approval of this manuscript for submission.; Dr Reeves receives salary support from the Michigan Stroke Registry and serves as a member of the American Heart Association's Get With the Guidelines Quality Improvement Subcommittee. Dr Vaidya has no disclosures to report. Dr Fonarow chairs the American Heart Association GWTG Steering Committee; serves as a consultant to Pfizer, Merck, Schering Plough, Bristol Myers Squibb, and Sanofi-Aventis; receives speaker honoraria from Pfizer, Merck, Schering Plough, Bristol Myers Squibb, and Sanofi-Aventis; and receives research support from Pfizer and National Institutes of Health. Dr Liang is a member of the Duke Clinical Research Institute, which serves as the American Heart Association GWTG data coordinating center. Dr Smith serves as a member of the Get With the Guidelines Science Subcommittee and receives research support from the NIH (NINDS R01 NS062028) and the Canadian Stroke Network, and received salary support from the Heart and Stroke Foundation of Canada and the Canadian Institute for Health Research. Mr Matulonis has no disclosures to report. Dr Olson is a member of the Duke Clinical Research Institute, which serves as the American Heart Association GWTG data coordinating center. Dr Schwamm serves as vice chair of the American Heart Association GWTG Steering Committee; serves as a consultant to the Research Triangle Institute, CryoCath, and the Massachusetts Department of Public Health; and has provided expert medical opinions in malpractice lawsuits regarding stroke treatment and prevention. NR 27 TC 25 Z9 27 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAY PY 2010 VL 41 IS 5 BP E409 EP E417 DI 10.1161/STROKEAHA.109.572693 PG 9 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 588IY UT WOS:000277064300041 PM 20224058 ER PT J AU Sylla, P Rattner, DW Delgado, S Lacy, AM AF Sylla, Patricia Rattner, David W. Delgado, Salvadora Lacy, Antonio M. TI NOTES transanal rectal cancer resection using transanal endoscopic microsurgery and laparoscopic assistance SO SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES LA English DT Article DE Natural Orifice Translumenal Endoscopic Surgery; Transanal endoscopic microsurgery; Transanal; Rectal cancer ID SURGERY NOTES; PORCINE MODEL; NOTES SURVIVAL; CHOLECYSTECTOMY; EXPERIENCE AB The feasibility and safety of Natural Orifice Translumenal Endoscopic Surgery (NOTES) transanal endoscopic rectosigmoid resection using transanal endoscopic microsurgery (TEM) was previously demonstrated in human cadavers and a porcine survival model. We report the first clinical case of a NOTES transanal resection for rectal cancer using TEM and laparoscopic assistance, performed by a team of surgeons from Barcelona and Boston with extensive experience with NOTES and minimally invasive approaches to colorectal diseases. Transanal endoscopic rectal resection with total mesorectal excision using the TEM platform was performed in a 76-year-old woman with a T2N2 rectal cancer treated with preoperative chemoradiation. Laparoscopic visualization and assistance with retraction and exposure during rectosigmoid mobilization was provided through one 5-mm port, which was later used as the stoma site, and 2-mm needle ports, one of which was used as a drain site. The specimen was transected transanally followed by handsewn coloanal anastomosis. The procedure was completed successfully with an operative time of 4 hours and 30 minutes. Mesorectal excision was complete. The postoperative course was uneventful, and the patient was discharged on the fourth postoperative day. The final pathology demonstrated pT1N0 with 23 negative lymph nodes and negative proximal, distal, and radial margins. NOTES transanal endoscopic rectosigmoid resection using TEM and laparoscopic assistance is feasible and safe. Careful patient selection and improvement in NOTES instrumentation are critical to optimize this approach before widespread clinical application. C1 [Delgado, Salvadora; Lacy, Antonio M.] Univ Barcelona, Dept Gastrointestinal Surg, Ctr Invest Biomed Esther Koplowitz, CIBERehd,IDIBAPS,Hosp Clin, E-08036 Barcelona, Spain. [Sylla, Patricia; Rattner, David W.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Lacy, AM (reprint author), Univ Barcelona, Dept Gastrointestinal Surg, Ctr Invest Biomed Esther Koplowitz, CIBERehd,IDIBAPS,Hosp Clin, Villarroel 170, E-08036 Barcelona, Spain. EM alacy@clinic.ub.es NR 25 TC 166 Z9 193 U1 1 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0930-2794 J9 SURG ENDOSC JI Surg. Endosc. PD MAY PY 2010 VL 24 IS 5 BP 1205 EP 1210 DI 10.1007/s00464-010-0965-6 PG 6 WC Surgery SC Surgery GA 589LF UT WOS:000277148500036 PM 20186432 ER PT J AU Scheurer, RA Kosmorsky, GS Hoffman, GS Farver, C Lee, MS Cestari, DM AF Scheurer, Ryan A. Kosmorsky, Gregory S. Hoffman, Gary S. Farver, Carol Lee, Michael S. Cestari, Dean M. TI Can't Hear, Can't See, and Too Sore to Play SO SURVEY OF OPHTHALMOLOGY LA English DT Review DE branch retinal artery occlusion; eye infections; bacterial; leukocytosis; migratory polyarthralgias; Tropheryma; vitritis; Whipple disease ID WHIPPLES-DISEASE; VITREOPAPILLARY TRACTION; OCULAR INVOLVEMENT; DIAGNOSIS AB A 52-year-old man developed transient, migratory polyarthralgias in the presence of hearing loss. He then developed persistent leukocytosis and thrombocytosis. His initial transient, bilateral visual obscurations happened in context with bilateral disk edema and an enlarged blind spot. Visual Symptoms progressed to vision loss and multiple branch retinal artery occlusions. It was not until later in the disease progression that gastrointestinal symptoms occurred. Electron microscopy of duodenal biopsies confirmed a diagnosis of Whipple disease. (Surv Ophthalmol 55:290-296, 2010. (C) 2010 Elsevier Inc. All rights reserved.) C1 [Scheurer, Ryan A.; Lee, Michael S.] Univ Minnesota, Dept Ophthalmol, Minneapolis, MN 55455 USA. [Kosmorsky, Gregory S.] Cleveland Clin Fdn, Dept Ophthalmol, Cleveland, OH 44195 USA. [Farver, Carol; Cestari, Dean M.] Massachusetts Eye & Ear Infirm, Neuroophthalmol Unit, Boston, MA 02114 USA. RP Lee, MS (reprint author), Univ Minnesota, Dept Ophthalmol, 420 Delaware St SE,MMC 493, Minneapolis, MN 55455 USA. EM mikelee@umn.edu FU Research to Prevent Blindness, New York, NY; Lions Club of Minnesota FX The authors reported no proprietary or commercial interest in any product mentioned or concept discussed in this article. This article was supported by an unrestricted grant from Research to Prevent Blindness, New York, NY and the Lions Club of Minnesota. NR 18 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 0039-6257 J9 SURV OPHTHALMOL JI Surv. Ophthalmol. PD MAY-JUN PY 2010 VL 55 IS 3 BP 290 EP 296 DI 10.1016/j.survophthal.2009.09.002 PG 7 WC Ophthalmology SC Ophthalmology GA 592HR UT WOS:000277369700008 PM 20083288 ER PT J AU Castillo, M Freitas, BCG Rosene, ML Drigo, RA Grozovsky, R Maciel, RMB Patti, ME Ribeiro, MO Bianco, AC AF Castillo, Melany Freitas, Beatriz C. G. Rosene, Matthew L. Drigo, Rafael A. Grozovsky, Renata Maciel, Rui M. B. Patti, Mary Elizabeth Ribeiro, Miriam O. Bianco, Antonio C. TI Impaired Metabolic Effects of a Thyroid Hormone Receptor Beta-Selective Agonist in a Mouse Model of Diet-Induced Obesity SO THYROID LA English DT Article ID TYPE-2 IODOTHYRONINE DEIODINASE; BROWN ADIPOSE-TISSUE; ADAPTIVE THERMOGENESIS; ENERGY-EXPENDITURE; MOLECULAR-BASIS; FATTY LIVER; GC-1; RATS; EXPRESSION; GENE AB Background: The use of selective agonists of the thyroid hormone receptor isoform beta (TR beta) has been linked to metabolic improvement in animal models of diet-induced obesity, nonalcoholic liver disease, and genetic hypercholesterolemia. Methods: To identify potential target tissues of such compounds, we exposed primary murine brown adipocytes and skeletal myocytes for 24 hours to 50 nM GC-24, a highly selective TR beta agonist. GC-24 (17 ng/[g BWday] for 36 days) was also tested in a mouse model of diet-induced obesity. Results: While the brown adipocytes responded to GC-24, with 17%-400% increases in the expression of 12 metabolically relevant genes, the myocytes remained largely unresponsive to GC-24 treatment. In control mice kept on chow diet, GC-24 treatment accelerated energy expenditure by about 15% and limited body weight gain by about 50%. However, in the obese animals the GC-24-mediated reduction in body weight gain dropped to only 20%, while energy expenditure remained unaffected. In addition, an analysis of gene expression in the skeletal muscle, brown adipose tissue, and liver of these obese animals failed to identify a conclusive GC-24 transcriptome footprint. Conclusion: Feeding a high-fat diet impairs most of the beneficial metabolic effects associated with treatment with TR beta-selective agonists. C1 [Castillo, Melany; Rosene, Matthew L.; Drigo, Rafael A.; Grozovsky, Renata; Bianco, Antonio C.] Univ Miami, Miller Sch Med, Div Endocrinol Diabet & Metab, Miami, FL 33136 USA. [Freitas, Beatriz C. G.; Maciel, Rui M. B.] Univ Fed Sao Paulo, Dept Med, Div Endocrinol, Mol Endocrinol Lab, Sao Paulo, Brazil. [Patti, Mary Elizabeth] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Ribeiro, Miriam O.] Univ Prebiteriana Mackenzie, Dept Biosci, Sao Paulo, Brazil. RP Bianco, AC (reprint author), Univ Miami, Miller Sch Med, Div Endocrinol Diabet & Metab, 1400 NW 10th Ave,Suite 816, Miami, FL 33136 USA. EM abianco@deiodinase.org RI Bianco, Antonio/A-4965-2008; Ribeiro, Miriam/A-9367-2013; Ribeiro, Miriam/B-6085-2015; Ribeiro, Miriam/C-6364-2016; OI Bianco, Antonio/0000-0001-7737-6813; Ribeiro, Miriam/0000-0002-7870-9701; Arrojo e Drigo, Rafael/0000-0001-7712-013X; Maciel, Rui/0000-0002-6123-6098 FU National Institute for Diabetes and Digestive and Kidney Diseases [DK65055] FX The authors are grateful to Ms. Jessica Hall for critically reviewing this article. This work was supported in part by the National Institute for Diabetes and Digestive and Kidney Diseases (DK65055). NR 30 TC 1 Z9 1 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 J9 THYROID JI Thyroid PD MAY PY 2010 VL 20 IS 5 BP 245 EP 553 DI 10.1089/thy.2009.0318 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592UV UT WOS:000277407000013 ER PT J AU Randolph, GW AF Randolph, Gregory W. TI The Importance of Pre- and Postoperative Laryngeal Examination for Thyroid Surgery SO THYROID LA English DT Editorial Material ID UNITED-STATES; NERVE PALSY; VOICE; DIAGNOSIS; COMPLICATIONS; MALPRACTICE; PARALYSIS; SPEAKING; DISEASE; INJURY C1 [Randolph, Gregory W.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Massachutts Gen Hosp, Boston, MA 02114 USA. RP Randolph, GW (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM gregory_randolph@meei.harvard.edu NR 33 TC 14 Z9 14 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 J9 THYROID JI Thyroid PD MAY PY 2010 VL 20 IS 5 BP 453 EP 458 DI 10.1089/thy.2010.1632 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592UV UT WOS:000277407000002 PM 20450429 ER PT J AU Hoganson, DM Pryor, HI Spool, ID Burns, OH Gilmore, JR Vacanti, JP AF Hoganson, David M. Pryor, Howard I., II Spool, Ira D. Burns, Owen H. Gilmore, J. Randall Vacanti, Joseph P. TI Principles of Biomimetic Vascular Network Design Applied to a Tissue-Engineered Liver Scaffold SO TISSUE ENGINEERING PART A LA English DT Article ID AORTIC WAVE REFLECTION; SHEAR-STRESS; BLOOD-FLOW; PLATELET ACTIVATION; ENDOTHELIAL-CELLS; IN-VITRO; CHANNELS; VESSELS; MODELS; SYSTEM AB Branched vascular networks are a central component of scaffold architecture for solid organ tissue engineering. In this work, seven biomimetic principles were established as the major guiding technical design considerations of a branched vascular network for a tissue-engineered scaffold. These biomimetic design principles were applied to a branched radial architecture to develop a liver-specific vascular network. Iterative design changes and computational fluid dynamic analysis were used to optimize the network before mold manufacturing. The vascular network mold was created using a new mold technique that achieves a 1:1 aspect ratio for all channels. In vitro blood flow testing confirmed the physiologic hemodynamics of the network as predicted by computational fluid dynamic analysis. These results indicate that this biomimetic liver vascular network design will provide a foundation for developing complex vascular networks for solid organ tissue engineering that achieve physiologic blood flow. C1 [Hoganson, David M.; Pryor, Howard I., II; Spool, Ira D.; Burns, Owen H.; Vacanti, Joseph P.] Massachusetts Gen Hosp, Dept Surg, Ctr Regenerat Med, Boston, MA 02114 USA. [Burns, Owen H.] Univ Wollongong, Wollongong, NSW, Australia. [Gilmore, J. Randall] Ex One Co, Irwin, PA USA. RP Vacanti, JP (reprint author), Massachusetts Gen Hosp, Dept Surg, Ctr Regenerat Med, 185 Cambridge St,Suite 4-809, Boston, MA 02114 USA. EM jvacanti@partners.org OI Hoganson, David/0000-0002-8141-7793 FU NIH [F32 DK076349-01, T32 DK07754-09] FX The authors gratefully acknowledge support from the NIH (F32 DK076349-01 to D.M.H., and T32 DK07754-09 to H.I.P.). The authors would like to thank the Ex One Corporation for their generous contribution of machining the molds for this project. The authors would like to thank Ali Hart for her technical assistance. NR 42 TC 26 Z9 28 U1 0 U2 20 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3341 J9 TISSUE ENG PT A JI Tissue Eng. Part A PD MAY PY 2010 VL 16 IS 5 BP 1469 EP 1477 DI 10.1089/ten.tea.2009.0118 PG 9 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA 589SG UT WOS:000277173100002 PM 20001254 ER PT J AU Karel, MJ Knight, BG Duffy, M Hinrichsen, GA Zeiss, AM AF Karel, Michele J. Knight, Bob G. Duffy, Michael Hinrichsen, Gregory A. Zeiss, Antonette M. TI Attitude, Knowledge, and Skill Competencies for Practice in Professional Geropsychology: Implications for Training and Building a Geropsychology Workforce SO TRAINING AND EDUCATION IN PROFESSIONAL PSYCHOLOGY LA English DT Article DE geropsychology; older adults; competencies; training; continuing education ID GERIATRIC MENTAL-HEALTH; OLDER-ADULTS; PSYCHOLOGICAL TREATMENTS; PRIMARY-CARE; CORE COMPETENCES; OF-LIFE; SERVICES; EDUCATION; MODEL; RECOMMENDATIONS AB Professional geropsychology is a growing area of practice and training. To meet the mental health needs of an aging population, increasing numbers of psychologists need to develop competence to work with older adults, their families, and related care systems. The Pikes Peak model for geropsychology training (Knight, Karel, Hinrichsen, Qualls, & Duffy, 2009) delineates attitude, knowledge, and skill competencies for professional geropsychology practice and makes recommendations for training. In this paper. we define and illustrate the Pikes Peak geropsychology practice competencies through a case example. In the case, an older man with complex needs seeks care through a generalist psychologist in an outpatient setting. The attitudes, knowledge, and skills that the psychologist needs to consider, and implications for training, are reviewed. Training recommendations and resources are provided, with a focus on the training needs of psychologists who wish to expand their practices to include older adults. C1 [Karel, Michele J.] VA Boston Healthcare Syst, Boston, MA USA. [Karel, Michele J.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Knight, Bob G.] Univ So Calif, Los Angeles, CA 90089 USA. [Duffy, Michael] Texas A&M Univ, Counseling Psychol Program, College Stn, TX 77843 USA. [Hinrichsen, Gregory A.] Albert Einstein Coll Med, New York, NY USA. [Zeiss, Antonette M.] Dept Vet Affairs, Off Mental Hlth Serv, Washington, DC USA. RP Karel, MJ (reprint author), Brockton VA Med Ctr, 3-5-C,940 Belmont St, Brockton, MA 02301 USA. EM michele.karel@va.gov NR 67 TC 18 Z9 18 U1 0 U2 8 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1931-3918 EI 1931-3926 J9 TRAIN EDUC PROF PSYC JI Train. Educ. Prof. Psychol. PD MAY PY 2010 VL 4 IS 2 BP 75 EP 84 DI 10.1037/a0018372 PG 10 WC Psychology, Educational SC Psychology GA 603JA UT WOS:000278203600001 ER PT J AU Hinrichsen, GA Zeiss, AM Karel, MJ Molinari, VA AF Hinrichsen, Gregory A. Zeiss, Antonette M. Karel, Michele J. Molinari, Victor A. TI Competency-Based Geropsychology Training in Doctoral Internships and Postdoctoral Fellowships SO TRAINING AND EDUCATION IN PROFESSIONAL PSYCHOLOGY LA English DT Article DE internship; postdoctoral fellowship; older adults; training; geropsychology ID OLDER-ADULTS; PROFESSIONAL GEROPSYCHOLOGY; CONTINUING-EDUCATION; CURRENT PATTERNS; MENTAL-HEALTH; PSYCHOLOGISTS; SUPERVISION; WORKING; ISSUES AB Opportunities for geropsychology training in doctoral internships and postdoctoral fellowships have slowly grown over the years. There will be a need for more geropsychology training programs as the U.S. population ages concurrent with increased demand for mental health services from older adults. This article provides recommendations for competency-based geropsychology training that derive from the Pikes Peak Model for Training in Professional Geropsychology. We believe the recommendations provide useful guidance to existing internships and postdoctoral fellowships that offer geropsychology training, as well as to those who would like to establish programs. C1 [Hinrichsen, Gregory A.] Albert Einstein Coll Med, New York, NY USA. [Zeiss, Antonette M.] Dept Vet Affairs, Off Mental Hlth Serv, Washington, DC USA. [Karel, Michele J.] VA Boston Hlth Care Syst, Boston, MA USA. [Karel, Michele J.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Molinari, Victor A.] Univ S Florida, Florida Mental Hlth Inst, Dept Aging & Mental Hlth Dispar, Tampa, FL 33620 USA. RP Hinrichsen, GA (reprint author), 200 W 16 St,5B, New York, NY 10011 USA. EM geropsychgah@aol.com NR 45 TC 13 Z9 13 U1 0 U2 2 PU EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1931-3918 J9 TRAIN EDUC PROF PSYC JI Train. Educ. Prof. Psychol. PD MAY PY 2010 VL 4 IS 2 BP 91 EP 98 DI 10.1037/a0018149 PG 8 WC Psychology, Educational SC Psychology GA 603JA UT WOS:000278203600003 ER PT J AU AuBuchon, JP Dzik, WS AF AuBuchon, James P. Dzik, Walter Sunny TI Reports on clinical transfusion medicine in the early days of TRANSFUSION SO TRANSFUSION LA English DT Editorial Material ID HOSPITAL BLOOD BANK; STORED BLOOD; PLASMA; PRESERVATION; MULTICENTER; PLATELETS; PROGRAM C1 [AuBuchon, James P.] Univ Washington, Dept Lab Med, Dept Med, Puget Sound Blood Ctr, Seattle, WA 98195 USA. [Dzik, Walter Sunny] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP AuBuchon, JP (reprint author), Univ Washington, Dept Lab Med, Dept Med, Puget Sound Blood Ctr, Seattle, WA 98195 USA. EM jima@psbc.org NR 29 TC 1 Z9 1 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD MAY PY 2010 VL 50 IS 5 BP 963 EP 967 DI 10.1111/j.1537-2995.2009.02457.x PG 5 WC Hematology SC Hematology GA 589CY UT WOS:000277123900003 PM 19906039 ER PT J AU Benacerraf, BR AF Benacerraf, B. R. TI A technical tip on scanning obese gravidae SO ULTRASOUND IN OBSTETRICS & GYNECOLOGY LA English DT Editorial Material DE obesity; pregnancy; ultrasound ID WOMEN C1 [Benacerraf, B. R.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Benacerraf, B. R.] Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. [Benacerraf, B. R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. [Benacerraf, B. R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA USA. RP Benacerraf, BR (reprint author), Diagnost Ultrasound Associates, 333 Longwood Ave, Boston, MA 02115 USA. EM bbsono@aol.com NR 5 TC 8 Z9 8 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0960-7692 J9 ULTRASOUND OBST GYN JI Ultrasound Obstet. Gynecol. PD MAY PY 2010 VL 35 IS 5 BP 615 EP 616 DI 10.1002/uog.7550 PG 2 WC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging GA 603LR UT WOS:000278210600019 PM 20052658 ER PT J AU Basch, E Reeve, B Cleeland, C Sloan, J Mendoza, T Abernethy, A Bruner, D Hay, J Atkinson, T Sit, L Minasian, L O'Mara, A Burke, L Schrag, D AF Basch, E. Reeve, B. Cleeland, C. Sloan, J. Mendoza, T. Abernethy, A. Bruner, D. Hay, J. Atkinson, T. Sit, L. Minasian, L. O'Mara, A. Burke, L. Schrag, D. TI DEVELOPMENT OF THE PATIENT-REPORTED VERSION OF THE COMMON TERMINOLOGY CRITERIA FOR ADVERSE EVENTS ( PRO-CTCAE) SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Basch, E.; Hay, J.; Atkinson, T.; Sit, L.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Reeve, B.; Minasian, L.; O'Mara, A.] Natl Canc Inst, Bethesda, MD USA. [Cleeland, C.; Mendoza, T.] UTMD Anderson Canc Ctr, Houston, TX USA. [Sloan, J.] Mayo Clin, Rochester, MN USA. [Abernethy, A.] Duke Univ, Durham, NC USA. [Bruner, D.] Univ Penn, Philadelphia, PA 19104 USA. [Burke, L.] Food & Drug Adm, Silver Spring, MD USA. [Schrag, D.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY PY 2010 VL 13 IS 3 BP A44 EP A44 DI 10.1016/S1098-3015(10)72198-7 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 589CJ UT WOS:000277121900215 ER PT J AU Dial, E Duh, MS Antras, L Rodermund, D Neary, MP Choueiri, TK Oh, WK AF Dial, E. Duh, M. S. Antras, L. Rodermund, D. Neary, M. P. Choueiri, T. K. Oh, W. K. TI INCIDENCE AND COST OF ADVERSE EVENTS (AES) IN PATIENTS WITH RENAL CELL CARCINOMA (RCC) TREATED WITH ANGIOGENESIS INHIBITORS (AIS) SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Dial, E.; Duh, M. S.; Antras, L.; Rodermund, D.] Anal Grp Inc, Boston, MA USA. [Neary, M. P.] GlaxoSmithKline Inc, Collegeville, PA USA. [Choueiri, T. K.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Oh, W. K.] Mt Sinai Sch Med, New York, NY USA. RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY PY 2010 VL 13 IS 3 BP A76 EP A76 DI 10.1016/S1098-3015(10)72356-1 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 589CJ UT WOS:000277121900373 ER PT J AU Guerin, A Bollu, V Guo, A Wu, EQ Yu, AP Sirulnik, LA Griffin, JD AF Guerin, A. Bollu, V Guo, A. Wu, E. Q. Yu, A. P. Sirulnik, L. A. Griffin, J. D. TI NON-ADHERENCE TO IMATINIB IN CHRONIC MYELOID LEUKEMIA (CML) PATIENTS IS ASSOCIATED WITH SHORT- AND LONG-TERM NEGATIVE IMPACTS ON HEALTH CARE RESOURCE UTILIZATION AND COSTS SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Guerin, A.] Analysis Grp Ltee, Montreal, PQ, Canada. [Bollu, V; Guo, A.; Sirulnik, L. A.] Novartis Pharmaceut, E Hanover, NJ USA. [Wu, E. Q.; Yu, A. P.] Analysis Grp Inc, Boston, MA USA. [Griffin, J. D.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY PY 2010 VL 13 IS 3 BP A32 EP A32 DI 10.1016/S1098-3015(10)72137-9 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 589CJ UT WOS:000277121900154 ER PT J AU Jackson, DJ Earnshaw, S Farkouh, R Schwamm, LH AF Jackson, D. J. Earnshaw, S. Farkouh, R. Schwamm, L. H. TI COST-EFFECTIVENESS OF PERFUSION IMAGING WITH COMPUTED TOMOGRAPHY TO IDENTIFY PATIENTS FOR INTRAVENOUS THROMBOLYSIS: A HOSPITAL PERSPECTIVE SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Jackson, D. J.] GE Healthcare, Buckingham, England. [Earnshaw, S.] RTI Hlth Solut, Res Triangle Pk, NC USA. [Farkouh, R.; Schwamm, L. H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY PY 2010 VL 13 IS 3 BP A175 EP A175 DI 10.1016/S1098-3015(10)72850-3 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 589CJ UT WOS:000277121901095 ER PT J AU Oh, WK McDermott, DF Duh, MS Antras, L Chen, K Sarda, SP Luka, A Whittemore, S Ramamurthy, P Neary, MP Choueiri, TK AF Oh, W. K. McDermott, D. F. Duh, M. S. Antras, L. Chen, K. Sarda, S. P. Luka, A. Whittemore, S. Ramamurthy, P. Neary, M. P. Choueiri, T. K. TI COSTS OF TREATMENT WITH ANGIOGENESIS INHIBITORS (AIS) IN PATIENTS WITH METASTATIC RENAL CELL CARCINOMA (MRCC): RESULTS FROM A MEDICAL CHART REVIEW STUDY SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Oh, W. K.] Mt Sinai Sch Med, New York, NY USA. [McDermott, D. F.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Duh, M. S.; Antras, L.; Chen, K.; Sarda, S. P.; Luka, A.; Whittemore, S.; Ramamurthy, P.] Anal Grp Inc, Boston, MA USA. [Neary, M. P.] GlaxoSmithKline Inc, Collegeville, PA USA. [Choueiri, T. K.] Dana Farber Canc Inst, Brigham & Womens Hosp, Boston, MA 02115 USA. RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY PY 2010 VL 13 IS 3 BP A32 EP A32 DI 10.1016/S1098-3015(10)72139-2 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 589CJ UT WOS:000277121900156 ER PT J AU Ramsey, S Zeliadt, SB Blough, DK Fedorenko, CR Moinpour, CM Hall, IJH Smith, JL Ekwueme, DU Fairweather, ME Thompson, IM Keane, TE Penson, D AF Ramsey, S. Zeliadt, S. B. Blough, D. K. Fedorenko, C. R. Moinpour, C. M. Hall, I. J. H. Smith, Lee J. Ekwueme, D. U. Fairweather, M. E. Thompson, Jr I. M. Keane, T. E. Penson, D. TI A COMPARISON OF PHYSICIAN AND PATIENT DECISION MAKING FOR FIRST VERSUS SECOND OPINIONS AMONG MEN WITH LOCAL STAGE PROSTATE CANCER SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Ramsey, S.; Fedorenko, C. R.; Moinpour, C. M.; Fairweather, M. E.] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. [Zeliadt, S. B.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Hall, I. J. H.; Smith, Lee J.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Ekwueme, D. U.] Ctr Dis Control & Prevent, Snellville, GA USA. [Thompson, Jr I. M.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Keane, T. E.] Med Univ S Carolina, Med Ctr, Charleston, SC 29425 USA. [Penson, D.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY PY 2010 VL 13 IS 3 BP A51 EP A51 DI 10.1016/S1098-3015(10)72233-6 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 589CJ UT WOS:000277121900250 ER PT J AU Taneja, C Oster, G Jing, Y Baker, RA Forbes, RA Papakostas, GI AF Taneja, C. Oster, G. Jing, Y. Baker, R. A. Forbes, R. A. Papakostas, G., I TI COST-EFFECTIVENESS OF ATYPICAL ANTIPSYCHOTICS AS ADJUNCTIVE THERAPY IN ADULT PATIENTS WITH MAJOR DEPRESSIVE DISORDER (MDD) SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Taneja, C.; Oster, G.] Policy Anal Inc, Brookline, MA USA. [Jing, Y.; Baker, R. A.] Bristol Myers Squibb Co, Plainsboro, NJ USA. [Forbes, R. A.] Otsuka Pharmaceut Dev & Commercializat, Princeton, NJ USA. [Papakostas, G., I] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY PY 2010 VL 13 IS 3 BP A113 EP A113 DI 10.1016/S1098-3015(10)72544-4 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 589CJ UT WOS:000277121900561 ER PT J AU Wu, EQ Bollu, V Guo, A Guerin, A Tsaneva, M Williams, D Griffin, JD AF Wu, E. Q. Bollu, V Guo, A. Guerin, A. Tsaneva, M. Williams, D. Griffin, J. D. TI COMPARISON OF HEALTH CARE RESOURCE UTILIZATION AND COSTS BETWEEN NILOTINIB AND DASATINIB AS SECOND LINE THERAPIES IN CHRONIC MYELOID LEUKEMIA (CML) SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Wu, E. Q.; Tsaneva, M.] Analysis Grp Inc, Boston, MA USA. [Bollu, V; Guo, A.; Williams, D.] Novartis Pharmaceut, E Hanover, NJ USA. [Guerin, A.] Analysis Grp Ltee, Montreal, PQ, Canada. [Griffin, J. D.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY PY 2010 VL 13 IS 3 BP A32 EP A32 DI 10.1016/S1098-3015(10)72136-7 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 589CJ UT WOS:000277121900153 ER PT J AU Yeh, YC Clapp, MD Churchill, WW O'Day, J Reddy, P AF Yeh, Y. C. Clapp, M. D. Churchill, W. W. O'Day, J. Reddy, P. TI ADHERENCE TO A GUIDELINE FOR ERYTHROPOIESIS STIMULATING AGENTS IN CHRONIC KIDNEY DISEASE SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Yeh, Y. C.; Reddy, P.] Partners Healthcare, Needham, MA USA. [Clapp, M. D.] Massachusetts Gen Hosp, Boston, MA USA. [Churchill, W. W.] Brigham & Womens Hosp, Boston, MA 02115 USA. [O'Day, J.] Faulkner Hosp, Jamaica Plain, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY PY 2010 VL 13 IS 3 BP A80 EP A80 DI 10.1016/S1098-3015(10)72378-0 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 589CJ UT WOS:000277121900395 ER PT J AU Pukkila-Worley, R Mylonakis, E AF Pukkila-Worley, Read Mylonakis, Eleftherios TI From the outside in and the inside out Antifungal immune responses in Caenorhabditis elegans SO VIRULENCE LA English DT Editorial Material ID INNATE IMMUNITY; C. ELEGANS; PROTEIN; CONIOSPORA; INFECTION; ADHESION C1 [Pukkila-Worley, Read] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Pukkila-Worley, R (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM rpukkilaworley@partners.org FU NIAID NIH HHS [T32 AI007061, K08 AI081747, AI075286] NR 16 TC 11 Z9 19 U1 0 U2 3 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2150-5594 J9 VIRULENCE JI Virulence PD MAY-JUN PY 2010 VL 1 IS 3 BP 111 EP 112 DI 10.4161/viru.1.3.11746 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 788UF UT WOS:000292469200001 PM 21178428 ER PT J AU Arnold, J Janoska, M Kajon, AE Metzgar, D Hudson, NR Torres, S Harrach, B Seto, D Chodosh, J Jones, MS AF Arnold, John Janoska, Mate Kajon, Adriana E. Metzgar, David Hudson, Nolan Ryan Torres, Sarah Harrach, Balazs Seto, Donald Chodosh, James Jones, Morris S. TI Genomic characterization of human adenovirus 36, a putative obesity agent SO VIRUS RESEARCH LA English DT Article DE Human adenovirus; Bioinformatics; Genomics ID EPIDEMIC KERATOCONJUNCTIVITIS; PROTEIN; INTERNALIZATION; ADIPOSITY; GENE; DIFFERENTIATION; OVERWEIGHT; CHICKEN; BINDING; WEIGHT AB Increased levels of serum antibody titers against human adenovirus 36 (HAdV-D36) are associated with human obesity and experimental obesity in laboratory animals. While HAdV-D36 has been studied as an infectious agent implicated in obesity for over a decade, the complete genome sequence and its analysis have yet to be reported. A detailed analysis of the genome sequence of HAdV-D36 may be important to understand its role in obesity. Genomic and bioinformatic comparisons with other HAdVs identified differences that suggested unique functions. Global pairwise genome alignment with all sequenced human adenovirus D (HAdV-D) genomes revealed areas of nonconserved sequences in the hexon, E3 CR1 beta, E3 CR1 gamma, and fiber genes. Phylogenetic analysis of all HAdV-D36 proteins confirmed that this virus belongs to species Human adenovirus D. This genomic analysis of HAdV-D36 provides an important tool for comprehending the role that this unique adenovirus may play in human obesity. Low amino acid sequence identity in the E3 CR1 beta and CR1 gamma genes may suggest distinctive roles for these proteins. Furthermore, the predicted molecular models of the HAdV-D36 fiber protein seem to implicate a unique tissue tropism for HAdV-D36. Published by Elsevier B.V. C1 [Jones, Morris S.] David Grant USAF Med Ctr, Clin Invest Facil, Travis, CA USA. [Arnold, John] USN, San Diego Med Ctr, Dept Pediat, Div Infect Dis, San Diego, CA 92152 USA. [Janoska, Mate; Harrach, Balazs] Hungarian Acad Sci, Vet Med Res Inst, H-1581 Budapest, Hungary. [Kajon, Adriana E.] Lovelace Resp Res Inst, Albuquerque, NM USA. [Metzgar, David] USN, Hlth Res Ctr, Dept Resp Dis Res, San Diego, CA 92152 USA. [Hudson, Nolan Ryan; Torres, Sarah; Seto, Donald] George Mason Univ, Dept Bioinformat & Computat Biol, Manassas, VA USA. [Chodosh, James] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Howe Lab, Boston, MA USA. RP Jones, MS (reprint author), David Grant USAF Med Ctr, Clin Invest Facil, Travis, CA USA. EM drmorrisj@yahoo.com RI Harrach, Balazs/A-3680-2008; Valle, Ruben/A-7512-2013 OI Harrach, Balazs/0000-0002-1410-6469; FU Hungarian Research Fund [K72484]; U.S. Public Health Service NIH [EY013124, P30EY013104]; Massachusetts Lions Eye Research Fund, Inc.; Research to Prevent Blindness, Inc FX BH was supported by Hungarian Research Fund grant K72484. JC was supported in part by U.S. Public Health Service NIH grants EY013124 and P30EY013104, Massachusetts Lions Eye Research Fund, Inc., and an unrestricted grant to the Department of Ophthalmology, Harvard Medical School from Research to Prevent Blindness, Inc. NR 43 TC 20 Z9 22 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1702 J9 VIRUS RES JI Virus Res. PD MAY PY 2010 VL 149 IS 2 BP 152 EP 161 DI 10.1016/j.virusres.2010.01.011 PG 10 WC Virology SC Virology GA 587BU UT WOS:000276962700003 PM 20109503 ER PT J AU Targett-Adams, P Boulant, S Douglas, MW McLauchlan, J AF Targett-Adams, Paul Boulant, Steeve Douglas, Mark W. McLauchlan, John TI Lipid Metabolism and HCV Infection SO VIRUSES-BASEL LA English DT Review DE hepatitis C virus; HCV; lipid metabolism; lipid droplets; fatty acid biosynthesis; cholesterol biosynthesis; VLDL assembly; RNA replication; virus assembly ID HEPATITIS-C-VIRUS; NONSTRUCTURAL PROTEIN 5A; LOW-DENSITY-LIPOPROTEIN; B TYPE-I; TRIGLYCERIDE TRANSFER PROTEIN; VIRAL-RNA REPLICATION; SIGNAL PEPTIDE PEPTIDASE; SCAVENGER RECEPTOR BI; FATTY-ACID SYNTHASE; DOUBLE-STRANDED-RNA AB Chronic infection by hepatitis C virus (HCV) can lead to severe liver disease and is a global healthcare problem. The liver is highly metabolically active and one of its key functions is to control the balance of lipid throughout the body. A number of pathologies have been linked to the impact of HCV infection on liver metabolism. However, there is also growing evidence that hepatic metabolic processes contribute to the HCV life cycle. This review summarizes the relationship between lipid metabolism and key stages in the production of infectious HCV. C1 [McLauchlan, John] MRC, Virol Unit, Glasgow G11 5JR, Lanark, Scotland. [Targett-Adams, Paul] Pfizer Global Res & Dev, Infect Dis Grp, Sandwich Labs, Sandwich CT13 9NJ, Kent, England. [Boulant, Steeve] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Immune Dis Inst, Boston, MA 02115 USA. [Douglas, Mark W.] Univ Sydney, Westmead Hosp, Westmead Millennium Inst, Storr Liver Unit, Westmead, NSW 2145, Australia. RP McLauchlan, J (reprint author), MRC, Virol Unit, Church St, Glasgow G11 5JR, Lanark, Scotland. EM Paul.Targett-Adams@pfizer.com; Steeve_Boulant@hms.harvard.edu; mark.douglas@usyd.edu.au; j.mclauchlan@mrcvu.gla.ac.uk FU UK Medical Research Council; Marie Curie Intra-European Fellowship [025198]; Australian NHMRC [358772]; European Union [HEALTH-F4-2008-202272] FX The authors' experimental work was supported by the UK Medical Research Council, a Marie Curie Intra-European Fellowship to S.B. (contract number 025198), a CJ Martin Fellowship awarded by the Australian NHMRC (Grant ID 358772) to M.W.D and funds provided by the European Union Project LipidomicNet (HEALTH-F4-2008-202272) to J.M. NR 143 TC 20 Z9 20 U1 3 U2 12 PU MDPI AG PI BASEL PA KANDERERSTRASSE 25, CH-4057 BASEL, SWITZERLAND SN 1999-4915 J9 VIRUSES-BASEL JI Viruses-Basel PD MAY PY 2010 VL 2 IS 5 BP 1195 EP 1217 DI 10.3390/v2051195 PG 23 WC Virology SC Virology GA 632HQ UT WOS:000280413700010 PM 21994676 ER PT J AU Haun, JB Yoon, TJ Lee, H Weissleder, R AF Haun, Jered B. Yoon, Tae-Jong Lee, Hakho Weissleder, Ralph TI Magnetic nanoparticle biosensors SO WILEY INTERDISCIPLINARY REVIEWS-NANOMEDICINE AND NANOBIOTECHNOLOGY LA English DT Review ID IRON-OXIDE NANOPARTICLES; CIRCULATING TUMOR-CELLS; SPIN-VALVE SENSORS; ULTRASENSITIVE DETECTION; MOLECULAR-INTERACTIONS; CANCER-CELLS; RELAXATION; NANOSENSORS; ASSAYS; MAGNETORESISTANCE AB One of the major challenges in medicine is the rapid and accurate measurement of protein biomarkers, cells, and pathogens in biological samples. A number of new diagnostic platforms have recently been developed to measure biomolecules and cells with high sensitivity that could enable early disease detection or provide valuable insights into biology at the systems level. Most biological samples exhibit negligible magnetic susceptibility; therefore, magnetic nanoparticles have been used for diverse applications including biosensing, magnetic separation, and thermal ablation therapy. This review focuses on the use of magnetic nanoparticles for detection of biomolecules and cells based on magnetic resonance effects using a general detection platform termed diagnostic magnetic resonance (DMR). DMR technology encompasses numerous assay configurations and sensing principles, and to date magnetic nanoparticle biosensors have been designed to detect a wide range of targets including DNA/mRNA, proteins, enzymes, drugs, pathogens, and tumor cells. The core principle behind DMR is the use of magnetic nanoparticles as proximity sensors that modulate the spin-spin relaxation time of neighboring water molecules, which can be quantified using clinical MRI scanners or benchtop nuclear magnetic resonance (NMR) relaxometers. Recently, the capabilities of DMR technology were advanced considerably with the development of miniaturized, chip-based NMR (mu NMR) detector systems that are capable of performing highly sensitive measurements on microliter sample volumes and in multiplexed format. With these and future advances in mind, DMR biosensor technology holds considerable promise to provide a high-throughput, low-cost, and portable platform for large scale molecular and cellular screening in clinical and point-of-care settings. (C) 2010 John Wiley & Sons, Inc. WIREs Nanomed Nanobiotechnol 2010 2 291-304 C1 [Haun, Jered B.; Yoon, Tae-Jong; Lee, Hakho; Weissleder, Ralph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. RP Weissleder, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu FU National Institutes of Health [U01-HL080731, U54-CA119349, R01-EB004626] FX The authors acknowledge funding support from the National Institutes of Health (U01-HL080731, U54-CA119349 and R01-EB004626). NR 64 TC 186 Z9 187 U1 22 U2 269 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1939-5116 J9 WIRES NANOMED NANOBI JI Wiley Interdiscip. Rev.-Nanomed. Nanobiotechnol. PD MAY-JUN PY 2010 VL 2 IS 3 BP 291 EP 304 DI 10.1002/wnan.84 PG 14 WC Nanoscience & Nanotechnology; Medicine, Research & Experimental SC Science & Technology - Other Topics; Research & Experimental Medicine GA 590JN UT WOS:000277221800007 PM 20336708 ER PT J AU Geraldes, P King, GL AF Geraldes, Pedro King, George L. TI Activation of Protein Kinase C Isoforms and Its Impact on Diabetic Complications SO CIRCULATION RESEARCH LA English DT Review DE protein kinase C; vascular cell biology; diabetes; cardiovascular diseases ID ENDOTHELIAL GROWTH-FACTOR; PKC-BETA INHIBITOR; FOAM CELL-FORMATION; RETINAL BLOOD-FLOW; HIGH-GLUCOSE; INSULIN-RESISTANCE; OXIDATIVE STRESS; MESANGIAL CELLS; ELEVATED GLUCOSE; CARDIAC-FUNCTION AB Both cardio-and microvascular complications adversely affect the life quality of patients with diabetes and have been the leading cause of mortality and morbidity in this population. Cardiovascular pathologies of diabetes have an effect on microvenules, arteries, and myocardium. It is believed that hyperglycemia is one of the most important metabolic factors in the development of both micro-and macrovascular complications in diabetic patients. Several prominent hypotheses exist to explain the adverse effect of hyperglycemia. One of them is the chronic activation by hyperglycemia of protein kinase (PK)C, a family of enzymes that are involved in controlling the function of other proteins. PKC has been associated with vascular alterations such as increases in permeability, contractility, extracellular matrix synthesis, cell growth and apoptosis, angiogenesis, leukocyte adhesion, and cytokine activation and inhibition. These perturbations in vascular cell homeostasis caused by different PKC isoforms (PKC-alpha, -beta 1/2, and PKC-delta) are linked to the development of pathologies affecting large vessel (atherosclerosis, cardiomyopathy) and small vessel (retinopathy, nephropathy and neuropathy) complications. Clinical trials using a PKC-beta isoform inhibitor have been conducted, with some positive results for diabetic nonproliferative retinopathy, nephropathy, and endothelial dysfunction. This article reviews present understanding of how PKC isoforms cause vascular dysfunctions and pathologies in diabetes. (Circ Res. 2010; 106: 1319-1331.) C1 [Geraldes, Pedro; King, George L.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Dianne Nunnally Hoppes Lab Diabet Complicat, Boston, MA 02115 USA. [King, George L.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP King, GL (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Dianne Nunnally Hoppes Lab Diabet Complicat, 1 Joslin Pl, Boston, MA 02115 USA. EM george.king@joslin.harvard.edu FU American Diabetes Association [1-08-RA-93]; NIH [R01 EY016150, R01 DK071359]; Diabetes Endocrinology Research Centers [5 P30 DK36836-23]; Juvenile Diabetes Research Foundation [1-2008-330, 8-2008363, 25-2008-383] FX G.K. is supported by American Diabetes Association grant 1-08-RA-93; NIH grants R01 EY016150 and R01 DK071359; Diabetes Endocrinology Research Centers grant 5 P30 DK36836-23; and Juvenile Diabetes Research Foundation grants 1-2008-330, 8-2008363, and 25-2008-383. NR 145 TC 260 Z9 281 U1 8 U2 42 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD APR 30 PY 2010 VL 106 IS 8 BP 1319 EP 1331 DI 10.1161/CIRCRESAHA.110.217117 PG 13 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 589PR UT WOS:000277165100002 PM 20431074 ER PT J AU Chopra, SS Stroud, DM Watanabe, H Bennett, JS Burns, CG Wells, KS Yang, T Zhong, TP Roden, DM AF Chopra, Sameer S. Stroud, Dina Myers Watanabe, Hiroshi Bennett, Jeffrey S. Burns, C. Geoffrey Wells, K. Sam Yang, Tao Zhong, Tao P. Roden, Dan M. TI Voltage-Gated Sodium Channels Are Required for Heart Development in Zebrafish SO CIRCULATION RESEARCH LA English DT Article DE ion channels; heart development; zebrafish; scn5La ID TRANSCRIPTION FACTOR; MOUSE HEART; GROWTH; DIFFERENTIATION; GATA5; PHARMACOLOGY; EVOLUTION; SUBUNIT; CELLS AB Rationale: Voltage-gated sodium channels initiate action potentials in excitable tissues. Mice in which Scn5A (the predominant sodium channel gene in heart) has been knocked out die early in development with cardiac malformations by mechanisms which have yet to be determined. Objective: Here we addressed this question by investigating the role of cardiac sodium channels in zebrafish heart development. Methods and Results: Transcripts of the functionally-conserved Scn5a homologs scn5Laa and scn5Lab were detected in the gastrulating zebrafish embryo and subsequently in the embryonic myocardium. Antisense knockdown of either channel resulted in marked cardiac chamber dysmorphogenesis and perturbed looping. These abnormalities were associated with decreased expression of the myocardial precursor genes nkx2.5, gata4, and hand2 in anterior lateral mesoderm and significant deficits in the production of cardiomyocyte progenitors. These early defects did not appear to result from altered membrane electrophysiology, as prolonged pharmacological blockade of sodium current failed to phenocopy channel knockdown. Moreover, embryos grown in calcium channel blocker-containing medium had hearts that did not beat but developed normally. Conclusions: These findings identify a novel and possibly nonelectrogenic role for cardiac sodium channels in heart development. (Circ Res. 2010; 106: 1342-1350.) C1 [Stroud, Dina Myers; Zhong, Tao P.; Roden, Dan M.] Vanderbilt Univ, Dept Med, Sch Med, Nashville, TN 37232 USA. [Chopra, Sameer S.; Watanabe, Hiroshi; Yang, Tao; Zhong, Tao P.; Roden, Dan M.] Vanderbilt Univ, Sch Med, Dept Pharmacol, Nashville, TN 37212 USA. [Wells, K. Sam] Vanderbilt Univ, Sch Med, Dept Physiol & Biophys, Nashville, TN 37212 USA. [Zhong, Tao P.] Vanderbilt Univ, Sch Med, Dept Cell & Dev Biol, Nashville, TN 37212 USA. [Bennett, Jeffrey S.] Vanderbilt Univ, Sch Med, Ctr Human Genet Res, Nashville, TN 37212 USA. [Burns, C. Geoffrey] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Roden, DM (reprint author), Vanderbilt Univ, Dept Med, Sch Med, 2215B Garland Ave,1275 MRBIV Light Hall, Nashville, TN 37232 USA. EM tao.zhong@vanderbilt.edu; dan.roden@vanderbilt.edu FU National Institute of General Medical Studies for the Vanderbilt Medical-Scientist Training Program [T32 GM07347]; Vanderbilt University Functional Genomics Initiative; NIH [HL49989] FX This work was supported by Public Health Service award T32 GM07347 from the National Institute of General Medical Studies for the Vanderbilt Medical-Scientist Training Program, funding from the Vanderbilt University Functional Genomics Initiative, and NIH grant HL49989. NR 38 TC 36 Z9 38 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD APR 30 PY 2010 VL 106 IS 8 BP 1342 EP U93 DI 10.1161/CIRCRESAHA.109.213132 PG 34 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 589PR UT WOS:000277165100004 PM 20339120 ER PT J AU Carrera, S de Verdier, PJ Khan, Z Zhao, B Mahale, A Bowman, KJ Zainol, M Jones, GDD Lee, SW Aaronson, SA Macip, S AF Carrera, Samantha de Verdier, Petra J. Khan, Zahid Zhao, Bo Mahale, Alka Bowman, Karen J. Zainol, Muri Jones, George D. D. Lee, Sam W. Aaronson, Stuart A. Macip, Salvador TI Protection of Cells in Physiological Oxygen Tensions against DNA Damage-induced Apoptosis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HYPOXIA-INDUCED APOPTOSIS; REPLICATIVE LIFE-SPAN; TUMOR-SUPPRESSOR P53; ACTIVATION; FIBROBLASTS; PROTEIN; STRESS; EXPRESSION; CARCINOMA; RADIATION AB Oxygen availability has important effects on cell physiology. Although hyperoxic and hypoxic stresses have been well characterized, little is known about cellular functions in the oxygen levels commonly found in vivo. Here, we show that p53-dependent apoptosis in response to different DNA-damaging agents was reduced when normal and cancer cells were cultured at physiological oxygen tensions instead of the usual atmospheric levels. Different from what has been described in hypoxia, this was neither determined by decreases in p53 induction or its transactivation activity, nor by differences in the intracellular accumulation of reactive oxygen species. At these physiological oxygen levels, we found a constitutive activation of the ERK1/2 MAPK in all the models studied. Inhibition of this signaling pathway reversed the protective effect in some but not all cell lines. We conclude that a stress-independent constitutive activation of prosurvival pathways, including but probably not limited to MAPK, can protect cells in physiological oxygen tensions against genotoxic stress. Our results underscore the need of considering the impact of oxygen levels present in the tissue microenvironment when studying cell sensitivity to treatments such as chemotherapy and radiotherapy. C1 [Carrera, Samantha; Macip, Salvador] Univ Leicester, Dept Biochem, Leicester LE1 9HN, Leics, England. [de Verdier, Petra J.] Karolinska Inst, Dept Mol Med & Surg, Urol Lab, S-17176 Stockholm, Sweden. [Khan, Zahid; Zhao, Bo; Mahale, Alka; Aaronson, Stuart A.] Mt Sinai Sch Med, Dept Oncol Sci, New York, NY 10029 USA. [Bowman, Karen J.; Zainol, Muri; Jones, George D. D.] Univ Leicester, Radiat & Oxidat Stress Grp, Dept Canc Studies & Mol Med, Leicester LE1 7RH, Leics, England. [Lee, Sam W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harvard Cutaneous Biol Res Ctr, Boston, MA 02129 USA. RP Macip, S (reprint author), Univ Leicester, Dept Biochem, Lancaster Rd, Leicester LE1 9HN, Leics, England. EM sm460@le.ac.uk RI Macip, Salvador/K-5985-2014 FU National Institutes of Health [CA80058, CA85214, CA78356, CA82211]; Medical Research Council FX This work supported, in whole or in part, by National Institutes of Health Grants CA80058 and CA85214 (to S. A. A.) and CA78356 and CA82211 (to S. W. L.). This work was also supported by the Medical Research Council (New Blood Lectureship Research support funding). NR 34 TC 13 Z9 14 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 30 PY 2010 VL 285 IS 18 BP 13658 EP 13665 DI 10.1074/jbc.M109.062562 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 587JL UT WOS:000276987700040 PM 20228054 ER PT J AU Gohil, VM Nilsson, R Belcher-Timme, CA Luo, B Root, DE Mootha, VK AF Gohil, Vishal M. Nilsson, Roland Belcher-Timme, Casey A. Luo, Biao Root, David E. Mootha, Vamsi K. TI Mitochondrial and Nuclear Genomic Responses to Loss of LRPPRC Expression SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PENTATRICOPEPTIDE REPEAT PROTEINS; CYCLOOXYGENASE-2 EXPRESSION; INTEGRATIVE GENOMICS; OXIDASE DEFICIENCY; GENE-EXPRESSION; COMPLEX; DYSFUNCTION; LRP130; CELL; RNA AB Rapid advances in genotyping and sequencing technology have dramatically accelerated the discovery of genes underlying human disease. Elucidating the function of such genes and understanding their role in pathogenesis, however, remain challenging. Here, we introduce a genomic strategy to characterize such genes functionally, and we apply it to LRPPRC, a poorly studied gene that is mutated in Leigh syndrome, French-Canadian type (LSFC). We utilize RNA interference to engineer an allelic series of cellular models in which LRPPRC has been stably silenced to different levels of knockdown efficiency. We then combine genome-wide expression profiling with gene set enrichment analysis to identify cellular responses that correlate with the loss of LRPPRC. Using this strategy, we discovered a specific role for LRPPRC in the expression of all mitochondrial DNA-encoded mRNAs, but not the rRNAs, providing mechanistic insights into the enzymatic defects observed in the disease. Our analysis shows that nuclear genes encoding mitochondrial proteins are not collectively affected by the loss of LRPPRC. We do observe altered expression of genes related to hexose metabolism, prostaglandin synthesis, and glycosphingolipid biology that may either play an adaptive role in cell survival or contribute to pathogenesis. The combination of genetic perturbation, genomic profiling, and pathway analysis represents a generic strategy for understanding disease pathogenesis. C1 [Gohil, Vishal M.; Nilsson, Roland; Belcher-Timme, Casey A.; Mootha, Vamsi K.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Gohil, Vishal M.; Nilsson, Roland; Belcher-Timme, Casey A.; Luo, Biao; Root, David E.; Mootha, Vamsi K.] Broad Inst Massachusetts Inst Technol & Harvard, Cambridge, MA 02142 USA. [Gohil, Vishal M.; Nilsson, Roland; Belcher-Timme, Casey A.; Mootha, Vamsi K.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02446 USA. RP Mootha, VK (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St,CPZN 5-806, Boston, MA 02114 USA. EM vamsi@hms.harvard.edu FU National Institutes of Health [R01DK081457]; United Mitochondrial Disease Foundation; Broad Institute Scientific Planning and Allocation of Resources Committee; American Diabetes Association FX This work was supported, in whole or in part, by National Institutes of Health Grant R01DK081457 (to V. K. M.). This work was also supported by grants from the United Mitochondrial Disease Foundation (to V. M. G.), the Broad Institute Scientific Planning and Allocation of Resources Committee, and the American Diabetes Association. NR 25 TC 45 Z9 46 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 30 PY 2010 VL 285 IS 18 BP 13742 EP 13747 DI 10.1074/jbc.M109.098400 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 587JL UT WOS:000276987700049 PM 20220140 ER PT J AU Nguyen, HM Rocha, MA Chintalacharuvu, KR Beenhouwer, DO AF Nguyen, Hien M. Rocha, Miguel A. Chintalacharuvu, Koteswara R. Beenhouwer, David O. TI Detection and quantification of Panton-Valentine leukocidin in Staphylococcus aureus cultures by ELISA and Western blotting: Diethylpyrocarbonate inhibits binding of protein A to IgG SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE Staphylococcus aureus; Protein A; Panton-Valentine leukocidin; Diethylpyrocarbonate; ELISA; Western Blot ID ENTEROTOXIN-B; IMMUNOGLOBULIN; FC AB Enzyme-linked immunosorbent assay (ELISA) and Western blotting are common techniques used to detect and quantify proteins in Staphylococcus aureus culture supernatants, such as Panton-Valentine leukocidin (PVL). However, protein A (Spa) secreted by most S. aureus strains may interfere with these assays by binding to the capturing and detecting antibodies. Here, we have shown that the addition of diethylpyrocarbonate (DEPC) inhibits the binding of Spa to rabbit anti-PVL used as the capturing antibody in ELISA. In Western blotting, the presence of DEPC prevented the binding of detecting antibody to Spa. These modified ELISA and Western blot techniques should prove useful for detecting and quantifying proteins in S. aureus culture supernatants. (C) 2010 Elsevier B.V. All rights reserved. C1 [Nguyen, Hien M.; Rocha, Miguel A.; Chintalacharuvu, Koteswara R.; Beenhouwer, David O.] Vet Affairs Greater Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA USA. [Beenhouwer, David O.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. RP Beenhouwer, DO (reprint author), VA Greater Los Angeles, Div Infect Dis 111F, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM dbeenhou@ucla.edu FU National Institutes of Health [AI071025] FX This work was supported by National Institutes of Health grant AI071025 to DOB. NR 17 TC 11 Z9 11 U1 2 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD APR 30 PY 2010 VL 356 IS 1-2 BP 1 EP 5 DI 10.1016/j.jim.2010.03.005 PG 5 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 599OY UT WOS:000277924200001 PM 20303971 ER PT J AU Huang, XM Auinger, P Eberly, S Oakes, D Schwarzschild, M Ascherio, A Mailman, R Chen, HL AF Huang, Xuemei Auinger, Peggy Eberly, Shirley Oakes, David Schwarzschild, Michael Ascherio, Alberto Mailman, Richard Chen, Honglei CA Parkinson Study Grp DATATOP Invest TI Serum Cholesterol as a Predictor of the Rate of Clinical Decline in Parkinson Disease: Results from DATATOP. SO MOVEMENT DISORDERS LA English DT Meeting Abstract CT 24th Annual Symposium on Etiology, Pathogenesis and Treatment of Parkinson's Disease and Other Movement Disorders CY MAY 15, 2010 CL Irving, TX C1 [Huang, Xuemei; Mailman, Richard] Penn State Univ, Milton S Hershey Med Ctr, Dept Neurol, Hershey, PA 17033 USA. [Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Neurosurg, Hershey, PA 17033 USA. [Huang, Xuemei; Mailman, Richard] Penn State Univ, Milton S Hershey Med Ctr, Dept Pharmacol, Hershey, PA 17033 USA. [Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Radiol, Hershey, PA 17033 USA. [Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Kinesiol, Hershey, PA 17033 USA. [Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Bioengn, Hershey, PA 17033 USA. [Auinger, Peggy] Univ Rochester, Sch Med & Dent, Ctr Human Expt Therapeut, Rochester, NY USA. [Eberly, Shirley; Oakes, David] Univ Rochester, Dept Biostat, Rochester, NY USA. [Schwarzschild, Michael] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Sch Med, Dept Nutr, Boston, MA 02115 USA. [Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Sch Med, Dept Epidemiol, Boston, MA 02115 USA. [Chen, Honglei] Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD APR 30 PY 2010 VL 25 IS 6 BP II EP II PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 591OS UT WOS:000277311500035 ER PT J AU Leverenz, JB Kim, HM Samii, A Gerton, B Baca, M Pate, J Martinez, E Thomas, S Tsuang, DW Zabetian, CP AF Leverenz, J. B. Kim, H. M. Samii, A. Gerton, B. Baca, M. Pate, J. Martinez, E. Thomas, S. Tsuang, D. W. Zabetian, C. P. TI The Washington State Parkinson Disease Registry. SO MOVEMENT DISORDERS LA English DT Meeting Abstract CT 24th Annual Symposium on Etiology, Pathogenesis and Treatment of Parkinson's Disease and Other Movement Disorders CY MAY 15, 2010 CL Irving, TX C1 [Leverenz, J. B.; Kim, H. M.; Samii, A.; Gerton, B.; Baca, M.; Pate, J.; Martinez, E.; Thomas, S.; Tsuang, D. W.; Zabetian, C. P.] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Leverenz, J. B.; Samii, A.; Zabetian, C. P.] Univ Washington, Parkinson Dis Res Ctr, Seattle, WA 98195 USA. [Leverenz, J. B.; Samii, A.; Zabetian, C. P.] Univ Washington, Educ Ctr, Seattle, WA 98195 USA. [Leverenz, J. B.; Samii, A.; Zabetian, C. P.] Univ Washington, Ctr Clin, Seattle, WA 98195 USA. [Leverenz, J. B.; Kim, H. M.; Samii, A.; Gerton, B.; Zabetian, C. P.] Univ Washington, Dept Neurol & Psychiat, Seattle, WA 98195 USA. [Leverenz, J. B.; Tsuang, D. W.] Univ Washington, Dept Behav Sci, Seattle, WA 98195 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD APR 30 PY 2010 VL 25 IS 6 BP VI EP VI PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 591OS UT WOS:000277311500046 ER PT J AU Freudenreich, O Brockman, MA Henderson, DC Evins, AE Fan, XD Walsh, JP Goff, DC AF Freudenreich, Oliver Brockman, Mark A. Henderson, David C. Evins, A. Eden Fan, Xiaoduo Walsh, Jared P. Goff, Donald C. TI Analysis of peripheral immune activation in schizophrenia using quantitative reverse-transcription polymerase chain reaction (RT-PCR) SO PSYCHIATRY RESEARCH LA English DT Article; Proceedings Paper CT 11th International Congress on Schizophrenia Research/8th Biennial Mt Sinai Conference on Cognition in Schizophrenia CY MAR 27-APR 01, 2007 CL Colorado Springs, CO DE Schizophrenia; Immune function; Gene expression; Cytokine; Interferon gamma; Tumor necrosis factor; Interleukin-10 ID INTERFERON-GAMMA; GENE-EXPRESSION; RISPERIDONE; CYTOKINES; TH1; INTERLEUKIN-10; HALOPERIDOL; ANTIBODIES; RECEPTOR; BRAIN AB Immune system abnormalities in schizophrenia include a shift from a Type 1 (cellular) to a Type 2 (humoral) immune response. To characterize the activation status of the immune system in schizophrenia, we examined the pattern of gene expression in peripheral blood cells for three Th1 cytokines (interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2)), and one Th2 cytokine (interleukin-10 (IL-10)). In a cross-sectional study, we used quantitative reverse-transcription polymerase chain reaction (RT-PCR) to compare the mRNA levels of IFN-gamma, TNF-alpha. IL-2, and IL-10 in peripheral blood mononuclear cells (PBMCs) between 15 schizophrenia patients and 15 matched healthy controls. Expression of IFN-gamma and TNF-alpha was significantly reduced in patients with schizophrenia compared with normal controls. No differences in IL-2 and IL-10 gene expression were observed. These results are consistent with impaired Type 1 cellular immunity in schizophrenia. While the data illustrate the potential utility of mRNA-based approaches for the identification and analysis of immune biomarkers for neuropsychiatric disorders, correlation of gene expression with direct measures of cytokine concentrations is required. (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Freudenreich, Oliver; Henderson, David C.; Evins, A. Eden; Fan, Xiaoduo; Walsh, Jared P.; Goff, Donald C.] Massachusetts Gen Hosp, Schizophrenia Program, Boston, MA 02114 USA. [Brockman, Mark A.] Partners AIDS Res Ctr, Boston, MA USA. [Freudenreich, Oliver; Brockman, Mark A.; Henderson, David C.; Evins, A. Eden; Fan, Xiaoduo; Walsh, Jared P.; Goff, Donald C.] Harvard Univ, Sch Med, Boston, MA USA. RP Freudenreich, O (reprint author), Freedom Trail Clin, MGH Schizophrenia Program, 25 Staniford St,2nd Floor, Boston, MA 02114 USA. EM ofreudenreich@partners.org OI Brockman, Mark/0000-0001-6432-1426 FU NIMH NIH HHS [K24 MH002025, K24 MH002025-06] NR 28 TC 20 Z9 21 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD APR 30 PY 2010 VL 176 IS 2-3 BP 99 EP 102 DI 10.1016/j.psychres.2008.11.007 PG 4 WC Psychiatry SC Psychiatry GA 585MP UT WOS:000276830000001 PM 20132993 ER PT J AU Townsend, J Bookheimer, SY Foland-Ross, LC Sugar, CA Altshuler, LL AF Townsend, Jennifer Bookheimer, Susan Y. Foland-Ross, Lara C. Sugar, Catherine A. Altshuler, Lori L. TI fMRI abnormalities in dorsolateral prefrontal cortex during a working memory task in manic, euthymic and depressed bipolar subjects SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE Bipolar disorder; Dorsolateral prefrontal cortex; Parietal cortex; Mania; Depression; Euthymia; Working memory ID MOOD-REGULATING CIRCUIT; COGNITIVE IMPAIRMENT; FUNCTIONAL-MRI; AFFECTIVE-DISORDERS; INCREASED AMYGDALA; BRAIN IMAGES; SCHIZOPHRENIA; ACTIVATION; DYSFUNCTION; ROBUST AB Neuropsychological studies of subjects with bipolar disorder suggest impairment of working memory not only in acute mood states, but also while subjects are euthymic. Using fMRI to probe working memory regions in bipolar subjects in different mood states, we sought to determine the functional neural basis for these impairments. Typical working memory areas in normal populations include dorsolateral prefrontal cortex (BA9/46) and the posterior parietal cortex (BA40). We evaluated the activation in these regions using an n-back task in 42 bipolar subjects (13 manic, 15 euthymic and 14 depressed subjects) and 14 control subjects. While both control and bipolar subjects performed similarly on the task, bipolar subjects in all three mood states showed a significant reduction in activation in right BA9/46 and right BA40. Patients with bipolar disorder exhibit significantly attenuated neural activation in working memory circuits, independent of mood state. The reduction of neural activation may suggest a trait-related deficit. Subjects with bipolar disorder activated other additional frontal and temporal regions, perhaps as a compensatory mechanism, but this remains to be further explored. (C) 2010 Elsevier Ireland Ltd. All rights reserved. C1 [Townsend, Jennifer; Bookheimer, Susan Y.; Altshuler, Lori L.] Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Foland-Ross, Lara C.] Univ Calif Los Angeles, Sch Med, Dept Neurol, Lab NeuroImaging, Los Angeles, CA 90024 USA. [Sugar, Catherine A.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90024 USA. [Sugar, Catherine A.] Univ Calif Los Angeles, Jane & Terry Semel Inst Neurosci & Human Behav, Los Angeles, CA USA. [Altshuler, Lori L.] W Los Angeles Healthcare Ctr, Dept Psychiat, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Altshuler, LL (reprint author), 300 UCLA Med Plaza,Suite 1544,Box 957057, Los Angeles, CA 90095 USA. EM laltshuler@mednet.ucla.edu FU Stanley Medical Research Institute; NARSAD (National Association for Research on Schizophrenia and Affective Disorders); National Institute of Mental Health [K24 MH001848, R21 MH075944, 5F31MH078556]; Brain Mapping Medical Research Organization; Brain Mapping Support Foundation; Pierson-Lovelace Foundation; Ahmanson Foundation; William M. and Linda R. Dietel Philanthropic Fund at the Northern Piedmont Community Foundation; Tamkin Foundation; Jennifer Jones-Simon Foundation; Capital Group Companies Charitable Foundation; Northstar Fund; National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) [RR12169, RR13642, RR00865] FX The authors gratefully acknowledge The Stanley Medical Research Institute, NARSAD (National Association for Research on Schizophrenia and Affective Disorders), and the National Institute of Mental Health (K24 MH001848, R21 MH075944, 5F31MH078556) for their financial support of this study. For generous support the authors also wish to thank the Brain Mapping Medical Research Organization, Brain Mapping Support Foundation, Pierson-Lovelace Foundation, The Ahmanson Foundation, William M. and Linda R. Dietel Philanthropic Fund at the Northern Piedmont Community Foundation, Tamkin Foundation, Jennifer Jones-Simon Foundation, Capital Group Companies Charitable Foundation, Robson Family and Northstar Fund. The project described was supported by Grant Numbers RR12169, RR13642 and RR00865 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH); its contents are solely the responsibility of the authors and do not necessarily represent the official views of NCR or NIH. NR 70 TC 56 Z9 61 U1 1 U2 11 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD APR 30 PY 2010 VL 182 IS 1 BP 22 EP 29 DI 10.1016/j.pscychresns.2009.11.010 PG 8 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 594KJ UT WOS:000277536200004 PM 20227857 ER PT J AU Tulpule, A Lensch, MW Miller, JD Austin, K D'Andrea, A Schlaeger, TM Shimamura, A Daley, GQ AF Tulpule, Asmin Lensch, M. William Miller, Justine D. Austin, Karyn D'Andrea, Alan Schlaeger, Thorsten M. Shimamura, Akiko Daley, George Q. TI Knockdown of Fanconi anemia genes in human embryonic stem cells reveals early developmental defects in the hematopoietic lineage SO BLOOD LA English DT Article ID DNA-CROSS-LINKING; MONOUBIQUITINATED FANCD2; TARGETED DISRUPTION; GAMMA-INTERFERON; REGISTRY IFAR; HOX GENES; C CELLS; DIFFERENTIATION; PATHWAY; PROTEIN AB Fanconi anemia (FA) is a genetically heterogeneous, autosomal recessive disorder characterized by pediatric bone marrow failure and congenital anomalies. The effect of FA gene deficiency on hematopoietic development in utero remains poorly described as mouse models of FA do not develop hematopoietic failure and such studies cannot be performed on patients. We have created a human-specific in vitro system to study early hematopoietic development in FA using a lentiviral RNA interference (RNAi) strategy in human embryonic stem cells (hESCs). We show that knockdown of FANCA and FANCD2 in hESCs leads to a reduction in hematopoietic fates and progenitor numbers that can be rescued by FA gene complementation. Our data indicate that hematopoiesis is impaired in FA from the earliest stages of development, suggesting that deficiencies in embryonic hematopoiesis may underlie the progression to bone marrow failure in FA. This work illustrates how hESCs can provide unique insights into human development and further our understanding of genetic disease. (Blood. 2010; 115(17): 3453-3462) C1 [Daley, George Q.] Childrens Hosp, Div Pediat Hematol Oncol, Stem Cell Transplantat Program, Boston, MA 02115 USA. [Tulpule, Asmin; Lensch, M. William; Miller, Justine D.; Austin, Karyn; Schlaeger, Thorsten M.; Shimamura, Akiko; Daley, George Q.] Dana Farber Canc Inst, Boston, MA USA. [Tulpule, Asmin; Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Tulpule, Asmin; Lensch, M. William; Miller, Justine D.; Schlaeger, Thorsten M.; Daley, George Q.] Harvard Stem Cell Inst, Boston, MA USA. [Lensch, M. William; Daley, George Q.] Howard Hughes Med Inst, Boston, MA 02115 USA. [D'Andrea, Alan] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Shimamura, Akiko] Univ Washington, Childrens Hosp, Dept Pediat Hematol Oncol, Seattle, WA 98195 USA. [Shimamura, Akiko] Reg Med Ctr, Seattle, WA USA. [Daley, George Q.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. RP Daley, GQ (reprint author), Childrens Hosp, Div Pediat Hematol Oncol, Stem Cell Transplantat Program, Karp Bldg,7th Fl, Boston, MA 02115 USA. EM george.daley@childrens.harvard.edu FU National Institutes of Health; Burroughs Welcome Fund; Leukemia & Lymphoma Society; Howard Hughes Medical Institute; Harvard Stem Cell Institute FX This work was supported by the National Institutes of Health, National Institutes of Health Director's Pioneer Award, Burroughs Welcome Fund, Leukemia & Lymphoma Society, Howard Hughes Medical Institute, and the Harvard Stem Cell Institute. NR 50 TC 48 Z9 50 U1 1 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 29 PY 2010 VL 115 IS 17 BP 3453 EP 3462 DI 10.1182/blood-2009-10-246694 PG 10 WC Hematology SC Hematology GA 591WL UT WOS:000277335800010 PM 20089964 ER PT J AU Lane, SW Sykes, SM Al-Shahrour, F Shterental, S Paktinat, M Lo Celso, C Jesneck, JL Ebert, BL Williams, DA Gilliland, DG AF Lane, Steven W. Sykes, Stephen M. Al-Shahrour, Fatima Shterental, Sebastian Paktinat, Mahnaz Lo Celso, Cristina Jesneck, Jonathan L. Ebert, Benjamin L. Williams, David A. Gilliland, D. Gary TI The Apc(min) mouse has altered hematopoietic stem cell function and provides a model for MPD/MDS SO BLOOD LA English DT Article ID MULTIPLE INTESTINAL NEOPLASIA; ACUTE MYELOGENOUS LEUKEMIA; GENE-EXPRESSION; BETA-CATENIN; CD34(+) CELLS; LONG-TERM; MYELODYSPLASTIC SYNDROME; MYELOID DISORDERS; SELF-RENEWAL; IN-VIVO AB Apc, a negative regulator of the canonical Wnt signaling pathway, is a bona-fide tumor suppressor whose loss of function results in intestinal polyposis. APC is located in a commonly deleted region on human chromosome 5q, associated with myelodysplastic syndrome (MDS), suggesting that haploinsufficiency of APC contributes to the MDS phenotype. Analysis of the hematopoietic system of mice with the Apc(min) allele that results in a premature stop codon and loss of function showed no abnormality in steady state hematopoiesis. Bone marrow derived from Apc(min) mice showed enhanced repopulation potential, indicating a cell intrinsic gain of function in the long-term hematopoietic stem cell (HSC) population. However, Apc(min) bone marrow was unable to repopulate secondary recipients because of loss of the quiescent HSC population. Apc(min) mice developed a MDS/myeloproliferative phenotype. Our data indicate that Wnt activation through haploinsufficiency of Apc causes insidious loss of HSC function that is only evident in serial transplantation strategies. These data provide a cautionary note for HSC-expansion strategies through Wnt pathway activation, provide evidence that cell extrinsic factors can contribute to the development of myeloid disease, and indicate that loss of function of APC may contribute to the phenotype observed in patients with MDS and del(5q). (Blood. 2010; 115(17): 3489-3497) C1 [Lane, Steven W.; Sykes, Stephen M.; Al-Shahrour, Fatima; Shterental, Sebastian; Paktinat, Mahnaz; Ebert, Benjamin L.; Gilliland, D. Gary] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Hematol, Boston, MA 02115 USA. [Lane, Steven W.; Williams, David A.] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Hematol Oncol, Cambridge, MA 02138 USA. [Lane, Steven W.] Univ Queensland, Sch Med, Brisbane, Qld, Australia. [Sykes, Stephen M.; Lo Celso, Cristina] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Stem Cell & Regenerat Biol, Boston, MA USA. [Jesneck, Jonathan L.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Jesneck, Jonathan L.] Broad Inst, Canc Program, Cambridge, MA USA. [Gilliland, D. Gary] Merck Res Labs, N Wales, PA USA. RP Lane, SW (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Hematol, Karp 8,1 Blackfan Cir, Boston, MA 02115 USA. EM Steven.lane@childrens.harvard.edu RI Lane, Steven/C-3215-2012 OI Lane, Steven/0000-0002-8050-6209 FU National Health and Medical Research Council Australia; Australia/US Fulbright Commission; Hematology Society of Australia; Hematology Society of New Zealand; Royal Brisbane; Women's Hospital Foundation; US National Institutes of Health [DK62757]; US National Institutes of Health; Howard Hughes Medical Institute; Leukemia & Lymphoma Society; Myeloproliferative Disorders Foundation FX ~S. W. L. has received funding support from the National Health and Medical Research Council Australia, Australia/US Fulbright Commission, Hematology Society of Australia and New Zealand, and Royal Brisbane and Women's Hospital Foundation. D. A. W. has received funding support from the US National Institutes of Health (DK62757). D. G. G. received funding support from the US National Institutes of Health, the Howard Hughes Medical Institute, the Leukemia & Lymphoma Society, and the Myeloproliferative Disorders Foundation. NR 44 TC 54 Z9 57 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 29 PY 2010 VL 115 IS 17 BP 3489 EP 3497 DI 10.1182/blood-2009-11-251728 PG 9 WC Hematology SC Hematology GA 591WL UT WOS:000277335800014 PM 20197553 ER PT J AU Duewell, P Kono, H Rayner, KJ Sirois, CM Vladimer, G Bauernfeind, FG Abela, GS Franchi, L Nunez, G Schnurr, M Espevik, T Lien, E Fitzgerald, KA Rock, KL Moore, KJ Wright, SD Hornung, V Latz, E AF Duewell, Peter Kono, Hajime Rayner, Katey J. Sirois, Cherilyn M. Vladimer, Gregory Bauernfeind, Franz G. Abela, George S. Franchi, Luigi Nunez, Gabriel Schnurr, Max Espevik, Terje Lien, Egil Fitzgerald, Katherine A. Rock, Kenneth L. Moore, Kathryn J. Wright, Samuel D. Hornung, Veit Latz, Eicke TI NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals SO NATURE LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; NALP3 INFLAMMASOME; ATHEROSCLEROTIC LESIONS; MASSIVE XANTHOMATOSIS; HYPERLIPIDEMIC MICE; APOLIPOPROTEIN-E; ACAT INHIBITION; PROGRESSION; CELLS; HYPERCHOLESTEROLEMIA AB The inflammatory nature of atherosclerosis is well established but the agent(s) that incite inflammation in the artery wall remain largely unknown. Germ-free animals are susceptible to atherosclerosis, suggesting that endogenous substances initiate the inflammation(1). Mature atherosclerotic lesions contain macroscopic deposits of cholesterol crystals in the necrotic core, but their appearance late in atherogenesis had been thought to disqualify them as primary inflammatory stimuli. However, using a new microscopic technique, we revealed that minute cholesterol crystals are present in early diet-induced atherosclerotic lesions and that their appearance in mice coincides with the first appearance of inflammatory cells. Other crystalline substances can induce inflammation by stimulating the caspase-1-activating NLRP3 (NALP3 or cryopyrin) inflammasome(2,3), which results in cleavage and secretion of interleukin (IL)-1 family cytokines. Here we show that cholesterol crystals activate the NLRP3 inflammasome in phagocytes in vitro in a process that involves phagolysosomal damage. Similarly, when injected intraperitoneally, cholesterol crystals induce acute inflammation, which is impaired in mice deficient in components of the NLRP3 inflammasome, cathepsin B, cathepsin L or IL-1 molecules. Moreover, when mice deficient in low-density lipoprotein receptor (LDLR) were bone-marrow transplanted with NLRP3-deficient, ASC (also known as PYCARD)-deficient or IL-1 alpha/beta-deficient bone marrow and fed on a high-cholesterol diet, they had markedly decreased early atherosclerosis and inflammasome-dependent IL-18 levels. Minimally modified LDL can lead to cholesterol crystallization concomitant with NLRP3 inflammasome priming and activation in macrophages. Although there is the possibility that oxidized LDL activates the NLRP3 inflammasome in vivo, our results demonstrate that crystalline cholesterol acts as an endogenous danger signal and its deposition in arteries or elsewhere is an early cause rather than a late consequence of inflammation. These findings provide new insights into the pathogenesis of atherosclerosis and indicate new potential molecular targets for the therapy of this disease. C1 [Duewell, Peter; Sirois, Cherilyn M.; Vladimer, Gregory; Lien, Egil; Fitzgerald, Katherine A.; Latz, Eicke] Univ Massachusetts, Sch Med, Dept Immunol & Infect Dis, Worcester, MA 01605 USA. [Kono, Hajime; Rock, Kenneth L.] Univ Massachusetts, Sch Med, Dept Pathol, Worcester, MA 01605 USA. [Duewell, Peter; Schnurr, Max] Univ Munich, Div Gastroenterol, Dept Med, D-80336 Munich, Germany. [Rayner, Katey J.; Moore, Kathryn J.] NYU, Leon H Charney Div Cardiol, New York, NY 10016 USA. [Rayner, Katey J.; Moore, Kathryn J.; Hornung, Veit] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lipid Metab Unit, Boston, MA 02114 USA. [Bauernfeind, Franz G.] Univ Bonn, Inst Clin Chem & Pharmacol, D-53127 Bonn, Germany. [Latz, Eicke] Univ Bonn, Univ Hosp, Inst Innate Immunol, D-53127 Bonn, Germany. [Abela, George S.] Michigan State Univ, Dept Med, Div Cardiol, E Lansing, MI 48824 USA. [Franchi, Luigi; Nunez, Gabriel] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA. [Espevik, Terje; Latz, Eicke] Norwegian Univ Sci & Technol, Inst Canc Res & Mol Med, N-7491 Trondheim, Norway. [Wright, Samuel D.] CSL Ltd, Cardiovasc Therapeut, Parkville, Vic 3052, Australia. RP Latz, E (reprint author), Univ Massachusetts, Sch Med, Dept Immunol & Infect Dis, Worcester, MA 01605 USA. EM eicke.latz@umassmed.edu RI Rayner, Katey/K-8914-2012; Duewell, Peter/C-4576-2014; Latz, Eicke/H-3951-2014; Hornung, Veit/C-3565-2012; OI Latz, Eicke/0000-0003-1488-5666; Hornung, Veit/0000-0002-4150-194X; Sirois, Cherilyn M./0000-0002-5472-4288; Duewell, Peter/0000-0003-0836-6448; Moore, kathryn/0000-0003-2505-2547 FU National Institutes of Health; Deutsche Forschungsgemeinschaft [GK 1202] FX This work was supported by grants from the National Institutes of Health (to E. L. and K. L. R.) and from the Deutsche Forschungsgemeinschaft (GK 1202, to M. S. and P. D.). NR 28 TC 976 Z9 1020 U1 14 U2 169 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 29 PY 2010 VL 464 IS 7293 BP 1357 EP U7 DI 10.1038/nature08938 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 589LI UT WOS:000277149000048 PM 20428172 ER PT J AU Greenberg, JO Dudley, JC Ferris, TG AF Greenberg, Jeffrey O. Dudley, Jessica C. Ferris, Timothy G. TI Engaging Specialists in Performance-Incentive Programs SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Greenberg, Jeffrey O.; Dudley, Jessica C.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Greenberg, Jeffrey O.; Dudley, Jessica C.] Brigham & Womens Phys Org, Boston, MA USA. [Ferris, Timothy G.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Ferris, Timothy G.] Massachusetts Gen Phys Org, Boston, MA USA. [Greenberg, Jeffrey O.; Dudley, Jessica C.; Ferris, Timothy G.] Harvard Univ, Sch Med, Boston, MA USA. RP Greenberg, JO (reprint author), Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. NR 5 TC 17 Z9 17 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 29 PY 2010 VL 362 IS 17 BP 1558 EP 1560 DI 10.1056/NEJMp1000650 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 589AX UT WOS:000277117400003 PM 20410500 ER PT J AU Cushman, WC Evans, GW Byington, RP Goff, DC Grimm, RH Cutler, JA Simons-Morton, DG Basile, JN Corson, MA Probstfield, JL Katz, L Peterson, KA Friedewald, WT Buse, JB Bigger, JT Gerstein, HC Ismail-Beigi, F AF Cushman, William C. Evans, Gregory W. Byington, Robert P. Goff, David C., Jr. Grimm, Richard H., Jr. Cutler, Jeffrey A. Simons-Morton, Denise G. Basile, Jan N. Corson, Marshall A. Probstfield, Jeffrey L. Katz, Lois Peterson, Kevin A. Friedewald, William T. Buse, John B. Bigger, J. Thomas Gerstein, Hertzel C. Ismail-Beigi, Faramarz TI Effects of Intensive Blood-Pressure Control in Type 2 Diabetes Mellitus SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID MICROVASCULAR COMPLICATIONS; RISK; DISEASE; TRIAL; PREVENTION; HOT AB BACKGROUND There is no evidence from randomized trials to support a strategy of lowering systolic blood pressure below 135 to 140 mm Hg in persons with type 2 diabetes mellitus. We investigated whether therapy targeting normal systolic pressure (i.e., < 120 mm Hg) reduces major cardiovascular events in participants with type 2 diabetes at high risk for cardiovascular events. METHODS A total of 4733 participants with type 2 diabetes were randomly assigned to intensive therapy, targeting a systolic pressure of less than 120 mm Hg, or standard therapy, targeting a systolic pressure of less than 140 mm Hg. The primary composite outcome was nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. The mean follow-up was 4.7 years. RESULTS After 1 year, the mean systolic blood pressure was 119.3 mm Hg in the intensive-therapy group and 133.5 mm Hg in the standard-therapy group. The annual rate of the primary outcome was 1.87% in the intensive-therapy group and 2.09% in the standard-therapy group (hazard ratio with intensive therapy, 0.88; 95% confidence interval [CI], 0.73 to 1.06; P = 0.20). The annual rates of death from any cause were 1.28% and 1.19% in the two groups, respectively (hazard ratio, 1.07; 95% CI, 0.85 to 1.35; P = 0.55). The annual rates of stroke, a prespecified secondary outcome, were 0.32% and 0.53% in the two groups, respectively (hazard ratio, 0.59; 95% CI, 0.39 to 0.89; P = 0.01). Serious adverse events attributed to antihypertensive treatment occurred in 77 of the 2362 participants in the intensive-therapy group (3.3%) and 30 of the 2371 participants in the standard-therapy group (1.3%) (P<0.001). CONCLUSIONS In patients with type 2 diabetes at high risk for cardiovascular events, targeting a systolic blood pressure of less than 120 mm Hg, as compared with less than 140 mm Hg, did not reduce the rate of a composite outcome of fatal and nonfatal major cardiovascular events. (ClinicalTrials.gov number, NCT00000620.) C1 [Cushman, William C.] Memphis Vet Affairs VA Med Ctr, Prevent Med Sect, Memphis, TN USA. [Evans, Gregory W.; Byington, Robert P.; Goff, David C., Jr.] Wake Forest Univ, Sch Med, Div Publ Hlth Sci, Winston Salem, NC 27109 USA. [Grimm, Richard H., Jr.] Univ Minnesota, Berman Ctr Outcomes & Clin Res, Minneapolis, MN USA. [Peterson, Kevin A.] Univ Minnesota, Dept Family Practice & Community Med, Minneapolis, MN USA. [Cutler, Jeffrey A.; Simons-Morton, Denise G.] NHLBI, Bethesda, MD 20892 USA. [Basile, Jan N.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Corson, Marshall A.; Probstfield, Jeffrey L.] Univ Washington, Dept Med, Seattle, WA USA. [Buse, John B.] Univ N Carolina, Sch Med, Div Endocrinol, Chapel Hill, NC USA. [Gerstein, Hertzel C.] McMaster Univ, Dept Med, Hamilton, ON, Canada. [Gerstein, Hertzel C.] McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada. [Ismail-Beigi, Faramarz] Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA. [Ismail-Beigi, Faramarz] Case Western Reserve Univ, Dept Physiol & Biophys, Cleveland, OH 44106 USA. RP Cushman, WC (reprint author), Vet Affairs Med Ctr, Cushman Prevent Med Sect 111Q, 1030 Jefferson Ave, Memphis, TN 38104 USA. EM william.cushman@va.gov RI Friedewald, William/C-8034-2011; OI Peterson, Kevin/0000-0002-6914-8586 FU National Heart, Lung, and Blood Institute [N01-HC-95178, N01-HC-95179, N01-HC-95180, N01-HC-95181, N01-HC-95182, N01-HC-95183, N01-HC-95184, IAA Y1-HC-9035, IAA Y1-HC-1010]; National Institutes of Health; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute on Aging; National Eye Institute; Centers for Disease Control and Prevention FX Supported by contracts from the National Heart, Lung, and Blood Institute (N01-HC-95178, N01-HC-95179, N01-HC-95180, N01-HC-95181, N01-HC-95182, N01-HC-95183, N01-HC-95184, and IAA#Y1-HC-9035 and IAA#Y1-HC-1010). Other components of the National Institutes of Health, including the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging, and the National Eye Institute, contributed funding. The Centers for Disease Control and Prevention funded substudies within ACCORD on cost-effectiveness and health-related quality of life. General Clinical Research Centers provide support at many sites. The following companies provided study medications, equipment, or supplies: Abbott Laboratories, Amylin Pharmaceutical, AstraZeneca Pharmaceuticals, Bayer HealthCare, Closer Healthcare, GlaxoSmithKline Pharmaceuticals, King Pharmaceuticals, Merck, Novartis Pharmaceuticals, Novo Nordisk, Omron Healthcare, Sanofi-Aventis U.S., and Takeda. NR 19 TC 1153 Z9 1190 U1 6 U2 58 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 29 PY 2010 VL 362 IS 17 BP 1575 EP 1585 DI 10.1056/NEJMoa1001286 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 589AX UT WOS:000277117400006 ER PT J AU LeLeiko, NS Gee, MS Sadow, PM AF LeLeiko, Neal S. Gee, Michael S. Sadow, Peter M. TI Case 13-2010: An 18.5-Month-Old Girl with Watery Diarrhea and Poor Weight Gain - Ganglioneuroma with immunoreactivity to vasoactive intestinal peptide antigen SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CYSTIC-FIBROSIS; NEUROBLASTOMA; TUMORS; PHEOCHROMOCYTOMA; AEROMONAS; SYMPTOMS; CHILDREN; GLAND C1 [LeLeiko, Neal S.] Brown Univ, Dept Pediat, Alpert Sch Med, Providence, RI 02912 USA. [LeLeiko, Neal S.] Brown Univ, Rhode Isl Hosp, Div Pediat Gastroenterol Nutr & Liver Dis, Hasbro Childrens Hosp, Providence, RI 02903 USA. [Gee, Michael S.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Sadow, Peter M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Gee, Michael S.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Sadow, Peter M.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP LeLeiko, NS (reprint author), Brown Univ, Dept Pediat, Alpert Sch Med, Providence, RI 02912 USA. NR 27 TC 1 Z9 1 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 29 PY 2010 VL 362 IS 17 BP 1619 EP 1626 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 589AX UT WOS:000277117400012 PM 20427811 ER PT J AU Berny, MA Munnix, ICA Auger, JM Schols, SEM Cosemans, JMEM Panizzi, P Bock, PE Watson, SP McCarty, OJT Heemskerk, JWM AF Berny, Michelle A. Munnix, Imke C. A. Auger, Jocelyn M. Schols, Saskia E. M. Cosemans, Judith M. E. M. Panizzi, Peter Bock, Paul E. Watson, Steve P. McCarty, Owen J. T. Heemskerk, Johan W. M. TI Spatial Distribution of Factor Xa, Thrombin, and Fibrin(ogen) on Thrombi at Venous Shear SO PLOS ONE LA English DT Article ID VON-WILLEBRAND-FACTOR; FLOWING HUMAN BLOOD; IN-VIVO; PLATELET ACTIVATION; GAMMA-CHAIN; ANNEXIN-V; FIBRINOGEN; COMPLEX; COLLAGEN; BINDING AB Background: The generation of thrombin is a critical process in the formation of venous thrombi. In isolated plasma under static conditions, phosphatidylserine (PS)-exposing platelets support coagulation factor activation and thrombin generation; however, their role in supporting coagulation factor binding under shear conditions remains unclear. We sought to determine where activated factor X (FXa), (pro) thrombin, and fibrin(ogen) are localized in thrombi formed under venous shear. Methodology/Principal Findings: Fluorescence microscopy was used to study the accumulation of platelets, FXa, (pro) thrombin, and fibrin(ogen) in thrombi formed in vitro and in vivo. Co-perfusion of human blood with tissue factor resulted in formation of visible fibrin at low, but not at high shear rate. At low shear, platelets demonstrated increased Ca(2+) signaling and PS exposure, and supported binding of FXa and prothrombin. However, once cleaved, (pro) thrombin was observed on fibrin fibers, covering the whole thrombus. In vivo, wild-type mice were injected with fluorescently labeled coagulation factors and venous thrombus formation was monitored in mesenteric veins treated with FeCl(3). Thrombi formed in vivo consisted of platelet aggregates, focal spots of platelets binding FXa, and large areas binding (pro) thrombin and fibrin(ogen). Conclusions/Significance: FXa bound in a punctate manner to thrombi under shear, while thrombin and fibrin(ogen) distributed ubiquitously over platelet-fibrin thrombi. During thrombus formation under venous shear, thrombin may relocate from focal sites of formation (on FXa-binding platelets) to dispersed sites of action (on fibrin fibers). C1 [Berny, Michelle A.; Munnix, Imke C. A.; Schols, Saskia E. M.; Cosemans, Judith M. E. M.; Heemskerk, Johan W. M.] Maastricht Univ, CARIM, Dept Biochem, Maastricht, Netherlands. [Berny, Michelle A.; McCarty, Owen J. T.] Oregon Hlth & Sci Univ, Dept Biomed Engn, Portland, OR 97201 USA. [Auger, Jocelyn M.; Watson, Steve P.] Univ Birmingham, Ctr Cardiovasc Sci, Birmingham, W Midlands, England. [Panizzi, Peter] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Panizzi, Peter; Bock, Paul E.] Vanderbilt Univ, Sch Med, Dept Pathol, Nashville, TN 37212 USA. RP Berny, MA (reprint author), Maastricht Univ, CARIM, Dept Biochem, Maastricht, Netherlands. EM mccartyo@ohsu.edu; jwm.heemskerk@biochem.unimaas.nl RI Watson, Stephen/Q-6292-2016; OI Watson, Stephen/0000-0002-7846-7423; Panizzi, Peter/0000-0003-0141-8807 FU American Heart Association [09PRE2230117, 09GRNT2150003]; Netherlands Organization for Scientific Research [11-400-0076]; Wellcome Trust [073107]; National Institutes of Health [R37HL071544, RO1HL038779] FX This work was supported by the American Heart Association (http://www.americanheart.org; M. A. B. - 09PRE2230117 and O.J.T.M. - 09GRNT2150003), the Netherlands Organization for Scientific Research (http://www.nwo.nl; J.W.M.H. and J.M.E.M.C. - 11-400-0076), the Wellcome Trust (http://www.wellcome.ac.uk; J.M.A. and S. P. W. - 073107), and the National Institutes of Health (http://www.nih.gov; P. E. B. - R37HL071544 and RO1HL038779 from the National Heart, Lung, and Blood Institute). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 43 TC 35 Z9 35 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 29 PY 2010 VL 5 IS 4 AR e10415 DI 10.1371/journal.pone.0010415 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 590PU UT WOS:000277240100022 PM 20454680 ER PT J AU Rajamani, S Ichida, JK Antal, T Treco, DA Leu, K Nowak, MA Szostak, JW Chen, IA AF Rajamani, Sudha Ichida, Justin K. Antal, Tibor Treco, Douglas A. Leu, Kevin Nowak, Martin A. Szostak, Jack W. Chen, Irene A. TI Effect of Stalling after Mismatches on the Error Catastrophe in Nonenzymatic Nucleic Acid Replication SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID CHEMICAL PRIMER EXTENSION; DNA POLYMERASE-ALPHA; PREBIOTIC CHEMISTRY; HIGH-FIDELITY; RNA WORLD; EVOLUTION; THRESHOLD; SELECTION; MISPAIRS; MODEL AB The frequency of errors during genome replication limits the amount of functionally important information that can be passed on from generation to generation. During the origin of life, mutation rates are thought to have been quite high, raising a classic chicken-and-egg paradox: could nonenzymatic replication propagate sequences accurately enough to allow for the emergence of heritable function? Here we show that the theoretical limit on genomic information content may increase substantially as a consequence of dramatically slowed polymerization after mismatches. As a result of postmismatch stalling, accurate copies of a template tend to be completed more rapidly than mutant copies and the accurate copies can therefore begin a second round of replication more quickly. To quantify this effect, we characterized an experimental model of nonenzymatic, template-directed nucleic acid polymerization. We found that most mismatches decrease the rate of primer extension by more than 2 orders of magnitude relative to a matched (Watson Crick) control. A chemical replication system with this property would be able to propagate sequences long enough to have function. Our study suggests that the emergence of functional sequences during the origin of life would be possible even in the face of the high intrinsic error rates of chemical replication. C1 [Rajamani, Sudha; Leu, Kevin; Chen, Irene A.] Harvard Univ, FAS Ctr Syst Biol, Cambridge, MA 02138 USA. [Antal, Tibor; Nowak, Martin A.] Harvard Univ, Program Evolutionary Dynam, Cambridge, MA 02138 USA. [Ichida, Justin K.; Treco, Douglas A.; Szostak, Jack W.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Dept Mol Biol, Boston, MA 02114 USA. [Ichida, Justin K.; Treco, Douglas A.; Szostak, Jack W.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. RP Chen, IA (reprint author), Harvard Univ, FAS Ctr Syst Biol, Cambridge, MA 02138 USA. EM ichen@post.harvard.edu RI Antal, Tibor/A-4512-2008; Nowak, Martin/A-6977-2008 FU NIH [GM068763]; NSF [CHE0434507]; Ford Foundation FX We thank Jason Schrum, Sylvia Tobe, Michael Lawrence, Ching-Hsuan Tsai, John B. Randolph, Pierre-Alain Monnard, Andrew Murray, David Liu, Johan Paulsson, Eugene Shakhnovich, and Bodo Stern for advice. This work was supported by NIH grant GM068763 to the National Centers of Systems Biology and the Bauer Fellows Program at Harvard University (I.A.C.) and by NSF grant CHE0434507 (J.W.S.). J.W.S. is an Investigator at the Howard Hughes Medical Institute. J.K.I. received a predoctoral fellowship from the Ford Foundation. NR 33 TC 50 Z9 52 U1 2 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD APR 28 PY 2010 VL 132 IS 16 BP 5880 EP 5885 DI 10.1021/ja100780p PG 6 WC Chemistry, Multidisciplinary SC Chemistry GA 587KS UT WOS:000276991700072 PM 20359213 ER PT J AU Lambertini, C Pantano, S Dotto, GP AF Lambertini, Chiara Pantano, Serafino Dotto, G. Paolo TI Differential Control of Notch1 Gene Transcription by Klf4 and Sp3 Transcription Factors in Normal versus Cancer-Derived Keratinocytes SO PLOS ONE LA English DT Article ID TUMOR-SUPPRESSOR; SIGNALING PATHWAY; FACTOR FAMILY; CELL-GROWTH; EXPRESSION; P53; PROMOTER; COMPLEX; SKIN; TRANSFORMATION AB In specific cell types like keratinocytes, Notch signaling plays an important pro-differentiation and tumor suppressing function, with down-modulation of the Notch1 gene being associated with cancer development. Besides being controlled by p53, little else is known on regulation of Notch1 gene expression in this context. We report here that transcription of this gene is driven by a TATA-less "sharp peak'' promoter and that the minimal functional region of this promoter, which extends from the -342 bp position to the initiation codon, is differentially active in normal versus cancer cells. This GC rich region lacks p53 binding sites, but binds Klf4 and Sp3. This finding is likely to be of biological significance, as Klf4 and, to a lesser extent, Sp3 are up-regulated in a number of cancer cells where Notch1 expression is down-modulated, and Klf4 overexpression in normal cells is sufficient to down-modulate Notch1 gene transcription. The combined knock-down of Klf4 and Sp3 was necessary for the reverse effect of increasing Notch1 transcription, consistent with the two factors exerting an overlapping repressor function through their binding to the Notch1 promoter. C1 [Lambertini, Chiara; Pantano, Serafino; Dotto, G. Paolo] Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland. [Dotto, G. Paolo] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. RP Lambertini, C (reprint author), Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland. EM Gian-Paolo.Dotto@unil.ch FU Swiss National Foundation; European Union [LSHB-CT-2005-019067]; NIH [AR39190, AR054856] FX This work was supported by a grant from the Swiss National Foundation, a grant from the European Union (Epistem, Sixth Framework Program, LSHB-CT-2005-019067), and NIH Grants AR39190 and AR054856 and to G. P. D. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 54 TC 19 Z9 19 U1 1 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 28 PY 2010 VL 5 IS 4 AR e10369 DI 10.1371/journal.pone.0010369 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 589MV UT WOS:000277154200011 PM 20442780 ER PT J AU Weiser, SD Tuller, DM Frongillo, EA Senkungu, J Mukiibi, N Bangsberg, DR AF Weiser, Sheri D. Tuller, David M. Frongillo, Edward A. Senkungu, Jude Mukiibi, Nozmu Bangsberg, David R. TI Food Insecurity as a Barrier to Sustained Antiretroviral Therapy Adherence in Uganda SO PLOS ONE LA English DT Article ID HIV-POSITIVE INDIVIDUALS; INFECTED INDIVIDUALS; MEDICATION ADHERENCE; IMPROVE ADHERENCE; DRUG-RESISTANCE; AFRICAN ADULTS; FACILITATORS; SURVIVAL; AIDS; METAANALYSIS AB Background: Food insecurity is emerging as an important barrier to antiretroviral (ARV) adherence in sub-Saharan Africa and elsewhere, but little is known about the mechanisms through which food insecurity leads to ARV non-adherence and treatment interruptions. Methodology: We conducted in-depth, open-ended interviews with 47 individuals (30 women, 17 men) living with HIV/AIDS recruited from AIDS treatment programs in Mbarara and Kampala, Uganda to understand how food insecurity interferes with ARV therapy regimens. Interviews were transcribed, coded for key themes, and analyzed using grounded theory. Findings: Food insecurity was common and an important barrier to accessing medical care and ARV adherence. Five mechanisms emerged for how food insecurity can contribute to ARV non-adherence and treatment interruptions or to postponing ARV initiation: 1) ARVs increased appetite and led to intolerable hunger in the absence of food; 2) Side effects of ARVs were exacerbated in the absence of food; 3) Participants believed they should skip doses or not start on ARVs at all if they could not afford the added nutritional burden; 4) Competing demands between costs of food and medical expenses led people either to default from treatment, or to give up food and wages to get medications; 5) While working for food for long days in the fields, participants sometimes forgot medication doses. Despite these obstacles, many participants still reported high ARV adherence and exceptional motivation to continue therapy. Conclusions: While reports from sub-Saharan Africa show excellent adherence to ARVs, concerns remain that these successes are not sustainable in the presence of widespread poverty and food insecurity. We provide further evidence on how food insecurity can compromise sustained ARV therapy in a resource-limited setting. Addressing food insecurity as part of emerging ARV treatment programs is critical for their long-term success. C1 [Weiser, Sheri D.] San Francisco Gen Hosp, Div HIV AIDS, San Francisco, CA 94110 USA. [Weiser, Sheri D.] Univ Calif San Francisco, Ctr AIDS Prevent Studies, San Francisco, CA 94143 USA. [Tuller, David M.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. [Frongillo, Edward A.] Univ S Carolina, Dept Hlth Promot Educ & Behav, Arnold Sch Publ Hlth, Columbia, SC 29208 USA. [Senkungu, Jude; Mukiibi, Nozmu; Bangsberg, David R.] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Bangsberg, David R.] Massachusetts Inst Technol & Harvard, Ragon Inst, Massachusetts Gen Hosp, Boston, MA USA. [Bangsberg, David R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Global Hlth, Cambridge, MA 02138 USA. [Bangsberg, David R.] Harvard Initiat Global Hlth, Boston, MA USA. RP Weiser, SD (reprint author), San Francisco Gen Hosp, Div HIV AIDS, San Francisco, CA 94110 USA. EM Sheri.Weiser@ucsf.edu FU National Institute of Mental Health [K23 MH079713-01]; NIMH [RO-1 54907, K24 87227]; Meyers Family Foundation FX This study was funded by National Institute of Mental Health K23 MH079713-01, NIMH RO-1 54907, and the Meyers Family Foundation. Dr. Bangsberg received support from NIMH K24 87227. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 43 TC 77 Z9 78 U1 2 U2 12 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 28 PY 2010 VL 5 IS 4 AR e10340 DI 10.1371/journal.pone.0010340 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 589MV UT WOS:000277154200004 PM 20442769 ER PT J AU Sox, HC Helfand, M Grimshaw, J Dickersin, K Tovey, D Knottnerus, JA Tugwell, P AF Sox, Harold C. Helfand, Mark Grimshaw, Jeremy Dickersin, Kay Tovey, David Knottnerus, J. Andre Tugwell, Peter CA PLoS Med Editors TI Comparative effectiveness research: Challenges for medical journals SO TRIALS LA English DT Editorial Material AB Editors from a number of medical journals lay out principles for journals considering publication of Comparative Effectiveness Research (CER). In order to encourage dissemination of this editorial, this article is freely available in PLoS Medicine and will be also published in Medical Decision Making, Croatian Medical Journal, The Cochrane Library, Trials, The American Journal of Managed Care, and Journal of Clinical Epidemiology. C1 [Helfand, Mark] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97201 USA. [Helfand, Mark] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Sox, Harold C.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dartmouth Inst, Hanover, NH 03756 USA. [Grimshaw, Jeremy] Ottawa Hosp Res Inst, Clin Epidemiol Program, Ottawa, ON, Canada. [Dickersin, Kay] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Tovey, David; PLoS Med Editors] Cochrane Lib, London, England. [Knottnerus, J. Andre] Univ Maastricht, Dept Gen Practice, Maastricht, Netherlands. [Tugwell, Peter] Univ Ottawa, Dept Med, Ottawa, ON, Canada. [Tugwell, Peter] Univ Ottawa, Dept Epidemiol, Ottawa, ON, Canada. [Tugwell, Peter] Univ Ottawa, Dept Community Med, Ottawa, ON, Canada. RP Helfand, M (reprint author), Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97201 USA. EM helfand@ohsu.edu RI Knottnerus, Johannes/A-3829-2009; OI Grimshaw, Jeremy/0000-0001-8015-8243; Tugwell, Peter/0000-0001-5062-0556 NR 7 TC 3 Z9 3 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6215 J9 TRIALS JI Trials PD APR 28 PY 2010 VL 11 AR 45 DI 10.1186/1745-6215-11-45 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 605FS UT WOS:000278333700001 PM 20426805 ER PT J AU Bao, Y Ng, K Wolpin, BM Michaud, DS Giovannucci, E Fuchs, CS AF Bao, Y. Ng, K. Wolpin, B. M. Michaud, D. S. Giovannucci, E. Fuchs, C. S. TI Predicted vitamin D status and pancreatic cancer risk in two prospective cohort studies SO BRITISH JOURNAL OF CANCER LA English DT Article DE vitamin D; pancreatic cancer; epidemiology ID UNITED-STATES; MALE SMOKERS; MORTALITY; MEN AB BACKGROUND: Studies evaluating vitamin D status in relation to pancreatic cancer risk have yielded inconsistent results. METHODS: We prospectively followed 118 597 participants in the Nurses' Health Study and Health Professionals Follow-up Study from 1986 to 2006. We calculated a 25-hydroxyvitamin D (25(OH) D) score from known predictors of vitamin D status for each individual and then examined the predicted 25(OH) D levels in relation to pancreatic cancer risk. Relative risks (RRs) and 95% confidence intervals (95% CIs) were estimated using Cox proportional hazards models adjusted for age, sex, race, height, smoking, and diabetes. We then further adjusted for body mass index (BMI) and physical activity in a sensitivity analysis. RESULTS: During 20 years of follow-up, we identified 575 incident pancreatic cancer cases. Higher 25(OH) D score was associated with a significant reduction in pancreatic cancer risk; compared with the lowest quintile, participants in the highest quintile of 25(OH) D score had an adjusted RR of 0.65 (95% CI = 0.50-0.86; P(trend) = 0.001). Results were similar when we further adjusted for BMI and physical activity. CONCLUSIONS: Higher 25(OH) D score was associated with a lower risk of pancreatic cancer in these two prospective cohort studies. British Journal of Cancer (2010) 102, 1422-1427. doi:10.1038/sj.bjc.6605658 www.bjcancer.com Published online 13 April 2010 (C) 2010 Cancer Research UK C1 [Bao, Y.; Giovannucci, E.; Fuchs, C. S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab,Dept Med, Boston, MA 02115 USA. [Ng, K.; Wolpin, B. M.; Fuchs, C. S.] Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. [Michaud, D. S.; Giovannucci, E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Michaud, D. S.] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Publ Hlth, London, England. [Giovannucci, E.] Harvard Univ, Dept Nutr, Sch Publ Hlth, Boston, MA 02115 USA. RP Bao, Y (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab,Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. EM ying.bao@channing.harvard.edu RI Michaud, Dominique/I-5231-2014 FU National Cancer Institute, National Institutes of Health, Bethesda, MD [CA124908]; Conquer Cancer Coalition of Massachusetts FX This study was supported by grants from the National Cancer Institute, National Institutes of Health, Bethesda, MD (Grant Number CA124908) and by the Conquer Cancer Coalition of Massachusetts. NR 18 TC 37 Z9 39 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD APR 27 PY 2010 VL 102 IS 9 BP 1422 EP 1427 DI 10.1038/sj.bjc.6605658 PG 6 WC Oncology SC Oncology GA 588UF UT WOS:000277098900018 PM 20389298 ER PT J AU Mega, JL Hochman, JS Scirica, BM Murphy, SA Sloan, S McCabe, CH Merlini, P Morrow, DA AF Mega, Jessica L. Hochman, Judith S. Scirica, Benjamin M. Murphy, Sabina A. Sloan, Sarah McCabe, Carolyn H. Merlini, Piera Morrow, David A. TI Clinical Features and Outcomes of Women With Unstable Ischemic Heart Disease Observations From Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndromes-Thrombolysis in Myocardial Infarction 36 (MERLIN-TIMI 36) SO CIRCULATION LA English DT Article DE angina, unstable; heart disease; sex; women ID SYNDROME EVALUATION WISE; RANDOMIZED CONTROLLED-TRIAL; GENDER-DIFFERENCES; ANGINA-PECTORIS; ARTERY-DISEASE; CHEST-PAIN; MEN; REGISTRY; RISK; AMLODIPINE AB Background-The pathobiological basis of ischemic heart disease and thus the manifestations and response to therapy can differ between women and men. In prior studies, sex-based treatment differences have been observed with the antiischemic ranolazine, with a possibly diminished effect in women. Methods and Results-We conducted a prospectively planned analysis of the clinical, biomarker, angiographic, and continuous ECG features and 1-year outcomes of women with unstable ischemic heart disease randomized to ranolazine or placebo in Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndromes-Thrombolysis in Myocardial Infarction 36 (MERLIN-TIMI 36). Compared with men (n=4269), women (n=2291) were older with more risk factors (P<0.001). On presentation, women were less likely than men to have significant epicardial coronary artery disease ( no stenosis >= 50% on angiography, 19.4% versus 8.6%; P<0.001) or elevated troponin (57.1% versus 68.9%; P<0.001). Yet, women were more likely to have an elevated B-type natriuretic peptide (47.0% versus 40.2%; P<0.001), worse median angina frequency scores ( 80 versus 100; P<0.001), and an ischemic episode on continuous ECG administered during the first 7 days (22.5% versus 19.3%; P=0.0025). Women and men were at similar adjusted risk for the primary end point of cardiovascular death, myocardial infarction, or recurrent ischemia ( adjusted hazard ratio, 1.11; 95% confidence interval, 0.96 to 1.29; P=0.15). Ranolazine was associated with a significant reduction in recurrent ischemia in women (13.0% versus 18.2%; hazard ratio, 0.71; 95% confidence interval, 0.57 to 0.88; P=0.002). Conclusions-Women with a clinical syndrome consistent with unstable ischemic heart disease, despite having less obstructive coronary artery disease, were more likely than men to report anginal episodes and had more recorded ischemic periods on continuous ECG. In this setting, ranolazine may be a particularly useful antiischemic agent in women. C1 [Mega, Jessica L.; Scirica, Benjamin M.; Murphy, Sabina A.; Sloan, Sarah; McCabe, Carolyn H.; Morrow, David A.] Brigham & Womens Hosp, TIMI Study Grp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. [Mega, Jessica L.; Scirica, Benjamin M.; Murphy, Sabina A.; Sloan, Sarah; McCabe, Carolyn H.; Morrow, David A.] Harvard Univ, Sch Med, Boston, MA USA. [Hochman, Judith S.] NYU, Med Ctr, Dept Med, New York, NY 10016 USA. [Hochman, Judith S.] Sch Med, New York, NY USA. [Merlini, Piera] Osped Maggiore Niguarda, Div Cardiol, Milan, Italy. RP Mega, JL (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Dept Med, Div Cardiovasc, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM jmega@partners.org FU CV Therapeutics FX The MERLIN-TIMI 36 trial was funded by CV Therapeutics. NR 31 TC 32 Z9 35 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 27 PY 2010 VL 121 IS 16 BP 1809 EP 1817 DI 10.1161/CIRCULATIONAHA.109.897231 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 588HD UT WOS:000277058500004 PM 20385930 ER PT J AU Kenet, G Lutkhoff, LK Albisetti, M Bernard, T Bonduel, M Brandao, L Chabrier, S Chan, A deVeber, G Fiedler, B Fullerton, HJ Goldenberg, NA Grabowski, E Gunther, G Heller, C Holzhauer, S Iorio, A Journeycake, J Junker, R Kirkham, FJ Kurnik, K Lynch, JK Male, C Manco-Johnson, M Mesters, R Monagle, P van Ommen, CH Raffini, L Rostasy, K Simioni, P Strater, RD Young, G Nowak-Gottl, U AF Kenet, Gili Luetkhoff, Lisa K. Albisetti, Manuela Bernard, Timothy Bonduel, Mariana Brandao, Leonardo Chabrier, Stephane Chan, Anthony deVeber, Gabrielle Fiedler, Barbara Fullerton, Heather J. Goldenberg, Neil A. Grabowski, Eric Guenther, Gudrun Heller, Christine Holzhauer, Susanne Iorio, Alfonso Journeycake, Janna Junker, Ralf Kirkham, Fenella J. Kurnik, Karin Lynch, John K. Male, Christoph Manco-Johnson, Marilyn Mesters, Rolf Monagle, Paul van Ommen, C. Heleen Raffini, Leslie Rostasy, Kevin Simioni, Paolo Straeter, Ronald D. Young, Guy Nowak-Goettl, Ulrike TI Impact of Thrombophilia on Risk of Arterial Ischemic Stroke or Cerebral Sinovenous Thrombosis in Neonates and Children A Systematic Review and Meta-Analysis of Observational Studies SO CIRCULATION LA English DT Article DE cerebrovascular disorders; meta-analysis; pediatrics; thrombophilia ID FACTOR-V-LEIDEN; VENOUS SINUS THROMBOSIS; GENE G20210A MUTATION; PROTHROMBIN 20210 G; CHILDHOOD STROKE; PROTEIN-C; PEDIATRIC STROKE; METHYLENETETRAHYDROFOLATE REDUCTASE; ANTIPHOSPHOLIPID ANTIBODIES; HOMOCYSTEINE METABOLISM AB Background-The aim of this study was to estimate the impact of thrombophilia on risk of first childhood stroke through a meta-analysis of published observational studies. Methods and Results-A systematic search of electronic databases (Medline via PubMed, EMBASE, OVID, Web of Science, The Cochrane Library) for studies published from 1970 to 2009 was conducted. Data on year of publication, study design, country of origin, number of patients/control subjects, ethnicity, stroke type (arterial ischemic stroke [AIS], cerebral venous sinus thrombosis [CSVT]) were abstracted. Publication bias indicator and heterogeneity across studies were evaluated, and summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with fixed-effects or random-effects models. Twenty-two of 185 references met inclusion criteria. Thus, 1764 patients (arterial ischemic stroke [AIS], 1526; cerebral sinus venous thrombosis [CSVT], 238) and 2799 control subjects (neonate to 18 years of age) were enrolled. No significant heterogeneity was discerned across studies, and no publication bias was detected. A statistically significant association with first stroke was demonstrated for each thrombophilia trait evaluated, with no difference found between AIS and CSVT. Summary ORs (fixed-effects model) were as follows: antithrombin deficiency, 7.06 (95% CI, 2.44 to 22.42); protein C deficiency, 8.76 (95% CI, 4.53 to 16.96); protein S deficiency, 3.20 (95% CI, 1.22 to 8.40), factor V G1691A, 3.26 (95% CI, 2.59 to 4.10); factor II G20210A, 2.43 (95% CI, 1.67 to 3.51); MTHFR C677T (AIS), 1.58 (95% CI, 1.20 to 2.08); antiphospholipid antibodies (AIS), 6.95 (95% CI, 3.67 to 13.14); elevated lipoprotein(a), 6.27 (95% CI, 4.52 to 8.69), and combined thrombophilias, 11.86 (95% CI, 5.93 to 23.73). In the 6 exclusively perinatal AIS studies, summary ORs were as follows: factor V, 3.56 (95% CI, 2.29 to 5.53); and factor II, 2.02 (95% CI, 1.02 to 3.99). Conclusions-The present meta-analysis indicates that thrombophilias serve as risk factors for incident stroke. However, the impact of thrombophilias on outcome and recurrence risk needs to be further investigated. (Circulation. 2010; 121: 1838-1847) C1 [Luetkhoff, Lisa K.; Straeter, Ronald D.; Nowak-Goettl, Ulrike] Univ Hosp Munster, Dept Pediat Hematol Oncol, D-48149 Munster, Germany. [Kenet, Gili] Chaim Sheba Med Ctr, Israel Natl Haemophilia Ctr, IL-52621 Tel Hashomer, Israel. [Albisetti, Manuela] Univ Childrens Hosp, Div Hematol, Zurich, Switzerland. [Bernard, Timothy; Goldenberg, Neil A.; Manco-Johnson, Marilyn] Univ Colorado, Dept Pediat Hematol Oncol BMT, Denver, CO 80202 USA. [Bernard, Timothy; Goldenberg, Neil A.; Manco-Johnson, Marilyn] Univ Colorado, Mt States Reg Hemophilia & Thrombosis Ctr, Denver, CO 80202 USA. [Bernard, Timothy; Goldenberg, Neil A.; Manco-Johnson, Marilyn] Childrens Hosp, Denver, CO 80218 USA. [Bonduel, Mariana] Hosp Pediat Prof Dr JP Garrahan, Serv Hematolgia & Oncol, Buenos Aires, DF, Argentina. [Brandao, Leonardo; deVeber, Gabrielle] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Chabrier, Stephane] CHU, Unit Neonatol & Reanimat Pediat, St Etienne, France. [Chan, Anthony] McMaster Univ, Hamilton, ON, Canada. [Fiedler, Barbara] Univ Hosp Munster, Dept Pediat Neurol, D-48149 Munster, Germany. [Fullerton, Heather J.] Univ Calif San Francisco, Dept Neurol & Pediat, San Francisco, CA 94143 USA. [Grabowski, Eric] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Guenther, Gudrun] Univ Hosp Magdeburg, Dept Pediat, Magdeburg, Germany. [Heller, Christine] Univ Hosp Frankfurt, Dept Pediat Hematol Oncol, Frankfurt, Germany. [Holzhauer, Susanne] Charite, Dept Pediat Hematol Oncol, Berlin, Germany. [Iorio, Alfonso] Univ Perugia, Internal & Vasc Med & Hemophilia Ctr, I-06100 Perugia, Italy. [Journeycake, Janna] Univ Texas SW Med Ctr Dallas, Dept Pediat, Childrens Med Ctr Dallas, Dallas, TX 75390 USA. [Junker, Ralf] Univ Hosp Kiel, Dept Clin Chem, Kiel, Germany. [Kirkham, Fenella J.] UCL, Neurosci Unit, Inst Child Hlth, London, England. [Kirkham, Fenella J.] Southampton Gen Hosp, Dept Child Hlth, Southampton SO9 4XY, Hants, England. [Kurnik, Karin] Univ Hosp Munich, Dept Pediat, Munich, Germany. [Lynch, John K.] Natl Inst Neurol Disorders & Stroke, Div Stroke Diagnost & Therapeut, Bethesda, MD USA. [Male, Christoph] Med Univ Vienna, Dept Pediat, Vienna, Austria. [Mesters, Rolf] Univ Hosp Munster, Dept Internal Med, D-48149 Munster, Germany. [Monagle, Paul] Royal Childrens Hosp, Parkville, Vic, Australia. [van Ommen, C. Heleen] Emma Childrens Hosp AMC, Dept Pediat Hematol, Amsterdam, Netherlands. [Raffini, Leslie] Univ Penn, Sch Med, Div Hematol, Dept Pediat,Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Rostasy, Kevin] Med Univ Innsbruck, Dept Pediat 4, Div Pediat Neurol & Inherited Metab Disorders, Innsbruck, Austria. [Simioni, Paolo] Univ Padua, Dept Cardiol Thorac & Vasc Sci, Chair Internal Med 2, Padua, Italy. [Young, Guy] Childrens Hosp, Div Hematol Oncol, Los Angeles, CA 90027 USA. RP Nowak-Gottl, U (reprint author), Univ Hosp Munster, Dept Pediat Hematol Oncol, Albert Schweitzer Str 33, D-48149 Munster, Germany. EM leagottl@uni-muenster.de RI Kirkham, Fenella/C-2442-2009; Young, Guy/I-1880-2012; Junker, Ralf/M-2358-2013; OI Iorio, Alfonso/0000-0002-3331-8766; Kirkham, Fenella/0000-0002-2443-7958; Young, Guy/0000-0001-6013-1254; SIMIONI, PAOLO/0000-0002-6744-383X; Chan, Anthony K. C./0000-0003-1551-3995 FU Forderverein "Schlaganfall und Thrombosen im Kindesalter e.V.,"; Deutsche Schlaganfall-Hilfe; Interdisziplinares Zentrum fur Klinische Forschung [CRA01-09]; University of Munster FX The study was supported by grants from the Forderverein "Schlaganfall und Thrombosen im Kindesalter e.V.," Deutsche Schlaganfall-Hilfe, and Interdisziplinares Zentrum fur Klinische Forschung (CRA01-09), University of Munster. These study supporters had no role in study design, data collection, data analysis, data interpretation, or writing of the report. NR 93 TC 156 Z9 173 U1 2 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 27 PY 2010 VL 121 IS 16 BP 1838 EP U92 DI 10.1161/CIRCULATIONAHA.109.913673 PG 25 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 588HD UT WOS:000277058500007 PM 20385928 ER PT J AU Linn, J Halpin, A Demaerel, P Ruhland, J Giese, AD Dichgans, M van Buchem, MA Bruckmann, H Greenberg, SM AF Linn, J. Halpin, A. Demaerel, P. Ruhland, J. Giese, A. D. Dichgans, M. van Buchem, M. A. Bruckmann, H. Greenberg, S. M. TI Prevalence of superficial siderosis in patients with cerebral amyloid angiopathy SO NEUROLOGY LA English DT Article ID BOSTON CRITERIA; POPULATION AB Background: Cerebral amyloid angiopathy (CAA) typically presents with lobar intracerebral macrohemorrhages (ICH) or microbleeds (MBs). Several case reports also found superficial siderosis (SS) in patients with CAA. We aimed to assess the value of SS for the in vivo diagnosis of CAA, and tested whether the inclusion of SS as a criterion alters the sensitivity and specificity of the Boston criteria for CAA-related hemorrhage. Methods: We retrospectively analyzed the T2*-weighted MRIs of 38 patients with histopathologically proven CAA and of 22 control patients with histopathologically proven non-CAA ICHs regarding the presence of ICHs, MBs, and SS. We compared the sensitivity and specificity of the classic Boston criteria to that of modified criteria, which included SS as a criterion. Results: ICHs were present in 71% of the patients with CAA, and in all control patients. MBs were found in 47.4% of patients with CAA and in 22.7% of controls. SS was detected in 60.5% of patients with CAA, but in none of the controls. The classic criteria had a sensitivity of 89.5% for CAA-related hemorrhage, while inclusion of SS increased their sensitivity to 94.7% (not significant). On the contrary, the specificity of the Boston criteria was 81.2% both for the classic and for the modified criteria. Conclusions: Superficial siderosis (SS) occurs with high prevalence in cerebral amyloid angiopathy (CAA) and is rare in non-CAA forms of intracerebral hemorrhages. Thus, we propose that inclusion of SS in the Boston criteria might enhance their sensitivity for CAA-related hemorrhage without loss of specificity. Neurology (R) 2010; 74: 1346-1350 C1 [Linn, J.; Ruhland, J.; Bruckmann, H.] Univ Hosp Munich, Dept Neuroradiol, D-81377 Munich, Germany. [Giese, A. D.] Univ Hosp Munich, Zentrum Neuropathol & Prionforsch, D-81377 Munich, Germany. [Dichgans, M.] Univ Hosp Munich, Dept Neurol, D-81377 Munich, Germany. [Halpin, A.; Greenberg, S. M.] Massachusetts Gen Hosp, Dept Neurol, Hemorrhag Stroke Res Program, Boston, MA 02114 USA. [Demaerel, P.] Univ Hosp KU Leuven, Dept Radiol, Leuven, Belgium. [van Buchem, M. A.] Leiden Univ, Med Ctr, Dept Radiol, Leiden, Netherlands. RP Linn, J (reprint author), Univ Hosp Munich, Dept Neuroradiol, Marchioninistr 15, D-81377 Munich, Germany. EM linn@nrad.de RI Giese, Armin/F-3271-2010; Linn, Jennifer/H-8202-2013 OI Giese, Armin/0000-0002-8238-4102; FU B. Braun Stiftung; Friedrich-Baur Stiftung; Forderprogramm fur Forschung und Lehre; Bayerische Gleichstellungsforderung (BGF); Boehringer Ingelheim; DFG [SFB596-B13]; Luneburg-Stiftung fur Parkinsonforschung; Studienstiftung des Deutschen Volkes; BMBF; Wellcome Trust; Foundation for Vascular Dementia Research; NIH [R01AG026484, K24NS056207, R01AG021084, R01NS042147, U54NS057405]; Alzheimer's Association FX Dr. Linn has received research support from B. Braun Stiftung, Friedrich-Baur Stiftung, and the Forderprogramm fur Forschung und Lehre, and a grant from the Bayerische Gleichstellungsforderung (BGF). Dr. Halpin, Dr. Demaerel, and J. Ruhland report no disclosures. Dr. Giese has received research support from Boehringer Ingelheim, the DFG, SFB596-B13, Luneburg-Stiftung fur Parkinsonforschung, and Studienstiftung des Deutschen Volkes. Dr. Dichgans served as a Section Editor for Stroke and receives research support from BMBF, Wellcome Trust, and the Foundation for Vascular Dementia Research. Dr. van Buchem and Dr. Bruckmann report no disclosures. Dr. Greenberg serves on a scientific advisory board for Hoffman-LaRoche; has received travel expenses and/or honoraria for lectures or educational activities not funded by industry; serves on the editorial boards of Stroke, Cerebrovascular Disease, Neurology (R), and the Journal of Alzheimer's Disease and Other Dementias; and receives research support from the NIH (R01AG026484 [PI], K24NS056207 [PI], R01AG021084 [Co-I], R01NS042147 [PI], and U54NS057405 [Co-I]) and the Alzheimer's Association. NR 10 TC 164 Z9 174 U1 1 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR 27 PY 2010 VL 74 IS 17 BP 1346 EP 1350 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 588GS UT WOS:000277057200004 PM 20421578 ER PT J AU Nahrendorf, M Keliher, E Marinelli, B Waterman, P Feruglio, PF Fexon, L Pivovarov, M Swirski, FK Pittet, MJ Vinegoni, C Weissleder, R AF Nahrendorf, Matthias Keliher, Edmund Marinelli, Brett Waterman, Peter Feruglio, Paolo Fumene Fexon, Lioubov Pivovarov, Misha Swirski, Filip K. Pittet, Mikael J. Vinegoni, Claudio Weissleder, Ralph TI Hybrid PET-optical imaging using targeted probes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE fluorescence-mediated tomography; molecular imaging; multimodal image fusion; computed tomography ID NANOPARTICLE; CANCER; ATHEROSCLEROSIS; CT; IDENTIFICATION; INFORMATION; MACROPHAGES; EXPRESSION AB Fusion imaging of radionuclide-based molecular (PET) and structural data [x-ray computed tomography (CT)] has been firmly established. Here we show that optical measurements [fluorescence-mediated tomography (FMT)] show exquisite congruence to radionuclide measurements and that information can be seamlessly integrated and visualized. Using biocompatible nanoparticles as a generic platform (containing a (18)F isotope and a far red fluorochrome), we show good correlations between FMT and PET in probe concentration (r(2) > 0.99) and spatial signal distribution (r(2) > 0.85). Using a mouse model of cancer and different imaging probes to measure tumoral proteases, macrophage content and integrin expression simultaneously, we demonstrate the distinct tumoral locations of probes in multiple channels in vivo. The findings also suggest that FMT can serve as a surrogate modality for the screening and development of radionuclide-based imaging agents. C1 [Nahrendorf, Matthias] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Nahrendorf, M (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. EM MNahrendorf@mgh.harvard.edu; rweissleder@mgh.harvard.edu FU National Institutes of Health [R01 EB006432, P50-CA86355, R24 CA92782, U54 CA126515, UO1 HL08073, R01HL096576]; American Heart Association [0835623D]; Regione Veneto and CARIVERONA Foundation FX We thank Andita Newton, the Center for Systems Biology Mouse Imaging Program (Yoshiko Iwamoto and Jessica Sullivan), Nikolai Sergeyev, and Wael Yared for technical support and helpful discussions. We also thank Michael J. Welch (Washington University) for providing the 64Cu used in this study. This work was funded in part by National Institutes of Health Grants R01 EB006432, P50-CA86355, R24 CA92782, U54 CA126515, and UO1 HL08073 (to R. W.), R01HL096576 and American Heart Association Grant 0835623D (to M.N.), and the Regione Veneto and CARIVERONA Foundation (P.F.F.). NR 37 TC 119 Z9 121 U1 4 U2 45 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 27 PY 2010 VL 107 IS 17 BP 7910 EP 7915 DI 10.1073/pnas.0915163107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 588QQ UT WOS:000277088700056 PM 20385821 ER PT J AU Luthi-Carter, R Taylor, DM Pallos, J Lambert, E Amore, A Parker, A Moffitt, H Smith, DL Runne, H Gokce, O Kuhn, A Xiang, ZM Maxwell, MM Reeves, SA Bates, GP Neri, C Thompson, LM Marsh, JL Kazantsev, AG AF Luthi-Carter, Ruth Taylor, David M. Pallos, Judit Lambert, Emmanuel Amore, Allison Parker, Alex Moffitt, Hilary Smith, Donna L. Runne, Heike Gokce, Ozgun Kuhn, Alexandre Xiang, Zhongmin Maxwell, Michele M. Reeves, Steven A. Bates, Gillian P. Neri, Christian Thompson, Leslie M. Marsh, J. Lawrence Kazantsev, Aleksey G. TI SIRT2 inhibition achieves neuroprotection by decreasing sterol biosynthesis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cholesterol; Huntington's disease; metabolism; sirtuin; transcription factor SREBP-2 ID HUNTINGTONS-DISEASE; CHOLESTEROL-BIOSYNTHESIS; HISTONE DEACETYLASE; ALZHEIMERS-DISEASE; IN-VITRO; PARKINSONS-DISEASE; MOUSE MODEL; BRAIN; GENE; MICE AB Huntington's disease (HD), an incurable neurodegenerative disorder, has a complex pathogenesis including protein aggregation and the dysregulation of neuronal transcription and metabolism. Here, we demonstrate that inhibition of sirtuin 2 (SIRT2) achieves neuroprotection in cellular and invertebrate models of HD. Genetic or pharmacologic inhibition of SIRT2 in a striatal neuron model of HD resulted in gene expression changes including significant down-regulation of RNAs responsible for sterol biosynthesis. Whereas mutant huntingtin fragments increased sterols in neuronal cells, SIRT2 inhibition reduced sterol levels via decreased nuclear trafficking of SREBP-2. Importantly, manipulation of sterol biosynthesis at the transcriptional level mimicked SIRT2 inhibition, demonstrating that the metabolic effects of SIRT2 inhibition are sufficient to diminish mutant huntingtin toxicity. These data identify SIRT2 inhibition as a promising avenue for HD therapy and elucidate a unique mechanism of SIRT2-inhibitor-mediated neuroprotection. Furthermore, the ascertainment of SIRT2's role in regulating cellular metabolism demonstrates a central function shared with other sirtuin proteins. C1 [Luthi-Carter, Ruth; Taylor, David M.; Runne, Heike; Gokce, Ozgun; Kuhn, Alexandre] Ecole Polytech Fed Lausanne, Brain Mind Inst, CH-1015 Lausanne, Switzerland. [Pallos, Judit; Marsh, J. Lawrence] Univ Calif Irvine, Ctr Dev Biol, Irvine, CA 92697 USA. [Thompson, Leslie M.] Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92697 USA. [Thompson, Leslie M.] Univ Calif Irvine, Dept Neurobiol & Behav, Irvine, CA 92697 USA. [Thompson, Leslie M.] Univ Calif Irvine, Dept Biol Chem, Irvine, CA 92697 USA. [Marsh, J. Lawrence] Univ Calif Irvine, Dept Dev & Cell Biol, Irvine, CA 92697 USA. [Marsh, J. Lawrence] Univ Calif Irvine, Dept Pathol, Irvine, CA 92697 USA. [Lambert, Emmanuel; Parker, Alex; Neri, Christian] INSERM, U894, Lab Neuronal Cell Biol & Pathol, F-75014 Paris, France. [Lambert, Emmanuel; Parker, Alex; Neri, Christian] Univ Paris 05, EA 4059, F-75014 Paris, France. [Amore, Allison; Xiang, Zhongmin; Maxwell, Michele M.; Reeves, Steven A.; Kazantsev, Aleksey G.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Boston, MA 02129 USA. [Moffitt, Hilary; Smith, Donna L.; Bates, Gillian P.] Kings Coll London, Dept Med & Mol Genet, London SE1 9RT, England. [Maxwell, Michele M.; Kazantsev, Aleksey G.] Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Luthi-Carter, R (reprint author), Ecole Polytech Fed Lausanne, Brain Mind Inst, CH-1015 Lausanne, Switzerland. EM ruth.luthi-carter@epfl.ch; akazantsev@partners.org RI Neri, Christian/F-6729-2013; Parker, Alex/F-4953-2014; OI Parker, Alex/0000-0002-3333-2445; gokce, ozgun/0000-0001-6319-404X; Bates, Gillian/0000-0002-4041-6305 FU National Drosophila Stock Center in Bloomington, IN; CHDI Foundation; Swiss National Science Foundation; Ecole Polytechnique Federale de Lausanne; Institut National de la Sante et de la Recherche Medicale; Wellcome Trust; Medical Research Council; Hereditary Disease Foundation; Huntington's Disease Society of America Coalition for the Cure; National Institutes of Health [NS52789, HD36081, NS045283] FX We thank A. Pailluson, O. Hagenbuchle, and the Lausanne DNA Array facility; C. Wellington and M. Hayden (University of British Columbia, Vancouver) for Htt constructs; M. Rey, M. Dixon, M. Forrest, and L. Feletti for cloning and primary cultures; and the National Drosophila Stock Center in Bloomington, IN, for clones and support. We also thank J. Auwerx, H. Yamamoto, and L. Quinti for helpful discussions and critical reading of the manuscript. This work was supported by a generous gift for Discovery Novel Neurodegenerative Disease Therapeutics to MassGeneral Institute for Neurodegenerative Disease and grants from the CHDI Foundation (to A.A., A.G.K., G.P.B., L.M.T., and J.L.M.), the Swiss National Science Foundation (to R. L.-C. and H. R.), the Ecole Polytechnique Federale de Lausanne (to R.L.-C. and A.K.), Institut National de la Sante et de la Recherche Medicale (to J.P. and C.N.), the Wellcome Trust (to G. P. B.), Medical Research Council (to G. P. B.), the Hereditary Disease Foundation (to L.M.T. and J.L.M.), the Huntington's Disease Society of America Coalition for the Cure (to L.M.T.), and National Institutes of Health Awards NS52789 (to L.M.T. and J.L.M.), HD36081 (to J.L.M.), and NS045283 (to J. NR 42 TC 137 Z9 141 U1 0 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 27 PY 2010 VL 107 IS 17 BP 7927 EP 7932 DI 10.1073/pnas.1002924107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 588QQ UT WOS:000277088700059 PM 20378838 ER PT J AU Campbell, EG AF Campbell, Eric G. TI Public Disclosure of Conflicts of Interest Moving the Policy Debate Forward SO ARCHIVES OF INTERNAL MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. RP Campbell, EG (reprint author), Massachusetts Gen Hosp, Inst Hlth Policy, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM ecampbell@partners.org NR 4 TC 5 Z9 5 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD APR 26 PY 2010 VL 170 IS 8 BP 667 EP 667 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 588JD UT WOS:000277064800001 PM 20421548 ER PT J AU Murphy, RA Sunpath, H Lu, ZG Chelin, N Losina, E Gordon, M Ross, D Ewusi, AD Matthews, LT Kuritzkes, DR Marconi, VC AF Murphy, Richard A. Sunpath, Henry Lu, Zhigang Chelin, Neville Losina, Elena Gordon, Michelle Ross, Douglas Ewusi, Aba D. Matthews, Lynn T. Kuritzkes, Daniel R. Marconi, Vincent C. CA S Africa Resistance Cohort Study T TI Outcomes after virologic failure of first-line ART in South Africa SO AIDS LA English DT Article DE HIV-1 drug resistance; resource-limited settings; second-line antiretroviral therapy; South Africa; virologic failure ID ANTIRETROVIRAL THERAPY; ADHERENCE; HIV; ADULTS; HAART AB Objective: To determine initial 24-week outcomes among prospectively enrolled patients with failure of initial antiretroviral therapy (ART). Methods: Baseline virologic failure was defined as HIV-1 viral load greater than 1000 copies/ml. Second-line ART was informed by results of genotype testing and selected from agents in the South-African public sector. Twenty-four week endpoints included virologic suppression and mortality. Results: The cohort consisted of 141 patients (median CD4 cell count and viral load at failure of 173 cells/mu l and 17 500 copies/ml). The median prior duration of initial ART was 12.0 months. At least one major resistance mutation was found in 87% of patients. After 24 weeks of follow-up, intent-to-treat virologic suppression (<50 copies/ml) was 65%, as-treated virologic suppression was 78%, the median CD4 cell count improvement was 88 cells/mu l and the mortality was 6%. The median CD4 cell count at initial virologic failure among those who died was 70 cells/mu l, compared to 182 cells/mu l among patients who survived (P = 0.01). Patients with wild-type virus at initial failure (N = 19) had inferior outcomes after switch. The presence of nucleoside analogue resistance mutations at failure did not affect early efficacy of boosted-protease inhibitor regimens. Conclusions: Virologic monitoring linked to resistance testing helped demonstrate the efficacy of lopinavir/ritonavir-containing second-line regimens in South Africa. A switch to second-line regimens in patients with virologic failure and drug resistance has substantial and rapid immunological and clinical benefits. Resistance testing identified a high-risk group without resistance who might benefit from increased medication access and/or adherence support. (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins C1 [Murphy, Richard A.] Doctors Without Borders, Operat Support Unit, New York, NY USA. [Sunpath, Henry; Chelin, Neville] McCord Hosp, Durban, South Africa. [Lu, Zhigang; Losina, Elena] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gordon, Michelle] Nelson Mandela Sch Med, Durban, South Africa. [Ross, Douglas] St Marys Hosp, Mariannhill, South Africa. [Ewusi, Aba D.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Matthews, Lynn T.] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA USA. [Kuritzkes, Daniel R.] Brigham & Womens Hosp, Sect Retroviral Therapeut, Boston, MA 02115 USA. [Marconi, Vincent C.] San Antonio Mil Med Ctr, Infect Dis Serv, Ft Sam Houston, TX USA. [Marconi, Vincent C.] Emory Univ, Sch Med, Atlanta, GA USA. RP Murphy, RA (reprint author), Doctors Without Borders USA, 333 7th Ave,2nd Floor, New York, NY 10001 USA. EM ramurphy@gmail.com RI Marconi, Vincent/N-3210-2014; OI Marconi, Vincent/0000-0001-8409-4689; Reddi, Anand/0000-0002-8360-8737 FU NIH [P30 AI60354, K24 RR16482]; Harvard Program on AIDS, CDC Cooperative Agreement [U62/CCU123541-01]; Schwartz Global Health Fellowship and Elizabeth Glaser Pediatric AIDS Foundation [HEART] FX Grant support from Gilead, NIH (P30 AI60354 to Harvard CFAR and K24 RR16482 to D. R. K.), Harvard Program on AIDS, CDC Cooperative Agreement (U62/CCU123541-01), Schwartz Global Health Fellowship and Elizabeth Glaser Pediatric AIDS Foundation (Project HEART). NR 10 TC 37 Z9 38 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD APR 24 PY 2010 VL 24 IS 7 BP 1007 EP 1012 DI 10.1097/QAD.0b013e3283333639 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 582AN UT WOS:000276567500009 PM 20397305 ER PT J AU Scher, HI Beer, TM Higano, CS Anand, A Taplin, ME Efstathiou, E Rathkopf, D Shelkey, J Yu, EY Alumkal, J Hung, D Hirmand, M Seely, L Morris, MJ Danila, DC Humm, J Larson, S Fleisher, M Sawyers, CL AF Scher, Howard I. Beer, Tomasz M. Higano, Celestia S. Anand, Aseem Taplin, Mary-Ellen Efstathiou, Eleni Rathkopf, Dana Shelkey, Julia Yu, Evan Y. Alumkal, Joshi Hung, David Hirmand, Mohammad Seely, Lynn Morris, Michael J. Danila, Daniel C. Humm, John Larson, Steve Fleisher, Martin Sawyers, Charles L. CA Prostate Canc Fdn TI Antitumour activity of MDV3100 in castration-resistant prostate cancer: a phase 1-2 study SO LANCET LA English DT Article ID CIRCULATING TUMOR-CELLS; METASTATIC COLORECTAL-CANCER; HORMONAL-THERAPY; CLINICAL-TRIALS; SURVIVAL; PROGRESSION; MUTATIONS; IMATINIB; GENE; TESTOSTERONE AB Background MDV3100 is an androgen-receptor antagonist that blocks androgens from binding to the androgen receptor and prevents nuclear translocation and co-activator recruitment of the ligand-receptor complex. It also induces tumour cell apoptosis, and has no agonist activity. Because growth of castration-resistant prostate cancer is dependent on continued androgen-receptor signalling, we assessed the antitumour activity and safety of MDV3100 in men with this disease. Methods This phase 1-2 study was undertaken in five US centres in 140 patients. Patients with progressive, metastatic, castration-resistant prostate cancer were enrolled in dose-escalation cohorts of three to six patients and given an oral daily starting dose of MDV3100 30 mg. The final daily doses studied were 30 mg (n=3), 60 mg (27), 150 mg (28), 240 mg (29), 360 mg (28), 480 mg (22), and 600 mg (3). The primary objective was to identify the safety and tolerability profile of MDV3100 and to establish the maximum tolerated dose. The trial is registered with ClinicalTrials.gov, number NCT00510718. Findings We noted antitumour effects at all doses, including decreases in serum prostate-specific antigen of 50% or more in 78 (56%) patients, responses in soft tissue in 13 (22%) of 59 patients, stabilised bone disease in 61 (56%) of 109 patients, and conversion from unfavourable to favourable circulating tumour cell counts in 25 (49%) of the 51 patients. PET imaging of 22 patients to assess androgen-receptor blockade showed decreased (18)F-fluoro-5 alpha-dihydrotestosterone binding at doses from 60 mg to 480 mg per day (range 20-100%). The median time to progression was 47 weeks (95% CI 34 not reached) for radiological progression. The maximum tolerated dose for sustained treatment (>28 days) was 240 mg. The most common grade 3-4 adverse event was dose-dependent fatigue (16 [11%] patients), which generally resolved after dose reduction. Interpretation We recorded encouraging antitumour activity with MDV3100 in patients with castration-resistant prostate cancer. The results of this phase 1-2 trial validate in man preclinical studies implicating sustained androgen-receptor signalling as a driver in this disease. C1 [Scher, Howard I.] Mem Sloan Kettering Canc Ctr, Dept Med, Genitourinary Oncol Serv, Sidney Kimmel Ctr Prostate & Urol Canc, New York, NY 10021 USA. [Larson, Steve] Mem Sloan Kettering Canc Ctr, Dept Med Phys, New York, NY 10021 USA. [Humm, John] Mem Sloan Kettering Canc Ctr, Nucl Med Serv, Dept Med Imaging, New York, NY 10021 USA. [Fleisher, Martin] Mem Sloan Kettering Canc Ctr, Dept Clin Labs, New York, NY 10021 USA. [Sawyers, Charles L.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10021 USA. [Beer, Tomasz M.; Alumkal, Joshi] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Sawyers, Charles L.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Higano, Celestia S.; Yu, Evan Y.] Univ Washington, Seattle, WA 98195 USA. [Taplin, Mary-Ellen] Dana Farber Canc Inst, Boston, MA 02115 USA. [Efstathiou, Eleni] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Hung, David; Hirmand, Mohammad; Seely, Lynn] Medivation, San Francisco, CA USA. RP Scher, HI (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, Genitourinary Oncol Serv, Sidney Kimmel Ctr Prostate & Urol Canc, 1275 York Ave, New York, NY 10021 USA. EM scherh@mskcc.org RI Sawyers, Charles/G-5327-2016; Anand, Aseem/P-1214-2014; OI Anand, Aseem/0000-0002-3606-540X; Rathkopf, Dana/0000-0002-4503-7582; Morris, Michael J./0000-0002-9454-0096 FU Medivation; National Cancer Institute [P50-CA92629, P50-CA97186, P50-CA086438]; Howard Hughes Medical Institute; Doris Duke Charitable Foundation; Department of Defense Prostate Cancer Research Program Clinical Consortium [W81XWH-06-2-0011, W81XWH-06-1-0237, W81XWH-07-1-0097, W81XWH-06-1-0261, W81XWH-06-1-0203] FX Support for this research came from Medivation; the Prostate Cancer Foundation, P50-CA92629 MSKCC Specialized Program in Research Excellence in Prostate Cancer grant from the National Cancer Institute; P50-CA97186 The University of Washington and Oregon Health and Science University Knight Cancer Institute Specialized Program in Research Excellence in Prostate Cancer Grant from the National Cancer Institute; P50-CA086438 MSKCC Center for Molecular Imaging in Cancer from the National Cancer Institute; the Howard Hughes Medical Institute; Doris Duke Charitable Foundation; and Department of Defense Prostate Cancer Research Program Clinical Consortium (Memorial Sloan-Kettering Cancer Center W81XWH-06-2-0011; Oregon Health and Science University Knight Cancer Institute: W81XWH-06-1-0237; The University of Washington: W81XWH-07-1-0097; Dana-Farber Cancer Institute: W81XWH-06-1-0261; MD Anderson Cancer Center W81XWH-06-1-0203). We thank Janet Novak of Helix Editing for editing of the report. Janet Novak was paid for her work by Memorial Sloan-Kettering Cancer Center. NR 30 TC 545 Z9 556 U1 3 U2 44 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD APR 24 PY 2010 VL 375 IS 9724 BP 1437 EP 1446 DI 10.1016/S0140-6736(10)60172-9 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 590FL UT WOS:000277210000030 PM 20398925 ER PT J AU Sharma, S Liao, SL AF Sharma, Shikha Liao, Steve L. TI Chest pain? Bridging the gap in diagnosis SO LANCET LA English DT Editorial Material ID MYOCARDIAL BRIDGE C1 [Sharma, Shikha; Liao, Steve L.] James J Peters VA Med Ctr, Dept Med, Cardiol Sect, Bronx, NY 10468 USA. [Liao, Steve L.] Mt Sinai Sch Med, Ctr Cardiovasc Hlth, Zena & Michael A Wiener Cardiovasc Inst, New York, NY USA. RP Liao, SL (reprint author), James J Peters VA Med Ctr, Dept Med, Cardiol Sect, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Steve.Liao@va.gov NR 5 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD APR 24 PY 2010 VL 375 IS 9724 BP 1494 EP 1494 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 590FL UT WOS:000277210000036 PM 20417860 ER PT J AU Yoo, AJ Romero, J Hakimelahi, R Nogueira, RG Rabinov, JD Pryor, JC Gonzalez, G Hirsch, JA Schaefer, PW AF Yoo, Albert J. Romero, Javier Hakimelahi, Reza Nogueira, Raul G. Rabinov, James D. Pryor, Johnny C. Gonzalez, Gilberto Hirsch, Joshua A. Schaefer, Pamela W. TI Predictors of functional outcome vary by the hemisphere of involvement in major ischemic stroke treated with intra-arterial therapy: a retrospective cohort study SO BMC NEUROLOGY LA English DT Article ID CEREBRAL-ARTERY OCCLUSION; FINAL INFARCT; MERCI TRIAL; PROACT-II; FOLLOW-UP; THROMBOLYSIS; SCALE; LATERALIZATION; RECANALIZATION; CLASSIFICATION AB Background: Conflicting data exists regarding the effect of hemispheric lateralization on acute ischemic stroke outcome. Some of this variability may be related to heterogeneous study populations, particularly with respect to the level of arterial occlusion. Furthermore, little is known about the relationship between stroke lateralization and predictors of outcome. The purpose of this study was to characterize the impact of stroke lateralization on both functional outcome and its predictors in a well-defined population of anterior circulation proximal artery occlusions treated with IAT. Methods: Thirty-five consecutive left-and 35 consecutive right-sided stroke patients with intracranial ICA and/or MCA occlusions who underwent IAT were retrospectively analyzed. Ischemic change on pre-treatment imaging was quantified. Reperfusion success was graded using the Mori scale. Good outcome at three months was defined as an mRS <= 2. Left-and right-sided strokes were compared for outcome and its predictors. Result: Of 70 patients with median NIHSS score of 18 (IQR, 14-21), 19 (27.1%) had a good outcome. There were 21 terminal ICA and 49 MCA occlusions. There was no difference in the rate of good outcomes between left-(n = 9) and right-sided (n = 10) strokes (p = 0.99). There were no significant differences in occlusion level, age, ischemic change on initial imaging and degree of reperfusion between left-and right-sided strokes. Left-sided strokes had higher baseline NIHSS scores (p = 0.02) and lower admission SBP (p = 0.009). Independent predictors of outcome for left-sided strokes were NIHSS (p = 0.0002) and reperfusion (p = 0.006), and for right-sided strokes were age (p = 0.002) and reperfusion (p = 0.003). In univariate analysis, pre-treatment ischemic change on NCCT was associated with outcome only for left-sided strokes (p = 0.05). Conclusions: In anterior circulation proximal artery occlusions treated with IAT, hemispheric lateralization influences the clinical and imaging predictors of outcome. Most notably, NIHSS predicts outcome only for the left-sided strokes in this population. This finding has important implications for outcome prediction in the acute setting and indicates a need for stroke severity scales more sensitive to right hemispheric deficits. C1 [Yoo, Albert J.; Romero, Javier; Hakimelahi, Reza; Gonzalez, Gilberto; Schaefer, Pamela W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroradiol Div,Dept Radiol, Boston, MA 02114 USA. [Yoo, Albert J.; Nogueira, Raul G.; Rabinov, James D.; Pryor, Johnny C.; Hirsch, Joshua A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Intervent Neuroradiol Div,Dept Radiol, Boston, MA 02114 USA. [Nogueira, Raul G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. RP Yoo, AJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroradiol Div,Dept Radiol, Boston, MA 02114 USA. EM ajyoo@partners.org FU National Institutes of Health, National Institute of Neurological Disorders and Stroke [NS050041] FX Albert J. Yoo, M. D., was the 2006-7 recipient of the Neuroradiology Education and Research Foundation/Boston Scientific Fellowship in Cerebrovascular Disease Research. This study was supported in part by the National Institutes of Health through a grant from the National Institute of Neurological Disorders and Stroke NS050041 (to RGG). NR 36 TC 8 Z9 8 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2377 J9 BMC NEUROL JI BMC Neurol. PD APR 23 PY 2010 VL 10 AR 25 DI 10.1186/1471-2377-10-25 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA 603RY UT WOS:000278226900001 PM 20416087 ER PT J AU Astronomo, RD Kaltgrad, E Udit, AK Wang, SK Doores, KJ Huang, CY Pantophlet, R Paulson, JC Wong, CH Finn, MG Burton, DR AF Astronomo, Rena D. Kaltgrad, Eiton Udit, Andrew K. Wang, Sheng-Kai Doores, Katie J. Huang, Cheng-Yuan Pantophlet, Ralph Paulson, James C. Wong, Chi-Huey Finn, M. G. Burton, Dennis R. TI Defining Criteria for Oligomannose Immunogens for HIV Using Icosahedral Virus Capsid Scaffolds SO CHEMISTRY & BIOLOGY LA English DT Article ID COWPEA MOSAIC-VIRUS; AZIDE-ALKYNE CYCLOADDITION; NEUTRALIZING ANTIBODY 2G12; HUMAN MONOCLONAL-ANTIBODY; GP120 ENVELOPE GLYCOPROTEIN; CROSS-CLADE NEUTRALIZATION; 2.8 ANGSTROM RESOLUTION; BACTERIOPHAGE-Q-BETA; CRYSTAL-STRUCTURE; ANTI-HIV-1 ANTIBODY AB The broadly neutralizing antibody 2G12 recognizes a conserved cluster of high-mannose glycans on the surface envelope spike of HIV, suggesting that the "glycan shield" defense of the virus can be breached and may, under the right circumstances, serve as a vaccine target. In an attempt to recreate features of the glycan shield semisynthetically, oligomannosides were coupled to surface lysines on the icosahedral capsids of bacteriophage Q beta and cowpea mosaic virus (CPMV). The Q beta glycoconjugates, but not CPMV, presented oligomannose clusters that bind the antibody 2G12 with high affinity. However, antibodies against these 2G12 epitopes were not detected in immunized rabbits. Rather, alternative oligomannose epitopes on the conjugates were immunodominant and elicited high titers of anti-mannose antibodies that do not crossreact with the HIV envelope. The results presented reveal important design considerations for a carbohydrate-based vaccine component for HIV. C1 [Kaltgrad, Eiton; Udit, Andrew K.; Wang, Sheng-Kai; Huang, Cheng-Yuan; Wong, Chi-Huey; Finn, M. G.] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA. [Astronomo, Rena D.; Doores, Katie J.; Pantophlet, Ralph; Burton, Dennis R.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. [Kaltgrad, Eiton; Udit, Andrew K.; Wang, Sheng-Kai; Huang, Cheng-Yuan; Wong, Chi-Huey; Finn, M. G.] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. [Doores, Katie J.; Burton, Dennis R.] Massachusetts Gen Hosp, Ragon Inst, MIT, Boston, MA 02129 USA. [Doores, Katie J.; Burton, Dennis R.] Harvard Univ, Boston, MA 02129 USA. [Paulson, James C.] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. [Paulson, James C.] Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 USA. [Burton, Dennis R.] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA. RP Finn, MG (reprint author), Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA. EM mgfinn@scripps.edu; burton@scripps.edu OI Doores, Katie/0000-0002-5507-1725 FU NIGMS [GM062116]; Natural Sciences and Engineering Research Council of Canada; Canadian Institutes of Health Research; International AIDS Vaccine Initiative; Skaggs Institute for Chemical Biology; National Institutes of Health [AI33292, AI060425, GM083658]; Ragon Institute FX We greatly appreciate the gift of 2G12 from Gabriela Stiegler and Hermann Katinger (Polymun Scientific, Vienna, Austria; University of Natural Resources and Applied Life Sciences, Vienna, Austria) and the glycan array resources provided by Core D and Core H of the CFG funded by NIGMS (GM062116). We also thank Michael Huber for critical reading of the manuscript. The work was supported by the Natural Sciences and Engineering Research Council of Canada (to R.D.A.), the Canadian Institutes of Health Research (to A.K.U.), the Neutralizing Antibody Consortium of the International AIDS Vaccine Initiative (to D.R.B.), the Skaggs Institute for Chemical Biology (to M.G.F.), the National Institutes of Health (AI33292 and AI060425 to D.R.B. and GM083658 to M.G.F.), and the Ragon Institute (to D.R.B. and K.J.D.). NR 66 TC 67 Z9 67 U1 1 U2 20 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-5521 J9 CHEM BIOL JI Chem. Biol. PD APR 23 PY 2010 VL 17 IS 4 BP 357 EP 370 DI 10.1016/j.chembiol.2010.03.012 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 595TY UT WOS:000277637300010 PM 20416507 ER PT J AU Tsai, SE Shameli, A Yamanouchi, J Clemente-Casares, X Wang, JG Serra, P Yang, Y Medarova, Z Moore, A Santamaria, P AF Tsai, Sue Shameli, Afshin Yamanouchi, Jun Clemente-Casares, Xavier Wang, Jinguo Serra, Pau Yang, Yang Medarova, Zdravka Moore, Anna Santamaria, Pere TI Reversal of Autoimmunity by Boosting Memory-like Autoregulatory T Cells SO IMMUNITY LA English DT Article ID NONOBESE DIABETIC MICE; AVIDITY MATURATION; NOD MICE; POPULATION; EFFECTOR; TOLERANCE; RESPONSES; ANTIGENS; IMMUNITY; PEPTIDE AB Blunting autoreactivity without compromising immunity remains an elusive goal in the treatment of autoimmunity. We show that progression to autoimmune diabetes results in the conversion of naive low-avidity autoreactive CD8(+) T cells into memory-like autoregulatory cells that can be expanded in vivo with nanoparticles coated with disease-relevant peptide-major histocompatibility complexes (pMHC-NP). Treatment of NOD mice with monospecific pMHC-NPs expanded cognate autoregulatory T cells, suppressed the recruitment of noncognate specificities, prevented disease in prediabetic mice, and restored normoglycemia in diabetic animals. pMHC-NP therapy was inconsequential in mice engineered to bear an immune system unresponsive to the corresponding epitope, owing to absence of epitope-experienced autoregulatory T cells. pMHC-NP-expanded autoregulatory T cells suppressed local presentation of autoantigens in an interferon-gamma-, indoleamine 2,3-dioxygenase-, and perforin-dependent manner. Nanoparticles coated with human diabetes-relevant pHLA complexes restored normoglycemia in a humanized model of diabetes. These observations expose a paradigm in the pathogenesis of autoimmunity amenable for therapeutic intervention. C1 [Tsai, Sue; Shameli, Afshin; Yamanouchi, Jun; Clemente-Casares, Xavier; Wang, Jinguo; Serra, Pau; Yang, Yang; Santamaria, Pere] Univ Calgary, Dept Microbiol & Infect Dis, Julia McFarlane Diabet Res Ctr, Calgary, AB T2N 4N1, Canada. [Tsai, Sue; Shameli, Afshin; Yamanouchi, Jun; Clemente-Casares, Xavier; Wang, Jinguo; Serra, Pau; Yang, Yang; Santamaria, Pere] Univ Calgary, Inst Inflammat Infect & Immun, Calgary, AB T2N 4N1, Canada. [Yang, Yang] Univ Calgary, Fac Med, Dept Biochem & Mol Biol, Calgary, AB T2N 4N1, Canada. [Medarova, Zdravka; Moore, Anna] Massachusetts Gen Hosp, Dept Radiol, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Mol Imaging Lab, Charlestown, MA 02129 USA. RP Santamaria, P (reprint author), Univ Calgary, Dept Microbiol & Infect Dis, Julia McFarlane Diabet Res Ctr, 3330 Hosp Dr NW, Calgary, AB T2N 4N1, Canada. EM psantama@ucalgary.ca FU Canadian Institutes of Health Research; Juvenile Diabetes Research Foundation (JDRF); Natural Sciences and Engineering Research Council of Canada; Canadian Diabetes Association (CDA); Alberta Innovates-Health Solutions; Diabetes Association (Foothills) FX We thank N Ghyselinck for the pFIEx vector, V Cerundolo for the A2-Kb construct, D Serreze for NOD Ifng-/- and NOD HHD mice. S Bou, M DeCrom, M Foote. C Gwozd, B Han, T Irvine, J Mauricio, H Metselaar and S Thiessen for technical assistance. L Kennedy and L Robertson for FACS, C Huang for help with IPGTTs, and L Edelstein-Keshet, J Elliott, A Khadra, Y Shi, T Stratmann, and J Verdaguer for reading the manuscript This work was supported by the Canadian Institutes of Health Research, the Juvenile Diabetes Research Foundation (JDRF), the Natural Sciences and Engineering Research Council of Canada, and the Canadian Diabetes Association (CDA) S T,A S, and P Serra were supported by Alberta Innovates-Health Solutions, and J W is supported by the CDA P Santamaria is a Scientist of Alberta Innovates and a JDRF Scholar The JMDRC is supported by the Diabetes Association (Foothills) NR 33 TC 108 Z9 113 U1 4 U2 17 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD APR 23 PY 2010 VL 32 IS 4 BP 568 EP 580 DI 10.1016/j.immuni.2010.03.015 PG 13 WC Immunology SC Immunology GA 589RW UT WOS:000277171900015 PM 20381385 ER PT J AU Caccamo, A Majumder, S Richardson, A Strong, R Oddo, S AF Caccamo, Antonella Majumder, Smita Richardson, Arlan Strong, Randy Oddo, Salvatore TI Molecular Interplay between Mammalian Target of Rapamycin (mTOR), Amyloid-beta, and Tau EFFECTS ON COGNITIVE IMPAIRMENTS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PAIRED HELICAL FILAMENTS; TRIPLE-TRANSGENIC MODEL; P70 S6 KINASE; ALZHEIMERS-DISEASE; A-BETA; LIFE-SPAN; SIGNALING PATHWAY; PROTEIN-TAU; GLYCOPROTEIN COMPLEX; INDUCED APOPTOSIS AB Accumulation of amyloid-beta (A beta) and Tau is an invariant feature of Alzheimer disease (AD). The upstream role of A beta accumulation in the disease pathogenesis is widely accepted, and there is strong evidence showing that A beta accumulation causes cognitive impairments. However, the molecular mechanisms linking A beta to cognitive decline remain to be elucidated. Here we show that the buildup of A beta increases the mammalian target of rapamycin (mTOR) signaling, whereas decreasing mTOR signaling reduces A beta levels, thereby highlighting an interrelation between mTOR signaling and A beta. The mTOR pathway plays a central role in controlling protein homeostasis and hence, neuronal functions; indeed mTOR signaling regulates different forms of learning and memory. Using an animal model of AD, we show that pharmacologically restoring mTOR signaling with rapamycin rescues cognitive deficits and ameliorates A beta and Tau pathology by increasing autophagy. Indeed, we further show that autophagy induction is necessary for the rapamycin mediated reduction in A beta levels. The results presented here provide a molecular basis for the A beta-induced cognitive deficits and, moreover, show that rapamycin, an FDA approved drug, improves learning and memory and reduces A beta and Tau pathology. C1 [Caccamo, Antonella; Majumder, Smita; Oddo, Salvatore] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78245 USA. [Caccamo, Antonella; Majumder, Smita; Richardson, Arlan; Strong, Randy; Oddo, Salvatore] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78245 USA. [Strong, Randy] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78245 USA. [Richardson, Arlan] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78245 USA. [Richardson, Arlan; Strong, Randy] S Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA. [Richardson, Arlan; Strong, Randy] S Texas Vet Hlth Care Syst, Res Serv, San Antonio, TX 78229 USA. RP Oddo, S (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM oddo@uthscsa.edu FU NIA [AG29729-4]; San Antonio Nathan Shock Aging Center [1P30-AG-13319]; Department of Veterans Affairs FX This work was supported, in whole or in part, by National Institutes of Health Grant AG29729-4 from the NIA (to S. O.), San Antonio Nathan Shock Aging Center Grant 1P30-AG-13319, and a grant from the Department of Veterans Affairs Enhancement Award Program. NR 76 TC 305 Z9 325 U1 8 U2 43 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 23 PY 2010 VL 285 IS 17 BP 13107 EP 13120 DI 10.1074/jbc.M110.100420 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 584XO UT WOS:000276787800067 PM 20178983 ER PT J AU Jo, H Loison, F Hattori, H Silberstein, LE Yu, HT Luo, HR AF Jo, Hakryul Loison, Fabien Hattori, Hidenori Silberstein, Leslie E. Yu, Hongtao Luo, Hongbo R. TI Natural Product Celastrol Destabilizes Tubulin Heterodimer and Facilitates Mitotic Cell Death Triggered by Microtubule-Targeting Anti-Cancer Drugs SO PLOS ONE LA English DT Article ID KAPPA-B ACTIVATION; CAP-GLY DOMAINS; INDUCED APOPTOSIS; CANCER; PROTEIN; BINDING; ARREST; PARTHENOLIDE; PACLITAXEL; TRITERPENE AB Background: Microtubule drugs are effective anti-cancer agents, primarily due to their ability to induce mitotic arrest and subsequent cell death. However, some cancer cells are intrinsically resistant or acquire a resistance. Lack of apoptosis following mitotic arrest is thought to contribute to drug resistance that limits the efficacy of the microtubule-targeting anticancer drugs. Genetic or pharmacological agents that selectively facilitate the apoptosis of mitotic arrested cells present opportunities to strengthen the therapeutic efficacy. Methodology and Principal Findings: We report a natural product Celastrol targets tubulin and facilitates mitotic cell death caused by microtubule drugs. First, in a small molecule screening effort, we identify Celastrol as an inhibitor of neutrophil chemotaxis. Subsequent time-lapse imaging analyses reveal that inhibition of microtubule-mediated cellular processes, including cell migration and mitotic chromosome alignment, is the earliest events affected by Celastrol. Disorganization, not depolymerization, of mitotic spindles appears responsible for mitotic defects. Celastrol directly affects the biochemical properties of tubulin heterodimer in vitro and reduces its protein level in vivo. At the cellular level, Celastrol induces a synergistic apoptosis when combined with conventional microtubule-targeting drugs and manifests an efficacy toward Taxol-resistant cancer cells. Finally, by time-lapse imaging and tracking of microtubule drug-treated cells, we show that Celastrol preferentially induces apoptosis of mitotic arrested cells in a caspase-dependent manner. This selective effect is not due to inhibition of general cell survival pathways or mitotic kinases that have been shown to enhance microtubule drug-induced cell death. Conclusions and Significance: We provide evidence for new cellular pathways that, when perturbed, selectively induce the apoptosis of mitotic arrested cancer cells, identifying a potential new strategy to enhance the therapeutic efficacy of conventional microtubule-targeting anti-cancer drugs. C1 [Jo, Hakryul; Loison, Fabien; Hattori, Hidenori; Silberstein, Leslie E.; Luo, Hongbo R.] Harvard Univ, Sch Med, Dept Pathol, Dana Farber Harvard Canc Ctr, Boston, MA 02115 USA. [Yu, Hongtao] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dept Pharmacol, Dallas, TX 75390 USA. RP Jo, H (reprint author), Harvard Univ, Sch Med, Dept Pathol, Dana Farber Harvard Canc Ctr, Boston, MA 02115 USA. EM Hongbo.Luo@childrens.harvard.edu RI Loison, Fabien/G-3385-2014 OI Loison, Fabien/0000-0002-6678-1730 FU National Institutes of Health (NIH) [HL066987, HL085100, AI076471, HL092020, GM076084]; American Cancer Society FX H. Jo is supported by National Institutes of Health (NIH) Training Grant HL066987. H. Luo is supported by NIH grants HL085100, AI076471, HL092020, and GM076084 and a Research Scholar Grant from American Cancer Society. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 45 TC 22 Z9 23 U1 1 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 23 PY 2010 VL 5 IS 4 AR e10318 DI 10.1371/journal.pone.0010318 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 588NU UT WOS:000277079300010 PM 20428237 ER PT J AU Schemionek, M Elling, C Steidl, U Baumer, N Hamilton, A Spieker, T Gothert, JR Stehling, M Wagers, A Huettner, CS Tenen, DG Tickenbrock, L Berdel, WE Serve, H Holyoake, TL Muller-Tidow, C Koschmieder, S AF Schemionek, Mirle Elling, Christian Steidl, Ulrich Baeumer, Nicole Hamilton, Ashley Spieker, Tilmann Goethert, Joachim R. Stehling, Martin Wagers, Amy Huettner, Claudia S. Tenen, Daniel G. Tickenbrock, Lara Berdel, Wolfgang E. Serve, Hubert Holyoake, Tessa L. Mueller-Tidow, Carsten Koschmieder, Steffen TI BCR-ABL enhances differentiation of long-term repopulating hematopoietic stem cells SO BLOOD LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; BLAST-CRISIS CML; DOUBLE-STRAND BREAKS; PHILADELPHIA-CHROMOSOME; CHRONIC PHASE; IN-VIVO; MOLECULAR SIGNATURE; IMATINIB THERAPY; PROGENITOR CELLS AB In a previously developed inducible transgenic mouse model of chronic myeloid leukemia, we now demonstrate that the disease is transplantable using BCR-ABL(+) Lin(-)Sca-1(+)c-kit(+) (LSK) cells. Interestingly, the phenotype is more severe when unfractionated bone marrow cells are transplanted, yet neither progenitor cells (Lin(-)Sca-1(-)c-kit(+)), nor mature granulocytes (CD11b(+)Gr-1(+)), nor potential stem cell niche cells (CD45(-)Ter119(-)) are able to transmit the disease or alter the phenotype. The phenotype is largely independent of BCR-ABL priming before transplantation. However, prolonged BCR-ABL expression abrogates the potential of LSK cells to induce full-blown disease in secondary recipients and increases the fraction of multipotent progenitor cells at the expense of long-term hematopoietic stem cells (LT-HSCs) in the bone marrow. BCR-ABL alters the expression of genes involved in proliferation, survival, and hematopoietic development, probably contributing to the reduced LT-HSC frequency within BCR-ABL(+) LSK cells. Reversion of BCR-ABL, or treatment with imatinib, eradicates mature cells, whereas leukemic stem cells persist, giving rise to relapsed chronic myeloid leukemia on reinduction of BCR-ABL, or imatinib withdrawal. Our results suggest that BCR-ABL induces differentiation of LT-HSCs and decreases their self-renewal capacity. (Blood. 2010; 115(16): 3185-3195) C1 [Schemionek, Mirle; Elling, Christian; Baeumer, Nicole; Berdel, Wolfgang E.; Mueller-Tidow, Carsten; Koschmieder, Steffen] Univ Munster, Dept Med Hematol & Oncol, D-48149 Munster, Germany. [Steidl, Ulrich] Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10467 USA. [Hamilton, Ashley; Holyoake, Tessa L.] Univ Glasgow, Sect Expt Haematol, Glasgow, Lanark, Scotland. [Spieker, Tilmann] Univ Munster, Dept Pathol, Munster, Germany. [Goethert, Joachim R.] Univ Duisburg Essen, Dept Hematol, Essen, Germany. [Stehling, Martin] Max Planck Inst Mol Biomed, Munster, Germany. [Wagers, Amy] Harvard Univ, Dept Stem Cell & Regenerat Biol, Joslin Diabet Ctr, Boston, MA 02115 USA. [Huettner, Claudia S.] Dana Farber Canc Inst, Dept Mol Oncol, Boston, MA 02115 USA. [Tenen, Daniel G.] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Boston, MA 02115 USA. [Tenen, Daniel G.] Natl Univ Singapore, Canc Sci Inst, Singapore 117548, Singapore. [Tickenbrock, Lara] Univ Appl Sci, Hsch Hamm Lippstadt, Hamm, Germany. [Serve, Hubert] Goethe Univ Frankfurt, Dept Med Hematol & Oncol, Frankfurt, Germany. RP Koschmieder, S (reprint author), Univ Munster, Dept Med Hematol & Oncol, D-48149 Munster, Germany. EM Steffen.Koschmieder@ukmuenster.de RI Muller-Tidow, Carsten/B-5257-2014; Muller-Tidow, Carsten/L-4062-2015; OI holyoake, tessa/0000-0002-0608-6066; Tenen, Daniel/0000-0002-6423-3888 FU Deutsche Forschungsgemeinschaft [KO2155/1-1, KO2155/2-1]; Thyssen Foundation [Az. 10.05.2.178]; Medical Research Council [G0600782]; Deutsche Carreras Leukamie-Stiftung [DJCLS R 0608v]; IZKF Munster; National Institute of Health [CA66996, CA118316] FX This work was supported by the Deutsche Forschungsgemeinschaft (KO2155/1-1 and KO2155/2-1), the Thyssen Foundation (Az. 10.05.2.178), the Medical Research Council (G0600782), the Deutsche Carreras Leukamie-Stiftung (DJCLS R 0608v), the IZKF Munster, and the National Institute of Health (grants CA66996 and CA118316; D. G. T.). NR 44 TC 56 Z9 56 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 22 PY 2010 VL 115 IS 16 BP 3185 EP 3195 DI 10.1182/blood-2009-04-215376 PG 11 WC Hematology SC Hematology GA 586ZU UT WOS:000276956500004 PM 20053753 ER PT J AU Narla, A Ebert, BL AF Narla, Anupama Ebert, Benjamin L. TI Ribosomopathies: human disorders of ribosome dysfunction SO BLOOD LA English DT Review ID DIAMOND-BLACKFAN ANEMIA; CARTILAGE-HAIR HYPOPLASIA; TREACHER-COLLINS-SYNDROME; TELOMERASE REVERSE-TRANSCRIPTASE; PROTEIN S19 DEFICIENCY; DYSKERATOSIS-CONGENITA; MYELODYSPLASTIC SYNDROME; ERYTHROID-DIFFERENTIATION; EXTRARIBOSOMAL FUNCTIONS; MOLECULAR PATHOGENESIS AB Ribosomopathies compose a collection of disorders in which genetic abnormalities cause impaired ribosome biogenesis and function, resulting in specific clinical phenotypes. Congenital mutations in RPS19 and other genes encoding ribosomal proteins cause Diamond-Blackfan anemia, a disorder characterized by hypoplastic, macrocytic anemia. Mutations in other genes required for normal ribosome biogenesis have been implicated in other rare congenital syndromes, Schwachman-Diamond syndrome, dyskeratosis congenita, cartilage hair hypoplasia, and Treacher Collins syndrome. In addition, the 5q- syndrome, a subtype of myelodysplastic syndrome, is caused by a somatically acquired deletion of chromosome 5q, which leads to haploinsufficiency of the ribosomal protein RPS14 and an erythroid phenotype highly similar to Diamond-Blackfan anemia. Acquired abnormalities in ribosome function have been implicated more broadly in human malignancies. The p53 pathway provides a surveillance mechanism for protein translation as well as genome integrity and is activated by defects in ribosome biogenesis; this pathway appears to be a critical mediator of many of the clinical features of ribosomopathies. Elucidation of the mechanisms whereby selective abnormalities in ribosome biogenesis cause specific clinical syndromes will hopefully lead to novel therapeutic strategies for these diseases. (Blood. 2010; 115(16): 3196-3205) C1 [Narla, Anupama; Ebert, Benjamin L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Narla, Anupama; Ebert, Benjamin L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Narla, Anupama] Childrens Hosp, Dept Med, Boston, MA 02115 USA. [Ebert, Benjamin L.] Harvard Stem Cell Inst, Cambridge, MA USA. RP Ebert, BL (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Karp Res Bldg,1 Blackfan Cir,5th Fl,CHRB 05-211, Boston, MA 02115 USA. EM bebert@partners.org FU National Institutes of Health [R01 HL82945]; GlaxoSmithKline FX This work was supported by the National Institutes of Health (R01 HL82945).; B. L. E. received research funding from GlaxoSmithKline. A.N. declares no competing financial interests. NR 109 TC 267 Z9 275 U1 3 U2 34 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 22 PY 2010 VL 115 IS 16 BP 3196 EP 3205 DI 10.1182/blood-2009-10-178129 PG 10 WC Hematology SC Hematology GA 586ZU UT WOS:000276956500005 PM 20194897 ER PT J AU Smith, ACH Raimondi, AR Salthouse, CD Ignatius, MS Blackburn, JS Mizgirev, IV Storer, NY de Jong, JLO Chen, AT Zhou, Y Revskoy, S Zon, LI Langenau, DM AF Smith, Alexandra C. H. Raimondi, Aubrey R. Salthouse, Chris D. Ignatius, Myron S. Blackburn, Jessica S. Mizgirev, Igor V. Storer, Narie Y. de Jong, Jill L. O. Chen, Aye T. Zhou, Yi Revskoy, Sergei Zon, Leonard I. Langenau, David M. TI High-throughput cell transplantation establishes that tumor-initiating cells are abundant in zebrafish T-cell acute lymphoblastic leukemia SO BLOOD LA English DT Article ID TRANSGENIC ZEBRAFISH; STEM-CELLS; EXPRESSION; MODEL; GENE; MYC; MUTATIONS; MELANOMA; GROWTH; NOTCH1 AB Self-renewal is a feature of cancer and can be assessed by cell transplantation into immune-compromised or immune-matched animals. However, studies in zebrafish have been severely limited by lack of these reagents. Here, Myc-induced T-cell acute lymphoblastic leukemias (T-ALLs) have been made in syngeneic, clonal zebrafish and can be transplanted into sibling animals without the need for immune suppression. These studies show that self-renewing cells are abundant in T-ALL and comprise 0.1% to 15.9% of the T-ALL mass. Large-scale single-cell transplantation experiments established that T-ALLs can be initiated from a single cell and that leukemias exhibit wide differences in tumor-initiating potential. T-ALLs also can be introduced into clonal-outcrossed animals, and T-ALLs arising in mixed genetic backgrounds can be transplanted into clonal recipients without the need for major histocompatibility complex matching. Finally, high-throughput imaging methods are described that allow large numbers of fluorescent transgenic animals to be imaged simultaneously, facilitating the rapid screening of engrafted animals. Our experiments highlight the large numbers of zebrafish that can be experimentally assessed by cell transplantation and establish new high-throughput methods to functionally interrogate gene pathways involved in cancer self-renewal. (Blood. 2010; 115(16): 3296-3303) C1 [Langenau, David M.] Massachusetts Gen Hosp, Dept Pathol, Mol Pathol Unit, Charlestown, MA 02129 USA. [Smith, Alexandra C. H.] Huntsman Canc Inst, Salt Lake City, UT USA. [Raimondi, Aubrey R.; Ignatius, Myron S.; Blackburn, Jessica S.; Langenau, David M.] Massachusetts Gen Hosp, Ctr Canc, Ctr Canc Res, Charlestown, MA 02129 USA. [Salthouse, Chris D.] Harvard Univ, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02115 USA. [Mizgirev, Igor V.; Revskoy, Sergei] Northwestern Univ, Feinberg Sch Med, Dept Med, Div Hepatol, Chicago, IL 60611 USA. [Storer, Narie Y.; de Jong, Jill L. O.; Chen, Aye T.; Zhou, Yi; Zon, Leonard I.] Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. [Storer, Narie Y.; de Jong, Jill L. O.; Chen, Aye T.; Zhou, Yi; Zon, Leonard I.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Zon, Leonard I.; Langenau, David M.] Harvard Stem Cell Inst, Boston, MA USA. RP Langenau, DM (reprint author), Massachusetts Gen Hosp, Dept Pathol, Mol Pathol Unit, 149 13th St,6th Fl,6012, Charlestown, MA 02129 USA. EM dlangenau@partners.org FU National Institutes of Health [K01 AR055619-01A1, 3 K01 AR055619-03S1, 5 R01 CA103846-04]; Sarcoma Foundation of America; Alex Lemonade Stand; Harvard Stem Cell Institute FX D. M. L. is supported by National Institutes of Health grant K01 AR055619-01A1 and 3 K01 AR055619-03S1, a grant from the Sarcoma Foundation of America, a New Investigator Award from Alex Lemonade Stand, and a pilot project grant from the Harvard Stem Cell Institute. L.I.Z. is supported by National Institutes of Health 5 R01 CA103846-04. NR 28 TC 48 Z9 49 U1 0 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 22 PY 2010 VL 115 IS 16 BP 3296 EP 3303 DI 10.1182/blood-2009-10-246488 PG 8 WC Hematology SC Hematology GA 586ZU UT WOS:000276956500016 PM 20056790 ER PT J AU Yecies, D Carlson, NE Deng, J Letai, A AF Yecies, Derek Carlson, Nicole E. Deng, Jing Letai, Anthony TI Acquired resistance to ABT-737 in lymphoma cells that up-regulate MCL-1 and BFL-1 SO BLOOD LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; BCL-2 FAMILY-MEMBERS; BH3 MIMETIC ABT-737; MITOCHONDRIAL APOPTOSIS; CHROMOSOMAL BREAKPOINT; FOLLICULAR LYMPHOMA; TRANSGENIC MICE; DOWN-REGULATION; IN-VIVO; X-L AB ABT-737 is a small-molecule antagonist of BCL-2 currently under evaluation in clinical trials in the oral form of ABT-263. We anticipate that acquired resistance to this promising drug will inevitably arise. To study potential mechanisms of resistance to ABT-737, we derived resistant lines from initially sensitive OCI-Ly1 and SU-DHL-4 lymphoma cell lines via long-term exposure. Resistance was based in the mitochondria and not due to an inability of the drug to bind BCL-2. Resistant cells had increased levels of BFL-1 and/or MCL-1 proteins, which are not targeted by ABT-737. Proapoptotic BIM was displaced from BCL-2 by ABT-737 in both parental and resistant cells, but in resistant cells, BIM was sequestered by the additional BFL-1 and/or MCL-1. Decreasing MCL-1 levels with flavopiridol, PHA 767491, or shRNA restored sensitivity to ABT-737 resistant cells. MCL-1 was up-regulated not by protein stabilization but rather by increased transcript levels. Surprisingly, in addition to stable increases in MCL-1 transcript and protein in resistant cells, there was a dynamic increase within hours after ABT-737 treatment. BFL-1 protein and transcript levels in resistant cells were similarly dynamically up-regulated. This dynamic increase suggests a novel mechanism whereby modulation of antiapoptotic protein function communicates with nuclear transcriptional machinery. (Blood. 2010; 115(16): 3304-3313) C1 [Yecies, Derek; Carlson, Nicole E.; Deng, Jing; Letai, Anthony] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Letai, A (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM anthony_letai@dfci.harvard.edu OI Yecies, Derek/0000-0001-8534-4651 FU National Institutes of Health (NIH) [K08 CA10254, R01CA129974]; Leukemia & Lymphoma Society [7391-07] FX The authors would like to gratefully acknowledge support from National Institutes of Health (NIH) grant nos. K08 CA10254 (A. L.) and R01CA129974, and Leukemia & Lymphoma Society grant SCOR no. 7391-07. NR 42 TC 165 Z9 167 U1 1 U2 14 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 22 PY 2010 VL 115 IS 16 BP 3304 EP 3313 DI 10.1182/blood-2009-07-233304 PG 10 WC Hematology SC Hematology GA 586ZU UT WOS:000276956500017 PM 20197552 ER PT J AU Bolli, N Payne, EM Grabher, C Lee, JS Johnston, AB Falini, B Kanki, JP Look, AT AF Bolli, Niccolo Payne, Elspeth M. Grabher, Clemens Lee, Jeong-Soo Johnston, Adam B. Falini, Brunangelo Kanki, John P. Look, A. Thomas TI Expression of the cytoplasmic NPM1 mutant (NPMc plus ) causes the expansion of hematopoietic cells in zebrafish SO BLOOD LA English DT Article ID ACUTE MYELOID-LEUKEMIA; TRANSGENIC ZEBRAFISH; NUCLEAR EXPORT; NUCLEOPHOSMIN; ARF; GENE; SUPPRESSOR; PROMOTER; AML; P53 AB Mutations in the human nucleophosmin (NPM1) gene are the most frequent genetic alteration in adult acute myeloid leukemias (AMLs) and result in aberrant cytoplasmic translocation of this nucleolar phosphoprotein (NPMc+). However, underlying mechanisms leading to leukemogenesis remain unknown. To address this issue, we took advantage of the zebrafish model organism, which expresses 2 genes orthologous to human NPM1, referred to as npm1a and npm1b. Both genes are ubiquitously expressed, and their knockdown produces a reduction in myeloid cell numbers that is specifically rescued by NPM1 expression. In zebrafish, wild-type human NPM1 is nucleolar while NPMc+ is cytoplasmic, as in human AML, and both interact with endogenous zebrafish Npm1a and Npm1b. Forced NPMc+ expression in zebrafish causes an increase in pu.1(+) primitive early myeloid cells. A more marked perturbation of myelopoiesis occurs in p53(m/m) embryos expressing NPMc+, where mpx(+) and csf1r(+) cell numbers are also expanded. Importantly, NPMc+ expression results in increased numbers of definitive hematopoietic cells, including erythromyeloid progenitors in the posterior blood island and c-myb/cd41(+) cells in the ventral wall of the aorta. These results are likely to be relevant to human NPMc+ AML, where the observed NPMc+ multilineage expression pattern implies transformation of a multipotent stem or progenitor cell. (Blood. 2010; 115(16): 3329-3340) C1 [Bolli, Niccolo; Payne, Elspeth M.; Grabher, Clemens; Lee, Jeong-Soo; Johnston, Adam B.; Kanki, John P.; Look, A. Thomas] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Bolli, Niccolo; Falini, Brunangelo] Univ Perugia, Inst Hematol, I-06100 Perugia, Italy. [Payne, Elspeth M.] Barts & London Queen Marys Sch Med & Dent, Inst Canc, London, England. [Grabher, Clemens] Forschungszentrum Karlsruhe, Karlsruhe Inst Technol, D-76021 Karlsruhe, Germany. [Look, A. Thomas] Harvard Univ, Sch Med, Dept Pediat, Childrens Hosp,Div Hematol Oncol, Boston, MA 02115 USA. RP Bolli, N (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Mayer Bldg,Rm M630,44 Binney St, Boston, MA 02115 USA. EM niccolo_bolli@dfci.harvard.edu; thomas_look@dfci.harvard.edu RI Grabher, Clemens/H-2064-2013; Bolli, Niccolo/D-4057-2011 OI Bolli, Niccolo/0000-0002-1018-5139 FU American-Italian Cancer Foundation; Leukemia & Lymphoma Research UK; National Institutes of Health [5T32-CA009382-26] FX N.B. has been supported by a Princess Borghese and Anna Bulgari Fellowship from The American-Italian Cancer Foundation, and is currently a Leukemia & Lymphoma Society Special Fellow. E. M. P. is the recipient of a Clinical Research Training Fellowship from Leukemia & Lymphoma Research UK and was formerly supported by National Institutes of Health grant 5T32-CA009382-26. NR 52 TC 35 Z9 36 U1 0 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 22 PY 2010 VL 115 IS 16 BP 3329 EP 3340 DI 10.1182/blood-2009-02-207225 PG 12 WC Hematology SC Hematology GA 586ZU UT WOS:000276956500020 PM 20197555 ER PT J AU Zaret, KS White, MF AF Zaret, Kenneth S. White, Morris F. TI DIABETES FORUM Extreme makeover of pancreatic alpha-cells SO NATURE LA English DT Editorial Material ID BETA-CELLS; DIFFERENTIATION; LIVER C1 [Zaret, Kenneth S.] Univ Penn, Sch Med, Inst Regenerat Med, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA. [White, Morris F.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. [White, Morris F.] Childrens Hosp Boston, Howard Hughes Med Inst, Div Endocrinol, Boston, MA 02115 USA. RP Zaret, KS (reprint author), Univ Penn, Sch Med, Inst Regenerat Med, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA. EM zaret@upenn.edu; morris.white@childrens.harvard.edu FU NIDDK NIH HHS [R01 DK055326] NR 10 TC 5 Z9 5 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 22 PY 2010 VL 464 IS 7292 BP 1132 EP 1133 DI 10.1038/4641132a PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 586FR UT WOS:000276891100020 PM 20414295 ER PT J AU de Calignon, A Fox, LM Pitstick, R Carlson, GA Bacskai, BJ Spires-Jones, TL Hyman, BT AF de Calignon, Alix Fox, Leora M. Pitstick, Rose Carlson, George A. Bacskai, Brian J. Spires-Jones, Tara L. Hyman, Bradley T. TI Caspase activation precedes and leads to tangles SO NATURE LA English DT Article ID ALZHEIMERS-DISEASE; MOUSE MODEL; NEUROFIBRILLARY TANGLES; NEURONAL LOSS; TAU-PHOSPHORYLATION; BEARING NEURONS; HUMAN TAUOPATHY; CONGO RED; IN-VIVO; CLEAVAGE AB Studies of post-mortem tissue have shown that the location of fibrillar tau deposits, called neurofibrillary tangles (NFT), matches closely with regions of massive neuronal death(1,2), severe cytological abnormalities(3), and markers of caspase activation and apoptosis(4-6), leading to the idea that tangles cause neurodegeneration in Alzheimer's disease and tau-related frontotemporal dementia. However, using in vivo multiphoton imaging to observe tangles and activation of executioner caspases in living tau transgenic mice (Tg4510 strain), we find the opposite: caspase activation occurs first, and precedes tangle formation by hours to days. New tangles form within a day. After a new tangle forms, the neuron remains alive and caspase activity seems to be suppressed. Similarly, introduction of wild-type 4-repeat tau (tau-4R) into wild-type animals triggered caspase activation, tau truncation and tau aggregation. Adeno-associated virus-mediated expression of a construct mimicking caspase-cleaved tau into wild-type mice led to the appearance of intracellular aggregates, tangle-related conformational-and phospho-epitopes, and the recruitment of full-length endogenous tau to the aggregates. On the basis of these data, we propose a new model in which caspase activation cleaves tau to initiate tangle formation, then truncated tau recruits normal tau to misfold and form tangles. Because tangle-bearing neurons are long-lived, we suggest that tangles are 'off pathway' to acute neuronal death. Soluble tau species, rather than fibrillar tau, may be the critical toxic moiety underlying neurodegeneration. C1 [de Calignon, Alix; Fox, Leora M.; Bacskai, Brian J.; Spires-Jones, Tara L.; Hyman, Bradley T.] Harvard Univ, Alzheimers Dis Res Lab, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis,Dept Neurol,Med S, Charlestown, MA 02129 USA. [de Calignon, Alix] Univ Paris 06, F-75005 Paris, France. [Pitstick, Rose; Carlson, George A.] McLaughlin Res Inst, Great Falls, MT 59401 USA. RP Hyman, BT (reprint author), Harvard Univ, Alzheimers Dis Res Lab, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis,Dept Neurol,Med S, Charlestown, MA 02129 USA. EM bhyman@partners.org OI Spires-Jones, Tara/0000-0003-2530-0598 FU Alzheimer's disease Drug Discovery Foundation; Harvard Medical School Shore Award; [AG08487]; [AG 026249]; [K99 AG033670-01A1] FX This work was supported by AG08487, AG 026249, K99 AG033670-01A1, Alzheimer's disease Drug Discovery Foundation, Harvard Medical School Shore Award. We thank W. E. Klunk for his generous gift of compound X-34. A. d. C. is a student in the B2M programme (Universite Pierre and Marie Curie, Paris, France) and the results in this manuscript will be presented in her thesis. NR 30 TC 229 Z9 233 U1 4 U2 37 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 22 PY 2010 VL 464 IS 7292 BP 1201 EP U123 DI 10.1038/nature08890 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 586FR UT WOS:000276891100039 PM 20357768 ER PT J AU Herman, JB AF Herman, John B. TI Increasing the Value of the State Medical License SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Herman, JB (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 22 PY 2010 VL 362 IS 16 BP 1459 EP 1461 DI 10.1056/NEJMp0912754 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 586GP UT WOS:000276894700003 PM 20410513 ER PT J AU Holman, RR Haffner, SM McMurray, JJ Bethel, MA Holzhauer, B Hua, TA Belenkov, Y Boolell, M Buse, JB Buckley, BM Chacra, AR Chiang, FT Charbonnel, B Chow, CC Davies, MJ Deedwania, P Diem, P Einhorn, D Fonseca, V Fulcher, GR Gaciong, Z Gaztambide, S Giles, T Horton, E Ilkova, H Jenssen, T Kahn, SE Krum, H Laakso, M Leiter, LA Levitt, NS Mareev, V Martinez, F Masson, C Mazzone, T Meaney, E Nesto, R Pan, CY Prager, R Raptis, SA Rutten, GEHM Sandstroem, H Schaper, F Scheen, A Schmitz, O Sinay, I Soska, V Stender, S Tamas, G Tognoni, G Tuomilehto, J Villamil, AS Vozar, J Califf, RM AF Holman, Rury R. Haffner, Steven M. McMurray, John J. Bethel, M. Angelyn Holzhauer, Bjoern Hua, Tsushung A. Belenkov, Yuri Boolell, Mitradev Buse, John B. Buckley, Brendan M. Chacra, Antonio R. Chiang, Fu-Tien Charbonnel, Bernard Chow, Chun-Chung Davies, Melanie J. Deedwania, Prakash Diem, Peter Einhorn, Daniel Fonseca, Vivian Fulcher, Gregory R. Gaciong, Zbigniew Gaztambide, Sonia Giles, Thomas Horton, Edward Ilkova, Hasan Jenssen, Trond Kahn, Steven E. Krum, Henry Laakso, Markku Leiter, Lawrence A. Levitt, Naomi S. Mareev, Viacheslav Martinez, Felipe Masson, Chantal Mazzone, Theodore Meaney, Eduardo Nesto, Richard Pan, Changyu Prager, Rudolf Raptis, Sotirios A. Rutten, Guy E. H. M. Sandstroem, Herbert Schaper, Frank Scheen, Andre Schmitz, Ole Sinay, Isaac Soska, Vladimir Stender, Steen Tamas, Gyula Tognoni, Gianni Tuomilehto, Jaako Villamil, Alberto S. Vozar, Juraj Califf, Robert M. CA NAVIGATOR Study Grp TI Effect of Nateglinide on the Incidence of Diabetes and Cardiovascular Events SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; RANDOMIZED CONTROLLED-TRIAL; PHASE INSULIN-SECRETION; 10-YEAR FOLLOW-UP; FASTING GLUCOSE; LIFE-STYLE; PREVENTION; MELLITUS; NIDDM; CLASSIFICATION AB BACKGROUND The ability of short-acting insulin secretagogues to reduce the risk of diabetes or cardiovascular events in people with impaired glucose tolerance is unknown. METHODS In a double-blind, randomized clinical trial, we assigned 9306 participants with impaired glucose tolerance and either cardiovascular disease or cardiovascular risk factors to receive nateglinide (up to 60 mg three times daily) or placebo, in a 2-by-2 factorial design with valsartan or placebo, in addition to participation in a lifestyle modification program. We followed the participants for a median of 5.0 years for incident diabetes (and a median of 6.5 years for vital status). We evaluated the effect of nateglinide on the occurrence of three coprimary outcomes: the development of diabetes; a core cardiovascular outcome that was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure; and an extended cardiovascular outcome that was a composite of the individual components of the core composite cardiovascular outcome, hospitalization for unstable angina, or arterial revascularization. RESULTS After adjustment for multiple testing, nateglinide, as compared with placebo, did not significantly reduce the cumulative incidence of diabetes (36% and 34%, respectively; hazard ratio, 1.07; 95% confidence interval [CI], 1.00 to 1.15; P = 0.05), the core composite cardiovascular outcome (7.9% and 8.3%, respectively; hazard ratio, 0.94, 95% CI, 0.82 to 1.09; P = 0.43), or the extended composite cardiovascular outcome (14.2% and 15.2%, respectively; hazard ratio, 0.93, 95% CI, 0.83 to 1.03; P = 0.16). Nateglinide did, however, increase the risk of hypoglycemia. CONCLUSIONS Among persons with impaired glucose tolerance and established cardiovascular disease or cardiovascular risk factors, assignment to nateglinide for 5 years did not reduce the incidence of diabetes or the coprimary composite cardiovascular outcomes. (ClinicalTrials.gov number, NCT00097786.) C1 [Holman, Rury R.; Bethel, M. Angelyn] Univ Oxford, Diabet Trials Unit, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. [McMurray, John J.] Univ Glasgow, British Heart Fdn, Glasgow Cardiovasc Res Ctr, Glasgow, Lanark, Scotland. [Davies, Melanie J.] Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England. [Haffner, Steven M.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Bethel, M. Angelyn] Duke Univ, Duke Clin Res Inst, Durham, NC 27706 USA. [Califf, Robert M.] Duke Univ, Duke Translat Med Inst, Durham, NC 27706 USA. [Buse, John B.] Univ N Carolina, Sch Med, Div Gen Med, Chapel Hill, NC USA. [Buse, John B.] Univ N Carolina, Sch Med, Clin Epidemiol & Diabet Care Ctr, Chapel Hill, NC USA. [Holzhauer, Bjoern; Boolell, Mitradev; Masson, Chantal] Novartis Pharmaceut, Basel, Switzerland. [Diem, Peter] Univ Hosp Bern, Inselspital, Div Endocrinol Diabet & Clin Nutr, CH-3010 Bern, Switzerland. [Diem, Peter] Univ Bern, Bern, Switzerland. [Hua, Tsushung A.] Novartis Pharmaceut, E Hanover, NJ USA. [Belenkov, Yuri; Mareev, Viacheslav] Moscow MV Lomonosov State Univ, Moscow 117234, Russia. [Buckley, Brendan M.] Natl Univ Ireland Univ Coll Cork, Cork, Ireland. [Chacra, Antonio R.] Univ Fed Sao Paulo, Sao Paulo, Brazil. [Chiang, Fu-Tien] Natl Taiwan Univ Hosp, Dept Cardiol, Taipei, Taiwan. [Charbonnel, Bernard] Univ Hosp, Dept Endocrinol, Nantes, France. [Chow, Chun-Chung] Chinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China. [Pan, Changyu] 301 Hosp, Dept Endocrinol, Beijing, Peoples R China. [Deedwania, Prakash] Calif State Univ Fresno, San Francisco Program Fresno, Div Cardiol, Fresno, CA 93740 USA. [Deedwania, Prakash] VA Cent Calif Hlth Care Syst, Fresno, CA USA. [Einhorn, Daniel] Univ Calif San Diego, La Jolla, CA 92093 USA. [Einhorn, Daniel] Scripps Whittier Diabet Inst, La Jolla, CA USA. [Fonseca, Vivian] Tulane Univ, Sch Med, Dept Endocrinol, New Orleans, LA 70112 USA. [Giles, Thomas] Tulane Univ, Sch Med, Inst Heart & Vasc, New Orleans, LA 70112 USA. [Fulcher, Gregory R.] Univ Sydney, Royal N Shore Hosp, Sydney, NSW 2006, Australia. [Krum, Henry] Monash Univ, Alfred Hosp, Clin Pharmacol Unit, Dept Epidemiol & Prevent Med, Prahran, Vic, Australia. [Gaciong, Zbigniew] Warsaw Med Univ, Dept Internal Med Hypertens & Vasc Dis, Warsaw, Poland. [Gaztambide, Sonia] Hosp Univ Cruces, Dept Endocrinol, Ctr Invest Biomed Red Diabet & Enfermedades Metab, Baracaldo, Spain. [Horton, Edward] Joslin Diabet Ctr, Boston, MA 02215 USA. [Ilkova, Hasan] Istanbul Univ, Dept Diabet Endocrinol & Metab, Istanbul, Turkey. [Jenssen, Trond] Oslo Univ Hosp, Rikshosp, Oslo Inst Clin Med, Tromso, Norway. [Jenssen, Trond] Univ Tromso, Tromso, Norway. [Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Kahn, Steven E.] Univ Washington, Seattle, WA 98195 USA. [Laakso, Markku] Univ Kuopio, FIN-70211 Kuopio, Finland. [Laakso, Markku] Kuopio Univ Hosp, SF-70210 Kuopio, Finland. [Tuomilehto, Jaako] Univ Helsinki, Dept Publ Hlth, Hjelt Inst, Helsinki, Finland. [Tuomilehto, Jaako] S Ostrobothnia Cent Hosp, Seinajoki, Finland. [Leiter, Lawrence A.] Univ Toronto, St Michaels Hosp, Li Ka Shing Knowledge Inst, Keenan Res Ctr, Toronto, ON M5B 1W8, Canada. [Levitt, Naomi S.] Univ Cape Town, Dept Med, Endocrine Unit, Groote Schuur Hosp, ZA-7925 Cape Town, South Africa. [Martinez, Felipe] Natl Univ Cordoba, Cordoba, Spain. [Sinay, Isaac] Univ Buenos Aires, Inst Cardiovasc Buenos Aires, Buenos Aires, DF, Argentina. [Villamil, Alberto S.] Univ Buenos Aires, Hypertens Unit, Div Cardiol, Argerich Hosp, Buenos Aires, DF, Argentina. [Mazzone, Theodore] Univ Illinois, Dept Diabet & Metab, Chicago, IL USA. [Meaney, Eduardo] Hosp 10 Octubre, Inst Seguridad & Serv Sociales Trabajadores Estad, Mexico City, DF, Mexico. [Nesto, Richard] Lahey Clin Fdn, Burlington, MA USA. [Prager, Rudolf] Krankenhaus Hietzing Neurolog, Zentrum Rosenhugel, Hietzig Hosp, Vienna, Austria. [Raptis, Sotirios A.] Attikon Univ Hosp, Hellen Natl Diabet Ctr, Dept Internal Med Endocrinol & Diabetol 2, Athens, Greece. [Rutten, Guy E. H. M.] Univ Med Ctr, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands. [Sandstroem, Herbert] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden. [Schaper, Frank] Tech Univ Dresden, Ctr Clin Studies Metab & Endocrinol Knowledge & T, D-8027 Dresden, Germany. [Scheen, Andre] Univ Liege, Div Diabet, Liege, Belgium. [Scheen, Andre] Univ Liege, Clin Pharmacol Unit, Ctr Hosp Univ Liege, Liege, Belgium. [Schmitz, Ole] Aarhus Univ, Med Dept Endocrinol & Diabet M, Arhus Univ Hosp, Aarhus, Denmark. [Schmitz, Ole] Aarhus Univ, Dept Clin Pharmacol, Aarhus, Denmark. [Stender, Steen] Univ Copenhagen, Gentofte Hosp, Dept Clin Biochem, Copenhagen, Denmark. [Soska, Vladimir] Fac Hosp St Anna, Clin Internal Med 2, Brno, Czech Republic. [Soska, Vladimir] Fac Hosp St Anna, Dept Clin Biochem, Brno, Czech Republic. [Tamas, Gyula] Semmelweis Univ, Diabet Unit, Dept Med 1, H-1085 Budapest, Hungary. [Tognoni, Gianni] Ist Ric Farmacol Mario Negri, Consorzio Mario Negri Sud, I-66030 Santa Maria Imbaro, Italy. [Vozar, Juraj] Diabetol Outpatient Clin, Jesenius Samaria, Samorin, Slovakia. RP Holman, RR (reprint author), Churchill Hosp, Diabet Trials Unit, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7LJ, England. EM rury.holman@dtu.ox.ac.uk RI Diem, Peter/A-7650-2008; Gaztambide, Sonia/E-1760-2012; OI Holzhauer, Bjorn/0000-0002-9209-757X; Mareev, Vyacheslav Yurievich/0000-0002-7285-2048; Kahn, Steven/0000-0001-7307-9002; mcmurray, john/0000-0002-6317-3975; CHIANG, FU-TIEN/0000-0003-4936-8968 FU Novartis Pharma FX Supported by Novartis Pharma. NR 29 TC 191 Z9 199 U1 1 U2 31 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 22 PY 2010 VL 362 IS 16 BP 1463 EP 1476 DI 10.1056/NEJMoa1001122 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 586GP UT WOS:000276894700006 ER PT J AU McMurray, JJ Holman, RR Haffner, SM Bethel, MA Holzhauer, B Hua, TA Belenkov, Y Boolell, M Buse, JB Buckley, BM Chacra, AR Chiang, FT Charbonnel, B Chow, CC Davies, MJ Deedwania, P Diem, P Einhorn, D Fonseca, V Fulcher, GR Gaciong, Z Gaztambide, S Giles, T Horton, E Ilkova, H Jenssen, T Kahn, SE Krum, H Laakso, M Leiter, LA Levitt, NS Mareev, V Martinez, F Masson, C Mazzone, T Meaney, E Nesto, R Pan, CY Prager, R Raptis, SA Rutten, GEHM Sandstroem, H Schaper, F Scheen, A Schmitz, O Sinay, I Soska, V Stender, S Tamas, G Tognoni, G Tuomilehto, J Villamil, AS Vozar, J Califf, RM AF McMurray, John J. Holman, Rury R. Haffner, Steven M. Bethel, M. Angelyn Holzhauer, Bjoern Hua, Tsushung A. Belenkov, Yuri Boolell, Mitradev Buse, John B. Buckley, Brendan M. Chacra, Antonio R. Chiang, Fu-Tien Charbonnel, Bernard Chow, Chun-Chung Davies, Melanie J. Deedwania, Prakash Diem, Peter Einhorn, Daniel Fonseca, Vivian Fulcher, Gregory R. Gaciong, Zbigniew Gaztambide, Sonia Giles, Thomas Horton, Edward Ilkova, Hasan Jenssen, Trond Kahn, Steven E. Krum, Henry Laakso, Markku Leiter, Lawrence A. Levitt, Naomi S. Mareev, Viacheslav Martinez, Felipe Masson, Chantal Mazzone, Theodore Meaney, Eduardo Nesto, Richard Pan, Changyu Prager, Rudolf Raptis, Sotirios A. Rutten, Guy E. H. M. Sandstroem, Herbert Schaper, Frank Scheen, Andre Schmitz, Ole Sinay, Isaac Soska, Vladimir Stender, Steen Tamas, Gyula Tognoni, Gianni Tuomilehto, Jaako Villamil, Alberto S. Vozar, Juraj Califf, Robert M. CA NAVIGATOR Study Grp TI Effect of Valsartan on the Incidence of Diabetes and Cardiovascular Events SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; CONVERTING-ENZYME-INHIBITORS; RANDOMIZED CONTROLLED-TRIAL; LIFE-STYLE INTERVENTIONS; CORONARY-ARTERY-DISEASE; HIGH-RISK PATIENTS; FASTING GLUCOSE; HEART-FAILURE; METABOLIC SYNDROME; CLINICAL-TRIALS AB BACKGROUND It is not known whether drugs that block the renin-angiotensin system reduce the risk of diabetes and cardiovascular events in patients with impaired glucose tolerance. METHODS In this double-blind, randomized clinical trial with a 2-by-2 factorial design, we assigned 9306 patients with impaired glucose tolerance and established cardiovascular disease or cardiovascular risk factors to receive valsartan (up to 160 mg daily) or placebo (and nateglinide or placebo) in addition to lifestyle modification. We then followed the patients for a median of 5.0 years for the development of diabetes (6.5 years for vital status). We studied the effects of valsartan on the occurrence of three coprimary outcomes: the development of diabetes; an extended composite outcome of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure, arterial revascularization, or hospitalization for unstable angina; and a core composite outcome that excluded unstable angina and revascularization. RESULTS The cumulative incidence of diabetes was 33.1% in the valsartan group, as compared with 36.8% in the placebo group (hazard ratio in the valsartan group, 0.86; 95% confidence interval [CI], 0.80 to 0.92; P<0.001). Valsartan, as compared with placebo, did not significantly reduce the incidence of either the extended cardiovascular outcome (14.5% vs. 14.8%; hazard ratio, 0.96; 95% CI, 0.86 to 1.07; P = 0.43) or the core cardiovascular outcome (8.1% vs. 8.1%; hazard ratio, 0.99; 95% CI, 0.86 to 1.14; P = 0.85). CONCLUSIONS Among patients with impaired glucose tolerance and cardiovascular disease or risk factors, the use of valsartan for 5 years, along with lifestyle modification, led to a relative reduction of 14% in the incidence of diabetes but did not reduce the rate of cardiovascular events. (ClinicalTrials.gov number, NCT00097786.) C1 [McMurray, John J.] Univ Glasgow, British Heart Fdn, Glasgow Cardiovasc Res Ctr, Glasgow, Lanark, Scotland. [Holman, Rury R.; Bethel, M. Angelyn] Univ Oxford, Diabet Trials Unit, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. [Haffner, Steven M.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Bethel, M. Angelyn] Duke Univ, Duke Clin Res Inst, Durham, NC USA. [Holzhauer, Bjoern; Boolell, Mitradev; Masson, Chantal] Novartis Pharmaceut, Basel, Switzerland. [Hua, Tsushung A.] Novartis Pharmaceut, E Hanover, NJ USA. [Belenkov, Yuri; Fonseca, Vivian] Moscow MV Lomonosov State Univ, Moscow 117234, Russia. [Buse, John B.] Univ N Carolina, Sch Med, Div Gen Med & Clin Epidemiol, Diabet Care Ctr, Chapel Hill, NC USA. [Buckley, Brendan M.] Natl Univ Ireland Univ Coll Cork, Cork, Ireland. [Chacra, Antonio R.] Univ Fed Sao Paulo, Sao Paulo, Brazil. [Chiang, Fu-Tien] Natl Taiwan Univ Hosp, Dept Cardiol, Taipei, Taiwan. [Charbonnel, Bernard] Univ Hosp, Dept Endocrinol, Nantes, France. [Chow, Chun-Chung] Chinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China. [Davies, Melanie J.] Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England. [Deedwania, Prakash] Calif State Univ Fresno, San Francisco Program Fresno, Div Cardiol, Fresno, CA 93740 USA. [Deedwania, Prakash] VA Cent Calif Hlth Care Syst, Fresno, CA USA. [Diem, Peter] Univ Hosp Bern, Inselspital, Div Endocrinol Diabet & Clin Nutr, CH-3010 Bern, Switzerland. [Diem, Peter] Univ Bern, Bern, Switzerland. [Einhorn, Daniel] Univ Calif San Diego, La Jolla, CA 92093 USA. [Einhorn, Daniel] Scripps Whittier Diabet Inst, La Jolla, CA USA. [Fonseca, Vivian] Tulane Univ, Dept Endocrinol, New Orleans, LA 70118 USA. [Fulcher, Gregory R.] Univ Sydney, Royal N Shore Hosp, Sydney, NSW 2006, Australia. [Gaciong, Zbigniew] Warsaw Med Univ, Dept Internal Med Hypertens & Vasc Dis, Warsaw, Poland. [Gaztambide, Sonia] Hosp Univ Cruces, CIBERDEM, Dept Endocrinol, Baracaldo, Spain. [Giles, Thomas] Tulane Univ, Sch Med, Inst Heart & Vasc, New Orleans, LA 70112 USA. [Horton, Edward] Joslin Diabet Ctr, Boston, MA 02215 USA. [Ilkova, Hasan] Istanbul Univ, Dept Diabet Endocrinol & Metab, Istanbul, Turkey. [Jenssen, Trond] Oslo Univ Hosp, Rikshosp, Oslo, Norway. [Jenssen, Trond] Univ Tromso, Inst Clin Med, Tromso, Norway. [Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Kahn, Steven E.] Univ Washington, Seattle, WA 98195 USA. [Krum, Henry] Monash Univ, Alfred Hosp, Dept Epidemiol & Prevent Med, Clin Pharmacol Unit, Prahran, Vic, Australia. [Laakso, Markku] Univ Kuopio, FIN-70211 Kuopio, Finland. [Laakso, Markku] Kuopio Univ Hosp, SF-70210 Kuopio, Finland. [Leiter, Lawrence A.] Univ Toronto, St Michaels Hosp, Li Ka Shing Knowledge Inst, Keenan Res Ctr, Toronto, ON M5B 1W8, Canada. [Levitt, Naomi S.] Univ Cape Town, Dept Med, Groote Schuur Hosp, ZA-7925 Cape Town, South Africa. [Martinez, Felipe] Natl Univ Cordoba, Cordoba, Argentina. [Mazzone, Theodore] Univ Illinois, Dept Diabet & Metab, Chicago, IL USA. [Meaney, Eduardo] Hosp Primero Octubre, Mexico City, DF, Mexico. [Nesto, Richard] Lahey Clin Fdn, Burlington, MA USA. [Pan, Changyu] 301 Hosp, Dept Endocrinol, Beijing, Peoples R China. [Prager, Rudolf] Krankenhaus Hietzing Neurol, Zentrum Rosenhugel, Hietzig Hosp, Vienna, Austria. [Raptis, Sotirios A.] Attikon Univ Hosp, Hellen Natl Diabet Ctr, Dept Internal Med Endocrinol & Diabetol 2, Athens, Greece. [Rutten, Guy E. H. M.] Univ Med Ctr, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands. [Sandstroem, Herbert] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden. [Schaper, Frank] Tech Univ Dresden, Ctr Clin Studies Metab & Endocrinol Knowledge & T, D-8027 Dresden, Germany. [Scheen, Andre] Univ Liege, Div Diabet, Liege, Belgium. [Scheen, Andre] Univ Liege, Clin Pharmacol Unit, Ctr Hosp Univ Liege, Liege, Belgium. [Schmitz, Ole] Aarhus Univ, Med Dept Endocrinol & Diabet M, Aarhus, Denmark. [Schmitz, Ole] Aarhus Univ, Dept Clin Pharmacol, Aarhus, Denmark. [Sinay, Isaac] Inst Cardiovasc Buenos Aires, Buenos Aires, DF, Argentina. [Soska, Vladimir] Fac Hosp St Anna, Dept Clin Biochem, Brno, Czech Republic. [Soska, Vladimir] Fac Hosp St Anna, Clin Internal Med 2, Brno, Czech Republic. [Stender, Steen] Univ Copenhagen, Gentofte Hosp, Dept Clin Biochem, Copenhagen, Denmark. [Tamas, Gyula] Semmelweis Univ, Diabet Unit, Dept Med 1, H-1085 Budapest, Hungary. [Tognoni, Gianni] Ist Ric Farmacol Mario Negri, Consorzio Mario Negri Sud, I-66030 Santa Maria Imbaro, Italy. [Tuomilehto, Jaako] Univ Helsinki, Hjelt Inst, Helsinki, Finland. [Tuomilehto, Jaako] Univ Helsinki, Dept Publ Hlth, Helsinki, Finland. [Tuomilehto, Jaako] S Ostrobothnia Cent Hosp, Seinajoki, Finland. [Villamil, Alberto S.] Univ Buenos Aires, Div Cardiol, Hypertens Unit, Argerich Hosp, Buenos Aires, DF, Argentina. [Vozar, Juraj] Diabetol Outpatient Clin, Jesenius Samaria, Samorin, Slovakia. [Califf, Robert M.] Duke Univ, Duke Translat Med Inst, Durham, NC USA. RP Califf, RM (reprint author), Duke Translat Med Inst, POB 17969, Durham, NC 27715 USA. EM calif001@mc.duke.edu RI Diem, Peter/A-7650-2008; Gaztambide, Sonia/E-1760-2012; OI Davies, Melanie/0000-0002-9987-9371; Holzhauer, Bjorn/0000-0002-9209-757X; Mareev, Vyacheslav Yurievich/0000-0002-7285-2048; Kahn, Steven/0000-0001-7307-9002; mcmurray, john/0000-0002-6317-3975; CHIANG, FU-TIEN/0000-0003-4936-8968 FU Novartis Pharma FX Supported by Novartis Pharma. NR 42 TC 290 Z9 299 U1 1 U2 43 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 22 PY 2010 VL 362 IS 16 BP 1477 EP 1490 DI 10.1056/NEJMoa1001121 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 586GP UT WOS:000276894700007 ER PT J AU Kradin, RL Digumarthy, SR Baggish, AL Mark, EJ AF Kradin, Richard L. Digumarthy, Subba R. Baggish, Aaron L. Mark, Eugene J. TI A Man with Progressive Dyspnea Pulmonary asbestosis, evolving into an accelerated phase. Pleural hyaline plaque SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID LUNG-DISEASE; EXPOSURE; CRITERIA; CT C1 [Kradin, Richard L.] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Kradin, Richard L.; Mark, Eugene J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Digumarthy, Subba R.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Baggish, Aaron L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Kradin, Richard L.; Mark, Eugene J.] Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. [Digumarthy, Subba R.] Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. [Kradin, Richard L.; Baggish, Aaron L.] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. RP Kradin, RL (reprint author), Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. NR 18 TC 2 Z9 2 U1 1 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 22 PY 2010 VL 362 IS 16 BP 1522 EP 1531 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 586GP UT WOS:000276894700014 PM 20410518 ER PT J AU Nathan, DM AF Nathan, David M. TI Navigating the Choices for Diabetes Prevention SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID IMPAIRED GLUCOSE-TOLERANCE; CARDIOVASCULAR-DISEASE; FASTING GLUCOSE; PROGRESSION; RAMIPRIL; OUTCOMES; TRIAL; RISK C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Diabet, Boston, MA 02115 USA. RP Nathan, DM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Diabet, Boston, MA 02115 USA. NR 12 TC 14 Z9 14 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 22 PY 2010 VL 362 IS 16 BP 1533 EP 1535 DI 10.1056/NEJMe1002322 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 586GP UT WOS:000276894700015 PM 20228400 ER PT J AU Warshaw, AL AF Warshaw, Andrew L. TI Improving the Treatment of Necrotizing Pancreatitis - A Step Up SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID SURGICAL-TREATMENT; NECROSIS C1 [Warshaw, Andrew L.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Warshaw, Andrew L.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Warshaw, AL (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 10 TC 17 Z9 26 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 22 PY 2010 VL 362 IS 16 BP 1535 EP 1537 DI 10.1056/NEJMe1001835 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 586GP UT WOS:000276894700016 PM 20410519 ER PT J AU Rosand, J Meschia, JF Singleton, AB AF Rosand, Jonathan Meschia, James F. Singleton, Andrew B. CA Int Stroke Genetics Consortium Wellcome Trust Case-Control Consor TI Failure to Validate Association between 12p13 Variants and Ischemic Stroke SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Rosand, Jonathan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Meschia, James F.] Mayo Clin, Jacksonville, FL 32224 USA. [Singleton, Andrew B.] NIA, Bethesda, MD 20892 USA. RP Rosand, J (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Singleton, Andrew/C-3010-2009; Hardy, John/C-2451-2009; Deloukas, Panos/B-2922-2013; Ross, Owen/D-7573-2013; Matarin, Mar/F-1771-2016; OI Deloukas, Panos/0000-0001-9251-070X; Matarin, Mar/0000-0002-4717-5735; Jackson, Caroline/0000-0002-2067-2811; Jankowski, Janusz/0000-0003-2130-9181 NR 3 TC 1 Z9 1 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 22 PY 2010 VL 362 IS 16 BP 1547 EP 1550 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 586GP UT WOS:000276894700032 ER PT J AU Tsai, TT Nallamothu, BK Rumsfeld, JS AF Tsai, Thomas T. Nallamothu, Brahmajee K. Rumsfeld, John S. TI Contraindicated Medication Use in Dialysis Patients Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 [Tsai, Thomas T.; Rumsfeld, John S.] Denver VA Med Ctr, Denver, CO USA. [Nallamothu, Brahmajee K.] Ann Arbor VA Med Ctr, Ann Arbor, MI USA. RP Tsai, TT (reprint author), Denver VA Med Ctr, Denver, CO USA. EM thomas.tsai@va.gov NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 21 PY 2010 VL 303 IS 15 BP 1482 EP 1482 DI 10.1001/jama.2010.444 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 585SJ UT WOS:000276849000022 ER PT J AU Nelson, HD Naik, A Humphrey, L Tyne, K AF Nelson, Heidi D. Naik, Arpana Humphrey, Linda Tyne, Kari TI The Background Review for the USPSTF Recommendation on Screening for Breast Cancer Response SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 [Nelson, Heidi D.; Naik, Arpana] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. [Humphrey, Linda] Portland VA Med Ctr, Portland, OR 97239 USA. [Tyne, Kari] HealthPartners, St Paul, MN 55114 USA. RP Nelson, HD (reprint author), Oregon Hlth & Sci Univ, Portland, OR 97239 USA. NR 2 TC 1 Z9 1 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD APR 20 PY 2010 VL 152 IS 8 BP 538 EP 539 DI 10.7326/0003-4819-152-8-201004200-00199 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 588FV UT WOS:000277054400013 ER PT J AU Enshell-Seijffers, D Lindon, C Kashiwagi, M Morgan, BA AF Enshell-Seijffers, David Lindon, Catherine Kashiwagi, Mariko Morgan, Bruce A. TI beta-catenin Activity in the Dermal Papilla Regulates Morphogenesis and Regeneration of Hair SO DEVELOPMENTAL CELL LA English DT Article ID FOLLICLE STEM-CELLS; GROWTH-FACTOR; TRANSIENT ACTIVATION; KERATINOCYTE GROWTH; DIFFERENTIATION; MICE; SKIN; EPIDERMIS; PATHWAY; TUMORS AB The activity of keratinocytes in the hair follicle is regulated by signals from a specialized mesenchymal niche, the dermal papilla (DP). Here, mice expressing cre recombinase in the DP were developed to probe the interaction between follicular keratinocytes and the DP in vivo. Inactivation of the beta-catenin gene within DP of fully developed hair follicles results in dramatically reduced proliferation of the progenitors and their progeny that generate the hair shaft, and, subsequently, premature induction of the destructive phase of the hair cycle. It also prevents regeneration of the cycling follicle from stem cells. Gene expression analysis reveals that beta-catenin activity in the DP regulates signaling pathways, including FGF and IGF, that can mediate the DP's inductive effects. This study reveals a signaling loop that employs Wnt/beta-catenin signaling in both epithelial progenitor cells and their mesenchymal niche to govern and coordinate the interactions between these compartments to guide hair morphogenesis. C1 [Enshell-Seijffers, David; Lindon, Catherine; Kashiwagi, Mariko; Morgan, Bruce A.] Harvard Univ, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. [Enshell-Seijffers, David; Lindon, Catherine; Kashiwagi, Mariko; Morgan, Bruce A.] Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Morgan, BA (reprint author), Harvard Univ, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. EM bruce.morgan@cbrc2.mgh.harvard.edu OI Enshell-Seijffers, David/0000-0002-8228-2659 FU National Institute of Arthritis, Musculoskeletal and Skin Diseases [R01AR055256]; Shiseido, Ltd. FX We thank Eleanor Wu and Ying Zheng for technical assistance and F. Costantini and G. Martin for providing mice. This work was supported by grants from the National Institute of Arthritis, Musculoskeletal and Skin Diseases (R01AR055256, B.A.M.), and Shiseido, Ltd. (B.A.M.). NR 39 TC 127 Z9 131 U1 0 U2 11 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD APR 20 PY 2010 VL 18 IS 4 BP 633 EP 642 DI 10.1016/j.devcel.2010.01.016 PG 10 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 588WR UT WOS:000277105800015 PM 20412777 ER PT J AU Wen, PY AF Wen, Patrick Y. TI Therapy for Recurrent High-Grade Gliomas: Does Continuous Dose-Intense Temozolomide Have a Role? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID BEVACIZUMAB PLUS IRINOTECAN; MGMT PROMOTER METHYLATION; PROGRESSION-FREE SURVIVAL; PHASE-III TRIAL; MALIGNANT GLIOMAS; ADJUVANT TEMOZOLOMIDE; GLIOBLASTOMA; RADIOTHERAPY; CHEMOTHERAPY; CONCOMITANT C1 [Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA USA. [Wen, Patrick Y.] Brigham & Womens Hosp, Dept Neurol, Div Neurooncol, Boston, MA 02115 USA. RP Wen, PY (reprint author), Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA USA. NR 27 TC 7 Z9 8 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 20 PY 2010 VL 28 IS 12 BP 1977 EP 1979 DI 10.1200/JCO.2009.27.6014 PG 3 WC Oncology SC Oncology GA 584PF UT WOS:000276764000003 PM 20308652 ER PT J AU Friedman, HS Prados, MD Wen, PY Mikkelsen, T Schiff, D Abrey, LE Yung, WKA Paleologos, N Nicholas, MK Jensen, R Vredenburgh, J Huang, J Zheng, MX Cloughesy, T AF Friedman, Henry S. Prados, Michael D. Wen, Patrick Y. Mikkelsen, Tom Schiff, David Abrey, Lauren E. Yung, W. K. Alfred Paleologos, Nina Nicholas, Martin K. Jensen, Randy Vredenburgh, James Huang, Jane Zheng, Maoxia Cloughesy, Timothy TI Bevacizumab and Recurrent Malignant Gliomas: A European Perspective Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID CELL LUNG-CANCER; PHASE-III TRIAL; GLIOBLASTOMA-MULTIFORME; PLUS IRINOTECAN; CLINICAL-TRIALS; THERAPY; SURVIVAL; EFFICACY; PATTERNS; CRITERIA C1 [Friedman, Henry S.] Duke Univ, Preston Robert Tisch Brain Tumor Ctr Duke, Durham, NC 27710 USA. [Prados, Michael D.] Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA 94143 USA. [Wen, Patrick Y.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Wen, Patrick Y.] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. [Mikkelsen, Tom] Henry Ford Hosp, Hermelin Brain Tumor Ctr, Detroit, MI 48202 USA. [Schiff, David] Univ Virginia, Dept Neurol, Charlottesville, VA USA. [Abrey, Lauren E.] Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10021 USA. [Yung, W. K. Alfred] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. [Paleologos, Nina] NorthShore Univ Hlth Syst, Dept Neurol, Evanston, IL USA. [Nicholas, Martin K.] Univ Chicago, Dept Neurol, Chicago, IL 60637 USA. [Jensen, Randy] Univ Utah Hosp, Salt Lake City, UT USA. [Vredenburgh, James] Duke Univ, Preston Robert Tisch Brain Tumor Ctr Duke, Durham, NC USA. [Huang, Jane; Zheng, Maoxia] Genentech Inc, San Francisco, CA 94080 USA. [Cloughesy, Timothy] Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90024 USA. RP Friedman, HS (reprint author), Duke Univ, Preston Robert Tisch Brain Tumor Ctr Duke, Durham, NC 27710 USA. NR 23 TC 4 Z9 4 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 20 PY 2010 VL 28 IS 12 BP E190 EP E192 DI 10.1200/JCO.2009.26.9472 PG 3 WC Oncology SC Oncology GA 584PF UT WOS:000276764000029 ER PT J AU Sondergaard, JN Nazarian, R Wang, Q Guo, DL Hsueh, T Mok, S Sazegar, H MacConaill, LE Barretina, JG Kehoe, SM Attar, N von Euw, E Zuckerman, JE Chmielowski, B Comin-Anduix, B Koya, RC Mischel, PS Lo, RS Ribas, A AF Sondergaard, Jonas N. Nazarian, Ramin Wang, Qi Guo, Deliang Hsueh, Teli Mok, Stephen Sazegar, Hooman MacConaill, Laura E. Barretina, Jordi G. Kehoe, Sarah M. Attar, Narsis von Euw, Erika Zuckerman, Jonathan E. Chmielowski, Bartosz Comin-Anduix, Begona Koya, Richard C. Mischel, Paul S. Lo, Roger S. Ribas, Antoni TI Differential sensitivity of melanoma cell lines with BRAF(V600E) mutation to the specific Raf inhibitor PLX4032 SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Article ID B-RAF; TARGETED THERAPY; HUMAN CANCER; BRAF; ACTIVATION; PATHWAY; KINASE; RESISTANCE; MECHANISM; GENE AB Blocking oncogenic signaling induced by the BRAF(V600E) mutation is a promising approach for melanoma treatment. We tested the anti-tumor effects of a specific inhibitor of Raf protein kinases, PLX4032/RG7204, in melanoma cell lines. PLX4032 decreased signaling through the MAPK pathway only in cell lines with the BRAF(V600E) mutation. Seven out of 10 BRAF(V600E) mutant cell lines displayed sensitivity based on cell viability assays and three were resistant at concentrations up to 10 mu M. Among the sensitive cell lines, four were highly sensitive with IC50 values below 1 mu M, and three were moderately sensitive with IC50 values between 1 and 10 mu M. There was evidence of MAPK pathway inhibition and cell cycle arrest in both sensitive and resistant cell lines. Genomic analysis by sequencing, genotyping of close to 400 oncogeninc mutations by mass spectrometry, and SNP arrays demonstrated no major differences in BRAF locus amplification or in other oncogenic events between sensitive and resistant cell lines. However, metabolic tracer uptake studies demonstrated that sensitive cell lines had a more profound inhibition of FDG uptake upon exposure to PLX4032 than resistant cell lines. In conclusion, BRAF(V600E) mutant melanoma cell lines displayed a range of sensitivities to PLX4032 and metabolic imaging using PET probes can be used to assess sensitivity. C1 [Sondergaard, Jonas N.; Hsueh, Teli; Mok, Stephen; Sazegar, Hooman; Attar, Narsis; Zuckerman, Jonathan E.; Chmielowski, Bartosz; Ribas, Antoni] Univ Calif Los Angeles, Dept Med, Div Hematol Oncol, Los Angeles, CA 90024 USA. [Sondergaard, Jonas N.; von Euw, Erika; Comin-Anduix, Begona; Koya, Richard C.; Ribas, Antoni] Univ Calif Los Angeles, Dept Surg, Div Surg Oncol, Los Angeles, CA 90024 USA. [Nazarian, Ramin; Wang, Qi; Lo, Roger S.] Univ Calif Los Angeles, Dept Med, Div Dermatol, Los Angeles, CA 90024 USA. [Guo, Deliang; Mischel, Paul S.] Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA USA. [MacConaill, Laura E.; Barretina, Jordi G.; Kehoe, Sarah M.] MIT & Harvard, Broad Inst, Cambridge, MA USA. [MacConaill, Laura E.; Barretina, Jordi G.; Kehoe, Sarah M.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [MacConaill, Laura E.; Barretina, Jordi G.; Kehoe, Sarah M.] Harvard Univ, Sch Med, Dept Pediat Oncol, Boston, MA USA. [MacConaill, Laura E.; Barretina, Jordi G.; Kehoe, Sarah M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Mischel, Paul S.; Lo, Roger S.; Ribas, Antoni] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. RP Ribas, A (reprint author), Univ Calif Los Angeles, Dept Med, Div Hematol Oncol, Los Angeles, CA 90024 USA. EM aribas@mednet.ucla.edu RI Guo, Deliang/I-3735-2014; Norskov Sondergaard, Jonas/P-6147-2015; OI Guo, Deliang/0000-0002-8359-390X; Norskov Sondergaard, Jonas/0000-0002-4438-6756; Chmielowski, Bartosz/0000-0002-2374-3320 FU Jonsson Cancer Center Foundation (JCCF); NIH [P50 CA086306]; Caltech-UCLA Joint Center for Translational Medicine; Dermatology Foundation; STOP CANCER Foundation; Burroughs Welcome Fund FX We would like to thank Dr. Gideon Bollag from Plexxikon for providing PLX4032 and for helpful discussions regarding these studies. We would also like to thank Drs. William Tap and Dennis Slamon at UCLA, and Peter Hirth at Plexxikon for helpful discussions. This work was funded in part by the Jonsson Cancer Center Foundation (JCCF), the NIH award P50 CA086306 and by the Caltech-UCLA Joint Center for Translational Medicine (to AR); and the Dermatology Foundation, the STOP CANCER Foundation and the Burroughs Welcome Fund (to RSL). NR 26 TC 117 Z9 118 U1 0 U2 11 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD APR 20 PY 2010 VL 8 AR 39 DI 10.1186/1479-5876-8-39 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 604RC UT WOS:000278295200002 PM 20406486 ER PT J AU Hacke, K Rincon-Orozco, B Buchwalter, G Siehler, SY Wasylyk, B Wiesmuller, L Rosl, F AF Hacke, Katrin Rincon-Orozco, Bladimiro Buchwalter, Gilles Siehler, Simone Y. Wasylyk, Bohdan Wiesmueller, Lisa Roesl, Frank TI Research Regulation of MCP-1 chemokine transcription by p53 SO MOLECULAR CANCER LA English DT Article ID NF-KAPPA-B; CHEMOATTRACTANT PROTEIN-1 GENE; TUMOR-NECROSIS-FACTOR; CERVICAL-CARCINOMA CELLS; JE GENE; CANCER SYNDROME; SUPPRESSOR P53; IN-VIVO; EXPRESSION; ACTIVATION AB Background: Our previous studies showed that the expression of the monocyte-chemoattractant protein (MCP)-1, a chemokine, which triggers the infiltration and activation of cells of the monocyte-macrophage lineage, is abrogated in human papillomavirus (HPV)-positive premalignant and malignant cells. In silico analysis of the MCP-1 upstream region proposed a putative p53 binding side about 2.5 kb upstream of the transcriptional start. The aim of this study is to monitor a physiological role of p53 in this process. Results: The proposed p53 binding side could be confirmed in vitro by electrophoretic-mobility-shift assays and in vivo by chromatin immunoprecipitation. Moreover, the availability of p53 is apparently important for chemokine regulation, since TNF-alpha can induce MCP-1 only in human keratinocytes expressing the viral oncoprotein E7, but not in HPV16 E6 positive cells, where p53 becomes degraded. A general physiological role of p53 in MCP-1 regulation was further substantiated in HPV-negative cells harboring a temperature-sensitive mutant of p53 and in Li-Fraumeni cells, carrying a germ-line mutation of p53. In both cases, non-functional p53 leads to diminished MCP-1 transcription upon TNF-alpha treatment. In addition, siRNA directed against p53 decreased MCP-1 transcription after TNF-alpha addition, directly confirming a crosstalk between p53 and MCP-1. Conclusion: These data support the concept that p53 inactivation during carcinogenesis also affects immune surveillance by interfering with chemokine expression and in turn communication with cells of the immunological compartment. C1 [Rincon-Orozco, Bladimiro; Roesl, Frank] Deutsch Krebsforschungszentrum, Forsch Schwerpunkt Infekt & Krebs, Abt Virale Transformat Mech, D-6900 Heidelberg, Germany. [Hacke, Katrin] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Buchwalter, Gilles] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hacke, Katrin] Deutsch Krebsforschungszentrum, Forsch Schwerpunkt Infekt & Krebs, Abt Genomveranderung & Karzinogenese, D-6900 Heidelberg, Germany. [Siehler, Simone Y.; Wiesmueller, Lisa] Univ Frauenklin, Sekt Gynakol Onkol, Ulm, Germany. [Buchwalter, Gilles; Wasylyk, Bohdan] Inst Genet & Biol Mol & Cellulaire, Illkirch Graffenstaden, France. RP Rosl, F (reprint author), Deutsch Krebsforschungszentrum, Forsch Schwerpunkt Infekt & Krebs, Abt Virale Transformat Mech, D-6900 Heidelberg, Germany. FU Deutsche Krebshilfe [10-1983 RoI.]; Deutsche Forschungsgemeinschaft [Wi 1376/3-1, Wi 1376/3-2]; CNRS; INSERM; ARC LNCC; INCa FX The authors thank Moshe Oren (Weizmann Institute of Science, Rehovot, Israel) for providing the stable Hep3B clones and Michael Tainsky (Wayne State University School of Medicine, Detroit, MI 48201, USA) for providing the Li-Fraumeni cells. The pSUPER vector system was kindly made available by Reuven Agami (The Netherlands Cancer Institute, Amsterdam, Netherlands). The excellent technical support of Regina Ly, Nadine Gmelin and Corinna Klein is appreciated. The authors thank Michael Stoehr (DKFZ, Heidelberg) for his help in flow cytometric analysis. We also appreciate the engagement of Patrick Finzer (Bioscientia, Institute for Medical Diagnostics, Moers, Germany), who was initially involved in this study. In particular his special part in the supervision of Katrin Hacke's PhD thesis has to be emphasized. This work was primarily supported by the Deutsche Krebshilfe, (grant 10-1983 RoI.) and partially by the Deutsche Forschungsgemeinschaft, (grants Wi 1376/3-1 and -2). Work done in the Wasylyk laboratory was financed by the CNRS, INSERM, ARC LNCC and INCa. NR 61 TC 23 Z9 25 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1476-4598 J9 MOL CANCER JI Mol. Cancer PD APR 20 PY 2010 VL 9 AR 82 DI 10.1186/1476-4598-9-82 PG 12 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 592TF UT WOS:000277402500001 PM 20406462 ER PT J AU Fiocco, AJ Lindquist, K Ferrell, R Li, R Simonsick, EM Nalls, M Harris, TB Yaffe, K AF Fiocco, A. J. Lindquist, K. Ferrell, R. Li, R. Simonsick, E. M. Nalls, M. Harris, T. B. Yaffe, K. CA Hlth ABC Study TI COMT genotype and cognitive function An 8-year longitudinal study in white and black elders SO NEUROLOGY LA English DT Article ID CATECHOL-O-METHYLTRANSFERASE; OLDER-ADULTS; PREFRONTAL FUNCTION; ALZHEIMER-DISEASE; BODY-COMPOSITION; MESSENGER-RNA; POLYMORPHISM; DOPAMINE; DEMENTIA; BRAIN AB Objective: Catechol-O-methyltransferase (COMT), an enzyme that catalyzes the degradation of dopamine, is necessary for cognitive function. Few studies have examined the prospective association between COMT (val(158)met) genotype and cognition in older adults. Methods: We assessed a biracial cohort of 2,858 elderly subjects without dementia who were followed for 8 years. The Modified Mini-Mental State Examination (3MS) and Digit Symbol Substitution Test (DSST) were administered at baseline and years 3, 5, and 8. COMT by race, gender, and APOE status interactions were examined. Results: Stratified by race and adjusted for covariates, repeated-measures mixed-effects models showed no association between COMT genotype and baseline cognitive function in black or white subjects. In white subjects, COMT was associated with change in 3MS (Met/Met: -2.3 [0.60], Met/Val: -1.7 [0.40], and Val/Val: -1.2 [0.50]) and DSST (Met/Met: -5.60 [1.00], Met/Val: -4.80 [0.70], Val/Val: -4.00 [0.90]). In black subjects, COMT was associated with change in the DSST (Met/Met: -4.10 [2.1], Met/Val: -4.80 [0.90], Val/Val -2.60 [1.00]). Conclusion: These findings suggest that the Val allele has a protective impact on cognitive decline in late life. Neurology (R) 2010;74:1296-1302 C1 [Fiocco, A. J.; Yaffe, K.] Univ Calif San Francisco, Sch Med, Dept Psychiat, San Francisco, CA 94121 USA. [Yaffe, K.] Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA 94121 USA. [Yaffe, K.] Univ Calif San Francisco, Sch Med, Dept Neurol, San Francisco, CA 94121 USA. [Lindquist, K.] Univ Calif San Francisco, Sch Med, Dept Med, San Francisco, CA 94121 USA. [Yaffe, K.] San Francisco VA Med Ctr, San Francisco, CA USA. [Ferrell, R.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA. [Li, R.] Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN USA. [Simonsick, E. M.] NIA, Clin Res Branch, Baltimore, MD 21224 USA. [Nalls, M.] NIA, Neurogenet Lab, Bethesda, MD 20892 USA. [Harris, T. B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA. RP Fiocco, AJ (reprint author), Univ Calif San Francisco, Sch Med, Dept Psychiat, 4150 Clement St,Box 116H, San Francisco, CA 94121 USA. EM afiocco@klaru-baycrest.on.ca RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Kritchevsky, Stephen/0000-0003-3336-6781 FU NIH, National Institute on Aging; Canadian Institute of Health; [N01-AG-6-2101]; [N01-AG-6-2103]; [N01-AG-6-2106]; [1R21DK068608-01A2]; [AG031155] FX Funded by N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106. The measurement of F2-isoprostane was funded by 1R21DK068608-01A2. This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging. Dr. Fiocco is supported by the Canadian Institute of Health Research Fellowship in the area of Longitudinal Study on Aging. Dr. Yaffe was supported in part by AG031155 and an anonymous foundation. NR 40 TC 13 Z9 13 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR 20 PY 2010 VL 74 IS 16 BP 1296 EP 1302 DI 10.1212/WNL.0b013e3181d9edba PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 585HQ UT WOS:000276816200010 PM 20404311 ER PT J AU Neale, BM Fagerness, J Reynolds, R Sobrin, L Parker, M Raychaudhuri, S Tan, PL Oh, EC Merriam, JE Souied, E Bernstein, PS Li, BX Frederick, JM Zhang, K Brantley, MA Lee, AY Zack, DJ Campochiaro, B Campochiaro, P Ripke, S Smith, RT Barile, GR Katsanis, N Allikmets, R Daly, MJ Seddon, JM AF Neale, Benjamin M. Fagerness, Jesen Reynolds, Robyn Sobrin, Lucia Parker, Margaret Raychaudhuri, Soumya Tan, Perciliz L. Oh, Edwin C. Merriam, Joanna E. Souied, Eric Bernstein, Paul S. Li, Binxing Frederick, Jeanne M. Zhang, Kang Brantley, Milam A., Jr. Lee, Aaron Y. Zack, Donald J. Campochiaro, Betsy Campochiaro, Peter Ripke, Stephan Smith, R. Theodore Barile, Gaetano R. Katsanis, Nicholas Allikmets, Rando Daly, Mark J. Seddon, Johanna M. TI Genome-wide association study of advanced age-related macular degeneration identifies a role of the hepatic lipase gene (LIPC) SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE complex disease; HDL; lipid pathway; retinal degeneration ID COMPLEMENT FACTOR-H; VARIANT; RISK; SUSCEPTIBILITY; POLYMORPHISM; INCREASES; HAPLOTYPE; PROMOTER; LINKAGE; POWER AB Advanced age-related macular degeneration (AMD) is the leading cause of late onset blindness. We present results of a genome-wide association study of 979 advanced AMD cases and 1,709 controls using the Affymetrix 6.0 platform with replication in seven additional cohorts (totaling 5,789 unrelated cases and 4,234 unrelated controls). We also present a comprehensive analysis of copy-number variations and polymorphisms for AMD. Our discovery data implicated the association between AMD and a variant in the hepatic lipase gene (LIPC) in the high-density lipoprotein cholesterol (HDL) pathway (discovery P = 4.53e-05 for rs493258). Our LIPC association was strongest for a functional promoter variant, rs10468017, (P = 1.34e-08), that influences LIPC expression and serum HDL levels with a protective effect of the minor T allele (HDL increasing) for advanced wet and dry AMD. The association we found with LIPC was corroborated by the Michigan/Penn/Mayo genome-wide association study; the locus near the tissue inhibitor of metalloproteinase 3 was corroborated by our replication cohort for rs9621532 with P = 3.71e-09. We observed weaker associations with other HDL loci (ABCA1, P = 9.73e-04; cholesterylester transfer protein, P = 1.41e-03; FADS1-3, P = 2.69e-02). Based on a lack of consistent association between HDL increasing alleles and AMD risk, the LIPC association may not be the result of an effect on HDL levels, but it could represent a pleiotropic effect of the same functional component. Results implicate different biologic pathways than previously reported and provide new avenues for prevention and treatment of AMD. C1 [Neale, Benjamin M.; Fagerness, Jesen; Raychaudhuri, Soumya; Ripke, Stephan; Daly, Mark J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Neale, Benjamin M.; Fagerness, Jesen; Raychaudhuri, Soumya; Ripke, Stephan; Daly, Mark J.] Harvard & Massachusetts Inst Technol, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Neale, Benjamin M.] Kings Coll London, Inst Psychiat, Social Genet & Dev Psychiat Ctr, London SE5 8AF, England. [Reynolds, Robyn; Parker, Margaret] Tufts Univ, Sch Med, Tufts Med Ctr, Ophthalm Epidemiol & Genet Serv,New England Eye C, Boston, MA 02111 USA. [Sobrin, Lucia] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Tan, Perciliz L.; Oh, Edwin C.; Zack, Donald J.; Campochiaro, Betsy; Campochiaro, Peter] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, McKusick Nathans Inst Genet Med,Dept Ophthalmol, Baltimore, MD 21205 USA. [Merriam, Joanna E.; Smith, R. Theodore; Barile, Gaetano R.; Allikmets, Rando] Columbia Univ, Dept Ophthalmol, New York, NY 10032 USA. [Souied, Eric] Univ Paris 12, Dept Ophthalmol, Hop Intercommunal Creteil, F-94000 Creteil, France. [Bernstein, Paul S.; Li, Binxing; Frederick, Jeanne M.; Zhang, Kang] Univ Utah, Sch Med, Moran Eye Ctr, Dept Ophthalmol & Visual Sci, Salt Lake City, UT 84132 USA. [Zhang, Kang] Univ Calif San Diego, Inst Genom Med, San Diego, CA 92093 USA. [Zhang, Kang] Univ Calif San Diego, Shiley Eye Ctr, San Diego, CA 92093 USA. [Brantley, Milam A., Jr.; Lee, Aaron Y.] Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, St Louis, MO 63110 USA. [Brantley, Milam A., Jr.] Barnes Retina Inst, St Louis, MO 63144 USA. [Katsanis, Nicholas] Duke Univ, Ctr Human Dis Modeling, Durham, NC 27710 USA. [Katsanis, Nicholas] Duke Univ, Dept Cell Biol, Durham, NC 27710 USA. [Katsanis, Nicholas] Duke Univ, Dept Pediat, Durham, NC 27710 USA. [Allikmets, Rando] Columbia Univ, Dept Pathol & Cell Biol, New York, NY 10032 USA. [Seddon, Johanna M.] Tufts Univ, Sch Med, Dept Ophthalmol, Boston, MA 02111 USA. RP Daly, MJ (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. EM mjdaly@chgr.mgh.harvard.edu; jseddon@tuftsmedicalcenter.org RI Li, Binxing/C-9153-2012; Katsanis, Nicholas/E-1837-2012; OI Zack, Don/0000-0002-7966-1973; Lee, Aaron/0000-0002-7452-1648; smith, theodore/0000-0002-1693-943X; Katsanis, Nicholas/0000-0002-2480-0171 FU National Institutes of Health [R01-EY11309, R01-EY13435, R24-EY017404, K12-EY16335, R01 HL087676, R01-EY11600, U54 RR020278]; Massachusetts Lions Eye Research Fund, Inc.; Research to Prevent Blindness, Inc.; Macula Vision Research Foundation; Kaplen Foundation; Widgeon Point Charitable Foundation; Alcon Research institute; Fight for Sight; Ophthalmic Epidemiology and Genetics Service, New England Eye Center, Tufts Medical Center, Tufts University School of Medicine FX We appreciate the contribution of an anonymous donor to the research of J.M.S., without whom this genome-wide association study would not have been possible. We thank the participants and numerous ophthalmologists throughout the country who participated in this study, the Age Related Eye Disease Study Research Group, Daniel Mirel at the Broad Institute Center for Genotyping and Analysis for help with the execution of the SNP genotyping. We thank the Michigan/Penn/Mayo genome-wide association study group for providing results from their study for some of our top SNPs. We thank the MIGen study for the use of their genotype data, and the Brigham Research Institute for the contribution of control DNA samples. This research was supported in part by Grants R01-EY11309, R01-EY13435, R24-EY017404, K12-EY16335, R01 HL087676, R01-EY11600, and U54 RR020278 from the National Institutes of Health, Massachusetts Lions Eye Research Fund, Inc., unrestricted grants and a Career Development Award from Research to Prevent Blindness, Inc., Macula Vision Research Foundation, Kaplen Foundation, Widgeon Point Charitable Foundation, Alcon Research institute, Fight for Sight postdoctoral award, and the Macular Degeneration Research Fund of the Ophthalmic Epidemiology and Genetics Service, New England Eye Center, Tufts Medical Center, Tufts University School of Medicine. NR 30 TC 214 Z9 221 U1 0 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 20 PY 2010 VL 107 IS 16 BP 7395 EP 7400 DI 10.1073/pnas.0912019107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 586FU UT WOS:000276892300053 PM 20385826 ER PT J AU Chen, W Stambolian, D Edwards, AO Branham, KE Othman, M Jakobsdottir, J Tosakulwong, N Pericak-Vance, MA Campochiaro, PA Klein, ML Tan, PL Conley, YP Kanda, A Kopplin, L Li, YM Augustaitis, KJ Karoukis, AJ Scott, WK Agarwal, A Kovach, JL Schwartz, SG Postel, EA Brooks, M Baratz, KH Brown, WL Brucker, AJ Orlin, A Brown, G Ho, A Regillo, C Donoso, L Tian, LF Kaderli, B Hadley, D Hagstrom, SA Peachey, NS Klein, R Klein, BEK Gotoh, N Yamashiro, K Ferris, F Fagerness, JA Reynolds, R Farrer, LA Kim, IK Miller, JW Corton, M Carracedo, A Sanchez-Salorio, M Pugh, EW Doheny, KF Brion, M DeAngelis, MM Weeks, DE Zack, DJ Chew, EY Heckenlively, JR Yoshimura, N Iyengar, SK Francis, PJ Katsanis, N Seddon, JM Haines, JL Gorin, MB Abecasis, GR Swaroop, A AF Chen, Wei Stambolian, Dwight Edwards, Albert O. Branham, Kari E. Othman, Mohammad Jakobsdottir, Johanna Tosakulwong, Nirubol Pericak-Vance, Margaret A. Campochiaro, Peter A. Klein, Michael L. Tan, Perciliz L. Conley, Yvette P. Kanda, Atsuhiro Kopplin, Laura Li, Yanming Augustaitis, Katherine J. Karoukis, Athanasios J. Scott, William K. Agarwal, Anita Kovach, Jaclyn L. Schwartz, Stephen G. Postel, Eric A. Brooks, Matthew Baratz, Keith H. Brown, William L. Brucker, Alexander J. Orlin, Anton Brown, Gary Ho, Allen Regillo, Carl Donoso, Larry Tian, Lifeng Kaderli, Brian Hadley, Dexter Hagstrom, Stephanie A. Peachey, Neal S. Klein, Ronald Klein, Barbara E. K. Gotoh, Norimoto Yamashiro, Kenji Ferris, Frederick, III Fagerness, Jesen A. Reynolds, Robyn Farrer, Lindsay A. Kim, Ivana K. Miller, Joan W. Corton, Marta Carracedo, Angel Sanchez-Salorio, Manuel Pugh, Elizabeth W. Doheny, Kimberly F. Brion, Maria DeAngelis, Margaret M. Weeks, Daniel E. Zack, Donald J. Chew, Emily Y. Heckenlively, John R. Yoshimura, Nagahisa Iyengar, Sudha K. Francis, Peter J. Katsanis, Nicholas Seddon, Johanna M. Haines, Jonathan L. Gorin, Michael B. Abecasis, Goncalo R. Swaroop, Anand CA Complications Age-Related Macular TI Genetic variants near TIMP3 and high-density lipoprotein-associated loci influence susceptibility to age-related macular degeneration SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE genome-wide association study; single nucleotide polymorphism ID COMPLEMENT FACTOR-H; GENOME-WIDE ASSOCIATION; RISK-FACTORS; DISEASE; POLYMORPHISM; MACULOPATHY; COMMON; METAANALYSIS; DEPOSITS; DRUSEN AB We executed a genome-wide association scan for age-related macular degeneration (AMD) in 2,157 cases and 1,150 controls. Our results validate AMD susceptibility loci near CFH (P < 10(-75)), ARMS2 (P < 10(-59)), C2/CFB (P < 10(-20)), C3 (P < 10(-9)), and CFI (P < 10(-6)). We compared our top findings with the Tufts/Massachusetts General Hospital genome-wide association study of advanced AMD (821 cases, 1,709 controls) and genotyped 30 promising markers in additional individuals (up to 7,749 cases and 4,625 controls). With these data, we identified a susceptibility locus near TIMP3 (overall P = 1.1 x 10(-11)), a metalloproteinase involved in degradation of the extracellular matrix and previously implicated in early-onset maculopathy. In addition, our data revealed strong association signals with alleles at two loci (LIPC, P = 1.3 x 10(-7); CETP, P = 7.4 x 10(-7)) that were previously associated with high-density lipoprotein cholesterol (HDL-c) levels in blood. Consistent with the hypothesis that HDL metabolism is associated with AMD pathogenesis, we also observed association with AMD of HDL-c-associated alleles near LPL (P = 3.0 x 10(-3)) and ABCA1 (P = 5.6 x 10(-4)). Multilocus analysis including all susceptibility loci showed that 329 of 331 individuals (99%) with the highest-risk genotypes were cases, and 85% of these had advanced AMD. Our studies extend the catalog of AMD associated loci, help identify individuals at high risk of disease, and provide clues about underlying cellular pathways that should eventually lead to new therapies. C1 [Chen, Wei; Li, Yanming; Abecasis, Goncalo R.] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Edwards, Albert O.; Tosakulwong, Nirubol; Baratz, Keith H.; Brown, William L.] Mayo Clin, Rochester, MN 55906 USA. [Branham, Kari E.; Othman, Mohammad; Augustaitis, Katherine J.; Karoukis, Athanasios J.; Heckenlively, John R.] Univ Michigan, Ann Arbor, MI 48105 USA. [Jakobsdottir, Johanna; Conley, Yvette P.; Weeks, Daniel E.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Pericak-Vance, Margaret A.; Scott, William K.; Kovach, Jaclyn L.; Schwartz, Stephen G.] Univ Miami, Miller Sch Med, Miami, FL USA. [Campochiaro, Peter A.; Tan, Perciliz L.; Zack, Donald J.; Katsanis, Nicholas] Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. [Klein, Michael L.; Francis, Peter J.] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. [Kanda, Atsuhiro; Brooks, Matthew] NEI, Neurobiol Neurodegenerat & Repair Lab, Bethesda, MD 20892 USA. [Kopplin, Laura; Hagstrom, Stephanie A.; Peachey, Neal S.; Iyengar, Sudha K.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Agarwal, Anita; Haines, Jonathan L.] Vanderbilt Univ, Med Ctr, Nashville, TN 37232 USA. [Postel, Eric A.] Duke Univ, Med Ctr, Durham, NC 27705 USA. [Complications Age-Related Macular] Univ Penn, CAPT Coordinating Ctr, Philadelphia, PA 19104 USA. [Brown, Gary; Ho, Allen; Regillo, Carl] Mid Atlantic Retina, Cherry Hill, NJ 08002 USA. [Brown, Gary; Ho, Allen; Regillo, Carl] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Donoso, Larry] Philadelphia Retina Endowment Fund, Philadelphia, PA 19107 USA. [Hagstrom, Stephanie A.; Peachey, Neal S.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Peachey, Neal S.] Vet Affairs Med Ctr, Louis Stokes Cleveland Dept, Cleveland, OH 44106 USA. [Klein, Ronald; Klein, Barbara E. K.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53705 USA. [Gotoh, Norimoto; Yamashiro, Kenji; Yoshimura, Nagahisa] Kyoto Univ, Grad Sch Med, Kyoto 6068501, Japan. [Fagerness, Jesen A.] Massachusetts Gen Hosp, Cambridge, MA 02114 USA. [Fagerness, Jesen A.] Broad Inst, Cambridge, MA 02114 USA. [Reynolds, Robyn; Seddon, Johanna M.] Tufts Med Ctr, Boston, MA 02111 USA. [Farrer, Lindsay A.] Boston Univ, Boston, MA 02215 USA. [Kim, Ivana K.; Miller, Joan W.; DeAngelis, Margaret M.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Corton, Marta; Brion, Maria] Complexo Hosp Univ Santiago, Santiago De Compostela 15706, Spain. [Corton, Marta; Carracedo, Angel; Brion, Maria] Univ Santiago de Compostela, Santiago De Compostela 15705, Spain. [Sanchez-Salorio, Manuel] Inst Gallego Oftalmol, Santiago De Compostela 15706, Spain. [Pugh, Elizabeth W.; Doheny, Kimberly F.] Johns Hopkins Sch Med, Ctr Inherited Dis Res, Baltimore, MD 21287 USA. [Seddon, Johanna M.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Gorin, Michael B.] Univ Calif Los Angeles, Los Angeles, CA 90095 USA. RP Abecasis, GR (reprint author), Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA. EM goncalo@umich.edu; swaroopa@nei.nih.gov RI Peachey, Neal/G-5533-2010; Abecasis, Goncalo/B-7840-2010; Weeks, Daniel/B-2995-2012; Haines, Jonathan/C-3374-2012; Katsanis, Nicholas/E-1837-2012; DeAngelis, e/J-7863-2015 OI Klein, Ronald/0000-0002-4428-6237; Weeks, Daniel/0000-0001-9410-7228; Katsanis, Nicholas/0000-0002-2480-0171; Farrer, Lindsay/0000-0001-5533-4225; Brion, Maria/0000-0001-7463-2148; Zack, Don/0000-0002-7966-1973; Abecasis, Goncalo/0000-0003-1509-1825; Swaroop, Anand/0000-0002-1975-1141; Carracedo, Angel/0000-0003-1085-8986; FU National Eye Institute; National Institutes of Health [EY016862, EY007758, EY09859, EY012118, P30-EY014801, EY-014458, EY014467, HL084729, HG002651, HHSN268200782096C]; Foundation Fighting Blindness; Macula Vision Research Foundation; American Health Assistance Foundation; Research to Prevent Blindness; Pew Charitable Trusts; Mayo Clinic Foundation; Casey Macular Degeneration Center; Marion W. and Edward F. Knight AMD Fund; Harold and Pauline Price Foundation; National Genotyping Centre of Spain; Elmer and Sylvia Sramek Foundation; Center for Inherited Disease Research FX We thank numerous clinicians, clinical staff, patients, and their families for their participation in and dedication to the project; the Kellogg Eye Center AMD group, the Complications of Age-Related Macular Degeneration Prevention Trial consortium, the Spanish AMD research group, staff at the National Center for Biotechnology Information, and Dr. Hemin Chin; and the Tufts Medical Center/Massachusetts General Hospital group for sharing genome-wide association results. This research was supported in part by the intramural program of the National Eye Institute and by National Institutes of Health Grants EY016862, EY007758, EY09859, EY012118, P30-EY014801, EY-014458, EY014467, HL084729, and HG002651, by the Foundation Fighting Blindness, the Macula Vision Research Foundation, the American Health Assistance Foundation, Research to Prevent Blindness, the Pew Charitable Trusts, the Mayo Clinic Foundation, the Casey Macular Degeneration Center Fund, the Marion W. and Edward F. Knight AMD Fund, the Harold and Pauline Price Foundation, National Genotyping Centre of Spain, and the Elmer and Sylvia Sramek Foundation. The Center for Inherited Disease Research, fully funded through a federal contract (HHSN268200782096C) from National Institutes of Health to The Johns Hopkins University, performed genotyping of the discovery cohort. NR 36 TC 261 Z9 266 U1 0 U2 13 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 20 PY 2010 VL 107 IS 16 BP 7401 EP 7406 DI 10.1073/pnas.0912702107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 586FU UT WOS:000276892300054 PM 20385819 ER PT J AU Wood, KB DeVine, J Fischer, D Dettori, JR Janssen, M AF Wood, Kirkham B. DeVine, John Fischer, Dena Dettori, Joseph R. Janssen, Michael TI Vascular Injury in Elective Anterior Lumbosacral Surgery SO SPINE LA English DT Article DE vascular injury; anterior approach; lumbosacral; access surgeon ID LUMBAR INTERBODY FUSION; MINIMUM FOLLOW-UP; TOTAL DISC REPLACEMENT; LOW-BACK-PAIN; CHARITE(TM) ARTIFICIAL DISC; LAPAROSCOPIC SPINAL-FUSION; OPERATIVE COMPLICATIONS; PRODISC PROSTHESIS; ACCESS STRATEGIES; MULTICENTER AB Study Design. Systematic review. Objective. To document the incidence and consequences of vascular injury in lumbosacral surgery, to identify factors contributing to this injury, and to determine whether there are any effective measures to decrease the occurrence of vascular injury. Summary of Background Data. Anterior lumbosacral surgery encompasses all aspects of spine surgery, including trauma, deformity, and degenerative conditions. Although it has theoretical advantages, anterior lumbosacral surgery carries with it certain definite risks, one of the most critical of which is injury to the surrounding vasculature. It is important for both the patient and the surgeon to understand the risks, patterns, and outcomes of injury to the vascular structures associated with this surgery. Methods. A systematic review of the English-language literature was undertaken for articles published between January 1993 and December 2008. Electronic databases and reference lists of key articles were searched to identify published studies examining vascular injury in anterior lumbosacral surgery. Vascular injury was defined as any case in which a suture was required to control bleeding. Two independent reviewers assessed the strength of literature using the Grading of Recommendations Assessment, Development, and Evaluation criteria assessing quality, quantity, and consistency of results. Disagreements were resolved by consensus. Results. A total of 88 articles were initially screened, and 40 ultimately met the predetermined inclusion criteria. Vascular injuries after anterior lumbosacral surgeries were rare (<5%). Venous laceration was more common than arterial laceration, and most venous injuries occurred during retraction of the great vessels. In most cases, the overall clinical outcome after vascular injury was not adversely affected. L4-L5 exposure was associated with increased vascular injury in some studies but not others. Vascular injury occurred more frequently in laparoscopic compared with open anterior lumbar interbody fusion. Conclusion. Vascular injury in anterior lumbosacral surgery remains low, with reports being <5%. The consequences of injury seem rare, but may include thrombosis, pulmonary embolism, and prolonged hospitalization. Exposure and surgery at L4-L5 may be associated with a higher risk of injury than that at L5-S1, though the data are not consistent. C1 [Wood, Kirkham B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed, Boston, MA 02114 USA. [DeVine, John] Madigan Army Med Ctr, Orthoped Serv, Dept Surg, USUHS, Tacoma, WA 98431 USA. [Fischer, Dena] Univ Illinois, Coll Dent, Dept Oral Med & Diagnost Sci, Chicago, IL USA. [Fischer, Dena; Dettori, Joseph R.] Spectrum Res Inc, Tacoma, WA USA. [Janssen, Michael] Univ Colorado, Spine Educ & Res Inst, Denver, CO USA. RP Wood, KB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed, 55 Fruit St,Suite 3800, Boston, MA 02114 USA. EM kbwood@partners.org FU AOSpine North America FX Supported by AOSpine North America. Analytic support for this work was provided by Spectrum Research, Inc. with funding from AOSpine North America. No benefits in any form have been or will be received from a commercial party related directly or indirectly to the subject of this manuscript. NR 50 TC 40 Z9 44 U1 9 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD APR 20 PY 2010 VL 35 IS 9 SU S BP S66 EP S75 DI 10.1097/BRS.0b013e3181d83411 PG 10 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 590KI UT WOS:000277224100008 PM 20407353 ER PT J AU Yates, MA Li, YX Chlebeck, PJ Offner, H AF Yates, Melissa A. Li, Yuexin Chlebeck, Peter J. Offner, Halina TI GPR30, but not estrogen receptor-alpha, is crucial in the treatment of experimental autoimmune encephalomyelitis by oral ethinyl estradiol SO BMC IMMUNOLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; MULTIPLE-SCLEROSIS; GLIAL-CELLS; EXPRESSION; PREGNANCY; MICE; SUPPRESSES; CYTOKINE; THERAPY; PD-1 AB Background: Remission of multiple sclerosis during periods of high ovarian hormone secretion (such as pregnancy) has led to a great deal of interest in the potential for estrogens to treat autoimmune disease. Previous work has established that 17 beta-estradiol can inhibit onset of experimental autoimmune encephalomyelitis (EAE), while ethinyl estradiol (EE) can reduce the severity of established disease. In the current study, the influence of estrogen receptor-alpha (ER alpha) and the G-protein coupled estrogen receptor (GPR30 or GPER) on EE's ability to treat EAE was explored. Results: EE reduced disease severity in wild-type and ERa knockout (ERKO) mice, but did not alter disease in the GPR30KO group. Production of anti-inflammatory IL-10 increased in EE-ERKO mice (which showed reduced disease) but not in EE-GPR30KO mice (who did not have improved disease). Conclusions: Differential production of IL-10 following EE treatment in ERKO and GPR30KO animals may be responsible for the distinctly different effects on disease severity. Increased IL-10 in ERKO-EE compared to ERKO-Controls is likely to be an important factor in reducing established disease. The inability of EE to reduce disease in GPR30KO mice indicates an important but still undefined role for GPR30 in regulating immune reactivity. C1 [Yates, Melissa A.; Li, Yuexin; Chlebeck, Peter J.; Offner, Halina] Portland VA Med Ctr, Portland, OR USA. [Yates, Melissa A.; Li, Yuexin; Offner, Halina] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Yates, Melissa A.; Li, Yuexin; Chlebeck, Peter J.; Offner, Halina] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA. [Offner, Halina] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97201 USA. RP Offner, H (reprint author), Portland VA Med Ctr, Portland, OR USA. EM offnerva@ohsu.edu FU National Multiple Sclerosis Society [FG1832-A-1, RG3405-B-5]; NIH [NS45445, NS49210]; Biomedical Laboratory R&D Service, Department of Veterans Affairs FX M.A.Y. was supported by a Postdoctoral Fellowship FG1832-A-1 from the National Multiple Sclerosis Society, and this work was supported in part by National Multiple Sclerosis Society grant RG3405-B-5; NIH grants NS45445, and NS49210; and the Biomedical Laboratory R&D Service, Department of Veterans Affairs. The authors would also like to thank Eva Niehaus for her assistance in manuscript preparation. NR 24 TC 29 Z9 31 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2172 J9 BMC IMMUNOL JI BMC Immunol. PD APR 19 PY 2010 VL 11 AR 20 DI 10.1186/1471-2172-11-20 PG 5 WC Immunology SC Immunology GA 591FU UT WOS:000277286100001 PM 20403194 ER PT J AU Figlewicz, DP Ioannou, G Jay, JB Kittleson, S Savard, C Roth, CL AF Figlewicz, D. P. Ioannou, G. Jay, J. Bennett Kittleson, S. Savard, C. Roth, C. L. TI Effect of moderate intake of sweeteners on metabolic health in the rat (vol 98, pg 618, 2009) SO PHYSIOLOGY & BEHAVIOR LA English DT Correction C1 [Figlewicz, D. P.; Jay, J. Bennett; Kittleson, S.] VA Puget Sound Hlth Care Syst, R&D 151, Seattle, WA 98108 USA. [Figlewicz, D. P.; Jay, J. Bennett] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Ioannou, G.; Savard, C.] VA Puget Sound Hlth Care Syst, Dept Med, Div Gastroenterol, Seattle, WA 98108 USA. [Roth, C. L.] Seattle Childrens Res Inst, Seattle, WA 98101 USA. RP Figlewicz, DP (reprint author), VA Puget Sound Hlth Care Syst, R&D 151, Seattle, WA 98108 USA. EM latte@u.washington.edu NR 1 TC 1 Z9 1 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD APR 19 PY 2010 VL 99 IS 5 BP 691 EP 691 DI 10.1016/j.physbeh.2009.11.011 PG 1 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA 586FA UT WOS:000276887100023 ER PT J AU Bagayoko, CO Dufour, JC Chaacho, S Bouhaddou, O Fieschi, M AF Bagayoko, Cheick-Oumar Dufour, Jean-Charles Chaacho, Saad Bouhaddou, Omar Fieschi, Marius TI Open source challenges for hospital information system (HIS) in developing countries: a pilot project in Mali SO BMC MEDICAL INFORMATICS AND DECISION MAKING LA English DT Article AB Background: We are currently witnessing a significant increase in use of Open Source tools in the field of health. Our study aims to research the potential of these software packages for developing countries. Our experiment was conducted at the Centre Hospitalier Mere Enfant in Mali. Methods: After reviewing several Open Source tools in the field of hospital information systems, Mediboard software was chosen for our study. To ensure the completeness of Mediboard in relation to the functionality required for a hospital information system, its features were compared to those of a well-defined comprehensive record management tool set up at the University Hospital "La Timone" of Marseilles in France. It was then installed on two Linux servers: a first server for testing and validation of different modules, and a second one for the deployed full implementation. After several months of use, we have evaluated the usability aspects of the system including feedback from end-users through a questionnaire. Results: Initial results showed the potential of Open Source in the field of health IT for developing countries like Mali. Five main modules have been fully implemented: patient administrative and medical records management of hospital activities, tracking of practitioners' activities, infrastructure management and the billing system. This last component of the system has been fully developed by the local Mali team. The evaluation showed that the system is broadly accepted by all the users who participated in the study. 77% of the participants found the system useful; 85% found it easy; 100% of them believe the system increases the reliability of data. The same proportion encourages the continuation of the experiment and its expansion throughout the hospital. Conclusions: In light of the results, we can conclude that the objective of our study was reached. However, it is important to take into account the recommendations and the challenges discussed here to avoid several potential pitfalls specific to the context of Africa. Our future work will target the full integration of the billing module in Mediboard and an expanded implementation throughout the hospital. C1 [Bagayoko, Cheick-Oumar] Fac Med Pharm & Odontostomatol, DER Sante Publ, Bamako, Mali. [Bagayoko, Cheick-Oumar; Dufour, Jean-Charles; Fieschi, Marius] Univ Aix Marseille 2, Fac Med, Lab Enseignement & Rech Traitement Informat Med, F-13385 Marseille 5, France. [Chaacho, Saad] Ctr Hosp Ibn Sina de Rabat, Unite Veille Technol & Dev Logiciel, Rabat, Morocco. [Bouhaddou, Omar] Hewlett Packard Enterprise Serv, San Diego, CA USA. [Bouhaddou, Omar] US Dept Vet Affairs, San Diego, CA USA. RP Bagayoko, CO (reprint author), Fac Med Pharm & Odontostomatol, DER Sante Publ, Bamako, Mali. EM cob281@yahoo.fr RI Dufour, Jean-Charles/E-2481-2013 OI Dufour, Jean-Charles/0000-0003-2392-1817 NR 13 TC 4 Z9 4 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6947 J9 BMC MED INFORM DECIS JI BMC Med. Inform. Decis. Mak. PD APR 16 PY 2010 VL 10 AR 22 DI 10.1186/1472-6947-10-22 PG 13 WC Medical Informatics SC Medical Informatics GA 594DX UT WOS:000277515200001 PM 20398366 ER PT J AU Siskind, LJ Mullen, TD Rosales, KR Clarke, CJ Hernandez-Corbacho, MJ Edinger, AL Obeid, LM AF Siskind, Leah J. Mullen, Thomas D. Rosales, Kimberly Romero Clarke, Christopher J. Hernandez-Corbacho, Maria Jose Edinger, Aimee L. Obeid, Lina M. TI The BCL-2 Protein BAK Is Required for Long-chain Ceramide Generation during Apoptosis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL-DEATH; SPHINGOSINE KINASE-1; PROAPOPTOTIC BAX; MITOCHONDRIAL APOPTOSIS; ACID SPHINGOMYELINASE; ENDOPLASMIC-RETICULUM; CANCER-CELLS; ER STRESS; ACTIVATION; RESISTANCE AB The BCL-2 family members BAK and BAX are required for apoptosis and trigger mitochondrial outer membrane permeabilization (MOMP). Here we identify a MOMP-independent function of BAK as a required factor for long-chain ceramide production in response to pro-apoptotic stress. UV-C irradiation of wild-type (WT) cells increased long-chain ceramides; blocking ceramide generation prevented caspase activation and cell death, demonstrating that long-chain ceramides play a key role in UV-C-induced apoptosis. In contrast, UV-C irradiation did not increase long-chain ceramides in BAK and BAX double knock-out cells. Notably, this was not specific to the cell type (baby mouse kidney cells, hematopoietic) nor the apoptotic stimulus employed (UV-C, cisplatin, and growth factor withdrawal). Importantly, long-chain ceramide generation was dependent on the presence of BAK, but not BAX. However, ceramide generation was independent of the known downstream actions of BAK in apoptosis(MOMP or caspase activation), suggesting a novel role for BAK in apoptosis. Finally, enzymatic assays identified ceramide synthase as the mechanism by which BAK regulates ceramide metabolism. There was no change in CerS expression at the message or protein level, indicating regulation at the post-translational level. Moreover, CerS activity in BAK KO microsomes can be reactivated upon addition of BAK-containing microsomes. The data presented indicate that ceramide-induced apoptosis is dependent upon BAK and identify a novel role for BAK during apoptosis. By establishing a unique role for BAK in long-chain ceramide metabolism, these studies further demonstrate that the seemingly redundant proteins BAK and BAX have distinct mechanisms of action during apoptosis induction. C1 [Siskind, Leah J.; Mullen, Thomas D.; Hernandez-Corbacho, Maria Jose; Obeid, Lina M.] Med Univ S Carolina, Dept Med, Div Gen Internal Med Geriatr, Charleston, SC 29425 USA. [Obeid, Lina M.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. [Rosales, Kimberly Romero; Edinger, Aimee L.] Univ Calif Irvine, Dept Dev & Cell Biol, Irvine, CA 92697 USA. [Clarke, Christopher J.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. RP Siskind, LJ (reprint author), Med Univ S Carolina, Dept Med, Div Gen Internal Med Geriatr, 114 Doughty St,MSC 779, Charleston, SC 29425 USA. EM siskind@musc.edu OI obeid, lina/0000-0002-0734-0847 FU NIEHS [1F30 ES016975-01]; NIA [F31 CA126494, K08 CA100526, R01 AG016583]; NCI [P01 CA097132]; Veterans Administration; American Cancer Society [IRG-97-219-11]; Cancer Center Support Grant [P30 CA138313] FX This work was supported, in whole or in part, by National Institutes of Health Grants 1F30 ES016975-01 (to T. D. M.) from NIEHS, F31 CA126494 (to K. R. R.), K08 CA100526 (to A. L. E.), and R01 AG016583 from NIA and P01 CA097132 from NCI (to L. M. O.). This work was also supported by a Veterans Administration Career Development Award-2 (to L. J. S.), pilot project funding from a Veterans Administration REAP (to L. J. S. and L. M. O.), and American Cancer Society Institutional Research Grant IRG-97-219-11 (sub-award to L. J. S.). The shared resources of the Hollings Cancer Center were supported in part by a Cancer Center Support Grant (P30 CA138313). NR 46 TC 59 Z9 64 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 16 PY 2010 VL 285 IS 16 BP 11818 EP 11826 DI 10.1074/jbc.M109.078121 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 584XI UT WOS:000276787100009 PM 20172858 ER PT J AU Thukkani, N Sonnenberg, A AF Thukkani, N. Sonnenberg, A. TI The influence of environmental risk factors in hospitalization for gastro-oesophageal reflux disease-related diagnoses in the United States SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID BARRETTS-ESOPHAGUS; HIATAL-HERNIA; EROSIVE ESOPHAGITIS; GERD SYMPTOMS; PREVALENCE; POPULATION; FREQUENCY; SEVERITY; OBESITY; GENDER AB P>Background The impact of gastro-oesophageal reflux disease on hospitalization is unknown. Aim To describe the characteristics of patients hospitalized for diagnoses related to gastro-oesophageal reflux disease (GERD) and find potential environmental influences that affect their hospitalization. Methods Data from the Healthcare Cost and Utilization Project were used to study the demographic characteristics of hospitalizations associated with GERD during 2003-2006. Data from the Centers for Disease Control were used for information about the US prevalence of obesity. Results During 2003-2006, 0.5 million patients with a primary and 14.5 million patients with a secondary GERD-related diagnosis became hospitalized in the US. Oesophageal reflux and hiatal hernia were more common in female than in male inpatients, whereas Barrett's oesophagus and oesophageal adenocarcinoma were more common in male than in female inpatients. All GERD-related diagnoses were more common in white people than non-white people. Hospitalizations associated with oesophageal reflux, reflux oesophagitis and Barrett's oesophagus showed resembling geographical distributions among different US states. The prevalence of obesity and the hospitalization for hiatal hernia or reflux oesophagitis were also characterized by similar geographical distributions. Conclusion The large numbers of inpatients with a discharge diagnosis of GERD-related conditions attest to the frequent occurrence and relevance of GERD in contributing to hospitalization in the US. C1 [Thukkani, N.; Sonnenberg, A.] Portland VA Med Ctr, Div Gastroenterol, Portland, OR USA. [Thukkani, N.; Sonnenberg, A.] Oregon Hlth & Sci Univ, Div Gastroenterol, Portland, OR 97201 USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr P3 GI, Div Gastroenterol, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 33 TC 5 Z9 5 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0269-2813 J9 ALIMENT PHARM THER JI Aliment. Pharmacol. Ther. PD APR 15 PY 2010 VL 31 IS 8 BP 852 EP 861 DI 10.1111/j.1365-2036.2010.04245.x PG 10 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 571CC UT WOS:000275726100008 PM 20102354 ER PT J AU Ebbel, EN Leymarie, N Schiavo, S Sharma, S Gevorkian, S Hersch, S Matson, WR Costello, CE AF Ebbel, Erika N. Leymarie, Nancy Schiavo, Susan Sharma, Swati Gevorkian, Sona Hersch, Steven Matson, Wayne R. Costello, Catherine E. TI Identification of phenylbutyrate-generated metabolites in Huntington disease patients using parallel liquid chromatography/electrochemical array/mass spectrometry and off-line tandem mass spectrometry SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE Sodium phenylbutyrate; Huntington disease; LCECA; Metabolites; Parallel LC/EC array/MS; Tandem mass spectrometry ID HISTONE DEACETYLASE INHIBITORS; ORAL SODIUM PHENYLBUTYRATE; TRANSCRIPTIONAL ABNORMALITIES; OXIDATIVE DAMAGE; KYNURENIC ACID; SEROTONIN; POLYGLUTAMINE; TRYPTAMINE-4,5-DIONE; PHENOTYPE; PROTEINS AB Oral sodium phenylbutyrate (SPB) is currently under investigation as a histone deacetylation (HDAC) inhibitor in Huntington disease (HD). Ongoing studies indicate that symptoms related to HD genetic abnormalities decrease with SPB therapy. In a recently reported safety and tolerability study of SPB in HD, we analyzed overall chromatographic patterns from a method that employs gradient liquid chromatography with series electrochemical array, ultraviolet (UV), and fluorescence (LCECA/UV/F) for measuring SPB and its metabolite phenylacetate (PA). We found that plasma and urine from SPB-treated patients yielded individual-specific patterns of approximately 20 metabolites that may provide a means for the selection of subjects for extended trials of SPB. The structural identification of these metabolites is of critical importance because their characterization will facilitate understanding the mechanisms of drug action and possible side effects. We have now developed an iterative process with LCECA, parallel LCECA/LCMS, and high-performance tandem MS for metabolite characterization. Here we report the details of this method and its use for identification of 10 plasma and urinary metabolites in treated subjects, including indole species in urine that are not themselves metabolites of SPB. Thus, this approach contributes to understanding metabolic pathways that differ among HID patients being treated with SPB. (C) 2010 Elsevier Inc. All rights reserved. C1 [Ebbel, Erika N.; Leymarie, Nancy; Costello, Catherine E.] Boston Univ, Sch Med, Ctr Biomed Mass Spectrometry, Boston, MA 02118 USA. [Ebbel, Erika N.; Leymarie, Nancy; Costello, Catherine E.] Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA. [Schiavo, Susan] Northeastern Univ, Barnett Inst, Boston, MA 02115 USA. [Schiavo, Susan] Northeastern Univ, Dept Chem & Chem Biol, Boston, MA 02115 USA. [Sharma, Swati; Matson, Wayne R.] Bedford VA Med Ctr, Dept Syst Biochem, Bedford, MA 01430 USA. [Gevorkian, Sona; Hersch, Steven] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. RP Costello, CE (reprint author), Boston Univ, Sch Med, Ctr Biomed Mass Spectrometry, Boston, MA 02118 USA. EM cecmsms@bu.edu OI Costello, Catherine/0000-0003-1594-5122 FU National Institutes of Health (NIH) [P41 RR010888, S10 RR020946, R33 DK070326, P01 NS045242]; HIQ Foundation FX This research was supported by National Institutes of Health (NIH) grants P41 RR010888 (C.E.C.), S10 RR020946 (J. Zaia), R33 DK070326 (W.R.M.), and P01 NS045242 (S.H.) and by the HIQ Foundation (S.H.). NR 41 TC 19 Z9 19 U1 1 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD APR 15 PY 2010 VL 399 IS 2 BP 152 EP 161 DI 10.1016/j.ab.2010.01.010 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 567XJ UT WOS:000275481400002 PM 20074541 ER PT J AU Vander Heiden, MG Christofk, HR Schuman, E Subtelny, AO Sharfi, H Harlow, EE Xian, J Cantley, LC AF Vander Heiden, Matthew G. Christofk, Heather R. Schuman, Eli Subtelny, Alexander O. Sharfi, Hadar Harlow, Edward E. Xian, Jun Cantley, Lewis C. TI Identification of small molecule inhibitors of pyruvate kinase M2 SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE Pyruvate kinase M2; Glycolysis; Cellular metabolism; Small molecule inhibitors; High-throughput screening ID CELL-METABOLISM; ALLOSTERIC REGULATION; TUMOR-GROWTH; CANCERS; GENE; ISOZYMES AB A common feature of tumors arising from diverse tissue types is a reliance on aerobic glycolysis for glucose metabolism. This metabolic difference between cancer cells and normal cells could be exploited for therapeutic benefit in patients. Cancer cells universally express the M2 isoform of the glycolytic enzyme pyruvate kinase (PKM2), and previous work has demonstrated that PKM2 expression is necessary for aerobic glycolysis and cell proliferation in vivo. Because most normal tissues express an isoform of pyruvate kinase other than PKM2, selective targeting of PKM2 provides an opportunity to target cell metabolism for cancer therapy. PKM2 has an identical catalytic site as the related M1 splice variant (PKM1). However, isoform selective inhibition is possible as PKM2 contains a unique region for allosteric regulation. We have screened a library of greater than 1,00,000 small molecules to identify such inhibitors. The inhibitors identified for PKM2 fell primarily into three distinct structural classes. The most potent PKM2 inhibitor resulted in decreased glycolysis and increased cell death following loss of growth factor signaling. At least part of this effect was due to on-target PKM2 inhibition as less cell death was observed in cells engineered to express PKM1. These data suggest that isoform, selective inhibition of PKM2 with small molecules is feasible and support the hypothesis that inhibition of glucose metabolism in cancer cells is a viable strategy to treat human malignancy. (C) 2009 Elsevier Inc. All rights reserved. C1 [Schuman, Eli; Harlow, Edward E.; Xian, Jun] Dana Farber Harvard Canc Ctr, Canc Drug Assays, Boston, MA 02115 USA. [Vander Heiden, Matthew G.; Christofk, Heather R.; Schuman, Eli; Subtelny, Alexander O.; Sharfi, Hadar; Harlow, Edward E.; Xian, Jun; Cantley, Lewis C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Vander Heiden, Matthew G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Vander Heiden, Matthew G.; Christofk, Heather R.; Subtelny, Alexander O.; Sharfi, Hadar; Cantley, Lewis C.] Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. RP Xian, J (reprint author), Dana Farber Harvard Canc Ctr, Canc Drug Assays, Boston, MA 02115 USA. EM lewis_cantley@hms.harvard.edu RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU Dana-Farber/Harvard Cancer Center; Damon Runyon Cancer Research Foundation FX We thank the Dana-Farber/Harvard Cancer Center Cancer Drug Assays screening facility for supporting this project. We thank J. Engelman for Gefitinib and HCC827 cells, C. Rudin and D. Plas for FL5.12 cells, and Agios Pharmaceuticals for providing independently synthesized Compound 3. MGVH was a fellow supported by the Damon Runyon Cancer Research Foundation when much of this work was performed. NR 23 TC 89 Z9 90 U1 4 U2 28 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD APR 15 PY 2010 VL 79 IS 8 BP 1118 EP 1124 DI 10.1016/j.bcp.2009.12.003 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 566RT UT WOS:000275391400005 PM 20005212 ER PT J AU Janes, AC Pizzagalli, DA Richardt, S Frederick, BD Chuzi, S Pachas, G Culhane, MA Holmes, AJ Fava, M Evins, AE Kaufman, MJ AF Janes, Amy C. Pizzagalli, Diego A. Richardt, Sarah Frederick, Blaise deB. Chuzi, Sarah Pachas, Gladys Culhane, Melissa A. Holmes, Avram J. Fava, Maurizio Evins, A. Eden Kaufman, Marc J. TI Brain Reactivity to Smoking Cues Prior to Smoking Cessation Predicts Ability to Maintain Tobacco Abstinence SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Dorsal anterior cingulate cortex; emotional Stroop task; fMRI; insula; relapse; smoking cessation; tobacco ID NICOTINE DEPENDENCE; CIGARETTE-SMOKING; RELAPSE; METAANALYSIS; ACTIVATION; ADDICTION; INSULA; FMRI; CONNECTIVITY; REPLACEMENT AB Background: Developing the means to identify smokers at high risk for relapse could advance relapse prevention therapy. We hypothesized that functional magnetic resonance imaging (fMRI) reactivity to smoking-related cues, measured before a quit attempt, could identify smokers with heightened relapse vulnerability. Methods: Before quitting smoking, 21 nicotine-dependent women underwent fMRI during which smoking-related and neutral images were shown. These smokers also were tested for possible attentional biases to smoking-related words using a computerized emotional Stroop (ES) task previously found to predict relapse. Smokers then made a quit attempt and were grouped based on outcomes (abstinence vs. slip: smoking >= 1 cigarette after attaining abstinence). Prequit fMRI and ES measurements in these groups were compared. Results: Slip subjects had heightened fMRI reactivity to smoking-related images in brain regions implicated in emotion, interoceptive awareness, and motor planning and execution. Insula and dorsal anterior cingulate cortex (dACC) reactivity induced by smoking images correlated with an attentional bias to smoking-related words. A discriminant analysis of ES and fMRI data predicted outcomes with 79% accuracy. Additionally, smokers who slipped had decreased fMRI functional connectivity between an insula-containing network and brain regions involved in cognitive control, including the dACC and dorsal lateral prefrontal cortex, possibly reflecting reduced top-down control of cue-induced emotions. Conclusions: These findings suggest that the insula and dACC are important substrates of smoking relapse vulnerability. The data also suggest that relapse-vulnerable smokers can be identified before quit attempts, which could enable personalized treatment, improve tobacco-dependence treatment outcomes, and reduce smoking-related morbidity and mortality. C1 [Janes, Amy C.; Richardt, Sarah; Frederick, Blaise deB.; Kaufman, Marc J.] Harvard Univ, McLean Hosp, Sch Med, Brain Imaging Ctr, Belmont, MA 02478 USA. [Pizzagalli, Diego A.; Holmes, Avram J.] Harvard Univ, Dept Psychol, Cambridge, England. [Chuzi, Sarah; Pachas, Gladys; Culhane, Melissa A.; Fava, Maurizio; Evins, A. Eden] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Janes, AC (reprint author), Harvard Univ, McLean Hosp, Sch Med, Brain Imaging Ctr, 115 Mill St, Belmont, MA 02478 USA. EM ajanes@mclean.harvard.edu RI Frederick, Blaise/G-6098-2012; Janes, Amy/A-5322-2013 OI Frederick, Blaise/0000-0001-5832-5279; Janes, Amy/0000-0002-3749-5006 FU National institute on Drag Abuse [U01DA019378, R01DA022276, R01DA014674, R01DA09448, K02DA017324, T32DA015036]; Counter-Drug Technology Assessment Center (CTAC); Office of National Drug Control Policy (ONDCP) Army Contracting Agency [BK39-03-C-0075]; GlaxoSmithkline FX This research was supported in part by National institute on Drag Abuse Grant Nos. U01DA019378, R01DA022276, R01DA014674, R01DA09448 K02DA017324, and T32DA015036; by funding from the Counter-Drug Technology Assessment Center (CTAC), an Office within the Office of National Drug Control Policy (ONDCP) via Army Contracting Agency Contract BK39-03-C-0075; and by research support from GlaxoSmithkline. We thank Dr. David Schoenfeld (Massachusetts General Hospital) for his contributions to this study. We thank Drs. Robert S. Ross, Bruce M. Cohen, and Elizabeth Quattrocki-Knight for comments on the original manuscript. NR 55 TC 165 Z9 173 U1 4 U2 23 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 APR 15 PY 2010 VL 67 IS 8 BP 722 EP 729 DI 10.1016/j.biopsych.2009.12.034 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 584EE UT WOS:000276732600005 PM 20172508 ER PT J AU Chen, RC Mamon, HJ Chen, YH Gelman, RS Suh, WW Talcott, JA Clark, JW Hong, TS AF Chen, Ronald C. Mamon, Harvey J. Chen, Yu-Hui Gelman, Rebecca S. Suh, W. Warren Talcott, James A. Clark, Jeffrey W. Hong, Theodore S. TI Patient-Reported Acute Gastrointestinal Symptoms During Concurrent Chemoradiation Treatment for Rectal Cancer SO CANCER LA English DT Article DE quality of life; rectal neoplasms; drug therapy; radiotherapy ID QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; CLINICAL-TRIALS; OUTCOMES ASSESSMENT; PROGNOSTIC-FACTORS; RADIATION-THERAPY; ONCOLOGY-GROUP; PHASE-II; RADIOTHERAPY; TOXICITY AB BACKGROUND: Although it is known that standard 5-fluorouracil-based chemoradiation therapy for rectal cancer causes significant acute gastrointestinal (GI) toxicity, research on patient-reported outcomes (PROs) is limited. The authors undertook the current study to assess the feasibility of incorporating PRO measurement into routine clinical practice and to describe the trajectory of symptom development during treatment. METHODS: Seventy-seven consecutive patients who were treated between 2006 and 2008 were eligible. Patients completed the 7-item Bowel Problems Scale immediately before weekly physician visits. RESULTS: The questionnaire completion rate was 95%. Individual GI symptoms had different trajectories of development. By Week 5, approximately 40% of all patients developed clinically meaningful pain, bowel urgency, or tenesmus that was not present during Week 1; 30% developed diarrhea, abdominal cramping, and passing mucus. However, overall symptom burden was moderate. Seventy-five percent of patients who presented with rectal bleeding at Week 1 improved by Week 3 of treatment. Within each physician-assessed grade of diarrhea, patient experience varied widely. For example, of the 50 patients who developed grade 2 diarrhea on the Radiation Therapy Oncology Group Acute Morbidity Scale, the numbers of patients reporting only occasional symptoms versus those reporting frequent or very frequent symptoms were similar. CONCLUSIONS: PROs provided information on patient symptoms during chemoradiation treatment for rectal cancer that was not captured otherwise, and it was feasible to incorporate PROs into routine clinical practice. The current results may be used by physicians to counsel their patients before treatment initiation and to provide a benchmark against which trials that use new therapies may be compared. Cancer 2010;116:1879-86. (C) 2070 American Cancer Society C1 [Chen, Ronald C.; Hong, Theodore S.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Chen, Ronald C.; Mamon, Harvey J.; Suh, W. Warren] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Chen, Ronald C.] Univ N Carolina, Dept Radiat Oncol, Chapel Hill, NC USA. [Chen, Ronald C.; Talcott, James A.] Massachusetts Gen Hosp, Ctr Canc, Ctr Outcomes Res, Boston, MA 02114 USA. [Chen, Yu-Hui; Gelman, Rebecca S.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Clark, Jeffrey W.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. RP Hong, TS (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 55 Fruit St, Boston, MA 02114 USA. EM tshong1@partners.org NR 31 TC 8 Z9 8 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD APR 15 PY 2010 VL 116 IS 8 BP 1879 EP 1886 DI 10.1002/cncr.24963 PG 8 WC Oncology SC Oncology GA 582GM UT WOS:000276584700006 PM 20166212 ER PT J AU Choueiri, TK Chen, MH D'Amico, AV Sun, L Nguyen, PL Hayes, JH Robertson, CN Walther, PJ Polascik, TJ Albala, DM Moul, JW AF Choueiri, Toni K. Chen, Ming-Hui D'Amico, Anthony V. Sun, Leon Nguyen, Paul L. Hayes, Julia H. Robertson, Cary N. Walther, Philip J. Polascik, Thomas J. Albala, David M. Moul, Judd W. TI Impact of Postoperative Prostate-Specific Antigen Disease Recurrence and the Use of Salvage Therapy on the Risk of Death SO CANCER LA English DT Article DE prostate-specific antigen; prostatectomy; time-dependent covariate; radiotherapy; hormonal therapy ID CANCER-SPECIFIC MORTALITY; RADICAL PROSTATECTOMY; BIOCHEMICAL RECURRENCE; SURVIVAL; PSA; DEFINITION; FAILURE; MEN AB BACKGROUND: This report evaluated whether biochemical recurrence (BCR) as a time-dependent covariate (t) after radical prostatectomy (RP) for prostate cancer was associated with the risk of death and whether salvage therapy with radiotherapy (RT) and/or hormonal therapy (HT) can lessen this risk METHODS: This was a retrospective cohort study of 3071 men who underwent RP at Duke University between 1988 and 2008 and had complete follow-up data. A Cox regression multivariable analysis was used to determine whether BCR (t) was associated with the risk of death in men after adjusting for age, prostatectomy findings, and the use of salvage RT and/or HT. RESULTS: After a median follow-up of 7.4 years, 546 (17.8%) men experienced BCR and 454 (14.8%) died. The median follow-up after prostate-specific antigen (PSA) failure was 11.2 years (interquartile range, 5.8-16.0 years). BCR (t) was associated with an increased risk of death (adjusted hazards ratio [AHR], 1.03; 95% confidence interval [95% CI], 1.004-1.06 [P=.025]). In men who experienced BCR, a PSA doubling time <6 months was associated with an increased risk of death (AHR, 1.55; 95% Cl, 1.15-2.1 [P=.004]); whereas a decrease in the risk of death was observed in men who received RT (AHR, 0.58; 95% CI, 0.40-0.58 [P=.002]) or HT (AHR, 0.56; 95% Cl, 0.37-0.84 [P=.005]) after BCR. CONCLUSIONS: The occurrence of BCR was found to increase the risk of death in men undergoing RP for prostate cancer, and this risk appeared to increase as the time to BCR shortened. However, the addition of RT and/or HT in men with BCR significantly lowered this risk. Cancer 2010;116:1887-92. 2070 American Cancer Society. C1 [Choueiri, Toni K.] Brigham & Womens Hosp, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Dept Med Oncol, Boston, MA 02115 USA. [Choueiri, Toni K.; D'Amico, Anthony V.; Nguyen, Paul L.; Hayes, Julia H.] Harvard Univ, Sch Med, Boston, MA USA. [Chen, Ming-Hui] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. [Sun, Leon; Robertson, Cary N.; Walther, Philip J.; Polascik, Thomas J.; Albala, David M.; Moul, Judd W.] Duke Univ, Med Ctr, Dept Surg, Duke Prostate Ctr, Durham, NC 27710 USA. [Sun, Leon; Robertson, Cary N.; Walther, Philip J.; Polascik, Thomas J.; Albala, David M.; Moul, Judd W.] Duke Univ, Med Ctr, Dept Surg, Div Urol Surg, Durham, NC 27710 USA. RP Choueiri, TK (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Dept Med Oncol, 44 Binney St,Dana 1230, Boston, MA 02115 USA. EM toni_choueiri@dfci.harvard.edu NR 21 TC 17 Z9 17 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD APR 15 PY 2010 VL 116 IS 8 BP 1887 EP 1892 DI 10.1002/cncr.25013 PG 6 WC Oncology SC Oncology GA 582GM UT WOS:000276584700007 PM 20162710 ER PT J AU Lathan, CS Okechukwu, C Drake, BF Bennett, GG AF Lathan, Christopher S. Okechukwu, Cassandra Drake, Bettina F. Bennett, Gary G. TI Racial Differences in the Perception of Lung Cancer The 2005 Health Information National Trends Survey SO CANCER LA English DT Article DE racial disparities; lung; risk perception; nonsmall cell lung cancer ID AFRICAN-AMERICANS; EPIDEMIOLOGY; DISPARITIES; CHEMOTHERAPY; CARCINOMA; SURGERY AB BACKGROUND: Racial disparities in lung cancer have been described well in the literature; however, little is known about perceptions of lung cancer in the general population and whether these perceptions differ by race. METHODS: Data were obtained from the 2005 Health Information National Trends Survey (HINTS) survey. The authors used a sample design of random digit dialing of listed telephone exchanges in the United States. Complete interviews were conducted with 5491 adults, including 1872 respondents who were assigned to receive questions pertaining to lung cancer. All analyses were conducted on this subset of respondents. A statistical software program was used to calculate chi-square tests and to perform logistic regression analyses that would model racial differences in perceptions of lung cancer. All estimates were weighted to be nationally representative of the US population; a jack-knife weighting method was used for parameter estimation. RESULTS: Black patients and white patients shared many of the same beliefs about lung cancer mortality, and etiology. African Americans were more likely than whites 1) to agree that it is hard to follow recommendations about preventing lung cancer (odds ratio [OR], 2.05; 95% confidence interval [CI], 1.19-153), 2) to avoid an evaluation for lung cancer for fear that they have the disease (OR, 3.32; 95% CI, 1.84-5.98), and 3) to believe that patients with lung cancer would have pain or other symptoms before diagnosis (OR, 2.20; 95% CI, 1.27-3.79). CONCLUSIONS: African Americans were more likely to hold beliefs about lung cancer that could interfere with prevention and treatment. Cancer 2010;116:1981-6. (C) 2010 American Cancer Society. C1 [Lathan, Christopher S.] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Med Oncol, Div Populat Sci, Boston, MA 02115 USA. [Okechukwu, Cassandra] Univ Calif San Francisco, Robert Wood Johnson Hlth & Soc Scholars Program, San Francisco, CA 94143 USA. [Drake, Bettina F.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Bennett, Gary G.] Duke Univ, Duke Global Hlth Inst, Durham, NC USA. RP Lathan, CS (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Med Oncol, Div Populat Sci, 44 Binney St,454 STE 21-24, Boston, MA 02115 USA. EM christopher_lathan@dfci.harvard.edu OI Drake, Bettina/0000-0001-9340-5848 FU National Cancer Institute (NCI) [KO1 CA124581]; NCI-funded Program in Cancer Outcomes Research Training [5R25CA092203] FX Dr. Lathan is supported by National Cancer Institute (NCI) grant KO1 CA124581 and by the NCI-funded Program in Cancer Outcomes Research Training (5R25CA092203) NR 31 TC 18 Z9 18 U1 1 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD APR 15 PY 2010 VL 116 IS 8 BP 1981 EP 1986 DI 10.1002/cncr.24923 PG 6 WC Oncology SC Oncology GA 582GM UT WOS:000276584700018 PM 20186766 ER PT J AU Zimmer, M Lamb, J Ebert, BL Lynch, M Neil, C Schmidt, E Golub, TR Iliopoulos, O AF Zimmer, Michael Lamb, Justin Ebert, Benjamin L. Lynch, Mary Neil, Christopher Schmidt, Emmett Golub, Todd R. Iliopoulos, Othon TI The Connectivity Map Links Iron Regulatory Protein-1-Mediated Inhibition of Hypoxia-Inducible Factor-2a Translation to the Anti-inflammatory 15-deoxy-Delta(12,14)-Prostaglandin J(2) SO CANCER RESEARCH LA English DT Article ID PROSTAGLANDIN E-2; RESPONSIVE ELEMENT; GENE-EXPRESSION; ADENOMA GROWTH; CANCER; CELLS; INFLAMMATION; HIF-1-ALPHA; DEFICIENCY; RECEPTOR AB Hypoxia-inducible factors 1 and 2 (HIF1 and HIF2) are heterodimeric transcription factors consisting of a regulatory subunits and a constitutively expressed beta subunit. The expression of a regulatory subunits is promoted by hypoxia, cancer-associated mutations, and inflammatory cytokines. Thus, HIF1 and HIF2 provide a molecular link between cancer and inflammation. We have recently identified novel small molecules that selectively inhibit translation of the HIF2a message and thereby powerfully inhibit the expression of HIF2a target genes. We report here that Connectivity Map analysis links three of these compounds to the anti-inflammatory cytokine 15-deoxy-Delta(12,14)-prostaglandin J(2) (PGJ(2)). As with our identified compounds, PGJ(2) inhibits translation of the HIF2a message in a mammalian target of rapamycin-independent manner by promoting the binding of iron regulatory protein-1 (IRP1) to a noncanonical iron responsive element (IRE) embedded within the 5'-untranslated region of the HIF2a message. The IRE is necessary and sufficient for mediating the effect. Mutation of the IRE sequence, or downregulation of IRP1 expression, blocks the effect of PGJ(2) on HIF2a translation. This is the first report of an endogenous natural molecule regulating HIF2a translation, and it suggests that part of the anti-inflammatory and putative antineoplastic effects of PGJ(2) may be mediated through inhibition of HIF2a within tumor epithelial cells themselves and/or mesenchymal cells of the tumor microenvironment. Cancer Res; 70(8); 3071-9. (C) 2010 AACR. C1 [Zimmer, Michael; Neil, Christopher; Iliopoulos, Othon] Massachusetts Gen Hosp, Ctr Canc, Ctr Canc Res, Charlestown, MA 02129 USA. [Zimmer, Michael; Neil, Christopher; Iliopoulos, Othon] Massachusetts Gen Hosp, Dept Med, Hematol Oncol Unit, Charlestown, MA 02129 USA. [Lynch, Mary; Schmidt, Emmett] Massachusetts Gen Hosp, Serv Pediat, Charlestown, MA 02129 USA. [Ebert, Benjamin L.] Brigham & Womens Hosp, Harvard Stem Cell Inst, Boston, MA 02115 USA. [Lamb, Justin; Ebert, Benjamin L.; Golub, Todd R.] Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. [Lamb, Justin; Ebert, Benjamin L.; Golub, Todd R.] MIT, Cambridge, MA 02139 USA. RP Iliopoulos, O (reprint author), Massachusetts Gen Hosp, Ctr Canc, Ctr Canc Res, 13th St,Bldg 149, Charlestown, MA 02129 USA. EM oiliopoulos@partners.org FU NIH [5R01CA104574, RL1HG004671, RL1CA133834, RL1GM084437, UL1RR024924]; MGH Bertucci Center for Genitourinary Oncology; VHL Family Alliance; DF/HCC Kidney Cancer Program FX Grant Support; NIH grant 5R01CA104574 and the MGH Bertucci Center for Genitourinary Oncology Award (O. Iliopoulos), the VHL Family Alliance, the DF/HCC Kidney Cancer Program Career Development Award (M. Zimmer), and NIH Genomics Based Drug Discovery-Target ID Project grant RL1HG004671, administratively linked to NIH grants RL1CA133834, RL1GM084437, and UL1RR024924 (J. Lamb and T. R. Golub). NR 38 TC 25 Z9 26 U1 1 U2 3 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 APR 15 PY 2010 VL 70 IS 8 BP 3071 EP 3079 DI 10.1158/0008-5472.CAN-09-2877 PG 9 WC Oncology SC Oncology GA 607GC UT WOS:000278486100011 PM 20354189 ER PT J AU Fiorentino, M Judson, G Penney, K Flavin, R Stark, J Fiore, C Fall, K Martin, N Ma, J Sinnott, J Giovannucci, E Stampfer, M Sesso, HD Kantoff, PW Finn, S Loda, M Mucci, L AF Fiorentino, Michelangelo Judson, Gregory Penney, Kathryn Flavin, Richard Stark, Jennifer Fiore, Christopher Fall, Katja Martin, Neil Ma, Jing Sinnott, Jennifer Giovannucci, Edward Stampfer, Meir Sesso, Howard D. Kantoff, Philip W. Finn, Stephen Loda, Massimo Mucci, Lorelei TI Immunohistochemical Expression of BRCA1 and Lethal Prostate Cancer SO CANCER RESEARCH LA English DT Article ID MAMMARY EPITHELIAL-CELLS; MUTATION CARRIERS; GLEASON SCORE; CYCLE CONTROL; DNA-DAMAGE; GENE; TRANSCRIPTION; PHYSICIANS; TRIAL; MEN AB BRCA1 functions as a tumor suppressor; recent work suggests that BRCA1 may also induce cell cycle arrest to allow for DNA repair. We hypothesized that BRCA1 expression in prostate tumor tissue may be associated with prostate cancer progression through regulation of the cell cycle. We used immunohistochemistry to evaluate BRCA1 protein expression in archival tumor samples from 393 prostate cancer cases in the Physicians' Health Study. The men were followed prospectively from diagnosis to development of metastases and mortality. Fifteen percent of tumors stained positive for BRCA1. BRCA1-positive tumors had substantially increased tumor proliferation index compared with negative tumors (47.0 Ki67-positive nuclei versus 10.3, P = 0.0016) and were more likely to develop lethal cancer compared with BRCA1-negative tumors (hazard ratio, 4.6; 95% confidence interval, 2.4-8.7). These findings strengthen the hypothesis that BRCA1 plays a role in cell cycle control and show that BRCA1 is a marker of clinical prostate cancer prognosis. Cancer Res; 70(8); 3136-9. (C) 2010 AACR. C1 [Fiorentino, Michelangelo] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Mol Oncol Pathol,Dept Pathol, Boston, MA 02115 USA. [Judson, Gregory; Penney, Kathryn; Stark, Jennifer; Fall, Katja; Ma, Jing; Sinnott, Jennifer; Giovannucci, Edward; Stampfer, Meir; Mucci, Lorelei] Harvard Univ, Sch Med, Channing Lab, Brigham & Womens Hosp,Dept Med, Boston, MA 02115 USA. [Judson, Gregory; Penney, Kathryn; Stark, Jennifer; Fall, Katja; Martin, Neil; Giovannucci, Edward; Stampfer, Meir; Sesso, Howard D.; Mucci, Lorelei] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Giovannucci, Edward; Stampfer, Meir] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Sinnott, Jennifer] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Martin, Neil] Brigham & Womens Hosp, Boston, MA 02115 USA. [Sesso, Howard D.] Harvard Univ, Sch Med, Div Prevent Med, Brigham & Womens Hosp,Dept Med, Boston, MA 02115 USA. [Kantoff, Philip W.] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Fiorentino, Michelangelo] St Orsola Marcello Malpighi Hosp, Pathol Unit, Addarii Inst, Bologna, Italy. [Fall, Katja] Univ Uppsala Hosp, Uppsala, Sweden. [Kantoff, Philip W.; Loda, Massimo] Broad Inst, Cambridge, MA USA. RP Fiorentino, M (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Mol Oncol Pathol,Dept Pathol, 44 Binney St,JF215H, Boston, MA 02115 USA. EM michelangelo_fiorentino@dfci.harvard.edu RI Rider, Jennifer/A-5371-2011; Fall, Katja/A-9186-2012; Martin, Neil/E-2193-2014; OI Martin, Neil/0000-0002-8164-8516; Finn, Stephen/0000-0002-8628-5814; Fall, Katja/0000-0002-3649-2639 FU Department of Defense [W81XWH-05-1-0562]; Dana-Farber/Harvard Cancer Center; National Cancer Institute [CA34944, CA40360, CA097193]; National Heart, Lung, and Blood Institute [HL-26490, HL-34595] FX Grant Support; Department of Defense (W81XWH-05-1-0562) and the Dana-Farber/Harvard Cancer Center Prostate Specialized Programs of Research Excellence. The Physicians' Health Study is supported by grants CA34944, CA40360, and CA097193 from the National Cancer Institute, and grants HL-26490 and HL-34595 from the National Heart, Lung, and Blood Institute. L. Mucci is a Michael Milken Scholar of the Prostate Cancer Foundation. NR 21 TC 12 Z9 12 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2010 VL 70 IS 8 BP 3136 EP 3139 DI 10.1158/0008-5472.CAN-09-4100 PG 4 WC Oncology SC Oncology GA 607GC UT WOS:000278486100018 PM 20388772 ER PT J AU Geng, H Rademacher, BL Pittsenbarger, J Huang, CY Harvey, CT Lafortune, MC Myrthue, A Garzotto, M Nelson, PS Beer, TM Qian, DZ AF Geng, Hao Rademacher, Brooks L. Pittsenbarger, Janet Huang, Chung-Ying Harvey, Christopher T. Lafortune, Marie C. Myrthue, Anne Garzotto, Mark Nelson, Peter S. Beer, Tomasz M. Qian, David Z. TI ID1 Enhances Docetaxel Cytotoxicity in Prostate Cancer Cells through Inhibition of p21 SO CANCER RESEARCH LA English DT Article ID ACTIVATED PROTEIN-KINASE; MITOXANTRONE PLUS PREDNISONE; ENDOTHELIAL GROWTH-FACTOR; LOOP-HELIX PROTEINS; NEOADJUVANT DOCETAXEL; SIGNALING PATHWAY; EPITHELIAL-CELLS; GENE-EXPRESSION; DNA-DAMAGE; IN-VIVO AB To identify potential mechanisms underlying prostate cancer chemotherapy response and resistance, we compared the gene expression profiles in high-risk human prostate cancer specimens before and after neoadjuvant chemotherapy and radical prostatectomy. Among the molecular signatures associated with chemotherapy, transcripts encoding inhibitor of DNA binding 1 (ID1) were significantly upregulated. The patient biochemical relapse status was monitored in a long-term follow-up. Patients with ID1 upregulation were found to be associated with longer relapse-free survival than patients without ID1 increase. This in vivo clinical association was mechanistically investigated. The chemotherapy-induced ID1 upregulation was recapitulated in the prostate cancer cell line LNCaP. Docetaxel dose-dependently induced ID1 transcription, which was mediated by ID1 promoter E-box chromatin modification and c-Myc binding. Stable ID1 overexpression in LNCaP increased cell proliferation, promoted G(1) cell cycle progression, and enhanced docetaxel-induced cytotoxicity. These changes were accompanied by a decrease in cellular mitochondria content, an increase in BCL2 phosphorylation at serine 70, caspase-3 activation, and poly(ADP-ribose) polymerase cleavage. In contrast, ID1 siRNA in the LNCaP and C42B cell lines reduced cell proliferation and decreased docetaxel-induced cytotoxicity by inhibiting cell death. ID1-mediated chemosensitivity enhancement was in part due to ID1 suppression of p21. Overexpression of p21 in LNCaP-ID1-overexpressing cells restored the p21 level and reversed ID1-enhanced chemosensitivity. These molecular data provide a mechanistic rationale for the observed in vivo clinical association between ID1 upregulation and relapse-free survival. Taken together, it shows that ID1 expression has a novel therapeutic role in prostate cancer chemotherapy and prognosis. Cancer Res; 70(8); 3239-48. (C)2010 AACR. C1 [Geng, Hao; Rademacher, Brooks L.; Pittsenbarger, Janet; Harvey, Christopher T.; Lafortune, Marie C.; Myrthue, Anne; Beer, Tomasz M.; Qian, David Z.] Oregon Hlth & Sci Univ, Dept Med, Div Hematol & Med Oncol, Portland, OR 97239 USA. [Garzotto, Mark] Oregon Hlth & Sci Univ, Div Urol, Portland, OR 97239 USA. [Garzotto, Mark] Portland VA Med Ctr, Portland, OR USA. [Huang, Chung-Ying; Nelson, Peter S.] Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98104 USA. [Huang, Chung-Ying; Nelson, Peter S.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Nelson, Peter S.] Univ Washington, Div Med Oncol, Seattle, WA 98195 USA. RP Beer, TM (reprint author), Oregon Hlth & Sci Univ, Dept Med, Div Hematol & Med Oncol, 3303 SW Bond,CH14R, Portland, OR 97239 USA. EM beert@ohsu.edu; qianzh@ohsu.edu FU Aventis Pharmaceuticals [GIA US 16080]; Serono, Inc. [031.G0008]; NIH [3M01RR00334-33S2, 1 R01 CA119125-01, U54CA126540]; PNW Prostate Specialized Programs of Research Excellence [CA97186] FX Grant GIA US 16080 from Aventis Pharmaceuticals; grant 031.G0008 from Serono, Inc.; and NIH grants 3M01RR00334-33S2, 1 R01 CA119125-01, U54CA126540, and PNW Prostate Specialized Programs of Research Excellence grant CA97186. NR 50 TC 19 Z9 19 U1 0 U2 0 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 APR 15 PY 2010 VL 70 IS 8 BP 3239 EP 3248 DI 10.1158/0008-5472.CAN-09-3186 PG 10 WC Oncology SC Oncology GA 607GC UT WOS:000278486100029 PM 20388787 ER PT J AU Yoo, BK Chen, D Su, ZZ Gredler, R Yoo, J Shah, K Fisher, PB Sarkar, D AF Yoo, Byoung Kwon Chen, Dong Su, Zhao-zhong Gredler, Rachel Yoo, Jinsang Shah, Khalid Fisher, Paul B. Sarkar, Devanand TI Molecular Mechanism of Chemoresistance by Astrocyte Elevated Gene-1 SO CANCER RESEARCH LA English DT Article ID HUMAN HEPATOCELLULAR-CARCINOMA; MUSCLE PROTEIN-SYNTHESIS; RAT SKELETAL-MUSCLE; MULTIDRUG-RESISTANCE; TRANSLATION INITIATION; DRUG-RESISTANCE; P-GLYCOPROTEIN; EXPRESSION; DOXORUBICIN; CANCER AB Our recent findings show that astrocyte elevated gene-1 (AEG-1) is overexpressed in >90% of human hepatocellular carcinoma (HCC) samples, and AEG-1 plays a central role in regulating development and progression of HCC. In the present study, we elucidate a molecular mechanism of AEG-1-induced chemoresistance, an important characteristic of aggressive cancers. AEG-1 increases the expression of multidrug resistance gene 1 (MDR1) protein, resulting in increased efflux and decreased accumulation of doxorubicin, promoting doxorubicin resistance. Suppression of MDR1 by small interfering RNA or chemical reagents, or inhibition of AEG-1 or a combination of both genes, significantly increases in vitro sensitivity to doxorubicin. In nude mice xenograft studies, a lentivirus expressing AEG-1 short hairpin RNA, in combination with doxorubicin, profoundly inhibited growth of aggressive human HCC cells compared with either agent alone. We document that although AEG-1 does not affect MDR1 gene transcription, it facilitates association of MDR1 mRNA to polysomes, resulting in increased translation, and AEG-1 also inhibits ubiquitination and subsequent proteasome-mediated degradation of MDR1 protein. This study is the first documentation of a unique aspect of AEG-1 function (i.e., translational and posttranslational regulation of proteins). Inhibition of AEG-1 might provide a means of more effectively using chemotherapy to treat HCC, which displays inherent chemoresistance with aggressive pathology. Cancer Res; 70(8); 3249-58. (C)2010 AACR. C1 [Yoo, Byoung Kwon; Su, Zhao-zhong; Gredler, Rachel; Yoo, Jinsang; Fisher, Paul B.; Sarkar, Devanand] Virginia Commonwealth Univ, Sch Med, Dept Human & Mol Genet, Richmond, VA 23298 USA. [Chen, Dong; Sarkar, Devanand] Virginia Commonwealth Univ, Sch Med, Dept Pathol, Richmond, VA 23298 USA. [Fisher, Paul B.; Sarkar, Devanand] Virginia Commonwealth Univ, Sch Med, VCU Inst Mol Med, Richmond, VA 23298 USA. [Fisher, Paul B.; Sarkar, Devanand] Virginia Commonwealth Univ, Sch Med, VCU Massey Canc Ctr, Richmond, VA 23298 USA. [Shah, Khalid] Harvard Univ, Sch Med, Dept Radiol, Mol Neuropathy & Imaging Lab, Boston, MA 02115 USA. [Shah, Khalid] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Sarkar, D (reprint author), Virginia Commonwealth Univ, Sch Med, Dept Human & Mol Genet, 1220 E Broad St,POB 980035, Richmond, VA 23298 USA. EM dsarkar@vcu.edu RI chen, dong/A-6889-2012 FU The Goldhirsh Foundation; The Dana Foundation; NIH [R01 CA134721, R01 CA035675] FX The Goldhirsh Foundation and The Dana Foundation (D. Sarkar) and NIH grants R01 CA134721 and R01 CA035675 (P.B. Fisher). D. Sarkar is the Harrison Endowed Scholar in Cancer Research. P.B. Fisher holds the Thelma Newmeyer Corman Chair in Cancer Research and is a Samuel Waxman Cancer Research Foundation Investigator. NR 40 TC 60 Z9 67 U1 2 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2010 VL 70 IS 8 BP 3249 EP 3258 DI 10.1158/0008-5472.CAN-09-4009 PG 10 WC Oncology SC Oncology GA 607GC UT WOS:000278486100030 PM 20388796 ER PT J AU Scott, KL Chin, L AF Scott, Kenneth L. Chin, Lynda TI Signaling From the Golgi: Mechanisms and Models for Golgi Phosphoprotein 3-Mediated Oncogenesis SO CLINICAL CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR RECEPTOR; HUNTINGTIN-INTERACTING PROTEIN-1; RAB-COUPLING PROTEIN; SACCHAROMYCES-CEREVISIAE; PHOSPHATIDYLINOSITOL 4-KINASE; RETROMER COMPLEX; A-431 CELLS; CANCER; TRAFFICKING; REQUIRES AB Golgi phosphoprotein 3 (GOLPH3; also known as GPP34/GMx33/MIDAS) represents an exciting new class of oncoproteins involved in vesicular trafficking. Encoded by a gene residing on human chromosome 5p13, which is frequently amplified in multiple solid tumor types, GOLPH3 was initially discovered as a phosphorylated protein localized to the Golgi apparatus. Recent functional, cell biological, and biochemical analyses show that GOLPH3 can function as an oncoprotein to promote cell transformation and tumor growth by enhancing activity of the mammalian target of rapamycin, a serine/threonine protein kinase known to regulate cell growth, proliferation, and survival. Although its precise mode of action in cancer remains to be elucidated, the fact that GOLPH3 has been implicated in protein trafficking, receptor recycling, and glycosylation points to potential links of these cellular processes to tumorigenesis. Understanding how these processes may be deregulated and contribute to cancer pathogenesis and drug response will uncover new avenues for therapeutic intervention. Clin Cancer Res; 16(8); 2229-34. (C) 2010 AACR. C1 [Chin, Lynda] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Scott, Kenneth L.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Chin, Lynda] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. RP Chin, L (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM lynda_chin@dfci.harvard.edu FU NIH [RO1 CA93947, P50 CA93683, 5-T32-AR07098-31]; American Cancer Society [PF-07-039-01-CSM] FX NIH grants RO1 CA93947, P50 CA93683 (L. Chin), and 5-T32-AR07098-31 (K. L. Scott), and American Cancer Society grant PF-07-039-01-CSM (K. L. Scott). NR 50 TC 51 Z9 61 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 15 PY 2010 VL 16 IS 8 BP 2229 EP 2234 DI 10.1158/1078-0432.CCR-09-1695 PG 6 WC Oncology SC Oncology GA 608OW UT WOS:000278595900001 PM 20354134 ER PT J AU Winter, JN Li, SL Aurora, V Variakojis, D Nelson, B Krajewska, M Zhang, LJ Habermann, TM Fisher, RI Macon, WR Chhanabhai, M Felgar, RE Hsi, ED Medeiros, LJ Weick, JK Weller, EA Melnick, A Reed, JC Horning, SJ Gascoyne, RD AF Winter, Jane N. Li, Shuli Aurora, Vikas Variakojis, Daina Nelson, Beverly Krajewska, Maryla Zhang, Lijun Habermann, Thomas M. Fisher, Richard I. Macon, William R. Chhanabhai, Mukesh Felgar, Raymond E. Hsi, Eric D. Medeiros, L. Jeffrey Weick, James K. Weller, Edie A. Melnick, Ari Reed, John C. Horning, Sandra J. Gascoyne, Randy D. TI Expression of p21 Protein Predicts Clinical Outcome in DLBCL Patients Older than 60 Years Treated with R-CHOP but not CHOP: A Prospective ECOG and Southwest Oncology Group Correlative Study on E4494 SO CLINICAL CANCER RESEARCH LA English DT Article ID B-CELL LYMPHOMA; 2-STAGE RANDOMIZATION DESIGNS; CHEMOTHERAPY PLUS RITUXIMAB; GERMINAL CENTER PHENOTYPE; IMMUNOHISTOCHEMICAL ANALYSIS; TREATMENT POLICIES; ELDERLY-PATIENTS; POOR SURVIVAL; P53 GENE; INHIBITOR AB Purpose: To prospectively investigate the prognostic significance of p21 and p53 expression in diffuse large B-cell lymphoma in the context of the U. S. Intergroup trial comparing conventional cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy to rituximab-CHOP (R-CHOP) induction, with or without maintenance rituximab. Experimental Design: Immunohistochemical staining of 197 paraffin-embedded biopsy specimens was scored by an independent panel of experts. Results: The cyclin-dependent kinase inhibitor, p21, was expressed in 55% of cases examined. In a multivariable analysis adjusting for International Prognostic Index score and BCL2 status, p21 expression was a significant, independent, favorable predictive factor for failure-free survival (relative risk, 0.3; P = 0.001) and overall survival (relative risk, 0.3; P = 0.003) for patients treated with R-CHOP. Expression of p21 was not predictive of outcome for CHOP-treated patients. Only p21-positive cases benefited from the addition of rituximab to CHOP. Among p21-positive patients, treatment with R-CHOP was associated with a higher failure-free survival rate at 5 years compared with CHOP (61% versus 24%; P = 0.01). In contrast, no significant differences were detected in failure-free survival according to treatment arm for p21-negative patients. Expression of p53, alone or in combination with p21, did not predict for outcome in univariable or multivariable analyses. Conclusions: In this study, p21 protein expression emerged as an important independent predictor of a favorable clinical outcome when rituximab was added to CHOP therapy. These data suggest that rituximab-related effects on lymphoma survival pathways may be functionally linked to p21 activity. Clin Cancer Res; 16(8); 2435-42. (C) 2010 AACR. C1 [Winter, Jane N.; Aurora, Vikas; Variakojis, Daina; Nelson, Beverly] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Feinberg Sch Med, Chicago, IL 60611 USA. [Li, Shuli; Zhang, Lijun; Weller, Edie A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Krajewska, Maryla; Reed, John C.] Burnham Inst Med Res, La Jolla, CA USA. [Habermann, Thomas M.; Macon, William R.] Mayo Clin & Mayo Fdn, Mayo Med Sch, Rochester, MN 55905 USA. [Fisher, Richard I.] Univ Rochester, Med Ctr, James P Wilmot Canc Ctr, Rochester, NY 14642 USA. [Chhanabhai, Mukesh] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [Felgar, Raymond E.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Hsi, Eric D.] Cleveland Clin, Cleveland, OH 44106 USA. [Medeiros, L. Jeffrey] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Weick, James K.] Hematol Oncol Associates, Lake Worth, FL USA. [Melnick, Ari] Cornell Weill Med Coll, New York, NY USA. [Horning, Sandra J.] Stanford Univ, Stanford, CA 94305 USA. RP Winter, JN (reprint author), Div Hematol Oncol, Suite 850,676 N St Clair St, Chicago, IL 60611 USA. EM j-winter@northwestern.edu FU ECOG; Public Health Service [CA23318, CA66636, CA21115, CA38926, CA32102, CA04919, CA11083, CA13650, CA17145, CA81534, CA39229]; National Cancer Institute of the NIH; Department of Health and Human Services; Genentech FX ECOG (Robert L. Comis, M. D., Chair); grants CA23318, CA66636, CA21115, CA38926, CA32102, CA04919, CA11083, CA13650, CA17145, CA81534, CA39229, CA81534 from the Public Health Service, the National Cancer Institute of the NIH; the Department of Health and Human Services; and commercial research grant from Genentech. NR 51 TC 16 Z9 18 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 15 PY 2010 VL 16 IS 8 BP 2435 EP 2442 DI 10.1158/1078-0432.CCR-09-1219 PG 8 WC Oncology SC Oncology GA 608OW UT WOS:000278595900022 PM 20371683 ER PT J AU Pappas, PG Alexander, BD Andes, DR Hadley, S Kauffman, CA Freifeld, A Anaissie, EJ Brumble, LM Herwaldt, L Ito, J Kontoyiannis, DP Lyon, GM Marr, KA Morrison, VA Park, BJ Patterson, TF Perl, TM Oster, RA Schuster, MG Walker, R Walsh, TJ Wannemuehler, KA Chiller, TM AF Pappas, Peter G. Alexander, Barbara D. Andes, David R. Hadley, Susan Kauffman, Carol A. Freifeld, Alison Anaissie, Elias J. Brumble, Lisa M. Herwaldt, Loreen Ito, James Kontoyiannis, Dimitrios P. Lyon, G. Marshall Marr, Kieren A. Morrison, Vicki A. Park, Benjamin J. Patterson, Thomas F. Perl, Trish M. Oster, Robert A. Schuster, Mindy G. Walker, Randall Walsh, Thomas J. Wannemuehler, Kathleen A. Chiller, Tom M. TI Invasive Fungal Infections among Organ Transplant Recipients: Results of the Transplant-Associated Infection Surveillance Network (TRANSNET) SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID SOLID-ORGAN; RISK-FACTORS; AMPHOTERICIN-B; ASPERGILLOSIS; KIDNEY; PROPHYLAXIS; CANDIDIASIS; VORICONAZOLE; FLUCONAZOLE AB Background. Invasive fungal infections (IFIs) are a major cause of morbidity and mortality among organ transplant recipients. Multicenter prospective surveillance data to determine disease burden and secular trends are lacking. Methods. The Transplant-Associated Infection Surveillance Network (TRANSNET) is a consortium of 23 US transplant centers, including 15 that contributed to the organ transplant recipient dataset. We prospectively identified IFIs among organ transplant recipients from March, 2001 through March, 2006 at these sites. To explore trends, we calculated the 12-month cumulative incidence among 9 sequential cohorts. Results. During the surveillance period, 1208 IFIs were identified among 1063 organ transplant recipients. The most common IFIs were invasive candidiasis (53%), invasive aspergillosis (19%), cryptococcosis (8%), non-Aspergillus molds (8%), endemic fungi (5%), and zygomycosis (2%). Median time to onset of candidiasis, aspergillosis, and cryptococcosis was 103, 184, and 575 days, respectively. Among a cohort of 16,808 patients who underwent transplantation between March 2001 and September 2005 and were followed through March 2006, a total of 729 IFIs were reported among 633 persons. One-year cumulative incidences of the first IFI were 11.6%, 8.6%, 4.7%, 4.0%, 3.4%, and 1.3% for small bowel, lung, liver, heart, pancreas, and kidney transplant recipients, respectively. One-year incidence was highest for invasive candidiasis (1.95%) and aspergillosis (0.65%). Trend analysis showed a slight increase in cumulative incidence from 2002 to 2005. Conclusions. We detected a slight increase in IFIs during the surveillance period. These data provide important insights into the timing and incidence of IFIs among organ transplant recipients, which can help to focus effective prevention and treatment strategies. C1 [Pappas, Peter G.] Univ Alabama, Dept Med, Div Infect Dis, Med Ctr, Birmingham, AL 35294 USA. [Oster, Robert A.] Univ Alabama, Dept Med, Div Prevent Med, Med Ctr, Birmingham, AL 35294 USA. [Alexander, Barbara D.] Duke Univ, Med Ctr, Durham, NC USA. [Andes, David R.] Univ Wisconsin, Madison, WI 53706 USA. [Hadley, Susan] Tufts Med Ctr, Boston, MA USA. [Kauffman, Carol A.] Univ Michigan, Ann Arbor, MI 48109 USA. [Kauffman, Carol A.] Vet Affairs Ann Arbor Healthcare Syst, Ann Arbor, MI USA. [Freifeld, Alison] Univ Nebraska Med Ctr, Omaha, NE USA. [Anaissie, Elias J.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Brumble, Lisa M.] Mayo Clin, Jacksonville, FL 32224 USA. [Herwaldt, Loreen] Univ Iowa Hosp, Iowa City, IA USA. [Ito, James] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Kontoyiannis, Dimitrios P.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Patterson, Thomas F.] Univ Texas Hlth Sci Ctr San Antonio, S Texas Vet Healthcare Syst, San Antonio, TX 78229 USA. [Lyon, G. Marshall] Emory Univ, Sch Med, Atlanta, GA USA. [Park, Benjamin J.; Wannemuehler, Kathleen A.; Chiller, Tom M.] Ctr Dis Control & Prevent, Mycot Dis Branch, Atlanta, GA USA. [Marr, Kieren A.; Perl, Trish M.] Johns Hopkins Univ, Med Ctr, Baltimore, MD 21218 USA. [Marr, Kieren A.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Morrison, Vicki A.] Univ Minnesota, Minneapolis, MN USA. [Morrison, Vicki A.] Vet Affairs Med Ctr, Minneapolis, MN USA. [Walker, Randall] Mayo Clin, Rochester, MN USA. [Schuster, Mindy G.] Hosp Univ Penn, Philadelphia, PA 19104 USA. [Walsh, Thomas J.] NCI, NIH, Bethesda, MD 20892 USA. RP Pappas, PG (reprint author), Univ Alabama, Dept Med, Div Infect Dis, Med Ctr, 1900 Univ Blvd,229 THT, Birmingham, AL 35294 USA. EM pappas@uab.edu FU Merck; Pfizer; Schereing-Plough; Astellas; Nektar Therapeutics; Enzon FX P. G. P. has received grant support from Merck, Pfizer, Schereing-Plough, and Astellas and served as an adhoc advisor for Novartis, Basilea, Merck, Pfizer, and Astellas. D. R. A. has received grant support and served as an ad hoc advisor for Merck, Pfizer, and Schering-Plough. T. F. P. has received research support and honoraria from Merck, Pfizer, Schering-Plough, and Nektar Therapeutics and has served as a consultant for Basilea, Merck, Nektar, and Pfizer. K. A. M. has received grant support from Merck and Enzon and served as an ad hoc advisor and/or consultant for Astellas, Basilea, Enzon, Merck, Pfizer, and Schering-Plough. J.I.I. has received honoraria from Astellas, Enzon, Pfizer, and Schering-Plough. VAM is on the speakers' bureau for Amgen, Merck, Pfizer, Schering-Plough, and Celgene. All other authors: no conflicts. NR 40 TC 414 Z9 425 U1 2 U2 29 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD APR 15 PY 2010 VL 50 IS 8 BP 1101 EP 1111 DI 10.1086/651262 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 570BF UT WOS:000275645900004 PM 20218876 ER PT J AU Parienti, JJ Ragland, K Lucht, F de la Blanchardiere, A Dargere, S Yazdanpanah, Y Dutheil, JJ Perre, P Verdon, R Bangsberg, DR AF Parienti, Jean-Jacques Ragland, Kathleen Lucht, Frederic de la Blanchardiere, Arnaud Dargere, Sylvie Yazdanpanah, Yazdan Dutheil, Jean-Jacques Perre, Philippe Verdon, Renaud Bangsberg, David R. CA ESPOIR Study Grp REACH Study Grp TI Average Adherence to Boosted Protease Inhibitor Therapy, rather than the Pattern of Missed Doses, as a Predictor of HIV RNA Replication SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID PATIENTS RECEIVING LOPINAVIR/RITONAVIR; COMBINATION ANTIRETROVIRAL THERAPY; LESS-THAN 95-PERCENT; POSITIVE INDIVIDUALS; VIROLOGICAL FAILURE; VIRAL SUPPRESSION; DRUG-RESISTANCE; INTERRUPTIONS; OUTCOMES; REGIMEN AB Consecutive missed doses may differentially impact the efficacy of antiretroviral therapy associated with the use of a nonnucleoside reverse-transcriptase inhibitor (NNRTI) and a ritonavir-boosted protease inhibitor (PI). In a cohort of 72 subjects receiving a boosted PI, average adherence to dosage was a better predictor of human immunodeficiency virus (HIV) replication than was the duration or frequency of treatment interruption. In contrast with an NNRTI, consecutive missed doses of a boosted PI did not emerge as a major risk factor for HIV replication. C1 [Parienti, Jean-Jacques; Dutheil, Jean-Jacques] Cote de Nacre Univ Hosp, Dept Clin Res & Biostat, Caen, France. [Parienti, Jean-Jacques; de la Blanchardiere, Arnaud; Dargere, Sylvie; Verdon, Renaud] Cote de Nacre Univ Hosp, Dept Infect Dis, Caen, France. [Parienti, Jean-Jacques] Univ Paris 06, Unite Mixte Rech Sante 707, Paris, France. [Parienti, Jean-Jacques] INSERM, U707, Paris, France. [Lucht, Frederic] Univ Hosp, Dept Infect Dis, St Etienne, France. [Yazdanpanah, Yazdan] Univ Hosp, Dept Infect Dis, Tourcoing, France. [Perre, Philippe] Gen Hosp, Dept Infect Dis, La Roche Sur Yon, France. [Ragland, Kathleen] Univ Calif San Francisco, San Francisco Gen Hosp, Div Infect Dis, Epidemiol & Prevent Intervent Ctr, San Francisco, CA USA. [Bangsberg, David R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Global Hlth,Harvard Initiat Global Hlth, Boston, MA USA. RP Parienti, JJ (reprint author), CHU Caen, Dept Clin Res & Biostat, Ave Cote de Nacre, F-14033 Caen, France. EM parienti-jj@chu-caen.fr FU Abbott Laboratories; National Institute of Mental Health [RO-54907]; National Institute on Alcohol Abuse and Alcoholism [K-24 015287]; Abbott; Boehringer Ingelheim; Bristol-Myers Squibb; Gilead; GlaxoSmithKline; Merck; Pfizer; Roche; Tibotec FX We thank Veronique Ronat, Isabelle Suaud, Anne-Catherine Cordier, and Pascale Goubin for their help in data collection and Fabien Chaillot for his expert administrative and regulatory support. We are grateful for the scientific collaboration of Isabelle Cohen-Codar and Richard A. Rhode. The ESPOIR cohort was supported by an Abbott Laboratories unrestricted grant (to Caen Cote de Nacre University hospital). The REACH cohort was supported by the National Institute of Mental Health (grant RO-54907) and the National Institute on Alcohol Abuse and Alcoholism (grant K-24 015287). We also acknowledge helpful suggestions regarding wording of the summary findings by 2 anonymous reviewers.; J.-J.P. reports that he has received travel grants, honoraria for presentation at workshops, and consultancy honoraria from Abbott, Boehringer Ingelheim, and Bristol-Myers Squibb; Y.Y. reports that he has received travel grants, honoraria for presentation at workshops, and consultancy honoraria from Bristol-Myers Squibb, Boehringer Ingelheim, Gilead, GlaxoSmithKline, Merck, Pfizer, Roche, and Tibotec. All other authors: no conflicts. NR 24 TC 46 Z9 47 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD APR 15 PY 2010 VL 50 IS 8 BP 1192 EP 1197 DI 10.1086/651419 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 570BF UT WOS:000275645900016 PM 20210643 ER PT J AU Xu, J Sankaran, VG Ni, M Menne, TF Puram, RV Kim, W Orkin, SH AF Xu, Jian Sankaran, Vijay G. Ni, Min Menne, Tobias F. Puram, Rishi V. Kim, Woojin Orkin, Stuart H. TI Transcriptional silencing of gamma-globin by BCL11A involves long-range interactions and cooperation with SOX6 SO GENES & DEVELOPMENT LA English DT Article DE Hemoglobin switching; fetal hemoglobin; BCL11A; transcription regulation ID LOCUS-CONTROL REGION; YEAST ARTIFICIAL CHROMOSOME; ELEMENT ANNOTATION SYSTEM; QUANTITATIVE TRAIT LOCUS; FETAL-HEMOGLOBIN LEVELS; HUMAN ERYTHROID-CELLS; TRANSGENIC MICE; DEVELOPMENTAL REGULATION; REGULATORY ELEMENT; GENE-EXPRESSION AB The developmental switch from human fetal (gamma) to adult (beta) hemoglobin represents a clinically important example of developmental gene regulation. The transcription factor BCL11A is a central mediator of gamma-globin silencing and hemoglobin switching. Here we determine chromatin occupancy of BCL11A at the human beta-globin locus and other genomic regions in vivo by high-resolution chromatin immunoprecipitation (ChIP)-chip analysis. BCL11A binds the upstream locus control region (LCR), epsilon-globin, and the intergenic regions between gamma-globin and delta-globin genes. A chromosome conformation capture (3C) assay shows that BCL11A reconfigures the beta-globin cluster by modulating chromosomal loop formation. We also show that BCL11A and the HMG-box-containing transcription factor SOX6 interact physically and functionally during erythroid maturation. BCL11A and SOX6 co-occupy the human beta-globin cluster along with GATA1, and cooperate in silencing gamma-globin transcription in adult human erythroid progenitors. These findings collectively demonstrate that transcriptional silencing of gamma-globin genes by BCL11A involves long-range interactions and cooperation with SOX6. Our findings provide insight into the mechanism of BCL11A action and new clues for the developmental gene regulatory programs that function at the beta-globin locus. C1 [Xu, Jian; Sankaran, Vijay G.; Menne, Tobias F.; Kim, Woojin; Orkin, Stuart H.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Xu, Jian; Sankaran, Vijay G.; Menne, Tobias F.; Kim, Woojin; Orkin, Stuart H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol,Harvard Stem Cell Inst, Boston, MA 02115 USA. [Xu, Jian; Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Sankaran, Vijay G.; Puram, Rishi V.] Harvard Mit Div Hlth Sci & Technol, Boston, MA 02115 USA. [Ni, Min] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Div Mol & Cellular Oncol, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. EM stuart_orkin@dfci.harvard.edu RI cheng, yong/I-4270-2012 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National Institutes of Health (NIH); Kay Kendall Leukaemia Fund FX We are grateful to P. Sassone-Corsi for providing alpha-SOX6 antibodies. We thank members of the Orkin laboratory for technical assistance and comments. We thank M. Lupien, H. He, S. Baily, X. S. Liu, M. H. Brilliant, and N. Hagiwara for helpful advice and discussions. This work was supported by funding from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) (to S. H. O.). S. H. O. is an Investigator of the Howard Hughes Medical Institute (HHMI). T. F. M. is supported by the Kay Kendall Leukaemia Fund. NR 68 TC 143 Z9 151 U1 4 U2 14 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD APR 15 PY 2010 VL 24 IS 8 BP 783 EP 798 DI 10.1101/gad.1897310 PG 16 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 584DK UT WOS:000276730300007 PM 20395365 ER PT J AU de la Torre-Ubieta, L Gaudilliere, B Yang, Y Ikeuchi, Y Yamada, T DiBacco, S Stegmuller, J Schuller, U Salih, DA Rowitch, D Brunet, A Bonni, A AF de la Torre-Ubieta, Luis Gaudilliere, Brice Yang, Yue Ikeuchi, Yoshiho Yamada, Tomoko DiBacco, Sara Stegmueller, Judith Schueller, Ulrich Salih, Dervis A. Rowitch, David Brunet, Anne Bonni, Azad TI A FOXO-Pak1 transcriptional pathway controls neuronal polarity SO GENES & DEVELOPMENT LA English DT Article DE FOXO; neuronal polarity; Pak1; transcription; axons; dendrites ID P21-ACTIVATED KINASE; POSTMITOTIC NEURONS; SAD KINASES; CELL-CYCLE; FOXO; AXON; MORPHOLOGY; CDH1-APC; PHOSPHORYLATION; POLARIZATION AB Neuronal polarity is essential for normal brain development and function. However, cell-intrinsic mechanisms that govern the establishment of neuronal polarity remain to be identified. Here, we report that knockdown of endogenous FOXO proteins in hippocampal and cerebellar granule neurons, including in the rat cerebellar cortex in vivo, reveals a requirement for the FOXO transcription factors in the establishment of neuronal polarity. The FOXO transcription factors, including the brain-enriched protein FOXO6, play a critical role in axo-dendritic polarization of undifferentiated neurites, and hence in a switch from unpolarized to polarized neuronal morphology. We also identify the gene encoding the protein kinase Pak1, which acts locally in neuronal processes to induce polarity, as a critical direct target gene of the FOXO transcription factors. Knockdown of endogenous Pak1 phenocopies the effect of FOXO knockdown on neuronal polarity. Importantly, exogenous expression of Pak1 in the background of FOXO knockdown in both primary neurons and postnatal rat pups in vivo restores the polarized morphology of neurons. These findings define the FOXO proteins and Pak1 as components of a cell-intrinsic transcriptional pathway that orchestrates neuronal polarity, thus identifying a novel function for the FOXO transcription factors in a unique aspect of neural development. C1 [de la Torre-Ubieta, Luis; Gaudilliere, Brice; Yang, Yue; Ikeuchi, Yoshiho; Yamada, Tomoko; DiBacco, Sara; Stegmueller, Judith; Bonni, Azad] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [de la Torre-Ubieta, Luis; Yang, Yue; Bonni, Azad] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. [Schueller, Ulrich; Rowitch, David] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Salih, Dervis A.; Brunet, Anne] Stanford Univ, Dept Genet, Stanford, CA 94305 USA. RP Bonni, A (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. EM azad_bonni@hms.harvard.edu RI ikeuchi, yoshiho/C-1713-2014 OI ikeuchi, yoshiho/0000-0002-2829-3840 FU NIH [NS041021, NS051255, AG026648]; National Science Foundation; Albert J. Ryan Foundation; Edward and Anne Lefler Fellowship; Human Frontier Science Program Long-term Fellowship; Japan Society for the Promotion of Science Fellowship; Deutsche Forschungsgemeinschaft FX We thank Constance Cepko, Gabriel Corfas, and David van Vactor for helpful discussions; Marten P. Smidt for the FOXO1-GFP, FOXO3-GFP, and FOXO6-GFP plasmids; Jonathan Chernoff for the Pak1 plasmid; Margareta Nikolic for the Pak1 shRNA; and members of the Bonni laboratory for helpful discussions and critical reading of the manuscript. This work was supported by NIH grants to A. Bonni (NS041021 and NS051255), A. Brunet (AG026648), the National Science Foundation (L. T. U. and Y. Y.), the Albert J. Ryan Foundation (L. T. U. and Y. Y.) the Edward and Anne Lefler Fellowship (Y. Y.), the Human Frontier Science Program Long-term Fellowship (Y. I.), the Japan Society for the Promotion of Science Fellowship (T. Y.), and the Deutsche Forschungsgemeinschaft (J. S.). NR 58 TC 38 Z9 38 U1 0 U2 5 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD APR 15 PY 2010 VL 24 IS 8 BP 799 EP 813 DI 10.1101/gad.1880510 PG 15 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 584DK UT WOS:000276730300008 PM 20395366 ER PT J AU Oliver, TG Mercer, KL Sayles, LC Burke, JR Mendus, D Lovejoy, KS Cheng, MH Subramanian, A Mu, D Powers, S Crowley, D Bronson, RT Whittaker, CA Bhutkar, A Lippard, SJ Golub, T Thomale, J Jacks, T Sweet-Cordero, EA AF Oliver, Trudy G. Mercer, Kim L. Sayles, Leanne C. Burke, James R. Mendus, Diana Lovejoy, Katherine S. Cheng, Mei-Hsin Subramanian, Aravind Mu, David Powers, Scott Crowley, Denise Bronson, Roderick T. Whittaker, Charles A. Bhutkar, Arjun Lippard, Stephen J. Golub, Todd Thomale, Juergen Jacks, Tyler Sweet-Cordero, E. Alejandro TI Chronic cisplatin treatment promotes enhanced damage repair and tumor progression in a mouse model of lung cancer SO GENES & DEVELOPMENT LA English DT Article DE Mouse models; cisplatin; Kras; p53; chemotherapy resistance; lung cancer ID NON-SMALL-CELL; PLATINUM-BASED CHEMOTHERAPY; NUCLEOTIDE EXCISION-REPAIR; INDUCED DNA-DAMAGE; ADJUVANT CHEMOTHERAPY; TRANSPORTER CTR1; GENOTOXIC STRESS; TYROSINE KINASE; GENE-EXPRESSION; P53 MUTATIONS AB Chemotherapy resistance is a major obstacle in cancer treatment, yet the mechanisms of response to specific therapies have been largely unexplored in vivo. Employing genetic, genomic, and imaging approaches, we examined the dynamics of response to a mainstay chemotherapeutic, cisplatin, in multiple mouse models of human non-small-cell lung cancer (NSCLC). We show that lung tumors initially respond to cisplatin by sensing DNA damage, undergoing cell cycle arrest, and inducing apoptosis-leading to a significant reduction in tumor burden. Importantly, we demonstrate that this response does not depend on the tumor suppressor p53 or its transcriptional target, p21. Prolonged cisplatin treatment promotes the emergence of resistant tumors with enhanced repair capacity that are cross-resistant to platinum analogs, exhibit advanced histopathology, and possess an increased frequency of genomic alterations. Cisplatin-resistant tumors express elevated levels of multiple DNA damage repair and cell cycle arrest-related genes, including p53-inducible protein with a death domain (Pidd). We demonstrate a novel role for PIDD as a regulator of chemotherapy response in human lung tumor cells. C1 [Oliver, Trudy G.; Mercer, Kim L.; Burke, James R.; Lovejoy, Katherine S.; Crowley, Denise; Whittaker, Charles A.; Bhutkar, Arjun; Lippard, Stephen J.; Jacks, Tyler] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Oliver, Trudy G.; Mercer, Kim L.; Burke, James R.; Cheng, Mei-Hsin; Crowley, Denise; Jacks, Tyler] MIT, Dept Biol, Cambridge, MA 02139 USA. [Mercer, Kim L.; Burke, James R.; Crowley, Denise; Golub, Todd; Jacks, Tyler] Howard Hughes Med Inst, Chevy Chase, MD 20185 USA. [Sayles, Leanne C.; Sweet-Cordero, E. Alejandro] Stanford Univ, Sch Med, Canc Biol Program, Stanford, CA 94305 USA. [Mendus, Diana; Thomale, Juergen] Univ Duisburg Essen, Sch Med, Inst Cell Biol Canc Res, D-45122 Essen, Germany. [Lovejoy, Katherine S.; Lippard, Stephen J.] MIT, Dept Chem, Cambridge, MA 02139 USA. [Subramanian, Aravind; Golub, Todd] Harvard & Massachusetts Inst Technol, Eli & Lily Broad Inst, Cambridge, MA 02139 USA. [Mu, David] Penn State Univ, Coll Med, Dept Pathol, Hershey, PA 17033 USA. [Powers, Scott] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11797 USA. [Bronson, Roderick T.] Tufts Univ, Sch Med & Vet Med, Dept Pathol, Boston, MA 02155 USA. [Golub, Todd] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Sweet-Cordero, E. Alejandro] Stanford Univ, Sch Med, Dept Pediat, Div Pediat Hematol Oncol, Stanford, CA 94305 USA. RP Jacks, T (reprint author), MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM tjacks@mit.edu RI Mu, David/E-8933-2011; Lovejoy, Katherine/H-5139-2011 OI Mu, David/0000-0002-7762-0182; Lovejoy, Katherine/0000-0002-9606-9453 FU National Institutes of Health; National Cancer Institute [5-UO1-CA84306, CA034992]; Cancer Center Support [P30CA14051]; J. Manchot Foundation; Deutsche Forschungsgemeinschaft; Robert Woods Johnson Foundation; National Cancer Institute; American Cancer Society Research Scholar Award FX We thank Etienne Meylan for helpful discussions and critical reading of the manuscript, and Antoine Tinel for kindly providing PIDD constructs. We thank the Koch Institute Core Facilities for technical support, including Eliza Vasile (microscopy) and Glenn Paradis (flow cytometry). This work was supported by the National Institutes of Health and the National Cancer Institute (5-UO1-CA84306 to T. J. and CA034992 to S. J. L.), and in part by Cancer Center Support (core) grant P30CA14051 (T. J.) and a grant from the J. Manchot Foundation and Deutsche Forschungsgemeinschaft (J. T.). T. J. and T. G. are Investigators of the Howard Hughes Medical Institute, and T. J. is a Daniel K. Ludwig Scholar. A. S. C. was supported by grants from the Robert Woods Johnson Foundation (Harold Amos Medical Faculty Development Program), by a mentored clinical scientist grant from the National Cancer Institute, and by an American Cancer Society Research Scholar Award. T. O. is an ASPETMerck post-doctoral fellow. NR 59 TC 95 Z9 97 U1 1 U2 12 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD APR 15 PY 2010 VL 24 IS 8 BP 837 EP 852 DI 10.1101/gad.1897010 PG 16 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 584DK UT WOS:000276730300011 PM 20395368 ER PT J AU Yeh, CC Li, HZ Malhotra, D Turcato, S Nicholas, S Tu, R Zhu, BQ Cha, J Swigart, PM Myagmar, BE Baker, AJ Simpson, PC Mann, MJ AF Yeh, Che-Chung Li, Hongzhe Malhotra, Deepak Turcato, Sally Nicholas, Susan Tu, Richard Zhu, Bo-Qing Cha, John Swigart, Philip M. Myagmar, Bat-Erdene Baker, Anthony J. Simpson, Paul C. Mann, Michael J. TI Distinctive ERK and p38 Signaling in Remote and Infarcted Myocardium During Post-MI Remodeling in the Mouse SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE MYOCARDIAL INFARCTION; MAP KINASE; REMODELING; APOPTOSIS ID MITOGEN-ACTIVATED PROTEIN; CARDIAC-HYPERTROPHY; P38-ALPHA MAPK; PRESSURE-OVERLOAD; HEART-FAILURE; APOPTOSIS; KINASE; INHIBITION; CARDIOMYOPATHY; PATHWAY AB Global activation of MAP kinases has been reported in both human and experimental heart failure. Chronic remodeling of the surviving ventricular wall after myocardial infarction (MI) involves both myocyte loss and fibrosis; we hypothesized that this cardiomyopathy involves differential shifts in pro- and anti-apoptotic MAP kinase signaling in cardiac myocyte (CM) and non-myocyte. Cardiomyopathy after coronary artery ligation in mice was characterized by echocardiography, ex vivo Langendorff preparation, histologic analysis and measurements of apoptosis. Phosphorylation (activation) of signaling molecules was analyzed by Western blot, ELISA and immunohistochemistry. Post-MI remodeling involved dramatic changes in the phosphorylation of both stress-activated MAP (SAP) kinase p38 as well as ERK, a known mediator of cell survival, but not of SAP kinase JNK or the anti-apoptotic mediator of PI3K, Akt. Phosphorylation of p38 rose early after MI in the infarct, whereas a more gradual rise in the remote myocardium accompanied a rise in apoptosis in that region. In both areas, ERK phosphorylation was lowest early after MI and rose steadily thereafter, though infarct phosphorylation was consistently higher. Immunostaining of p-ERK localized to fibrotic areas populated primarily by non-myocytes, whereas staining of p38 phosphorylation was stronger in areas of progressive CM apoptosis. Relative segregation of CMs and non-myocytes in different regions of the post-MI myocardium revealed signaling patterns that imply cell type-specific changes in pro- and anti-apoptotic MAP kinase signaling. Prevention of myocyte loss and of LV remodeling after MI may therefore require cell type-specific manipulation of p38 and ERK activation. J. Cell. Biochem. 109: 11851191, 2010. (C) 2010 Wiley-Liss, Inc. C1 [Yeh, Che-Chung; Li, Hongzhe; Malhotra, Deepak; Nicholas, Susan; Tu, Richard; Cha, John; Mann, Michael J.] Univ Calif San Francisco, Div Cardiothorac Surg, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. [Zhu, Bo-Qing; Swigart, Philip M.; Myagmar, Bat-Erdene; Baker, Anthony J.; Simpson, Paul C.] Univ Calif San Francisco, Div Cardiol, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. [Turcato, Sally] Univ Calif San Francisco, Dept Radiol, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. RP Mann, MJ (reprint author), Univ Calif San Francisco, Div Cardiothorac Surg, San Francisco VA Med Ctr, 500 Parnassus Ave,Suite W420, San Francisco, CA 94143 USA. EM michael.mann@ucsfmedctr.org FU National Institutes of Health [1R01 HL083118, 1K08HL079239]; American Heart Associstion [0465090Y] FX Grant sponsor: National Institutes of Health; Grant numbers: 1R01 HL083118, 1K08HL079239; Grant sponsor: American Heart Associstion; Grant number: 0465090Y. NR 30 TC 20 Z9 22 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD APR 15 PY 2010 VL 109 IS 6 BP 1185 EP 1191 DI 10.1002/jcb.22498 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 587AI UT WOS:000276958200014 PM 20186881 ER PT J AU Johnson, KG Johnson, DC AF Johnson, Karin G. Johnson, Douglas C. TI Frequency of Sleep Apnea in Stroke and TIA Patients: A Meta-analysis SO JOURNAL OF CLINICAL SLEEP MEDICINE LA English DT Article DE Stroke prevention; all cerebrovascular disease/strok; sleep apne; prevalence studies; screening in epidemiology ID POSITIVE AIRWAY PRESSURE; ACUTE ISCHEMIC-STROKE; 1ST-EVER STROKE; RISK-FACTORS; FOLLOW-UP; PREVALENCE; ASSOCIATION; EVOLUTION; DIAGNOSIS; DISEASE AB Study Objectives: To determine the frequency of sleep disordered breathing (SDB) in ischemic and hemorrhagic stroke and transient ischemic attack (TIA) patients by meta-analysis Methods: A systematic literature search using Medline. EM-BASE and CINAHL and a manual review of references through December 2008 was conducted using specific search terms The frequency of SDB stratified by apnea hypopnea index (AHI) was extracted by the author Weighted averages using a random-effects model are reported with 95% confidence intervals Results: Twenty-nine articles evaluating patients with auto-CPAP, limited-channel sleep study, or full polysomnography were included in this study In meta-analysis of 2,343 ischemic or hemorrhagic stroke and TIA patients, the frequency of SDB with AHI > 5 was 72% and with AHI > 20 was 38% Only 7% of the SDB was primarily central apnea There was no significant difference in SOB prevalence by event type, timing after stroke, or type of monitoring Males had a higher percentage of SDB (AHI > 10) than females (65% compared to 48% p = 0 001) Patients with recurrent strokes had a higher percentage of SDB (AHI > 10) than initial strokes (74% compared to 57% p = 0 013) Patients with unknown etiology of stroke had a higher and cardioembolic etiology a lower percentage of SDB than other etiologies Conclusions: SDB is very common in stroke patients irrespective of type of stroke or timing after stroke and is typically obstructive in nature. Since clinical history alone does not identify many patients with SDB, sleep studies should be considered in all stroke and TIA patients C1 [Johnson, Karin G.] Baystate Med Ctr, Dept Neurol, Springfield, MA 01199 USA. [Johnson, Douglas C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Johnson, KG (reprint author), Baystate Med Ctr, Dept Neurol, 3300 Main St,Suite 3C, Springfield, MA 01199 USA. NR 40 TC 91 Z9 99 U1 0 U2 6 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 1550-9389 J9 J CLIN SLEEP MED JI J. Clin. Sleep Med. PD APR 15 PY 2010 VL 6 IS 2 BP 131 EP 137 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 584XV UT WOS:000276788500004 PM 20411688 ER PT J AU Drummond, F Doelken, P Ahmed, QA Gilbert, GE Strange, C Herpel, L Frye, MD AF Drummond, Fitzgerald Doelken, Peter Ahmed, Qanta A. Gilbert, Gregory E. Strange, Charlie Herpel, Laura Frye, Michael D. TI Empiric Auto-Titrating CPAP in People with Suspected Obstructive Sleep Apnea SO JOURNAL OF CLINICAL SLEEP MEDICINE LA English DT Article DE Auto-CPAP; OSAS; OSA; obstructive sleep apnea; Epworth sleepiness Scale; Functional Outcomes of Sleep Questionnaire ID POSITIVE AIRWAY PRESSURE; INDEPENDENT RISK-FACTOR; APNEA/HYPOPNEA SYNDROME; PRACTICE PARAMETERS; DAYTIME SLEEPINESS; HYPOPNEA SYNDROME; UNITED-STATES; OLDER-ADULTS; MORTALITY; TRIAL AB Objective: Efficient diagnosis and treatment of obstructive sleep apnea (OSA) can be difficult because of time delays imposed by clinic visits and serial overnight polysomnography. In some cases, it may be desirable to initiate treatment for suspected OSA prior to polysomnography Our objective was to compare the improvement of daytime sleepiness and sleep-related quality of life of patients with high clinical likelihood of having OSA who were randomly assigned to receive empiric auto-titrating continuous positive airway pressure (CPAP) while awaiting polysomnogram versus current usual care. Methods: Serial patients referred for overnight polysomnography who had high clinical likelihood of having OSA were randomly assigned to usual care or immediate initiation of auto-titrating CPAP. Epworth Sleepiness Scale (ESS) scores and the Functional Outcomes of Sleep Questionnaire (FOSQ) scores were obtained at baseline, 1 month after randomization, and again after initiation of fixed CPAP in control subjects and after the sleep study in auto-CPAP patients Results: One hundred nine patients were randomized. Baseline demographics, daytime sleepiness, and sleep-related quality of life scores were similar between groups One-month ESS and FOSQ scores were improved in the group empirically treated with auto-titrating CPAP ESS scores improved in the first month by a mean of -3 2 (confidence interval -1 6 to -48, p < 0.001) and FOSQ scores improved by a mean of 1 5, (confidence interval 0 5 to 2 7, p = 0 02), whereas scores in the usual-care group did not change (p = NS) Following therapy directed by overnight polysomnography in the control group, there were no differences in ESS or FOSQ between the groups No adverse events were observed Conclusion: Empiric auto-CPAP resulted in symptomatic improvement of daytime sleepiness and sleep-related quality of life in a cohort of patients awaiting polysomnography who had a high pretest probability of having OSA. Additional studies are needed to evaluate the applicability of empiric treatment to other populations C1 [Frye, Michael D.] Ralph H Johnson VA Med Ctr, Pulm Sect, Med Specialties Serv, Div Pulm Crit Care Allergy & Sleep Med, Charleston, SC 29425 USA. [Gilbert, Gregory E.] Med Univ S Carolina, Dept Biometry Bioinformat & Epidemiol, Charleston, SC 29425 USA. RP Frye, MD (reprint author), Ralph H Johnson VA Med Ctr, Pulm Sect, Med Specialties Serv, Div Pulm Crit Care Allergy & Sleep Med, Charleston, SC 29425 USA. RI Gilbert, Gregory/C-7735-2016; OI Gilbert, Gregory/0000-0003-0879-5496; Strange, Charlie/0000-0002-8109-8067 NR 42 TC 7 Z9 7 U1 0 U2 2 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 1550-9389 J9 J CLIN SLEEP MED JI J. Clin. Sleep Med. PD APR 15 PY 2010 VL 6 IS 2 BP 140 EP 145 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 584XV UT WOS:000276788500006 PM 20411690 ER PT J AU Chenine, AL Siddappa, NB Kramer, VG Sciaranghella, G Rasmussen, RA Lee, SJ Santosuosso, M Poznansky, MC Velu, V Amara, RR Souder, C Anderson, DC Villinger, F Else, JG Novembre, FJ Strobert, E O'Neil, SP Secor, WE Ruprecht, RM AF Chenine, Agnes L. Siddappa, Nagadenahalli B. Kramer, Victor G. Sciaranghella, Gaia Rasmussen, Robert A. Lee, Sandra J. Santosuosso, Michael Poznansky, Mark C. Velu, Vijayakumar Amara, Rama R. Souder, Chris Anderson, Daniel C. Villinger, Francois Else, James G. Novembre, Francis J. Strobert, Elizabeth O'Neil, Shawn P. Secor, W. Evan Ruprecht, Ruth M. TI Relative Transmissibility of an R5 Clade C Simian-Human Immunodeficiency Virus Across Different Mucosae in Macaques Parallels the Relative Risks of Sexual HIV-1 Transmission in Humans via Different Routes SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID T-CELL DEPLETION; RHESUS MACAQUES; VAGINAL TRANSMISSION; COITAL ACT; FREE SIV; INFECTION; AIDS; SUSCEPTIBILITY; DISSEMINATION; EXPOSURE AB Background. Worldwide, similar to 90% of all human immunodeficiency virus (HIV) transmissions occur mucosally; almost all involve R5 strains. Risks of sexual HIV acquisition are highest for rectal, then vaginal, and finally oral exposures. Methods. Mucosal lacerations may affect the rank order of susceptibility to HIV but cannot be assessed in humans. We measured relative virus transmissibility across intact mucosae in macaques using a single stock of SHIV-1157ipd3N4, a simian-human immunodeficiency virus encoding a primary R5 HIV clade C env (SHIV-C). Results. The penetrability of rhesus macaque mucosae differed significantly, with rectal challenge requiring the least virus, followed by vaginal and then oral routes (P = 0.31, oral vs vaginal; P < .001 rectal vs vaginal). These findings imply that intrinsic mucosal properties are responsible for the differential mucosal permeability. The latter paralleled the rank order reported for humans, with relative risk estimates within the range of epidemiological human studies. To test whether inflammation facilitates virus transmission - as predicted from human studies we established a macaque model of localized buccal inflammation. Systemic infection occurred across inflamed but not normal buccal mucosa. Conclusion. Our primate data recapitulate virus transmission risks observed in humans, thus establishing R5 SHIV-1157ipd3N4 in macaques as a robust model system to study cofactors involved in human mucosal HIV transmission and its prevention. C1 [Chenine, Agnes L.; Siddappa, Nagadenahalli B.; Kramer, Victor G.; Sciaranghella, Gaia; Rasmussen, Robert A.; Ruprecht, Ruth M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Chenine, Agnes L.; Siddappa, Nagadenahalli B.; Sciaranghella, Gaia; Rasmussen, Robert A.; Santosuosso, Michael; Poznansky, Mark C.; O'Neil, Shawn P.; Ruprecht, Ruth M.] Harvard Univ, Sch Med, Boston, MA USA. [Lee, Sandra J.] Dept Biostat & Computat Biol, Boston, MA USA. [Santosuosso, Michael; Poznansky, Mark C.] Massachusetts Gen Hosp, Partners AIDS Res Ctr & Infect Dis Med, Boston, MA 02114 USA. [O'Neil, Shawn P.] New England Reg Primate Res Ctr, Southborough, MA 01772 USA. [Velu, Vijayakumar; Amara, Rama R.; Souder, Chris; Anderson, Daniel C.; Villinger, Francois; Else, James G.; Novembre, Francis J.; Strobert, Elizabeth] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. [Secor, W. Evan] Ctr Dis Control & Prevent, Div Parasit Dis, Atlanta, GA USA. RP Ruprecht, RM (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM ruth_ruprecht@dfci.harvard.edu OI Byrareddy, Siddappa /0000-0002-7423-1763; Velu, Vijayakumar/0000-0003-4238-1924 FU NCRR NIH HHS [RR-00165, P51 RR000165]; NIAID NIH HHS [P01 AI048240, P01 AI048240-08, R56 AI062515, R56 AI062515-01A1]; NIDCR NIH HHS [R01 DE012937, R01 DE012937-05, R01 DE016013, R01 DE016013-04] NR 50 TC 36 Z9 38 U1 0 U2 5 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR 15 PY 2010 VL 201 IS 8 BP 1155 EP 1163 DI 10.1086/651274 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 568AJ UT WOS:000275493400008 PM 20214475 ER PT J AU Santosuosso, M Righi, E Leblanc, PR Poznansky, MC AF Santosuosso, Michael Righi, Elda Leblanc, Pierre R. Poznansky, Mark C. TI How Much Gp120 Is There? Reply SO JOURNAL OF INFECTIOUS DISEASES LA English DT Letter ID T-CELL DEPLETION; GASTROINTESTINAL-TRACT; ENVELOPE PROTEIN; HIV-1 INFECTION; INDIVIDUALS; REPLICATION C1 [Santosuosso, Michael; Righi, Elda; Leblanc, Pierre R.; Poznansky, Mark C.] Massachusetts Gen Hosp, Div Infect Dis Med, Charlestown, MA USA. [Righi, Elda] Univ Genoa, Dept Infect Dis, San Martino Hosp, Genoa, Italy. RP Poznansky, MC (reprint author), Massachusetts Gen Hosp E, Bldg 149,Rm 5234, Charlestown, MA 02129 USA. EM mpoznansky@partners.org NR 13 TC 0 Z9 0 U1 1 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR 15 PY 2010 VL 201 IS 8 BP 1274 EP 1275 DI 10.1086/651435 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 568AJ UT WOS:000275493400028 ER PT J AU Li, K Fu, KY Light, AR Mao, JR AF Li, Kai Fu, Kai-Yuan Light, Alan R. Mao, Jianren TI Systemic minocycline differentially influences changes in spinal microglial markers following formalin-induced nociception SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE Microglia; OX-42; MHC class I; p38 MAPK; Minocycline; Formalin ID ACTIVATED PROTEIN-KINASE; PERIPHERAL-NERVE INJURY; P38 MAPK; NEUROPATHIC PAIN; CYTOKINE EXPRESSION; INFLAMMATORY PAIN; SENSORY NEURONS; DORSAL-HORN; RAT; INJECTION AB In the present study, intraperitoneal administration of minocycline attenuated enhancing nociceptive behaviors in those rats receiving dual formalin injections (5% formalin followed at 7 days later by 1% formalin). The minocycline treatment did not prevent the increase in OX-42 and MHC class I labeling and morphological changes, but significantly attenuated upregulation of phospho-p38 in activated microglia. These results suggest that the later days of microglial activation with upregulated immune markers in the spinal cord contributes to enhancing long-term pain response by a pathway of p38 activation in microglia. (C) 2010 Elsevier B.V. All rights reserved. C1 [Li, Kai; Fu, Kai-Yuan] Peking Univ, Sch Stomatol, Ctr TMD & Orofacial Pain, Beijing 100081, Peoples R China. [Li, Kai; Fu, Kai-Yuan] Hosp Stomatol, Beijing 100081, Peoples R China. [Light, Alan R.] Univ Utah, Dept Anesthesiol, Salt Lake City, UT 84132 USA. [Mao, Jianren] Harvard Univ, Sch Med, Massachusetts Gen Hosp,WACC 324, MGH Ctr Translat Pain Res,Dept Anesthesia & Crit, Boston, MA 02114 USA. RP Fu, KY (reprint author), Peking Univ, Sch Stomatol, Ctr TMD & Orofacial Pain, Zhong Guan Cun S Ave 22, Beijing 100081, Peoples R China. EM kqkyfu@bjmu.edu.cn OI Fu, Kai-Yuan/0000-0001-7049-9888 FU Program for New Century Excellent Talents in University; National Natural Science Foundation [30973337]; US PHS RO1 [DE18214, DE18538] FX This study was supported by Program for New Century Excellent Talents in University and the National Natural Science Foundation (30973337) (K.Y. Fu) and US PHS RO1 grants DE18214 and DE18538 (J.M.). NR 43 TC 4 Z9 4 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD APR 15 PY 2010 VL 221 IS 1-2 BP 25 EP 31 DI 10.1016/j.jneuroim.2010.02.003 PG 7 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 609JS UT WOS:000278653100004 PM 20202692 ER PT J AU Hilsabeck, RC Anstead, GM Webb, AL Hoyumpa, A Ingmundson, P Holliday, S Zhang, Q Casas, AM Jovel, M Stern, SL AF Hilsabeck, Robin C. Anstead, Gregory M. Webb, Amy L. Hoyumpa, Anastasio Ingmundson, Paul Holliday, Steve Zhang, Qiong Casas, Angela M. Jovel, Marci Stern, Stephen L. TI Cognitive efficiency is associated with endogenous cytokine levels in patients with chronic hepatitis C SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE Hepatitis C; Cytokines; Cognitive dysfunction; Interferon-alpha; Immune system; ANAM ID AICARDI-GOUTIERES-SYNDROME; SYSTEMIC-LUPUS-ERYTHEMATOSUS; CENTRAL-NERVOUS-SYSTEM; NECROSIS-FACTOR-ALPHA; AIDS DEMENTIA COMPLEX; INTERFERON-ALPHA; VIRUS-INFECTION; INFLAMMATORY MARKERS; QUANTITATIVE-EEG; IFN-ALPHA AB The etiology of cognitive dysfunction in chronic hepatitis C (CHC) infection is unknown. Among the possibilities is cytokine activation, which has been associated with cognitive dysfunction in other chronic conditions. The purpose of this study was to investigate the relationship between endogenous IFN-alpha, IL-6, and INF-alpha and cognitive functioning in CHC patients. Seventy-eight veterans with CHC underwent cognitive testing and measurement of serum cytokines. In patients with detectable IFN-alpha, higher levels of IL-6 and INF-alpha were related to poorer cognitive functioning. Findings suggest CHC patients with immune responses characterized by elevated IFN-alpha may be at risk for cognitive difficulties. Published by Elsevier B.V. C1 [Hilsabeck, Robin C.; Anstead, Gregory M.; Webb, Amy L.; Ingmundson, Paul; Holliday, Steve; Zhang, Qiong; Casas, Angela M.; Jovel, Marci; Stern, Stephen L.] S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Hilsabeck, Robin C.; Holliday, Steve; Stern, Stephen L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Anstead, Gregory M.; Webb, Amy L.; Hoyumpa, Anastasio] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. RP Hilsabeck, RC (reprint author), S Texas Vet Hlth Care Syst, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM Hilsabeck@uthscsa.edu FU Research and Development Office; Frederic C. Bartter General Clinical Research Center; Veterans Health Administration [VISN-17]; National Institutes of Health [K23 NS051244]; National Center for Research Resources [UL 1RR025767, M01-RR-01346] FX Our deepest thanks go to the incredibly knowledgeable staff of the Veterans Evidence Based Research Dissemination and Implementation Center (VERDICT) at Audie L Murphy VA Hospital. In particular, we would like to thank Polly Noel Hitchcock for help with study design, Chen-Pin Wang for consultation about appropriate statistical analyses, and Judith Patterson for database set-up. We gratefully acknowledge the support of staff in the Research and Development Office and the Frederic C. Bartter General Clinical Research Center, as well as the following colleagues for help with data collection and management (in alphabetical order): Olga Ali, Anna Dematatis, Stephanie Garcia, Geoffrey Hutchinson, Shawn Johnson, Shuko Lee, Kenneth Major, Emma Mata-Galan, Isela Poy, and Rebecca Stein. The authors would also like to thank Sunil Ahuja and his research group for their very helpful insights in interpreting the cytokine data and Robert A. Clark for helpful comments on the manuscript. Our sincerest appreciation goes to the veterans who volunteered to participate in this study.; This material is the result of work supported with resources and the use of facilities at the South Texas Veterans Health Care System and University of Texas Health Sciences Center at San Antonio. The work was supported by grants from VISN-17 of the Veterans Health Administration to SLS and National Institutes of Health (K23 NS051244) to RCH. In addition, this project was supported by Award Numbers UL 1RR025767 and M01-RR-01346 from the National Center for Research Resources. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Veterans Health Administration or the National Institutes of Health. NR 94 TC 15 Z9 15 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD APR 15 PY 2010 VL 221 IS 1-2 BP 53 EP 61 DI 10.1016/j.jneuroim.2010.01.017 PG 9 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 609JS UT WOS:000278653100008 PM 20181398 ER PT J AU Wade, HE Kobayashi, S Eaton, ML Jansen, MS Lobenhofer, EK Lupien, M Geistlinger, TR Zhu, WC Nevins, JR Brown, M Otteson, DC McDonnell, DP AF Wade, Hilary E. Kobayashi, Sakiko Eaton, Matthew L. Jansen, Michelle S. Lobenhofer, Edward K. Lupien, Mathieu Geistlinger, Timothy R. Zhu, Wencheng Nevins, Joseph R. Brown, Myles Otteson, Deborah C. McDonnell, Donald P. TI Multimodal Regulation of E2F1 Gene Expression by Progestins SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CELL-CYCLE PROGRESSION; BREAST-CANCER CELLS; HUMAN PROGESTERONE-RECEPTORS; ESTROGEN-RECEPTOR; TRANSCRIPTIONAL REGULATOR; RETINOBLASTOMA PROTEIN; FUNCTIONAL DOMAINS; ACTIVATION; PROLIFERATION; KINASES AB An analysis of mRNA expression in T47D breast cancer cells treated with the synthetic progestin R5020 revealed a subset of progesterone receptor (PR) target genes that are enriched for E2F binding sites. Following up on this observation, we determined that PR-B acts in both direct and indirect manners to positively upregulate E2F1 expression in T47D cells. The direct effects of PR on E2F1 expression were confirmed by chromatin immunoprecipitation (ChIP) analysis, which indicated that the agonist-bound receptor was recruited to several enhancer elements proximal to the E2F1 transcript. However, we also noted that cycloheximide partially inhibits R5020 induction of E2F1 expression, indicating that the ligand-dependent actions of PR on this gene may involve additional indirect regulatory pathways. In support of this hypothesis, we demonstrated that treatment with R5020 significantly increases both hyperphosphorylation of Rb and recruitment of E2F1 to its own promoter, thus activating a positive feedback loop that further amplifies its transcription. Furthermore, we established that PR-mediated induction of Kruppel-like factor 15 (KLF15), which can bind to GC-rich DNA within the E2F1 promoter, is required for maximal induction of E2F1 expression by progestins. Taken together, these results suggest a new paradigm for multimodal regulation of target gene expression by PR. C1 [Wade, Hilary E.; Kobayashi, Sakiko; Eaton, Matthew L.; Jansen, Michelle S.; McDonnell, Donald P.] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA. [Lobenhofer, Edward K.] NIEHS, Natl Ctr Toxicogenom, Res Triangle Pk, NC 27709 USA. [Lupien, Mathieu; Geistlinger, Timothy R.; Brown, Myles] Dana Farber Canc Inst, Div Mol & Cellular Oncol, Dept Med Oncol, Boston, MA 02115 USA. [Zhu, Wencheng; Nevins, Joseph R.] Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA. [Otteson, Deborah C.] Univ Houston, Coll Optometry, Houston, TX 77204 USA. RP McDonnell, DP (reprint author), Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Box 3813, Durham, NC 27710 USA. EM donald.mcdonnell@duke.edu RI Eaton, Matthew/C-4408-2011; OI Brown, Myles/0000-0002-8213-1658; Otteson, Deborah/0000-0001-6093-6837 FU DOD [W81XWH-06-1-0745]; NIH [DK048807, EY13499, DK074967, CA089393, CA080111] FX This work was supported by DOD grant W81XWH-06-1-0745 (H. E. W.) and by NIH grants DK048807 (D. P. M.); EY13499 (D.C.O.); and DK074967, CA089393, and CA080111 (M. B.). NR 39 TC 18 Z9 18 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR 15 PY 2010 VL 30 IS 8 BP 1866 EP 1877 DI 10.1128/MCB.01060-09 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 574HV UT WOS:000275980900001 PM 20123965 ER PT J AU Chung, KA Lobb, BM Nutt, JG McNames, J Horak, F AF Chung, Kathryn A. Lobb, Brenna M. Nutt, John G. McNames, James Horak, Fay TI Objective Measurement of Dyskinesia in Parkinson's Disease using a Force Plate SO MOVEMENT DISORDERS LA English DT Article DE dyskinesia; objective measurements; Parkinson's; force plate ID LEVODOPA-INDUCED DYSKINESIAS; DEEP BRAIN-STIMULATION; RATING-SCALE; MOTOR; RELIABILITY; TASKS; LIFE AB Clinical investigation of levodopa-induced dyskinesia (LID) in Parkinson's disease (PD) is limited because of lack of objective measurements and no consensus on use of a standard measuring tool. Currently, clinical trials use subject-completed diaries of dyskinesia throughout the day or investigator-administered clinical rating scales. An objective and valid method of measuring LID would reduce bias, variability, and decrease the time and number needed in trials of potential anti-dyskinetic agents. We have investigated using a force plate under standing subjects, which records movement of the center of pressure (CoP) to quantify LID over a levodopa (L-dopa) cycle. Twenty-two PD subjects (15 with LID, 7 without LID) admitted to an inpatient research facility had their PD meds withheld overnight, followed by a 2 hours intravenous L-dopa infusion the next day. The root mean squared of the velocity in the anterior-posterior direction (RMSV) derived from an analysis of the CoP, and, the modified Abnormal Involuntary Movement Scale (mAIMS) were performed repeatedly for 6 hours, initially as subjects were OFF before the infusion, through infusion until OFF again. There was a high correlation between the area under the curve (AUC) of the mAIMS and the RMSV within and between subjects. As a measure of LID, RMSV had excellent validity and reliability between subjects, and using a force plate was feasible. Sensitivity to changes in LID was initially demonstrated but should be repeated. Thus. CoP recordings on a force plate can objectively quantify LID in PD and may be very useful in clinical trials or other investigations of dyskinesia. (C) 2010 Movement Disorder Society C1 [Chung, Kathryn A.; Nutt, John G.; Horak, Fay] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Lobb, Brenna M.] Portland VA Med Ctr, Portland, OR USA. [McNames, James] Portland State Univ, Dept Elect & Comp Engn, Portland, OR 97207 USA. RP Chung, KA (reprint author), OP 32,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM chungka@ohsu.edu FU US Public Health Service [ULIRR024140-02]; NIH [R01-NS21062]; National Institutes on Aging [AG006457]; Intel Corporation; Schering-Plough; Novartis Inc. FX Supported by a Veteran's Administration Career Development Award, US Public Health Service Grant ULIRR024140-02, NIH R01-NS21062, National Institutes on Aging AG006457, and a grant from ,.; Dr. Nutt has received grants/research from Schering-Plough, speaking fees from Novartis Inc., and has served as a consultant for XenoPort Inc., Impax Laboratories. Neurogen Inc., and Synosia. NR 21 TC 18 Z9 20 U1 1 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD APR 15 PY 2010 VL 25 IS 5 BP 602 EP 608 DI 10.1002/mds.22856 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 590TJ UT WOS:000277250600012 PM 20213818 ER PT J AU Hudson, TJ Anderson, W Aretz, A Barker, AD Bell, C Bernabe, RR Bhan, MK Calvo, F Eerola, I Gerhard, DS Guttmacher, A Guyer, M Hemsley, FM Jennings, JL Kerr, D Klatt, P Kolar, P Kusuda, J Lane, DP Laplace, F Lu, YY Nettekoven, G Ozenberger, B Peterson, J Rao, TS Remacle, J Schafer, AJ Shibata, T Stratton, MR Vockley, JG Watanabe, K Yang, HM Yuen, MMF Knoppers, M Bobrow, M Cambon-Thomsen, A Dressler, LG Dyke, SOM Joly, Y Kato, K Kennedy, KL Nicolas, P Parker, MJ Rial-Sebbag, E Romeo-Casabona, CM Shaw, KM Wallace, S Wiesner, GL Zeps, N Lichter, P Biankin, AV Chabannon, C Chin, L Clement, B de Alava, E Degos, F Ferguson, ML Geary, P Hayes, DN Johns, AL Nakagawa, H Penny, R Piris, MA Sarin, R Scarpa, A Shibata, T van de Vijver, M Futreal, PA Aburatani, H Bayes, M Bowtell, DDL Campbell, PJ Estivill, X Grimmond, SM Gut, I Hirst, M Lopez-Otin, C Majumder, P Marra, M Nakagawa, H Ning, ZM Puente, XS Ruan, YJ Shibata, T Stratton, MR Stunnenberg, HG Swerdlow, H Velculescu, VE Wilson, RK Xue, HH Yang, L Spellman, PT Bader, GD Boutros, PC Campbell, PJ Flicek, P Getz, G Guigo, R Guo, GW Haussler, D Heath, S Hubbard, TJ Jiang, T Jones, SM Li, QB Lopez-Bigas, N Luo, RB Pearson, JV Puente, XS Quesada, V Raphael, BJ Sander, C Shibata, T Speed, TP Stuart, JM Teague, JW Totoki, Y Tsunoda, T Valencia, A Wheeler, DA Wu, HL Zhao, SC Zhou, GY Stein, LD Guigo, R Hubbard, TJ Joly, Y Jones, SM Lathrop, M Lopez-Bigas, N Ouellette, BFF Spellman, PT Teague, JW Thomas, G Valencia, A Yoshida, T Kennedy, KL Axton, M Dyke, SOM Futreal, PA Gunter, C Guyer, M McPherson, JD Miller, LJ Ozenberger, B Kasprzyk, A Zhang, JJ Haider, SA Wang, JX Yung, CK Cross, A Liang, Y Gnaneshan, S Guberman, J Hsu, J Bobrow, M Chalmers, DRC Hasel, KW Joly, Y Kaan, TSH Kennedy, KL Knoppers, BM Lowrance, WW Masui, T Nicolas, P Rial-Sebbag, E Rodriguez, LL Vergely, C Yoshida, T Grimmond, SM Biankin, AV Bowtell, DDL Cloonan, N Defazio, A Eshleman, JR Etemadmoghadam, D Gardiner, BA Kench, JG Scarpa, A Sutherland, RL Tempero, MA Waddell, NJ Wilson, PJ Gallinger, S Tsao, MS Shaw, PA Petersen, GM Mukhopadhyay, D Chin, L DePinho, RA Thayer, S Muthuswamy, L Shazand, K Beck, T Sam, M Timms, L Ballin, V Lu, YY Ji, JF Zhang, XQ Chen, F Hu, XD Zhou, GY Yang, Q Tian, G Zhang, LH Xing, XF Li, XH Zhu, ZG Yu, YY Yu, J Yang, HM Lathrop, M Tost, J Brennan, P Holcatova, I Zaridze, D Brazma, A Egevad, L Prokhortchouk, E Banks, RE Uhlen, M Cambon-Thomsen, A Viksna, J Ponten, F Skryabin, K Stratton, MR Futreal, PA Birney, E Borg, A Borresen-Dale, AL Caldas, C Foekens, JA Martin, S Reis-Filho, JS Richardson, AL Sotiriou, C Stunnenberg, HG Thomas, G van de Vijver, M van't Veer, L Birnbaum, D Blanche, H Boucher, P Boyault, S Chabannon, C Gut, I Masson-Jacquemier, JD Lathrop, M Pauporte, I Pivot, X Vincent-Salomon, A Tabone, E Theillet, C Thomas, G Tost, J Treilleux, I Bioulac-Sage, P Clement, B Decaens, T Degos, F Franco, D Gut, I Gut, M Heath, S Lathrop, M Samuel, D Thomas, G Zucman-Rossi, J Lichter, P Eils, R Brors, B Korbel, JO Korshunov, A Landgraf, P Lehrach, H Pfister, S Radlwimmer, B Reifenberger, G Taylor, MD von Kalle, C Majumder, PP Sarin, R Scarpa, A Pederzoli, P Lawlor, RT Delledonne, M Bardelli, A Biankin, AV Grimmond, SM Gress, T Klimstra, D Zamboni, G Shibata, T Nakamura, Y Nakagawa, H Kusuda, J Tsunoda, T Miyano, S Aburatani, H Kato, K Fujimoto, A Yoshida, T Campo, E Lopez-Otin, C Estivill, X Guigo, R de Sanjose, S Piris, MA Montserrat, E Gonzalez-Diaz, M Puente, XS Jares, P Valencia, A Himmelbaue, H Quesada, V Bea, S Stratton, MR Futreal, PA Campbell, PJ Vincent-Salomon, A Richardson, AL Reis-Filho, JS van de Vijver, M Thomas, G Masson-Jacquemier, JD Aparicio, S Borg, A Borresen-Dale, AL Caldas, C Foekens, JA Stunnenberg, HG van't Veer, L Easton, DF Spellman, PT Martin, S Chin, L Collins, FS Compton, CC Ferguson, ML Getz, G Gunter, C Guyer, M Hayes, DN Lander, ES Ozenberger, B Penny, R Peterson, J Sander, C Speed, TP Spellman, PT Wheeler, DA Wilson, RK Chin, L Knoppers, BM Lander, ES Lichter, P Stratton, MR Bobrow, M Burke, W Collins, FS DePinho, RA Easton, DF Futreal, PA Green, AR Guyer, M Hamilton, SR Hubbard, TJ Kallioniemi, OP Kennedy, KL Ley, TJ Liu, ET Lu, YY Majumder, P Marra, M Ozenberger, B Peterson, J Schafer, AJ Spellman, PT Stunnenberg, HG Wainwright, BJ Wilson, RK Yang, HM AF Hudson, Thomas J. Anderson, Warwick Aretz, Axel Barker, Anna D. Bell, Cindy Bernabe, Rosa R. Bhan, M. K. Calvo, Fabien Eerola, Iiro Gerhard, Daniela S. Guttmacher, Alan Guyer, Mark Hemsley, Fiona M. Jennings, Jennifer L. Kerr, David Klatt, Peter Kolar, Patrik Kusuda, Jun Lane, David P. Laplace, Frank Lu, Youyong Nettekoven, Gerd Ozenberger, Brad Peterson, Jane Rao, T. S. Remacle, Jacques Schafer, Alan J. Shibata, Tatsuhiro Stratton, Michael R. Vockley, Joseph G. Watanabe, Koichi Yang, Huanming Yuen, Matthew M. F. Knoppers, M. Bobrow, Martin Cambon-Thomsen, Anne Dressler, Lynn G. Dyke, Stephanie O. M. Joly, Yann Kato, Kazuto Kennedy, Karen L. Nicolas, Pilar Parker, Michael J. Rial-Sebbag, Emmanuelle Romeo-Casabona, Carlos M. Shaw, Kenna M. Wallace, Susan Wiesner, Georgia L. Zeps, Nikolajs Lichter, Peter Biankin, Andrew V. Chabannon, Christian Chin, Lynda Clement, Bruno de Alava, Enrique Degos, Francoise Ferguson, Martin L. Geary, Peter Hayes, D. Neil Johns, Amber L. Nakagawa, Hidewaki Penny, Robert Piris, Miguel A. Sarin, Rajiv Scarpa, Aldo Shibata, Tatsuhiro van de Vijver, Marc Futreal, P. Andrew Aburatani, Hiroyuki Bayes, Monica Bowtell, David D. L. Campbell, Peter J. Estivill, Xavier Grimmond, Sean M. Gut, Ivo Hirst, Martin Lopez-Otin, Carlos Majumder, Partha Marra, Marco Nakagawa, Hidewaki Ning, Zemin Puente, Xose S. Ruan, Yijun Shibata, Tatsuhiro Stratton, Michael R. Stunnenberg, Hendrik G. Swerdlow, Harold Velculescu, Victor E. Wilson, Richard K. Xue, Hong H. Yang, Liu Spellman, Paul T. Bader, Gary D. Boutros, Paul C. Campbell, Peter J. Flicek, Paul Getz, Gad Guigo, Roderic Guo, Guangwu Haussler, David Heath, Simon Hubbard, Tim J. Jiang, Tao Jones, Steven M. Li, Qibin Lopez-Bigas, Nuria Luo, Ruibang Pearson, John V. Puente, Xose S. Quesada, Victor Raphael, Benjamin J. Sander, Chris Shibata, Tatsuhiro Speed, Terence P. Stuart, Joshua M. Teague, Jon W. Totoki, Yasushi Tsunoda, Tatsuhiko Valencia, Alfonso Wheeler, David A. Wu, Honglong Zhao, Shancen Zhou, Guangyu Stein, Lincoln D. Guigo, Roderic Hubbard, Tim J. Joly, Yann Jones, Steven M. Lathrop, Mark Lopez-Bigas, Nuria Ouellette, B. F. Francis Spellman, Paul T. Teague, Jon W. Thomas, Gilles Valencia, Alfonso Yoshida, Teruhiko Kennedy, Karen L. Axton, Myles Dyke, Stephanie O. M. Futreal, P. Andrew Gunter, Chris Guyer, Mark McPherson, John D. Miller, Linda J. Ozenberger, Brad Kasprzyk, Arek Zhang, Junjun Haider, Syed A. Wang, Jianxin Yung, Christina K. Cross, Anthony Liang, Yong Gnaneshan, Saravanamuttu Guberman, Jonathan Hsu, Jack Bobrow, Martin Chalmers, Don R. C. Hasel, Karl W. Joly, Yann Kaan, Terry S. H. Kennedy, Karen L. Knoppers, Bartha M. Lowrance, William W. Masui, Tohru Nicolas, Pilar Rial-Sebbag, Emmanuelle Rodriguez, Laura Lyman Vergely, Catherine Yoshida, Teruhiko Grimmond, Sean M. Biankin, Andrew V. Bowtell, David D. L. Cloonan, Nicole Defazio, Anna Eshleman, James R. Etemadmoghadam, Dariush Gardiner, Brooke A. Kench, James G. Scarpa, Aldo Sutherland, Robert L. Tempero, Margaret A. Waddell, Nicola J. Wilson, Peter J. Gallinger, Steve Tsao, Ming-Sound Shaw, Patricia A. Petersen, Gloria M. Mukhopadhyay, Debabrata Chin, Lynda DePinho, Ronald A. Thayer, Sarah Muthuswamy, Lakshmi Shazand, Kamran Beck, Timothy Sam, Michelle Timms, Lee Ballin, Vanessa Lu, Youyong Ji, Jiafu Zhang, Xiuqing Chen, Feng Hu, Xueda Zhou, Guangyu Yang, Qi Tian, Geng Zhang, Lianhai Xing, Xiaofang Li, Xianghong Zhu, Zhenggang Yu, Yingyan Yu, Jun Yang, Huanming Lathrop, Mark Tost, Joerg Brennan, Paul Holcatova, Ivana Zaridze, David Brazma, Alvis Egevad, Lars Prokhortchouk, Egor Banks, Rosamonde Elizabeth Uhlen, Mathias Cambon-Thomsen, Anne Viksna, Juris Ponten, Fredrik Skryabin, Konstantin Stratton, Michael R. Futreal, P. Andrew Birney, Ewan Borg, Ake Borresen-Dale, Anne-Lise Caldas, Carlos Foekens, John A. Martin, Sancha Reis-Filho, Jorge S. Richardson, Andrea L. Sotiriou, Christos Stunnenberg, Hendrik G. Thomas, Gilles van de Vijver, Marc van't Veer, Laura Birnbaum, Daniel Blanche, Helene Boucher, Pascal Boyault, Sandrine Chabannon, Christian Gut, Ivo Masson-Jacquemier, Jocelyne D. Lathrop, Mark Pauporte, Iris Pivot, Xavier Vincent-Salomon, Anne Tabone, Eric Theillet, Charles Thomas, Gilles Tost, Joerg Treilleux, Isabelle Bioulac-Sage, Paulette Clement, Bruno Decaens, Thomas Degos, Francoise Franco, Dominique Gut, Ivo Gut, Marta Heath, Simon Lathrop, Mark Samuel, Didier Thomas, Gilles Zucman-Rossi, Jessica Lichter, Peter Eils, Roland Brors, Benedikt Korbel, Jan O. Korshunov, Andrey Landgraf, Pablo Lehrach, Hans Pfister, Stefan Radlwimmer, Bernhard Reifenberger, Guido Taylor, Michael D. von Kalle, Christof Majumder, Partha P. Sarin, Rajiv Scarpa, Aldo Pederzoli, Paolo Lawlor, Rita T. Delledonne, Massimo Bardelli, Alberto Biankin, Andrew V. Grimmond, Sean M. Gress, Thomas Klimstra, David Zamboni, Giuseppe Shibata, Tatsuhiro Nakamura, Yusuke Nakagawa, Hidewaki Kusuda, Jun Tsunoda, Tatsuhiko Miyano, Satoru Aburatani, Hiroyuki Kato, Kazuto Fujimoto, Akihiro Yoshida, Teruhiko Campo, Elias Lopez-Otin, Carlos Estivill, Xavier Guigo, Roderic de Sanjose, Silvia Piris, Miguel A. Montserrat, Emili Gonzalez-Diaz, Marcos Puente, Xose S. Jares, Pedro Valencia, Alfonso Himmelbaue, Heinz Quesada, Victor Bea, Silvia Stratton, Michael R. Futreal, P. Andrew Campbell, Peter J. Vincent-Salomon, Anne Richardson, Andrea L. Reis-Filho, Jorge S. van de Vijver, Marc Thomas, Gilles Masson-Jacquemier, Jocelyne D. Aparicio, Samuel Borg, Ake Borresen-Dale, Anne-Lise Caldas, Carlos Foekens, John A. Stunnenberg, Hendrik G. van't Veer, Laura Easton, Douglas F. Spellman, Paul T. Martin, Sancha Chin, Lynda Collins, Francis S. Compton, Carolyn C. Ferguson, Martin L. Getz, Gad Gunter, Chris Guyer, Mark Hayes, D. Neil Lander, Eric S. Ozenberger, Brad Penny, Robert Peterson, Jane Sander, Chris Speed, Terence P. Spellman, Paul T. Wheeler, David A. Wilson, Richard K. Chin, Lynda Knoppers, Bartha M. Lander, Eric S. Lichter, Peter Stratton, Michael R. Bobrow, Martin Burke, Wylie Collins, Francis S. DePinho, Ronald A. Easton, Douglas F. Futreal, P. Andrew Green, Anthony R. Guyer, Mark Hamilton, Stanley R. Hubbard, Tim J. Kallioniemi, Olli P. Kennedy, Karen L. Ley, Timothy J. Liu, Edison T. Lu, Youyong Majumder, Partha Marra, Marco Ozenberger, Brad Peterson, Jane Schafer, Alan J. Spellman, Paul T. Stunnenberg, Hendrik G. Wainwright, Brandon J. Wilson, Richard K. Yang, Huanming CA Int Canc Genome Consortium TI International network of cancer genome projects SO NATURE LA English DT Article ID MYELOID-LEUKEMIA GENOME; SOMATIC MUTATIONS; BREAST-CANCER; GENE; PATHWAYS; LANDSCAPES; DATABASE AB The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies. C1 [Jennings, Jennifer L.; Boutros, Paul C.; Stein, Lincoln D.; Ouellette, B. F. Francis; McPherson, John D.; Kasprzyk, Arek; Zhang, Junjun; Wang, Jianxin; Yung, Christina K.; Cross, Anthony; Liang, Yong; Gnaneshan, Saravanamuttu; Guberman, Jonathan; Hsu, Jack; Muthuswamy, Lakshmi; Shazand, Kamran; Beck, Timothy; Sam, Michelle; Timms, Lee; Ballin, Vanessa] Ontario Inst Canc Res, Toronto, ON M5G 0A3, Canada. Univ Toronto, Dept Med Biophys, Toronto, ON M5S 1A1, Canada. Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A1, Canada. [Hudson, Thomas J.; Anderson, Warwick] Natl Hlth & Med Res Council, Canberra, ACT 2601, Australia. [Aretz, Axel] German Aerosp Ctr DLR, Project Management Agcy, D-53175 Bonn, Germany. [Barker, Anna D.; Gerhard, Daniela S.; Vockley, Joseph G.; Shaw, Kenna M.; Compton, Carolyn C.] NCI, US Natl Inst Hlth, Bethesda, MD 20892 USA. [Bell, Cindy; Hasel, Karl W.] Genome Canada, Ottawa, ON K2P 1P1, Canada. [Bernabe, Rosa R.; Klatt, Peter] Minist Sci & Innovat, Secretariat State Res, Madrid 28027, Spain. [Bhan, M. K.; Rao, T. S.] Govt India, Minist Sci & Technol, Dept Biotechnol, New Delhi 110003, India. [Calvo, Fabien; Chabannon, Christian; Boucher, Pascal; Pauporte, Iris] Natl Canc Inst, F-92513 Boulogne, France. [Eerola, Iiro; Kolar, Patrik; Remacle, Jacques] European Commiss, Hlth Res Directorate, Genom & Syst Biol Unit, B-1049 Brussels, Belgium. [Guttmacher, Alan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, US Natl Inst Hlth, Bethesda, MD 20892 USA. [Guyer, Mark; Ozenberger, Brad; Peterson, Jane; Rodriguez, Laura Lyman] NHGRI, US Natl Inst Hlth, Bethesda, MD 20892 USA. [Hemsley, Fiona M.; Lane, David P.] Canc Res UK, London WC2A 3PX, England. [Kerr, David] Qatar Fdn, Sidra Med & Res Ctr, Doha, Qatar. Univ Oxford, Dept Clin Pharmacol, Oxford OX2 6HE, England. [Kusuda, Jun; Masui, Tohru] Natl Inst Biomed Innovat, Osaka 5670085, Japan. [Laplace, Frank] Fed Minist Educ & Res, Div Mol Life Sci, D-11055 Berlin, Germany. [Lu, Youyong; Ji, Jiafu; Chen, Feng; Zhang, Lianhai; Xing, Xiaofang; Li, Xianghong] Peking Univ, Sch Oncol, Beijing Canc Inst & Hosp, Beijing 100142, Peoples R China. [Nettekoven, Gerd] German Canc Aid, D-53113 Bonn, Germany. [Schafer, Alan J.] Wellcome Trust Res Labs, London NW1 2BE, England. [Shibata, Tatsuhiro; Totoki, Yasushi; Yoshida, Teruhiko; Zaridze, David] Natl Canc Ctr, Chuo Ku, Tokyo 1040045, Japan. [Stratton, Michael R.; Dyke, Stephanie O. M.; Kennedy, Karen L.; Futreal, P. Andrew; Campbell, Peter J.; Ning, Zemin; Swerdlow, Harold; Hubbard, Tim J.; Teague, Jon W.; Martin, Sancha] Hinxton, Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. [Watanabe, Koichi] RIKEN, Yokohama Inst, Kanagawa, Japan. [Yang, Huanming; Guo, Guangwu; Jiang, Tao; Li, Qibin; Luo, Ruibang; Wu, Honglong; Zhao, Shancen; Zhou, Guangyu; Zhang, Xiuqing; Hu, Xueda; Yang, Qi; Tian, Geng] BGI Shenzhen, Shenzhen 518083, Guangdong, Peoples R China. [Yuen, Matthew M. F.] Hong Kong Univ Sci & Technol, Hong Kong, Hong Kong, Peoples R China. [Knoppers, M.; Joly, Yann; Wallace, Susan; Knoppers, Bartha M.] McGill Univ, Ctr Genom & Policy, Montreal, PQ H3A 1A4, Canada. [Knoppers, M.; Wallace, Susan] Genome Quebec Innovat Ctr, Montreal, PQ H3A 1A4, Canada. [Bobrow, Martin] Univ Cambridge, Cambridge Inst Med Res, Dept Med Genet, Cambridge CB2 0XY, England. [Cambon-Thomsen, Anne; Rial-Sebbag, Emmanuelle] Fac Med Toulouse, INSERM, U558, F-31073 Toulouse, France. [Dressler, Lynn G.] Univ N Carolina, Sch Pharm, Div Pharmaceut Outcomes & Policy, Inst Pharmacogen & Individualized Therapy, Chapel Hill, NC 27599 USA. [Kato, Kazuto] Kyoto Univ, Grad Sch Biostudies, Inst Integrated Cell Mat Sci, Inst Res Humanities, Kyoto 6068501, Japan. [Nicolas, Pilar; Romeo-Casabona, Carlos M.] Univ Deusto, Interuniv Chair Law & Human Genome, Bizkaia 48007, Spain. [Parker, Michael J.] Univ Oxford, Ethox Ctr, Oxford OX3 7LF, England. [Wiesner, Georgia L.] Case Western Reserve Univ, Dept Genet, Cleveland, OH 44106 USA. [Wiesner, Georgia L.] Univ Hosp Cleveland, Case Med Ctr, Ctr Human Genet, Cleveland, OH 44106 USA. St John God Pathol, Subiaco, WA 6008, Australia. Univ Western Australia, Sch Pathol & Lab Med, Nedlands, WA 6009, Australia. [Zeps, Nikolajs] Univ Western Australia, Sch Surg, Nedlands, WA 6009, Australia. [Lichter, Peter; Eils, Roland; Brors, Benedikt; Pfister, Stefan; Radlwimmer, Bernhard] German Canc Res Ctr, D-69120 Heidelberg, Germany. [Biankin, Andrew V.; Johns, Amber L.; Kench, James G.; Sutherland, Robert L.] Univ New S Wales, Garvan Inst Med Res, Sydney, NSW 2010, Australia. Bankstown Hosp, Dept Surg, Sydney, NSW 2200, Australia. [Birnbaum, Daniel; Chabannon, Christian; Masson-Jacquemier, Jocelyne D.] Inst J Paoli I Calmettes, F-13273 Marseille, France. [Chin, Lynda; DePinho, Ronald A.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA. [Chin, Lynda] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Clement, Bruno] INSERM, U991, F-35043 Rennes, France. [de Alava, Enrique; Gonzalez-Diaz, Marcos] Univ Salamanca, Ctr Invest Canc, Univ Hosp, Dept Hematol, Salamanca 37007, Spain. [Degos, Francoise] Hop Beaujon, F-92110 Clichy, France. [Ferguson, Martin L.] MLF Consulting, Arlington, MA 02474 USA. [Geary, Peter] Canadian Tumour Repository Network, Winnipeg, MB R3M 0V5, Canada. [Hayes, D. Neil] Univ N Carolina, Div Med Oncol, Lineberger Comprehens Canc Ctr, Dept Internal Med, Chapel Hill, NC 27599 USA. [Nakagawa, Hidewaki; Tsunoda, Tatsuhiko; Nakamura, Yusuke; Fujimoto, Akihiro] RIKEN, Ctr Genom Med, Kanagawa 2300045, Japan. [Penny, Robert] Int Genom Consortium, Phoenix, AZ 85004 USA. [Piris, Miguel A.] Spanish Natl Canc Res Ctr, Mol Pathol Programme, Madrid 28029, Spain. [Sarin, Rajiv] Tata Mem Hosp, Adv Ctr Treatment, Res & Educ Canc, Navi Mumbai 41021, Maharashtra, India. [Scarpa, Aldo; Zamboni, Giuseppe] Univ Verona, Dept Pathol, I-37134 Verona, Italy. [Scarpa, Aldo; Lawlor, Rita T.] Verona Univ Hosp, Ctr Appl Res Canc ARC NET, I-37134 Verona, Italy. [van de Vijver, Marc; van't Veer, Laura] Netherlands Canc Inst, NL-1066 CX Amsterdam, Netherlands. [van de Vijver, Marc] Acad Med Ctr, NL-1015 AZ Amsterdam, Netherlands. [Aburatani, Hiroyuki] Univ Tokyo, Res Ctr Adv Sci & Technol, Meguro Ku, Tokyo 1538904, Japan. [Bayes, Monica; Estivill, Xavier; Himmelbaue, Heinz] Pompeu Fabra Univ, Ctr Genom Regulat, Barcelona 08003, Spain. [Bayes, Monica] Biomed Res Ctr CIBERESP, Publ Hlth & Epidemiol Network, Barcelona 08003, Catalonia, Spain. [Bowtell, David D. L.; Etemadmoghadam, Dariush] Peter MacCallum Canc Ctr, Melbourne, Vic 3002, Australia. [Etemadmoghadam, Dariush] Univ Melbourne, Dept Biochem & Mol Biol, Parkville, Vic 3010, Australia. Univ Cambridge, Dept Haematol, Cambridge CB2 2XY, England. [Grimmond, Sean M.; Pearson, John V.; Cloonan, Nicole; Gardiner, Brooke A.; Waddell, Nicola J.] Univ Queensland, Inst Mol Biosci, Queensland Ctr Med Genom, Brisbane, Qld 4067, Australia. [Gut, Ivo; Heath, Simon; Lathrop, Mark; Tost, Joerg] CEA, DSV, IG Ctr Natl Genotypage, F-91057 Evry, France. [Hirst, Martin; Marra, Marco; Jones, Steven M.] British Columbia Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada. [Lopez-Otin, Carlos; Puente, Xose S.; Quesada, Victor] Univ Oviedo, Inst Univ Oncol, Dept Bioquim & Biol Mol, E-33006 Oviedo, Spain. [Majumder, Partha; Majumder, Partha P.] Natl Inst Biomed Genom, Kalyani 741251, W Bengal, India. [McPherson, John D.] Univ Toronto, Dept Med Biophys, Toronto, ON M5S 1A1, Canada. [Ruan, Yijun; Liu, Edison T.] Agcy Sci Technol & Res, Genome Inst Singapore, Singapore 138672, Singapore. [Stunnenberg, Hendrik G.] Radboud Univ Nijmegen, Nijmegen Ctr Mol Life Sci, NL-6500 HB Nijmegen, Netherlands. [Velculescu, Victor E.] Johns Hopkins Kimmel Canc Ctr, Ludwig Ctr Canc Genet & Therapeut, Baltimore, MD 21231 USA. [Wilson, Richard K.; Ley, Timothy J.] Washington Univ, Sch Med, Genome Ctr, St Louis, MO 63108 USA. Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO 63108 USA. [Xue, Hong H.] HKUST, Appl Genom Ctr, Fok Ying Grad Sch, Hong Kong, Hong Kong, Peoples R China. [Xue, Hong H.] Hong Kong Univ Sci & Technol, Dept Biochem, Hong Kong, Hong Kong, Peoples R China. [Yang, Liu] Zhejiang Univ, Inst Canc, Hangzhou 310009, Zhejiang, Peoples R China. [Spellman, Paul T.] Lawrence Berkeley Natl Lab, Div Life Sci, Berkeley, CA 94510 USA. [Bader, Gary D.] Univ Toronto, Donnelly Ctr Cellular & Biomol Res, Toronto, ON M5S 3E1, Canada. [Bader, Gary D.] Univ Toronto, Banting & Best Dept Med Res, Toronto, ON M5S 3E1, Canada. [Flicek, Paul; Brazma, Alvis; Birney, Ewan; Korbel, Jan O.] Hinxton, European Bioinformat Inst, European Mol Biol Lab, Cambridge CB10 1SD, England. [Getz, Gad; Lander, Eric S.] MIT, Cambridge, MA 02142 USA. [Getz, Gad] Broad Inst Harvard, Cambridge, MA 02142 USA. [Guigo, Roderic] Univ Pompeu Fabra, Spanish Natl Bioinformat Inst, Barcelona 08003, Spain. Univ Pompeu Fabra, Ctr Genom Regulat, Barcelona 08003, Spain. [Haussler, David] Univ Calif Santa Cruz, Howard Hughes Med Inst, Santa Cruz, CA 95064 USA. [Haussler, David] Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA. [Lopez-Bigas, Nuria] Pompeu Fabra Univ, Dept Expt & Hlth Sci, Res Unit Biomed Informat, Barcelona 08003, Spain. [Raphael, Benjamin J.] Brown Univ, Ctr Computat Mol Biol, Providence, RI 02912 USA. [Raphael, Benjamin J.] Brown Univ, Dept Comp Sci, Providence, RI 02912 USA. [Sander, Chris] Mem Sloan Kettering Canc Ctr, Computat Biol Ctr, New York, NY 10065 USA. [Speed, Terence P.] Walter & Eliza Hall Inst Med Res, Parkville, Vic 3052, Australia. [Speed, Terence P.] Univ Calif Berkeley, Dept Stat, Berkeley, CA 94720 USA. [Stuart, Joshua M.] Univ Calif Santa Cruz, Dept Biomol Engn, Santa Cruz, CA 95064 USA. [Valencia, Alfonso] Spanish Natl Canc Res Ctr CNIO, Spanish Natl Bioinformat Inst, Madrid 28029, Spain. [Valencia, Alfonso] Spanish Natl Canc Res Ctr CNIO, Struct Biol & Biocomputing Programme, Madrid 28029, Spain. [Wheeler, David A.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Blanche, Helene; Gut, Marta] Ctr Etud Polymorphisme Humain, Fdn Jean Dausset, F-75010 Paris, France. [Thomas, Gilles] Univ Lyon 1, F-69622 Villeurbanne, France. Fdn Synergie Lyon Canc, F-69008 Lyon, France. [Axton, Myles] Natl Genet, New York, NY 10013 USA. [Gunter, Chris] HudsonAlpha Inst Biotechnol, Huntsville, AL 35806 USA. [Miller, Linda J.] Nat & Nat Res Journals, New York, NY 10013 USA. [Haider, Syed A.] Univ Cambridge, Comp Lab, Cambridge CB3 0FD, England. [Chalmers, Don R. C.] Univ Tasmania, Fac Law, Hobart, Tas 7001, Australia. [Kaan, Terry S. H.] Natl Univ Singapore, Fac Law, Singapore 259776, Singapore. [Lowrance, William W.] Consultant Hlth Res Eth & Policy, F-34280 La Grande Motte, France. [Vergely, Catherine] Inst Gustave Roussy, ISIS 39, F-94805 Villejuif, France. [Defazio, Anna] Westmead Hosp, Dept Gynaecol Oncol, Westmead, NSW 2145, Australia. [Defazio, Anna] Univ Sydney, Westmead Millennium Inst, Westmead Inst Canc Res, Westmead, NSW 2145, Australia. [Eshleman, James R.] Johns Hopkins Med Inst, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD 21231 USA. [Kench, James G.] Univ Sydney, Royal Prince Alfred Hosp, Dept Anat Pathol, Sydney, NSW 2050, Australia. [Tempero, Margaret A.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94115 USA. [Gallinger, Steve] Toronto Gen Hosp, Dept Gen Surg, Toronto, ON M5G 2C4, Canada. [Gallinger, Steve] Samuel Lunenfeld Res Inst, Toronto, ON M5S 1A1, Canada. [Tsao, Ming-Sound] Ontario Canc Inst, Univ Hlth Network, Toronto, ON M5G 2M9, Canada. [Tsao, Ming-Sound] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5S 1A1, Canada. [Shaw, Patricia A.] Univ Hlth Network, Dept Pathol, Toronto, ON M5G 2C4, Canada. [Petersen, Gloria M.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA. [Mukhopadhyay, Debabrata] Mayo Clin, Dept Biochem & Mol Biol, Rochester, MN 55905 USA. [DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Med & Genet, Boston, MA 02115 USA. [Thayer, Sarah] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Zhu, Zhenggang; Yu, Yingyan] Shanghai Jiao Tong Univ, Sch Med, Shanghai Ruijin Hosp, Shanghai 200025, Peoples R China. [Yu, Jun] Chinese Univ Hong Kong, Inst Digest Dis, Hong Kong, Hong Kong, Peoples R China. [Brennan, Paul] Int Agcy Res Canc, F-69372 Lyon, France. [Holcatova, Ivana] Charles Univ Prague, Fac Med 1, Inst Hyg & Epidemiol, Prague 12108, Czech Republic. [Zaridze, David] NN Blokhin Russian Canc Res Ctr, Dept Epidemiol & Prevent, Moscow 115478, Russia. [Egevad, Lars] Karolinska Univ Hosp, Karolinska Inst, SE-17176 Stockholm, Sweden. [Prokhortchouk, Egor] Russian Acad Sci, Ctr Bioengn, Moscow 117312, Russia. [Banks, Rosamonde Elizabeth] St James Univ Hosp, Leeds Inst Mol Med, Canc Res UK Ctr, Leeds LS9 7TF, W Yorkshire, England. [Uhlen, Mathias] KTH Royal Inst Technol, Sci Life Lab, SE-10044 Stockholm, Sweden. [Viksna, Juris] Univ Latvia, Inst Math & Comp Sci, LV-1459 Riga, Latvia. [Ponten, Fredrik] Uppsala Univ, SE-75105 Uppsala, Sweden. [Skryabin, Konstantin] Kurchatov Sci Ctr, Moscow 123182, Russia. [Borg, Ake] Lund Univ, Dept Oncol, SE-22185 Lund, Sweden. [Borresen-Dale, Anne-Lise] Oslo Univ Hosp, Radiumhosp, Inst Canc Res, N-0310 Oslo, Norway. [Borresen-Dale, Anne-Lise] Univ Oslo, Fac Med, N-0316 Oslo, Norway. [Caldas, Carlos] Univ Cambridge, Dept Oncol, Cambridge CB2 0RE, England. [Caldas, Carlos] Li Ka Shing Ctr, Canc Res UK Cambridge Res Inst, Cambridge CB2 0RE, England. [Foekens, John A.] Josephine Nefkens Inst, Erasmus MC Rotterdam, Dept Med Oncol, NL-3015 CE Rotterdam, Netherlands. [Foekens, John A.] Canc Genom Ctr, NL-3015 CE Rotterdam, Netherlands. [Reis-Filho, Jorge S.] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England. [Richardson, Andrea L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Richardson, Andrea L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Boyault, Sandrine; Tabone, Eric; Treilleux, Isabelle] Ctr Leon Berard, F-69373 Lyon, France. [Sotiriou, Christos] Inst Jules Bordet, B-1000 Brussels, Belgium. [Pivot, Xavier] Hop Jean Minjoz, F-25030 Besancon, France. [Vincent-Salomon, Anne] Inst Curie, F-75231 Paris, France. [Theillet, Charles] Ctr Val Aurelle, F-34298 Montpellier, France. [Bioulac-Sage, Paulette] Hop Pellegrin, F-33076 Bordeaux, France. [Decaens, Thomas] Hop Henri Mondor, F-94010 Creteil, France. [Decaens, Thomas] INSERM, U955, F-94000 Creteil, France. [Franco, Dominique] Hop Antoine Beclere, F-92141 Clamart, France. [Samuel, Didier] Hop Paul Brousse, AP HP, Ctr Hepatobilaire, F-94800 Villejuif, France. [Samuel, Didier] INSERM, U785, F-94800 Villejuif, France. [Zucman-Rossi, Jessica] INSERM, U674, F-75010 Paris, France. [Eils, Roland] Heidelberg Univ, D-69120 Heidelberg, Germany. [Korbel, Jan O.] European Mol Biol Lab, Genome Biol Unit, D-69126 Heidelberg, Germany. [Korshunov, Andrey] Univ Heidelberg Hosp, Dept Neuropathol, D-69120 Heidelberg, Germany. [Landgraf, Pablo] Univ Dusseldorf, Clin Pediat Oncol Hematol & Immunol, D-40225 Dusseldorf, Germany. [Lehrach, Hans] Max Planck Inst Mol Genet, D-14195 Berlin, Germany. [Pfister, Stefan] Univ Heidelberg Hosp, Dept Pediat Hematol & Oncol, D-69120 Heidelberg, Germany. [Reifenberger, Guido] Univ Dusseldorf, Inst Neuropathol, D-40001 Dusseldorf, Germany. [Taylor, Michael D.] Hosp Sick Children, Div Neurosurg, Toronto, ON M5G 1X8, Canada. [Taylor, Michael D.] Hosp Sick Children, Arthur & Sonia Labatt Brain Tumour Res Ctr, Toronto, ON M5G 1X8, Canada. [von Kalle, Christof] Natl Ctr Tumor Dis, D-69120 Heidelberg, Germany. [von Kalle, Christof] German Canc Res Ctr, Div Translat Oncol, D-69120 Heidelberg, Germany. [Pederzoli, Paolo] Univ Hosp Trust Verona, Dept Surg, I-37134 Verona, Italy. [Delledonne, Massimo] Univ Verona, Dept Biotechnol, Funct Genom Ctr, I-37134 Verona, Italy. [Bardelli, Alberto] Univ Torino, Inst Canc Res & Treatment, Mol Genet Lab, I-10060 Turin, Italy. [Bardelli, Alberto] FIRC Inst Mol Oncol, I-20139 Milan, Italy. [Gress, Thomas] Univ Marburg, Dept Gastroenterol Endocrinol Metab & Infectiol, D-35043 Marburg, Germany. [Klimstra, David] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA. [Nakamura, Yusuke; Miyano, Satoru] Univ Tokyo, Inst Med Sci, Ctr Human Genome, Minato Ku, Tokyo 1088639, Japan. Univ Barcelona, Hosp Clin, E-08036 Barcelona, Spain. [Wilson, Peter J.; de Sanjose, Silvia] Hosp Llobregat, Inst Catala Oncol IDIBELL, Unit Infect & Canc,CIBER Epidemiol & Salud Publ, Canc Epidemiol Res Programme, Lhospitalet De Llobregat 08907, Spain. [Aparicio, Samuel] British Columbia Canc Agcy, BC Canc Res Ctr, Vancouver, BC V5Z 1L3, Canada. [Easton, Douglas F.] Univ Cambridge, Dept Primary Care & Oncol, Dept Publ Hlth, Cambridge CB1 8RN, England. [Collins, Francis S.] US Natl Inst Hlth, Bethesda, MD 20892 USA. [Burke, Wylie] Univ Washington, Dept Bioeth & Humanities, Seattle, WA 98195 USA. [Green, Anthony R.] Univ Cambridge, Dept Haematol, Cambridge CB2 2XY, England. [Green, Anthony R.] Univ Cambridge, Cambridge Inst Med Res, Cambridge CB2 2XY, England. [Hamilton, Stanley R.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Kallioniemi, Olli P.] Univ Helsinki, Inst Mol Med Finland, FIN-00290 Helsinki, Finland. [Ley, Timothy J.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. [Ley, Timothy J.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. [Wainwright, Brandon J.] Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4072, Australia. RP Hudson, TJ (reprint author), Ontario Inst Canc Res, Toronto, ON M5G 0A3, Canada. EM tom.hudson@oicr.on.ca RI Gill, Anthony/D-4215-2015; Guigo, Roderic/D-1303-2010; Lopez-Bigas, Nuria/F-6193-2011; Hubbard, Tim/C-2567-2008; Chalmers, Don/J-7658-2014; Valencia, Alfonso/I-3127-2015; Radlwimmer, Bernhard/I-3229-2013; IBIS, SARCOMAS/O-1893-2015; Giuseppe, Zamboni/A-5991-2016; Hirst, Martin/B-7684-2016; Quesada, Victor/B-6557-2014; Gardiner, Brooke/C-7773-2011; Marra, Marco/B-5987-2008; McPherson, John/D-2633-2017; Bea, Silvia/K-7699-2014; Eils, Roland/B-6121-2009; Pfister, Stefan/F-6860-2013; Clement, Bruno/E-5546-2016; Bowtell, David/H-1007-2016; Waddell, Nic/H-4929-2015; Prokhortchouk, Egor/I-9108-2014; Yu, Jun /D-8569-2015; Grimmond, Sean/J-5304-2016; Jones, Steven/C-3621-2009; Lopez-Otin, Carlos/C-6657-2013; Pearson, John/F-2249-2011; scarpa, aldo/K-6832-2016; Gasull, Martina/A-6630-2013; Heath, Simon/J-4138-2012; Ning, Zemin/D-2411-2013; Brors, Benedikt/E-5620-2013; Gallinger, Steven/E-4575-2013; Zaridze, David/K-5605-2013; Kallioniemi, Olli/H-4738-2012; Decaens, Thomas/L-9483-2013; Tang, Macy/B-9798-2014; deFazio, Anna/D-3939-2013; de Sanjose Llongueras, Silvia/H-6339-2014; Tsunoda, Tatsuhiko/K-2061-2014; Estivill, Xavier/A-3125-2013; Stunnenberg, Hendrik/D-6875-2012; Liu, Edison/C-4141-2008; Speed, Terence /B-8085-2009; Bader, Gary/C-1176-2009; Caldas, Carlos/A-7543-2008; Cloonan, Nicole/B-5272-2008; Kallioniemi, Olli/H-5111-2011; Gnaneshan, Saravanamuttu/D-2305-2012; Yuen, Matthew /E-5621-2011; Estivill, Xavier/E-2957-2012; Korbel, Jan/G-6470-2012; Piris, Miguel/B-7067-2008; sander, chris/H-1452-2011; IBSAL, Secretaria/H-3719-2011; OI Egevad, Lars/0000-0001-8531-222X; Suarez-Puente, Xose/0000-0001-9525-1483; Yung, Christina/0000-0003-2958-150X; zucman-rossi, Jessica/0000-0002-5687-0334; Banks, Rosamonde/0000-0002-0042-8715; Tost, Jorg/0000-0002-2683-0817; Flicek, Paul/0000-0002-3897-7955; Gill, Anthony/0000-0002-9447-1967; Guigo, Roderic/0000-0002-5738-4477; Lopez-Bigas, Nuria/0000-0003-4925-8988; Hubbard, Tim/0000-0002-1767-9318; Chalmers, Don/0000-0002-7925-8818; Valencia, Alfonso/0000-0002-8937-6789; Radlwimmer, Bernhard/0000-0002-4553-7800; Giuseppe, Zamboni/0000-0001-7428-4673; Quesada, Victor/0000-0002-8398-3457; Gardiner, Brooke/0000-0003-3740-3244; McPherson, John/0000-0001-8049-9347; Sarin, Rajiv/0000-0002-6405-8282; Bea, Silvia/0000-0001-7192-2385; Hayes, D. Neil/0000-0001-6203-7771; Ning, Zemin/0000-0003-4359-776X; Eils, Roland/0000-0002-0034-4036; Pfister, Stefan/0000-0002-5447-5322; Bowtell, David/0000-0001-9089-7525; Grimmond, Sean/0000-0002-8102-7998; Lopez-Otin, Carlos/0000-0001-6964-1904; Pearson, John/0000-0003-0904-4598; scarpa, aldo/0000-0003-1678-739X; Brors, Benedikt/0000-0001-5940-3101; Kallioniemi, Olli/0000-0002-3231-0332; deFazio, Anna/0000-0003-0057-4744; Estivill, Xavier/0000-0002-0723-2256; Speed, Terence /0000-0002-5403-7998; Bader, Gary/0000-0003-0185-8861; Kallioniemi, Olli/0000-0002-3231-0332; Gnaneshan, Saravanamuttu/0000-0002-0455-8701; Yuen, Matthew /0000-0002-6773-328X; Korbel, Jan/0000-0002-2798-3794; Piris, Miguel/0000-0001-5839-3634; Campo, elias/0000-0001-9850-9793; Brazma, Alvis/0000-0001-5988-7409; lawlor, Rita/0000-0003-3160-0634; Birney, Ewan/0000-0001-8314-8497; Martin, Sancha/0000-0001-6213-5259; Biankin, Andrew/0000-0002-0362-5597; Gonzalez Diaz, Marcos/0000-0001-6637-1072 NR 35 TC 714 Z9 725 U1 16 U2 224 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD APR 15 PY 2010 VL 464 IS 7291 BP 993 EP 998 DI 10.1038/nature08987 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 582XW UT WOS:000276635000029 ER PT J AU Bigler, ED Abildskov, TJ Wilde, EA McCauley, SR Li, XQ Merkley, TL Fearing, MA Newsome, MR Scheibel, RS Hunter, JV Chu, ZL Levin, HS AF Bigler, Erin D. Abildskov, Tracy J. Wilde, Elisabeth A. McCauley, Stephen R. Li, Xiaoqi Merkley, Tricia L. Fearing, Michael A. Newsome, Mary R. Scheibel, Randall S. Hunter, Jill V. Chu, Zili Levin, Harvey S. TI Diffuse damage in pediatric traumatic brain injury: A comparison of automated versus operator-controlled quantification methods SO NEUROIMAGE LA English DT Article ID HUMAN CEREBRAL-CORTEX; MAGNETIC-RESONANCE IMAGES; CORTICAL SURFACE; GEOMETRICALLY ACCURATE; LONGITUDINAL CHANGES; MRI FINDINGS; SEGMENTATION; MODERATE; HIPPOCAMPAL; CHILDREN AB This investigation had two main objectives: 1) to assess the comparability Of volumes determined by operator-controlled image quantification with automated image analysis in evaluating atrophic brain changes related to traumatic brain injury (TBI) in children, and 2) to assess the extent of diffuse structural changes throughout the brain as determined by reduced volume of a brain Structure or region of interest (ROI). Operator-control led methods used ANALYZE (R) software for segmentation and tracing routines of pre-defined brain structures and Rots. For automated image analyses, the open-access FreeSurfer program was used. Sixteen children with moderate-to-severe TBI were compared to individually matched, typically developing control children and the Volumes of 18 brain structures and/or ROIs were compared between the two methods. Both methods detected atrophic changes but differed in the magnitude of the atrophic effect with the best agreement in subcortical Structures. The volumes of all brain structures/ROIs were smaller in the TBI group regardless of method used; overall effect size differences were minimal for caudate and putamen but moderate to large for all other measures. This is reflective of the diffuse nature of TBI and its widespread impact on structural brain integrity, indicating that both FreeSurfer and operator-control led methods can reliably assess cross-sectional volumetric changes in pediatric TBI. (C) 2010 Elsevier Inc. All rights reserved. C1 [Bigler, Erin D.; Abildskov, Tracy J.; Merkley, Tricia L.] Brigham Young Univ, Dept Psychol, Provo, UT 84602 USA. [Bigler, Erin D.] Brigham Young Univ, Ctr Neurosci, Provo, UT 84602 USA. [Bigler, Erin D.] Univ Utah, Dept Psychiat, Salt Lake City, UT USA. [Bigler, Erin D.] Univ Utah, Utah Brain Inst, Salt Lake City, UT USA. [Wilde, Elisabeth A.; Hunter, Jill V.; Chu, Zili] Baylor Coll Med, Dept Radiol, Houston, TX 77030 USA. [Wilde, Elisabeth A.] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. [Wilde, Elisabeth A.; McCauley, Stephen R.; Li, Xiaoqi; Newsome, Mary R.; Scheibel, Randall S.; Levin, Harvey S.] Univ Texas Houston, Sch Med, Houston, TX USA. [McCauley, Stephen R.] Baylor Coll Med, Dept Pediat, Hematol Oncol Sect, Houston, TX 77030 USA. [Fearing, Michael A.] Hebrew SeniorLife, Dept Med Neuropyschol, Boston, MA USA. [Hunter, Jill V.; Chu, Zili] Texas Childrens Hosp, EB Singleton Dept Diagnost Imaging, Houston, TX 77030 USA. [Levin, Harvey S.] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. [Levin, Harvey S.] Baylor Coll Med, Dept Neurosurg, Houston, TX 77030 USA. [Wilde, Elisabeth A.; Newsome, Mary R.; Scheibel, Randall S.; Levin, Harvey S.] Michael E De Bakey Vet Affairs Med Ctr, Houston, TX USA. RP Bigler, ED (reprint author), Brigham Young Univ, Dept Psychol, 1001 SWKT, Provo, UT 84602 USA. EM erin-bigler@byu.edu FU National Institutes of Health [NS-21889]; TIRR Foundation. Erin D. Bigler [1 R01 HD048946-01] FX This research was supported by grant NS-21889 awarded to Harvey S. Levin by the National Institutes of Health. We also acknowledge the generous Support of Mission Connect of the TIRR Foundation. Erin D. Bigler was partially supported by grant 1 R01 HD048946-01A.Z. We acknowledge the contribution of Stacey K. Martin and Jo Ann Petrie for assistance in manuscript preparation. We would also like to thank Paul Swank, PhD, for his helpful advice regarding statistical methodology. Finally, we thank the participants and their farnilies for their interest and involvement in this study. NR 56 TC 46 Z9 46 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD APR 15 PY 2010 VL 50 IS 3 BP 1017 EP 1026 DI 10.1016/j.neuroimage.2010.01.003 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 566YA UT WOS:000275408200016 PM 20060915 ER PT J AU Cohen-Adad, J Gauthier, CJ Brooks, JCW Slessarev, M Han, J Fisher, JA Rossignol, S Hoge, RD AF Cohen-Adad, J. Gauthier, C. J. Brooks, J. C. W. Slessarev, M. Han, J. Fisher, J. A. Rossignol, S. Hoge, R. D. TI BOLD signal responses to controlled hypercapnia in human spinal cord SO NEUROIMAGE LA English DT Article ID CEREBRAL-BLOOD-FLOW; INDEPENDENT COMPONENT ANALYSIS; VOLUME-WEIGHTED FMRI; GRADIENT-ECHO FMRI; FUNCTIONAL MRI; HUMAN BRAIN; PHYSIOLOGICAL NOISE; TO-NOISE; 3 TESLA; SPATIAL LOCALIZATION AB Functional MRI of the spinal cord is challenging due to the small cross section of the cord and high level of physiological noise. Though blood oxygenation level-dependent (BOLD) contrast has been used to study specific responses of the spinal cord to various stimuli, it has not been demonstrated using a controlled stimulus. In this paper, we use hypercapnic manipulation to study the sensitivity and specificity of functional MRI in the human cervical spinal cord. Simultaneous MR imaging in the brain and spinal cord was performed for direct comparison with the brain, in which responses to hypercapnia have been more extensively characterized. Original contributions include: (i) prospectively controlled hypercapnic changes in end-tidal PCO2 (ii) simultaneous recording of BOLD responses in the brain and spinal cord, and (iii) generation of statistical maps of BOLD responses throughout the brain and spinal cord, taking into account physiological noise sources. Results showed significant responses in all subjects both in the brain and the spinal cord. In anatomically-defined regions of interest, mean percent changes were 0.6% in the spinal cord and 1% in the brain. Analysis of residual variance demonstrated significantly larger contribution of physiological noise in the spinal cord (P<0.005). To obtain more reliable results from fMRI in the spinal cord, it will be necessary to improve sensitivity through the use of highly parallelized coil arrays and better modeling of physiological noise. Finely, we believe that the use of controlled global stimuli, such as hypercapnia, will help assess the effectiveness of new acquisition techniques. (C) 2010 Elsevier Inc. All rights reserved. C1 [Cohen-Adad, J.; Gauthier, C. J.; Rossignol, S.; Hoge, R. D.] Univ Montreal, Dept Physiol,Grp Rech Syst Nerveux Cent, Unite Neuroimageri Fonct,Inst Genie Biomed, Ctr Rech,Inst Univ Geriatrie Montreal, Montreal, PQ H3C 3J7, Canada. [Cohen-Adad, J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Brooks, J. C. W.] Univ Oxford, Ctr Funct Magnet Resonance Imaging Brain, Oxford OX1 2JD, England. [Slessarev, M.; Han, J.; Fisher, J. A.] Univ Toronto, Dept Physiol, Dept Anaesthesiol, Univ Hlth Network, Toronto, ON, Canada. RP Cohen-Adad, J (reprint author), Univ Montreal, Dept Physiol,Grp Rech Syst Nerveux Cent, Unite Neuroimageri Fonct,Inst Genie Biomed, Ctr Rech,Inst Univ Geriatrie Montreal, Montreal, PQ H3C 3J7, Canada. EM jcohen@nmr.mgh.harvard.edu FU Canada Research Chair on the Spinal Cord; Multidisciplinary Team in Locomotor Rehabilitation; Canadian Institutes of Health Research [CIHR-84378]; Canada Foundation for Innovation; French Multiple Sclerosis Research Society; Canadian Institutes of Health Research; United Kingdom Medical Research Council FX We thank Carollyn Hurst and Andr Cyr for data acquisition, Jeanette Mumford and Christina Triantafyllou for helpful discussions. We also thank the reviewers for their helpful comments that greatly improved the quality of the final manuscript. This work was supported by the Canada Research Chair on the Spinal Cord (S.R.), the Multidisciplinary Team in Locomotor Rehabilitation (S.R.), the Canadian Institutes of Health Research (CIHR-84378) and Canada Foundation for Innovation (R.H.), the French Multiple Sclerosis Research Society (J.C-A), the Canadian Institutes of Health Research (C.J.G.) and the United Kingdom Medical Research Council (J.C.W.B.). NR 94 TC 25 Z9 25 U1 1 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD APR 15 PY 2010 VL 50 IS 3 BP 1074 EP 1084 DI 10.1016/j.neuroimage.2009.12.122 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 566YA UT WOS:000275408200022 PM 20060914 ER PT J AU Bar, M AF Bar, Moshe TI Wait for the Second Marshmallow? Future-Oriented Thinking and Delayed Reward Discounting in the Brain SO NEURON LA English DT Editorial Material ID PREDICTIONS AB Humans tend to discount the value of delayed rewards. Peters and Buchel show in this issue of Neuron that the ability to appraise the value of such future rewards improves when future-oriented cognitive processes in the brain are recruited using personally relevant information. These results provide the platform for exciting new questions. C1 Harvard Univ, Sch Med, Martinos Ctr, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Bar, M (reprint author), Harvard Univ, Sch Med, Martinos Ctr, Massachusetts Gen Hosp, 149 13th St, Charlestown, MA 02129 USA. EM bar@nmr.mgh.harvard.edu FU NINDS NIH HHS [R01 NS050615, R01 NS050615-01] NR 16 TC 8 Z9 8 U1 2 U2 11 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD APR 15 PY 2010 VL 66 IS 1 BP 4 EP 5 DI 10.1016/j.neuron.2010.04.001 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 587TP UT WOS:000277016200002 PM 20399722 ER PT J AU Venna, N Gonzalez, RG Camelo-Piragua, SI AF Venna, Nagagopal Gonzalez, R. Gilberto Camelo-Piragua, Sandra I. TI A Woman with Lethargy, Confusion, and Abnormalities on Brain Imaging Progressive multifocal leukoencephalopathy. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID RHEUMATIC-DISEASES; ENCEPHALOPATHY; ENCEPHALITIS; DIAGNOSIS; THERAPY; ADULTS; LUPUS C1 [Venna, Nagagopal] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Gonzalez, R. Gilberto] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Camelo-Piragua, Sandra I.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Venna, Nagagopal] Harvard Univ, Sch Med, Dept Neurol, Cambridge, MA 02138 USA. [Gonzalez, R. Gilberto] Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. [Camelo-Piragua, Sandra I.] Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Venna, N (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. NR 22 TC 2 Z9 4 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 15 PY 2010 VL 362 IS 15 BP 1431 EP 1437 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 582XY UT WOS:000276635300013 PM 20393180 ER PT J AU Greenstein, RJ Brown, ST AF Greenstein, Robert J. Brown, Sheldon T. TI Genomewide Association Study of Leprosy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID CROHNS-DISEASE; MYCOBACTERIUM C1 [Greenstein, Robert J.; Brown, Sheldon T.] James J Peters VA Med Ctr, Bronx, NY USA. RP Greenstein, RJ (reprint author), James J Peters VA Med Ctr, Bronx, NY USA. EM bgaxis@aol.com NR 5 TC 3 Z9 3 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 15 PY 2010 VL 362 IS 15 BP 1447 EP 1447 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 582XY UT WOS:000276635300023 PM 20397291 ER PT J AU Pober, B AF Pober, Barbara TI Williams-Beuren Syndrome REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID VOIDING DYSFUNCTION C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Pober, B (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM pober.barbara@mgh.harvard.edu NR 2 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 15 PY 2010 VL 362 IS 15 BP 1450 EP 1450 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 582XY UT WOS:000276635300028 ER PT J AU Wines-Samuelson, M Schulte, EC Smith, MJ Aoki, C Liu, XR Kelleher, RJ Shen, J AF Wines-Samuelson, Mary Schulte, Eva C. Smith, Miriam J. Aoki, Chiye Liu, Xinran Kelleher, Raymond J., III Shen, Jie TI Characterization of Age-Dependent and Progressive Cortical Neuronal Degeneration in Presenilin Conditional Mutant Mice SO PLOS ONE LA English DT Article ID TRAUMATIC BRAIN-INJURY; INDUCED APOPTOTIC NEURODEGENERATION; FETAL ALCOHOL SYNDROME; SYNAPTIC PLASTICITY; ALZHEIMERS-DISEASE; CELL-DEATH; ACTIVATION; MEMORY; RESPONSES; KNOCKOUT AB Presenilins are the major causative genes of familial Alzheimer's disease ( AD). Our previous study has demonstrated essential roles of presenilins in memory and neuronal survival. Here, we explore further how loss of presenilins results in age-related, progressive neurodegeneration in the adult cerebral cortex, where the pathogenesis of AD occurs. To circumvent the requirement of presenilins for embryonic development, we used presenilin conditional double knockout (Psen cDKO) mice, in which presenilin inactivation is restricted temporally and spatially to excitatory neurons of the postnatal forebrain beginning at 4 weeks of age. Increases in the number of degenerating (Fluoro-Jade B+, 7.6-fold) and apoptotic (TUNEL+, 7.4-fold) neurons, which represent similar to 0.1% of all cortical neurons, were first detected at 2 months of age when there is still no significant loss of cortical neurons and volume in Psen cDKO mice. By 4 months of age, significant loss of cortical neurons (similar to 9%) and gliosis was found in Psen cDKO mice. The apoptotic cell death is associated with caspase activation, as shown by increased numbers of cells immunoreactive for active caspases 9 and 3 in the Psen cDKO cortex. The vulnerability of cortical neurons to loss of presenilins is region-specific with cortical neurons in the lateral cortex most susceptible. Compared to the neocortex, the increase in apoptotic cell death and the extent of neurodegeneration are less dramatic in the Psen cDKO hippocampus, possibly in part due to increased neurogenesis in the aging dentate gyrus. Neurodegeneration is also accompanied with mitochondrial defects, as indicated by reduced mitochondrial density and altered mitochondrial size distribution in aging Psen cortical neurons. Together, our findings show that loss of presenilins in cortical neurons causes apoptotic cell death occurring in a very small percentage of neurons, which accumulates over time and leads to substantial loss of cortical neurons in the aging brain. The low occurrence and significant delay of apoptosis among cortical neurons lacking presenilins suggest that loss of presenilins may induce apoptotic neuronal death through disruption of cellular homeostasis rather than direct activation of apoptosis pathways. C1 [Wines-Samuelson, Mary; Schulte, Eva C.; Smith, Miriam J.; Shen, Jie] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis,Dept Neurol, Boston, MA 02115 USA. [Aoki, Chiye] NYU, Ctr Neural Sci, New York, NY 10003 USA. [Liu, Xinran] Univ Texas SW Med Ctr Dallas, Dept Neurosci, Dallas, TX 75390 USA. [Kelleher, Raymond J., III] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA. RP Wines-Samuelson, M (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis,Dept Neurol, Boston, MA 02115 USA. EM jshen@rics.bwh.harvard.edu RI Smith, Miriam/J-4001-2015; OI Smith, Miriam/0000-0002-3184-0817; Schulte, Eva Christina/0000-0003-3105-5672 FU National Institutes of Health [5R01NS41783]; Alzheimer's Association (IIRG) FX This work was supported by grants from the National Institutes of Health (5R01NS41783) and the Alzheimer's Association (IIRG). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 37 TC 26 Z9 28 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 15 PY 2010 VL 5 IS 4 AR e10195 DI 10.1371/journal.pone.0010195 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 583VD UT WOS:000276707100011 PM 20419112 ER PT J AU Kotton, CN Kumar, D Caliendo, AM Asberg, A Chou, SW Snydman, DR Allen, U Humar, A AF Kotton, Camille N. Kumar, Deepali Caliendo, Angela M. Asberg, Anders Chou, Sunwen Snydman, David R. Allen, Upton Humar, Atul CA Transplantat Soc Int CMV Consensu TI International Consensus Guidelines on the Management of Cytomegalovirus in Solid Organ Transplantation SO TRANSPLANTATION LA English DT Article DE Cytomegalovirus; Prophylaxis; Resistance; Ganciclovir; Valganciclovir ID GANCICLOVIR-RESISTANT CYTOMEGALOVIRUS; STEM-CELL TRANSPLANTATION; PEDIATRIC LUNG TRANSPLANTATION; BRONCHOALVEOLAR LAVAGE FLUID; GUIDING PREEMPTIVE THERAPY; AMPLICOR CMV MONITOR; LIVER-TRANSPLANT; RENAL-TRANSPLANT; DRUG-RESISTANCE; T-CELLS AB Cytomegalovirus (CMV) remains one of the most common infections after solid organ transplantation, resulting in significant morbidity, graft loss, and occasional mortality. Management of CMV varies considerably among transplant centers. A panel of experts on CMV and solid organ transplant was convened by The Infectious Diseases Section of The Transplantation Society to develop evidence and expert opinion-based consensus guidelines on CMV management including diagnostics, immunology, prevention, treatment, drug resistance, and pediatric issues. C1 [Kotton, Camille N.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Univ Alberta, Transplant Infect Dis, Katz Rexall Ctr Hlth Res 6 030, Dept Med, Edmonton, AB, Canada. [Caliendo, Angela M.] Emory Univ Hosp, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. [Asberg, Anders] Univ Oslo, Sch Pharm, Dept Pharmaceut Biosci, Oslo, Norway. [Chou, Sunwen] Oregon Hlth & Sci Univ, Div Infect Dis L457, Portland, OR 97201 USA. [Snydman, David R.] Tufts Univ, Sch Med, Div Geog Med & Infect Dis, Boston, MA 02111 USA. [Snydman, David R.] Tufts Univ, Sch Med, Tufts Med Ctr, Boston, MA 02111 USA. [Allen, Upton] Univ Toronto, Hosp Sick Children, Dept Pediat, Div Infect Dis, Toronto, ON M5G 1X8, Canada. RP Kotton, CN (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St,Cox 5, Boston, MA 02114 USA. EM ckotton@partners.org RI Montejo, Jose Miguel/E-1755-2012; David-Neto, Elias/C-9112-2012; Snydman, David/O-3889-2014; Lilleri, Daniele/K-7776-2016; OI Snydman, David/0000-0003-0119-3978; Emery, Vincent/0000-0001-5893-9756; Munoz Garcia, Patricia Carmen/0000-0001-5706-5583 FU Roche FX The CMV Consensus Conference was organized by The Infectious Diseases Section of The Transplantation Society. An independent, nonrestricted grant from Roche made this conference possible. The authors thank Filomena Picciano, Frank Lindo Verissimo, and Catherin Parker of The Transplantation Society for their administrative support. NR 151 TC 318 Z9 330 U1 2 U2 23 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 15 PY 2010 VL 89 IS 7 BP 779 EP 795 DI 10.1097/TP.0b013e3181cee42f PG 17 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 585EL UT WOS:000276807100002 PM 20224515 ER PT J AU Tilney, NL Chapman, JR Delmonico, FL AF Tilney, Nicholas L. Chapman, Jeremy R. Delmonico, Francis L. TI Debate on Financial Incentives Is Off the Mark of National and International Realities SO TRANSPLANTATION LA English DT Letter C1 [Tilney, Nicholas L.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Chapman, Jeremy R.] Univ Sydney, Westmead Hosp, Ctr Transplant & Renal Res, Westmead, NSW 2145, Australia. [Delmonico, Francis L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Tilney, NL (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM ntilney@partners.org NR 2 TC 6 Z9 6 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 15 PY 2010 VL 89 IS 7 BP 906 EP 907 DI 10.1097/TP.0b013e3181cf5052 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 585EL UT WOS:000276807100023 PM 20386300 ER PT J AU Smolderen, KG Spertus, JA Nallamothu, BK Krumholz, HM Tang, FM Ross, JS Ting, HH Alexander, KP Rathore, SS Chan, PS AF Smolderen, Kim G. Spertus, John A. Nallamothu, Brahmajee K. Krumholz, Harlan M. Tang, Fengming Ross, Joseph S. Ting, Henry H. Alexander, Karen P. Rathore, Saif S. Chan, Paul S. TI Health Care Insurance, Financial Concerns in Accessing Care, and Delays to Hospital Presentation in Acute Myocardial Infarction SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ACUTE CORONARY SYNDROME; PREHOSPITAL DELAY; PERCEIVED STRESS; UNINSURED ADULTS; EMTALA PARADOX; HEART; TIME; THERAPY; DISEASE; TRENDS AB Context Little is known about how health insurance status affects decisions to seek care during emergency medical conditions such as acute myocardial infarction (AMI). Objective To examine the association between lack of health insurance and financial concerns about accessing care among those with health insurance, and the time from symptom onset to hospital presentation (prehospital delays) during AMI. Design, Setting, and Patients Multicenter, prospective study using a registry of 3721 AMI patients enrolled between April 11, 2005, and December 31, 2008, at 24 US hospitals. Health insurance status was categorized as insured without financial concerns, insured but have financial concerns about accessing care, and uninsured. Insurance information was determined from medical records while financial concerns among those with health insurance were determined from structured interviews. Main Outcome Measure Prehospital delay times (<= 2 hours, >2-6 hours, or >6 hours), adjusted for demographic, clinical, and social and psychological factors using hierarchical ordinal regression models. Results Of 3721 patients, 2294 were insured without financial concerns (61.7%), 689 were insured but had financial concerns about accessing care (18.5%), and 738 were uninsured (19.8%). Uninsured and insured patients with financial concerns were more likely to delay seeking care during AMI and had prehospital delays of greater than 6 hours among 48.6% of uninsured patients and 44.6% of insured patients with financial concerns compared with only 39.3% of insured patients without financial concerns. Prehospital delays of less than 2 hours during AMI occurred among 36.6% of those insured without financial concerns compared with 33.5% of insured patients with financial concerns and 27.5% of uninsured patients (P < .001). After adjusting for potential confounders, prehospital delays were associated with insured patients with financial concerns (adjusted odds ratio, 1.21 [95% confidence interval, 1.05-1.41]; P=.01) and with uninsured patients (adjusted odds ratio, 1.38 [95% confidence interval, 1.17-1.63]; P < .001). Conclusion Lack of health insurance and financial concerns about accessing care among those with health insurance were each associated with delays in seeking emergency care for AMI. JAMA. 2010; 303(14): 1392-1400 C1 [Smolderen, Kim G.] Tilburg Univ, Ctr Res Psychol Somat Dis, Dept Med Psychol & Neuropsychol, NL-5000 LE Tilburg, Netherlands. [Spertus, John A.; Tang, Fengming; Chan, Paul S.] St Lukes Mid Amer Heart Inst, Kansas City, MO USA. [Spertus, John A.; Chan, Paul S.] Univ Missouri, Sch Med, Dept Internal Med, Kansas City, MO USA. [Nallamothu, Brahmajee K.] Univ Michigan, Sch Med, VA Hlth Serv Res & Dev Ctr Excellence, Ann Arbor, MI USA. [Nallamothu, Brahmajee K.] Univ Michigan, Sch Med, Dept Med, Ann Arbor, MI 48104 USA. [Krumholz, Harlan M.] Yale Univ, Sch Med, Robert Wood Johnson Clin Scholars Program, New Haven, CT USA. [Krumholz, Harlan M.; Rathore, Saif S.] Yale Univ, Sch Med, MD PhD Program, New Haven, CT USA. [Krumholz, Harlan M.] Yale New Haven Med Ctr, Sect Hlth Policy & Adm, Dept Epidemiol & Publ Hlth, New Haven, CT 06504 USA. [Krumholz, Harlan M.] Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, New Haven, CT 06504 USA. [Ross, Joseph S.] Mt Sinai Sch Med, Dept Geriatr & Palliat Med, New York, NY USA. [Ross, Joseph S.] James J Peters VA Med Ctr, HSR&D Res Enhancement Award Program, Bronx, NY USA. [Ross, Joseph S.] James J Peters VA Med Ctr, Ctr Geriatr Res Educ & Clin, Bronx, NY USA. [Ting, Henry H.] Mayo Clin, Coll Med, Div Cardiovasc Dis, Rochester, MN USA. [Alexander, Karen P.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. RP Chan, PS (reprint author), St Lukes Hosp, Mid Amer Heart Inst, 5th Floor,4401 Wornall Rd, Kansas City, MO 64111 USA. EM pchan@cc-pc.com RI Smolderen, Kim/B-8078-2015 FU National Heart, Lung, and Blood Institute Specialized Center of Clinically Oriented Research in Cardiac Dysfunction and Disease [P50 HL077113]; National Institute on Aging [K08 AG032886]; American Federation of Aging Research; National Institutes of Health's Center for Research Resources [UL1 RR024139]; National Institute of General Medical Sciences [5T32GM07205]; Agency for Healthcare Research and Quality [1R36HS018283-01] FX The Translational Research Investigating Underlying Disparities in Acute Myocardial Infarction Patients' Health Status (TRIUMPH) study was supported by grant P50 HL077113 from the National Heart, Lung, and Blood Institute Specialized Center of Clinically Oriented Research in Cardiac Dysfunction and Disease. Dr Ross is supported by grant K08 AG032886 from the National Institute on Aging and by the American Federation of Aging Research through the Paul B. Beeson Career Development Award Program. Mr Rathore is supported, in part, by CTSA grant UL1 RR024139 from the National Institutes of Health's Center for Research Resources, grant 5T32GM07205 from the National Institute of General Medical Sciences Medical Scientist Training Program, and dissertation grant 1R36HS018283-01 from the Agency for Healthcare Research and Quality. NR 38 TC 47 Z9 47 U1 1 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 14 PY 2010 VL 303 IS 14 BP 1392 EP 1400 DI 10.1001/jama.2010.409 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 582KX UT WOS:000276597300024 PM 20388895 ER PT J AU El-Khatib, FH Russell, SJ Nathan, DM Sutherlin, RG Damiano, ER AF El-Khatib, Firas H. Russell, Steven J. Nathan, David M. Sutherlin, Robert G. Damiano, Edward R. TI A Bihormonal Closed-Loop Artificial Pancreas for Type 1 Diabetes SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID INTENSIVE TREATMENT; INSULIN DELIVERY; IN-VIVO; COMPLICATIONS; MELLITUS; ASSAY AB Automated control of blood glucose (BG) concentration is a long-sought goal for type 1 diabetes therapy. We have developed a closed-loop control system that uses frequent measurements of BG concentration along with subcutaneous delivery of both the fast-acting insulin analog lispro and glucagon (to imitate normal physiology) as directed by a computer algorithm. The algorithm responded only to BG concentrations and incorporated a pharmacokinetic model for lispro. Eleven subjects with type 1 diabetes and no endogenous insulin secretion were studied in 27-hour experiments, which included three carbohydrate-rich meals. In six subjects, the closed-loop system achieved a mean BG concentration of 140 mg/dl, which is below the mean BG concentration target of <= 154 mg/dl recommended by the American Diabetes Association. There were no instances of treatment-requiring hypoglycemia. Five other subjects exhibited hypoglycemia that required treatment; however, these individuals had slower lispro absorption kinetics than the six subjects that did not become hypoglycemic. The time-to-peak plasma lispro concentrations of subjects that exhibited hypoglycemia ranged from 71 to 191 min (mean, 117 +/- 48 min) versus 56 to 72 min (mean, 64 +/- 6 min) in the group that did not become hypoglycemic (aggregate mean of 84 min versus 31 min longer than the algorithm's assumption of 33 min, P = 0.07). In an additional set of experiments, adjustment of the algorithm's pharmacokinetic parameters (time-to-peak plasma lispro concentration set to 65 min) prevented hypoglycemia in both groups while achieving an aggregate mean BG concentration of 164 mg/dl. These results demonstrate the feasibility of safe BG control by a bihormonal artificial endocrine pancreas. C1 [Russell, Steven J.; Nathan, David M.; Sutherlin, Robert G.] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. [Russell, Steven J.; Nathan, David M.; Sutherlin, Robert G.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Russell, Steven J.; Nathan, David M.; Sutherlin, Robert G.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [El-Khatib, Firas H.; Damiano, Edward R.] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. RP Russell, SJ (reprint author), Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. EM sjrussell@partners.org FU NCRR NIH HHS [1-UL1-RR025758-01, M01 RR001066, RR01066, UL1 RR025758] NR 23 TC 116 Z9 117 U1 2 U2 18 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 J9 SCI TRANSL MED JI Sci. Transl. Med. PD APR 14 PY 2010 VL 2 IS 27 AR 27ra27 DI 10.1126/scitranslmed.3000619 PG 12 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 591MJ UT WOS:000277304500002 PM 20393188 ER PT J AU Tokbtaeva, E Munson, K Sachs, G Vagin, O AF Tokbtaeva, Elmira Munson, Keith Sachs, George Vagin, Olga TI N-Glycan-Dependent Quality Control of the Na,K-ATPase beta 2 Subunit SO BIOCHEMISTRY LA English DT Article ID RETICULUM-ASSOCIATED DEGRADATION; NA+-K+-ATPASE; ENDOPLASMIC-RETICULUM; GLYCOSYLATION SITES; XENOPUS-OOCYTES; ALPHA-SUBUNIT; PROTEIN; CALNEXIN; CELLS; ER AB Bulky hydrophilic N-glycans stabilize the proper tertiary structure of glycoproteins. In addition, N-glycans comprise the binding sites for the endoplasmic reticulum (ER)-resident lectins that assist correct folding of newly synthesized glycoproteins. To reveal the role of N-glycans in maturation of the Na,K-ATPase beta(2) subunit in the ER, the effects of preventing or modifying the beta(2) subunit N-glycosylation on trafficking of the subunit and its binding to the ER lectin chaperone, calnexin, were studied in M DCK cells. Preventing N-glycosylation abolishes binding of the beta(2) subunit to calnexin and results in the ER retention of the subunit. Furthermore, the fully N-glycosylated beta(2) subunit is retained in the ER when glycan calnexin interactions are prevented by castanospermine, showing that N-glycan-mediated calnexin binding is required for correct subunit folding. Calnexin binding persists for several hours after translation is stopped with cycloheximide, suggesting that the beta(2) subunit undergoes repeated post-translational calnexin-assisted folding attempts. Homology modeling of the beta(2) subunit using the crystal structure of the alpha(1)-beta(1) Na,K-ATPase shows the presence of a relatively hydrophobic amino acid cluster proximal to N-glycosylation sites 2 and 7. Combined, but not separate, removal of sites 2 and 7 dramatically impairs calnexin binding and prevents the export of the beta(2) subunit from the ER. Similarly, hydrophilic substitution of two hydrophobic amino acids in this cluster disrupts both beta(2)-calnexin binding and trafficking of the subunit to the Golgi. Therefore, the hydrophobic residues in the proximity of N-glycans 2 and 7 are required for post-translational calnexin binding to these N-glycans in incompletely folded conformers, which, in turn, is necessary for maturation of the Na,K-ATPase beta(2) subunit. C1 [Vagin, Olga] Univ Calif Los Angeles, Sch Med, Dept Physiol, Los Angeles, CA 90073 USA. Vet Adm Greater Los Angeles Hlth Care Syst, VAGLAHS W LA, Los Angeles, CA 90073 USA. RP Vagin, O (reprint author), Univ Calif Los Angeles, Sch Med, Dept Physiol, Bldg 113,Room 324,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM olgav@ucla.edu FU National Institutes of Health [DK077149, DK058333] FX Supported by National Institutes of Health Grants DK077149 and DK058333. NR 49 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 13 PY 2010 VL 49 IS 14 BP 3116 EP 3128 DI 10.1021/bi100115a PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 577YB UT WOS:000276258800015 ER PT J AU Loda, M Kaelin, WG AF Loda, Massimo Kaelin, William G., Jr. TI Prostate Cancer: Beta Control Your Hormones SO CANCER CELL LA English DT Editorial Material ID EPITHELIAL-MESENCHYMAL TRANSITION; TRANSCRIPTION; MORTALITY AB Differentiation status influences the prognosis for localized prostate cancer. In this issue of Cancer Cell, Mak and coworkers describe a signaling pathway involving estrogen receptor beta (ER beta) that governs whether prostate carcinoma cells maintain an epithelial phenotype or undergo epithelial-mesenchymal transition, suggesting that ER beta would have prognostic or therapeutic value. C1 [Loda, Massimo; Kaelin, William G., Jr.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Kaelin, William G., Jr.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Loda, M (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM massimo_loda@dfci.harvard.edu; william_kaelin@dfci.harvard.edu NR 11 TC 3 Z9 3 U1 2 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD APR 13 PY 2010 VL 17 IS 4 BP 311 EP 312 DI 10.1016/j.ccr.2010.03.013 PG 2 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 586CS UT WOS:000276879700001 PM 20385354 ER PT J AU Hirsch, HA Iliopoulos, D Joshi, A Zhang, Y Jaeger, SA Bulyk, M Tsichlis, PN Liu, XS Struhl, K AF Hirsch, Heather A. Iliopoulos, Dimitrios Joshi, Amita Zhang, Yong Jaeger, Savina A. Bulyk, Martha Tsichlis, Philip N. Liu, X. Shirley Struhl, Kevin TI A Transcriptional Signature and Common Gene Networks Link Cancer with Lipid Metabolism and Diverse Human Diseases SO CANCER CELL LA English DT Article ID FATTY-ACID SYNTHASE; NF-KAPPA-B; BREAST-CANCER; EXPRESSION; INFLAMMATION; MICROARRAYS; KINASE; CELLS; LIVER; ADENOCARCINOMA AB Transcriptional profiling of two isogenic models of transformation identifies a gene signature linking cancer with inflammatory and metabolic diseases. In accord with this common transcriptional program, many drugs used for treatment of diabetes and cardiovascular diseases inhibit transformation and tumor growth. Unexpectedly, lipid metabolism genes are important for transformation and are upregulated in cancer tissues. As in atherosclerosis, oxidized LDL and its receptor OLR1 activate the inflammatory pathway through NF-kappa B, leading to transformation. OLR1 is important for maintaining the transformed state in developmentally diverse cancer cell lines and for tumor growth, suggesting a molecular connection between cancer and atherosclerosis. We suggest that the interplay between this common transcriptional program and cell-type-specific factors gives rise to phenotypically disparate human diseases. C1 [Hirsch, Heather A.; Iliopoulos, Dimitrios; Joshi, Amita; Struhl, Kevin] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Zhang, Yong; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Jaeger, Savina A.; Bulyk, Martha] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. [Bulyk, Martha] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Bulyk, Martha] Harvard Univ, Sch Med, Harvard Mit Div Hlth Sci & Technol, Boston, MA 02115 USA. [Tsichlis, Philip N.] Tufts Med Ctr, Mol Oncol Res Inst, Boston, MA 02111 USA. RP Struhl, K (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM kevin@hms.harvard.edu RI Zhang, Yong/B-4838-2011 OI Zhang, Yong/0000-0001-6316-2734 FU NSF; American Cancer Society; Alfred P. Sloan Research; National Institutes of Health [HG2966, CA57486, HG4069-02, CA107486] FX We thank Joan Brugge for the ER-Src and control cell lines, Bill Hahn for the fibroblast cell lines, and Konstantinos Drosatos for helpful discussions and suggestions regarding the involvement of lipid metabolism pathways in cancer. We thank members of the Bulyk lab, in particular Mike Berger, Andrew Gehrke, and Anthony Philippakis, and members of Tim Hughes' lab, in particular Gwenael Badis and Shaheynoor Talukder, for sharing prepublication PBM data on 104 mouse transcription factors. This project was supported by an NSF Postdoctoral Fellowship in Biological Informatics to S.J., a postdoctoral fellowship from the American Cancer Society to H.A.H., an Alfred P. Sloan Research Fellowship to X.S.L., and research grants from the National Institutes of Health to M.L.B (HG2966), P.N.T. (CA57486), X.S.L. (HG4069-02), and K.S. (CA107486). NR 42 TC 142 Z9 144 U1 4 U2 16 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD APR 13 PY 2010 VL 17 IS 4 BP 348 EP 361 DI 10.1016/j.ccr.2010.01.022 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 586CS UT WOS:000276879700007 PM 20385360 ER PT J AU Gleimer, M von Boehmer, H AF Gleimer, Michael von Boehmer, Harald TI Thymocyte Selection: Chemokine Signaling Is Not Only about the Destination SO CURRENT BIOLOGY LA English DT Editorial Material ID T-CELL-RECEPTOR; THYMUS; EXPRESSION; GENES; MICE; CXCR4 C1 [Gleimer, Michael; von Boehmer, Harald] Dana Farber Canc Inst, Lab Lymphocyte Biol Canc Immunol & AIDS, Boston, MA 02115 USA. RP Gleimer, M (reprint author), Dana Farber Canc Inst, Lab Lymphocyte Biol Canc Immunol & AIDS, 44 Binney St,Smith 736, Boston, MA 02115 USA. EM Harald_von_Boehmer@dfci.harvard.edu NR 19 TC 2 Z9 2 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD APR 13 PY 2010 VL 20 IS 7 BP R316 EP R318 DI 10.1016/j.cub.2010.02.018 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 584LK UT WOS:000276753100013 PM 20392421 ER PT J AU Panizzi, P Swirski, FK Figueiredo, JL Waterman, P Sosnovik, DE Aikawa, E Libby, P Pittet, M Weissleder, R Nahrendorf, M AF Panizzi, Peter Swirski, Filip K. Figueiredo, Jose-Luiz Waterman, Peter Sosnovik, David E. Aikawa, Elena Libby, Peter Pittet, Mikael Weissleder, Ralph Nahrendorf, Matthias TI Impaired Infarct Healing in Atherosclerotic Mice With Ly-6C(hi) Monocytosis SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE FMT; healing; heart failure; monocytes; myocardial infarction ID ACUTE MYOCARDIAL-INFARCTION; LEFT-VENTRICULAR DYSFUNCTION; DISEASE; TRIAL; INFLAMMATION; REPERFUSION; MORTALITY; SUBSETS; INJURY AB Objectives The aim of this study was to test whether blood monocytosis in mice with atherosclerosis affects infarct healing. Background Monocytes are cellular protagonists of tissue repair, and their specific subtypes regulate the healing program after myocardial infarction (MI). Inflammatory Ly-6C(hi) monocytes dominate on Day 1 to Day 4 and digest damaged tissue; reparative Ly-6C(lo) monocytes dominate on Day 5 to Day 10 and promote angiogenesis and scar formation. However, the monocyte repertoire is disturbed in atherosclerotic mice: Ly-6C(hi) monocytes expand selectively, which might disrupt the resolution of inflammation. Methods Ex vivo analysis of infarcts included flow cytometric monocyte enumeration, immunoactive staining, and quantitative polymerase chain reaction. To relate inflammatory activity to left ventricular remodeling, we used a combination of noninvasive fluorescence molecular tomography (FMT-CT) and physiologic imaging (magnetic resonance imaging). Results Five-day-old infarcts showed >10x more Ly-6C(hi) monocytes in atherosclerotic (apoE(-/-)) mice compared with wild-type mice. The injured tissue in apoE(-/-) mice also showed a more pronounced inflammatory gene expression profile (e.g., increased tumor necrosis factor-alpha and myeloperoxidase and decreased transforming growth factor-beta) and a higher abundance of proteases, which are associated with the activity of Ly-6C(hi) monocytes. The FMT-CT on Day 5 after MI showed higher proteolysis and phagocytosis in infarcts of atherosclerotic mice. Serial magnetic resonance imaging showed accelerated deterioration of ejection fraction between Day 1 and Day 21 after MI in apoE(-/-). Finally, we could recapitulate these features in wild-type mice with artificially induced Ly-6C(hi) monocytosis. Conclusions Ly-6C(hi) monocytosis disturbs resolution of inflammation in murine infarcts and consequently enhances left ventricular remodeling. These findings position monocyte subsets as potential therapeutic targets to augment tissue repair after infarction and to prevent post-MI heart failure. (J Am Coll Cardiol 2010;55:1629-38) (C) 2010 by the American College of Cardiology Foundation C1 [Panizzi, Peter; Swirski, Filip K.; Figueiredo, Jose-Luiz; Waterman, Peter; Pittet, Mikael; Weissleder, Ralph; Nahrendorf, Matthias] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Sosnovik, David E.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Sosnovik, David E.] Harvard Univ, Sch Med, Boston, MA USA. [Panizzi, Peter; Swirski, Filip K.; Figueiredo, Jose-Luiz; Waterman, Peter; Sosnovik, David E.; Aikawa, Elena; Weissleder, Ralph; Nahrendorf, Matthias] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. [Panizzi, Peter; Swirski, Filip K.; Figueiredo, Jose-Luiz; Waterman, Peter; Sosnovik, David E.; Aikawa, Elena; Weissleder, Ralph; Nahrendorf, Matthias] Harvard Univ, Sch Med, Charlestown, MA USA. [Libby, Peter] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu; mnahrendorf@mgh.harvard.edu OI Panizzi, Peter/0000-0003-0141-8807 FU National Institutes of Health [UO1-HL-080731, RO1-EB006432, T32-CA79443, R24-CA92782, P50-CA86355, R01HL096576]; American Heart Association [0835623D] FX This work was funded in part by National Institutes of Health grants to Dr. Weissleder (UO1-HL-080731, RO1-EB006432, T32-CA79443, R24-CA92782, P50-CA86355) and Dr. Nahrendorf (R01HL096576) and an American Heart Association grant (0835623D) to Dr. Nahrendorf. Dr. Weissleder and Mr. Waterman own shares of VisEn Medical. Manuscript received July 2, 2009, accepted August 16, 2009. NR 30 TC 111 Z9 114 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 13 PY 2010 VL 55 IS 15 BP 1629 EP 1638 DI 10.1016/j.jacc.2009.08.089 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 583AR UT WOS:000276644100013 PM 20378083 ER PT J AU Ettenhofer, ML Foley, J Castellon, SA Hinkin, CH AF Ettenhofer, Mark L. Foley, Jessica Castellon, Steven A. Hinkin, Charles H. TI Reciprocal prediction of medication adherence and neurocognition in HIV/AIDS SO NEUROLOGY LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; HIV-INFECTED ADULTS; MEMORY; METAANALYSIS; IMPAIRMENT; VALIDATION AB Background: Antiretroviral medications have been shown to benefit neurocognition in HIV/AIDS, and neurocognitive deficits are a risk factor for poor adherence to these medications. However, little is known about the predictive pathways linking medication adherence with cognitive ability. Methods: In the current 6-month cohort study, antiretroviral medication adherence was tracked prospectively among 91 HIV-positive adults using electronic monitoring. Comprehensive neuropsychological evaluations were performed at baseline and 6 months. Results: Multivariate path analyses provided evidence that antiretroviral adherence and cognitive ability are reciprocally related, although the neurocognitive pathways of this relationship appear to vary by predictive direction. Executive function and learning/ memory were most strongly predictive of levels of medication adherence achieved, whereas higher levels of adherence were predictive of relative improvements in a wide range of frontostriatal brain functions including processing speed, attention, executive functions, and motor functioning. Conclusions: These data provide evidence that cognition and adherence are reciprocally related in HIV/ AIDS. In particular, executive dysfunction may play a key role in this relationship. Interventions aimed at improving or preserving executive functions could hold promise for interrupting progressive declines in adherence and neurocognitive ability in HIV/ AIDS. Neurology (R) 2010;74:1217-1222 C1 [Ettenhofer, Mark L.; Foley, Jessica; Castellon, Steven A.; Hinkin, Charles H.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Castellon, Steven A.; Hinkin, Charles H.] VA Greater Los Angeles Hlth Care Syst, Psychol Serv, Los Angeles, CA USA. RP Ettenhofer, ML (reprint author), USUHS Dept Med & Clin Psychol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM mark.ettenhofer@usuhs.mil FU NIH [RO1 MH083553, T32 MH19535]; Veterans Administration; Breast Cancer Research Foundation FX Dr. Ettenhofer and Dr. Foley report no disclosures. Dr. Castellon performs and bills for neuropsychological assessment in his clinical practice ( 5% effort) and receives research support from the NIH (RO1 MH083553 [Co-I] and T32 MH19535 [Co-I]), the Veterans Administration ( Merit Review Grant), and the Breast Cancer Research Foundation. Dr. Hinkin performs and bills for neuropsychological assessment in his clinical practice (15% effort) and receives research support from the NIH ( RO1 MH083553 [ PI] and T32 MH19535 [ PI]) and the Veterans Administration ( Merit Review Grant). NR 19 TC 40 Z9 40 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR 13 PY 2010 VL 74 IS 15 BP 1217 EP 1222 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 581NT UT WOS:000276531400010 PM 20220123 ER PT J AU Park, Y Best, CA Badizadegan, K Dasari, RR Feld, MS Kuriabova, T Henle, ML Levine, AJ Popescu, G AF Park, YongKeun Best, Catherine A. Badizadegan, Kamran Dasari, Ramachandra R. Feld, Michael S. Kuriabova, Tatiana Henle, Mark L. Levine, Alex J. Popescu, Gabriel TI Measurement of red blood cell mechanics during morphological changes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE membrane dynamics; microrheology; quantitative phase imaging ID LIPID-BILAYER MEMBRANES; HUMAN-ERYTHROCYTES; PLASMODIUM-FALCIPARUM; DIFFRACTION PHASE; ELASTIC NETWORKS; OPTICAL TWEEZERS; TEMPERATURE; MICROSCOPY; DYNAMICS; VESICLES AB The human red blood cell (RBC) membrane, a fluid lipid bilayer tethered to an elastic 2D spectrin network, provides the principal control of the cell's morphology and mechanics. These properties, in turn, influence the ability of RBCs to transport oxygen in circulation. Current mechanical measurements of RBCs rely on external loads. Here we apply a noncontact optical interferometric technique to quantify the thermal fluctuations of RBC membranes with 3 nm accuracy over a broad range of spatial and temporal frequencies. Combining this technique with a new mathematical model describing RBC membrane undulations, we measure the mechanical changes of RBCs as they undergo a transition from the normal discoid shape to the abnormal echinocyte and spherical shapes. These measurements indicate that, coincident with this morphological transition, there is a significant increase in the membrane's shear, area, and bending moduli. This mechanical transition can alter cell circulation and impede oxygen delivery. C1 [Levine, Alex J.] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA. [Park, YongKeun; Badizadegan, Kamran; Dasari, Ramachandra R.; Feld, Michael S.; Popescu, Gabriel] MIT, George R Harrison Spect Lab, Cambridge, MA 02139 USA. [Best, Catherine A.] Univ Illinois, Coll Med, Urbana, IL 61801 USA. [Badizadegan, Kamran] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02114 USA. [Badizadegan, Kamran] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kuriabova, Tatiana] Univ Colorado, Dept Phys, Boulder, CO 80309 USA. [Henle, Mark L.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Popescu, Gabriel] Univ Illinois, Quantitat Light Imaging Lab, Dept Elect & Comp Engn, Beckman Inst Adv Sci & Technol, Urbana, IL 61801 USA. RP Levine, AJ (reprint author), Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA. EM alevine@chem.ucla.edu; gpopescu@illinois.edu RI Park, YongKeun/B-9017-2009 FU National Institutes of Health [P41-RR02594-18]; Cambridge Foundation Fellowship; Whitaker Health Sciences Fellowship; Samsung Scholarship; National Science Foundation [08-46660 CAREER, NSF-DMR-0907212] FX A.J.L. thanks W. Gelbart for enjoyable conversations. This research was supported by the National Institutes of Health (P41-RR02594-18). Y.P. was supported by Cambridge Foundation Fellowship, Whitaker Health Sciences Fellowship, and Samsung Scholarship. G.P. was partially supported by the National Science Foundation (08-46660 CAREER). A.J.L. acknowledges partial support from NSF-DMR-0907212. NR 40 TC 159 Z9 161 U1 5 U2 67 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 13 PY 2010 VL 107 IS 15 BP 6731 EP 6736 DI 10.1073/pnas.0909533107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 583AC UT WOS:000276642100033 PM 20351261 ER PT J AU Koharudin, LMI Liu, H Di Maio, R Kodali, RB Graham, SH Gronenborn, AM AF Koharudin, Leonardus M. I. Liu, Hao Di Maio, Roberto Kodali, Ravindra B. Graham, Steven H. Gronenborn, Angela M. TI Cyclopentenone prostaglandin-induced unfolding and aggregation of the Parkinson disease-associated UCH-L1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ubiquitin; NMR; neurodegeneration; protein modification; oxidative damage ID CARBOXYL-TERMINAL HYDROLASE; 15-DEOXY-DELTA(12,14)-PROSTAGLANDIN J(2); PROTEIN OXIDATION; UBIQUITIN; CYCLOOXYGENASE; PEROXIDATION; PRODUCTS; INSIGHTS; BRAIN; GENE AB Ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) has been implicated in Parkinson's disease (PD) and is present in neurofibrillary tangles or Lewy bodies. However, the molecular basis for UCH-L1s involvement in proteinacious fibril formation is still elusive, especially in regard to the pathogenicity of the I93M mutation. Here we show that modification of UCH-L1 by cyclopentenone prostaglandins causes unfolding and aggregation. A single thiol group on Cys152 reacts with the alpha,beta-unsaturated carbonyl center in the cyclopentenone ring of prostaglandins, resulting in a covalent adduct. We also show that the PD-associated I93M mutant of UCH-L1 is well-folded, structurally similar to the wild-type protein, and aggregates upon conjugation by cyclopentenone prostaglandins. Our findings suggest a possible mechanistic link between UCH-L1 modification by cyclopentenone prostaglandins and the etiology of neurodegeneration. C1 [Koharudin, Leonardus M. I.; Kodali, Ravindra B.; Gronenborn, Angela M.] Univ Pittsburgh, Sch Med, Dept Biol Struct, Pittsburgh, PA 15260 USA. [Liu, Hao; Di Maio, Roberto; Graham, Steven H.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15260 USA. [Liu, Hao; Graham, Steven H.] VA Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA 15240 USA. RP Gronenborn, AM (reprint author), Univ Pittsburgh, Sch Med, Dept Biol Struct, Pittsburgh, PA 15260 USA. EM amg100@pitt.edu RI kodali, ravindra/D-1543-2010; Di Maio, Roberto/G-1788-2015; OI Gronenborn, Angela M/0000-0001-9072-3525 FU University of Pittsburgh School of Medicine; National Institutes of Health [NS037459-10]; Fondazione Ri.MED (Sicily, Italy) fellowship [NS037459-10] FX We thank Guillermo Calero, Rieko Ishima, and In-Ja Byeon (Department of Structural Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260) for useful discussions and Mike Delk for NMR technical support. This work was a collaboration between the laboratories of S.G. and A.M.G. and was supported by startup funds from the University of Pittsburgh School of Medicine to A.M.G. and by the National Institutes of Health Grant (NS037459-10) to S.G.R.D.M. is supported by a Fondazione Ri.MED (Sicily, Italy) fellowship. NR 21 TC 35 Z9 37 U1 2 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 13 PY 2010 VL 107 IS 15 BP 6835 EP 6840 DI 10.1073/pnas.1002295107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 583AC UT WOS:000276642100051 PM 20231490 ER PT J AU Ying, HQ Zheng, HW Scott, K Wiedemeyer, R Yan, HY Lim, C Huang, J Dhakal, S Ivanova, E Xiao, YH Zhang, HL Hu, J Stommel, JM Lee, MA Chen, AJ Paik, JH Segatto, O Brennan, C Elferink, LA Wang, YA Chin, L DePinho, RA AF Ying, Haoqiang Zheng, Hongwu Scott, Kenneth Wiedemeyer, Ruprecht Yan, Haiyan Lim, Carol Huang, Joseph Dhakal, Sabin Ivanova, Elena Xiao, Yonghong Zhang, Hailei Hu, Jian Stommel, Jayne M. Lee, Michelle A. Chen, An-Jou Paik, Ji-Hye Segatto, Oreste Brennan, Cameron Elferink, Lisa A. Wang, Y. Alan Chin, Lynda DePinho, Ronald A. TI Mig-6 controls EGFR trafficking and suppresses gliomagenesis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE glioblastoma; vesicle; STX8 ID TUMOR-SUPPRESSOR; GLIOBLASTOMA-MULTIFORME; SYNTAXIN 8; CANCER; GENE; 1P; ASSOCIATION; PROGRESSION; EXPRESSION; RECEPTOR AB Glioblastoma multiforme (GBM) is the most common and lethal primary brain cancer that is driven by aberrant signaling of growth factor receptors, particularly the epidermal growth factor receptor (EGFR). EGFR signaling is tightly regulated by receptor endocytosis and lysosome-mediated degradation, although the molecular mechanisms governing such regulation, particularly in the context of cancer, remain poorly delineated. Here, high-resolution genomic profiles of GBM identified a highly recurrent focal 1p36 deletion encompassing the putative tumor suppressor gene, Mig-6. We show that Mig-6 quells the malignant potential of GBM cells and dampens EGFR signaling by driving EGFR into late endosomes and lysosome-mediated degradation upon ligand stimulation. Mechanistically, this effect is mediated by the binding of Mig-6 to a SNARE protein STX8, a protein known to be required for late endosome trafficking. Thus, Mig-6 functions to ensure recruitment of internalized receptor to late endosomes and subsequently the lysosomal degradation compartment through its ability to specifically link EGFR and STX8 during ligand-stimulated EGFR trafficking. In GBM, the highly frequent loss of Mig-6 would therefore serve to sustain aberrant EGFR-mediated oncogenic signaling. Together, these data uncover a unique tumor suppression mechanism involving the regulation of receptor trafficking. C1 [Ying, Haoqiang; Zheng, Hongwu; Scott, Kenneth; Wiedemeyer, Ruprecht; Yan, Haiyan; Lim, Carol; Huang, Joseph; Dhakal, Sabin; Hu, Jian; Stommel, Jayne M.; Lee, Michelle A.; Chen, An-Jou; Paik, Ji-Hye; Wang, Y. Alan; Chin, Lynda; DePinho, Ronald A.] Dana Farber Canc Inst, Belfer Fdn Inst Innovat Canc Sci, Dept Med Oncol, Boston, MA 02115 USA. [Ivanova, Elena; Xiao, Yonghong; Zhang, Hailei; Wang, Y. Alan; Chin, Lynda; DePinho, Ronald A.] Dana Farber Canc Inst, Belfer Fdn Inst Innovat Canc Sci, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. [Segatto, Oreste] Ist Regina Elena, Immunol Lab, I-00158 Rome, Italy. [Brennan, Cameron] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA. [Brennan, Cameron] Mem Sloan Kettering Canc Ctr, Dept Neurosurg, New York, NY 10065 USA. [Elferink, Lisa A.] Univ Texas Med Branch, Dept Neurosci & Cell Biol, Galveston, TX 77555 USA. [Chin, Lynda] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. [DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Med & Genet, Boston, MA 02115 USA. RP DePinho, RA (reprint author), Dana Farber Canc Inst, Belfer Fdn Inst Innovat Canc Sci, Dept Med Oncol, Boston, MA 02115 USA. EM ron_depinho@dfci.harvard.edu OI Zheng, Hongwu/0000-0002-5823-4913; Brennan, Cameron/0000-0003-4064-8891 FU Helen Hay Whitney Foundation; American Cancer Society [PF-07-039-01CSM]; Mildred Scheel Fellowship (Deutsche Krebshilfe).; Ruth L. Kirschstein National Research Service Award Fellowship; Damon Runyon Cancer Research Foundation; National Institutes of Health [RO1CA99041]; Foundation Institute for Innovative Cancer Science [CA119075] FX H. Ying is a recipient of the Marsha Mae Moeslein Fellowship from the American Brain Tumor Association. H. Zheng was supported by Helen Hay Whitney Foundation. K.L.S. is supported by a Postdoctoral Fellowship from the American Cancer Society (PF-07-039-01CSM). R. W. is supported by a Mildred Scheel Fellowship (Deutsche Krebshilfe). J.M.S. is supported by a Ruth L. Kirschstein National Research Service Award Fellowship. J.-H.P. was supported by the Damon Runyon Cancer Research Foundation. Grant support comes from the Goldhirsh Foundation (R.A.D.) and from National Institutes of Health Grants RO1CA99041 (to L.C.), 5P01CA95616 (to L.C., and R.A.D), and CA119075 (to L. A. E.). R. A. D. is an American Cancer Society Research Professor supported by the Robert A. and Renee E. Belfer Foundation Institute for Innovative Cancer Science. NR 24 TC 51 Z9 53 U1 1 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 13 PY 2010 VL 107 IS 15 BP 6912 EP 6917 DI 10.1073/pnas.0914930107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 583AC UT WOS:000276642100064 PM 20351267 ER PT J AU Poliseno, L Salmena, L Riccardi, L Fornari, A Song, MS Hobbs, RM Sportoletti, P Varmeh, S Egia, A Fedele, G Rameh, L Loda, M Pandolfi, PP AF Poliseno, Laura Salmena, Leonardo Riccardi, Luisa Fornari, Alessandro Song, Min Sup Hobbs, Robin M. Sportoletti, Paolo Varmeh, Shorheh Egia, Ainara Fedele, Giuseppe Rameh, Lucia Loda, Massimo Pandolfi, Pier Paolo TI Identification of the miR-106b similar to 25 MicroRNA Cluster as a Proto-Oncogenic PTEN-Targeting Intron That Cooperates with Its Host Gene MCM7 in Transformation SO SCIENCE SIGNALING LA English DT Article ID MAINTENANCE PROTEIN MCM7; PROSTATE-CANCER; CELLULAR-TRANSFORMATION; TUMOR SUPPRESSION; MYC PROTEIN; EXPRESSION; NEUROBLASTOMA; TUMORIGENESIS; SPECIFICITY; ACTIVATION AB PTEN (phosphatase and tensin homolog deleted on chromosome 10) is a tumor suppressor that antagonizes signaling through the phosphatidylinositol-3-kinase-Akt pathway. We have demonstrated that subtle decreases in PTEN abundance can have critical consequences for tumorigenesis. Here, we used a computational approach to identify miR-22, miR-25, and miR-302 as three PTEN-targeting microRNA (miRNA) families found within nine genomic loci. We showed that miR-22 and the miR-106b similar to 25 cluster are aberrantly overexpressed in human prostate cancer, correlate with abundance of the miRNA processing enzyme DICER, and potentiate cellular transformation both in vitro and in vivo. We demonstrated that the intronic miR-106b similar to 25 cluster cooperates with its host gene MCM7 in cellular transformation both in vitro and in vivo, so that the concomitant overexpression of MCM7 and the miRNA cluster triggers prostatic intraepithelial neoplasia in transgenic mice. Therefore, the MCM7 gene locus delivers two simultaneous oncogenic insults when amplified or overexpressed in human cancer. Thus, we have uncovered a proto-oncogenic miRNA-dependent network for PTEN regulation and defined the MCM7 locus as a critical factor in initiating prostate tumorigenesis. C1 [Poliseno, Laura; Salmena, Leonardo; Riccardi, Luisa; Song, Min Sup; Hobbs, Robin M.; Sportoletti, Paolo; Varmeh, Shorheh; Egia, Ainara; Pandolfi, Pier Paolo] Harvard Univ, Beth Israel Deaconess Med Ctr, Canc Genet Program, Sch Med,Dept Med, Boston, MA 02215 USA. [Poliseno, Laura; Salmena, Leonardo; Riccardi, Luisa; Song, Min Sup; Hobbs, Robin M.; Sportoletti, Paolo; Varmeh, Shorheh; Egia, Ainara; Pandolfi, Pier Paolo] Harvard Univ, Beth Israel Deaconess Med Ctr, Canc Genet Program, Sch Med,Dept Pathol, Boston, MA 02215 USA. [Fornari, Alessandro; Fedele, Giuseppe; Loda, Massimo] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Fornari, Alessandro] Univ Turin, Molinette Hosp, Dept Biomed Sci & Human Oncol, I-10126 Turin, Italy. [Fedele, Giuseppe; Loda, Massimo] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Rameh, Lucia] Boston Biomed Res Inst, Watertown, MA 02472 USA. RP Pandolfi, PP (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Canc Genet Program, Sch Med,Dept Med, Boston, MA 02215 USA. EM ppandolf@bidmc.harvard.edu RI Poliseno, Laura/B-5711-2012; OI Poliseno, Laura/0000-0001-6557-955X; Hobbs, Robin/0000-0002-3853-2614; SPORTOLETTI, PAOLO/0000-0002-5630-9862 FU Canadian Institutes of Health Research; NCI NIH HHS [P50 CA092629, P50 CA092629-09, R01 CA-82328-0, R01 CA082328, R01 CA082328-14, R01 CA102142] NR 54 TC 229 Z9 238 U1 2 U2 7 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1945-0877 EI 1937-9145 J9 SCI SIGNAL JI Sci. Signal. PD APR 13 PY 2010 VL 3 IS 117 AR ra29 DI 10.1126/scisignal.2000594 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 583AY UT WOS:000276644900002 PM 20388916 ER PT J AU Fletcher, AL Lukacs-Kornek, V Reynoso, ED Pinner, SE Bellemare-Pelletier, A Curry, MS Collier, AR Boyd, RL Turley, SJ AF Fletcher, Anne L. Lukacs-Kornek, Veronika Reynoso, Erika D. Pinner, Sophie E. Bellemare-Pelletier, Angelique Curry, Mark S. Collier, Ai-Ris Boyd, Richard L. Turley, Shannon J. TI Lymph node fibroblastic reticular cells directly present peripheral tissue antigen under steady-state and inflammatory conditions SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID THYMIC EPITHELIAL-CELLS; GENE-EXPRESSION; STROMAL CELLS; CUTTING EDGE; TOLERANCE; SELF; HETEROGENEITY; AUTOIMMUNITY; PATHWAYS; REVEALS AB Lymph node stromal cells (LNSCs) can induce potent, antigen-specific T cell tolerance under steady-state conditions. Although expression of various peripheral tissue-restricted antigens (PTAs) and presentation to naive CD8(+) T cells has been demonstrated, the stromal subsets responsible have not been identified. We report that fibroblastic reticular cells (FRCs), which reside in the T cell zone of the LN, ectopically express and directly present a model PTA to naive T cells, inducing their proliferation. However, we found that no single LNSC subset was responsible for PTA expression; rather, each subset had its own characteristic antigen display. Studies to date have concentrated on PTA presentation under steady-state conditions; however, because LNs are frequently inflammatory sites, we assessed whether inflammation altered stromal cell-T cell interactions. Strikingly, FRCs showed reduced stimulation of T cells after Toll-like receptor 3 ligation. We also characterize an LNSC subset expressing the highest levels of autoimmune regulator, which responds potently to bystander inflammation by up-regulating PTA expression. Collectively, these data show that diverse stromal cell types have evolved to constitutively express PTAs, and that exposure to viral products alters the interaction between T cells and LNSCs. C1 [Fletcher, Anne L.; Lukacs-Kornek, Veronika; Reynoso, Erika D.; Pinner, Sophie E.; Bellemare-Pelletier, Angelique; Collier, Ai-Ris; Turley, Shannon J.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Curry, Mark S.] Dana Farber Canc Inst, Flow Cytometry Core Facil, Boston, MA 02115 USA. [Reynoso, Erika D.] Harvard Univ, Sch Med, Div Med Sci, Boston, MA 02115 USA. [Turley, Shannon J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Boyd, Richard L.] Monash Univ, Monash Immunol & Stem Cell Labs, Clayton, Vic 3800, Australia. RP Turley, SJ (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM Shannon_Turley@dfci.harvard.edu RI Acton, Sophie/G-9784-2012 OI Acton, Sophie/0000-0003-2704-716X FU National Institutes of Health [R01 DK074500, P01 AI045757]; National Health Medical Research Council FX This work was supported by National Institutes of Health grants R01 DK074500 and P01 AI045757 (to S. J. Turley), and a National Health Medical Research Council Postdoctoral Biomedical Training Fellowship (to A. L. Fletcher). NR 28 TC 144 Z9 148 U1 0 U2 7 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD APR 12 PY 2010 VL 207 IS 4 BP 689 EP 697 DI 10.1084/jem.20092642 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 581VJ UT WOS:000276552700004 PM 20308362 ER PT J AU Sweet, RA Bennett, DA Graff-Radford, NR Mayeux, R AF Sweet, Robert A. Bennett, David A. Graff-Radford, Neill R. Mayeux, Richard CA Natl Inst Aging TI Assessment and familial aggregation of psychosis in Alzheimer's disease from the National Institute on Aging Late Onset Alzheimer's Disease Family Study SO BRAIN LA English DT Article DE Alzheimer's disease; family study; genetics; psychiatric comorbidity ID GENOME-WIDE ASSOCIATION; NEUROPSYCHIATRIC INVENTORY; COGNITIVE IMPAIRMENT; IDENTIFIES VARIANTS; SYMPTOMS; SORL1; RISK; DEMENTIA; GENE; PHENOTYPE AB Determining the genetic architecture of late onset Alzheimer's disease remains an important research objective. One approach to the identification of novel genetic variants contributing to the disease is the classification of biologically meaningful subgroups within the larger late-onset Alzheimer's disease phenotype. The occurrence of psychotic symptoms in patients with late-onset Alzheimer's disease may identify one such group. We attempted to establish methods for the reliable assessment of psychotic symptoms in a large, geographically dispersed collection of families, multiply affected with late onset Alzheimer's disease, who were participants in the larger National Institute on Aging Late Onset Alzheimer's Disease Family Study; and to characterize the correlates and familial aggregation of psychosis within this cohort. We found that reliable assessments of psychotic symptoms during in-person or phone interviews were readily implemented. The presence of psychosis in late onset Alzheimer's disease was significantly associated with degree of cognitive impairment, and significantly, albeit modestly, correlated with the severity of other behavioural symptoms. Psychosis significantly aggregated within late onset Alzheimer's disease families suggesting that it may identify a genetically determined subgroup. Future studies should examine the linkage and association of psychosis with genetic variation within these families. C1 [Sweet, Robert A.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Sweet, Robert A.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Sweet, Robert A.] VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr 4, Pittsburgh, PA USA. [Bennett, David A.] Rush Univ, Med Ctr, Dept Neurol, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA. [Graff-Radford, Neill R.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Mayeux, Richard] Columbia Univ, Dept Neurol, New York, NY 10027 USA. [Mayeux, Richard] Columbia Univ, Dept Psychiat, New York, NY 10027 USA. [Mayeux, Richard] Columbia Univ, Dept Epidemiol, New York, NY 10027 USA. RP Sweet, RA (reprint author), Biomed Sci Tower,Rm W-1645,3811 OHara St, Pittsburgh, PA 15213 USA. EM sweetra@upmc.edu OI Farrer, Lindsay/0000-0001-5533-4225 FU NIA NIH HHS [P30AG008017, P01AG02219, P01AG03991, P01AG05138, P30 AG013854, P30 AG013854-14, P30 AG013854-15, P30AG010133, P30AG028377, P30AG028383, P30AG10124, P30AG10161, P30AG12300, P30AG13854, P50 AG005133, P50 AG005133-210020, P50 AG005136, P50 AG005136-28, P50AG005133, P50AG016579, P50AG016582, P50AG05134, P50AG05136, P50AG05138, P50AG05142, P50AG05681, P50AG08702, P50AG165574, R01 AG027224, R01 AG027224-04, R01 AG027342, R01AG027224, U24 AG021886, U24AG021886, U24AG026395] NR 35 TC 25 Z9 25 U1 2 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD APR 10 PY 2010 VL 133 BP 1155 EP 1162 DI 10.1093/brain/awq001 PN 4 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 590KU UT WOS:000277225600018 PM 20147454 ER PT J AU Rickards, LD McGraw, SA Araki, L Casey, RJ High, CW Hombs, ME Raysor, RS AF Rickards, Lawrence D. McGraw, Sarah A. Araki, Lynnette Casey, Roger J. High, Cynthia W. Hombs, Mary Ellen Raysor, Robyn S. TI Collaborative Initiative to Help End Chronic Homelessness: Introduction SO JOURNAL OF BEHAVIORAL HEALTH SERVICES & RESEARCH LA English DT Article ID SEVERE MENTAL-ILLNESS; SUBSTANCE USE DISORDERS; NEW-YORK-CITY; DUAL DIAGNOSIS; HEALTH-SERVICES; PSYCHIATRIC DISABILITIES; COST-EFFECTIVENESS; HOUSING 1ST; CARE; INDIVIDUALS AB The Collaborative Initiative to Help End Chronic Homelessness was a coordinated effort by the US Departments of Health and Human Services (HHS), Housing and Urban Development (HUD), and Veterans Affairs (VA), and the US Interagency Council on Homelessness to house and provide comprehensive supportive services to individuals with serious psychiatric, substance use, health, and related disabilities who were experiencing long-term chronic homelessness. Eleven communities received 3-year grants from HHS and VA (2003-2006) and up to 5-year grants from HUD (2003-2008) to implement the initiative. This article provides background on chronic homelessness, describes the federal collaboration to comprehensively address chronic homelessness, and introduces the seven articles in this special issue that describe the findings and lessons learned from the participating communities in addressing chronic homelessness. Collectively, these articles offer insight into the challenges and benefits of providing housing and services to individuals experiencing chronic homelessness. C1 [McGraw, Sarah A.] New England Res Inst, Ctr Qualitat Res, Watertown, MA 02472 USA. [Rickards, Lawrence D.] Subst Abuse & Mental Hlth Serv Adm, Homeless Programs Branch, Ctr Mental Hlth Serv, US Dept HHS, Rockville, MD 20420 USA. [Araki, Lynnette] US Hlth Resources & Serv Adm, Off Planning Evaluat & Legislat, US Dept HHS, Rockville, MD 20857 USA. [Casey, Roger J.] US Dept Vet Affairs, Homeless Grant Per Diem Program, Off Mental Hlth Serv 116E, Washington, DC 20420 USA. [High, Cynthia W.] US Dept Housing & Urban Dev, Special Needs Assistance Program, Off Community Planning & Dev, Washington, DC 20036 USA. [Hombs, Mary Ellen] US Interagcy Council Homelessness, Washington, DC USA. [Raysor, Robyn S.] US Dept Housing & Urban Dev, Special Needs Assistance Program, Off Community Planning & Dev, Washington, DC 20041 USA. RP McGraw, SA (reprint author), New England Res Inst, Ctr Qualitat Res, 9 Galen St, Watertown, MA 02472 USA. EM LDRickards@msn.com; smcgraw@neriscience.com; laraki@hrsa.gov; Roger.Casey@va.gov; Cynthia.W.High@HUD.gov; Maryellen.Hombs@USICH.gov; Robyn.S.Raysor@HUD.gov NR 62 TC 11 Z9 11 U1 1 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1094-3412 J9 J BEHAV HEALTH SER R JI J. Behav. Health Serv. Res. PD APR 10 PY 2010 VL 37 IS 2 BP 149 EP 166 DI 10.1007/s11414-009-9175-1 PG 18 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 580HJ UT WOS:000276438400003 PM 19337841 ER PT J AU Bellmunt, J Choueiri, TK Fougeray, R Schutz, FAB Salhi, Y Winquist, E Culine, S von der Maase, H Vaughn, DJ Rosenberg, JE AF Bellmunt, Joaquim Choueiri, Toni K. Fougeray, Ronan Schutz, Fabio A. B. Salhi, Yacine Winquist, Eric Culine, Stephane von der Maase, Hans Vaughn, David J. Rosenberg, Jonathan E. TI Prognostic Factors in Patients With Advanced Transitional Cell Carcinoma of the Urothelial Tract Experiencing Treatment Failure With Platinum-Containing Regimens SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID LONG-TERM-SURVIVAL; PHASE-II TRIAL; GEMCITABINE PLUS CISPLATIN; BLADDER-CANCER; CHEMOTHERAPY; METHOTREXATE; VINFLUNINE; TUMORS; VINBLASTINE; DOXORUBICIN AB Purpose The present study sought to identify pretreatment [prognostic factors for overall survival (OS) in patients with metastatic transitional cell carcinoma of the urothelial tract (TCCU) who experienced treatment failure with the first-line, platinum-based regimen included in the phase III vinflunine trial. Patients and Methods In total, 370 patients with platinum-refractory TCCU were included in this analysis. Potential prognostic factors were recorded prospectively. Univariate analysis was used to identify clinical and laboratory factors that significantly impact survival. Multivariate analysis was used to identify independent prognostic factors, and bootstrap analysis was performed for internal validation, forming a prognostic model. External validation was performed on the phase II vinflunine study CA183001. Results Multivariate analysis and the internal validation identified Eastern Cooperative Oncology Group performance status (PS) more than 0, hemoglobin level less than 10 g/dL, and the presence of liver metastasis as the main adverse prognostic factors for OS. External validation confirmed these prognostic factors. Four subgroups were formed based on the presence of zero, one, two, or three prognostic factors; the median OS times for these groups were 14.2, 7.3, 3.8, and 1.7 months (P < .001), respectively. Conclusion We identified and both internally and externally validated three adverse risk factors (PS, hemoglobin level, and liver metastasis) that predict for OS and developed a scoring system that classifies patients with platinum-refractory disease on second-line chemotherapy into four risk groups with different outcome. Similar to the first-line setting, the presence of visceral metastases and poor PS predict a worse prognosis. These factors, together with low hemoglobin, can be used for prognostication and future patient stratification in clinical trials. C1 [Bellmunt, Joaquim] Univ Hosp Del Mar, Dept Med Oncol, Inst Municipal Invest Med, E-08003 Barcelona, Spain. Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Inst Rech Pierre Fabre, Boulogne, France. Hop Henri Mondor, F-94010 Creteil, France. Univ Western Ontario, London, ON, Canada. Rigshosp, DK-2100 Copenhagen, Denmark. RP Bellmunt, J (reprint author), Univ Hosp Del Mar, Dept Med Oncol, Inst Municipal Invest Med, Passeig Maritim 25-29, E-08003 Barcelona, Spain. EM jbellmunt@imas.imim.es FU Pierre Fabre Medicament, Boulogne, France FX Supported by Pierre Fabre Medicament, Boulogne, France. NR 20 TC 134 Z9 134 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 APR 10 PY 2010 VL 28 IS 11 BP 1850 EP 1855 DI 10.1200/JCO.2009.25.4599 PG 6 WC Oncology SC Oncology GA 580OC UT WOS:000276457800008 PM 20231682 ER PT J AU Wen, PY Macdonald, DR Reardon, DA Cloughesy, TF Sorensen, AG Galanis, E DeGroot, J Wick, W Gilbert, MR Lassman, AB Tsien, C Mikkelsen, T Wong, ET Chamberlain, MC Stupp, R Lamborn, KR Vogelbaum, MA van den Bent, MJ Chang, SM AF Wen, Patrick Y. Macdonald, David R. Reardon, David A. Cloughesy, Timothy F. Sorensen, A. Gregory Galanis, Evanthia DeGroot, John Wick, Wolfgang Gilbert, Mark R. Lassman, Andrew B. Tsien, Christina Mikkelsen, Tom Wong, Eric T. Chamberlain, Marc C. Stupp, Roger Lamborn, Kathleen R. Vogelbaum, Michael A. van den Bent, Martin J. Chang, Susan M. TI Updated Response Assessment Criteria for High-Grade Gliomas: Response Assessment in Neuro-Oncology Working Group SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RECURRENT MALIGNANT GLIOMA; MAGNETIC-RESONANCE-SPECTROSCOPY; BEVACIZUMAB PLUS IRINOTECAN; ADULT BRAIN-TUMORS; GLIOBLASTOMA PATIENTS; PHASE-II; CLINICAL-APPLICATIONS; CONTRAST ENHANCEMENT; RADIATION-THERAPY; IMAGING CHANGES AB Currently, the most widely used criteria for assessing response to therapy in high-grade gliomas are based on two-dimensional tumor measurements on computed tomography (CO or magnetic resonance imaging (MRI), in conjunction with clinical assessment and corticosteroid dose (the Macdonald Criteria). It is increasingly apparent that there are significant limitations to these criteria, which only address the contrast-enhancing component of the tumor. For example, chemoradiotherapy for newly diagnosed glioblastomas results in transient increase in tumor enhancement (pseudoprogression) in 20% to 30% of patients, which is difficult to differentiate from true tumor progression. Antiangiogenic agents produce high radiographic response rates, as defined by a rapid decrease in contrast enhancement on CT/MRI that occurs within days of initiation of treatment and that is partly a result of reduced vascular permeability to contrast agents rather than a true antitumor effect. In addition, a subset of patients treated with antiangiogenic agents develop tumor recurrence characterized by an increase in the nonenhancing component depicted on T2-weighted/fluid-attenuated inversion recovery sequences. The recognition that contrast enhancement is nonspecific and may not always be a true surrogate of tumor response and the need to account for the nonenhancing component of the tumor mandate that new criteria be developed and validated to permit accurate assessment of the efficacy of novel therapies. The Response Assessment in Neuro-Oncology Working Group is an international effort to develop new standardized response criteria for clinical trials in brain tumors. In this proposal, we present the recommendations for updated response criteria for high-grade gliomas. C1 [Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Neurol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Dept Neurol, Brain Tumor Ctr, Boston, MA 02215 USA. Duke Univ, Med Ctr, Preston Robert Tisch Brain Tumor Ctr, Durham, NC USA. Univ Calif Los Angeles, David Geffen Sch Med, Neurooncol Program, Los Angeles, CA 90095 USA. Univ Calif San Francisco, Dept Neurol Surg, Div Neurooncol, San Francisco, CA 94143 USA. Mayo Clin, Dept Med Oncol, Rochester, MN USA. Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Brain Tumor Ctr, New York, NY 10021 USA. Univ Michigan, Med Ctr, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. Henry Ford Hosp, Dept Neurooncol, Detroit, MI 48202 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Cleveland Clin, Dept Neurol, Brain Tumor & Neurooncol Ctr, Cleveland, OH 44106 USA. Univ Western Ontario, London Reg Canc Program, Dept Med Oncol, London, ON, Canada. Univ Heidelberg, Dept Neurooncol, Heidelberg, Germany. CHU Vaudois, CH-1011 Lausanne, Switzerland. Univ Lausanne, Lausanne, Switzerland. Erasmus Univ Hosp, Dr Daniel Den Hoed Canc Ctr, Neurooncol Unit, Rotterdam, Netherlands. RP Wen, PY (reprint author), Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, SW430D,44 Binney St, Boston, MA 02115 USA. EM pwen@partners.org RI leng, xianwei/F-9073-2011; Gilbert, Mark/J-7494-2016 OI Gilbert, Mark/0000-0003-2556-9722 NR 56 TC 991 Z9 1002 U1 6 U2 53 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 APR 10 PY 2010 VL 28 IS 11 BP 1963 EP 1972 DI 10.1200/JCO.2009.26.3541 PG 10 WC Oncology SC Oncology GA 580OC UT WOS:000276457800023 PM 20231676 ER PT J AU Lasky-Su, J Won, S Mick, E Anney, RJL Franke, B Neale, B Biederman, J Smalley, SL Loo, SK Todorov, A Faraone, SV Weiss, ST Lange, C AF Lasky-Su, Jessica Won, Sungho Mick, Eric Anney, Richard J. L. Franke, Barbara Neale, Benjamin Biederman, Joseph Smalley, Susan L. Loo, Sandra K. Todorov, Alexandre Faraone, Stephen V. Weiss, Scott T. Lange, Christoph TI On Genome-wide Association Studies for Family-Based Designs: An Integrative Analysis Approach Combining Ascertained Family Samples with Unselected Controls SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; SCAN; GENE; REPLICATION; VARIANTS; TESTS; RISK; ADHD; SET AB Large numbers of control individuals with genome-wide genotype data are now available through various databases. These controls are regularly used in case-control genome-wide association studies (GWAS) to increase the statistical power. Controls are often "unselected" for the disease of interest and are not matched to cases in terms of confounding factors, making the studies more vulnerable to confounding as a result of population stratification. In this communication, we demonstrate that family-based designs can integrate unselected controls from other studies into the analysis without compromising the robustness of family-based designs against genetic confounding. The result is a hybrid case-control family-based analysis that achieves higher power levels than population-based studies with the same number of cases and controls. This strategy is widely applicable and works ideally for all situations in which both family and case-control data are available. The approach consists of three steps. First, we perform a standard family-based association test that does not utilize the between-family component. Second, we use the between-family information in conjunction with the genotypes from unselected controls in a Cochran-Armitage trend test. The p values from this step are then calculated by rank ordering the individual Cochran-Armitage trend test statistics for the genotype markers. Third, we generate a combined p value with the association p values from the first two steps. Simulation studies are used to assess the achievable power levels of this method compared to standard analysis approaches. We illustrate the approach by an application to a GWAS of attention deficit hyperactivity disorder parent-offspring trios and publicly available controls. C1 [Lasky-Su, Jessica; Weiss, Scott T.; Lange, Christoph] Brigham & Womens Hosp, Channing Labs, Boston, MA 02115 USA. [Lasky-Su, Jessica; Weiss, Scott T.; Lange, Christoph] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Lasky-Su, Jessica; Weiss, Scott T.; Lange, Christoph] Brigham & Womens Hosp, Ctr Genom Med, Boston, MA 02115 USA. [Won, Sungho] Chung Ang Univ, Dept Stat, Coll Nat Sci, Seoul 156756, South Korea. [Won, Sungho] Chung Ang Univ, Res Ctr Data Sci, Seoul 156756, South Korea. [Mick, Eric; Biederman, Joseph] Massachusetts Gen Hosp, Clin & Res Programs Pediat Psychiat & Adult ADHD, Dept Psychiat, Boston, MA 02114 USA. [Anney, Richard J. L.] Trinity Coll Dublin, Neuropsychiat Genet Res Grp, Dept Psychiat, Dublin 8, Ireland. [Franke, Barbara] Radboud Univ Nijmegen, Dept Human Genet, Med Ctr, Donders Inst Brain Cognit & Behav, NL-6500 HB Nijmegen, Netherlands. [Franke, Barbara] Radboud Univ Nijmegen, Dept Psychiat, Med Ctr, Donders Inst Brain Cognit & Behav, NL-6500 HB Nijmegen, Netherlands. [Neale, Benjamin] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Neale, Benjamin] Broad Inst, Cambridge, MA 02142 USA. [Smalley, Susan L.; Loo, Sandra K.] Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA 90095 USA. [Todorov, Alexandre] Washington Univ, Dept Psychiat, St Louis, MO 63130 USA. [Faraone, Stephen V.; Weiss, Scott T.] SUNY Upstate Med Univ, Syracuse, NY 13210 USA. [Lange, Christoph] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Lasky-Su, J (reprint author), Brigham & Womens Hosp, Channing Labs, Boston, MA 02115 USA. EM rejas@channing.harvard.edu RI Franke, Barbara/D-4836-2009; OI Franke, Barbara/0000-0003-4375-6572; Mick, Eric/0000-0001-8505-8145; Anney, Richard/0000-0002-6083-407X; Faraone, Stephen/0000-0002-9217-3982 FU McNeil Pediatrics; Ortho-McNeil Janssen Scientific Affairs; Pfizer; Shire Pharmaceuticals; National Institute of Mental Health; Eli Lilly; National institutes of Health (NIH); McNeil; Janssen; Novartis; Alza; AstraZeneca; Bristol Myers Squibb; Merck; Organon; Otsuka; National Institute of Child Health and Human Development; Fundacion Areces; Medice Pharmaceuticals; Spanish Child Psychiatry Association; Abbott; Celltech; Cephalon; Esai; Forest; Glaxo; Gliatech; National Alliance for Research on Schizophrenia and Depression; National Institute on Drug Abuse; New River; Noven; Neurosearch; Pharmacia; Prechter Foundation; Stanley Foundation; UCB Pharma; Wyeth; [KHL096840A]; [R01MH081862]; [1R01MH087590]; [P01 HL083069]; [mu 63706]; [NS54124]; [R01MH062873]; [U01MH085518]; [R01MH081803] FX This work is supported by the following grants: KHL096840A awarded to J.L.-S., R01MH081862 and 1R01MH087590 awarded to CL., P01 HL083069 awarded to s.T.w., mu 63706 awarded to S.L.S., NS54124 awarded to S.K.L., and R01MH062873, U01MH085518, and R01MH081803 awarded to S.V.F. E.M. receives research support from McNeil Pediatrics, Ortho-McNeil Janssen Scientific Affairs, Pfizer, Shire Pharmaceuticals, and the National Institute of Mental Health and has had a consulting relationship with Shire Pharmaceuticals. In the past year, S.V.F. has received consulting fees and been on advisory boards for Eli Lilly, Ortho-McNeil, and Shire Development and has received research support from Eli Lilly, Pfizer, Shire, and the National institutes of Health (NIH). In previous years, he has received research support and/or consulting fees from Eli Lilly, McNeil, Janssen, Novartis, Shire, Pfizer, and NIH. J.B. is currently receiving research support from the following: Alza, AstraZeneca, Bristol Myers Squibb, Eli Lilly, Janssen Pharmaceuticals, McNeil, Merck, Organon, Otsuka, Shire, the National Institute of Mental Health, and the National Institute of Child Health and Human Development. In 2009, J.B. received a speaker's fee from the following sources: Fundacion Areces, Medice Pharmaceuticals, and the Spanish Child Psychiatry Association. In previous years, J.B. received research support, consultation fees, or speaker's fees for and/or from the following additional sources: Abbott, AstraZeneca, Celltech, Cephalon, Eli Lilly, Esai, Forest, Glaxo, Gliatech, Janssen, McNeil, the National Alliance for Research on Schizophrenia and Depression, the National Institute on Drug Abuse, New River, Novartis, Noven, Neurosearch, Pfizer, Pharmacia, The Prechter Foundation, Shire, The Stanley Foundation, UCB Pharma, and Wyeth. NR 27 TC 21 Z9 22 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD APR 9 PY 2010 VL 86 IS 4 BP 573 EP 580 DI 10.1016/j.ajhg.2010.02.019 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 583YP UT WOS:000276716800007 PM 20346434 ER PT J AU Izawa, A Schatton, T Frank, NY Ueno, T Yamaura, K Pendse, SS Margaryan, A Grimm, M Gasser, M Waaga-Gasser, AM Sayegh, MH Frank, MH AF Izawa, Atsushi Schatton, Tobias Frank, Natasha Y. Ueno, Takuya Yamaura, Kazuhiro Pendse, Shona S. Margaryan, Armen Grimm, Martin Gasser, Martin Waaga-Gasser, Ana Maria Sayegh, Mohamed H. Frank, Markus H. TI A novel in vivo regulatory role of P-glycoprotein in alloimmunity SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE P-glycoprotein; Immunity; Transplantation; T cell; Antigen presenting cell; CD86 ID CYTOTOXIC EFFECTOR FUNCTION; T-CELLS; EXPRESSION; DIFFERENTIATION; LYMPHOCYTES; CYTOKINES; TRANSPORT; BLOCKADE; RELEASE; PRODUCT AB P-glycoprotein (P-gp) is required for adaptive immunity through defined functions in T cell activation and antigen presenting cell (APC) maturation The potential role of P-gp as an in vivo regulator of alloimmunity is currently unknown Here we show that P-gp blockade prolongs graft survival in a murine heterotopic cardiac allotransplantation model through in vivo inhibition of the T helper 1 (Th1) cytokine IFN-gamma and the Th2 product IL-4, and via downregulation of the APC-expressed positive costimulatory molecule CD80 In vitro, the P-gp antagonist PSC833, a non-calcineurin-inhibitory cyclosporine A analogue, specifically inhibited cellular efflux of the P-gp substrate rhodamine-123 in wild-type CD3(+) T cells and MHC class II(+) APCs but not their P-gp knockout counterparts that lacked rhodamine-123 efflux capacity Additionally, P-gp blockade significantly inhibited murine alloimmune T cell activation in a dose-dependent fashion In vivo, P-gp blockade significantly prolonged graft survival in Balb/c recipients of C57BL/6 cardiac allografts from 85 +/- 05 to 117 +/- 05 days (P < 001), similar in magnitude to the effects of monotherapy with cyclosporine A Moreover, P-gp blockade. compared to controls, attenuated intragraft expression of CD3 and CD80, but not CD86, and inhibited IFN-gamma and IL-4 production (P < 0 05) In the setting of systemic CD86 inhibition, P-gp blockade suppressed IFN-gamma and IL-4 production significantly further (to 98% and 89% inhibition, respectively) compared to either P-gp or anti-CD86 blockade alone, and markedly prolonged allograft survival compared to anti-CD86 blockade alone (40 5 4 6 versus 225 +/- 26 days, respectively, P < 0.01) Our findings define a novel in vivo regulatory role of P-gp in alloimmunity and identify P-gp as a potential therapeutic target in allotransplantation (C) 2010 Elsevier Inc All rights reserved C1 [Frank, Natasha Y.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Genet, Boston, MA 02115 USA. [Izawa, Atsushi; Schatton, Tobias; Ueno, Takuya; Yamaura, Kazuhiro; Pendse, Shona S.; Margaryan, Armen; Sayegh, Mohamed H.; Frank, Markus H.] Childrens Hosp, Transplantat Res Ctr, Boston, MA 02115 USA. [Frank, Natasha Y.] VA Boston Healthcare Syst, Dept Med, Boston, MA USA. [Grimm, Martin; Gasser, Martin; Waaga-Gasser, Ana Maria] Univ Wurzburg, Sch Med, Dept Surg, Wurzburg, Germany. [Frank, Markus H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Dermatol, Boston, MA 02115 USA. RP Frank, MH (reprint author), Childrens Hosp, Transplantat Res Ctr, 300 Longwood Ave, Boston, MA 02115 USA. RI Frank, Markus/O-1625-2014 OI Frank, Markus/0000-0002-1312-0488 FU National Institutes of Health [KO8AI50783, 1RO1CA113796, KO8NS051349, P01A150151]; American Society of Transplantation; National Kidney Foundation of MA/RI/NH/VT; American Heart Association Founders Affiliate FX We thank Novartis Pharmaceuticals (East Hanover, NJ) for providing PSC833 This work was supported by the National Institutes of Health (NIH Grants KO8AI50783 and 1RO1CA113796 to M H F., KO8NS051349 to N.Y.F., and P01A150151 to M.H S.), the AST Council Faculty Grant Award of the American Society of Transplantation (M H.F.), the Theodore Steinman Award in Clinical Research of the National Kidney Foundation of MA/RI/NH/VT (M H F.), and a Post-doctoral Fellowship Award from the American Heart Association Founders Affiliate (T S) NR 22 TC 6 Z9 7 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 9 PY 2010 VL 394 IS 3 BP 646 EP 652 DI 10.1016/j.bbrc.2010.03.040 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 584WY UT WOS:000276785900037 PM 20230790 ER PT J AU Penno, A Reilly, MM Houlden, H Laura, M Rentsch, K Niederkofler, V Stoeckli, ET Nicholson, G Eichler, F Brown, RH von Eckardstein, A Hornemann, T AF Penno, Anke Reilly, Mary M. Houlden, Henry Laura, Matilde Rentsch, Katharina Niederkofler, Vera Stoeckli, Esther T. Nicholson, Garth Eichler, Florian Brown, Robert H., Jr. von Eckardstein, Arnold Hornemann, Thorsten TI Hereditary Sensory Neuropathy Type 1 Is Caused by the Accumulation of Two Neurotoxic Sphingolipids SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SERINE-PALMITOYLTRANSFERASE; CERAMIDE SYNTHASE; NERVOUS-SYSTEM; CELL-SURFACE; IN-VIVO; HSAN-I; SPTLC1; METABOLISM; MUTATIONS; 1-PHOSPHATE AB HSAN1 is an inherited neuropathy found to be associated with several missense mutations in the SPTLC1 subunit of serine palmitoyltransferase (SPT). SPT catalyzes the condensation of serine and palmitoyl-CoA, the initial step in the de novo synthesis of sphingolipids. Here we show that the HSAN1 mutations induce a shift in the substrate specificity of SPT, which leads to the formation of the two atypical deoxy-sphingoid bases (DSBs) 1-deoxy-sphinganine and 1-deoxymethyl-sphinganine. Both metabolites lack the C(1) hydroxyl group of sphinganine and can therefore neither be converted to complex sphingolipids nor degraded. Consequently, they accumulate in the cell, as demonstrated in HEK293 cells over-expressing mutant SPTLC1 and lymphoblasts of HSAN1 patients. Elevated DSB levels were also found in the plasma of HSAN1 patients and confirmed in three groups of HSAN1 patients with different SPTLC1mutations. The DSBs show pronounced neurotoxic effects on neurite formation in cultured sensory neurons. The neurotoxicity co-occurs with a disturbed neurofilament structure in neurites when cultured in the presence of DSBs. Based on these observations, we conclude that HSAN1 is caused by a gain of function mutation, which results in the formation of two atypical and neurotoxic sphingolipid metabolites. C1 [Penno, Anke; Rentsch, Katharina; von Eckardstein, Arnold; Hornemann, Thorsten] Univ Zurich Hosp, Inst Clin Chem, CH-8091 Zurich, Switzerland. [Penno, Anke; von Eckardstein, Arnold; Hornemann, Thorsten] ETH, Competence Ctr Syst Physiol & Metab Dis, CH-8093 Zurich, Switzerland. [Reilly, Mary M.; Houlden, Henry; Laura, Matilde] Natl Hosp Neurol & Neurosurg, MRC, Ctr Neuromuscular Dis, London WC1N 3BG, England. [Reilly, Mary M.; Houlden, Henry; Laura, Matilde] UCL, Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England. [Niederkofler, Vera; Stoeckli, Esther T.] Univ Zurich, Inst Zool, CH-8057 Zurich, Switzerland. [Nicholson, Garth] Concord Repatriat Gen Hosp, Mol Med Lab, Sydney, NSW 2139, Australia. [Nicholson, Garth] Concord Repatriat Gen Hosp, Australian & New Zealand Army Corps Res Inst, Sydney, NSW 2139, Australia. [Eichler, Florian; Brown, Robert H., Jr.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Neurosci,Day Lab Neuromuscular Res, Boston, MA 02115 USA. [Brown, Robert H., Jr.] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA 01605 USA. RP Hornemann, T (reprint author), Univ Zurich Hosp, Inst Clin Chem, Raemistr 100, CH-8091 Zurich, Switzerland. EM thorsten.hornemann@usz.ch RI Houlden, Henry/C-1532-2008 OI Houlden, Henry/0000-0002-2866-7777 FU National Institutes of Health through the NINDS [K08NS52550]; Deater Foundation; MRC; Muscular Dystrophy Campaign; Hartmann Muller Foundation; Herzog-Egli Foundation; Olga Mayenfisch Foundation; Foundation for Scientific Research (University of Zurich); German Society for Clinical Chemistry; Laboratory Medicine (DGKL); European Commission [LSHM-CT-2006-037631] FX This work was supported, in whole or in part, by National Institutes of Health Grant K08NS52550 (to F. E.) through the NINDS. This work was also supported by grants from the Deater Foundation (to R. H. B. and F. E.) and from the MRC (to M. M. R. and H. H.) and the Muscular Dystrophy Campaign (to M. M. R. and M. L.). The work undertaken at the University Hospital of Zurich and was supported by grants from the Hartmann Muller Foundation, the Herzog-Egli Foundation, the Olga Mayenfisch Foundation, and the Foundation for Scientific Research (University of Zurich) as well as the German Society for Clinical Chemistry and Laboratory Medicine (DGKL) and the European Commission (LSHM-CT-2006-037631). NR 33 TC 100 Z9 102 U1 1 U2 15 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 9 PY 2010 VL 285 IS 15 BP 11178 EP 11187 DI 10.1074/jbc.M109.092973 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 578IF UT WOS:000276286200023 PM 20097765 ER PT J AU Kee, Y Yang, KL Cohn, MA Haas, W Gygi, SP D'Andrea, AD AF Kee, Younghoon Yang, Kailin Cohn, Martin A. Haas, Wilhelm Gygi, Steven P. D'Andrea, Alan D. TI WDR20 Regulates Activity of the USP12 center dot UAF1 Deubiquitinating Enzyme Complex SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NF-KAPPA-B; FANCONI-ANEMIA PATHWAY; PROTEASOME; UCH37; SUBUNIT AB The UAF1 (Usp1-associated factor 1) protein binds and stimulates three deubiquitinating enzymes: USP1, USP12, and USP46. Although the USP1 center dot UAF1 complex is required for regulation of the Fanconi anemia (FA) DNA repair pathway, less is known about the USP12 center dot UAF1 and the USP46 center dot UAF1 complexes. To understand further the nature of the USP12 and USP46 complexes, we attempted to identify proteins that interact with the USP12 and USP46 deubiquitinating enzyme complexes. We identified WDR20, a WD40-repeat containing protein, as a common binding partner of UAF1, USP12, and USP46. Further analysis showed that WDR20 associates exclusively with USP12 and USP46, not with USP1. Furthermore, we demonstrate the purification of a ternary USP12 center dot UAF1 center dot WDR20 complex. Interestingly, and consistent with the binding assays, WDR20 stimulated the enzymatic activity of USP12 center dot UAF1, but not of USP1 center dot UAF1. Consistent with our previous report that USP12 and USP46 do not regulate the FA pathway, small interference RNA-mediated depletion of WDR20 protein did not affect the FA pathway or DNA damage responses. We provide a model in which WDR20 serves as a stimulatory subunit for preserving and regulating the activity of the subset of the UAF1 center dot USP complexes. C1 [Kee, Younghoon; Yang, Kailin; Cohn, Martin A.; D'Andrea, Alan D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Yang, Kailin] Harvard Univ, Sch Med, Leder Human Biol Program, Biol & Biomed Sci Program, Boston, MA 02115 USA. [Haas, Wilhelm; Gygi, Steven P.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP D'Andrea, AD (reprint author), 44 Binney St, Boston, MA 02115 USA. EM alan_dandrea@dfci.harvard.edu RI Yang, Kailin/D-7966-2013; Yang, Kailin/L-2205-2013 OI Yang, Kailin/0000-0001-5968-6738 FU National Institutes of Health [R01DK43889, R01HL52725, P01CA092584, U19A1067751] FX This work was supported, in whole or in part, by National Institutes of Health Grants R01DK43889, R01HL52725, P01CA092584, and U19A1067751. NR 21 TC 43 Z9 45 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 9 PY 2010 VL 285 IS 15 BP 11252 EP 11257 DI 10.1074/jbc.M109.095141 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 578IF UT WOS:000276286200031 PM 20147737 ER PT J AU Driscoll, JJ Pelluru, D Lefkimmiatis, K Fulciniti, M Prabhala, RH Greipp, PR Barlogie, B Tai, YT Anderson, KC Shaughnessy, JD Annunziata, CM Munshi, NC AF Driscoll, James J. Pelluru, Dheeraj Lefkimmiatis, Konstantinos Fulciniti, Mariateresa Prabhala, Rao H. Greipp, Philip R. Barlogie, Bart Tai, Yu-Tzu Anderson, Kenneth C. Shaughnessy, John D., Jr. Annunziata, Christina M. Munshi, Nikhil C. TI The sumoylation pathway is dysregulated in multiple myeloma and is associated with adverse patient outcome SO BLOOD LA English DT Article ID NF-KAPPA-B; DNA-REPAIR; SUMO; EXPRESSION; UBIQUITIN; TRANSPLANTATION; DEGRADATION; THERAPY; UBC9; RNF4 AB Multiple myeloma (MM) is a plasma cell neoplasm that proceeds through a premalignant state of monoclonal gammopathy of unknown significance; however, the molecular events responsible for myelomagenesis remain uncharacterized. To identify cellular pathways deregulated in MM, we addressed that sumoylation is homologous to ubiquitination and results in the attachment of the ubiquitin-like protein Sumo onto target proteins. Sumoylation was markedly enhanced in MM patient lysates compared with normal plasma cells and expression profiling indicated a relative induction of sumoylation pathway genes. The Sumo-conjugating enzyme Ube2I, the Sumo-ligase PIAS1, and the Sumo-inducer ARF were elevated in MM patient samples and cell lines. Survival correlated with expression because 80% of patients with low UBE2I and PIAS1 were living 6 years after transplantation, whereas only 45% of patients with high expression survived 6 years. UBE2I encodes the sole Sumo-conjugating enzyme in mammalian cells and cells transfected with a dominant-negative sumoylation-deficient UBE2I mutant exhibited decreased survival after radiation exposure, impaired adhesion to bone marrow stroma cell and decreased bone marrow stroma cell-induced proliferation. UBE2I confers cells with multiple advantages to promote tumorigenesis and predicts decreased survival when combined with PIAS1. The sumoylation pathway is a novel therapeutic target with implications for existing proteasomal-based treatment strategies. (Blood. 2010; 115(14): 2827-2834) C1 [Driscoll, James J.; Annunziata, Christina M.] NCI, Med Oncol Branch, Bethesda, MD 20892 USA. [Driscoll, James J.; Pelluru, Dheeraj; Lefkimmiatis, Konstantinos; Prabhala, Rao H.; Munshi, Nikhil C.] Vet Adm Boston Healthcare, Dept Res, W Roxbury, MA USA. [Driscoll, James J.; Pelluru, Dheeraj; Fulciniti, Mariateresa; Prabhala, Rao H.; Tai, Yu-Tzu; Anderson, Kenneth C.; Munshi, Nikhil C.] Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Driscoll, James J.; Pelluru, Dheeraj; Lefkimmiatis, Konstantinos; Fulciniti, Mariateresa; Prabhala, Rao H.; Tai, Yu-Tzu; Anderson, Kenneth C.; Munshi, Nikhil C.] Harvard Univ, Sch Med, Boston, MA USA. [Lefkimmiatis, Konstantinos] Brigham & Womens Hosp, Boston, MA 02115 USA. [Greipp, Philip R.] Mayo Clin, Dept Internal Med, Div Hematol, Rochester, MN USA. [Barlogie, Bart; Shaughnessy, John D., Jr.] Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Donna D & Donald M Lambert Lab Myeloma Genet, Little Rock, AR 72205 USA. RP Driscoll, JJ (reprint author), NCI, Med Oncol Branch, Bethesda, MD 20892 USA. EM driscollj@mail.nih.gov; nikhil_munshi@dfci.harvard.edu RI Lefkimmiatis, Konstantinos/I-1239-2016; Annunziata, Christina/L-3219-2016 OI Lefkimmiatis, Konstantinos/0000-0001-7137-7866; Annunziata, Christina/0000-0003-2033-6532 FU National Institutes of Health [RO1-124929, P50-100007, PO1-78378]; Myeloma Research Fellow SPORE FX This work was supported in part by the Department of Veterans Affairs Merit Review Awards and the National Institutes of Health (grants RO1-124929, N.C.M.; P50-100007 and PO1-78378, N.C.M., K.C.A.), and a Myeloma Research Fellow SPORE Grant (J.J.D.). NR 38 TC 35 Z9 38 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 8 PY 2010 VL 115 IS 14 BP 2827 EP 2834 DI 10.1182/blood-2009-03-211045 PG 8 WC Hematology SC Hematology GA 580MY UT WOS:000276454600017 PM 19965618 ER PT J AU Gutierrez, A Sanda, T Ma, WX Zhang, JH Grebliunaite, R Dahlberg, S Neuberg, D Protopopov, A Winter, SS Larson, RS Borowitz, MJ Silverman, LB Chin, L Hunger, SP Jamieson, C Sallan, SE Look, AT AF Gutierrez, Alejandro Sanda, Takaomi Ma, Wenxue Zhang, Jianhua Grebliunaite, Ruta Dahlberg, Suzanne Neuberg, Donna Protopopov, Alexei Winter, Stuart S. Larson, Richard S. Borowitz, Michael J. Silverman, Lewis B. Chin, Lynda Hunger, Stephen P. Jamieson, Catriona Sallan, Stephen E. Look, A. Thomas TI Inactivation of LEF1 in T-cell acute lymphoblastic leukemia SO BLOOD LA English DT Article ID GENE-EXPRESSION SIGNATURES; TRANSCRIPTION FACTORS; C-MYC; DIFFERENTIATION; MUTATIONS; CANCER; TUMORS; WNT; IDENTIFICATION; ISOFORMS AB To further unravel the molecular pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL), we performed high-resolution array comparative genomic hybridization on diagnostic specimens from 47 children with T-ALL and identified monoallelic or biallelic LEF1 microdeletions in 11% (5 of 47) of these primary samples. An additional 7% (3 of 44) of the cases harbored nonsynonymous sequence alterations of LEF1, 2 of which produced premature stop codons. Gene expression microarrays showed increased expression of MYC and MYC targets in cases with LEF1 inactivation, as well as differentiation arrest at an early cortical stage of thymocyte development characterized by expression of CD1B, CD1E, and CD8, with absent CD34 expression. LEF1 inactivation was associated with a younger age at the time of T-ALL diagnosis, as well as activating NOTCH1 mutations, biallelic INK4a/ARF deletions, and PTEN loss-of-function mutations or activating mutations of PI3K or AKT genes. These cases generally lacked overexpression of the TAL1, HOX11, HOX11L2, or the HOXA cluster genes, which have been used to define separate molecular pathways leading to T-ALL. Our findings suggest that LEF1 inactivation is an important step in the molecular pathogenesis of T-ALL in a subset of young children. (Blood. 2010; 115(14): 2845-2851) C1 [Gutierrez, Alejandro; Sanda, Takaomi; Grebliunaite, Ruta; Silverman, Lewis B.; Sallan, Stephen E.; Look, A. Thomas] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Gutierrez, Alejandro; Silverman, Lewis B.; Sallan, Stephen E.; Look, A. Thomas] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Ma, Wenxue; Jamieson, Catriona] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. [Ma, Wenxue; Jamieson, Catriona] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA. [Zhang, Jianhua; Protopopov, Alexei; Chin, Lynda] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA. [Dahlberg, Suzanne; Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Winter, Stuart S.] Univ New Mexico, Dept Pediat, Hlth Sci Ctr, Albuquerque, NM 87131 USA. [Larson, Richard S.] Univ New Mexico, Dept Pathol, Hlth Sci Ctr, Albuquerque, NM 87131 USA. [Borowitz, Michael J.] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. [Borowitz, Michael J.] Johns Hopkins Med Inst, Dept Oncol, Baltimore, MD 21205 USA. [Silverman, Lewis B.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Hunger, Stephen P.] Univ Colorado, Sch Med, Sect Pediat Hematol Oncol, Aurora, CO USA. [Hunger, Stephen P.] Childrens Hosp, Aurora, CO USA. RP Look, AT (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Mayer 630,44 Binney St, Boston, MA 02115 USA. EM thomas_look@dfci.harvard.edu OI Gutierrez, Alejandro/0000-0002-0249-9007 FU National Institutes of Health [5P01CA68484, 1K08CA133103]; Community Foundation of the National Capital Region; William Lawrence Foundation; American Society of Hematology; Belfer Institute for Applied Cancer Science; [CA98543]; [CA114766]; [CA98413] FX This work was supported by the National Institutes of Health (grant 5P01CA68484; S.E.S. and A.T.L.; and grant 1K08CA133103; A.G.); by an award from the Wine Advocate Fund for Philanthropy of The Community Foundation of the National Capital Region; the William Lawrence Foundation (A.G.); and the American Society of Hematology-Amos Medical Faculty Development program (A.G.). Children's Oncology Group (COG) cell banking and sample distribution were supported by the COG 9900 cell biology study and grants CA98543, CA114766, and CA98413. S.P.H. is the Ergen Family Chair in Pediatric Cancer at The Children's Hospital, Aurora, CO. The array CGH analyses were performed and supported in part by the Belfer Institute for Applied Cancer Science. NR 43 TC 48 Z9 50 U1 1 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 8 PY 2010 VL 115 IS 14 BP 2845 EP 2851 DI 10.1182/blood-2009-07-234377 PG 7 WC Hematology SC Hematology GA 580MY UT WOS:000276454600019 PM 20124220 ER PT J AU Will, B Siddiqi, T Jorda, MA Shimamura, T Luptakova, K Staber, PB Costa, DB Steidl, U Tenen, DG Kobayashi, S AF Will, Britta Siddiqi, Tanya Jorda, Meritxell Alberich Shimamura, Takeshi Luptakova, Katarina Staber, Philipp B. Costa, Daniel B. Steidl, Ulrich Tenen, Daniel G. Kobayashi, Susumu TI Apoptosis induced by JAK2 inhibition is mediated by Bim and enhanced by the BH3 mimetic ABT-737 in JAK2 mutant human erythroid cells SO BLOOD LA English DT Article ID GROWTH-FACTOR-RECEPTOR; TYROSINE KINASE JAK2; MYELOPROLIFERATIVE DISORDERS; POLYCYTHEMIA-VERA; BCL-2 FAMILY; ACTIVATING MUTATION; BH3-ONLY PROTEINS; LEUKEMIC-CELLS; PROMOTES; PHOSPHORYLATION AB The activating mutation JAK2 V617F plays a central role in the pathogenesis of polycythemia vera, essential thrombocythemia, and primary myelofibrosis. Inhibition of JAK2 activity leads to growth inhibition and apoptosis in cells with mutated JAK2. However, the proapoptotic proteins involved in JAK2 inhibition-induced apoptosis remain unclear. In this study, we show that JAK2 inhibition-induced apoptosis correlated with upregulation of the nonphosphorylated form of the BH3-only protein Bim in hematopoietic cell lines bearing JAK2 mutations. Knockdown of Bim dramatically inhibited apoptosis induced by JAK2 inhibition, which was reversed by the BH3 mimetic agent ABT-737. In addition, ABT-737 enhanced the apoptosis induced by JAK2 inhibition in JAK2 V617F(+) HEL and SET-2 cells. The combination of JAK inhibitor I and ABT-737 reduced the number of erythroid colonies derived from CD34(+) cells isolated from JAK2 V617F(+) polycythemia vera patients more efficiently than either drug alone. These data suggest that Bim is a key effector molecule in JAK2 inhibition-induced apoptosis and that targeting this apoptotic pathway could be a novel therapeutic strategy for patients with activating JAK2 mutations. (Blood. 2010; 115(14): 2901-2909) C1 [Will, Britta; Siddiqi, Tanya; Jorda, Meritxell Alberich; Luptakova, Katarina; Staber, Philipp B.; Costa, Daniel B.; Kobayashi, Susumu] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. [Will, Britta; Steidl, Ulrich] Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10467 USA. [Will, Britta; Steidl, Ulrich] Albert Einstein Canc Ctr, Bronx, NY USA. [Jorda, Meritxell Alberich; Tenen, Daniel G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Life Sci, Boston, MA 02115 USA. [Jorda, Meritxell Alberich; Tenen, Daniel G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Harvard Stem Cell Inst, Boston, MA 02115 USA. [Shimamura, Takeshi] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Staber, Philipp B.] Med Univ Graz, Div Hematol, Graz, Austria. [Tenen, Daniel G.] Natl Univ Singapore, Canc Sci Inst, Singapore 117548, Singapore. RP Kobayashi, S (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Hematol Oncol, E CLS 0430,330 BrooklineAve, Boston, MA 02215 USA. EM skobayas@bidmc.harvard.edu RI Alberich Jorda, Meritxell/G-3137-2014; OI Costa, Daniel/0000-0002-0689-395X; Tenen, Daniel/0000-0002-6423-3888 FU National Institutes of Health [R00CA126026, R00CA131503]; American Association for Cancer Research-AstraZeneca-Cancer Research; Dana-Farber Cancer Institute Claudia Adams Barr Program in Innovative Basic Cancer Research; German Jose Carreras Leukemia Foundation; [CA66996]; [CA118316] FX This work was supported by National Institutes of Health (grant R00CA126026, S.K.; grant R00CA131503, U.S.; and grants CA66996 and CA118316, D.G.T.), American Association for Cancer Research-AstraZeneca-Cancer Research (D.B.C), Dana-Farber Cancer Institute Claudia Adams Barr Program in Innovative Basic Cancer Research (T. Shimamura), and a Predoctoral Fellowship from German Jose Carreras Leukemia Foundation (B.W.). NR 47 TC 25 Z9 28 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 8 PY 2010 VL 115 IS 14 BP 2901 EP 2909 DI 10.1182/blood-2009-03-209544 PG 9 WC Hematology SC Hematology GA 580MY UT WOS:000276454600025 PM 20160166 ER PT J AU Strandberg-Larsen, M Schiotz, ML Silver, JD Frolich, A Andersen, JS Graetz, I Reed, M Bellows, J Krasnik, A Rundall, T Hsu, J AF Strandberg-Larsen, Martin Schiotz, Michaela L. Silver, Jeremy D. Frolich, Anne Andersen, John S. Graetz, Ilana Reed, Mary Bellows, Jim Krasnik, Allan Rundall, Thomas Hsu, John TI Is the Kaiser Permanente model superior in terms of clinical integration?: a comparative study of Kaiser Permanente, Northern California and the Danish healthcare system SO BMC HEALTH SERVICES RESEARCH LA English DT Article ID ORGANIZED DELIVERY SYSTEMS; HOSPITAL BED UTILIZATION; RESPONSE RATES; NHS; MANAGEMENT AB Background: Integration of medical care across clinicians and settings could enhance the quality of care for patients. To date, there is limited data on the levels of integration in practice. Our objective was to compare primary care clinicians' perceptions of clinical integration and three sub-aspects in two healthcare systems: Kaiser Permanente, Northern California (KPNC) and the Danish healthcare system (DHS). Further, we examined the associations between specific organizational factors and clinical integration within each system. Methods: Comparable questionnaires were sent to a random sample of primary care clinicians in KPNC (n = 1103) and general practitioners in DHS (n = 700). Data were analysed using multiple logistic regression models. Results: More clinicians in KPNC perceived to be part of a clinical integrated environment than did general practitioners in the DHS (OR = 3.06, 95% CI: 2.28, 4.12). Further, more KPNC clinicians reported timeliness of information transfer (OR = 2.25, 95% CI: 1.62, 3.13), agreement on roles and responsibilities (OR = 1.79, 95% CI: 1.30, 2.47) and established coordination mechanisms in place to ensure effective handoffs (OR = 6.80, 95% CI: 4.60, 10.06). None of the considered organizational factors in the sub-country analysis explained a substantial proportion of the variation in clinical integration. Conclusions: More primary care clinicians in KPNC reported clinical integration than did general practitioners in the DHS. Focused measures of clinical integration are needed to develop the field of clinical integration and to create the scientific foundation to guide managers searching for evidence based approaches. C1 [Strandberg-Larsen, Martin; Schiotz, Michaela L.; Krasnik, Allan] Univ Copenhagen, Dept Publ Hlth, Fac Hlth Sci, Sect Hlth Serv Res, DK-1014 Copenhagen K, Denmark. [Silver, Jeremy D.] Univ Copenhagen, Dept Publ Hlth, Fac Hlth Sci, Dept Biostat, DK-1014 Copenhagen, Denmark. [Frolich, Anne] Bispebjerg Hosp, Copenhagen Hosp Cooperat, DK-2400 Copenhagen NV, Denmark. [Andersen, John S.] Univ Copenhagen, Dept Publ Hlth, Fac Hlth Sci, Sect Gen Practice, DK-1014 Copenhagen K, Denmark. [Graetz, Ilana; Reed, Mary] Kaiser Permanente, Div Res, Oakland, CA 94612 USA. [Bellows, Jim] Kaiser Permanente, Care Management Inst, Oakland, CA 94612 USA. [Rundall, Thomas; Hsu, John] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. [Hsu, John] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Hsu, John] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. RP Strandberg-Larsen, M (reprint author), Univ Copenhagen, Dept Publ Hlth, Fac Hlth Sci, Sect Hlth Serv Res, Oster Farimagsgade 5,Bldg 10,Stairway B, DK-1014 Copenhagen K, Denmark. EM m.strandberg-larsen@ifsv.ku.dk RI Graetz, Ilana/N-1189-2016 OI Graetz, Ilana/0000-0003-3664-5815 FU Health Insurance Foundation; Rockwool Foundation; Agency for Healthcare Research and Quality (AHRQ); Danish Graduate School in Public Health Science, Faculty of Health Sciences, University of Copenhagen; Augustinus Fonden; Frimodt-Heineke Fonden; Julie von Mullens Fond; Knud Hojgaards Fond; Oticon Fonden FX We thank the Danish Graduate School in Public Health Science, Faculty of Health Sciences, University of Copenhagen; the Health Insurance Foundation, and the Rockwool Foundation who funded this study. We also thank: Augustinus Fonden, Frimodt-Heineke Fonden, Julie von Mullens Fond, Knud Hojgaards Fond, Oticon Fonden, and the Faculty of Health Sciences, University of Copenhagen for providing funding for a research stay at the School of Public Health, University of California, Berkeley. Thanks to the Agency for Healthcare Research and Quality (AHRQ), who funded the collection of data in KPNC. A final thanks to Research Assistant, Mikkel B. Nielsen, MScPH who contributed to the questionnaire construction and data collection in the Danish setting and Associate Professor Thomas Alexander Gerds for biostatistical advice. NR 47 TC 10 Z9 10 U1 3 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6963 J9 BMC HEALTH SERV RES JI BMC Health Serv. Res. PD APR 8 PY 2010 VL 10 AR 91 DI 10.1186/1472-6963-10-91 PG 13 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 600OF UT WOS:000277995800001 PM 20374667 ER PT J AU Raaijmakers, MHGP Mukherjee, S Guo, SQ Zhang, SY Kobayashi, T Schoonmaker, JA Ebert, BL Al-Shahrour, F Hasserjian, RP Scadden, EO Aung, Z Matza, M Merkenschlager, M Lin, C Rommens, JM Scadden, DT AF Raaijmakers, Marc H. G. P. Mukherjee, Siddhartha Guo, Shangqin Zhang, Siyi Kobayashi, Tatsuya Schoonmaker, Jesse A. Ebert, Benjamin L. Al-Shahrour, Fatima Hasserjian, Robert P. Scadden, Edward O. Aung, Zinmar Matza, Marc Merkenschlager, Matthias Lin, Charles Rommens, Johanna M. Scadden, David. T. TI Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia SO NATURE LA English DT Article ID STEM-CELL NICHE; SHWACHMAN-DIAMOND-SYNDROME; HEMATOPOIETIC PROGENITORS; MARROW MICROENVIRONMENT; DIFFERENTIATION; CANCER; DICER; IDENTIFICATION; EXPRESSION; PATHWAYS AB Mesenchymal cells contribute to the 'stroma' of most normal and malignant tissues, with specific mesenchymal cells participating in the regulatory niches of stem cells. By examining how mesenchymal osteolineage cells modulate haematopoiesis, here we show that deletion of Dicer1 specifically in mouse osteoprogenitors, but not in mature osteoblasts, disrupts the integrity of haematopoiesis. Myelodysplasia resulted and acute myelogenous leukaemia emerged that had acquired several genetic abnormalities while having intact Dicer1. Examining gene expression altered in osteoprogenitors as a result of Dicer1 deletion showed reduced expression of Sbds, the gene mutated in Schwachman-Bodian-Diamond syndrome-a human bone marrow failure and leukaemia pre-disposition condition. Deletion of Sbds in mouse osteoprogenitors induced bone marrow dysfunction with myelodysplasia. Therefore, perturbation of specific mesenchymal subsets of stromal cells can disorder differentiation, proliferation and apoptosis of heterologous cells, and disrupt tissue homeostasis. Furthermore, primary stromal dysfunction can result in secondary neoplastic disease, supporting the concept of niche-induced oncogenesis. C1 [Raaijmakers, Marc H. G. P.; Mukherjee, Siddhartha; Guo, Shangqin; Zhang, Siyi; Schoonmaker, Jesse A.; Scadden, Edward O.; Aung, Zinmar; Matza, Marc; Scadden, David. T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Raaijmakers, Marc H. G. P.; Mukherjee, Siddhartha; Guo, Shangqin; Zhang, Siyi; Schoonmaker, Jesse A.; Scadden, Edward O.; Aung, Zinmar; Matza, Marc; Scadden, David. T.] Harvard Univ, Sch Med, CPZN, Boston, MA 02114 USA. [Mukherjee, Siddhartha; Scadden, David. T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Kobayashi, Tatsuya] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Hasserjian, Robert P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Lin, Charles] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Raaijmakers, Marc H. G. P.; Mukherjee, Siddhartha; Guo, Shangqin; Zhang, Siyi; Schoonmaker, Jesse A.; Scadden, Edward O.; Aung, Zinmar; Matza, Marc; Scadden, David. T.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Raaijmakers, Marc H. G. P.; Mukherjee, Siddhartha; Guo, Shangqin; Zhang, Siyi; Schoonmaker, Jesse A.; Scadden, Edward O.; Aung, Zinmar; Matza, Marc; Scadden, David. T.] Harvard Univ, Stem Cell Inst, Cambridge, MA 02138 USA. [Ebert, Benjamin L.; Al-Shahrour, Fatima] Broad Inst, Cambridge, MA 02138 USA. [Ebert, Benjamin L.; Al-Shahrour, Fatima] Massachusetts Gen Hosp, Div Hematol, Boston, MA 02115 USA. [Merkenschlager, Matthias] Univ London Imperial Coll Sci Technol & Med, Ctr Clin Sci, MRC, Lymphocyte Dev Grp, London W12 0NN, England. [Rommens, Johanna M.] Univ Toronto, Program Genet & Genome Biol, Hosp Sick Children, Dept Mol Genet, Toronto, ON M5S 1A8, Canada. RP Raaijmakers, MHGP (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, Room 4265A,185 Cambridge St, Boston, MA 02114 USA. EM hraaijmakers@partners.org; dscadden@mgh.harvard.edu OI Merkenschlager, Matthias/0000-0003-2889-3288 FU Dutch Cancer Society; Leukemia & Lymphoma Society; National Institutes of Health; Harvard Stem Cell Institute; Ellison Medical Foundation FX We thank E. Schipani, E. Attar and H. Kronenberg for advice and discussion, A. McMahon for providing the Osx-Cre mice, J. Fujisaki, D. Wilpitz, M. Ohishi, S. Vallet, M. Churchill and G. Frankl for technical assistance, the Histocore (Endocrine Unit), Flow Core at the Center for Regenerative Medicine, Massachusetts General Hospital (L. Pickett and K. Folz-Donahue), and F. Preffer and D. Dombrowski for assistance with histology and flow-cytometry. We thank D. Machon for help preparing the manuscript and the Cytogenetics Core at Brigham Women/Dana Farber (Y. Xiao and C. Lee) for performing CGH analyses. This work was supported by a Fellowship Award of the Dutch Cancer Society (KWF) and a Special Fellowship Award of The Leukemia & Lymphoma Society to M. H. G. P. R. and grants of the National Institutes of Health, the Harvard Stem Cell Institute and the Ellison Medical Foundation to D. T. S. NR 39 TC 410 Z9 427 U1 0 U2 25 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 8 PY 2010 VL 464 IS 7290 BP 852 EP U58 DI 10.1038/nature08851 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 579TM UT WOS:000276397300029 PM 20305640 ER PT J AU Vastenhouw, NL Zhang, Y Woods, IG Imam, F Regev, A Liu, XS Rinn, J Schier, AF AF Vastenhouw, Nadine L. Zhang, Yong Woods, Ian G. Imam, Farhad Regev, Aviv Liu, X. Shirley Rinn, John Schier, Alexander F. TI Chromatin signature of embryonic pluripotency is established during genome activation SO NATURE LA English DT Article ID RNA-POLYMERASE; STEM-CELLS; HISTONE-H3 LYSINE-4; ZYGOTIC TRANSITION; XENOPUS-EMBRYOS; TRANSCRIPTION; ZEBRAFISH; GENES; TRIMETHYLATION; POLYCOMB AB After fertilization the embryonic genome is inactive until transcription is initiated during the maternal-zygotic transition(1-3). This transition coincides with the formation of pluripotent cells, which in mammals can be used to generate embryonic stem cells. To study the changes in chromatin structure that accompany pluripotency and genome activation, we mapped the genomic locations of histone H3 molecules bearing lysine trimethylation modifications before and after the maternal-zygotic transition in zebrafish. Histone H3 lysine 27 trimethylation (H3K27me3), which is repressive, and H3K4me3, which is activating, were not detected before the transition. After genome activation, more than 80% of genes were marked by H3K4me3, including many inactive developmental regulatory genes that were also marked by H3K27me3. Sequential chromatin immunoprecipitation demonstrated that the same promoter regions had both trimethylation marks. Such bivalent chromatin domains also exist in embryonic stem cells and are thought to poise genes for activation while keeping them repressed(4-8). Furthermore, we found many inactive genes that were uniquely marked by H3K4me3. Despite this activating modification, these monovalent genes were neither expressed nor stably bound by RNA polymerase II. Inspection of published data sets revealed similar monovalent domains in embryonic stem cells. Moreover, H3K4me3 marks could form in the absence of both sequence-specific transcriptional activators and stable association of RNA polymerase II, as indicated by the analysis of an inducible transgene. These results indicate that bivalent and monovalent domains might poise embryonic genes for activation and that the chromatin profile associated with pluripotency is established during the maternal-zygotic transition. C1 [Zhang, Yong; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Vastenhouw, Nadine L.; Woods, Ian G.; Imam, Farhad; Schier, Alexander F.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Zhang, Yong] Tongji Univ, Sch Life Sci & Technol, Shanghai 200092, Peoples R China. [Regev, Aviv; Rinn, John; Schier, Alexander F.] MIT, Broad Inst, Cambridge, MA 02142 USA. [Regev, Aviv; Rinn, John; Schier, Alexander F.] Harvard Univ, Cambridge, MA 02142 USA. [Rinn, John] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Schier, Alexander F.] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Schier, Alexander F.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA. RP Liu, XS (reprint author), Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. EM xsliu@jimmy.harvard.edu; schier@fas.harvard.edu RI Zhang, Yong/B-4838-2011; OI Zhang, Yong/0000-0001-6316-2734; Imam, Farhad/0000-0003-2854-2568 FU NIH [1R01 HG004069, 5R01 GM56211]; EMBO [LT-00090/2007]; HFSP [LT-00090/2007] FX We thank members of the Schier laboratory for help and advice; H. G. Shin, L. Taing and Z. J. Wufor computational analysis and discussions; N. Follmer and B. Lilley for technical advice; and J. Dubrulle, N. Francis, R. Losick, S. Mango, T. van Opijnen and W. Talbot for discussions and critical reading of the manuscript. This work was supported by NIH grants to X. S. L. (1R01 HG004069) and A. F. S. (5R01 GM56211), and by EMBO and HFSP (LT-00090/2007) fellowships to N. L. V. NR 35 TC 171 Z9 173 U1 2 U2 24 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 8 PY 2010 VL 464 IS 7290 BP 922 EP U143 DI 10.1038/nature08866 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 579TM UT WOS:000276397300044 PM 20336069 ER PT J AU Cahill, DP Barker, FG Davis, KR Kalva, SP Sahai, I Frosch, MP AF Cahill, Daniel P. Barker, Fred G. Davis, Kenneth R. Kalva, Sanjeeva P. Sahai, Inderneel Frosch, Matthew P. TI Case 10-2010: A 37-Year-Old Woman with Weakness and a Mass in the Brain. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID MAGNETIC-RESONANCE SPECTROSCOPY; REACTIVE PROTEIN-LEVELS; OF-THE-LITERATURE; DIFFERENTIAL-DIAGNOSIS; MANAGEMENT; LOCUS; MAPS C1 [Cahill, Daniel P.; Barker, Fred G.] Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. [Davis, Kenneth R.; Kalva, Sanjeeva P.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Sahai, Inderneel] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Frosch, Matthew P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Cahill, Daniel P.; Barker, Fred G.] Harvard Univ, Sch Med, Dept Surg, Cambridge, MA 02138 USA. [Davis, Kenneth R.; Kalva, Sanjeeva P.] Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. [Sahai, Inderneel] Harvard Univ, Sch Med, Dept Pediat, Cambridge, MA 02138 USA. [Frosch, Matthew P.] Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Cahill, DP (reprint author), Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. NR 24 TC 4 Z9 4 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 8 PY 2010 VL 362 IS 14 BP 1326 EP 1333 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 579SN UT WOS:000276393700013 PM 20375410 ER PT J AU Wolpin, BM Mayer, RJ AF Wolpin, Brian M. Mayer, Robert J. TI A Step Forward in the Treatment of Advanced Biliary Tract Cancer. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID RANDOMIZED PHASE-II; GEMCITABINE; CARCINOMA; SURVIVAL; THERAPY; TRIALS C1 [Wolpin, Brian M.] Brigham & Womens Hosp, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Wolpin, BM (reprint author), Brigham & Womens Hosp, Dept Med Oncol, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. NR 14 TC 13 Z9 13 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 8 PY 2010 VL 362 IS 14 BP 1335 EP 1337 DI 10.1056/NEJMe1001183 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 579SN UT WOS:000276393700014 PM 20375411 ER PT J AU Saxon, AJ AF Saxon, Andrew J. TI Morphine after Combat Injury and Post-Traumatic Stress Disorder SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Saxon, AJ (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. EM asaxon@uw.edu NR 0 TC 0 Z9 0 U1 1 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 8 PY 2010 VL 362 IS 14 BP 1342 EP 1342 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 579SN UT WOS:000276393700019 PM 20380026 ER PT J AU Firth, PG AF Firth, Paul G. TI Disaster-Relief Anesthesia - Notes on Coming Home SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 8 PY 2010 VL 362 IS 14 DI 10.1056/NEJMpv1003218 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 579SN UT WOS:000276393700035 PM 20335576 ER PT J AU Kajimura, S Seale, P Spiegelman, BM AF Kajimura, Shingo Seale, Patrick Spiegelman, Bruce M. TI Transcriptional Control of Brown Fat Development SO CELL METABOLISM LA English DT Review ID ADIPOSE-TISSUE; WHITE FAT; ADULT HUMANS; PGC-1-ALPHA; GENE; DIFFERENTIATION; ADIPOCYTES; SWITCH; ADIPOGENESIS; EXPRESSION AB Deconvoluting the natural pathway of BAT development has defined key molecular events, which enables researchers to manipulate the amount or activity of brown fat. We review recent advances on the transcriptional regulation of BAT development and discuss the emerging questions. C1 [Kajimura, Shingo; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Kajimura, Shingo; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Seale, Patrick] Univ Penn, Sch Med, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA. RP Spiegelman, BM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM bruce_spiegelman@dfci.harvard.edu FU AHA [0930125N]; NIH [DK081605, DK31405] FX We are grateful to R. Gupta and M. Khandekar for their critical comments on the manuscript. We apologize for the inability to cite a vast number of papers that contribute to this field due to a space limit. S.K. is supported by AHA scientist development grant (0930125N). P.S. is supported by a NIH grant (DK081605). This work is funded by a NIH grant to B.M.S. (DK31405). NR 27 TC 172 Z9 179 U1 4 U2 35 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD APR 7 PY 2010 VL 11 IS 4 BP 257 EP 262 DI 10.1016/j.cmet.2010.03.005 PG 6 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 581TE UT WOS:000276546700007 PM 20374957 ER PT J AU Chang, VW Asch, DA Werner, RM AF Chang, Virginia W. Asch, David A. Werner, Rachel M. TI Quality of Care Among Obese Patients SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID COLORECTAL-CANCER; MEDICARE BENEFICIARIES; PREVENTIVE SERVICES; BODY-WEIGHT; HEALTH-CARE; CLAIMS DATA; SELF-REPORT; US ADULTS; WOMEN; MAMMOGRAPHY AB Context Clinicians often have negative attitudes toward obesity and express dissatisfaction in caring for obese patients. Moreover, obese patients often feel that clinicians are biased or disrespectful because of their weight. These observations raise the concern that obese patients may receive lower quality of care. Objective To determine whether performance on common outpatient quality measures differs by patient weight status. Design, Setting, and Participants Eight different performance measures were examined in 2 national-level patient populations: (1) Medicare beneficiaries (n=36 122) using data from the Medicare Beneficiary Survey (1994-2006); and (2) recipients of care from the Veterans Health Administration (VHA) (n=33 550) using data from an ongoing performance-evaluation program (2003-2004). Main Outcome Measures Performance measures among eligible patients for diabetes care (eye examination, glycated hemoglobin [HbA(1c)] testing, and lipid screening), pneumococcal vaccination, influenza vaccination, screening mammography, colorectal cancer screening, and cervical cancer screening. Measures were based on a combination of administrative claims, survey, and chart review data. Results We found no evidence that obese or overweight patients were less likely to receive recommended care relative to normal-weight patients. Moreover, success rates were marginally higher for obese and/or overweight patients on several measures. The most notable differentials were observed for recommended diabetes care among Medicare beneficiaries: comparing obese vs normal-weight patients with diabetes, obese patients were more likely to receive recommended care on lipid screening (72% vs 65%; odds ratio, 1.37 [95% confidence interval, 1.09-1.73]) and HbA(1c) testing (74% vs 62%; odds ratio, 1.73 [95% confidence interval, 1.41-2.11]). All analyses were adjusted for sociodemographic factors, health status, clinical complexity, and visit frequency. Conclusions Among samples of patients from the Medicare and VHA populations, there was no evidence across 8 performance measures that obese or overweight patients received inferior care when compared with normal-weight patients. Being obese or overweight was associated with a marginally higher rate of recommended care on several measures. JAMA. 2010;303(13):1274-1281 C1 [Chang, Virginia W.; Asch, David A.; Werner, Rachel M.] Univ Penn, Sch Med, Dept Med, Ctr Hlth Equ Res & Promot,Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Chang, Virginia W.; Asch, David A.; Werner, Rachel M.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Chang, Virginia W.] Univ Penn, Dept Sociol, Philadelphia, PA 19104 USA. RP Chang, VW (reprint author), Univ Penn, Sch Med, Dept Med, Ctr Hlth Equ Res & Promot,Philadelphia VA Med Ctr, 1233 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM vwchang@mail.med.upenn.edu OI Asch, David/0000-0002-7970-286X FU Veterans Administration Health Services [IIR 06-096]; Robert Wood Johnson Foundation FX This work was supported by a Veterans Administration Health Services Research and Development Merit Award (IIR 06-096); the Robert Wood Johnson Foundation Physician Faculty Scholars Program; and a Veterans Administration Health Services Research and Development Career Development Award (to Dr Werner). NR 40 TC 38 Z9 38 U1 2 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 7 PY 2010 VL 303 IS 13 BP 1274 EP 1281 DI 10.1001/jama.2010.339 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 579FM UT WOS:000276353700027 PM 20371786 ER PT J AU Chou, R Shekelle, P AF Chou, Roger Shekelle, Paul TI Will This Patient Develop Persistent Disabling Low Back Pain? SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID PRIMARY-CARE; INCEPTION COHORT; PROGNOSTIC-FACTORS; CLINICAL-COURSE; SCREENING QUESTIONNAIRE; GENERAL-PRACTICE; WORK DISABILITY; PREDICTORS; RISK; FEAR AB Context Low back pain is extremely common. Early identification of patients more likely to develop persistent disabling symptoms could help guide decisions regarding follow-up and management. Objective To systematically review the usefulness of individual risk factors or risk prediction instruments for identifying patients more likely to develop persistent disabling low back pain. Data Sources Electronic searches of MEDLINE (1966-January 2010) and EMBASE (1974-February 2010) and review of the bibliographies of retrieved articles. Study Selection Prospective studies of patients with fewer than 8 weeks of low back pain from which likelihood ratios (LRs) were calculated for prediction of persistent disabling low back pain for findings attainable during the clinical evaluation. Data Extraction Two authors independently assessed studies and extracted data to estimate LRs. Data Synthesis A total of 20 studies evaluating 10 842 patients were identified. Presence of nonorganic signs (median [range] LR, 3.0 [1.7-4.6]), high levels of maladaptive pain coping behaviors (median [range] LR, 2.5 [2.2-2.8]), high baseline functional impairment (median [range] LR, 2.1 [1.2-2.7]), presence of psychiatric comorbidities (median [range] LR, 2.2 [1.9-2.3]), and low general health status (median [range] LR, 1.8 [1.1-2.0]) were the most useful predictors of worse outcomes at 1 year. Low levels of fear avoidance (median [range] LR, 0.39 [0.38-0.40]) and low baseline functional impairment (median [range] LR, 0.40 [0.10-0.52]) were the most useful items for predicting recovery at 1 year. Results were similar for outcomes at 3 to 6 months. Variables related to the work environment, baseline pain, and presence of radiculopathy were less useful for predicting worse outcomes (median LRs approximately 1.5), and a history of prior low back pain episodes and demographic variables were not useful (median LRs approximately 1.0). Several risk prediction instruments were useful for predicting outcomes, but none were extensively validated, and some validation studies showed LRs similar to estimates for individual risk factors. Conclusion The most helpful components for predicting persistent disabling low back pain were maladaptive pain coping behaviors, nonorganic signs, functional impairment, general health status, and presence of psychiatric comorbidities. JAMA. 2010;303(13):1295-1302 C1 [Chou, Roger] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97239 USA. [Chou, Roger] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97239 USA. [Shekelle, Paul] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Chou, R (reprint author), Oregon Hlth & Sci Univ, Dept Med, 3181 SW Sam Jackson Pk Rd,MC BICC, Portland, OR 97239 USA. EM chour@ohsu.edu NR 52 TC 197 Z9 199 U1 3 U2 24 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 7 PY 2010 VL 303 IS 13 BP 1295 EP 1302 DI 10.1001/jama.2010.344 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 579FM UT WOS:000276353700030 PM 20371789 ER PT J AU Pagani, O Senkus, E Wood, W Colleoni, M Cufer, T Kyriakides, S Costa, A Winer, EP Cardoso, F AF Pagani, Olivia Senkus, Elzbieta Wood, William Colleoni, Marco Cufer, Tanja Kyriakides, Stella Costa, Alberto Winer, Eric P. Cardoso, Fatima CA ESO-MBC Task Force TI International Guidelines for Management of Metastatic Breast Cancer: Can Metastatic Breast Cancer Be Cured? SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID HIGH-DOSE CHEMOTHERAPY; LONG-TERM SURVIVAL; STEM-CELL TRANSPLANTATION; DOXORUBICIN-CONTAINING CHEMOTHERAPY; POSITRON-EMISSION-TOMOGRAPHY; SOLITARY PULMONARY NODULE; HEPATIC ARTERIAL INFUSION; PROGRESSION-FREE SURVIVAL; DISEASE-FREE SURVIVAL; SURROGATE END-POINT AB A distinctive subset of metastatic breast cancer (MBC) is oligometastatic disease, which is characterized by single or few detectable metastatic lesions. The existing treatment guidelines for patients with localized MBC include surgery, radiotherapy, and regional chemotherapy. The European School of Oncology-Metastatic Breast Cancer Task Force addressed the management of these patients in its first consensus recommendations published in 2007. The Task Force endorsed the possibility of a more aggressive and multidisciplinary approach for patients with oligometastatic disease, stressing also the need for clinical trials in this patient population. At the sixth European Breast Cancer Conference, held in Berlin in March 2008, the second public session on MBC guidelines addressed the controversial issue of whether MBC can be cured. In this commentary, we summarize the discussion and related recommendations regarding the available therapeutic options that are possibly associated with cure in these patients. In particular, data on local (surgery and radiotherapy) and chemotherapy options are discussed. Large retrospective series show an association between surgical removal of the primary tumor or of lung metastases and improved long-term outcome in patients with oligometastatic disease. In the absence of data from prospective randomized studies, removal of the primary tumor or isolated metastatic lesions may be an attractive therapeutic strategy in this subset of patients, offering rapid disease control and potential for survival benefit. Some improvement in outcome may also be achieved with optimization of systemic therapies, possibly in combination with optimal local treatment. C1 [Cardoso, Fatima] Inst Jules Bordet, Dept Med Oncol, B-1000 Brussels, Belgium. [Pagani, Olivia] Oncol Inst So Switzerland, Osped Italiano, Lugano, Switzerland. [Pagani, Olivia] Swiss Grp Clin Canc Res SAKK, Bern, Switzerland. [Senkus, Elzbieta] Med Univ Gdansk, Dept Radiotherapy & Oncol, Gdansk, Poland. [Wood, William] Emory Univ, Sch Med, Dept Surg, Atlanta, GA 30322 USA. [Colleoni, Marco] European Inst Oncol, Med Senol Res Unit, Milan, Italy. [Cufer, Tanja] Univ Clin Golnik, Dept Med Oncol, Golnik, Slovenia. [Costa, Alberto] European Sch Oncol, Milan, Italy. [Kyriakides, Stella] European Breast Canc Coalit, Nicosia, Cyprus. [Costa, Alberto] Maugeri Fdn, Breast Unit, Pavia, Italy. [Winer, Eric P.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Sch Med,Dept Med Oncol, Boston, MA 02115 USA. RP Cardoso, F (reprint author), Inst Jules Bordet, Dept Med Oncol, Blvd Waterloo 125, B-1000 Brussels, Belgium. EM fatima.cardoso@bordet.be OI Senkus, Elzbieta/0000-0001-6855-397X; Cardoso, Fatima/0000-0002-6692-2249 NR 101 TC 107 Z9 111 U1 1 U2 13 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD APR 7 PY 2010 VL 102 IS 7 BP 456 EP 463 DI 10.1093/jnci/djq029 PG 8 WC Oncology SC Oncology GA 581MN UT WOS:000276527800006 PM 20220104 ER PT J AU Kuntz, J Dinkel, J Zwick, S Bauerle, T Grasruck, M Kiessling, F Gupta, R Semmler, W Bartling, SH AF Kuntz, J. Dinkel, J. Zwick, S. Baeuerle, T. Grasruck, M. Kiessling, F. Gupta, R. Semmler, W. Bartling, S. H. TI Fully automated intrinsic respiratory and cardiac gating for small animal CT SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID MICRO-COMPUTED-TOMOGRAPHY; FREE-BREATHING RODENTS; SYSTEM; 4D AB A fully automated, intrinsic gating algorithm for small animal cone-beam CT is described and evaluated. A parameter representing the organ motion, derived from the raw projection images, is used for both cardiac and respiratory gating. The proposed algorithm makes it possible to reconstruct motion-corrected still images as well as to generate four-dimensional (4D) datasets representing the cardiac and pulmonary anatomy of free-breathing animals without the use of electrocardiogram ( ECG) or respiratory sensors. Variation analysis of projections from several rotations is used to place a region of interest (ROI) on the diaphragm. The ROI is cranially extended to include the heart. The centre of mass (COM) variation within this ROI, the filtered frequency response and the local maxima are used to derive a binary motion-gating parameter for phase-sensitive gated reconstruction. This algorithm was implemented on a flat-panel-based cone-beam CT scanner and evaluated using amoving phantom and animal scans ( seven rats and eight mice). Volumes were determined using a semiautomatic segmentation. In all cases robust gating signals could be obtained. The maximum volume error in phantom studies was less than 6%. By utilizing extrinsic gating via externally placed cardiac and respiratory sensors, the functional parameters ( e. g. cardiac ejection fraction) and image quality were equivalent to this current gold standard. This algorithm obviates the necessity of both gating hardware and user interaction. The simplicity of the proposed algorithm enables adoption in a wide range of small animal cone-beam CT scanners. C1 [Kuntz, J.; Baeuerle, T.; Semmler, W.; Bartling, S. H.] German Canc Res Ctr, Dept Med Phys Radiol, D-6900 Heidelberg, Germany. [Dinkel, J.] German Canc Res Ctr, Dept Radiol, D-6900 Heidelberg, Germany. [Zwick, S.] Univ Freiburg, Dept Diagnost Radiol, D-7800 Freiburg, Germany. [Grasruck, M.] Siemens Healthcare, Forchheim, Germany. [Kiessling, F.] Rhein Westfal TH Aachen, Fac Med, Chair Expt Mol Imaging, Aachen, Germany. [Gupta, R.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Kuntz, J (reprint author), German Canc Res Ctr, Dept Med Phys Radiol, D-6900 Heidelberg, Germany. EM j.kuntz@dkfz.de FU Deutsche Forschungsgemeinschaft (German Research Foundation) [TR23] FX The authors thank Karin Leotta for her excellent technical assistance during data acquisition and post-processing. The work was supported by the transregional grant 'Vascular Differentiation and Remodeling' from the Deutsche Forschungsgemeinschaft (German Research Foundation) TR23, DFG. NR 22 TC 7 Z9 7 U1 1 U2 2 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD APR 7 PY 2010 VL 55 IS 7 BP 2069 EP 2085 DI 10.1088/0031-9155/55/7/018 PG 17 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 571MP UT WOS:000275756200018 PM 20299735 ER PT J AU Yeh, JM Nekhlyudov, L Goldie, SJ Mertens, AC Diller, L AF Yeh, Jennifer M. Nekhlyudov, Larissa Goldie, Sue J. Mertens, Ann C. Diller, Lisa TI A Model-Based Estimate of Cumulative Excess Mortality in Survivors of Childhood Cancer SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID LONG-TERM SURVIVORS; 5-YEAR SURVIVORS; ADOLESCENT CANCER; ADULT SURVIVORS; DEATH; OUTCOMES; COHORT AB Background: Although childhood cancer survival rates have dramatically increased, survivors face elevated risk for life-threatening late effects, including secondary cancer. Objective: To estimate the cumulative effect of disease-and treatment-related mortality risks on survivor life expectancy. Design: State-transition model to simulate the lifetime clinical course of childhood cancer survivors. Setting: Childhood Cancer Survivor Study. Patients: Five-year survivors of childhood cancer. Measurements: Probabilities of risk for death from the original cancer diagnosis, excess mortality from subsequent cancer and cardiac, pulmonary, external, and other complications, and background mortality (age-specific mortality rates for the general population) were estimated over the lifetime of survivors of childhood cancer. Results: For a cohort of 5-year survivors aged 15 years who received a diagnosis of cancer at age 10 years, the average lifetime probability was 0.10 for late-recurrence mortality; 0.15 for treatment-related subsequent cancer and death from cardiac, pulmonary, and external causes; and 0.05 for death from other excess risks. Life expectancy for the cohort of persons aged 15 years was 50.6 years, a loss of 10.4 years (17.1%) compared with the general population. Reduction in life expectancy varied by diagnosis, ranging from 4.0 years (6.0%) for kidney tumor survivors to more than 17.8 years (>= 28.0%) for brain and bone tumor survivors, and was sensitive to late-recurrence mortality risk and duration of excess mortality risk. Limitation: Estimates are based on data for survivors who received treatment 20 to 40 years ago; patients who received treatment more recently may have more favorable outcomes. Conclusion: Childhood cancer survivors face considerable mortality during adulthood, with excess risks reducing life expectancy by as much as 28%. Monitoring the health of current survivors and carefully evaluating therapies with known late toxicities in patients with newly diagnosed cancer are needed. C1 [Yeh, Jennifer M.] Harvard Univ, Sch Publ Hlth, Ctr Hlth Decis Sci, Med Sch,Harvard Pilgrim Hlth Care Inst, Boston, MA 02115 USA. Harvard Vanguard Med Associates, Dana Farber Canc Inst, Boston, MA USA. Childrens Hosp, Boston, MA 02115 USA. Emory Univ, Atlanta, GA 30322 USA. RP Yeh, JM (reprint author), Harvard Univ, Sch Publ Hlth, Ctr Hlth Decis Sci, Med Sch,Harvard Pilgrim Hlth Care Inst, 718 Huntington Ave,2nd Floor, Boston, MA 02115 USA. EM jyeh@hsph.harvard.edu FU National Cancer Institute [R25-CA057711] FX Grant Support: By the National Cancer Institute (R25-CA057711; Dr. Yeh). NR 29 TC 36 Z9 36 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD APR 6 PY 2010 VL 152 IS 7 BP 409 EP W138 DI 10.7326/0003-4819-152-7-201004060-00005 PG 17 WC Medicine, General & Internal SC General & Internal Medicine GA 579QI UT WOS:000276386900001 PM 20368646 ER PT J AU Rosenquist, JN Murabito, J Fowler, JH Christakis, NA AF Rosenquist, J. Niels Murabito, Joanne Fowler, James H. Christakis, Nicholas A. TI The Spread of Alcohol Consumption Behavior in a Large Social Network SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID CORONARY-HEART-DISEASE; LONGITUDINAL ANALYSIS; COGNITIVE FUNCTION; COLLEGE DRINKING; PEER INFLUENCES; RISK; ADOLESCENTS; SMOKING; MODELS; ONSET AB Background: Alcohol consumption has important health-related consequences and numerous biological and social determinants. Objective: To explore quantitatively whether alcohol consumption behavior spreads from person to person in a large social network of friends, coworkers, siblings, spouses, and neighbors, followed for 32 years. Design: Longitudinal network cohort study. Setting: The Framingham Heart Study. Participants: 12 067 persons assessed at several time points between 1971 and 2003. Measurements: Self-reported alcohol consumption (number of drinks per week on average over the past year and number of days drinking within the past week) and social network ties, measured at each time point. Results: Clusters of drinkers and abstainers were present in the network at all time points, and the clusters extended to 3 degrees of separation. These clusters were not only due to selective formation of social ties among drinkers but also seem to reflect interpersonal influence. Changes in the alcohol consumption behavior of a person's social network had a statistically significant effect on that person's subsequent alcohol consumption behavior. The behaviors of immediate neighbors and coworkers were not significantly associated with a person's drinking behavior, but the behavior of relatives and friends was. Limitations: A nonclinical measure of alcohol consumption was used. Also, it is unclear whether the effects on long-term health are positive or negative, because alcohol has been shown to be both harmful and protective. Finally, not all network ties were observed. Conclusion: Network phenomena seem to influence alcohol consumption behavior. This has implications for clinical and public health interventions and further supports group-level interventions to reduce problematic drinking. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Univ Calif San Diego, San Diego, CA 92103 USA. Harvard Univ, Cambridge, MA USA. RP Christakis, NA (reprint author), Harvard Univ, Sch Med, 180-A Longwood Ave, Boston, MA 02115 USA. EM christakis@hcp.med.harvard.edu RI Christakis, Nicholas/C-3205-2009; Fowler, James/C-2750-2008; OI Fowler, James/0000-0001-7795-1638; Murabito, Joanne/0000-0002-0192-7516 FU National Institutes of Health [R01AG2444801]; Robert Wood Johnson Foundation; National Heart, Lung, and Blood Institute [N01HC25195] FX Grant Support: By the National Institutes of Health (grant R01AG2444801) and a Pioneer Award from the Robert Wood Johnson Foundation. The Framingham Heart Study is supported by the National Heart, Lung, and Blood Institute (grant N01HC25195). NR 48 TC 158 Z9 161 U1 8 U2 51 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD APR 6 PY 2010 VL 152 IS 7 BP 426 EP W141 DI 10.7326/0003-4819-152-7-201004060-00007 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 579QI UT WOS:000276386900003 PM 20368648 ER PT J AU Stein, PD Chenevert, TL Fowler, SE Goodman, LR Gottschalk, A Hales, CA Hull, RD Jablonski, KA Leeper, KV Naidich, DP Sak, DJ Sostman, D Tapson, VF Weg, JG Woodard, PK AF Stein, Paul D. Chenevert, Thomas L. Fowler, Sarah E. Goodman, Lawrence R. Gottschalk, Alexander Hales, Charles A. Hull, Russell D. Jablonski, Kathleen A. Leeper, Kenneth V., Jr. Naidich, David P. Sak, Daniel J. Sostman, Dirk Tapson, Victor F. Weg, John G. Woodard, Pamela K. CA PIOPED III Investigators TI Gadolinium-Enhanced Magnetic Resonance Angiography for Pulmonary Embolism A Multicenter Prospective Study (PIOPED III) SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID VENTILATION-PERFUSION SCINTIGRAPHY; TOTAL HIP-REPLACEMENT; DEEP-VEIN THROMBOSIS; MR-ANGIOGRAPHY; VENOUS THROMBOSIS; DIAGNOSTIC-TEST; CLINICAL-MODEL; DOUBLE-BLIND; D-DIMER; ENOXAPARIN AB Background: The accuracy of gadolinium-enhanced magnetic resonance pulmonary angiography and magnetic resonance venography for diagnosing pulmonary embolism has not been determined conclusively. Objective: To investigate performance characteristics of magnetic resonance angiography, with or without magnetic resonance venography, for diagnosing pulmonary embolism. Design: Prospective, multicenter study from 10 April 2006 to 30 September 2008. (ClinicalTrials.gov registration number: NCT00241826) Setting: 7 hospitals and their emergency services. Patients: 371 adults with diagnosed or excluded pulmonary embolism. Measurements: Sensitivity, specificity, and likelihood ratios were measured by comparing independently read magnetic resonance imaging with the reference standard for diagnosing pulmonary embolism. Reference standard diagnosis or exclusion was made by using various tests, including computed tomographic angiography and venography, ventilation-perfusion lung scan, venous ultrasonography, D-dimer assay, and clinical assessment. Results: Magnetic resonance angiography, averaged across centers, was technically inadequate in 25% of patients (92 of 371). The proportion of technically inadequate images ranged from 11% to 52% at various centers. Including patients with technically inadequate images, magnetic resonance angiography identified 57% (59 of 104) with pulmonary embolism. Technically adequate magnetic resonance angiography had a sensitivity of 78% and a specificity of 99%. Technically adequate magnetic resonance angiography and venography had a sensitivity of 92% and a specificity of 96%, but 52% of patients (194 of 370) had technically inadequate results. Limitation: A high proportion of patients with suspected embolism was not eligible or declined to participate. Conclusion: Magnetic resonance pulmonary angiography should be considered only at centers that routinely perform it well and only for patients for whom standard tests are contraindicated. Magnetic resonance pulmonary angiography and magnetic resonance venography combined have a higher sensitivity than magnetic resonance pulmonary angiography alone in patients with technically adequate images, but it is more difficult to obtain technically adequate images with the 2 procedures. C1 [Stein, Paul D.] Michigan State Univ, Coll Osteopath Med, Venous Thromboembolism Res Unit, Dept Internal Med,St Joseph Mercy Oakland Hosp, Pontiac, MI 48341 USA. Michigan State Univ, Coll Osteopath Med, E Lansing, MI 48824 USA. Univ Michigan, Ann Arbor, MI 48109 USA. George Washington Univ, Rockville, MD USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Calgary, Calgary, AB, Canada. Emory Univ, Atlanta, GA 30322 USA. NYU, Med Ctr, New York, NY 10016 USA. Weill Cornell Med Coll, Houston, TX USA. Methodist Hosp, Houston, TX 77030 USA. Duke Univ, Durham, NC USA. Washington Univ, St Louis, MO USA. RP Stein, PD (reprint author), Michigan State Univ, Coll Osteopath Med, Venous Thromboembolism Res Unit, Dept Internal Med,St Joseph Mercy Oakland Hosp, 44405 Woodward Ave, Pontiac, MI 48341 USA. EM steinp@trinity-health.org RI Staff, Roger/G-1826-2011; OI Staff, Roger/0000-0003-0620-8673; naidich, david/0000-0003-3751-5836 FU U.S. Department of Health and Human Service, Public Health Service, National Heart, Lung, and Blood Institute (NHLBI), Bethesda, Maryland [HL081593, HL177150, HL077149, HL077151, HL077154, HL081594, HL077358, HL077155, HL077153] FX Grant Support: By the U.S. Department of Health and Human Service, Public Health Service, National Heart, Lung, and Blood Institute (NHLBI), Bethesda, Maryland (grants HL081593, HL177150, HL077149, HL077151, HL077154, HL081594, HL077358, HL077155, and HL077153). NR 39 TC 148 Z9 161 U1 0 U2 10 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD APR 6 PY 2010 VL 152 IS 7 BP 434 EP W143 DI 10.7326/0003-4819-152-7-201004060-00008 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 579QI UT WOS:000276386900004 PM 20368649 ER PT J AU Henderson, TO Amsterdam, A Bhatia, S Hudson, MM Meadows, AT Neglia, JP Diller, LR Constine, LS Smith, RA Mahoney, MC Morris, EA Montgomery, LL Landier, W Smith, SM Robison, LL Oeffinger, KC AF Henderson, Tara O. Amsterdam, Alison Bhatia, Smita Hudson, Melissa M. Meadows, Anna T. Neglia, Joseph P. Diller, Lisa R. Constine, Louis S. Smith, Robert A. Mahoney, Martin C. Morris, Elizabeth A. Montgomery, Leslie L. Landier, Wendy Smith, Stephanie M. Robison, Leslie L. Oeffinger, Kevin C. TI Systematic Review: Surveillance for Breast Cancer in Women Treated With Chest Radiation for Childhood, Adolescent, or Young Adult Cancer SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID LONG-TERM SURVIVORS; BRCA2 MUTATION CARRIERS; HODGKINS-DISEASE; RISK-FACTORS; SCREENING-PROGRAM; SUPRADIAPHRAGMATIC RADIATION; COST-EFFECTIVENESS; FEMALE SURVIVORS; 2ND CANCERS; FOLLOW-UP AB Background: Women treated with therapeutic chest radiation may develop breast cancer. Purpose: To summarize breast cancer risk and breast cancer surveillance in women after chest radiation for pediatric or young adult cancer. Data Sources: Studies from MEDLINE, EMBASE, the Cochrane Library, and CINAHL (1966 to December 2008). Study Selection: Articles were selected to answer any of 3 questions: What is the incidence and excess risk for breast cancer in women after chest radiation for pediatric or young adult cancer? For these women, are the clinical characteristics of breast cancer and the outcomes after therapy different from those of women with sporadic breast cancer in the general population? What are the potential benefits and harms associated with breast cancer surveillance among women exposed to chest radiation? Data Extraction: Three investigators independently extracted data and assessed study quality. Data Synthesis: Standardized incidence ratios ranged from 13.3 to 55.5; cumulative incidence of breast cancer by age 40 to 45 years ranged from 13% to 20%. Risk for breast cancer increased linearly with chest radiation dose. Available limited evidence suggests that the characteristics of breast cancer in these women and the outcomes after diagnosis are similar to those of women in the general population; mammography can detect breast cancer, although sensitivity is limited. Limitation: The quality of evidence for key questions 2 and 3 is limited by substantial study heterogeneity, variation in study design, and small sample size. Conclusion: Women treated with chest radiation have a substantially elevated risk for breast cancer at a young age, which does not seem to plateau. In this high-risk population, there seems to be a benefit associated with early detection. Further research is required to better define the harms and benefits of lifelong surveillance. C1 [Oeffinger, Kevin C.] Mem Sloan Kettering Canc Ctr, Dept Pediat, Mt Sinai Med Ctr, New York, NY 10065 USA. Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Univ Minnesota, Minneapolis, MN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Rochester, Med Ctr, Rochester, NY 14642 USA. Montefiore Einstein Ctr Canc Care, Bronx, NY USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. RP Oeffinger, KC (reprint author), Mem Sloan Kettering Canc Ctr, Dept Pediat, Mt Sinai Med Ctr, 1275 York Ave,Box 396, New York, NY 10065 USA. EM oeffingk@mskcc.org FU National Cancer Institute [U10 CA098543] FX Grant Support: By the National Cancer Institute (grant U10 CA098543). NR 83 TC 76 Z9 78 U1 0 U2 12 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD APR 6 PY 2010 VL 152 IS 7 BP 444 EP W154 DI 10.7326/0003-4819-152-7-201004060-00009 PG 23 WC Medicine, General & Internal SC General & Internal Medicine GA 579QI UT WOS:000276386900005 PM 20368650 ER PT J AU Schwamm, LH Reeves, MJ Pan, WQ Smith, EE Frankel, MR Olson, D Zhao, X Peterson, E Fonarow, GC AF Schwamm, Lee H. Reeves, Mathew J. Pan, Wenqin Smith, Eric E. Frankel, Michael R. Olson, DaiWai Zhao, Xin Peterson, Eric Fonarow, Gregg C. TI Race/Ethnicity, Quality of Care, and Outcomes in Ischemic Stroke SO CIRCULATION LA English DT Article DE stroke; thrombolysis; epidemiology; race; ethnicity; quality of health care ID NORTHERN MANHATTAN STROKE; BRAIN ATTACK SURVEILLANCE; NON-HISPANIC WHITES; ETHNIC DISPARITIES; MEXICAN-AMERICANS; PLASMINOGEN-ACTIVATOR; POSTACUTE OUTCOMES; URBAN-COMMUNITY; BASIC PROJECT; UNITED-STATES AB Background-Prior studies suggest differences in stroke care associated with race/ethnicity. We sought to determine whether such differences existed in a population of black, Hispanic, and white patients hospitalized with stroke among hospitals participating in a quality-improvement program. Methods and Results-We analyzed in-hospital mortality and 7 stroke performance measures among 397 257 patients admitted with ischemic stroke to 1181 hospitals participating in the Get With The Guidelines-Stroke program 2003 through 2008. Relative to white patients, black and Hispanic patients were younger and more often had diabetes mellitus and hypertension. After adjustment for both patient-and hospital-level variables, black patients had lower odds relative to white patients of receiving intravenous thrombolysis (odds ratio [OR], 0.84; 95% confidence interval [CI], 0.77 to 0.91), deep vein thrombosis prophylaxis (OR, 0.88; 95% CI, 0.83 to 0.92), smoking cessation (OR, 0.85; 95% CI, 0.79 to 0.91), discharge antithrombotics (OR, 0.88; 95% CI, 0.84 to 0.92), anticoagulants for atrial fibrillation (OR, 0.84; 95% CI, 0.75 to 0.94), and lipid therapy (OR, 0.91; 95% CI, 0.88 to 0.96), and of dying in-hospital (OR, 0.90; 95% CI, 0.85 to 0.95). Hispanic patients received similar care as their white counterparts on all 7 measures and had similar in-hospital mortality. Black (OR, 1.31; 95% CI, 1.28 to 1.35) and Hispanic (OR, 1.16; 95% CI, 1.11 to 1.20) patients had higher odds of exceeding the median length of hospital stay relative to whites. During the study, quality of care improved in all 3 race/ethnicity groups. Conclusions-Black patients with stroke received fewer evidence-based care processes than Hispanic or white patients. These differences could lead to increased risk of recurrent stroke. Quality of care improved substantially in the Get With The Guidelines-Stroke Program over time for all 3 racial/ethnic groups. (Circulation. 2010;121:1492-1501.) C1 [Schwamm, Lee H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Reeves, Mathew J.] Michigan State Univ, E Lansing, MI 48824 USA. [Pan, Wenqin; Olson, DaiWai; Zhao, Xin; Peterson, Eric] Duke Clin Res Inst, Durham, NC USA. [Smith, Eric E.] Univ Calgary, Hotchkiss Brain Inst, Calgary, AB, Canada. [Frankel, Michael R.] Emory Univ, Atlanta, GA 30322 USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. RP Schwamm, LH (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM lschwamm@partners.org RI Smith, Eric/C-5443-2012; OI Smith, Eric/0000-0003-3956-1668; Schwamm, Lee/0000-0003-0592-9145 FU American Heart Association; American Stroke Association; Pfizer Inc, New York, NY; Merck-Schering Plough Partnership (North Wales, Pa) FX Get With the Guidelines-Stroke is funded by the American Heart Association and the American Stroke Association. 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, manuscript preparation, or approval. NR 41 TC 99 Z9 102 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 6 PY 2010 VL 121 IS 13 BP 1492 EP U71 DI 10.1161/CIRCULATIONAHA.109.881490 PG 13 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 579DX UT WOS:000276348600005 PM 20308617 ER PT J AU Marcus, FI McKenna, WJ Sherrill, D Basso, C Bauce, B Bluemke, DA Calkins, H Corrado, D Cox, MGPJ Daubert, JP Fontaine, G Gear, K Hauer, R Nava, A Picard, MH Protonotarios, N Saffitz, JE Sanborn, DMY Steinberg, JS Tandri, H Thiene, G Towbin, JA Tsatsopoulou, A Wichter, T Zareba, W AF Marcus, Frank I. McKenna, William J. Sherrill, Duane Basso, Cristina Bauce, Barbara Bluemke, David A. Calkins, Hugh Corrado, Domenico Cox, Moniek G. P. J. Daubert, James P. Fontaine, Guy Gear, Kathleen Hauer, Richard Nava, Andrea Picard, Michael H. Protonotarios, Nikos Saffitz, Jeffrey E. Sanborn, Danita M. Yoerger Steinberg, Jonathan S. Tandri, Harikrishna Thiene, Gaetano Towbin, Jeffrey A. Tsatsopoulou, Adalena Wichter, Thomas Zareba, Wojciech TI Diagnosis of Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia Proposed Modification of the Task Force Criteria SO CIRCULATION LA English DT Article DE arrhythmias, cardiac; arrhythmogenic right ventricular cardiomyopathy/dysplasia; death, sudden, cardiac; diagnosis; echocardiography; electrocardiography; magnetic resonance imaging ID GENOTYPE-PHENOTYPE ASSESSMENT; MAGNETIC-RESONANCE; NAXOS-DISEASE; WOOLLY HAIR; PALMOPLANTAR KERATODERMA; QUANTITATIVE ASSESSMENT; DILATED CARDIOMYOPATHY; ENDOMYOCARDIAL BIOPSY; WALL-MOTION; DYSPLASIA/CARDIOMYOPATHY AB Background-In 1994, an International Task Force proposed criteria for the clinical diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) that facilitated recognition and interpretation of the frequently nonspecific clinical features of ARVC/D. This enabled confirmatory clinical diagnosis in index cases through exclusion of phenocopies and provided a standard on which clinical research and genetic studies could be based. Structural, histological, electrocardiographic, arrhythmic, and familial features of the disease were incorporated into the criteria, subdivided into major and minor categories according to the specificity of their association with ARVC/D. At that time, clinical experience with ARVC/D was dominated by symptomatic index cases and sudden cardiac death victims-the overt or severe end of the disease spectrum. Consequently, the 1994 criteria were highly specific but lacked sensitivity for early and familial disease. Methods and Results-Revision of the diagnostic criteria provides guidance on the role of emerging diagnostic modalities and advances in the genetics of ARVC/D. The criteria have been modified to incorporate new knowledge and technology to improve diagnostic sensitivity, but with the important requisite of maintaining diagnostic specificity. The approach of classifying structural, histological, electrocardiographic, arrhythmic, and genetic features of the disease as major and minor criteria has been maintained. In this modification of the Task Force criteria, quantitative criteria are proposed and abnormalities are defined on the basis of comparison with normal subject data. Conclusions-The present modifications of the Task Force Criteria represent a working framework to improve the diagnosis and management of this condition. C1 [Marcus, Frank I.; Sherrill, Duane; Gear, Kathleen] Univ Arizona, Tucson, AZ USA. [McKenna, William J.] Heart Hosp, London, England. [Basso, Cristina; Bauce, Barbara; Corrado, Domenico; Nava, Andrea; Thiene, Gaetano] Univ Padua, Sch Med, Padua, Italy. [Bluemke, David A.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Calkins, Hugh; Tandri, Harikrishna] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Cox, Moniek G. P. J.; Hauer, Richard] Univ Med Ctr Utrecht, Utrecht, Netherlands. [Daubert, James P.] Univ Rochester, Strong Mem Hosp, Rochester, NY 14642 USA. [Zareba, Wojciech] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Steinberg, Jonathan S.] St Lukes Roosevelt Hosp, New York, NY USA. [Fontaine, Guy] Hop La Pitie Salpetriere, Paris, France. [Picard, Michael H.; Sanborn, Danita M. Yoerger] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Saffitz, Jeffrey E.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Protonotarios, Nikos; Tsatsopoulou, Adalena] Yannis Protonotarios Med Ctr, Hora Naxos, Greece. [Towbin, Jeffrey A.] Cincinnati Childrens Hosp, Cincinnati, OH USA. [Wichter, Thomas] Marien Hosp, Osnabruck, Germany. RP Marcus, FI (reprint author), Sarver Heart Ctr, 1501 N Campbell,Rm 5153,Box 245037, Tucson, AZ USA. EM fmarcus@u.arizona.edu RI McKenna, William/C-3243-2008; OI McKenna, William/0000-0001-7994-2460; Picard, Michael/0000-0002-9264-3243; Bluemke, David/0000-0002-8323-8086 FU National Institutes of Health [R13 HL086825]; National Heart, Lung & Blood Institute; National Heart, Lung and Blood Institute of the National Institutes of Health, Bethesda, Md [U01-HL65594, U01-HL65652, U01-HL65691, K23-HL093350]; European Commission, Brussels, Belgium [QLG1-CT-2000-01091]; International Society for Holter; Peter French Memorial Foundation; United Desert Charities; Podolsky Family Foundation FX This project was supported by National Institutes of Health research grant R13 HL086825, funded by the National Heart, Lung & Blood Institute and the Office of Rare Disorders, and was supported in part by research grants U01-HL65594, U01-HL65652, U01-HL65691, and K23-HL093350 from the National Heart, Lung and Blood Institute of the National Institutes of Health, Bethesda, Md, and by research grant QLG1-CT-2000-01091 5th Framework Programme from the European Commission, Brussels, Belgium. Additional funding was obtained from the International Society for Holter and Noninvasive Electrocardiography and donations from the Peter French Memorial Foundation, United Desert Charities, the Podolsky Family Foundation, and private donors Mr and Mrs L. Becker, Mr and Mrs H. Danz, Mr K. Dorn, Mr T. Livolsi, Mr and Mrs L. Long, and Mr and Mrs H. Wilmerding. NR 59 TC 547 Z9 569 U1 4 U2 25 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 6 PY 2010 VL 121 IS 13 BP 1533 EP U118 DI 10.1161/CIRCULATIONAHA.108.840827 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 579DX UT WOS:000276348600010 PM 20172911 ER PT J AU Scirica, BM AF Scirica, Benjamin M. TI Acute Coronary Syndrome Emerging Tools for Diagnosis and Risk Assessment SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Review DE acute coronary syndrome; diagnosis; myocardial infarction; risk stratification ID ACUTE MYOCARDIAL-INFARCTION; C-REACTIVE PROTEIN; ACUTE CHEST-PAIN; GROWTH-DIFFERENTIATION FACTOR-15; CARDIAC TROPONIN-T; MULTIDETECTOR COMPUTED-TOMOGRAPHY; BRAIN NATRIURETIC PEPTIDE; ST-SEGMENT RESOLUTION; PROGNOSTIC VALUE; ARTERY-DISEASE AB Acute coronary syndrome encompasses a broad and heterogeneous population that challenges the clinician at each step of treatment in terms of: 1) diagnosis; 2) appropriate risk stratification; 3) therapeutic decision making; and 4) monitoring response to therapy. Although there are many established tools for diagnosis, prognosis, and clinical decision making, understanding the advantages and limitations of each tool according the clinical scenario is essential. Several emerging tools, such as novel biomarkers (e.g., high-sensitivity troponin and growth differential factor-15), ECG techniques (e.g., heart rate turbulence or T-wave alternans), and imaging modalities (computed tomography angiography and cardiac magnetic resonance) may potentially improve clinical care; however, they must be fully evaluated and validated in different scenarios and patient cohorts before they are incorporated into clinical practice. This review identifies promising new or emerging techniques, as well as established tools, and reviews their current or potential role in clinical practice. (J Am Coll Cardiol 2010; 55: 1403-15) (C) 2010 by the American College of Cardiology Foundation C1 Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Boston, MA 02115 USA. RP Scirica, BM (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM bscirica@partners.org FU TIMI Study Group; Brigham and Women's Hospital FX From the TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts. Dr. Scirica has received research grants via the TIMI Study Group and Brigham and Women's Hospital from CV Therapeutics, Novartis, AstraZeneca, Daiichi-Sankyo, Merck, Johnson and Johnson, Bayer Healthcare, and Bristol-Myers Squibb. He has received honoraria for educational presentations from CV Therapeutics, Novartis, Merck, and Schering-Plough; and has served as a consultant for AstraZeneca, Novartis, CV Therapeutics, Congentus, Shionegi, and Gilead Sciences. NR 101 TC 47 Z9 50 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 6 PY 2010 VL 55 IS 14 BP 1403 EP 1415 DI 10.1016/j.jacc.2009.09.071 PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 583AV UT WOS:000276644500001 PM 20359589 ER PT J AU Stolker, JM McCullough, PA Rao, S Inzucchi, SE Spertus, JA Maddox, TM Masoudi, FA Xiao, L Kosiborod, M AF Stolker, Joshua M. McCullough, Peter A. Rao, Seshu Inzucchi, Silvio E. Spertus, John A. Maddox, Thomas M. Masoudi, Frederick A. Xiao, Lan Kosiborod, Mikhail TI Pre-Procedural Glucose Levels and the Risk for Contrast-Induced Acute Kidney Injury in Patients Undergoing Coronary Angiography SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE contrast nephropathy; acute kidney injury; glucose; diabetes; myocardial infarction; coronary angiography ID ACUTE MYOCARDIAL-INFARCTION; CRITICALLY-ILL PATIENTS; ACUTE-RENAL-FAILURE; INTENSIVE INSULIN THERAPY; INDUCED NEPHROPATHY; ACUTE HYPERGLYCEMIA; DIABETES-MELLITUS; BLOOD-GLUCOSE; NITRIC-OXIDE; PRIMARY ANGIOPLASTY AB Objectives We sought to evaluate whether pre-procedural glucose levels are associated with contrast-induced acute kidney injury (CI-AKI) after coronary angiography. Background Although diabetes is a known risk factor for CI-AKI in patients undergoing coronary angiography, whether elevated pre-procedural glucose levels (regardless of pre-existing diabetes) are associated with higher risk for CI-AKI is unknown. Methods We evaluated 6,358 patients with acute myocardial infarctions undergoing coronary angiography. Patients were stratified into 5 pre-procedural glucose groups: <110 mg/dl, 110 to <140 mg/dl, 140 to <170 mg/dl, 170 to <200 mg/dl, and >= 200 mg/dl. Logistic regression models were used to evaluate the relationship between glucose levels and risk for CI-AKI, first in the entire cohort and then in patients with and without established diabetes. The primary outcome was CI-AKI (>= 0.3 mg/dl absolute or >= 50% relative serum creatinine increase during 48 h after the procedure). Results The relationship between pre-procedural glucose and CI-AKI varied markedly in patients with and without diabetes. There was a strong association between glucose and CI-AKI risk in patients without diabetes (CI-AKI rates across the 5 glucose groups from lowest to highest: 8.2%, 9.9%, 12.4%, 14.9%, and 24.3%; p < 0.001), but not in patients with diabetes (20.9%, 16.1%, 16.3%, 14.8%, and 19.2%, respectively; p = 0.24; p for glucose X diabetes interaction <0.001). After adjusting for confounders (including baseline glomerular filtration rate), the relationship between higher glucose and greater CI-AKI risk persisted in patients without diabetes (odds ratios [95% confidence intervals] for glucose groups of 110 to <140 mg/dl, 140 to <170, mg/dl 170 to <200 mg/dl, and >= 200 mg/dl: 1.31 [1.00 to 1.71], 1.51 [1.11 to 2.10], 1.58 [1.03 to 2.43], and 2.14 [1.46 to 3.14] vs. glucose <110 mg/dl, respectively), but this relationship was not seen in patients with established diabetes. Conclusions Elevated pre-procedural glucose is associated with greater risk for CI-AKI in patients without known diabetes who undergo coronary angiography in the setting of acute myocardial infarction. Measures used to prevent CI-AKI should be considered in these patients. (J Am Coll Cardiol 2010; 55: 1433-40) (C) 2010 by the American College of Cardiology Foundation C1 [Stolker, Joshua M.; Rao, Seshu; Spertus, John A.; Xiao, Lan; Kosiborod, Mikhail] St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA. [Stolker, Joshua M.; Rao, Seshu; Spertus, John A.; Kosiborod, Mikhail] Univ Missouri, Kansas City, MO 64110 USA. [McCullough, Peter A.] William Beaumont Hosp, Royal Oak, MI 48072 USA. [Inzucchi, Silvio E.] Yale Univ, New Haven, CT USA. [Inzucchi, Silvio E.] Yale New Haven Med Ctr, New Haven, CT 06504 USA. [Maddox, Thomas M.] Denver VA Med Ctr, Denver, CO USA. [Masoudi, Frederick A.] Denver Hlth Med Ctr, Denver, CO USA. [Masoudi, Frederick A.] Univ Colorado, Hlth Sci Ctr, Denver, CO USA. RP Kosiborod, M (reprint author), St Lukes Hosp, Mid Amer Heart Inst, 4401 Wornall Rd, Kansas City, MO 64111 USA. EM mkosiborod@cc-pc.com FU American Heart Association Career Development Award in Implementation Research; AstraZeneca Pharmaceuticals; Pfizer Pharmaceuticals; Eli Lilly; Sanofi-Aventis FX The research for this analysis was supported by the American Heart Association Career Development Award in Implementation Research, awarded to Dr. Kosiborod. Dr. Stolker has received speaking honoraria from AstraZeneca Pharmaceuticals and Pfizer Pharmaceuticals; has served as a consultant to Novo Nordisk; and has served on the advisory board of Educational Testing Consultants, LLC. Dr. Inzucchi has received research grant support from Eli Lilly. Dr. Spertus has received research grant support from Sanofi-Aventis and Eli Lilly. Dr. Masoudi was previously a member of the advisory board of Takeda Pharmaceuticals. Dr. Kosiborod has served on the advisory board of Sanofi-Aventis and has received speaking honoraria from the Vascular Biology Working Group and DiaVed, Inc. The Cerner Corporation collected deidentified clinical information for the Health Facts database. The Cerner Corporation had no role in study design, data analysis, interpretation of findings, or writing of the manuscript. The American Heart Association had no role in the study. NR 47 TC 34 Z9 36 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 6 PY 2010 VL 55 IS 14 BP 1433 EP 1440 DI 10.1016/j.jacc.2009.09.072 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 583AV UT WOS:000276644500005 PM 20359592 ER PT J AU Bratlie, KM Dang, TT Lyle, S Nahrendorf, M Weissleder, R Langer, R Anderson, DG AF Bratlie, Kaitlin M. Dang, Tram T. Lyle, Stephen Nahrendorf, Matthias Weissleder, Ralph Langer, Robert Anderson, Daniel G. TI Rapid Biocompatibility Analysis of Materials via In Vivo Fluorescence Imaging of Mouse Models SO PLOS ONE LA English DT Article ID FOREIGN-BODY REACTION; NEUTROPHIL GRANULES; ALGINATE; ISLETS; MICROSPHERES; INFLAMMATION; FIBROBLASTS; MACROPHAGES; ARTHRITIS; HISTOLOGY AB Background: Many materials are unsuitable for medical use because of poor biocompatibility. Recently, advances in the high throughput synthesis of biomaterials has significantly increased the number of potential biomaterials, however current biocompatibility analysis methods are slow and require histological analysis. Methodology/Principal Findings: Here we develop rapid, non-invasive methods for in vivo quantification of the inflammatory response to implanted biomaterials. Materials were placed subcutaneously in an array format and monitored for host responses as per ISO 10993-6: 2001. Host cell activity in response to these materials was imaged kinetically, in vivo using fluorescent whole animal imaging. Data captured using whole animal imaging displayed similar temporal trends in cellular recruitment of phagocytes to the biomaterials compared to histological analysis. Conclusions/Significance: Histological analysis similarity validates this technique as a novel, rapid approach for screening biocompatibility of implanted materials. Through this technique there exists the possibility to rapidly screen large libraries of polymers in vivo. C1 [Bratlie, Kaitlin M.; Dang, Tram T.; Langer, Robert] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Bratlie, Kaitlin M.; Dang, Tram T.; Langer, Robert; Anderson, Daniel G.] Childrens Hosp, Dept Anesthesiol, Boston, MA 02115 USA. [Lyle, Stephen] Univ Massachusetts, Sch Med, Dept Canc Biol, Worcester, MA USA. [Nahrendorf, Matthias; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Langer, Robert; Anderson, Daniel G.] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. RP Bratlie, KM (reprint author), MIT, Dept Chem Engn, Cambridge, MA 02139 USA. EM dgander@mit.edu RI Dang, Tram/E-7966-2011 FU Juvenile Diabetes Research Foundation [17-2007-1063]; Agency for Science, Technology and Research of Singapore FX This work was supported by grant 17-2007-1063 from the Juvenile Diabetes Research Foundation. T. D. is grateful to the support from the Agency for Science, Technology and Research of Singapore for the A*STAR National Science graduate fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 42 TC 26 Z9 26 U1 0 U2 19 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 6 PY 2010 VL 5 IS 3 AR e10032 DI 10.1371/journal.pone.0010032 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 580BA UT WOS:000276420400009 PM 20386609 ER PT J AU Pegtel, DM Cosmopoulos, K Thorley-Lawson, DA van Eijndhoven, MAJ Hopmans, ES Lindenberg, JL de Gruijl, TD Wurdinger, T Middeldorp, JM AF Pegtel, D. Michiel Cosmopoulos, Katherine Thorley-Lawson, David A. van Eijndhoven, Monique A. J. Hopmans, Erik S. Lindenberg, Jelle L. de Gruijl, Tanja D. Wurdinger, Thomas Middeldorp, Jaap M. TI Functional delivery of viral miRNAs via exosomes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE intercellular communication; exosomes; Epstein-Barr virus; small RNA; gene repression ID EPSTEIN-BARR-VIRUS; DENDRITIC CELLS; IMMUNE-SYSTEM; MICRORNA EXPRESSION; ENCODED MICRORNAS; SMALL RNAS; EBV; MECHANISM; MICROVESICLES; PERSISTENCE AB Noncoding regulatorymicroRNAs (miRNAs) of cellular and viral origin control gene expression by repressing the translation of mRNAs into protein. Interestingly, miRNAs are secreted actively through small vesicles called "exosomes" that protect them from degradation by RNases, suggesting that these miRNAs may function outside the cell in which they were produced. Here we demonstrate that miRNAs secreted by EBV-infected cells are transferred to and act in uninfected recipient cells. Using a quantitative RT-PCR approach, we demonstrate thatmature EBV-encoded miRNAs are secreted by EBV-infected B cells through exosomes. These EBV-miRNAs are functional because internalization of exosomes by MoDCresults in a dose-dependent, miRNA-mediated repression of confirmed EBV target genes, including CXCL11/ITAC, an immunoregulatory gene down-regulated in primary EBVassociated lymphomas. We demonstrate that throughout coculture of EBV-infected B cells EBV-miRNAs accumulate in noninfected neighboring MoDC and show that this accumulation is mediated by transfer of exosomes. Thus, the exogenous EBV-miRNAs transferred through exosomes are delivered to subcellular sites of gene repression in recipient cells. Finally, we show in peripheral blood mononuclear cells from patients with increased EBV load that, although EBV DNA is restricted to the circulating B-cell population, EBV BART miRNAs are present in both B-cell and non-B-cell fractions, suggestive of miRNA transfer. Taken together our findings are consistent with miRNA-mediated gene silencing as a potential mechanism of intercellular communication between cells of the immune system that maybe exploited by the persistent human gamma-herpesvirus EBV. C1 [Pegtel, D. Michiel; van Eijndhoven, Monique A. J.; Hopmans, Erik S.; Middeldorp, Jaap M.] Vrije Univ Amsterdam, Med Ctr, Canc Ctr Amsterdam, Dept Pathol, NL-1081 HV Amsterdam, Netherlands. [Cosmopoulos, Katherine; Thorley-Lawson, David A.] Tufts Univ, Sch Med, Dept Pathol, Boston, MA 02111 USA. [Wurdinger, Thomas] Vrije Univ Amsterdam, Med Ctr, Dept Neurosurg, Neurooncol Res Grp, NL-1081 HV Amsterdam, Netherlands. [Lindenberg, Jelle L.; de Gruijl, Tanja D.] Vrije Univ Amsterdam, Med Ctr, Dept Med Oncol, NL-1081 HV Amsterdam, Netherlands. [Wurdinger, Thomas] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Neurogenet Unit, Boston, MA 02115 USA. RP Pegtel, DM (reprint author), Vrije Univ Amsterdam, Med Ctr, Canc Ctr Amsterdam, Dept Pathol, NL-1081 HV Amsterdam, Netherlands. EM d.pegtel@vumc.nl RI Pegtel, Dirk/M-8393-2015; OI Pegtel, Dirk/0000-0002-7357-4406; Middeldorp, Jaap/0000-0002-0765-4125 FU Dutch Cancer Foundation [KWF2007-3775] FX The authors thank Drs. W. Stoorvogel for the B95-8 RN LCL cell line and J. Neefjes for the CD63 and anti-HLA-DR antibodies, Tineke Vendrig and H. Janssen for assisting with EM analysis, Dr. D. Hayward for providing EBV-miRNA BART cluster constructs, Drs. C. Jimenez and S. Piersma for helpful assistance with proteomic analysis, and A. Zomer, A. Muggen, J. Oldenburg, and B. van Thiel for their contributions to the LCL-MoDC co-culture model. D.M.P. is funded by the Netherlands Organization for Scientific Research (NWO-Veni). The work was funded in part by Grant KWF2007-3775 from the Dutch Cancer Foundation. NR 35 TC 545 Z9 580 U1 6 U2 75 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 6 PY 2010 VL 107 IS 14 BP 6328 EP 6333 DI 10.1073/pnas.0914843107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 579MH UT WOS:000276374400038 PM 20304794 ER PT J AU Jang, H Arce, FT Ramachandran, S Capone, R Azimova, R Kagan, BL Nussinov, R Lal, R AF Jang, Hyunbum Arce, Fernando Teran Ramachandran, Srinivasan Capone, Ricardo Azimova, Rushana Kagan, Bruce L. Nussinov, Ruth Lal, Ratnesh TI Truncated beta-amyloid peptide channels provide an alternative mechanism for Alzheimer's Disease and Down syndrome SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE atomic force microscopy; molecular dynamics; cell calcium imaging; neurite degeneration and cell death assays; single-channel conductance ID PRION PROTEIN-FRAGMENT; HEPARIN-BINDING DOMAIN; ION CHANNELS; ZN2+-SENSITIVE CHANNEL; COMMON MECHANISM; MOUSE MODELS; GRAMICIDIN-A; 3D STRUCTURE; CONGO RED; IN-VITRO AB Full-length amyloid beta peptides (A beta(1-40/42)) form neuritic amyloid plaques in Alzheimer's disease (AD) patients and are implicated in AD pathology. However, recent transgenic animal models cast doubt on their direct role in AD pathology. Nonamyloidogenic truncated amyloid-beta fragments (A beta(11-42) and A beta(17-42)) are also found in amyloid plaques of AD and in the preamyloid lesions of Down syndrome, a model system for early-onset AD study. Very little is known about the structure and activity of these smaller peptides, although they could be the primary AD and Down syndrome pathological agents. Using complementary techniques of molecular dynamics simulations, atomic force microscopy, channel conductance measurements, calcium imaging, neuritic degeneration, and cell death assays, we show that nonamyloidogenic A beta(9-42) and A beta(17-42) peptides form ion channels with loosely attached subunits and elicit single-channel conductances. The subunits appear mobile, suggesting insertion of small oligomers, followed by dynamic channel assembly and dissociation. These channels allow calcium uptake in amyloid precursor protein-deficient cells. The channel mediated calcium uptake induces neurite degeneration in human cortical neurons. Channel conductance, calcium uptake, and neurite degeneration are selectively inhibited by zinc, a blocker of amyloid ion channel activity. Thus, truncated A beta fragments could account for undefined roles played by full length A beta s and provide a unique mechanism of AD and Down syndrome pathologies. The toxicity of nonamyloidogenic peptides via an ion channel mechanism necessitates a reevaluation of the current therapeutic approaches targeting the nonamyloidogenic pathway as avenue for AD treatment. C1 [Jang, Hyunbum; Nussinov, Ruth] Natl Canc Inst, SAIC Frederick Inc, Ctr Canc Res, Nanobiol Program, Frederick, MD 21702 USA. [Arce, Fernando Teran; Ramachandran, Srinivasan; Capone, Ricardo; Lal, Ratnesh] Univ Chicago, Ctr Nanomed, Chicago, IL 60637 USA. [Arce, Fernando Teran; Ramachandran, Srinivasan; Capone, Ricardo; Lal, Ratnesh] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Azimova, Rushana; Kagan, Bruce L.] Univ Calif Los Angeles, David Geffen Sch Med, Semel Neuropsychiat Inst, Los Angeles, CA 90024 USA. [Azimova, Rushana; Kagan, Bruce L.] Greater Los Angeles Vet Adm Hlth Syst, Los Angeles, CA 90024 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Mol Genet & Biochem, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), Natl Canc Inst, SAIC Frederick Inc, Ctr Canc Res, Nanobiol Program, Frederick, MD 21702 USA. EM ruthnu@helix.nih.gov; rlal@ucsd.edu RI Capone, Ricardo/D-1943-2010 OI Capone, Ricardo/0000-0002-7327-9837 FU National Institutes of Health [IIRG-05-14089]; National Cancer Institute, National Institutes of Health [HHSN261200800001E]; National Institutes of Health, National Cancer Institute, Center for Cancer Research FX We thank Dr. Robert Tycko for providing the A beta9-40 oligomer coordinates, Dr. Jeremy Marks for providing primary hippocampal neurons, Dr Gopal Thinakaran for providing APP-null cells, and Drs. Thinakaran and Sangram Sisodia for invaluable insights, as well as for critical editing of the manuscript. This research was supported by the National Institutes of Health (National Institute on Aging) extramural program (R. L) and Alzheimer's Association Award IIRG-05-14089 (to B.L.K.). This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under contract number HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This research was supported (in part) by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 50 TC 105 Z9 107 U1 3 U2 40 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 6 PY 2010 VL 107 IS 14 BP 6538 EP 6543 DI 10.1073/pnas.0914251107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 579MH UT WOS:000276374400074 PM 20308552 ER PT J AU Conen, D Chae, CU Guralnik, JM Glynn, RJ AF Conen, David Chae, Claudia U. Guralnik, Jack M. Glynn, Robert J. TI Influence of blood pressure and blood pressure change on the risk of congestive heart failure in the elderly SO SWISS MEDICAL WEEKLY LA English DT Article DE hypertension; blood pressure; pulse pressure; heart failure; mortality ID INCREASED PULSE PRESSURE; CARDIOVASCULAR EVENTS; DISEASE RISK; HYPERTENSION; MORTALITY; PROGRESSION; PREDICTORS; RELEVANCE; WOMEN AB Background: While elevated blood pressure (BP) has been consistently associated with incident congestive heart failure (CHF), much less is known about the effect of BP change. We therefore assessed the association of BP change over time with subsequent risk of CHF. Methods: 4655 participants >= 65 years old from the prospective Established Populations for Epidemiologic Studies of the Elderly program who were alive and free of CHF after six years of follow-up were included. Categories of sustained high BP, sustained low BP, BP progression and BP regression were defined according to BP differences between study entry and six years of follow-up. The primary endpoint was incident CHF subsequent to the six year examination. Results: During 4.3 years of follow-up after the six year examination, 642 events occurred. The hazard ratio (HR) (95% confidence interval (CI)) for systolic BP >= 160 compared to <120 mm Hg at six years was 1.39 (1.04-1.86). Conversely, the lowest diastolic BP category at six years was associated with an increased risk of incident CHF (FIR (95% CI) <70 mm Hg versus 70-79 mm Hg 1.42 (1.18-1.71)). Systolic and diastolic BP were better predictors than pulse pressure. The HRs (95% CI) for incident CHF associated with sustained high systolic BP >= 160 mm Fig and systolic BP progression were 1.35 (0.97-1.89) and 1.45 (1.14-1.85), respectively. Conversely, significant associations were found in those with sustained low diastolic BP or diastolic BP regression (HR (95% CI) 1.42 (1.11-1.83) and 1.45 (1.19-1.76), respectively). Conclusion: While persistently elevated systolic BP and systolic BP progression were strong predictors of CHF in the elderly, inverse associations were found with regard to diastolic BP. Systolic and diastolic BP were better predictors of CHF than pulse pressure. C1 [Conen, David] Univ Basel Hosp, Dept Med, CH-4031 Basel, Switzerland. [Conen, David; Chae, Claudia U.; Glynn, Robert J.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. [Chae, Claudia U.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Guralnik, Jack M.] NIA, Bethesda, MD 20892 USA. RP Conen, D (reprint author), Univ Basel Hosp, Dept Med, Petersgraben 4, CH-4031 Basel, Switzerland. EM conend@uhbs.ch FU National Institute on Aging, Bethesda, Md [AG02107]; Swiss National Science Foundation [PASMA 118586/1] FX This study was supported by contract AG02107 from the National Institute on Aging, Bethesda, Md. David Conen was supported by grants of the Swiss National Science Foundation (PASMA 118586/1). NR 28 TC 6 Z9 7 U1 0 U2 0 PU E M H SWISS MEDICAL PUBLISHERS LTD PI MUTTENZ PA FARNSBURGERSTR 8, CH-4132 MUTTENZ, SWITZERLAND SN 1424-7860 EI 1424-3997 J9 SWISS MED WKLY JI Swiss Med. Wkly. PD APR 3 PY 2010 VL 140 IS 13-14 BP 202 EP 208 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 583IL UT WOS:000276667500004 PM 20072936 ER PT J AU Lee, KY Yang, K Cohn, MA Sikdar, N D'Andrea, AD Myung, K AF Lee, Kyoo-young Yang, Kailin Cohn, Martin A. Sikdar, Nilabja D'Andrea, Alan D. Myung, Kyungjae TI Human ELG1 Regulates the Level of Ubiquitinated Proliferating Cell Nuclear Antigen (PCNA) through Its Interactions with PCNA and USP1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID REPLICATION-FACTOR-C; DNA-POLYMERASE-ETA; GENOME STABILITY; COHESION ESTABLISHMENT; MONOUBIQUITINATED PCNA; COMPLEX-FORMATION; S-PHASE; INSTABILITY; DAMAGE; FORMS AB The level of monoubiquitinated proliferating cell nuclear antigen (PCNA) is closely linked with DNA damage bypass to protect cells from a high level of mutagenesis. However, it remains unclear how the level of monoubiquitinated PCNA is regulated. Here, we demonstrate that human ELG1 protein, which comprises an alternative replication factor C (RFC) complex and plays an important role in preserving genomic stability, as an interacting partner for the USP1 (ubiquitin-specific protease 1)-UAF1 (USP1-associated factor 1) complex, a deubiquitinating enzyme complex for PCNA and FANCD2. ELG1 protein interacts with PCNAs that are localized at stalled replication forks. ELG1 knockdown specifically resulted in an increase in the level of PCNA monoubiquitination without affecting the level of FANCD2 ubiquitination. It is a novel function of ELG1 distinct from its role as an alternative RFC complex because knockdowns of any other RFC subunits or other alternative RFCs did not affect PCNA monoubiquitination. Lastly, we identified a highly conserved N-terminal domain in ELG1 that was responsible for the USP1-UAF1 interaction as well as the activity to down-regulate PCNA monoubiquitination. Taken together, ELG1 specifically directs USP1-UAF1 complex for PCNA deubiquitination. C1 [Lee, Kyoo-young; Sikdar, Nilabja; Myung, Kyungjae] NHGRI, Genome Instabil Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. [Yang, Kailin; Cohn, Martin A.; D'Andrea, Alan D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Myung, K (reprint author), NHGRI, Genome Instabil Sect, Genet & Mol Biol Branch, NIH, Bldg 49,Rm 4A22, Bethesda, MD 20892 USA. EM kmyung@nhgri.nih.gov RI Yang, Kailin/D-7966-2013; Yang, Kailin/L-2205-2013; OI Yang, Kailin/0000-0001-5968-6738; Cohn, Martin/0000-0002-2988-3009 FU National Institutes of Health [RO1-HL52725, RO1-DK43889, PO1-CA092584]; National Institutes of Health, National Human Genome Research Institute, Intramural Research Program [HG012003-07]; Korean Government [KRF-2007-357C00092] FX This work was supported, in whole or in part, by National Institutes of Health Grants RO1-HL52725, RO1-DK43889, and PO1-CA092584 (to A. D.) and National Institutes of Health, National Human Genome Research Institute, Intramural Research Program Grant HG012003-07 (to K. M.). This work was also supported by Korea Research Foundation Grant KRF-2007-357C00092 funded by the Korean Government (to K. Y. L.). NR 34 TC 60 Z9 62 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 2 PY 2010 VL 285 IS 14 BP 10362 EP 10369 DI 10.1074/jbc.M109.092544 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 578AC UT WOS:000276264600021 PM 20147293 ER PT J AU Cornu, M Modi, H Kawamori, D Kulkarni, RN Joffraud, M Thorens, B AF Cornu, Marion Modi, Honey Kawamori, Dan Kulkarni, Rohit N. Joffraud, Magali Thorens, Bernard TI Glucagon-like Peptide-1 Increases beta-Cell Glucose Competence and Proliferation by Translational Induction of Insulin-like Growth Factor-1 Receptor Expression SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE; CAMP; SECRETION; EXOCYTOSIS; HORMONES; MASS; SURVIVAL; LOCALIZATION; PANCREAS; RELEASE AB Glucagon-like peptide-1 (GLP-1) protects beta-cells against apoptosis, increases their glucose competence, and induces their proliferation. We previously demonstrated that the antiapoptotic effect was mediated by an increase in insulin-like growth factor-1 receptor (IGF-1R) expression and signaling, which was dependent on autocrine secretion of insulin-like growth factor 2 (IGF-2). Here, we further investigated how GLP-1 induces IGF-1R expression and whether the IGF-2/IGF-1R autocrine loop is also involved in mediating GLP-1-increase in glucose competence and proliferation. We show that GLP-1 up-regulated IGF-1R expression by a protein kinase Adependent translational control mechanism, whereas isobutylmethylxanthine, which led to higher intracellular accumulation of cAMP than GLP-1, increased both IGF-1R transcription and translation. We then demonstrated, using MIN6 cells and primary islets, that the glucose competence of these cells was dependent on the level of IGF-1R expression and on IGF-2 secretion. We showed that GLP-1-induced primary beta-cell proliferation was suppressed by Igf-1r gene inactivation and by IGF-2 immunoneutralization or knockdown. Together our data show that regulation of beta-cell number and function by GLP-1 depends on the cAMP/protein kinase A mediated-induction of IGF-1R expression and the increased activity of an IGF-2/ IGF-1R autocrine loop. C1 [Cornu, Marion; Modi, Honey; Joffraud, Magali; Thorens, Bernard] Univ Lausanne, Dept Physiol, CH-1015 Lausanne, Switzerland. [Cornu, Marion; Modi, Honey; Joffraud, Magali; Thorens, Bernard] Univ Lausanne, Ctr Integrat Genom, CH-1015 Lausanne, Switzerland. [Kawamori, Dan; Kulkarni, Rohit N.] Joslin Diabet Ctr, Dept Cellular & Mol Physiol, Boston, MA 02215 USA. [Kawamori, Dan; Kulkarni, Rohit N.] Harvard Univ, Sch Med, Boston, MA 02139 USA. RP Thorens, B (reprint author), Univ Lausanne, Dept Physiol, Genopode Bldg, CH-1015 Lausanne, Switzerland. EM Bernard.Thorens@unil.ch FU National Institutes of Health [RO1 DK67536]; Swiss National Science Foundation [31003A-113525]; Juvenile Diabetes Research Foundation [7-2005-1158]; European Community [LSHM-CT-2006 518153]; Juvenile Diabetes Research Foundation FX This work was supported, in whole or in part, by National Institutes of Health Grant RO1 DK67536 (to R. N. K.). This work was also supported by Swiss National Science Foundation Grant 31003A-113525, Juvenile Diabetes Research Foundation Program Project 7-2005-1158, the Integrated Project Eurodia LSHM-CT-2006 518153 Framework Programme 6 of the European Community (to B. T.), and a Juvenile Diabetes Research Foundation Fellowship (to D. K.). NR 36 TC 39 Z9 46 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 2 PY 2010 VL 285 IS 14 BP 10538 EP 10545 DI 10.1074/jbc.M109.091116 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 578AC UT WOS:000276264600040 PM 20145256 ER PT J AU Itaka, K Osada, K Morii, K Kim, P Yun, SH Kataoka, K AF Itaka, Keiji Osada, Kensuke Morii, Katsue Kim, Pilhan Yun, Seok-Hyun Kataoka, Kazunori TI Polyplex nanomicelle promotes hydrodynamic gene introduction to skeletal muscle SO JOURNAL OF CONTROLLED RELEASE LA English DT Article DE Muscle gene delivery; Hydrodynamic delivery; Polyplex nanomicelle; Plasmid DNA; Intravenous injection ID ENDOTHELIAL GROWTH-FACTOR; GLYCOL)-POLY(L-LYSINE) BLOCK-COPOLYMER; POLYION COMPLEX MICELLES; PLASMID DNA; FACTOR RECEPTOR; EFFICIENT EXPRESSION; NONHUMAN-PRIMATES; SOLUBLE FORM; DELIVERY; THERAPY AB Skeletal muscle is an interesting target for gene therapy. To achieve effective gene introduction in skeletal muscle, a hydrodynamic approach by intravenous injection of plasmid DNA (pDNA) with transient isolation of the limb has attracted attention. In this study, we demonstrated that polyplex nanomicelle, composed of poly(ethyleneglycol) (PEG)-block-polycation and pDNA, showed excellent capacity of gene introduction to skeletal muscle. The evaluation of luciferase expression in the muscle revealed that the nanomicelle provided higher and sustained profiles of transgene expression compared with naked pDNA. Real-time in vivo imaging using a video-rate confocal imaging system suggested that the nanomicelle showed tolerability in the intracellular environment, resulting in the slow but sustained transgene expression. The nanomicelle induced less TNF alpha induction in the muscle than naked pDNA, indicating the safety of nanomicelle-based gene delivery into the skeletal muscle. Moreover, the nanomicelle showed significant tumor growth suppression for almost a month by introducing a pDNA expressing a soluble form of vascular endothelial growth factor (VEGF) receptor-1 (sFlt-1) to skeletal muscle to obtain anti-angiogenic effect on tumor growth. This feature of sustained effect gives an important advantage of gene therapy, especially on the points of cost effectiveness and high compliance. These results suggest that the hydrodynamic gene introduction to skeletal muscle using polyplex nanomicelle system possesses the potential for effective gene therapy. (C) 2009 Elsevier B.V. All rights reserved. C1 [Itaka, Keiji; Morii, Katsue; Kataoka, Kazunori] Univ Tokyo, Grad Sch Med, Ctr Dis Biol & Integrat Med, Div Clin Biotechnol, Tokyo 1130033, Japan. [Osada, Kensuke; Kataoka, Kazunori] Univ Tokyo, Grad Sch Engn, Dept Mat Sci & Engn, Tokyo 1130033, Japan. [Itaka, Keiji; Osada, Kensuke; Kataoka, Kazunori] Univ Tokyo, Ctr Nanobio Integrat, Bunkyo Ku, Tokyo 1130033, Japan. [Kim, Pilhan; Yun, Seok-Hyun] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Kim, Pilhan; Yun, Seok-Hyun] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Kataoka, K (reprint author), Univ Tokyo, Grad Sch Engn, Dept Mat Engn, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan. EM kataoka@bmw.t.u-tokyo.ac.jp RI Kim, Pilhan/C-1836-2011; Kataoka, Kazunori/K-7108-2012 OI Kim, Pilhan/0000-0001-8388-1840; Kataoka, Kazunori/0000-0002-8591-413X FU Japanese Ministry of Education, Culture, Sports, Science and Technology, Japan; General Insurance Association of Japan; Japan Science and Technology Corporation (JST) FX This work was financially supported in part by Grants-in-Aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology, Japan (K. L), Medical Research Grant on Traffic Accident from the General Insurance Association of Japan (K. I.), and the Core Research Program for Evolutional Science and Technology (CREST) from Japan Science and Technology Corporation (JST) (K. K.). We thank Dr. Masabumi Shibuya (Tokyo Medical and Dental University) for providing pVL 1393 baculovirus vector pDNA encoding human sFlt-1. We appreciate Ms. Noriko Oshima (GE Healthcare Bio-Sciences KK) for technical support of operating the image analysis software. We also appreciate Dr. Makoto Oba, Dr. Yu Matsumoto and Ms. Yoko Hasegawa (The University of Tokyo) for technical assistance. NR 40 TC 27 Z9 27 U1 1 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-3659 J9 J CONTROL RELEASE JI J. Control. Release PD APR 2 PY 2010 VL 143 IS 1 BP 112 EP 119 DI 10.1016/j.jconrel.2009.12.014 PG 8 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 584QF UT WOS:000276766600015 PM 20043959 ER PT J AU Das, BC McCartin, K Liu, TC Peterson, RT Evans, T AF Das, Bhaskar C. McCartin, Kellie Liu, Ting-Chun Peterson, Randall T. Evans, Todd TI A Forward Chemical Screen in Zebrafish Identifies a Retinoic Acid Derivative with Receptor Specificity SO PLOS ONE LA English DT Article ID VERTEBRATE DEVELOPMENT; GENETICS; DISEASE AB Background: Retinoids regulate key developmental pathways throughout life, and have potential uses for differentiation therapy. It should be possible to identify novel retinoids by coupling new chemical reactions with screens using the zebrafish embryonic model. Principal Findings: We synthesized novel retinoid analogues and derivatives by amide coupling, obtaining 80-92% yields. A small library of these compounds was screened for bioactivity in living zebrafish embryos. We found that several structurally related compounds significantly affect development. Distinct phenotypes are generated depending on time of exposure, and we characterize one compound (BT10) that produces specific cardiovascular defects when added 1 day post fertilization. When compared to retinoic acid (ATRA), BT10 shows similar but not identical changes in the expression pattern of embryonic genes that are known targets of the retinoid pathway. Reporter assays determined that BT10 interacts with all three RAR receptor sub-types, but has no activity for RXR receptors, at all concentrations tested. Conclusions: Our screen has identified a novel retinoid with specificity for retinoid receptors. This lead compound may be useful for manipulating components of retinoid signaling networks, and may be further derivatized for enhanced activity. C1 [Das, Bhaskar C.] Albert Einstein Coll Med, Dept Dev & Mol Biol, New York, NY USA. [Das, Bhaskar C.] Albert Einstein Coll Med, Dept Nucl Med, New York, NY USA. [McCartin, Kellie; Liu, Ting-Chun; Evans, Todd] Cornell Univ, Weill Cornell Med Coll, Dept Surg, New York, NY 10021 USA. [Peterson, Randall T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. RP Das, BC (reprint author), Albert Einstein Coll Med, Dept Dev & Mol Biol, New York, NY USA. EM bhaskar.das@einstein.yu.edu; tre2003@med.cornell.edu FU Albert Einstein College of Medicine; National Science Foundation (NSF) [DBI9601607, DBI0331934]; National Institutes of Health (NIH) [RR017998, HL056182, HL064282]; Howard Hughes Medical Institute (HHMI) Research Resources for Biomedical Sciences FX B. C. D. is thankful to the Albert Einstein College of Medicine for start up funding. The instrumentation in the Structural Nuclear Magnetic Resonance Resource is supported by the Albert Einstein College of Medicine and in part by Grants from the National Science Foundation (NSF) (DBI9601607 and DBI0331934), the National Institutes of Health (NIH) (RR017998) and the Howard Hughes Medical Institute (HHMI) Research Resources for Biomedical Sciences. T. E. is supported by the NIH (HL056182, HL064282). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 24 TC 14 Z9 14 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 2 PY 2010 VL 5 IS 3 AR e10004 DI 10.1371/journal.pone.0010004 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 580AW UT WOS:000276419900008 PM 20368991 ER PT J AU Fiedler, A Sanchez, C McSwain, A Damle, S Teal, C AF Fiedler, Amy Sanchez, Caroline McSwain, Anita Damle, Sameer Teal, Christine TI Upper Extremity Lymphedema Rates Following Sentinel Lymph Node Biopsy for Breast Cancer SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 11th Annual Meeting of the American-Society-of-Breast-Surgeons CY APR 28-MAY 02, 2010 CL Las Vegas, NV SP Amer Soc Breast Surg C1 [Fiedler, Amy] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Sanchez, Caroline; McSwain, Anita; Damle, Sameer; Teal, Christine] George Washington Univ, Washington, DC USA. 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 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD APR PY 2010 VL 17 IS 2 SU 2 BP S172 EP S172 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 752HJ UT WOS:000289681900064 ER PT J AU Kim, EMH Drohan, B Roche, C Smith, BL Hughes, KS AF Kim, Elizabeth M. H. Drohan, Brian Roche, Constance Smith, Barbara Lynn Hughes, Kevin S. TI To Screen or Not to Screen: American Cancer Society Guideline for MRI Screening in Patients Who Are Diagnosed With LCIS SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 11th Annual Meeting of the American-Society-of-Breast-Surgeons CY APR 28-MAY 02, 2010 CL Las Vegas, NV SP Amer Soc Breast Surg C1 [Kim, Elizabeth M. H.; Drohan, Brian; Roche, Constance; Smith, Barbara Lynn; Hughes, Kevin S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD APR PY 2010 VL 17 IS 2 SU 2 BP S179 EP S179 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 752HJ UT WOS:000289681900089 ER PT J AU Norwood, A Mansbach, JM Clark, S Waseem, M Camargo, CA AF Norwood, Agatha Mansbach, Jonathan M. Clark, Sunday Waseem, Muhammad Camargo, Carlos A., Jr. TI Prospective Multicenter Study of Bronchiolitis: Predictors of an Unscheduled Visit After Discharge From the Emergency Department SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE bronchiolitis; emergency department; risk factors; prediction rules; unscheduled visits ID RISK-FACTORS; HOSPITALIZED INFANTS; US CHILDREN; INFECTIONS; MANAGEMENT; ADMISSION; ILLNESS; DEATHS; APNEA AB Objectives: There is little evidence about which children with bronchiolitis will have worsened disease after discharge from the emergency department (ED). The objective of this study was to determine predictors of post-ED unscheduled visits. Methods: The authors conducted a prospective cohort study of patients discharged from 2004 to 2006 at 30 EDs in 15 U.S. states. Inclusion criteria were diagnosis of bronchiolitis, age < 2 years, and discharge home; the exclusion criterion was previous enrollment. Unscheduled visits were defined as urgent visits to an ED/clinic for worsened bronchiolitis within 2 weeks. Results: Of 722 patients eligible for the current analysis, 717 (99%) had unscheduled visit data, of whom 121 (17%; 95% confidence interval [CI] = 14% to 20%) had unscheduled visits. Unscheduled visits were more likely for children age < 2 months (11% vs. 6%; p = 0.04), males (70% vs. 57%; p = 0.007), and those with history of hospitalization (27% vs. 18%; p = 0.01). The two groups were similar in other demographic and clinical factors (all p > 0.10). Using multivariable logistic regression, independent predictors of unscheduled visits were age < 2 months, male, and history of hospitalization. Conclusions: In this study of children age younger than 2 years with bronchiolitis, one of six children had unscheduled visits within 2 weeks of ED discharge. The three predictors of unscheduled visits were age under 2 months, male sex, and previous hospitalization. ACADEMIC EMERGENCY MEDICINE 2010; 17:376-382 (C) 2010 by the Society for Academic Emergency Medicine. C1 [Norwood, Agatha; Mansbach, Jonathan M.] Harvard Univ, Sch Med, Dept Med, Childrens Hosp Boston, Boston, MA 02115 USA. [Clark, Sunday] Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA USA. [Waseem, Muhammad] Lincoln Med Ctr, Dept Emergency Med, Bronx, NY USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Mansbach, JM (reprint author), Harvard Univ, Sch Med, Dept Med, Childrens Hosp Boston, Boston, MA 02115 USA. EM Jonathan.Mansbach@childrens.harvard.edu FU Thrasher Research Fund; Merck (Rahway, NJ); National Institutes of Health (Bethesda, MD) [K23 AI07780] FX This study was supported by the Thrasher Research Fund (Salt Lake City, UT), an unrestricted data analysis grant from Merck (Rahway, NJ), and the National Institutes of Health (Bethesda, MD): K23 AI07780. NR 23 TC 16 Z9 16 U1 0 U2 1 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 APR PY 2010 VL 17 IS 4 BP 376 EP 382 DI 10.1111/j.1553-2712.2010.00699.x PG 7 WC Emergency Medicine SC Emergency Medicine GA 577SR UT WOS:000276244800009 PM 20370776 ER PT J AU Landman, A Meisel, ZF AF Landman, Adam Meisel, Zachary F. TI The Robert Wood Johnson Foundation Clinical Scholars Program and Emergency Medicine SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE Robert Wood Johnson Foundation; Clinical Scholars Program; fellowship training; research; health policy; leadership ID PREDICT HOSPITAL ADMISSION; CARDIAC-ARREST; RESUSCITATION; VALIDATION; RULE AB P>Specialized research training for emergency physicians (EPs) may strengthen overall patient care through the development and improvement of clinical evidence in emergency care. One way an increasing number of emergency physicians have acquired these skills is through the Robert Wood Johnson Foundation Clinical Scholars Program (CSP), a 2-year fellowship that trains physicians to be leaders in improving health care. In addition to providing training in health policy and health services research, the CSP emphasizes the translation of research into action through leadership training, program development, and community-based participatory research. This article provides an in-depth look at the CSP and its impact on emergency medicine (EM). To date, 41 EPs have trained through the program, with increasing numbers in recent years. Graduates have gone on to become leaders in academia, public health, private industry, and foundations. Past and present EM-trained Clinical Scholars are working to find creative solutions for the challenges posed by the U.S. health care system and improve the delivery of emergency care. Emergency physicians who wish to conduct research or work with communities, organizations, practitioners, and policy-makers to address issues essential to the health and well-being of all Americans should consider the Robert Wood Johnson Foundation CSP. C1 [Landman, Adam] Yale Univ, Robert Wood Johnson Fdn Clin Scholars Program, New Haven, CT 06520 USA. [Landman, Adam] Yale Univ, Dept Emergency Med, New Haven, CT USA. [Landman, Adam] US Dept Vet Affairs, West Haven, CT USA. [Meisel, Zachary F.] Univ Penn, Robert Wood Johnson Fdn Clin Scholars Program, Philadelphia, PA 19104 USA. [Meisel, Zachary F.] Univ Penn, Dept Emergency Med, Philadelphia, PA 19104 USA. RP Landman, A (reprint author), Yale Univ, Robert Wood Johnson Fdn Clin Scholars Program, New Haven, CT 06520 USA. EM Adam.Landman@yale.edu OI Landman, Adam/0000-0002-2166-0521 FU U.S. Department of Veterans Affairs; Robert Wood Johnson Foundation FX Dr. Landman is a Robert Wood Johnson Clinical Scholar at Yale University, supported by the U.S. Department of Veterans Affairs and the Robert Wood Johnson Foundation. Dr. Meisel is a Robert Wood Johnson Clinical Scholar at the University of Pennsylvania, supported by the Robert Wood Johnson Foundation.; The Robert Wood Johnson Foundation and U.S. Department of Veterans Affairs had no role in the preparation, review, or approval of the manuscript. NR 11 TC 5 Z9 5 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD APR PY 2010 VL 17 IS 4 BP E17 EP E22 DI 10.1111/j.1553-2712.2010.00692.x PG 6 WC Emergency Medicine SC Emergency Medicine GA 577SR UT WOS:000276244800001 PM 20148769 ER PT J AU Harper, GM Lyss-Lerman, P AF Harper, G. Michael Lyss-Lerman, Pamela TI Longitudinal Integrated Clerkships Reply SO ACADEMIC MEDICINE LA English DT Letter C1 [Harper, G. Michael] Univ Calif San Francisco, Sch Med, Dept Med, San Francisco, CA 94143 USA. [Harper, G. Michael] San Francisco VA Med Ctr, San Francisco, CA USA. [Lyss-Lerman, Pamela] Univ Calif San Francisco, Sch Med, Dept Psychiat, San Francisco, CA 94143 USA. RP Harper, GM (reprint author), Univ Calif San Francisco, Sch Med, Dept Med, San Francisco, CA 94143 USA. EM Michael.harper3@va.gov NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD APR PY 2010 VL 85 IS 4 BP 569 EP 569 DI 10.1097/ACM.0b013e3181d308bb PG 1 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 576GL UT WOS:000276132300005 ER PT J AU Carnes, M AF Carnes, Molly TI Commentary: Deconstructing Gender Difference SO ACADEMIC MEDICINE LA English DT Editorial Material ID STEREOTYPES; PERFORMANCE; COMPETENCE; IDENTITY; THREAT; WOMEN; AIR AB In Japan, as in the United States, a growing proportion of physicians are women. Hence, the different social roles that men and women occupy and the gendered norms for behavior are increasingly relevant in ensuring that male and female physicians have equal opportunity to participate and advance in all aspects of medicine. Elsewhere in this issue, Nomura and colleagues report on a large survey of primary care residents in Japan. They found that on average women's self-rated confidence on many clinical tasks was lower than men's. This is not surprising given similar gender differences in self-assessed competence in other research and the socialization of women in virtually all cultures to be modest. The actual differences in average scores were small suggesting considerable overlap in the distributions of responses from male and female residents. In addition, research from other countries finds no association between physicians' self-reported confidence in clinical tasks and objective measures of competence on which female physicians rate at or above the level of their male counterparts. Congruent with different social roles for men and women, Nomura and colleagues also found gender differences in the average responses about work-family priorities and aspirations toward leadership, but some women indicated a desire for research careers and some men were "life-oriented." The author of this commentary argues that to draw conclusions about all male or all female physicians from average differences of a large group of residents may reinforce gender stereotypes that continue to impede each individual female physician's career advancement and each individual male physician's struggle for work-life balance. Acad Med. 2010; 85: 575-577. C1 [Carnes, Molly] Univ Wisconsin, Ctr Womens Hlth Res, Madison, WI 53715 USA. [Carnes, Molly] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Madison, WI 53715 USA. [Carnes, Molly] Univ Wisconsin, Sch Med & Publ Hlth, Dept Psychiat, Madison, WI 53715 USA. [Carnes, Molly] Univ Wisconsin, Coll Engn, Dept Ind & Syst Engn, Madison, WI 53715 USA. [Carnes, Molly] Univ Wisconsin, Coll Engn, Women Sci & Engn Leadership Inst, Madison, WI 53715 USA. [Carnes, Molly] William S Middleton Mem Vet Adm Med Ctr, Women Vet Hlth Program, Madison, WI USA. RP Carnes, M (reprint author), Univ Wisconsin, Ctr Womens Hlth Res, 700 Regent St,Suite 301, Madison, WI 53715 USA. EM mlcarnes@wisc.edu FU NIGMS NIH HHS [R01 GM088477, R01 GM088477-01] NR 10 TC 12 Z9 12 U1 2 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD APR PY 2010 VL 85 IS 4 BP 575 EP 577 DI 10.1097/ACM.0b013e3181d983de PG 3 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 576GL UT WOS:000276132300011 PM 20354367 ER PT J AU Betancourt, JR Green, AR AF Betancourt, Joseph R. Green, Alexander R. TI Commentary: Linking Cultural Competence Training to Improved Health Outcomes: Perspectives From the Field SO ACADEMIC MEDICINE LA English DT Editorial Material ID CARE AB The Institute of Medicine report entitled Unequal Treatment recommended that all health care professionals receive training in cross-cultural communication-also called "cultural competence"-as one potential strategy for addressing racial or ethnic disparities in health care. Although evidence shows that cultural competence training improves the attitudes, knowledge, and skills of physicians as well as patients' ratings of care, no definitive evidence has yet linked this training to improved health outcomes. Recently, there has been great interest in the field of cultural competence, including an expressed desire for a better understanding of its key principles, of effective ways of engaging clinicians in this area of instruction, and of the link between training and health outcomes. On the basis of years of experience in the field, the authors share key perspectives in all of these areas, with particular focus on a set of guidelines for measuring the impact of cultural competence training on health care outcomes. The authors maintain that cultural competence represents an important building block of clinical care, as well as a skill set that is central to professionalism and quality. Cultural competence training should be evaluated in a stepwise fashion by using the tools of health services research and the principles of quality improvement, and it should be held to the same standards as other educational interventions and activities. Just as medicine strives to meet other challenges in U. S. health care, so should it focus on developing the skills needed to care for the country's diverse population. Acad Med. 2010; 85: 583-585. C1 [Betancourt, Joseph R.; Green, Alexander R.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Betancourt, Joseph R.] Massachusetts Gen Hosp, Multicultural Affairs Off, Boston, MA 02114 USA. [Betancourt, Joseph R.; Green, Alexander R.] Massachusetts Gen Hosp, Dispar Solut Ctr, Boston, MA 02114 USA. [Betancourt, Joseph R.; Green, Alexander R.] Harvard Univ, Sch Med, Boston, MA USA. RP Betancourt, JR (reprint author), Massachusetts Gen Hosp, Mongan Inst Hlth Policy, 50 Staniford St,Suite 942, Boston, MA 02114 USA. EM jbetancourt@partners.org NR 6 TC 41 Z9 41 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD APR PY 2010 VL 85 IS 4 BP 583 EP 585 DI 10.1097/ACM.0b013e3181d2b2f3 PG 3 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 576GL UT WOS:000276132300014 PM 20354370 ER PT J AU DesRoches, CM Zinner, DE Rao, SR Iezzoni, LI Campbell, EG AF DesRoches, Catherine M. Zinner, Darren E. Rao, Sowmya R. Iezzoni, Lisa I. Campbell, Eric G. TI Activities, Productivity, and Compensation of Men and Women in the Life Sciences SO ACADEMIC MEDICINE LA English DT Article ID ACADEMIC MEDICINE; INDUSTRY; FACULTY; SEX AB Purpose To determine whether professional activities, professional productivity, and salaries of life sciences faculty differ by gender. The authors undertook this study because previous studies found differences in the academic experiences of women and men. Method In 2007, the authors conducted a mailed survey of 3,080 life sciences faculty at the 50 universities whose medical schools received the greatest amount of National Institutes of Health funding in 2004. The response rate was 74% (n = 2,168). The main outcome measures were a faculty member's total number of publications; number of publications in the past three years; average impact score of the journals in which he or she had published; professional activities; work hours per week; the numbers of hours spent specifically in teaching, patient care, research, professional activities, and administrative activities; and annual income. Results Among professors, the women reported greater numbers of hours worked per week and greater numbers of administrative and professional activities than did the men. Female faculty members reported fewer publications across all ranks. After control for professional characteristics and productivity, female researchers in the life sciences earned, on average, approximately $13,226 less annually than did their male counterparts. Conclusions Men and women in the academic life sciences take on different roles as they advance through their careers. A substantial salary gap still exists between men and women that cannot be explained by productivity or other professional factors. Compensation and advancement policies should recognize the full scope of the roles that female researchers play. Acad Med. 2010; 85: 631-639. C1 [DesRoches, Catherine M.; Rao, Sowmya R.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Ctr Biostat, Boston, MA 02114 USA. [Zinner, Darren E.] Brandeis Univ, Heller Sch Social Policy & Management, Waltham, MA USA. [Zinner, Darren E.] Brandeis Univ, Hlth Ind Forum, Waltham, MA USA. [Iezzoni, Lisa I.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP DesRoches, CM (reprint author), Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Ctr Biostat, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM cdesroches@partners.org FU National Institutes of Health [5R01GM074915-02]; Massachusetts General Hospital; University of Massachusetts-Boston FX Funding for this study was provided by the National Institutes of Health, Human Genome Project, under grant no. 5R01GM074915-02.; Granted by the institutional review boards of Massachusetts General Hospital and the University of Massachusetts-Boston. NR 20 TC 28 Z9 28 U1 1 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD APR PY 2010 VL 85 IS 4 BP 631 EP 639 DI 10.1097/ACM.0b013e3181d2b095 PG 9 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 576GL UT WOS:000276132300022 PM 20354379 ER PT J AU Kuai, LT Wang, X Madison, JM Schreiber, SL Scolnick, EM Haggarty, SJ AF Kuai, Letian Wang, Xiang Madison, Jon M. Schreiber, Stuart L. Scolnick, Edward M. Haggarty, Stephen J. TI Chemical Genetics Identifies Small-Molecule Modulators of Neuritogenesis Involving Neuregulin-1/ErbB4 Signaling SO ACS CHEMICAL NEUROSCIENCE LA English DT Article DE Neuregulin; ErbB4; automated imaging; neuritogenesis; quinazoline; indolocarbazole ID NERVE GROWTH-FACTOR; TYROSINE KINASE INHIBITOR; PC12 CELLS; PREFRONTAL CORTEX; ERBB RECEPTORS; SCHIZOPHRENIA; EXPRESSION; DIFFERENTIATION; SUSCEPTIBILITY; ACTIVATION AB Genetic findings have suggested that neuregulin-1 (Nrg1) and its receptor v-erb-a erythroblastic leukemia viral oncogene homologue 4 (ErbB4) may play a role in neuropsychiatric diseases. However, the downstream signaling events and relevant phenotypic consequences of altered Nrg1 signaling in the nervous system remain poorly understood. To identify small molecules for probing Nrg1-ErbB4 signaling, a PC12-cell model was developed and used to perform a live-cell, image-based screen of the effects of small molecules on Nrg1-induced neuritogenesis. By comparison of the resulting phenotypic data to that of a similar screening performed with nerve growth factor (NGF), this multidimensional screen identified compounds that directly inhibit Nrg1-ErbB4 signaling, such as the 4-anilinoquinazoline Iressa (gefitinib), as well as compounds that potentiate Nrg1-ErbB4 signaling, such as the indolocarbazole K-252a. These findings provide new insights into the regulation of Nrg1-ErbB4 signaling events and demonstrate the feasibility of using such a multidimensional, chemical-genetic approach for discovering probes of pathways implicated in neuropsychiatric diseases. C1 [Haggarty, Stephen J.] Harvard Univ, Sch Med,Harvard & MIT, Massachusetts Gen Hosp,Ctr Human Genet Res, Stanley Ctr Psychiat Res,Broad Inst,Dept Neurol, Boston, MA 02114 USA. [Kuai, Letian; Madison, Jon M.; Scolnick, Edward M.; Haggarty, Stephen J.] Harvard & MIT, Broad Inst, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA. [Wang, Xiang] Univ Colorado, Dept Chem & Biochem, Boulder, CO 80309 USA. [Schreiber, Stuart L.] Harvard & MIT, Broad Inst, Chem Biol Program, Cambridge, MA 02142 USA. RP Haggarty, SJ (reprint author), Harvard Univ, Sch Med,Harvard & MIT, Massachusetts Gen Hosp,Ctr Human Genet Res, Stanley Ctr Psychiat Res,Broad Inst,Dept Neurol, 185 Cambridge St,5-412 Off, Boston, MA 02114 USA. EM haggarty@chgr.mgh.harvard.edu OI Haggarty, Stephen J./0000-0002-7872-168X FU Stanley Medical Research Institute; Broad Institute SPARC; NIMH [1R21MH076146-01, 1R21MH087896-01]; National Cancer Institute [N01-CO-12400] FX L.K. and S.J.H were supported by funds from the Stanley Medical Research Institute and the Broad Institute SPARC program. S.J.H. was also supported in part by Grants 1R21MH076146-01 (NIMH) and 1R21MH087896-01 (NIMH). The National Cancer Institute's Initiative for Chemical Genetics (Contract No. N01-CO-12400) provided support for the Broad Chemical Biology Platform. NR 51 TC 3 Z9 3 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1948-7193 J9 ACS CHEM NEUROSCI JI ACS Chem. Neurosci. PD APR PY 2010 VL 1 IS 4 BP 325 EP 342 DI 10.1021/cn900046a PG 18 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Neurosciences SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Neurosciences & Neurology GA 600JE UT WOS:000277981200009 PM 20495671 ER PT J AU Kraemer, BC Schuck, T Wheeler, JM Robinson, LC Trojanowski, JQ Lee, VMY Schellenberg, GD AF Kraemer, Brian C. Schuck, Theresa Wheeler, Jeanna M. Robinson, Linda C. Trojanowski, John Q. Lee, Virginia M. Y. Schellenberg, Gerard D. TI Loss of murine TDP-43 disrupts motor function and plays an essential role in embryogenesis SO ACTA NEUROPATHOLOGICA LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; FRONTOTEMPORAL LOBAR DEGENERATION; MOUSE MODEL; TARDBP MUTATIONS; DEMENTIA FTDP-17; BINDING PROTEIN; STEM-CELLS; DISEASE; GENE; TAU AB Abnormal TDP-43 aggregation is a prominent feature in the neuropathology of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration. Mutations in TARDBP, the gene encoding TDP-43, cause some cases of ALS. The normal function of TDP-43 remains incompletely understood. To better understand TDP-43 biology, we generated mutant mice carrying a genetrap disruption of Tardbp. Mice homozygous for loss of TDP-43 are not viable. TDP-43 deficient embryos die about day 7.5 of embryonic development thereby demonstrating that TDP-43 protein is essential for normal prenatal development and survival. However, heterozygous Tardbp mutant mice exhibit signs of motor disturbance and muscle weakness. Compared with wild type control littermates, Tardbp (+/-) animals have significantly decreased forelimb grip strength and display deficits in a standard inverted grid test despite no evidence of pathologic changes in motor neurons. Thus, TDP-43 is essential for viability, and mild reduction in TDP-43 function is sufficient to cause motor deficits without degeneration of motor neurons. C1 [Kraemer, Brian C.; Wheeler, Jeanna M.] Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98104 USA. [Kraemer, Brian C.; Wheeler, Jeanna M.; Robinson, Linda C.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Schuck, Theresa; Trojanowski, John Q.; Lee, Virginia M. Y.; Schellenberg, Gerard D.] Univ Penn, Sch Med, Inst Aging, Philadelphia, PA 19104 USA. [Schuck, Theresa; Trojanowski, John Q.; Lee, Virginia M. Y.; Schellenberg, Gerard D.] Univ Penn, Sch Med, Ctr Neurodegenerat Dis Res, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. RP Kraemer, BC (reprint author), Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98104 USA. EM kraemerb@u.washington.edu FU NIH [AG17586, NS064131]; Office of Research and Development Medical Research Service, Department of Veterans Affairs FX This work was supported by NIH grant AG17586 to GDS, VMYL, and JQT. This work was also supported by grants to BCK from the Office of Research and Development Medical Research Service, Department of Veterans Affairs and NIH (NS064131). This work utilized facilities at the VA Puget Sound Health Care System, Seattle, Washington. We thank Eddie Lee for outstanding assistance examining neuropathology of Tardbp+/- animals and Elaine Loomis, Leojean Anderson, and Harmony Danner for excellent technical assistance. The lacZ monoclonal antibody was obtained from the Developmental Studies Hybridoma Bank maintained by the University of Iowa. NR 52 TC 119 Z9 121 U1 1 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD APR PY 2010 VL 119 IS 4 BP 409 EP 419 DI 10.1007/s00401-010-0659-0 PG 11 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 571LE UT WOS:000275752500002 PM 20198480 ER PT J AU Camelo-Piragua, S Jansen, M Ganguly, A Kim, JC Louis, DN Nutt, CL AF Camelo-Piragua, Sandra Jansen, Michael Ganguly, Aniruddha Kim, J. ChulMin Louis, David N. Nutt, Catherine L. TI Mutant IDH1-specific immunohistochemistry distinguishes diffuse astrocytoma from astrocytosis SO ACTA NEUROPATHOLOGICA LA English DT Letter ID IDH1 MUTATIONS; BRAIN-TUMORS; GLIOMAS; P53 C1 [Nutt, Catherine L.] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA. [Camelo-Piragua, Sandra; Jansen, Michael; Ganguly, Aniruddha; Kim, J. ChulMin; Louis, David N.; Nutt, Catherine L.] Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. [Louis, David N.] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. [Camelo-Piragua, Sandra; Louis, David N.; Nutt, Catherine L.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Nutt, CL (reprint author), Massachusetts Gen Hosp, Mol Pathol Unit, CNY 6014,Bldg 149,13th St, Charlestown, MA 02129 USA. EM cnutt@partners.org RI Nutt, Catherine/K-8794-2012 FU NCI NIH HHS [CA57683, R01 CA057683, R01 CA057683-17] NR 12 TC 51 Z9 52 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD APR PY 2010 VL 119 IS 4 BP 509 EP 511 DI 10.1007/s00401-009-0632-y PG 3 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 571LE UT WOS:000275752500011 PM 20044756 ER PT J AU Kelly, JF Stout, RL Magill, M Tonigan, JS Pagano, ME AF Kelly, John F. Stout, Robert L. Magill, Molly Tonigan, J. Scott Pagano, Maria E. TI Mechanisms of behavior change in alcoholics anonymous: does Alcoholics Anonymous lead to better alcohol use outcomes by reducing depression symptoms? SO ADDICTION LA English DT Article DE Alcohol dependence; Alcoholics Anonymous; depression; mechanisms; mutual-help groups; self-help groups ID SUBSTANCE USE DISORDERS; UNTREATED INDIVIDUALS; RELAPSE PREVENTION; ANXIETY DISORDERS; CLINICAL-COURSE; PROJECT MATCH; INVENTORY; DRINKING; DEPENDENCE; ABUSE AB Rationale Indices of negative affect, such as depression, have been implicated in stress-induced pathways to alcohol relapse. Empirically supported continuing care resources, such as Alcoholics Anonymous (AA), emphasize reducing negative affect to reduce relapse risk, but little research has been conducted to examine putative affective mechanisms of AA's effects. Methods Using lagged, controlled, hierarchical linear modeling and mediational analyses this study investigated whether AA participation mobilized changes in depression symptoms and whether such changes explained subsequent reductions in alcohol use. Alcohol-dependent adults (n = 1706), receiving treatment as part of a clinical trial, were assessed at intake, 3, 6, 9, 12 and 15 months. Results Findings revealed elevated levels of depression compared to the general population, which decreased during treatment and then remained stable over follow-up. Greater AA attendance was associated with better subsequent alcohol use outcomes and decreased depression. Greater depression was associated with heavier and more frequent drinking. Lagged mediation analyses revealed that the effects of AA on alcohol use was mediated partially by reductions in depression symptoms. However, this salutary effect on depression itself appeared to be explained by AA's proximal effect on reducing concurrent drinking. Conclusions AA attendance was associated both concurrently and predictively with improved alcohol outcomes. Although AA attendance was associated additionally with subsequent improvements in depression, it did not predict such improvements over and above concurrent alcohol use. AA appears to lead both to improvements in alcohol use and psychological and emotional wellbeing which, in turn, may reinforce further abstinence and recovery-related change. C1 [Kelly, John F.] Massachusetts Gen Hosp, Dept Psychiat, Ctr Addict Med, Boston, MA 02114 USA. [Kelly, John F.] Harvard Univ, Sch Med, Boston, MA USA. [Stout, Robert L.] PIRE, Decis Sci Inst, Pawtucket, RI USA. [Magill, Molly] Brown Univ, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA. [Tonigan, J. Scott] CASAA, Albuquerque, NM USA. [Pagano, Maria E.] Case Western Reserve Univ, Sch Med, Dept Psychiat, Div Child Psychiat,WO Walker Ctr, Cleveland, OH 44106 USA. RP Kelly, JF (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Ctr Addict Med, 60 Staniford St,Suite 120, Boston, MA 02114 USA. EM jkelly11@partners.org FU National Institute on Alcohol Abuse and Alcoholism (NIAAA) [R21AA016762] FX Support for this project was provided by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) through an R21 award (R21AA016762) 'Mechanisms and Moderators of Behavior Change In Alcoholics Anonymous'. Content is solely the responsibility of the authors, and does not necessarily represent the official views of the NIAAA or the NIH. NR 64 TC 35 Z9 35 U1 5 U2 16 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0965-2140 J9 ADDICTION JI Addiction PD APR PY 2010 VL 105 IS 4 BP 626 EP 636 DI 10.1111/j.1360-0443.2009.02820.x PG 11 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 567IX UT WOS:000275441400010 PM 20102345 ER PT J AU Stephens, DN Duka, T Crombag, HS Cunningham, CL Heilig, M Crabbe, JC AF Stephens, David N. Duka, Theodora Crombag, Hans S. Cunningham, Christopher L. Heilig, Markus Crabbe, John C. TI Reward sensitivity: issues of measurement, and achieving consilience between human and animal phenotypes SO ADDICTION BIOLOGY LA English DT Review DE Animal models; conditioned place preference; craving; progressive ratio; reward dysregulation; self administration ID CONDITIONED PLACE PREFERENCE; PROGRESSIVE RATIO SCHEDULE; DRUG-SEEKING BEHAVIOR; 5-HYDROXYINDOLEACETIC ACID CONCENTRATIONS; INCENTIVE-SENSITIZATION THEORY; DIMINISHED SOCIAL COMPETENCE; SELF-ADMINISTERED COCAINE; MEDIAL PREFRONTAL CORTEX; ADDICTION-LIKE BEHAVIOR; NONHUMAN PRIMATE MODEL AB Reward is a concept fundamental to discussions of drug abuse and addiction. The idea that altered sensitivity to either drug-reward, or to rewards in general, contributes to, or results from, drug-taking is a common theme in several theories of addiction. However, the concept of reward is problematic in that it is used to refer to apparently different behavioural phenomena, and even to diverse neurobiological processes (reward pathways). Whether these different phenomena are different behavioural expressions of a common underlying process is not established, and much research suggests that there may be only loose relationships among different aspects of reward. Measures of rewarding effects of drugs in humans often depend upon subjective reports. In animal studies, such insights are not available, and behavioural measures must be relied upon to infer rewarding effects of drugs or other events. In such animal studies, but also in many human methods established to objectify measures of reward, many other factors contribute to the behaviour being studied. For that reason, studying the biological (including genetic) bases of performance of tasks that ostensibly measure reward cannot provide unequivocal answers. The current overview outlines the strengths and weaknesses of current approaches that hinder the conciliation of cross-species studies of the genetics of reward sensitivity and the dysregulation of reward processes by drugs of abuse. Some suggestions are made as to how human and animal studies may be made to address more closely homologous behaviours, even if those processes are only partly able to isolate 'reward' from other factors contributing to behavioural output. C1 [Stephens, David N.; Duka, Theodora; Crombag, Hans S.] Univ Sussex, Dept Psychol, Brighton BN1 9QG, E Sussex, England. [Cunningham, Christopher L.; Crabbe, John C.] Oregon Hlth & Sci Univ, Sch Med, Dept Behav Neurosci, Portland, OR 97201 USA. [Heilig, Markus] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD USA. [Crabbe, John C.] Portland Alcohol Res Ctr, Portland, OR USA. [Crabbe, John C.] Portland VA Med Ctr, Portland, OR USA. RP Stephens, DN (reprint author), Univ Sussex, Dept Psychol, Brighton BN1 9QG, E Sussex, England. EM d.stephens@sussex.ac.uk RI Stephens, David/G-2384-2012; OI Heilig, Markus/0000-0003-2706-2482 FU Medical Research Council [G0802642, G0400568] NR 195 TC 50 Z9 50 U1 3 U2 17 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1355-6215 J9 ADDICT BIOL JI Addict. Biol. PD APR PY 2010 VL 15 IS 2 BP 145 EP 168 DI 10.1111/j.1369-1600.2009.00193.x PG 24 WC Biochemistry & Molecular Biology; Substance Abuse SC Biochemistry & Molecular Biology; Substance Abuse GA 554AB UT WOS:000274406800004 PM 20148777 ER PT J AU Ehlers, CL Walter, NAR Dick, DM Buck, KJ Crabbe, JC AF Ehlers, Cindy L. Walter, Nicole A. R. Dick, Danielle M. Buck, Kari J. Crabbe, John C. TI A comparison of selected quantitative trait loci associated with alcohol use phenotypes in humans and mouse models SO ADDICTION BIOLOGY LA English DT Review DE Alcohol dependence; genetics; linkage analyses; mouse models of alcoholism; phenotypes; QTL ID RECOMBINANT INBRED MICE; GENOME-WIDE SEARCH; SOUTHWEST CALIFORNIA INDIANS; IDENTIFY CANDIDATE GENES; LINKAGE ANALYSIS; ETHANOL WITHDRAWAL; SUSCEPTIBILITY LOCI; PHYSICAL-DEPENDENCE; GABA(A) RECEPTOR; CONDUCT DISORDER AB Evidence for genetic linkage to alcohol and other substance dependence phenotypes in areas of the human and mouse genome have now been reported with some consistency across studies. However, the question remains as to whether the genes that underlie the alcohol-related behaviors seen in mice are the same as those that underlie the behaviors observed in human alcoholics. The aims of the current set of analyses were to identify a small set of alcohol-related phenotypes in human and in mouse by which to compare quantitative trait locus (QTL) data between the species using syntenic mapping. These analyses identified that QTLs for alcohol consumption and acute and chronic alcohol withdrawal on distal mouse chromosome 1 are syntenic to a region on human chromosome 1q where a number of studies have identified QTLs for alcohol-related phenotypes. Additionally, a QTL on human chromosome 15 for alcohol dependence severity/withdrawal identified in two human studies was found to be largely syntenic with a region on mouse chromosome 9, where two groups have found QTLs for alcohol preference. In both of these cases, while the QTLs were found to be syntenic, the exact phenotypes between humans and mice did not necessarily overlap. These studies demonstrate how this technique might be useful in the search for genes underlying alcohol-related phenotypes in multiple species. However, these findings also suggest that trying to match exact phenotypes in humans and mice may not be necessary or even optimal for determining whether similar genes influence a range of alcohol-related behaviors between the two species. C1 [Ehlers, Cindy L.] Scripps Res Inst, Dept Mol & Integrat Neurosci, La Jolla, CA 92037 USA. [Walter, Nicole A. R.; Buck, Kari J.; Crabbe, John C.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Walter, Nicole A. R.; Buck, Kari J.; Crabbe, John C.] Portland VA Med Ctr, Dept Behav Neurosci, Portland Alcohol Res Ctr, Portland, OR USA. [Dick, Danielle M.] Virginia Commonwealth Univ, Dept Psychiat, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA. RP Ehlers, CL (reprint author), Scripps Res Inst, Dept Mol & Integrat Neurosci, 10550 N Torrey Pines Rd,SP30-1501, La Jolla, CA 92037 USA. EM cindye@scripps.edu FU National Institute on Alcohol Abuse and Alcoholism [AA 006059, AA010201]; National Center on Minority Health and Health Disparities (NCMHD) [U54 RR025204, AA010760, AA12714, AA011114, DA005228] FX Supported in part by the National Institute on Alcohol Abuse and Alcoholism Grants AA 006059, AA010201, the National Center on Minority Health and Health Disparities (NCMHD), and U54 RR025204 to CLE, AA010760, and AA12714 to JCC, AA011114 and DA005228 to KJB, and VA Merit Review awards to KJB and JCC. DMD acknowledges support from a NARSAD young investigator award. The authors thank Shirley Sanchez for editing the manuscript. NR 138 TC 35 Z9 36 U1 4 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1355-6215 J9 ADDICT BIOL JI Addict. Biol. PD APR PY 2010 VL 15 IS 2 BP 185 EP 199 DI 10.1111/j.1369-1600.2009.00195.x PG 15 WC Biochemistry & Molecular Biology; Substance Abuse SC Biochemistry & Molecular Biology; Substance Abuse GA 554AB UT WOS:000274406800006 PM 20148779 ER PT J AU Kelly, JF Magill, M Slaymaker, V Kahler, C AF Kelly, John F. Magill, Molly Slaymaker, Valerie Kahler, Christopher TI Psychometric validation of the Leeds Dependence Questionnaire (LDQ) in a young adult clinical sample SO ADDICTIVE BEHAVIORS LA English DT Article DE Assessment; Substance abuse or dependence severity; Psychometric; Young adults ID SUBSTANCE-ABUSE TREATMENT; ALCOHOL-USE DISORDERS; WOMEN; RELIABILITY; ADOLESCENTS; SEVERITY; SYMPTOMS; SCALE; AUDIT AB Objective: Measures of substance dependence severity that are both clinically efficient and sensitive to change can facilitate assessment of clinical innovation necessary for improving current evidence-based practices. The Leeds Dependence Questionnaire (LDQ) is a 10-item, continuous, self-report measure Of dependence that is not specific to any particular Substance and has shown promise in preliminary psychometric research. The present study investigates its psychometric properties in a large clinical sample of young adults. Method: Young adults (N=300) were enrolled in a naturalistic treatment process and Outcome study of residential substance dependence treatment (mean age 20.4 [1.6], range 18-25; 27% female; 95% White). Dependence severity by demographic and diagnostic groupings, factor structure and internal consistency, and criterion- and construct-related validity were examined. Results: Dependence severity in this cohort Of Youth overall was high (M=18.65 [8.65]). LDQ scores were highest among opiate and stimulant users, and there was a trend for higher scores among women compared to men (t=1.869. p=.063). Factor analysis using a robust alpha factoring extraction revealed a single factor accounting for 63% of the variance in reported dependence severity. The internal consistency was also very high (alpha=.93). Concurrent and convergent validity with dependence criteria, Substance use frequency, and general symptom severity, respectively, were also acceptable. Conclusions: The LDQ shows considerable promise as a brief, psychometrically sound, measure of substance dependence useful across a variety of substances, that has clinical and research utility. This study supports its use among young adults. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Kelly, John F.] Harvard Univ, Sch Med, Ctr Addict Med, Massachusetts Gen Hosp,Dept Psychiat, Cambridge, MA 02138 USA. [Magill, Molly; Kahler, Christopher] Brown Univ, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA. [Slaymaker, Valerie] Hazelden Fdn, Hazelden Butler Ctr Res, Ctr City, MN USA. RP Kelly, JF (reprint author), 60 Staniford St, Boston, MA 02114 USA. EM jkelly11@partners.org FU [HAZ9606] FX Funding for this project was provided by an anonymous donation Made to the Hazelden Butler Center for Research (HAZ9606) for clinical studies specifically related to youth. Content is solely the responsibility of the authors and does not necessarily represent the official views of the Hazelden Foundation or other affiliated institutions of the authors. The Hazelden Foundation had no role in the study design. collection, analysis or interpretation of the data, writing the manuscript. or the decision to submit the paper for publication. NR 38 TC 13 Z9 13 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD APR PY 2010 VL 35 IS 4 BP 331 EP 336 DI 10.1016/j.addbeh.2009.11.005 PG 6 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 563MF UT WOS:000275135900006 PM 20004062 ER PT J AU Sueoka, K Goulet, JL Fiellin, DA Rimland, D Butt, AA Gibert, C Rodriguez-Barradas, MC Bryant, K Crystal, S Justice, AC AF Sueoka, Kristen Goulet, Joseph L. Fiellin, David A. Rimland, David Butt, Adeel A. Gibert, Cynthia Rodriguez-Barradas, Maria C. Bryant, Kendall Crystal, Stephen Justice, Amy C. TI Depression Symptoms and Treatment Among HIV Infected and Uninfected Veterans SO AIDS AND BEHAVIOR LA English DT Article DE HIV-infection; Depression; Psychiatric status rating scales; Anti-depressive agents ID PRIMARY-CARE PATIENTS; PATIENT HEALTH QUESTIONNAIRE-9; DISORDERS; VALIDITY; PHQ-9; PHYSICIANS; DIAGNOSIS; SEVERITY; DISEASES AB Depression is one of the most common comorbid conditions affecting persons with HIV. We compared depressive symptoms and depression treatment using data from the Veterans Aging Cohort Study (VACS), a prospective cohort of HIV-infected and uninfected subjects. We identified subjects with a Patient Health Questionnaire score of 10 or greater. Treatment was defined as prescription of a selective serotonin reuptake inhibitor (SSRI) or mental health counseling. Overall, 16% of 4,480 subjects had depressive symptoms, and HIV-infected patients were more likely to have had depressive symptoms (OR = 1.38, 95% CI = 1.18, 1.62). Geographic site of care and having a mental health provider at the clinic was associated with treatment. In multivariable models restricted to 732 patients with depressive symptoms, receipt of depression treatment did not differ by HIV status (Adjusted OR = 1.11, 95% CI = 0.80, 1.54). Non-Hispanic whites were more likely to receive treatment (Adjusted OR = 2.09, 95% CI 1.04, 4.24). Primary care and HIV providers were equally unlikely to treat active depressive symptoms. Treatment variation by race, site, and availability of a mental health provider, suggests targets for intervention. C1 [Goulet, Joseph L.; Justice, Amy C.] VA Connecticut Healthcare Syst, West Haven, CT 06516 USA. [Sueoka, Kristen; Goulet, Joseph L.; Fiellin, David A.; Justice, Amy C.] Yale Univ, Sch Med, New Haven, CT USA. [Rimland, David] VA Med Ctr, Atlanta, GA USA. [Rimland, David] Emory Univ, Sch Med, Atlanta, GA USA. [Butt, Adeel A.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Butt, Adeel A.] Univ Pittsburgh, Pittsburgh, PA USA. [Gibert, Cynthia] VA Med Ctr, Washington, DC USA. [Gibert, Cynthia] George Washington Univ, Med Ctr, Washington, DC 20037 USA. [Rodriguez-Barradas, Maria C.] Michael E De Bakey VAMC, Houston, TX USA. [Rodriguez-Barradas, Maria C.] Baylor Coll Med, Houston, TX 77030 USA. [Bryant, Kendall] NIAAA, NIH, Bethesda, MD USA. [Crystal, Stephen] Rutgers State Univ, Inst Hlth Hlth Care Policy & Aging Res, New Brunswick, NJ 08903 USA. RP Justice, AC (reprint author), VA Connecticut Healthcare Syst, 11ACSLG,Bldg 35A,Room 2-212,950 Campbell Ave, West Haven, CT 06516 USA. EM amy.justice2@va.gov OI Goulet, Joseph/0000-0002-0842-804X; Fiellin, David/0000-0002-4006-010X FU NIA NIH HHS [K23 AG00826]; NIAAA NIH HHS [U01 AA 13566, U01 AA013566, U10 AA 13566, U10 AA013566, U10 AA013566-08, U10 AA013566-09] NR 25 TC 6 Z9 6 U1 2 U2 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 EI 1573-3254 J9 AIDS BEHAV JI AIDS Behav. PD APR PY 2010 VL 14 IS 2 BP 272 EP 279 DI 10.1007/s10461-008-9428-7 PG 8 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 567EB UT WOS:000275424800005 PM 18648927 ER PT J AU Banerjee, K Klasse, PJ Sanders, RW Pereyra, F Michael, E Lu, M Walker, BD Moore, JP AF Banerjee, Kaustuv Klasse, P. J. Sanders, Rogier W. Pereyra, Florencia Michael, Elizabeth Lu, Min Walker, Bruce D. Moore, John P. TI IgG Subclass Profiles in Infected HIV Type 1 Controllers and Chronic Progressors and in Uninfected Recipients of Env Vaccines SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; RECOMBINANT GLYCOPROTEIN-120 VACCINE; HUMAN MONOCLONAL-ANTIBODIES; T-CELL RESPONSES; HUMAN B-CELLS; NEUTRALIZING ANTIBODIES; ANTIRETROVIRAL THERAPY; DISEASE PROGRESSION; TAT PROTEIN; VIRAL LOAD AB We have studied IgG subclass responses to the HIV-1 proteins gp120, gp41, p24, and Tat in individuals who control their infection without using antiretroviral drugs (HIV-1 controllers; HC) or who progress to disease (chronic progressors; CP). We also measured IgG subclass titers to gp120 in vaccinated individuals. In all cases, the IgG1 subclass dominated the overall response to each antigen. The only IgG titer that differed significantly between the HC and CP groups was to the p24 Gag protein, which was higher in the HC group. IgG1 titers to both p24 and gp120 were significantly higher in the HC group, and IgG3 anti-gp120 antibodies, although rare, were detected more frequently in that group than in CP. Overall, significantly more patients had IgG2 antibodies to gp120 than to gp41. Antibodies to other IgG subclasses were infrequent and their frequency or titers did not differ between the two patient groups. Anti-gp41 and anti-Tat responses also did not correlate with immune control, and anti-Tat antibodies were infrequently detected. Although we found isotypic differences in IgG responses to HIV-1 antigens among vaccinees and the HC and CP individuals, there were no indications of differential T(H)1:T(H)2 polarization between the different groups. C1 [Banerjee, Kaustuv; Klasse, P. J.; Sanders, Rogier W.; Michael, Elizabeth; Moore, John P.] Cornell Univ, Weill Cornell Med Coll, Dept Microbiol & Immunol, New York, NY 10065 USA. [Sanders, Rogier W.] Univ Amsterdam, Acad Med Ctr, Dept Med Microbiol, NL-1105 AZ Amsterdam, Netherlands. [Pereyra, Florencia; Walker, Bruce D.] Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, Boston, MA 02114 USA. [Pereyra, Florencia; Walker, Bruce D.] Harvard Univ, Sch Med, Div Aids, Boston, MA USA. [Lu, Min] Weill Cornell Med Coll, Dept Biochem, New York, NY USA. [Walker, Bruce D.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. RP Moore, JP (reprint author), Cornell Univ, Weill Med Coll, Dept Microbiol & Immunol, 1300 York Ave, New York, NY 10065 USA. EM jpm2003@med.cornell.edu FU NIH [AI 36082, AI 45463, AI 30914]; Bristol Myers Squibb Foundation FX We appreciate the advice on antihuman subclass conjugates that we received from Dr. Bharat S. Parekh (Chief, Serology/Incidence and Diagnostics Team) and Ms. Debra B. Kuehl of the Center for Disease Control and Prevention, Atlanta. We thank Dr. Andrea Cerutti (Weill Cornell Medical College) for helpful discussions on the TH polarization of human IgG subclasses. We are grateful to Dr. Georgia Tomaras for providing the gp41-SP400 peptide. This work was supported by NIH Grants AI 36082, AI 45463, and AI 30914 and by an Unrestricted Grant for Infectious Diseases Research from the Bristol Myers Squibb Foundation. We thank the HIV Vaccine Trials Network (HVTN) and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (NIAID-NIH) for plasma samples from vaccinee samples, and in particular David Montefiori for facilitating this interaction. NR 71 TC 47 Z9 48 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD APR PY 2010 VL 26 IS 4 BP 445 EP 458 DI 10.1089/aid.2009.0223 PG 14 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 587XY UT WOS:000277031100010 PM 20377426 ER PT J AU Wong, AHW Williams, K Reddy, S Wilson, D Giddy, J Alter, G Ghebremichael, M Carrington, MN Ndung'u, T Walker, BD Altfeld, M Carr, WH AF Wong, Ambrose H. W. Williams, Katie Reddy, Sharon Wilson, Douglas Giddy, Janet Alter, Galit Ghebremichael, Musie Carrington, Mary N. Ndung'u, Thumbi Walker, Bruce D. Altfeld, Marcus Carr, William H. TI Alterations in Natural Killer Cell Receptor Profiles During HIV Type 1 Disease Progression Among Chronically Infected South African Adults SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HLA CLASS-I; HIV-1-INFECTED PATIENTS; CYTOLYTIC FUNCTION; 5 CONTINENTS; NK CLONES; T-CELLS; POPULATIONS; ALLELES; ACTIVATION; RECOGNITION AB Recent studies suggest that innate immune responses by natural killer (NK) cells play a significant role in restricting human immunodeficiency virus type-1 (HIV-1) pathogenesis. Our aim was to characterize changes in NK cells associated with HIV-1 clade C disease progression. Here we used multiparametric flow cytometry (LSRII) to quantify phenotype and function of NK cells in a cross-sectional analysis of cryopreserved blood samples from a cohort of 41 chronically HIV-1-infected, treatment-naive adult South Africans. These individuals ranged in disease severity from early (CD4 count >500) to advanced HIV-1 disease (CD4 count <50). We found that the frequency of NK cells expressing KIR2DL1, an inhibitory receptor, and/or KIR2DS1, an activating receptor, tended to decrease with increasing HIV-1 viral load. We also discovered a significant increase (p<0.05) in overall NK cell degranulation with disease progression. We found that acutely activated NK cells (CD69(pos)) were deficient in NKp46 expression ex vivo. In conclusion, we observed that with viremia and advanced HIV-1 disease, activated NK cells lack NKp46 expression, and KIR2DS1(pos) and/or KIR2DL1(pos) NK cells are reduced in frequency. These findings suggest that modulation of receptor expression on NK cells may play a role in HIV-1 pathogenesis, and provide new insights on immunological changes in advanced HIV-1 disease. C1 [Wong, Ambrose H. W.; Williams, Katie; Alter, Galit; Walker, Bruce D.; Altfeld, Marcus; Carr, William H.] Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, Charlestown, MA 02129 USA. [Wong, Ambrose H. W.; Reddy, Sharon; Ndung'u, Thumbi; Walker, Bruce D.; Altfeld, Marcus; Carr, William H.] Univ KwaZulu Natal, HIV Pathogenesis Programme, Nelson R Mandela Sch Med, ZA-4013 Durban, South Africa. [Wilson, Douglas] Edendale Hosp, Dept Med, Edendale, South Africa. [Giddy, Janet] McCords Hosp, Durban, South Africa. [Ghebremichael, Musie] Harvard Univ, Sch Med, Ctr AIDS Res, Boston, MA USA. [Carrington, Mary N.] NCI, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Carr, WH (reprint author), Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, 149 13th St, Charlestown, MA 02129 USA. EM wcarr@partners.org OI Wong, Ambrose/0000-0001-7471-1647; Ndung'u, Thumbi/0000-0003-2962-3992 FU NIH-FIC [K01-TW007703-01A1]; HHMI; Harvard CFAR; NIH [R01-A1067031]; National Cancer Institute, National Institutes of Health [HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer Research FX We thank Dudu Ndlovu and Pat Bartman for assistance in subject recruitment and sample collection. We thank Karen Bishop and the HPP Blood Processing Core Facility for assistance in sample processing. This work was supported by an NIH-FIC K01-TW007703-01A1 to W. H. C., HHMI Research Fellowship to A. W., Harvard CFAR grant to M. A., and also in part by NIH R01-A1067031 to M. A. M. A. is a Distinguished Clinical Scientist of the Doris Duke Charitable Foundation. This project also has been funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U. S. Government. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 39 TC 18 Z9 18 U1 0 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD APR PY 2010 VL 26 IS 4 BP 459 EP 469 DI 10.1089/aid.2009.0176 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 587XY UT WOS:000277031100011 PM 20380481 ER PT J AU Olivieri, KC Agopian, KA Mukerji, J Gabuzda, D AF Olivieri, Kevin C. Agopian, Kristin A. Mukerji, Joya Gabuzda, Dana TI Evidence for Adaptive Evolution at the Divergence Between Lymphoid and Brain HIV-1 nef Genes SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HCK TYROSINE KINASE; ACTIVATION; SELECTION; AIDS; ANTI-CD45RO; INFECTION; APOPTOSIS; ALLELES; TISSUES; BLOOD AB Human immunodeficiency virus type 1 (HIV) infection of the central nervous system frequently causes HIV-associated neurocognitive disorders (HAND). The role of HIV Nef and other accessory proteins in HAND pathogenesis is unclear. To determine whether HIV nef undergoes adaptive selection in brain, we cloned 100 nef sequences (n = 30 brain and n = 70 lymphoid) from four patients with AIDS and HIV-associated dementia (HAD). Normalized nonsynonymous substitutions were more frequent at the divergence of lymphoid and brain sequences, indicating stronger adaptive selection in brain compared to lymphoid tissue. Brain-specific nonsynonymous substitutions were found within an NH(3)-terminal CTL epitope, the PACS1 binding motif, or positions predicted to be important for activation of the myeloid-restricted Src family tyrosine kinase Hck. These results suggest that adaptive selection of HIV nef in brain may reflect altered requirements for efficient replication in macrophages and brain-specific immune selection pressures. C1 [Olivieri, Kevin C.; Agopian, Kristin A.; Mukerji, Joya; Gabuzda, Dana] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Gabuzda, Dana] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Gabuzda, D (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, CLS 1010,44 Binney St, Boston, MA 02115 USA. EM dana_gabuzda@dfci.harvard.edu FU NIH [AI73415, MH83588, T32 AI007386, T32 AG00222] FX This work was supported by NIH Grants AI73415 and MH83588. K.O. was supported in part by the Dana-Farber AIDS training grant (NIH #T32 AI007386). K.O. and J.M. were supported in part by the Harvard Medical School Neurodegeneration and Repair training grant (NIH #T32 AG00222). NR 23 TC 15 Z9 16 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD APR PY 2010 VL 26 IS 4 BP 495 EP 500 DI 10.1089/aid.2009.0257 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 587XY UT WOS:000277031100015 PM 20377428 ER PT J AU Snow, KK Bonkovsky, HL Fontana, RJ Kim, HY Sterling, RK Di Bisceglie, AM Morgan, TR Dienstag, JL Ghany, MG AF Snow, K. K. Bonkovsky, H. L. Fontana, R. J. Kim, H. -Y. Sterling, R. K. Di Bisceglie, A. M. Morgan, T. R. Dienstag, J. L. Ghany, M. G. CA Halt C Trial Grp TI Changes in quality of life and sexual health are associated with low-dose peginterferon therapy and disease progression in patients with chronic hepatitis C SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID CHRONIC LIVER-DISEASE; VIRUS-INFECTION; COMBINATION THERAPY; PLUS RIBAVIRIN; BIOPSYCHOSOCIAL PREDICTORS; PEGYLATED INTERFERON; VIROLOGICAL RESPONSE; MAINTENANCE THERAPY; COGNITIVE FUNCTION; WORK PRODUCTIVITY AB P>Background Primary analysis of the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) Trial showed long-term peginterferon therapy did not reduce complications in patients with chronic hepatitis C and advanced fibrosis or cirrhosis. Aim To assess the effects of long-term peginterferon therapy and disease progression on health-related quality of life (HRQOL), symptoms and sexual health in HALT-C patients. Methods A total of 517 HALT-C patients received peginterferon alfa-2a (90 mu g/week); 532 received no additional treatment for 3.5 years. Patients were followed up for outcomes of death, hepatocellular carcinoma and hepatic decompensation. Sexual health, SF-36 scores and symptoms were serially assessed by repeated-measures analyses of covariance. Results Patients with cirrhosis (n = 427) reported lower general well-being and more fatigue (P < 0.001) than patients with fibrosis (n = 622). Physical scores declined significantly over time, independent of treatment, and patients with cirrhosis reported lower scores. Vitality scores were lower in those with cirrhosis, and treated patients experienced a greater decline over time than untreated patients; HRQOL rebounded after treatment ended. Patients with a clinical outcome had significantly greater declines in all SF-36 and symptom scores. Among men, Sexual Health scores were significantly worse in treated patients and in those with a clinical outcome. Conclusion Clinical progression of chronic hepatitis C and maintenance peginterferon therapy led to worsening of symptoms, HRQOL and, in men, sexual health in a large patient cohort followed up over 4 years (NCT00006164). C1 [Snow, K. K.; Kim, H. -Y.] New England Res Inst, Watertown, MA 02472 USA. [Bonkovsky, H. L.] Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT USA. [Bonkovsky, H. L.] Univ Connecticut, Ctr Hlth, Dept Mol & Struct Biol, Farmington, CT USA. [Bonkovsky, H. L.] Univ Connecticut, Ctr Hlth, Liver Biliary Pancreat Ctr, Farmington, CT USA. [Fontana, R. J.] Univ Michigan, Med Ctr, Dept Internal Med, Ann Arbor, MI 48109 USA. [Sterling, R. K.] Virginia Commonwealth Univ, Hepatol Sect, Med Ctr, Richmond, VA USA. [Di Bisceglie, A. M.] St Louis Univ, Div Gastroenterol & Hepatol, Sch Med, St Louis, MO USA. [Morgan, T. R.] Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA. [Morgan, T. R.] VA Long Beach Healthcare Syst, Gastroenterol Serv, Long Beach, CA USA. [Dienstag, J. L.] Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA. [Dienstag, J. L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Ghany, M. G.] NIDDKD, Liver Dis Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Snow, KK (reprint author), New England Res Inst, 9 Galen St, Watertown, MA 02472 USA. EM ksnow@neriscience.com FU National Institute of Diabetes & Digestive & Kidney Diseases; National Institute of Allergy and Infectious Diseases (NIAID); National Cancer Institute; National Center for Minority Health and Health Disparities; National Center for Research Resources; National Institutes of Health; Hoffmann-La Roche, Inc., through a Cooperative Research and Development Agreement (CRADA); HoffmannLa Roche, Inc. FX Declaration of personal interests: We acknowledge the contribution of Jay H. Hoofnagle, MD, for the design of the symptom and sexual health questionnaires. In addition to the authors of this manuscript, the individuals in Appendix B were instrumental in the planning, conduct and/or care of patients enrolled in this study at each of the participating institutions (see Appendix B). Declaration of funding interests: This study was supported by the National Institute of Diabetes & Digestive & Kidney Diseases (contract numbers are listed in Appendix B). 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 and by General Clinical Research Center and Clinical and Translational Science Center grants from the National Center for Research Resources, National Institutes of Health (grant numbers are listed in Appendix B). 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., through a Cooperative Research and Development Agreement (CRADA) with the National Institutes of Health. H. L. Bonkovsky receives research support from HoffmannLa Roche, Inc. R. J. Fontana is on the speaker's bureau for Hoffmann-La Roche, Inc. R. K. Sterling is a consultant, receives research support and is on the speaker's bureau for Hoffmann-La Roche, Inc. A. M. Di Bisceglie is a consultant and receives research support from Hoffmann-La Roche, Inc. T. R. Morgan is a consultant, on the speaker's bureau and receives research support Hoffmann- La Roche, Inc. Authors with no financial relationships related to this project are K. K. Snow, H.-Y. Kim, J. L. Dienstag and M. G. Ghany. NR 48 TC 14 Z9 15 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0269-2813 J9 ALIMENT PHARM THER JI Aliment. Pharmacol. Ther. PD APR 1 PY 2010 VL 31 IS 7 BP 719 EP 734 DI 10.1111/j.1365-2036.2010.04235.x PG 16 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 562ZE UT WOS:000275094000004 PM 20070284 ER PT J AU Galvin, JE Duda, JE Kaufer, DI Lippa, CF Taylor, A Zarit, SH AF Galvin, James E. Duda, John E. Kaufer, Daniel I. Lippa, Carol F. Taylor, Angela Zarit, Steven H. TI Lewy Body Dementia Caregiver Burden and Unmet Needs SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Article DE Lewy body dementia; caregiver burden; stress ID ALZHEIMERS-DISEASE; FAMILY CAREGIVERS; BODIES; IMPACT; INTERVENTION; DEPRESSION; PREVALENCE; PREDICTORS; DIAGNOSIS; STRESS AB Lewy body dementia (LBD) is a common cause of dementia but to date, little is known about caregiver burden. The Lewy Body Dementia Association (www.LBDA.org) conducted a web-based survey of 962 caregivers (mean age 56 y; 88% women). The most common initial symptoms were cognitive (48%), motor (39%), or both (13%). Caregivers expressed concerns about fear of future (77%), feeling stressed (54%), loss of social life (52%), and uncertainty about what to do next (50%). Caregivers reported moderate-to-severe burden; 80% felt the people around them did not understand their burden and 54% reported feelings of isolation with spousal caregivers reporting more burden than nonspousal caregivers. Only 29% hired in-home assistance, whereas less than 40% used respite or adult day care, geriatric case managers, or attended a support group meeting. Lack of service utilization occurred despite two-thirds of caregivers reporting medical crises requiring emergency services, psychiatric care, or law enforcement. Caregivers reported preferences for web-based information, directories of LBD expert providers, information on LBD research, and location of local support groups. These findings highlight significant unmet needs for LBD caregivers and provide targets for intervention to reduce caregiver burden. Community resources such as the Lewy Body Dementia Association may serve this end, while also providing practical information and support for caregivers. C1 [Galvin, James E.] Washington Univ, Alzheimer Dis Res Ctr, Sch Med, Dept Neurol, St Louis, MO 63108 USA. [Duda, John E.] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Duda, John E.] Philadelphia VA Med Ctr, PADRECC, Philadelphia, PA USA. [Lippa, Carol F.] Drexel Univ, Coll Med, Dept Neurol, Philadelphia, PA 19104 USA. [Zarit, Steven H.] Penn State Univ, Dept Psychol, University Pk, PA 16802 USA. [Kaufer, Daniel I.] Univ N Carolina, Dept Neurol, Chapel Hill, NC USA. [Taylor, Angela] Lewy Body Dementia Assoc, Atlanta, GA USA. RP Galvin, JE (reprint author), Washington Univ, Alzheimer Dis Res Ctr, Sch Med, Dept Neurol, 4488 Forest Pk,Suite 130, St Louis, MO 63108 USA. EM galvinj@neuro.wustl.edu FU Lewy Body Dementia Association FX The study was supported by the Lewy Body Dementia Association (www.LBDA.org). NR 26 TC 14 Z9 15 U1 3 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-0341 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PD APR-JUN PY 2010 VL 24 IS 2 BP 177 EP 181 DI 10.1097/WAD.0b013e3181c72b5d PG 5 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA 607WJ UT WOS:000278537700011 PM 20505434 ER PT J AU Dauerman, HL Bhatt, DL Gretler, DD French, PA Smyth, SS Becker, RC AF Dauerman, Harold L. Bhatt, Deepak L. Gretler, Daniel D. French, Patricia A. Smyth, Susan S. Becker, Richard C. TI Bridging the gap between clinical trials of antiplatelet therapies and applications among elderly patients SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE CORONARY SYNDROMES; ACUTE MYOCARDIAL-INFARCTION; ST-SEGMENT-ELEVATION; GLYCOPROTEIN IIB/IIIA INHIBITION; PLACEBO-CONTROLLED TRIAL; RANDOMIZED-TRIAL; FIBRINOLYTIC THERAPY; EARLY REVASCULARIZATION; CARDIOGENIC-SHOCK; GLOBAL REGISTRY AB Although patients aged >= 75 years represent nearly 40% of all those hospitalized with acute coronary syndromes, their enrollment in trials of therapeutic interventions has been relatively modest. Thus, scarce information exists to guide clinicians in decision-making and assessing projections of safety and efficacy for antiplatelet agents. The pathobiology of aging, including age-related changes in vascular repair and integrity, applies to patient management and offers a platform for investigation. Because older patients receive excess dosing of antithrombotic agents much more often than their younger counterparts do, initial steps toward optimized care include attention to indications, dosing, and duration of treatment. This review, representing a summary of information presented at the Fourth Annual Platelet Colloquium held in Washington, DC, in January 2009 and supplemented with recent clinical trial results, underscores an increasingly narrow safety index for antiplatelet agents in the elderly and the all-important balance of safety and efficacy-a dynamic continuum that remains paramount in quality of care. Considerations for future trial designs, registries, and analyses of existing data are highlighted to better guide clinicians toward the optimal management of this rapidly growing, high-risk group. (Am Heart J 2010; 159: 508-517. e1.) C1 [Dauerman, Harold L.] Univ Vermont, Coll Med, Burlington, VT 05403 USA. [Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Gretler, Daniel D.] Portola Pharmaceut Inc, San Francisco, CA USA. [French, Patricia A.] Left Lane Commun, Chapel Hill, NC USA. [Smyth, Susan S.] Univ Kentucky, Lexington, KY USA. [Becker, Richard C.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. RP Dauerman, HL (reprint author), Univ Vermont, Coll Med, 111 Colchester Ave, Burlington, VT 05403 USA. EM harold.dauerman@vtmednet.org FU AstraZeneca; Ortho-McNeil-Janssen Pharmaceuticals; Ortho- McNeil Janssen Scientific Affairs; Portola Pharmaceuticals; Regado Biosciences; Schering Corporation; The Medicines Company; Daiichi/Eli Lilly FX The 2009 Platelet Colloquium was supported by educational grants from AstraZeneca; Ortho-McNeil-Janssen Pharmaceuticals, administered by Ortho- McNeil Janssen Scientific Affairs; Portola Pharmaceuticals; Regado Biosciences; Schering Corporation; and The Medicines Company. This manuscript was supported by an unrestricted educational grant from Daiichi/Eli Lilly. The authors are solely responsible for drafting and editing of the paper and its final contents, and received no honoraria for development of this manuscript. NR 61 TC 10 Z9 10 U1 0 U2 0 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 APR PY 2010 VL 159 IS 4 BP 508 EP U24 DI 10.1016/j.ahj.2010.01.010 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 577ZC UT WOS:000276261600002 PM 20362707 ER PT J AU Bhardwaj, A Rehman, SU Mohammed, A Baggish, AL Moore, SA Januzzi, JL AF Bhardwaj, Anju Rehman, Shafiq U. Mohammed, Asim Baggish, Aaron L. Moore, Stephanie A. Januzzi, James L., Jr. TI Design and methods of the Pro-B Type Natriuretic Peptide Outpatient Tailored Chronic Heart Failure Therapy (PROTECT) Study SO AMERICAN HEART JOURNAL LA English DT Article ID LEFT-VENTRICULAR DYSFUNCTION; MYOCARDIAL-INFARCTION; PROGNOSTIC VALUE; RANDOMIZED-TRIAL; BNP; VALSARTAN; MORTALITY; SURVIVAL; BLOCKER; MULTICENTER AB Background Serial measurements of N-terminal pro-B type natriuretic peptide (NT-proBNP) provide prognostic information in patients with chronic heart failure (HF). Changes in NT-proBNP concentrations parallel prognosis; however, it remains unclear whether HF care with a goal to maximize medical therapy and also lower NT-proBNP concentrations is superior to standard HF care alone. Aims The aim of the study was to evaluate the hypothesis that an HF strategy guided by NT-proBNP reduces cardiovascular events compared to standard of care HF management. Methods In a prospective randomized single-center trial, subjects with New York Heart Association class II to IV systolic HF (left ventricular ejection fraction <= 40%) will be enrolled. Both groups will receive standard HF management (with a goal for minimizing HF symptoms and achieving maximal dosages of therapies with proven mortality benefit in HF), whereas one group ("NT-proBNP") will also have treatment adjustments to reduce NT-proBNP concentrations <= 1,000 pg/mL. The primary end point of the trial is total cardiovascular events for a 1-year period; secondary end points will include effects of NT-proBNP-guided care on cardiac structure and function, quality of life, and total costs of care. Results Enrollment began in 2006; of the original 300 planned, thus far, 151 subjects have been randomized. Interim analysis in November 2009 indicated significant reduction of events in the NT-proBNP arm. Full results are expected in 2010. Conclusions The Pro-B Type Natriuretic Peptide Outpatient Tailored Chronic Heart Failure Therapy (PROTECT) Study will test the hypothesis that therapy guided by NT-proBNP concentrations will be superior to standard of care HF management (www.clinicaltrials.gov identifier NCT00351390). (Am Heart J 2010; 159: 532-538. e1.) C1 [Bhardwaj, Anju; Rehman, Shafiq U.; Mohammed, Asim; Baggish, Aaron L.; Moore, Stephanie A.; Januzzi, James L., Jr.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Div Cardiol, 32 Fruit St,Yawkey 5984, Boston, MA 02114 USA. EM jjanuzzi@Partners.org FU Dennis and Marilyn Barry Fellowship in Cardiology; Balson Cardiac Scholar Fund FX Drs Bhardwaj, Rehman, and Mohammed are supported by the Dennis and Marilyn Barry Fellowship in Cardiology. Dr Januzzi is supported in part by the Balson Cardiac Scholar Fund. NR 32 TC 43 Z9 44 U1 1 U2 3 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 APR PY 2010 VL 159 IS 4 BP 532 EP U46 DI 10.1016/j.ahj.2010.01.005 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 577ZC UT WOS:000276261600004 PM 20362709 ER PT J AU Singh, TP Givertz, MM Semigran, M DeNofrio, D Costantino, F Gauvreau, K AF Singh, Tajinder P. Givertz, Michael M. Semigran, Marc DeNofrio, David Costantino, Fred Gauvreau, Kimberlee TI Socioeconomic Position, Ethnicity, and Outcomes in Heart Transplant Recipients SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID DISPARITIES GEOCODING PROJECT; C-REACTIVE PROTEIN; HEALTH DISPARITIES; RISK-FACTORS; REJECTION; MORTALITY; ATHEROSCLEROSIS; RACE/ETHNICITY; INEQUALITIES; EDUCATION AB The purpose of the present study was to assess whether a low socioeconomic (SE) position is associated with outcomes in heart transplant recipients. We used the US Census 2000 database to derive a summary SE score for 520 patients who had undergone underwent a first heart transplant at 1 of 4 Boston hospitals during 1996 to 2005 and compared the outcomes in the lowest quartile SE group (n = 129) to those for the remaining patients (n = 391). The low SE group and controls were similar with respect to cardiac diagnosis, hemodynamic support, listing status, year of transplant, and initial immune suppression. Low SE patients were more likely to be nonwhite. Graft loss occurred in 142 patients (135 deaths and 7 repeat transplants). Hospital mortality after transplantation was not associated with race/ethnicity or low SE position. In patients who survived the transplant hospitalization, nonwhite ethnicity (hazard ratio 1.8, 95% confidence interval 1.1 to 2.9) and low SE group (hazard ratio 1.7, 95% confidence interval 1.1 to 2.5) were associated with a greater risk of subsequent graft loss. In the adjusted analysis, the risk of graft loss remained greater for both nonwhite race/ethnicity (hazard ratio 1.7, 95% confidence interval 1.0 to 2.9) and low SE position (hazard ratio 1.5, 95% confidence interval 1.0 to 2.4). Rejection episodes were more frequent in nonwhite transplant recipients and in those in the low SE group. In conclusion, among heart transplant recipients who survive the transplant hospitalization, nonwhite recipients and those in a low SE position are at greater risk of rejection and graft loss. (C) 2010 Elsevier Inc. All rights reserved. (Am J Cardiol 2010;105:1024-1029) C1 [Singh, Tajinder P.; Gauvreau, Kimberlee] Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. [Givertz, Michael M.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Semigran, Marc] Massachusetts Gen Hosp, Heart Failure & Transplant Serv, Boston, MA 02114 USA. [DeNofrio, David] Tufts Med Ctr, Dept Cardiol, Boston, MA USA. [Costantino, Fred] New England Organ Bank Inc, Newton, MA USA. [Singh, Tajinder P.; Givertz, Michael M.; Semigran, Marc] Harvard Univ, Sch Med, Boston, MA USA. [Gauvreau, Kimberlee] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Singh, TP (reprint author), Childrens Hosp, Dept Cardiol, 300 Longwood Ave, Boston, MA 02115 USA. EM TP.Singh@cardio.chboston.org FU Heart Transplant Education and Research Fund, Children's Hospital Boston, Boston, Massachusetts FX This study was supported by the Heart Transplant Education and Research Fund, Children's Hospital Boston, Boston, Massachusetts. NR 20 TC 21 Z9 21 U1 1 U2 2 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 APR 1 PY 2010 VL 105 IS 7 BP 1024 EP 1029 DI 10.1016/j.amjcard.2009.11.015 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 582DP UT WOS:000276576200022 PM 20346325 ER PT J AU Rao, UNM Lee, SJ Luo, WX Mihm, MC Kirkwood, JM AF Rao, Uma N. M. Lee, Sandra J. Luo, Weixiu Mihm, Martin C., Jr. Kirkwood, John M. TI Presence of Tumor-infiltrating Lymphocytes and a Dominant Nodule Within Primary Melanoma Are Prognostic Factors for Relapse-Free Survival of Patients With Thick (T4) Primary Melanoma SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE Primary melanoma; Tumor-infiltrating lymphocytes; Dominat nodule; Relapse-free survival; Overall survival; Histology ID CUTANEOUS MALIGNANT-MELANOMA; LYMPH-NODE POSITIVITY; VERTICAL GROWTH-PHASE; HIGH-RISK MELANOMA; METASTATIC MELANOMA; STAGE-I; CELLS; TRIAL; VASCULARITY; INTERFERON AB Lymphocytic infiltration of primary cutaneous melanoma has been demostrated to be prognostic significance Tumor infiltrating lymphocytes (TILs) were evaluated on histologic sections of pT4 primary cutaneious melanoma from 293 patients, accrued in protocols 1690 and 1694 of the Easterb Cooperative Oncology Group Data for the 60-month follow-up were available. Statistical analysis of the pathologic data evaluated the correlation of regional lymph node metastasis and response to interferon therapy, overall survival, and relapse-free survival In multivariate analysis, there was significant correlation of the presence of TILs and improved survival The presence of TILs did not affect the survival of patients trated with interferon alfa-2b Presence of a localized dominant tumor nodule within the primary tumor had an adverse effect on relapse-free survival (P = 044) that was also marginally present for overall survival (P = 112) The presence of TILs has prognostic but not predictive value, and the presence of a dominant nodule in the primary lesion represents a new adverse prognostic factor that should be incorporated in the evaluation of primary melanoma This study confirmed the importance of tumor ulceration and the number of positive lymph nodes on outcome. C1 [Rao, Uma N. M.] Univ Pittsburgh, Med Ctr, Presbyterian Shadyside Hosp, Dept Pathol, Pittsburgh, PA USA. [Lee, Sandra J.; Luo, Weixiu] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Mihm, Martin C., Jr.] Massachusetts Gen Hosp, Dept Dermatopathol, Boston, MA 02114 USA. [Kirkwood, John M.] Univ Pittsburgh, Inst Canc, Melanoma Program, Pittsburgh, PA 15260 USA. RP Rao, UNM (reprint author), UPMC Presbyterian Shadyside, Room 2 9WG,5230 Ctr Ave, Pittsburgh, PA 15232 USA. FU NCATS NIH HHS [UL1 TR000005]; NCI NIH HHS [U10 CA021115, U24 CA114737, U10 CA066636, U10 CA039229, U10 CA023318] NR 33 TC 26 Z9 26 U1 0 U2 2 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 APR PY 2010 VL 133 IS 4 BP 646 EP 653 DI 10.1309/AJCPTXMEFOVYWDA6 PG 8 WC Pathology SC Pathology GA 572ID UT WOS:000275821400016 PM 20231618 ER PT J AU O'Brien, C True, LD Higano, CS Rademacher, BLS Garzotto, M Beer, TM AF O'Brien, Catherine True, Lawrence D. Higano, Celestia S. Rademacher, Brooks L. S. Garzotto, Mark Beer, Tomasz M. TI Histologic Changes Associated With Neoadjuvant Chemotherapy Are Predictive of Nodal Metastases in Patients With High-Risk Prostate Cancer SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE Neoadjuvant; Chemotherapy; Prostate; Carcinoma; Intraductal; Cribriform ID ANDROGEN DEPRIVATION THERAPY; PHASE-II TRIAL; RADICAL PROSTATECTOMY; HORMONAL-THERAPY; INTRADUCTAL CARCINOMA; INTRAEPITHELIAL NEOPLASIA; PATHOLOGICAL-CHANGES; RANDOMIZED-TRIAL; FOLLOW-UP; ADENOCARCINOMA AB Clinical trials are evaluating the effect of neoadjuvant chemotherapy on men with high-risk prostate cancer Little is known about the clinical significance of postchemotherapy tumor histopathologic features. We assessed the prognostic and predictive value of histologic features (intraductal carcinoma, vacuolated cell morphologic features, inconspicuous glands, cribriform architecture, and inconspicuous cancer cells) observed in 50 high-risk prostate cancers treated with preprostatectomy docetaxel and mitoxantrone At a median follow-up of 65 months, the overall relapse-free survival (RFS) rates at 2 and 5 years were 65% and 49% respectively. In univariate analyses (using the Kaplan-Meier method and log-rank tests), intraductal (P = 001) and cribriform (P = 014) histologic features were associated with shorter RFS In multivariate analyses, using the Cox proportioanl hazards regression, baseline prostate-specific antigen (P = 004), lymph node metastases (P < .007) were associated with shorter RFS In multivariable logistic regression analysis, only intraductal pattern (P = 007) predicted lymph node metastases Intraductal and cribriform histologic features apparently predict postchemotherapy outcome C1 [Beer, Tomasz M.] Oregon Hlth & Sci Univ, Dept Med, Div Hematol & Med Oncol, Portland, OR 97239 USA. [Garzotto, Mark] Oregon Hlth & Sci Univ, Div Urol, Portland, OR 97239 USA. [True, Lawrence D.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Higano, Celestia S.] Univ Washington, Div Med Oncol, Seattle, WA 98195 USA. [Garzotto, Mark] Portland VA Med Ctr, Portland, OR USA. RP Beer, TM (reprint author), Oregon Hlth & Sci Univ, Dept Med, Div Hematol & Med Oncol, 3303 SW Bond,CH14R, Portland, OR 97239 USA. FU NCI NIH HHS [R01 CA119125-01, R01 CA119125, 1 R01CA119125-01]; NCRR NIH HHS [3M01RR00334-33S2, M01 RR000334-33S2, M01 RR000334] NR 38 TC 15 Z9 15 U1 0 U2 0 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 APR PY 2010 VL 133 IS 4 BP 654 EP 661 DI 10.1309/AJCP8EL5FTZSOBIH PG 8 WC Pathology SC Pathology GA 572ID UT WOS:000275821400017 PM 20231619 ER PT J AU Morgan, EA Henrich, TJ Jarell, AD Shieh, WJ Zaki, SR Marty, FM Thorner, AR Milner, DA Velazquez, EF AF Morgan, Elizabeth A. Henrich, Timothy J. Jarell, Abel D. Shieh, Wun-Ju Zaki, Sherif R. Marty, Francisco M. Thorner, Anna R. Milner, Dan A. Velazquez, Elsa F. TI Infectious Granulomatous Dermatitis Associated With Rothia mucilaginosa Bacteremia: A Case Report SO AMERICAN JOURNAL OF DERMATOPATHOLOGY LA English DT Article DE Rothia mucilaginosa; Stomatococcus mucilaginosus; neutropenia; dermatitis; granulomatous ID STOMATOCOCCUS-MUCILAGINOSUS; NEUTROPENIC PATIENTS; SP-NOV; PATIENT; SEPTICEMIA; CANCER; LEUKEMIA; ENDOCARDITIS; MENINGITIS; BLOOD AB Infections with rare pathogens are being recognized with increasing frequency in severely immunocompromised patients. As a result of these patients' underlying compromised defenses and susceptibility to atypical organisms, tissue biopsies from patients within this population may demonstrate nonclassical histopathological findings. Here, we describe an unusual granulomatous reaction to gram-positive cocci in the skin of a 52-year-old man undergoing salvage chemotherapy for acute myeloid leukemia. The patient presented with a papular eruption on the arms, trunk, and face and fever; concomitant blood cultures were positive for Rothia mucilaginosa and Streptococcus salivarius. Histologic evaluation revealed a granulomatous dermatitis associated with numerous small, round, predominantly intracellular bacteria. Classically, cutaneous infiltrates associated with coccoid bacterial infections are suppurative and not granulomatous. The intracellular organisms stained positive for Gram, periodic acid-Schiff, and Grocott methenamine silver stains, suggestive of R. mucilaginosa. Rothia mucilaginosa, a component of the oral flora, was first reported as a human pathogen in 1978. Although the majority of cases in the literature have described R. mucilaginosa bacteremia, other reported manifestations include meningitis, endocarditis, pneumonia, osteomyelitis, and peritonitis. To our knowledge, however, only 1 prior report has described a cutaneous manifestation of R. mucilaginosa septicemia, which occurred in a patient with neutropenia. This is the second reported case of an infectious granulomatous dermatitis associated with R. mucilaginosa bacteremia and raises awareness of this unusual histopathological presentation in the setting of a bacterial infection affecting the skin. C1 [Morgan, Elizabeth A.; Milner, Dan A.; Velazquez, Elsa F.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Henrich, Timothy J.; Marty, Francisco M.; Thorner, Anna R.] Brigham & Womens Hosp, Div Infect Dis, Dept Med, Boston, MA 02115 USA. [Jarell, Abel D.] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. [Shieh, Wun-Ju; Zaki, Sherif R.] Ctr Dis Control & Prevent, Infect Dis Pathol Branch, Atlanta, GA USA. [Marty, Francisco M.; Thorner, Anna R.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Velazquez, EF (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM efvelazquez@partners.org OI Morgan, Elizabeth/0000-0001-5880-9337 NR 39 TC 10 Z9 10 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0193-1091 J9 AM J DERMATOPATH JI Am. J. Dermatopathol. PD APR PY 2010 VL 32 IS 2 BP 175 EP 179 DI 10.1097/DAD.0b013e3181b1c5ad PG 5 WC Dermatology SC Dermatology GA 581ZM UT WOS:000276564600011 PM 19940746 ER PT J AU Varraso, R Willett, WC Camargo, CA AF Varraso, Raphaelle Willett, Walter C. Camargo, Carlos A., Jr. TI Prospective Study of Dietary Fiber and Risk of Chronic Obstructive Pulmonary Disease Among US Women and Men SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE diet; dietary fiber; pulmonary disease; chronic obstructive; sex ID C-REACTIVE PROTEIN; LUNG-FUNCTION; GLYCEMIC LOAD; REDUCED RISK; CURED MEATS; CONSUMPTION; COHORT; HEALTH; QUESTIONNAIRE; ASSOCIATION AB Little is known about the relation between dietary fiber intake and the incidence of respiratory diseases, especially chronic obstructive pulmonary disease (COPD). The authors investigated this issue among 111,580 US women and men (Nurses' Health Study and Health Professionals Follow-up Study), with 832 cases of newly diagnosed COPD being reported between 1984 and 2000. The cumulative average intake of total fiber and of fiber from specific sources (cereal, fruit, and vegetables) was calculated from food frequency questionnaires and a food composition database and divided into quintiles. After adjustment for 11 factors (age, sex, smoking, energy intake, body mass index, US region, physician visits, physical activity, diabetes, and intakes of omega-3 and cured meat), total dietary fiber intake was negatively associated with risk of newly diagnosed COPD (for highest vs. lowest intake, relative risk = 0.67, 95% confidence interval: 0.50, 0.90; P(trend) = 0.03). For specific fiber sources (cereal, fruit, and vegetables), only cereal fiber was significantly associated with newly diagnosed COPD independently of other fiber sources (for highest vs. lowest intake, relative risk = 0.77, 95% confidence interval: 0.59, 0.99; P(trend) = 0.04). These data suggest that a diet high in fiber, and possibly specifically cereal fiber, may reduce risk of developing COPD. C1 [Varraso, Raphaelle] INSERM, U780, IFR69, F-94807 Villejuif, France. [Varraso, Raphaelle] Univ Paris Sud, Villejuif, France. [Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Willett, Walter C.; Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Channing Lab, Brigham & Womens Hosp,Dept Med,Med Sch, Boston, MA 02115 USA. [Willett, Walter C.; Camargo, Carlos A., Jr.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Dept Emergency Med, Massachusetts Gen Hosp, Boston, MA USA. RP Varraso, R (reprint author), INSERM, CESP, U1018, 16 Ave Paul Vaillant Couturier, F-94807 Villejuif, France. EM raphaelle.varraso@inserm.fr RI Varraso, Raphaelle/R-8740-2016 OI Varraso, Raphaelle/0000-0002-3338-7825 FU National Institutes of Health, Bethesda, Maryland [CA-87969, HL-63841, HL-60712, HL-77612, AI-52338, CA-55075] FX Supported by research grants CA-87969, HL-63841, HL-60712, HL-77612, AI-52338, and CA-55075 from the National Institutes of Health, Bethesda, Maryland. NR 29 TC 21 Z9 23 U1 2 U2 9 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 APR 1 PY 2010 VL 171 IS 7 BP 776 EP 784 DI 10.1093/aje/kwp455 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 578IL UT WOS:000276286800003 PM 20172921 ER PT J AU Spiegel, BMR Farid, M Esrailian, E Talley, J Chang, L AF Spiegel, Brennan M. R. Farid, Mary Esrailian, Eric Talley, Jennifer Chang, Lin TI Is Irritable Bowel Syndrome a Diagnosis of Exclusion?: A Survey of Primary Care Providers, Gastroenterologists, and IBS Experts SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID COMMUNITY GASTROENTEROLOGISTS; PAINFUL CONSTIPATION; QUALITY; GUIDELINES; MANAGEMENT; DISORDERS; VIGNETTES; COLITIS AB OBJECTIVES: Guidelines emphasize that irritable bowel syndrome (IBS) is not a diagnosis of exclusion and encourage clinicians to make a positive diagnosis using the Rome criteria alone. Yet many clinicians are concerned about overlooking alternative diagnoses. We measured beliefs about whether IBS is a diagnosis of exclusion, and measured testing proclivity between IBS experts and community providers. METHODS: We developed a survey to measure decision-making in two standardized patients with Rome III-positive IBS, including IBS with diarrhea (D-IBS) and IBS with constipation (C-IBS). The survey elicited provider knowledge and beliefs about IBS, including testing proclivity and beliefs regarding IBS as a diagnosis of exclusion. We surveyed nurse practitioners, primary care physicians, community gastroenterologists, and IBS experts. RESULTS: Experts were less likely than nonexperts to endorse IBS as a diagnosis of exclusion (8 vs. 72%; P < 0.0001). In the D-IBS vignette, experts were more likely to make a positive diagnosis of IBS (67 vs. 38%; P < 0.001), to perform fewer tests (2.0 vs. 4.1; P < 0.01), and to expend less money on testing (US$297 vs. $658; P < 0.01). Providers who believed IBS is a diagnosis of exclusion ordered 1.6 more tests and consumed $364 more than others (P < 0.0001). Experts only rated celiac sprue screening and complete blood count as appropriate in D-IBS; nonexperts rated most tests as appropriate. Parallel results were found in the C-IBS vignette. CONCLUSIONS: Most community providers believe IBS is a diagnosis of exclusion; this belief is associated with increased resource use. Experts comply more closely with guidelines to diagnose IBS with minimal testing. This disconnect suggests that better implementation of guidelines is warranted to minimize variation and improve cost-effectiveness of care. C1 [Spiegel, Brennan M. R.; Farid, Mary; Talley, Jennifer; Chang, Lin] VA Greater Los Angeles Healthcare Syst, Dept Gastroenterol, Los Angeles, CA 90073 USA. [Spiegel, Brennan M. R.; Farid, Mary; Esrailian, Eric; Chang, Lin] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Los Angeles, CA 90095 USA. [Spiegel, Brennan M. R.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90095 USA. [Spiegel, Brennan M. R.] CURE Digest Dis Res Ctr, Los Angeles, CA USA. [Spiegel, Brennan M. R.; Talley, Jennifer; Chang, Lin] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Neurobiol Stress, Los Angeles, CA 90095 USA. [Spiegel, Brennan M. R.; Chang, Lin] Univ Calif Los Angeles, VA Ctr Outcomes Res & Educ, Los Angeles, CA 90095 USA. RP Spiegel, BMR (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Gastroenterol, 11301 Wilshire Blvd,Bldg 115,Room 215, Los Angeles, CA 90073 USA. EM bspiegel@mednet.ulca.edu FU Veteran's Affairs Health Services Research and Development (HSR&D) Career Development Transition Award [RCD 03-179-2]; NIH [P50 DK64539, R01 AR46122, GCRC M01-RR00865]; [R24 AT002681] FX Financial support : Spiegel was supported by a Veteran's Affairs Health Services Research and Development (HSR&D) Career Development Transition Award (RCD 03-179-2). Chang was supported by NIH Grants P50 DK64539, R01 AR46122, and GCRC M01-RR00865. Spiegel and Chang were supported by Grant R24 AT002681. NR 27 TC 73 Z9 74 U1 0 U2 7 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 APR PY 2010 VL 105 IS 4 BP 848 EP 858 DI 10.1038/ajg.2010.47 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 582FQ UT WOS:000276582300018 PM 20197761 ER PT J AU Weintraub, D Rosenberg, PB Drye, LT Martin, BK Frangakis, C Mintzer, JE Porsteinsson, AP Schneider, LS Rabins, PV Munro, CA Meinert, CL Lyketsos, CG AF Weintraub, Daniel Rosenberg, Paul B. Drye, Lea T. Martin, Barbara K. Frangakis, Constantine Mintzer, Jacobo E. Porsteinsson, Anton P. Schneider, Lon S. Rabins, Peter V. Munro, Cynthia A. Meinert, Curtis L. Lyketsos, Constantine G. CA Diads-2 Res Grp TI Sertraline for the Treatment of Depression in Alzheimer Disease: Week-24 Outcomes SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE Alzheimer disease; depression; sertraline ID PROVISIONAL DIAGNOSTIC-CRITERIA; DOUBLE-BLIND; COGNITIVE IMPAIRMENT; CACHE COUNTY; DEMENTIA; PLACEBO; ANTIDEPRESSANTS; EFFICACY; TRIAL; DISTURBANCES AB Background: Depression and antidepressant use are common in Alzheimer disease (AD), but the effect of antidepressant treatment for depression on longer term outcomes is unknown. The authors report the Week-24 outcomes of patients who participated in a 12-week efficacy study of sertraline for depression of AD. Methods: One hundred thirty-one participants (sertraline = 67, placebo = 64) with mild-moderate AD and depression participated in the study. Patients who showed improvement on the modified Alzheimer's Disease Cooperative Study Clinical Global Impression-Change (mADCS-CGIC) after 12 weeks of randomized treatment with sertraline or placebo continued double-blinded treatment for an additional 12 weeks. Depression response and remission at 24 weeks were based on mADCS-CGIC score and change in Cornell Scale for Depression in Dementia (CSDD) score. Secondary outcome measures included time to remission, nonmood neuropsychiatric symptoms, global cognition, function, and quality of life. Results: One hundred seventeen (89.3%) participants completed all study assessments and 74 (56.5%; sertraline = 38, placebo = 36) completed all 24 weeks on randomized treatment. By 24 weeks, there were no between-group differences in depression response (sertraline = 44.8%, placebo = 35.9%; odds ratio [95% CI] = 1.23 [0.64-2.35]), change in CSDD score (median difference = 0.6 [95% CI: -2.26 to 3.46], chi(2) [df = 2] = 1.03), remission rates (sertraline = 32.8%, placebo = 21.8%; odds ratio [95% CI] = 1.61 [0.70-3.68]), or secondary outcomes. Common selective serotonin reuptake inhibitor-associated adverse events, specifically diarrhea, dizziness, and dry mouth, and pulmonary serious adverse events were more frequent in sertraline-randomized patients than in placebo subjects. Conclusions: Sertraline treatment is not associated with delayed improvement between 12 and 24 weeks of treatment and may not be indicated for the treatment of depression of AD. (Am J Geriatr Psychiatry 2010; 18:332-340) C1 [Rosenberg, Paul B.; Lyketsos, Constantine G.] Johns Hopkins Univ, Sch Med, Div Geriatr Psychiat & Neuropsychiat, Baltimore, MD 21218 USA. [Rosenberg, Paul B.; Munro, Cynthia A.; Lyketsos, Constantine G.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21218 USA. [Lyketsos, Constantine G.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA. [Martin, Barbara K.; Frangakis, Constantine; Meinert, Curtis L.] Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Clin Trials, Baltimore, MD USA. [Munro, Cynthia A.] Johns Hopkins Univ, Sch Med, Div Med Psychol, Baltimore, MD 21218 USA. [Mintzer, Jacobo E.] Med Univ S Carolina, Dept Neurosci, Div Translat Res, Charleston, SC 29425 USA. [Mintzer, Jacobo E.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Weintraub, Daniel] Univ Penn, Sect Geriatr Psychiat, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, MIRECC, Philadelphia, PA USA. [Porsteinsson, Anton P.] Univ Rochester, Sch Med & Dent, Dept Psychiat, AD CARE Program, Rochester, NY 14627 USA. [Schneider, Lon S.] Univ So Calif, Keck Sch Med, Dept Psychiat, Los Angeles, CA 90033 USA. [Schneider, Lon S.] Univ So Calif, Keck Sch Med, Dept Neurol, Los Angeles, CA 90033 USA. Univ So Calif, Leonard Davis Sch Gerontol, Los Angeles, CA 90089 USA. Johns Hopkins Bayview, Baltimore, MD USA. RP Weintraub, D (reprint author), 3615 Chestnut St,330, Philadelphia, PA 19104 USA. EM daniel.weintraub@uphs.upenn.edu OI Drye, Lea/0000-0002-2964-1878 FU NIA NIH HHS [K08 AG029157]; NIMH NIH HHS [1U01MH066136, 1U01MH066174, 1U01MH066175, 1U01MH066176, 1U01MH066177, 1U01MH068014, U01 MH066136, U01 MH066136-05, U01 MH066174, U01 MH066175, U01 MH066175-05, U01 MH066176, U01 MH066177, U01 MH068014] NR 34 TC 59 Z9 60 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1064-7481 EI 1545-7214 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD APR PY 2010 VL 18 IS 4 BP 332 EP 340 DI 10.1097/JGP.0b013e3181cc0333 PG 9 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 576RI UT WOS:000276164700007 PM 20220589 ER PT J AU Van Cott, EM AF Van Cott, Elizabeth M. TI All that glitters is gold? SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Editorial Material ID PROTEIN-C RESISTANCE C1 [Van Cott, Elizabeth M.] Massachusetts Gen Hosp, Coagulat Lab, Boston, MA 02114 USA. RP Van Cott, EM (reprint author), Jackson 235,55 Fruit St, Boston, MA 02114 USA. EM evancott@partners.org NR 7 TC 5 Z9 5 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD APR PY 2010 VL 85 IS 4 BP 223 EP 224 DI 10.1002/ajh.21641 PG 2 WC Hematology SC Hematology GA 581JW UT WOS:000276519700001 PM 20162542 ER PT J AU Babitt, JL Lin, HY AF Babitt, Jodie L. Lin, Herbert Y. TI Molecular Mechanisms of Hepcidin Regulation: Implications for the Anemia of CKD SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Anemia; chronic kidney disease; dialysis; inflammation; hepcidin ID TRANSFERRIN RECEPTOR 2; HEREDITARY HEMOCHROMATOSIS PROTEIN; IRON-DEFICIENCY ANEMIA; CHRONIC KIDNEY-DISEASE; ANTIMICROBIAL PEPTIDE HEPCIDIN; TANDEM MASS-SPECTROMETRY; HUMAN SERUM HEPCIDIN; JUVENILE HEMOCHROMATOSIS; HEMODIALYSIS-PATIENTS; TWISTED GASTRULATION AB Anemia is prevalent in patients with chronic kidney disease (CKD) and is associated with lower quality of life and higher risk of adverse outcomes, including cardiovascular disease and death. Anemia management in patients with CKD currently revolves around the use of erythropoiesis-stimulating agents and supplemental iron. However, many patients do not respond adequately and/or require high doses of these medications. Furthermore, recent clinical trials have shown that targeting higher hemoglobin levels with conventional therapies leads to increased cardiovascular morbidity and mortality, particularly when higher doses of erythropoiesis-stimulating agents are used and in patients who are poorly responsive to therapy. One explanation for the poor response to conventional therapies in some patients is that these treatments do not fully address the underlying cause of the anemia. In many patients with CKD, as with patients with other chronic inflammatory diseases, poor absorption of dietary iron and the inability to use the body's iron stores contribute to the anemia. Recent research suggests that these abnormalities in iron balance may be caused by increased levels of the key iron regulatory hormone hepcidin. This article reviews the pathogenesis of anemia in CKD, the role and regulation of hepcidin in systemic iron homeostasis and the anemia of CKD, and the potential diagnostic and therapeutic implications of these findings. Am J Kidney Dis 55:726-741. (C) 2010 by the National Kidney Foundation, Inc. C1 [Babitt, Jodie L.; Lin, Herbert Y.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Program Membrane Biol,Ctr Syst Biol,Div Nephrol, Boston, MA 02114 USA. RP Babitt, JL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Program Membrane Biol,Ctr Syst Biol,Div Nephrol, 185 Cambridge St,CPZN 8218, Boston, MA 02114 USA. EM babitt.jodie@mgh.harvard.edu FU National Institutes of Health (NIH) [K08 DK-075846, ROI DK-069533, RO1 DK-071837]; National Kidney Foundation; Massachusetts General Hospital FX Dr Babitt is supported in part by National Institutes of Health (NIH) grant K08 DK-075846, the Satellite Dialysis Young Investigator Grant of the National Kidney Foundation, and a Claflin Distinguished Scholar Award from the Massachusetts General Hospital. Dr Lin is supported in part by NIH grants ROI DK-069533 and RO1 DK-071837. NR 149 TC 73 Z9 78 U1 2 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 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 2010 VL 55 IS 4 BP 726 EP 741 DI 10.1053/j.ajkd.2009.12.030 PG 16 WC Urology & Nephrology SC Urology & Nephrology GA 575GH UT WOS:000276054500018 PM 20189278 ER PT J AU Bhan, I Tamez, H Ye, J Ankers, E Thadhani, R AF Bhan, Ishir Tamez, Hector Ye, Jun Ankers, Elizabeth Thadhani, Ravi TI ERGOCALCIFEROL INCREASES CIRCULATING LEVELS OF HUMAN CATHELICIDIN (hCAP18) SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Meeting Abstract CT Spring Clinical Meeting of the National-Kidney-Foundation CY APR 13-17, 2010 CL Orlando, FL SP Natl Kidney Fdn C1 Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 2010 VL 55 IS 4 MA 52 BP A44 EP A44 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 575GH UT WOS:000276054500075 ER PT J AU Isakova, T Gutierrez, O Smith, K Epstein, M Patel, N Juppner, H Wolf, M AF Isakova, Tamara Gutierrez, O. Smith, K. Epstein, M. Patel, N. Jueppner, H. Wolf, M. TI SHORT-TERM EFFECT OF DIETARY PHOSPHORUS RESTRICTION AND LANTHANUM CARBONATE ON FGF23 IN CHRONIC KIDNEY DISEASE PATIENTS SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Meeting Abstract CT Spring Clinical Meeting of the National-Kidney-Foundation CY APR 13-17, 2010 CL Orlando, FL SP Natl Kidney Fdn C1 [Isakova, Tamara; Smith, K.; Epstein, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gutierrez, O.; Patel, N.; Wolf, M.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 2010 VL 55 IS 4 MA 137 BP A66 EP A66 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 575GH UT WOS:000276054500160 ER PT J AU Waheed, S Williams, ME AF Waheed, Salman Williams, Mark E. TI IMPACT OF IMPAIRED eGFR ON HEMOGLOBIN A1C AND AVERAGE GLUCOSE CORRELATION IN DIABETES MELLITUS SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Meeting Abstract CT Spring Clinical Meeting of the National-Kidney-Foundation CY APR 13-17, 2010 CL Orlando, FL SP Natl Kidney Fdn C1 [Waheed, Salman; Williams, Mark E.] Joslin Diabet Ctr, Renal Unit, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 2010 VL 55 IS 4 MA 314 BP A110 EP A110 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 575GH UT WOS:000276054500337 ER PT J AU Lischko, AM Burgess, JF AF Lischko, Amy M. Burgess, James F., Jr. TI Knowledge of Cost Sharing and Decisions to Seek Care SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID HEALTH; COVERAGE AB Objectives: To assess knowledge and understanding of cost-sharing responsibilities and whether that knowledge and understanding influence actual and perceived use of healthcare services. Study Design: A 3000-person random sample was drawn from a state employee database in Massachusetts. Methods: Survey responses and claims analyses were used to assess knowledge of cost sharing and healthcare utilization over a 3-year study period. Trend models and logistic regression were used. Results: Nearly two-thirds of respondents (62%) accurately recalled the percentage of premium that they paid; 67% recalled the correct copayment for a doctor's visit. Younger, less educated, and lower-income employees recalled their copayment more accurately than older, more educated, higher-income colleagues. Half of the respondents accurately reported the copayment amount for an emergency department visit. Greater knowledge of overall healthcare costs was positively associated with higher utilization of office visits (P < .01). Knowledge of specific office visit and emergency department copayments had no significant relationship with utilization. Self-reported delays and reductions in utilization were much more pronounced than the actual claims data indicated. Conclusions: Employees were reasonably well informed about their cost-sharing responsibilities. Knowledge of costs was associated with higher office visit utilization during the study period. Respondents who were more knowledgeable about their specific copayments for office visits and emergency department visits also were more likely to behave in what appeared to be a more cost-efficient manner, with more office visits and fewer emergency department visits. (Am J Manag Care. 2010; 16(4): 298-304) C1 [Lischko, Amy M.] Tufts Univ, Sch Med, Dept Publ Hlth & Community Med, Boston, MA 02111 USA. [Burgess, James F., Jr.] VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, Boston, MA USA. [Burgess, James F., Jr.] Boston Univ, Dept Hlth Policy & Management, Boston, MA 02215 USA. RP Lischko, AM (reprint author), Tufts Univ, Sch Med, Dept Publ Hlth & Community Med, 136 Harrison Ave, Boston, MA 02111 USA. EM amy.lischko@tufts.edu NR 17 TC 1 Z9 1 U1 0 U2 1 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD APR PY 2010 VL 16 IS 4 BP 298 EP 304 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 584ZJ UT WOS:000276793300008 PM 20394467 ER PT J AU Zavala, J Ramirez, M Medina, R Heard, P Carter, E Crandall, AL Hale, D Cody, J Escamilla, M AF Zavala, Juan Ramirez, Mercedes Medina, Rolando Heard, Patricia Carter, Erika Crandall, Ana Lisa Hale, Daniel Cody, Jannine Escamilla, Michael TI Psychiatric Syndromes in Individuals With Chromosome 18 Abnormalities SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE 18p; 18q; deletions; tetrasomy; psychiatric disorders ID LINKAGE DISEQUILIBRIUM ANALYSIS; SEVERE BIPOLAR DISORDER; IN-SITU HYBRIDIZATION; INTERSTITIAL DELETION; MENTAL-RETARDATION; LONG ARM; MOLECULAR CHARACTERIZATION; 18Q DELETIONS; SPEECH DELAY; FOLLOW-UP AB Chromosome 18 abnormalities are associated with a range of physical abnormalities such as short stature and hearing impairments. Psychiatric manifestations have also been observed. This study focuses on the presentations of psychiatric syndromes as they relate to specific chromosomal abnormalities of chromosome 18. Twenty-five subjects (13 with an 18q deletion, 9 with 18p tetrasomy, and 3 with an 18p deletion), were interviewed by psychiatrists (blind to specific chromosomal abnormality) using the DIGS (subjects 18 and older) or KSADS-PL (subjects under 18). A consensus best estimation diagnostic process was employed to determine psychiatric syndromes. Oligonucleotide Array Comparative Genomic Hybridization (Agilent Technologies) was utilized to define specific regions of chromosome 18 that were deleted or duplicated. These data were further analyzed to determine critical regions of the chromosome as they relate to phenotypic manifestations in these subjects. 58.3% of the chromosome 18q- deletion subjects had depressive symptoms, 58.3% had anxiety symptoms, 25% had manic symptoms, and 25% had psychotic symptoms. 66.6% of the chromosome 18p- deletion subjects had anxiety symptoms, and none had depressive, manic, or psychotic symptoms. Fifty percent of the chromosome 18p tetrasomy subjects had anxiety symptoms, 12.5% had psychotic symptoms, and 12.5% had a mood disorder. All three chromosomal disorders were associated with high anxiety rates. Psychotic, manic and depressive disorders were seen mostly in 18q- subjects and this may be helpful in narrowing regions for candidate genes for these psychiatric conditions. (C) 2009 Wiley-Liss, Inc. C1 [Escamilla, Michael] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, S Texas Psychiat Genet Res Ctr, San Antonio, TX 78205 USA. [Medina, Rolando] S Texas Vet Hlth Care Syst, Audie L Murphy Div, Psychiat Serv, San Antonio, TX USA. [Heard, Patricia; Carter, Erika; Crandall, Ana Lisa; Hale, Daniel; Cody, Jannine] Univ Texas Hlth Sci Ctr San Antonio, Dept Pediat, San Antonio, TX 78229 USA. [Escamilla, Michael] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Escamilla, Michael] Reg Acad Hlth Ctr, S Texas Med Genet Res Grp, Edinburg, TX USA. RP Escamilla, M (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, S Texas Psychiat Genet Res Ctr, 454 Soledad,Suite 200, San Antonio, TX 78205 USA. EM escamillam@uthscsa.edu NR 59 TC 6 Z9 6 U1 3 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD APR PY 2010 VL 153B IS 3 BP 837 EP 845 DI 10.1002/ajmg.b.31047 PG 9 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 582CX UT WOS:000276574300014 PM 19927307 ER PT J AU Kimball, AB Guerin, A Latremouille-Viau, D Yu, AP Gupta, S Bao, YJ Mulani, P AF Kimball, Alexa Boer Guerin, Annie Latremouille-Viau, Dominick Yu, Andrew P. Gupta, Shiraz Bao, Yanjun Mulani, Parvez TI Coronary Heart Disease and Stroke Risk in Patients with Psoriasis: Retrospective Analysis SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Coronary heart disease; Psoriasis; Stroke ID RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-LIFE; RHEUMATOID-ARTHRITIS; METABOLIC SYNDROME; VASCULAR-DISEASES; FOLLOW-UP; FRAMINGHAM; COMORBIDITIES; POPULATION; EQUATIONS AB BACKGROUND: Past studies suggest an association between psoriasis and the risk of developing coronary heart disease. The objectives of this study were to estimate the 10-year risks of coronary heart disease and stroke in patients with moderate to severe psoriasis, to compare risks between patients and the general population, and to determine whether risk profiles are affected by disease severity. METHODS: Data were pooled from patients with moderate to severe psoriasis (Psoriasis Area and Severity Index [PASI] score >= 10) who were enrolled in Phase II (M02-528) or Phase III trials (Comparative Study of HUMIRA vs Methotrexate vs Placebo In PsOriasis PatieNts[CHAMPION], Randomized Controlled EValuation of Adalimumab Every Other Week Dosing in Moderate to Severe Psoriasis TriAL[REVEAL]) evaluating adalimumab. Risks of coronary heart disease and stroke were estimated using the Framingham risk score algorithm and a stroke risk function based on the Framingham Heart Study cohorts. To compare risks between patients with psoriasis and the general population, average population risks were imputed on the basis of age and gender. Wilcoxon rank-sum tests evaluated risk differences between patients with psoriasis and the general population and between patients with moderate psoriasis and patients with severe psoriasis. RESULTS: A total of 1591 patients were identified, including 1082 patients with PASI scores >= 10 and <= 20 and 509 patients with PASI scores > 20. Patients with PAST scores from 10 to 20 and PASI scores > 20 had similar 10-year risks of coronary heart disease (12.3% and 12.2%; P = .49) and stroke (8.3% and 8.7%; P = .28). Compared with the general population, 10-year risks of patients with psoriasis were 28% greater for coronary heart disease (P < .001) and 11.8% greater for stroke (P = .02). CONCLUSION: Patients with moderate to severe psoriasis had increased risks of coronary heart disease and stroke compared with the general population. (C) 2010 Elsevier Inc. All rights reserved. The American Journal of Medicine (2010) 123, 350-357 C1 [Kimball, Alexa Boer] Harvard Univ, Sch Med, Boston, MA USA. [Guerin, Annie; Latremouille-Viau, Dominick; Yu, Andrew P.] Anal Grp, Boston, MA USA. [Gupta, Shiraz; Bao, Yanjun; Mulani, Parvez] Abbott Labs, Abbott Pk, IL 60064 USA. RP Kimball, AB (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. EM akimball@partners.org RI Max, Mad/E-5238-2010 OI Max, Mad/0000-0001-6966-6829 NR 46 TC 53 Z9 54 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD APR PY 2010 VL 123 IS 4 BP 350 EP 357 DI 10.1016/j.amjmed.2009.08.022 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 584VT UT WOS:000276782300013 PM 20362755 ER PT J AU Ament, JD Todani, A Pineda, R Shen, TT Aldave, AJ Dohlman, CH Chodosh, J AF Ament, Jared D. Todani, Amit Pineda, Roberto, II Shen, Tueng T. Aldave, Anthony J. Dohlman, Claes H. Chodosh, James TI Global Corneal Blindness and the Boston Keratoprosthesis Type I SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Editorial Material ID TRANSPLANTATION C1 [Ament, Jared D.; Todani, Amit; Pineda, Roberto, II; Dohlman, Claes H.; Chodosh, James] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Aldave, Anthony J.] Univ Calif Los Angeles, Jules Stein Eye Inst, Los Angeles, CA 90024 USA. [Shen, Tueng T.] Univ Washington, Inst Eye, Seattle, WA 98195 USA. RP Chodosh, J (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM james_chodosh@meei.hardvard.edu NR 14 TC 10 Z9 11 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 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD APR PY 2010 VL 149 IS 4 BP 537 EP 539 DI 10.1016/j.ajo.2009.11.001 PG 3 WC Ophthalmology SC Ophthalmology GA 582DK UT WOS:000276575700001 PM 20346774 ER PT J AU Risbud, MV Schipani, E Shapiro, IM AF Risbud, Makarand V. Schipani, Ernestina Shapiro, Irving M. TI Hypoxic Regulation of Nucleus Pulposus Cell Survival From Niche to Notch SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Review ID HUMAN INTERVERTEBRAL DISC; ENDOTHELIAL GROWTH-FACTOR; INDUCIBLE FACTOR; EXTRACELLULAR-MATRIX; FACTOR (HIF)-1-ALPHA; PROLYL HYDROXYLASES; STEM-CELLS; FACTOR-I; EXPRESSION; HIF-1-ALPHA AB This minireview examines the role of hypoxia, and hypoxia inducible factors (HIF-1 and HIF-2), in regulating the metabolism, function, and fate of cells of the nucleus pulposus in the intervertebral disk. We focus on the mechanisms by which both these hypoxia-sensitive transcription factors influence energy metabolism, radical dismutation, and expression of survival proteins. In addition, we discuss how cells of the nucleus respond to a number of hypoxia-sensitive proteins, including galectin-3, Akt, and VEGF. Where applicable, these discussions are extended to include the impact of these molecules and hypoxia on degenerating resident cells in the intervertebral niche. Finally, because the notch signaling pathway is responsive to hypoxia, we speculate that in the intervertebral niche, notch proteins participate in the regulation of disk precursor cell proliferation and differentiation. We predict that knowledge of each of these interactive proteins within the disk niche could be used to enhance renewal and promote differentiation and function of cells of the nucleus pulposus. (Am J Pathol 2010, 176:1577-1583; DOI: 10.2353/ajpath.2010.090734) C1 [Risbud, Makarand V.] Thomas Jefferson Univ, Dept Orthopaed Surg, Grad Program Tissue Engn & Regenerat Med, Philadelphia, PA 19107 USA. [Schipani, Ernestina] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH,Endocrine Unit, Boston, MA USA. RP Risbud, MV (reprint author), Thomas Jefferson Univ, Dept Orthopaed Surg, Grad Program Tissue Engn & Regenerat Med, 1015 Walnut St,Suite 501 Curtis Bldg, Philadelphia, PA 19107 USA. EM makarand.risbud@jefferson.edu FU NIH [R01AR050087, R01AR055655, R01AR048191] FX Supported by NIH grants R01AR050087 and R01AR055655 (to M.V.R. and I.M.S.) and R01AR048191 (to ES.). NR 52 TC 36 Z9 38 U1 3 U2 7 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD APR PY 2010 VL 176 IS 4 BP 1577 EP 1583 DI 10.2353/ajpath.2010.090734 PG 7 WC Pathology SC Pathology GA 580SX UT WOS:000276471500002 PM 20133815 ER PT J AU Tomidokoro, Y Rostagno, A Neubert, TA Lu, Y Rebeck, GW Frangione, B Greenberg, SM Ghiso, J AF Tomidokoro, Yasushi Rostagno, Agueda Neubert, Thomas A. Lu, Yun Rebeck, G. William Frangione, Blas Greenberg, Steven M. Ghiso, Jorge TI Iowa Variant of Familial Alzheimer's Disease Accumulation of Posttranslationally Modified A beta D23N in Parenchymal and Cerebrovascular Amyloid Deposits SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID HEREDITARY CEREBRAL-HEMORRHAGE; AMYLOID-BETA-PROTEIN; IMMUNOPRECIPITATION-MASS-SPECTROMETRY; WILD-TYPE TRANSTHYRETIN; A-BETA; DUTCH TYPE; CEREBROSPINAL-FLUID; APP GENE; SECRETASE ACTIVITY; ENDOTHELIAL-CELLS AB Mutations within the arnyloid-beta (A beta) sequence, especially those clustered at residues 21-23, which are linked to early onset familial Alzheimer's disease (AD), are primarily associated with cerebral amyloid angiopathy (CAA). The basis for this predominant vascular amyloid burden and the differential clinical phenotypes of cerebral hemorrhage/stroke in some patients and dementia in others remain unknown. The A beta D23N Iowa mutation is associated with progressive AD-like dementia, often without clinically manifested intracerebral hemorrhage. Neuropathologically, the disease is characterized by predominant preamyloid deposits, severe CAA, and abundant neurofibrillary tangles in the presence of remarkably few mature plaques. Biochemical analyses using a combination of immunoprecipitation, mass spectrometry, amino acid sequence, and Western blot analysis performed after sequential tissue extractions to separately isolate soluble components, preamyloid, and fibrillar amyloid species indicated that the Iowa deposits are complex mixtures of mutated and nonmutated A beta molecules. These molecules exhibited various degrees of solubility, were highly heterogeneous at both the N- and C-termini, and showed partial aspartate isomerization at positions 1,7, and 23. This collection of A beta species-the Iowa brain A beta peptidome contained clear imprints of amyloid clearance mechanisms yet highlighted the unique neuropathological features shared by a non-A beta cerebral amyloidosis, familial Danish dementia, in which neurofibrillary tangles coexist with extensive pre-amyloid deposition in the virtual absence of fibrillar lesions. These data therefore challenge the importance of neuritic plaques as the sole contributors for the development of dementia. (Am J Pathol 2010, 176:1841-1854; DOI: 10.2353/ajpath.2010.090636) C1 [Tomidokoro, Yasushi; Rostagno, Agueda; Frangione, Blas; Ghiso, Jorge] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA. [Neubert, Thomas A.] NYU, Sch Med, Dept Pharmacol, New York, NY 10016 USA. [Frangione, Blas; Ghiso, Jorge] NYU, Sch Med, Dept Psychiat, New York, NY 10016 USA. [Neubert, Thomas A.; Lu, Yun] NYU, Sch Med, Kimmel Ctr Biol & Med, Skirball Inst, New York, NY 10016 USA. [Rebeck, G. William] Georgetown Univ, Dept Neurosci, Washington, DC USA. [Greenberg, Steven M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Ghiso, J (reprint author), NYU, Sch Med, Dept Pathol, 550 1St Ave TH-432, New York, NY 10016 USA. EM jorge.ghiso@nyumc.org FU National Institutes of Health [AG10491, AG005891, AG30539, NS051715, P30 NS050276]; Shared Instrumentation grant [RR14662]; Alzheimer's Association; American Heart Association FX Supported by National Institutes of Health grants AG10491, AG005891, AG30539, NS051715, and P30 NS050276 and Shared Instrumentation grant RR14662, the Alzheimer's Association, and the American Heart Association. NR 80 TC 20 Z9 21 U1 0 U2 4 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD APR PY 2010 VL 176 IS 4 BP 1841 EP 1854 DI 10.2353/ajpath.2010.090636) PG 14 WC Pathology SC Pathology GA 580SX UT WOS:000276471500030 PM 20228223 ER PT J AU Priolo, C Agostini, M Vena, N Ligon, AH Fiorentino, M Shin, E Farsetti, A Pontecorvi, A Sicinska, E Loda, M AF Priolo, Carmen Agostini, Michelle Vena, Natalie Ligon, Azra H. Fiorentino, Michelangelo Shin, Eyoung Farsetti, Antonella Pontecorvi, Alfredo Sicinska, Ewa Loda, Massimo TI Establishment and Genomic Characterization of Mouse Xenografts of Human Primary Prostate Tumors SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID PRIMARY CULTURES; CANCER RESEARCH; ANIMAL-MODELS; GENE FUSIONS; MICE; COMPENDIUM; ONCOGENE; ANTIGEN; TMPRSS2; GROWTH AB Serum prostate-specific antigen screening has led to earlier detection and surgical treatment of prostate cancer, favoring an increasing incidence-to-mortality ratio. However, about one third of tumors that are diagnosed when still confined to the prostate can relapse within 10 years from the first treatment. The challenge is therefore to identify prognostic markers of aggressive versus indolent tumors. Although several preclinical models of advanced prostate tumors are available, a model that recapitulates the genetic and growth behavior of primary tumors is still lacking. Here, we report a complete histopathological and genomic characterization of xenografts derived from primary localized low- and high-grade human prostate tumors that were implanted under the renal capsule of immunodeficient mice. We obtained a tumor take of 56% and show that these xenografts maintained the histological as well as most genomic features of the parental tumors. Serum prostate-specific antigen levels were measurable only in tumor xenograft-bearing mice, but not in those implanted with either normal prostate tissue or in tumors that likely regressed. Finally, we show that a high proliferation rate, but not the pathological stage or the Gleason grade of the original tumor, was a fundamental prerequisite for tumor take in mice. This mouse xenograft model represents a useful preclinical model of primary prostate tumors for their biological characterization, biomarker discovery, and drug testing. (Am J Pathol 2010, 176:1901-1913; DOI: 10.2353/ajpath.2010.090873) C1 [Priolo, Carmen; Agostini, Michelle; Shin, Eyoung; Loda, Massimo] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Med Oncol, Boston, MA 02115 USA. [Ligon, Azra H.; Loda, Massimo] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Pathol, Boston, MA 02115 USA. [Vena, Natalie; Ligon, Azra H.; Fiorentino, Michelangelo; Sicinska, Ewa; Loda, Massimo] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Farsetti, Antonella] CNR, INMM, Rome, Italy. [Pontecorvi, Alfredo] Univ Cattolica Sacro Cuore, Dept Endocrinol, Rome, Italy. RP Loda, M (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Med Oncol, D1536,44 Binney St, Boston, MA 02115 USA. EM massimo_loda@dfci.harvard.edu RI Agostini, Michelle/I-1275-2012 FU Department of Defense [W81XWH-06-1-0053]; National Cancer Institute [RO1CA131945, PO1CA89021, P50CA90381]; Catholic University of Rome (Italy) FX Supported by Department of Defense grant W81XWH-06-1-0053 and National Cancer Institute RO1CA131945, PO1CA89021 and P50CA90381 (to M.L.). O.P. was funded by a Ph.D. program from the Catholic University of Rome (Italy). NR 33 TC 25 Z9 26 U1 0 U2 8 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD APR PY 2010 VL 176 IS 4 BP 1901 EP 1913 DI 10.2353/ajpath.2010.090873 PG 13 WC Pathology SC Pathology GA 580SX UT WOS:000276471500035 PM 20167861 ER PT J AU Abangan, RS Williams, CR Mehrotra, M Duncan, JD LaRue, AC AF Abangan, Romeo S., Jr. Williams, Christopher R. Mehrotra, Meenal Duncan, James D. LaRue, Amanda C. TI MCP1 Directs Trafficking of Hematopoietic Stem Cell-Derived Fibroblast Precursors in Solid Tumor SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID BONE-MARROW; IN-VITRO; FIBROCYTE DIFFERENTIATION; CIRCULATING FIBROCYTES; MESENCHYMAL PROGENITOR; MONOLAYER CULTURES; EPITHELIAL-CELLS; BREAST-CANCER; RECEPTOR; ORIGIN AB Our previous studies have demonstrated that hematopoietic stem cells (HSCs) are a novel source of carcinoma-associated fibroblasts. However, the mechanisms regulating recruitment and homing of HSC-derived carcinoma-associated fibroblasts or their precursors to the tumor microenvironment are unknown. Herein, we demonstrate using a single cell transplantation model that circulating fibroblast precursors (CFPs) are of HSC origin. This population increased with tumor burden in vivo and functional in vitro studies showed that CFPs preferentially migrated and differentiated into fibroblasts in response to tumor, suggesting that HSC-derived CFPs serve as an intermediate between the bone marrow and tumor. Based on this chemotactic ability and our demonstration of a monocyte lineage origin for CFPs, we investigated the role of monocyte chemoattractant protein (MCP1) in mediating CFP recruitment/homing. Blocking tumor-produced MCP1 inhibited in vitro migration of CFPs in response to multiple tumor types, indicating broad biological significance for this CFP/chemokine interaction. In vivo, CCR2-expressing CFPs increased in circulation during the period of active tumor growth and stromal development. Inhibition of MCP1 during tumor development resulted in decreased tumor volume in tumor-bearing mice. Together these findings confirm an HSC origin for CFPs, demonstrate a role for MCP1 in regulating their contribution to the tumor microenvironment, and suggest a potential therapeutic target for limiting tumor growth. (An, J Pathol 2010,176:1914-1924. DOI: 10.2353/ajpath.2010.080839) C1 [Abangan, Romeo S., Jr.; Williams, Christopher R.; Mehrotra, Meenal; Duncan, James D.; LaRue, Amanda C.] Med Univ S Carolina, Dept Vet Affairs Med Ctr, Charleston, SC 29425 USA. [Abangan, Romeo S., Jr.; Williams, Christopher R.; Mehrotra, Meenal; Duncan, James D.; LaRue, Amanda C.] Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. [Abangan, Romeo S., Jr.] Med Univ S Carolina, Coll Pharm, Charleston, SC 29425 USA. [LaRue, Amanda C.] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA. RP LaRue, AC (reprint author), Ralph H Johnson VA Med Ctr, 109 Bee St, Charleston, SC 29401 USA. EM laruerc@musc.edu FU Research and Development, Medical Research Services, Department of Veterans Affairs; American Cancer Society [IRG 97-219-08] FX Supported by the office of Research and Development, Medical Research Services, Department of Veterans Affairs to A.C.L. and the American Cancer Society Institutional Research grant (IRG 97-219-08 to A.C.L.). NR 47 TC 9 Z9 9 U1 0 U2 1 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 APR PY 2010 VL 176 IS 4 BP 1914 EP 1926 DI 10.2353/ajpath.2010.080839 PG 13 WC Pathology SC Pathology GA 580SX UT WOS:000276471500036 PM 20167869 ER PT J AU Recio, AC Bohart, ZW Havens, SR Stiens, SA AF Recio, Albert C. Bohart, Zachary W. Havens, Spencer R. Stiens, Steven A. TI Acute Spinal Cord Injury and Infection with Multidrug-Resistant Acinetobacter calcoaceticus-baumannii Complex Among Returning Operation Iraqi Freedom Soldiers Successful Innovations in Rehabilitation during Isolation SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE Isolation; Spinal Cord Injury (SCI); Rehabilitation; Acinetobacter calcoaceticus-baumannii Complex ID STAPHYLOCOCCUS-AUREUS; CLOSTRIDIUM-DIFFICILE; IMPACT; EPIDEMIOLOGY; UNIT; SKIN AB Recio AC, Bohart ZW, Havens SR, Stiens SA: Acute spinal cord injury and infection with multidrug-resistant Acinetobacter calcoaceticus-baumannii complex among returning Operation Iraqi Freedom soldiers: Successful innovations in rehabilitation during isolation. Am J Phys Med Rehabil 2009;89:331-335. Concerns about drug-resistant infectious organisms are increasing in rehabilitation facilities. Resulting isolation protocols can potentially challenge the patients' access to medical care, psychological adaptation, mobility, and environmental interaction and therefore hinder the rehabilitation process. We report a systematic, retrospective case review of an active-duty Army sergeant who sustained a C5 American Spinal Cord Injury Association Impairment Scale A spinal cord injury while serving in Operation Iraqi Freedom. The patient's acute rehabilitation was complicated by an Acinetobacter calcoaceticus-baumannii complex infection, in the blood and urine, contracted while in Iraq. Isolation protocols were designed to enable regular hands-on contact for proprioceptive neuromuscular facilitation, transfers, wheelchair fitting, mobility training, and environmental control. After 1 mo of comprehensive acute interdisciplinary rehabilitation, delivered in a single room on the spinal cord injury unit, the patient acquired functional skills comparable with other complete C5 tetraplegics in our unit. If a patient with spinal cord injury must be placed in isolation, it is still feasible to conduct a comprehensive interdisciplinary rehabilitation program while strictly adhering to contact isolation protocols. C1 [Recio, Albert C.] Johns Hopkins Sch Med, Hugo W Moser Res Inst Kennedy Krieger, Int Ctr Spinal Cord Injury, Baltimore, MD USA. [Bohart, Zachary W.] Tufts Med Ctr, Dept Phys Med & Rehabil, Boston, MA USA. [Havens, Spencer R.; Stiens, Steven A.] Univ Washington, VA Puget Sound Hlth Care Syst, Spinal Cord Injury Unit, Dept Rehabil Med, Seattle, WA 98195 USA. RP Recio, AC (reprint author), Kennedy Krieger Inst, 707 N Broadway, Baltimore, MD 21205 USA. NR 16 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD APR PY 2010 VL 89 IS 4 BP 331 EP 335 DI 10.1097/PHM.0b013e3181c9d847 PG 5 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 584CA UT WOS:000276726400008 PM 20068440 ER PT J AU Kraft, M Amick, MM Barth, JT French, LM Lew, HL AF Kraft, Malissa Amick, Melissa M. Barth, Jeffrey T. French, Louis M. Lew, Henry L. TI A Review of Driving Simulator Parameters Relevant to the Operation Enduring Freedom/Operation Iraqi Freedom Veteran Population SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Review DE Brain Injury; Driving; Virtual Reality; Posttraumatic Stress Disorder ID TRAUMATIC BRAIN-INJURY; OBSTRUCTIVE SLEEP-APNEA; POSTTRAUMATIC-STRESS-DISORDER; ALZHEIMER-DISEASE; WAKEFULNESS TEST; MEDICAL FITNESS; PERSIAN-GULF; PERFORMANCE; ALCOHOL; US AB Kraft M, Amick MM, Barth JT, French LM, Lew HL: A review of driving simulator parameters relevant to the Operation Enduring Freedom/Operation Iraqi Freedom veteran population. Am J Phys Med Rehabil 2010;89:336-344. There is currently a pressing need for safe, reliable, cost-effective methods of evaluating driving ability. With recent improvements in virtual reality technology, driving simulators seem to offer a promising alternative to on-road methods of driving assessment. One population at risk for driving difficulties may be veterans returning from combat in Iraq or Afghanistan. The use of driving simulators to evaluate and remediate veterans' abilities to operate a motor vehicle is a rehabilitative goal. However, there are no consistent standardized procedures for determining safe from unsafe driving using driving simulators, which limit the clinical utility of this important tool. The purposes of this article are (1) to give the reader a better understanding of the parameters that are most commonly measured in the driving simulation literature and (2) to review parameters that are most relevant for the Operation Enduring Freedom/Operation Iraqi Freedom veteran population. C1 [Lew, Henry L.] VA Boston Hlth Care Syst, PM&R Serv, Dept Vet Affairs, Boston, MA 02130 USA. [Kraft, Malissa; Amick, Melissa M.; Lew, Henry L.] VA Boston Healthcare Syst, Polytrauma & Traumat Brain Injury Ctr, Boston, MA USA. [Lew, Henry L.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. [Barth, Jeffrey T.; Lew, Henry L.] Virginia Neurocare, Def & Vet Brain Injury Ctr, Charlottesville, VA USA. [Barth, Jeffrey T.] Lakeview Healthcare Syst, Charlottesville, VA USA. [Barth, Jeffrey T.] Univ Virginia, Sch Med, Div Neuropsychol, Charlottesville, VA 22908 USA. [French, Louis M.] Walter Reed Army Med Ctr, Def & Vet Brain Injury Ctr, Washington, DC 20307 USA. [French, Louis M.] Walter Reed Army Med Ctr, Dept Orthoped & Rehabil, Washington, DC 20307 USA. [French, Louis M.] Uniformed Serv Univ Hlth Sci, Dept Neurol, Bethesda, MD 20814 USA. RP Lew, HL (reprint author), VA Boston Hlth Care Syst, PM&R Serv, Dept Vet Affairs, 150 S Huntington Ave, Boston, MA 02130 USA. NR 69 TC 12 Z9 12 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD APR PY 2010 VL 89 IS 4 BP 336 EP 344 DI 10.1097/PHM.0b013e3181d3eb5f PG 9 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 584CA UT WOS:000276726400009 PM 20299851 ER PT J AU Belleannee, C Da Silva, N Shum, WWC Brown, D Breton, S AF Belleannee, Clemence Da Silva, Nicolas Shum, Winnie W. C. Brown, Dennis Breton, Sylvie TI Role of purinergic signaling pathways in V-ATPase recruitment to apical membrane of acidifying epididymal clear cells SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE calcium; cAMP; epididymis; H(+)-ATPase; luminal acidification ID TRANSMEMBRANE CONDUCTANCE REGULATOR; MALE REPRODUCTIVE-TRACT; VACUOLAR H+-ATPASE; DEPENDENT LUMINAL ACIDIFICATION; TRANSCRIPTION FACTOR FOXI1; BRUSH-BORDER MEMBRANES; RAT VAS-DEFERENS; EPITHELIAL-CELLS; ANION SECRETION; SMOOTH-MUSCLE AB Belleannee C, Da Silva N, Shum WW, Brown D, Breton S. Role of purinergic signaling pathways in V-ATPase recruitment to apical membrane of acidifying epididymal clear cells. Am J Physiol Cell Physiol 298: C817-C830, 2010. First published January 13, 2010; doi:10.1152/ajpcell.00460.2009.-Extracellular purinergic agonists regulate a broad range of physiological functions via P1 and P2 receptors. Using the epididymis as a model system in which luminal acidification is essential for sperm maturation and storage, we show here that extracellular ATP and its hydrolysis product adenosine trigger the apical accumulation of vacuolar H(+)-ATPase (V-ATPase) in acidifying clear cells. We demonstrate that the epididymis can hydrolyze luminal ATP into other purinergic agonists such as ADP via the activity of nucleotidases located in the epididymal fluid and in the apical membrane of epithelial cells. Alkaline phosphatase activity and abundant ecto-5'-nucleotidase protein were detected in the apical pole of principal cells. In addition, we show that nine nucleotidase genes (Nt5e, Alpl, Alpp, Enpp1, 2, and 3, and Entpd 2, 4, and 5), seven ATP P2 receptor genes (P2X1, P2X2, P2X3, P2X4, P2X6, P2Y2, P2Y5), and three adenosine P1 receptor genes (A1, A2B, and A3) are expressed in epithelial cells isolated by laser cut microdissection (LCM). The calcium chelator BAPTA-AM abolished the apical V-ATPase accumulation induced by ATP, supporting the contribution of P2X or P2Y in this response. The PKA inhibitor myristoylated protein kinase inhibitor (mPKI) inhibited adenosine-dependent V-ATPase apical accumulation, indicating the participation of the P1 A2B receptor. Altogether, these results suggest that the activation of P1 and P2 purinergic receptors by ATP and adenosine might play a significant role in luminal acidification in the epididymis, a process that is crucial for the establishment of male fertility. C1 Massachusetts Gen Hosp, Div Nephrol, Program Membrane Biol, Ctr Syst Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Breton, S (reprint author), Massachusetts Gen Hosp, Simches Res Ctr, Program Membrane Biol, 185 Cambridge St,Suite 8204, Boston, MA 02114 USA. EM sbreton@partners.org FU National Institutes of Health [HD-40793, DK-38452, DK-42956]; Boston Area Diabetes and Endocrinology Research Center [DK-57521]; Center for the Study of Inflammatory Bowel Disease [DK-43341] FX This work was supported by National Institutes of Health Grants HD-40793 (S. Breton), DK-38452 (S. Breton and D. Brown), and DK-42956 (D. Brown). The Microscopy Core Facility of the Massachusetts General Hospital Program in Membrane Biology receives support from the Boston Area Diabetes and Endocrinology Research Center (DK-57521) and the Center for the Study of Inflammatory Bowel Disease (DK-43341). NR 77 TC 27 Z9 27 U1 0 U2 4 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 APR PY 2010 VL 298 IS 4 BP C817 EP C830 DI 10.1152/ajpcell.00460.2009 PG 14 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 574VP UT WOS:000276022600006 PM 20071692 ER PT J AU Sharoff, CG Hagobian, TA Malin, SK Chipkin, SR Yu, HY Hirshman, MF Goodyear, LJ Braun, B AF Sharoff, Carrie G. Hagobian, Todd A. Malin, Steven K. Chipkin, Stuart R. Yu, Haiyan Hirshman, Michael F. Goodyear, Laurie J. Braun, Barry TI Combining short-term metformin treatment and one bout of exercise does not increase insulin action in insulin-resistant individuals SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article ID HUMAN SKELETAL-MUSCLE; ACTIVATED PROTEIN-KINASE; DEPENDENT DIABETES-MELLITUS; GLUCOSE-UPTAKE; DOSE-RESPONSE; SENSITIVITY; METABOLISM; TOLERANCE; MEN; ROSIGLITAZONE AB Sharoff CG, Hagobian TA, Malin SK, Chipkin SR, Yu H, Hirshman MF, Goodyear LJ, Braun B. Combining short-term metformin treatment and one bout of exercise does not increase insulin action in insulin-resistant individuals. Am J Physiol Endocrinol Metab 298: E815-E823, 2010. First published January 13, 2010; doi:10.1152/ajpendo.00517.2009.-Results from the Diabetes Prevention Program highlight the effectiveness of metformin or regular physical activity in the prevention of type 2 diabetes. Independently, metformin and exercise increase insulin sensitivity, but they have not been studied in combination. To assess the combined effects, insulin-resistant subjects (n = 9) matched for weight, body fat, and aerobic fitness were studied before any treatment (B), after 2-3 wk of 2,000 mg/day metformin (MET), and after metformin plus 40 min of exercise at 65% Vo(2peak) (MET + Ex). A second group (n = 7) was studied at baseline and after an identical bout of exercise with no metformin ( Ex). Biopsies of the vastus lateralis were taken at B, after MET, immediately after MET + Ex (group 1), or immediately after Ex (group 2). Insulin sensitivity was assessed 4 h postexercise with a euglycemic hyperinsulinemic (40 mU . m(2) . min(-1)) clamp enriched with [6,6-H-2] glucose. Insulin sensitivity was 54% higher after Ex (P < 0.01), but there was no change with Met + Ex. Skeletal muscle AMPK alpha 2 activity was elevated threefold (P < 0.01) after Ex, but there was no increase with MET + Ex. These findings suggest that the combination of short- term metformin treatment and an acute bout of exercise does not enhance insulin sensitivity, and the addition of metformin may attenuate the well-documented effects of exercise alone. C1 [Sharoff, Carrie G.; Hagobian, Todd A.; Malin, Steven K.; Chipkin, Stuart R.; Braun, Barry] Univ Massachusetts Amherst, Dept Kinesiol, Energy Metab Lab, Amherst, MA 01003 USA. [Yu, Haiyan; Hirshman, Michael F.; Goodyear, Laurie J.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Metab Sect, Boston, MA 02115 USA. RP Braun, B (reprint author), Univ Massachusetts Amherst, Dept Kinesiol, Energy Metab Lab, 107 Totman Bldg,30 Eastman Ln, Amherst, MA 01003 USA. EM bbraun@kin.umass.edu OI Chipkin, Stuart/0000-0003-2114-9480; Malin, Steven/0000-0002-7360-6711 FU American Diabetes Association [7-04-JF-10]; National Institute of Diabetes and Digestive and Kidney Diseases [RO1-DK-068626] FX This study was funded by American Diabetes Association Grant 7-04-JF-10 and National Institute of Diabetes and Digestive and Kidney Diseases Grant RO1-DK-068626. NR 43 TC 32 Z9 32 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 EI 1522-1555 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD APR PY 2010 VL 298 IS 4 BP E815 EP E823 DI 10.1152/ajpendo.00517.2009 PG 9 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 571PY UT WOS:000275768100010 PM 20071560 ER PT J AU Biederman, J Petty, CR Monuteaux, MC Fried, R Byrne, D Mirto, T Spencer, T Wilens, TE Faraone, SV AF Biederman, Joseph Petty, Carter R. Monuteaux, Michael C. Fried, Ronna Byrne, Deirdre Mirto, Tara Spencer, Thomas Wilens, Timothy E. Faraone, Stephen V. TI Adult Psychiatric Outcomes of Girls With Attention Deficit Hyperactivity Disorder: 11-Year Follow-Up in a Longitudinal Case-Control Study SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID PEDIATRIC BIPOLAR DISORDER; DEFICIT/HYPERACTIVITY DISORDER; SUBTHRESHOLD DIAGNOSES; MAJOR DEPRESSION; SUBSTANCE USE; LATE-ONSET; ADHD; COMORBIDITY; CHILDREN; ADOLESCENCE AB Objective: Few follow-up studies have been conducted of girls with ADHD, and none have followed girls into adulthood. The authors sought to estimate the prevalence of psychopathology in girls with and without ADHD followed into young adulthood. Method: The authors conducted a longitudinal case-control study of 6- to 18-year-old girls with (N=140) and without (N=122) ADHD ascertained from psychiatric and pediatric sources. At the 11-year follow-up, 96 (69%) of the girls with ADHD and 91 (75%) of the comparison girls were reassessed (mean age=22 years). Participants were blindly assessed by structured diagnostic interviews. Results: Lifetime and 1-year risks for all composite categories of psychopathology were significantly greater in girls with ADHD grown up relative to comparison girls; lifetime hazard ratios were 7.2 (95% CI=4.0-12.7) for antisocial disorders, 6.8 (95% CI=3.7-12.6) for mood disorders, 2.1 (95% CI=1.6-2.9) for anxiety disorders, 3.2 (95% CI=2.0-5.3) for developmental disorders, 2.7 (95% CI=1.6-4.3) for addictive disorders, and 3.5 (95% CI=1.6-7.3) for eating disorders. For lifetime psychopathology, all six composite categories remained statistically significant after controlling for other baseline psychopathology. Except for addictive disorders, significant 1-year findings remained significant after controlling for baseline psychopathology. The 1-year prevalences of composite disorders were not associated with lifetime or 1-year use of ADHD medication. Conclusions: By young adulthood, girls with ADHD were at high risk for antisocial, addictive, mood, anxiety, and eating disorders. These prospective findings, previously documented in boys with ADHD, provide further evidence for the high morbidity associated with ADHD across the life cycle. C1 Massachusetts Gen Hosp, Clin Program Pediat Psychopharmacol, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Res Program Pediat Psychopharmacol, Dept Psychiat, Boston, MA 02114 USA. SUNY Upstate Med Univ, Dept Psychiat & Behav Sci, Syracuse, NY USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Yawkey Ctr Outpatient Care, Pediat Psychopharmacol Program, YAW 6A 6900,32 Fruit St, Boston, MA 02114 USA. EM jbiederman@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU Abbott; Alza; AstraZeneca; Bristol-Myers Squibb; Celltech; Cephalon; Eli Lilly; Esai; Forest; GlaxoSmithKline; Gliatech; Janssen Pharmaceuticals; McNeil; Merck; NARSAD; National Institute on Drug Abuse; National Institute of Child Health and Human Development; NIMH; New River; Novartis; Noven; Neurosearch; Organon; Otsuka; Pfizer; Pharmacia; Prechter Foundation; Shire; Stanley Foundation; UCB Pharma; Wyeth; Pediatric Psychopharmacology Philanthropy Fund FX Dr. Biederman has received research support, consultation fees, or speaker's fees from Abbott, Alza, AstraZeneca, Bristol-Myers Squibb, Celltech, Cephalon, Eli Lilly, Esai, Forest, GlaxoSmithKline, Gliatech, Janssen Pharmaceuticals, McNeil, Merck, NARSAD, National Institute on Drug Abuse, National Institute of Child Health and Human Development, NIMH, New River, Novartis, Noven, Neurosearch, Organon, Otsuka, Pfizer, Pharmacia, Prechter Foundation, Shire, Stanley Foundation, UCB Pharma, and Wyeth. Dr. Fried has received honoraria from Shire. Dr. Spencer has received research support from or has served as speaker or on advisory boards for Cephalon, Eli Lilly, GlaxoSmithKline, Janssen, McNeil, NIMH, New River, Novartis, Pfizer, and Shire. Dr. Wilens has received research support from or has served as speaker or on advisory boards for Abbott, AstraZeneca, Eli Lilly, GlaxoSmithKline, Merck, National Institute on Drug Abuse, NIH, Neurosearch, Novartis, Ortho-McNeil, Pfizer, and Shire and received royalties from Guilford Press. Dr. Faraone has received research support or consulting or speaking fees from or has served on advisory boards for Eli Lilly, McNeil, Pfizer, NIH, and Shire. The others authors report no financial relationships with commercial interests.; Supported in part by a grant from the Eli Lilly and Company Foundation and the Pediatric Psychopharmacology Philanthropy Fund. NR 40 TC 104 Z9 105 U1 0 U2 13 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 APR PY 2010 VL 167 IS 4 BP 409 EP 417 DI 10.1176/appi.ajp.2009.09050736 PG 9 WC Psychiatry SC Psychiatry GA 577LE UT WOS:000276223800011 PM 20080984 ER PT J AU Satterthwaite, TD Wolf, DH Loughead, J Ruparel, K Valdez, JN Siegel, SJ Kohler, CG Gur, RE Gur, RC AF Satterthwaite, Theodore D. Wolf, Daniel H. Loughead, James Ruparel, Kosha Valdez, Jeffrey N. Siegel, Steven J. Kohler, Christian G. Gur, Raquel E. Gur, Ruben C. TI Association of Enhanced Limbic Response to Threat With Decreased Cortical Facial Recognition Memory Response in Schizophrenia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID BRAIN SYSTEMS; EMOTION; ACTIVATION; RETRIEVAL; COGNITION; NETWORK; FMRI; CONNECTIVITY; EXPRESSIONS; SPECIFICITY AB Objective: Recognition memory of faces is impaired in patients with schizophrenia, as is the neural processing of threat-related signals, but how these deficits interact to produce symptoms is unclear. The authors used an affective face recognition paradigm to examine possible interactions between cognitive and affective neural systems in schizophrenia. Method: Blood-oxygen-level-dependent response was examined by means of functional magnetic resonance imaging (3 Tesla) in healthy comparison subjects (N=21) and in patients with schizophrenia (N=12) or schizoaffective disorder, depressed type (N=4), during a two-choice recognition task that used images of human faces. Each target face, previously displayed with a threatening or nonthreatening affect, was displayed with neutral affect. Responses to successful recognition and responses to the effect of previously threatening versus nonthreatening affect were evaluated, and correlations with symptom severity (total Brief Psychiatric Rating Scale score) were examined. Functional connectivity analyses examined the relationship between activation in the amygdala and cortical regions involved in recognition memory. Results: Patients performed the task more slowly than healthy comparison subjects. Comparison subjects recruited the expected cortical regions to a greater degree than patients, and patients with more severe symptoms demonstrated proportionally less recruitment. Increased symptoms were also correlated with augmented amygdala and orbitofrontal cortex response to threatening faces. Comparison subjects exhibited a negative correlation between activity in the amygdala and cortical regions involved in cognition, while patients showed weakening of this relationship. Conclusions: Increased symptoms were related to an enhanced threat response in limbic regions and a diminished recognition memory response in cortical regions, supporting a link between these two brain systems that are often examined in isolation. This finding suggests that abnormal processing of threat-related signals in the environment may exacerbate cognitive impairment in schizophrenia. C1 [Satterthwaite, Theodore D.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Satterthwaite, TD (reprint author), Univ Penn, Sch Med, Dept Psychiat, 3535 Market St,2nd Floor, Philadelphia, PA 19104 USA. EM Ted.Satterthwaite@uphs.upenn.edu RI Wolf, Daniel/H-2581-2013; OI Siegel, Steven/0000-0001-8058-9713 FU AstraZeneca; Pfizer; NARSAD; NIMH [MH-19112, MH-060722-09] FX Dr. Siegel has received grant support from AstraZeneca and is a consultant for NuPathe. Drs. Raquel Gur and Ruben Gur have received investigator-initiated grants from Pfizer and AstraZeneca. Drs. Satterthwaite, Wolf, Loughead, and Kohler and Ms. Ruparel and Mr. Valdez report no financial relationships with commercial interests.; Supported by NARSAD (Dr. Wolf) and NIMH grants MH-19112 and MH-060722-09. NR 40 TC 35 Z9 35 U1 1 U2 4 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 APR PY 2010 VL 167 IS 4 BP 418 EP 426 DI 10.1176/appi.ajp.2009.09060808 PG 9 WC Psychiatry SC Psychiatry GA 577LE UT WOS:000276223800012 PM 20194482 ER PT J AU Calkins, ME Tepper, P Gur, RC Ragland, JD Klei, L Wiener, HW Richard, J Savage, RM Allen, TB O'Jile, J Devlin, B Kwentus, J Aliyu, MH Bradford, LD Edwards, N Lyons, PD Nimgaonkar, VL Santos, AB Go, RCP Gur, RE AF Calkins, Monica E. Tepper, Ping Gur, Ruben C. Ragland, J. Daniel Klei, Lambertus Wiener, Howard W. Richard, Jan Savage, Robert M. Allen, Trina B. O'Jile, Judith Devlin, Bernie Kwentus, Joseph Aliyu, Muktar H. Bradford, L. DiAnne Edwards, Neil Lyons, Paul D. Nimgaonkar, Vishwajit L. Santos, Alberto B. Go, Rodney C. P. Gur, Raquel E. TI Project Among African-Americans to Explore Risks for Schizophrenia (PAARTNERS): Evidence for Impairment and Heritability of Neurocognitive Functioning in Families of Schizophrenia Patients SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID CEREBRAL BLOOD-FLOW; COGNITIVE DEFICITS; WORKING-MEMORY; 1ST-DEGREE RELATIVES; RECOGNITION MEMORY; BIPOLAR DISORDER; ENDOPHENOTYPES; PERFORMANCE; GENETICS; GENES AB Objective: Neurocognitive impairments in schizophrenia are well replicated and widely regarded as candidate endophenotypes that may facilitate understanding of schizophrenia genetics and pathophysiology. The Project Among African-Americans to Explore Risks for Schizophrenia (PAARTNERS) aims to identify genes underlying liability to schizophrenia. The unprecedented size of its study group (N=1,872), made possible through use of a computerized neurocognitive battery, can help further investigation of the genetics of neurocognition. The current analysis evaluated two characteristics not fully addressed in prior research: 1) heritability of neurocognition in African American families and 2) relationship between neurocognition and psychopathology in families of African American probands with schizophrenia or schizoaffective disorder. Method: Across eight data collection sites, patients with schizophrenia or schizoaffective disorder (N=610), their biological relatives (N=928), and community comparison subjects (N=334) completed a standardized diagnostic evaluation and the computerized neurocognitive battery. Performance accuracy and response time (speed) were measured separately for 10 neurocognitive domains. Results: The patients with schizophrenia or schizoaffective disorder exhibited less accuracy and speed in most neurocognitive domains than their relatives both with and without other psychiatric disorders, who in turn were more impaired than comparison subjects in most domains. Estimated trait heritability after inclusion of the mean effect of diagnostic status, age, and sex revealed significant heritabilities for most neurocognitive domains, with the highest for accuracy of abstraction/flexibility, verbal memory, face memory, spatial processing, and emotion processing and for speed of attention. Conclusions: Neurocognitive functions in African American families are heritable and associated with schizophrenia. They show potential for gene-mapping studies. C1 [Calkins, Monica E.] Univ Penn, Schizophrenia Res Ctr, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Pittsburgh, Dept Epidemiol, Dept Psychiat, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA 15260 USA. Univ Calif Davis, Dept Psychiat & Behav Sci, Sacramento, CA 95817 USA. Univ Alabama, Dept Epidemiol & Int Hlth, Birmingham, AL USA. Univ Alabama, Dept Psychiat & Behav Neurobiol, Birmingham, AL USA. Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27706 USA. Durham VA Med Ctr, Dept Res, Durham, NC USA. Univ Mississippi, Dept Psychiat & Human Behav, Med Ctr, Jackson, MS USA. Vanderbilt Univ, Dept Prevent Med, Inst Global Hlth, Nashville, TN USA. Morehouse Sch Med, Dept Psychiat, Atlanta, GA 30310 USA. Univ Tennessee, Dept Psychiat, Coll Med, Memphis, TN USA. Univ Virginia, Dept Neurol, Charlottesville, VA USA. Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Calkins, ME (reprint author), Univ Penn, Schizophrenia Res Ctr, Sch Med, Dept Psychiat, 9 Maloney,3600 Spruce St, Philadelphia, PA 19104 USA. EM mcalkins@upenn.edu FU University of Pennsylvania; AstraZeneca; Pfizer; Merck; Lundbeck; NIMH [MH-66006, MH-66278, MH-066049, MH-66181, MH-66121, MH-066005, MH-66050, MH-66263, MH-66004, K08-MH-79364] FX Dr. Ruben Gur receives grant support through collaborations of the University of Pennsylvania with AstraZeneca, Pfizer, and Merck and may receive royalties from future commercial use of the Penn Computerized Neurocognitive Battery. Dr. Ragland may receive royalties from future commercial use of the Penn Computerized Neurocognitive Battery. Ms. Richard may receive royalties from future commercial use of Penn Computerized Neurocognitive Battery. Dr. Nimgaonkar received a research grant from Lundbeck on an unrelated topic when this article was in preparation. Dr. Raquel Gur receives grant support through collaborations of the University of Pennsylvania with AstraZeneca and Pfizer and may receive royalties from future commercial use of the Penn Computerized Neurocognitive Battery. The remaining authors report no financial relationships with commercial interests.; Supported by NIMH RO1 grants MH-66006, MH-66278, MH-066049, MH-66181, MH-66121, MH-066005, MH-66050, MH-66263, and MH-66004 and NIMH grant K08-MH-79364. NR 42 TC 38 Z9 40 U1 1 U2 5 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 APR PY 2010 VL 167 IS 4 BP 459 EP 472 DI 10.1176/appi.ajp.2009.08091351 PG 14 WC Psychiatry SC Psychiatry GA 577LE UT WOS:000276223800017 PM 20194479 ER PT J AU Lucan, SC Barg, FK Long, JA AF Lucan, Sean C. Barg, Frances K. Long, Judith A. TI Promoters and Barriers to Fruit, Vegetable, and Fast-Food Consumption Among Urban, Low-Income African Americans-A Qualitative Approach SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID UNITED-STATES; DIABETES-MELLITUS; PHYSICAL-ACTIVITY; NUTRITION; HEALTH; RISK; CHOICES; ADULTS; DIET; US AB To identify promoters of and barriers to fruit, vegetable, and fast-food consumption, we interviewed low-income African Americans in Philadelphia. Salient promoters and barriers were distinct from each other and differed by food type: taste was a promoter and cost a barrier to all foods; convenience, cravings, and preferences promoted consumption of fast foods; health concerns promoted consumption of fruits and vegetables and avoidance of fast foods. Promoters and barriers differed by gender and age. Strategies for dietary change should consider food type, gender, and age. (Am J Public Health. 2010;100:631-635. doi:10.2105/AJPH.2009.172692) C1 [Lucan, Sean C.; Barg, Frances K.] Univ Penn, Dept Family Med & Community Hlth, Philadelphia, PA 19104 USA. [Barg, Frances K.] Univ Penn, Dept Anthropol, Philadelphia, PA 19104 USA. [Long, Judith A.] Vet Affairs Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Long, Judith A.] Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. RP Lucan, SC (reprint author), Albert Einstein Coll Med, Dept Family & Social Med, Montefiore Med Ctr, 1300 Morris Pk Ave,Mazer Bldg,4th Floor, Bronx, NY 10461 USA. EM slucan@yahoo.com RI Lucan, Sean/B-3815-2009 OI Lucan, Sean/0000-0002-4447-9709 FU Robert Wood Johnson Clinical Scholars Program; Pisacano Leadership Foundation; National Institutes of Health; Robert Wood,Johnson Clinical Scholars Program FX Salary support and it research stipend for this project were provided by the Robert Wood Johnson Clinical Scholars Program. The Pisacano Leadership Foundation, the National Institutes of Health Local Repayment Program for Health Disparities, and the Robert Wood,Johnson Clinical Scholars Program provided financial support for S.C. Lucan's training. NR 57 TC 48 Z9 48 U1 4 U2 14 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 APR PY 2010 VL 100 IS 4 BP 631 EP 635 DI 10.2105/AJPH.2009.172692 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 573TG UT WOS:000275937200013 PM 20167885 ER PT J AU Williams, BA Baillargeon, JG Lindquist, K Walter, LC Covinsky, KE Whitson, HE Steinman, MA AF Williams, Brie A. Baillargeon, Jacques G. Lindquist, Karla Walter, Louise C. Covinsky, Kenneth E. Whitson, Heather E. Steinman, Michael A. TI Medication Prescribing Practices for Older Prisoners in the Texas Prison System SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID QUALITY-OF-CARE; INAPPROPRIATE MEDICATION; HEALTH-CARE; PHARMACOLOGICAL CARE; DISEASE PROFILE; CRITERIA; INMATES; ADULTS AB Objectives. We sought to assess appropriateness of medication prescribing for older Texas prisoners. Methods. In this 12-month cross-sectional study of 13117 prisoners (aged >= 55 years), we assessed medication use with Zhan criteria and compared our results to prior studies of community prescribing. We assessed use of indicated medications with 6 Assessing Care of Vulnerable Elders indicators. Results. Inappropriate medications were prescribed to a third of older prisoners; half of inappropriate use was attributable to over-the-counter antihistamines. When these antihistamines were excluded, inappropriate use dropped to 14% (>= 55 years) and 17% (>= 65 years), equivalent to rates in a Department of Veterans Affairs study (17%) and lower than rates in a health maintenance organization study (26%). Median rate of indicated medication use for the 6 indicators was 80% (range=12%-95%); gastrointestinal prophylaxis for patients on nonsteroidal anti-inflammatories at high risk for gastrointestinal bleed constituted the lowest rate. Conclusions. Medication prescribing for older prisoners in Texas was similar to that for older community adults. However, overuse of antihistamines and underuse of gastrointestinal prophylaxis suggests a need for education of prison health care providers in appropriate prescribing practices for older adults. (Am J Public Health. 2010;100:756-761. doi:10.2105/AJPH.2008.154591) C1 [Williams, Brie A.; Lindquist, Karla; Walter, Louise C.; Covinsky, Kenneth E.; Steinman, Michael A.] Univ Calif San Francisco, Div Geriatr, Dept Med, San Francisco, CA 94121 USA. [Williams, Brie A.; Walter, Louise C.; Covinsky, Kenneth E.; Steinman, Michael A.] San Francisco VA Med Ctr, Hlth Serv Res & Dev Res Enhancement Award Program, San Francisco, CA USA. [Baillargeon, Jacques G.] Univ Texas Med Branch, Dept Prevent Med & Community Hlth, Galveston, TX 77550 USA. [Baillargeon, Jacques G.] Univ Texas Med Branch, Div Epidemiol, Galveston, TX 77550 USA. [Whitson, Heather E.] Duke Univ, Dept Med, Div Geriatr, Durham, NC USA. RP Williams, BA (reprint author), Univ Calif San Francisco, Div Geriatr, Dept Med, 4150 Clement St Box 181-G, San Francisco, CA 94121 USA. EM brie.williams@ucsf.edu FU Hartford Outcomes Research Scholars Award; Hellman Family Award; Brookdale Leadership in Aging Fellowship; Veterans Affairs Health Services Research and Development service [CDTA 01-013]; National Institute on Aging; American Federation for Aging Research [K23 AG030999] FX B.A. Williams was supported in part by the Hartford Outcomes Research Scholars Award, the Hellman Family Award, and the Brookdale Leadership in Aging Fellowship. M.A. Steinman was supported by grants from the Veterans Affairs Health Services Research and Development service (CDTA 01-013) and the National Institute on Aging and the American Federation for Aging Research (K23 AG030999).; We thank Leonard Pechacek for providing copyediting support, Stephanie Zepeda for her knowledge of the pharmacy system in the Texas Department of Criminal justice, and Neil Nusbaum for his helpful insights.; The research described herein was coordinated in part by the Texas Department of Criminal justice research agreement (515-MR07). NR 36 TC 11 Z9 11 U1 0 U2 4 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 APR PY 2010 VL 100 IS 4 BP 756 EP 761 DI 10.2105/AJPH.2008.154591 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 573TG UT WOS:000275937200031 PM 19762661 ER PT J AU Donati, OF Scheffel, H Stolzmann, P Baumuller, S Plass, A Leschka, S Alkadhi, H AF Donati, Olivio F. Scheffel, Hans Stolzmann, Paul Baumueller, Stephan Plass, Andre Leschka, Sebastian Alkadhi, Hatem TI Combined Cardiac CT and MRI for the Comprehensive Workup of Hemodynamically Relevant Coronary Stenoses SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE catheter coronary angiography; coronary angiography; CT; MRI; myocardial perfusion ID EMISSION COMPUTED-TOMOGRAPHY; DIAGNOSTIC-ACCURACY; ARTERY-DISEASE; MAGNETIC-RESONANCE; STABLE ANGINA; HEART-DISEASE; SHOOT MODE; K-SPACE; ANGIOGRAPHY; METAANALYSIS AB OBJECTIVE. The purpose of our study was to prospectively evaluate the accuracy of a comprehensive assessment of coronary artery disease (CAD) with prospectively ECG-gated coronary CT angiography (CTA) and perfusion-cardiac MRI for the detection of hemodynamically relevant coronary stenoses. SUBJECTS AND METHODS. Forty-seven consecutive patients underwent k-space and time broad-use linear acquisition speed-up technique accelerated perfusion-cardiac MRI at 1.5 T and dual-source coronary CTA. Catheter coronary angiography (CA), coronary CTA, and perfusion-cardiac MRI were all performed within a median time interval of 7.5 days. Detection of hemodynamically relevant stenoses by the combination of coronary CTA plus perfusion-cardiac MRI was compared with the combination of CA plus perfusion-cardiac MRI, the latter serving as the standard of reference. RESULTS. CA identified stenoses in 75 of 141 coronary arteries (53.2%) in 33 of 47 patients (70.2%). Cardiac MRI revealed perfusion defects in 30 of 47 patients (63.8%). Image quality of coronary CTA was diagnostic in 635 of 638 segments (99.5%). Coronary CTA revealed stenoses greater than 50% in 76 of 141 coronary arteries (53.9%) of 33 of 47 patients (70.2%). Sensitivity, specificity, negative and positive predictive value, and accuracy of coronary CTA and perfusion-cardiac MRI versus CA and perfusion-cardiac MRI for the detection of hemodynamically relevant stenoses were 96.7%, 100%, 94.4%, 100%, and 97.9%, respectively. CONCLUSION. The combination of coronary CTA and perfusion-cardiac MRI shows diagnostic performance comparable to that of CA and perfusion-cardiac MRI. Preliminary data suggest that coronary CTA may replace CA in the diagnosis of hemodynamically relevant CAD. C1 [Donati, Olivio F.; Scheffel, Hans; Stolzmann, Paul; Baumueller, Stephan; Leschka, Sebastian; Alkadhi, Hatem] Univ Zurich Hosp, Inst Diagnost Radiol, CH-8091 Zurich, Switzerland. [Plass, Andre] Univ Zurich Hosp, Cardiovasc Surg Clin, CH-8091 Zurich, Switzerland. RP Alkadhi, H (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, 100 Charles River Plaza, Boston, MA 02114 USA. EM halkadhi@partners.org NR 27 TC 17 Z9 18 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD APR PY 2010 VL 194 IS 4 BP 920 EP 926 DI 10.2214/AJR.09.3225 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 572VX UT WOS:000275863300011 PM 20308492 ER PT J AU Goetti, R Baumuller, S Feuchtner, G Stolzmann, P Karlo, C Alkadhi, H Leschka, S AF Goetti, Robert Baumueller, Stephan Feuchtner, Gudrun Stolzmann, Paul Karlo, Christoph Alkadhi, Hatem Leschka, Sebastian TI High-Pitch Dual-Source CT Angiography of the Thoracic and Abdominal Aorta: Is Simultaneous Coronary Artery Assessment Possible? SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE aorta; coronary arteries; dual-source CT; high pitch; radiation dose ID HEART-RATE-VARIABILITY; IMAGE QUALITY; VENTRICULAR FUNCTION; VALVE AREA; ROW CT; PLANIMETRY; MOTION; RECONSTRUCTION; MDCT AB OBJECTIVE. The purpose of this study was to prospectively evaluate the average heart rate and heart rate variability required for diagnostic imaging of the coronary arteries with high-pitch dual-source CT angiography of the thoracic and thoracoabdominal aorta. SUBJECTS AND METHODS. One hundred consecutively registered patients (82 men, 18 women; mean age, 68 +/- 13 years) underwent clinically indicated CT angiography of the thoracic (n = 33) and thoracoabdominal (n = 67) aorta with a dual-source 128-MDCT scanner in ECG-synchronized high-pitch (pitch, 3.2) data acquisition mode. No beta-blockers were administered. The image quality of the coronary arteries was graded on a 3-point scale by two independent blinded readers. The average heart rate and heart rate variability before data acquisition were noted. Effective radiation doses were calculated. RESULTS. Interobserver agreement on grade of image quality for the 1,414 coronary segments evaluated by both observers was good (kappa = 0.68). Diagnostic image quality was found for 1,375 of the 1,414 segments (97.2%) in 83 of 100 patients (83%). In 17% of the patients, image quality was nondiagnostic for at least one coronary artery segment. Average heart rate and heart rate variability (each p < 0.05) were significantly higher in patients with at least one nondiagnostic coronary segment compared with those without. All patients with an average heart rate less than 63 beats/min and heart rate variability less than 1.2 beats/min had diagnostic image quality in all coronary segments. Effective radiation doses were 2.3 +/- 0.3 mSv for thoracic and 4.4 +/- 0.5 mSv for thoracoabdominal CT angiography. The average scan times were 0.88 +/- 0.06 second for thoracic and 1.67 +/- 0.15 seconds for thoracoabdominal CT angiography. CONCLUSION. For patients with an average heart rate less than 63 beats/min and heart rate variability less than 1.2 beats/min, dual-source CT angiography of the thoracoabdominal aorta at a high pitch of 3.2 delivers diagnostic depiction of the coronary arteries at a low radiation dose. C1 [Goetti, Robert; Baumueller, Stephan; Feuchtner, Gudrun; Stolzmann, Paul; Karlo, Christoph; Alkadhi, Hatem; Leschka, Sebastian] Univ Zurich Hosp, Inst Diagnost Radiol, CH-8091 Zurich, Switzerland. [Alkadhi, Hatem] Massachusetts Gen Hosp, Cardiac MR PET CT Grp, Boston, MA 02114 USA. [Alkadhi, Hatem] Harvard Univ, Sch Med, Boston, MA USA. RP Leschka, S (reprint author), Univ Zurich Hosp, Inst Diagnost Radiol, Raemistr 100, CH-8091 Zurich, Switzerland. EM sebastian.leschka@usz.ch RI Goetti, Robert/I-8961-2012 NR 28 TC 55 Z9 58 U1 0 U2 3 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD APR PY 2010 VL 194 IS 4 BP 938 EP 944 DI 10.2214/AJR.09.3482 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 572VX UT WOS:000275863300014 PM 20308495 ER PT J AU Forman, HP Javitt, MC Monsees, B Crowe, JK Beauchamp, NJ Larson, DB Kaye, A Kazerooni, EA Norbash, A Messinger, N Hricak, H Thrall, JH AF Forman, Howard P. Javitt, Marcia C. Monsees, Barbara Crowe, John K. Beauchamp, Norman J., Jr. Larson, David B. Kaye, Alan Kazerooni, Ella A. Norbash, Alexander Messinger, Neil Hricak, Hedvig Thrall, James H. TI Masters of Radiology Panel Discussion: Role of Communication in Today's Radiologic Practices SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Editorial Material DE communications; critical reports; MQSA; technology C1 [Forman, Howard P.] Yale Univ, MBA Program, New Haven, CT 06520 USA. [Forman, Howard P.] Yale Univ, MBA Execut, New Haven, CT USA. [Javitt, Marcia C.] Walter Reed Army Med Ctr, Dept Radiol, Washington, DC 20307 USA. [Monsees, Barbara] Washington Univ, Med Ctr, Mallinckrodt Inst Radiol, Breast Imaging Sect, St Louis, MO 63110 USA. [Crowe, John K.] Scottsdale Med Imaging, Scottsdale, AZ USA. [Beauchamp, Norman J., Jr.] Univ Washington, Dept Radiol, Seattle, WA 98195 USA. [Larson, David B.] Cincinnati Childrens Hosp, Med Ctr, Dept Radiol, Cincinnati, OH USA. [Kaye, Alan] Bridgeport Hosp, Dept Radiol, Westport, CT USA. [Kazerooni, Ella A.] Univ Michigan Hosp, Dept Radiol, Ann Arbor, MI 48109 USA. [Norbash, Alexander] Boston Univ, Med Ctr, Dept Radiol, Boston, MA 02118 USA. [Messinger, Neil] Baptist Hlth Syst, Dept Radiol, Miami, FL USA. [Hricak, Hedvig] Mem Sloan Kettering Canc Ctr, Dept Radiol, Seattle, WA USA. [Thrall, James H.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Forman, HP (reprint author), Yale Univ, MBA Program, New Haven, CT 06520 USA. EM howard.forman@yale.edu OI Norbash, Alexander/0000-0003-2986-2563; Hricak, Hedvig/0000-0003-2240-9694 NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD APR PY 2010 VL 194 IS 4 BP 1014 EP 1017 DI 10.2214/AJR.09.4060 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 572VX UT WOS:000275863300023 PM 20308504 ER PT J AU Khosa, F Otero, HJ Prevedello, LM Rybicki, FJ Di Salvo, DN AF Khosa, Faisal Otero, Hansel J. Prevedello, Luciano M. Rybicki, Frank J. Di Salvo, Donald N. TI Imaging Presentation of Venous Thrombosis in Patients With Cancer SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE CT; MR; PET; ultrasound; venous thrombosis ID MAGNETIC-RESONANCE ANGIOGRAPHY; RESOLVED MR-ANGIOGRAPHY; PORTAL-VEIN THROMBOSIS; PULMONARY-EMBOLISM; UPPER EXTREMITY; DIAGNOSIS; CT; THROMBOEMBOLISM; TOMOGRAPHY; VENOGRAPHY AB OBJECTIVE. The purpose of this article is to review the imaging of venous thrombosis in patients with cancer. CONCLUSION. Multiple imaging techniques have the capacity to display thrombosis accurately. The optimal choice is dictated by the location and duration of symptoms and by the availability of imaging techniques. Peripheral and superficial thrombi are best managed with ultrasound, whereas central thrombi require CT or MRI. If CT and MRI are contraindicated, flow studies are appropriate. FDG PET/CT appropriately shows venous thrombosis and might play a prominent role in the future. C1 [Otero, Hansel J.] Tufts Med Ctr, Dept Radiol, Boston, MA 02111 USA. [Khosa, Faisal; Di Salvo, Donald N.] Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. [Prevedello, Luciano M.; Rybicki, Frank J.; Di Salvo, Donald N.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Otero, HJ (reprint author), Tufts Med Ctr, Dept Radiol, Washington St, Boston, MA 02111 USA. EM hotero@tuftsmedicalcenter.org RI Prevedello, Luciano/G-8650-2014; OI Prevedello, Luciano/0000-0002-6768-6452; Khosa, Faisal/0000-0001-5681-7683 NR 40 TC 9 Z9 14 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD APR PY 2010 VL 194 IS 4 BP 1099 EP 1108 DI 10.2214/AJR.09.2501 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 572VX UT WOS:000275863300037 PM 20308518 ER PT J AU Gadikota, HR Wu, JL Seon, JK Sutton, K Gill, TJ Li, GA AF Gadikota, Hemanth R. Wu, Jia-Lin Seon, Jong Keun Sutton, Karen Gill, Thomas J. Li, Guoan TI Single-Tunnel Double-Bundle Anterior Cruciate Ligament Reconstruction With Anatomical Placement of Hamstring Tendon Graft Can It Restore Normal Knee Joint Kinematics? SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article DE anterior cruciate ligament (ACL); anatomical single-tunnel double-bundle reconstruction; single-bundle reconstruction; knee kinematics; robotic testing system ID SIMULATED MUSCLE LOADS; PATELLAR TENDON; ACL RECONSTRUCTION; BIOMECHANICAL ANALYSIS; TIBIOFEMORAL JOINT; TIBIAL ROTATION; BONE GRAFT; LONG-TERM; FIXATION; STABILITY AB Background: Anatomical reconstruction techniques that can restore normal joint kinematics without increasing surgical complications could potentially improve clinical outcomes and help manage anterior cruciate ligament injuries more efficiently. Hypothesis: Single-tunnel double-bundle anterior cruciate ligament reconstruction with anatomical placement of hamstring tendon graft can more closely restore normal knee anterior-posterior, medial-lateral, and internal-external kinematics than can conventional single-bundle anterior cruciate ligament reconstruction. Study Design: Controlled laboratory study. Methods: Kinematic responses after single-bundle anterior cruciate ligament reconstruction and single-tunnel double-bundle anterior cruciate ligament reconstruction with anatomical placement of hamstring tendon graft were compared with the intact knee in 9 fresh-frozen human cadaveric knee specimens using a robotic testing system. Kinematics of each knee were determined under an anterior tibial load (134 N), a simulated quadriceps load (400 N), and combined torques (10 N.m valgus and 5 N.m internal tibial torques) at 0 degrees, 15 degrees, 30 degrees, 60 degrees, and 90 degrees of flexion. Results: Anterior tibial translations were more closely restored to the intact knee level after single-tunnel double-bundle reconstruction with anatomical placement of hamstring tendon graft than with a single-bundle reconstruction under the 3 external loading conditions. Under simulated quadriceps load, the mean internal tibial rotations after both reconstructions were lower than that of the anterior cruciate ligament-intact knee with no significant differences between these 3 knee conditions at 0 degrees and 30 degrees of flexion (P > .05). The increased medial tibial shifts of the anterior cruciate ligament-deficient knees were restored to the intact level by both reconstruction techniques under the 3 external loading conditions. Conclusion: Single-tunnel double-bundle anterior cruciate ligament reconstruction with anatomical placement of hamstring tendon graft can better restore the anterior knee stability compared with a conventional single-bundle reconstruction. Both reconstruction techniques are efficient in restoring the normal medial-lateral stability but overcorrect the internal tibial rotations. Clinical Relevance: Single-tunnel double-bundle anterior cruciate ligament reconstruction with anatomical placement of hamstring tendon graft could provide improved clinical outcomes over a conventional single-bundle reconstruction. C1 [Li, Guoan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bioengn Lab,Dept Orthopaed Surg, Boston, MA 02114 USA. [Wu, Jia-Lin] Triserv Gen Hosp, Natl Def Med Ctr, Dept Orthopaed Surg, Taipei, Taiwan. [Seon, Jong Keun] Chonnam Natl Univ, Hwasun Hosp, Dept Orthopaed, Jeonnam, South Korea. RP Li, GA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bioengn Lab,Dept Orthopaed Surg, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@partners.org FU National Institutes of Health [R01AR055612]; DePuy Mitek, Raynham, Massachusetts FX The authors gratefully acknowledge the support of the National Institutes of Health (R01AR055612) and DePuy Mitek, Raynham, Massachusetts. NR 38 TC 13 Z9 18 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0363-5465 J9 AM J SPORT MED JI Am. J. Sports Med. PD APR PY 2010 VL 38 IS 4 BP 713 EP 720 DI 10.1177/0363546509353406 PG 8 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 576RZ UT WOS:000276167200008 PM 20139332 ER PT J AU Mekel, M Stephen, AE Gaz, RD Randolph, GW Richer, S Perry, ZH Lubitz, CC Nehs, MA Parangi, S Hodin, RA AF Mekel, Michal Stephen, Antonia E. Gaz, Randall D. Randolph, Gregory W. Richer, Sara Perry, Zvi H. Lubitz, Carrie C. Nehs, Matthew A. Parangi, Sareh Hodin, Richard A. TI Surgical drains can be safely avoided in lateral neck dissections for papillary thyroid cancer SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Thyroid cancer; Papillary; Neck dissection; Drain ID RANDOMIZED-TRIAL; AXILLARY LYMPHADENECTOMY; BREAST-CANCER; SURGERY; CHOLECYSTECTOMY; COMPLICATIONS; MORBIDITY AB BACKGROUND: Drains are widely used in lateral neck dissections (LNDs). Our objective was to compare outcomes of LNDs for papillary thyroid cancer (PTC) with and without drains. METHODS: One hundred sixty-five LNDs in 129 patients operated on from July 2001 to October 2008 were analyzed retrospectively. LNDs were divided according to the number of excised lymph nodes as follows: group A < median and group B > median. Further categorization was based on the use of a drain. Main outcome measures were wound complications requiring intervention. RESULTS: One hundred two LNDs were performed with a drain and 63 without. The overall rate of wound complications was 3%. There was no significant difference in complication rate between the drain and the non-drain group (group A: 1.8% vs 0; group B: 2.2% vs 7.9%, respectively). CONCLUSIONS: Significant seromas/hematomas are rare complications of LNDs. Patients who undergo LND for PTC without a drain show no significantly increased rate of these complications. (C) 2010 Elsevier Inc. All rights reserved. C1 [Mekel, Michal; Stephen, Antonia E.; Gaz, Randall D.; Randolph, Gregory W.; Lubitz, Carrie C.; Nehs, Matthew A.; Parangi, Sareh; Hodin, Richard A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Surg Unit, Boston, MA 02114 USA. [Randolph, Gregory W.; Richer, Sara] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. [Perry, Zvi H.] Tufts Med Ctr, Boston, MA USA. RP Hodin, RA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Surg Unit, Boston, MA 02114 USA. EM rhodin@partners.org OI Perry, Zvi/0000-0002-1131-5230 FU American Physicians Fellowship for Medicine in Israel; Rambam-Health Care Campus, Israel; American Friends of Rambam, Israel Medical Association; Israel Cancer Association FX Dr. Mekel is a recipient of fellowship grant from the American Physicians Fellowship for Medicine in Israel. Dr. Mekel is also supported in part by Rambam-Health Care Campus, Israel, the American Friends of Rambam, Israel Medical Association and the Israel Cancer Association. NR 28 TC 6 Z9 7 U1 0 U2 2 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD APR PY 2010 VL 199 IS 4 BP 485 EP 490 DI 10.1016/j.amjsurg.2009.04.006 PG 6 WC Surgery SC Surgery GA 587GC UT WOS:000276977000008 PM 20359568 ER PT J AU Deshpande, V Hsu, M Kumarasinghe, MP Lauwers, GY AF Deshpande, Vikram Hsu, MayLee Kumarasinghe, M. Priyanthi Lauwers, Gregory Y. TI The Clinical Significance of Incidental Chronic Colitis: A Study of 17 Cases SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE chronic colitis; NSAIDs; asymptomatic; ulcerative colitis; crohn's disease ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; INFLAMMATORY-BOWEL-DISEASE; ULCERATIVE-COLITIS; YERSINIA-ENTEROCOLITICA; BIOPSIES; INTESTINE; PATHOLOGY; SPECTRUM; DIARRHEA; FEATURES AB Introduction: A histologic diagnosis of chronic colitis raises a relatively limited differential diagnosis that includes inflammatory bowel disease, long-standing infections, and chronic ischemia. In routine clinical practice, inflammatory bowel disease accounts for the majority of cases of chronic colitis. Although a variety of drug-induced injury patterns in the colon have been recognized, there are few well-documented examples of drug-induced chronic colitis. In this study, we report the clinical, histologic, and follow-up data on 17 cases of histologically documented cases of chronic colitis in which a definitive etiologic factor could not be identified. Methods: Using our electronic databases we recorded all cases of chronic colitis in adults over an 8-year period. Patients with a history (prior or subsequent) of inflammatory bowel disease were excluded. Cases showing histologic features of ischemic, pseudomembranous, or granulomatous colitis were excluded. The biopsies were evaluated and semiquantitatively scored for established histologic features of activity and chronicity. The clinical, endoscopic, and follow-up data, including drug usage, was recorded. Results: There were 10 males and 7 females and the mean age was 59 years. The majority of cases involved the cecum or ascending colon (16 of 17 cases). A majority of patients were asymptomatic (n = 11), and in others, indications for colonoscopy were occult blood (n = 3), hematochezia (n = 2), and melena (n = 1). The most common mucosal abnormality was erythema (n = 10), ulcers (n = 3), congestion (n = 3), and edematous mucosa (n = 1). All cases showed histologic features of chronicity and showed either basal plasmacytosis (94%) or crypt architectural distortion (94%). Eight (47%) patients reported nonsteroidal anti-inflammatory drugs (NSAID) use. Withdrawal of NSAIDs in 2 cases resulted in normalization of the colonic mucosa. On follow-up, all 17 patients were asymptomatic (median follow-up 42.8 mo) and did not progress to in. ammatory bowel disease. Conclusions: We report a series of 17 histologically documented cases of incidental chronic colitis without a conventional etiology. However, both the frequent usage of NSAIDs, and normalization of mucosal changes after withdrawal of this drug suggest that NSAIDs may account for this cecal-based chronic colitis. The awareness of this histologically dramatic but clinically innocuous form of chronic colitis may avoid errors in mucosal biopsy diagnosis. C1 [Deshpande, Vikram; Hsu, MayLee; Lauwers, Gregory Y.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Deshpande, Vikram; Hsu, MayLee; Lauwers, Gregory Y.] Harvard Univ, Sch Med, Boston, MA USA. [Kumarasinghe, M. Priyanthi] Univ Western Australia, Dept Anat Pathol, QE Med Ctr 2, Sch Pathol & Lab Med, Nedlands Perth, WA, Australia. RP Deshpande, V (reprint author), Massachusetts Gen Hosp, Pathol Dept Warren 2, 55 Fruit St, Boston, MA 02114 USA. EM vdeshpande@partners.org NR 30 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 APR PY 2010 VL 34 IS 4 BP 463 EP 469 DI 10.1097/PAS.0b013e3181d0fd76 PG 7 WC Pathology; Surgery SC Pathology; Surgery GA 584CC UT WOS:000276726600003 PM 20154590 ER PT J AU Hsu, DJ Stone, RA Obrosky, DS Yealy, DM Meehan, TP Fine, JM Graff, LG Fine, MJ AF Hsu, Douglas J. Stone, Roslyn A. Obrosky, D. Scott Yealy, Donald M. Meehan, Thomas P. Fine, Jonathan M. Graff, Louis G. Fine, Michael J. TI Predictors of Timely Antibiotic Administration for Patients Hospitalized With Community-Acquired Pneumonia From the Cluster-Randomized EDCAP Trial SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE Pneumonia; Quality of care; Process of care ID RESPIRATORY-TRACT INFECTIONS; ELDERLY PATIENTS; OF-CARE; QUALITY; OUTCOMES; IMPROVE; INTERVENTION; GUIDELINES; MANAGEMENT; DELIVERY AB Introduction: To identify factors associated with timely initiation of antibiotic therapy for patients hospitalized with pneumonia. Design: Secondary analysis of a cluster-randomized, controlled trial. Setting: Thirty-two emergency departments (EDs) in Pennsylvania and Connecticut. Subjects: Patients with a clinical and radiographic diagnosis of community-acquired pneumonia. Interventions: From January to December 2001, EDs were randomly allocated to guideline implementation strategies of low (n = 8), moderate (n = 12), and high intensity (n = 12) to improve the initial site of treatment and the performance of evidence-based processes of care. Our primary outcome was antibiotic initiation within 4 hours of presentation, which at that time was the recommended process of care for inpatients. Results: Of the 2076 inpatients enrolled, 1632 (78.6%) received antibiotic therapy within 4 hours of presentation. Antibiotic timeliness ranged from 55.6% to 100% (P < 0.001) by ED and from 77.0% to 79.7% (P = 0.2) across the 3 guideline implementation arms. In multivariable analysis, heart rate >= 125 per minute (OR = 1.6, 95% CI 1.1-2.3), respiratory rate >= 30 per minute (OR = 2.3, 95% CI 1.6-3.4), and aspiration pneumonia (OR = 3.7, 95% CI 1.1-12.7) were positively associated with timely initiation of antibiotic therapy, whereas a hematocrit <30% (OR = 0.6, 95% CI 0.4-1.0) was negatively associated with this outcome. Conclusions: Timely initiation of antibiotic therapy is associated primarily with patient-related factors that reflect severity of illness at presentation. Although this study demonstrates an opportunity to improve performance on this quality measure in nearly one quarter of inpatients with pneumonia, we failed to identify any modifiable patient, provider, or hospital level factors to target in such quality improvement efforts. C1 [Hsu, Douglas J.; Stone, Roslyn A.; Obrosky, D. Scott; Fine, Michael J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15206 USA. [Hsu, Douglas J.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Hsu, Douglas J.] Harvard Univ, Sch Med, Boston, MA USA. [Meehan, Thomas P.] Qualidigm, Middletown, CT USA. [Fine, Jonathan M.] Norwalk Hosp, Norwalk, CT 06856 USA. [Graff, Louis G.] New Britain Gen Hosp, Dept Emergency Med, New Britain, CT USA. [Stone, Roslyn A.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Yealy, Donald M.] Univ Pittsburgh, Dept Emergency Med, Pittsburgh, PA 15261 USA. [Obrosky, D. Scott; Fine, Michael J.] Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA 15261 USA. [Stone, Roslyn A.] Univ Pittsburgh, Ctr Res Hlth Care, Dept Med, Pittsburgh, PA 15261 USA. RP Fine, MJ (reprint author), Vet Adm Pittsburgh Healthcare Syst 151 CH, Ctr Hlth Equ Res & Promot, 7180 Highland Dr,Room 4059E, Pittsburgh, PA 15206 USA. EM Michael.Fine@va.gov FU Agency for Healthcare Research and Quality [RO1 HS10049]; National Institute for Allergy and Infectious Diseases [K24 AI001769] FX This study was supported by the Agency for Healthcare Research and Quality grant RO1 HS10049 and in part by a career developmental award from the National Institute for Allergy and Infectious Diseases grant K24 AI001769 (to MJF). NR 28 TC 2 Z9 2 U1 0 U2 1 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 APR PY 2010 VL 339 IS 4 BP 307 EP 313 DI 10.1097/MAJ.0b013e3181d3cd63 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 582WA UT WOS:000276629600002 PM 20224313 ER PT J AU Cadena, J Thompson, GR Patterson, JE Nakashima, B Owens, A Echevarria, K Mortensen, EM AF Cadena, Jose Thompson, George R., III Patterson, Jan E. Nakashima, Brandy Owens, Aaron Echevarria, Kelly Mortensen, Eric M. TI Clinical Predictors and Risk Factors for Relapsing Clostridium difficile Infection SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE Relapse; Clostridium difficile; Antibiotic-associated diarrhea; CDI; Mortality ID PROTON-PUMP INHIBITORS; FLUOROQUINOLONE USE; DIARRHEA; DISEASE; EPIDEMIC; COLITIS; QUEBEC; ASSOCIATION; STRAIN; VALIDATION AB Background: Clostridium difficile infection (CDI) is a common cause of morbidity among hospitalized patients. Multiple factors have been associated with primary CDI, but risk factors for CDI relapses are less well described. Methods: This was a retrospective cohort study of patients with CDI over a 15-month period. We compared patients with relapsing and nonrelapsing CDI, including risk factors associated with primary CDI and other variables hypothesized to be associated with relapsing CDI and 90-day mortality. Multivariable logistic regression models were created to examine risk factors for relapse and 90-day mortality. Results: One hundred twenty-nine consecutive patients with CDI were included; 38 (29%) had relapsing CDI. Factors associated with relapsing CDI included fluoroquinolone use (71% versus 49%, P = 0.04) and incidence of stroke (29% versus 12%, P = 0.02). In a regression model, use of a fluoroquinolone was associated with relapsing CDI (OR = 2.52, 95% CI = 1.11-5.72). Factors associated with 90-day mortality included higher Charlson comorbidity index score (4.34 +/- 1.71 versus 3.42 +/- 2.08, P = 0.02), severe CDI (58% versus 32%, P = 0.01), and the use of piperacillin/tazobactam (45% versus 23%, P = 0.03) or meropenem (10% versus 1%, P = 0.04). In the regression analysis, 90-day mortality was associated with severe CDI (OR = 1.76; 95% CI = 1.19-2.59). Conclusion: Fluoroquinolone use and prior stroke are associated with an increased risk of relapsing CDI. Relapsing CDI and severe CDI are both associated with increased 90-day mortality. C1 [Cadena, Jose; Thompson, George R., III; Patterson, Jan E.; Nakashima, Brandy; Echevarria, Kelly; Mortensen, Eric M.] S Texas Vet Hlth Care Syst, Dept Med, San Antonio, TX 78229 USA. [Echevarria, Kelly] S Texas Vet Hlth Care Syst, Dept Pharm, San Antonio, TX 78229 USA. [Nakashima, Brandy; Mortensen, Eric M.] S Texas Vet Hlth Care Syst, VERDICT Res Unit, San Antonio, TX 78229 USA. [Cadena, Jose; Thompson, George R., III; Patterson, Jan E.; Owens, Aaron] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Infect Dis, San Antonio, TX 78229 USA. [Mortensen, Eric M.] Univ Texas Hlth Sci Ctr San Antonio, Div Gen Internal Med, San Antonio, TX 78229 USA. [Owens, Aaron] Univ Texas Hlth Sci Ctr San Antonio, Hosp Med, San Antonio, TX 78229 USA. [Echevarria, Kelly] Univ Texas Hlth Sci Ctr San Antonio, Pharmacotherapy Educ & Resource Ctr, San Antonio, TX 78229 USA. RP Cadena, J (reprint author), S Texas Vet Hlth Care Syst, Dept Med, MC 7881,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM josecadenaz@yahoo.com OI Mortensen, Eric/0000-0002-3880-5563 NR 34 TC 24 Z9 26 U1 0 U2 1 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 APR PY 2010 VL 339 IS 4 BP 350 EP 355 DI 10.1097/MAJ.0b013e3181d3cdaa PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 582WA UT WOS:000276629600009 PM 20224312 ER PT J AU Koulmanda, M Qipo, A Fan, ZG Bhasin, M Singh, G Movahedi, B Duggan, M Kawai, T Libermann, TA Strom, TB AF Koulmanda, Maria Qipo, Andi Fan, Zhigang Bhasin, Manoj Singh, Gurbakhshish Movahedi, Babak Duggan, Michael Kawai, Tatsuo Libermann, Towia A. Strom, Terry B. TI The Cytoprotective Effect of Alpha-1-Antitrypsin upon Murine and Non-Human Primate Islet Transplants. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 10th American Transplant Congress CY MAY 01-05, 2010 CL San Diego, CA SP Amer Soc Transplantat C1 [Koulmanda, Maria; Qipo, Andi; Fan, Zhigang; Bhasin, Manoj; Singh, Gurbakhshish; Movahedi, Babak; Libermann, Towia A.; Strom, Terry B.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Transplant Inst, Boston, MA 02215 USA. [Duggan, Michael; Kawai, Tatsuo] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2010 VL 10 SU 4 SI SI BP 48 EP 48 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 573NX UT WOS:000275921701034 ER PT J AU Woodle, ES Light, J Rubin, M Thielke, J Morrow, WR Mahle, W Franklin, C Gabardi, S Gill, J Roberti, I Shapiro, R Wall, GE Walsh, RC Zand, M Alloway, RR AF Woodle, E. S. Light, J. Rubin, M. Thielke, J. Morrow, W. R. Mahle, W. Franklin, C. Gabardi, S. Gill, J. Roberti, I. Shapiro, R. Wall, G. E. Walsh, R. C. Zand, M. Alloway, R. R. TI Proteasome Inhibitor Therapy for Antibody Mediated Rejection: Initial Report from a Multicenter Collaborative SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 10th American Transplant Congress CY MAY 01-05, 2010 CL San Diego, CA SP Amer Soc Transplantat C1 [Woodle, E. S.; Wall, G. E.; Walsh, R. C.; Alloway, R. R.] Univ Cincinnati, Cincinnati, OH 45221 USA. [Light, J.] Washington Hosp Ctr, Washington, DC USA. [Rubin, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Thielke, J.] Univ Illinois, Chicago, IL 60680 USA. [Morrow, W. R.] Univ Arkansas, Fayetteville, AR 72701 USA. [Mahle, W.] Emory Univ, Atlanta, GA 30322 USA. [Franklin, C.] Iowa Methodist, Iowa City, IA USA. [Shapiro, R.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Zand, M.] Univ Rochester, Rochester, NY 14627 USA. RI Zand, Martin/A-8612-2015 NR 0 TC 11 Z9 11 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2010 VL 10 SU 4 SI SI BP 83 EP 84 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 573NX UT WOS:000275921701146 ER PT J AU Tocco, G Kim, PH Kant, CD Lin, C Yun, SH Benichou, G AF Tocco, Georges Kim, Pilhan Kant, Cavit D. Lin, Charles Yun, Seok-Hyun Benichou, Gilles TI Allorecognition after Skin Transplantation: Potential for Semi-Direct Pathway? SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 10th American Transplant Congress CY MAY 01-05, 2010 CL San Diego, CA SP Amer Soc Transplantat C1 [Tocco, Georges; Kant, Cavit D.; Benichou, Gilles] Massachusetts Gen Hosp, Surg Transplant Unit, Boston, MA 02114 USA. [Kim, Pilhan; Lin, Charles; Yun, Seok-Hyun] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2010 VL 10 SU 4 SI SI BP 94 EP 94 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 573NX UT WOS:000275921701180 ER PT J AU Restrepo, A Fishman, JA Kotton, C AF Restrepo, Alejandro Fishman, Jay A. Kotton, Camille TI Nocardia Infections in Solid Organ Transplant Recipients: A Review of 307 Cases. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 10th American Transplant Congress CY MAY 01-05, 2010 CL San Diego, CA SP Amer Soc Transplantat C1 [Restrepo, Alejandro; Fishman, Jay A.; Kotton, Camille] Massachusetts Gen Hosp, Transplant Infect Dis & Compromised Host Program, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2010 VL 10 SU 4 SI SI BP 96 EP 96 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 573NX UT WOS:000275921701188 ER PT J AU Bagley, J Godwin, J Madsen, J Iacomini, J AF Bagley, Jessamyn Godwin, Jonathan Madsen, Joren Iacomini, John TI NK Cells Prevent the Development and Function of Regulatory T Cells SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 10th American Transplant Congress CY MAY 01-05, 2010 CL San Diego, CA SP Amer Soc Transplantat C1 [Bagley, Jessamyn; Godwin, Jonathan; Iacomini, John] Brigham & Womens Hosp, Div Renal, Transplantat Res Ctr, Boston, MA 02115 USA. [Bagley, Jessamyn; Godwin, Jonathan; Iacomini, John] Childrens Hosp, Boston, MA 02115 USA. [Bagley, Jessamyn; Godwin, Jonathan; Iacomini, John] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Madsen, Joren] Massachusetts Gen Hosp, MGH Transplantat Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2010 VL 10 SU 4 SI SI BP 161 EP 161 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 573NX UT WOS:000275921701411 ER PT J AU Hirohashi, T Chase, CM Alessandrini, A Colvin, RB Russell, PS Madsen, JC AF Hirohashi, Tsutomu Chase, Catharine M. Alessandrini, Alessandro Colvin, Robert B. Russell, Paul S. Madsen, Joren C. TI Relationship between NK Cells and Regulatory T Cells in the Development of Coronary Allograft Vasculopathy SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 10th American Transplant Congress CY MAY 01-05, 2010 CL San Diego, CA SP Amer Soc Transplantat C1 [Hirohashi, Tsutomu; Chase, Catharine M.; Alessandrini, Alessandro; Russell, Paul S.; Madsen, Joren C.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Colvin, Robert B.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Russell, Paul S.; Madsen, Joren C.] Massachusetts Gen Hosp, Transplant Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2010 VL 10 SU 4 SI SI BP 161 EP 161 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 573NX UT WOS:000275921701410 ER PT J AU Myaskovsky, L McNulty, M Dew, MA Kormos, RL AF Myaskovsky, Larissa McNulty, Mary Dew, Mary Amanda Kormos, Robert L. TI Predictors of Quality of Life in Caregivers to Cardiothoracic Transplant Recipients. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 10th American Transplant Congress CY MAY 01-05, 2010 CL San Diego, CA SP Amer Soc Transplantat C1 [Myaskovsky, Larissa; McNulty, Mary; Dew, Mary Amanda; Kormos, Robert L.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Myaskovsky, Larissa] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2010 VL 10 SU 4 SI SI BP 204 EP 204 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 573NX UT WOS:000275921701564 ER PT J AU Fan, ZG Spencer, JA Lin, CP Strom, TB Koulmanda, M AF Fan, Zhigang Spencer, Joel A. Lin, Charles P. Strom, Terry B. Koulmanda, Maria TI IL-6 Promotes Accelerated Allograft Rejection by Disarming Natural- and Preventing Conversion of Induced- Regulatory T Cells. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 10th American Transplant Congress CY MAY 01-05, 2010 CL San Diego, CA SP Amer Soc Transplantat C1 [Fan, Zhigang; Strom, Terry B.; Koulmanda, Maria] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Transplant Inst, Boston, MA 02115 USA. [Spencer, Joel A.; Lin, Charles P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Adv Microscopy Program,Ctr Syst Biol,Wellman Ctr, Boston, MA 02115 USA. RI Spencer, Joel/A-4590-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2010 VL 10 SU 4 SI SI BP 205 EP 205 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 573NX UT WOS:000275921701566 ER PT J AU Miyajima, M Chase, CM Graham, JA Farkash, EA Alessandrini, A Madsen, JC Russell, PS Colvin, RB AF Miyajima, Masahiro Chase, Catharine M. Graham, Jay A. Farkash, Evan A. Alessandrini, Alessandro Madsen, Joren C. Russell, Paul S. Colvin, Robert B. TI Spontaneous Renal Allograft Acceptance in Mice Requires Foxp3 Cells. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 10th American Transplant Congress CY MAY 01-05, 2010 CL San Diego, CA SP Amer Soc Transplantat C1 [Miyajima, Masahiro; Chase, Catharine M.; Graham, Jay A.; Alessandrini, Alessandro; Madsen, Joren C.; Russell, Paul S.] Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. [Farkash, Evan A.; Colvin, Robert B.] Massachusetts Gen Hosp, Pathol Serv, Boston, MA 02114 USA. RI Graham, Jay/A-4896-2014 OI Graham, Jay/0000-0003-2054-1253 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2010 VL 10 SU 4 SI SI BP 205 EP 206 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 573NX UT WOS:000275921701570 ER PT J AU Kim, JI Lee, KM O'Connor, MR Duff, PE Yeh, HD Deng, SP Caton, AJ Markmann, JF AF Kim, James I. Lee, Kang Mi O'Connor, Matthew R. Duff, Patrick E. Yeh, Heidi Deng, Shaoping Caton, Andrew J. Markmann, James F. TI Antigen-Specific T-Regs Promote Long-Term Islet Allograft Survival by Linked Suppression SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 10th American Transplant Congress CY MAY 01-05, 2010 CL San Diego, CA SP Amer Soc Transplantat C1 [Kim, James I.; Lee, Kang Mi; O'Connor, Matthew R.; Duff, Patrick E.; Yeh, Heidi; Deng, Shaoping; Markmann, James F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Caton, Andrew J.] Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2010 VL 10 SU 4 SI SI BP 209 EP 209 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 573NX UT WOS:000275921701583 ER PT J AU Alessandrini, A Miyayama, M De Haseth, S Fray, M Chase, CM Benichou, G Colvin, RB Cosimi, AB AF Alessandrini, Alessandro Miyayama, Masahiro De Haseth, Stephanie Fray, Michael Chase, Catharine M. Benichou, Gilles Colvin, Robert B. Cosimi, A. Benedict TI Identification of a Population of FoxP3loCD25+Bone Marrow Cells That Exhibit Suppressive Activity SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 10th American Transplant Congress CY MAY 01-05, 2010 CL San Diego, CA SP Amer Soc Transplantat C1 [Alessandrini, Alessandro; Miyayama, Masahiro; Chase, Catharine M.; Benichou, Gilles; Colvin, Robert B.; Cosimi, A. Benedict] Massachusetts Gen Hosp, Boston, MA 02114 USA. [De Haseth, Stephanie] Leiden Univ, Med Ctr, Leiden, Netherlands. [Fray, Michael] Tufts Univ, Sch Med, Sackler Sch Grad Biomed Sci, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2010 VL 10 SU 4 SI SI BP 218 EP 218 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 573NX UT WOS:000275921702021 ER PT J AU Graham, JA Fray, MA de Haseth, S Lee, KM Lian, MM Chase, CM Madsen, JC Markmann, JF Benichou, G Colvin, RB Cosimi, AB Deng, SP Kim, J Alessandrini, AA AF Graham, Jay A. Fray, Michael A. de Haseth, Stephanie Lee, Kang Mi Lian, Moh-Moh Chase, Catharine M. Madsen, Joren C. Markmann, James F. Benichou, Gilles Colvin, Robert B. Cosimi, A. B. Deng, Shaoping Kim, James Alessandrini, Alessandro A. TI Regulatory T Cells Showed Enhanced Activity through Inhibition of the Kinase, GSK-3beta, Which Leads to Prolongation of Islet Allograft Survival. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 10th American Transplant Congress CY MAY 01-05, 2010 CL San Diego, CA SP Amer Soc Transplantat C1 [Graham, Jay A.; Fray, Michael A.; de Haseth, Stephanie; Lee, Kang Mi; Lian, Moh-Moh; Chase, Catharine M.; Madsen, Joren C.; Markmann, James F.; Benichou, Gilles; Cosimi, A. B.; Deng, Shaoping; Kim, James; Alessandrini, Alessandro A.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Colvin, Robert B.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RI Graham, Jay/A-4896-2014 OI Graham, Jay/0000-0003-2054-1253 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2010 VL 10 SU 4 SI SI BP 228 EP 228 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 573NX UT WOS:000275921702054 ER PT J AU Myaskovsky, L Almario, D Dew, MA Switzer, GE Unruh, M Ramkumar, M Shapiro, R AF Myaskovsky, Larissa Almario, Donna Dew, Mary Amanda Switzer, Galen E. Unruh, Mark Ramkumar, Mohan Shapiro, Ron TI Racial Disparities in Kidney Transplant: Beyond Medical Factors. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 10th American Transplant Congress CY MAY 01-05, 2010 CL San Diego, CA SP Amer Soc Transplantat C1 [Myaskovsky, Larissa; Almario, Donna; Switzer, Galen E.; Ramkumar, Mohan] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Myaskovsky, Larissa; Dew, Mary Amanda; Switzer, Galen E.; Unruh, Mark; Shapiro, Ron] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Almario, Donna] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2010 VL 10 SU 4 SI SI BP 282 EP 282 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 573NX UT WOS:000275921702253 ER PT J AU Yang, J Riella, LV Robles, S Zhao, XZ Yuan, XL Vanguri, V Paterson, AM Sharpe, AH Freeman, GJ Sayegh, MH Chandraker, A AF Yang, Jun Riella, Leonardo V. Robles, Susanne Zhao, Xiaozhi Yuan, Xueli Vanguri, Vijay Paterson, Alison M. Sharpe, Arlene H. Freeman, Gordon J. Sayegh, Mohamed H. Chandraker, Anil TI Blockade of the PDL1:B7.1 Pathway Enhances the Alloimmune Response In Vivo SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 10th American Transplant Congress CY MAY 01-05, 2010 CL San Diego, CA SP Amer Soc Transplantat C1 [Yang, Jun; Riella, Leonardo V.; Robles, Susanne; Zhao, Xiaozhi; Yuan, Xueli; Sayegh, Mohamed H.; Chandraker, Anil] Harvard Univ, Brigham & Womens Hosp, Childrens Hosp Boston, Transplantat Res Ctr,Sch Med, Boston, MA 02115 USA. [Paterson, Alison M.; Sharpe, Arlene H.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Freeman, Gordon J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Vanguri, Vijay] Univ Massachusetts, Sch Med, Dept Pathol, Worcester, MA 01605 USA. NR 0 TC 1 Z9 1 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2010 VL 10 SU 4 SI SI BP 361 EP 361 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 573NX UT WOS:000275921702534 ER PT J AU Kim, JI Duff, PE O'Connor, MR Zhao, GP Lee, KM Deng, SP Yeh, HD Caton, AJ Markmann, JF AF Kim, James I. Duff, Patrick E. O'Connor, Matthew R. Zhao, Gaoping Lee, Kang Mi Deng, Shaoping Yeh, Heidi Caton, Andrew J. Markmann, James F. TI Generation of Adaptive T-regs by Alloantigen Is a Necessary Step for Transplant Tolerance SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 10th American Transplant Congress CY MAY 01-05, 2010 CL San Diego, CA SP Amer Soc Transplantat C1 [Kim, James I.; Duff, Patrick E.; O'Connor, Matthew R.; Zhao, Gaoping; Lee, Kang Mi; Deng, Shaoping; Yeh, Heidi; Markmann, James F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Caton, Andrew J.] Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2010 VL 10 SU 4 SI SI BP 362 EP 362 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 573NX UT WOS:000275921702538 ER PT J AU Delmonico, FL Ghimire, V Danovitch, G AF Delmonico, Francis L. Ghimire, Vipra Danovitch, Gabriel TI Nonresident Alien Transplantation in the United States SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 10th American Transplant Congress CY MAY 01-05, 2010 CL San Diego, CA SP Amer Soc Transplantat C1 [Delmonico, Francis L.] Massachusetts Gen Hosp, Transplantat Ctr, Boston, MA 02114 USA. [Ghimire, Vipra] United Network Organ Sharing, Richmond, VA USA. [Danovitch, Gabriel] Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2010 VL 10 SU 4 SI SI BP 369 EP 369 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 573NX UT WOS:000275921702566 ER PT J AU Rogal, SS Surman, O Chung, RT Rutherford, A AF Rogal, Shari S. Surman, Owen Chung, Raymond T. Rutherford, Anna TI The Impact of Depression and Antidepressant Use on Outcomes of Orthotopic Liver Transplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 10th American Transplant Congress CY MAY 01-05, 2010 CL San Diego, CA SP Amer Soc Transplantat C1 [Rogal, Shari S.; Rutherford, Anna] Brigham & Womens Hosp, Boston, MA 02115 USA. [Surman, Owen; Chung, Raymond T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2010 VL 10 SU 4 SI SI BP 378 EP 378 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 573NX UT WOS:000275921702597 ER PT J AU Aoyama, A Millington, TM Boskovic, S Wain, JC Madsen, JC Kawai, T Benichou, G Allan, JS AF Aoyama, Akihiro Millington, Timothy M. Boskovic, Svjetlan Wain, John C. Madsen, Joren C. Kawai, Tatsuo Benichou, Gilles Allan, James S. TI Memory T Cells Appear To Drive Acute Rejection and Alloantibody Formation in Non-Human Primate Lung Transplantation Using Conventional Triple-Drug Immunosuppression SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 10th American Transplant Congress CY MAY 01-05, 2010 CL San Diego, CA SP Amer Soc Transplantat C1 [Aoyama, Akihiro; Millington, Timothy M.; Boskovic, Svjetlan; Wain, John C.; Madsen, Joren C.; Kawai, Tatsuo; Benichou, Gilles; Allan, James S.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Aoyama, Akihiro; Millington, Timothy M.; Boskovic, Svjetlan; Wain, John C.; Madsen, Joren C.; Kawai, Tatsuo; Benichou, Gilles; Allan, James S.] Massachusetts Gen Hosp, Div Thorac Surg & Transplant Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2010 VL 10 SU 4 SI SI BP 389 EP 389 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 573NX UT WOS:000275921702638 ER PT J AU Zhao, GP Moore, DJ Lee, KM Kim, JI Duff, PE O'Connor, MR Hirohashi, T Markmann, J Deng, SP AF Zhao, Gaoping Moore, Daniel J. Lee, Kang Mi Kim, James I. Duff, Patrick Edward O'Connor, Matthew Ryan Hirohashi, Tsutomu Markmann, James Deng, Shaoping TI An Unexpected Counter-Regulatory Role of IL-10 in B Lymphocyte-Mediated Transplantation Tolerance. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 10th American Transplant Congress CY MAY 01-05, 2010 CL San Diego, CA SP Amer Soc Transplantat C1 [Zhao, Gaoping; Lee, Kang Mi; Kim, James I.; Duff, Patrick Edward; O'Connor, Matthew Ryan; Markmann, James; Deng, Shaoping] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02115 USA. [Zhao, Gaoping; Deng, Shaoping] Sichuan Acad Med Sci, Chengdu, Sichuan, Peoples R China. [Zhao, Gaoping; Deng, Shaoping] Sichuan Prov Peoples Hosp, Dept Surg, Chengdu, Sichuan, Peoples R China. [Moore, Daniel J.] Vanderbilt Childrens Hosp, Ian Burr Div Endocrinol & Diabet, Dept Pediat, Nashville, TN USA. [Hirohashi, Tsutomu] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. RI Moore, Daniel/A-4924-2008 OI Moore, Daniel/0000-0002-6889-9345 NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2010 VL 10 SU 4 SI SI BP 400 EP 401 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 573NX UT WOS:000275921702681 ER PT J AU Carvello, MM Vergani, A Petrelli, A Jurewicz, M D'addio, F Rodig, S Watanabe, T Dunussi, K Sayegh, M Fiorina, P AF Carvello, Michele M. Vergani, Andrea Petrelli, Alessandra Jurewicz, Mollie D'addio, Francesca Rodig, Scott Watanabe, Toshihiko Dunussi, Kyri Sayegh, Mohamed Fiorina, Paolo TI Anti-CD22/Calicheamycin Immunotoxin-Mediated B-Cell Depletion Prolongs Islet Allograft Survival in NOD Mice by Regulating Autoimmune Response. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 10th American Transplant Congress CY MAY 01-05, 2010 CL San Diego, CA SP Amer Soc Transplantat C1 [Vergani, Andrea; Petrelli, Alessandra; Jurewicz, Mollie; D'addio, Francesca; Watanabe, Toshihiko; Sayegh, Mohamed; Fiorina, Paolo] Harvard Univ, Sch Med, Transplant Res Ctr, Boston, MA 02115 USA. [Carvello, Michele M.; Vergani, Andrea; Petrelli, Alessandra; Fiorina, Paolo] Ist Sci San Raffaele, I-20132 Milan, Italy. [Carvello, Michele M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rodig, Scott] Brigham & Womens Hosp, Dept Pathol, Div Hematopathol, Boston, MA 02115 USA. [Dunussi, Kyri] Wyeth Ayerst Res, Cambridge, MA USA. RI Petrelli, Alessandra/B-7972-2011; Petrelli, Alessandra/M-7004-2015; D'Addio, Francesca/F-3417-2017 OI Petrelli, Alessandra/0000-0002-5639-9415; D'Addio, Francesca/0000-0002-0345-0694 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2010 VL 10 SU 4 SI SI BP 403 EP 403 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 573NX UT WOS:000275921702689 ER PT J AU Cacciarelli, TV Sun, HY Singh, N AF Cacciarelli, Thomas V. Sun, H. Y. Singh, Nina TI Human Aging and Its Impact on Infections and Infectious Outcomes after Orthotopic Liver Transplantation (OLTx). SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 10th American Transplant Congress CY MAY 01-05, 2010 CL San Diego, CA SP Amer Soc Transplantat C1 [Cacciarelli, Thomas V.; Sun, H. Y.; Singh, Nina] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Cacciarelli, Thomas V.; Singh, Nina] Univ Pittsburgh, Pittsburgh, PA USA. [Sun, H. Y.] NTUH, Taipei, Taiwan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2010 VL 10 SU 4 SI SI BP 426 EP 426 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 573NX UT WOS:000275921703045 ER PT J AU Kaneku, H Wong, WC Everly, M DeVito, J Porcheray, F Zorn, E Terasaki, PI AF Kaneku, Hugo Wong, Waichi Everly, Matthew DeVito, Julie Porcheray, Fabrice Zorn, Emmanuel Terasaki, Paul I. TI Elution of Anti-HLA Antibodies from Nephrectomies after Allograft Failure and Characterization of Eluted Antibodies. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 10th American Transplant Congress CY MAY 01-05, 2010 CL San Diego, CA SP Amer Soc Transplantat C1 [Kaneku, Hugo; Terasaki, Paul I.] Terasaki Fdn Lab, Los Angeles, CA USA. [Wong, Waichi; DeVito, Julie; Porcheray, Fabrice; Zorn, Emmanuel] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Everly, Matthew] One Lambda Inc, Canoga Pk, CA USA. RI Everly, Matthew/E-6583-2011; porcheray, fabrice/B-9505-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2010 VL 10 SU 4 SI SI BP 475 EP 476 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 573NX UT WOS:000275921703229 ER PT J AU Tsai, EW Ettenger, RB Reed, EF Juppner, H Salusky, IB Wesseling-Perry, K AF Tsai, Eileen W. Ettenger, Robert B. Reed, Elaine F. Juppner, Harald Salusky, Isidro B. Wesseling-Perry, Katherine TI FGF-23 Predicts Acute Rejection in Pediatric Renal Allograft Recipients. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 10th American Transplant Congress CY MAY 01-05, 2010 CL San Diego, CA SP Amer Soc Transplantat C1 [Tsai, Eileen W.; Ettenger, Robert B.; Reed, Elaine F.; Salusky, Isidro B.; Wesseling-Perry, Katherine] Univ Calif Los Angeles, Mattel Childrens Hosp, Los Angeles, CA USA. [Juppner, Harald] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2010 VL 10 SU 4 SI SI BP 484 EP 484 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 573NX UT WOS:000275921703260 ER PT J AU Smith, RN Frazier, E Howard, E Collins, AB Weynand, B AF Smith, Rex N. Frazier, Elizabeth Howard, Emily Collins, Alfred B. Weynand, Birgit TI C4d and C3d Immunofluorescence in Human Heart Transplants and the Diagnosis of Alloantibody Mediated Rejection. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 10th American Transplant Congress CY MAY 01-05, 2010 CL San Diego, CA SP Amer Soc Transplantat C1 [Weynand, Birgit] Clin Univ St Luc, B-1200 Brussels, Belgium. [Frazier, Elizabeth; Howard, Emily] Arkansas Childrens Hosp, Little Rock, AR 72202 USA. [Smith, Rex N.; Collins, Alfred B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2010 VL 10 SU 4 SI SI BP 487 EP 488 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 573NX UT WOS:000275921703273 ER PT J AU Aoyama, A Boskovic, S Yamada, Y Nadazdin, O Murakami, T Ochiai, T Smith, RN Colvin, RB Benichou, G Sachs, DH Cosimi, AB Kawai, T AF Aoyama, Akihiro Boskovic, Svjetlan Yamada, Yohei Nadazdin, Ognjenka Murakami, Toru Ochiai, Takanori Smith, Rex-Neal Colvin, Robert B. Benichou, Gilles Sachs, David H. Cosimi, A. Benedict Kawai, Tatsuo TI Superior Induction of Mixed Chimerism and Renal Allograft Tolerance in Cyclosporine over Tacrolimus in Delayed Tolerance Induction. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 10th American Transplant Congress CY MAY 01-05, 2010 CL San Diego, CA SP Amer Soc Transplantat C1 [Aoyama, Akihiro; Boskovic, Svjetlan; Yamada, Yohei; Nadazdin, Ognjenka; Murakami, Toru; Ochiai, Takanori; Benichou, Gilles; Cosimi, A. Benedict; Kawai, Tatsuo] Massachusetts Gen Hosp, Transplant Ctr, Boston, MA 02114 USA. [Smith, Rex-Neal; Colvin, Robert B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sachs, David H.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2010 VL 10 SU 4 SI SI BP 488 EP 488 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 573NX UT WOS:000275921703275 ER PT J AU Kawai, T Sachs, D Spitzer, T Tolkoff-Rubin, N Ko, DSC Wong, WC Williams, W Saidman, S LoCascio, SA Colvin, RB Sykes, M Cosimi, AB AF Kawai, Tatsuo Sachs, David Spitzer, Thomas Tolkoff-Rubin, Nina Ko, Dicken S. C. Wong, Waichi Williams, Winfred Saidman, Susan LoCascio, Samuel A. Colvin, Robert B. Sykes, Megan Cosimi, A. Benedict TI Progress Report of the Mixed Chimerism Clinical Trial for Tolerance Induction in HLA Mismatched Kidney Transplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 10th American Transplant Congress CY MAY 01-05, 2010 CL San Diego, CA SP Amer Soc Transplantat C1 [Kawai, Tatsuo; Tolkoff-Rubin, Nina; Ko, Dicken S. C.; Wong, Waichi; Williams, Winfred; Cosimi, A. Benedict] Massachusetts Gen Hosp, Transplant Ctr, Boston, MA 02114 USA. [Sachs, David; LoCascio, Samuel A.; Sykes, Megan] Massachusetts Gen Hosp, Transplant Biol Res Ctr, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2010 VL 10 SU 4 SI SI BP 502 EP 502 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 573NX UT WOS:000275921703327 ER PT J AU Myaskovsky, L Dew, MA Crowley-Matoka, M Unruh, M Dabbs, AD Shapiro, R Tan, H AF Myaskovsky, Larissa Dew, Mary Amanda Crowley-Matoka, Megan Unruh, Mark Dabbs, Annette DeVito Shapiro, Ron Tan, Henkie TI Is Donating a Kidney Associated with Changes in Health Habits? SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 10th American Transplant Congress CY MAY 01-05, 2010 CL San Diego, CA SP Amer Soc Transplantat C1 [Myaskovsky, Larissa; Dew, Mary Amanda; Crowley-Matoka, Megan; Unruh, Mark; Dabbs, Annette DeVito; Shapiro, Ron; Tan, Henkie] Univ Pittsburgh, Pittsburgh, PA USA. [Myaskovsky, Larissa; Crowley-Matoka, Megan] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2010 VL 10 SU 4 SI SI BP 536 EP 536 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 573NX UT WOS:000275921703445 ER PT J AU Millington, TM Boskovic, S Aoyama, A Allan, JS Benichou, G Kawai, T Cosimi, B Sachs, DH Madsen, JC AF Millington, Timothy M. Boskovic, Svjetlan Aoyama, Akihiro Allan, James S. Benichou, Gilles Kawai, Tatsuo Cosimi, Benedict Sachs, David H. Madsen, Joren C. TI Cardiac Allograft Survival Is Prolonged by the Induction of Mixed Hematopoietic Chimerism Two Months after Heart Transplant SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 10th American Transplant Congress CY MAY 01-05, 2010 CL San Diego, CA SP Amer Soc Transplantat C1 [Millington, Timothy M.; Boskovic, Svjetlan; Aoyama, Akihiro; Allan, James S.; Benichou, Gilles; Kawai, Tatsuo; Cosimi, Benedict; Sachs, David H.; Madsen, Joren C.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2010 VL 10 SU 4 SI SI BP 554 EP 554 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 573NX UT WOS:000275921703511 ER PT J AU Yamada, Y Boskovic, S Aoyama, A Nadazdin, O Murakami, T Ochiai, T Smith, RN Colvin, RB Benichou, G Sachs, DH Cosimi, AB Kawai, T AF Yamada, Yohei Boskovic, Svjetlan Aoyama, Akihiro Nadazdin, Ognjenka Murakami, Toru Ochiai, Takanori Smith, Rex-Neal Colvin, Robert B. Benichou, Gilles Sachs, David H. Cosimi, A. Benedict Kawai, Tatsuo TI The Optimal Timing for Delayed Tolerance Induction with Minimal Alloimmune Responses SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 10th American Transplant Congress CY MAY 01-05, 2010 CL San Diego, CA SP Amer Soc Transplantat C1 [Yamada, Yohei; Boskovic, Svjetlan; Aoyama, Akihiro; Nadazdin, Ognjenka; Murakami, Toru; Ochiai, Takanori; Benichou, Gilles; Cosimi, A. Benedict; Kawai, Tatsuo] Massachusetts Gen Hosp, Transplant Ctr, Boston, MA 02114 USA. [Sachs, David H.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2010 VL 10 SU 4 SI SI BP 554 EP 554 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 573NX UT WOS:000275921703512 ER PT J AU Farkash, E Miyajima, M Alessandrini, A Chase, C Della Pelle, P Cook, C Russell, P Colvin, R AF Farkash, Evan Miyajima, Masahiro Alessandrini, Alessandro Chase, Catharine Della Pelle, Patricia Cook, Charles Russell, Paul Colvin, Robert TI Treg-Rich Organized Lymphoid Structures (TOLS) in Spontaneously Accepted Renal Allografts in Mice SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 10th American Transplant Congress CY MAY 01-05, 2010 CL San Diego, CA SP Amer Soc Transplantat C1 [Farkash, Evan; Miyajima, Masahiro; Alessandrini, Alessandro; Chase, Catharine; Della Pelle, Patricia; Russell, Paul; Colvin, Robert] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cook, Charles] Ohio State Univ, Columbus, OH 43210 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2010 VL 10 SU 4 SI SI BP 555 EP 555 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 573NX UT WOS:000275921703517 ER PT J AU Aoyama, A Putheti, P Yamada, Y Boskovic, S Sachs, DH Strom, TB Cosimi, AB Kawai, T AF Aoyama, Akihiro Putheti, Prabhakar Yamada, Yohei Boskovic, Svjetlan Sachs, David H. Strom, Terry B. Cosimi, A. Benedict Kawai, Tatsuo TI Inflammatory Responses and the Induction of Renal Allograft Tolerance. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 10th American Transplant Congress CY MAY 01-05, 2010 CL San Diego, CA SP Amer Soc Transplantat C1 [Aoyama, Akihiro; Putheti, Prabhakar; Yamada, Yohei; Boskovic, Svjetlan; Sachs, David H.; Strom, Terry B.; Cosimi, A. Benedict; Kawai, Tatsuo] Massachusetts Gen Hosp, Transplant Ctr, Boston, MA 02114 USA. [Aoyama, Akihiro; Putheti, Prabhakar; Yamada, Yohei; Boskovic, Svjetlan; Sachs, David H.; Strom, Terry B.; Cosimi, A. Benedict; Kawai, Tatsuo] Beth Israel Deaconess Med Ctr, Transplant Inst, Boston, MA 02215 USA. [Aoyama, Akihiro; Putheti, Prabhakar; Yamada, Yohei; Boskovic, Svjetlan; Sachs, David H.; Strom, Terry B.; Cosimi, A. Benedict; Kawai, Tatsuo] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2010 VL 10 SU 4 SI SI BP 569 EP 570 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 573NX UT WOS:000275921703566 ER PT J AU Williams, WW Cherikh, W Cheng, YL Young, C Fan, PY Bryan, C AF Williams, Winfred W. Cherikh, Wida Cheng, Yulin Young, Carlton Fan, Pan-Yen Bryan, Christopher TI Updated Report on the OPTN/UNOS Voluntary Variance To Allocate A2/A2B Deceased Donor Kidneys to Blood Group B Candidates. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 10th American Transplant Congress CY MAY 01-05, 2010 CL San Diego, CA SP Amer Soc Transplantat C1 [Williams, Winfred W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Renal Transplantat Unit, Boston, MA 02115 USA. [Cherikh, Wida; Cheng, Yulin] UNOS, Richmond, VA USA. [Young, Carlton] Univ Alabama, Div Transplantat, Birmingham, AL USA. [Fan, Pan-Yen] Univ Massachusetts, Med Ctr, Worcester, MA 01605 USA. [Bryan, Christopher] Midwest Transplant Network, Westwood, KS USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2010 VL 10 SU 4 SI SI BP 570 EP 570 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 573NX UT WOS:000275921703567 ER PT J AU Zhao, G Moore, DJ Lee, KM Kim, JI Duff, PE O'Connor, MR Hirohashi, T Lei, J Yang, M Markmann, JF Deng, S AF Zhao, G. Moore, D. J. Lee, K. M. Kim, J. I. Duff, P. E. O'Connor, M. R. Hirohashi, T. Lei, J. Yang, M. Markmann, J. F. Deng, S. TI An Unexpected Counter-Regulatory Role of IL-10 in B-Lymphocyte-Mediated Transplantation Tolerance SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE B lymphocyte; IL-10; regulation; tolerance; transplantation ID CARDIAC ALLOGRAFT VASCULOPATHY; T-CELLS; ANTIBODY; MICE; COLITIS AB Monoclonal antibody against the CD45RB protein induces stable transplantation tolerance to multiple types of allograft. We have previously established that this tolerance protocol relies on the regulatory function of B lymphocytes for its effect. B lymphocytes have also been reported to participate in immune regulation in several other settings. In most of these systems, the regulatory function of B lymphocytes depends on the production of IL-10. Therefore, we investigated the role of IL-10 in the anti-CD45RB model of B-cell-mediated transplantation tolerance. Surprisingly, using antibody-mediated neutralization of IL-10, IL-10-deficient recipients and adoptive transfer of IL-10-deficient B lymphocytes, we found that IL-10 actually counter-regulates tolerance induced by anti-CD45RB. Furthermore, neutralization of IL-10 reduced the development of chronic allograft vasculopathy compared to anti-CD45RB alone and reduced the production of graft reactive alloantibodies. These data suggest that the participation of regulatory B lymphocytes in transplantation tolerance may be distinct from how they operate in other systems. Identifying the specific B lymphocytes that mediate transplantation tolerance and defining their mechanism of action may yield new insights into the complex cellular network through which antigen-specific tolerance is established and maintained. C1 [Zhao, G.; Lee, K. M.; Kim, J. I.; Duff, P. E.; O'Connor, M. R.; Lei, J.; Yang, M.; Markmann, J. F.; Deng, S.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Zhao, G.; Yang, M.; Deng, S.] Sichuan Prov Peoples Hosp, Dept Surg, Chengdu, Sichuan Prov, Peoples R China. [Zhao, G.; Yang, M.; Deng, S.] Sichuan Acad Med Sci, Chengdu, Sichuan Prov, Peoples R China. [Moore, D. J.] Vanderbilt Childrens Hosp, Dept Pediat, Ian Burr Div Endocrinol & Diabet, Nashville, TN USA. [Hirohashi, T.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Deng, S (reprint author), Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM sdeng1@partners.org OI Moore, Daniel/0000-0002-6889-9345 FU National Institutes of Health [DK54215, AI-057851, P01-DK-49814]; [NNSF30772042] FX This work was supported by grants DK54215, AI-057851 and P01-DK-49814 from the National Institutes of Health and NNSF30772042. NR 19 TC 23 Z9 28 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2010 VL 10 IS 4 BP 796 EP 801 DI 10.1111/j.1600-6143.2010.03027.x PG 6 WC Surgery; Transplantation SC Surgery; Transplantation GA 571QA UT WOS:000275768300015 PM 20199511 ER PT J AU Humar, A Morris, M Blumberg, E Freeman, R Preiksaitis, J Kiberd, B Schweitzer, E Ganz, S Caliendo, A Orlowski, JP Wilson, B Kotton, C Michaels, M Kleinman, S Geier, S Murphy, B Green, M Levi, M Knoll, G Segev, DL Brubaker, S Hasz, R Lebovitz, DJ Mulligan, D O'Connor, K Pruett, T Mozes, M Lee, I Delmonico, FL Fischer, S AF Humar, A. Morris, M. Blumberg, E. Freeman, R. Preiksaitis, J. Kiberd, B. Schweitzer, E. Ganz, S. Caliendo, A. Orlowski, J. P. Wilson, B. Kotton, C. Michaels, M. Kleinman, S. Geier, S. Murphy, B. Green, M. Levi, M. Knoll, G. Segev, D. L. Brubaker, S. Hasz, R. Lebovitz, D. J. Mulligan, D. O'Connor, K. Pruett, T. Mozes, M. Lee, I. Delmonico, F. L. Fischer, S. TI Nucleic Acid Testing (NAT) of Organ Donors: Is the 'Best' Test the Right Test? A Consensus Conference Report SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Editorial Material DE Donor screening; hepatitis B virus (HBV); hepatitis C virus; HIV; Nucleic acid diagnostics; organ and tissue donation; transplantation ID HEPATITIS-C VIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; INJECTION-DRUG USERS; B-VIRUS; UNITED-STATES; LIVER-TRANSPLANTATION; PROVIDER UTILIZATION; COMBINATION ASSAYS; PRISON-INMATES; RISK-FACTORS AB Nucleic acid testing (NAT) for HIV, HBV and HCV shortens the time between infection and detection by available testing. A group of experts was selected to develop recommendations for the use of NAT in the HIV/HBV/HCV screening of potential organ donors. The rapid turnaround times needed for donor testing and the risk of death while awaiting transplantation make organ donor screening different from screening blood-or tissue donors. In donors with no identified risk factors, there is insufficient evidence to recommend routine NAT, as the benefits of NAT may not outweigh the disadvantages of NAT especially when false-positive results can lead to loss of donor organs. For donors with identified behavioral risk factors, NAT should be considered to reduce the risk of transmission and increase organ utilization. Informed consent balancing the risks of donor-derived infection against the risk of remaining on the waiting list should be obtained at the time of candidate listing and again at the time of organ offer. In conclusion, there is insufficient evidence to recommend universal prospective screening of organ donors for HIV, HCV and HBV using current NAT platforms. Further study of viral screening modalities may reduce disease transmission risk without excessive donor loss. C1 [Humar, A.; Preiksaitis, J.] Univ Alberta, Edmonton, AB T6G 2M7, Canada. [Morris, M.; Ganz, S.] Univ Miami, Miller Sch Med, Coral Gables, FL 33124 USA. [Blumberg, E.; Lee, I.] Univ Penn, Philadelphia, PA 19104 USA. [Schweitzer, E.] Univ Maryland, College Pk, MD 20742 USA. [Caliendo, A.] Emory Univ, Sch Med Pathol & Lab Med, Atlanta, GA 30322 USA. [Kotton, C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Michaels, M.] Childrens Hosp Pittsburgh, Pittsburgh, PA USA. [Kleinman, S.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Murphy, B.] Mt Sinai Sch Med, New York, NY 10029 USA. [Green, M.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. [Levi, M.] Univ Colorado Denver, Denver, CO USA. [Knoll, G.] Univ Ottawa, Ottawa, ON K1N 6N5, Canada. [Segev, D. L.] Johns Hopkins Univ, Baltimore, MD 21218 USA. [Lebovitz, D. J.] Childrens Hosp, Cleveland Clin, Cleveland, OH 44106 USA. [Pruett, T.] Univ Virginia Hlth Syst, Charlottesville, VA USA. [Delmonico, F. L.] New England Organ Bank Inc, Newton, MA USA. [Fischer, S.] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. [Fischer, S.] Rhode Isl Hosp, Providence, RI 02903 USA. RP Humar, A (reprint author), Univ Alberta, Edmonton, AB T6G 2M7, Canada. EM ahumar@ualberta.ca NR 56 TC 60 Z9 63 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2010 VL 10 IS 4 BP 889 EP 899 DI 10.1111/j.1600-6143.2009.02992.x PG 11 WC Surgery; Transplantation SC Surgery; Transplantation GA 571QA UT WOS:000275768300027 PM 20121734 ER PT J AU Treon, SP Hanzis, C Ioakimidis, L Patterson, C Hunter, ZR Sheehy, PS Manning, RJ AF Treon, S. P. Hanzis, C. Ioakimidis, L. Patterson, C. Hunter, Z. R. Sheehy, P. S. Manning, R. J. TI Clinical characteristics and treatment outcome of amyloid and IgM-related peripheral neuropathy in Waldenstrom's macroglobulinemia SO AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS LA English DT Meeting Abstract CT 12th International Symposium on Amyloidosis from Molecular Mechanisms Toward the Cure of Systemic Amyloidoses CY APR 18-21, 2010 CL Rome, ITALY C1 [Treon, S. P.; Hanzis, C.; Ioakimidis, L.; Patterson, C.; Hunter, Z. R.; Sheehy, P. S.; Manning, R. J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. RI Hunter, Zachary/H-3018-2013 OI Hunter, Zachary/0000-0002-1689-1691 NR 0 TC 0 Z9 0 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1350-6129 J9 AMYLOID JI Amyloid-J. Protein Fold. Disord. PD APR PY 2010 VL 17 SU 1 BP 64 EP 65 PG 2 WC Biochemistry & Molecular Biology; Medicine, General & Internal; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; General & Internal Medicine; Research & Experimental Medicine GA 624FG UT WOS:000279801500054 ER PT J AU Dember, LM Gillmore, JD Lewis, WD Pasquali, S Schoenland, SO Semigran, MJ Hawkins, PN AF Dember, L. M. Gillmore, J. D. Lewis, W. D. Pasquali, S. Schoenland, S. O. Semigran, M. J. Hawkins, P. N. TI Solid organ transplantation for non-TTR amyloidoses: consensus opinion SO AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS LA English DT Meeting Abstract CT 12th International Symposium on Amyloidosis from Molecular Mechanisms Toward the Cure of Systemic Amyloidoses CY APR 18-21, 2010 CL Rome, ITALY C1 [Dember, L. M.] Boston Univ, Amyloid Treatment & Res Program, Boston, MA 02215 USA. [Gillmore, J. D.; Hawkins, P. N.] UCL, Natl Amyloidosis Ctr, London, England. [Lewis, W. D.] Tufts Med Sch, Lahey Clin, Burlington, MA USA. [Pasquali, S.] Arcispedale S Maria Nuova, Nephrol Unit, Reggio Emilia, Italy. [Schoenland, S. O.] Univ Heidelberg, Dept Internal Med, D-6900 Heidelberg, Germany. [Semigran, M. J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1350-6129 J9 AMYLOID JI Amyloid-J. Protein Fold. Disord. PD APR PY 2010 VL 17 SU 1 BP 75 EP 75 PG 1 WC Biochemistry & Molecular Biology; Medicine, General & Internal; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; General & Internal Medicine; Research & Experimental Medicine GA 624FG UT WOS:000279801500072 ER PT J AU Peterfreund, RA Akhtar, S AF Peterfreund, Robert A. Akhtar, Shamsuddin TI How Sweet It Is ... (or Isn't)! SO ANESTHESIA AND ANALGESIA LA English DT Editorial Material ID CRITICALLY-ILL PATIENTS; INTENSIVE INSULIN THERAPY; RANDOMIZED PILOT TRIAL; TIGHT GLYCEMIC CONTROL; GLUCOSE CONTROL; CARDIAC-SURGERY; BLOOD-GLUCOSE; ISCHEMIC-STROKE; HYPERGLYCEMIA; MORTALITY C1 [Peterfreund, Robert A.] Harvard Univ, Dept Anesthesia Crit Care & Pain Med, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Akhtar, Shamsuddin] Yale Univ, Sch Med, Dept Anesthesiol, New Haven, CT 06510 USA. RP Peterfreund, RA (reprint author), Harvard Univ, Dept Anesthesia Crit Care & Pain Med, Sch Med, Massachusetts Gen Hosp, Jackson 439,55 Fruit St, Boston, MA 02114 USA. EM rpeterfreund@partners.org OI Akhtar, Shamsuddin/0000-0002-1127-0538 NR 39 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD APR PY 2010 VL 110 IS 4 BP 979 EP 981 DI 10.1213/ANE.0b013e3181d4527e PG 3 WC Anesthesiology SC Anesthesiology GA 575YL UT WOS:000276109200001 PM 20357141 ER PT J AU Bateman, BT Schmidt, U Berman, MF Bittner, EA AF Bateman, Brian T. Schmidt, Ulrich Berman, Mitchell F. Bittner, Edward A. TI Temporal Trends in the Epidemiology of Severe Postoperative Sepsis after Elective Surgery A Large, Nationwide Sample SO ANESTHESIOLOGY LA English DT Article ID CRITICALLY-ILL PATIENTS; UNITED-STATES; CRITICAL-CARE; PREVENTION; INFECTIONS; GUIDELINE; DEFINITIONS; MULTICENTER; VENTILATION; THERAPY AB Introduction: Multiple studies have used administrative datasets to examine the epidemiology of sepsis in general, but the entity of postoperative sepsis has been studied less intensively. Therefore, we undertook an analysis of the epidemiology of postoperative sepsis using the Nationwide Inpatient Sample, the largest in-patient dataset available in the United States. Methods: Elective admissions of patients aged 18 yr or older with a length of stay more than 3 days for any 1 of the 20 most common elective operative procedures were extracted from the dataset for the years 1997-2006. Postoperative sepsis was defined using the appropriate International Classification of Diseases, Ninth Revision, Clinical Modification codes; severe sepsis was defined as sepsis along with organ dysfunction. Logistic regression was used to assess the significance of temporal trends after adjusting for relevant demographic characteristics, operative procedure, and comorbid conditions. Results: We identified 2,039,776 admissions for analysis. The rate of severe sepsis increased from 0.3% in 1997 to 0.9% in 2006. This trend persisted after adjusting for relevant covariables-the adjusted odds ratio of severe sepsis per year increase in the study period was 1.12 (95% CI, 1.11-1.13; P < 0.001). The in-hospital mortality rate for patients with severe postoperative sepsis declined from 44.4% in 1997 to 34.0% in 2006; this trend also persisted after adjustment for relevant covariables-the adjusted odds ratio per year was 0.94 (95% CI, 0.93-0.95; P < 0.001). Conclusion: During the 10-yr period that we studied, there was a marked increase in the rate of severe postoperative sepsis but a concomitant decrease in the in-hospital mortality rate in severe sepsis. C1 [Bateman, Brian T.; Schmidt, Ulrich; Berman, Mitchell F.; Bittner, Edward A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Bateman, BT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM bbateman@partners.org NR 32 TC 33 Z9 33 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD APR PY 2010 VL 112 IS 4 BP 917 EP 925 DI 10.1097/ALN.0b013e3181cea3d0 PG 9 WC Anesthesiology SC Anesthesiology GA 576HG UT WOS:000276134500018 PM 20357565 ER PT J AU Vassallo, MF Banerji, A Rudders, SA Clark, S Mullins, RJ Camargo, CA AF Vassallo, Milo F. Banerji, Aleena Rudders, Susan A. Clark, Sunday Mullins, Raymond J. Camargo, Carlos A., Jr. TI Season of birth and food allergy in children SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Article ID VITAMIN-D; ATOPIC-DERMATITIS; UNITED-STATES; PREVALENCE; ASTHMA; ASSOCIATION; ANAPHYLAXIS; CHILDHOOD; DISEASE; PRESCRIPTIONS AB Background: The prevalence of food allergy is rising, and etiologic factors remain uncertain. Evidence implicates a role for vitamin D in the development of atopic diseases. Based on seasonal patterns of UV-B exposure (and consequent vitamin D status), we hypothesized that patients with food allergy are more often born in fall or winter. Objective: To investigate whether season of birth is associated with food allergy. Methods: We performed a multicenter medical record review of all patients presenting to 3 Boston emergency departments (EDs) for food-related acute allergic reactions between January 1, 2001, and December 31, 2006. Months of birth in patients with food allergy were compared with that of patients visiting the ED for reasons other than food allergy. Results: We studied 1002 patients with food allergy. Of younger children with food allergy (age <5 years), but not older children or adults, 41% were born in spring or summer compared with 59% in fall or winter (P=.002). This approximately 40: 60 ratio differed from birth season in children treated in the ED for non-food allergy reasons (P=.002). Children younger than 5 years born in fall or winter had a 53% higher odds of food allergy compared with controls. This finding was independent of the suspected triggering food and allergic comorbidities. Conclusions: Food allergy is more common in Boston children born in the fall and winter seasons. We propose that these findings are mediated by seasonal differences in UV-B exposure. These results add support to the hypothesis that seasonal fluctuations in sunlight and perhaps vitamin D may be involved in the pathogenesis of food allergy. Ann Allergy Asthma Immunol. 2010;104:307-313. C1 [Vassallo, Milo F.; Banerji, Aleena; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. [Vassallo, Milo F.; Rudders, Susan A.; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Rudders, Susan A.] Childrens Hosp, Dept Allergy & Immunol, Boston, MA 02115 USA. [Clark, Sunday] Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA USA. [Mullins, Raymond J.] Australian Natl Univ, Sch Med, Canberra, ACT, Australia. RP Camargo, CA (reprint author), Massachusetts Gen Hosp, Dept Med, Div Rheumatol Allergy & Immunol, 326 Cambridge St,Ste 410, Boston, MA 02114 USA. EM ccamargo@partners.org OI Mullins, Raymond/0000-0002-0267-1591 FU National Institutes of Health [T32 AI-60548, T32 AI-007512]; Massachusetts General Hospital Center for D-receptor Activation Research FX Dr Vassallo was supported by T32 AI-60548 and Dr Rudders by T32 AI-007512 from the National Institutes of Health. Dr Camargo was supported, in part, by the Massachusetts General Hospital Center for D-receptor Activation Research. NR 42 TC 43 Z9 44 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1081-1206 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD APR PY 2010 VL 104 IS 4 BP 307 EP 313 DI 10.1016/j.anai.2010.01.019 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 701OK UT WOS:000285829400006 PM 20408340 ER PT J AU Wilson, DA Bork, K Shea, EP Rentz, AM Blaustein, MB Pullman, WE AF Wilson, David A. Bork, Konrad Shea, Elizabeth P. Rentz, Anne M. Blaustein, Marc B. Pullman, William E. TI Economic costs associated with acute attacks and long-term management of hereditary angioedema SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Article ID C1 INHIBITOR DEFICIENCY; US AB Background: Hereditary angioedema (HAE) is a rare autosomal dominant disorder characterized by recurrent acute attacks of swelling of the larynx, abdomen, and periphery. Objective: To assess the economic burden associated with acute attacks and long-term management of HAE. Methods: Burden was assessed via a Web-based survey of HAE patients (>= 18 years old) that solicited information on attack characterization, short-term treatment, long-term disease management, impact on work, and patient costs. A standardized instrument, the Work Productivity and Activity Impairment questionnaire, was included to assess impact on work productivity. Standard medical costs and US average wage costs were assigned to survey items to assess direct medical and indirect costs, respectively. Results: Total annual per-patient costs are estimated at $42,000 for the average HAE patient, with costs totaling $14,000 for patients with mild attacks, $27,000 for patients with moderate attacks, and $96,000 for patients with severe attacks. Hospital costs account for 67% of direct medical costs. Respondents reported high rates of missed work, lost productivity, and lost income, contributing to indirect costs totaling $16,000 annually for the average patient. Almost all costs increase with disease severity, although the distribution varies with severity: indirect costs account for 75% of costs for patients with mild attacks, whereas emergency department and hospital costs account for 68% of costs for patients with severe attacks. Conclusions: HAE results in considerable economic burden to patients, payers, and society in terms of direct medical and indirect costs and compounds the substantial humanistic burdens, which will be reported separately. Ann Allergy Asthma Immunol. 2010;104:314-320. C1 [Wilson, David A.] Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. [Bork, Konrad] Johannes Gutenberg Univ Mainz, Mainz, Germany. [Shea, Elizabeth P.; Blaustein, Marc B.; Pullman, William E.] Dyax Corp, Cambridge, MA USA. [Rentz, Anne M.] United BioSource Corp, Ctr Hlth Outcomes Res, Bethesda, MD USA. RP Wilson, DA (reprint author), MGH Inst Hlth Profess, 36 1st Ave, Charlestown, MA 02129 USA. EM dwilson@mghihp.edu FU Dyax Corp. FX This study was supported by Dyax Corp. NR 23 TC 66 Z9 66 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1081-1206 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD APR PY 2010 VL 104 IS 4 BP 314 EP U127 DI 10.1016/j.anai.2010.01.024 PG 9 WC Allergy; Immunology SC Allergy; Immunology GA 701OK UT WOS:000285829400007 PM 20408341 ER PT J AU Knight, SJ Studts, JL Latini, DM Sands, LP AF Knight, Sara J. Studts, Jamie L. Latini, David M. Sands, Laura P. TI UNDERSTANDING PATIENT PREFERENCES FOR PREVENTION AND TREATMENT SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Knight, Sara J.] San Francisco VA Med Ctr, Program Improve Care Vet Complex Comorbid Condit, San Francisco, CA 94121 USA. [Knight, Sara J.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Studts, Jamie L.] Univ Kentucky, Coll Med, Dept Behav Sci, Lexington, KY 40536 USA. [Latini, David M.] Michael E DeBakey VA Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. [Latini, David M.] Baylor Coll Med, Houston, TX 77030 USA. [Sands, Laura P.] Purdue Univ, Sch Nursing, W Lafayette, IN 47907 USA. EM sara.knight@ucsf.edu NR 0 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 2 EP 2 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700005 ER PT J AU Zeliadt, S Penson, DF Moinpour, AM Blough, DK Fedorenko, CR Hall, IJ Smith, JL Ekwueme, D Thompson, IM Keane, TE Ramsey, SD AF Zeliadt, Steven Penson, David F. Moinpour, Arol M. Blough, David K. Fedorenko, Catherine R. Hall, Ingrid J. Smith, Judith Lee Ekwueme, Donatus Thompson, Ian M. Keane, Thomas E. Ramsey, Scott D. TI PROVIDER INTERACTIONS WITH PARTNERS OF MEN NEWLY DIAGNOSED WITH PROSTATE CANCER SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Zeliadt, Steven] VA Puget Sound Hlth Care Syst, Seattle, WA 98101 USA. [Zeliadt, Steven; Penson, David F.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Moinpour, Arol M.; Fedorenko, Catherine R.; Ramsey, Scott D.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Blough, David K.] Univ Washington, Seattle, WA 98195 USA. [Hall, Ingrid J.; Smith, Judith Lee; Ekwueme, Donatus] Ctr Dis Control & Prevent, Atlanta, GA USA. [Thompson, Ian M.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Keane, Thomas E.] Med Univ S Carolina, Charleston, SC 29425 USA. EM szeliadt@u.washington.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 5 EP 5 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700017 ER PT J AU Galarce, EM Ramanadhan, S Crisostomo, J Alexander-Molloy, J Weeks, JC Schneider, EC Viswanath, K AF Galarce, Ezequiel M. Ramanadhan, Shoba Crisostomo, Josephine Alexander-Molloy, Jaclyn Weeks, Jane C. Schneider, Eric C. Viswanath, Kasisomayajula TI BARRIERS TO ACCESSING INTERNET HEALTH INFORMATION AMONG CANCER PATIENTS AND SURVIVORS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Galarce, Ezequiel M.; Ramanadhan, Shoba; Crisostomo, Josephine; Alexander-Molloy, Jaclyn; Weeks, Jane C.; Viswanath, Kasisomayajula] Dana Farber Canc Inst, Boston, MA 02115 USA. [Galarce, Ezequiel M.; Schneider, Eric C.; Viswanath, Kasisomayajula] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. EM ezequiel_galarce@dfci.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 7 EP 7 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700024 ER PT J AU Ramanadhan, S Crisostomo, J Alexander-Molloy, J Galarce, E Weeks, J Schneider, E Viswanath, K AF Ramanadhan, Shoba Crisostomo, Josephine Alexander-Molloy, Jaclyn Galarce, Ezequiel Weeks, Jane Schneider, Eric Viswanath, K. TI PROXY INFORMATION AGENTS (PIAS) THROUGH THE EYES OF CANCER PATIENTS AND SURVIVORS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Ramanadhan, Shoba; Crisostomo, Josephine; Alexander-Molloy, Jaclyn; Galarce, Ezequiel; Weeks, Jane; Viswanath, K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Weeks, Jane; Schneider, Eric; Viswanath, K.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. EM shoba_ramanadhan@dfci.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 8 EP 8 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700029 ER PT J AU Cooley, ME Johnson, BE Wang, QA Catalano, P Haddad, R Posner, M Emmons, KM AF Cooley, Mary E. Johnson, Bruce E. Wang, Qian Catalano, Paul Haddad, Robert Posner, Marshall Emmons, Karen M. TI FACTORS ASSOCIATED WITH SMOKING ABSTINENCE AMONG CANCER PATIENTS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Cooley, Mary E.; Johnson, Bruce E.; Wang, Qian; Catalano, Paul; Haddad, Robert; Posner, Marshall; Emmons, Karen M.] Dana Farber Canc Inst, Boston, MA 02115 USA. EM mary_cooley@dfci.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 36 EP 36 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700141 ER PT J AU Myaskovsky, L McNulty, M Kormos, R Dew, MA AF Myaskovsky, Larissa McNulty, Mary Kormos, Robert Dew, Mary Amanda TI PREDICTORS OF QUALITY OF LIFE IN CAREGIVERS TO CARDIOTHORACIC TRANSPLANT RECIPIENTS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Myaskovsky, Larissa; McNulty, Mary; Kormos, Robert; Dew, Mary Amanda] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15206 USA. [Myaskovsky, Larissa] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. EM larissa.myaskovsky@va.gov 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 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 39 EP 39 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700152 ER PT J AU Reisner, SL Mimiaga, MJ Pantalone, D Bland, S O'Cleirigh, C Mayer, KH Safren, SA AF Reisner, Sari L. Mimiaga, Matthew J. Pantalone, David Bland, Sean O'Cleirigh, Conall Mayer, Kenneth H. Safren, Steven A. TI BASELINE FINDINGS FROM PROJECT IMPACT: HIV-UNINFECTED MEN WHO HAVE SEX WITH MEN PRESENTING FOR TREATMENT OF CRYSTAL METHAMPHETAMINE ABUSE ARE AT HIGH-RISK FOR HIV INFECTION SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Reisner, Sari L.; Mimiaga, Matthew J.; Pantalone, David; Bland, Sean; O'Cleirigh, Conall; Mayer, Kenneth H.; Safren, Steven A.] Fenway Inst, Boston, MA 02215 USA. [Reisner, Sari L.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Mimiaga, Matthew J.; O'Cleirigh, Conall; Safren, Steven A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Pantalone, David] Suffolk Univ, Boston, MA 02114 USA. [Mayer, Kenneth H.] Miriam Hosp, Brown Med Sch, Providence, RI 02906 USA. EM sreisner@fenwayhealth.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 52 EP 52 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700199 ER PT J AU Beverly, EA Ritholz, MD Brooks, KM Hultgren, BA Weinger, K AF Beverly, Elizabeth A. Ritholz, Marilyn D. Brooks, Kelly M. Hultgren, Brittney A. Weinger, Katie TI PERCEPTIONS OF TYPE 2 DIABETES PATIENTS' HONESTY IN THE PHYSICIAN-PATIENT RELATIONSHIP SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Beverly, Elizabeth A.; Ritholz, Marilyn D.; Brooks, Kelly M.; Hultgren, Brittney A.; Weinger, Katie] Joslin Diabet Ctr, Boston, MA 02215 USA. [Beverly, Elizabeth A.; Ritholz, Marilyn D.; Weinger, Katie] Harvard Univ, Sch Med, Boston, MA 02215 USA. EM katie.weinger@joslin.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 54 EP 54 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700205 ER PT J AU Ritholz, MD Beverly, EA Brooks, KM Hultgren, BA Abrahamson, M Weinger, K AF Ritholz, Marilyn D. Beverly, Elizabeth A. Brooks, Kelly M. Hultgren, Brittney A. Abrahamson, Martin Weinger, Katie TI PHYSICIANS' AND PATIENTS' PERCEPTIONS OF FACTORS PROMOTING OR IMPEDING TYPE 2 DIABETES MANAGEMENT SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Ritholz, Marilyn D.; Beverly, Elizabeth A.; Brooks, Kelly M.; Hultgren, Brittney A.; Abrahamson, Martin; Weinger, Katie] Joslin Diabet Ctr, Boston, MA 02215 USA. [Ritholz, Marilyn D.; Beverly, Elizabeth A.; Abrahamson, Martin; Weinger, Katie] Harvard Univ, Sch Med, Boston, MA 02215 USA. EM weinger@joslin.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 54 EP 54 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700206 ER PT J AU Whiteley, JA Pischke, CR Bennett, GG AF Whiteley, Jessica A. Pischke, Claudia R. Bennett, Gary G. TI COACHING DOES NOT CONFER ADDITIONAL BENEFIT FOR WEIGHT LOSS AMONG LOWER INCOME WOMEN USING HANDHELD COMPUTERS FOR SELF-MONITORING SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Pischke, Claudia R.] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. [Whiteley, Jessica A.] Univ Massachusetts, Boston, MA 02125 USA. [Bennett, Gary G.] Duke Univ, Durham, NC USA. EM claudia_pischke@dfci.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 58 EP 58 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700224 ER PT J AU Littman, AJ McDonell, M Boyko, EJ Fihn, SD AF Littman, Alyson J. McDonell, M. Boyko, E. J. Fihn, S. D. TI IMPLEMENTATION OF A VA WEIGHT MANAGEMENT PROGRAM: WHO ENROLLS AND IS THERE A BENEFIT? SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Littman, Alyson J.] Univ Washington, Seattle, WA 98101 USA. [Littman, Alyson J.; McDonell, M.; Boyko, E. J.; Fihn, S. D.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 59 EP 59 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700226 ER PT J AU Hatzenbuehler, ML O'Cleirigh, C Mayer, K Safren, S AF Hatzenbuehler, Mark L. O'Cleirigh, Conall Mayer, Kenneth Safren, Steven TI IS HIV-RELATED STIGMA A VULNERABILITY FOR MENTAL HEALTH, SUBSTANCE ABUSE, AND SEXUAL TRANSMISSION RISK BEHAVIOR AMONG HIV-INFECTED MSM? SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Hatzenbuehler, Mark L.] Yale Univ, Boston, MA 02116 USA. [O'Cleirigh, Conall; Safren, Steven] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Hatzenbuehler, Mark L.; O'Cleirigh, Conall; Mayer, Kenneth; Safren, Steven] Fenway Inst, Boston, MA USA. [Mayer, Kenneth] Brown Univ, Providence, RI 02912 USA. EM mark.hatzenbuehler@yale.edu 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 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 85 EP 85 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700329 ER PT J AU Littman, AJ Forsberg, CW Yancy, WS Boyko, EJ Koepsell, TD AF Littman, Alyson J. Forsberg, C. W. Yancy, W. S. Boyko, E. J. Koepsell, T. D. TI DO OBESE INDIVIDUALS GET LESS PREVENTIVE CARE? SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Littman, Alyson J.; Koepsell, T. D.] Univ Washington, Seattle, WA 98101 USA. [Littman, Alyson J.; Forsberg, C. W.; Boyko, E. J.; Koepsell, T. D.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Yancy, W. S.] Ctr Hlth Serv Res Primary Care, Durham, NC USA. 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 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 89 EP 89 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700345 ER PT J AU Bachand, AE Allsup, K Mori, D Niles, B Collins, A Brown, K Forman, DE AF Bachand, Amy E. Allsup, Kelly Mori, DeAnna Niles, Barbara Collins, Allison Brown, Kirstin Forman, Daniel E. TI INDIVIDUAL CALIBRATION OF THE ACTIGRAPH GT1M ACCELEROMETER IN SEDENTARY ADULTS WITH TYPE 2 DIABETES SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Bachand, Amy E.; Allsup, Kelly; Mori, DeAnna; Niles, Barbara; Collins, Allison; Brown, Kirstin; Forman, Daniel E.] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Bachand, Amy E.; Mori, DeAnna; Niles, Barbara; Collins, Allison] Boston Univ, Sch Med, Boston, MA 02118 USA. [Forman, Daniel E.] Harvard Univ, Sch Med, Boston, MA USA. EM amy.bachand@va.gov NR 0 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 98 EP 98 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700382 ER PT J AU Shelton, RC Snavely, AC De Jesus, M Othus, MD Allen, JD AF Shelton, Rachel C. Snavely, Anna C. De Jesus, Maria Othus, Megan D. Allen, Jennifer D. TI RELIGIOUS FACTORS AND HPV VACCINE ACCEPTANCE AMONG MULTIETHNIC CAREGIVERS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Shelton, Rachel C.] Mt Sinai Sch Med, New York, NY 10029 USA. [Snavely, Anna C.; De Jesus, Maria] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [De Jesus, Maria; Allen, Jennifer D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Othus, Megan D.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Allen, Jennifer D.] Harvard Univ, Sch Med, Boston, MA USA. EM rshelton@post.harvard.edu RI Allen, Jennifer/M-2113-2015 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 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 135 EP 135 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700521 ER PT J AU Rees, C Karter, AJ Young, BA Schillinger, D Adler, N AF Rees, Courtney Karter, Andrew J. Young, Bessie A. Schillinger, Dean Adler, Nancy TI PREDICTORS OF SELF-REPORTED DISCRIMINATION IN THE DIABETES STUDY OF NORTHERN CALIFORNIA SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Rees, Courtney; Karter, Andrew J.; Young, Bessie A.] Univ Washington, Seattle, WA 98195 USA. [Karter, Andrew J.] Kaiser Permanente No Calif, Oakland, CA USA. [Young, Bessie A.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Schillinger, Dean; Adler, Nancy] UCSF, San Francisco, CA USA. EM crees@u.washington.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 137 EP 137 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700529 ER PT J AU Reisner, SL O'Cleirigh, C Hendriksen, ES McLain, J Ebin, J Lew, K Callis, BP Cranston, K Carr, R Giovanniello, C Gonzalez, D VanDerwarker, R Mimiaga, MJ AF Reisner, Sari L. O'Cleirigh, Conall Hendriksen, Ellen S. McLain, Jennifer Ebin, Julie Lew, Katherine Callis, Barry P. Cranston, Kevin Carr, Robert Giovanniello, Chuck Gonzalez, Daniel VanDerwarker, Rodney Mimiaga, Matthew J. TI "40 & FORWARD": A PILOT GROUP INTERVENTION TO REDUCE HIV SEXUAL RISK BEHAVIOR AND IMPROVE MENTAL HEALTH OUTCOMES AMONG OLDER AGE MEN WHO HAVE SEX WITH MEN SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Reisner, Sari L.; O'Cleirigh, Conall; Hendriksen, Ellen S.; McLain, Jennifer; Ebin, Julie; Giovanniello, Chuck; Gonzalez, Daniel; VanDerwarker, Rodney; Mimiaga, Matthew J.] Fenway Inst, Boston, MA 02215 USA. [Reisner, Sari L.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [O'Cleirigh, Conall; Hendriksen, Ellen S.; Mimiaga, Matthew J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Lew, Katherine; Callis, Barry P.; Cranston, Kevin; Carr, Robert] Massachusetts Dept Publ Hlth, Boston, MA USA. EM sreisner@fenwayhealth.org NR 0 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 140 EP 140 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700542 ER PT J AU Traeger, L Applebaum, A O'Cleirigh, C Israel, J Bullis, J Safren, S AF Traeger, Lara Applebaum, Allison O'Cleirigh, Conall Israel, Jared Bullis, Jacqueline Safren, Steven TI HIV STATUS IMPACTS PSYCHOSOCIAL RISK AND RECENT HEROIN USE IN DEPRESSED PATIENTS ON METHADONE MAINTENANCE FOR OPIOID DEPENDENCE SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Traeger, Lara; O'Cleirigh, Conall; Israel, Jared; Bullis, Jacqueline; Safren, Steven] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Applebaum, Allison] Boston Univ, Boston, MA 02215 USA. [O'Cleirigh, Conall; Safren, Steven] Fenway Inst, Boston, MA USA. EM lara.traeger@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 140 EP 140 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700543 ER PT J AU Straits-Troster, K Acheson, S Beckham, J Calhoun, P Gierisch, JM Hamlett-Berry, K AF Straits-Troster, Kristy Acheson, Shawn Beckham, Jean Calhoun, Patrick Gierisch, Jennifer M. Hamlett-Berry, Kim TI TOBACCO USE AND CESSATION AMONG RETURNING COMBAT VETERANS: A MIXED METHODS STUDY SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Straits-Troster, Kristy; Acheson, Shawn; Beckham, Jean; Calhoun, Patrick; Gierisch, Jennifer M.] Duke Univ, Durham, NC 27705 USA. [Calhoun, Patrick; Gierisch, Jennifer M.] US Dept Vet Affairs, HSR&D, Durham, NC USA. [Hamlett-Berry, Kim] US Dept Vet Affairs, Off Publ Hlth & Prevent, Durham, NC USA. EM kristy.straits-troster2@va.gov NR 0 TC 0 Z9 0 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 158 EP 158 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700616 ER PT J AU Myaskovsky, L Almario, D Dew, MA Switzer, G Unruh, M Ramkumar, M Shapiro, R AF Myaskovsky, Larissa Almario, Donna Dew, Mary Amanda Switzer, Galen Unruh, Mark Ramkumar, Mohan Shapiro, Ron TI RACIAL DISPARITIES IN KIDNEY TRANSPLANT: BEYOND MEDICAL FACTORS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Myaskovsky, Larissa; Almario, Donna; Dew, Mary Amanda; Switzer, Galen; Unruh, Mark; Ramkumar, Mohan; Shapiro, Ron] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15206 USA. [Myaskovsky, Larissa; Almario, Donna; Switzer, Galen; Ramkumar, Mohan] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. EM larissa.myaskovsky@va.gov 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 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 161 EP 161 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700628 ER PT J AU Cadmus, L McTiernan, A Ceballos, R McGregor, B Ramaprasad, J Ulrich, C Littman, A AF Cadmus, Lisa McTiernan, Anne Ceballos, Rachael McGregor, Bonnie Ramaprasad, Jaya Ulrich, Cornelia Littman, Alyson TI PREDICTORS OF ADHERENCE TO A SIX-MONTH YOGA INTERVENTION AMONG BREAST CANCER SURVIVORS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Cadmus, Lisa] UCSD Moores Canc Ctr, San Diego, CA 92102 USA. [McTiernan, Anne; Ceballos, Rachael; McGregor, Bonnie; Ulrich, Cornelia] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Ramaprasad, Jaya; Littman, Alyson] Univ Washington, Seattle, WA 98195 USA. [Littman, Alyson] US Dept Vet Affairs, Seattle, WA USA. EM lcadmus@ucsd.edu NR 0 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 168 EP 168 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700652 ER PT J AU Wilkinson, JL Psaros, C Carper, MM Gonzalez, JS Safren, SA AF Wilkinson, Jesse L. Psaros, Christina Carper, Matthew M. Gonzalez, Jeffrey S. Safren, Steven A. TI ASSOCIATION OF SPECIFIC CLINICALLY-RATED SYMPTOMS OF DEPRESSION TO ADHERENCE IN POORLY-CONTROLLED TYPE 2 DIABETICS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Wilkinson, Jesse L.; Psaros, Christina; Carper, Matthew M.; Safren, Steven A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Gonzalez, Jeffrey S.] Yeshiva Univ Albert Einstein Coll Med, Bronx, NY 10461 USA. EM jlwilkinson@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 171 EP 171 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700666 ER PT J AU Reisner, SL Mimiaga, MJ Bland, S Cranston, K Isenberg, D Driscoll, MA VanDerwarker, R Mayer, KH AF Reisner, Sari L. Mimiaga, Matthew J. Bland, Sean Cranston, Kevin Isenberg, Deborah Driscoll, Maura A. VanDerwarker, Rodney Mayer, Kenneth H. TI DIFFERENCES IN SEXUAL TRANSMISSION RISK BEHAVIORS BY HIV SEROSTATUS AMONG MEN WHO HAVE SEX WITH MEN ATTENDING SEX PARTIES IN MASSACHUSETTS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Reisner, Sari L.; Mimiaga, Matthew J.; Bland, Sean; VanDerwarker, Rodney; Mayer, Kenneth H.] Fenway Hlth, Fenway Inst, Boston, MA 02215 USA. [Reisner, Sari L.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Cranston, Kevin; Isenberg, Deborah; Driscoll, Maura A.] Massachusetts Dept Publ Hlth, Boston, MA USA. [Mayer, Kenneth H.] Brown Univ, Miriam Hosp, Providence, RI USA. [Mimiaga, Matthew J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. EM sreisner@fenwayhealth.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 175 EP 175 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700682 ER PT J AU Steffen, LE Kimbrel, NA Meyer, EC Kruse, MI Knight, JA Zimering, RT Gulliver, SB AF Steffen, Laurie E. Kimbrel, Nathan A. Meyer, Eric C. Kruse, Marc I. Knight, Jeffrey A. Zimering, Rose T. Gulliver, Suzy B. TI PSYCHOMETRIC PROPERTIES OF TWO ABBREVIATED VERSIONS OF THE SOURCES OF OCCUPATIONAL STRESS (SOOS) SCALE: THE SOOS-33 AND THE SOOS-14 SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Steffen, Laurie E.; Kimbrel, Nathan A.; Meyer, Eric C.; Kruse, Marc I.; Gulliver, Suzy B.] VISN 17 Ctr Excellence Res Returning War Vet, Waco, TX USA. [Steffen, Laurie E.; Kimbrel, Nathan A.; Meyer, Eric C.; Kruse, Marc I.; Gulliver, Suzy B.] Texas A&M Hlth Sci Ceter, College Stn, TX USA. [Knight, Jeffrey A.; Zimering, Rose T.] VA Boston Healthcare Syst, Boston, MA USA. [Knight, Jeffrey A.; Zimering, Rose T.] Boston Univ, Sch Med, Boston, MA 02118 USA. EM steffen@gmail.com RI Kimbrel, Nathan/P-3109-2016 OI Kimbrel, Nathan/0000-0001-7218-1005 NR 0 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 181 EP 181 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700703 ER PT J AU Markowitz, SM O'Cleirigh, C Hendriksen, E Bullis, J Safren, SA AF Markowitz, Sarah M. O'Cleirigh, Conall Hendriksen, Ellen Bullis, Jacqueline Safren, Steven A. TI THE RELATIONSHIP BETWEEN CHILDHOOD SEXUAL ABUSE AND HEALTH RISK BEHAVIORS IN PATIENTS WITH HIV IN TREATMENT FOR OPIATE DEPENDENCE SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Markowitz, Sarah M.; O'Cleirigh, Conall; Hendriksen, Ellen; Bullis, Jacqueline; Safren, Steven A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Markowitz, Sarah M.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [O'Cleirigh, Conall; Hendriksen, Ellen; Safren, Steven A.] Fenway Community Hlth, Boston, MA USA. EM smarkowitz@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 204 EP 204 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700794 ER PT J AU Hausmann, L Kressin, NR Hanusa, BH Ibrahim, SA AF Hausmann, Leslie Kressin, Nancy R. Hanusa, Barbara H. Ibrahim, Said A. TI THE ASSOCIATION OF PERCEIVED RACIAL DISCRIMINATION WITH PATIENTS' HEALTH CARE EXPERIENCES: CHOICE OF MEASURE MATTERS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Hausmann, Leslie; Hanusa, Barbara H.; Ibrahim, Said A.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. [Hanusa, Barbara H.; Ibrahim, Said A.] Univ Pittsburgh, Pittsburgh, PA USA. [Kressin, Nancy R.] VA Boston Healthcare Syst, Boston, MA USA. [Kressin, Nancy R.] Boston Univ, Sch Med, Boston, MA 02118 USA. EM leslie.hausmann@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 208 EP 208 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700813 ER PT J AU Preczewski, PJ Bossarte, RM He, H Tu, X AF Preczewski, Paul J. Bossarte, Robert M. He, Hua Tu, Xin TI BINGE DRINKING FREQUENCY PREDICTED BY VETERAN STATUS AND THE INTERACTIVE RELATIONSHIP BETWEEN HISPANIC ETHNICITY AND VETERAN STATUS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Preczewski, Paul J.] Syracuse Univ, Syracuse, NY 13244 USA. [Preczewski, Paul J.; Bossarte, Robert M.; He, Hua; Tu, Xin] US Dept Vet Affairs, Ctr Excellence, VMAC, Canandaigua, NY USA. [Bossarte, Robert M.; He, Hua; Tu, Xin] Univ Rochester, Rochester, NY USA. EM pjprecze@syr.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 213 EP 213 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700831 ER PT J AU Hendriksen, E Hlubinka, D Chariyalertsak, S Chingono, A Gray, G Mbwambo, J Richter, L Kulich, M Coates, TJ AF Hendriksen, Ellen Hlubinka, Daniel Chariyalertsak, Suwat Chingono, Alfred Gray, Glenda Mbwambo, Jessie Richter, Linda Kulich, Michal Coates, Thomas J. TI HIV/AIDS-RELATED COMMUNICATION AND PRIOR HIV TESTING IN TANZANIA, SOUTH AFRICA, ZIMBABWE, AND THAILAND SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Hendriksen, Ellen] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hlubinka, Daniel; Kulich, Michal] Charles Univ Prague, Dept Probabil & Stat, Prague, Czech Republic. [Chariyalertsak, Suwat] Chiang Mai Univ, Res Inst Hlth Sci, Chiang Mai 50000, Thailand. [Chingono, Alfred] Univ Zimbabwe, Sch Med, Dept Psychiat, Harare, Zimbabwe. [Gray, Glenda] Univ Witwatersrand, Perinatal HIV Res Unit, Chris Hani Baragwanath Hosp, Johannesburg, South Africa. [Mbwambo, Jessie] Muhimbili Univ, Coll Hlth Sci, Dept Psychiat, Dar Es Salaam, Tanzania. [Richter, Linda] Human Sci Res Council, Durban, South Africa. [Coates, Thomas J.] Univ Calif Los Angeles, David Geffen Sch Med, Div Infect Dis, Los Angeles, CA 90095 USA. EM ehendriksen@partners.org RI Kulich, Michal/B-1483-2013; Hlubinka, Daniel/C-6385-2017 OI Kulich, Michal/0000-0002-2812-8968; Hlubinka, Daniel/0000-0003-4016-3632 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 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 217 EP 217 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700848 ER PT J AU Martinez, R Fierro, CA Shireman, PK Han, HC AF Martinez, Ricky Fierro, Cesar A. Shireman, Paula K. Han, Hai-Chao TI Mechanical Buckling of Veins Under Internal Pressure SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Article DE Critical buckling pressure; Mechanical stability; Tortuosity; Porcine jugular veins ID VARICOSE-VEINS; ELDERLY POPULATION; HYPERTENSION; TORTUOSITY; GRAFTS; PREVALENCE; DISEASE; ABNORMALITIES; LEUKOARAIOSIS; ADAPTATION AB Venous tortuosity is associated with multiple disease states and is often thought to be a consequence of venous hypertension and chronic venous disease. However, the underlying mechanisms of vein tortuosity are unclear. We hypothesized that increased pressure causes vein buckling that leads to a tortuous appearance. The specific aim of this study was to determine the critical buckling pressure of veins. We determined the buckling pressure of porcine jugular veins and measured the mechanical properties of these veins. Our results showed that the veins buckle when the transmural pressure exceeds a critical pressure that is strongly related to the axial stretch ratio in the veins. The critical pressures of the eight veins tested were 14.2 +/- A 5.4 and 26.4 +/- A 9.0 mmHg at axial stretch ratio 1.5 and 1.7, respectively. In conclusion, veins buckle into a tortuous shape at high lumen pressures or reduced axial stretch ratios. Our results are useful in understanding the development of venous tortuosity associated with varicose veins, venous valvular insufficiency, diabetic retinopathy, and vein grafts. C1 [Martinez, Ricky; Fierro, Cesar A.; Han, Hai-Chao] Univ Texas San Antonio, Dept Mech Engn, San Antonio, TX 78249 USA. [Shireman, Paula K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Surg, San Antonio, TX 78229 USA. [Shireman, Paula K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Shireman, Paula K.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Han, HC (reprint author), Univ Texas San Antonio, Dept Mech Engn, San Antonio, TX 78249 USA. EM haichao.han@utsa.edu RI Han, Hai-Chao/B-5003-2012 FU CAREER [0646646]; National Science Foundation [0602834]; Veterans Administration; National Institute of Health [HL074236, HL095852] FX This work was supported by a CAREER award # 0646646 and a REU supplement from the National Science Foundation. It was also partially supported by research grants from NSF (0602834), the Veterans Administration, and the National Institute of Health (HL074236& HL095852). Wethank Dr. Yong-Ung Lee and Miss Danika Hayman for their help in this study. NR 44 TC 22 Z9 22 U1 0 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0090-6964 J9 ANN BIOMED ENG JI Ann. Biomed. Eng. PD APR PY 2010 VL 38 IS 4 BP 1345 EP 1353 DI 10.1007/s10439-010-9929-1 PG 9 WC Engineering, Biomedical SC Engineering GA 575DL UT WOS:000276046600007 PM 20094913 ER PT J AU Courtney, DM Kline, JA Kabrhel, C Moore, CL Smithline, HA Nordenholz, KE Richman, PB Plewa, MC AF Courtney, D. Mark Kline, Jeffrey A. Kabrhel, Christopher Moore, Christopher L. Smithline, Howard A. Nordenholz, Kristen E. Richman, Peter B. Plewa, Michael C. TI Clinical Features From the History and Physical Examination That Predict the Presence or Absence of Pulmonary Embolism in Symptomatic Emergency Department Patients: Results of a Prospective, Multicenter Study SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID DEEP-VEIN THROMBOSIS; D-DIMER; COMPUTED-TOMOGRAPHY; RISK-FACTORS; CRITERIA; PROBABILITY; MANAGEMENT; DIAGNOSIS; TRIAL; SCORE AB Study objective: Prediction rules for pulmonary embolism use variables explicitly shown to estimate the probability of pulmonary embolism. However, clinicians often use variables that have not been similarly validated, yet are implicitly believed to modify probability of pulmonary embolism. The objective of this study is to measure the predictive value of 13 implicit variables. Methods: Patients were enrolled in a prospective cohort study from 12 centers in the United States; all had an objective test for pulmonary embolism (D-dimer, computed tomographic angiography, or ventilation-perfusion scan). Clinical features including 12 predefined previously validated (explicit) variables and 13 variables not part of existing prediction rules (implicit) were prospectively recorded at presentation. The primary outcome was venous thromboembolism (pulmonary embolism or deep venous thrombosis), diagnosed by imaging up to 45 days after enrollment. Variables with adjusted odds ratios from logistic regression with 95% confidence intervals not crossing unity were considered significant. Results: Seven thousand nine hundred forty patients (7.2% venous thromboembolism positive) were enrolled. Mean age was 49 years (standard deviation 17 years) and 67% were female patients. Eight of 13 implicit variables were significantly associated with venous thromboembolism; those with an adjusted odds ratio (OR) greater than 1.5 included non-cancer-related thrombophilia (OR 1.99), pleuritic chest pain (OR 1.53), and family history of venous thromboembolism (OR 1.51). Implicit variables that predicted no venous thromboembolism outcome included substernal chest pain, female sex, and smoking. Nine of 12 explicit variables predicted a positive outcome of venous thromboembolism, including patient history of pulmonary embolism or deep venous thrombosis in the past, unilateral leg swelling, recent surgery, estrogen, hypoxemia, and active malignancy. Conclusion: In symptomatic outpatients being considered for possible pulmonary embolism, non-cancer-related thrombophilia, pleuritic chest pain, and family history of venous thromboembolism increase probability of pulmonary embolism or deep venous thrombosis. Other variables that are part of existing pretest probability systems were validated as important predictors in this diverse sample of US emergency department patients. [Ann Emerg Med. 2010;55:307-315.] C1 [Kline, Jeffrey A.] Carolinas Med Ctr, Dept Emergency Med, Charlotte, NC 28203 USA. [Courtney, D. Mark] Northwestern Univ, Dept Emergency Med, Chicago, IL 60611 USA. [Kabrhel, Christopher] Massachusetts Gen Hosp, Dept Emergency Serv, Boston, MA 02114 USA. [Moore, Christopher L.] Yale Univ, Dept Emergency Med, Med Ctr, New Haven, CT USA. [Smithline, Howard A.] Baystate Med Ctr, Dept Emergency Med, Springfield, MA USA. [Nordenholz, Kristen E.] Univ Colorado, Dept Surg, Sch Hlth Sci, Div Emergency Med, Denver, CO 80202 USA. [Richman, Peter B.] Mayo Clin Arizona, Dept Emergency Med, Scottsdale, AZ USA. [Plewa, Michael C.] St Vincent Mercy Med Ctr, Dept Emergency Med, Toledo, OH USA. RP Kline, JA (reprint author), Carolinas Med Ctr, Dept Emergency Med, 1000 Blythe Blvd, Charlotte, NC 28203 USA. EM jkline@carolinas.org OI Kabrhel, Christopher/0000-0002-8699-7176 FU National Institutes of Health [5K23HL077404(01-05), 1K23HL077404-01, 2R42HL074415-02A1, 5R42HL074415-03, R41HL074415, R42HL074415, R01HL074384] FX Funding and support: By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article that might create any potential conflict of interest. See the Manuscript Submission Agreement in this issue for examples of specific conflicts covered by this statement. National Institutes of Health grants 5K23HL077404(01-05) and 1K23HL077404-01 (Dr. Courtney) and 2R42HL074415-02A1, 5R42HL074415-03, R41HL074415, R42HL074415, and R01HL074384 (Dr. Kline). NR 21 TC 22 Z9 23 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD APR PY 2010 VL 55 IS 4 BP 307 EP 315 DI 10.1016/j.annemergmed.2009.11.010 PG 9 WC Emergency Medicine SC Emergency Medicine GA 582XL UT WOS:000276633700003 PM 20045580 ER PT J AU Marchick, MR Courtney, DM Kabrhel, C Nordenholz, KE Plewa, MC Richman, PB Smithline, HA Kline, JA AF Marchick, Michael R. Courtney, D. Mark Kabrhel, Christopher Nordenholz, Kristen E. Plewa, Michael C. Richman, Peter B. Smithline, Howard A. Kline, Jeffrey A. TI 12-Lead ECG Findings of Pulmonary Hypertension Occur More Frequently in Emergency Department Patients With Pulmonary Embolism Than in Patients Without Pulmonary Embolism SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID ELECTROCARDIOGRAPHIC FINDINGS; DISEASE; SCORE AB Study objective: Acute pulmonary embolism can produce abnormalities on ECG that reflect severity of pulmonary hypertension. Early recognition of these findings may alter the estimated pretest probability of pulmonary embolism and prompt more aggressive treatment before hemodynamic instability ensues, but it is first important to test whether these findings are specific to patients with pulmonary embolism. We hypothesize that ECG findings consistent with pulmonary hypertension would be observed more frequently in patients with pulmonary embolism. Methods: Secondary analysis of a prospective, observational cohort of emergency department patients who were tested for pulmonary embolism. ECGs were ordered at clinician's discretion and interpreted at presentation. Results: Six thousand forty-nine patients had an ECG, 354 (5.9%) of whom were diagnosed with pulmonary embolism. The frequency, positive likelihood ratio (LR+) and 95% confidence interval (CI) of each predictor were as follows: S1Q3T3 8.5% with pulmonary embolism versus 3.3% without pulmonary embolism (LR+ 3.7; 95% CI 2.5 to 5.4); nonsinus rhythm, 23.5% versus 16.6% (LR+ 1.4; 95% CI 1.2 to 1.7); inverted T waves in V1 to V2, 14.4% versus 8.1% (LR+ 1.8; 95% CI 1.3 to 2.3); inversion in V1 to V3, 10.5% versus 4.0% (LR+ 2.6; 95% CI 1.9 to 3.6); inversion in V1 to V4, 7.3% versus 2.0% (LR+ 3.7; 95% CI 2.4 to 5.5); incomplete right bundle branch block, 4.8% versus 2.8% (LR+ 1.7; 95% CI 1.0 to 2.7); tachycardia (pulse rate >100 beats/min), 28.8% versus 15.7% (LR+ 1.8; 95% CI 1.5 to 2.2). Likelihood ratios and specificities were similar when patients with previous cardiopulmonary disease were excluded from analysis. Conclusion: Findings of acute pulmonary hypertension were infrequent overall but were observed more frequently in patients with the final diagnosis of pulmonary embolism compared with patients who do not have pulmonary embolism. [Ann Emerg Med. 2010;55:331-335.] C1 [Marchick, Michael R.; Kline, Jeffrey A.] Carolinas Med Ctr, Dept Emergency Med, Charlotte, NC 28323 USA. [Courtney, D. Mark] Northwestern Univ, Dept Emergency Med, Chicago, IL 60611 USA. [Kabrhel, Christopher] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Nordenholz, Kristen E.] Univ Colorado, Dept Surg, Denver, CO 80202 USA. [Plewa, Michael C.] St Vincent Mercy Med, Dept Emergency Med, Toledo, OH USA. [Richman, Peter B.] Mayo Clin, Dept Emergency Med, Scottsdale, AZ USA. [Smithline, Howard A.] Baystate Med Ctr, Dept Emergency Med, Springfield, MA USA. RP Kline, JA (reprint author), Carolinas Med Ctr, Dept Emergency Med, POB 32861, Charlotte, NC 28323 USA. EM jkline@carolinas.org OI Kabrhel, Christopher/0000-0002-8699-7176 FU National Institutes of Health [R41HL074415, R42HL074415, K23HL077404, R01 HL074384] FX Funding and support: By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article that might create any potential conflict of interest. See the Manuscript Submission Agreement in this issue for examples of specific conflicts covered by this statement. Supported by grants from the National Institutes of Health, R41HL074415 and R42HL074415, K23HL077404 and R01 HL074384. NR 10 TC 7 Z9 8 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD APR PY 2010 VL 55 IS 4 BP 331 EP 335 DI 10.1016/j.annemergmed.2009.07.025 PG 5 WC Emergency Medicine SC Emergency Medicine GA 582XL UT WOS:000276633700006 PM 19766353 ER PT J AU Manzini, MC Rajab, A Maynard, TM Mochida, GH Tan, WH Nasir, R Hill, RS Gleason, D Al Saffar, M Partlow, JN Barry, BJ Vernon, M LaMantia, AS Walsh, CA AF Manzini, M. Chiara Rajab, Anna Maynard, Thomas M. Mochida, Ganeshwaran H. Tan, Wen-Hann Nasir, Ramzi Hill, R. Sean Gleason, Danielle Al Saffar, Muna Partlow, Jennifer N. Barry, Brenda J. Vernon, Mike LaMantia, Anthony-Samuel Walsh, Christopher A. TI Developmental and Degenerative Features in a Complicated Spastic Paraplegia SO ANNALS OF NEUROLOGY LA English DT Article ID 22Q11 DELETION SYNDROME; MOTOR-NEURON DISEASE; TROYER-SYNDROME; MENTAL-RETARDATION; LINKAGE ANALYSIS; RECESSIVE FORM; SPARTIN; LOCALIZATION; MUTATIONS; PROTEIN AB Objective: We sought to explore the genetic and molecular causes of Troyer syndrome, one of several complicated hereditary spastic paraplegias (HSPs). Troyer syndrome had been thought to be restricted to the Amish; however, we identified 2 Omani families with HSP, short stature, dysarthria and developmental delay-core features of Troyer syndrome and a novel mutation in the SPG20 gene, which is also mutated in the Amish. In addition, we analyzed SPG20 expression throughout development to infer how disruption of this gene might generate the constellation of developmental and degenerative Troyer syndrome phenotypes. Methods: Clinical characterization of 2 non-Amish families with Troyer syndrome was followed by linkage and sequencing analysis. Quantitative polymerase chain reaction and in situ hybridization analysis of SPG20 expression were carried out in embryonic and adult human and mouse tissue. Results: Two Omani families carrying a novel SPG20 mutation displayed clinical features remarkably similar to the Amish patients with Troyer syndrome. SPG20 mRNA is expressed broadly but at low relative levels in the adult brain; however, it is robustly and specifically expressed in the limbs, face, and brain during early morphogenesis. Interpretation: Null mutations in SPG20 cause Troyer syndrome, a specific clinical entity with developmental and degenerative features. Maximal expression of SPG20 in the limb buds and forebrain during embryogenesis may explain the developmental origin of the skeletal and cognitive defects observed in this disorder. ANN NEUROL 2010;67:516-525 C1 [Walsh, Christopher A.] Harvard Univ, Beth Israel Deaconess Med Ctr, Howard Hughes Med Inst, Div Genet,Childrens Hosp Boston,Med Sch, Boston, MA 02115 USA. [Manzini, M. Chiara; Mochida, Ganeshwaran H.; Hill, R. Sean; Al Saffar, Muna; Partlow, Jennifer N.; Barry, Brenda J.; Walsh, Christopher A.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Howard Hughes Med Inst,Dept Neurol, Boston, MA 02115 USA. [Rajab, Anna] Minist Hlth, Directorate Gen Hlth Affairs, Genet Unit, Muscat, Oman. [Maynard, Thomas M.; Vernon, Mike; LaMantia, Anthony-Samuel] Univ N Carolina, Sch Med, Dept Cell & Mol Physiol, Chapel Hill, NC USA. [Maynard, Thomas M.; Vernon, Mike; LaMantia, Anthony-Samuel] Univ N Carolina, Sch Med, UNC Neurosci Ctr, Chapel Hill, NC USA. [Mochida, Ganeshwaran H.] Massachusetts Gen Hosp, Pediat Neurol Unit, Boston, MA 02114 USA. [Maynard, Thomas M.; Mochida, Ganeshwaran H.; Tan, Wen-Hann; Gleason, Danielle; Al Saffar, Muna; Partlow, Jennifer N.; Barry, Brenda J.; Walsh, Christopher A.] Childrens Hosp, Manton Ctr Orphan Dis Res, Boston, MA 02115 USA. [Nasir, Ramzi] Childrens Hosp, Div Dev Med, Boston, MA 02115 USA. RP Walsh, CA (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Howard Hughes Med Inst, Div Genet,Childrens Hosp Boston,Med Sch, Room 14047-1,Ctr Life Sci Bldg,300 Longwood Ave C, Boston, MA 02115 USA. EM christopher.walsh@childrens.harvard.edu RI Maynard, Thomas/I-9039-2012; OI Maynard, Thomas/0000-0001-6976-3936; Manzini, M. Chiara/0000-0001-7175-1096 FU NINDS [RO1 NS 35129]; NICHD; Dubai Harvard Foundation for Medical Research; Manton Center for Orphan Disease Research; Muscular Dystrophy Association; University of North Carolina FX This work was supported by the NINDS (grant RO1 NS 35129, C.A.W.), NICHD (grant RO1 HD029178, A.-S.L.), the Dubai Harvard Foundation for Medical Research (C.A.W.), the Manton Center for Orphan Disease Research (C.A.W.), the Muscular Dystrophy Association (Development Grant, M.C.M.), and the University of North Carolina (Reynolds Faculty Fellowship, A.-S.L.). C.A.W. is an Investigator of the Howard Hughes Medical Institute. We thank the families for their cooperation and their hospitality; the local nurses and doctors for their assistance; Megumi Aita at the University of North Carolina In Situ Core for help with the in situ analysis; Daniel Rakiec at Children's Hospital, Boston for help with the sample preparation and analysis; and the following colleagues at Children's Hospital Boston for helpful discussion on the clinical features of the patients: Hope E. Dickinson, a speech pathologist from the Department of Otolaryngology and Communication Enhancement, and Janice Ware, a child psychologist and associate director of the Developmental Medicine Center. NR 27 TC 12 Z9 12 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD APR PY 2010 VL 67 IS 4 BP 516 EP 525 DI 10.1002/ana.21923 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 590HK UT WOS:000277215900016 PM 20437587 ER PT J AU Ruddy, KJ Gelber, S Shin, J Garber, JE Rosenberg, R Przypysny, M Partridge, AH AF Ruddy, K. J. Gelber, S. Shin, J. Garber, J. E. Rosenberg, R. Przypysny, M. Partridge, A. H. TI Genetic testing in young women with breast cancer: results from a Web-based survey SO ANNALS OF ONCOLOGY LA English DT Article DE BRCA1; BRCA2; breast neoplasms; female; genetic counseling; genetic polymorphism ID BRCA2 MUTATION; OVARIAN-CANCER; POPULATION; FERTILITY; SURVIVORS; CARRIERS; ISSUES; RISK AB Background: Young women with breast cancer have an increased risk for harboring a BRCA1 or BRCA2 mutation. Frequency of genetic testing and factors associated with testing have not been well described in this population. Patients and methods: We evaluated the rate of genetic testing among young breast cancer survivors identified through the Young Survival Coalition (YSC), an advocacy group for young women with breast cancer. Items regarding family history and genetic testing were included in a Web-based cross-sectional survey. Results: A total of 701 women were eligible based on a history of breast cancer diagnosed <= 40 years. Mean age at diagnosis was 32.9 years and mean age at survey 35.7 years. About 41% reported a first-or second-degree relative with breast or ovarian cancer. About 24% had undergone genetic testing, and 26% of those tested reported that a mutation was found. By multivariate logistic regression, likelihood of having undergone testing was higher in women who were younger at diagnosis, were more educated, had a first-or second-degree relative with breast or ovarian cancer, had a mastectomy rather than breast conservation, and considered themselves at high risk for a cancer-predisposing mutation. Conclusion: Most women diagnosed with breast cancer <= 40 years do not undergo genetic testing. C1 [Ruddy, K. J.; Gelber, S.; Garber, J. E.; Partridge, A. H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol,Breast Oncol Ctr, Boston, MA 02115 USA. [Shin, J.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Rosenberg, R.; Przypysny, M.] Young Survival Coalit, New York, NY USA. RP Ruddy, KJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol,Breast Oncol Ctr, 44 Binney St, Boston, MA 02115 USA. EM kruddy@partners.org FU Dana-Farber Cancer Institute FX Dana-Farber Cancer Institute. NR 23 TC 12 Z9 12 U1 1 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD APR PY 2010 VL 21 IS 4 BP 741 EP 747 DI 10.1093/annonc/mdp355 PG 7 WC Oncology SC Oncology GA 575DG UT WOS:000276045600010 PM 19713245 ER PT J AU Boss, DS Schwartz, GK Middleton, MR Amakye, DD Swaisland, H Midgley, RS Ranson, M Danson, S Calvert, H Plummer, R Morris, C Carvajal, RD Chirieac, LR Schellens, JHM Shapiro, GI AF Boss, D. S. Schwartz, G. K. Middleton, M. R. Amakye, D. D. Swaisland, H. Midgley, R. S. Ranson, M. Danson, S. Calvert, H. Plummer, R. Morris, C. Carvajal, R. D. Chirieac, L. R. Schellens, J. H. M. Shapiro, G. I. TI Safety, tolerability, pharmacokinetics and pharmacodynamics of the oral cyclin-dependent kinase inhibitor AZD5438 when administered at intermittent and continuous dosing schedules in patients with advanced solid tumours SO ANNALS OF ONCOLOGY LA English DT Editorial Material DE AZD5438; cyclin-dependent kinase inhibitor; hair follicle analysis; pharmacodynamics ID HEALTHY MALE-VOLUNTEERS; CELL-CYCLE; RETINOBLASTOMA PROTEIN; PHASE-I; CANCER; PHOSPHORYLATION; FLAVOPIRIDOL; INACTIVATION; CARBOPLATIN; APOPTOSIS AB Background: AZD5438 is an orally bioavailable inhibitor of cyclin E-cdk2, cyclin A-cdk2 and cyclin B-cdk1 complexes. Three phase I studies assessed the clinical safety, tolerability, pharmacokinetics and pharmacodynamics of AZD5438 when administered in different dosing schedules. Patients and methods: AZD5438 was administered four times daily, once every 7 days (study 1), for 14 consecutive days followed by 7 days of rest (study 2), or continuously (study 3), to patients with advanced solid tumours. Dose escalation proceeded until the emergence of dose-limiting toxic effects. Results: Sixty-four patients were included across the three studies (19, 17 and 28, respectively). Nausea and vomiting were the most common adverse events. When dosed continuously, 40 mg four times daily was considered intolerable, and due to safety issues, all studies were terminated prematurely. Consequently, no intolerable dose was identified during the weekly schedule. Pharmacokinetics demonstrated dose-proportional exposure, high interpatient variability and accumulation after multiple doses. Skin biopsies indicated reduced retinoblastoma protein phosphorylation at cdk2 phospho-sites; other pharmacodynamic assessments did not reveal consistent trends. Conclusions: AZD5438 was generally well tolerated in a weekly dosing schedule, but not in continuous schedules. The clinical development programme for AZD5438 was discontinued owing to tolerability and exposure data from these studies. C1 [Boss, D. S.; Schellens, J. H. M.] Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, Dept Med Oncol, NL-1066 CX Amsterdam, Netherlands. [Schwartz, G. K.; Carvajal, R. D.] Mem Sloan Kettering Canc Ctr, Gastrointestinal Oncol Serv, New York, NY 10021 USA. [Middleton, M. R.; Midgley, R. S.] Oxford Radcliffe Hosp, Dept Oncol, Oxford, England. [Middleton, M. R.; Midgley, R. S.] Oxford Radcliffe Hosp, Dept Clin Pharmacol, Oxford, England. [Amakye, D. D.; Swaisland, H.; Morris, C.] AstraZeneca, Macclesfield, Cheshire, England. [Ranson, M.] Christie Hosp NHS Trust, Derek Crowther Clin Trials Unit, Manchester M20 4BX, Lancs, England. [Danson, S.] Univ Manchester, Paterson Inst Canc Res, Manchester, Lancs, England. [Calvert, H.; Plummer, R.] Newcastle Gen Hosp, No Ctr Canc Treatment, Newcastle Upon Tyne NE4 6BE, Tyne & Wear, England. [Chirieac, L. R.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Chirieac, L. R.; Shapiro, G. I.] Harvard Univ, Sch Med, Boston, MA USA. [Shapiro, G. I.] Dana Farber Canc Inst, Dept Med Oncol, Early Drug Dev Ctr, Boston, MA 02115 USA. [Shapiro, G. I.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Schellens, JHM (reprint author), Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, Dept Med Oncol, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands. EM jhm@nki.nl FU NCI NIH HHS [P20 CA90578, R01 CA90687, R01 CA090687] NR 24 TC 19 Z9 19 U1 2 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD APR PY 2010 VL 21 IS 4 BP 884 EP 894 DI 10.1093/annonc/mdp377 PG 11 WC Oncology SC Oncology GA 575DG UT WOS:000276045600033 PM 19825886 ER PT J AU Bilimoria, KY Bentrem, DJ Talamonti, MS Stewart, AK Winchester, DP Ko, CY AF Bilimoria, Karl Y. Bentrem, David J. Talamonti, Mark S. Stewart, Andrew K. Winchester, David P. Ko, Clifford Y. TI Risk-based Selective Referral for Cancer Surgery A Potential Strategy to Improve Perioperative Outcomes SO ANNALS OF SURGERY LA English DT Article ID HIGH-VOLUME HOSPITALS; LONG-TERM SURVIVAL; UNITED-STATES; SURGICAL OUTCOMES; OPERATIVE MORTALITY; HEALTH-CARE; QUALITY; REGIONALIZATION; EXPERIENCE; COMORBIDITY AB Background: Studies have demonstrated volume-outcome relationships for numerous operations, providing an impetus for regionalization; however, volume-based regionalization may not be feasible or necessary. Our objective was to determine if low-risk patients undergoing surgery at Community Hospitals have perioperative mortality rates comparable with Specialized Centers. Methods: From the National Cancer Data Base, 940,718 patients from similar to 1430 hospitals were identified who underwent resection for 1 of 15 cancers (2003-2005). Patients were stratified by preoperative risk according to age and comorbidities. Separately for each cancer, regression modeling stratified by high-and low-risk groups was used to compare 60-day mortality at Specialized Centers (National Cancer Institute-designated and/or highest-volume quintile institutions), Other Academic Institutions (lower-volume, non-National Cancer Institute), and Community Hospitals. Results: Low-risk patients had statistically similar perioperative mortality rates at Specialized Centers and Community Hospitals for 13 of 15 operations. High-risk patients had significantly lower perioperative mortality rates at Specialized Centers compared with Community Hospitals for 9 of 15 cancers. Regardless of risk group, perioperative mortality rates were significantly lower for pancreatectomy and esophagectomy at Specialized Centers. Risk-based referral compared with volume-based regionalization of most patients would require fewer patients to change to Specialized Centers. Conclusions: Perioperative mortality for low-risk patients was comparable at Specialized Centers and Community Hospitals for all cancers except esophageal and pancreatic, thus questioning volume-based regionalization of all patients. Rather, only high-risk patients may need to change hospitals. Mortality rates could be reduced if factors at Specialized Centers resulting in better outcomes for high-risk patients can be identified and transferred to other hospitals. C1 [Bilimoria, Karl Y.; Stewart, Andrew K.; Winchester, David P.; Ko, Clifford Y.] Amer Coll Surg, Div Res & Optimal Patient Care, Canc Programs, Chicago, IL 60611 USA. [Bilimoria, Karl Y.; Bentrem, David J.; Winchester, David P.] Northwestern Univ, Dept Surg, Feinberg Sch Med, Chicago, IL 60611 USA. [Talamonti, Mark S.; Winchester, David P.] NorthShore Univ Hlth Syst, Dept Surg, Evanston, IL USA. [Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Bilimoria, KY (reprint author), Amer Coll Surg, Div Res & Optimal Patient Care, Canc Programs, 633 N St Clair St,22nd Floor, Chicago, IL 60611 USA. EM kbilimoria@facs.org FU Northwestern University (KYB); American Cancer Society FX Supported by the American College of Surgeons Clinical Scholars in Residence Program and a Priority Grant from Northwestern University (KYB). The NCDB is supported by the American College of Surgeons, Commission on Cancer, and the American Cancer Society. NR 51 TC 27 Z9 27 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 APR PY 2010 VL 251 IS 4 BP 708 EP 716 DI 10.1097/SLA.0b013e3181c1bea2 PG 9 WC Surgery SC Surgery GA 580QS UT WOS:000276464900020 PM 19898231 ER PT J AU Singhal, S Ferraris, VA Bridges, CR Clough, ER Mitchell, JD Fernando, HC Shrager, JB AF Singhal, Sunil Ferraris, Victor A. Bridges, Charles R. Clough, Ellen R. Mitchell, John D. Fernando, Hiran C. Shrager, Joseph B. TI Management of Alveolar Air Leaks After Pulmonary Resection SO ANNALS OF THORACIC SURGERY LA English DT Review ID AUTOLOGOUS BLOOD PATCH; CHEST TUBE MANAGEMENT; LUNG RESECTION; WATER SEAL; SPONTANEOUS PNEUMOTHORAX; BRONCHOPLEURAL FISTULA; REDUCTION SURGERY; RANDOMIZED-TRIAL; SPACE PROBLEMS; RISK-FACTORS AB Air leaks are a common problem after pulmonary resection and can be a source of significant morbidity and mortality. Air leaks are associated with prolonged hospital stays, and infectious and cardiopulmonary complications, and they occasionally require reoperation. Despite reasonably robust literature on the topic, the optimal approaches to manage postoperative air leaks remain controversial. We used available literature and expert consensus to formulate suggestions regarding the preferred approaches to both routine and prolonged alveolar air leaks. This review summarizes our findings. (Ann Thorac Surg 2010;89:1327-35) (C) 2010 by The Society of Thoracic Surgeons C1 Univ Penn, Sch Med, Div Thorac Surg, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Div Cardiovasc Surg, Philadelphia, PA 19104 USA. Univ Kentucky, Albert B Chandler Med Ctr, Div Cardiovasc & Thorac Surg, Lexington, KY 40536 USA. Soc Thorac Surg, Chicago, IL USA. Univ Colorado, Sch Med, Dept Surg, Div Cardiothorac Surg, Denver, CO USA. Boston Med Ctr, Dept Cardiothorac Surg, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Stanford Univ, Sch Med, Dept Cardiothorac Surg, Div Thorac Surg, Stanford, CA 94305 USA. Palo Alto Vet Affairs Hlth Care Syst, Palo Alto, CA USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Shrager, JB (reprint author), Falk Bldg,2nd Fl,300 Pasteur Dr, Stanford, CA 94305 USA. EM shrager@stanford.edu OI Fernando, Hiran/0000-0002-5330-7036 NR 65 TC 21 Z9 22 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD APR PY 2010 VL 89 IS 4 BP 1327 EP 1335 DI 10.1016/j.athoracsur.2009.09.020 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 573CK UT WOS:000275885800068 PM 20338378 ER PT J AU Penney, KL Sinnott, JA Falla, K Pawitan, Y Hoshida, Y Kraft, P Fiorentino, M Perner, S Finn, S Calza, S Flavin, R Freedman, ML Setlur, S Andersson, SO Martin, N Kantoff, PW Johansson, JE Adami, HO Rubin, M Loda, M Golub, TR Andre, O Stampfer, MJ Mucci, LA AF Penney, Kathryn L. Sinnott, Jennifer A. Falla, Katja Pawitan, Yudi Hoshida, Yujin Kraft, Peter Fiorentino, Michelangelo Perner, Sven Finn, Stephen Calza, Stefano Flavin, Richard Freedman, Matthew L. Setlur, Sunita Andersson, Swen-Olof Martin, Neil Kantoff, Philip W. Johansson, Jan-Erik Adami, Hans-Olov Rubin, Mark Loda, Massimo Golub, Todd R. Andre, Ove Stampfer, Meir J. Mucci, Lorelei A. TI DEFINING AN mRNA EXPRESSION SIGNATURE OF GLEASON GRADE SO ANTICANCER RESEARCH LA English DT Meeting Abstract C1 [Penney, Kathryn L.; Falla, Katja; Kraft, Peter; Adami, Hans-Olov; Stampfer, Meir J.; Mucci, Lorelei A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Penney, Kathryn L.; Sinnott, Jennifer A.; Stampfer, Meir J.; Mucci, Lorelei A.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [Penney, Kathryn L.; Sinnott, Jennifer A.; Stampfer, Meir J.; Mucci, Lorelei A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Falla, Katja; Pawitan, Yudi; Calza, Stefano; Adami, Hans-Olov] Karolinska Inst, Dept Med Epidemiol & Biostatist, Stockholm, Sweden. [Hoshida, Yujin; Freedman, Matthew L.; Loda, Massimo; Golub, Todd R.] Broad Inst, Cambridge, MA USA. [Fiorentino, Michelangelo; Finn, Stephen; Flavin, Richard; Loda, Massimo] Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. [Perner, Sven] Univ Ulm, Dept Pathol, Ulm, Germany. Univ Brescia, Dept Biomed Sci & Biotechnol, Brescia, Italy. [Freedman, Matthew L.; Kantoff, Philip W.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Setlur, Sunita; Loda, Massimo; Andre, Ove] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Andersson, Swen-Olof; Johansson, Jan-Erik] Orebro Univ Hosp, Dept Urol, Orebro, Sweden. [Martin, Neil] Harvard Radiat Oncol Program, Dept Radiat Oncol, Boston, MA USA. [Rubin, Mark] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY USA. [Golub, Todd R.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RI Calza, Stefano/B-1915-2010; Martin, Neil/E-2193-2014 OI Calza, Stefano/0000-0003-4996-7995; Martin, Neil/0000-0002-8164-8516 NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD APR PY 2010 VL 30 IS 4 MA 276 BP 1534 EP 1535 PG 2 WC Oncology SC Oncology GA 609VS UT WOS:000278686600305 ER PT J AU Kasperzyk, J Finn, S Hendrickson, W Flavin, R Fiorentino, M Giovannucci, E Stampfer, M Loda, M Mucci, L AF Kasperzyk, Julie Finn, Stephen Hendrickson, Whitney Flavin, Richard Fiorentino, Michelangelo Giovannucci, Edward Stampfer, Meir Loda, Massimo Mucci, Lorelei TI PROSTATE-SPECIFIC MEMBRANE ANTIGEN (PSMA) EXPRESSION AND PROSTATE CANCER SURVIVAL SO ANTICANCER RESEARCH LA English DT Meeting Abstract C1 [Kasperzyk, Julie; Hendrickson, Whitney; Giovannucci, Edward; Stampfer, Meir; Mucci, Lorelei] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Kasperzyk, Julie; Giovannucci, Edward; Stampfer, Meir; Mucci, Lorelei] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Loda, Massimo] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Loda, Massimo] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Finn, Stephen; Flavin, Richard; Fiorentino, Michelangelo; Loda, Massimo] Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. [Fiorentino, Michelangelo] St Orsola Marcello Malpighi Hosp, Addari Inst Oncol, Pathol Unit, Bologna, Italy. NR 0 TC 0 Z9 0 U1 0 U2 1 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD APR PY 2010 VL 30 IS 4 MA 277 BP 1535 EP 1536 PG 2 WC Oncology SC Oncology GA 609VS UT WOS:000278686600306 ER PT J AU Asgari, MM Chren, MM Warton, EM Friedman, GD White, E AF Asgari, Maryam M. Chren, Mary-Margaret Warton, E. Margaret Friedman, Gary D. White, Emily TI Association Between Nonsteroidal Anti-inflammatory Drug Use and Cutaneous Squamous Cell Carcinoma SO ARCHIVES OF DERMATOLOGY LA English DT Article ID NONMELANOMA SKIN-CANCER; HAIRLESS MICE; CYCLOOXYGENASE-2 INHIBITOR; COLORECTAL ADENOMAS; LIFE-STYLE; COHORT; RISK; PHOTOCARCINOGENESIS; INDOMETHACIN; METAANALYSIS AB Objective: To examine the association between nonsteroidal anti-inflammatory drug (NSAID) use and cutaneous squamous cell carcinoma (SCC). Design: Retrospective case-control study. Setting: Kaiser Permanente Northern California(KPNC), a large population based-health maintenance organization. Patients: Random sample of 415 KPNC members diagnosed as having a pathologically verified SCC in 2004 and 415 age-, sex-, and race-matched controls with no history of skin cancer. Main Exposure Measure: Self-reported NSAID use in the 10 years prior to baseline. Use of NSAIDs was categorized based on type (any NSAIDs, aspirin, ibuprofen, and nonaspirin NSAIDs). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression to estimate the association of SCC with regular use, dose, and duration of exposure to the different NSAID types. Information on pharmacy-dispensed NSAIDs was also examined to assess its association with SCC risk. Models were adjusted for all ascertained SCC risk factors (fully adjusted model) and only those variables associated with both SCC risk and NSAID use (parsimonious model). Results: Fully adjusted analyses showed no statistically significant reduction in SCC risk with self-reported regular use of any NSAID (OR, 1.32; 95% CI, 0.92-1.89), aspirin (OR, 1.38; 95% CI, 0.96-1.97), ibuprofen (OR, 0.74; 95% CI, 0.46-1.19), or nonaspirin NSAIDs (OR, 0.84; 95% CI, 0.56-1.26). Analyses examining duration, dose, and variables combining duration and dose of NSAID exposure did not appreciably change results. An analysis using the parsimonious model showed similar results. The data on pharmacy-dispensed NSAIDs also showed no association with SCC risk. Conclusion: Neither self-reported nor pharmacy-dispensed NSAID exposure was associated with cutaneous SCC risk. Arch Dermatol. 2010; 146(4): 388-395 C1 [Asgari, Maryam M.; Warton, E. Margaret; Friedman, Gary D.] Kaiser Permanente No Calif, Div Res, Oakland, CA 94612 USA. [Asgari, Maryam M.; Chren, Mary-Margaret] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [Friedman, Gary D.] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA. [White, Emily] Univ Washington, Dept Epidemiol, Med Ctr, Seattle, WA 98195 USA. [White, Emily] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA. [Chren, Mary-Margaret] San Francisco VA Med Ctr, Hlth Serv Res Enhancement Award Program, San Francisco, CA USA. RP Asgari, MM (reprint author), Kaiser Permanente No Calif, Div Res, 2000 Broadway, Oakland, CA 94612 USA. EM maryam.m.asgari@kp.org RI Asgari, Maryam/O-4947-2016 FU National Institute of Arthritis Musculoskeletal and Skin Diseases [K23 AR 051037, K24 AR 052667]; National Cancer Institute [R01 CA 098838] FX Funding/Support: This study was supported by grants from the National Institute of Arthritis Musculoskeletal and Skin Diseases (K23 AR 051037 [Dr Asgari] and K24 AR 052667 [Dr Chren]) and from the National Cancer Institute (R01 CA 098838 [Dr Friedman]). NR 25 TC 18 Z9 19 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD APR PY 2010 VL 146 IS 4 BP 388 EP 395 PG 8 WC Dermatology SC Dermatology GA 585GS UT WOS:000276813500005 PM 20157019 ER PT J AU Watson, AJ Bergman, H Williams, CM Kvedar, JC AF Watson, Alice J. Bergman, Hagit Williams, Christy M. Kvedar, Joseph C. TI A Randomized Trial to Evaluate the Efficacy of Online Follow-up Visits in the Management of Acne SO ARCHIVES OF DERMATOLOGY LA English DT Article ID DIGITAL SKIN IMAGES; TELEDERMATOLOGY; PATIENT; DERMATOLOGISTS; SATISFACTION; TIMES; LONG; TOO AB Objective: To evaluate whether delivering acne follow-up care via an asynchronous, remote online visit (e-visit) platform produces equivalent clinical outcomes to office care. Design: A prospective, randomized controlled study. Setting: Two teaching hospitals in Boston between September 2005 and May 2007. Participants: A total of 151 patients with mild to moderate facial acne. Interventions: Subjects were asked to carry out 4 follow-up visits using either an e-visit platform or conventional office care. At 6-week intervals, subjects in the e-visit group were prompted to send images of their skin and an update, via a secure Web site, to their dermatologist. Dermatologists responded with advice and electronic prescriptions. Main Outcome Measures: The primary outcome measure was change in total inflammatory lesion count between the first and last visit. The major secondary outcomes were subject and dermatologist satisfaction with care and length of time to complete visits. Results: The mean age of subjects was 28 years; most were female (78%), white (65%), and college educated (69%). One hundred twenty-one of the initial 151 subjects completed the study. The decrease in total inflammatory lesion count was similar in the e-visit and office visit groups (6.67 and 9.39, respectively) (P = .49). Both subjects and dermatologists reported comparable satisfaction with care regardless of visit type (P = .06 and P = .16, respectively). Compared with office visits, e-visits were time saving for subjects and time neutral for dermatologists (4 minutes, 8 seconds vs 4 minutes, 42 seconds) (P = .57). Conclusion: Delivering follow-up care to acne patients via an e-visit platform produced clinical outcomes equivalent to those of conventional office visits. C1 Ctr Connected Hlth, Boston, MA USA. Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Watson, AJ (reprint author), 25 New Chardon St,Ste 400D, Boston, MA 02114 USA. EM ajwatson@partners.org FU Information Systems Research Council at Partners Healthcare, Boston, Massachusetts FX Funding/Support: This study was supported in part by a grant from the Information Systems Research Council at Partners Healthcare, Boston, Massachusetts. NR 16 TC 25 Z9 25 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD APR PY 2010 VL 146 IS 4 BP 406 EP 411 PG 6 WC Dermatology SC Dermatology GA 585GS UT WOS:000276813500007 PM 20404229 ER PT J AU Binder, EB Owens, MJ Liu, W Deveau, TC Rush, AJ Trivedi, MH Fava, M Bradley, B Ressler, KJ Nemeroff, CB AF Binder, Elisabeth B. Owens, Michael J. Liu, Wei Deveau, Todd C. Rush, A. John Trivedi, Madhukar H. Fava, Maurizio Bradley, Bekh Ressler, Kerry J. Nemeroff, Charles B. TI Association of Polymorphisms in Genes Regulating the Corticotropin-Releasing Factor System With Antidepressant Treatment Response SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID STAR-ASTERISK-D; FACTOR-LIKE IMMUNOREACTIVITY; MAJOR DEPRESSIVE DISORDER; ELECTROCONVULSIVE-THERAPY; PARAVENTRICULAR NUCLEUS; ELEVATED CONCENTRATIONS; ARGININE-VASOPRESSIN; EXPRESSING NEURONS; BINDING-PROTEIN; MOOD DISORDERS AB Context: The corticotropin-releasing factor (CRF, or corticotropin-releasing hormone) and arginine vasopressin systems have been implicated in the pathophysiology of anxiety and depressive disorders and response to antidepressant treatment. Objective: To study the association of genetic variants in 10 genes that regulate the CRF and arginine vasopressin systems with treatment response to citalopram in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) sample (N=1768). Design: Pharmacogenetic association study derived from the STAR*D study, a multicenter, prospective, open, 12-week effectiveness trial. Setting: Out patient primary care and psychiatric clinics. Patients: Individuals with nonpsychotic major depressive disorder for whom DNA was available who were subsequently treated with citalopram hydrobromide for 4 to 12 weeks. Intervention: Flexible doses of citalopram. Main Outcome Measure: Association of genetic polymorphisms in genes encoding the CRF system with response and remission to citalopram treatment at exit visit. Results: One single-nucleotide polymorphism (SNP) (rs10473984) within the CRHBP locus showed a significant association with both remission (P=6.0 x 10(-6); corrected, P=.0026) and reduction in depressive symptoms (P=7.0 x 10(-7); corrected, P=.00031) in response to citalopram. The T allele of this SNP was associated with poorer treatment outcome in 2 of the 3 ethnic subsamples (African American and Hispanic), despite large differences in minor allele frequency. This association was more pronounced in patients with features of anxious depression (P=.008). The nonresponse allele was shown to be associated with overall higher plasma corticotropin levels and more pronounced dexamethasone suppression of corticotropin. Conclusions: These data indicate that a genetic variant within the CRHBP locus affects response to citalopram in African American and Hispanic patients, suggesting a role for this gene and for the CRF system in antidepressant treatment response. C1 [Binder, Elisabeth B.] Max Planck Inst Psychiat, D-80804 Munich, Germany. [Binder, Elisabeth B.; Owens, Michael J.; Liu, Wei; Deveau, Todd C.; Bradley, Bekh; Ressler, Kerry J.] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA USA. [Binder, Elisabeth B.] Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA USA. [Liu, Wei] Beijing Inst Microbiol & Epidemiol, State Key Lab Pathogen & Biosecur, Beijing, Peoples R China. [Rush, A. John; Trivedi, Madhukar H.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Rush, A. John; Trivedi, Madhukar H.] Duke NUS Grad Med Sch Singapore, Singapore, Singapore. [Fava, Maurizio] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Bradley, Bekh] Atlanta VA Med Ctr, Atlanta, GA USA. [Ressler, Kerry J.] Yerkes Natl Primate Res Ctr, Atlanta, GA USA. [Ressler, Kerry J.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Nemeroff, Charles B.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. RP Binder, EB (reprint author), Max Planck Inst Psychiat, Kraepelinstr 2-10, D-80804 Munich, Germany. EM ebinder@emory.edu RI Owens, Michael/G-5191-2012; Bradley, Bekh/H-8399-2012; Binder, Elisabeth/K-8905-2014; OI Rush, Augustus/0000-0003-2004-2382; Ressler, Kerry/0000-0002-5158-1103 FU GlaxoSmithKline; National Institutes of Health [MH-90003, MH-077083-01, MH-58922]; Doris Duke Clinical Scientist Development Award FX This work was supported by GlaxoSmithKline; grants MH-90003, MH-077083-01, and MH-58922 from the National Institutes of Health; and the Doris Duke Clinical Scientist Development Award. NR 51 TC 57 Z9 62 U1 1 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD APR PY 2010 VL 67 IS 4 BP 369 EP 379 PG 11 WC Psychiatry SC Psychiatry GA 578RM UT WOS:000276312800007 PM 20368512 ER PT J AU Krainc, D AF Krainc, Dimitri TI Clearance of Mutant Proteins as a Therapeutic Target in Neurodegenerative Diseases SO ARCHIVES OF NEUROLOGY LA English DT Review ID HISTONE DEACETYLASE INHIBITORS; INCLUSION-BODY FORMATION; HUNTINGTONS-DISEASE; AUTOPHAGY; MICE; ACETYLATION; DEGRADATION; SYSTEM; AGGREGATION; DYSFUNCTION AB Accumulation and aggregation of disease-causing proteins is a hallmark of several neurodegenerative disorders such as Parkinson, Alzheimer, and Huntington diseases. One of the main goals of research in neurodegenerative disorders has been to improve clearance of these accumulated proteins. Using the example of Huntington disease, I discuss strategies to selectively activate cellular degradation machinery to improve clearance of the mutant protein and to identify therapeutic targets for the treatment of Huntington disease and related neurodegenerative disorders. Arch Neurol. 2010; 67(4): 388-392 C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. RP Krainc, D (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,MassGen Inst Neurodegenerat Dis, 114 16th St,Room 2007, Charlestown, MA 02129 USA. EM dkrainc@partners.org NR 36 TC 16 Z9 17 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD APR PY 2010 VL 67 IS 4 BP 388 EP 392 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 581XQ UT WOS:000276559500002 PM 20385902 ER PT J AU Berson, EL Rosner, B Sandberg, MA Weigel-DiFranco, C Brockhurst, RJ Hayes, KC Johnson, EJ Anderson, EJ Johnson, CA Gaudio, AR Willett, WC Schaefer, EJ AF Berson, Eliot L. Rosner, Bernard Sandberg, Michael A. Weigel-DiFranco, Carol Brockhurst, Robert J. Hayes, K. C. Johnson, Elizabeth J. Anderson, Ellen J. Johnson, Chris A. Gaudio, Alexander R. Willett, Walter C. Schaefer, Ernst J. TI Clinical Trial of Lutein in Patients With Retinitis Pigmentosa Receiving Vitamin A SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID HUMPHREY FIELD ANALYZER; HUMAN MACULAR PIGMENT; DOCOSAHEXAENOIC ACID; PRIMATE RETINAS; CATARACT-EXTRACTION; CAROTENOID INTAKE; PLUS ZEAXANTHIN; NATIONAL-HEALTH; VISUAL-FIELDS; BETA-CAROTENE AB Objective: To determine whether lutein supplementation will slow visual function decline in patients with retinitis pigmentosa receiving vitamin A. Design: Randomized, controlled, double-masked trial of 225 nonsmoking patients, aged 18 to 60 years, evaluated over a 4-year interval. Patients received 12 mg of lutein or a control tablet daily. All were given 15 000 IU/d of vitamin A palmitate. Randomization took into account genetic type and baseline serum lutein level. Main Outcome Measures: The primary outcome was the total point score for the Humphrey Field Analyzer (HFA) 30-2 program; prespecified secondary outcomes were the total point scores for the 60-4 program and for the 30-2 and 60-4 programs combined, 30-Hz electroretinogram amplitude, and Early Treatment Diabetic Retinopathy Study acuity. Results: No significant difference in rate of decline was found between the lutein plus vitamin A and control plus vitamin A groups over a 4-year interval for the HFA 30-2 program. For the HFA 60-4 program, a decrease in mean rate of sensitivity loss was observed in the lutein plus vitamin A group (P=.05). Mean decline with the 60-4 program was slower among those with the highest serum lutein level or with the highest increase in macular pigment optical density at follow-up(P=.01 and P=.006, respectively). Those with the highest increase in macular pigment optical density also had the slowest decline in HFA 30-2 and 60-4 combined field sensitivity (P=.005). No significant toxic effects of lutein supplementation were observed. Conclusion: Lutein supplementation of 12 mg/d slowed loss of mid peripheral visual field on average among non smoking adults with retinitis pigmentosa taking vitamin A. Application to Clinical Practice: Data are presented that support use of 12 mg/d of lutein to slow visual field loss among nonsmoking adults with retinitis pigmentosa taking vitamin A. C1 [Berson, Eliot L.; Rosner, Bernard; Sandberg, Michael A.; Weigel-DiFranco, Carol; Brockhurst, Robert J.; Anderson, Ellen J.; Gaudio, Alexander R.] Harvard Univ, Berman Gund Lab Study Retinal Degenerat, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Johnson, Elizabeth J.] Tufts Univ, Carotenoids & Hlth Lab, Medford, MA 02155 USA. [Schaefer, Ernst J.] Tufts Univ, Jean Mayer USDA, Human Nutr Res Ctr Aging, Lipid Metab Lab, Medford, MA 02155 USA. [Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Hayes, K. C.] Brandeis Univ, Foster Biomed Res Lab, Waltham, MA 02254 USA. [Johnson, Chris A.] Univ Iowa, Dept Ophthalmol, Iowa City, IA 52242 USA. RP Berson, EL (reprint author), Massachusetts Eye & Ear Infirm, Berman Gund Lab, 243 Charles St, Boston, MA 02114 USA. EM linda_berard@meei.harvard.edu FU National Eye Institute, Bethesda, Maryland [U10EY13945]; Foundation Fighting Blindness, Owings Mills, Maryland FX This research was supported by grant U10EY13945 from the National Eye Institute, Bethesda, Maryland, and in part by the Foundation Fighting Blindness, Owings Mills, Maryland. NR 47 TC 57 Z9 61 U1 1 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD APR PY 2010 VL 128 IS 4 BP 403 EP 411 PG 9 WC Ophthalmology SC Ophthalmology GA 581YC UT WOS:000276560800001 PM 20385935 ER PT J AU Rubin, BP Cooper, K Fletcher, CDM Folpe, AL Gannon, FH Hunt, JL Lazar, AJ Montag, AG Peabody, TD Pollock, RE Reith, JD Qualman, SJ Rosenberg, AE Weiss, SW Krausz, T AF Rubin, Brian P. Cooper, Kumarasen Fletcher, Christopher D. M. Folpe, Andrew L. Gannon, Francis H. Hunt, Jennifer L. Lazar, Alexander J. Montag, Anthony G. Peabody, Terrance D. Pollock, Raphael E. Reith, John D. Qualman, Stephen J. Rosenberg, Andrew E. Weiss, Sharon W. Krausz, Thomas CA Canc Comm Coll Amer Pathologists TI Protocol for the Examination of Specimens From Patients With Tumors of Soft Tissue SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID SARCOMAS C1 [Rubin, Brian P.] Cleveland Clin, Dept Anat Pathol, Lerner Res Inst, Cleveland, OH 44195 USA. [Rubin, Brian P.] Cleveland Clin, Dept Mol Genet, Lerner Res Inst, Cleveland, OH 44195 USA. [Rubin, Brian P.] Taussig Canc Ctr, Cleveland, OH USA. [Cooper, Kumarasen] Univ Vermont, Dept Pathol, Burlington, VT 05405 USA. [Cooper, Kumarasen] Fletcher Allen Hlth Care, Burlington, VT USA. [Fletcher, Christopher D. M.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Folpe, Andrew L.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Gannon, Francis H.] Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. [Hunt, Jennifer L.; Rosenberg, Andrew E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Lazar, Alexander J.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Sarcoma Res Ctr, Houston, TX 77030 USA. [Pollock, Raphael E.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Sarcoma Res Ctr, Houston, TX 77030 USA. [Montag, Anthony G.; Krausz, Thomas] Univ Chicago, Med Ctr, Dept Pathol, Chicago, IL 60637 USA. [Peabody, Terrance D.] Univ Chicago, Med Ctr, Dept Orthopaed Surg, Chicago, IL 60637 USA. [Reith, John D.] Univ Florida, Dept Pathol Immunol & Lab Med, Gainesville, FL USA. [Qualman, Stephen J.] Childrens Hosp, Dept Lab Med, Columbus, OH 43205 USA. [Weiss, Sharon W.] Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. RP Rubin, BP (reprint author), Cleveland Clin, Dept Anat Pathol, Lerner Res Inst, L25,9500 Euclid Ave, Cleveland, OH 44195 USA. EM rubinb2@ccf.org RI Lazar, Alexander/A-3416-2008 OI Lazar, Alexander/0000-0002-6395-4499 NR 12 TC 12 Z9 13 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD APR PY 2010 VL 134 IS 4 BP E31 EP E39 PG 9 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 580EK UT WOS:000276429800006 PM 20367297 ER PT J AU Rubin, BP Antonescu, CR Gannon, FH Hunt, JL Inwards, CY Klein, MJ Kneisl, JS Montag, AG Peabody, TD Reith, JD Rosenberg, AE Krausz, T AF Rubin, Brian P. Antonescu, Cristina R. Gannon, Francis H. Hunt, Jennifer Leigh Inwards, Carrie Y. Klein, Michael Jeffrey Kneisl, Jeffrey S. Montag, Anthony G. Peabody, Terrance D. Reith, John D. Rosenberg, Andrew E. Krausz, Thomas CA Canc Comm Coll Amer Pathologists TI Protocol for the Examination of Specimens From Patients With Tumors of Bone SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID PROGNOSTIC-FACTOR; EWINGS-SARCOMA; ADULT PATIENTS; CHEMOTHERAPY; CLASSIFICATION; OSTEOSARCOMA; NECROSIS C1 [Rubin, Brian P.] Cleveland Clin, Dept Anat Pathol, Lerner Res Inst, Cleveland, OH 44195 USA. [Rubin, Brian P.] Cleveland Clin, Dept Mol Genet, Lerner Res Inst, Cleveland, OH 44195 USA. [Rubin, Brian P.] Taussig Canc Ctr, Cleveland, OH USA. [Antonescu, Cristina R.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. [Gannon, Francis H.] Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. [Hunt, Jennifer Leigh; Rosenberg, Andrew E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Inwards, Carrie Y.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Klein, Michael Jeffrey] Hosp Special Surg, Dept Pathol & Lab Med, New York, NY 10021 USA. [Kneisl, Jeffrey S.] Carolinas Med Ctr, Dept Orthopaed Surg, Charlotte, NC 28203 USA. [Montag, Anthony G.; Krausz, Thomas] Univ Chicago, Med Ctr, Dept Pathol, Chicago, IL 60637 USA. [Peabody, Terrance D.] Univ Chicago, Med Ctr, Dept Orthopaed Surg, Chicago, IL 60637 USA. [Reith, John D.] Univ Florida, Coll Med, Dept Pathol Immunol & Lab Med, Gainesville, FL USA. RP Rubin, BP (reprint author), Cleveland Clin, Dept Anat Pathol, Lerner Res Inst, L25,9500 Euclid Ave, Cleveland, OH 44195 USA. EM rubinb2@ccf.org NR 15 TC 10 Z9 10 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD APR PY 2010 VL 134 IS 4 BP E1 EP E7 PG 7 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 580EK UT WOS:000276429800001 PM 20367293 ER PT J AU Velmahos, GC AF Velmahos, George C. TI Seek Tricks for Leaks? No Answer in the Mix SO ARCHIVES OF SURGERY LA English DT Editorial Material ID BLOOD-TRANSFUSION C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. RP Velmahos, GC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM gvelmahos@partners.org NR 2 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 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD APR PY 2010 VL 145 IS 4 BP 376 EP 376 PG 1 WC Surgery SC Surgery GA 829ME UT WOS:000295585200016 ER PT J AU Viguera, AC Cohen, LS Whitfield, T Reminick, AM Bromfield, E Baldessarini, RJ AF Viguera, Adele C. Cohen, Lee S. Whitfield, Theodore Reminick, Alison M. Bromfield, Edward Baldessarini, Ross J. TI Perinatal use of anticonvulsants: differences in attitudes and recommendations among neurologists and psychiatrists SO ARCHIVES OF WOMENS MENTAL HEALTH LA English DT Article DE Anticonvulsants; Neurologists; Psychiatrists; Pregnancy; Breastfeeding; Neurobehavioral risk; Neonatal toxicity ID BIPOLAR DISORDER; WOMEN; PREGNANCY; MANAGEMENT; RECURRENCE; RISK AB We surveyed opinions and recommendations about perinatal anticonvulsant (AC) treatment among 166 neurologists (n = 88) and psychiatrists (n = 78) practicing in Massachusetts. They were similar in the recommendation of routinely informing patients of potential teratogenic risks of ACs and avoiding valproate during pregnancy. Neurologists were more likely to encourage pregnancy and nursing during AC-use than psychiatrists, and psychiatrist were more cautious regarding perinatal safety, citing potential neurobehavioral risks and complications of breastfeeding. These observations indicate substantial differences in opinions between psychiatrists and neurologists regarding AC use during pregnancy. C1 [Viguera, Adele C.] Cleveland Clin, Cleveland Clin Neurol Inst, Dept Psychiat & Psychol, Cleveland, OH 44106 USA. [Viguera, Adele C.; Cohen, Lee S.; Reminick, Alison M.; Baldessarini, Ross J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Viguera, Adele C.; Cohen, Lee S.; Reminick, Alison M.] Massachusetts Gen Hosp, Perinatal Psychiat Program, Boston, MA 02114 USA. [Whitfield, Theodore] Biostat Solut, Boston, MA USA. [Reminick, Alison M.] Univ Calif Los Angeles, Inst Neuropsychiat, Los Angeles, CA 90024 USA. [Bromfield, Edward] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Bromfield, Edward] Brigham & Womens Hosp, Boston, MA 02115 USA. [Baldessarini, Ross J.] McLean Hosp, Int Consortium Bipolar Disorders Res, Belmont, MA 02178 USA. RP Viguera, AC (reprint author), Cleveland Clin, Cleveland Clin Neurol Inst, Dept Psychiat & Psychol, Cleveland, OH 44106 USA. EM Viguera@ccf.org FU NIH [MH-011609, MH-071762]; National Alliance for Research in Schizophrenia and Depression; Harvard Medical School Scholars in Medicine Fellowship; Stanley Foundation; Bruce J. Anderson Foundation; McLean Private Donors Psychopharmacology Research Fund FX Supported in part by NIH grants MH-011609 and MH-071762, a National Alliance for Research in Schizophrenia and Depression grant, and Harvard Medical School Scholars in Medicine Fellowship Awards (to ACV); a Stanley Foundation grant (to LSC); and by a grant from the Bruce J. Anderson Foundation and by the McLean Private Donors Psychopharmacology Research Fund (to RJB). Our late colleague John Hennen, Ph. D. provided valuable assistance with the design and analysis of the study. NR 12 TC 2 Z9 3 U1 0 U2 1 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 1434-1816 J9 ARCH WOMEN MENT HLTH JI Arch. Womens Ment. Health PD APR PY 2010 VL 13 IS 2 BP 175 EP 178 DI 10.1007/s00737-009-0130-1 PG 4 WC Psychiatry SC Psychiatry GA 571JE UT WOS:000275747300007 PM 20049492 ER PT J AU Diaz, LA Llaurado, M Rello, J Restrepo, MI AF Diaz, Luis Aurelio Llaurado, Mireia Rello, Jordi Restrepo, Marcos I. TI Non-Pharmacological Prevention of Ventilator Associated Pneumonia SO ARCHIVOS DE BRONCONEUMOLOGIA LA Spanish DT Review DE Ventilator-associated pneumonia; Artificial respiration; Cross infection; Intensive care unit; Disease prevention ID CRITICALLY-ILL PATIENTS; NOSOCOMIAL MAXILLARY SINUSITIS; RECEIVING MECHANICAL VENTILATION; SUBGLOTTIC SECRETION DRAINAGE; EVIDENCE-BASED GUIDELINES; POSITIVE-PRESSURE VENTILATION; RANDOMIZED CONTROLLED-TRIAL; INTENSIVE-CARE-UNIT; NNIS SYSTEM REPORT; RISK-FACTORS AB Ventilator-associated pneumonia (VAP) is the first cause of mortality clue to nosocomial infections in the intensive care unit Its incidence ranges nom 9% to 67% of patients on mechanical ventilation Risk factors are multiple and are associated with prolonged stays in hospital and intensive care units Additional costs for each episode of VAP range from 9,000 (sic) to 31,000 (sic) Thus, its prevention should be considered as a priority This prevention could decrease associated morbidity, mortality, costs, and increase patient safety (C) 2009 SEPAR Published by Elsevier Espana, S L All rights reserved C1 [Restrepo, Marcos I.] Univ Texas Hlth Sci Ctr San Antonio, Div Pulm & Crit Care Med, S Texas Vet Hlth Care Syst Audie L Murphy Div, VERDICT, San Antonio, TX 78229 USA. [Diaz, Luis Aurelio] Geisinger Hlth Syst, Danville, PA USA. [Llaurado, Mireia; Rello, Jordi] Hosp Univ Joan XXIII, CIBER Enfermedades Resp CibeRes, Tarragona, Spain. [Rello, Jordi] Univ Rovira & Virgili, IISPV, Tarragona, Spain. RP Restrepo, MI (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Div Pulm & Crit Care Med, S Texas Vet Hlth Care Syst Audie L Murphy Div, VERDICT, San Antonio, TX 78229 USA. RI Restrepo, Marcos/H-4442-2014; OI LLAURADO-SERRA, MIREIA/0000-0002-5123-0581; Rello, Jordi/0000-0003-0676-6210 NR 121 TC 8 Z9 12 U1 2 U2 8 PU EDICIONES DOYMA S A PI BARCELONA PA TRAV DE GRACIA 17-21, 08021 BARCELONA, SPAIN SN 0300-2896 J9 ARCH BRONCONEUMOL JI Arch. Bronconeumol. PD APR PY 2010 VL 46 IS 4 BP 188 EP 195 DI 10.1016/j.arbres.2009.08.001 PG 8 WC Respiratory System SC Respiratory System GA 589AL UT WOS:000277116000006 PM 19819060 ER EF